\r\n\tIn the last decades, particular attention to this field has been paid to the coastal erosion problem all over the world. Indeed, the deployment of artificial reservoirs, modification of the runoff characteristics of internal areas, sand extraction from rivers, and harbor siltation, caused a decrease of sediment input on the coastal environments, and, therefore, a generalized deficit in the sediment budget. Often, dredging activities are required to collect sediment finalized to “soft” techniques to restore beaches or to move the sand trapped in the harbor (clean or contaminated). \r\n\tMoreover, the coastal protections induced hydrodynamics and morphodynamics modifications inducing sometimes strong variations to the sediment transport regime.
\r\n
\r\n\tHistorically, all these aspects are related to specific research areas ranging from engineering, geology, geomorphology, biology, etc, but it is difficult to find a comprehensive overview of these topics.
\r\n
\r\n\tThis book is intended to collect original works and review concerning numerical and experimental investigation, theoretical works, methodological approaches, and any other technique that allow giving the actual state-of-the-art in the field of sediment transport.
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1. Introduction
Avermectins are a complex of 16-membered macrocyclic lactones produced from soil fermentation of the actinomycete S. avermitilis [1, 2]. There exist eight avermectin compounds (A1a, A1b, A2a, A2b, B1a, B1b, B2a, and B2b), of which ivermectin is the most commonly employed due to its semi-synthetic mixture (80% B1a and 20% B1b), and its potent antiparasitic activity as well as its safety [3]. The family of compounds from which Ivermectin is derived was discovered by Nobel laureates Satoshi Omura and William Campbell in the 1970s. The chemical is effective against a wide number of parasites and arthropods - pinworms, mites, lice, heartworms and fleas in dogs, parasitic worms in pasture animals by disrupting the fluid exchange through the insect’s cell membrane, and in the past 40 years, ivermectin has been used extensively for agriculture and veterinary purposes [4, 5, 6, 7].
The success of ivermectin treatment as antiparasitic is due to its high affinity for the glutamate-gated chloride channels (Glu-Cl) present in parasite cells but absent in vertebrates. The ivermectin-channel-interaction prevents channel closure, leading to plasma membrane hyperpolarization, paralyzing the target parasite’s pharyngeal and somatic muscles, triggering its death [2]. In addition to activating the Glu-Cl parasites channels, ivermectin acts as a dose-dependent positive allosteric regulator of several vertebrate ligand-gated channels, including the γ-aminobutyric acid type-A receptor (GABA receptor), glycine receptor, neuronal α7-nicotinic receptor, and purinergic P2X4 receptor. The effects of ivermectin over these receptors include the potentiation of agonist-induced currents at low concentrations and channel opening at higher concentrations [8]. However, GABA-sensitive neurons are protected by the blood–brain barrier within the central nervous system, protecting vertebrates against the potentially harmful effects of Ivermectin [3, 6].
2. Drug repurposing in cancer therapy
Effective, safe, and affordable cancer drugs are highly needed to reduce cancer mortality. The field of drug repurposing emerged in the early 1990s as an alternative to the conventional drug discovery model. This model entails targeting discovery and validation, lead identification by high-throughput screening, and lead optimization by medicinal chemistry. Drug repurposing surged to overcome the pharmaceutical industry’s limited productivity regarding the number of approved drugs concerning the long time and huge money required to develop a drug. Classical drug discovery requires an average of 15 years of research, whereas drug development by repurposing is portended to be cheaper, faster, and safer. The significant advantage of drug repurposing is that the pharmacokinetics, pharmacodynamics, and toxicity profiles of drugs are, in general, well known; thus, its rapid translation into phase II and III clinical trials is feasible [9]. Among the different drugs currently studied under the focus of therapeutic repositioning, ivermectin is very promising. It has been shown to have antitumor effects in vitro and in vivo (Figure 1).
Figure 1.
Cancer targets of ivermectin. 1. Decreasing the function of the mitochondrial complex I, Ivermectin, limits the electronic movement in the oxidative phosphorylation pathway that stimulates oxygen consumption rate to generate ATP for the cell. Low ATP levels are related to a failure in the P-glycoprotein pump to extrude chemotherapy drugs. Concomitantly there is a reduction in the phosphorylation levels of Akt, impacting the mitochondrial biogenesis process. Furthermore, alterations in the mitochondrial machinery are related to increased levels of reactive oxygen species that damage DNA. 2. Ivermectin limits the function of the RNA helicases NS3 and DDX23, both of which are related to ribosome biogenesis and post-transcriptional modifications, as well as with mRNA degradation. DDX23 acts as a promoter of miR-21, which is a well-recognized stimulator of tumor progression. 3. The WNT-TCF pathway, involved in cancer progression and metastases, is inhibited by Ivermectin. Indeed, this compound represses AXIN2, LGR5, and ASCL2, all of them WNT-TCF targets. At the same time, it promotes the repressor of the WNT signaling FILIP1L. Both effects inhibit the ability of WNT-TCF to downregulate the tumor suppressor APC and limit the translocation of β–catenin to the nucleus for epithelial to mesenchymal transition in metastatic events. 4. Ivermectin acts as an ionophore by the up-regulation of chloride channels to generate apoptosis and osmotic cell death. 5. Ivermectin induces immunogenic cell death by stimulating an ATP- and HMGB1-enriched microenvironment, which promotes inflammation. This drug also increases ATP sensitivity and calcium signals in P2X membranal receptors, particularly P2X4 and P2X7, to induce ATP-dependent immune responses. 6. Ivermectin promotes the poly-ubiquitination of the kinase PAK1, which directs it to degradation in the proteasome. Defective PAK1, in turn, inhibits the Akt/mTOR pathway. At the same time, Ivermectin stimulates the expression of Beclin1 and Atg5, both related to induction of autophagy. Particularly, Beclin1 increases the expression of the positive autophagy regulators Atg14L and Vps34 and reduces the negative regulator of apoptosis Bcl-2. Together, this generates autophagy and apoptosis. 7,8. Ivermectin modifies the epigenetic signature and the self-renewal activity in the malignant cell due to its ability to mimic the SIN3-interaction that binds to the PAH2 motif of the ca.
3. Antitumor effects of Ivermectin-mechanisms of action and in vitro data
Ivermectin has demonstrated antitumor effects in different types of cancers. Among mechanisms of action reported, ivermectin interacts and affects the function of 1) mitochondrial I complex, the multidrug resistance protein (MDR), 2) RNA helicases, 3) the WNT-TCF pathway, 4) chloride channel receptor, 5) immunogenic cell death via ATP- and HMGB1, 6) PAK-1, 7,8) epigenetic signature and sel-renewal of stem cells [10]. Preclinical testing have demonstrated inhibition of cell growth, induction of apoptosis in different cancer cell lines and antitumor effects in murine models (Figure 1) [11, 12, 13, 14, 15, 16, 17, 18, 19]. The in vitro antitumor effects are observed at a median concentration of 5 μM (0.01–100 μM), which is clinically attainable according to the pharmacokinetic data in humans shown in Table 1. We present a review of the laboratory results of ivermectin on various cancer cell lines below.
Illness/Adverse effects
Mild
Intermediate
Severe
Onchocerciasis
Myalgia, skin eruptions, joints swelling, limbs or face, itching, fever and cold
Skin pain and edema, arthralgia, bone pain, severe dizziness, high fever, dyspnea, and hypotension
NA
Filariasis
Headache and nausea
NA
Encephalopathy
Scabies
Nausea
Severe headache, abdominal pain, and tachycardia
NA
Table 1.
Adverse effects caused by Ivermectin.
3.1 Ovarian cancer
Ivermectin blocks the oncogenic kinase PAK1 in human ovarian cancer and in NF2-deficient Schwannoma cell lines to suppress their PAK1-dependent growth in cell culture at a half maximal inhibitory concentration (IC50) between 5 and 20 μM [14]. PAK1 is involved in various signaling pathways that play an essential role in cytoskeletal dynamics, cell adhesion, migration, proliferation, apoptosis, and mitosis. It is required for the growth of approximately 70% of neoplasms [20]. Additionally, cancer stem-like cells derived from SKOV-3 cell line treated with 5 μM ivermectin showed a significant decrease in cell viability and clonogenic capacity. Also, the expression levels of Nanog, Sox2, and Oct4 are reduced after treatment with ivermectin 5 μM [11].
3.2 Breast cancer
Ivermectin inhibits the ATK/mTOR pathway in breast cancer cell lines by promoting ubiquitination of PAK1. Ivermectin disrupts the binding of PAK1 protein with AKT, and in turn hinders the phosphorylation and activation of AKT; resulting in AKT/mTOR pathway inactivation. These effects of ivermectin are observed at concentrations above 10 μM [15]. Additionally, ivermectin preferentially inhibits the viability of cancer stem-like cells enriched populations (CD44+/ CD24−) in the range of 0.2–8 μM via reducing the expression of maintenance of the pluripotency and self-renewal markers Nanog, Oct4, and Sox2 at both mRNA and protein levels [11]. Separately, a study demonstrated that 1 μM ivermectin treatment inhibits the function of SIN3 [16], which is part of a complex that positively regulates Nanog and Sox2, leading to a decrease in mammospheres number [21]. Furthermore, ivermectin was reported to induce E-cadherin and Estrogen Receptor 1 expression and the restoration of tamoxifen sensitivity in a triple-negative breast cancer model. According to these observations, ivermectin has potential antitumor effects in triple-negative breast cancer [16]. Another study demonstrated a synergy between ivermectin with docetaxel or cyclophosphamide in estrogen receptor-negative breast cancer cells and a synergistic effect with tamoxifen in estrogen receptor-positive breast cancer cell lines [22].
3.3 Liver cancer
In human combined hepatocellular-cholangiocarcinomas and intrahepatic cholangiocarcinomas (cHC-CCs and ICCs), there is robust YAP1 activation. YAP1 is a transcriptional regulator of genes involved in cell proliferation and suppression of apoptotic genes, and itis inhibited in the Hippo signaling pathway which allows tumor suppression. Nuclear translocation of YAP1/TAZ also increases transcription of TGF-βs [23]. Thus, it is possible that coordinated targeting of YAP1/TAZ and TGF-β signaling may be a treatment for cHC-CCs and ICCs displaying dysregulated Hippo signaling and meanwhile drug screening revealed ivermectin to inhibit YAP1 activation [23].
3.4 Cervical cancer
Ivermectin inhibits the viability of HeLa cells and induces a G1/S cell cycle arrest leading to apoptosis and morphological changes of DNA fragmentation and chromatin condensation of such cells. Additionally, ivermectin can significantly increase intracellular ROS content and inhibit the migration of HeLa cells [24].
3.5 Glioblastoma
Ivermectin inhibits the growth of glioma cells by inducing cell cycle arrest and apoptosis in vitro and in vivo [25]. Specifically, in glioblastoma and brain endothelial cells, ivermectin has been reported to induce mitochondrial dysfunction. It inhibits cell growth and colony formation and blocks the enzymatic activity of the respiratory chain complex I, thereby decreases mitochondrial respiration, membrane potential, and ATP levels while increasing the generation of superoxides that in turn induces cell death by caspase-dependent apoptosis. Additionally, ivermectin also inhibits angiogenesis at concentrations above 5 μM [12].
