\r\n\tThis book chapter’s main theme will be focused on transmission dynamics, pathogenesis, mechanisms of host interaction and response, epigenetics and markers, molecular diagnosis, RNA interacting proteins, RNA binding proteins, advanced development of tools for diagnosis, possible development of concepts for vaccines and anti drugs for RNA viruses, immunological mechanisms, treatment, prevention and control. \r\n\t
",isbn:"978-1-80355-667-3",printIsbn:"978-1-80355-666-6",pdfIsbn:"978-1-80355-668-0",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"52f8a3a1486912beae40b34ac557fed3",bookSignature:"Ph.D. Yogendra Shah",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11369.jpg",keywords:"HIV, Dengue, Zika, West Nile Virus, Chikungunya, Rabies, SARS-CoV2, MERS-CoV, Hanta Virus, Influenza, Whole Genome Sequencing, DNA Sequencing",numberOfDownloads:217,numberOfWosCitations:0,numberOfCrossrefCitations:0,numberOfDimensionsCitations:0,numberOfTotalCitations:0,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"October 4th 2021",dateEndSecondStepPublish:"November 1st 2021",dateEndThirdStepPublish:"December 31st 2021",dateEndFourthStepPublish:"March 21st 2022",dateEndFifthStepPublish:"May 20th 2022",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"10 months",secondStepPassed:!0,areRegistrationsClosed:!0,currentStepOfPublishingProcess:5,editedByType:null,kuFlag:!1,biosketch:"Dr. Shah obtained his Ph.D. degree in Veterinary Medicine from Hokkaido University, Japan. He was awarded the Young Science and Technology Award from the Nepal Academy of Science and Technology (NAST) in 2019. His research interests include infectious diseases, zoonotic infectious diseases, and vector-borne diseases.",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",middleName:null,surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah",profilePictureURL:"https://mts.intechopen.com/storage/users/278914/images/system/278914.jpg",biography:"Dr. Yogendra Shah is a consultant microbiologist/virologist, senior research microbiologist, and lecturer at Seti Provincial Hospital, COVID-19 PCR laboratory, National Zoonoses and Food Hygiene Research Center, and Kathmandu College of Science and Technology, Nepal. He obtained a Ph.D. in Veterinary Medicine (Bacteriology) from the Graduate School of Veterinary Medicine, Hokkaido University, Japan, in 2017. His research focuses on better understanding the molecular epidemiological features/transmission dynamics of infectious diseases and zoonotic infectious diseases in Nepal by employing molecular techniques like ELISA, polymerase chain reaction (PCR), loop-mediated isothermal amplification (LAMP), and DNA sequencing. He was awarded the Young Science and Technology Award from the Nepal Academy of Science and Technology (NAST) in 2019. His research interests include infectious diseases, zoonotic infectious diseases, and vector-borne diseases. He has published more than thirty-five research articles in peer-reviewed journals and twelve books.",institutionString:"National Zoonoses and Food Hygiene Research Centre",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"2",institution:{name:"National Zoonoses and Food Hygiene Research Centre",institutionURL:null,country:{name:"Nepal"}}}],coeditorOne:null,coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"13",title:"Immunology and Microbiology",slug:"immunology-and-microbiology"}],chapters:[{id:"80540",title:"Neurotropic Virus-Induced Meningoencephalomyelitis",slug:"neurotropic-virus-induced-meningoencephalomyelitis",totalDownloads:47,totalCrossrefCites:0,authors:[null]},{id:"81675",title:"Influenza Viruses: Targetting Conserved Viral Ha-Stem, Matrix and Nucleo-Proteins to Disarm a Resilient and Recurring Pandemic",slug:"influenza-viruses-targetting-conserved-viral-ha-stem-matrix-and-nucleo-proteins-to-disarm-a-resilien",totalDownloads:15,totalCrossrefCites:0,authors:[null]},{id:"81283",title:"COVID-19 Prevention through Vitamin C, D, and Zinc Supplementation: A Small Clinical Study in Two Parts",slug:"covid-19-prevention-through-vitamin-c-d-and-zinc-supplementation-a-small-clinical-study-in-two-parts",totalDownloads:26,totalCrossrefCites:0,authors:[{id:"232234",title:"Dr.",name:"Chanda",surname:"Siddoo-Atwal",slug:"chanda-siddoo-atwal",fullName:"Chanda Siddoo-Atwal"}]},{id:"81859",title:"Respiratory Syncytial Virus",slug:"respiratory-syncytial-virus",totalDownloads:6,totalCrossrefCites:0,authors:[null]},{id:"82086",title:"The Role of IL-6 in RNA Virus Infection",slug:"the-role-of-il-6-in-rna-virus-infection",totalDownloads:15,totalCrossrefCites:0,authors:[null]},{id:"81733",title:"Impairment of the Cardiovascular System during SARS-CoV-2 Infection",slug:"impairment-of-the-cardiovascular-system-during-sars-cov-2-infection",totalDownloads:13,totalCrossrefCites:0,authors:[null]},{id:"80052",title:"Chronic Inflammatory Bowel Disease and Demyelination of the Central Nervous System: A Report on Two Cases",slug:"chronic-inflammatory-bowel-disease-and-demyelination-of-the-central-nervous-system-a-report-on-two-c",totalDownloads:67,totalCrossrefCites:0,authors:[null]},{id:"80935",title:"Ageing and HIV-Risk in Non-Gravid Female Humans",slug:"ageing-and-hiv-risk-in-non-gravid-female-humans",totalDownloads:29,totalCrossrefCites:0,authors:[null]}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},personalPublishingAssistant:{id:"429343",firstName:"Martina",lastName:"Ivancic",middleName:null,title:"Ms.",imageUrl:"https://mts.intechopen.com/storage/users/429343/images/19998_n.jpg",email:"martina@intechopen.com",biography:"As an Author Service Manager, my responsibilities include monitoring and facilitating all publishing activities for authors and editors. From chapter submission and review to approval and revision, copyediting and design, until final publication, I work closely with authors and editors to ensure a simple and easy publishing process. I maintain constant and effective communication with authors, editors and reviewers, which allows for a level of personal support that enables contributors to fully commit and concentrate on the chapters they are writing, editing, or reviewing. I assist authors in the preparation of their full chapter submissions and track important deadlines and ensure they are met. I help to coordinate internal processes such as linguistic review, and monitor the technical aspects of the process. As an ASM I am also involved in the acquisition of editors. Whether that be identifying an exceptional author and proposing an editorship collaboration, or contacting researchers who would like the opportunity to work with IntechOpen, I establish and help manage author and editor acquisition and contact."}},relatedBooks:[{type:"book",id:"9018",title:"Some RNA Viruses",subtitle:null,isOpenForSubmission:!1,hash:"a5cae846dbe3692495fc4add2f60fd84",slug:"some-rna-viruses",bookSignature:"Yogendra Shah and Eltayb Abuelzein",coverURL:"https://cdn.intechopen.com/books/images_new/9018.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"10542",title:"Molecular Epidemiology Study of Mycobacterium Tuberculosis Complex",subtitle:null,isOpenForSubmission:!1,hash:"29279e34f971687dc28de62534335ac4",slug:"molecular-epidemiology-study-of-mycobacterium-tuberculosis-complex",bookSignature:"Yogendra Shah",coverURL:"https://cdn.intechopen.com/books/images_new/10542.jpg",editedByType:"Edited by",editors:[{id:"278914",title:"Ph.D.",name:"Yogendra",surname:"Shah",slug:"yogendra-shah",fullName:"Yogendra Shah"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1591",title:"Infrared Spectroscopy",subtitle:"Materials Science, Engineering and Technology",isOpenForSubmission:!1,hash:"99b4b7b71a8caeb693ed762b40b017f4",slug:"infrared-spectroscopy-materials-science-engineering-and-technology",bookSignature:"Theophile Theophanides",coverURL:"https://cdn.intechopen.com/books/images_new/1591.jpg",editedByType:"Edited by",editors:[{id:"37194",title:"Dr.",name:"Theophile",surname:"Theophanides",slug:"theophile-theophanides",fullName:"Theophile Theophanides"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3161",title:"Frontiers in Guided Wave Optics and Optoelectronics",subtitle:null,isOpenForSubmission:!1,hash:"deb44e9c99f82bbce1083abea743146c",slug:"frontiers-in-guided-wave-optics-and-optoelectronics",bookSignature:"Bishnu Pal",coverURL:"https://cdn.intechopen.com/books/images_new/3161.jpg",editedByType:"Edited by",editors:[{id:"4782",title:"Prof.",name:"Bishnu",surname:"Pal",slug:"bishnu-pal",fullName:"Bishnu Pal"}],productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"371",title:"Abiotic Stress in Plants",subtitle:"Mechanisms and Adaptations",isOpenForSubmission:!1,hash:"588466f487e307619849d72389178a74",slug:"abiotic-stress-in-plants-mechanisms-and-adaptations",bookSignature:"Arun Shanker and B. 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\n\t\t\t
1. Introduction
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Over the last decades, several studies have demonstrated that cancer cells have a unique metabolism compared to normal cells (Herling et al., 2011). Metabolic changes occurring in cancer cells are considered to be fundamental for the transformation of normal cells into cancer cells and are also responsible for the resistance to different types of chemotherapeutic drugs (Cree, 2011). Therefore, resistance to chemotherapy represents a major problem in the treatment of several tumor types. Among the different metabolic and signalling pathways that are altered in cancer cells, variations in the expression and activity of several drug- metabolizing enzymes play a critical role in drug resistance (Rochat, 2009). Resistance can occur prior to drug treatment (primary or innate resistance) or may develop over time following exposure to the drug (acquired resistance). In some patients, prolonged exposure to a single chemotherapeutic agent may lead to the development of resistance to multiple other structurally unrelated compounds, known as cross resistance or multidrug resistance.
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Cancer cell metabolism is also closely linked to molecular oxygen concentration. Indeed, weak blood irrigation is frequently encountered in solid tumors and is responsible for hypoxic environment which is associated with invasive/aggressive phenotype and therapeutic resistance (Shannon et al., 2003). Hypoxia also contributes to drug resistance because some chemotherapeutic drugs require oxygen to generate free radicals that contribute to toxicity. Moreover, hypoxia might modulate expression of enzymes directly involved in metabolism of chemotherapeutic drugs, thereby limiting the toxic effects of these drugs on cancer cells. On the other hand, new therapeutic strategies aim at using bioreductive drugs that are selectively toxic to hypoxic cells (McKeown et al., 2007).
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The proposal of this chapter is to describe the role of anticancer drug metabolism in chemotherapy resistance but also its importance for the development of new approaches, taking advantage of the specificity of cancer cells metabolism.
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2. Anticancer drugs
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Anticancer or chemotherapy drugs are powerful chemicals that kill cancer cells by arresting their growth at one or more checkpoints in their cell cycle. Their main role is thus to reduce and prevent the growth and spread of cancer cells. However, because anticancer agents rapidly affect dividing cells, normal cells are also affected. This is especially true in tissue with high cell turnover such as the gastrointestinal tract, bone marrow, skin, hair roots, nails... Consequently, side effects are commonly observed with various types of chemotherapies. More than 100 different drugs are used today for chemotherapy, either alone or in combination with other treatments.
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For several years, the most effective drugs used in cancer chemotherapy were DNA-damaging agents (Gurova, 2009). These drugs can be divided into different categories based on their mechanism of action. Inhibitors of DNA synthesis inhibit essential biosynthetic processes or are incorporated into macromolecules (DNA and RNA). These drugs are either structural analogues for heterocyclic bases or agents interfering with folate metabolism (heterocyclic bases and folic acid are DNA building blocks) and they inhibit main steps in the formation of purine and pyrimidine bases as well as nucleotides (Parker, 2009). This class of agent includes antifolates (methotrexate, pemetrixed) (Goldman et al., 2010), antipyrimidines (5-fluorouracil, capecitabine, eniluracile, hydroxyurea) (Longley et al., 2003) and antipurines (6-mercaptopurine, 6-thioguanine). Another class of drugs directly damages DNA by adding methyl or other alkyl groups onto nucleotide bases (Izbicka and Tolcher, 2004). This in turn inhibits their correct utilization by base pairing leading to mutation, DNA fragmentation as well as inhibition of DNA replication and transcription. These anticancer drugs include alkylating agents (cyclophosphamide, ifosfamide, melphalan, chlorambucil), platinum-based drugs (cisplatin, carboplatin), antibiotics (anthracyclines, dactinomycin, bleomycin, adriamycin, etoposide) and topoisomerase II inhibitors (camptothecine, irinotecan, topotecan). Molecules belonging to the third class affect synthesis or breakdown of the mitotic spindle (Risinger et al., 2009). These drugs disrupt the cell division by either inhibiting the tubulin polymerization and therefore the formation of the mitotic spindle (vinblastine, vincristine) or by stabilizing microtubules (paclitaxel, docetaxel).
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Over the past 20 years, the elucidation of different signal-transduction networks that are responsible for neoplastic transformation has led to rationally designed anticancer drugs that target specific molecular events. These targeted cancer drug candidates include protein kinase inhibitors that represent an important and still emerging class of therapeutic agents. Clinically approved kinase-targeted oncology agents include 1) small molecules such as imatinib (targeting Abl, Platelet-Derivated Growth Factor Receptor (PDGFR)), gefitinib and erlotinib (targeting epidermal growth factor Receptor (EGFR)), sorafenib (targeting PDGFR, EGFR, Raf-1, c-kit) or 2) antibodies such as Cetuximab or Bevacizumab that inhibit EGFR and vascular endothelial growth factor receptor (VEGFR), respectively (Sebolt-Leopold and English, 2006). Unfortunately, these new targeted drugs also face major obstacles similar to those that challenge traditional agents.
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3. Anticancer drug metabolism and resistance
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3.1. Anticancer drug metabolism
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\n\t\t\t\t\tIn vivo, after absorption in the organism, xenobiotics (including anticancer drugs) are typically metabolized through a number of parallel and/or sequential reactions. Metabolism occurred through two distinct consecutive phases named “phase I” and “phase II”, although this order is not exclusive (phase I not always followed by phase II; phase II not always preceded by phase I) (Iyanagi, 2007). Phase I reactions are most commonly described as “functionalization” reactions and include oxidations, reductions, and hydrolysis (Guengerich, 2007, 2008). These reactions introduce a new polar functional group to the parent drug (oxidation), modify an existing functional group in order to be more polar (reduction) or unmask existing polar functional group (hydrolysis). The most common functional groups exposed or introduced in the phase I reactions are hydroxyl (-OH), amino (-NH2), and carboxylic acid (-COOH).
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Phase II reactions are most commonly described as conjugation reactions and include glucuronidation, sulfonation, glycine/glutamine conjugation, acetylation, methylation, and glutathione (GSH) conjugation (Bock et al., 1987, Jancova et al., 2010). Conjugations allow linking a new group either to the parent drug or to phase I metabolites. Some conjugations cause a dramatic increase in the polarity and thus favor excretion of a drug by adding an ionized functional group: sulfonation, glucuronidation, and amino acid conjugation. Other conjugation reactions are just likely to cause termination of therapeutic activity: methylation and acetylation. GSH conjugation reaction protects against reactive metabolites.
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In this chapter, we will be interested mainly by two distinct families of enzymes, cytochrome P450s (CYP) and glutathione transferases (GST) belonging to phase I and phase II metabolism, respectively.
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3.1.1. Cytochrome P450s
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CYP enzymes are key players in the phase I-dependent metabolism, mostly catalyse oxidations of drugs and other xenobiotics. More than 57 active human CYP genes and 58 pseudogenes have been described (Sim and Ingelman-Sundberg, 2010). Most of these genes are polymorphic and more than 434 different alleles of genes encoding CYP enzymes have been identified. The CYP3A (CYP belonging to family 3, subfamily A) enzymes are involved in the metabolism of about 50% of all drugs currently on the market (Bu, 2006). CYPs also participate in the metabolic activation of several carcinogens such as aflatoxin B1 (Langouet et al., 1995). As a result of the CYP-dependent metabolism, intermediates that exert toxicity or carcinogenicity can be formed. In most cases, these metabolites are targets for phase II enzyme dependent reactions, rendering them inactive polar products suitable for excretion via the kidneys. Concerning anticancer agents, CYPs are involved not only in cytotoxic drugs detoxication but also in the activation of prodrugs making them therapeutically effective (McFadyen et al., 2004). Prodrugs are inactive agents that are converted to active cytotoxic drugs upon exposure to tumor tissues exhibiting high expression of activating enzymes. This targeting strategy minimizes toxicity towards normal tissues while it increases delivery of active agent to the tumor tissue. Cyclophosphamide, ifosfamide, dacarbazine, procarbazine, tegafur, and thiotepa are metabolized by CYPs in the liver and this activation reaction is required for therapeutic activity (Rodriguez-Antona and Ingelman-Sundberg, 2006). Another example is 1,4-bis-([2-(dimethylamino-N-oxide)ethyl]amino)5,8-dihydroxy anthracene-9,10-dione (AQ4N), a bioreductive prodrug that needs activation by CYP2S1 and CYP2W1 in tumor tissues to be converted to a topoisomerase II inhibitor (Nishida et al., 2010). Therefore, because CYPs are involved in either the bioactivation or the inactivation of both carcinogens and anticancer drugs (Huttunen et al., 2008), they play important roles in the etiology of cancer diseases and as determinants of cancer therapy (Oyama et al., 2004).
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3.1.2. Glutathione transferases
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GSTs are a family of ubiquitous intracellular enzymes that catalyze the conjugation of GSH to many exogenous and endogenous compounds (Hayes et al., 2005). These include chemical carcinogens, therapeutic drugs and products of oxidative stress. In addition to their major role in catalyzing the conjugation of electrophilic substrates to GSH, these enzymes have GSH-dependent peroxidase (Hurst et al., 1998) and isomerase (Johansson and Mannervik, 2001) activities. GSTs play an important role in the protection against reactive molecules such as electrophilic xenobiotics (anticancer drugs, pollutants or carcinogens) or endogenous alpha,beta-unsaturated aldehydes, quinones, epoxides, and hydroperoxides formed as secondary metabolites during oxidative stress. Over the last decade, different studies have demonstrated that GSTs also have a non-catalytic function via their interaction with some kinases (Adler et al., 1999, Cho et al., 2001, Gilot et al., 2002) or other proteins (Dulhunty et al., 2001, Wu et al., 2006) thus playing critical roles in stress response, apoptosis and proliferation. GSTs are members of at least three gene families: the cytosolic (or soluble) GSTs that are divided in seven families: alpha, mu, pi, theta, sigma, zeta and omega (Hayes et al., 2005); the mitochondrial GST (kappa class) (Morel and Aninat, 2011) and the membrane-associated proteins involved in eicosanoid and glutathione metabolism (MAPEG) (Jakobsson et al., 2000, Jakobsson et al., 1999). The cancer chemotherapeutic agents adriamycin, 1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU), busulfan, carmustine, chlorambucil, cisplatin, crotonyloxymethyl-2-cyclohexenone, cyclophosphamide, melphalan, mitozantrone and thiotepa are potent substrates of GSTs (Hamilton et al., 2003, Hayes and Pulford, 1995, Lien et al., 2002). Metabolism of these anticancer drugs by GSTs is related to several drug resistance phenomena and adverse toxicity effects (Townsend and Tew, 2003b).
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3.1.3. Drug transporters
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Drug passage across biological membranes is possible through two different mechanisms. The first one involves passive trans-cellular transport and concerned lipophilic molecules. The second one depends on carrier-mediated transporters, among which, we distinguish those requiring ATP-dependent hydrolysis as the first step in catalysis (ABC transporters such as multidrug resistance protein (MDR), multidrug resistance-associated protein (MRP), and breast cancer resistance protein (BCRP)) from those driven by an exchange or co-transport of intracellular and/or extracellular ions with the substrate (organic anion transporter (OAT), organic anion-transporting polypeptide (OATP), sodium taurocholate co-transporting peptide (NTCP), organic cation transporter (OCT), novel organic cation transporter (OCTN) and oligopeptide transporter (PEPT)) (Keppler, 2011, Li et al., 2010; Ni et al., 2010, Svoboda et al., 2011).
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Active transporters are of great interest to pharmacologists since they are responsible for both the uptake and the efflux of drugs and are key elements of the pharmacokinetic characteristics of a drug (Degorter et al., 2011). Indeed, it has now become clear that transporters are essential for the uptake, accumulation, distribution and efflux of drugs. For example, drug efflux transporters including the P-glycoprotein pump (Pgp), the multidrug-resistant protein-1 (MRP1) and the BCRP actively pump drugs such as chemotherapeutics out of the cells, thereby reducing their intracellular accumulation and making the cell insensitive to different drugs such as anthracyclines, vinca-alkaloids or taxanes. Among the major known ABC transporters, ABCB1 gene, also known as MDR1, encoding Pgp is by far the best characterized and understood efflux transporter (Goda et al., 2009, Wu et al., 2011). It is predominantly expressed in several tissues including the luminal surface of intestinal epithelia, the renal proximal tubule, the bile canalicular membrane of hepatocytes and the blood brain barrier (Ho and Kim, 2005). Pgp plays an important role in limiting intestinal drug absorption and brain penetration as well as in facilitating renal or biliary excretion of drugs. The MRPs are involved in the drug efflux from the liver or kidney into the peripheral blood (e.g. MRP1, MRP3, and MRP6), or from the liver, kidney and small intestines into the bile, urine and intestinal lumen respectively (MRP2) (Keppler, 2011). Since GSH-, glucuronide-, sulfate-conjugates and organic anions such as methotrexate, indinavir, cisplatin, vincristine and etoposide are all MRP substrates, MRPs are also crucial in human drug disposition and toxicity.
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3.2. Anticancer drug resistance
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The development of chemotherapy resistance remains a major problem to the effective treatment of many tumor types. Resistance can occur prior to drug treatment (primary or innate resistance) or may develop over time following exposure (acquired resistance). In some patients, prolonged exposure to a single chemotherapeutic agent may lead to the development of resistance to multiple other structurally unrelated compounds. This process is known as cross resistance or multidrug resistance (MDR). In primary resistance, MDR can occur without prior exposure to chemotherapy. Several mechanisms, including alterations in drug pharmacokinetic and metabolism, modification of drug target expression or function, drug compartmentalization in cellular organelles, altered repair of drug-induced DNA damages, changes in apoptotic signaling pathways or expression of proteins directly affecting cellular drug transport are responsible of anticancer drug resistance (Figure 1).
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Figure 1.
Representation of different mechanisms involved in anticancer drug resistance. ↗: increase; ↘: decrease; OATP: organic anion-transporting polypeptide ; OCT : organic cation transporter ; Pgp: P-glycoprotein; MRP: multidrug resistance associated proteins; CYP: cytochrome P-450; SOD: superoxide dismutase; GST: glutathione transferase; MAPK: mitogen activated protein kinase.
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3.2.1. Drug transport
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Drug transporters are the key determinants for the uptake, accumulation, distribution and efflux of several chemotherapeutic drugs. Interestingly, overexpression of these drug transporters in tumors has been demonstrated by several studies. Pgp is expressed in approximately 40% of all breast carcinomas (Trock et al., 1997), although another study reported values as high as 66% (Larkin et al., 2004). MRP3 was found to be the predominant MRP isoform in gallbladder carcinomas and cholangiocellular carcinomas and the intrinsic multidrug resistance in these carcinomas seems to be dependent on the expression of MRP3 (Rau et al., 2008). The MRP4 (also named cMOAT or ABCC4) gene is overexpressed in cisplatin resistant human cancer cell lines with decreased drug accumulation (Taniguchi et al., 1996). Platinum-resistant tumor cells are capable of eliminating platinum GSH-conjugates in an ATP-dependent manner through an active efflux mechanism mediated by a GS-X pumps (Ishikawa et al., 2000, Suzuki et al., 2001). MRP8, encoded by ABCC11 gene, is able to confer resistance to fluoropyrimidines by mediating the MgATP-dependent transport of the cytotoxic metabolite 5\'-fluoro-2\'-deoxyuridine monophosphate (Guo et al., 2003). MRP2 expression has been suggested to affect the efficacy of cisplatin treatment in patients with hepatocellular carcinoma (Korita et al., 2010). Overexpression of these pumps in tumor cells gives them the ability to evade the treatment by drugs such as cisplatin, fluoropyrimidines, doxorubicin and etoposide in different types of cancer (Jedlitschky et al., 1996, Kool et al., 1997, Xu et al., 2010, Zelcer et al., 2001). Therefore, the use of chemomodulators to inhibit efflux transport has been tested in an attempt to overcome this resistance (Baumert and Hilgeroth, 2009, Zhou et al., 2008). In this way, a recent study has demonstrated that indomethacin and SC236 inhibit Pgp and MRP1 expression and thus enhance the cytotoxicity of doxorubicin in human hepatocellular carcinoma cells (Ye et al., 2011).
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3.2.2. Drug inactivation/detoxification
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Drug-metabolizing enzymes can also play an important role in reducing the intracellular concentration of drugs and in affecting cancer drug resistance. Interestingly, certain drugs require to be metabolized by these enzymes before exerting their cytotoxic effects. The expression of drug-metabolizing enzymes can therefore either potentiate or reduce the toxicity of chemicals and variations in both the activation and the inactivation pathways are important variables that can lead to drug resistance. In model systems, it appears that both oxidation (phase I) and conjugation (phase II) enzymes play critical roles in protecting cells against many drugs and thus play a key role in drug resistance.
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3.2.2.1. Involvement of cytochrome P450s
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As previously mentioned, CYPs are involved in both activation and detoxication of xenobiotics, including therapeutic drugs. CYP3A4 plays an important role in the metabolism of several anticancer agents (e.g. taxanes, vinca-alkaloids and new drugs such as imatinib, sorafenib and gefitinib). CYP3A4 metabolizes docetaxel to inactive hydroxylated derivatives. Therefore, a high CYP3A4 activity would result in a poor therapeutic outcome of the drug. Accordingly, in cancer patients treated with docetaxel in combination with the potent CYP3A4 inhibitor ketoconazole, a 49% decrease in docetaxel clearance was found (Engels et al., 2004). A low expression of CYP3A4 in breast tumors resulted in a better response to docetaxel (Miyoshi et al., 2005). Similarly, hepatic CYP3A4 activity measured by the erythromycin breath test and midazolam clearance predicted docetaxel clearance and demonstrated a higher toxicity in patients with the lowest CYP3A4 activity (Goh et al., 2002). Similarly to docetaxel, irinotecan is inactivated by CYP3A4 and induction of CYP3A4 in patients receiving irinotecan results in a significant decrease in the formation of the toxic metabolite of this drug (Mathijssen et al., 2002). Additionally, CYP3A4 phenotype, as assessed by midazolam clearance, is significantly associated with irinotecan pharmacokinetic (Mathijssen et al., 2004). More recently, a study suggested that the Pregnane X-Receptor (PXR) pathway is also involved in irinotecan resistance in colon cancer cell line via the upregulation of drug-metabolizing genes such as CYP3A4 (Basseville et al., 2011).
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Other CYP families also participate to anticancer drugs metabolism. For example, CYP2C19 and CYP2B6 are involved in the activation of the chemotherapeutic agent cyclophosphamide (Helsby et al., 2010) and reduced expression of these CYPs is a potential mechanism of resistance. An interesting study showed a mechanism of acquired resistance to anticancer therapy based on the induction of CYP2C8 and MDR1. In this study, Caco-2 cells were capable of increasing the expression of CYP2C8 as a response to long-term exposure to paclitaxel (Garcia-Martin et al., 2006). Furthermore, the correlation between CYP polymorphism and anticancer drug response has been demonstrated for CYP2B6. Indeed, CYP2B6*2, CYP2B6*8, CYP2B6*9, CYP2B6*4 variant alleles are associated with response to doxorubicin- cyclophosphamide therapy in the treatment of breast cancer and with a worse outcome (Bray et al., 2010). In another study, it has been demonstrated that CYP1B1 inactivates docetaxel and showed that the overexpression of CYP1B1 in a Chinese hamster ovary fibroblast cell line (V79MZ) was correlated to a significantly decreased sensitivity towards docetaxel (McFadyen et al., 2001a, McFadyen et al., 2001b). Finally, other authors suggested that CYP1B1 does not directly inactivate docetaxel but promotes cell survival by another unknown mechanism (Martinez et al., 2008).
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Altogether, these studies demonstrate that altered levels of expression or inhibition of CYPs can have profound effects on the sensitivity of target cell to toxic compounds.
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3.2.2.2. Involvement of glutathione transferases
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GSTs are involved in the development of resistance to anticancer drugs by different ways. Indeed, they play a role in the metabolism of a diverse array of cancer chemotherapeutic agents including adriamycin, BCNU, busulfan, carmustine, chlorambucil, cisplatin, cyclophosphamide, ethacrynic acid, melphalan or thiotepa (Chen and Waxman, 1994, Dirven et al., 1994, Paumi et al., 2001). The roles of GSTs in the metabolism of these anticancer drugs and the correlation between GST expression levels and drug sensitivity have been demonstrated in several studies. For example, the inhibition of GST Pi 1 (GSTP1) expression, through antisense cDNA, has been shown to increase the tumor sensitivity to adriamicin, cisplatin, melphalan and etoposide (Ban et al., 1996). By contrast, the overexpression of GSTP1 in human renal UOK130 tumor cells was accompanied by a decreased sensitivity to cisplatin, melphalan and chlorambucil (Wang et al., 2007). Similarly, overexpression of Alpha class GST has been correlated with the resistance to alkylating agents in Colo 320HSR cells (Xie et al., 2005) and to doxorubicin in MCF-7 human breast cancer and small cell lung cancer (H69) cell lines (Sharma et al., 2006, Wang et al., 1999). Overexpression of Mu class GST has been associated with chlorambucil resistance in human ovarian carcinoma cell line (Horton et al., 1999) and with poor prognosis in childhood acute lymphoblastic leukaemia (Hall et al., 1994).
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Interestingly, high levels of GSTs are linked either with drug resistance or cancer incidence. GSTP1 has retained much attention because many tumors and cancer cell lines are characterized by high GSTP1 expression. Moreover, increased expression of GSTP1 has been associated to acquired resistance to cancer drugs (Tew, 1994). It is noteworthy that several studies have demonstrated that altered GST catalytic activities caused by genetic polymorphisms are linked to cancer susceptibility and prognosis (McIlwain et al., 2006). For example, GST genotypes are associated with primary and post-chemotherapy tumor histology in testicular germ cell tumors (Kraggerud et al., 2009); GST polymorphisms may have a role in treatment response and osteosarcoma progression (Salinas-Souza et al., 2010) and null genotypes of GSTM1 and GSTT1 contribute to hepatocellular carcinoma risk (Wang et al., 2010).
