\\n\\n
More than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\\n\\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\\n\\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\\n\\nAdditionally, each book published by IntechOpen contains original content and research findings.
\\n\\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\\n\\n\\n\\n
\\n"}]',published:!0,mainMedia:{caption:"IntechOpen Maintains",originalUrl:"/media/original/113"}},components:[{type:"htmlEditorComponent",content:'
Simba Information has released its Open Access Book Publishing 2020 - 2024 report and has again identified IntechOpen as the world’s largest Open Access book publisher by title count.
\n\nSimba Information is a leading provider for market intelligence and forecasts in the media and publishing industry. The report, published every year, provides an overview and financial outlook for the global professional e-book publishing market.
\n\nIntechOpen, De Gruyter, and Frontiers are the largest OA book publishers by title count, with IntechOpen coming in at first place with 5,101 OA books published, a good 1,782 titles ahead of the nearest competitor.
\n\nSince the first Open Access Book Publishing report published in 2016, IntechOpen has held the top stop each year.
\n\n\n\nMore than half of the publishers listed alongside IntechOpen (18 out of 30) are Social Science and Humanities publishers. IntechOpen is an exception to this as a leader in not only Open Access content but Open Access content across all scientific disciplines, including Physical Sciences, Engineering and Technology, Health Sciences, Life Science, and Social Sciences and Humanities.
\n\nOur breakdown of titles published demonstrates this with 47% PET, 31% HS, 18% LS, and 4% SSH books published.
\n\n“Even though ItechOpen has shown the potential of sci-tech books using an OA approach,” other publishers “have shown little interest in OA books.”
\n\nAdditionally, each book published by IntechOpen contains original content and research findings.
\n\nWe are honored to be among such prestigious publishers and we hope to continue to spearhead that growth in our quest to promote Open Access as a true pioneer in OA book publishing.
\n\n\n\n
\n'}],latestNews:[{slug:"webinar-introduction-to-open-science-wednesday-18-may-1-pm-cest-20220518",title:"Webinar: Introduction to Open Science | Wednesday 18 May, 1 PM CEST"},{slug:"step-in-the-right-direction-intechopen-launches-a-portfolio-of-open-science-journals-20220414",title:"Step in the Right Direction: IntechOpen Launches a Portfolio of Open Science Journals"},{slug:"let-s-meet-at-london-book-fair-5-7-april-2022-olympia-london-20220321",title:"Let’s meet at London Book Fair, 5-7 April 2022, Olympia London"},{slug:"50-books-published-as-part-of-intechopen-and-knowledge-unlatched-ku-collaboration-20220316",title:"50 Books published as part of IntechOpen and Knowledge Unlatched (KU) Collaboration"},{slug:"intechopen-joins-the-united-nations-sustainable-development-goals-publishers-compact-20221702",title:"IntechOpen joins the United Nations Sustainable Development Goals Publishers Compact"},{slug:"intechopen-signs-exclusive-representation-agreement-with-lsr-libros-servicios-y-representaciones-s-a-de-c-v-20211123",title:"IntechOpen Signs Exclusive Representation Agreement with LSR Libros Servicios y Representaciones S.A. de C.V"},{slug:"intechopen-expands-partnership-with-research4life-20211110",title:"IntechOpen Expands Partnership with Research4Life"},{slug:"introducing-intechopen-book-series-a-new-publishing-format-for-oa-books-20210915",title:"Introducing IntechOpen Book Series - A New Publishing Format for OA Books"}]},book:{item:{type:"book",id:"10321",leadTitle:null,fullTitle:"Advances in Precision Medicine Oncology",title:"Advances in Precision Medicine Oncology",subtitle:null,reviewType:"peer-reviewed",abstract:"Recent advances in precision medicine and immuno-oncology have led to highly specific and efficacious cancer therapies such as monoclonal antibodies and immune checkpoint inhibitors (ICIs). This book provides an up-to-date overview of advances in the field of immuno-oncology. Chapters cover such topics as ICIs and how they mount a robust immune response against cancer cells as well as the response of ICIs to treatment predictive biomarkers and their potential immune-related adverse events (irAEs). Additionally, the book includes a comprehensive review of the powerful FDA-approved therapeutic agent doxorubicin, highlighting the molecular mechanisms behind doxorubicin’s drug resistance and critical side effects.",isbn:"978-1-83968-868-3",printIsbn:"978-1-83968-867-6",pdfIsbn:"978-1-83968-869-0",doi:"10.5772/intechopen.91507",price:119,priceEur:129,priceUsd:155,slug:"advances-in-precision-medicine-oncology",numberOfPages:260,isOpenForSubmission:!1,isInWos:null,isInBkci:!1,hash:"043ad1c1a6bbdcd5604917ccbff003d8",bookSignature:"Hilal Arnouk and Bassam Abdul Rasool Hassan",publishedDate:"July 21st 2021",coverURL:"https://cdn.intechopen.com/books/images_new/10321.jpg",numberOfDownloads:4204,numberOfWosCitations:0,numberOfCrossrefCitations:2,numberOfCrossrefCitationsByBook:0,numberOfDimensionsCitations:4,numberOfDimensionsCitationsByBook:0,hasAltmetrics:0,numberOfTotalCitations:6,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"September 24th 2020",dateEndSecondStepPublish:"October 22nd 2020",dateEndThirdStepPublish:"December 21st 2020",dateEndFourthStepPublish:"March 11th 2021",dateEndFifthStepPublish:"May 10th 2021",currentStepOfPublishingProcess:5,indexedIn:"1,2,3,4,5,6",editedByType:"Edited by",kuFlag:!1,featuredMarkup:null,editors:[{id:"76431",title:"Dr.",name:"Hilal",middleName:null,surname:"Arnouk",slug:"hilal-arnouk",fullName:"Hilal Arnouk",profilePictureURL:"https://mts.intechopen.com/storage/users/76431/images/system/76431.jpg",biography:"Hilal Arnouk, MD, Ph.D., is an Associate Professor at the Department of Pathology, Midwestern University, Downers Grove, Illinois. Dr. Arnouk received his education and post-doctorate training at Roswell Park Cancer Institute, the State University of New York at Buffalo, the Medical College of Georgia, and the University of Alabama at Birmingham. He has directed research studies in academia and biotech industry settings. His major areas of expertise include cancer immunotherapy, biomarker discovery, and precision medicine. Additionally, Dr. Arnouk tremendously enjoys being an educator and a mentor for professional students in the medical and biomedical sciences.",institutionString:null,position:null,outsideEditionCount:null,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"3",institution:{name:"Midwestern University",institutionURL:null,country:{name:"United States of America"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,coeditorOne:{id:"155124",title:"Dr.",name:"Bassam",middleName:"Abdul Rasool",surname:"Hassan",slug:"bassam-hassan",fullName:"Bassam Hassan",profilePictureURL:"https://mts.intechopen.com/storage/users/155124/images/system/155124.png",biography:"Bassam Abdul Rasool Hassan obtained a Ph.D. in Clinical Pharmacy from the School of Pharmacy, Universiti Sains Malaysia (USM). He worked as a senior lecturer at the Department of Pharmacy, Faculty of Medicine, Universiti Malaya (UM), in 2014–2017, and at the Department of Pharmacy Practice, Faculty of Pharmacy, Universiti Teknologi MARA (UiTM), Shah Alam, Malaysia, in 2017–2019. Dr. Hassan currently works as a senior lecturer at the Department of Pharmacy, Al-Rafidain University College, Baghdad, Iraq.",institutionString:"Al-Rafidain University College",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"1",institution:null},coeditorTwo:null,coeditorThree:null,coeditorFour:null,coeditorFive:null,topics:[{id:"1083",title:"Medical Oncology",slug:"medical-oncology"}],chapters:[{id:"76212",title:"Immune and Cell Cycle Checkpoint Inhibitors for Cancer Immunotherapy",doi:"10.5772/intechopen.96664",slug:"immune-and-cell-cycle-checkpoint-inhibitors-for-cancer-immunotherapy",totalDownloads:301,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The rational design of immunotherapeutic agents has advanced with a fundamental understanding that both innate and adaptive immunity play important roles in cancer surveillance and tumor destruction; given that oncogenesis occurs and cancer progresses through the growth of tumor cells with low immunogenicity in an increasingly immunosuppressive tumor microenvironment. Checkpoint inhibitors in the form of monoclonal antibodies that block cancer’s ability to deactivate and evade the immune system have been widely indicated for a variety of tumor types. Through targeting the biological mechanisms and pathways that cancer cells use to interact with and suppress the immune system, immunotherapeutic agents have achieved success in inhibiting tumor growth while eliciting lesser toxicities, compared to treatments with standard chemotherapy. Development of “precise” bio-active tumor-targeted gene vectors, biotechnologies, and reagents has also advanced. This chapter presents ongoing clinical research involving immune checkpoint inhibitors, while addressing the clinical potential for tumor-targeted gene blockade in combination with tumor-targeted cytokine delivery, in patients with advanced metastatic disease, providing strategic clinical approaches to precision cancer immunotherapy.",signatures:"Erlinda M. Gordon, Nicole L. Angel, Ted T. Kim, Don A. Brigham, Sant P. Chawla and Frederick L. Hall",downloadPdfUrl:"/chapter/pdf-download/76212",previewPdfUrl:"/chapter/pdf-preview/76212",authors:[{id:"333221",title:"Dr.",name:"Erlinda M.",surname:"Gordon",slug:"erlinda-m.-gordon",fullName:"Erlinda M. Gordon"},{id:"337003",title:"Dr.",name:"Sant",surname:"Chawla",slug:"sant-chawla",fullName:"Sant Chawla"},{id:"337004",title:"Dr.",name:"Frederick",surname:"Hall",slug:"frederick-hall",fullName:"Frederick Hall"},{id:"346195",title:"Ms.",name:"Nicole",surname:"Angel",slug:"nicole-angel",fullName:"Nicole Angel"},{id:"346196",title:"Mr.",name:"Ted",surname:"Kim",slug:"ted-kim",fullName:"Ted Kim"},{id:"346197",title:"Dr.",name:"Don",surname:"Brigham",slug:"don-brigham",fullName:"Don Brigham"}],corrections:null},{id:"75496",title:"Evolving Dynamic Biomarkers for Prediction of Immune Responses to Checkpoint Inhibitors in Cancer",doi:"10.5772/intechopen.96494",slug:"evolving-dynamic-biomarkers-for-prediction-of-immune-responses-to-checkpoint-inhibitors-in-cancer",totalDownloads:284,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Immune checkpoint inhibitors (ICIs) have been approved as first or second line therapy in a large group of cancers. However, the observation of potentially long-lasting responses was restricted to limited subset of patients. Efforts have been made to identify predictive factors of response to ICIs in order to select eligible patients and to avoid exposing non-responding patients to treatment side effects. Although several biomarkers have been identified, their predictive potential remains unsatisfactory. One promising emerging approach is to focus on dynamic biomarkers to directly characterize the response and, more importantly, to identify those patients presenting an immune response failure. Several studies have shown a strong correlation between specific circulating immune cell subsets and tumor immune infiltrates. Moreover, liquid biomarkers including soluble immune checkpoint molecules have potential in predicting the modulation of the immune response under immune checkpoint blockade. In this chapter, we will discuss current advances in the study of circulatory and intra-tumoral dynamic biomarkers as predictors of responses to ICIs therapy in cancer.",signatures:"Afsheen Raza, Maysaloun Merhi, Allan Relecom, Queenie Fernandes, Varghese Inchakalody, Abdul Rahman Zar Gul, Shahab Uddin, Mohammed Ussama Al Homsi and Said Dermime",downloadPdfUrl:"/chapter/pdf-download/75496",previewPdfUrl:"/chapter/pdf-preview/75496",authors:[{id:"336904",title:"Dr.",name:"Said",surname:"Dermime",slug:"said-dermime",fullName:"Said Dermime"},{id:"339275",title:"Dr.",name:"Maysaloun",surname:"Merhi",slug:"maysaloun-merhi",fullName:"Maysaloun Merhi"},{id:"339295",title:"MSc.",name:"Queenie",surname:"Fernandes",slug:"queenie-fernandes",fullName:"Queenie Fernandes"},{id:"339296",title:"Dr.",name:"Afsheen",surname:"Raza",slug:"afsheen-raza",fullName:"Afsheen Raza"},{id:"339297",title:"Dr.",name:"Varghese",surname:"Inchakalody",slug:"varghese-inchakalody",fullName:"Varghese Inchakalody"},{id:"339298",title:"Dr.",name:"Shahab",surname:"Uddin",slug:"shahab-uddin",fullName:"Shahab Uddin"},{id:"344921",title:"Dr.",name:"Allan",surname:"Relecom",slug:"allan-relecom",fullName:"Allan Relecom"},{id:"344923",title:"Dr.",name:"Abdul Rahman",surname:"Gul",slug:"abdul-rahman-gul",fullName:"Abdul Rahman Gul"},{id:"344924",title:"Dr.",name:"Mohammed",surname:"Al Homsi",slug:"mohammed-al-homsi",fullName:"Mohammed Al Homsi"}],corrections:null},{id:"75485",title:"The Endocrinological Side Effects of Immunotherapies",doi:"10.5772/intechopen.96491",slug:"the-endocrinological-side-effects-of-immunotherapies",totalDownloads:205,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"The use of immunotherapies is gaining importance in the treatment of advanced malignancies. There are many checkpoints in the immune system which prevents T-cells from attacking one’s own body cells. The cancer cells can camouflage from the T-cells and the immune system is unable to mount an effective anti-tumor response. The immunotherapies, mainly monoclonal antibodies anti-cytotoxic T-lymphocyte antigen 4 (CTLA-4), anti-programmed cell death protein-1 (PD-1) and anti-PD-1 ligand molecules (PD-L1 and L2) reactivate the immune system to act against cancerous cells but they can also cause T-cells to attack healthy cells causing various autoimmune diseases, which are known as immune related adverse events (irAEs). Current clinical data shows increased incidence of pituitary disorders with CTLA4 inhibitors and thyroid dysfunction in patients with PD-1/PD L-1 1 blockade. There have also been association of type 1 diabetes mellitus and primary adrenal insufficiency in patients with immune check point inhibitors. In this chapter we will discuss the incidence, characteristic findings, diagnosis and management of various endocrinological side effects due to targeted immunotherapies used in various malignancies.",signatures:"Anush Patel, Haisam Abid and Amrat Kumar",downloadPdfUrl:"/chapter/pdf-download/75485",previewPdfUrl:"/chapter/pdf-preview/75485",authors:[{id:"58496",title:"Dr.",name:"Anush",surname:"Patel",slug:"anush-patel",fullName:"Anush Patel"},{id:"336269",title:"Dr.",name:"Haisam",surname:"Abid",slug:"haisam-abid",fullName:"Haisam Abid"},{id:"336271",title:"Dr.",name:"Amrat",surname:"Kumar",slug:"amrat-kumar",fullName:"Amrat Kumar"}],corrections:null},{id:"75020",title:"Immunotherapy in Malignant Pleural Mesothelioma",doi:"10.5772/intechopen.95823",slug:"immunotherapy-in-malignant-pleural-mesothelioma",totalDownloads:285,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Malignant pleural mesothelioma (MPM) is an extremely aggressive plural malignancy mainly caused by asbestos exposure. Basic research about the immune suppressive tumor microenvironment in MPM has suggested that MPM might be a good candidate for immune therapy. Immunocheckpoint inhibitors have shown some promising results. A phase Ib trial with pembrolizumab, an antibody specific for the programmed cell death 1 protein (anti-PD-1), showed efficacy in patients with programmed death-ligand 1 (PD-L1)-positive MPM. Among 25 patients tested, 5 patients (20%) achieved a partial response. A Japanese group evaluated the efficacy and safety of nivolumab, an anti-PD-L1 antibody, for patients with advanced MPM in a phase II study. Ten (29%) patients showed an objective response. Based on those results, nivolumab was approved in Japan for unresectable recurrent MPM. A phase III randomized study was conducted to compare nivolumab plus ipilimumab to platinum doublet chemotherapy as a first-line therapy in unresectable MPM. The primary endpoint, overall survival (OS), was significantly improved in the nivolumab plus ipilimumab group. Cellular therapies and cancer vaccines are limited by many challenges; therefore, improvements to overcome these difficulties are urgently warranted. Further research is needed, including large-scale clinical trials, to clarify the utility and safety of immunotherapy in MPM.",signatures:"Asako Matsuda and Nobukazu Fujimoto",downloadPdfUrl:"/chapter/pdf-download/75020",previewPdfUrl:"/chapter/pdf-preview/75020",authors:[{id:"307730",title:"Dr.",name:"Nobukazu",surname:"Fujimoto",slug:"nobukazu-fujimoto",fullName:"Nobukazu