3.6 Leukemia and prostate cancer
The treatment of OCI-AML2 cells with ivermectin increased the concentration of intracellular chloride ions, leading to hyperpolarization of the plasma and mitochondrial membranes and ROS production [18]. In contrast, DU145 and PPC-1 cells and primary normal hematopoietic cells that were resistant to ivermectin did not demonstrate changes in their plasma membrane potential when treated with up to 6 μM ivermectin. Moreover, the in vitro antitumor effect of ivermectin on various cancer cell lines at a concentration of 5 μM showed that DU145 is only minimally reduced in viability and clonogenic capacity, but when it is treated in combination with docetaxel cells demonstrated strong inhibition [22]. In myeloid leukemia cells ivermectin strongly synergizes with daunorubicin and cytarabine [18].
3.7 Colon and lung cancer
The WNT/TCF signaling pathway is constitutively active in many tumors and it regulates genes for cell growth and proliferation. Ivermectin can inhibit the WNT-TCF signaling pathway by decreasing cyclin D1, which is a direct target in this pathway and ivermectin also affects the phosphorylation of β-catenin, which leads to inhibition of proliferation and increased apoptosis in lung and colon tumor cells at concentrations above 5 μM [13].
4. Antitumor effects of ivermectin-animal data
In a wide-range of pre-clinical studies, rodent models of human xenografts of glioblastoma, leukemia, breast and colon carcinomas, as well as a variety of murine cell lines in syngeneic models have consistently shown ivermectin to possess robust antitumor effect at a median dose of 5 mg/Kg [12, 13, 15, 17, 18]. We present a review of some results of anticancer studies of ivermectin in animal below.
4.1 Glioblastoma
Two independent glioblastoma xenograft SCID mice models were established by subcutaneous injection of U87 or T98G cells, and the rodents were subsequently treated with intraperitoneal ivermectin at 40 mg/Kg. The treated mice had demonstrated significant tumor growth inhibition but maintained normal behavior and retained their weight [12]. A separate study using 3 mg/Kg of ivermectin showed a 50% decrease in tumor size and there was near complete regression of tumors at 10 mg/Kg. Ki67 staining also confirmed that glioma cell proliferation was decreased in ivermectin-treated animals compared to controls [17].
4.2 Colon and lung cancers
Melotti et al. used H358 human metastatic lung bronchioalveolar carcinoma cells and DLD1 colorectal adenocarcinoma cells to test the antitumor effects of ivermectin. The animals received intraperitoneal injections of cyclodextrin-conjugated ivermectin daily at 10 mg/kg after tumor establishment. Subsequently, it was found that tumors responded to ivermectin with a near 50% reduction of growth and a repressed lung cancer WNT-TCF signature and enhanced p21 levels [13].
4.3 Breast cancer
Ivermectin was evaluated in an orthotopic breast cancer model with human MDA-MB-231 cells subcutaneously injected in the mammary fat pad of NOD-SCID mice. Xenografts treated with ivermectin grew at a slower rate than those of the control group, and the size and weight of control tumors were macroscopically larger than that of ivermectin-treated tumors [15]. Another study tested JC murine breast cancer cells in Balb/c mice treated with a dose of 3 mg/Kg of ivermectin. Treatment reduced tumor size more than 60% with no changes in weight or behavior of the study animals when compared with controls [22]. Recently it was demonstrated the ivermectin at a dose of 5 mg/Kg induces immunogenic cell death hallmarks with large numbers of intratumoral CDA4+ and CD8+ T cells in a 4 T1 murine tumor model. Thus, ivermectin turns cold tumors into hot ones which allows for marked synergy with check point inhibitor nivolumab, leading to major antitumor effects and most importantly, protective immunity [26].
4.4 Leukemia
Human leukemia (OCI-AML2 and K562) and murine leukemia (MDAY-D2) cells were injected subcutaneously into NOD/SCID mice which were subsequently treated with 3 mg/Kg (human equivalent dose of 0.240 mg/Kg) of ivermectin or control in water via oral gavage. Upon follow-up, the treated mice had up to 70% decrease in their tumor burden without any gross sign of organ toxicity, and treatment led to increased apoptosis in OCI-AML2 xenografts [18]. It must be remarked that most of the in vivo studies to evaluate the antitumor effects of ivermectin dose ranging from 3 to 10 mg/Kg. These mice doses translate into human to 0.240 to 0.810 mg/Kg which are clinically attainable [27].
5. Clinical experience with ivermectin
As mentioned above, there has been extensive clinical use of ivermectin as an anti-parasitic, and the drug has been repurposed for use against other pathogens and non-parasitic conditions in humans. However, despite considerable preclinical evidence of antitumor effects of ivermectin, it is curious that no clinical studies of ivermectin against cancer have been reported nor clinical trials launched. However, there is a case report on three children with refractory and heavily pretreated acute myeloblastyic leukemia. In the three cases, ivermectin was at 1 mg/Kg either alone or in combination with Ara-C. Two of them had clinical improvement with durable stable disease in one, a and complete hematological response the second. The third one receiving ivermectin alone had no response. Though anecdotic, these data demonstrate that ivermectin can be safely administered at dosis five times higher the recommended dose of 0.200 mg/Kg, and that can show efficacy combined with cytotoxics [28].
Here, we briefly review the clinical experience with ivermectin as an antiparasitic as well as in other repurposed indications, with special attention to its toxicities and safety and its clinical pharmacology, the data of which can be a basis for future clinical trials of ivermectin against cancer.
5.1 Ivermectin use as anti-parasitic
Because of its broad spectrum applicability, ivermectin can be applied to treat onchocerciasis, lymphatic filariasis, strongyloidiasis, ascariasis, scabiasis, and enterobiasis. Since its discovery, ivermectin has been administered to millions of patients with the above parasitic infections around the world. Mild adverse effects of oral ivermectin therapy against certain parasites are common; many of them appear within 24-48 hours of the onset of therapy and are related to ivermectin dose as well as the microfilariae load in the skin in case of filiariasis [29, 30]. Some of these adverse effects include myalgia, skin rashes, joints swelling, limbs or face itching, fever, and chills. These effects are usually transient and do not require treatment [31, 32]. Moderate to severe effects are less common and may include skin edema with the presence of pain, arthralgia, severe dizziness, high fever, dyspnea, and hypotension (Mazzotti’s Reaction). It is known that such reaction is not related to the administration of Ivermectin but with the parasite amount present in the host [30, 31]. In addition to Mazzotti’s reaction, there have been cases of severe encephalopathy that can be fatal in patients with onchocerciasis and filariasis after treatment with ivermectin. The symptoms of encephalopathy include altered mental status, incontinence, and difficulty standing or walking 48 hours after ivermectin treatment [32, 33]. This effect is again probably due to the obstruction of the cerebral microcirculation due to the accumulation of paralyzed or killed parasites and not by ivermectin itself [34, 35]. Also, toxic effects have been linked to ivermectin’s interaction with P-glycoprotein [8]. The absence of P-glycoprotein determines the accumulation of Ivermectin in the brain of transgenic mice who do not express it and dogs with impaired P-glycoprotein function (commonly a 4 base-pair deletion of the MDR-1 gene that produces a stop codon) have increased neurotoxicity to ivermectin [36]. Table 2 summarizes ivermectin’s adverse effects. The dose and schedules vary but human doses are standardized for approved indications within the range of 0.15 to 0.4 mg/Kg. For onchocerciasis, the recommended dose is 0.15 mg/Kg once every 12 months, though patients with heavy ocular infection may require retreatment every 3 or 6 months. Filariasis usually requires a single dose of 0.4 mg/Kg. In strongyloidiasis, a single dose of 0.2 mg/Kg is recommended; however, in immunocompromised (including HIV) patients, the treatment may require repeated administration (i.e. every two weeks) and continued suppressive therapy (i.e. once a month). A single dose of 0.2 mg/Kg is also used to treat ascariasis, while the same dose repeated once at two weeks is recommended for scabiasis [37].
Group
Dose (mg/kg)
Drug delivery
Cmax (ng/mL)
Tmax (h)
AUC μg/h/mL
Onchocercosis patients
0.1–0.2
Oral
52.0
5.2
2.852
Healthy volunteers
0.35–0.6
Oral
87.0
4.2
1.444
Healthy volunteers
0.7–1.1
Oral
165.2
3.6
2.099
Healthy volunteers
1.4–2.0
Oral
247.8
4.2
4.547
Table 2.
Pharmacokinetic data of Ivermectin in humans infected with parasites and in healthy volunteers.
Recently, there has been a growing interest in newer anti-parasitic indications of ivermectin such as against soil-transmitted helminths and malaria, hence doses above 0.4 mg/Kg are being evaluated for achieving higher plasma levels [38, 39].
An example is a pharmacokinetic trial using 18 mg ivermectin tablets in 54 healthy adult volunteers to evaluate the safety of fixed regimens of 18 and 36 mg [40]. A meta-analysis to investigate the safety of higher doses of ivermectin identified four studies for inclusion, and found no differences in the number of individuals experiencing adverse events at higher doses. A descriptive analysis of these clinical trials for a variety of indications also showed no difference in the severity of the adverse events between standard (up to 0.4 mg/Kg) and higher doses of Ivermectin (0.4-0.7 mg/Kg; 0.6 mg/Kg, and 0.8 mg/Kg). Only one trial showed an increase in transient and mild to moderate subjective ocular events such as transitory blurring of vision, itching or pain of the eye, and dyschromatopsia in the higher-dose group in a trial to treat onchocerciasis. Meanwhile, severe adverse events described as life-threatening, was reported in only one out of the four studies with one case of anaphylaxis at the standard dose and another case of QTc prolongation likely due to drug-drug interaction in a higher-dose group [41]. The result of this small meta-analysis is suggestive of relatively safety of higher doses of ivermectin.
5.2 Ivermectin’s potential as an anti-viral
Ivermectin exhibits anti-viral activity against viruses both in vitro and in vivo. The antiviral activity is thought to be related to tthe inhibition of nuclear translocation of viral proteins, facilitated by mammalian host importin also known as karyopherin α/β‐1 heterodimerization [42]. It is partially upon this basis that ivermectin has been tested as a treatment in the current COVID-19 pandemic. A recent meta-analysis and systematic review involving 629 COVID-19 patients from 4 observational studies (3 with control arms and 1 without) found that adding ivermectin led to significant clinical improvement compared to control (OR=1.98, 95% CI: 1.11 - 3.53, p=0.02) [43]. however, the authors did caution on the interpretation of their analysis because the low quality of evidence, and it should be noted that one of the trials included in the analysis was subsequently retracted. Meanwhile, several randomized studies evaluating ivermectin against COVID-19 have recently been published. An Iranian trial demonstrated that a single 0.2 mg/Kg dose of ivermectin was well-tolerated in symptomatic COVID-19 patients, and dyspnea, cough and lymphopenia associated with COVID-19 were significantly improved [44]. In two other randomized trials, the time to viral clearance was statistically reduced. The doses and schedules in these two trials were ivermectin at a fixed 12 mg daily for 5 days [45] and ivermectin at 0.1, 0.2, and 0.4 mg/Kg once at admission [46]. These were underpowered trials so that further evidence is still required to confirm the clinical usefulness of ivermectin under various COVID-19 clinical scenarios.