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The non-catalytic functions of GST might also play a key role in the anticancer drug sensitivity. Indeed, the direct interaction and inhibition of various MAP Kinases by GSTs have been demonstrated. These MAP kinases are involved in cell proliferation and apoptosis but also in anticancer drug responses. In the last decade, several studies have demonstrated that GSTs are involved in the control of apoptosis through the inhibition of the Jun N-terminal Kinase (JNK) signaling pathway. Indeed, JNK is inactive and sequestered into a GSTP1-JNK complex (Adler et al., 1999) whereas Apoptosis Signal Kinase 1 (ASK1) and Mitogen-activated protein kinase kinase kinase (MEKK1) interact with GSTM1 leading to their inactivation (Gilot et al., 2002, Ryoo et al., 2004). Thus, the overexpression of GSTs in many tumors or their up-regulation by drugs could represent another mechanism of drug resistance, independent of their enzymatic activity. As an example, cisplatin, chlorambucil, doxorubicin, 5-fluorouracil and carboplatin are among anticancer drugs whose toxicity require the activation of JNK and resistance to these drugs is highly associated to overexpression of GSTs in tumors (Townsend and Tew, 2003a). Therefore, development of GST inhibitors that could prevent MAPK inhibition is considered as a promising strategy to achieve new anticancer drugs in order to increase chemotherapeutic efficiency.
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3.2.3. Involvement of nuclear transcription factors in drug resistance
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Nuclear receptors are a superfamily of transcription factors with 48 distinct members identified within the human genome (Germain et al., 2006). In addition to the classic steroidal hormone receptors, other nuclear receptors act as metabolic sensors that respond to compounds of dietary origin, intermediates in metabolic pathways, drugs and other environmental factors, integrating homeostatic control over many metabolic processes (Sonoda et al., 2008). For example, some aspects of drug metabolism and transport are regulated by pregnane X receptor (PXR) and constitutive androstane receptor (CAR); energy and glucose metabolism are regulated in part by peroxisome proliferator-activated receptor gamma (PPARγ); fatty acid, triglyceride and lipoprotein metabolisms are controlled by PPARα, δ, and γ; reverse cholesterol transport and cholesterol absorption depends on liver X receptor (LXR) activation and bile acid metabolism is regulated by farnesoid X receptor (FXR) (Evans, 2005, Francis et al., 2003).
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PXR and CAR are master xenobiotic receptors that regulate the expression of genes involved in drug metabolism and clearance, including drug-metabolizing enzymes and transporters (Evans, 2005). In this part, we will focus on nuclear factors involved in the regulation drug-metabolizing enzymes and drug transporters (PXR, CAR and Nrf2) and on their specific roles in drug resistance.
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3.2.3.1. Pregnane X receptor (PXR)
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In 1998, a new member of the nuclear hormone receptor family, named PXR (NR1I2), has been identified (Kliewer et al., 1998). PXR is activated primarily by pregnanes and dimerizes with retinoid X receptor (RXR) immediately after its activation by ligand binding. PXR is present in the cytoplasm where it interacts with a protein complex. After its activation, PXR translocates into the nucleus to regulate gene transcription (Squires et al., 2004). PXR recognizes a wide variety of ligands including dexamethasone, rifampicin, spironolactone and pregnenolone 16α-carbonitrile being among the best characterized (Timsit and Negishi, 2007) as well as many anticancer drugs such as microtubule-binding drugs (Raynal et al., 2010). Targets genes of PXR are CYP3A4, MDR1, CYP2B6, members of UGTs superfamily and MRP3 and OATP2 transporters (Klaassen and Slitt, 2005; Tolson and Wang, 2010).
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Due to its capacity to recognize such compounds and to induce transcription of genes involved in the detoxification process, PXR is considered as one of the master regulator of xenobiotic clearance. Moreover, because PXR controls the expression of key genes involved in anticancer drugs disposition, recent works have focused on its potential role in drug resistance (Chen, 2010). The mechanisms of resistance induced by PXR activation probably involve up-regulation of drug-detoxifying enzymes and transporters. Supporting this hypothesis, it has been shown that PXR activation by different ligands induces PXR target genes (CYP2B6, CYP3A4 and UGT1A1) and consequently drug resistance in ovarian cancer cells (Gupta et al., 2008). Moreover, PXR induces expression of CYP3A4 and MDR1 genes in multiple cell types and the products of these genes are known to detoxify microtubule-binding and topoisomerase-binding drugs. Previous studies have shown that PXR activation regulates Pgp in the blood-brain barrier (Bauer et al., 2004). Interestingly, anticancer drugs such as vincristine, tamoxifen, vinblastine, docetaxel, cyclophosphamide, flutamide, ifosfamide and paclitaxel activate PXR-mediated Pgp induction and thus affect the cytotoxic activity and accumulation of the Pgp substrate rhodamine 123 (Harmsen et al., 2010).
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Increased expression of PXR leads to higher resistance of HEC-1 cells to paclitaxel and cisplatin (Chen, 2010) and of human colon adenocarcinoma to doxorubicin (Harmsen et al., 2010). In osteocarcinoma, the effectiveness of etoposide was reduced due to activation of PXR and the co-administration of PXR agonists enhanced the clearance of all-trans-retinoic acid (ATRA). This mechanism could potentially contribute to ATRA resistance in the treatment of acute promyelocytic leukemia (APL) and several solid tumors (Wang, T. et al., 2008). However, other mechanisms of resistance (e.g., down-regulation of apoptotic genes) may also play a dominant role (Zhou et al., 2008).
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3.2.3.2. Constitutive androstane receptor (CAR)
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The constitutive androstane receptor (CAR) is a sister xenobiotic receptor of PXR. CAR was first purified from hepatocytes as a protein bound to the phenobarbital responsive element in the CYP2B gene promoter. CAR was subsequently shown to bind to the CYP2B gene promoter as a heterodimer with retinoid X receptor (RXR). Transfected CAR exhibited a high basal activity and was once termed a “constitutively active receptor.” The name of constitutive androstane receptor was conceived due to the binding and inhibition of CAR activity by androstanes (Forman et al., 1998). CAR is retained in the cytoplasm by forming a complex with phosphatase 2A, HSP90 and cytosolic CAR retention protein (Kobayashi et al., 2003). Phenobarbital, 5β-pregnane-3,20-dione, and 5-androstan-3-ol are known CAR ligands (Moore et al., 2000). The hepatomitogen 1,4-Bis[2-(3,5-dichloropyridyloxy)] benzene (TCPOBOP) is a synthetic agonist for murine CAR (Tzameli et al., 2000) and 6-(4-chlorophenyl)imidazo[2,1-b] [1,3]thiazole-5-carbaldehydeO-(3,4-dichlorobenzyl)oxime (CITCO) is an imidazothiazole derivative that functions as a selective agonist for human CAR (Ikeda et al., 2005). Upon activation with specific agonist, CAR translocates into the nucleus and binds to the response elements as monomer or CAR/RXR heterodimer. CAR functions as a xenobiotic receptor that participates in the regulation of transcription of drug transporter genes such as MRPs (MRP2, MRP3 and MRP4), OATP2 and MDR1 ((Urquhart et al., 2007). CAR promotes the detoxification and elimination of potentially toxic compounds by modulating the phase I and phase II drug-metabolizing enzymes. Therefore, CAR-mediated expression of xenobiotic-metabolizing enzymes is generally protective, but can be deleterious if toxic metabolites are produced. CAR agonists are able to induce hepatocyte proliferation that depends on c-Myc-FoxM1 function (Blanco-Bose et al., 2008) but also to inhibit Fas-induced hepatocyte apoptosis by depleting the proapoptotic proteins Bak (Bcl-2 antagonistic killer) and Bax (Bcl-2-associated X protein) and increasing the expression of the antiapoptotic effector myeloid cell leukaemia factor-1 (Baskin-Bey et al., 2006).
The transcription factor Nrf2 (nuclear factor-erythroid 2p45 (NF-E2)-related factor 2) is a major regulator in the basal and inducible expression of various phase II detoxifying and antioxidant enzymes. In the resting state, kelch-like ECH-associated protein 1 (Keap1) functions as an intracellular redox receptor, which binds Nrf2 and targets it for proteosomal degradation. When cells are exposed to oxidative damage, Nrf2 is liberated from Keap1 and translocated into the nucleus where it specifically recognizes an enhancer sequence known as Antioxidant Response Element (ARE). This binding of Nrf2 on ARE sequence results in the activation of redox balancing genes (e.g. heme-oxygenase–1), phase II detoxifying genes (e.g. GSTs and NAD(P)H quinine oxidoreductase-1) and drug transporters (e.g. MRP) (Baird and Dinkova-Kostova, 2011; Taguchi et al., 2011). Several studies have suggested that the activation of Nrf2 protects against chronic diseases such as cardiovascular diseases, neurodegenerative disorders, lung inflammation, fibrosis, diabetes and nephropathy. However, in recent years, the dark side of Nrf2 has emerged and growing evidences suggest that Nrf2 constitutive up-regulation is associated with cancer development, progression and resistance to chemotherapy (Hayes and McMahon, 2006, 2009, Konstantinopoulos et al., 2011, Wang X.J. et al., 2008). Many anticancer drugs are responsible for the production of ROS in cancer cells, a phenomenon which contributes to drug-induced apoptosis. Such species are scavenged by the catalytic activities of superoxide dismutase, catalase, GSH peroxidase, γ-glutamylcysteine synthetase and heme oxygenase-1. These enzymes are members of the ARE-gene battery and are often overexpressed during carcinogenesis and it seems likely that Nrf2 may be responsible for this phenotype.
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The down-regulation of Nrf2-dependent response by overexpression of its negative regulator, Keap1, or transient-transfection of Nrf2-siRNA in lung carcinoma, breast adenocarcinoma, neuroblastoma, ovarian cancer and colon cancer rendered cancer cells more susceptible to cisplatin, etoposide, doxorubicin and 5-fluorouracil (Akhdar et al., 2009, Cho et al., 2008, Homma et al., 2009, Wang, X.J. et al., 2008). Induction of nuclear translocation and activation of Nrf2 by 5-fluorouracil, which in turn leads to antioxidant enzymes up-regulation and increases resistance toward cytotoxic effects of this anticancer drug has been recently demonstrated (Akhdar et al., 2009). The inhibition of Nrf2 by a specific flavone, lutolein, leads to negative regulation of the Nrf2/ARE pathway and to the sensitization of human lung carcinoma cells to therapeutic drugs (Tang et al., 2011). KEAP1 gene deletion provoked an aberrant Nrf2 activation and is one of the molecular mechanisms explaining chemotherapeutic resistance against 5-FU in gallbladder cells (Shibata et al., 2008a, Shibata et al., 2008b). Several studies have reported mutations of the interacting domain between Keap1 and Nrf2 leading to a permanent Nrf2 activation in non-small cell lung cancer (Ohta et al., 2008, Padmanabhan et al., 2006). Somatic mutations of the KEAP1 gene were also reported in patients affected by gall bladder tumors and in breast cancer cell line (Nioi and Nguyen, 2007, Shibata et al., 2008a). Although recent studies demonstrated low or no expression of KEAP1 in more than half of non-small cell lung cancers, only two papers investigated the epigenetic alterations of KEAP1 in this type of tumor. An aberrant hypermethylation at the KEAP1 gene promoter in lung cancer cell lines and in five lung cancer tissues has been demonstrated (Wang, R. et al., 2008). More recently, two alterations in KEAP1 gene were detected in one third of the non-small cell lung cancers suggesting that both copies of the gene might be inactivated (Muscarella et al., 2011). In these cases, Keap1 function is impaired, leading to constitutive stabilization of Nrf2 and increased activation of its cytoprotective target genes (Okawa et al., 2006).
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All of these findings support the idea that increased Nrf2 expression could facilitate cell growth, survival, resistance to chemotherapy through the activation of cytoprotective factors. Thus, investigating the deregulation of Keap1/Nrf2 pathway may shed light into the understanding of molecular mechanism of chemoresistance.
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3.2.3.4. Hypoxia and Hypoxia Inducible Factor-1 (HIF-1)
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\n\t\t\t\t\t\t\tHypoxia and HIF-1α are found in solid tumors\n\t\t\t\t\t\t
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Around fifty percent of locally advanced solid tumors exhibit hypoxic and/or anoxic tissue areas, heterogeneously distributed within the mass tumors (Vaupel and Mayer, 2007). Consequently, partial pressure of oxygen (PO2) in tumors is variable and can reach values between 10 to 30 mmHg (equivalent to 1 to 3% O2), in contrast to a PO2 of 50–80 mmHg in most normal tissues (Grigoryan et al., 2005). Three converging mechanisms lead to this limited oxygenation in cancer cells. The first one is due to cell proliferation which is responsible for an increase of the tumor mass. The second one is characterized by a loss of structural organization of blood vessels already present or newly formed (angiogenesis) in the solid tumor. This process leads to a decreased irrigation of the tumor. In addition, hematologic status of patients with cancer is frequently modified by the disease itself or by chemotherapy and numbers of them suffer from anemia triggering a reduced oxygen-carrying capacity of the blood (Vaupel and Harrison, 2004, Vaupel and Mayer, 2007). HIF-1 transcription factor is a master regulator of the hypoxic response and HIF-1α subunit is stabilized during hypoxia. Therefore, overexpression of HIF-1α has been found in many human cancers such as bladder, brain, breast, colon, ovarian, pancreatic, prostate and renal carcinomas (Talks et al., 2000).
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\n\t\t\t\t\t\t\tMetabolic adaptation to hypoxia and angiogenesis in solid tumor: HIF-1 and HIF-target genes\n\t\t\t\t\t\t
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In order to fight against hypoxia, a metabolic adaptation of solid tumors is observed compared to the surrounding normal tissue. This phenomena has been first described by Otto Warburg (Warburg, 1956) fifty years ago. He found that, in contrast to normal tissue where glycolysis is used to produce approximately 10% of ATP (the remaining 90% being obtained by oxidative phosphorylation via the tricarboxylic acid (TCA) cycle); solid tumors produced over 50% of ATP by anaerobic glycolysis, i.e. without oxidative phosphorylation and with lactate production. Interestingly, this phenomenon occurs even if oxygen is available for the mitochondrial function. This altered energy dependency is known as the “Warburg effect” and is a hallmark of cancer cells. Several explanations have been given to understand the use of anaerobic glycolysis rather than oxidative phosphorylation for production of ATP, while this is less efficient for energy production. The first one is linked to the accumulation of mutations in the mitochondrial genome that prevent the proper functioning of mitochondria (Carew and Huang, 2002). As a consequence, oxidative phosphorylation is not enough efficient, forcing the cancer cells to use anaerobic glycolysis for ATP production. The second one involves the activation of a transcription factor specifically activated in cell response to hypoxia: the transcription factor hypoxia-inducible factor-1 (HIF-1).
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HIF-1 transcription factor is composed of two protein subunits, HIF-1α and HIF-1β (Wang and Semenza, 1995). Its transcriptional activity depends on the stabilization of HIF-1α. While HIF-1β subunit is constitutively expressed into the cells, expression of HIF-1α protein is thinly regulated at a post-translational level. Hydroxylation of HIF-1α by prolyl hydroxylase domain (PHD) proteins, which target its subsequent proteasomal degradation, is one of the major mechanisms of regulation of HIF-1α cellular levels (Jaakkola et al., 2001). Since the activity of PHD enzymes is inhibited by low oxygen tension, HIF-1α protein is stabilized during hypoxia. As a result, upon hypoxic signal, HIF-1α subunit is stabilized translocated into the nucleus where it binds to HIF-1β to form the active HIF-1 complex. HIF-1 binds to hypoxia-responsive elements (HRE), consensus sequences in the promoter region of more than one hundred genes involved in cell proliferation, differentiation and survival, angiogenesis and energy metabolism that allow the cell, tissue, and organism to adapt to reduced oxygen conditions (Semenza, 2003).
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Regarding glycolysis metabolism, several HIF-1 gene targets are directly involved in the switch between aerobic to anaerobic glycolysis. Glucose cell uptake and its metabolism are very active in cancer cells. This high activity is correlated with the induction of expression of both the glucose transporter GLUT1 and the glycolysis enzymes aldolase C and phosphoglycerate kinase 1 (PGK1) (Seagroves et al., 2001; Semenza, 2003). Furthermore, HIF-1 facilitates the conversion of pyruvate into lactic acid by the induction of lactate dehydrogenase A (LDHA) (Firth et al., 1995) and pyruvate dehydrogenase kinase 1 (PDK1) expressions (Kim et al., 2006, Papandreou et al., 2006). PDK1, by inhibiting the activity of the pyruvate dehydrogenase (PDH) (Patel and Korotchkina, 2001), prevents conversion of pyruvate into acetyl-CoA, promotes the conversion of pyruvate into lactate and reduces the metabolic activities of the TCA cycle and the mitochondrial oxidative phosphorylation. Finally, in order to prevent acidosis due to lactate accumulation, intracellular pH homeostasis is maintained by induction of the expression of the carbonic anhydrase 9 and 12 (CA9 and CA12) (Potter and Harris, 2004), the lactate transporter MCT-4 (Ullah et al., 2006) and the Na+/H+ exchanger NHE1 (Shimoda et al., 2006), all direct gene targets of HIF-1. Thus, those metabolic adaptations confer a selective growth advantage and, combined with angiogenesis, are a prerequisite for metastasis.
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HIF-1 also plays a key role in angiogenesis, which is a process describing the growth of new blood vessels (neovascularization) from preexisting vessels. Angiogenesis is critical for tumor development since supply of oxygen and nutriments becomes limited to cancer cells located around 70-100 microns of a blood vessel (Carmeliet and Jain, 2000). Ability of tumor cells to induce angiogenesis occurs by a multi-step process, regulated by many pro-angiogenic factors. One of the strongest stimuli of angiogenesis is hypoxia and its transcription factor HIF-1 (Pugh and Ratcliffe, 2003). Indeed, HIF-1 can directly induce the expression of a number of proangiogenic factors such as the vascular endothelial growth factor (VEGF) and its receptors VEGFR1 and VEGFR2, the angiopoietins (ANG-1 and -2) and their receptors (Tie-1 and Tie-2) and the platelet-derived growth factor PDGF-β (Hickey and Simon, 2006). Of all the pro-angiogenic factors induced by HIF-1, VEGF is the factor that is most expressed in tumors (Dvorak, 2002). In several in vitro and in vivo models, HIF-1 signaling is required for VEGF production and the ability of tumor cells to promote angiogenesis. As such, stem cells HIF-1α-/- injected into nude mice form teratocarcinomas substantially smaller and less vascularized than WT embryonic cells (Ryan et al., 1998).
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Hypoxia and HIF-1 contribute to the poor response to anticancer therapy by several mechanisms (Cosse and Michiels, 2008, Tredan et al., 2007, Wouters et al., 2007). Indeed, HIF-1 activation allows expression of a battery of genes involved in survival and cell resistance to chemotherapy. For examples, studies have shown that hypoxia is directly involved in the induction of genes coding for the ABC transporters (MDR1, MRP1 and LRP), responsible for HepG2 cells resistance toward 5-Fluorouracil (Comerford et al., 2002, Zhu et al., 2005). Moreover, a recent study has demonstrated that, by down-regulating the expression of the MAPK-specific phosphatase dual-specificity phosphatase–2 (DUSP2), HIF-1 is involved in the resistance of HeLa and HCT116 cells to cisplatin, oxaliplatin, and paclitaxel (Lin et al., 2011). Hypoxia, by modulating expression of enzymes directly involved in metabolism of chemotherapeutic drugs, such as CYPs, could also limit the toxic effects of these drugs on cancer cells. As such, paclitaxel metabolism into 6α-hydroxypaclitaxel is reduced upon hypoxic conditions compared to normoxic conditions in HepaRG cells (Legendre et al., 2009). Furthermore, cytotoxic anticancer drugs require the presence of oxygen to exert their effects via the production of ROS, damaging DNA and inducing cell cycle arrest and death by apoptosis. Therefore, lack of oxygen could interfere for the efficiency of those molecules such as doxorubicin, which exerts its cytotoxic effect by the production of superoxide anion (Grigoryan et al., 2005). Another important point is that solid tumors are often poorly irrigated, leading to a decreased accessibility of anticancer agents to the tumor. Decreased drug concentrations, because of limited drug penetration into tumor masses, participates actively to resistance of the tumor to chemotherapy (Tredan et al., 2007). Finally, hypoxic environment of solid tumors is often correlated with a decrease of extracellular pH (acidosis) that also modulates the accumulation and/or cell toxicity of anticancer agents (Gerweck, 1998, Reichert et al., 2002). For example, resistance to mitoxantrone in MCF-7 cells is related to the acidification of extracellular pH (Greijer et al., 2005). Taken together, hypoxia and HIF-1 play a key role in anticancer drug resistance.
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3.2.4. Other mechanisms
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\n\t\t\t\t\t\tModification of drug target\n\t\t\t\t\t
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Cells survival depends on a balanced assembly and disassembly of the highly conserved cytoskeletal filaments formed from actin and tubulin. Microtubules are assembled from α-tubulin and β-tubulin heterodimers, along with other proteins such as microtubule-associated proteins. Some anticancer drugs (such as vinca-alkaloids) bind to and stabilize free tubulin, causing microtubule depolymerization and others (such as taxanes) bind to and stabilize microtubules, causing a net increase in tubulin polymerization (Zhou and Giannakakou, 2005). These two mechanisms of action inhibit cell division and thereby trigger apoptosis of cells. Altered expression of β-tubulin isotypes (overexpression or mutation) and microtubule-associated proteins is found in many cancer cell lines and xenografts resistant to microtubule inhibitors. These alterations may be associated with the primary or acquired resistance to tubulin-binding agents observed clinically in many tumors (Kamath et al., 2005, Wang and Cabral, 2005). Recently, a novel skeleton microtubule inhibitor, chamaecypanone C, with anticancer activity triggering caspase 8-Fas/FasL dependent apoptotic pathway in human cancer cells has been identified and its cytotoxicity in a variety human tumor cell lines has been studied (Hsieh et al., 2010). The authors considered that chamaecypanone C is a promising anticancer compound that has potential for management of various malignancies, particularly for patients with drug resistance.
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Many anticancer drugs exert their effects by inducing DNA damages. Thus, alterations in enzymes involved in DNA repair can affect drug resistance. Topoisomerase II is a critical enzyme that is involved in DNA replication and repair and reduced topoisomerase II expression or function can contribute to resistance to agents such as anthracyclines (Nitiss, 2009). DNA mismatch repair mediates damage repair from many drugs including alkylating agents, platinum compounds and anthracyclines and this mechanism has been implicated in drug resistance in cancer cells (Bignami et al., 2003).
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\n\t\t\t\t\t\tApoptosis\n\t\t\t\t\t
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Resistance can also arise from a failure of the cells to undergo apoptosis following DNA damages or other cellular injuries. Alterations in genes regulating the apoptotic pathway such as BCL2, BCLX (anti-apoptotic proteins) or TP53 promote resistance to anticancer drugs (O\'Connor et al., 1997). P53 can trigger elimination of the damaged cells by promoting apoptosis through the induction of pro-apoptotic genes, such as FAS and BAX, and the down-regulation of anti-apoptotic BCL2. Studies have reported that loss of p53 function reduces cellular sensitivity to anticancer drugs. Mutations in the TP53 gene are found in most human breast cancer cell lines, and certain mutations have been linked to de novo resistance to doxorubicin (Aas et al., 1996). On the other hand, the use of adenovirus-mediated TP53 gene therapy reverses resistance of breast cancer cells to adriamycin (Qi et al., 2011).
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4. Taking advantage of cancer cell metabolism for drug targeting
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4.1. Nuclear factors: Targets for new therapeutic strategies
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4.1.1. PXR and CAR
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During the last years, several groups have studied the role of PXR antagonists as potential pharmaceuticals for the reversal of drug resistance and enhancement of drug delivery (Biswas et al., 2009, Harmsen et al., 2010). Ketoconazole was originally described as a PXR antagonist (Takeshita et al., 2002). However, significant side effects of ketoconazole were reported mainly because of its off-target effects (e.g., cortisol synthesis, hepatic toxicity), some of which are related to its capacity to inhibit CYP activities. Recently, the development and characterization of a first-in-class novel azole analog [1-(4-(4-(((2R,4S)-2-(2,4-difluorophenyl)-2-methyl-1,3-dioxolan-4-yl)methoxy)phenyl)piperazin-1-yl)ethanone (FLB- 12)] that antagonizes the activated state of PXR has been published (Venkatesh et al., 2011). This analog has limited effects on other related nuclear receptors LXR, FXR, estrogen receptor α, PPARγ, and mouse CAR. FLB-12 was demonstrated to abrogate endogenous PXR activation in vitro and in vivo and was less toxic to liver cells in vivo compared to ketoconazole. Interestingly, FLB-12 significantly abrogates PXR-mediated resistance to 7-ethyl-10-hydroxycamptothecin (SN-38) in colon cancer cells in vitro. These drugs will not only serve as valuable chemical tools for probing PXR action but will also be important adjuncts for novel targeted approaches against cancer drug resistance.
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Thus, the concept that down-regulating PXR can sensitize cancer cells to chemotherapeutic agents has been proposed and investigated in several studies. In the prostate cancer cell line PC-3, treatment with the PXR agonist SR12813 activates PXR and increases both the expression of MDR1 and the resistance of PC-3 cells to the anticancer drugs paclitaxel and vinblastine. Inversely, the targeted knock-down of PXR by using short hairpin RNA (shRNA) enhanced the sensitivity of PC-3 to paclitaxel and vinblastine, suggesting that the effectiveness of anticancer drugs can be enhanced in PXR-positive cancers by decreasing the expression of PXR. Down-regulation of PXR by small interfering RNA (siRNA) in the endometrial cancer cell line HEC-1 also decreased the expression of MDR1 and sensitized cells to anticancer agent and PXR agonist paclitaxel and cisplatin (Masuyama et al., 2003, Masuyama et al., 2007). Other reports suggest that down-regulation of PXR may contribute to apoptotic and drug sensitivity in cancer cells (Gong et al., 2006, Masuyama et al., 2007). Finally, expression of PXR in human colorectal cancer cells led to irinotecan chemoresistance through enhancement of its glucuronidation catalyzed by UGT1A1. The opposite effect was obtained with pharmacological inactivation of PXR or shRNA-mediated PXR down-regulation, confirming the direct involvement of PXR in irinotecan chemoresistance (Raynal et al., 2010). Altogether, these studies demonstrate that PXR represents a potential therapeutic target for clinical applications relevant drug resistance.
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Although the properties of CAR and its agonists in xenobiotic metabolism have been extensively studied, its anticancer property was not known until very recently. Indeed, a recent study showed that CAR is a positive regulator of MDR1 (Pgp), MRP2 and BCRP expression in rat and mouse brain capillaries (Wang, B. et al., 2010). Moreover, another study demonstrated that CITCO inhibits the growth and expansion of brain tumor cancer stem cells by inducing cell cycle arrest and apoptosis in vitro (Chakraborty et al., 2011). Although the CAR-mediated antineoplastic effect is not known, these results support the use of CAR agonists as a new therapy to target brain tumor cancer stem cells for the treatment of glioma.
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4.1.2. HIF-1 and its target genes
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The adaptive cellular response of cancer cells to hypoxia offers new pharmacological targets, including the central regulator of molecular and cellular response to hypoxia HIF-1 as well as some of its target genes, particularly the VEGF and the carbonic CA9 (see Table 1). Validation of HIF-1 as a therapeutic target has been based on studies using genetic manipulation. When HIF-1α expression is increased in human cancer cells, angiogenesis capacity and metastasis spread are observed. Conversely, inhibition of the HIF-1α expression reverses those effects (Semenza, 2007). Accordingly, injection of tumor cells overexpressing HIF-1α into immunodeficient mice has demonstrated the capacity of HIF-1 to promote tumorigenesis (Maxwell et al., 1997). A growing number of novel anticancer agents have been shown to inhibit HIF-1 through a variety of molecular mechanisms. One of these promising molecules, the YC-1 ((3-(5\'-Hydroxymethyl-2\'-furyl)-1-benzylindazole), decreases the levels of HIF-1α protein through inhibition of the PI3K/AKT/mTor pathway (Sun et al., 2007). It has been shown that inhibition of HIF-1α activity in tumors from YC-1-treated mice is associated with blocked angiogenesis and an inhibition of tumor growth (Yeo et al., 2003).
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\n\t\t\t\t\t\t\t
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Target
\n\t\t\t\t\t\t\t\t
Agent
\n\t\t\t\t\t\t\t\t
Mechanism of action
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
Hypoxia
\n\t\t\t\t\t\t\t\t
Mitomycin C
\n\t\t\t\t\t\t\t\t
DNA damages
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
Banoxantrone (AQ4N)
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DNA damages and topoisomerase II inhibitor
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\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
Tirapazamine (TPZ)
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DNA damages
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
HIF-1 pathway
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YC-1a\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
PI3K/AKT/mTor inhibitor
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\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
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Tanespimycin (17-AAG)
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HSP90 inhibitor
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\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
PX-12b\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
Thioredoxin inhibitor
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\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
Topotecan
\n\t\t\t\t\t\t\t\t
Topoisomerase I inhibitor
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\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
HIF-1 target genes
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\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
CA9
\n\t\t\t\t\t\t\t\t
CAI17
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CA9-specific small molecule inhibitor
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
VEGF
\n\t\t\t\t\t\t\t\t
Sorafenib
\n\t\t\t\t\t\t\t\t
Tyrosine kinase inhibitor
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
Bevacizumab
\n\t\t\t\t\t\t\t\t
Anti-VEGF antibody
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t\t\t
GLUT1
\n\t\t\t\t\t\t\t\t
Fasentin
\n\t\t\t\t\t\t\t\t
Interacts with GLUT1 transporter and block glucose uptake
\n\t\t\t\t\t\t\t
\n\t\t\t\t\t\t
Table 1.
Examples of pharmacological approaches to target hypoxic cancer cells. a 3-(5\'-Hydroxymethyl-2\'-furyl)-1-benzylindazole; b 1-methylpropyl 2-imidazolyl disulfide.
