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Testis cancer: Genes, environment, hormones

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889196722 Year: Pages: 86 DOI: 10.3389/978-2-88919-672-2 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Internal medicine
Added to DOAB on : 2016-08-16 10:34:25
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Abstract

Testicular cancer (TC) is the most common cancer in males aged 20-40 years, with a worldwide incidence of 7.5 per 100,000, but the rates vary considerably between countries and ethnic groups and there is evidence also for an increasing incidence in last decades. About 95% of all TCs are represented by testicular germ cell tumors (TGCTs), which include seminoma and non-seminoma histological types. It is generally assumed that the development of TGCT is under endocrine control. In particular, unbalanced androgen/estrogen levels and/or activity are believed to represent the key events for TGCT development and progression. Furthermore, recent evidence has suggested genetic association of TGCT with variations in genes involved in hypothalamic-pituitary-testicular axis and steroidogenic enzymes. This recent evidence expands the current knowledge on the role of genetic contribution in testicular cancer susceptibility, and supports the hypothesis that variations in hormone metabolism genes might change the hormonal environment implicated in testicular carcinogenesis. Therefore, hormonal carcinogenesis is an important and controversial area of current research in TGCT, and further attention is given to genetic factors influencing hormone-related cancer risk. The genetic component to TGCT is in general strong. In fact, although environmental factors clearly contribute to TGCT development (and probably to its increasing incidence in some geographical areas), the proportion of TGCT susceptibility accounted for by the genetic effects is estimated at 25%. TGCT has high familial risks compared with most other cancer types that are generally no more than two-fold: brothers of individuals with TGCT have an 8- to 12-fold increased risk of disease, and sons of affected individuals have a 4- to 6-fold increased risk. Despite this strong familial relative risk, early results from linkage studies identified a limited relationship with genetic factors, suggesting that TGCT is a genetically complex trait. However, more recently, four genome-wide association studies (GWAS) from the UK and USA have reported association of TGCTs with six new loci (KITLG, SPRY4, BAK1, DMRT1, TERT, and ATF7IP). The strongest association for TGCT susceptibility was found for SNPs in KITLG (ligand for the membrane-bound receptor tyrosine kinase KIT) gene with a greater than 2.5-fold increased risk of disease per major allele, which is the highest reported for any cancer to date. These studies are being now replicated by other researches and attention is given to the relationship between these genetic variations, TGCT risk and frequently associated anomalies of the reproductive tract, such as cryptorchidism and infertility. Finally, over the past few decades, TCGT research has focused also on external environmental causes acting mainly as endocrine disrupters of androgen and oestrogen pathways, even during the foetal development of the testis. It is well known that the testicular dysgenesis syndrome (TDS) hypothesis, proposed ten years ago, suggests that disturbed testicular development in fetal life may result in one or more of four disorders postnatally, named cryptorchidism, hypospadias, poor semen quality, and TGCT. These four disorders are therefore considered as one clinical entity and are linked together by epidemiological and pathophysiological relations. The relative contribution of genetics and environment in TGCT development, and the interactions between endocrine disruptors and variations in genes involved in hormonal carcinogenesis is therefore another interesting area of research.

New Advances on Zika Virus Research

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ISBN: 9783038977643 Year: Pages: 552 DOI: 10.3390/books978-3-03897-765-0 Language: eng
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Subject: Internal medicine --- Medicine (General)
Added to DOAB on : 2019-04-05 10:34:31
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Abstract

Zika virus (ZIKV) is a mosquito-borne member of the Flaviviridae family that historically has been associated with mild febrile illness. However, the recent outbreaks in Brazil in 2015 and its rapid spread throughout South and Central America and the Caribbean, together with its association with severe neurological disorders—including fetal microcephaly and Guillain-Barré syndrome in adults—have changed the historic perspective of ZIKV. Currently, ZIKV is considered an important public health concern that has the potential to affect millions of people worldwide. The significance of ZIKV in human health and the lack of approved vaccines and/or antiviral drugs to combat ZIKV infection have triggered a global effort to develop effective countermeasures to prevent and/or treat ZIKV infection. In this Special Issue of Viruses, we have assembled a collection of 32 research and review articles that cover the more recent advances on ZIKV molecular biology, replication and transmission, virus–host interactions, pathogenesis, epidemiology, vaccine development, antivirals, and viral diagnosis.