5.3 Other uses of ivermectin
Ivermectin possesses possible agonistic bioactivity against the γ-aminobutyric acid (GABA) receptor [47] and it was upon this premise that it was used in a patient with severe spasticity caused by spinal cord damage at a dose of 1.6 mg/Kg subcutaneously twice a week for 12 weeks. The patients had decreased spasm scores, suggesting that ivermectin may reduce spasticity in the spine without adverse effects at this high dose [48].
6. Pharmacokinetics and dose considerations for ivermectin as cancer therapy
Due to its relatively long history of extensive use, the pharmacokinetics of ivermectin has been well studied. The oral route is the only approved for ivermectin administration in humans although it can be given subcutaneously and the intravenous route of administration has also been investigated. Ivermectin is a fat-soluble compound and reaches a peak concentration 4-5 hours after oral administration, and it has a half-life of approximately 19 hours. After administration, it is subsequently extensively metabolized in human liver microsomes by cytochrome P-4503A4, converting the drug to at least ten metabolites, most of them hydroxylated and demethylated derivatives. Its excretion is mainly by the fecal route, and only 1% is excreted in the urine [49]. In healthy individuals and patients infected with onchocerciasis treated with a dose of 0.150 mg /Kg of Ivermectin, significant variability in pharmacokinetic parameters such as absorption, distribution, metabolism, and excretion is not observed [49].
The therapeutic dose for ivermectin as an anti-parasitic compound for human use is is between 0.1 and 0.4 mg/ Kg [4, 5, 6, 7], resulting in an AUC of 1,444 μg/h/mL. This drug exposure, which translates to a plasma concentration of 1.65 μM, is however less than concentrations of 5 μM or greater that has been found necessary to inhibit tumor cells in vitro In a phase I pharmacokinetic study done in healthy volunteers, it was demonstrated that doses up to 2 mg/Kg which leads to an AUC of 4,547 μg/h/mL can translate into a plasma concentration of 5 μM [50], thus the recommended dose for cancer therapy should likely be 2 mg/kg or higher.
7. Discussion
Currently, various efforts to facilitate the discovery of drug repurposing candidates for cancer and a large number of drug candidates do exist [51]. As an example, the Repurposing Drugs in Oncology (ReDO) Project, which is initiated by a non-profit international collaboration of researchers, clinicians, and cancer patient advocates whose goal is to find efficacious, minimally toxic, and affordable cancer treatments identified a total of 268 drugs that matched the following two criteria: i) the drug is licensed for non-cancer indications in at least one country in the world, and ii) the drug is the subject of one or more peer-reviewed publications showing a specific anticancer effect based on in vitro, in vivo, or clinical research in one or more malignancies. According to these criteria, ivermectin can be a potential repurposing candidate for cancer. Ivermectin has extensive preclinical in vitro and in vivo anticancer data and is thus an ideal candidate for clinical trials. An especially promising feature with ivermectin is that its anti-cancer concentration in vitro should be attainable clinically, inexpensively, and without undue toxicity.
8. Conclusion
Ivermectin has been administered to millions of patients as an anti-parasitic drug exhibiting a wide margin of clinical safety. There exists a large body of in vitroand in vivo evidence demonstrating ivermectin’s anti-tumor potential, and ivermectin’s anti-tumor efficacy can be demonstrated at concentrations that are clinically attainable based on clinical pharmacokinetics. We thus propose that ivermectin be considered urgently for clinical trials either as a single agent or in combination with existing antineoplastics for cancer.
\n',keywords:"Drug repurposing, ivermectin, cancer",chapterPDFUrl:"https://cdn.intechopen.com/pdfs/78376.pdf",chapterXML:"https://mts.intechopen.com/source/xml/78376.xml",downloadPdfUrl:"/chapter/pdf-download/78376",previewPdfUrl:"/chapter/pdf-preview/78376",totalDownloads:366,totalViews:0,totalCrossrefCites:1,dateSubmitted:"June 5th 2021",dateReviewed:"August 5th 2021",datePrePublished:"September 1st 2021",datePublished:"June 1st 2022",dateFinished:"September 1st 2021",readingETA:"0",abstract:"Drug repositioning is a alternative strategy to discover and develop anticancer drugs based on identification of new mechanisms of actions and indications for existing compounds. Ivermectin belongs to the avermectin group of compounds, a series of 16-membered macrocyclic lactone moieties discovered in 1967 and FDA-approved for human use since 1987. Ivermectin has since been used by millions of people worldwide, and have demonstrated a wide margin of clinical safety. Here we summarize the in vitro and in vivo evidence demonstrating ivermectin\\'s potential as a multitargeting anticancer drug that exerts antitumor effects against different tumor types. Notably, the in vitro and in vivo antitumor activities of ivermectin are achieved at concentrations that can be clinically achieved based on human pharmacokinetic studies done in the clinical studies. Moreover, repurposed ivermectin safety has been well established recently in clinical studies against COVID-19. Consequently, we believe that ivermectin is an excellent potential candidate drug that can be repurposed for cancer and deserves rigorous evaluation against a variety of cancers in well-designed clinical trials.",reviewType:"peer-reviewed",bibtexUrl:"/chapter/bibtex/78376",risUrl:"/chapter/ris/78376",signatures:"Alfonso Dueñas-González and Mandy Juárez-Rodríguez",book:{id:"10881",type:"book",title:"Drug Repurposing",subtitle:"Molecular Aspects and Therapeutic Applications",fullTitle:"Drug Repurposing - Molecular Aspects and Therapeutic Applications",slug:"drug-repurposing-molecular-aspects-and-therapeutic-applications",publishedDate:"June 1st 2022",bookSignature:"Shailendra K. Saxena",coverURL:"https://cdn.intechopen.com/books/images_new/10881.jpg",licenceType:"CC BY 3.0",editedByType:"Edited by",isbn:"978-1-83969-958-0",printIsbn:"978-1-83969-957-3",pdfIsbn:"978-1-83969-959-7",isAvailableForWebshopOrdering:!0,editors:[{id:"158026",title:"Prof.",name:"Shailendra K.",middleName:null,surname:"Saxena",slug:"shailendra-k.-saxena",fullName:"Shailendra K. Saxena"}],productType:{id:"1",title:"Edited Volume",chapterContentType:"chapter",authoredCaption:"Edited by"}},authors:[{id:"421841",title:"Prof.",name:"Alfonso",middleName:null,surname:"Dueñas-González",fullName:"Alfonso Dueñas-González",slug:"alfonso-duenas-gonzalez",email:"alfonso_duenasg@yahoo.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null},{id:"421846",title:"Dr.",name:"Mandy",middleName:null,surname:"Juárez-Rodríguez",fullName:"Mandy Juárez-Rodríguez",slug:"mandy-juarez-rodriguez",email:"mandy.juarezr@gmail.com",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",institution:null}],sections:[{id:"sec_1",title:"1. Introduction",level:"1"},{id:"sec_2",title:"2. Drug repurposing in cancer therapy",level:"1"},{id:"sec_3",title:"3. Antitumor effects of Ivermectin-mechanisms of action and in vitro data",level:"1"},{id:"sec_3_2",title:"3.1 Ovarian cancer",level:"2"},{id:"sec_4_2",title:"3.2 Breast cancer",level:"2"},{id:"sec_5_2",title:"3.3 Liver cancer",level:"2"},{id:"sec_6_2",title:"3.4 Cervical cancer",level:"2"},{id:"sec_7_2",title:"3.5 Glioblastoma",level:"2"},{id:"sec_8_2",title:"3.6 Leukemia and prostate cancer",level:"2"},{id:"sec_9_2",title:"3.7 Colon and lung cancer",level:"2"},{id:"sec_11",title:"4. Antitumor effects of ivermectin-animal data",level:"1"},{id:"sec_11_2",title:"4.1 Glioblastoma",level:"2"},{id:"sec_12_2",title:"4.2 Colon and lung cancers",level:"2"},{id:"sec_13_2",title:"4.3 Breast cancer",level:"2"},{id:"sec_14_2",title:"4.4 Leukemia",level:"2"},{id:"sec_16",title:"5. Clinical experience with ivermectin",level:"1"},{id:"sec_16_2",title:"5.1 Ivermectin use as anti-parasitic",level:"2"},{id:"sec_17_2",title:"5.2 Ivermectin’s potential as an anti-viral",level:"2"},{id:"sec_18_2",title:"5.3 Other uses of ivermectin",level:"2"},{id:"sec_20",title:"6. Pharmacokinetics and dose considerations for ivermectin as cancer therapy",level:"1"},{id:"sec_21",title:"7. Discussion",level:"1"},{id:"sec_22",title:"8. Conclusion",level:"1"}],chapterReferences:[{id:"B1",body:'Omura S, Crump A (2004) The life and times of Ivermectin - a success story. Nat Rev Microbiol 2 (12):984-989.'},{id:"B2",body:'Omura S (2008) Ivermectin: 25 years and still going strong. Int J Antimicrob Agents 31 (2):91-98.'},{id:"B3",body:'Chabala JC, Mrozik H, Tolman RL, Eskola P, Lusi A, Peterson LH, Woods MF, Fisher MH, Campbell WC, Egerton JR, Ostlind DA (1980) Ivermectin, a new broad-spectrum antiparasitic agent. 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DOI: 10.18433/jpps31457.'},{id:"B44",body:'Shahbaznejad L, Davoudi A, Eslami G, Markowitz JS, Navaeifar MR, Hosseinzadeh F, Movahedi FS, Rezai MS (2021) Effects of Ivermectin in Patients With COVID-19: A Multicenter, Double-Blind, Randomized, Controlled Clinical Trial. Clin Ther S0149-2918(21)00201-0. doi: 10.1016/j.clinthera.2021.04.007.'},{id:"B45",body:'Ahmed S, Karim MM, Ross AG, Hossain MS, Clemens JD, Sumiya MK, Phru CS, Rahman M, Zaman K, Somani J, Yasmin R, Hasnat MA, Kabir A, Aziz AB, Khan WA (2020) A five-day course of Ivermectin for the treatment of COVID-19 may reduce the duration of illness. Int J Infect Dis 103:214-216. DOI: 10.1016/j.ijid.2020.11.191.'},{id:"B46",body:'Pott-Junior H, Bastos Paoliello MM, Miguel AQC, da Cunha AF, de Melo Freire CC, Neves FF, da Silva de Avó LR, Roscani MG, Dos Santos SS, Chachá SGF (2021) Use of ivermectin in the treatment of Covid-19: A pilot trial. 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Repurposing non-cancer drugs in oncology-How many drugs are out there? bioRxiv 2017; 197434.doi: https://doi.org/10.1101/197434'}],footnotes:[],contributors:[{corresp:"yes",contributorFullName:"Alfonso Dueñas-González",address:"alfonso_duenasg@yahoo.com",affiliation:'
Departamento de Medicina Genómica y Toxicologia Ambiental, Instituto de Investigaciones Biomédicas, Universidad Nacional Autonoma de Mexico, Mexico
Subidreccion de Investigacion Básica, Instituto Nacional de Cancerología, Mexico
Desarrollos Especializados en Biotecnología y Diagnóstico Molecular, SA de CV, Mexico
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The Open Access Scholarly Publishers Association (OASPA) was established in 2008 to represent the interests of Open Access (OA) publishers globally in all scientific, technical and scholarly disciplines. Its mission is carried out through exchange of information, the setting of standards, advancing models, advocacy, education, and the promotion of innovation.