Fujimoto"},{id:"337549",title:"Dr.",name:"Asako",surname:"Matsuda",slug:"asako-matsuda",fullName:"Asako Matsuda"}],corrections:null},{id:"75475",title:"Targeted Cancer Therapy Using Nanoparticles and Antibody Fragments",doi:"10.5772/intechopen.96550",slug:"targeted-cancer-therapy-using-nanoparticles-and-antibody-fragments",totalDownloads:372,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Cancer is caused by an uncontrolled cell division, forming a tumor capable of metastasis. Cancer is the second leading cause of death worldwide. Conventional treatments kill healthy cells, causing side effects. Recently, nanomaterials are explored due to properties such as as- nano-size, high loading, and ligands’ attachment for a selective delivery. Apart from normal body cells, cancer cells express many receptors in excess, which serve as ‘targets’ for attacking the cells. Various ligands like proteins, peptides, polysaccharides can be attached to nanoparticles to allow proper and specific reach to the tumor. Such nanoparticles go to their desired site and stick onto the receptors, taken inside the cells by various methods. Antibodies are natural proteins that bind to foreign substances and remove them. IgG being the most explored antibody, suffers from many disadvantages such as non-specificity for required antigen, limited binding sites, low tumor penetration. Hence many researchers experimented by removing and adjusting the binding sites, using only the binding sites, enhancing the valency of naturally available IgG. It gave many benefits such as enhanced penetration, reduced immunogenicity, better delivery of drugs with fewer side effects. Continuing advancements in the field of protein engineering will help scientists to come up with better solutions. The properties allow easy surface interaction and entry, achieve better biodistribution, and reduce the amount of drug required. Targeting is based on Paul Ehrlich’s ‘magic bullet, ‘where the therapeutic moiety has two parts-one to identify the target and the second to eliminate it. This concept is revised to incorporate a third component, a carrier. Many nanocarriers can be used to target cancer cells containing ligands to identify malignant cells. Approaches to targeting are passive, active and physical targeting. Many such nanoparticles are in clinical trials and can be a better solution to cancer therapy.",signatures:"Sankha Bhattacharya and Kapil Gore",downloadPdfUrl:"/chapter/pdf-download/75475",previewPdfUrl:"/chapter/pdf-preview/75475",authors:[{id:"250076",title:"Dr.",name:"Sankha",surname:"Bhattacharya",slug:"sankha-bhattacharya",fullName:"Sankha Bhattacharya"},{id:"344172",title:"Mr.",name:"Kapil",surname:"Gore",slug:"kapil-gore",fullName:"Kapil Gore"}],corrections:null},{id:"75838",title:"Antibody Therapy Targeting Cancer-Specific Cell Surface Antigen AGR2",doi:"10.5772/intechopen.96492",slug:"antibody-therapy-targeting-cancer-specific-cell-surface-antigen-agr2",totalDownloads:293,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"For anterior gradient 2 (AGR2), normal cells express the intracellular form iAGR2 localized to the endoplasmic reticulum while cancer cells express the extracellular form eAGR2 localized on the cell surface and secreted. Antibodies targeting eAGR2+ cancer cells for eradication will spare normal cells. Two AGR2 monoclonal antibodies, P1G4 and P3A5, were shown to recognize specifically eAGR2+ pancreatic tumors implanted in mice. In addition, P1G4 showed enhancement in drug inhibition of tumor growth. Human:mouse chimeric antibodies of IgG1, IgG2, IgG4 were generated for both antibodies. These human IgG were shown to lyse eAGR2+ prostate cancer cells in vitro with human serum. AGR2 has an important function in distal spread of cancer cells, and is highly expressed in prostate, pancreatic, bladder metastases. Therefore, immunotherapy based on AGR2 antibody-mediated ADCC and CDC is highly promising. Cancer specificity of eAGR2 predicts possibly minimal collateral damage to healthy tissues and organs. Moreover, AGR2 therapy, once fully developed and approved, can be used to treat other solid tumors since AGR2 is an adenocarcinoma antigen found in many common malignancies.",signatures:"Alvin Y. Liu, Tatjana Crnogorac-Jurcevic, James J. Lai and Hung-Ming Lam",downloadPdfUrl:"/chapter/pdf-download/75838",previewPdfUrl:"/chapter/pdf-preview/75838",authors:[{id:"337480",title:"Associate Prof.",name:"Alvin Y.",surname:"Liu",slug:"alvin-y.-liu",fullName:"Alvin Y. Liu"},{id:"345022",title:"Dr.",name:"Tatjana",surname:"Crnogorac-Jurcevic",slug:"tatjana-crnogorac-jurcevic",fullName:"Tatjana Crnogorac-Jurcevic"},{id:"345023",title:"Dr.",name:"James J.",surname:"Lai",slug:"james-j.-lai",fullName:"James J. Lai"},{id:"345024",title:"Dr.",name:"Hung-Ming",surname:"Lam",slug:"hung-ming-lam",fullName:"Hung-Ming Lam"}],corrections:null},{id:"74972",title:"Advances in Adoptive Cellular Therapy (ACT)",doi:"10.5772/intechopen.95854",slug:"advances-in-adoptive-cellular-therapy-act-",totalDownloads:207,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Adoptive T cell therapy (ACT) is getting acknowledged as the Advanced Therapy Medicinal Products (ATMPs) in many countries and it has evolved as one of the newest regimens to treat cancer. Developed gradually by the basic understanding of cells, involved in innate and adaptive immunity, ACT has emerged as one of the successful immunotherapies in recent times. It broadly includes various cell types such as stem cells, T cells, dendritic cells and Natural Killer cells. By the applications of genetic engineering and advanced cell culture techniques, these cells from patients’ blood, can be manipulated to train them for better efficacy against specific tumor cells. However, only some cells’ subsets have shown promising regression for certain cancer cells types. To understand the reason behind this, technical knowledge about the tumor antigens presentation, tumor microenvironment (TME), hosts’ immune responses and possible issues in the manufacturing of adoptive cellular material for infusion in patients are being explored further. This chapter brings together development of immune cells from basic research to clinical use, newer approaches which have been taken to address the resistance of ACT and future promises of this therapy.",signatures:"Rajesh Kumar Yadav, Bandana Kumari, Pritanjali Singh, Asgar Ali, Sadhana Sharma and Krishnan Hajela",downloadPdfUrl:"/chapter/pdf-download/74972",previewPdfUrl:"/chapter/pdf-preview/74972",authors:[{id:"335174",title:"Prof.",name:"Sadhana",surname:"Sharma",slug:"sadhana-sharma",fullName:"Sadhana Sharma"},{id:"335348",title:"Dr.",name:"Rajesh Kumar",surname:"Yadav",slug:"rajesh-kumar-yadav",fullName:"Rajesh Kumar Yadav"},{id:"344952",title:"Dr.",name:"Bandana",surname:"Kumari",slug:"bandana-kumari",fullName:"Bandana Kumari"},{id:"344953",title:"Dr.",name:"Asgar",surname:"Ali",slug:"asgar-ali",fullName:"Asgar Ali"},{id:"344954",title:"Dr.",name:"Pritanjali",surname:"Singh",slug:"pritanjali-singh",fullName:"Pritanjali Singh"},{id:"420204",title:"Dr.",name:"Krishnan",surname:"Hajela",slug:"krishnan-hajela",fullName:"Krishnan Hajela"}],corrections:null},{id:"76116",title:"Mathematical Modeling and Dynamics of Oncolytic Virotherapy",doi:"10.5772/intechopen.96963",slug:"mathematical-modeling-and-dynamics-of-oncolytic-virotherapy",totalDownloads:208,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Oncolytic virotherapy is a cancer treatment that uses competent replicating viruses to destroy cancer cells. This field progressed from earlier observations of accidental viral infections causing remission in many malignancies to virus drugs targeting and killing cancer cells. In this chapter, we study some basic models of the oncolytic virotherapy and their dynamics. We show how the dynamical system’s theory can capture the behavior of the solutions of those models and provide different approaches to studying the models. We study the thresholds that enable us to classify asymptotic dynamics of the solutions. Fractional-derivative approach tells us about the memory of the derivative and related solutions of the models. We also study the affect of introducing control parameters on the cost of the therapy.",signatures:"Abdullah Abu-Rqayiq",downloadPdfUrl:"/chapter/pdf-download/76116",previewPdfUrl:"/chapter/pdf-preview/76116",authors:[{id:"315106",title:"Dr.",name:"Abdullah",surname:"Abu-Rqayiq",slug:"abdullah-abu-rqayiq",fullName:"Abdullah Abu-Rqayiq"}],corrections:null},{id:"73668",title:"Molecular-Level Understanding of the Anticancer Action Mechanism of Anthracyclines",doi:"10.5772/intechopen.94180",slug:"molecular-level-understanding-of-the-anticancer-action-mechanism-of-anthracyclines",totalDownloads:551,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Anthracyclines drugs are used as a treatment regime to combat cancer owing to their great chemotherapeutic potential. They are characterized by the presence of a wide range of derivatives, the most famous are doxorubicin and daunorubicin. The proposed action mechanism of anthracyclines and their derivatives to exert cytotoxic effect involves the intercalation of the drug molecule into nucleic acid and inhibition of the activity of topoisomerases. These events consequences in halting DNA replication and transcription mechanisms of the cell. Understanding of the structural and conformational changes associated with nucleic acid after binding with drugs provides significant knowledge for the development of more effective drugs. A comprehensive elucidation of the molecular mechanism(s) of action of anthracyclines drugs plays a significant role in the rational drug designing to obtain an effective, selective, and safe anti-cancer drugs.",signatures:"Manish Shandilya, Shrutika Sharma, Prabhu Prasad Das and Sonika Charak",downloadPdfUrl:"/chapter/pdf-download/73668",previewPdfUrl:"/chapter/pdf-preview/73668",authors:[{id:"325803",title:"Dr.",name:"Sonika",surname:"Charak",slug:"sonika-charak",fullName:"Sonika Charak"},{id:"326284",title:"Dr.",name:"Manish",surname:"Shandilya",slug:"manish-shandilya",fullName:"Manish Shandilya"},{id:"326287",title:"Ms.",name:"Shrutika",surname:"Sharma",slug:"shrutika-sharma",fullName:"Shrutika Sharma"},{id:"330638",title:"Dr.",name:"Prabhu Prasad",surname:"Das",slug:"prabhu-prasad-das",fullName:"Prabhu Prasad Das"}],corrections:null},{id:"74276",title:"Overview on the Side Effects of Doxorubicin",doi:"10.5772/intechopen.94896",slug:"overview-on-the-side-effects-of-doxorubicin",totalDownloads:538,totalCrossrefCites:1,totalDimensionsCites:2,hasAltmetrics:0,abstract:"Doxorubicin is an anthracycline antibiotic extracted from the bacterium Streptomyces peucetius. Its cytotoxic effect produced by intercalating with DNA causing breakdown of DNA strand which causes cancer cell apoptosis. Despite being an effective anticancer agent it causes several crucial side effects like carditoxicity, neuropathy, hepatotoxicity, nephrotoxicity, alopecia, typhlitis, myelosuppression, neutropenia, anaemia, thrombocytopenia, nausea, and diarrhoea were caused mainly due to the inability to distinguish between cancer cells and normal cells. This chapter mainly focuses on doxorubicin’s side effects, current understanding of the molecular mechanisms, and management and preventive strategies of doxorubicin’s cardiotoxicity during the treatment of various type of cancer.",signatures:"Chittipolu Ajaykumar",downloadPdfUrl:"/chapter/pdf-download/74276",previewPdfUrl:"/chapter/pdf-preview/74276",authors:[{id:"327203",title:"Assistant Prof.",name:"Chittipolu",surname:"Ajaykumar",slug:"chittipolu-ajaykumar",fullName:"Chittipolu Ajaykumar"}],corrections:null},{id:"74811",title:"Overcoming P-Glycoprotein-Mediated Doxorubicin Resistance",doi:"10.5772/intechopen.95553",slug:"overcoming-p-glycoprotein-mediated-doxorubicin-resistance",totalDownloads:484,totalCrossrefCites:0,totalDimensionsCites:1,hasAltmetrics:0,abstract:"Intracellular concentration of doxorubicin in target cancer cells is a major determinant of therapeutic success of doxorubicin-based regimens. As known, doxorubicin is a substrate of P-glycoprotein (P-gp), the drug efflux transporter in the ABC superfamily. High expression level of P-gp in cancer cells can prevent intracellular accumulation of doxorubicin up to its effective level, leading to doxorubicin resistance and treatment failure. Moreover, these P-gp-overexpressed cells display multi-drug resistance (MDR) phenotype. Regarding this, application of P-gp modulators (suppressor of P-gp activity and expression) is likely to reverse MDR and restore cell sensitivity to doxorubicin treatment. In searching for potential chemo-sensitizer against resistant cancer, a number of phytochemicals or dietary compounds have been studied extensively for their P-gp modulating effects. Furthermore, combination between doxorubicin and P-gp modulators (e.g., plant-derived compounds, siRNA) given through specific target delivery platforms have been an effective strategic approach for MDR reversal and restore doxorubicin effectiveness for cancer treatment.",signatures:"Suree Jianmongkol",downloadPdfUrl:"/chapter/pdf-download/74811",previewPdfUrl:"/chapter/pdf-preview/74811",authors:[{id:"317928",title:"Associate Prof.",name:"Suree",surname:"Jianmongkol",slug:"suree-jianmongkol",fullName:"Suree Jianmongkol"}],corrections:null},{id:"76820",title:"Improving the Antitumor Effect of Doxorubicin in the Treatment of Eyeball and Orbital Tumors",doi:"10.5772/intechopen.95080",slug:"improving-the-antitumor-effect-of-doxorubicin-in-the-treatment-of-eyeball-and-orbital-tumors",totalDownloads:253,totalCrossrefCites:0,totalDimensionsCites:0,hasAltmetrics:0,abstract:"Malignant tumors of the orbit are the main cause for 41–45.9% of orbital tumor, and they will threaten both the organ of vision and the life of the patient. In our opinion, improving the effectiveness of treatment of malignant tumors can be implemented in the following areas: a) immobilization of doxorubicin in synthetic polymeric materials, which will fill the tissue structures that were resected and reduce the percentage of tumor recurrence. b) the use of nanomaterials for the delivery of doxorubicin to tumor cells. To develop a hydrogel implant and nanoparticles, to study the diffusion kinetics of doxorubicin in a hydrogel implant and the ability of nanoparticles to transport doxorubicin. The developed gels based on acrylic acid (AAc) were obtained by radical polymerization of an aqueous solution of monomers (AAc and N, N-methylenebisacrylamide (MBA)) at a temperature of 70°C. Matrices based on polyvinyl formal (PVF) were obtained by treatment of polyvinyl alcohol (PVA) with formaldehyde in the presence of a strong acid. Experimental studies were performed on rabbits of the Chinchilla breed, weighing 2–3 kg, aged 5–6 months, which during the study were in the same conditions. We implanted the hybrid gel in the scleral sac; orbital tissue and in the ear tissue of rabbits: Evaluation of the response of soft tissues and bone structures to implant materials was carried out on the basis of analysis of changes in clinical and pathomorphological parameters was performed after 10, 30 and 60 days. Diffusion of doxorubicin was examined by using UV spectroscopy [spectrophotometer-fluorimeter DS-11 FX + (DeNovix, USA)], analyzing samples at regular intervals during the day at a temperature of 25° C. The concentration of active substances was determined by the normalized peak absorption of doxorubicin at 480 nm. The release kinetics of the antitumor drug doxorubicin were investigated by using a UV spectrometer “Specord M 40” (maximum absorption 480 nm). The developed hydrogel implant has good biocompatibility and germination of surrounding tissues in the structure of the implant, as well as the formation of a massive fibrous capsule around it. An important advantage of the implant is also the lack of its tendency to resorption. Moreover, the results showed that the diffusion kinetics of doxorubicin from a liquid-crosslinked hydrogel reaches a minimum therapeutic level within a few minutes, while in the case of a tightly crosslinked - after a few hours. It was also found that the liquid-crosslinked hydrogel adsorbs twice as much as the cytostatic - doxorubicin. The analysis of the research results approved that the size of the nanoparticles is the main factor for improving drug delevary and penetration. Thus, nanoparticles with a diameter of less than 200 nm can penetrate into cells and are not removed from the circulatory system by macrophages, thereby prolonging their circulation in the body. About 10 nm. The developed hybrid hydrogel compositions have high mechanical