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Angiogenesis has been described as one of the hallmarks of cancer, playing an essential role in tumor growth, invasion, and metastasis. For this reason, inhibition of angiogenesis has become a major challenge in the development of new anticancer agents, particularly in targeting the VEGF pathway. Sorafenib, a multitargeted inhibitor of tyrosine kinase, inhibits the receptor tyrosine kinase VEGFR2 and PDGFR and the Ras/Raf pathway (Keating and Santoro, 2009). Currently, this anticancer molecule demonstrated encouraging result for palliative therapy and can prolong the overall survival for patients with advanced hepatocellular carcinoma (Cheng et al., 2009). Moreover, anti-angiogenic therapy seems efficient to improve survival from patients with hepatocellular carcinoma and the anti-VEGF monoclonal antibody bevacizumab has shown promising results (Llovet and Bruix, 2008).
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Increased expression of CA9 has been found in many cancers and has been associated to an unfavorable prognosis (Kaluz et al., 2009, Pastorekova et al., 2008, Potter and Harris, 2004). Silencing both CA9 and CA12 resulted in marked inhibition of the growth of LS174 human colon carcinoma cell xenograft tumors (Chiche et al., 2010). Therefore, CA9 seems to be a new candidate for the development of new anticancer strategy. Interestingly, novel CA9-specific small molecule inhibitors such as the sulfonamide-based CAIX inhibitor CAI17 resulted in significant inhibition of tumor growth and metastasis formation in both spontaneous and experimental models of metastasis.
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\n\t\t\t
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4.2. Bioreductive agents
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It has been suggested that hypoxic environment in tumor tissues could be used as an advantage to target cancer cells with prodrugs that are metabolized into toxic metabolites only in hypoxic areas (McKeown et al., 2007). These drugs, also named bioreductive agents, are divided into 4 groups: quinones, nitroaromatics or nitro-heterocyclic, aliphatic N-oxides and heteroaromatic N-oxides.
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Mitomycin C that belongs to the quinone family is an alkylating antineoplastic agent and is frequently used for chemoembolization therapy. Bioreduction and activation of mitomycin C are facilitated upon a hypoxic environment. Indeed, electrons gain (reduction) of mitomycin products a semiquinone radical anion, which forms a covalent interaction with DNA. In the presence of oxygen, this radical anion is quickly degraded, thus giving the selectivity of hypoxia for generation of cytotoxic species (Kennedy et al., 1980).
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AQ4N or banoxantrone, is part of the aliphatic N-oxides. AQ4N is reduced into AQ4 under hypoxic condition. AQ4 exerts its cytotoxic activity by binding DNA and acting as an inhibitor of topoisomerase II. Used in combination with other anticancer agents, it has anti-proliferative effects on tumor cells (Patterson and McKeown, 2000).
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4.3. Activation of prodrugs by glutathione transferases
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As previously mentioned, a feature of cancer cell is to overexpress certain drug-metabolizing enzymes and transporters. Pathways involving such proteins that are aberrantly expressed in cancer cells are preferentially targeted for drug intervention. For example, the enhanced expression of GSTP1 in several tumors makes this protein a promising target for prodrug therapy. In order to take advantage of GSTP1 overexpression in cancer cells, two strategies have been performed. The first one consists in designing and developing inhibitors of GSTP1. Initially, this strategy was developed in order to decrease the metabolism of several active anticancer drugs known to be inactivated by GST. Furthermore, in 1999, evidence for a direct interaction of mouse GST pi with JNK was demonstrated (Adler et al., 1999). Their work showed that, under a monomeric state, GST pi acts as a direct JNK inhibitor in non-stressed cells by forming a complex with JNK and c-Jun. Oxidative stress (UV, H2O2…) induces the dimerization of GST pi and activation of c-jun through its phosphorylation on Ser-63 and Ser-73 residues. Subsequently, several other studies have corroborated this model in other cell lines (Bernardini et al., 2000, Castro-Caldas et al., 2009) and have shown that overexpression of GSTP1 in several tumor tissues lead to an inhibition of apoptosis pathways. Thus, inhibitor of GSTP1 triggering the disruption of this interaction could induce apoptosis in the cancer cell. TLK199 is one of them (Raza et al., 2009). The second strategy consists in designing prodrug activated by this enzyme in order to target specifically the tumor cells overexpressing GSTP1. Thus, novel alkylating agents have been synthetized (Lyttle et al., 1994, Satyam et al., 1996). Cleavage of these molecules by GSTP1 lead to the release of two metabolites: an inactive GSH conjugate and a phosphorodiamide compound. The phosphorodiamide spontaneously gives an alkylating moiety (a nitrogen mustard alkylating agent) which is responsible for the cytotoxicity. Among all the products synthetized, one has been actively studied and is tested in phase 2 and 3 studies (Kavanagh et al., 2010, Vergote et al., 2009). Initially named TER286, then TLK286, it is now designate with the International Nonproprietary Name (INN) canfosfamide (Telcita®). Several in vitro and in vivo studies, either on cell lines or on xenograft models, have linked the cytotoxicity of this molecule with the high level expression of GSTP1 and the formation of the alkylating moiety (Izbicka et al., 1997, Morgan et al., 1998, Rosario et al., 2000). Furthermore, Townsend et al. (Townsend et al., 2002) have demonstrated that canfosfamide is able to inhibit an enzyme involved in double strand break DNA repair, the DNA-dependent protein-kinase (DNA-PK). Interestingly, up-regulation of this DNA-PK leads to a resistance of adriamycin and cisplatin, suggesting that canfosfamide could be used in combination with these drugs. Several phase I studies have been realized in order to determine the safety and the pharmacokinetic of canfosfamide in human. These tests have been performed in advanced refractory solid cancers and have shown that canfosfamide is well tolerated with mild or moderate adverse effects such as nausea, vomiting, fatigue and anemia (grade 1 or 2) (Rosen et al., 2003, Rosen et al., 2004). Furthermore canfosfamide seems to be active in a large range of cancer including advanced non-small cell lung tumor (Sequist et al., 2009). Phase 2 and 3 clinical studies have also been done on resistant epithelial ovarian cancer (Kavanagh et al., 2010, Vergote et al., 2009).
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Another family of compounds is under development. These compounds own an O2-aryl diazeniumdiolate structure and are also metabolized by GSTP1 in a non-stable metabolite owning a Meisenheimer complex intermediate, which gives a GSH metabolite (PABA-GSH) and nitrogen monoxide (NO). Several of them have been designed (Andrei et al., 2008, Chakrapani et al., 2008, Saavedra et al., 2006) but the most specific and the most studied is the PABA/NO (O2-[2,4-dinitro-5-(p-methylaminobenzoato)] 1-(N, N-dimethylamino)diazen-1-ium-1,2-diolate) (Ji et al., 2008). Antiproliferative proprieties have been observed in several cell lines, including the mouse skin fibroblast NIH3T3 (Findlay et al., 2004), the human promyelocytic leukemia HL60 (Hutchens et al., 2010), the human leukemia U-937, the non-small-cell lung cancer H441, the colon cancer (HCT-116, HCT-15 and HT-29), the ovarian cancer OVCAR-3 (Andrei et al., 2008) and the U87 gliomas cell lines (Kogias et al., 2011). Antitumor activity was also demonstrated in an A2780 human ovarian cancer xenograft model in female SCID mice (Findlay et al., 2004). Mechanisms of cytotoxicity of PABA/NO involve several pathways which are due to the NO production and the nitrosylation and S-glutathionylation of some proteins. Townsend et al. (2005) have shown that PABA/NO is able to induce S-glutathionylation of several proteins, including the protein disulfide isomerase (PDI) (Townsend et al., 2005). Glutathionylation of PDI triggers a decrease of the folding protein capacity response, leading to cytotoxic effects. Activation of the apoptosis pathway through activation of JNK and p38 has also been observed (Townsend et al., 2005). Furthermore, GSH metabolite of PABA/NO is also able to inhibit sarco/endoplasmic reticulum calcium ATPases iso-enzymes, leading to an intracellular Ca2+ increase, triggering activation of the calmodulin pathway and thus increasing production of NO by endothelial Nitric Oxide Synthase (Manevich et al., 2010).
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5. Conclusion
\n\t\t\t
During the last years, several mechanisms involved in resistance phenomena have been elucidated and showed that, in many cases, drug-metabolizing enzymes and drug transporters are key factors in the failure of cancer therapies. In some cases, these discoveries led to useful strategies to identify “sensitive” tumors and direct clinical decisions for the choice of therapy. Furthermore, the molecular classification of several tumor types based on genome-wide investigations and identification of patient subclasses according to drug responsiveness should help to propose a more personalized medicine and to overcome anticancer drug resistance. Another promising field of investigation is to take advantage of cancer cell specificity in order to develop new tumor-targeted approaches that afford tumor specificity and limited toxicity.
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\n\t\n',keywords:null,chapterPDFUrl:"https://cdn.intechopen.com/pdfs/29245.pdf",chapterXML:"https://mts.intechopen.com/source/xml/29245.xml",downloadPdfUrl:"/chapter/pdf-download/29245",previewPdfUrl:"/chapter/pdf-preview/29245",totalDownloads:9288,totalViews:1094,totalCrossrefCites:11,totalDimensionsCites:30,totalAltmetricsMentions:0,introChapter:null,impactScore:21,impactScorePercentile:99,impactScoreQuartile:4,hasAltmetrics:0,dateSubmitted:"March 14th 2011",dateReviewed:"October 10th 2011",datePrePublished:null,datePublished:"February 22nd 2012",dateFinished:null,readingETA:"0",abstract:null,reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/29245",risUrl:"/chapter/ris/29245",book:{id:"672",slug:"topics-on-drug-metabolism"},signatures:"Hanane Akhdar, Claire Legendre, Caroline Aninat and Fabrice More",authors:[{id:"80375",title:"Dr.",name:"Fabrice",middleName:null,surname:"Morel",fullName:"Fabrice Morel",slug:"fabrice-morel",email:"Fabrice.Morel@rennes.inserm.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Inserm",institutionURL:null,country:{name:"France"}}},{id:"82193",title:"Dr.",name:"Hanane",middleName:null,surname:"Akhdar",fullName:"Hanane Akhdar",slug:"hanane-akhdar",email:"akhdar_hanan@hotmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Inserm",institutionURL:null,country:{name:"France"}}},{id:"82195",title:"Dr.",name:"Claire",middleName:null,surname:"Legendre",fullName:"Claire Legendre",slug:"claire-legendre",email:"claire_legendre@yahoo.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Inserm",institutionURL:null,country:{name:"France"}}},{id:"82197",title:"Dr.",name:"Caroline",middleName:null,surname:"Aninat",fullName:"Caroline Aninat",slug:"caroline-aninat",email:"Caroline.Aninat@univ-rennes1.fr",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:{name:"Inserm",institutionURL:null,country:{name:"France"}}}],sections:[{id:"sec_1",title:"1. Introduction ",level:"1"},{id:"sec_2",title:"2. Anticancer drugs",level:"1"},{id:"sec_3",title:"3. Anticancer drug metabolism and resistance ",level:"1"},{id:"sec_3_2",title:"3.1. Anticancer drug metabolism",level:"2"},{id:"sec_3_3",title:"3.1.1. Cytochrome P450s",level:"3"},{id:"sec_4_3",title:"3.1.2. Glutathione transferases",level:"3"},{id:"sec_5_3",title:"3.1.3. Drug transporters ",level:"3"},{id:"sec_7_2",title:"3.2. Anticancer drug resistance",level:"2"},{id:"sec_7_3",title:"3.2.1. Drug transport ",level:"3"},{id:"sec_8_3",title:"3.2.2. Drug inactivation/detoxification ",level:"3"},{id:"sec_8_4",title:"3.2.2.1. Involvement of cytochrome P450s",level:"4"},{id:"sec_9_4",title:"3.2.2.2. Involvement of glutathione transferases",level:"4"},{id:"sec_11_3",title:"3.2.3. Involvement of nuclear transcription factors in drug resistance ",level:"3"},{id:"sec_11_4",title:"3.2.3.1. Pregnane X receptor (PXR) ",level:"4"},{id:"sec_12_4",title:"3.2.3.2. Constitutive androstane receptor (CAR) ",level:"4"},{id:"sec_13_4",title:"3.2.3.3. Nuclear factor-erythroid 2p45 (NF-E2)-related factor 2 (NRF2)",level:"4"},{id:"sec_14_4",title:"3.2.3.4. Hypoxia and Hypoxia Inducible Factor-1 (HIF-1) ",level:"4"},{id:"sec_16_3",title:"3.2.4. Other mechanisms",level:"3"},{id:"sec_19",title:"4. Taking advantage of cancer cell metabolism for drug targeting",level:"1"},{id:"sec_19_2",title:"4.1. Nuclear factors: Targets for new therapeutic strategies",level:"2"},{id:"sec_19_3",title:"4.1.1. PXR and CAR",level:"3"},{id:"sec_20_3",title:"Table 1.",level:"3"},{id:"sec_22_2",title:"4.2. Bioreductive agents",level:"2"},{id:"sec_23_2",title:"4.3. Activation of prodrugs by glutathione transferases",level:"2"},{id:"sec_25",title:"5. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAas\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBorresen\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGeisler\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSmith-Sorensen\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJohnsen\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVarhaug\n\t\t\t\t\t\t\tJ. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAkslen\n\t\t\t\t\t\t\tL. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLonning\n\t\t\t\t\t\t\tP. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1996 Specific 53 mutations are associated with de novo resistance to doxorubicin in breast cancer patients. Nat Med, 2\n\t\t\t\t\t7 811-814.\n\t\t\t'},{id:"B2",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAdler\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYin\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFuchs\n\t\t\t\t\t\t\tS. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBenezra\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRosario\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTew\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPincus\n\t\t\t\t\t\t\tM. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSardana\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHenderson\n\t\t\t\t\t\t\tC. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWolf\n\t\t\t\t\t\t\tC. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDavis\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRonai\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999 Regulation of JNK signaling by GSTp. EMBO J, 18\n\t\t\t\t\t5 1321-1334.\n\t\t\t'},{id:"B3",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAkhdar\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLoyer\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRauch\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCorlu\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuillouzo\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorel\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Involvement of Nrf2 activation in resistance to 5-fluorouracil in human colon cancer HT-29 cells. Eur J Cancer, 45\n\t\t\t\t\t12 2219-2227.\n\t\t\t'},{id:"B4",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAndrei\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMaciag\n\t\t\t\t\t\t\tA. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChakrapani\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCitro\n\t\t\t\t\t\t\tM. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeefer\n\t\t\t\t\t\t\tL. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaavedra\n\t\t\t\t\t\t\tJ. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Aryl bis(diazeniumdiolates): potent inducers of S-glutathionylation of cellular proteins and their in vitro antiproliferative activities. J Med Chem, 51\n\t\t\t\t\t24 7944-7952.\n\t\t\t'},{id:"B5",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBaird\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDinkova-Kostova\n\t\t\t\t\t\t\tA. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 The cytoprotective role of the Keap1-Nrf2 pathway. Arch Toxicol, 85\n\t\t\t\t\t4 241-272.\n\t\t\t'},{id:"B6",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBan\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakahashi\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakayama\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKura\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKatahira\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSakamaki\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNiitsu\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1996 Transfection of glutathione S-transferase (GST)-pi antisense complementary DNA increases the sensitivity of a colon cancer cell line to adriamycin, cisplatin, melphalan, and etoposide. Cancer Res, 56\n\t\t\t\t\t15 3577-3582.\n\t\t\t'},{id:"B7",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBaskin-Bey\n\t\t\t\t\t\t\tE. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHuang\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIshimura\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIsomoto\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBronk\n\t\t\t\t\t\t\tS. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBraley\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCraig\n\t\t\t\t\t\t\tR. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoore\n\t\t\t\t\t\t\tD. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGores\n\t\t\t\t\t\t\tG. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 Constitutive androstane receptor (CAR) ligand, TCPOBOP, attenuates Fas-induced murine liver injury by altering Bcl-2 proteins. Hepatology, 44\n\t\t\t\t\t1 252-262.\n\t\t\t'},{id:"B8",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBasseville\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPreisser\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tde Carne\n\t\t\t\t\t\t\tTrecesson. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoisdron-Celle\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGamelin\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCoqueret\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorel\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Irinotecan induces steroid and xenobiotic receptor (SXR) signaling to detoxification pathway in colon cancer cells. Mol Cancer, 10\n\t\t\t\t\t1 80.\n\t\t\t'},{id:"B9",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBauer\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHartz\n\t\t\t\t\t\t\tA. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFricker\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiller\n\t\t\t\t\t\t\tD. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Pregnane X receptor up-regulation of P-glycoprotein expression and transport function at the blood-brain barrier. Mol Pharmacol, 66\n\t\t\t\t\t3 413-419.\n\t\t\t'},{id:"B10",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBaumert\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHilgeroth\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Recent advances in the development of P-gp inhibitors. Anticancer Agents Med Chem, 9\n\t\t\t\t\t4 415-436.\n\t\t\t'},{id:"B11",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBernardini\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBernassola\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCortese\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBallerini\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMelino\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMotti\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBellincampi\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIori\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFederici\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000 Modulation of GST P1-1 activity by polymerization during apoptosis. J Cell Biochem, 77\n\t\t\t\t\t4 645-653.\n\t\t\t'},{id:"B12",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBignami\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCasorelli\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKarran\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003 Mismatch repair and response to DNA-damaging antitumour therapies. Eur J Cancer, 39\n\t\t\t\t\t15 2142-2149.\n\t\t\t'},{id:"B13",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBiswas\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMani\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRedinbo\n\t\t\t\t\t\t\tM. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKrasowski\n\t\t\t\t\t\t\tM. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEkins\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Elucidating the’Jekyll and Hyde’ nature of PXR: the case for discovering antagonists or allosteric antagonists. Pharm Res, 26\n\t\t\t\t\t8 1807-1815.\n\t\t\t'},{id:"B14",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBlanco-Bose\n\t\t\t\t\t\t\tW. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMurphy\n\t\t\t\t\t\t\tM. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEhninger\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOffner\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDubey\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHuang\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoore\n\t\t\t\t\t\t\tD. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTrumpp\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 C-Myc and its target FoxM1 are critical downstream effectors of constitutive androstane receptor (CAR) mediated direct liver hyperplasia. Hepatology, 48\n\t\t\t\t\t4 1302-1311.\n\t\t\t'},{id:"B15",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBock\n\t\t\t\t\t\t\tK. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLilienblum\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFischer\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchirmer\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBock-Henning\n\t\t\t\t\t\t\tB. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1987 The role of conjugation reactions in detoxication. Arch Toxicol, 60\n\t\t\t\t\t1-3 , 22-29.\n\t\t\t'},{id:"B16",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBray\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSludden\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGriffin\n\t\t\t\t\t\t\tM. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCole\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVerrill\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJamieson\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoddy\n\t\t\t\t\t\t\tA. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Influence of pharmacogenetics on response and toxicity in breast cancer patients treated with doxorubicin and cyclophosphamide. Br J Cancer, 102\n\t\t\t\t\t6 1003-1009.\n\t\t\t'},{id:"B17",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBu\n\t\t\t\t\t\t\tH. Z.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 A literature review of enzyme kinetic parameters for CYP3A4-mediated metabolic reactions of 113 drugs in human liver microsomes: structure-kinetics relationship assessment. Curr Drug Metab, 7\n\t\t\t\t\t3 231-249.\n\t\t\t'},{id:"B18",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCarew\n\t\t\t\t\t\t\tJ. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHuang\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002 Mitochondrial defects in cancer. Mol Cancer, 1 9.\n\t\t\t'},{id:"B19",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCarmeliet\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJain\n\t\t\t\t\t\t\tR. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000 Angiogenesis in cancer and other diseases. Nature, 407\n\t\t\t\t\t6801 249-257.\n\t\t\t'},{id:"B20",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCastro-Caldas\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMilagre\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRodrigues\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGama\n\t\t\t\t\t\t\tM. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Glutathione S-transferase pi regulates UV-induced JNK signaling in SH-SY5Y neuroblastoma cells. Neurosci Lett, 451\n\t\t\t\t\t3 241-245.\n\t\t\t'},{id:"B21",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChakraborty\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKanakasabai\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBright\n\t\t\t\t\t\t\tJ. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Constitutive androstane receptor agonist CITCO inhibits growth and expansion of brain tumour stem cells. Br J Cancer, 104\n\t\t\t\t\t3 448-459.\n\t\t\t'},{id:"B22",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChakrapani\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilde\n\t\t\t\t\t\t\tT. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCitro\n\t\t\t\t\t\t\tM. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoodblatt\n\t\t\t\t\t\t\tM. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeefer\n\t\t\t\t\t\t\tL. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaavedra\n\t\t\t\t\t\t\tJ. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Synthesis, nitric oxide release, and anti-leukemic activity of glutathione-activated nitric oxide prodrugs: Structural analogues of PABA/NO, an anti-cancer lead compound. Bioorg Med Chem, 16\n\t\t\t\t\t5 2657-2664.\n\t\t\t'},{id:"B23",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWaxman\n\t\t\t\t\t\t\tD. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1994 Role of cellular glutathione and glutathione S-transferase in the expression of alkylating agent cytotoxicity in human breast cancer cells. Biochem Pharmacol, 47\n\t\t\t\t\t6 1079-1087.\n\t\t\t'},{id:"B24",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Overcoming drug resistance by regulating nuclear receptors. Adv Drug Deliv Rev, 62\n\t\t\t\t\t13 1257-1264.\n\t\t\t'},{id:"B25",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCheng\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKang\n\t\t\t\t\t\t\tY. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTsao\n\t\t\t\t\t\t\tC. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tQin\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tJ. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLuo\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFeng\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYe\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang\n\t\t\t\t\t\t\tT. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\tet al.\n\t\t\t\t\t\n\t\t\t\t\t2009 Efficacy and safety of sorafenib in patients in the Asia-Pacific region with advanced hepatocellular carcinoma: a phase III randomised, double-blind, placebo-controlled trial. Lancet Oncol, 10\n\t\t\t\t\t1 25-34.\n\t\t\t'},{id:"B26",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChiche\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrahimi-Horn\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPouyssegur\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Tumour hypoxia induces a metabolic shift causing acidosis: a common feature in cancer. J Cell Mol Med, 14\n\t\t\t\t\t4 771-794.\n\t\t\t'},{id:"B27",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCho\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tManandhar\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tH. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPark\n\t\t\t\t\t\t\tH. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKwak\n\t\t\t\t\t\t\tM. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Role of the Nrf2-antioxidant system in cytotoxicity mediated by anticancer cisplatin: implication to cancer cell resistance. Cancer Lett, 260\n\t\t\t\t\t1-2 , 96-108.\n\t\t\t'},{id:"B28",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCho\n\t\t\t\t\t\t\tS. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tY. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPark\n\t\t\t\t\t\t\tH. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRyoo\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKang\n\t\t\t\t\t\t\tK. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPark\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEom\n\t\t\t\t\t\t\tS. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tM. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChang\n\t\t\t\t\t\t\tT. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChoi\n\t\t\t\t\t\t\tS. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShim\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDong\n\t\t\t\t\t\t\tM. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tM. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tS. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIchijo\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChoi\n\t\t\t\t\t\t\tE. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001 Glutathione S-transferase mu modulates the stress-activated signals by suppressing apoptosis signal-regulating kinase 1. J Biol Chem, 276\n\t\t\t\t\t16 12749-12755.\n\t\t\t'},{id:"B29",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tComerford\n\t\t\t\t\t\t\tK. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWallace\n\t\t\t\t\t\t\tT. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKarhausen\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLouis\n\t\t\t\t\t\t\tN. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMontalto\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tColgan\n\t\t\t\t\t\t\tS. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002 Hypoxia-inducible factor-1-dependent regulation of the multidrug resistance (MDR1) gene. Cancer Res, 62\n\t\t\t\t\t12 3387-3394.\n\t\t\t'},{id:"B30",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCosse\n\t\t\t\t\t\t\tJ. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMichiels\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Tumour hypoxia affects the responsiveness of cancer cells to chemotherapy and promotes cancer progression. Anticancer Agents Med Chem, 8\n\t\t\t\t\t7 790-797.\n\t\t\t'},{id:"B31",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCree\n\t\t\t\t\t\t\tI. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Cancer biology. Methods Mol Biol, 731 1-11.\n\t\t\t'},{id:"B32",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDegorter\n\t\t\t\t\t\t\tM. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXia\n\t\t\t\t\t\t\tC. Q.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang\n\t\t\t\t\t\t\tJ. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tR. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Drug Transporters in Drug Efficacy and Toxicity. Annu Rev Pharmacol Toxicol.\n\t\t\t'},{id:"B33",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDirven\n\t\t\t\t\t\t\tH. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tvan Ommen\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tvan Bladeren\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1994 Involvement of human glutathione S-transferase isoenzymes in the conjugation of cyclophosphamide metabolites with glutathione. Cancer Res, 54\n\t\t\t\t\t23 6215-6220.\n\t\t\t'},{id:"B34",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDulhunty\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGage\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCurtis\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChelvanayagam\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoard\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001 The glutathione transferase structural family includes a nuclear chloride channel and a ryanodine receptor calcium release channel modulator. J Biol Chem, 276\n\t\t\t\t\t5 3319-3323.\n\t\t\t'},{id:"B35",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDvorak\n\t\t\t\t\t\t\tH. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002 Vascular permeability factor/vascular endothelial growth factor: a critical cytokine in tumor angiogenesis and a potential target for diagnosis and therapy. J Clin Oncol, 20\n\t\t\t\t\t21 4368-4380.\n\t\t\t'},{id:"B36",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEngels\n\t\t\t\t\t\t\tF. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTen\n\t\t\t\t\t\t\tTije. A. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBaker\n\t\t\t\t\t\t\tS. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tC. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLoos\n\t\t\t\t\t\t\tW. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVulto\n\t\t\t\t\t\t\tA. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVerweij\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSparreboom\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Effect of cytochrome 450 3A4 inhibition on the pharmacokinetics of docetaxel. Clin Pharmacol Ther, 75\n\t\t\t\t\t5 448-454.\n\t\t\t'},{id:"B37",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEvans\n\t\t\t\t\t\t\tR. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 The nuclear receptor superfamily: a rosetta stone for physiology. Mol Endocrinol, 19\n\t\t\t\t\t6 1429-1438.\n\t\t\t'},{id:"B38",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFindlay\n\t\t\t\t\t\t\tV. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTownsend\n\t\t\t\t\t\t\tD. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaavedra\n\t\t\t\t\t\t\tJ. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBuzard\n\t\t\t\t\t\t\tG. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCitro\n\t\t\t\t\t\t\tM. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeefer\n\t\t\t\t\t\t\tL. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJi\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTew\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Tumor cell responses to a novel glutathione S-transferase-activated nitric oxide-releasing prodrug. Mol Pharmacol, 65\n\t\t\t\t\t5 1070-1079.\n\t\t\t'},{id:"B39",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFirth\n\t\t\t\t\t\t\tJ. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEbert\n\t\t\t\t\t\t\tB. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRatcliffe\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1995 Hypoxic regulation of lactate dehydrogenase A. Interaction between hypoxia-inducible factor 1 and cAMP response elements. J Biol Chem, 270\n\t\t\t\t\t36 21021-21027.\n\t\t\t'},{id:"B40",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tForman\n\t\t\t\t\t\t\tB. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTzameli\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChoi\n\t\t\t\t\t\t\tH. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSimha\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSeol\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEvans\n\t\t\t\t\t\t\tR. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoore\n\t\t\t\t\t\t\tD. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1998 Androstane metabolites bind to and deactivate the nuclear receptor CAR-beta. Nature, 395\n\t\t\t\t\t6702 612-615.\n\t\t\t'},{id:"B41",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFrancis\n\t\t\t\t\t\t\tG. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFayard\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPicard\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAuwerx\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003 Nuclear receptors and the control of metabolism. Annu Rev Physiol, 65 261-311.\n\t\t\t'},{id:"B42",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGarcia-Martin\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPizarro\n\t\t\t\t\t\t\tR. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMartinez\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGutierrez-Martin\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPerez\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJover\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAgundez\n\t\t\t\t\t\t\tJ. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 Acquired resistance to the anticancer drug paclitaxel is associated with induction of cytochrome 450 2C8. Pharmacogenomics, 7\n\t\t\t\t\t4 575-585.\n\t\t\t'},{id:"B43",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGermain\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStaels\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDacquet\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpedding\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLaudet\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 Overview of nomenclature of nuclear receptors. Pharmacol Rev, 58\n\t\t\t\t\t4 685-704.\n\t\t\t'},{id:"B44",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGerweck\n\t\t\t\t\t\t\tL. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1998 Tumor pH: implications for treatment and novel drug design. Seminars in radiation oncology, 8\n\t\t\t\t\t3 176-182.\n\t\t\t'},{id:"B45",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGilot\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLoyer\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCorlu\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGlaise\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLagadic-Gossmann\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAtfi\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorel\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIchijo\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuguen-Guillouzo\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002 Liver protection from apoptosis requires both blockage of initiator caspase activities and inhibition of ASK1/JNK pathway via glutathione S-transferase regulation. J Biol Chem, 277\n\t\t\t\t\t51 49220-49229.\n\t\t\t'},{id:"B46",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoda\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBacso\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSzabo\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Multidrug resistance through the spectacle of P-glycoprotein. Curr Cancer Drug Targets, 9\n\t\t\t\t\t3 281-297.\n\t\t\t'},{id:"B47",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoh\n\t\t\t\t\t\t\tB. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tS. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tL. Z.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFan\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuo\n\t\t\t\t\t\t\tJ. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLamba\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchuetz\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLim\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLim\n\t\t\t\t\t\t\tH. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOng\n\t\t\t\t\t\t\tA. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tH. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002 Explaining interindividual variability of docetaxel pharmacokinetics and pharmacodynamics in Asians through phenotyping and genotyping strategies. J Clin Oncol, 20\n\t\t\t\t\t17 3683-3690.\n\t\t\t'},{id:"B48",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoldman\n\t\t\t\t\t\t\tI. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChattopadhyay\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhao\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoran\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 The antifolates: evolution, new agents in the clinic, and how targeting delivery via specific membrane transporters is driving the development of a next generation of folate analogs. Curr Opin Investig Drugs, 11\n\t\t\t\t\t12 1409-1423.\n\t\t\t'},{id:"B49",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGong\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSingh\n\t\t\t\t\t\t\tS. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSingh\n\t\t\t\t\t\t\tS. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMu\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tJ. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaini\n\t\t\t\t\t\t\tS. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tToma\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRen\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKagan\n\t\t\t\t\t\t\tV. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDay\n\t\t\t\t\t\t\tB. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZimniak\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXie\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 Orphan nuclear receptor pregnane X receptor sensitizes oxidative stress responses in transgenic mice and cancerous cells. Mol Endocrinol, 20\n\t\t\t\t\t2 279-290.\n\t\t\t'},{id:"B50",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGreijer\n\t\t\t\t\t\t\tA. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tde Jong\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tScheffer\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShvarts\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tvan Diest\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tvan der Wall\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 Hypoxia-induced acidification causes mitoxantrone resistance not mediated by drug transporters in human breast cancer cells. Cellular oncology : the official journal of the International Society for Cellular Oncology, 27\n\t\t\t\t\t1 43-49.\n\t\t\t'},{id:"B51",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrigoryan\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeshelava\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAnderson\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReynolds\n\t\t\t\t\t\t\tC. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 In vitro testing of chemosensitivity in physiological hypoxia. Methods Mol Med, 110 87-100.\n\t\t\t'},{id:"B52",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuengerich\n\t\t\t\t\t\t\tF. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 Mechanisms of cytochrome 450 substrate oxidation: MiniReview. J Biochem Mol Toxicol, 21\n\t\t\t\t\t4 163-168.\n\t\t\t'},{id:"B53",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuengerich\n\t\t\t\t\t\t\tF. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Cytochrome 450 and chemical toxicology. Chem Res Toxicol, 21\n\t\t\t\t\t1 70-83.\n\t\t\t'},{id:"B54",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuo\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKotova\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tZ. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHopper-Borge\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBelinsky\n\t\t\t\t\t\t\tM. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKruh\n\t\t\t\t\t\t\tG. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003 MRP8, ATP-binding cassette C11 (ABCC11), is a cyclic nucleotide efflux pump and a resistance factor for fluoropyrimidines 2’,3’-dideoxycytidine and 9’-(2’-phosphonylmethoxyethyl)adenine. J Biol Chem, 278\n\t\t\t\t\t32 29509-29514.\n\t\t\t'},{id:"B55",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGupta\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVenkatesh\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSinz\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoldberg\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWhitney\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLongley\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMani\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Expanding the roles for pregnane X receptor in cancer: proliferation and drug resistance in ovarian cancer. Clin Cancer Res, 14\n\t\t\t\t\t17 5332-5340.\n\t\t\t'},{id:"B56",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGurova\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 New hopes from old drugs: revisiting DNA-binding small molecules as anticancer agents. Future Oncol, 5\n\t\t\t\t\t10 1685-1704.\n\t\t\t'},{id:"B57",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHall\n\t\t\t\t\t\t\tA. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAutzen\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCattan\n\t\t\t\t\t\t\tA. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMalcolm\n\t\t\t\t\t\t\tA. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCole\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKernahan\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReid\n\t\t\t\t\t\t\tM. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1994 Expression of mu class glutathione S-transferase correlates with event-free survival in childhood acute lymphoblastic leukemia. Cancer Res, 54\n\t\t\t\t\t20 5251-5254.\n\t\t\t'},{id:"B58",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHamilton\n\t\t\t\t\t\t\tD. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDing\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHubatsch\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMannervik\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHouk\n\t\t\t\t\t\t\tK. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGanem\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCreighton\n\t\t\t\t\t\t\tD. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003 Mechanism of the glutathione transferase-catalyzed conversion of antitumor 2-crotonyloxymethyl-2-cycloalkenones to GSH adducts. J Am Chem Soc, 125\n\t\t\t\t\t49 15049-15058.\n\t\t\t'},{id:"B59",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHarmsen\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMeijerman\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFebus\n\t\t\t\t\t\t\tC. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMaas-Bakker\n\t\t\t\t\t\t\tR. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBeijnen\n\t\t\t\t\t\t\tJ. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchellens\n\t\t\t\t\t\t\tJ. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 PXR-mediated induction of P-glycoprotein by anticancer drugs in a human colon adenocarcinoma-derived cell line. Cancer Chemother Pharmacol, 66\n\t\t\t\t\t4 765-771.