\\n
\\n\\n
STM
\\n\\n
\\n\\t
The International Association of Scientific, Technical and Medical Publishers (STM) is the leading global trade association for academic and professional publishers. As a member, IntechOpen has not only made a commitment to STM's Ethical Principles.
\\n
\\n\\n
COPE
\\n\\n
\\n\\t
The Committee on Publication Ethics (COPE) provides advice to editors and publishers on all aspects of publication ethics and, in particular, how to handle cases of misconduct in research and publication. IntechOpen has been a member of COPE since 2013 and adheres to the COPE Code of Conduct and Best Practice Guidelines, ensuring that we maintain the highest ethical standards.
\\n
\\n\\n
Creative Commons
\\n\\n
\\n\\t
Creative Commons (CC) is a nonprofit organization that enables the sharing and use of creativity and knowledge through free legal tools. IntechOpen uses the CC BY 3.0 license for chapters, meaning Authors retain copyright and their work can be reused and adapted as long as the source is properly cited and Authors are acknowledged.
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\\n\\n
Crossref
\\n\\n
\\n\\t
Crossref is the official Digital Object Identifier (DOI) Registration Agency for scholarly and professional publications with a goal of making scholarly communications more effective. IntechOpen deposits metadata and registers DOIs for all content using the Crossref System. IntechOpen also deposits its references and uses the Crossref Cited-by service that enables researchers to track citation statistics.
\\n
\\n\\n
Altmetric and Dimensions from Digital Science
\\n\\n
\\n\\t
Digital Science is a technology company serving the needs of scientific and research communities at key points along the full cycle of research. They support innovative businesses and technologies that make all parts of the research process more open, efficient and effective. IntechOpen integrates tools such as Altmetric to enable our researchers to track and measure the activity around their academic research and Dimensions, to ease access to the most relevant information and better understand and analyze the global research landscape.
\\n
\\n\\n
CLOCKSS
\\n\\n
\\n\\t
CLOCKSS preserves scholarly publications in original formats, ensuring that they always remain available and openly accessible to everyone.
\\n
\\n\\n
Counter
\\n\\n
\\n\\t
COUNTER provides the Code of Practice that enables publishers and vendors to report usage of their electronic resources in a consistent way. This enables libraries to compare data received from different publishers and vendors.
\\n
\\n\\n
DORA
\\n\\n
\\n\\t
DORA is a worldwide initiative covering all scholarly disciplines which recognizes the need to improve the ways in which the outputs of scholarly research are evaluated and seeks to develop and promote best practice. To date it has been signed by over 1500 organizations and around 14,700 individuals.
\\n
\\n\\n
iThenticate
\\n\\n
\\n\\t
iThenticate is the leading provider of professional plagiarism detection and prevention technology and is used worldwide by scholarly publishers and research institutions to ensure the originality of written work before publication. IntechOpen uses the iThenticate plagiarism software to ensure content originality and the research integrity of our published work.
\\n
\\n\\n
Enago
\\n\\n
\\n\\t
IntechOpen collaborates with Enago, through its sister brand, Ulatus, one of the world’s leading providers of book translation services. Their services are designed to convey the essence of your work to readers from across the globe in the language they understand.
\\n\\t
IntechOpen Authors that wish to use this service will receive a 20% discount on all translation services. To find out more information or obtain a quote, please visit https://www.enago.com/intech
\\n
\\n\\n
Straive
\\n\\n
\\n\\t
Straive is the market leader in technology-driven solutions for the extraction, enrichment and transformation of content assets. IntechOpen publishing services are designed to meet the unique needs of Authors. As part of our commitment to that objective, we have an ongoing partnership agreement for production solutions.
\\n
\\n\\n
Amazon
\\n\\n
\\n\\t
Amazon is the world’s largest online retailer and cloud services provider. IntechOpen books have been available on Amazon since 2017, guaranteeing more visibility for our Authors and Academic Editors.
\\n
\\n\\n
DHL
\\n\\n
\\n\\t
IntechOpen has partnered with DHL since 2011 to ensure the fastest delivery of Print on Demand books.
\\n
\\n\\n
United Nations Sustainable Development Goals Publishers Compact
\\n\\n
\\n\\t
The Compact is designed to inspire action among publishers. Launched in collaboration with the International Publishers Association, the Compact aims to accelerate progress to achieve the Sustainable Development Goals (SDGs) by 2030. Signatories aspire to develop sustainable practices and act as champions of the SDGs during the Decade of Action (2020-2030), publishing books and journals that will help inform, develop, and inspire action in that direction. Learn more here
\\n
\\n\\n
River Valley Technology
\\n\\n
\\n\\t
River Valley Technology is the world’s first XML-based publishing solution from submission to peer review to production and to final hosting, giving full control to publishers, with full transparency of data.
\\n
\\n\\n
Figshare
\\n\\n
\\n\\t
Figshare is an online open access repository where researchers can preserve and share their research outputs, including figures, datasets, images, and videos. It is free to upload content and free to access, in adherence to the principle of open data.
The Association of Learned and Professional Society Publishers (ALPSP) is the largest association of scholarly and professional publishers in the world. Its mission is to connect, inform, develop and represent the international scholarly and professional publishing community. IntechOpen has been a member of ALPSP since 2016 and has consequently stayed informed about industry trends through connecting with peers and developing jointly.
\n
\n\n
OASPA
\n\n
\n\t
The Open Access Scholarly Publishers Association (OASPA) was established in 2008 to represent the interests of Open Access (OA) publishers globally in all scientific, technical and scholarly disciplines. Its mission is carried out through exchange of information, the setting of standards, advancing models, advocacy, education, and the promotion of innovation.
\n
\n\n
STM
\n\n
\n\t
The International Association of Scientific, Technical and Medical Publishers (STM) is the leading global trade association for academic and professional publishers. As a member, IntechOpen has not only made a commitment to STM's Ethical Principles.
\n
\n\n
COPE
\n\n
\n\t
The Committee on Publication Ethics (COPE) provides advice to editors and publishers on all aspects of publication ethics and, in particular, how to handle cases of misconduct in research and publication. IntechOpen has been a member of COPE since 2013 and adheres to the COPE Code of Conduct and Best Practice Guidelines, ensuring that we maintain the highest ethical standards.
\n
\n\n
Creative Commons
\n\n
\n\t
Creative Commons (CC) is a nonprofit organization that enables the sharing and use of creativity and knowledge through free legal tools. IntechOpen uses the CC BY 3.0 license for chapters, meaning Authors retain copyright and their work can be reused and adapted as long as the source is properly cited and Authors are acknowledged.
\n
\n\n
Crossref
\n\n
\n\t
Crossref is the official Digital Object Identifier (DOI) Registration Agency for scholarly and professional publications with a goal of making scholarly communications more effective. IntechOpen deposits metadata and registers DOIs for all content using the Crossref System. IntechOpen also deposits its references and uses the Crossref Cited-by service that enables researchers to track citation statistics.
\n
\n\n
Altmetric and Dimensions from Digital Science
\n\n
\n\t
Digital Science is a technology company serving the needs of scientific and research communities at key points along the full cycle of research. They support innovative businesses and technologies that make all parts of the research process more open, efficient and effective. IntechOpen integrates tools such as Altmetric to enable our researchers to track and measure the activity around their academic research and Dimensions, to ease access to the most relevant information and better understand and analyze the global research landscape.
\n
\n\n
CLOCKSS
\n\n
\n\t
CLOCKSS preserves scholarly publications in original formats, ensuring that they always remain available and openly accessible to everyone.
\n
\n\n
Counter
\n\n
\n\t
COUNTER provides the Code of Practice that enables publishers and vendors to report usage of their electronic resources in a consistent way. This enables libraries to compare data received from different publishers and vendors.
\n
\n\n
DORA
\n\n
\n\t
DORA is a worldwide initiative covering all scholarly disciplines which recognizes the need to improve the ways in which the outputs of scholarly research are evaluated and seeks to develop and promote best practice. To date it has been signed by over 1500 organizations and around 14,700 individuals.
\n
\n\n
iThenticate
\n\n
\n\t
iThenticate is the leading provider of professional plagiarism detection and prevention technology and is used worldwide by scholarly publishers and research institutions to ensure the originality of written work before publication. IntechOpen uses the iThenticate plagiarism software to ensure content originality and the research integrity of our published work.
\n
\n\n
Enago
\n\n
\n\t
IntechOpen collaborates with Enago, through its sister brand, Ulatus, one of the world’s leading providers of book translation services. Their services are designed to convey the essence of your work to readers from across the globe in the language they understand.
\n\t
IntechOpen Authors that wish to use this service will receive a 20% discount on all translation services. To find out more information or obtain a quote, please visit https://www.enago.com/intech
\n
\n\n
Straive
\n\n
\n\t
Straive is the market leader in technology-driven solutions for the extraction, enrichment and transformation of content assets. IntechOpen publishing services are designed to meet the unique needs of Authors. As part of our commitment to that objective, we have an ongoing partnership agreement for production solutions.
\n
\n\n
Amazon
\n\n
\n\t
Amazon is the world’s largest online retailer and cloud services provider. IntechOpen books have been available on Amazon since 2017, guaranteeing more visibility for our Authors and Academic Editors.
\n
\n\n
DHL
\n\n
\n\t
IntechOpen has partnered with DHL since 2011 to ensure the fastest delivery of Print on Demand books.
\n
\n\n
United Nations Sustainable Development Goals Publishers Compact
\n\n
\n\t
The Compact is designed to inspire action among publishers. Launched in collaboration with the International Publishers Association, the Compact aims to accelerate progress to achieve the Sustainable Development Goals (SDGs) by 2030. Signatories aspire to develop sustainable practices and act as champions of the SDGs during the Decade of Action (2020-2030), publishing books and journals that will help inform, develop, and inspire action in that direction. Learn more here
\n
\n\n
River Valley Technology
\n\n
\n\t
River Valley Technology is the world’s first XML-based publishing solution from submission to peer review to production and to final hosting, giving full control to publishers, with full transparency of data.
\n
\n\n
Figshare
\n\n
\n\t
Figshare is an online open access repository where researchers can preserve and share their research outputs, including figures, datasets, images, and videos. It is free to upload content and free to access, in adherence to the principle of open data.