strength, porosity, which provides 100% penetration of doxorubicin into experimental animal tissues. It was found that the kinetics of diffusion of drugs from liquid-crosslinked hydrogel reaches a minimum therapeutic level within a few minutes, whereas in the case of densely crosslinked hydrogel diffusion begins with a delay of several hours and the amount of drug released at equilibrium reaches much lower values (20–25%). The obtained preliminary experimental results allow us to conclude that our developed pathways for the delivery of drugs, in particular, doxorubicin to tumor cells will increase the effectiveness of antitumor therapy.",signatures:"Anatoliy Parfentievich Maletskyy, Yuriy Markovich Samchenko and Natalia Mikhailivna Bigun",downloadPdfUrl:"/chapter/pdf-download/76820",previewPdfUrl:"/chapter/pdf-preview/76820",authors:[{id:"325981",title:"Prof.",name:"Anatoliy Parfentievich",surname:"Maletskyy",slug:"anatoliy-parfentievich-maletskyy",fullName:"Anatoliy Parfentievich Maletskyy"},{id:"326712",title:"Dr.",name:"Yuriy Markovich",surname:"Samchenko",slug:"yuriy-markovich-samchenko",fullName:"Yuriy Markovich Samchenko"},{id:"333970",title:"Dr.",name:"Natalia Mikhailivna",surname:"Bigun",slug:"natalia-mikhailivna-bigun",fullName:"Natalia Mikhailivna Bigun"}],corrections:null},{id:"76515",title:"The Paradigm of Targeting an Oncogenic Tyrosine Kinase: Lesson from BCR-ABL",doi:"10.5772/intechopen.97528",slug:"the-paradigm-of-targeting-an-oncogenic-tyrosine-kinase-lesson-from-bcr-abl",totalDownloads:223,totalCrossrefCites:1,totalDimensionsCites:1,hasAltmetrics:0,abstract:"The aberrant tyrosine phosphorylation, either due to constitutive tyrosine kinases (TKs) or to inactivation of protein tyrosine phosphatases (PTPs), is a widespread feature of many cancerous cells. The BCR-ABL fusion protein, which arises from the Philadelphia chromosome, is a molecular distinct and peculiar trait of some kind of leukemia, namely Chronic Myeloid and Acute Lymphoblastic Leukemia, and displays constitutive tyrosine kinase activity. In the chapter, we will highlight the milestones that had led to the identification of the BCR-ABL fusion gene and its role as the only molecular pathogenic event sufficient to elicit and sustain chronic myeloid leukemia. We will also discuss the effort made to unveil the molecular mechanisms of action of the chimeric tyrosine kinase that eventually lead to aberrant cell proliferation and impaired cell-death. Furthermore, we will also review the lesson learned from the selective inhibition of BCR-ABL which currently represent a breakthrough in the treatment of several tumors characterized by defective tyrosine kinase activity.",signatures:"Enrico Bracco, M. Shahzad Ali, Stefano Magnati and Giuseppe Saglio",downloadPdfUrl:"/chapter/pdf-download/76515",previewPdfUrl:"/chapter/pdf-preview/76515",authors:[{id:"58476",title:"Prof.",name:"Giuseppe",surname:"Saglio",slug:"giuseppe-saglio",fullName:"Giuseppe Saglio"},{id:"343243",title:"Assistant Prof.",name:"Enrico",surname:"Bracco",slug:"enrico-bracco",fullName:"Enrico Bracco"},{id:"352739",title:"Dr.",name:"Muhammad S.",surname:"Ali",slug:"muhammad-s.-ali",fullName:"Muhammad S. Ali"},{id:"352740",title:"BSc.",name:"Stefano",surname:"Magnati",slug:"stefano-magnati",fullName:"Stefano Magnati"}],corrections:null}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"},subseries:null,tags:null},relatedBooks:[{type:"book",id:"8025",title:"Cancer Immunotherapy and Biological Cancer Treatments",subtitle:null,isOpenForSubmission:!1,hash:"e9953ff7bc3b22ae75810e286dd86b73",slug:"cancer-immunotherapy-and-biological-cancer-treatments",bookSignature:"Hilal Arnouk",coverURL:"https://cdn.intechopen.com/books/images_new/8025.jpg",editedByType:"Edited by",editors:[{id:"76431",title:"Dr.",name:"Hilal",surname:"Arnouk",slug:"hilal-arnouk",fullName:"Hilal Arnouk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"946",title:"Advancements in Tumor Immunotherapy and Cancer Vaccines",subtitle:null,isOpenForSubmission:!1,hash:"aa9eb0c98931a6c6e516ecf1962f99a4",slug:"advancements-in-tumor-immunotherapy-and-cancer-vaccines",bookSignature:"Hilal Arnouk",coverURL:"https://cdn.intechopen.com/books/images_new/946.jpg",editedByType:"Edited by",editors:[{id:"76431",title:"Dr.",name:"Hilal",surname:"Arnouk",slug:"hilal-arnouk",fullName:"Hilal Arnouk"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"374",title:"Current Cancer Treatment",subtitle:"Novel Beyond Conventional Approaches",isOpenForSubmission:!1,hash:"d752cf5b05d575243ec2c2144073f579",slug:"current-cancer-treatment-novel-beyond-conventional-approaches",bookSignature:"Öner Özdemir",coverURL:"https://cdn.intechopen.com/books/images_new/374.jpg",editedByType:"Edited by",editors:[{id:"52298",title:"Prof.",name:"Oner",surname:"Ozdemir",slug:"oner-ozdemir",fullName:"Oner Ozdemir"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3273",title:"Cancer Treatment",subtitle:"Conventional and Innovative Approaches",isOpenForSubmission:!1,hash:"cdd9872a05001212b3583bff95bae979",slug:"cancer-treatment-conventional-and-innovative-approaches",bookSignature:"Letícia Rangel",coverURL:"https://cdn.intechopen.com/books/images_new/3273.jpg",editedByType:"Edited by",editors:[{id:"60359",title:"Dr.",name:"Letícia",surname:"Rangel",slug:"leticia-rangel",fullName:"Letícia Rangel"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1311",title:"Advances in Cancer Therapy",subtitle:null,isOpenForSubmission:!1,hash:"24db071212f134f4a7dc3dc0cc786fec",slug:"advances-in-cancer-therapy",bookSignature:"Hala Gali-Muhtasib",coverURL:"https://cdn.intechopen.com/books/images_new/1311.jpg",editedByType:"Edited by",editors:[{id:"57145",title:"Prof.",name:"Hala",surname:"Gali-Muhtasib",slug:"hala-gali-muhtasib",fullName:"Hala Gali-Muhtasib"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"3002",title:"Oncogenomics and Cancer Proteomics",subtitle:"Novel Approaches in Biomarkers Discovery and Therapeutic Targets in Cancer",isOpenForSubmission:!1,hash:"bc8990331803d9e6084b367163dcf218",slug:"oncogenomics-and-cancer-proteomics-novel-approaches-in-biomarkers-discovery-and-therapeutic-targets-in-cancer",bookSignature:"César López-Camarillo and Elena Aréchaga-Ocampo",coverURL:"https://cdn.intechopen.com/books/images_new/3002.jpg",editedByType:"Edited by",editors:[{id:"40928",title:"Dr.",name:"Cesar",surname:"Lopez-Camarillo",slug:"cesar-lopez-camarillo",fullName:"Cesar Lopez-Camarillo"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1001",title:"Tumor Microenvironment and Myelomonocytic Cells",subtitle:null,isOpenForSubmission:!1,hash:"a2392066cd104cd48f3b296bf72b97a6",slug:"tumor-microenvironment-and-myelomonocytic-cells",bookSignature:"Subhra K. 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Rosen, Mandi D. Conway, Charles P. Ingram, Robin D. Ross and Leonardo G. Montilla",dateSubmitted:"November 6th 2018",dateReviewed:"December 12th 2018",datePrePublished:"February 5th 2019",datePublished:"September 4th 2019",book:{id:"8633",title:"Novel Diagnostic Methods in Ophthalmology",subtitle:null,fullTitle:"Novel Diagnostic Methods in Ophthalmology",slug:"novel-diagnostic-methods-in-ophthalmology",publishedDate:"September 4th 2019",bookSignature:"Anna Nowinska",coverURL:"https://cdn.intechopen.com/books/images_new/8633.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"261466",title:"Dr.",name:"Anna",middleName:"Karolina",surname:"Nowińska",slug:"anna-nowinska",fullName:"Anna Nowińska"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"274007",title:"Prof.",name:"Mandi D.",middleName:null,surname:"Conway",fullName:"Mandi D. Conway",slug:"mandi-d.-conway",email:"mconway1@yahoo.com",position:null,institution:null},{id:"283754",title:"Dr.",name:"Robin",middleName:"Demi",surname:"Ross",fullName:"Robin Ross",slug:"robin-ross",email:"robindross@email.arizona.edu",position:null,institution:null},{id:"284051",title:"BSc.",name:"David",middleName:null,surname:"Rosen",fullName:"David Rosen",slug:"david-rosen",email:"davidrosen@email.arizona.edu",position:null,institution:null},{id:"284377",title:"BSc.",name:"Leonardo",middleName:null,surname:"Montilla",fullName:"Leonardo Montilla",slug:"leonardo-montilla",email:"funrunner13@gmail.com",position:null,institution:null},{id:"284378",title:"MSc.",name:"Charles",middleName:null,surname:"Ingram",fullName:"Charles Ingram",slug:"charles-ingram",email:"cingram@optics.arizona.edu",position:null,institution:null}]}},chapter:{id:"65491",slug:"a-brief-overview-of-ophthalmic-ultrasound-imaging",signatures:"David B. Rosen, Mandi D. Conway, Charles P. Ingram, Robin D. Ross and Leonardo G. Montilla",dateSubmitted:"November 6th 2018",dateReviewed:"December 12th 2018",datePrePublished:"February 5th 2019",datePublished:"September 4th 2019",book:{id:"8633",title:"Novel Diagnostic Methods in Ophthalmology",subtitle:null,fullTitle:"Novel Diagnostic Methods in Ophthalmology",slug:"novel-diagnostic-methods-in-ophthalmology",publishedDate:"September 4th 2019",bookSignature:"Anna Nowinska",coverURL:"https://cdn.intechopen.com/books/images_new/8633.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",editors:[{id:"261466",title:"Dr.",name:"Anna",middleName:"Karolina",surname:"Nowińska",slug:"anna-nowinska",fullName:"Anna Nowińska"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"274007",title:"Prof.",name:"Mandi D.",middleName:null,surname:"Conway",fullName:"Mandi D. 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\r\n\tIn the last two decades, an impeccable advancement in nanotechnology encouraged global scientific intellect for constant contemplation of its ramifications in biomedical applications. Nanomedicine, a medical specialty that uses the advances in nanotechnology, is mostly explored to prevent, detect and treat many diseases, cancer is the most pernicious among them. A wide range of engineered nanomaterials is used for a wide variety of biomedical applications, especially disease diagnostic, drug delivery, physiological state sensing or alteration of actuation functions in a living body, etc. Organic and inorganic nanomaterials are emerging as promising cancer therapeutic and diagnostic techniques. To target specific tumor tissues, polymeric micelles, liposomes, dendrimers, and other nanoparticles have been explored for their potential to assemble in leaky tumor circulatory networks. Further, targeting cancer at the cellular and molecular level has also been achieved by various surface-modified nanomaterials carrying specific cargo. Moreover, image and diagnostic-based nanometric multimodal therapeutic modalities will be explored as flexible theranostics having a dual potential to treat and diagnose cancer. Biogenic nanomaterials for cancer therapy and imaging will also be explored in this book. This book will concentrate on the use of nanotechnology in biomedical diagnostics, treatments, drug delivery systems, and other possible clinical applications.
",isbn:"978-1-83768-349-9",printIsbn:"978-1-83768-348-2",pdfIsbn:"978-1-83768-350-5",doi:null,price:0,priceEur:0,priceUsd:0,slug:null,numberOfPages:0,isOpenForSubmission:!0,isSalesforceBook:!1,isNomenclature:!1,hash:"3d98881cc9e323438670710d3aaaf71d",bookSignature:"Assistant Prof. Manash K. Paul, Dr. Jyotirmoi Aich, Prof. Soumya Basu and Dr. Anubhab Mukherjee",publishedDate:null,coverURL:"https://cdn.intechopen.com/books/images_new/11984.jpg",keywords:"Polymeric Nanoparticles, Lipoidal Nanoparticles, Therapy, Carbon Nanotube, Bioavailability, Theranostics, Nanobiotechnology, Nanoelectronics, Tumour Imaging, Novel Biomaterials, Regenerative Medicine, Stem Cell Therapy",numberOfDownloads:null,numberOfWosCitations:0,numberOfCrossrefCitations:null,numberOfDimensionsCitations:null,numberOfTotalCitations:null,isAvailableForWebshopOrdering:!0,dateEndFirstStepPublish:"June 8th 2022",dateEndSecondStepPublish:"July 6th 2022",dateEndThirdStepPublish:"September 4th 2022",dateEndFourthStepPublish:"November 23rd 2022",dateEndFifthStepPublish:"January 22nd 2023",dateConfirmationOfParticipation:null,remainingDaysToSecondStep:"2 days",secondStepPassed:!1,areRegistrationsClosed:!1,currentStepOfPublishingProcess:2,editedByType:null,kuFlag:!1,biosketch:"Dr. Paul is the recipient of many awards, including the prestigious UCLA Vice Chancellor’s Award, and was nominated for Paul Boyer’s award. He is a member of multiple editorial boards and has one registered patent. Dr. Paul is a senior member of the Institute of Electrical and Electronics Engineers (IEEE) and also a member of many esteemed societies, including the Royal Society of Biology (MRCB), the American Association for Cancer Research (AACR), and the International Society of Biotechnology (ISBT).",coeditorOneBiosketch:null,coeditorTwoBiosketch:null,coeditorThreeBiosketch:null,coeditorFourBiosketch:null,coeditorFiveBiosketch:null,editors:[{id:"319365",title:"Assistant Prof.",name:"Manash K.",middleName:null,surname:"Paul",slug:"manash-k.-paul",fullName:"Manash K. Paul",profilePictureURL:"https://mts.intechopen.com/storage/users/319365/images/system/319365.png",biography:"Manash K. Paul is a Principal Investigator and Scientist at the University of California Los Angeles. He has contributed significantly to the fields of stem cell biology, regenerative medicine, and lung cancer. His research focuses on various signaling processes involved in maintaining stem cell homeostasis during the injury-repair process, deciphering lung stem cell niche, pulmonary disease modeling, immuno-oncology, and drug discovery. He is currently investigating the role of extracellular vesicles in premalignant lung cell migration and detecting the metastatic phenotype of lung cancer via machine-learning-based analyses of exosomal signatures. Dr. Paul has published in more than fifty peer-reviewed international journals and is highly cited. He is the recipient of many awards, including the UCLA Vice Chancellor’s award, a senior member of the Institute of Electrical and Electronics Engineers (IEEE), and an editorial board member for several international journals.",institutionString:"University of California Los Angeles",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"3",totalChapterViews:"0",totalEditedBooks:"0",institution:{name:"University of California Los Angeles",institutionURL:null,country:{name:"United States of America"}}}],coeditorOne:{id:"418340",title:"Dr.",name:"Jyotirmoi",middleName:null,surname:"Aich",slug:"jyotirmoi-aich",fullName:"Jyotirmoi Aich",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000038Ugi5QAC/Profile_Picture_2022-04-15T07:48:28.png",biography:"Biotechnologist with 15 years of research including 6 years of teaching experience. Demonstrated record of scientific achievements through consistent publication record (H index = 13, with 874 citations) in high impact journals such as Nature Communications, Oncotarget, Annals of Oncology, PNAS, and AJRCCM, etc. Strong research professional with a post-doctorate from ACTREC where I gained experimental oncology experience in clinical settings and a doctorate from IGIB where I gained expertise in asthma pathophysiology. A well-trained biotechnologist with diverse experience on the bench across different research themes ranging from asthma to cancer and other infectious diseases. An individual with a strong commitment and innovative mindset. Have the ability to work on diverse projects such as regenerative and molecular medicine with an overall mindset of improving healthcare.",institutionString:"DY Patil Deemed to Be University",position:null,outsideEditionCount:0,totalCites:0,totalAuthoredChapters:"1",totalChapterViews:"0",totalEditedBooks:"0",institution:null},coeditorTwo:{id:"349288",title:"Prof.",name:"Soumya",middleName:null,surname:"Basu",slug:"soumya-basu",fullName:"Soumya Basu",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0033Y000035QxIDQA0/Profile_Picture_2022-04-15T07:47:01.jpg",biography:"Soumya Basu, Ph.D., is currently working as an Associate Professor at Dr. D. Y. Patil Biotechnology and Bioinformatics Institute, Dr. D. Y. Patil Vidyapeeth, Pune, Maharashtra, India. 