Keywords

Ziks virus --- silvestrol --- antiviral --- eIF4A --- hepatocytes --- flavivirus --- arbovirus --- Zika --- sexual transmission --- testis --- prostate --- Zika virus --- ZIKV --- rhesus macaques --- Non-human primates --- NHP --- infection --- natural history --- Asian-lineage --- African-lineage --- zika virus --- ZIKV–host interactions --- viral pathogenesis --- cell surface receptors --- antiviral responses --- viral counteraction --- cytopathic effects --- microcephaly --- ZIKV-associated neurologic disorders --- Zika virus --- serology --- flavivirus --- microsphere immunoassay --- validated --- optimised --- dengue virus --- ZIKV --- reporter virus --- cryptic promoter silencing --- full-length molecular clone --- subgenomic replicon --- plasmid toxicity --- Zika virus --- dengue viruses --- flavivirus --- ELISA --- indirect immunofluorescence --- plaque reduction neutralization test --- polymerase chain reaction --- cross-reactions --- Zika virus --- flavivirus --- infectious cDNA --- replication --- gene expression --- neuropathogenesis --- viral genetic variation --- host genetic variation --- flavivirus --- Zika virus --- therapy --- host-directed antivirals --- Aedes aegypti --- RNA-seq --- insecticide resistance --- Zika virus --- detoxification and immune system responses --- Zika virus --- mosquito-borne flavivirus --- emerging arbovirus --- outbreak control --- molecular diagnostics --- laboratory preparedness --- assay standardization --- external quality assessment --- EQA --- QCMD --- flavivirus --- eye --- zika virus --- blood-retinal barrier --- ocular --- innate response --- Zika virus --- pregnancy --- fetal infection --- congenital Zika syndrome --- Asian lineage --- Zika virus --- Full-length cDNA infectious clones --- Bacterial artificial chromosome --- NS2A protein --- Zika virus --- neural progenitor cells --- neurons --- Zika virus --- antivirals --- therapeutics --- research models and tools --- flavivirus --- Zika virus (ZIKV) --- reverse genetics --- infectious clone --- full-length molecular clone --- bacterial artificial chromosome --- replicon --- infectious RNA --- Zika virus --- flavivirus --- arbovirus --- sexual transmission --- host genetic variation --- immune response --- Zika virus --- flaviviruses --- vaccines --- virus like particles --- clinical trials --- ZIKV --- NS1 protein --- Zika virus --- diagnosis --- monoclonal antibodies --- ELISA --- zika virus --- placenta cells --- microglia cells --- siRNA --- TLR7/8 --- Zika --- viral evolution --- genetic variability --- Bayesian analyses --- Zika virus --- reverse genetics --- infectious cDNA --- Tet-inducible --- MR766 --- FSS13025 --- flavivirus --- ZIKV --- NS5 --- type I IFN antagonist --- point-of-care diagnostics --- isothermal nucleic acid amplification --- nucleic acid computation --- nucleic acid strand exchange --- zika virus --- mosquito --- mosquito surveillance --- multiplex nucleic acid detection --- boolean logic-processing nucleic acid probes --- Zika virus --- flavivirus --- astrocytomas --- dsRNA --- viral fitness --- antiviral --- heme-oxygenase 1 --- Zika virus --- viral replication --- Zika virus --- antiviral compounds --- neural cells --- viral replication --- flavivirus --- Zika virus --- viral persistence --- testicular cells --- testes --- Zika virus --- prM-E proteins --- viral pathogenicity --- virus attachment --- viral replication --- viral permissiveness --- viral survival --- apoptosis --- cytopathic effects --- mutagenesis --- chimeric viruses --- human brain glial cells --- Zika virus --- flavivirus --- microRNAs --- neurons --- neuroinflammation --- anti-viral immunity --- Zika virus --- dengue virus --- secondary infections --- cross-reactions --- IgA --- IgG avidity tests

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