\n
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Delac received his B.Sc.E.E. degree in 2003 and is currentlypursuing a Ph.D. degree at the University of Zagreb, Faculty of Electrical Engineering andComputing. His current research interests are digital image analysis, pattern recognition andbiometrics.",institutionString:null,institution:{name:"University of Zagreb",country:{name:"Croatia"}}},{id:"557",title:"Dr.",name:"Andon",middleName:"Venelinov",surname:"Topalov",slug:"andon-topalov",fullName:"Andon Topalov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/557/images/1927_n.jpg",biography:"Dr. Andon V. Topalov received the MSc degree in Control Engineering from the Faculty of Information Systems, Technologies, and Automation at Moscow State University of Civil Engineering (MGGU) in 1979. He then received his PhD degree in Control Engineering from the Department of Automation and Remote Control at Moscow State Mining University (MGSU), Moscow, in 1984. From 1985 to 1986, he was a Research Fellow in the Research Institute for Electronic Equipment, ZZU AD, Plovdiv, Bulgaria. In 1986, he joined the Department of Control Systems, Technical University of Sofia at the Plovdiv campus, where he is presently a Full Professor. He has held long-term visiting Professor/Scholar positions at various institutions in South Korea, Turkey, Mexico, Greece, Belgium, UK, and Germany. And he has coauthored one book and authored or coauthored more than 80 research papers in conference proceedings and journals. 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After finishing his P. hD degree in 1992, he served in the Industry as a Scientific Officer and continued his academic career as a visiting scholar for a number of educational institutions. In 1996 he joined National University of Science & Technology Pakistan (NUST) as an Associate Professor; NUST is one of the top few universities in Pakistan. In 1999 he joined an International Company Lineo Inc, Canada as Manager Compiler Group, where he headed the group for developing Compiler Tool Chain and Porting of Operating Systems for the BLACKfin processor. The processor development was a joint venture by Intel and Analog Devices. In 2002 Lineo Inc., was taken over by another company, so he joined Aalborg University Denmark as an Assistant Professor.\nProfessor Akbar has truly a multi-disciplined career and he continued his legacy and making progress in many areas of his interests both in teaching and research. 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He also has an honorary appointment to serve as a Collaborative Professor at Kanazawa University, Japan, from Mar 2015 to the present. \nFormerly, Dr. Rahman was a faculty member of the University of Chittagong, Bangladesh, affiliated with the Department of Chemistry (Oct 2002 to Mar 2012) and the Department of Applied Chemistry and Chemical Engineering (Mar 2012 to Sep 2015). Dr. Rahman was also adjunctly attached with Kanazawa University, Japan (Visiting Research Professor, Dec 2014 to Mar 2015; JSPS Postdoctoral Research Fellow, Apr 2012 to Mar 2014), and Tokyo Institute of Technology, Japan (TokyoTech-UNESCO Research Fellow, Oct 2004–Sep 2005). \nHe received his Ph.D. degree in Environmental Analytical Chemistry from Kanazawa University, Japan (2011). He also achieved a Diploma in Environment from the Tokyo Institute of Technology, Japan (2005). 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Radiotherapy and Nuclear Medicine Technology has always been my aspiration and my life. As years passed I accumulated a tremendous amount of skills and knowledge in Radiotherapy and Nuclear Medicine, Conventional Radiology, Radiation Protection, Bioinformatics Technology, PACS, Image processing, clinically and lecturing that will enable me to provide a valuable service to the community as a Researcher and Consultant in this field. My method of translating this into day to day in clinical practice is non-exhaustible and my habit of exchanging knowledge and expertise with others in those fields is the code and secret of success.",institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"313277",title:"Dr.",name:"Bartłomiej",middleName:null,surname:"Płaczek",slug:"bartlomiej-placzek",fullName:"Bartłomiej Płaczek",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/313277/images/system/313277.jpg",biography:"Bartłomiej Płaczek, MSc (2002), Ph.D. (2005), Habilitation (2016), is a professor at the University of Silesia, Institute of Computer Science, Poland, and an expert from the National Centre for Research and Development. His research interests include sensor networks, smart sensors, intelligent systems, and image processing with applications in healthcare and medicine. He is the author or co-author of more than seventy papers in peer-reviewed journals and conferences as well as the co-author of several books. He serves as a reviewer for many scientific journals, international conferences, and research foundations. Since 2010, Dr. Placzek has been a reviewer of grants and projects (including EU projects) in the field of information technologies.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"35000",title:"Prof.",name:"Ulrich H.P",middleName:"H.P.",surname:"Fischer",slug:"ulrich-h.p-fischer",fullName:"Ulrich H.P Fischer",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/35000/images/3052_n.jpg",biography:"Academic and Professional Background\nUlrich H. P. has Diploma and PhD degrees in Physics from the Free University Berlin, Germany. He has been working on research positions in the Heinrich-Hertz-Institute in Germany. Several international research projects has been performed with European partners from France, Netherlands, Norway and the UK. He is currently Professor of Communications Systems at the Harz University of Applied Sciences, Germany.\n\nPublications and Publishing\nHe has edited one book, a special interest book about ‘Optoelectronic Packaging’ (VDE, Berlin, Germany), and has published over 100 papers and is owner of several international patents for WDM over POF key elements.\n\nKey Research and Consulting Interests\nUlrich’s research activity has always been related to Spectroscopy and Optical Communications Technology. Specific current interests include the validation of complex instruments, and the application of VR technology to the development and testing of measurement systems. He has been reviewer for several publications of the Optical Society of America\\'s including Photonics Technology Letters and Applied Optics.\n\nPersonal Interests\nThese include motor cycling in a very relaxed manner and performing martial arts.",institutionString:null,institution:{name:"Charité",country:{name:"Germany"}}},{id:"341622",title:"Ph.D.",name:"Eduardo",middleName:null,surname:"Rojas Alvarez",slug:"eduardo-rojas-alvarez",fullName:"Eduardo Rojas Alvarez",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/341622/images/15892_n.jpg",biography:null,institutionString:null,institution:{name:"University of Cuenca",country:{name:"Ecuador"}}},{id:"215610",title:"Prof.",name:"Muhammad",middleName:null,surname:"Sarfraz",slug:"muhammad-sarfraz",fullName:"Muhammad Sarfraz",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/215610/images/system/215610.jpeg",biography:"Muhammad Sarfraz is a professor in the Department of Information Science, Kuwait University. His research interests include computer graphics, computer vision, image processing, machine learning, pattern recognition, soft computing, data science, intelligent systems, information technology, and information systems. Prof. Sarfraz has been a keynote/invited speaker on various platforms around the globe. He has advised various students for their MSc and Ph.D. theses. He has published more than 400 publications as books, journal articles, and conference papers. He is a member of various professional societies and a chair and member of the International Advisory Committees and Organizing Committees of various international conferences. Prof. Sarfraz is also an editor-in-chief and editor of various international journals.",institutionString:"Kuwait University",institution:{name:"Kuwait University",country:{name:"Kuwait"}}},{id:"32650",title:"Prof.",name:"Lukas",middleName:"Willem",surname:"Snyman",slug:"lukas-snyman",fullName:"Lukas Snyman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/32650/images/4136_n.jpg",biography:"Lukas Willem Snyman received his basic education at primary and high schools in South Africa, Eastern Cape. He enrolled at today's Nelson Metropolitan University and graduated from this university with a BSc in Physics and Mathematics, B.Sc Honors in Physics, MSc in Semiconductor Physics, and a Ph.D. in Semiconductor Physics in 1987. After his studies, he chose an academic career and devoted his energy to the teaching of physics to first, second, and third-year students. After positions as a lecturer at the University of Port Elizabeth, he accepted a position as Associate Professor at the University of Pretoria, South Africa.\r\n\r\nIn 1992, he motivates the concept of 'television and computer-based education” as means to reach large student numbers with only the best of teaching expertise and publishes an article on the concept in the SA Journal of Higher Education of 1993 (and later in 2003). The University of Pretoria subsequently approved a series of test projects on the concept with outreach to Mamelodi and Eerste Rust in 1993. In 1994, the University established a 'Unit for Telematic Education ' as a support section for multiple faculties at the University of Pretoria. In subsequent years, the concept of 'telematic education” subsequently becomes well established in academic circles in South Africa, grew in popularity, and is adopted by many universities and colleges throughout South Africa as a medium of enhancing education and training, as a method to reaching out to far out communities, and as a means to enhance study from the home environment.\r\n\r\nProfessor Snyman in subsequent years pursued research in semiconductor physics, semiconductor devices, microelectronics, and optoelectronics.\r\n\r\nIn 2000 he joined the TUT as a full professor. Here served for a period as head of the Department of Electronic Engineering. Here he makes contributions to solar energy development, microwave and optoelectronic device development, silicon photonics, as well as contributions to new mobile telecommunication systems and network planning in SA.\r\n\r\nCurrently, he teaches electronics and telecommunications at the TUT to audiences ranging from first-year students to Ph.D. level.\r\n\r\nFor his research in the field of 'Silicon Photonics” since 1990, he has published (as author and co-author) about thirty internationally reviewed articles in scientific journals, contributed to more than forty international conferences, about 25 South African provisional patents (as inventor and co-inventor), 8 PCT international patent applications until now. Of these, two USA patents applications, two European Patents, two Korean patents, and ten SA patents have been granted. A further 4 USA patents, 5 European patents, 3 Korean patents, 3 Chinese patents, and 3 Japanese patents are currently under consideration.\r\n\r\nRecently he has also published an extensive scholarly chapter in an internet open access book on 'Integrating Microphotonic Systems and MOEMS into standard Silicon CMOS Integrated circuitry”.