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Teng",authors:[{id:"39810",title:"Dr.",name:"Christina",middleName:"T",surname:"Teng",fullName:"Christina Teng",slug:"christina-teng"},{id:"139251",title:"Dr.",name:"Peggy",middleName:null,surname:"Teng",fullName:"Peggy Teng",slug:"peggy-teng"}]},{id:"23380",title:"The Role of MicroRNAs in Estrogen Receptor α-Positive Human Breast Cancer",slug:"the-role-of-micrornas-in-estrogen-receptor-positive-human-breast-cancer",signatures:"Hiroko Yamashita, Tatsuya Toyama, Nobuyasu Yoshimoto, Yumi Endo, Mai Iwasa and Yoshitaka Fujii",authors:[{id:"53692",title:"Dr.",name:"Hiroko",middleName:null,surname:"Yamashita",fullName:"Hiroko Yamashita",slug:"hiroko-yamashita"},{id:"55776",title:"Dr.",name:"Tatsuya",middleName:null,surname:"Toyama",fullName:"Tatsuya Toyama",slug:"tatsuya-toyama"},{id:"55778",title:"Dr.",name:"Nobuyasu",middleName:null,surname:"Yoshimoto",fullName:"Nobuyasu Yoshimoto",slug:"nobuyasu-yoshimoto"},{id:"55779",title:"Dr.",name:"Yumi",middleName:null,surname:"Endo",fullName:"Yumi Endo",slug:"yumi-endo"},{id:"55780",title:"Dr.",name:"Mai",middleName:null,surname:"Iwasa",fullName:"Mai Iwasa",slug:"mai-iwasa"},{id:"55781",title:"Prof.",name:"Yoshitaka",middleName:null,surname:"Fujii",fullName:"Yoshitaka Fujii",slug:"yoshitaka-fujii"}]},{id:"23381",title:"Roles of SWI/SNF Complex Genes in Breast Cancer",slug:"roles-of-swi-snf-complex-genes-in-breast-cancer",signatures:"Esra Gunduz, Mehmet Gunduz, Bunyamin Isik and Omer Faruk Hatipoglu",authors:[{id:"38384",title:"Prof.",name:"Mehmet",middleName:null,surname:"Gunduz",fullName:"Mehmet Gunduz",slug:"mehmet-gunduz"},{id:"61074",title:"Dr.",name:"Esra",middleName:null,surname:"Gunduz",fullName:"Esra Gunduz",slug:"esra-gunduz"},{id:"61084",title:"Dr.",name:"Omer Faruk",middleName:null,surname:"Hatipoglu",fullName:"Omer Faruk Hatipoglu",slug:"omer-faruk-hatipoglu"}]},{id:"23382",title:"p53, p63 and p73 Network in Breast Cancers",slug:"p53-p63-and-p73-network-in-breast-cancers",signatures:"Chee-Onn Leong",authors:[{id:"38496",title:"Dr.",name:"Chee-Onn",middleName:null,surname:"Leong",fullName:"Chee-Onn Leong",slug:"chee-onn-leong"}]},{id:"23383",title:"Role of ING Family Tumor Suppressors in Breast Cancer",slug:"role-of-ing-family-tumor-suppressors-in-breast-cancer",signatures:"Mehmet Gunduz, Esra Gunduz, Mikdat Bozer and Ramazan Yigitoglu",authors:[{id:"46056",title:"Prof.",name:"Mehmet",middleName:null,surname:"Gunduz",fullName:"Mehmet Gunduz",slug:"mehmet-gunduz"},{id:"61074",title:"Dr.",name:"Esra",middleName:null,surname:"Gunduz",fullName:"Esra Gunduz",slug:"esra-gunduz"},{id:"61075",title:"Prof.",name:"Ramazan",middleName:null,surname:"Yigitoglu",fullName:"Ramazan Yigitoglu",slug:"ramazan-yigitoglu"}]},{id:"23384",title:"Lipid Rafts as Master Regulators of Breast Cancer Cell Function",slug:"lipid-rafts-as-master-regulators-of-breast-cancer-cell-function",signatures:"Irina S. Babina, Simona Donatello, Ivan R. Nabi and Ann M. Hopkins",authors:[{id:"42686",title:"Dr.",name:"Ann",middleName:"M",surname:"Hopkins",fullName:"Ann Hopkins",slug:"ann-hopkins"},{id:"46276",title:"Ms.",name:"Irina",middleName:null,surname:"Babina",fullName:"Irina Babina",slug:"irina-babina"},{id:"46297",title:"Dr.",name:"Simona",middleName:null,surname:"Donatello",fullName:"Simona Donatello",slug:"simona-donatello"},{id:"57199",title:"Prof.",name:"I. Robert",middleName:null,surname:"Nabi",fullName:"I. Robert Nabi",slug:"i.-robert-nabi"}]},{id:"23385",title:"Differences in Membrane Composition and Organization of Crucial Molecules Define the Invasive Properties of MCF-7 Breast Cancer Cells",slug:"differences-in-membrane-composition-and-organization-of-crucial-molecules-define-the-invasive-proper",signatures:"Van slambrouck Séverine and Steelant Wim",authors:[{id:"57528",title:"Prof.",name:"Wim",middleName:null,surname:"Steelant",fullName:"Wim Steelant",slug:"wim-steelant"},{id:"57529",title:"Prof.",name:"Severine",middleName:null,surname:"Van Slambrouck",fullName:"Severine Van Slambrouck",slug:"severine-van-slambrouck"}]},{id:"23386",title:"Adipose Tissue and Desmoplastic Response in Breast Cancer",slug:"adipose-tissue-and-desmoplastic-response-in-breast-cancer",signatures:"Jorge Martinez and Mariana Cifuentes",authors:[{id:"50978",title:"Prof.",name:"Jorge",middleName:null,surname:"Martinez",fullName:"Jorge Martinez",slug:"jorge-martinez"},{id:"91867",title:"Dr.",name:"Mariana",middleName:null,surname:"Cifuentes",fullName:"Mariana Cifuentes",slug:"mariana-cifuentes"}]},{id:"23387",title:"Cross-Talk of Breast Cancer Cells with the Immune System",slug:"cross-talk-of-breast-cancer-cells-with-the-immune-system",signatures:"Sandra Demaria, Karsten A. Pilones and Sylvia Adams",authors:[{id:"48139",title:"Prof.",name:"Sandra",middleName:null,surname:"Demaria",fullName:"Sandra Demaria",slug:"sandra-demaria"},{id:"57383",title:"Dr.",name:"Karsten",middleName:null,surname:"Pilones",fullName:"Karsten Pilones",slug:"karsten-pilones"},{id:"57384",title:"Prof.",name:"Sylvia",middleName:null,surname:"Adams",fullName:"Sylvia Adams",slug:"sylvia-adams"}]},{id:"23388",title:"Engineering Transcription Factors in Breast Cancer Stem Cells",slug:"engineering-transcription-factors-in-breast-cancer-stem-cells",signatures:"Pilar Blancafort, Karla Oyuky Juarez, Sabine Stolzenburg and Adriana S. Beltran",authors:[{id:"53757",title:"Dr.",name:"Pilar",middleName:null,surname:"Blancafort",fullName:"Pilar Blancafort",slug:"pilar-blancafort"},{id:"139263",title:"Dr.",name:"Karla Oyuky",middleName:null,surname:"Juarez",fullName:"Karla Oyuky Juarez",slug:"karla-oyuky-juarez"},{id:"139264",title:"Dr.",name:"Sabine",middleName:null,surname:"Stolzenburg",fullName:"Sabine Stolzenburg",slug:"sabine-stolzenburg"},{id:"139265",title:"Dr.",name:"Adriana",middleName:null,surname:"Beltran",fullName:"Adriana Beltran",slug:"adriana-beltran"}]},{id:"23389",title:"Breast Cancer Stem Cells – A Review",slug:"breast-cancer-stem-cells-a-review",signatures:"Julia S. Samaddar and Edmond Ritter",authors:[{id:"62458",title:"Dr.",name:"Edmond",middleName:null,surname:"Ritter",fullName:"Edmond Ritter",slug:"edmond-ritter"},{id:"72228",title:"Ms",name:"Julia",middleName:null,surname:"Samaddar",fullName:"Julia Samaddar",slug:"julia-samaddar"}]},{id:"23390",title:"Potential Roles of miR-106a in Breast Cancer",slug:"potential-roles-of-mir-106a-in-breast-cancer",signatures:"KuanHui E. Chen and Ameae M. Walker",authors:[{id:"55411",title:"Prof.",name:"Ameae M.",middleName:null,surname:"Walker",fullName:"Ameae M. Walker",slug:"ameae-m.-walker"},{id:"55416",title:"MSc.",name:"KuanHui",middleName:null,surname:"Chen",fullName:"KuanHui Chen",slug:"kuanhui-chen"}]},{id:"23391",title:"Scleroderma and Breast Cancer",slug:"scleroderma-and-breast-cancer",signatures:"Adamantios Michalinos, Michalis Kontos and Ian S. Fentiman",authors:[{id:"119147",title:"Prof.",name:"Ian",middleName:null,surname:"Fentiman",fullName:"Ian Fentiman",slug:"ian-fentiman"}]},{id:"23392",title:"FZD7 in Triple Negative Breast Cancer Cells",slug:"fzd7-in-triple-negative-breast-cancer-cells",signatures:"Lixin Yang, Charles C.H. Kim and Yun Yen",authors:[{id:"38846",title:"Dr.",name:"Yun",middleName:null,surname:"Yen",fullName:"Yun Yen",slug:"yun-yen"}]},{id:"23393",title:"Dysregulation of Wnt Signaling in Breast Cancer",slug:"dysregulation-of-wnt-signaling-in-breast-cancer",signatures:"Taj D. King and Yonghe Li",authors:[{id:"44336",title:"Dr.",name:"Yonghe",middleName:null,surname:"Li",fullName:"Yonghe Li",slug:"yonghe-li"},{id:"107876",title:"Dr.",name:"Taj D.",middleName:null,surname:"King",fullName:"Taj D. King",slug:"taj-d.-king"}]},{id:"23394",title:"Interactions of STAP-2 with BRK and STAT3/5 in Breast Cancer Cells",slug:"interactions-of-stap-2-with-brk-and-stat3-5-in-breast-cancer-cells",signatures:"Osamu Ikeda, Yuichi Sekine and Tadashi Matsuda",authors:[{id:"52037",title:"Prof.",name:"Tadashi",middleName:null,surname:"Matsuda",fullName:"Tadashi Matsuda",slug:"tadashi-matsuda"},{id:"54431",title:"PhD.",name:"Osamu",middleName:null,surname:"Ikeda",fullName:"Osamu Ikeda",slug:"osamu-ikeda"},{id:"54432",title:"Dr.",name:"Yuichi",middleName:null,surname:"Sekine",fullName:"Yuichi Sekine",slug:"yuichi-sekine"}]},{id:"23395",title:"Histamine and Breast Cancer: A New Role for a Well Known Amine",slug:"histamine-and-breast-cancer-a-new-role-for-a-well-known-amine",signatures:"Graciela Cricco, Nora Mohamad, María Soledad Sáez, Eduardo Valli, Elena Rivera and Gabriela Martín",authors:[{id:"39853",title:"Dr.",name:"Gabriela",middleName:"A",surname:"Martin",fullName:"Gabriela Martin",slug:"gabriela-martin"},{id:"56303",title:"Dr.",name:"Graciela",middleName:"Patricia",surname:"Cricco",fullName:"Graciela Cricco",slug:"graciela-cricco"},{id:"56309",title:"Prof.",name:"Elena",middleName:null,surname:"Rivera",fullName:"Elena Rivera",slug:"elena-rivera"},{id:"56335",title:"MSc",name:"Maria Soledad",middleName:null,surname:"Saez",fullName:"Maria Soledad Saez",slug:"maria-soledad-saez"},{id:"56338",title:"MSc",name:"Eduardo",middleName:null,surname:"Valli",fullName:"Eduardo Valli",slug:"eduardo-valli"},{id:"56346",title:"Mrs",name:"Nora",middleName:null,surname:"Mohamad",fullName:"Nora Mohamad",slug:"nora-mohamad"}]},{id:"23396",title:"1,25(OH)2D3 and Cyclooxygenase-2: Possible Targets for Breast Cancer?",slug:"1-25-oh-2d3-and-cyclooxygenase-2-possible-targets-for-breast-cancer-",signatures:"M. Thill, S. Becker, D. Fischer, K. Diedrich, D. Salehin and M. Friedrich",authors:[{id:"45024",title:"Dr.",name:"Michael",middleName:null,surname:"Friedrich",fullName:"Michael Friedrich",slug:"michael-friedrich"}]},{id:"23397",title:"Calcium, Ca2+-Sensing Receptor and Breast Cancer",slug:"calcium-ca2-sensing-receptor-and-breast-cancer",signatures:"Chunfa Huang and R. Tyler Miller",authors:[{id:"44401",title:"Dr.",name:"Chunfa",middleName:null,surname:"Huang",fullName:"Chunfa Huang",slug:"chunfa-huang"},{id:"53288",title:"Dr.",name:"Richard",middleName:null,surname:"Miller",fullName:"Richard Miller",slug:"richard-miller"}]},{id:"23398",title:"Signal Transduction Pathways Mediated by Unsaturated Free Fatty Acids in Breast Cancer Cells",slug:"signal-transduction-pathways-mediated-by-unsaturated-free-fatty-acids-in-breast-cancer-cells",signatures:"Eduardo Perez Salazar, Luis Castro-Sanchez and Pedro Cortes-Reynosa",authors:[{id:"38838",title:"Dr.",name:"Eduardo",middleName:null,surname:"Perez Salazar",fullName:"Eduardo Perez Salazar",slug:"eduardo-perez-salazar"},{id:"115028",title:"Dr.",name:"Luis",middleName:null,surname:"Castro-Sanchez",fullName:"Luis Castro-Sanchez",slug:"luis-castro-sanchez"}]},{id:"23399",title:"Adrenoceptors and Breast Cancer: Review Article",slug:"adrenoceptors-and-breast-cancer-review-article",signatures:"Roisman Reuth, Alex Beny, Reznick Abraham Zeev, Klemm Ofer, Raphaeli Guy and Roisman Isaac",authors:[{id:"100139",title:"Dr.",name:"Isaac",middleName:null,surname:"Roisman",fullName:"Isaac Roisman",slug:"isaac-roisman"}]},{id:"23400",title:"Steroid Receptor Coactivators and Their Expression, Regulation and Functional Role in Endocrine Responsive and Resistant Breast Cancer",slug:"steroid-receptor-coactivators-and-their-expression-regulation-and-functional-role-in-endocrine-respo",signatures:"Line L. Haugan Moi, Marianne Hauglid Flågeng, Ingvild S. Fenne, Jennifer Gjerde, Ernst A. Lien and Gunnar Mellgren",authors:[{id:"46714",title:"Prof.",name:"Gunnar",middleName:null,surname:"Mellgren",fullName:"Gunnar Mellgren",slug:"gunnar-mellgren"},{id:"57258",title:"Mrs.",name:"Line",middleName:null,surname:"Haugan Moi",fullName:"Line Haugan Moi",slug:"line-haugan-moi"},{id:"57259",title:"Mrs.",name:"Marianne Hauglid",middleName:null,surname:"Flĺgeng",fullName:"Marianne Hauglid Flĺgeng",slug:"marianne-hauglid-flgeng"},{id:"57260",title:"Dr.",name:"Ingvild Sveinsgjerd",middleName:null,surname:"Fenne",fullName:"Ingvild Sveinsgjerd Fenne",slug:"ingvild-sveinsgjerd-fenne"},{id:"57261",title:"Mrs.",name:"Jennifer",middleName:null,surname:"Gjerde",fullName:"Jennifer Gjerde",slug:"jennifer-gjerde"},{id:"57262",title:"Prof.",name:"Ernst A.",middleName:null,surname:"Lien",fullName:"Ernst A. Lien",slug:"ernst-a.-lien"}]}]}],publishedBooks:[{type:"book",id:"329",title:"Breast Cancer",subtitle:"Carcinogenesis, Cell Growth and Signalling Pathways",isOpenForSubmission:!1,hash:"ebf7902b7672e9142e56de2289bcaa5a",slug:"breast-cancer-carcinogenesis-cell-growth-and-signalling-pathways",bookSignature:"Mehmet Gunduz and Esra Gunduz",coverURL:"https://cdn.intechopen.com/books/images_new/329.jpg",editedByType:"Edited by",editors:[{id:"46056",title:"Prof.",name:"Mehmet",surname:"Gunduz",slug:"mehmet-gunduz",fullName:"Mehmet Gunduz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1276",title:"Targeting New Pathways and Cell Death in Breast Cancer",subtitle:null,isOpenForSubmission:!1,hash:"e1541edf35e439e637938657d6ac482b",slug:"targeting-new-pathways-and-cell-death-in-breast-cancer",bookSignature:"Rebecca L. Aft",coverURL:"https://cdn.intechopen.com/books/images_new/1276.jpg",editedByType:"Edited by",editors:[{id:"45492",title:"Dr.",name:"Rebecca",surname:"Aft",slug:"rebecca-aft",fullName:"Rebecca Aft"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1277",title:"Breast Cancer",subtitle:"Current and Alternative Therapeutic Modalities",isOpenForSubmission:!1,hash:"9c0bc3b171254b2a3f7d52bee5c559aa",slug:"breast-cancer-current-and-alternative-therapeutic-modalities",bookSignature:"Esra Gunduz and Mehmet Gunduz",coverURL:"https://cdn.intechopen.com/books/images_new/1277.jpg",editedByType:"Edited by",editors:[{id:"61074",title:"Dr.",name:"Esra",surname:"Gunduz",slug:"esra-gunduz",fullName:"Esra Gunduz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1278",title:"Breast Cancer",subtitle:"Focusing Tumor Microenvironment, Stem cells and Metastasis",isOpenForSubmission:!1,hash:"bd2df7c338f309db645c7c183571f6a8",slug:"breast-cancer-focusing-tumor-microenvironment-stem-cells-and-metastasis",bookSignature:"Mehmet Gunduz and Esra Gunduz",coverURL:"https://cdn.intechopen.com/books/images_new/1278.jpg",editedByType:"Edited by",editors:[{id:"46056",title:"Prof.",name:"Mehmet",surname:"Gunduz",slug:"mehmet-gunduz",fullName:"Mehmet Gunduz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}},{type:"book",id:"1279",title:"Breast Cancer",subtitle:"Recent Advances in Biology, Imaging and Therapeutics",isOpenForSubmission:!1,hash:"eb213b69670bbf5c4c6ab643bb13c4d4",slug:"breast-cancer-recent-advances-in-biology-imaging-and-therapeutics",bookSignature:"Susan J. Done",coverURL:"https://cdn.intechopen.com/books/images_new/1279.jpg",editedByType:"Edited by",editors:[{id:"51859",title:"Dr.",name:"Susan",surname:"Done",slug:"susan-done",fullName:"Susan Done"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}],publishedBooksByAuthor:[{type:"book",id:"1278",title:"Breast Cancer",subtitle:"Focusing Tumor Microenvironment, Stem cells and Metastasis",isOpenForSubmission:!1,hash:"bd2df7c338f309db645c7c183571f6a8",slug:"breast-cancer-focusing-tumor-microenvironment-stem-cells-and-metastasis",bookSignature:"Mehmet Gunduz and Esra Gunduz",coverURL:"https://cdn.intechopen.com/books/images_new/1278.jpg",editedByType:"Edited by",editors:[{id:"46056",title:"Prof.",name:"Mehmet",surname:"Gunduz",slug:"mehmet-gunduz",fullName:"Mehmet Gunduz"}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null,productType:{id:"1",chapterContentType:"chapter",authoredCaption:"Edited by"}}]},onlineFirst:{chapter:{type:"chapter",id:"82383",title:"The Role of Immune Checkpoints in Cancer Progression",doi:"10.5772/intechopen.105628",slug:"the-role-of-immune-checkpoints-in-cancer-progression",body:'Cancer or tumor cells express neoantigens that the immune system can identify from healthy neighboring cells due to genetic mutations. These changes typically result in a tumor-reactive T cell response, most notably CD8+ T cells. However, this mechanism is frequently ineffective at eradicating cancer cells [1]. One cause for this failure is the suppression of invading T cells by a wide range of immunosuppressive mechanisms found in the tumor microenvironment (TME), such as regulatory T cells (Tregs) or immunosuppressive cytokines [2, 3].
Furthermore, binding of the T cell receptor (TCR) to the antigenic peptide bound to the major histocompatibility complex (MHC) of the antigen-presenting cell (APC) is not adequate to yield an immune response, particularly to eradicate cancer cells. Thus, the additional stimulatory co-signal produced by co-receptors is required. These co-receptors play an essential role in modulating T cell responsiveness and balancing co-stimulatory and inhibitory (i.e., immune checkpoint) signals [4]. Extended TCR signals generated from T cells exposure to their cognate antigen result in enhanced and persistent expression of inhibitory co-receptors like cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4), programmed death protein 1 (PD-1), or many other immune checkpoints. At this moment, T cells enter a state of dysfunction or exhaustion, allowing cancer cells to grow unchecked [5, 6]. Therefore, blockage to these immune checkpoints can reinvigorate the anti-tumor function of immune cells. This chapter aimed to elaborate on the involvement of immune checkpoints in cancer development. It includes the explanation of the normal trafficking and inhibitory signaling of each checkpoint, followed by discussions about how immune checkpoint contributes to cancer growth.