\n\t\t\t'},{id:"B60",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHayes\n\t\t\t\t\t\t\tJ. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPulford\n\t\t\t\t\t\t\tD. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1995 The glutathione S-transferase supergene family: regulation of GST and the contribution of the isoenzymes to cancer chemoprotection and drug resistance. Crit Rev Biochem Mol Biol, 30\n\t\t\t\t\t6 445-600.\n\t\t\t'},{id:"B61",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHayes\n\t\t\t\t\t\t\tJ. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFlanagan\n\t\t\t\t\t\t\tJ. U.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJowsey\n\t\t\t\t\t\t\tI. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 Glutathione transferases. Annu Rev Pharmacol Toxicol, 45 51-88.\n\t\t\t'},{id:"B62",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHayes\n\t\t\t\t\t\t\tJ. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Mahon\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 The double-edged sword of Nrf2: subversion of redox homeostasis during the evolution of cancer. Mol Cell, 21\n\t\t\t\t\t6 732-734.\n\t\t\t'},{id:"B63",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHayes\n\t\t\t\t\t\t\tJ. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Mahon\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 NRF2 and KEAP1 mutations: permanent activation of an adaptive response in cancer. Trends Biochem Sci, 34\n\t\t\t\t\t4 176-188.\n\t\t\t'},{id:"B64",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHelsby\n\t\t\t\t\t\t\tN. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHui\n\t\t\t\t\t\t\tC. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoldthorpe\n\t\t\t\t\t\t\tM. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tColler\n\t\t\t\t\t\t\tJ. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSoh\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGow\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDe Zoysa\n\t\t\t\t\t\t\tJ. Z.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTingle\n\t\t\t\t\t\t\tM. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 The combined impact of CYP2C19 and CYP2B6 pharmacogenetics on cyclophosphamide bioactivation. Br J Clin Pharmacol, 70\n\t\t\t\t\t6 844-853.\n\t\t\t'},{id:"B65",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHerling\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKonig\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBulik\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHolzhutter\n\t\t\t\t\t\t\tH. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Enzymatic features of the glucose metabolism in tumor cells. FEBS J, 278\n\t\t\t\t\t14 2436-2459.\n\t\t\t'},{id:"B66",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHickey\n\t\t\t\t\t\t\tM. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSimon\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 Regulation of angiogenesis by hypoxia and hypoxia-inducible factors. Current topics in developmental biology, 76 217-257.\n\t\t\t'},{id:"B67",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHo\n\t\t\t\t\t\t\tR. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tR. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 Transporters and drug therapy: implications for drug disposition and disease. Clin Pharmacol Ther, 78\n\t\t\t\t\t3 260-277.\n\t\t\t'},{id:"B68",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHomma\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIshii\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorishima\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamadori\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMatsuno\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHaraguchi\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKikuchi\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSatoh\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSakamoto\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHizawa\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tItoh\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamamoto\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Nrf2 enhances cell proliferation and resistance to anticancer drugs in human lung cancer. Clin Cancer Res, 15\n\t\t\t\t\t10 3423-3432.\n\t\t\t'},{id:"B69",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHorton\n\t\t\t\t\t\t\tJ. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRoy\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPiper\n\t\t\t\t\t\t\tJ. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVan Houten\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAwasthi\n\t\t\t\t\t\t\tY. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMitra\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlaoui-Jamali\n\t\t\t\t\t\t\tM. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoldogh\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSinghal\n\t\t\t\t\t\t\tS. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999 Characterization of a chlorambucil-resistant human ovarian carcinoma cell line overexpressing glutathione S-transferase mu. Biochem Pharmacol, 58\n\t\t\t\t\t4 693-702.\n\t\t\t'},{id:"B70",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHsieh\n\t\t\t\t\t\t\tC. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuo\n\t\t\t\t\t\t\tY. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuo\n\t\t\t\t\t\t\tC. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tL. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCheung\n\t\t\t\t\t\t\tC. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChao\n\t\t\t\t\t\t\tT. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLin\n\t\t\t\t\t\t\tC. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPan\n\t\t\t\t\t\t\tW. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChang\n\t\t\t\t\t\t\tC. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChien\n\t\t\t\t\t\t\tS. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tT. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLung\n\t\t\t\t\t\t\tC. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChang\n\t\t\t\t\t\t\tJ. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Chamaecypanone C, a novel skeleton microtubule inhibitor, with anticancer activity by trigger caspase 8-Fas/FasL dependent apoptotic pathway in human cancer cells. Biochem Pharmacol, 79\n\t\t\t\t\t9 1261-1271.\n\t\t\t'},{id:"B71",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHurst\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBao\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJemth\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMannervik\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilliamson\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1998 Phospholipid hydroperoxide glutathione peroxidase activity of human glutathione transferases. Biochem J, 332 Pt 1), 97-100.\n\t\t\t'},{id:"B72",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHutchens\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tManevich\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHe\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTew\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTownsend\n\t\t\t\t\t\t\tD. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Cellular resistance to a nitric oxide releasing glutathione S-transferase P-activated prodrug, PABA/NO. Invest New Drugs, 29\n\t\t\t\t\t5 719-729.\n\t\t\t'},{id:"B73",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHuttunen\n\t\t\t\t\t\t\tK. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMahonen\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRaunio\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRautio\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Cytochrome 450 prodrugs: targeted drug delivery. Curr Med Chem, 15\n\t\t\t\t\t23 2346-2365.\n\t\t\t'},{id:"B74",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIkeda\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKurose\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJinno\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSai\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOzawa\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHasegawa\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKomamura\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKotake\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorishita\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKamakura\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\tet al.\n\t\t\t\t\t\n\t\t\t\t\t2005 Functional analysis of four naturally occurring variants of human constitutive androstane receptor. Mol Genet Metab, 86\n\t\t\t\t\t1-2 , 314-319.\n\t\t\t'},{id:"B75",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIshikawa\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuo\n\t\t\t\t\t\t\tM. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFuruta\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSuzuki\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000 The human multidrug resistance-associated protein (MRP) gene family: from biological function to drug molecular design. Clin Chem Lab Med, 38\n\t\t\t\t\t9 893-897.\n\t\t\t'},{id:"B76",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIyanagi\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 Molecular mechanism of phase I and phase II drug-metabolizing enzymes: implications for detoxification. Int Rev Cytol, 260 35-112.\n\t\t\t'},{id:"B77",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIzbicka\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLawrence\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCerna\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVon\n\t\t\t\t\t\t\tHoff. D. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSanderson\n\t\t\t\t\t\t\tP. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1997 Activity of TER286 against human tumor colony-forming units. Anticancer Drugs, 8\n\t\t\t\t\t4 345-348.\n\t\t\t'},{id:"B78",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIzbicka\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTolcher\n\t\t\t\t\t\t\tA. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Development of novel alkylating drugs as anticancer agents. Curr Opin Investig Drugs, 5\n\t\t\t\t\t6 587-591.\n\t\t\t'},{id:"B79",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJaakkola\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMole\n\t\t\t\t\t\t\tD. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTian\n\t\t\t\t\t\t\tY. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilson\n\t\t\t\t\t\t\tM. I.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGielbert\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGaskell\n\t\t\t\t\t\t\tS. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKriegsheim\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHebestreit\n\t\t\t\t\t\t\tH. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMukherji\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchofield\n\t\t\t\t\t\t\tC. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMaxwell\n\t\t\t\t\t\t\tP. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPugh\n\t\t\t\t\t\t\tC. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRatcliffe\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001 Targeting of HIF-alpha to the von Hippel-Lindau ubiquitylation complex by O2-regulated prolyl hydroxylation. Science, 292\n\t\t\t\t\t5516 468-472.\n\t\t\t'},{id:"B80",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJakobsson\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tThoren\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorgenstern\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSamuelsson\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999 Identification of human prostaglandin E synthase: a microsomal, glutathione-dependent, inducible enzyme, constituting a potential novel drug target. Proc Natl Acad Sci U S A, 96\n\t\t\t\t\t13 7220-7225.\n\t\t\t'},{id:"B81",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJakobsson\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorgenstern\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMancini\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFord-Hutchinson\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPersson\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000 Membrane-associated proteins in eicosanoid and glutathione metabolism (MAPEG). A widespread protein superfamily. Am J Respir Crit Care Med, 161\n\t\t\t\t\t2 Pt 2, S20-24.\n\t\t\t'},{id:"B82",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJancova\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAnzenbacher\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAnzenbacherova\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Phase II drug metabolizing enzymes. Biomed Pap Med Fac Univ Palacky Olomouc Czech Repub, 154\n\t\t\t\t\t2 103-116.\n\t\t\t'},{id:"B83",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJedlitschky\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLeier\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBuchholz\n\t\t\t\t\t\t\tU.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBarnouin\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKurz\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeppler\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1996 Transport of glutathione, glucuronate, and sulfate conjugates by the MRP gene-encoded conjugate export pump. Cancer Res, 56\n\t\t\t\t\t5 988-994.\n\t\t\t'},{id:"B84",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJi\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPal\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKalathur\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHu\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGu\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaavedra\n\t\t\t\t\t\t\tJ. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBuzard\n\t\t\t\t\t\t\tG. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSrinivasan\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeefer\n\t\t\t\t\t\t\tL. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSingh\n\t\t\t\t\t\t\tS. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Structure-Based Design of Anticancer Prodrug PABA/NO. Drug Des Devel Ther, 2 123-130.\n\t\t\t'},{id:"B85",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJohansson\n\t\t\t\t\t\t\tA. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMannervik\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001 Human glutathione transferase A3-3, a highly efficient catalyst of double-bond isomerization in the biosynthetic pathway of steroid hormones. J Biol Chem, 276\n\t\t\t\t\t35 33061-33065.\n\t\t\t'},{id:"B86",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaluz\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaluzova\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiao\n\t\t\t\t\t\t\tS. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLerman\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStanbridge\n\t\t\t\t\t\t\tE. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Transcriptional control of the tumor- and hypoxia-marker carbonic anhydrase 9: A one transcription factor (HIF-1) show? Biochim Biophys Acta, 1795\n\t\t\t\t\t2 162-172.\n\t\t\t'},{id:"B87",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKamath\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilson\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCabral\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJordan\n\t\t\t\t\t\t\tM. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 BetaIII-tubulin induces paclitaxel resistance in association with reduced effects on microtubule dynamic instability. J Biol Chem, 280\n\t\t\t\t\t13 12902-12907.\n\t\t\t'},{id:"B88",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKavanagh\n\t\t\t\t\t\t\tJ. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLevenback\n\t\t\t\t\t\t\tC. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRamirez\n\t\t\t\t\t\t\tP. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWolf\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoore\n\t\t\t\t\t\t\tC. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJones\n\t\t\t\t\t\t\tM. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMeng\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrown\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBast\n\t\t\t\t\t\t\tR. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJr \n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Phase 2 study of canfosfamide in combination with pegylated liposomal doxorubicin in platinum and paclitaxel refractory or resistant epithelial ovarian cancer. J Hematol Oncol, 3 9.\n\t\t\t'},{id:"B89",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeating\n\t\t\t\t\t\t\tG. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSantoro\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Sorafenib: a review of its use in advanced hepatocellular carcinoma. Drugs, 69\n\t\t\t\t\t2 223-240.\n\t\t\t'},{id:"B90",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKennedy\n\t\t\t\t\t\t\tK. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTeicher\n\t\t\t\t\t\t\tB. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRockwell\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSartorelli\n\t\t\t\t\t\t\tA. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1980 The hypoxic tumor cell: a target for selective cancer chemotherapy. Biochem Pharmacol, 29\n\t\t\t\t\t1 1-8.\n\t\t\t'},{id:"B91",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeppler\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Multidrug resistance proteins (MRPs, ABCCs): importance for pathophysiology and drug therapy. Handb Exp Pharmacol, 201\n\t\t\t\t\t201\n\t\t\t\t\t299\n\t\t\t\t\t323 .\n\t\t\t'},{id:"B92",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tJ. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTchernyshyov\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSemenza\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDang\n\t\t\t\t\t\t\tC. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 HIF-1-mediated expression of pyruvate dehydrogenase kinase: a metabolic switch required for cellular adaptation to hypoxia. Cell metabolism, 3\n\t\t\t\t\t3 177-185.\n\t\t\t'},{id:"B93",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKlaassen\n\t\t\t\t\t\t\tC. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSlitt\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 Regulation of hepatic transporters by xenobiotic receptors. Curr Drug Metab, 6\n\t\t\t\t\t4 309-328.\n\t\t\t'},{id:"B94",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKliewer\n\t\t\t\t\t\t\tS. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoore\n\t\t\t\t\t\t\tJ. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWade\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStaudinger\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWatson\n\t\t\t\t\t\t\tM. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJones\n\t\t\t\t\t\t\tS. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Kee\n\t\t\t\t\t\t\tD. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOliver\n\t\t\t\t\t\t\tB. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWillson\n\t\t\t\t\t\t\tT. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZetterstrom\n\t\t\t\t\t\t\tR. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPerlmann\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLehmann\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1998 An orphan nuclear receptor activated by pregnanes defines a novel steroid signaling pathway. Cell, 92\n\t\t\t\t\t1 73-82.\n\t\t\t'},{id:"B95",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKobayashi\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSueyoshi\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInoue\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoore\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNegishi\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003 Cytoplasmic accumulation of the nuclear receptor CAR by a tetratricopeptide repeat protein in HepG2 cells. Mol Pharmacol, 64\n\t\t\t\t\t5 1069-1075.\n\t\t\t'},{id:"B96",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKogias\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOsterberg\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBaumer\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPsarras\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKoentges\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPapazoglou\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaavedra\n\t\t\t\t\t\t\tJ. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeefer\n\t\t\t\t\t\t\tL. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWeyerbrock\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Growth-inhibitory and chemosensitizing effects of the glutathione-S-transferase-pi-activated nitric oxide donor PABA/NO in malignant gliomas. Int J Cancer, in press.\n\t\t\t'},{id:"B97",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKonstantinopoulos\n\t\t\t\t\t\t\tP. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSpentzos\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFountzilas\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFrancoeur\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSanisetty\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGrammatikos\n\t\t\t\t\t\t\tA. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHecht\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCannistra\n\t\t\t\t\t\t\tS. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Keap1 mutations and Nrf2 pathway activation in epithelial ovarian cancer. Cancer Res, 71\n\t\t\t\t\t15 5081-5089\n\t\t\t'},{id:"B98",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKool\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tde Haas\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tScheffer\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tScheper\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tvan Eijk\n\t\t\t\t\t\t\tM. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJuijn\n\t\t\t\t\t\t\tJ. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBaas\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBorst\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1997 Analysis of expression of cMOAT (MRP2), MRP3, MRP4, and MRP5, homologues of the multidrug resistance-associated protein gene (MRP1), in human cancer cell lines. Cancer Res, 57\n\t\t\t\t\t16 3537-3547.\n\t\t\t'},{id:"B99",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKorita\n\t\t\t\t\t\t\tP. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWakai\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShirai\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMatsuda\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSakata\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakamura\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYano\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSanpei\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAoyagi\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHatakeyama\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAjioka\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Multidrug resistance-associated protein 2 determines the efficacy of cisplatin in patients with hepatocellular carcinoma. Oncol Rep, 23\n\t\t\t\t\t4 965-972.\n\t\t\t'},{id:"B100",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKraggerud\n\t\t\t\t\t\t\tS. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOldenburg\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAlnaes\n\t\t\t\t\t\t\tG. I.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBerg\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKristensen\n\t\t\t\t\t\t\tV. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFossa\n\t\t\t\t\t\t\tS. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLothe\n\t\t\t\t\t\t\tR. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Functional glutathione S-transferase genotypes among testicular germ cell tumor survivors: associations with primary and post-chemotherapy tumor histology. Pharmacogenet Genomics, 19\n\t\t\t\t\t10 751-759.\n\t\t\t'},{id:"B101",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLangouet\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tColes\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorel\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBecquemont\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBeaune\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuengerich\n\t\t\t\t\t\t\tF. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKetterer\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuillouzo\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1995 Inhibition of CYP1A2 and CYP3A4 by oltipraz results in reduction of aflatoxin B1 metabolism in human hepatocytes in primary culture. Cancer Res, 55\n\t\t\t\t\t23 5574-5579.\n\t\t\t'},{id:"B102",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLarkin\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tO’Driscoll\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKennedy\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPurcell\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoran\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCrown\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParkinson\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tClynes\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Investigation of MRP-1 protein and MDR-1 P-glycoprotein expression in invasive breast cancer: a prognostic study. Int J Cancer, 112\n\t\t\t\t\t2 286-294.\n\t\t\t'},{id:"B103",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLegendre\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHori\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLoyer\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAninat\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIshida\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGlaise\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLucas-Clerc\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoudjema\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuguen-Guillouzo\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCorlu\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorel\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Drug-metabolising enzymes are down-regulated by hypoxia in differentiated human hepatoma HepaRG cells: HIF-1alpha involvement in CYP3A4 repression. European journal of cancer, 45\n\t\t\t\t\t16 2882-2892.\n\t\t\t'},{id:"B104",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYuan\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYang\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXu\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTang\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 The structure and functions of P-glycoprotein. Curr Med Chem, 17\n\t\t\t\t\t8 786-800.\n\t\t\t'},{id:"B105",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLien\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLarsson\n\t\t\t\t\t\t\tA. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMannervik\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002 The polymorphic human glutathione transferase T1-1, the most efficient glutathione transferase in the denitrosation and inactivation of the anticancer drug 1,3-bis(2-chloroethyl)-1-nitrosourea. Biochem Pharmacol, 63\n\t\t\t\t\t2 191-197.\n\t\t\t'},{id:"B106",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLin\n\t\t\t\t\t\t\tS. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChien\n\t\t\t\t\t\t\tC. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tJ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYeh\n\t\t\t\t\t\t\tY. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHsu\n\t\t\t\t\t\t\tK. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLai\n\t\t\t\t\t\t\tY. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTsai\n\t\t\t\t\t\t\tS. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Suppression of dual-specificity phosphatase-2 by hypoxia increases chemoresistance and malignancy in human cancer cells. J Clin Invest, 121\n\t\t\t\t\t5 1905-1916.\n\t\t\t'},{id:"B107",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLlovet\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBruix\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Molecular targeted therapies in hepatocellular carcinoma. Hepatology, 48\n\t\t\t\t\t4 1312-1327.\n\t\t\t'},{id:"B108",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLongley\n\t\t\t\t\t\t\tD. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHarkin\n\t\t\t\t\t\t\tD. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJohnston\n\t\t\t\t\t\t\tP. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003 5-fluorouracil: mechanisms of action and clinical strategies. Nat Rev Cancer, 3\n\t\t\t\t\t5 330-338.\n\t\t\t'},{id:"B109",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLyttle\n\t\t\t\t\t\t\tM. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSatyam\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHocker\n\t\t\t\t\t\t\tM. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBauer\n\t\t\t\t\t\t\tK. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCaldwell\n\t\t\t\t\t\t\tC. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHui\n\t\t\t\t\t\t\tH. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorgan\n\t\t\t\t\t\t\tA. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMergia\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKauvar\n\t\t\t\t\t\t\tL. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1994 Glutathione-S-transferase activates novel alkylating agents. J Med Chem, 37\n\t\t\t\t\t10 1501-1507.\n\t\t\t'},{id:"B110",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tManevich\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTownsend\n\t\t\t\t\t\t\tD. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHutchens\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTew\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Diazeniumdiolate mediated nitrosative stress alters nitric oxide homeostasis through intracellular calcium and S-glutathionylation of nitric oxide synthetase. PLoS One, 5\n\t\t\t\t\t11 e14151.\n\t\t\t'},{id:"B111",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMartinez\n\t\t\t\t\t\t\tV. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tO’Connor\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiang\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tClynes\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 CYP1B1 expression is induced by docetaxel: effect on cell viability and drug resistance. Br J Cancer, 98\n\t\t\t\t\t3 564-570.\n\t\t\t'},{id:"B112",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMasuyama\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHiramatsu\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKodama\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKudo\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003 Expression and potential roles of pregnane X receptor in endometrial cancer. J Clin Endocrinol Metab, 88\n\t\t\t\t\t9 4446-4454.\n\t\t\t'},{id:"B113",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMasuyama\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNakatsukasa\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakamoto\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHiramatsu\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 Down-regulation of pregnane X receptor contributes to cell growth inhibition and apoptosis by anticancer agents in endometrial cancer cells. Mol Pharmacol, 72\n\t\t\t\t\t4 1045-1053.\n\t\t\t'},{id:"B114",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMathijssen\n\t\t\t\t\t\t\tR. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tde Jong\n\t\t\t\t\t\t\tF. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tvan Schaik\n\t\t\t\t\t\t\tR. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLepper\n\t\t\t\t\t\t\tE. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFriberg\n\t\t\t\t\t\t\tL. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRietveld\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tde Bruijn\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGraveland\n\t\t\t\t\t\t\tW. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFigg\n\t\t\t\t\t\t\tW. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVerweij\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSparreboom\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Prediction of irinotecan pharmacokinetics by use of cytochrome 450 3A4 phenotyping probes. J Natl Cancer Inst, 96\n\t\t\t\t\t21 1585-1592.\n\t\t\t'},{id:"B115",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMathijssen\n\t\t\t\t\t\t\tR. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVerweij\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tde Bruijn\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLoos\n\t\t\t\t\t\t\tW. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSparreboom\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002 Effects of St. John’s wort on irinotecan metabolism. J Natl Cancer Inst, 94\n\t\t\t\t\t16 1247-1249.\n\t\t\t'},{id:"B116",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMaxwell\n\t\t\t\t\t\t\tP. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDachs\n\t\t\t\t\t\t\tG. U.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGleadle\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNicholls\n\t\t\t\t\t\t\tL. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHarris\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStratford\n\t\t\t\t\t\t\tI. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHankinson\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPugh\n\t\t\t\t\t\t\tC. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRatcliffe\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1997 Hypoxia-inducible factor-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc Natl Acad Sci U S A, 94\n\t\t\t\t\t15 8104-8109.\n\t\t\t'},{id:"B117",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Fadyen\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCruickshank\n\t\t\t\t\t\t\tM. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiller\n\t\t\t\t\t\t\tI. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Leod\n\t\t\t\t\t\t\tH. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMelvin\n\t\t\t\t\t\t\tW. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHaites\n\t\t\t\t\t\t\tN. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParkin\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMurray\n\t\t\t\t\t\t\tG. I.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001a Cytochrome 450 CYP1B1 over-expression in primary and metastatic ovarian cancer. Br J Cancer, 85\n\t\t\t\t\t2 242-246.\n\t\t\t'},{id:"B118",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Fadyen\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Leod\n\t\t\t\t\t\t\tH. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJackson\n\t\t\t\t\t\t\tF. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMelvin\n\t\t\t\t\t\t\tW. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDoehmer\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMurray\n\t\t\t\t\t\t\tG. I.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001b Cytochrome 450 CYP1B1 protein expression: a novel mechanism of anticancer drug resistance. Biochem Pharmacol, 62\n\t\t\t\t\t2 207-212.\n\t\t\t'},{id:"B119",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Fadyen\n\t\t\t\t\t\t\tM. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMelvin\n\t\t\t\t\t\t\tW. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMurray\n\t\t\t\t\t\t\tG. I.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Cytochrome 450 enzymes: novel options for cancer therapeutics. Mol Cancer Ther, 3\n\t\t\t\t\t3 363-371.\n\t\t\t'},{id:"B120",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Ilwain\n\t\t\t\t\t\t\tC. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTownsend\n\t\t\t\t\t\t\tD. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTew\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 Glutathione S-transferase polymorphisms: cancer incidence and therapy. Oncogene, 25\n\t\t\t\t\t11 1639-1648.\n\t\t\t'},{id:"B121",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Keown\n\t\t\t\t\t\t\tS. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCowen\n\t\t\t\t\t\t\tR. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilliams\n\t\t\t\t\t\t\tK. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 Bioreductive drugs: from concept to clinic. Clinical oncology, 19\n\t\t\t\t\t6 427-442.\n\t\t\t'},{id:"B122",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiyoshi\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTaguchi\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tS. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTamaki\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNoguchi\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 Prediction of response to docetaxel by immunohistochemical analysis of CYP3A4 expression in human breast cancers. Breast Cancer, 12\n\t\t\t\t\t1 11-15.\n\t\t\t'},{id:"B123",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoore\n\t\t\t\t\t\t\tL. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParks\n\t\t\t\t\t\t\tD. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJones\n\t\t\t\t\t\t\tS. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBledsoe\n\t\t\t\t\t\t\tR. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tConsler\n\t\t\t\t\t\t\tT. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStimmel\n\t\t\t\t\t\t\tJ. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGoodwin\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiddle\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBlanchard\n\t\t\t\t\t\t\tS. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWillson\n\t\t\t\t\t\t\tT. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCollins\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKliewer\n\t\t\t\t\t\t\tS. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000 Orphan nuclear receptors constitutive androstane receptor and pregnane X receptor share xenobiotic and steroid ligands. J Biol Chem, 275\n\t\t\t\t\t20 15122-15127.\n\t\t\t'},{id:"B124",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorel\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAninat\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 The glutathione transferase kappa family. Drug Metab Rev, 43\n\t\t\t\t\t2 281-291.\n\t\t\t'},{id:"B125",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorgan\n\t\t\t\t\t\t\tA. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSanderson\n\t\t\t\t\t\t\tP. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBorch\n\t\t\t\t\t\t\tR. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTew\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNiitsu\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakayama\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVon\n\t\t\t\t\t\t\tHoff. D. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIzbicka\n\t\t\t\t\t\t\tE.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMangold\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPaul\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBroberg\n\t\t\t\t\t\t\tU.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMannervik\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHenner\n\t\t\t\t\t\t\tW. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKauvar\n\t\t\t\t\t\t\tL. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1998 Tumor efficacy and bone marrow-sparing properties of TER286, a cytotoxin activated by glutathione S-transferase. Cancer Res, 58\n\t\t\t\t\t12 2568-2575.\n\t\t\t'},{id:"B126",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMuscarella\n\t\t\t\t\t\t\tL. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParrella\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tD’Alessandro\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tla Torre\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBarbano\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFontana\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTancredi\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuarnieri\n\t\t\t\t\t\t\tV.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBalsamo\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCoco\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\tet al.\n\t\t\t\t\t\n\t\t\t\t\t2011 Frequent epigenetics inactivation of KEAP1 gene in non-small cell lung cancer. Epigenetics, 6\n\t\t\t\t\t6 710-719.\n\t\t\t'},{id:"B127",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNi\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBikadi\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRosenberg\n\t\t\t\t\t\t\tM. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMao\n\t\t\t\t\t\t\tQ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Structure and function of the human breast cancer resistance protein (BCRP/ABCG2). Curr Drug Metab, 11\n\t\t\t\t\t7 603-617.\n\t\t\t'},{id:"B128",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNioi\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNguyen\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 A mutation of Keap1 found in breast cancer impairs its ability to repress Nrf2 activity. Biochem Biophys Res Commun, 362\n\t\t\t\t\t4 816-821.\n\t\t\t'},{id:"B129",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNishida\n\t\t\t\t\t\t\tC. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tde Montellano\n\t\t\t\t\t\t\tP. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Efficient hypoxic activation of the anticancer agent AQ4N by CYP2S1 and CYP2W1. Mol Pharmacol, 78\n\t\t\t\t\t3 497-502.\n\t\t\t'},{id:"B130",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNitiss\n\t\t\t\t\t\t\tJ. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Targeting DNA topoisomerase II in cancer chemotherapy. Nat Rev Cancer, 9\n\t\t\t\t\t5 338-350.\n\t\t\t'},{id:"B131",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tO’Connor\n\t\t\t\t\t\t\tP. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJackman\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBae\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMyers\n\t\t\t\t\t\t\tT. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFan\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMutoh\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tScudiero\n\t\t\t\t\t\t\tD. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMonks\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSausville\n\t\t\t\t\t\t\tE. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWeinstein\n\t\t\t\t\t\t\tJ. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFriend\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFornace\n\t\t\t\t\t\t\tA. J.\n\t\t\t\t\t\t\tJr\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKohn\n\t\t\t\t\t\t\tK. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1997 Characterization of the 53 tumor suppressor pathway in cell lines of the National Cancer Institute anticancer drug screen and correlations with the growth-inhibitory potency of 123 anticancer agents. Cancer Res, 57\n\t\t\t\t\t19 4285-4300.\n\t\t\t'},{id:"B132",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhta\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIijima\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiyamoto\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNakahara\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTanaka\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhtsuji\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSuzuki\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKobayashi\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYokota\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSakiyama\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShibata\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamamoto\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHirohashi\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Loss of Keap1 function activates Nrf2 and provides advantages for lung cancer cell growth. Cancer Res, 68\n\t\t\t\t\t5 1303-1309.\n\t\t\t'},{id:"B133",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOkawa\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMotohashi\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKobayashi\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAburatani\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKensler\n\t\t\t\t\t\t\tT. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamamoto\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 Hepatocyte-specific deletion of the keap1 gene activates Nrf2 and confers potent resistance against acute drug toxicity. Biochem Biophys Res Commun, 339\n\t\t\t\t\t1 79-88.\n\t\t\t'},{id:"B134",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOyama\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKagawa\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKunugita\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKitagawa\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOgawa\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamaguchi\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSuzuki\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKinaga\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYashima\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOzaki\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIsse\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tY. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKawamoto\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Expression of cytochrome 450 in tumor tissues and its association with cancer development. Front Biosci, 9 1967-1976.\n\t\t\t'},{id:"B135",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPadmanabhan\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTong\n\t\t\t\t\t\t\tK. I.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhta\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNakamura\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tScharlock\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhtsuji\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKang\n\t\t\t\t\t\t\tM. I.