\r\n\r\nFurthermore, Professor Snyman recently steered a new initiative at the TUT by introducing a 'Laboratory for Innovative Electronic Systems ' at the Department of Electrical Engineering. The model of this laboratory or center is to primarily combine outputs as achieved by high-level research with lower-level system development and entrepreneurship in a technical university environment. Students are allocated to projects at different levels with PhDs and Master students allocated to the generation of new knowledge and new technologies, while students at the diploma and Baccalaureus level are allocated to electronic systems development with a direct and a near application for application in industry or the commercial and public sectors in South Africa.\r\n\r\nProfessor Snyman received the WIRSAM Award of 1983 and the WIRSAM Award in 1985 in South Africa for best research papers by a young scientist at two international conferences on electron microscopy in South Africa. He subsequently received the SA Microelectronics Award for the best dissertation emanating from studies executed at a South African university in the field of Physics and Microelectronics in South Africa in 1987. In October of 2011, Professor Snyman received the prestigious Institutional Award for 'Innovator of the Year” for 2010 at the Tshwane University of Technology, South Africa. This award was based on the number of patents recognized and granted by local and international institutions as well as for his contributions concerning innovation at the TUT.",institutionString:null,institution:{name:"University of South Africa",country:{name:"South Africa"}}},{id:"317279",title:"Mr.",name:"Ali",middleName:"Usama",surname:"Syed",slug:"ali-syed",fullName:"Ali Syed",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/317279/images/16024_n.png",biography:"A creative, talented, and innovative young professional who is dedicated, well organized, and capable research fellow with two years of experience in graduate-level research, published in engineering journals and book, with related expertise in Bio-robotics, equally passionate about the aesthetics of the mechanical and electronic system, obtained expertise in the use of MS Office, MATLAB, SolidWorks, LabVIEW, Proteus, Fusion 360, having a grasp on python, C++ and assembly language, possess proven ability in acquiring research grants, previous appointments with social and educational societies with experience in administration, current affiliations with IEEE and Web of Science, a confident presenter at conferences and teacher in classrooms, able to explain complex information to audiences of all levels.",institutionString:null,institution:{name:"Air University",country:{name:"Pakistan"}}},{id:"75526",title:"Ph.D.",name:"Zihni Onur",middleName:null,surname:"Uygun",slug:"zihni-onur-uygun",fullName:"Zihni Onur Uygun",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/75526/images/12_n.jpg",biography:"My undergraduate education and my Master of Science educations at Ege University and at Çanakkale Onsekiz Mart University have given me a firm foundation in Biochemistry, Analytical Chemistry, Biosensors, Bioelectronics, Physical Chemistry and Medicine. After obtaining my degree as a MSc in analytical chemistry, I started working as a research assistant in Ege University Medical Faculty in 2014. In parallel, I enrolled to the MSc program at the Department of Medical Biochemistry at Ege University to gain deeper knowledge on medical and biochemical sciences as well as clinical chemistry in 2014. In my PhD I deeply researched on biosensors and bioelectronics and finished in 2020. Now I have eleven SCI-Expanded Index published papers, 6 international book chapters, referee assignments for different SCIE journals, one international patent pending, several international awards, projects and bursaries. In parallel to my research assistant position at Ege University Medical Faculty, Department of Medical Biochemistry, in April 2016, I also founded a Start-Up Company (Denosens Biotechnology LTD) by the support of The Scientific and Technological Research Council of Turkey. Currently, I am also working as a CEO in Denosens Biotechnology. The main purposes of the company, which carries out R&D as a research center, are to develop new generation biosensors and sensors for both point-of-care diagnostics; such as glucose, lactate, cholesterol and cancer biomarker detections. My specific experimental and instrumental skills are Biochemistry, Biosensor, Analytical Chemistry, Electrochemistry, Mobile phone based point-of-care diagnostic device, POCTs and Patient interface designs, HPLC, Tandem Mass Spectrometry, Spectrophotometry, ELISA.",institutionString:null,institution:{name:"Ege University",country:{name:"Turkey"}}},{id:"267434",title:"Dr.",name:"Rohit",middleName:null,surname:"Raja",slug:"rohit-raja",fullName:"Rohit Raja",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/267434/images/system/267434.jpg",biography:"Dr. Rohit Raja received Ph.D. in Computer Science and Engineering from Dr. CVRAMAN University in 2016. His main research interest includes Face recognition and Identification, Digital Image Processing, Signal Processing, and Networking. Presently he is working as Associate Professor in IT Department, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur (CG), India. He has authored several Journal and Conference Papers. He has good Academics & Research experience in various areas of CSE and IT. He has filed and successfully published 27 Patents. He has received many time invitations to be a Guest at IEEE Conferences. He has published 100 research papers in various International/National Journals (including IEEE, Springer, etc.) and Proceedings of the reputed International/ National Conferences (including Springer and IEEE). He has been nominated to the board of editors/reviewers of many peer-reviewed and refereed Journals (including IEEE, Springer).",institutionString:"Guru Ghasidas Vishwavidyalaya",institution:{name:"Guru Ghasidas Vishwavidyalaya",country:{name:"India"}}},{id:"246502",title:"Dr.",name:"Jaya T.",middleName:"T",surname:"Varkey",slug:"jaya-t.-varkey",fullName:"Jaya T. Varkey",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/246502/images/11160_n.jpg",biography:"Jaya T. Varkey, PhD, graduated with a degree in Chemistry from Cochin University of Science and Technology, Kerala, India. She obtained a PhD in Chemistry from the School of Chemical Sciences, Mahatma Gandhi University, Kerala, India, and completed a post-doctoral fellowship at the University of Minnesota, USA. She is a research guide at Mahatma Gandhi University and Associate Professor in Chemistry, St. Teresa’s College, Kochi, Kerala, India.\nDr. Varkey received a National Young Scientist award from the Indian Science Congress (1995), a UGC Research award (2016–2018), an Indian National Science Academy (INSA) Visiting Scientist award (2018–2019), and a Best Innovative Faculty award from the All India Association for Christian Higher Education (AIACHE) (2019). She Hashas received the Sr. Mary Cecil prize for best research paper three times. She was also awarded a start-up to develop a tea bag water filter. \nDr. Varkey has published two international books and twenty-seven international journal publications. She is an editorial board member for five international journals.",institutionString:"St. Teresa’s College",institution:null},{id:"250668",title:"Dr.",name:"Ali",middleName:null,surname:"Nabipour Chakoli",slug:"ali-nabipour-chakoli",fullName:"Ali Nabipour Chakoli",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/250668/images/system/250668.jpg",biography:"Academic Qualification:\r\n•\tPhD in Materials Physics and Chemistry, From: Sep. 2006, to: Sep. 2010, School of Materials Science and Engineering, Harbin Institute of Technology, Thesis: Structure and Shape Memory Effect of Functionalized MWCNTs/poly (L-lactide-co-ε-caprolactone) Nanocomposites. Supervisor: Prof. Wei Cai,\r\n•\tM.Sc in Applied Physics, From: 1996, to: 1998, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Determination of Boron in Micro alloy Steels with solid state nuclear track detectors by neutron induced auto radiography, Supervisors: Dr. M. Hosseini Ashrafi and Dr. A. Hosseini.\r\n•\tB.Sc. in Applied Physics, From: 1991, to: 1996, Faculty of Physics & Nuclear Science, Amirkabir Uni. of Technology, Tehran, Iran, Thesis: Design of shielding for Am-Be neutron sources for In Vivo neutron activation analysis, Supervisor: Dr. M. Hosseini Ashrafi.\r\n\r\nResearch Experiences:\r\n1.\tNanomaterials, Carbon Nanotubes, Graphene: Synthesis, Functionalization and Characterization,\r\n2.\tMWCNTs/Polymer Composites: Fabrication and Characterization, \r\n3.\tShape Memory Polymers, Biodegradable Polymers, ORC, Collagen,\r\n4.\tMaterials Analysis and Characterizations: TEM, SEM, XPS, FT-IR, Raman, DSC, DMA, TGA, XRD, GPC, Fluoroscopy, \r\n5.\tInteraction of Radiation with Mater, Nuclear Safety and Security, NDT(RT),\r\n6.\tRadiation Detectors, Calibration (SSDL),\r\n7.\tCompleted IAEA e-learning Courses:\r\nNuclear Security (15 Modules),\r\nNuclear Safety:\r\nTSA 2: Regulatory Protection in Occupational Exposure,\r\nTips & Tricks: Radiation Protection in Radiography,\r\nSafety and Quality in Radiotherapy,\r\nCourse on Sealed Radioactive Sources,\r\nCourse on Fundamentals of Environmental Remediation,\r\nCourse on Planning for Environmental Remediation,\r\nKnowledge Management Orientation Course,\r\nFood Irradiation - Technology, Applications and Good Practices,\r\nEmployment:\r\nFrom 2010 to now: Academic staff, Nuclear Science and Technology Research Institute, Kargar Shomali, Tehran, Iran, P.O. Box: 14395-836.\r\nFrom 1997 to 2006: Expert of Materials Analysis and Characterization. Research Center of Agriculture and Medicine. Rajaeeshahr, Karaj, Iran, P. O. Box: 31585-498.",institutionString:"Atomic Energy Organization of Iran",institution:{name:"Atomic Energy Organization of Iran",country:{name:"Iran"}}},{id:"248279",title:"Dr.",name:"Monika",middleName:"Elzbieta",surname:"Machoy",slug:"monika-machoy",fullName:"Monika Machoy",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/248279/images/system/248279.jpeg",biography:"Monika Elżbieta Machoy, MD, graduated with distinction from the Faculty of Medicine and Dentistry at the Pomeranian Medical University in 2009, defended her PhD thesis with summa cum laude in 2016 and is currently employed as a researcher at the Department of Orthodontics of the Pomeranian Medical University. She expanded her professional knowledge during a one-year scholarship program at the Ernst Moritz Arndt University in Greifswald, Germany and during a three-year internship at the Technical University in Dresden, Germany. She has been a speaker at numerous orthodontic conferences, among others, American Association of Orthodontics, European Orthodontic Symposium and numerous conferences of the Polish Orthodontic Society. She conducts research focusing on the effect of orthodontic treatment on dental and periodontal tissues and the causes of pain in orthodontic patients.",institutionString:"Pomeranian Medical University",institution:{name:"Pomeranian Medical University",country:{name:"Poland"}}},{id:"252743",title:"Prof.",name:"Aswini",middleName:"Kumar",surname:"Kar",slug:"aswini-kar",fullName:"Aswini Kar",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/252743/images/10381_n.jpg",biography:"uploaded in cv",institutionString:null,institution:{name:"KIIT University",country:{name:"India"}}},{id:"204256",title:"Dr.",name:"Anil",middleName:"Kumar",surname:"Kumar Sahu",slug:"anil-kumar-sahu",fullName:"Anil Kumar Sahu",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/204256/images/14201_n.jpg",biography:"I have nearly 11 years of research and teaching experience. I have done my master degree from University Institute of Pharmacy, Pt. Ravi Shankar Shukla University, Raipur, Chhattisgarh India. I have published 16 review and research articles in international and national journals and published 4 chapters in IntechOpen, the world’s leading publisher of Open access books. I