Immune checkpoints serve as the immune system’s gatekeepers and are required for sustaining self-tolerance, thus protecting the host from tissue damage. These immunological checkpoint molecules have modulated T cell responses to self-proteins, persistent infections, and tumor antigens. A few of them, including but are not limited to PD-1, CTLA-4, Lymphocyte activation gene 3 (LAG3; or known as cluster of differentiation 223 [CD223]), T cell immunoglobulin and mucin-domain containing-3 (TIM-3), T cell immunoreceptor with immunoglobulin and ITIM—immunoreceptor tyrosine-based inhibitory motif—domain (TIGIT), and B and T lymphocyte attenuator (BTLA; or known as CD272), have been discovered and investigated as targets in cancer immunotherapy. In general, immune checkpoints are membrane proteins expressed in the endoplasmic reticulum (ER) and subsequently transported to the cell surface to perform their inhibitory roles, which requires the protein sorting system to transport them sequentially through the Golgi apparatus secretory vesicles. Glycosylation acts as quality control during surface delivery, ensuring that only mature and functional immunological checkpoints reach the cell surface. Immune checkpoints are internalized and recycled when they reach the cell surface, providing a quick regulatory pathway to control their surface levels. Immune checkpoints can be ubiquitinated and sorted to the proteasome or lysosome for destruction, another critical method for controlling protein levels. The surface level of immunological checkpoints is determined by several biological mechanisms, which affect cell signaling [7]. This section elaborates on the normal regulations and signaling of each immune checkpoints molecules before discussing its involvement in cancer development.
PD-1 trafficking in the membrane is regulated by the core fucosyltransferase 8 (fut8) in ER. Upon Tcell activation, PD-1 is internalized, then ubiquitinated by F-box protein 38 (FBXO38) for proteasome degradation or recycled back to the surface with the help of thymocyte selection-associated high mobility group box protein (Tox), thus prolonged PD-1 activity. Additionally, Tox expression induces Tcell depletion in hepatocellular cancer [7, 8]. Besides, another extension of PD-1 activity is caused by FBXO38’s low transcriptional level in the TME. Hence, the FBXO38-mediated PD-1 degradation pathway is defective. TCR signaling was the source of FBXO38 downregulation in the absence of concurrent CD28-CD80/86 signaling. CD28-CD80/86 binding provides critical signals for T cell activation in the presence of TCR stimulation. Persistent tumor antigen binding and low CD80/86 expression on cancerous cells might explain the lower FBXO38 expression in tumor-infiltrating lymphocytes (TILs) [7, 9].
Similar to PD-1, its first functionally identified ligand of PD-L1 (also known as B7 homolog 1 [B7-H1] or CD274) is constantly internalized, recycled, or degraded. Regulation of PD-L1 recycling is managed by CKLF-like MARVEL transmembrane domain containing 6 (CMTM6). Meanwhile, ubiquitination and degradation are regulated by multiple proteins such as cyclin D–CDK4 and the cullin 3–SPOP [10], β-TrCP [11], COP9 signalosome 5 (CSN5] [12], Huntingtin-interacting protein 1-related (HIP1R) [13], and others. Each protein is a drugable target to inhibit PD-L1 accumulation, thereby increasing T cell-mediated cytotoxicity.
Regarding the inhibitory signals following the binding of PD1 to PD-L1 or other ligands, it blocks kinases that play a role in activating T cells through the phosphatase SHP2. Besides, since PD1 inhibition blocks the TCR ‘stop signal’, this pathway can alter the length of T cell–APC or T cell–target cell interaction [14]. In detail, PD-1 is phosphorylated through immune receptor tyrosine-based switch motif (ITSM) and ITIM. Then, PD-1 binds the Src homology 2 (SH2) domains of SH2-containing phosphatase 2 (SHP2) or SHP1, which initiate its inhibitory effect by suppressing both TCR and CD28 co-stimulatory signaling [7, 15, 16, 17]. Moreover, PD-1 signaling also reduces cytokine production (interleukin [IL]-2, interferon [IFN]- α, tumor necrosis factor [TNF]-α), cell cycle progression, and pro-survival Bcl-xL gene expression by interfering with early TCR/CD28 signaling. PD-1/PD-L1 interaction is associated with IL-2-dependent positive feedback and transcription factors involved in effector functions such as GATA-3, T-bet, and Eomes. As signal transduction can only occur during TCR-dependent signaling, PD-1 activity is thus only relevant during simultaneous T cell activation. Mice without the receptor appear healthy at first. Still, they acquire autoimmune disorders such as lupus-like proliferative glomerulonephritis and arthritis, as well as enhanced inflammation after infections at a later age. In humans, genetic variations in the PD-1 region are more likely to suffer autoimmune disorders [18, 19].
Unlike PD-1/PD-L1, which is constitutively expressed on the membrane, CTLA-4 is primarily stored inside the cytoplasm of resting naïve T lymphocytes. The T cell receptor-interacting molecule (TRIM)/LAX/Rab8 complex and phospholipase D (PLD)/ADP ribosylation factor-1 (ARF1)-dependent exocytosis are required for CTLA-4 trafficking from trans Golgi network (TGN) to the cell surface [20]. Exocytosis of CTLA-4-containing vesicles causes upregulation of CTLA-4 on the cell surface due to stimulatory signals originating from TCR and CD28-B7 interaction. More robust TCR signaling causes more CTLA-4 to be translocated to the cell surface, and this process works in a graded feedback loop. CTLA-4 on the surface is rapidly internalized during normal physiologic conditions, resulting in relatively low expression. The clathrin-associated adaptor complex (AP-2) interaction to the unphosphorylated YVKM motif promotes rapid CTLA-4 internalization, which is then either destroyed in the lysosome or returned to the cell surface through LPS responsive beige-like anchor protein (LRBA). Besides, CTLA-4 in TGN may also be transported to the lysosome for destruction through AP-1 binding [7, 21, 22].
The intrinsic signaling of CTLA-4 that dampens T cell immune response has been widely contested with no agreement [23]. However, both CTLA-4 and CD28 interact with the identical ligands, CD80 (B7–1) and CD86 (B7–2). Because CTLA-4 has a 20-fold higher binding affinity than CD28, the intrinsic inhibitory signal rises once CTLA-4 outcompetes CD28, even if CTLA-4 is activated later [24, 25]. In addition to T cell response intrinsic inhibition, CTLA-4 is hypothesized to decrease extrinsic T cell signaling. For example, CTLA-4 suppresses CD80/86 expression on APCs via trans-endocytosis or by increasing tumor growth factor β (TGFβ), which in turn suppresses CD80/86 expression [26]. CTLA-4 is phosphorylated when it binds to its ligands, activating phosphoinositide 3-kinase (PI3K) pathways leading to dephosphorylation of the CD3 chain, decreasing the TCR’s signaling potential. CTLA-4 also prevents T cells from proliferating by inhibiting IL-2 transcription. Additionally, CTLA-4 stimulates the production of indoleamine 2,3-dioxygenase (IDO) in dendritic cells via CD80/86 ligation, resulting in T cell suppression [27].
TIM-3 is expressed on both T cells and innate immune cells. Four ligands have been identified: carcinoembryonic antigen cell adhesion molecule 1 (Ceacam1), C-type lectin galectin9 (Galectin9), high-mobility group box 1 (HMGB1), and non-protein ligand phosphatidylserine (PtdSer). Ceacam1 is a transmembrane protein that interacts in
TIM-3 is more related to co-stimulatory proteins induced in activated T cells than to a dominant inhibitory protein like PD-1; thus, TIM-3 signaling remains a matter of debate. As checkpoint proteins, TIM-3 is a repressor of IFN-γ-secreting CD4+ Th1 and CD8+ T cells. These findings confirmed that inhibiting TIM-3 might correct the defective phenotype of T cells in vivo. In contrast, TIM-3 lacks a conventional ITIM or ITSM in its intracellular domain and lacks structural features that facilitate the recruitment of inhibitory phosphatases. Rather than that, both murine and human TIM-3 cytoplasmic tails include five conserved tyrosine residues, two of which, Y256 and Y263 in mice (Y265, Y272 in humans), have been demonstrated to be crucial for coupling to downstream signaling pathways. Y256 and Y263 in TIM-3’s C-terminal tail interact with Bat3 in the absence of ligand-mediated TIM-3 signaling. Bat3 binds the catalytically active form of Lck in this state, resulting in the formation of an intracellular molecular complex with TIM-3 that retains and maybe enhances T cell signaling while repressing TIM-3-mediated cell death and exhaustion [31, 32]. TIM-3 activation on exhausted effector T cells is closely attributed to PD-1 expression, confirming the functional relationship between TIM-3 and PD-1 throughout the development of T cell exhaustion [33]. Concomitant therapy of anti-TIM-3 and anti-PD-1 is significantly more successful in these models, resulting in more significant tumor regression than either TIM-3 or PD-1 inhibition alone. TIM-3 inhibition in the setting of adaptive resistance to PD-1 treatment may be a useful way to treat individuals who develop resistance to anti-PD-1 therapy. This therapy regimen may be particularly beneficial for malignancies with resistance and immune escape from PD-1 inhibition [34, 35].
Like CTLA-4 and CD28, TIGIT and CD226 can interact with identical ligands, CD112 and CD155. TIGIT is a co-inhibitory receptor, while CD226 is a co-stimulatory receptor. Nevertheless, TIGIT possesses a higher affinity to its ligands than CD226; thus, TIGIT can inhibit co-stimulation signals by outcompeting CD226 ligands binding. TIGIT can bind directly to CD226 in
TIGIT’s signaling is mostly studied in natural killer (NK) cells and activated CD4 and CD8 T cells. The cytoplasmic region of TIGIT comprises an ITIM motif and an immunoglobulin tail tyrosine (ITT)-like motif. Several studies demonstrate that tyrosine (Tyr225) phosphorylation in either the ITIM or ITT-like motif is required for TIGIT’s inhibitory action in human NK cells. According to Liu et al. (2013), the ITT-like motif recruits Src homology domain-containing inositol phosphatases (SHIP1) via cytosolic adaptor proteins Grb2. Recruited SHIP1 then suppresses phosphatidyl-inositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signal to abolish NK cell function. Furthermore, TIGIT signaling can modulate the IFN-γ production of NK cells via the NF-κB pathway. In this context, β-arrestin 2, another TIGIT adaptor, is involved in phosphorylating TIGIT and then inhibits TNF receptor-associated factor 6 (TRAF6) autoubiquitination, hence inhibiting NF-κB activation and suppressing IFN-γ production [38, 39, 40].
LAG3 inhibits CD4-dependent T cell activity by binding to MHC-II due to being structurally homologous with four extracellular immunoglobulin superfamily-like domains. Other investigations demonstrated that LAG3’s inhibitory activity is not dependent on CD4 competition, but rather LAG-3 inhibited T cells responding to stable peptide-MHC-II by transducing inhibitory signals via its intracellular domain. Thus, LAG-3 may act more selectively, allowing tolerance to dominant autoantigens to persist [41, 42]. Alternatively, LAG3 can interact with another ligand like Galectin3 in TME and mediate the suppression of CD8 T cells [43]. Besides, liver sinusoidal endothelial cell lectin (LSECtin) can bind to LAG3 in human melanoma, causing tumor growth by abolishing IFN-γ production and proliferation of tumor-specific T cells [44]. Lastly, fibrinogen-like protein 1 (FGL1) was recently discovered as a novel LAG3 ligand. FGL1 is typically produced in trace amounts into the bloodstream by the liver. However, overexpression of FGL1 has been observed in some human malignancies. Inhibiting the interaction between FGL1 and LAG3 by monoclonal antibodies improves T cells’ anticancer activity [45].
The signal transduction mechanism of LAG3 is regulated by two transmembranes, a disintegrin and metalloproteinase domain-containing protein 10 and 17 (ADAM10 and ADAM17)-mediated cleavage. TCR signaling enhances ADAM10 and ADAM17 cleavage activity, releasing sLAG3. The function of sLAG3 remains controversial as some studies consider this does not have a biological process, while the others state that sLAG3 allows effective T cell proliferation and function [46]. Besides, sLAG3 affects monocyte differentiation into macrophages and DCs, which have decreased immunostimulatory capacity [47].
BTLA and CD160 inhibit T cell activity via the same ligand, herpesvirus entry mediator (HVEM). BTLA-HVEM is an example of crosstalk between two superfamilies in which the ligand is a member of the TNF/TNFR superfamily. However, HVEM interaction with members of the TNF superfamily LIGHT (Lymphotoxins, Inducible, competes with herpes simplex virus (HSV) Glycoprotein D for HVEM, expressed by T cells) produces a co-stimulatory signal on B and T cells. Hence, HVEM may be considered as a molecular switch that enables co-signaling between stimulatory and inhibitory T cells. Additionally, signaling between HVEM and its ligands appears to interact bidirectionally. The cis interaction between BTLA and HVEM inhibits the trans-ligation of HVEM by LIGHT and thus inhibits HVEM stimulatory signaling triggered by LIGHT binding [7, 48, 49].
Regarding the inhibitory signaling of BTLA, it follows the mechanism of PD-1/PD-L1 involving ITIM and ITSM to recruit SHP1/SHP2 [50]. In B-chronic lymphocytic leukemia (B-CLL), both HVEM and BTLA are overexpressed. This co-expression of HVEM and BTLA in CLL cells implies that an unsuccessful autocrine inhibitory loop is triggered. In addition, BTLA is typically downregulated during the development of human CD8+ T cells to effector cells. However, BTLA expression was more significant in melanoma-specific CD8+ T lymphocytes specialized for tumor antigens (TA). Despite effector differentiation, BTLA expression remained persistent, confounding T cell proliferation and IFN-y production. Thus, BTLA may function similarly to PD1 as a T-cell inhibitory receptor in TME [51].
Recent studies have established that immune checkpoint molecules drive cancer growth via various anticancer strategies. The first one is the overexpression of immune checkpoints in cancer cells, immune cells, or the surrounding environment leading to incapabilities of the tumor-specific immune response. Subsequently, immune checkpoints can interfere with metabolic pathways and deplete nutrients needed by immune cells. Lastly, immune checkpoints cripple cancer-specific immune responses by collaborating with regulatory T cells. This section deliberates each strategy thoroughly to get insight into how to combat those actions.
Accumulating evidence showed that several immune checkpoint molecules are overexpressed not only on the surface of cancer cells but also in T cells, Tregs, or even in TME. Here, we thoroughly describe how the immune checkpoint is upregulated and then inhibits antitumor activity. PD-1/PD-L1 are overexpressed on the surface of many cancer cells. Several proinflammatory mediators, which are secreted by activated T cells (types I and II IFN-γ, TNF-α, IL-10, and IL-4) or produced in TME (GM-CSF and VEGF), upregulate PD-L1 expression in the cancer cells resulting in suppression of PD1+ T cells activity. Moreover, cancer cells commonly carry altered PTEN (phosphatase and tension homolog deleted on chromosome ten)—PD-L1 suppressor gene—which may activate the S6K1 gene, resulting in a significant increase in PD-L1 mRNA to polysomes, which promotes PD-L1 mRNA translation and plasma membrane expression [6]. In pancreatic cancer cells, PTEN gene deletion influences PD-L1 expression at the translational level by activating the PI3K/AKT downstream mTOR-S6K1 signaling pathway, thereby increasing PD-L1 production and T lymphocyte apoptosis [52, 53].
Furthermore, amplification and translocation of CD274 on chromosome 9p24.1 have been associated with elevated expression of PD-L1 in Hodgkin’s lymphoma, small cell lung cancer (SCLC), non-small cell lung cancer (NSCLC), lymphoma, Epstein-Barr virus (EBV)-positive gastric cancer, and oral squamous cell carcinoma (OSCC). In SCLC, chromosomal rearrangements produce CD274 amplification without changing the open reading frame. It is found in various organs, but it is most commonly found in activated T and B lymphocyte cells, dendritic cells, monocytes, and other types of TCs. The CD274/PD-L1 gene is highly conserved, with homologs discovered across the vertebrate lineage (from
PD-L1 induction has also been associated with inflammatory stimuli such as IL-1b, IL-4, IL-6, IL-10, IL-12, IL-17, IL-27, tumor necrosis factor-α (TNF-α), and transforming growth factor-β (TGF-β). Among the several soluble inflammatory agents, IFN-ϒ is the most important in promoting PD-L1 expression. IFN-ϒ is a proinflammatory cytokine primarily generated by T and NK cells. IFN-ϒ attaches to its receptor, the interferon-gamma receptor (IFNGR), activating the JAK-STAT signaling pathway via STAT1. As a result, it increases the expression of transcription factors, particularly interferon-responsive factors (IRFs). IRF1 is a critical downstream signaling molecule of STAT1 that causes IFN-induced PD-L1. Other proinflammatory agents, IL-4 and TNF-α, have a synergistic impact on the activation of PD-L1 in renal cell carcinoma (RCC) via activating signaling molecules such as NF-κB, IκB, and STAT6. In dendritic cells and monocytes, blocking PD-L1 was associated with decreased IL-10 levels. Furthermore, IL-10 levels on Tyro3, Axl, and Mer (TAM) were closely connected to PD-L1 expression. In monocyte-derived macrophages, IL-12 upregulates PD-L1 expression, but in THP-1-derived macrophages, it downregulates PD-L1 expression. In monocytes, IL-17 is involved in the induction of PD-L1. IL-17 and TNF-α activate NF-κB signaling in prostate cancer and NF-κB and ERK1/2 in colon cancer, respectively, and upregulate PD-L1 expression. PD-L1 expression in dendritic cells is upregulated by IL-1b and IL-27. Furthermore, IL-27 activates phospho-STAT1 and phospho-STAT3 to enhance PD-L1 expression [54, 56].