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKobayashi\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYokoyama\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamamoto\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer. Mol Cell, 21\n\t\t\t\t\t5 689-700.\n\t\t\t'},{id:"B136",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPapandreou\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCairns\n\t\t\t\t\t\t\tR. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFontana\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLim\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDenko\n\t\t\t\t\t\t\tN. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 HIF-1 mediates adaptation to hypoxia by actively downregulating mitochondrial oxygen consumption. Cell metabolism, 3\n\t\t\t\t\t3 187-197.\n\t\t\t'},{id:"B137",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParker\n\t\t\t\t\t\t\tW. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Enzymology of purine and pyrimidine antimetabolites used in the treatment of cancer. Chem Rev, 109\n\t\t\t\t\t7 2880-2893.\n\t\t\t'},{id:"B138",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPastorekova\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZatovicova\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPastorek\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Cancer-associated carbonic anhydrases and their inhibition. Curr Pharm Des, 14\n\t\t\t\t\t7 685-698.\n\t\t\t'},{id:"B139",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPatel\n\t\t\t\t\t\t\tM. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKorotchkina\n\t\t\t\t\t\t\tL. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001 Regulation of mammalian pyruvate dehydrogenase complex by phosphorylation: complexity of multiple phosphorylation sites and kinases. Experimental & molecular medicine, 33\n\t\t\t\t\t4 191-197.\n\t\t\t'},{id:"B140",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPatterson\n\t\t\t\t\t\t\tL. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMc Keown\n\t\t\t\t\t\t\tS. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000 AQ4N: a new approach to hypoxia-activated cancer chemotherapy. Br J Cancer, 83\n\t\t\t\t\t12 1589-1593.\n\t\t\t'},{id:"B141",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPaumi\n\t\t\t\t\t\t\tC. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLedford\n\t\t\t\t\t\t\tB. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSmitherman\n\t\t\t\t\t\t\tP. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTownsend\n\t\t\t\t\t\t\tA. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorrow\n\t\t\t\t\t\t\tC. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001 Role of multidrug resistance protein 1 (MRP1) and glutathione S-transferase A1-1 in alkylating agent resistance. Kinetics of glutathione conjugate formation and efflux govern differential cellular sensitivity to chlorambucil versus melphalan toxicity. J Biol Chem, 276\n\t\t\t\t\t11 7952-7956.\n\t\t\t'},{id:"B142",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPotter\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHarris\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Hypoxia inducible carbonic anhydrase IX, marker of tumour hypoxia, survival pathway and therapy target. Cell Cycle, 3\n\t\t\t\t\t2 164-167.\n\t\t\t'},{id:"B143",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPugh\n\t\t\t\t\t\t\tC. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRatcliffe\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003 Regulation of angiogenesis by hypoxia: role of the HIF system. Nat Med, 9\n\t\t\t\t\t6 677-684.\n\t\t\t'},{id:"B144",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tQi\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChang\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSong\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGao\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShen\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Adenovirus-mediated 53 gene therapy reverses resistance of breast cancer cells to adriamycin. Anticancer Drugs, 22\n\t\t\t\t\t6 556-562.\n\t\t\t'},{id:"B145",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRau\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAutschbach\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRiedel\n\t\t\t\t\t\t\tH. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKonig\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKulaksiz\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tStiehl\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRiemann\n\t\t\t\t\t\t\tJ. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRost\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Expression of the multidrug resistance proteins MRP2 and MRP3 in human cholangiocellular carcinomas. Eur J Clin Invest, 38\n\t\t\t\t\t2 134-142.\n\t\t\t'},{id:"B146",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRaynal\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPascussi\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLeguelinel\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBreuker\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKantar\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLallemant\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPoujol\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBonnans\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJoubert\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHollande\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLumbroso\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrouillet\n\t\t\t\t\t\t\tJ. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEvrard\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Pregnane X Receptor (PXR) expression in colorectal cancer cells restricts irinotecan chemosensitivity through enhanced SN-38 glucuronidation. Mol Cancer, 9 46.\n\t\t\t'},{id:"B147",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRaza\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGalili\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSmith\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGodwin\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLancet\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMelchert\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJones\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeck\n\t\t\t\t\t\t\tJ. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMeng\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrown\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tList\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Phase 1 multicenter dose-escalation study of ezatiostat hydrochloride (TLK199 tablets), a novel glutathione analog prodrug, in patients with myelodysplastic syndrome. Blood, 113\n\t\t\t\t\t26 6533-6540.\n\t\t\t'},{id:"B148",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReichert\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSteinbach\n\t\t\t\t\t\t\tJ. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSupra\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWeller\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002 Modulation of growth and radiochemosensitivity of human malignant glioma cells by acidosis. Cancer, 95\n\t\t\t\t\t5 1113-1119.\n\t\t\t'},{id:"B149",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRisinger\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGiles\n\t\t\t\t\t\t\tF. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMooberry\n\t\t\t\t\t\t\tS. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Microtubule dynamics as a target in oncology. Cancer Treat Rev, 35\n\t\t\t\t\t3 255-261.\n\t\t\t'},{id:"B150",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRochat\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Importance of influx and efflux systems and xenobiotic metabolizing enzymes in intratumoral disposition of anticancer agents. Curr Cancer Drug Targets, 9\n\t\t\t\t\t5 652-674.\n\t\t\t'},{id:"B151",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRodriguez-Antona\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIngelman-Sundberg\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 Cytochrome 450 pharmacogenetics and cancer. Oncogene, 25\n\t\t\t\t\t11 1679-1691.\n\t\t\t'},{id:"B152",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRosario\n\t\t\t\t\t\t\tL. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tO’Brien\n\t\t\t\t\t\t\tM. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHenderson\n\t\t\t\t\t\t\tC. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWolf\n\t\t\t\t\t\t\tC. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTew\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000 Cellular response to a glutathione S-transferase 1\n\t\t\t\t\t1 activated prodrug. Mol Pharmacol, 58\n\t\t\t\t\t1 167-174.\n\t\t\t'},{id:"B153",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRosen\n\t\t\t\t\t\t\tL. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrown\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLaxa\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoulos\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReiswig\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHenner\n\t\t\t\t\t\t\tW. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLum\n\t\t\t\t\t\t\tR. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchow\n\t\t\t\t\t\t\tS. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMaack\n\t\t\t\t\t\t\tC. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeck\n\t\t\t\t\t\t\tJ. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMascavage\n\t\t\t\t\t\t\tJ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDombroski\n\t\t\t\t\t\t\tJ. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGomez\n\t\t\t\t\t\t\tR. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrown\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003 Phase I study of TLK286 (glutathione S-transferase 1\n\t\t\t\t\t1 activated glutathione analogue) in advanced refractory solid malignancies. Clin Cancer Res, 9\n\t\t\t\t\t5 1628-1638.\n\t\t\t'},{id:"B154",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRosen\n\t\t\t\t\t\t\tL. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLaxa\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoulos\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWiggins\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeck\n\t\t\t\t\t\t\tJ. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJameson\n\t\t\t\t\t\t\tA. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParra\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPatel\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrown\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Phase 1 study of TLK286 (Telcyta) administered weekly in advanced malignancies. Clin Cancer Res, 10\n\t\t\t\t\t11 3689-3698.\n\t\t\t'},{id:"B155",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRyan\n\t\t\t\t\t\t\tH. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLo\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJohnson\n\t\t\t\t\t\t\tR. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1998 HIF-1 alpha is required for solid tumor formation and embryonic vascularization. EMBO J, 17\n\t\t\t\t\t11 3005-3015.\n\t\t\t'},{id:"B156",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRyoo\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHuh\n\t\t\t\t\t\t\tS. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tY. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYoon\n\t\t\t\t\t\t\tK. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCho\n\t\t\t\t\t\t\tS. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChoi\n\t\t\t\t\t\t\tE. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Negative regulation of MEKK1-induced signaling by glutathione S-transferase Mu. J Biol Chem, 279\n\t\t\t\t\t42 43589-43594.\n\t\t\t'},{id:"B157",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaavedra\n\t\t\t\t\t\t\tJ. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSrinivasan\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBuzard\n\t\t\t\t\t\t\tG. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDavies\n\t\t\t\t\t\t\tK. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWaterhouse\n\t\t\t\t\t\t\tD. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tInami\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWilde\n\t\t\t\t\t\t\tT. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCitro\n\t\t\t\t\t\t\tM. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCuellar\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDeschamps\n\t\t\t\t\t\t\tJ. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tParrish\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShami\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFindlay\n\t\t\t\t\t\t\tV. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTownsend\n\t\t\t\t\t\t\tD. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTew\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSingh\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJia\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJi\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeefer\n\t\t\t\t\t\t\tL. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 PABA/NO as an anticancer lead: analogue synthesis, structure revision, solution chemistry, reactivity toward glutathione, and in vitro activity. J Med Chem, 49\n\t\t\t\t\t3 1157-1164.\n\t\t\t'},{id:"B158",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSalinas-Souza\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPetrilli\n\t\t\t\t\t\t\tA. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tde Toledo\n\t\t\t\t\t\t\tS. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Glutathione S-transferase polymorphisms in osteosarcoma patients. Pharmacogenet Genomics, 20\n\t\t\t\t\t8 507-515.\n\t\t\t'},{id:"B159",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSatyam\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHocker\n\t\t\t\t\t\t\tM. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKane-Maguire\n\t\t\t\t\t\t\tK. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMorgan\n\t\t\t\t\t\t\tA. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVillar\n\t\t\t\t\t\t\tH. O.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLyttle\n\t\t\t\t\t\t\tM. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1996 Design, synthesis, and evaluation of latent alkylating agents activated by glutathione S-transferase. J Med Chem, 39\n\t\t\t\t\t8 1736-1747.\n\t\t\t'},{id:"B160",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSeagroves\n\t\t\t\t\t\t\tT. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRyan\n\t\t\t\t\t\t\tH. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLu\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWouters\n\t\t\t\t\t\t\tB. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKnapp\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tThibault\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLaderoute\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJohnson\n\t\t\t\t\t\t\tR. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001 Transcription factor HIF-1 is a necessary mediator of the pasteur effect in mammalian cells. Mol Cell Biol, 21\n\t\t\t\t\t10 3436-3444.\n\t\t\t'},{id:"B161",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSebolt-Leopold\n\t\t\t\t\t\t\tJ. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEnglish\n\t\t\t\t\t\t\tJ. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 Mechanisms of drug inhibition of signalling molecules. Nature, 441\n\t\t\t\t\t7092 457-462.\n\t\t\t'},{id:"B162",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSemenza\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003 Targeting HIF-1 for cancer therapy. Nat Rev Cancer, 3\n\t\t\t\t\t10 721-732.\n\t\t\t'},{id:"B163",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSemenza\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 Evaluation of HIF-1 inhibitors as anticancer agents. Drug discovery today, 12\n\t\t\t\t\t19-20 , 853-859.\n\t\t\t'},{id:"B164",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSequist\n\t\t\t\t\t\t\tL. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFidias\n\t\t\t\t\t\t\tP. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTemel\n\t\t\t\t\t\t\tJ. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKolevska\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRabin\n\t\t\t\t\t\t\tM. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBoccia\n\t\t\t\t\t\t\tR. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBurris\n\t\t\t\t\t\t\tH. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBelt\n\t\t\t\t\t\t\tR. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHuberman\n\t\t\t\t\t\t\tM. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMelnyk\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMills\n\t\t\t\t\t\t\tG. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEnglund\n\t\t\t\t\t\t\tC. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCaldwell\n\t\t\t\t\t\t\tD. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKeck\n\t\t\t\t\t\t\tJ. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMeng\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJones\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrown\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEdelman\n\t\t\t\t\t\t\tM. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLynch\n\t\t\t\t\t\t\tT. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Phase 1-2a multicenter dose-ranging study of canfosfamide in combination with carboplatin and paclitaxel as first-line therapy for patients with advanced non-small cell lung cancer. J Thorac Oncol, 4\n\t\t\t\t\t11 1389-1396.\n\t\t\t'},{id:"B165",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShannon\n\t\t\t\t\t\t\tA. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBouchier-Hayes\n\t\t\t\t\t\t\tD. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCondron\n\t\t\t\t\t\t\tC. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tToomey\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003 Tumour hypoxia, chemotherapeutic resistance and hypoxia-related therapies. Cancer Treat Rev, 29\n\t\t\t\t\t4 297-307.\n\t\t\t'},{id:"B166",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSharma\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPatrick\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSharma\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJeyabal\n\t\t\t\t\t\t\tP. V.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReddy\n\t\t\t\t\t\t\tP. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAwasthi\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAwasthi\n\t\t\t\t\t\t\tY. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 Glutathione S-transferases as antioxidant enzymes: small cell lung cancer (H69) cells transfected with hGSTA1 resist doxorubicin-induced apoptosis. Arch Biochem Biophys, 452\n\t\t\t\t\t2 165-173.\n\t\t\t'},{id:"B167",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShibata\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKokubu\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGotoh\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOjima\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhta\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamamoto\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHirohashi\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008a Genetic alteration of Keap1 confers constitutive Nrf2 activation and resistance to chemotherapy in gallbladder cancer. Gastroenterology, 135\n\t\t\t\t\t4 1358-1368, 1368 e1351-1354.\n\t\t\t'},{id:"B168",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShibata\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOhta\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTong\n\t\t\t\t\t\t\tK. I.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKokubu\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOdogawa\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTsuta\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAsamura\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamamoto\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHirohashi\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008b Cancer related mutations in NRF2 impair its recognition by Keap1-Cul3 E3 ligase and promote malignancy. Proc Natl Acad Sci U S A, 105\n\t\t\t\t\t36 13568-13573.\n\t\t\t'},{id:"B169",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShimoda\n\t\t\t\t\t\t\tL. A.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFallon\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPisarcik\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSemenza\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 HIF-1 regulates hypoxic induction of NHE1 expression and alkalinization of intracellular pH in pulmonary arterial myocytes. American journal of physiology Lung cellular and molecular physiology, 291\n\t\t\t\t\t5 L941-949.\n\t\t\t'},{id:"B170",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSim\n\t\t\t\t\t\t\tS. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIngelman-Sundberg\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 The Human Cytochrome 450 CYP) Allele Nomenclature website: a peer-reviewed database of CYP variants and their associated effects. Hum Genomics, 4\n\t\t\t\t\t4 278-281.\n\t\t\t'},{id:"B171",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSonoda\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPei\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tEvans\n\t\t\t\t\t\t\tR. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Nuclear receptors: decoding metabolic disease. FEBS Lett, 582\n\t\t\t\t\t1 2-9.\n\t\t\t'},{id:"B172",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSquires\n\t\t\t\t\t\t\tE. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSueyoshi\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNegishi\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Cytoplasmic localization of pregnane X receptor and ligand-dependent nuclear translocation in mouse liver. J Biol Chem, 279\n\t\t\t\t\t47 49307-49314.\n\t\t\t'},{id:"B173",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSun\n\t\t\t\t\t\t\tH. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tY. N.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHuang\n\t\t\t\t\t\t\tY. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPan\n\t\t\t\t\t\t\tS. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHuang\n\t\t\t\t\t\t\tD. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuh\n\t\t\t\t\t\t\tJ. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tF. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuo\n\t\t\t\t\t\t\tS. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTeng\n\t\t\t\t\t\t\tC. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 YC-1 inhibits HIF-1 expression in prostate cancer cells: contribution of Akt/NF-kappaB signaling to HIF-1alpha accumulation during hypoxia. Oncogene, 26\n\t\t\t\t\t27 3941-3951.\n\t\t\t'},{id:"B174",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSuzuki\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNishio\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTanabe\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001 The MRP family and anticancer drug metabolism. Curr Drug Metab, 2\n\t\t\t\t\t4 367-377.\n\t\t\t'},{id:"B175",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSvoboda\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRiha\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWlcek\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJaeger\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tThalhammer\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Organic anion transporting polypeptides (OATPs): regulation of expression and function. Curr Drug Metab, 12\n\t\t\t\t\t2 139-153.\n\t\t\t'},{id:"B176",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTaguchi\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMotohashi\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYamamoto\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Molecular mechanisms of the Keap1-Nrf2 pathway in stress response and cancer evolution. Genes Cells, 16\n\t\t\t\t\t2 123-140.\n\t\t\t'},{id:"B177",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTakeshita\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTaguchi\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKoibuchi\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOzawa\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2002 Putative role of the orphan nuclear receptor SXR (steroid and xenobiotic receptor) in the mechanism of CYP3A4 inhibition by xenobiotics. J Biol Chem, 277\n\t\t\t\t\t36 32453-32458.\n\t\t\t'},{id:"B178",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTalks\n\t\t\t\t\t\t\tK. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTurley\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGatter\n\t\t\t\t\t\t\tK. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMaxwell\n\t\t\t\t\t\t\tP. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPugh\n\t\t\t\t\t\t\tC. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRatcliffe\n\t\t\t\t\t\t\tP. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHarris\n\t\t\t\t\t\t\tA. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000 The expression and distribution of the hypoxia-inducible factors HIF-1alpha and HIF-2alpha in normal human tissues, cancers, and tumor-associated macrophages. Am J Pathol, 157\n\t\t\t\t\t2 411-421.\n\t\t\t'},{id:"B179",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTang\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFan\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWu\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXin\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRen\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tX. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Luteolin inhibits Nrf2 leading to negative regulation of the Nrf2/ARE pathway and sensitization of human lung carcinoma A549 cells to therapeutic drugs. Free Radic Biol Med, 50\n\t\t\t\t\t11 1599-1609.\n\t\t\t'},{id:"B180",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTaniguchi\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWada\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKohno\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNakamura\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKawabe\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKawakami\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKagotani\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tOkumura\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAkiyama\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKuwano\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1996 A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation. Cancer Res, 56\n\t\t\t\t\t18 4124-4129.\n\t\t\t'},{id:"B181",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTew\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1994 Glutathione-associated enzymes in anticancer drug resistance. Cancer Res, 54\n\t\t\t\t\t16 4313-4320.\n\t\t\t'},{id:"B182",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTimsit\n\t\t\t\t\t\t\tY. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tNegishi\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 CAR and PXR: the xenobiotic-sensing receptors. Steroids, 72\n\t\t\t\t\t3 231-246.\n\t\t\t'},{id:"B183",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTolson\n\t\t\t\t\t\t\tA. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Regulation of drug-metabolizing enzymes by xenobiotic receptors: PXR and CAR. Adv Drug Deliv Rev, 62\n\t\t\t\t\t13 1238-1249.\n\t\t\t'},{id:"B184",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTownsend\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTew\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003a Cancer drugs, genetic variation and the glutathione-S-transferase gene family. Am J Pharmacogenomics, 3\n\t\t\t\t\t3 157-172.\n\t\t\t'},{id:"B185",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTownsend\n\t\t\t\t\t\t\tD. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFindlay\n\t\t\t\t\t\t\tV. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTew\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 Glutathione S-transferases as regulators of kinase pathways and anticancer drug targets. Methods Enzymol, 401 287-307.\n\t\t\t'},{id:"B186",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTownsend\n\t\t\t\t\t\t\tD. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShen\n\t\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t (2002). Efficacy of a glutathione S-transferase pi-activated prodrug in platinum-resistant ovarian cancer cells. Mol Cancer Ther, Vol.1, No.12, 1089-1095.\n\t\t\t'},{id:"B187",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTownsend\n\t\t\t\t\t\t\tD. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTew\n\t\t\t\t\t\t\tK. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003b The role of glutathione-S-transferase in anti-cancer drug resistance. Oncogene, 22\n\t\t\t\t\t47 7369-7375.\n\t\t\t'},{id:"B188",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTredan\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGalmarini\n\t\t\t\t\t\t\tC. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPatel\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTannock\n\t\t\t\t\t\t\tI. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 Drug resistance and the solid tumor microenvironment. J Natl Cancer Inst, 99\n\t\t\t\t\t19 1441-1454.\n\t\t\t'},{id:"B189",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTrock\n\t\t\t\t\t\t\tB. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLeonessa\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tClarke\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1997 Multidrug resistance in breast cancer: a meta-analysis of MDR1/gp170 expression and its possible functional significance. J Natl Cancer Inst, 89\n\t\t\t\t\t13 917-931.\n\t\t\t'},{id:"B190",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTzameli\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPissios\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSchuetz\n\t\t\t\t\t\t\tE. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMoore\n\t\t\t\t\t\t\tD. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2000 The xenobiotic compound 1,4-bis[2-(3,5-dichloropyridyloxy)]benzene is an agonist ligand for the nuclear receptor CAR. Mol Cell Biol, 20\n\t\t\t\t\t9 2951-2958.\n\t\t\t'},{id:"B191",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tUllah\n\t\t\t\t\t\t\tM. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDavies\n\t\t\t\t\t\t\tA. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHalestrap\n\t\t\t\t\t\t\tA. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 The plasma membrane lactate transporter MCT4, but not MCT1, is up-regulated by hypoxia through a HIF-1alpha-dependent mechanism. J Biol Chem, 281\n\t\t\t\t\t14 9030-9037.\n\t\t\t'},{id:"B192",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tUrquhart\n\t\t\t\t\t\t\tB. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tTirona\n\t\t\t\t\t\t\tR. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tR. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 Nuclear receptors and the regulation of drug-metabolizing enzymes and drug transporters: implications for interindividual variability in response to drugs. J Clin Pharmacol, 47\n\t\t\t\t\t5 566-578.\n\t\t\t'},{id:"B193",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVaupel\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHarrison\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2004 Tumor hypoxia: causative factors, compensatory mechanisms, and cellular response. Oncologist, 9 Suppl 5, 4-9.\n\t\t\t'},{id:"B194",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVaupel\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMayer\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 Hypoxia in cancer: significance and impact on clinical outcome. Cancer Metastasis Rev, 26\n\t\t\t\t\t2 225-239.\n\t\t\t'},{id:"B195",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVenkatesh\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCayer\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLeroux\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSalvail\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDas\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWrobel\n\t\t\t\t\t\t\tJ. E.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMani\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 In Vivo and In Vitro Characterization of a First-in-Class Novel Azole Analog That Targets Pregnane X Receptor Activation. Mol Pharmacol, 80\n\t\t\t\t\t1 124-135.\n\t\t\t'},{id:"B196",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVergote\n\t\t\t\t\t\t\tI.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFinkler\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tdel Campo\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLohr\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHunter\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMatei\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKavanagh\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVermorken\n\t\t\t\t\t\t\tJ. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMeng\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJones\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBrown\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKaye\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2009 Phase 3 randomised study of canfosfamide (Telcyta, TLK286) versus pegylated liposomal doxorubicin or topotecan as third-line therapy in patients with platinum-refractory or-resistant ovarian cancer. Eur J Cancer, 45\n\t\t\t\t\t13 2324-2332.\n\t\t\t'},{id:"B197",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHuang\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXu\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDong\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhou\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Null genotypes of GSTM1 and GSTT1 contribute to hepatocellular carcinoma risk: evidence from an updated meta-analysis. J Hepatol, 53\n\t\t\t\t\t3 508-518.\n\t\t\t'},{id:"B198",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSemenza\n\t\t\t\t\t\t\tG. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1995 Purification and characterization of hypoxia-inducible factor 1. J Biol Chem, 270\n\t\t\t\t\t3 1230-1237.\n\t\t\t'},{id:"B199",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRamji\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBhathena\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tC.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRiddick\n\t\t\t\t\t\t\tD. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1999 Glutathione S-transferases in wild-type and doxorubicin-resistant MCF-7 human breast cancer cell lines. Xenobiotica, 29\n\t\t\t\t\t2 155-170.\n\t\t\t'},{id:"B200",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tR.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tAn\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJi\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJiao\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSun\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhou\n\t\t\t\t\t\t\tD.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Hypermethylation of the Keap1 gene in human lung cancer cell lines and lung cancer tissues. Biochem Biophys Res Commun, 373\n\t\t\t\t\t1 151-154.\n\t\t\t'},{id:"B201",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMa\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKrausz\n\t\t\t\t\t\t\tK. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tIdle\n\t\t\t\t\t\t\tJ. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGonzalez\n\t\t\t\t\t\t\tF. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Role of pregnane X receptor in control of all-trans retinoic acid (ATRA) metabolism and its potential contribution to ATRA resistance. J Pharmacol Exp Ther, 324\n\t\t\t\t\t2 674-684.\n\t\t\t'},{id:"B202",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZheng\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 Human renal UOK130 tumor cells: a drug resistant cell line with highly selective over-expression of glutathione S-transferase-pi isozyme. Eur J Pharmacol, 568\n\t\t\t\t\t1-3 , 61-67.\n\t\t\t'},{id:"B203",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSykes\n\t\t\t\t\t\t\tD. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tMiller\n\t\t\t\t\t\t\tD. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Constitutive androstane receptor-mediated up-regulation of ATP-driven xenobiotic efflux transporters at the blood-brain barrier. Mol Pharmacol, 78\n\t\t\t\t\t3 376-383.\n\t\t\t'},{id:"B204",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tX. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSun\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVilleneuve\n\t\t\t\t\t\t\tN. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhao\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYi\n\t\t\t\t\t\t\tX.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZheng\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWondrak\n\t\t\t\t\t\t\tG. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWong\n\t\t\t\t\t\t\tP. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tD. D.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Nrf2 enhances resistance of cancer cells to chemotherapeutic drugs, the dark side of Nrf2. Carcinogenesis, 29\n\t\t\t\t\t6 1235-1243.\n\t\t\t'},{id:"B205",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCabral\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 Paclitaxel resistance in cells with reduced beta-tubulin. Biochim Biophys Acta, 1744\n\t\t\t\t\t2 245-255.\n\t\t\t'},{id:"B206",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWarburg\n\t\t\t\t\t\t\tO.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t1956 On respiratory impairment in cancer cells. Science, 124\n\t\t\t\t\t3215 269-270.\n\t\t\t'},{id:"B207",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWouters\n\t\t\t\t\t\t\tA.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPauwels\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLardon\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tVermorken\n\t\t\t\t\t\t\tJ. B.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2007 Review: implications of in vitro research on the effect of radiotherapy and chemotherapy under hypoxic conditions. Oncologist, 12\n\t\t\t\t\t6 690-712.\n\t\t\t'},{id:"B208",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWu\n\t\t\t\t\t\t\tC. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHsieh\n\t\t\t\t\t\t\tC. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWu\n\t\t\t\t\t\t\tY. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 The Emergence of Drug Transporter-Mediated Multidrug Resistance to Cancer Chemotherapy. Mol Pharm, in press.\n\t\t\t'},{id:"B209",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWu\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFan\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXue\n\t\t\t\t\t\t\tB.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLuo\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShen\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tS.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJiang\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYin\n\t\t\t\t\t\t\tZ.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2006 Human glutathione S-transferase 1\n\t\t\t\t\t1 interacts with TRAF2 and regulates TRAF2-ASK1 signals. Oncogene, 25\n\t\t\t\t\t42 5787-5800.\n\t\t\t'},{id:"B210",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXie\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tShults\n\t\t\t\t\t\t\tK.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFlye\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tJiang\n\t\t\t\t\t\t\tF.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHead\n\t\t\t\t\t\t\tD. R.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBriggs\n\t\t\t\t\t\t\tR. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 Overexpression of GSTA2 protects against cell cycle arrest and apoptosis induced by the DNA inter-strand crosslinking nitrogen mustard, mechlorethamine. J Cell Biochem, 95\n\t\t\t\t\t2 339-351.\n\t\t\t'},{id:"B211",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXu\n\t\t\t\t\t\t\tH. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXu\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tHao\n\t\t\t\t\t\t\tJ. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tQin\n\t\t\t\t\t\t\tC. Y.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2010 Expression of P-glycoprotein and multidrug resistance-associated protein is associated with multidrug resistance in gastric cancer. J Int Med Res, 38\n\t\t\t\t\t1 34-42.\n\t\t\t'},{id:"B212",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYe\n\t\t\t\t\t\t\tC. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWu\n\t\t\t\t\t\t\tW. K.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYeung\n\t\t\t\t\t\t\tJ. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tH. T.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tZ. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWong\n\t\t\t\t\t\t\tC. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tRen\n\t\t\t\t\t\t\tS. X.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tL.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tFung\n\t\t\t\t\t\t\tK. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCho\n\t\t\t\t\t\t\tC. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2011 Indomethacin and SC236 enhance the cytotoxicity of doxorubicin in human hepatocellular carcinoma cells via inhibiting P-glycoprotein and MRP1 expression. Cancer Lett, 304\n\t\t\t\t\t2 90-96.\n\t\t\t'},{id:"B213",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tYeo\n\t\t\t\t\t\t\tE. J.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChun\n\t\t\t\t\t\t\tY. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tCho\n\t\t\t\t\t\t\tY. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLee\n\t\t\t\t\t\t\tJ. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tKim\n\t\t\t\t\t\t\tM. S.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tPark\n\t\t\t\t\t\t\tJ. W.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2003 YC-1: a potential anticancer drug targeting hypoxia-inducible factor 1. J Natl Cancer Inst, 95\n\t\t\t\t\t7 516-525.\n\t\t\t'},{id:"B214",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZelcer\n\t\t\t\t\t\t\tN.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tSaeki\n\t\t\t\t\t\t\tT.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tReid\n\t\t\t\t\t\t\tG.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBeijnen\n\t\t\t\t\t\t\tJ. H.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tBorst\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2001 Characterization of drug transport by the human multidrug resistance protein 3 (ABCC3). J Biol Chem, 276\n\t\t\t\t\t49 46400-46407.\n\t\t\t'},{id:"B215",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhou\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGiannakakou\n\t\t\t\t\t\t\tP.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 Targeting microtubules for cancer chemotherapy. Curr Med Chem Anticancer Agents, 5\n\t\t\t\t\t1 65-71.\n\t\t\t'},{id:"B216",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhou\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLiu\n\t\t\t\t\t\t\tM.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhai\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXie\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 The antiapoptotic role of pregnane X receptor in human colon cancer cells. Mol Endocrinol, 22\n\t\t\t\t\t4 868-880.\n\t\t\t'},{id:"B217",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhou\n\t\t\t\t\t\t\tS. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tWang\n\t\t\t\t\t\t\tL. L.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDi \n\t\t\t\t\t\t\tY. M.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tXue\n\t\t\t\t\t\t\tC. C.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tDuan\n\t\t\t\t\t\t\tW.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tC. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLi\n\t\t\t\t\t\t\tY.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2008 Substrates and inhibitors of human multidrug resistance associated proteins and the implications in drug development. Curr Med Chem, 15\n\t\t\t\t\t20 1981-2039.\n\t\t\t'},{id:"B218",body:'\n\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhu\n\t\t\t\t\t\t\tH.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tChen\n\t\t\t\t\t\t\tX. P.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tLuo\n\t\t\t\t\t\t\tS. F.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tGuan\n\t\t\t\t\t\t\tJ.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tW. G.\n\t\t\t\t\t\t\n\t\t\t\t\t\t\n\t\t\t\t\t\t\tZhang\n\t\t\t\t\t\t\tB. X.\n\t\t\t\t\t\t\n\t\t\t\t\t\n\t\t\t\t\t2005 Involvement of hypoxia-inducible factor-1-alpha in multidrug resistance induced by hypoxia in HepG2 cells. J Exp Clin Cancer Res, 24\n\t\t\t\t\t4 565-574.\n\t\t\t'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Hanane Akhdar",address:null,affiliation:'
Inserm, UMR991, Liver Metabolisms and Cancer, Rennes, University of Rennes 1, Rennes,, France
Inserm, UMR991, Liver Metabolisms and Cancer, Rennes, University of Rennes 1, Rennes,, France
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1. Introduction
The COVID-19 pandemic rapidly swept through the world’s population affecting over 200 million people and causing over 5 million deaths. Clearly, the unprecedented global pandemic has affected every aspect of people’s lives [1] resulting in severe disruptions in livelihoods and access to social services for populations across the globe. Sub-Saharan Africa and similar low-income countries were severely hit by the pandemic disrupting the delivery of health, education, and other essential services as these countries were ill-prepared to deal with the effects of such a sudden major disaster [2].