have presented many papers at national and international conferences. I have received research award from Indian Drug Manufacturers Association in year 2015. My research interest extends from novel lymphatic drug delivery systems, oral delivery system for herbal bioactive to formulation optimization.",institutionString:null,institution:{name:"Chhattisgarh Swami Vivekanand Technical University",country:{name:"India"}}},{id:"253468",title:"Dr.",name:"Mariusz",middleName:null,surname:"Marzec",slug:"mariusz-marzec",fullName:"Mariusz Marzec",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/253468/images/system/253468.png",biography:"An assistant professor at Department of Biomedical Computer Systems, at Institute of Computer Science, Silesian University in Katowice. Scientific interests: computer analysis and processing of images, biomedical images, databases and programming languages. He is an author and co-author of scientific publications covering analysis and processing of biomedical images and development of database systems.",institutionString:"University of Silesia",institution:{name:"University of Silesia",country:{name:"Poland"}}},{id:"212432",title:"Prof.",name:"Hadi",middleName:null,surname:"Mohammadi",slug:"hadi-mohammadi",fullName:"Hadi Mohammadi",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/212432/images/system/212432.jpeg",biography:"Dr. Hadi Mohammadi is a biomedical engineer with hands-on experience in the design and development of many engineering structures and medical devices through various projects that he has been involved in over the past twenty years. Dr. Mohammadi received his BSc. and MSc. degrees in Mechanical Engineering from Sharif University of Technology, Tehran, Iran, and his PhD. degree in Biomedical Engineering (biomaterials) from the University of Western Ontario. He was a postdoctoral trainee for almost four years at University of Calgary and Harvard Medical School. He is an industry innovator having created the technology to produce lifelike synthetic platforms that can be used for the simulation of almost all cardiovascular reconstructive surgeries. He’s been heavily involved in the design and development of cardiovascular devices and technology for the past 10 years. He is currently an Assistant Professor with the University of British Colombia, Canada.",institutionString:"University of British Columbia",institution:{name:"University of British Columbia",country:{name:"Canada"}}},{id:"254463",title:"Prof.",name:"Haisheng",middleName:null,surname:"Yang",slug:"haisheng-yang",fullName:"Haisheng Yang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/254463/images/system/254463.jpeg",biography:"Haisheng Yang, Ph.D., Professor and Director of the Department of Biomedical Engineering, College of Life Science and Bioengineering, Beijing University of Technology. He received his Ph.D. degree in Mechanics/Biomechanics from Harbin Institute of Technology (jointly with University of California, Berkeley). Afterwards, he worked as a Postdoctoral Research Associate in the Purdue Musculoskeletal Biology and Mechanics Lab at the Department of Basic Medical Sciences, Purdue University, USA. He also conducted research in the Research Centre of Shriners Hospitals for Children-Canada at McGill University, Canada. Dr. Yang has over 10 years research experience in orthopaedic biomechanics and mechanobiology of bone adaptation and regeneration. He earned an award from Beijing Overseas Talents Aggregation program in 2017 and serves as Beijing Distinguished Professor.",institutionString:null,institution:{name:"Beijing University of Technology",country:{name:"China"}}},{id:"89721",title:"Dr.",name:"Mehmet",middleName:"Cuneyt",surname:"Ozmen",slug:"mehmet-ozmen",fullName:"Mehmet Ozmen",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/89721/images/7289_n.jpg",biography:null,institutionString:null,institution:{name:"Gazi University",country:{name:"Turkey"}}},{id:"265335",title:"Mr.",name:"Stefan",middleName:"Radnev",surname:"Stefanov",slug:"stefan-stefanov",fullName:"Stefan Stefanov",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/265335/images/7562_n.jpg",biography:null,institutionString:null,institution:{name:"Medical University Plovdiv",country:{name:"Bulgaria"}}},{id:"242893",title:"Ph.D. Student",name:"Joaquim",middleName:null,surname:"De Moura",slug:"joaquim-de-moura",fullName:"Joaquim De Moura",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/242893/images/7133_n.jpg",biography:"Joaquim de Moura received his degree in Computer Engineering in 2014 from the University of A Coruña (Spain). In 2016, he received his M.Sc degree in Computer Engineering from the same university. He is currently pursuing his Ph.D degree in Computer Science in a collaborative project between ophthalmology centers in Galicia and the University of A Coruña. His research interests include computer vision, machine learning algorithms and analysis and medical imaging processing of various kinds.",institutionString:null,institution:{name:"University of A Coruña",country:{name:"Spain"}}},{id:"294334",title:"B.Sc.",name:"Marc",middleName:null,surname:"Bruggeman",slug:"marc-bruggeman",fullName:"Marc Bruggeman",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/294334/images/8242_n.jpg",biography:"Chemical engineer graduate, with a passion for material science and specific interest in polymers - their near infinite applications intrigue me. \n\nI plan to continue my scientific career in the field of polymeric biomaterials as I am fascinated by intelligent, bioactive and biomimetic materials for use in both consumer and medical applications.",institutionString:null,institution:null},{id:"255757",title:"Dr.",name:"Igor",middleName:"Victorovich",surname:"Lakhno",slug:"igor-lakhno",fullName:"Igor Lakhno",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/255757/images/system/255757.jpg",biography:"Igor Victorovich Lakhno was born in 1971 in Kharkiv (Ukraine). \nMD – 1994, Kharkiv National Medical Univesity.\nOb&Gyn; – 1997, master courses in Kharkiv Medical Academy of Postgraduate Education.\nPh.D. – 1999, Kharkiv National Medical Univesity.\nDSC – 2019, PL Shupik National Academy of Postgraduate Education \nProfessor – 2021, Department of Obstetrics and Gynecology of VN Karazin Kharkiv National University\nHead of Department – 2021, Department of Perinatology, Obstetrics and gynecology of Kharkiv Medical Academy of Postgraduate Education\nIgor Lakhno has been graduated from international training courses on reproductive medicine and family planning held at Debrecen University (Hungary) in 1997. Since 1998 Lakhno Igor has worked as an associate professor in the department of obstetrics and gynecology of VN Karazin National University and an associate professor of the perinatology, obstetrics, and gynecology department of Kharkiv Medical Academy of Postgraduate Education. Since June 2019 he’s been a professor in the department of obstetrics and gynecology of VN Karazin National University and a professor of the perinatology, obstetrics, and gynecology department. He’s affiliated with Kharkiv Medical Academy of Postgraduate Education as a Head of Department from November 2021. Igor Lakhno has participated in several international projects on fetal non-invasive electrocardiography (with Dr. J. A. Behar (Technion), Prof. D. Hoyer (Jena University), and José Alejandro Díaz Méndez (National Institute of Astrophysics, Optics, and Electronics, Mexico). He’s an author of about 200 printed works and there are 31 of them in Scopus or Web of Science databases. Igor Lakhno is a member of the Editorial Board of Reproductive Health of Woman, Emergency Medicine, and Technology Transfer Innovative Solutions in Medicine (Estonia). He is a medical Editor of “Z turbotoyu pro zhinku”. Igor Lakhno is a reviewer of the Journal of Obstetrics and Gynaecology (Taylor and Francis), British Journal of Obstetrics and Gynecology (Wiley), Informatics in Medicine Unlocked (Elsevier), The Journal of Obstetrics and Gynecology Research (Wiley), Endocrine, Metabolic & Immune Disorders-Drug Targets (Bentham Open), The Open Biomedical Engineering Journal (Bentham Open), etc. He’s defended a dissertation for a DSc degree “Pre-eclampsia: prediction, prevention, and treatment”. Three years ago Igor Lakhno has participated in a training course on innovative technologies in medical education at Lublin Medical University (Poland). Lakhno Igor has participated as a speaker in several international conferences and congresses (International Conference on Biological Oscillations April 10th-14th 2016, Lancaster, UK, The 9th conference of the European Study Group on Cardiovascular Oscillations). His main scientific interests: are obstetrics, women’s health, fetal medicine, and cardiovascular medicine. \nIgor Lakhno is a consultant at Kharkiv municipal perinatal center. He’s graduated from training courses on endoscopy in gynecology. He has 28 years of practical experience in the field.",institutionString:null,institution:null},{id:"244950",title:"Dr.",name:"Salvatore",middleName:null,surname:"Di Lauro",slug:"salvatore-di-lauro",fullName:"Salvatore Di Lauro",position:null,profilePictureURL:"https://intech-files.s3.amazonaws.com/0030O00002bSF1HQAW/ProfilePicture%202021-12-20%2014%3A54%3A14.482",biography:"Name:\n\tSALVATORE DI LAURO\nAddress:\n\tHospital Clínico Universitario Valladolid\nAvda Ramón y Cajal 3\n47005, Valladolid\nSpain\nPhone number: \nFax\nE-mail:\n\t+34 983420000 ext 292\n+34 983420084\nsadilauro@live.it\nDate and place of Birth:\nID Number\nMedical Licence \nLanguages\t09-05-1985. Villaricca (Italy)\n\nY1281863H\n474707061\nItalian (native language)\nSpanish (read, written, spoken)\nEnglish (read, written, spoken)\nPortuguese (read, spoken)\nFrench (read)\n\t\t\nCurrent position (title and company)\tDate (Year)\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. Private practise.\t2017-today\n\n2019-today\n\t\n\t\nEducation (High school, university and postgraduate training > 3 months)\tDate (Year)\nDegree in Medicine and Surgery. University of Neaples 'Federico II”\nResident in Opthalmology. Hospital Clinico Universitario Valladolid\nMaster in Vitreo-Retina. IOBA. University of Valladolid\nFellow of the European Board of Ophthalmology. Paris\nMaster in Research in Ophthalmology. University of Valladolid\t2003-2009\n2012-2016\n2016-2017\n2016\n2012-2013\n\t\nEmployments (company and positions)\tDate (Year)\nResident in Ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl.\nFellow in Vitreo-Retina. IOBA. University of Valladolid\nVitreo-Retinal consultant in ophthalmology. Hospital Clinico Universitario Valladolid. Sacyl. National Health System.\nVitreo-Retinal consultant in ophthalmology. Instituto Oftalmologico Recoletas. Red Hospitalaria Recoletas. \n\t2012-2016\n2016-2017\n2017-today\n\n2019-Today\n\n\n\t\nClinical Research Experience (tasks and role)\tDate (Year)\nAssociated investigator\n\n' FIS PI20/00740: DESARROLLO DE UNA CALCULADORA DE RIESGO DE\nAPARICION DE RETINOPATIA DIABETICA BASADA EN TECNICAS DE IMAGEN MULTIMODAL EN PACIENTES DIABETICOS TIPO 1. Grant by: Ministerio de Ciencia e Innovacion \n\n' (BIO/VA23/14) Estudio clínico multicéntrico y prospectivo para validar dos\nbiomarcadores ubicados en los genes p53 y MDM2 en la predicción de los resultados funcionales de la cirugía del desprendimiento de retina regmatógeno. Grant by: Gerencia Regional de Salud de la Junta de Castilla y León.