Meanwhile, CTLA-4 is often constitutively overexpressed on Tregs and has been demonstrated to alter Tregs-mediated immune control. In multiple myeloma patients, FOXP3 and CTLA-4 genes from bone marrow samples were considerably overexpressed [57]. Another sample from peripheral blood mononuclear cells (PBMC) of breast cancer patients showed significantly higher mRNA expression of FOXP3 and CTLA-4 than healthy individuals [58]. Taken together, these results indicated the pivotal role of CTLA-4 in the accumulation of immunosuppressive Tregs in TME, leading to repression of anti-tumor immunity.
Regarding TIM-3 overexpression, it is induced by cytokine stimulation, especially in NK cells. TIM-3 is also extensively expressed on tumor-infiltrating lymphocytes. Similar to its expression pattern during persistent viral infection, TIM-3 is generally co-expressed with PD-1 and represents the most dysfunctional T cell subgroup. TIM-3 overexpression in human malignancies, particularly on immune cells, might be a predictive biomarker for a range of cancers. TIM-3 expression on CD4+ and CD8+ T lymphocytes was enhanced in individuals with hepatitis B virus-related hepatocellular carcinoma (HCC). TIM-3+T cells were replicative senescent and exhibited senescence-related surface and genomic markers. Furthermore, the quantity of tumor-infiltrating cells in TIM-3+ was inversely linked with HCC patient survival [59].
Furthermore, LAG3 is mainly expressed in activated T and natural killer (NK) cells, and it has been identified as a marker for CD4+ and CD8+ T cell activation. Increased LAG3 expression on T cells was observed in combination with other inhibitory receptors such as PD-1, TIGIT, TIM-3, CD160, and 2B4 under pathological conditions such as chronic inflammation or in TME, resulting in T cell exhaustion and reduced cytokine release. In melanoma and colon cancer, LAG3 expression was identified in tissue-infiltrating lymphocytes and peripheral Tregs, tumor-involved lymph nodes, and inside the tumor tissue itself. LAG3 was found on tumor-infiltrating Tregs in patients with head and neck squamous cell carcinoma and non-small cell lung cancer [60].
Similar to other checkpoint molecules, TIGIT is also significantly expressed on Tregs taken from PBMC of cancer patients, and it is further elevated in the TME. Increased TIGIT expression in Tregs is coupled with hypomethylation and FOXP3 binding at the TIGIT gene, distinguishing Tregs from activated effector CD4+ T cells. Furthermore, the Fap2 protein from
Due to cancer cells’ resource intake and vascularization defects, TME is typically deficient in nutrients and oxygen. Cancer cells’ increased need for glucose promotes competition in the TME, which has a detrimental effect on surrounding cells, such as immune cells. Immune checkpoint proteins have been shown to modulate the metabolic energetics of tumor cells, TME, and the tumor-specific immune response, resulting in metabolic reprogramming of both cancerous and immune cells. For instance, CD80 (B7–1) activated the mTOR kinase in naïve CD8+ T cells via the PI3K and STAT4 pathways in solid tumors. mTOR signaling is required to promote glycolysis via hypoxia-inducible factor-1α (HIF-1α) and protein synthesis for supporting cancer cell growth. This activation shifts nutrition balance, and cancerous cells outcompete the immune cells, then evading immune surveillance [62, 63].
Because amino acids are the building blocks of proteins, their availability is critical for tumor development. At the same time, immune cells need amino acids to differentiate and perform their effector activities, hence regulating tumor formation. Given this, a greater knowledge of how each cell species use amino acids in the TME looks critical for successfully stimulating anti-tumor immunity. Tryptophan deficiency impairs CD8+ T cell functions and enhances CD4+ Tregs cell functions, resulting in immunosuppression mediated by the CTLA-4 and PD-1/PD-L1 pathways. The effects are achieved mechanistically by activating the stress response kinase GCN2, which inhibits mTORC2 and its downstream target AKT [64, 65]. The other amino acids, such as glutamine and arginine, are also extensively consumed by the tumors and directly impoverish T cells, leading to the development of immunosuppressive TME [66]. Additionally, tumors may produce and accumulate toxic compounds like aerobic glycolysis byproduct (lactate) in TME, leading to local acidification. Lactate acidosis and hypoxia can activate HIF-1α and then upregulate PD-L1, further inhibiting T-cell responses specific to tumors. Besides, an acidic condition in the surrounding tumors environment suppresses cytokine production (IFN-γ) and limits the activity of T cell cytotoxic, NK cells, and dendritic cells [66, 67].
In contrast to the effector T cells, glucose deprivation may exert a negligible effect on intratumoral Tregs and lactic acid found in the TME may offer nourishment, thus supporting the immunosuppressive function of Tregs [68]. In addition, Tregs differentiation and recruitment is also supported by kynurenine, a metabolite produced from tryptophan through indoleamine 2,3 dioxygenase (IDO)-catabolization in TME [69]. Furthermore, hypoxia and fatty acids production may facilitate Tregs accumulation, thereby favoring its suppressive function [70].
Another immune checkpoint favoring cancer growth strategy is its interaction with Tregs cells either by the expression on Tregs surface or inducing Tregs population and function. Treg cells function in the immune system to regulate and suppress other effector T cells. These cells are responsible for the homeostatic process of the immune system to maintain its unresponsiveness to self-antigens and protect the body from autoimmune reactions or excessive inflammation [71]. However, in this context, the interaction of two immunosuppressive mechanistics is critical in cancer survival from immunosurveillance and progression.
Almost all of the immune checkpoint molecules discussed in this chapter, except BTLA, are expressed in Tregs [72]. CTLA-4 is expressed constitutively on Tregs and induced on effector T cells when activated. CTLA-4 deficiency in Tregs was shown to affect their suppressive effects in animal models. Upon TCR stimulation, CTLA-4 is constitutively recruited on the Tregs cell surface, allowing continuous transendocytosis signaling. Hence, Tregs (CD4+ Foxp3+) can outperformed activated conventional T cells (CD4+ Foxp3−) [73]. Subsequently, downregulation of B7 ligands on APCs leading to diminished CD28 co-stimulation is another way by which Tregs are hypothesized to govern effector T cells [74, 75].
In tumor tissue of non-small cell lung cancer (NSCLC) patients, the PD-L1 expressing CD25+ CD4+ (PD-L1hiTregs) population is higher than in blood or normal tissue. Interestingly, PD-L1hiTregs also correlated with PD-1+ CD8 [76]. In another cancer, highly expressed PD-L1 glioblastoma cells can induce Tregs expansion and maintain its immunosuppressives through PD-1/PD-L1 stimulation. Disrupting the PD-L1/PD-1 axis could target two immunosuppressive mechanisms: inhibition of signaling due to PD-1/PD-L1 ligation and stimulatory proliferation of Tregs cells, which indirectly promotes immunoresistance of high PD-L1 cancers. Thus, Tregs abundance may be a predictive biomarker for patients likely to react to anti-PD-1/anti-PD-L1 therapy or monitor treatment response [77].
Multiple immune checkpoints protein can coexpress and accumulate on the T cell surface, thus increasing dysfunctionality. On CD8+ TILs, it is found that TIGIT is coexpressed with TIM-3, PD-1, and LAG-3 [78]. Although, further investigation is needed to show whether these pathways synergize and whether coblockade is becoming a more efficient immunotherapeutic approach.
Immunological tolerance is normally maintained so that the immune system can recognize and distinguish between self and non-self antigens or neoantigens. Although the immune system is expected to protect the host from exposure to non-self antigens, its robust effector mechanism allows to reverse the attack and disrupt the homeostasis of the immune system. Immune checkpoints, which have gained notoriety as possible cancer therapy targets, are essential immunoregulatory processes found throughout the body. Dysregulation of immune checkpoints promotes tumor cell evasion and plays a significant role in cancer pathogenesis. Therefore, several monoclonal antibodies have been made to block the interaction between ligand and receptor of immune checkpoints, enhancing host immunologic competence against tumors. The list of immune checkpoints inhibitors (ICI), which gained Food and Drug Administration (FDA) approval or are in ongoing clinical trials, is comprehensively summarized in [79]. However, only a tiny proportion of patients respond meaningfully to these therapies due to the signaling complexity and overlapped pathways as mentioned above. Thus, new routes and compounds are being investigated to enhance therapeutic responsiveness and applicability. In clinical practice, the difficulties in treating cancer patients revolve on eliminating the tumor and alleviating symptoms such as pain, fatigue, nausea/vomiting, cough, and diarrhea. Then, concomitant use of medications is negligible and generates new threats for drug interaction such as analgesics [80], steroids [81], antibiotics [82], or many others. Moreover, the use of ICI is often associated with immune-related adverse effects (irAEs). A retrospective study reported that among 1091 patients receiving ICI therapy, 487 (44.63%) patients experienced adverse effects. The most common is fatigue (13.9%), then dermatologic irAEs (12%), endocrine-related irAEs (9.89%), gastrointestinal toxicities (8.4%) and hepatotoxicities (4.94%) [83].
The authors thank our institutions Akademi Farmasi Surabaya and the University of Surabaya, for the support.
The authors declare no conflict of interest.
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F. Kaiser, H.A. Aboulela, H. A. El-Serehy and H. Ezz El-Din",authors:[{id:"3900",title:"Dr.",name:"Mona",middleName:null,surname:"Kaiser",slug:"mona-kaiser",fullName:"Mona Kaiser"},{id:"126516",title:"Dr.",name:"Hamdy",middleName:null,surname:"Aboulela",slug:"hamdy-aboulela",fullName:"Hamdy Aboulela"},{id:"150469",title:"Dr.",name:"H.",middleName:null,surname:"El-Serehy",slug:"h.-el-serehy",fullName:"H. El-Serehy"}]},{id:"25547",doi:"10.5772/28978",title:"Fluorescently Labeled Phospholipids – New Class of Materials for Chemical Sensors for Environmental Monitoring",slug:"fluorescently-labeled-phospholipids-new-class-of-materials-for-chemical-sensors-for-environmental-mo",totalDownloads:1722,totalCrossrefCites:2,totalDimensionsCites:9,abstract:null,book:{id:"2110",slug:"relevant-perspectives-in-global-environmental-change",title:"Relevant Perspectives in Global Environmental Change",fullTitle:"Relevant Perspectives in Global Environmental Change"},signatures:"George R. Ivanov, Georgi Georgiev and Zdravko Lalchev",authors:[{id:"76075",title:"Dr.",name:"George",middleName:null,surname:"Ivanov",slug:"george-ivanov",fullName:"George Ivanov"},{id:"76526",title:"Dr.",name:"Georgi",middleName:null,surname:"Georgiev",slug:"georgi-georgiev",fullName:"Georgi Georgiev"},{id:"76527",title:"Prof.",name:"Zdravko",middleName:null,surname:"Lalchev",slug:"zdravko-lalchev",fullName:"Zdravko Lalchev"}]}],mostDownloadedChaptersLast30Days:[{id:"77362",title:"Role of Eco-Village Initiatives in Mitigating Desertification in Semi-Arid Areas of Tanzania",slug:"role-of-eco-village-initiatives-in-mitigating-desertification-in-semi-arid-areas-of-tanzania",totalDownloads:112,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Climate change adaptation actions for mitigating desertification and improving community livelihood in developing countries have attracted numerous scholarly works. However, there have been insufficient findings on the adaptation regarding the eco-village practices in semi-arid areas in particular. This inspired a study to assess the role of eco-village practices in strengthening climate change adaptive capacity and mitigating desertification in semi-arid areas of Chololo village, Dodoma region in central Tanzania. Data were collected using mixed methods, that is, household survey (92), focus group discussions (21), key informants interviews (6), field observation and documentary review. Statistical Package for Social Sciences (SPSS) and content analysis were used in analyzing quantitative and qualitative data respectively. The study found a relatively high level of community awareness on the eco-village initiative; the initiative rehabilitated village forest reserve; improved land productivity for sorghum and pearl millet; increased number of planted trees; and strengthening communities’ adaptation to climate change through improved households’ nutrition, income and reduced water stress.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Fredy S. Mswima and Abiud L. Kaswamila",authors:[{id:"115390",title:"Prof.",name:"Abiud L.",middleName:"Lucas",surname:"Kaswamila",slug:"abiud-l.-kaswamila",fullName:"Abiud L. Kaswamila"},{id:"415117",title:"Dr.",name:"Fredy S.",middleName:null,surname:"Mswima",slug:"fredy-s.-mswima",fullName:"Fredy S. Mswima"}]},{id:"77741",title:"Characteristic on the Stability of Haloxylon ammodendron Plantation in the Southern Fringe of Gurbantunggut Desert, Northwest China",slug:"characteristic-on-the-stability-of-em-haloxylon-ammodendron-em-plantation-in-the-southern-fringe-of-",totalDownloads:165,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Using chronosequence theory and method, the characteristics of vegetation-soil coupling and structure stability of Haloxylon ammodendron plantations in the southern fringe of Gurbantunggut Desert were analyzed. The results showed, the canopy storey of H. ammodendron plantation experienced three stages, rapid growth (the age of 7 to 20), then slow growth (the age of 20 to 28) and last decline (over the age of 28). The best natural regeneration started from 17-yr-old plantation. Vegetation-soil system coupling degree (C) and coupling coordinative degree (D) of plantations with different age were not one-to-one correspondence. The system of H. ammodendron plantations always stayed in disorder recession, vegetation and soil were prone to loss type during the process of sand-fixation. Five principal components evaluated that the first rank was 42-yr-old plantation. It was inferred that the trend of the vegetation and soil system was from senescence to harmonious development. So the trend of coordinated development between vegetation and soil would be promoted, if the artificial tending and management measures strengthened.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Qinghong Luo, Qimin Chen, Miao He and Na Li",authors:[{id:"340564",title:"Dr.",name:"Qinghong",middleName:null,surname:"Luo",slug:"qinghong-luo",fullName:"Qinghong Luo"},{id:"347848",title:"Mr.",name:"Qimin",middleName:null,surname:"Chen",slug:"qimin-chen",fullName:"Qimin Chen"},{id:"348214",title:"Associate Prof.",name:"Miao",middleName:null,surname:"He",slug:"miao-he",fullName:"Miao He"},{id:"348215",title:"Associate Prof.",name:"Na",middleName:null,surname:"Li",slug:"na-li",fullName:"Na Li"}]},{id:"77086",title:"Bowing Sand, Dust, and Dunes, Then and Now–A North American Perspective",slug:"bowing-sand-dust-and-dunes-then-and-now-a-north-american-perspective",totalDownloads:94,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Dune fields of the present day, the Dust Bowl disaster of the 1930s U.S. Great Plains, and contemporary efforts to forecast, simulate, and understand dust storms have a striking, uniform commonality. What these apparently diverse phenomena have in common is that they all result from blowing sand and dust. This review paper unifies these three disparate but related phenomena. Its over-arching goal is to clearly explain these manifestations of windblown sand and dust. First, for contemporary dune fields, we offer reviews of two technical papers that explain the eolian formation and the continuing development of two major dune fields in southeastern California and northwestern Sonora, Mexico: the Algodones Dunes and the Gran Desierto de Altar. Second, historical, geological, meteorological, and socioeconomic aspects of the 1930s Great Plains Dust Bowl are discussed. Third, and last, we return to the present day to summarize two lengthy reports on dust storms and to review two technical papers that concern their forecasting and simulation. The intent of this review is to acquaint the interested reader with how eolian transport of sand and dust affects the formation of present-day dune fields, human agricultural enterprises, and efforts to better forecast and simulate dust storms. Implications: Blowing sand and dust have drastically affected the geological landscape and continue to shape the formation of dune fields today. Nearly a century ago the U.S. Great Plains suffered through the Dust Bowl, yet another consequence of blowing sand and dust brought on by drought and mismanagement of agricultural lands. Today, this phenomenon adversely affects landscapes, transportation, and human respiratory health. A more complete understanding of this phenomenon could (and has) led to more effective mitigation of dust sources, as well as to a more accurate predictive system by which the public can be forewarned.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Peter Hyde and Alex Mahalov",authors:[{id:"348247",title:"Dr.",name:"Peter",middleName:null,surname:"Hyde",slug:"peter-hyde",fullName:"Peter Hyde"},{id:"419631",title:"Dr.",name:"Alex",middleName:null,surname:"Mahalov",slug:"alex-mahalov",fullName:"Alex Mahalov"}]},{id:"78428",title:"Jojoba - The Gold of Desert",slug:"jojoba-the-gold-of-desert",totalDownloads:246,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Jojoba [Simmondsia chinensis (Link) Schneider] is evergreen, perennial and drought resistant shrub belongs to the family of Simmondsiaceae. It is a multipurpose oil seed crop mainly grown in desert regions of world. This plant has unique oil among plant kingdom which is chemically a liquid-wax. The liquid-wax is made up of an ester of long chain fatty acids and alcohols. The liquid-wax is unique in nature because have no traces of glycerine and easily modified via hydrolysis, hydrogenation, halogenation, sulfurization, phosphosulfurization and ozonization techniques. The main uses of liquid-wax in various industries like cosmetics, pharmaceuticals, petrochemicals and lubricants. It is a potential seed oil crop for desert region so it is well known as the gold of desert. The main purpose of this chapter is to review the complete information about this plant so that it can produce and utilized maximally. Moreover, the review focuses on biology, biogeography, physico-chemical properties of jojoba oil and propagation techniques of the plant of desert regions.