The pandemic resulted in closure of schools in over 188 countries worldwide, affecting the learning, and threatening the future of over 1.5 billion learners, that is, 91% of all learners [3]. In Africa, about 250 million students were affected. Learning completely stopped for most of them, and millions of students were at risk for permanently dropping out of school, adding to the 100 million out-of-school children before the pandemic [4].
In Uganda, for example, during the 2020 wave, to control the rapidly transmissible infection, 51,000 learning institutions were closed between March and October, meaning that approximately 15 million children missed school for half a year. This was shortly followed by a second wave that resulted in a total lockdown and closure of schools from March 2021 for the rest of the year, amounting to almost 2 years of school closure, the longest on record. During the school closures, children not only lost substantial time of their learning, but they were also prone to several risks including abuse, neglect, teenage pregnancy, child labor, mental health disorders, and suicide, among others.
While all learners were affected, children with disabilities are believed to have been disproportionately disadvantaged by the pandemic since they were already grappling with challenges of access to education services due to disability. People with disabilities (PWD) are often overlooked, their capacities underestimated, and their needs given a low priority [5]. It is likely that as a result of COVID-19, preexisting learning challenges for learners with disabilities were complicated while new ones emerged, further widening the gap in access and learning between these learners with disabilities and their normal functioning counterparts. To date, there is little consolidated information on how the pandemic impacted the learning of early childhood education (ECE) learners with disabilities in sub-Saharan Africa, what approaches were used to tackle the challenges, and what lessons can be drawn for future improvement. In this chapter, we examine available evidence on the impact of COVID-19 pandemic on access to education/learning for early learners with disabilities in the context of sub-Saharan Africa, the challenges, and opportunities and possible strategies for bridging the gaps. We focus on three key questions:
What pedagogical approaches were used to enable access to education among ECE learners with disabilities during the COVID 19 pandemic?
How was access to education for ECE learners with disabilities, and what challenges and opportunities were experienced?
How can access to quality and equitable learning for ECE learners with disabilities during the current crisis be improved, and what can we learn for future crises?
Effective planning and institution of appropriate interventions to optimize learning for children with disabilities during the current and future crises will depend on a good understanding of these issues.
2. Methods
This chapter is based on review of literature on the topics above that was available between September 2021 and February 2022 when the chapter was written. We conducted literature review on the subject focusing on the sub-Saharan African context. We retrieved and included peer-reviewed and gray literature that reported on any of the areas listed above.
2.1 Literature search
Literature search was guided by the three research questions. Search terms were generated and used in the search across different databases including PUBMED, and Google scholar, and Google search for gray literature including reports, blogs, webinars etc. Key search terms included (COVID-19 OR SARS-VIRUS) AND (disabilities OR “special needs” OR “vulnerable populations”) AND (education OR learning OR schooling OR “pedagogical approaches”) AND (“early childhood” OR children) AND (Africa OR “sub-Saharan Africa” OR Africa OR “developing countries”) AND (barriers OR challenges) AND (access OR opportunities OR support). After the search was completed, the articles were compiled and screened for relevance and eligibility using the titles, abstracts, and/or on full texts. The selected articles were summarized in a table describing the type of literature, source, focus/objectives, geographical representation, and key findings.
2.2 Data extraction and synthesis
Full texts of the eligible articles were reviewed by the three reviewers working independently and focusing on our questions of interest, collaborating evidence from the diverse contexts within the continent, and key lessons for policy and practice but also identifying the important evidence gaps for future research, and any emerging perspectives related to our objectives. Based on this extraction approach, a narrative synthesis was used to describe and discuss the information as organized under the different headings below.
3. Results
A total of 41 articles including peer-reviewed and gray literature (reports, blogs, and other gray literature) were reviewed and discussed concisely, starting with a flashback on the status of ECE for children with disability before the emergence of COVID-19; followed by the pedagogical approaches that were adopted by educators in response to the pandemic; how ECE learners with disabilities accessed education during the pandemic, the challenges and opportunities they experienced; strategies through which access to quality and equitable learning for ECE learners with disabilities during the crisis can be improved; and a discussion of these perspectives bringing together the different experiences and highlighting key lessons in a local and global perspective and their implications for the current situation and future crises, in terms of policy, service provision, and research. We wind up the chapter with a conclusion highlighting the take-home message and future direction, along with the limitations of the review.
4. Early childhood education and learning for children with disabilities before the pandemic
Learners with disabilities include those who have sensory impairments, cognitive differences, physical difficulties, emotional and behavioral difficulties, communication disorders, and those with multiple disabilities [6]. Whereas some learners with disability may follow regular curriculum with adaptation or modification of the pedagogical approaches used, there are those who may need specialized syllabuses and intervention programs to access meaningful education. A majority of learners who follow regular curriculum with modification include children with visual impairment, hearing impairment, physical handicap, mild cerebral palsy, mild learning disabilities, mild autism, mild emotional and behavioral difficulties, communication disorders, and the gifted and talented [7]. They require additional support and care services such as therapy, assistive devices, and technology to access education. Leaners with disabilities who need special syllabus include those with mental handicap, deaf blindness, severe autism, severe cerebral palsy, multiple handicaps, and those with profound disabilities [8]. They learn social, communication, and activities of daily living skills at school [9]. In this chapter, we focus on reviewing literature on the pedagogical methods that were employed to enhance continuity of learning among millions of African children after the schools closed and how they favored or did not favor early childhood education (ECE) learners with disabilities.
Child-centered teaching approaches have been found to effectively enhance learning of children in early childhood education. This is predominantly learning by doing through imitation of teachers and their peers [10]. The approach has also been found to be crucial for learners with disabilities who have various challenges and need extra support [11]. Education for all children in their early years supports their development of social, communication, problem-solving, cognitive, and emotional skills [10]. This also applies to children with disabilities in early childhood education. According to Davis [9], the pedagogical approaches used for effective learning of these foundational skills among children with disabilities include: formulating clear expectations based on learning needs of the child, stimulating learning activities that enhances learners’ participation in classroom, use of audio-visual material, real objects, or simulations to make the learning process concrete, break tasks into less complex tasks and build on already acquired skills and knowledge, peer learning, sharing the learning objectives and process with parents so they can help with homework. Other strategies include carrying out every day routines consistently and aiding active learning by use of immediate reward for good behavior, completing work on time, and participating in class activities. In addition, individualized education plans where lessons are modified to meet each learner’s needs are also critical for children with disabilities [12]. Much as the approaches to support learning of these children are well articulated, they are often not practiced because of various reasons including lack of teacher skills, resources, and poor attitude of teachers among others [13, 14]. Moreover, children with disabilities are often stigmatized and discriminated against by teachers and pupils, further hindering them from full participation in learning.
Before the era of COVID-19 pandemic, access to education and other services was a major challenge for people with disabilities (PWD) including children in many low- and middle-income settings. There have been increasing efforts toward inclusive education, which recommends that children with special needs are accommodated within the mainstream teaching; however, implementation of this has been slow. Education for people with disability has been characterized by exclusion, stigma, discrimination, non-supportive attitudes of parents and community members, long distance to school, school environments that are not supportive (access, materials, equipment), and limited training for teachers on special needs education, limited involvement in planning and allocation of resources for learners with special needs as well as lack of enforcement and financing of the inclusive education policies [5, 15, 16]. As a result, there was a major gap in education access for children with disabilities in many countries in Africa prior to the pandemic. Clearly, as we will lean from subsequent sections, the pandemic and resulting school closures worsened the challenges for ECE learners with disabilities especially those in LMICs where governments were least prepared to deal with these challenges. In the section that follows, we take a critical look at the pedagogical approaches that were used to support continued learning for ECE learners with disabilities in Africa.
5. Pedagogical approaches for learners with disabilities during COVID-19 lockdown in African countries
COVID-19 severely affected education systems across the world [17], and the most affected were learners in pre-primary and primary level who have little experience of learning outside the classrooms, without support of their teachers, and could not be provided with adequate resources for learning at home (EdTech [18]). The situation was more difficult for learners with disabilities living in middle- and low-income African countries who for a long time have struggled to access quality education [7, 17]. Studies indicate that during the period when schools were closed (as a result of the pandemic), over 30% of learners with disabilities in Africa were not able to read by themselves or be read to by their parents [19]. This could have been due to the mismatch between the learners’ needs and the pedagogical approaches that were used to support them access education while at home. Learners with disabilities have unique learning styles such as visual, auditory, and kinesthetic styles that require teachers to employ different teaching strategies in the learning process to achieve effective learning. Apart from Benin, Burundi, Cote d’voire, Congo, Ethiopia, Madagascar, Malawi, Niger, and Togo that lacked remote learning readiness, most of the other African countries responded to the school closure due to COVID-19 in innovative ways by offering distance remote learning [20]. The strategies that were used combined high tech and low-cost solutions that included digital teaching and learning approaches as well as the use of paper-based take-home learning materials [21]. These pedagogical approaches were either audio-based where radios were the most common mode of audio learning, or audio-visual based where the television was the most popular form of instruction. A study established that almost all the countries in Middle East and North Africa (MENA) used television programs and print materials to deliver education content while 65% of countries in Eastern and Southern Africa (ESA) and 81% of countries in Western and Central Africa (WCA) used the television to deliver content [17]. The Ubongo Kids, Edu entertainment, and Akili Kids were the most common televised learning programs. It is estimated that over 25 million children across 40 African countries accessed Ubongo TV program that is broadcast in nine African languages including sign language [22]. The assumption of remote learning was that the intervention would meet the educational needs of all children including those in early childhood and with disability, whose schooling had also been disrupted by the pandemic [21]. However, this notion was biased because the learning platforms could not meet the diverse learning styles of children with different abilities in the early years of education. For example, whereas the deaf could benefit from sign language lessons on TV, they could not gain much from the radio lessons. Children with specific learning difficulties as well as those with mental challenges needed some extra individualized support to be able to follow the remote mode lessons.
Learning management systems using digital devices were the other pedagogical approach that was used in some African countries during the COVID-19 school closure to enhance continuity of learning. This included zoom, Google meet as well as WhatsApp and Facebook platforms [7]. Countries such as Kenya and Rwanda partnered with their telecommunication companies to lower cost of access to ICT devices and Internet connectivity alongside developing and implementing digital literacy programs. All these efforts were made to enhance innovative teaching and learning to achieve the child-centered learning. It was assumed that remote learning would meet the educational needs of all children including those in early childhood and with disability; however, this was not the case [21], as revealed by survey in 52 African countries that showed that early childhood and primary level learners could not access or effectively utilize these methods (EdTech [18]). The situation was worse for learners in early years of education with various disabilities. They not only needed support to migrate the digitalized learning but also needed the approaches to be customized to their needs. However, this support was only available in few countries. In Morocco, for example, Internet was used to aid learning. In rural areas, lessons were recorded and broadcast on Moroccan Television. The government through the Ministry of Education took steps to minimize learning loss for children with disabilities particularly the deaf by producing the educational content in sign language. Further, language teachers were recruited and trained on multisensory structured teaching and learning and later were provided with tablets to enable them deliver the content to the children through digital platforms [19]. These approaches may have achieved a certain degree of teaching; however, lack of child-centered pedagogical practices such as free-choice and small group activities, supportive and reciprocal interaction between teachers and children meant that the online approaches could not achieve optimum effectiveness [23].
In Uganda, children with disabilities were to access the learning materials that were provided by the Ministry of Education on radio and television. Home schooling was encouraged by the government, and parents were expected to support their children study using their school text books. Schools also sent learning materials on the phones or in form of printed booklets [24] but as mentioned above, there were no special considerations for children with disabilities. Moreover, as reported by Mbazzi et al. [25], the majority of the parents of children with disabilities in Uganda do not know how best to manage their children’s behavior and teach them at the same time.
In Malawi, the National COVID-19 preparedness and response plan was developed to ensure that teaching and learning continued during the lockdowns. Like in other countries, radio and televised lessons were used to reach out to learners at home and communities were mobilized to support home learning for children with disabilities. As revealed by a survey by Singal and colleagues, in addition to radio and TV lessons, learning materials were sent by the Ministry of Education in the form of ordinary print and could not be read by those who have visual impairment. Where Braille materials were provided, parents were unable to help their children read them since they lacked the skills to do so Singal et al. [24]. The survey showed that there were very few cases where parents of children with disabilities received home-based support on therapy, the absence of which must have further affected learning.
In Kenya, during the COVID-19 instigated school closures, distance learning solutions (DLS)/digital learning, also referred to as education technologies (EdTechs) [26], were adopted. The Teachers Service Commission (TSC) developed a teacher training manual through the collaborative efforts of various agencies in the education sector on remote learning. The aim was to engage learners in a variety of online environments using appropriate devices. The Kenya Institute of Curriculum Development (KICD) introduced programs on Edu channel TV and lessons from early childhood level. There was an increase in content on digital sites that was to be accessed by the learners. The television learning programs were supported with sign language interpreter as an adaptation to cater for learners who had hearing difficulties. This must have enriched the approach in terms of inclusivity; however, as mentioned earlier, delivery of content on television lacked the component of teacher-child interaction that is critical for ECE learners particularly those with special needs.
Moreover, a study indicated that the majority of teachers and parents were not sufficiently familiar with digital technologies that were used to deliver content to the learners at home [23]. Teachers noted that they lacked directions on how to support learners at home while parents indicated that they could not afford internet bundles required to download the learning materials that were sent online. It was reported in some cases that there was no sign language translator for those who had hearing impairments and that the lessons were too fast for those with learning impairments. Moreover, while learning gadgets such as braille and writing material were present at school, they were not provided at home, making home learning for children with visual impairments impossible. In the same way, deaf children were not able to communicate or get interpreter’s support at home, making it hard for them to utilize the teaching that was provided on these platforms [27].
In Ghana, the prolonged school closures placed children with disabilities at a risk of dropping out. Like in other countries, distance learning was rolled out by the Ministry of Education using television, mobile devices, and Internet. Remote learning materials were also sent to learners through postal mail. However, using this mode of teaching and learning, children with disabilities were still at risk of being left out [28].
The Zambian government strengthened radio-based learning programs by distributing solar radios and training of teachers to engage with learners through distance learning and radio programs. In Sierra Leone, the government made it a priority to leverage the radio learning programs that had been started even before the pandemic. However, these too did not provide specific support for children with different needs.
Overall, several pedagogical approaches were adopted in the different countries to enable learning continuation during the pandemic. It is imperative to note that ECE learners with disabilities were often not catered for in many of these strategies. Where special facilities were provided to cater for ECE learners with disabilities, they lacked real-time teacher-learner interaction and the additional individualized support that is critical for effective learning for children with different needs. This is because remote learning is more of teacher-directed rather than an interactive learning process that requires face-to-face presence. Effective teaching and learning of children with disabilities in their early years of education require individualized instructional practices tailored to their different educational needs. However, this was not possible since face-to-face engagements were strongly discouraged during the pandemic, putting the learners with special needs at a greater disadvantage than their normal counterparts.
6. Access to education, challenges and opportunities experienced by ECE learners with disabilities during the COVID-19 pandemic
Before the first case of COVID-19 was reported in Uganda in March 2020, a new school term for learners at all levels had just begun. In order to prevent the spread of the COVID 19 infection, the Government of Uganda decided to close all education institutions including those for early childhood learning. The closure of education institutions locked about 15 million Ugandan learners at home for a period of 2 years including young learners aged 1–8 years with disabilities. This was one of the longest lockdown of educational institutions globally. With the emergence of the pandemic, access to education for early childhood education (1–8 years) learners with disabilities faced a number of challenges but also some opportunities were experienced.
First of all, the closure of schools led school leaders to shift from physical contact with learners to online-based mode of instruction [29]. This necessitated use of technologies and digital platforms to deliver distance teaching and learning including computers, radios, and television sets to learners and distribution of printed materials to learners in their communities.
Although this development of technologies that could be used for distance learning was a very good innovation to keep learners engaged during the COVID-19 lockdown, it also created challenges to learners with disabilities. For example, the government of Uganda introduced long-distance teaching through the media, especially radio and television. These methods of teaching are not appropriate for young learners with disabilities especially those who are deaf and those who have visual impairments [30, 31, 32]. It is obvious that those with hearing impairments or visual impairments will not hear what is being taught on radio and television and will not see what is being taught on television respectively. Therefore, such platforms only benefited learners without disabilities.
Transitioning to a virtual setting required many educators to learn new technologies and skills and caused stress among both teachers and students [33]. However, both the teachers and learners were not given sufficient time to learn the new methods. In addition to moving to online learning platforms during the COVID-19 pandemic, special educators were faced with multiple challenges ranging from equity issues for learners, providing instruction in a virtual environment, and providing special education services as determined by the learner’s individual education plan. On equity, we know that the majority of the early childhood learners with disabilities in the Uganda and similar LMICs come from very poor families [34] and who therefore could not afford paying for online classes or teaching did not have televisions or radio sets in their households to access the content. There were attempts by governments to provide radio and television sets to rural communities; however, these were overtaken by other competing national priorities during the crisis.
Since these online and other distance learning technologies have been developed, education providers and the government must use this opportunity to continue developing these technologies to ensure that they remain prepared for other epidemics/and pandemics that may lead to school closure in future. This should also create an opportunity, for training and to continue delivering special education services for students with disabilities.
At a more global level, the UN guidelines for COVID-19 response recommended mainstreaming of disabilities in the planning and provision of any support and services [35, 36, 37, 38]. UNICEF provided guidance for staff and partners on supporting the learning of children in areas of school closures, which included making learning accessible to children with disabilities [39]. These also included provision of learning devices/equipment and connectivity, accessibility of instruction, individualized education plans, caregiver involvement, and the Build Back Better strategy among others. However, in many African countries, people with disabilities were neither involved in the development nor provided for during the implementation of COVID-19 response interventions [25], and as explained above, implementation of inclusive education policies was crippled by several systems’ challenges that were present before the pandemic.
7. How can access to quality and equitable learning for ECE learners with disabilities during the crisis be improved?
Several strategies have been proposed to support education of learners with disabilities in low- and middle-income countries, and this merits consideration by all stakeholders involved in education. General recommendations addressing pre-COVID-19 challenges are re-emphasized since these challenges have not gone away; they have actually become aggravated. At the global level, the Inclusive Education Initiative recommends first, strengthening teachers’ capacity (through training) and motivation to manage children with diverse needs and imparting into them the humane aspect for these children; secondly, constantly involving families in the initiatives that support inclusion since families play a critical role in leading and influencing communities and schools to embrace these innovations as well as making the voices of learners and generally PWD be heard at the local level; thirdly, executing inclusion as early as the planning stage of any initiative and at all subsequent stages and reflecting upon key aspects including curriculum, class sizes, teaching, and learning materials during the design and implementation; fourthly, to ensure that the innovations for inclusive education developed for LMICs are based on locally generated evidence and therefore which address local challenges to policy and practice [40].
The UN and UNICEF have provided guidelines to ensure access to education and other services for people with disabilities. In particular, the UNICEF’s Build Back Better guideline is based on the fact that many vulnerable children may not have been accessing quality and inclusive learning opportunities pre-COVID-19, and therefore, resumption of schooling presents an opportunity to “build back better” and capitalize on the strategies and resources being put in place during this crisis to increase access and improve learning opportunities for all children. “This includes ensuring that learning spaces are accessible to those experiencing physical disabilities, that all children – in particular girls- can access school safely, that there are gender-segregated latrines to encourage girls’ attendance, that schools are equipped for children experiencing learning impairments, that teachers are prepared to teach students of all abilities, and that communities and caregivers/parents are actively engaged and participate in the local education system and are well-informed of how to support their children” [39].
At the country level, several other strategies have been proposed. In Malawi, for example [41], parents proposed that there was need to prioritize continued learning for children with disabilities and for governments to make educational programs accessible for children with disabilities and actually provide the necessary equipment (e.g. TV, radio, parent training) for these children to access the learning. Intermittent physical access to school facilities, e.g., twice a week and permitting children to take scholastic materials home (e.g., books in Braille) as well as regular follow-up and support on home learning by teachers were also proposed by parents.
Providing parents of children with disabilities with the basic skills such a sign language and Braille to enable them to fully support their children’s learning at home, as well as financial support (loans) to enable them provide basic needs for their children was proposed. Furthermore, the need to invest in educational digital technological innovations for children with disabilities and developing teacher, parent, and learners’ capacity to use them as well as provide the necessary equipment, e.g., phones and computers to the teachers and learners was highlighted [41].
In summary, access and utilization of education services for children with disabilities during the COVID-19 pandemic have been difficult resulting in an escalation of the preexisting challenges and increasing the demands at the family, teacher, and policy levels, for which different stakeholders were not prepared. Concerted support and commitment through the several recommendations including policy improvements, and teacher, student, and learner-centered interventions, and further evidence generation could provide practical solutions to providing inclusive education services during and after the crisis to enable children with disabilities achieve their educational goals.
8. Discussion
COVID-19 pandemic has been a challenge for everyone; however, people with disability have experienced greater difficulties. The current chapter aimed at exploring the pedagogical approaches that were adopted to support continued learning for children with disabilities during the COVID-19 pandemic and the challenges experiences as well as key lessons to note.
The findings from the reviewed studies and reports suggest that COVID-19 significantly exacerbated the inequality to access to essential services particularly education for people with disabilities during the lockdown. Parent’s reports indicated that they had difficulties including children with disability in livelihood programs, yet they did this with ease to children without disability. The parents reported that the children were lonely further indicating the difficult parents had in socially including these children. Because of the physical, visual, hearing, or cognitive impairments, there is a communication barrier between the children and family members who are normal functioning jeopardizing interaction and socially isolating the child from the rest of the family. This was the case before COVID-19 but which became more evident when children were now spending the whole day at home. Moreover, it appears that parents have limited skills in sign language, let alone more advanced skills such as reading Braille that children with visual impairment need to read.
It is also imperative to note from the reviewed studies that active learning of children with disabilities mainly takes place at school. This finding indicates that parents are less involved in the actual training or learning activities of their children with disability. This could be partly attributed to lack of skills or poor attitude toward disability and education on the part of parents as revealed by the surveys. Furthermore, parents of children with disabilities usually have very low expectations from these children, and this bias down plays their motivation to support their learning in academic and everyday life activities. Consequently, the children have little contact with parents and other family members, and gradually the gap widens and further reducing the opportunity for the parents and siblings to learn how to interact with the child. This family exclusion and inability to support learning became apparent during the pandemic when all children were grounded at home and had to be supported by their parents to continue schooling. Appropriate steps should be taken to promote inclusion at family level through increased awareness and empowering families with skills to supporting learning for their children with different disabilities.
It is clear from the literature that learners with disabilities and their families struggled to access or utilize the education resources provided because they were provided in formats that were not appropriate for them or because the families lacked the necessary skills and technology to support the learner with disability with specialized material. However, in many cases, these resources were not provided at all. This was evidenced in their outcry of lack of contact between children and teachers, and the concern that a lot of the disability support services, e.g. physiotherapy, were school-based. This reveals a gap and a need for a continuum of care and support for learners with disabilities from home to school and within the wider community.
It is also important to note that disability and poverty have a synergistic relationship where disability causes poverty, and poverty aggravates effects of disability, and the two continuously enhance each other if no intervention is introduced [42]. The parents of children with disability decried their challenges in purchasing devices such as Braille machine and books, as well as voice-embedded computers for those with visual impairments to benefit from e-learning that emphasized during lockdown. Because of extreme poverty, these gadgets were not affordable by most parents from low- and middle-income countries. Financial support including cash transfers to families such as those that that were administered in African countries [4] could enable such parent to access these and other needs including electricity, which is needed for the equipment to work.
Notably, remote learning was academic-oriented with an aim of imparting knowledge for the purpose of mastering concepts and recall, whereas education for a majority of children with disability aims at making them self-reliant and emphasize acquisition of social skills, communication skills, and activities of daily living. Practically, learning for children with disability is individualized, targeting the strength of each individual learner. It is therefore implemented using an Individualized Education Plan (IEP) that could not be implemented using remote learning that replaced face-to-face learning as a result of COVID-19 school closure.
Lastly, we aimed to identify potential strategies and recommendations that could be undertaken to improve the status of learning for children with disabilities during the crisis. Our review indicates that parents need to be empowered through training and active engagements in helping their children with disability with home schooling. They need to be taught skills such as sign language, therapies, and Braille, but also be involved in interventions that aimed at bringing about attitudinal change toward disability and education. Furthermore, homes with children with disability need to be made safe against abusers, and children need to be taught how to protect themselves against abusers and where to seek support in case of abuse. Of note, the extreme poverty levels further incapacitated parents from providing the equipment needed for their children’s home schooling should be addressed. Indeed, in contexts where families of vulnerable children received cash transfers, it was clear that these had a significant impact on addressing some of the hardships that they were facing during the pandemic. Such financial supports should be considered by governments.
Importantly, there is need for proper disaster preparedness by governments to guard against adverse effects emerging from future eventualities that would necessitate closure of schools. Practically, this will include allocating sufficient budgets to support necessary response programs, but also involving people with disabilities and their families in making policies, in planning and implementation of the interventions. At the global level, funds such as the Marshall investment [4] should be dedicated to supporting children living in vulnerability including those with disabilities and to enable them recover from the adverse effects caused by the pandemic. However, this can only be achieved if there are sufficient data to enable evidence-informed policies, programs, and budgeting, as well as a deliberate commitment by government to support continued learning for children with disabilities in times of crisis. The immense data challenges on key issues were evident in this review and highlight the need for more research to generate local data on specific indicators of the burden of COVID-19 on education access and well-being of children with disabilities and PWD at large in the African context.