\n' Estudio multicéntrico, aleatorizado, con enmascaramiento doble, en 2 grupos\nparalelos y de 52 semanas de duración para comparar la eficacia, seguridad e inmunogenicidad de SOK583A1 respecto a Eylea® en pacientes con degeneración macular neovascular asociada a la edad' (CSOK583A12301; N.EUDRA: 2019-004838-41; FASE III). Grant by Hexal AG\n\n' Estudio de fase III, aleatorizado, doble ciego, con grupos paralelos, multicéntrico para comparar la eficacia y la seguridad de QL1205 frente a Lucentis® en pacientes con degeneración macular neovascular asociada a la edad. (EUDRACT: 2018-004486-13). Grant by Qilu Pharmaceutical Co\n\n' Estudio NEUTON: Ensayo clinico en fase IV para evaluar la eficacia de aflibercept en pacientes Naive con Edema MacUlar secundario a Oclusion de Vena CenTral de la Retina (OVCR) en regimen de tratamientO iNdividualizado Treat and Extend (TAE)”, (2014-000975-21). Grant by Fundacion Retinaplus\n\n' Evaluación de la seguridad y bioactividad de anillos de tensión capsular en conejo. Proyecto Procusens. Grant by AJL, S.A.\n\n'Estudio epidemiológico, prospectivo, multicéntrico y abierto\\npara valorar la frecuencia de la conjuntivitis adenovírica diagnosticada mediante el test AdenoPlus®\\nTest en pacientes enfermos de conjuntivitis aguda”\\n. National, multicenter study. Grant by: NICOX.\n\nEuropean multicentric trial: 'Evaluation of clinical outcomes following the use of Systane Hydration in patients with dry eye”. Study Phase 4. Grant by: Alcon Labs'\n\nVLPs Injection and Activation in a Rabbit Model of Uveal Melanoma. Grant by Aura Bioscience\n\nUpdating and characterization of a rabbit model of uveal melanoma. Grant by Aura Bioscience\n\nEnsayo clínico en fase IV para evaluar las variantes genéticas de la vía del VEGF como biomarcadores de eficacia del tratamiento con aflibercept en pacientes con degeneración macular asociada a la edad (DMAE) neovascular. Estudio BIOIMAGE. IMO-AFLI-2013-01\n\nEstudio In-Eye:Ensayo clínico en fase IV, abierto, aleatorizado, de 2 brazos,\nmulticçentrico y de 12 meses de duración, para evaluar la eficacia y seguridad de un régimen de PRN flexible individualizado de 'esperar y extender' versus un régimen PRN según criterios de estabilización mediante evaluaciones mensuales de inyecciones intravítreas de ranibizumab 0,5 mg en pacientes naive con neovascularización coriodea secunaria a la degeneración macular relacionada con la edad. CP: CRFB002AES03T\n\nTREND: Estudio Fase IIIb multicéntrico, randomizado, de 12 meses de\nseguimiento con evaluador de la agudeza visual enmascarado, para evaluar la eficacia y la seguridad de ranibizumab 0.5mg en un régimen de tratar y extender comparado con un régimen mensual, en pacientes con degeneración macular neovascular asociada a la edad. CP: CRFB002A2411 Código Eudra CT:\n2013-002626-23\n\n\n\nPublications\t\n\n2021\n\n\n\n\n2015\n\n\n\n\n2021\n\n\n\n\n\n2021\n\n\n\n\n2015\n\n\n\n\n2015\n\n\n2014\n\n\n\n\n2015-16\n\n\n\n2015\n\n\n2014\n\n\n2014\n\n\n\n\n2014\n\n\n\n\n\n\n\n2014\n\nJose Carlos Pastor; Jimena Rojas; Salvador Pastor-Idoate; Salvatore Di Lauro; Lucia Gonzalez-Buendia; Santiago Delgado-Tirado. Proliferative vitreoretinopathy: A new concept of disease pathogenesis and practical\nconsequences. Progress in Retinal and Eye Research. 51, pp. 125 - 155. 03/2016. DOI: 10.1016/j.preteyeres.2015.07.005\n\n\nLabrador-Velandia S; Alonso-Alonso ML; Di Lauro S; García-Gutierrez MT; Srivastava GK; Pastor JC; Fernandez-Bueno I. Mesenchymal stem cells provide paracrine neuroprotective resources that delay degeneration of co-cultured organotypic neuroretinal cultures.Experimental Eye Research. 185, 17/05/2019. DOI: 10.1016/j.exer.2019.05.011\n\nSalvatore Di Lauro; Maria Teresa Garcia Gutierrez; Ivan Fernandez Bueno. Quantification of pigment epithelium-derived factor (PEDF) in an ex vivo coculture of retinal pigment epithelium cells and neuroretina.\nJournal of Allbiosolution. 2019. ISSN 2605-3535\n\nSonia Labrador Velandia; Salvatore Di Lauro; Alonso-Alonso ML; Tabera Bartolomé S; Srivastava GK; Pastor JC; Fernandez-Bueno I. Biocompatibility of intravitreal injection of human mesenchymal stem cells in immunocompetent rabbits. Graefe's archive for clinical and experimental ophthalmology. 256 - 1, pp. 125 - 134. 01/2018. DOI: 10.1007/s00417-017-3842-3\n\n\nSalvatore Di Lauro, David Rodriguez-Crespo, Manuel J Gayoso, Maria T Garcia-Gutierrez, J Carlos Pastor, Girish K Srivastava, Ivan Fernandez-Bueno. A novel coculture model of porcine central neuroretina explants and retinal pigment epithelium cells. Molecular Vision. 2016 - 22, pp. 243 - 253. 01/2016.\n\nSalvatore Di Lauro. Classifications for Proliferative Vitreoretinopathy ({PVR}): An Analysis of Their Use in Publications over the Last 15 Years. Journal of Ophthalmology. 2016, pp. 1 - 6. 01/2016. DOI: 10.1155/2016/7807596\n\nSalvatore Di Lauro; Rosa Maria Coco; Rosa Maria Sanabria; Enrique Rodriguez de la Rua; Jose Carlos Pastor. Loss of Visual Acuity after Successful Surgery for Macula-On Rhegmatogenous Retinal Detachment in a Prospective Multicentre Study. Journal of Ophthalmology. 2015:821864, 2015. DOI: 10.1155/2015/821864\n\nIvan Fernandez-Bueno; Salvatore Di Lauro; Ivan Alvarez; Jose Carlos Lopez; Maria Teresa Garcia-Gutierrez; Itziar Fernandez; Eva Larra; Jose Carlos Pastor. Safety and Biocompatibility of a New High-Density Polyethylene-Based\nSpherical Integrated Porous Orbital Implant: An Experimental Study in Rabbits. Journal of Ophthalmology. 2015:904096, 2015. DOI: 10.1155/2015/904096\n\nPastor JC; Pastor-Idoate S; Rodríguez-Hernandez I; Rojas J; Fernandez I; Gonzalez-Buendia L; Di Lauro S; Gonzalez-Sarmiento R. Genetics of PVR and RD. Ophthalmologica. 232 - Suppl 1, pp. 28 - 29. 2014\n\nRodriguez-Crespo D; Di Lauro S; Singh AK; Garcia-Gutierrez MT; Garrosa M; Pastor JC; Fernandez-Bueno I; Srivastava GK. Triple-layered mixed co-culture model of RPE cells with neuroretina for evaluating the neuroprotective effects of adipose-MSCs. Cell Tissue Res. 358 - 3, pp. 705 - 716. 2014.\nDOI: 10.1007/s00441-014-1987-5\n\nCarlo De Werra; Salvatore Condurro; Salvatore Tramontano; Mario Perone; Ivana Donzelli; Salvatore Di Lauro; Massimo Di Giuseppe; Rosa Di Micco; Annalisa Pascariello; Antonio Pastore; Giorgio Diamantis; Giuseppe Galloro. Hydatid disease of the liver: thirty years of surgical experience.Chirurgia italiana. 59 - 5, pp. 611 - 636.\n(Italia): 2007. ISSN 0009-4773\n\nChapters in books\n\t\n' Salvador Pastor Idoate; Salvatore Di Lauro; Jose Carlos Pastor Jimeno. PVR: Pathogenesis, Histopathology and Classification. Proliferative Vitreoretinopathy with Small Gauge Vitrectomy. Springer, 2018. ISBN 978-3-319-78445-8\nDOI: 10.1007/978-3-319-78446-5_2. \n\n' Salvatore Di Lauro; Maria Isabel Lopez Galvez. Quistes vítreos en una mujer joven. Problemas diagnósticos en patología retinocoroidea. Sociedad Española de Retina-Vitreo. 2018.\n\n' Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor Jimeno. iOCT in PVR management. OCT Applications in Opthalmology. pp. 1 - 8. INTECH, 2018. DOI: 10.5772/intechopen.78774.\n\n' Rosa Coco Martin; Salvatore Di Lauro; Salvador Pastor Idoate; Jose Carlos Pastor. amponadores, manipuladores y tinciones en la cirugía del traumatismo ocular.Trauma Ocular. Ponencia de la SEO 2018..\n\n' LOPEZ GALVEZ; DI LAURO; CRESPO. OCT angiografia y complicaciones retinianas de la diabetes. PONENCIA SEO 2021, CAPITULO 20. (España): 2021.\n\n' Múltiples desprendimientos neurosensoriales bilaterales en paciente joven. Enfermedades Degenerativas De Retina Y Coroides. SERV 04/2016. \n' González-Buendía L; Di Lauro S; Pastor-Idoate S; Pastor Jimeno JC. Vitreorretinopatía proliferante (VRP) e inflamación: LA INFLAMACIÓN in «INMUNOMODULADORES Y ANTIINFLAMATORIOS: MÁS ALLÁ DE LOS CORTICOIDES. RELACION DE PONENCIAS DE LA SOCIEDAD ESPAÑOLA DE OFTALMOLOGIA. 10/2014.",institutionString:null,institution:null},{id:"243698",title:"Dr.",name:"Xiaogang",middleName:null,surname:"Wang",slug:"xiaogang-wang",fullName:"Xiaogang Wang",position:null,profilePictureURL:"https://mts.intechopen.com/storage/users/243698/images/system/243698.png",biography:"Dr. Xiaogang Wang, a faculty member of Shanxi Eye Hospital specializing in the treatment of cataract and retinal disease and a tutor for postgraduate students of Shanxi Medical University, worked in the COOL Lab as an international visiting scholar under the supervision of Dr. David Huang and Yali Jia from October 2012 through November 2013. Dr. Wang earned an MD from Shanxi Medical University and a Ph.D. from Shanghai Jiao Tong University. Dr. Wang was awarded two research project grants focused on multimodal optical coherence tomography imaging and deep learning in cataract and retinal disease, from the National Natural Science Foundation of China. He has published around 30 peer-reviewed journal papers and four book chapters and co-edited one book.",institutionString:null,institution:null},{id:"7227",title:"Dr.",name:"Hiroaki",middleName:null,surname:"Matsui",slug:"hiroaki-matsui",fullName:"Hiroaki Matsui",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Tokyo",country:{name:"Japan"}}},{id:"312999",title:"Dr.",name:"Bernard O.",middleName:null,surname:"Asimeng",slug:"bernard-o.-asimeng",fullName:"Bernard O. Asimeng",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"318905",title:"Prof.",name:"Elvis",middleName:"Kwason",surname:"Tiburu",slug:"elvis-tiburu",fullName:"Elvis Tiburu",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"University of Ghana",country:{name:"Ghana"}}},{id:"336193",title:"Dr.",name:"Abdullah",middleName:null,surname:"Alamoudi",slug:"abdullah-alamoudi",fullName:"Abdullah Alamoudi",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Majmaah University",country:{name:"Saudi Arabia"}}},{id:"318657",title:"MSc.",name:"Isabell",middleName:null,surname:"Steuding",slug:"isabell-steuding",fullName:"Isabell Steuding",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}},{id:"318656",title:"BSc.",name:"Peter",middleName:null,surname:"Kußmann",slug:"peter-kussmann",fullName:"Peter Kußmann",position:null,profilePictureURL:"//cdnintech.com/web/frontend/www/assets/author.svg",biography:null,institutionString:null,institution:{name:"Harz University of Applied Sciences",country:{name:"Germany"}}}]}},subseries:{item:{id:"17",type:"subseries",title:"Metabolism",keywords:"Biomolecules Metabolism, Energy Metabolism, Metabolic Pathways, Key Metabolic Enzymes, Metabolic Adaptation",scope:"Metabolism is frequently defined in biochemistry textbooks as the overall process that allows living systems to acquire and use the free energy they need for their vital functions or the chemical processes that occur within a living organism to maintain life. Behind these definitions are hidden all the aspects of normal and pathological functioning of all processes that the topic ‘Metabolism’ will cover within the Biochemistry Series. Thus all studies on metabolism will be considered for publication.",coverUrl:"https://cdn.intechopen.com/series_topics/covers/17.jpg",hasOnlineFirst:!0,hasPublishedBooks:!0,annualVolume:11413,editor:{id:"138626",title:"Dr.",name:"Yannis",middleName:null,surname:"Karamanos",slug:"yannis-karamanos",fullName:"Yannis Karamanos",profilePictureURL:"https://s3.us-east-1.amazonaws.com/intech-files/0030O00002g6Jv2QAE/Profile_Picture_1629356660984",biography:"Yannis Karamanos, born in Greece in 1953, completed his pre-graduate studies at the Université Pierre et Marie Curie, Paris, then his Masters and Doctoral degree at the Université de Lille (1983). He was associate professor at the University of Limoges (1987) before becoming full professor of biochemistry at the Université d’Artois (1996). He worked on the structure-function relationships of glycoconjugates and his main project was the investigations on the biological roles of the de-N-glycosylation enzymes (Endo-N-acetyl-β-D-glucosaminidase and peptide-N4-(N-acetyl-β-glucosaminyl) asparagine amidase). From 2002 he contributes to the understanding of the Blood-brain barrier functioning using proteomics approaches. He has published more than 70 papers. 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