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Raman Bala",authors:[{id:"347678",title:"Dr.",name:"Raman",middleName:null,surname:"Bala",slug:"raman-bala",fullName:"Raman Bala"}]},{id:"78099",title:"Water Source of Six Woody Plants in Different Habitats on Desertified Land of Ordos Plateau, Semi-Arid China",slug:"water-source-of-six-woody-plants-in-different-habitats-on-desertified-land-of-ordos-plateau-semi-ari",totalDownloads:165,totalCrossrefCites:0,totalDimensionsCites:0,abstract:"Water and soil erosion and sandy desertification are two mainly land desertification types on eastern and southern Ordos Plateau, north China. Hippophae rhamnoides, Armeniaca sibirica and Pinus tabuliformis are three woody plants for soil and water conservation on loess slope. Sabina vulgaris, Artemisia ordosica and Salix psammophila are three shrubs for sand control on sand dune. Water source of six woody plants were investigated by stable isotope technology. The results showed that the δ18O of shallow soil water was similar to that of rainwater in July and September in two habitats. Both of six woody plants in two habitats mainly used shallow soil water in May. However, three shrubs on sand dune mainly used both of shallow and deep soil water in July and September. Three woody plants on loess slope mainly used rainwater or deep soil water in July and September. Therefore, six woody plants utilized different depths of soil water or rain water based on their availability in different seasons, which is an adaptive strategy to the semiarid climate on Ordos Plateau.",book:{id:"8969",slug:"deserts-and-desertification",title:"Deserts and Desertification",fullTitle:"Deserts and Desertification"},signatures:"Yajuan Zhu",authors:[{id:"180427",title:"Dr.",name:"Yajuan",middleName:null,surname:"Zhu",slug:"yajuan-zhu",fullName:"Yajuan Zhu"}]}],onlineFirstChaptersFilter:{topicId:"869",limit:6,offset:0},onlineFirstChaptersCollection:[],onlineFirstChaptersTotal:0},preDownload:{success:null,errors:{}},subscriptionForm:{success:null,errors:{}},aboutIntechopen:{},privacyPolicy:{},peerReviewing:{},howOpenAccessPublishingWithIntechopenWorks:{},sponsorshipBooks:{sponsorshipBooks:[],offset:8,limit:8,total:0},allSeries:{pteSeriesList:[{id:"14",title:"Artificial Intelligence",numberOfPublishedBooks:9,numberOfPublishedChapters:89,numberOfOpenTopics:6,numberOfUpcomingTopics:0,issn:"2633-1403",doi:"10.5772/intechopen.79920",isOpenForSubmission:!0},{id:"7",title:"Biomedical Engineering",numberOfPublishedBooks:12,numberOfPublishedChapters:104,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2631-5343",doi:"10.5772/intechopen.71985",isOpenForSubmission:!0}],lsSeriesList:[{id:"11",title:"Biochemistry",numberOfPublishedBooks:32,numberOfPublishedChapters:318,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2632-0983",doi:"10.5772/intechopen.72877",isOpenForSubmission:!0},{id:"25",title:"Environmental Sciences",numberOfPublishedBooks:1,numberOfPublishedChapters:12,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2754-6713",doi:"10.5772/intechopen.100362",isOpenForSubmission:!0},{id:"10",title:"Physiology",numberOfPublishedBooks:11,numberOfPublishedChapters:141,numberOfOpenTopics:4,numberOfUpcomingTopics:0,issn:"2631-8261",doi:"10.5772/intechopen.72796",isOpenForSubmission:!0}],hsSeriesList:[{id:"3",title:"Dentistry",numberOfPublishedBooks:8,numberOfPublishedChapters:129,numberOfOpenTopics:2,numberOfUpcomingTopics:0,issn:"2631-6218",doi:"10.5772/intechopen.71199",isOpenForSubmission:!0},{id:"6",title:"Infectious Diseases",numberOfPublishedBooks:13,numberOfPublishedChapters:113,numberOfOpenTopics:3,numberOfUpcomingTopics:1,issn:"2631-6188",doi:"10.5772/intechopen.71852",isOpenForSubmission:!0},{id:"13",title:"Veterinary Medicine and Science",numberOfPublishedBooks:11,numberOfPublishedChapters:106,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2632-0517",doi:"10.5772/intechopen.73681",isOpenForSubmission:!0}],sshSeriesList:[{id:"22",title:"Business, Management and Economics",numberOfPublishedBooks:1,numberOfPublishedChapters:19,numberOfOpenTopics:3,numberOfUpcomingTopics:0,issn:"2753-894X",doi:"10.5772/intechopen.100359",isOpenForSubmission:!0},{id:"23",title:"Education and Human Development",numberOfPublishedBooks:0,numberOfPublishedChapters:5,numberOfOpenTopics:1,numberOfUpcomingTopics:1,issn:null,doi:"10.5772/intechopen.100360",isOpenForSubmission:!0},{id:"24",title:"Sustainable Development",numberOfPublishedBooks:0,numberOfPublishedChapters:15,numberOfOpenTopics:5,numberOfUpcomingTopics:0,issn:null,doi:"10.5772/intechopen.100361",isOpenForSubmission:!0}],testimonialsList:[{id:"6",text:"It is great to work with the IntechOpen to produce a worthwhile collection of research that also becomes a great educational resource and guide for future research endeavors.",author:{id:"259298",name:"Edward",surname:"Narayan",institutionString:null,profilePictureURL:"https://mts.intechopen.com/storage/users/259298/images/system/259298.jpeg",slug:"edward-narayan",institution:{id:"3",name:"University of Queensland",country:{id:null,name:"Australia"}}}},{id:"13",text:"The collaboration with and support of the technical staff of IntechOpen is fantastic. The whole process of submitting an article and editing of the submitted article goes extremely smooth and fast, the number of reads and downloads of chapters is high, and the contributions are also frequently cited.",author:{id:"55578",name:"Antonio",surname:"Jurado-Navas",institutionString:null,profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRisIQAS/Profile_Picture_1626166543950",slug:"antonio-jurado-navas",institution:{id:"720",name:"University of Malaga",country:{id:null,name:"Spain"}}}}]},series:{item:{id:"14",title:"Artificial Intelligence",doi:"10.5772/intechopen.79920",issn:"2633-1403",scope:"Artificial Intelligence (AI) is a rapidly developing multidisciplinary research area that aims to solve increasingly complex problems. In today's highly integrated world, AI promises to become a robust and powerful means for obtaining solutions to previously unsolvable problems. This Series is intended for researchers and students alike interested in this fascinating field and its many applications.",coverUrl:"https://cdn.intechopen.com/series/covers/14.jpg",latestPublicationDate:"June 11th, 2022",hasOnlineFirst:!0,numberOfPublishedBooks:9,editor:{id:"218714",title:"Prof.",name:"Andries",middleName:null,surname:"Engelbrecht",slug:"andries-engelbrecht",fullName:"Andries Engelbrecht",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRNR8QAO/Profile_Picture_1622640468300",biography:"Andries Engelbrecht received the Masters and PhD degrees in Computer Science from the University of Stellenbosch, South Africa, in 1994 and 1999 respectively. He is currently appointed as the Voigt Chair in Data Science in the Department of Industrial Engineering, with a joint appointment as Professor in the Computer Science Division, Stellenbosch University. Prior to his appointment at Stellenbosch University, he has been at the University of Pretoria, Department of Computer Science (1998-2018), where he was appointed as South Africa Research Chair in Artifical Intelligence (2007-2018), the head of the Department of Computer Science (2008-2017), and Director of the Institute for Big Data and Data Science (2017-2018). In addition to a number of research articles, he has written two books, Computational Intelligence: An Introduction and Fundamentals of Computational Swarm Intelligence.",institutionString:null,institution:{name:"Stellenbosch University",institutionURL:null,country:{name:"South Africa"}}},editorTwo:null,editorThree:null},subseries:{paginationCount:6,paginationItems:[{id:"22",title:"Applied Intelligence",coverUrl:"https://cdn.intechopen.com/series_topics/covers/22.jpg",isOpenForSubmission:!0,editor:{id:"27170",title:"Prof.",name:"Carlos",middleName:"M.",surname:"Travieso-Gonzalez",slug:"carlos-travieso-gonzalez",fullName:"Carlos Travieso-Gonzalez",profilePictureURL:"https://mts.intechopen.com/storage/users/27170/images/system/27170.jpeg",biography:"Carlos M. Travieso-González received his MSc degree in Telecommunication Engineering at Polytechnic University of Catalonia (UPC), Spain in 1997, and his Ph.D. degree in 2002 at the University of Las Palmas de Gran Canaria (ULPGC-Spain). He is a full professor of signal processing and pattern recognition and is head of the Signals and Communications Department at ULPGC, teaching from 2001 on subjects on signal processing and learning theory. His research lines are biometrics, biomedical signals and images, data mining, classification system, signal and image processing, machine learning, and environmental intelligence. He has researched in 52 international and Spanish research projects, some of them as head researcher. He is co-author of 4 books, co-editor of 27 proceedings books, guest editor for 8 JCR-ISI international journals, and up to 24 book chapters. He has over 450 papers published in international journals and conferences (81 of them indexed on JCR – ISI - Web of Science). He has published seven patents in the Spanish Patent and Trademark Office. He has been a supervisor on 8 Ph.D. theses (11 more are under supervision), and 130 master theses. He is the founder of The IEEE IWOBI conference series and the president of its Steering Committee, as well as the founder of both the InnoEducaTIC and APPIS conference series. He is an evaluator of project proposals for the European Union (H2020), Medical Research Council (MRC, UK), Spanish Government (ANECA, Spain), Research National Agency (ANR, France), DAAD (Germany), Argentinian Government, and the Colombian Institutions. He has been a reviewer in different indexed international journals (<70) and conferences (<250) since 2001. He has been a member of the IASTED Technical Committee on Image Processing from 2007 and a member of the IASTED Technical Committee on Artificial Intelligence and Expert Systems from 2011. \n\nHe has held the general chair position for the following: ACM-APPIS (2020, 2021), IEEE-IWOBI (2019, 2020 and 2020), A PPIS (2018, 2019), IEEE-IWOBI (2014, 2015, 2017, 2018), InnoEducaTIC (2014, 2017), IEEE-INES (2013), NoLISP (2011), JRBP (2012), and IEEE-ICCST (2005)\n\nHe is an associate editor of the Computational Intelligence and Neuroscience Journal (Hindawi – Q2 JCR-ISI). He was vice dean from 2004 to 2010 in the Higher Technical School of Telecommunication Engineers at ULPGC and the vice dean of Graduate and Postgraduate Studies from March 2013 to November 2017. He won the “Catedra Telefonica” Awards in Modality of Knowledge Transfer, 2017, 2018, and 2019 editions, and awards in Modality of COVID Research in 2020.\n\nPublic References:\nResearcher ID http://www.researcherid.com/rid/N-5967-2014\nORCID https://orcid.org/0000-0002-4621-2768 \nScopus Author ID https://www.scopus.com/authid/detail.uri?authorId=6602376272\nScholar Google https://scholar.google.es/citations?user=G1ks9nIAAAAJ&hl=en \nResearchGate https://www.researchgate.net/profile/Carlos_Travieso",institutionString:null,institution:{name:"University of Las Palmas de Gran Canaria",institutionURL:null,country:{name:"Spain"}}},editorTwo:null,editorThree:null},{id:"23",title:"Computational Neuroscience",coverUrl:"https://cdn.intechopen.com/series_topics/covers/23.jpg",isOpenForSubmission:!0,editor:{id:"14004",title:"Dr.",name:"Magnus",middleName:null,surname:"Johnsson",slug:"magnus-johnsson",fullName:"Magnus Johnsson",profilePictureURL:"https://mts.intechopen.com/storage/users/14004/images/system/14004.png",biography:"Dr Magnus Johnsson is a cross-disciplinary scientist, lecturer, scientific editor and AI/machine learning consultant from Sweden. \n\nHe is currently at Malmö University in Sweden, but also held positions at Lund University in Sweden and at Moscow Engineering Physics Institute. \nHe holds editorial positions at several international scientific journals and has served as a scientific editor for books and special journal issues. \nHis research interests are wide and include, but are not limited to, autonomous systems, computer modeling, artificial neural networks, artificial intelligence, cognitive neuroscience, cognitive robotics, cognitive architectures, cognitive aids and the philosophy of mind. \n\nDr. Johnsson has experience from working in the industry and he has a keen interest in the application of neural networks and artificial intelligence to fields like industry, finance, and medicine. \n\nWeb page: www.magnusjohnsson.se",institutionString:null,institution:{name:"Malmö University",institutionURL:null,country:{name:"Sweden"}}},editorTwo:null,editorThree:null},{id:"24",title:"Computer Vision",coverUrl:"https://cdn.intechopen.com/series_topics/covers/24.jpg",isOpenForSubmission:!0,editor:{id:"294154",title:"Prof.",name:"George",middleName:null,surname:"Papakostas",slug:"george-papakostas",fullName:"George Papakostas",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002hYaGbQAK/Profile_Picture_1624519712088",biography:"George A. Papakostas has received a diploma in Electrical and Computer Engineering in 1999 and the M.Sc. and Ph.D. degrees in Electrical and Computer Engineering in 2002 and 2007, respectively, from the Democritus University of Thrace (DUTH), Greece. Dr. Papakostas serves as a Tenured Full Professor at the Department of Computer Science, International Hellenic University, Greece. Dr. Papakostas has 10 years of experience in large-scale systems design as a senior software engineer and technical manager, and 20 years of research experience in the field of Artificial Intelligence. Currently, he is the Head of the “Visual Computing” division of HUman-MAchines INteraction Laboratory (HUMAIN-Lab) and the Director of the MPhil program “Advanced Technologies in Informatics and Computers” hosted by the Department of Computer Science, International Hellenic University. He has (co)authored more than 150 publications in indexed journals, international conferences and book chapters, 1 book (in Greek), 3 edited books, and 5 journal special issues. His publications have more than 2100 citations with h-index 27 (GoogleScholar). His research interests include computer/machine vision, machine learning, pattern recognition, computational intelligence. \nDr. Papakostas served as a reviewer in numerous journals, as a program\ncommittee member in international conferences and he is a member of the IAENG, MIR Labs, EUCogIII, INSTICC and the Technical Chamber of Greece (TEE).",institutionString:null,institution:{name:"International Hellenic University",institutionURL:null,country:{name:"Greece"}}},editorTwo:null,editorThree:null},{id:"25",title:"Evolutionary Computation",coverUrl:"https://cdn.intechopen.com/series_topics/covers/25.jpg",isOpenForSubmission:!0,editor:{id:"136112",title:"Dr.",name:"Sebastian",middleName:null,surname:"Ventura Soto",slug:"sebastian-ventura-soto",fullName:"Sebastian Ventura Soto",profilePictureURL:"https://mts.intechopen.com/storage/users/136112/images/system/136112.png",biography:"Sebastian Ventura is a Spanish researcher, a full professor with the Department of Computer Science and Numerical Analysis, University of Córdoba. Dr Ventura also holds the positions of Affiliated Professor at Virginia Commonwealth University (Richmond, USA) and Distinguished Adjunct Professor at King Abdulaziz University (Jeddah, Saudi Arabia). Additionally, he is deputy director of the Andalusian Research Institute in Data Science and Computational Intelligence (DaSCI) and heads the Knowledge Discovery and Intelligent Systems Research Laboratory. He has published more than ten books and over 300 articles in journals and scientific conferences. Currently, his work has received over 18,000 citations according to Google Scholar, including more than 2200 citations in 2020. 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Kasenga",hash:"91cde4582ead884cb0f355a19b67cd56",volumeInSeries:4,fullTitle:"Malaria",editors:[{id:"86725",title:"Dr.",name:"Fyson",middleName:"Hanania",surname:"Kasenga",slug:"fyson-kasenga",fullName:"Fyson Kasenga",profilePictureURL:"https://mts.intechopen.com/storage/users/86725/images/system/86725.jpg",institutionString:"Malawi Adventist University",institution:{name:"Malawi Adventist University",institutionURL:null,country:{name:"Malawi"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7123",title:"Current Topics in Neglected Tropical Diseases",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7123.jpg",slug:"current-topics-in-neglected-tropical-diseases",publishedDate:"December 4th 2019",editedByType:"Edited by",bookSignature:"Alfonso J. Rodriguez-Morales",hash:"61c627da05b2ace83056d11357bdf361",volumeInSeries:3,fullTitle:"Current Topics in Neglected Tropical Diseases",editors:[{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null},{type:"book",id:"7064",title:"Current Perspectives in Human Papillomavirus",subtitle:null,coverURL:"https://cdn.intechopen.com/books/images_new/7064.jpg",slug:"current-perspectives-in-human-papillomavirus",publishedDate:"May 2nd 2019",editedByType:"Edited by",bookSignature:"Shailendra K. Saxena",hash:"d92a4085627bab25ddc7942fbf44cf05",volumeInSeries:2,fullTitle:"Current Perspectives in Human Papillomavirus",editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002bRET3QAO/Profile_Picture_2022-05-10T10:10:26.jpeg",institutionString:"King George's Medical University",institution:{name:"King George's Medical University",institutionURL:null,country:{name:"India"}}}],equalEditorOne:null,equalEditorTwo:null,equalEditorThree:null}]},subseriesFiltersForPublishedBooks:[{group:"subseries",caption:"Bacterial Infectious Diseases",value:3,count:2},{group:"subseries",caption:"Parasitic Infectious Diseases",value:5,count:4},{group:"subseries",caption:"Viral Infectious Diseases",value:6,count:7}],publicationYearFilters:[{group:"publicationYear",caption:"2022",value:2022,count:2},{group:"publicationYear",caption:"2021",value:2021,count:4},{group:"publicationYear",caption:"2020",value:2020,count:3},{group:"publicationYear",caption:"2019",value:2019,count:3},{group:"publicationYear",caption:"2018",value:2018,count:1}],authors:{paginationCount:301,paginationItems:[{id:"116250",title:"Dr.",name:"Nima",middleName:null,surname:"Rezaei",slug:"nima-rezaei",fullName:"Nima Rezaei",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/116250/images/system/116250.jpg",biography:"Professor Nima Rezaei obtained an MD from Tehran University of Medical Sciences, Iran. He also obtained an MSc in Molecular and Genetic Medicine, and a Ph.D. in Clinical Immunology and Human Genetics from the University of Sheffield, UK. He also completed a short-term fellowship in Pediatric Clinical Immunology and Bone Marrow Transplantation at Newcastle General Hospital, England. Dr. Rezaei is a Full Professor of Immunology and Vice Dean of International Affairs and Research, at the School of Medicine, Tehran University of Medical Sciences, and the co-founder and head of the Research Center for Immunodeficiencies. He is also the founding president of the Universal Scientific Education and Research Network (USERN). Dr. Rezaei has directed more than 100 