9. Summary and conclusion
It is evident from the above literature that the COVID-19 pandemic made learning for ECE learners with disabilities in Africa extremely difficult and hence widened the disparities between these children and typically developing children and brought to the forefront the inequity and exclusion that prevail in planning, allocation, and utilization of education resources for people with disabilities. The literature highlights the difficulties in accessing and utilizing disability-specific pedagogical learning opportunities that early learners with disabilities experienced. It must be noted that these issues not only relate to young learners but to all learners with disabilities in Africa and similar LMICs, making the proposed recommendations relevant to a wider population. In line with the Sustainable Development Goal 4 (ensure inclusive and equitable quality education and promote lifelong learning opportunities for all) and leaving no one behind, deliberate efforts should be invested in addressing the gaps and challenges at all levels (system, school, and household) to enable children with disabilities achieve their educational goals. Concerted efforts through policy improvements, political will, and change of attitude of all stakeholders including decision-makers, teachers, and communities to promote inclusion and learner-centered interventions for learners with disabilities are likely to make significant impact in enabling these learners access education during the current and future crises.
Key lessons from this literature are that across Africa, children with disabilities still grapple with difficulty in accessing quality education due to exclusion, stigma, lack of specialized skills among teachers and parents, and weak government enforcement, and low financing, among other causes. COVID-19 clearly aggravated these challenges and brought about new ones, e.g., the lack of physical interaction between learners and educators and widened the gap. Nevertheless, all is not lost, and a lot can be done to improve the status quo.
It is important to recognize the urgent need for building the education system back better, through concerted efforts, at all levels, and combining the preexisting and new approaches to address the access and utilization gap for children with disabilities. Political will in terms of committing more government funds and enforcement into policies and their implementation, effective inclusive planning, capacity building, and skills strengthening as well as utilizing local evidence to develop the interventions are critical for rolling back the challenges affecting learning of children with disabilities in the pre and post COVID-19 era. Of note, contextual and system barriers particularly household poverty, and limited government resources, and the negative community attitude toward PLD in general, which act as substrates, the inequity must be addressed. Furthermore, innovations and technologies must take into account the diverse needs of all learners particularly those with disabilities, and they should be suited to the local context, for them to yield maximum benefit for all learners.
It is apparent that African governments were ill-prepared to deal with the sudden disruptions COVID-19 caused in the education system, and indeed these countries were hard hit. This is an eye opener for governments to invest in disaster preparedness not only for education but for all sectors. Our experience from this review reveals the fact that there is limited information on the impact COVID-19 had on education, how learners navigated the challenges but also to what extent education policies were aligned with inclusion of children with disabilities, and challenges that were encountered. More post-pandemic surveys are recommended to fully understand the impact in order to institute appropriate measures to roll back the effects, but also plan better pedagogical approaches that optimize learning for all learners today and in future crises.
9.1 Limitations
The evidence discussed above is based on literature currently available in the African countries on the impact of COVID-19 on education access for learners with disability, including gray literature, which may be subject to reporting bias. The findings are majorly obtained from qualitative self-reported experiences of learners with disabilities or their families and hence a risk for reporting or social desirability bias and subjectivity particularly exaggeration of the difficulties reported with expectation of some kind of support to be provided. To date, there are generally scanty data from the education service providers (teachers) perspective and policy, and hence, a knowledge gap that calls for more research.
Authors’ contribution
MN, LA, and RN contributed to the conceptualization of the idea, generation, and review of the literature; MN led the writing and revision of the chapter; all authors reviewed and edited the final version of the chapter.
\n',keywords:"COVID-19, pedagogical, education, access, learners, children, disabilities",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/82093.pdf",chapterXML:"https://mts.intechopen.com/source/xml/82093.xml",downloadPdfUrl:"/chapter/pdf-download/82093",previewPdfUrl:"/chapter/pdf-preview/82093",totalDownloads:16,totalViews:0,totalCrossrefCites:0,dateSubmitted:"February 22nd 2022",dateReviewed:"April 13th 2022",datePrePublished:"July 25th 2022",datePublished:null,dateFinished:"June 3rd 2022",readingETA:"0",abstract:"The COVID 19 pandemic suddenly hit the world disrupting access to education especially in Sub-Saharan Africa, threatening the future of millions of learners. This chapter discusses the effects of COVID-19 on early childhood education (ECE) for learners with disabilities in Africa, focusing on three questions: (1) What pedagogical approaches were used to enable access to education among ECE learners with disabilities during the COVID 19 pandemic? (2) How was access to education for ECE learners with disabilities, and what challenges and opportunities were experienced? (3) How can access to quality and equitable learning for ECE learners with disabilities during the crisis be improved? Literature revealed that the pandemic aggravated the hardships in accessing learning programs among learners with disabilities widening the gap between them and their counterparts. Countries resorted to remote and digital pedagogical approaches to enable continuity of learning; however, many did not cater for learners with disabilities. Where disabilities were catered for, the reach and utilization were limited by lack of resources and capacity. Concerted efforts promoting effective inclusive learning are critical for the current and future pandemics. Barriers to provision of equitable education, and long-term effects of COVID 19 on in ECE learners with disabilities should be investigated.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/82093",risUrl:"/chapter/ris/82093",signatures:"Margaret Nampijja, Lillian Ayiro and Ruth Nalugya",book:{id:"10912",type:"book",title:"Psychosocial, Educational, and Economic Impacts of COVID-19",subtitle:null,fullTitle:"Psychosocial, Educational, and Economic Impacts of COVID-19",slug:null,publishedDate:null,bookSignature:"Dr. Jose C. Sánchez-García, Dr. Brizeida Hernandez-Sanchez, Dr. António Carrizo Moreira and Associate Prof. Alcides Monteiro",coverURL:"https://cdn.intechopen.com/books/images_new/10912.jpg",licenceType:"CC BY 3.0",editedByType:null,isbn:"978-1-80355-040-4",printIsbn:"978-1-80355-039-8",pdfIsbn:"978-1-80355-041-1",isAvailableForWebshopOrdering:!0,editors:[{id:"105695",title:"Dr.",name:"Jose C.",middleName:null,surname:"Sánchez-García",slug:"jose-c.-sanchez-garcia",fullName:"Jose C. Sánchez-García"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:null,sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Methods",level:"1"},{id:"sec_2_2",title:"2.1 Literature search",level:"2"},{id:"sec_3_2",title:"2.2 Data extraction and synthesis",level:"2"},{id:"sec_5",title:"3. Results",level:"1"},{id:"sec_6",title:"4. Early childhood education and learning for children with disabilities before the pandemic",level:"1"},{id:"sec_7",title:"5. Pedagogical approaches for learners with disabilities during COVID-19 lockdown in African countries",level:"1"},{id:"sec_8",title:"6. Access to education, challenges and opportunities experienced by ECE learners with disabilities during the COVID-19 pandemic",level:"1"},{id:"sec_9",title:"7. How can access to quality and equitable learning for ECE learners with disabilities during the crisis be improved?",level:"1"},{id:"sec_10",title:"8. Discussion",level:"1"},{id:"sec_11",title:"9. Summary and conclusion",level:"1"},{id:"sec_11_2",title:"9.1 Limitations",level:"2"},{id:"sec_13",title:"Authors’ contribution",level:"1"}],chapterReferences:[{id:"B1",body:'United Nations Sustainable Development Group. Shared Responsibility, Global Solidarity: Responding To the Socio-Economic Impacts of Covid-19. Nairobi, Kenya, United Nations; 2020'},{id:"B2",body:'Ozili P. “COVID-19 in Africa: socio-economic impact, policy response and opportunities”, International Journal of Sociology and Social Policy. 2022;42:177-200. DOI: 10.1108/IJSSP-05-2020-0171'},{id:"B3",body:'UNESCO. Covid-19 Education: From Disruption to Recovery. UNESCO; 2020'},{id:"B4",body:'UNICEF. COVID 19: A Catastrophe for Children in Sub-Saharan Africa [Internet]. UNICEF. 2020. Available from: https://www.unicef.org/esa/media/7626/file/COVID-19-A Catastrophe-for-Children-in-SSA.pdf [cited 31 October 2021]'},{id:"B5",body:'Bannink F, Idro R, Van Hove G. Teachers’ and parents’ perspectives on inclusive education for children with Spina Bifida in Uganda. Journal of Childhood & Developmental Disorders. 2016;2:18'},{id:"B6",body:'Ndurumo M. Exceptional Children: Development Consequences and Interaction. Nairobi, Kenya: Longman; 1993'},{id:"B7",body:'McClain Nnlapo C. An Inclusive Response to COVID 19: Education for Children with Disabilities {BLOG}. 2020. Available from: https://www.ukfiet.org/2020/an-inclusive-response-to-covid-19-education-for-children-with-disabilities/'},{id:"B8",body:'Michael E, Oboegbulem A. Learners with disabilities in an inclusive education setting in Nigeria: Implications for administrators. US-China Education Review. 2013;3(5):313-318. Available from: https://files.eric.ed.gov/fulltext/ED543446.pdf'},{id:"B9",body:'Davis P. Teaching Strategies and Approaches for Pupils with SNE: A Scoping Study Research Report RR516. 2004. Available from: https://dera.ioe.ac.uk/6059/1/RR516.pdf'},{id:"B10",body:'Andiema NC. Effects of child centered methods on teaching and learning of science activities in pre-schools in Kenya. Journal of Education and Practice. 2016;7(27):1-9. Available from: https://files.eric.ed.gov'},{id:"B11",body:'Pedro A, Mthimunye B, Bust E. How lockdown could affect South Africa’s children with special needs. Health24. 2020. https://theconversation.com/how-lockdown-could-affect-south-africas-children-with-special-needs-137127'},{id:"B12",body:'Kartika A, Suminar D, Tairas M, Hendriani W. Individual Education Program (IEP) paperwork: A narrative review. International Journal of Engineering & Technology. 2018;7:682. DOI: 10.14419/ijet.v7i2.29.13997 Available from: https://www.researchgate.net/publication/326729522_Individual_Education_Program_IEP_Paperwork_A_Narrative_Review'},{id:"B13",body:'Avramidis E, Norwich B. Teachers’ attitude towards integration/inclusion: A review of the literature. European Journal of Special Needs Education. 2002;17:129-147'},{id:"B14",body:'Wanjiru NJ. Teachers knowledge on the implementation of inclusive education in early childhood development centers in Mwea East Sub County, Kirinyaga County, Kenya, [Masters published thesis]. Kenyatta University, Kenya; 2011. Available from: https://ir-library.ku.ac.ke/bitstream/handle/123456789/18124/Teachers%27%20knowledge%20on%20the%20iplementation…pdf?sequence=1&isAllowed=y'},{id:"B15",body:'Ajodhia-Andrews A, Frankel E. Inclusive Education in Guyana: A Call for Change. International Journal of Special Education. 2010;25(1):126-144'},{id:"B16",body:'Soni A, Reyes SM, Lynch P. A review of the factors affecting children with disabilities’ successful transition to early childhood care and primary education in sub-Saharan Africa. Journal of Early Childhood Research. 2022;20(1):59-79. DOI: 10.1177/1476718X211035428'},{id:"B17",body:'World Bank. The COVID-19 Pandemic: Shocks to Education and Policy Responses. Washington, DC: World Bank; 2020. https://openknowledge.worldbank.org/handle/10986/33696'},{id:"B18",body:'EdTech Hub. The Effect of Covid-19 on Education in Africa and its Implications for the Use of Technology: A Survey of the Experience and Opinions of Educators and Technology Specialists. EdTech Hub. 2020. http://www.guninetwork.org/files/the_effect_of_covid-19_on_education_in_africa.pdf'},{id:"B19",body:'UNICEF. Transforming Education in Africa: An Evidence Based Overview and Recommendation for Long Term Improvements. UNICEF. 2021a. Available from: https://www.unicef.org/media/106686/file/Transforming%20Education%20in%20Africa.pdf'},{id:"B20",body:'UNICEF Press Release. At Least 200 Million School Children Live in Countries that Remain Unprepared to Deploy Remote Learning in Future Emergency School Closures. 2021. Available from: https://www.unicef.org/eap/press-releases/least-200-million-schoolchildren-live-countries-remain-unprepared-deploy-remote#:~:text=NEW%20YORK%2C%2028%20October%202021'},{id:"B21",body:'Zacharia S., & Twinomugisha A (2020). Educational Television During Covid-19: How to Start and What to Consider. Available from: https://blogs.worldbank.org/education/educational-television-during-covid-19-how-start-and-what-consider'},{id:"B22",body:'Ubongo Kids.Org 2020—Kids’ Edutainment. 2021. Available from: www.ubongo.org'},{id:"B23",body:'James Angoye, Irene Mbari-Kirika, O.G.W, Bruce N. Walker, Ph.D. and Martin Kavua. inABLE, MOE & UKAID 2020 Distanced and Disadvantaged: A Study on the Effects of COVID-19 on Education for Learners with Disabilities in Kenya. inABLE. Available from: https://inable.org/wp-content/uploads/2020/11/Main-Report_Distance-and-Disadvantage_a11y_Oct2020.pdf'},{id:"B24",body:'Singal N, Mbukwa-Ngwira J, Taneja-Johansson S, Lynch P, Chatha G, Umar E. (2021): Impact of Covid-19 on the education of children with disabilities in Malawi: reshaping parental engagement for the future, International Journal of Inclusive Education, DOI: 10.1080/13603116.2021.1965804'},{id:"B25",body:'Mbazzi FB, Nalugya R, Kawesa E, Nimusiima C, King R, Geert van Hove & Seeley J. (2021) The impact of COVID-19 measures on children with disabilities and their families in Uganda, Disability & Society, DOI: 10.1080/09687599.2020.1867075'},{id:"B26",body:'Government of Kenya. Kenya Basic Education Covid-19 Emergency Response Plan. Government of Kenya; 2020 Available from: https://www.education.go.ke/images/Kenya_basic_Education_COVID-19_Emergency_Response_Plan-compressed.pdf'},{id:"B27",body:'Achieng VO, Ngware MW. Adoption of education technologies for learning during COVID 19 pandemic: The experiences of marginalized and vulnerable learner populations in Kenya. International Journal of Education. 2021:1-24'},{id:"B28",body:'UNICEF. Primary and Secondary Impact of Covid 19 Pandemic on Children in Ghana. UNICEF. 2021b. Available from: www.unicef.org/publications'},{id:"B29",body:'Tumwesige J. Covid-19 Educational Disruption and Response: Rethinking e-Learning in Uganda. Konrad Adnauer Stiftung; 2020; Nairobi, Kenya Paris, France. https://en.unesco.org/news/covid-19-learning-disruption-recovery-snapshot-unescos-work-education-2020'},{id:"B30",body:'Aljedaani W, Aljedaani M, AlOmar EA, Mkaouer MW, Ludi S, Khalaf YB. I cannot see you—The perspectives of deaf students to online learning during COVID 19 pandemic: Saudi Arabia case study. Education Sciences. 2021;11(11):712'},{id:"B31",body:'Alshawabkeh AA, Woolsey ML, Kharbat FF. Using online information technology for deaf students during COVID 19: A closer look from experience. Heliyon. 2021;7(5):e06915'},{id:"B32",body:'Gayatri M. The implementation of early childhood education in the time of COVID-19 pandemic: A systematic review. Humanities & Social Sciences Reviews. 2020;8(6):46-54'},{id:"B33",body:'Asri DN, Cahyono BEH. Trisnani RP. Early reading learning for special needs students: Challenges on inclusive primary school during COVID 19 pandemic. Linguistics and Culture Review. 2021;5(S1):1062-1074'},{id:"B34",body:'WHO. WORLD REPORT ON DISABILITY WHO Library Cataloguing-in-Publication Data. 2011 Available from: www.who.int/about/licensing/copyright_form/en/index.html [cited 31 October 2021]'},{id:"B35",body:'Armitage R, Nellums LB. The COVID-19 response must be disability inclusive. The Lancet Public Health. 2020;5(5):e257. DOI: 10.1016/S2468-2667(20)30076-1'},{id:"B36",body:'Banks LM, Davey C, Shakespeare T, Kuper H. Disability-inclusive responses to COVID-19: Lessons learnt from research on social protection in low- and middle-income countries. World Development. 2020;137:105178. DOI: 10.1016/j.worlddev.2020.105178'},{id:"B37",body:'Kuper H, Banks LM, Bright T, Davey C, Shakespeare T. Disability-inclusive COVID-19 response: What it is, why it is important and what we can learn from the United Kingdom’s response. Wellcome Open Research. 2020'},{id:"B38",body:'Sakellariou D, Malfitano APS, Rotarou ES. Disability inclusiveness of government responses to COVID-19 in South America: A framework analysis study. International Journal for Equity in Health. 2020;19:131. DOI: 10.1186/s12939-020-01244-x'},{id:"B39",body:'UNICEF. All Means All-How to Support Learning for the Most Vulnerable Children in Areas of School Closures A Checklist for UNICEF Staff on Factors to Consider When Planning COVID-19 Education Response 1 [Internet]. 2021c. Available from: https://sites.unicef.org/disabilities/files/All_means_All_-_Equity_and_Inclusion_in_COVID-19_EiE_Response.pdf [cited 31 October 2021]'},{id:"B40",body:'Singal N. How can we best support the education of children with disabilities in low and middle income countries? (2021). Inclusive Education Initiative July 6, 2021.. Available from: https://www.inclusive-education-initiative.org/index.php/blog/how-can-we-best-support-education-children-disabilities-low-and-middle-income-countries. 2021 [cited 31 October 2021]'},{id:"B41",body:'Mbukwa-Ngwira J, Johansson ST, Singal UE, Lynch P, Chatha G. Impact of COVID-19 on the education of children with disabilities in Malawi: Results from a survey with parents. Inclusive Education Initiative [Internet]. Available from: https://www.inclusive-education-initiative.org/blog/impact-covid-19-education-children-disabilities-malawi-results-survey-parents. 2021 [cited 31 October 2021]'},{id:"B42",body:'Pinilla-Roncancio M. Disability and poverty: Two related conditions. A review of the literature. Revista de la Facultad de Medicina, 2015;63:S113-23. doi: http://dx.doi'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Margaret Nampijja",address:"maggie.nampijja@gmail.com",affiliation:'
African Population and Health Research Center, Kenya
Spina Bifida and Hydrocephalus Association of Uganda, Uganda
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Its first known use in rehabilitation published by Max North named as “Virtual Environments and Psychological Disorders” (1994). Virtual reality uses special programmed computers, visual devices and artificial environments for the clients’ rehabilitation. Throughout technological improvements, virtual reality devices changed from therapeutic gloves to augmented reality environments. Virtual reality was being used in different rehabilitation professions such as occupational therapy, physical therapy, psychology and so on. In spite of common virtual reality approach of different professions, each profession aims different outcomes in rehabilitation. Virtual reality in occupational therapy generally focuses on hand and upper extremity functioning, cognitive rehabilitation, mental disorders, etc. Positive effects of virtual reality were mentioned in different studies, which are higher motivation than non‐simulated environments, active participation of the participants, supporting motor learning, fun environment and risk‐free environment. Additionally, virtual reality was told to be used as assessment. This chapter will focus on usage of virtual reality in occupational therapy, history and recent developments, types of virtual reality technologic equipment, pros and cons, usage for pediatric, adult and geriatric people and recent research and articles.",signatures:"Orkun Tahir Aran, Sedef Şahin, Berkan Torpil, Tarık Demirok and\nHülya Kayıhan",authors:[{id:"172938",title:"Prof.",name:"Hulya",surname:"Kayihan",fullName:"Hulya Kayihan",slug:"hulya-kayihan",email:"hkayihan@hacettepe.edu.tr"},{id:"183079",title:"Ph.D.",name:"Sedef",surname:"Şahin",fullName:"Sedef Şahin",slug:"sedef-sahin",email:"sedefkarayazgan88@hotmail.com"},{id:"196848",title:"M.Sc.",name:"Orkun Tahir",surname:"Aran",fullName:"Orkun Tahir Aran",slug:"orkun-tahir-aran",email:"orkunaran@gmail.com"},{id:"197159",title:"Mr.",name:"Tarık",surname:"Demirok",fullName:"Tarık Demirok",slug:"tarik-demirok",email:"tarikdemirok@gmail.com"},{id:"197312",title:"M.Sc.",name:"Berkan",surname:"Torpil",fullName:"Berkan Torpil",slug:"berkan-torpil",email:"berkantorpil@gmail.com"}],book:{id:"5711",title:"Occupational Therapy",slug:"occupational-therapy-occupation-focused-holistic-practice-in-rehabilitation",productType:{id:"1",title:"Edited Volume"}}}],collaborators:[{id:"32431",title:"Prof.",name:"Gonca",surname:"Bumin",slug:"gonca-bumin",fullName:"Gonca Bumin",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Hacettepe University",institutionURL:null,country:{name:"Turkey"}}},{id:"183078",title:"Dr.",name:"Burcu Semin",surname:"Akel",slug:"burcu-semin-akel",fullName:"Burcu Semin Akel",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Hacettepe University",institutionURL:null,country:{name:"Turkey"}}},{id:"183079",title:"Ph.D.",name:"Sedef",surname:"Şahin",slug:"sedef-sahin",fullName:"Sedef Şahin",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Hacettepe University",institutionURL:null,country:{name:"Turkey"}}},{id:"196167",title:"Dr.",name:"Pat",surname:"Precin",slug:"pat-precin",fullName:"Pat Precin",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Touro College",institutionURL:null,country:{name:"United States of America"}}},{id:"196227",title:"Prof.",name:"Michel",surname:"Probst",slug:"michel-probst",fullName:"Michel Probst",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"KU Leuven",institutionURL:null,country:{name:"Belgium"}}},{id:"197265",title:"Dr.",name:"Gokcen",surname:"Akyurek",slug:"gokcen-akyurek",fullName:"Gokcen Akyurek",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"197551",title:"Dr.",name:"Hatice",surname:"Abaoğlu",slug:"hatice-abaoglu",fullName:"Hatice Abaoğlu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/197551/images/system/197551.jpeg",biography:"Dear Abaoğlu has been working as research assistant in Hacettepe University since 2014. Prior to that time, she worked as a physiotherapist in various private education centers. She received her PhD degree in 2015 from Physical Therapy Department, Hacettepe University. Currently, she is working on her second doctorate in occupational therapy field at the same university. Her scientific interest field is focussed on occupational therapy in mental health. The title of her doctoral thesis is ”The effects of life skills training on personal management, productivity, social functioning and leisure time use in people with schizophrenia”",institutionString:"Hacettepe University",institution:{name:"Hacettepe University",institutionURL:null,country:{name:"Turkey"}}},{id:"197725",title:"Dr.",name:"Serkan",surname:"Pekcetin",slug:"serkan-pekcetin",fullName:"Serkan Pekcetin",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null},{id:"198859",title:"Dr.",name:"Meral",surname:"Zarif",slug:"meral-zarif",fullName:"Meral Zarif",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Hacettepe University",institutionURL:null,country:{name:"Turkey"}}},{id:"205143",title:"Dr.",name:"Ayla",surname:"Günal",slug:"ayla-gunal",fullName:"Ayla Günal",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:null}]},generic:{page:{slug:"content-alerts",title:"Content alerts",intro:"
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His studies in robotics lead him not only to a PhD degree but also inspired him to co-found and build the International Journal of Advanced Robotic Systems - world's first Open Access journal in the field of robotics.",institutionString:null,institution:{name:"TU Wien",country:{name:"Austria"}}},{id:"441",title:"Ph.D.",name:"Jaekyu",middleName:null,surname:"Park",slug:"jaekyu-park",fullName:"Jaekyu Park",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/441/images/1881_n.jpg",biography:null,institutionString:null,institution:{name:"LG Corporation (South Korea)",country:{name:"Korea, South"}}},{id:"465",title:"Dr.",name:"Christian",middleName:null,surname:"Martens",slug:"christian-martens",fullName:"Christian Martens",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Rheinmetall (Germany)",country:{name:"Germany"}}},{id:"479",title:"Dr.",name:"Valentina",middleName:null,surname:"Colla",slug:"valentina-colla",fullName:"Valentina Colla",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/479/images/358_n.jpg",biography:null,institutionString:null,institution:{name:"Sant'Anna School of Advanced Studies",country:{name:"Italy"}}},{id:"494",title:"PhD",name:"Loris",middleName:null,surname:"Nanni",slug:"loris-nanni",fullName:"Loris Nanni",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/494/images/system/494.jpg",biography:"Loris Nanni received his Master Degree cum laude on June-2002 from the University of Bologna, and the April 26th 2006 he received his Ph.D. in Computer Engineering at DEIS, University of Bologna. On September, 29th 2006 he has won a post PhD fellowship from the university of Bologna (from October 2006 to October 2008), at the competitive examination he was ranked first in the industrial engineering area. He extensively served as referee for several international journals. He is author/coauthor of more than 100 research papers. He has been involved in some projects supported by MURST and European Community. 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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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His research interests include the application of agent technology for achieving agile control in the manufacturing environment.",institutionString:null,institution:null},{id:"605",title:"Prof",name:"Dil",middleName:null,surname:"Hussain",slug:"dil-hussain",fullName:"Dil Hussain",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/605/images/system/605.jpg",biography:"Dr. Dil Muhammad Akbar Hussain is a professor of Electronics Engineering & Computer Science at the Department of Energy Technology, Aalborg University Denmark. Professor Akbar has a Master degree in Digital Electronics from Govt. College University, Lahore Pakistan and a P-hD degree in Control Engineering from the School of Engineering and Applied Sciences, University of Sussex United Kingdom. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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He has both an MS and Ph.D. in Biomedical Engineering. He was previously a research scientist at the University of California Los Angeles (UCLA) and visiting professor and researcher at the University of North Dakota. He is currently working in artificial intelligence and its applications in medical signal processing. In addition, he is using digital signal processing in medical imaging and speech processing. Dr. Asadpour has developed brain-computer interfacing algorithms and has published books, book chapters, and several journal and conference papers in this field and other areas of intelligent signal processing. He has also designed medical devices, including a laser Doppler monitoring system.",institutionString:"Kaiser Permanente Southern California",institution:null},{id:"169608",title:"Prof.",name:"Marian",middleName:null,surname:"Găiceanu",slug:"marian-gaiceanu",fullName:"Marian Găiceanu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/169608/images/system/169608.png",biography:"Prof. Dr. Marian Gaiceanu graduated from the Naval and Electrical Engineering Faculty, Dunarea de Jos University of Galati, Romania, in 1997. He received a Ph.D. (Magna Cum Laude) in Electrical Engineering in 2002. Since 2017, Dr. Gaiceanu has been a Ph.D. supervisor for students in Electrical Engineering. He has been employed at Dunarea de Jos University of Galati since 1996, where he is currently a professor. Dr. Gaiceanu is a member of the National Council for Attesting Titles, Diplomas and Certificates, an expert of the Executive Agency for Higher Education, Research Funding, and a member of the Senate of the Dunarea de Jos University of Galati. He has been the head of the Integrated Energy Conversion Systems and Advanced Control of Complex Processes Research Center, Romania, since 2016. He has conducted several projects in power converter systems for electrical drives, power quality, PEM and SOFC fuel cell power converters for utilities, electric vehicles, and marine applications with the Department of Regulation and Control, SIEI S.pA. (2002–2004) and the Polytechnic University of Turin, Italy (2002–2004, 2006–2007). He is a member of the Institute of Electrical and Electronics Engineers (IEEE) and cofounder-member of the IEEE Power Electronics Romanian Chapter. He is a guest editor at Energies and an academic book editor for IntechOpen. He is also a member of the editorial boards of the Journal of Electrical Engineering, Electronics, Control and Computer Science and Sustainability. Dr. Gaiceanu has been General Chairman of the IEEE International Symposium on Electrical and Electronics Engineering in the last six editions.",institutionString:'"Dunarea de Jos" University of Galati',institution:{name:'"Dunarea de Jos" University of Galati',country:{name:"Romania"}}},{id:"4519",title:"Prof.",name:"Jaydip",middleName:null,surname:"Sen",slug:"jaydip-sen",fullName:"Jaydip Sen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/4519/images/system/4519.jpeg",biography:"Jaydip Sen is associated with Praxis Business School, Kolkata, India, as a professor in the Department of Data Science. His research areas include security and privacy issues in computing and communication, intrusion detection systems, machine learning, deep learning, and artificial intelligence in the financial domain. He has more than 200 publications in reputed international journals, refereed conference proceedings, and 20 book chapters in books published by internationally renowned publishing houses, such as Springer, CRC press, IGI Global, etc. Currently, he is serving on the editorial board of the prestigious journal Frontiers in Communications and Networks and in the technical program committees of a number of high-ranked international conferences organized by the IEEE, USA, and the ACM, USA. He has been listed among the top 2% of scientists in the world for the last three consecutive years, 2019 to 2021 as per studies conducted by the Stanford University, USA.",institutionString:"Praxis Business School",institution:null},{id:"320071",title:"Dr.",name:"Sidra",middleName:null,surname:"Mehtab",slug:"sidra-mehtab",fullName:"Sidra Mehtab",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00002v6KHoQAM/Profile_Picture_1584512086360",biography:"Sidra Mehtab has completed her BS with honors in Physics from Calcutta University, India in 2018. She has done MS in Data Science and Analytics from Maulana Abul Kalam Azad University of Technology (MAKAUT), Kolkata, India in 2020. Her research areas include Econometrics, Time Series Analysis, Machine Learning, Deep Learning, Artificial Intelligence, and Computer and Network Security with a particular focus on Cyber Security Analytics. Ms. Mehtab has published seven papers in international conferences and one of her papers has been accepted for publication in a reputable international journal. She has won the best paper awards in two prestigious international conferences – BAICONF 2019, and ICADCML 2021, organized in the Indian Institute of Management, Bangalore, India in December 2019, and SOA University, Bhubaneswar, India in January 2021. Besides, Ms. Mehtab has also published two book chapters in two books. Seven of her book chapters will be published in a volume shortly in 2021 by Cambridge Scholars’ Press, UK. Currently, she is working as the joint editor of two edited volumes on Time Series Analysis and Forecasting to be published in the first half of 2021 by an international house. Currently, she is working as a Data Scientist with an MNC in Delhi, India.",institutionString:"NSHM College of Management and Technology",institution:{name:"Association for Computing Machinery",country:{name:"United States of America"}}},{id:"226240",title:"Dr.",name:"Andri Irfan",middleName:null,surname:"Rifai",slug:"andri-irfan-rifai",fullName:"Andri Irfan Rifai",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/226240/images/7412_n.jpg",biography:"Andri IRFAN is a Senior Lecturer of Civil Engineering and Planning. He completed the PhD at the Universitas Indonesia & Universidade do Minho with Sandwich Program Scholarship from the Directorate General of Higher Education and LPDP scholarship. He has been teaching for more than 19 years and much active to applied his knowledge in the project construction in Indonesia. His research interest ranges from pavement management system to advanced data mining techniques for transportation engineering. He has published more than 50 papers in journals and 2 books.",institutionString:null,institution:{name:"Universitas Internasional Batam",country:{name:"Indonesia"}}},{id:"314576",title:"Dr.",name:"Ibai",middleName:null,surname:"Laña",slug:"ibai-lana",fullName:"Ibai Laña",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314576/images/system/314576.jpg",biography:"Dr. Ibai Laña works at TECNALIA as a data analyst. He received his Ph.D. in Artificial Intelligence from the University of the Basque Country (UPV/EHU), Spain, in 2018. He is currently a senior researcher at TECNALIA. His research interests fall within the intersection of intelligent transportation systems, machine learning, traffic data analysis, and data science. He has dealt with urban traffic forecasting problems, applying machine learning models and evolutionary algorithms. He has experience in origin-destination matrix estimation or point of interest and trajectory detection. Working with large volumes of data has given him a good command of big data processing tools and NoSQL databases. He has also been a visiting scholar at the Knowledge Engineering and Discovery Research Institute, Auckland University of Technology.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"314575",title:"Dr.",name:"Jesus",middleName:null,surname:"L. Lobo",slug:"jesus-l.-lobo",fullName:"Jesus L. Lobo",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/314575/images/system/314575.png",biography:"Dr. Jesús López is currently based in Bilbao (Spain) working at TECNALIA as Artificial Intelligence Research Scientist. In most cases, a project idea or a new research line needs to be investigated to see if it is good enough to take into production or to focus on it. That is exactly what he does, diving into Machine Learning algorithms and technologies to help TECNALIA to decide whether something is great in theory or will actually impact on the product or processes of its projects. So, he is expert at framing experiments, developing hypotheses, and proving whether they’re true or not, in order to investigate fundamental problems with a longer time horizon. He is also able to design and develop PoCs and system prototypes in simulation. He has participated in several national and internacional R&D projects.\n\nAs another relevant part of his everyday research work, he usually publishes his findings in reputed scientific refereed journals and international conferences, occasionally acting as reviewer and Programme Commitee member. Concretely, since 2018 he has published 9 JCR (8 Q1) journal papers, 9 conference papers (e.g. ECML PKDD 2021), and he has co-edited a book. He is also active in popular science writing data science stories for reputed blogs (KDNuggets, TowardsDataScience, Naukas). Besides, he has recently embarked on mentoring programmes as mentor, and has also worked as data science trainer.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"103779",title:"Prof.",name:"Yalcin",middleName:null,surname:"Isler",slug:"yalcin-isler",fullName:"Yalcin Isler",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRyQ8QAK/Profile_Picture_1628834958734",biography:"Yalcin Isler (1971 - Burdur / Turkey) received the B.Sc. degree in the Department of Electrical and Electronics Engineering from Anadolu University, Eskisehir, Turkey, in 1993, the M.Sc. degree from the Department of Electronics and Communication Engineering, Suleyman Demirel University, Isparta, Turkey, in 1996, the Ph.D. degree from the Department of Electrical and Electronics Engineering, Dokuz Eylul University, Izmir, Turkey, in 2009, and the Competence of Associate Professorship from the Turkish Interuniversity Council in 2019.\n\nHe was Lecturer at Burdur Vocational School in Suleyman Demirel University (1993-2000, Burdur / Turkey), Software Engineer (2000-2002, Izmir / Turkey), Research Assistant in Bulent Ecevit University (2002-2003, Zonguldak / Turkey), Research Assistant in Dokuz Eylul University (2003-2010, Izmir / Turkey), Assistant Professor at the Department of Electrical and Electronics Engineering in Bulent Ecevit University (2010-2012, Zonguldak / Turkey), Assistant Professor at the Department of Biomedical Engineering in Izmir Katip Celebi University (2012-2019, Izmir / Turkey). He is an Associate Professor at the Department of Biomedical Engineering at Izmir Katip Celebi University, Izmir / Turkey, since 2019. In addition to academics, he has also founded Islerya Medical and Information Technologies Company, Izmir / Turkey, since 2017.\n\nHis main research interests cover biomedical signal processing, pattern recognition, medical device design, programming, and embedded systems. He has many scientific papers and participated in several projects in these study fields. He was an IEEE Student Member (2009-2011) and IEEE Member (2011-2014) and has been IEEE Senior Member since 2014.",institutionString:null,institution:{name:"Izmir Kâtip Çelebi University",country:{name:"Turkey"}}},{id:"339677",title:"Dr.",name:"Mrinmoy",middleName:null,surname:"Roy",slug:"mrinmoy-roy",fullName:"Mrinmoy Roy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/339677/images/16768_n.jpg",biography:"An accomplished Sales & Marketing professional with 12 years of cross-functional experience in well-known organisations such as CIPLA, LUPIN, GLENMARK, ASTRAZENECA across different segment of Sales & Marketing, International Business, Institutional Business, Product Management, Strategic Marketing of HIV, Oncology, Derma, Respiratory, Anti-Diabetic, Nutraceutical & Stomatological Product Portfolio and Generic as well as Chronic Critical Care Portfolio. A First Class MBA in International Business & Strategic Marketing, B.Pharm, D.Pharm, Google Certified Digital Marketing Professional. Qualified PhD Candidate in Operations and Management with special focus on Artificial Intelligence and Machine Learning adoption, analysis and use in Healthcare, Hospital & Pharma Domain. Seasoned with diverse therapy area of Pharmaceutical Sales & Marketing ranging from generating revenue through generating prescriptions, launching new products, and making them big brands with continuous strategy execution at the Physician and Patients level. Moved from Sales to Marketing and Business Development for 3.5 years in South East Asian Market operating from Manila, Philippines. Came back to India and handled and developed Brands such as Gluconorm, Lupisulin, Supracal, Absolut Woman, Hemozink, Fabiflu (For COVID 19), and many more. In my previous assignment I used to develop and execute strategies on Sales & Marketing, Commercialization & Business Development for Institution and Corporate Hospital Business portfolio of Oncology Therapy Area for AstraZeneca Pharma India Ltd. Being a Research Scholar and Student of ‘Operations Research & Management: Artificial Intelligence’ I published several pioneer research papers and book chapters on the same in Internationally reputed journals and Books indexed in Scopus, Springer and Ei Compendex, Google Scholar etc. Currently, I am launching PGDM Pharmaceutical Management Program in IIHMR Bangalore and spearheading the course curriculum and structure of the same. I am interested in Collaboration for Healthcare Innovation, Pharma AI Innovation, Future trend in Marketing and Management with incubation on Healthcare, Healthcare IT startups, AI-ML Modelling and Healthcare Algorithm based training module development. I am also an affiliated member of the Institute of Management Consultant of India, looking forward to Healthcare, Healthcare IT and Innovation, Pharma and Hospital Management Consulting works.",institutionString:null,institution:{name:"Lovely Professional University",country:{name:"India"}}},{id:"310576",title:"Prof.",name:"Erick Giovani",middleName:null,surname:"Sperandio Nascimento",slug:"erick-giovani-sperandio-nascimento",fullName:"Erick Giovani Sperandio Nascimento",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0033Y00002pDKxDQAW/ProfilePicture%202022-06-20%2019%3A57%3A24.788",biography:"Prof. Erick Sperandio is the Lead Researcher and professor of Artificial Intelligence (AI) at SENAI CIMATEC, Bahia, Brazil, also working with Computational Modeling (CM) and HPC. He holds a PhD in Environmental Engineering in the area of Atmospheric Computational Modeling, a Master in Informatics in the field of Computational Intelligence and Graduated in Computer Science from UFES. He currently coordinates, leads and participates in R&D projects in the areas of AI, computational modeling and supercomputing applied to different areas such as Oil and Gas, Health, Advanced Manufacturing, Renewable Energies and Atmospheric Sciences, advising undergraduate, master's and doctoral students. He is the Lead Researcher at SENAI CIMATEC's Reference Center on Artificial Intelligence. In addition, he is a Certified Instructor and University Ambassador of the NVIDIA Deep Learning Institute (DLI) in the areas of Deep Learning, Computer Vision, Natural Language Processing and Recommender Systems, and Principal Investigator of the NVIDIA/CIMATEC AI Joint Lab, the first in Latin America within the NVIDIA AI Technology Center (NVAITC) worldwide program. He also works as a researcher at the Supercomputing Center for Industrial Innovation (CS2i) and at the SENAI Institute of Innovation for Automation (ISI Automação), both from SENAI CIMATEC. He is a member and vice-coordinator of the Basic Board of Scientific-Technological Advice and Evaluation, in the area of Innovation, of the Foundation for Research Support of the State of Bahia (FAPESB). He serves as Technology Transfer Coordinator and one of the Principal Investigators at the National Applied Research Center in Artificial Intelligence (CPA-IA) of SENAI CIMATEC, focusing on Industry, being one of the six CPA-IA in Brazil approved by MCTI / FAPESP / CGI.br. He also participates as one of the representatives of Brazil in the BRICS Innovation Collaboration Working Group on HPC, ICT and AI. He is the coordinator of the Work Group of the Axis 5 - Workforce and Training - of the Brazilian Strategy for Artificial Intelligence (EBIA), and member of the MCTI/EMBRAPII AI Innovation Network Training Committee. He is the coordinator, by SENAI CIMATEC, of the Artificial Intelligence Reference Network of the State of Bahia (REDE BAH.IA). He leads the working group of experts representing Brazil in the Global Partnership on Artificial Intelligence (GPAI), on the theme \"AI and the Pandemic Response\".",institutionString:"Manufacturing and Technology Integrated Campus – SENAI CIMATEC",institution:null},{id:"1063",title:"Prof.",name:"Constantin",middleName:null,surname:"Volosencu",slug:"constantin-volosencu",fullName:"Constantin Volosencu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/1063/images/system/1063.png",biography:"Prof. Dr. Constantin Voloşencu graduated as an engineer from\nPolitehnica University of Timișoara, Romania, where he also\nobtained a doctorate degree. He is currently a full professor in\nthe Department of Automation and Applied Informatics at the\nsame university. Dr. Voloşencu is the author of ten books, seven\nbook chapters, and more than 160 papers published in journals\nand conference proceedings. He has also edited twelve books and\nhas twenty-seven patents to his name. He is a manager of research grants, editor in\nchief and member of international journal editorial boards, a former plenary speaker, a member of scientific committees, and chair at international conferences. His\nresearch is in the fields of control systems, control of electric drives, fuzzy control\nsystems, neural network applications, fault detection and diagnosis, sensor network\napplications, monitoring of distributed parameter systems, and power ultrasound\napplications. He has developed automation equipment for machine tools, spooling\nmachines, high-power ultrasound processes, and more.",institutionString:'"Politechnica" University Timişoara',institution:null},{id:"221364",title:"Dr.",name:"Eneko",middleName:null,surname:"Osaba",slug:"eneko-osaba",fullName:"Eneko Osaba",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/221364/images/system/221364.jpg",biography:"Dr. Eneko Osaba works at TECNALIA as a senior researcher. He obtained his Ph.D. in Artificial Intelligence in 2015. He has participated in more than twenty-five local and European research projects, and in the publication of more than 130 papers. He has performed several stays at universities in the United Kingdom, Italy, and Malta. Dr. Osaba has served as a program committee member in more than forty international conferences and participated in organizing activities in more than ten international conferences. He is a member of the editorial board of the International Journal of Artificial Intelligence, Data in Brief, and Journal of Advanced Transportation. He is also a guest editor for the Journal of Computational Science, Neurocomputing, Swarm, and Evolutionary Computation and IEEE ITS Magazine.",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"275829",title:"Dr.",name:"Esther",middleName:null,surname:"Villar-Rodriguez",slug:"esther-villar-rodriguez",fullName:"Esther Villar-Rodriguez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/275829/images/system/275829.jpg",biography:"Dr. Esther Villar obtained a Ph.D. in Information and Communication Technologies from the University of Alcalá, Spain, in 2015. She obtained a degree in Computer Science from the University of Deusto, Spain, in 2010, and an MSc in Computer Languages and Systems from the National University of Distance Education, Spain, in 2012. Her areas of interest and knowledge include natural language processing (NLP), detection of impersonation in social networks, semantic web, and machine learning. Dr. Esther Villar made several contributions at conferences and publishing in various journals in those fields. Currently, she is working within the OPTIMA (Optimization Modeling & Analytics) business of TECNALIA’s ICT Division as a data scientist in projects related to the prediction and optimization of management and industrial processes (resource planning, energy efficiency, etc).",institutionString:"TECNALIA Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"49813",title:"Dr.",name:"Javier",middleName:null,surname:"Del Ser",slug:"javier-del-ser",fullName:"Javier Del Ser",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/49813/images/system/49813.png",biography:"Prof. Dr. Javier Del Ser received his first PhD in Telecommunication Engineering (Cum Laude) from the University of Navarra, Spain, in 2006, and a second PhD in Computational Intelligence (Summa Cum Laude) from the University of Alcala, Spain, in 2013. He is currently a principal researcher in data analytics and optimisation at TECNALIA (Spain), a visiting fellow at the Basque Center for Applied Mathematics (BCAM) and a part-time lecturer at the University of the Basque Country (UPV/EHU). His research interests gravitate on the use of descriptive, prescriptive and predictive algorithms for data mining and optimization in a diverse range of application fields such as Energy, Transport, Telecommunications, Health and Industry, among others. In these fields he has published more than 240 articles, co-supervised 8 Ph.D. theses, edited 6 books, coauthored 7 patents and participated/led more than 40 research projects. He is a Senior Member of the IEEE, and a recipient of the Biscay Talent prize for his academic career.",institutionString:"Tecnalia Research & Innovation",institution:{name:"Tecnalia",country:{name:"Spain"}}},{id:"278948",title:"Dr.",name:"Carlos Pedro",middleName:null,surname:"Gonçalves",slug:"carlos-pedro-goncalves",fullName:"Carlos Pedro Gonçalves",position:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRcmyQAC/Profile_Picture_1564224512145",biography:'Carlos Pedro Gonçalves (PhD) is an Associate Professor at Lusophone University of Humanities and Technologies and a researcher on Complexity Sciences, Quantum Technologies, Artificial Intelligence, Strategic Studies, Studies in Intelligence and Security, FinTech and Financial Risk Modeling. He is also a progammer with programming experience in:\n\nA) Quantum Computing using Qiskit Python module and IBM Quantum Experience Platform, with software developed on the simulation of Quantum Artificial Neural Networks and Quantum Cybersecurity;\n\nB) Artificial Intelligence and Machine learning programming in Python;\n\nC) Artificial Intelligence, Multiagent Systems Modeling and System Dynamics Modeling in Netlogo, with models developed in the areas of Chaos Theory, Econophysics, Artificial Intelligence, Classical and Quantum Complex Systems Science, with the Econophysics models having been cited worldwide and incorporated in PhD programs by different Universities.\n\nReceived an Arctic Code Vault Contributor status by GitHub, due to having developed open source software preserved in the \\"Arctic Code Vault\\" for future generations (https://archiveprogram.github.com/arctic-vault/), with the Strategy Analyzer A.I. module for decision making support (based on his PhD thesis, used in his Classes on Decision Making and in Strategic Intelligence Consulting Activities) and QNeural Python Quantum Neural Network simulator also preserved in the \\"Arctic Code Vault\\", for access to these software modules see: https://github.com/cpgoncalves. He is also a peer reviewer with outsanding review status from Elsevier journals, including Physica A, Neurocomputing and Engineering Applications of Artificial Intelligence. Science CV available at: https://www.cienciavitae.pt//pt/8E1C-A8B3-78C5 and ORCID: https://orcid.org/0000-0002-0298-3974',institutionString:"University of Lisbon",institution:{name:"Universidade Lusófona",country:{name:"Portugal"}}},{id:"241400",title:"Prof.",name:"Mohammed",middleName:null,surname:"Bsiss",slug:"mohammed-bsiss",fullName:"Mohammed Bsiss",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/241400/images/8062_n.jpg",biography:null,institutionString:null,institution:null},{id:"276128",title:"Dr.",name:"Hira",middleName:null,surname:"Fatima",slug:"hira-fatima",fullName:"Hira Fatima",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/276128/images/14420_n.jpg",biography:"Dr. Hira Fatima\nAssistant Professor\nDepartment of Mathematics\nInstitute of Applied Science\nMangalayatan University, Aligarh\nMobile: no : 8532041179\nhirafatima2014@gmal.com\n\nDr. Hira Fatima has received his Ph.D. degree in pure Mathematics from Aligarh Muslim University, Aligarh India. Currently working as an Assistant Professor in the Department of Mathematics, Institute of Applied Science, Mangalayatan University, Aligarh. She taught so many courses of Mathematics of UG and PG level. Her research Area of Expertise is Functional Analysis & Sequence Spaces. She has been working on Ideal Convergence of double sequence. She has published 17 research papers in National and International Journals including Cogent Mathematics, Filomat, Journal of Intelligent and Fuzzy Systems, Advances in Difference Equations, Journal of Mathematical Analysis, Journal of Mathematical & Computer Science etc. She has also reviewed few research papers for the and international journals. She is a member of Indian Mathematical Society.",institutionString:null,institution:null},{id:"414880",title:"Dr.",name:"Maryam",middleName:null,surname:"Vatankhah",slug:"maryam-vatankhah",fullName:"Maryam Vatankhah",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Borough of Manhattan Community College",country:{name:"United States of America"}}},{id:"414879",title:"Prof.",name:"Mohammad-Reza",middleName:null,surname:"Akbarzadeh-Totonchi",slug:"mohammad-reza-akbarzadeh-totonchi",fullName:"Mohammad-Reza Akbarzadeh-Totonchi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Ferdowsi University of Mashhad",country:{name:"Iran"}}},{id:"414878",title:"Prof.",name:"Reza",middleName:null,surname:"Fazel-Rezai",slug:"reza-fazel-rezai",fullName:"Reza Fazel-Rezai",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"American Public University System",country:{name:"United States of America"}}},{id:"426586",title:"Dr.",name:"Oladunni A.",middleName:null,surname:"Daramola",slug:"oladunni-a.-daramola",fullName:"Oladunni A. Daramola",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Federal University of Technology",country:{name:"Nigeria"}}},{id:"357014",title:"Prof.",name:"Leon",middleName:null,surname:"Bobrowski",slug:"leon-bobrowski",fullName:"Leon Bobrowski",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Bialystok University of Technology",country:{name:"Poland"}}},{id:"302698",title:"Dr.",name:"Yao",middleName:null,surname:"Shan",slug:"yao-shan",fullName:"Yao Shan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Dalian University of Technology",country:{name:"China"}}},{id:"354126",title:"Dr.",name:"Setiawan",middleName:null,surname:"Hadi",slug:"setiawan-hadi",fullName:"Setiawan Hadi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Padjadjaran University",country:{name:"Indonesia"}}},{id:"125911",title:"Prof.",name:"Jia-Ching",middleName:null,surname:"Wang",slug:"jia-ching-wang",fullName:"Jia-Ching Wang",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"National Central University",country:{name:"Taiwan"}}},{id:"332603",title:"Prof.",name:"Kumar S.",middleName:null,surname:"Ray",slug:"kumar-s.-ray",fullName:"Kumar S. 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Sai Charan",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}},{id:"357086",title:"Prof.",name:"Sandeep K.",middleName:null,surname:"Shukla",slug:"sandeep-k.-shukla",fullName:"Sandeep K. Shukla",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Indian Institute of Technology Kanpur",country:{name:"India"}}}]}},subseries:{item:{id:"3",type:"subseries",title:"Bacterial Infectious Diseases",keywords:"Antibiotics, Biofilm, Antibiotic Resistance, Host-microbiota Relationship, Treatment, Diagnostic Tools",scope:"
\r\n\tThe era of antibiotics led us to the illusion that the problem of bacterial infection is over. However, bacterial flexibility and adaptation mechanisms allow them to survive and grow in extreme conditions. The best example is the formation of a sophisticated society of bacteria defined as a biofilm. Understanding the mechanism of bacterial biofilm formation has changed our perception of the development of bacterial infection but successfully eradicating biofilm remains a challenge. Considering the above, it is not surprising that bacteria remain a major public health threat despite the development of many groups of antibiotics. Additionally, increasing prevalence of acquired antibiotic resistance forces us to realize that we are far from controlling the development of bacterial infections. On the other hand, many infections are endogenous and result from an unbalanced relationship between the host and the microorganism. The increasing use of immunosuppressants, such as chemotherapy or organ transplantation, increases the incidence of patients highly susceptible to bacterial infections in the population.
\r\n
\r\n\tThis topic will focus on the current challenges and advantages in the diagnosis and treatment of bacterial infections. We will discuss the host-microbiota relationship, the treatment of chronic infections due to biofilm formation, and the development of new diagnostic tools to rapidly distinguish between colonization and probable infection.
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Since many years, he is a member of steering committee of Gdańsk branch of Polish Society of Microbiologists, a member of ESCMID. He is also a reviewer and a member of editorial boards of a number of international journals.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorTwo:{id:"484980",title:"Dr.",name:"Katarzyna",middleName:null,surname:"Garbacz",slug:"katarzyna-garbacz",fullName:"Katarzyna Garbacz",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y00003St8TAQAZ/Profile_Picture_2022-07-07T09:45:16.jpg",biography:"Katarzyna Maria Garbacz, MD, is an Associate Professor at the Medical University of Gdańsk, Poland and she is head of the Department of Oral Microbiology of the Medical University of Gdańsk. She has published more than 50 scientific publications in peer-reviewed journals. She has been a project leader funded by the National Science Centre of Poland. Prof. Garbacz is a microbiologist working on applied and fundamental questions in microbial epidemiology and pathogenesis. Her research interest is in antibiotic resistance, host-pathogen interaction, and therapeutics development for staphylococcal pathogens, mainly Staphylococcus aureus, which causes hospital-acquired infections. Currently, her research is mostly focused on the study of oral pathogens, particularly Staphylococcus spp.",institutionString:"Medical University of Gdańsk, Poland",institution:null},editorThree:null,series:{id:"6",title:"Infectious Diseases",doi:"10.5772/intechopen.71852",issn:"2631-6188"},editorialBoard:[{id:"190041",title:"Dr.",name:"Jose",middleName:null,surname:"Gutierrez Fernandez",slug:"jose-gutierrez-fernandez",fullName:"Jose Gutierrez Fernandez",profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institutionString:null,institution:{name:"University of Granada",institutionURL:null,country:{name:"Spain"}}},{id:"156556",title:"Prof.",name:"Maria Teresa",middleName:null,surname:"Mascellino",slug:"maria-teresa-mascellino",fullName:"Maria Teresa Mascellino",profilePictureURL:"https://mts.intechopen.com/storage/users/156556/images/system/156556.jpg",institutionString:"Sapienza University",institution:{name:"Sapienza University of Rome",institutionURL:null,country:{name:"Italy"}}},{id:"164933",title:"Prof.",name:"Mónica Alexandra",middleName:null,surname:"Sousa Oleastro",slug:"monica-alexandra-sousa-oleastro",fullName:"Mónica Alexandra Sousa Oleastro",profilePictureURL:"https://mts.intechopen.com/storage/users/164933/images/system/164933.jpeg",institutionString:"National Institute of Health Dr Ricardo Jorge",institution:{name:"National Institute of Health Dr. Ricardo Jorge",institutionURL:null,country:{name:"Portugal"}}}]},onlineFirstChapters:{paginationCount:2,paginationItems:[{id:"82936",title:"Soil Degradation Processes Linked to Long-Term Forest-Type Damage",doi:"10.5772/intechopen.106390",signatures:"Pavel Samec, Aleš Kučera and Gabriela Tomášová",slug:"soil-degradation-processes-linked-to-long-term-forest-type-damage",totalDownloads:3,totalCrossrefCites:0,totalDimensionsCites:0,authors:null,book:{title:"Forest Degradation Under Global Change",coverURL:"https://cdn.intechopen.com/books/images_new/11457.jpg",subseries:{id:"94",title:"Climate Change and Environmental Sustainability"}}},{id:"82124",title:"Assessment of Diversity, Growth Characteristics and Aboveground Biomass of Tree Species in Selected Urban Green Areas of Osogbo, Osun State",doi:"10.5772/intechopen.104982",signatures:"Omolara Aremu, Olusola O. 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\r\n\tThe era of antibiotics led us to the illusion that the problem of bacterial infection is over. However, bacterial flexibility and adaptation mechanisms allow them to survive and grow in extreme conditions. The best example is the formation of a sophisticated society of bacteria defined as a biofilm. Understanding the mechanism of bacterial biofilm formation has changed our perception of the development of bacterial infection but successfully eradicating biofilm remains a challenge. Considering the above, it is not surprising that bacteria remain a major public health threat despite the development of many groups of antibiotics. Additionally, increasing prevalence of acquired antibiotic resistance forces us to realize that we are far from controlling the development of bacterial infections. On the other hand, many infections are endogenous and result from an unbalanced relationship between the host and the microorganism. The increasing use of immunosuppressants, such as chemotherapy or organ transplantation, increases the incidence of patients highly susceptible to bacterial infections in the population.
\r\n
\r\n\tThis topic will focus on the current challenges and advantages in the diagnosis and treatment of bacterial infections. We will discuss the host-microbiota relationship, the treatment of chronic infections due to biofilm formation, and the development of new diagnostic tools to rapidly distinguish between colonization and probable infection.
",coverUrl:"https://cdn.intechopen.com/series_topics/covers/3.jpg",keywords:"Antibiotics, Biofilm, Antibiotic Resistance, Host-microbiota Relationship, Treatment, Diagnostic Tools"},{id:"4",title:"Fungal Infectious Diseases",scope:"Fungi are ubiquitous and there are almost no non-pathogenic fungi. Fungal infectious illness prevalence and prognosis are determined by the exposure between fungi and host, host immunological state, fungal virulence, and early and accurate diagnosis and treatment. \r\nPatients with both congenital and acquired immunodeficiency are more likely to be infected with opportunistic mycosis. Fungal infectious disease outbreaks are common during the post- disaster rebuilding era, which is characterised by high population density, migration, and poor health and medical conditions.\r\nSystemic or local fungal infection is mainly associated with the fungi directly inhaled or inoculated in the environment during the disaster. The most common fungal infection pathways are human to human (anthropophilic), animal to human (zoophilic), and environment to human (soilophile). Diseases are common as a result of widespread exposure to pathogenic fungus dispersed into the environment. \r\nFungi that are both common and emerging are intertwined. In Southeast Asia, for example, Talaromyces marneffei is an important pathogenic thermally dimorphic fungus that causes systemic mycosis. Widespread fungal infections with complicated and variable clinical manifestations, such as Candida auris infection resistant to several antifungal medicines, Covid-19 associated with Trichoderma, and terbinafine resistant dermatophytosis in India, are among the most serious disorders. \r\nInappropriate local or systemic use of glucocorticoids, as well as their immunosuppressive effects, may lead to changes in fungal infection spectrum and clinical characteristics. Hematogenous candidiasis is a worrisome issue that affects people all over the world, particularly ICU patients. CARD9 deficiency and fungal infection have been major issues in recent years. Invasive aspergillosis is associated with a significant death rate. Special attention should be given to endemic fungal infections, identification of important clinical fungal infections advanced in yeasts, filamentous fungal infections, skin mycobiome and fungal genomes, and immunity to fungal infections.\r\nIn addition, endemic fungal diseases or uncommon fungal infections caused by Mucor irregularis, dermatophytosis, Malassezia, cryptococcosis, chromoblastomycosis, coccidiosis, blastomycosis, histoplasmosis, sporotrichosis, and other fungi, should be monitored. \r\nThis topic includes the research progress on the etiology and pathogenesis of fungal infections, new methods of isolation and identification, rapid detection, drug sensitivity testing, new antifungal drugs, schemes and case series reports. It will provide significant opportunities and support for scientists, clinical doctors, mycologists, antifungal drug researchers, public health practitioners, and epidemiologists from all over the world to share new research, ideas and solutions to promote the development and progress of medical mycology.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/4.jpg",keywords:"Emerging Fungal Pathogens, Invasive Infections, Epidemiology, Cell Membrane, Fungal Virulence, Diagnosis, Treatment"},{id:"5",title:"Parasitic Infectious Diseases",scope:"Parasitic diseases have evolved alongside their human hosts. In many cases, these diseases have adapted so well that they have developed efficient resilience methods in the human host and can live in the host for years. Others, particularly some blood parasites, can cause very acute diseases and are responsible for millions of deaths yearly. Many parasitic diseases are classified as neglected tropical diseases because they have received minimal funding over recent years and, in many cases, are under-reported despite the critical role they play in morbidity and mortality among human and animal hosts. The current topic, Parasitic Infectious Diseases, in the Infectious Diseases Series aims to publish studies on the systematics, epidemiology, molecular biology, genomics, pathogenesis, genetics, and clinical significance of parasitic diseases from blood borne to intestinal parasites as well as zoonotic parasites. We hope to cover all aspects of parasitic diseases to provide current and relevant research data on these very important diseases. In the current atmosphere of the Coronavirus pandemic, communities around the world, particularly those in different underdeveloped areas, are faced with the growing challenges of the high burden of parasitic diseases. At the same time, they are faced with the Covid-19 pandemic leading to what some authors have called potential syndemics that might worsen the outcome of such infections. Therefore, it is important to conduct studies that examine parasitic infections in the context of the coronavirus pandemic for the benefit of all communities to help foster more informed decisions for the betterment of human and animal health.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/5.jpg",keywords:"Blood Borne Parasites, Intestinal Parasites, Protozoa, Helminths, Arthropods, Water Born Parasites, Epidemiology, Molecular Biology, Systematics, Genomics, Proteomics, Ecology"},{id:"6",title:"Viral Infectious Diseases",scope:"The Viral Infectious Diseases Book Series aims to provide a comprehensive overview of recent research trends and discoveries in various viral infectious diseases emerging around the globe. The emergence of any viral disease is hard to anticipate, which often contributes to death. A viral disease can be defined as an infectious disease that has recently appeared within a population or exists in nature with the rapid expansion of incident or geographic range. 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