research projects and has designed and participated in several international collaborative projects. He is an editor, editorial assistant, or editorial board member of more than forty international journals. He has edited more than 50 international books, presented more than 500 lectures/posters in congresses/meetings, and published more than 1,100 scientific papers in international journals.",institutionString:"Tehran University of Medical Sciences",institution:{name:"Tehran University of Medical Sciences",country:{name:"Iran"}}},{id:"180733",title:"Dr.",name:"Jean",middleName:null,surname:"Engohang-Ndong",slug:"jean-engohang-ndong",fullName:"Jean Engohang-Ndong",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/180733/images/system/180733.png",biography:"Dr. Jean Engohang-Ndong was born and raised in Gabon. After obtaining his Associate Degree of Science at the University of Science and Technology of Masuku, Gabon, he continued his education in France where he obtained his BS, MS, and Ph.D. in Medical Microbiology. He worked as a post-doctoral fellow at the Public Health Research Institute (PHRI), Newark, NJ for four years before accepting a three-year faculty position at Brigham Young University-Hawaii. Dr. Engohang-Ndong is a tenured faculty member with the academic rank of Full Professor at Kent State University, Ohio, where he teaches a wide range of biological science courses and pursues his research in medical and environmental microbiology. Recently, he expanded his research interest to epidemiology and biostatistics of chronic diseases in Gabon.",institutionString:"Kent State University",institution:{name:"Kent State University",country:{name:"United States of America"}}},{id:"188773",title:"Prof.",name:"Emmanuel",middleName:null,surname:"Drouet",slug:"emmanuel-drouet",fullName:"Emmanuel Drouet",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/188773/images/system/188773.png",biography:"Emmanuel Drouet, PharmD, is a Professor of Virology at the Faculty of Pharmacy, the University Grenoble-Alpes, France. As a head scientist at the Institute of Structural Biology in Grenoble, Dr. Drouet’s research investigates persisting viruses in humans (RNA and DNA viruses) and the balance with our host immune system. He focuses on these viruses’ effects on humans (both their impact on pathology and their symbiotic relationships in humans). He has an excellent track record in the herpesvirus field, and his group is engaged in clinical research in the field of Epstein-Barr virus diseases. He is the editor of the online Encyclopedia of Environment and he coordinates the Universal Health Coverage education program for the BioHealth Computing Schools of the European Institute of Science.",institutionString:null,institution:{name:"Grenoble Alpes University",country:{name:"France"}}},{id:"131400",title:"Prof.",name:"Alfonso J.",middleName:null,surname:"Rodriguez-Morales",slug:"alfonso-j.-rodriguez-morales",fullName:"Alfonso J. Rodriguez-Morales",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/131400/images/system/131400.png",biography:"Dr. Rodriguez-Morales is an expert in tropical and emerging diseases, particularly zoonotic and vector-borne diseases (especially arboviral diseases). He is the president of the Travel Medicine Committee of the Pan-American Infectious Diseases Association (API), as well as the president of the Colombian Association of Infectious Diseases (ACIN). He is a member of the Committee on Tropical Medicine, Zoonoses, and Travel Medicine of ACIN. He is a vice-president of the Latin American Society for Travel Medicine (SLAMVI) and a Member of the Council of the International Society for Infectious Diseases (ISID). Since 2014, he has been recognized as a Senior Researcher, at the Ministry of Science of Colombia. He is a professor at the Faculty of Medicine of the Fundacion Universitaria Autonoma de las Americas, in Pereira, Risaralda, Colombia. He is an External Professor, Master in Research on Tropical Medicine and International Health, Universitat de Barcelona, Spain. He is also a professor at the Master in Clinical Epidemiology and Biostatistics, Universidad Científica del Sur, Lima, Peru. In 2021 he has been awarded the “Raul Isturiz Award” Medal of the API. Also, in 2021, he was awarded with the “Jose Felix Patiño” Asclepius Staff Medal of the Colombian Medical College, due to his scientific contributions to COVID-19 during the pandemic. He is currently the Editor in Chief of the journal Travel Medicine and Infectious Diseases. His Scopus H index is 47 (Google Scholar H index, 68).",institutionString:"Institución Universitaria Visión de las Américas, Colombia",institution:null},{id:"332819",title:"Dr.",name:"Chukwudi Michael",middleName:"Michael",surname:"Egbuche",slug:"chukwudi-michael-egbuche",fullName:"Chukwudi Michael Egbuche",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/332819/images/14624_n.jpg",biography:"I an Dr. Chukwudi Michael Egbuche. I am a Senior Lecturer in the Department of Parasitology and Entomology, Nnamdi Azikiwe University, Awka.",institutionString:null,institution:{name:"Nnamdi Azikiwe University",country:{name:"Nigeria"}}},{id:"284232",title:"Mr.",name:"Nikunj",middleName:"U",surname:"Tandel",slug:"nikunj-tandel",fullName:"Nikunj Tandel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/284232/images/8275_n.jpg",biography:'Mr. Nikunj Tandel has completed his Master\'s degree in Biotechnology from VIT University, India in the year of 2012. He is having 8 years of research experience especially in the field of malaria epidemiology, immunology, and nanoparticle-based drug delivery system against the infectious diseases, autoimmune disorders and cancer. He has worked for the NIH funded-International Center of Excellence in Malaria Research project "Center for the study of complex malaria in India (CSCMi)" in collaboration with New York University. The preliminary objectives of the study are to understand and develop the evidence-based tools and interventions for the control and prevention of malaria in different sites of the INDIA. Alongside, with the help of next-generation genomics study, the team has studied the antimalarial drug resistance in India. Further, he has extended his research in the development of Humanized mice for the study of liver-stage malaria and identification of molecular marker(s) for the Artemisinin resistance. At present, his research focuses on understanding the role of B cells in the activation of CD8+ T cells in malaria. Received the CSIR-SRF (Senior Research Fellow) award-2018, FIMSA (Federation of Immunological Societies of Asia-Oceania) Travel Bursary award to attend the IUIS-IIS-FIMSA Immunology course-2019',institutionString:"Nirma University",institution:{name:"Nirma University",country:{name:"India"}}},{id:"334383",title:"Ph.D.",name:"Simone",middleName:"Ulrich",surname:"Ulrich Picoli",slug:"simone-ulrich-picoli",fullName:"Simone Ulrich Picoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/334383/images/15919_n.jpg",biography:"Graduated in Pharmacy from Universidade Luterana do Brasil (1999), Master in Agricultural and Environmental Microbiology from Federal University of Rio Grande do Sul (2002), Specialization in Clinical Microbiology from Universidade de São Paulo, USP (2007) and PhD in Sciences in Gastroenterology and Hepatology (2012). She is currently an Adjunct Professor at Feevale University in Medicine and Biomedicine courses and a permanent professor of the Academic Master\\'s Degree in Virology. She has experience in the field of Microbiology, with an emphasis on Bacteriology, working mainly on the following topics: bacteriophages, bacterial resistance, clinical microbiology and food microbiology.",institutionString:null,institution:{name:"Universidade Feevale",country:{name:"Brazil"}}},{id:"229220",title:"Dr.",name:"Amjad",middleName:"Islam",surname:"Aqib",slug:"amjad-aqib",fullName:"Amjad Aqib",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229220/images/system/229220.png",biography:"Dr. Amjad Islam Aqib obtained a DVM and MSc (Hons) from University of Agriculture Faisalabad (UAF), Pakistan, and a PhD from the University of Veterinary and Animal Sciences Lahore, Pakistan. Dr. Aqib joined the Department of Clinical Medicine and Surgery at UAF for one year as an assistant professor where he developed a research laboratory designated for pathogenic bacteria. Since 2018, he has been Assistant Professor/Officer in-charge, Department of Medicine, Manager Research Operations and Development-ORIC, and President One Health Club at Cholistan University of Veterinary and Animal Sciences, Bahawalpur, Pakistan. He has nearly 100 publications to his credit. His research interests include epidemiological patterns and molecular analysis of antimicrobial resistance and modulation and vaccine development against animal pathogens of public health concern.",institutionString:"Cholistan University of Veterinary and Animal Sciences",institution:null},{id:"62900",title:"Prof.",name:"Fethi",middleName:null,surname:"Derbel",slug:"fethi-derbel",fullName:"Fethi Derbel",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/62900/images/system/62900.jpeg",biography:"Professor Fethi Derbel was born in 1960 in Tunisia. He received his medical degree from the Sousse Faculty of Medicine at Sousse, University of Sousse, Tunisia. He completed his surgical residency in General Surgery at the University Hospital Farhat Hached of Sousse and was a member of the Unit of Liver Transplantation in the University of Rennes, France. He then worked in the Department of Surgery at the Sahloul University Hospital in Sousse. Professor Derbel is presently working at the Clinique les Oliviers, Sousse, Tunisia. His hospital activities are mostly concerned with laparoscopic, colorectal, pancreatic, hepatobiliary, and gastric surgery. He is also very interested in hernia surgery and performs ventral hernia repairs and inguinal hernia repairs. He has been a member of the GREPA and Tunisian Hernia Society (THS). During his residency, he managed patients suffering from diabetic foot, and he was very interested in this pathology. For this reason, he decided to coordinate a book project dealing with the diabetic foot. Professor Derbel has published many articles in journals and collaborates intensively with IntechOpen Access Publisher as an editor.",institutionString:"Clinique les Oliviers",institution:null},{id:"300144",title:"Dr.",name:"Meriem",middleName:null,surname:"Braiki",slug:"meriem-braiki",fullName:"Meriem Braiki",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/300144/images/system/300144.jpg",biography:"Dr. Meriem Braiki is a specialist in pediatric surgeon from Tunisia. She was born in 1985. She received her medical degree from the University of Medicine at Sousse, Tunisia. She achieved her surgical residency training periods in Pediatric Surgery departments at University Hospitals in Monastir, Tunis and France.\r\nShe is currently working at the Pediatric surgery department, Sidi Bouzid Hospital, Tunisia. Her hospital activities are mostly concerned with laparoscopic, parietal, urological and digestive surgery. She has published several articles in diffrent journals.",institutionString:"Sidi Bouzid Regional Hospital",institution:null},{id:"229481",title:"Dr.",name:"Erika M.",middleName:"Martins",surname:"de Carvalho",slug:"erika-m.-de-carvalho",fullName:"Erika M. de Carvalho",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/229481/images/6397_n.jpg",biography:null,institutionString:null,institution:{name:"Oswaldo Cruz Foundation",country:{name:"Brazil"}}},{id:"186537",title:"Prof.",name:"Tonay",middleName:null,surname:"Inceboz",slug:"tonay-inceboz",fullName:"Tonay Inceboz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/186537/images/system/186537.jfif",biography:"I was graduated from Ege University of Medical Faculty (Turkey) in 1988 and completed his Med. PhD degree in Medical Parasitology at the same university. I became an Associate Professor in 2008 and Professor in 2014. I am currently working as a Professor at the Department of Medical Parasitology at Dokuz Eylul University, Izmir, Turkey.\n\nI have given many lectures, presentations in different academic meetings. I have more than 60 articles in peer-reviewed journals, 18 book chapters, 1 book editorship.\n\nMy research interests are Echinococcus granulosus, Echinococcus multilocularis (diagnosis, life cycle, in vitro and in vivo cultivation), and Trichomonas vaginalis (diagnosis, PCR, and in vitro cultivation).",institutionString:"Dokuz Eylül University",institution:{name:"Dokuz Eylül University",country:{name:"Turkey"}}},{id:"71812",title:"Prof.",name:"Hanem Fathy",middleName:"Fathy",surname:"Khater",slug:"hanem-fathy-khater",fullName:"Hanem Fathy Khater",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/71812/images/1167_n.jpg",biography:"Prof. Khater is a Professor of Parasitology at Benha University, Egypt. She studied for her doctoral degree, at the Department of Entomology, College of Agriculture, Food and Natural Resources, University of Missouri, Columbia, USA. She has completed her Ph.D. degrees in Parasitology in Egypt, from where she got the award for “the best scientific Ph.D. dissertation”. She worked at the School of Biological Sciences, Bristol, England, the UK in controlling insects of medical and veterinary importance as a grant from Newton Mosharafa, the British Council. Her research is focused on searching of pesticides against mosquitoes, house flies, lice, green bottle fly, camel nasal botfly, soft and hard ticks, mites, and the diamondback moth as well as control of several parasites using safe and natural materials to avoid drug resistances and environmental contamination.",institutionString:null,institution:{name:"Banha University",country:{name:"Egypt"}}},{id:"99780",title:"Prof.",name:"Omolade",middleName:"Olayinka",surname:"Okwa",slug:"omolade-okwa",fullName:"Omolade Okwa",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/99780/images/system/99780.jpg",biography:"Omolade Olayinka Okwa is presently a Professor of Parasitology at Lagos State University, Nigeria. She has a PhD in Parasitology (1997), an MSc in Cellular Parasitology (1992), and a BSc (Hons) Zoology (1990) all from the University of Ibadan, Nigeria. She teaches parasitology at the undergraduate and postgraduate levels. She was a recipient of a Commonwealth fellowship supported by British Council tenable at the Centre for Entomology and Parasitology (CAEP), Keele University, United Kingdom between 2004 and 2005. She was awarded an Honorary Visiting Research Fellow at the same university from 2005 to 2007. \nShe has been an external examiner to the Department of Veterinary Microbiology and Parasitology, University of Ibadan, MSc programme between 2010 and 2012. She is a member of the Nigerian Society of Experimental Biology (NISEB), Parasitology and Public Health Society of Nigeria (PPSN), Science Association of Nigeria (SAN), Zoological Society of Nigeria (ZSN), and is Vice Chairperson of the Organisation of Women in Science (OWSG), LASU chapter. She served as Head of Department of Zoology and Environmental Biology, Lagos State University from 2007 to 2010 and 2014 to 2016. She is a reviewer for several local and international journals such as Unilag Journal of Science, Libyan Journal of Medicine, Journal of Medicine and Medical Sciences, and Annual Research and Review in Science. \nShe has authored 45 scientific research publications in local and international journals, 8 scientific reviews, 4 books, and 3 book chapters, which includes the books “Malaria Parasites” and “Malaria” which are IntechOpen access publications.",institutionString:"Lagos State University",institution:{name:"Lagos State University",country:{name:"Nigeria"}}},{id:"273100",title:"Dr.",name:"Vijay",middleName:null,surname:"Gayam",slug:"vijay-gayam",fullName:"Vijay Gayam",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/273100/images/system/273100.jpeg",biography:"Dr. Vijay Bhaskar Reddy Gayam is currently practicing as an internist at Interfaith Medical Center in Brooklyn, New York, USA. He is also a Clinical Assistant Professor at the SUNY Downstate University Hospital and Adjunct Professor of Medicine at the American University of Antigua. He is a holder of an M.B.B.S. degree bestowed to him by Osmania Medical College and received his M.D. at Interfaith Medical Center. His career goals thus far have heavily focused on direct patient care, medical education, and clinical research. He currently serves in two leadership capacities; Assistant Program Director of Medicine at Interfaith Medical Center and as a Councilor for the American\r\nFederation for Medical Research. As a true academician and researcher, he has more than 50 papers indexed in international peer-reviewed journals. He has also presented numerous papers in multiple national and international scientific conferences. His areas of research interest include general internal medicine, gastroenterology and hepatology. He serves as an editor, editorial board member and reviewer for multiple international journals. His research on Hepatitis C has been very successful and has led to multiple research awards, including the 'Equity in Prevention and Treatment Award” from the New York Department of Health Viral Hepatitis Symposium (2018) and the 'Presidential Poster Award” awarded to him by the American College of Gastroenterology (2018). He was also awarded 'Outstanding Clinician in General Medicine” by Venus International Foundation for his extensive research expertise and services, perform over and above the standard expected in the advancement of healthcare, patient safety and quality of care.",institutionString:"Interfaith Medical Center",institution:{name:"Interfaith Medical Center",country:{name:"United States of America"}}},{id:"93517",title:"Dr.",name:"Clement",middleName:"Adebajo",surname:"Meseko",slug:"clement-meseko",fullName:"Clement Meseko",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/93517/images/system/93517.jpg",biography:"Dr. Clement Meseko obtained DVM and PhD degree in Veterinary Medicine and Virology respectively. He has worked for over 20 years in both private and public sectors including the academia, contributing to knowledge and control of infectious disease. Through the application of epidemiological skill, classical and molecular virological skills, he investigates viruses of economic and public health importance for the mitigation of the negative impact on people, animal and the environment in the context of Onehealth. \r\nDr. Meseko’s field experience on animal and zoonotic diseases and pathogen dynamics at the human-animal interface over the years shaped his carrier in research and scientific inquiries. He has been part of the investigation of Highly Pathogenic Avian Influenza incursions in sub Saharan Africa and monitors swine Influenza (Pandemic influenza Virus) agro-ecology and potential for interspecies transmission. 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