140 research outputs found
Intake patterns of specific alcoholic beverages by prostate cancer status
Background: Previous studies have shown that different alcoholic beverage types impact prostate cancer (PCa) clinical outcomes differently. However, intake patterns of specific alcoholic beverages for PCa status are understudied. The study?s objective is to evaluate intake patterns of total alcohol and the three types of beverage (beer, wine, and spirits) by the PCa risk and aggressiveness status. Method: This is a cross-sectional study using 10,029 men (4676 non-PCa men and 5353 PCa patients) with European ancestry from the PCa consortium. Associations between PCa status and alcohol intake patterns (infrequent, light/moderate, and heavy) were tested using multinomial logistic regressions. Results: Intake frequency patterns of total alcohol were similar for non-PCa men and PCa patients after adjusting for demographic and other factors. However, PCa patients were more likely to drink wine (light/moderate, OR = 1.11, p = 0.018) and spirits (light/moderate, OR = 1.14, p = 0.003; and heavy, OR = 1.34, p = 0.04) than non-PCa men. Patients with aggressive PCa drank more beer than patients with non-aggressive PCa (heavy, OR = 1.48, p = 0.013). Interestingly, heavy wine intake was inversely associated with PCa aggressiveness (OR = 0.56, p = 0.009). Conclusions: The intake patterns of some alcoholic beverage types differed by PCa status. Our findings can provide valuable information for developing custom alcohol interventions for PCa patients
Procjena cito-/genotoksiÄnosti irinotekana u V79-stanicama primjenom komet-testa, mikronukleus-testa i testa kromosomskih aberacija
Irinotecan is a topoisomerase I interactive agent, widely used in the treatment of metastatic colorectal cancer. The genotoxic effects of the maximum single dose (18 ÎŒg mL-1), recommended monotherapy dose (9 ÎŒg mL-1), and recommended combined therapy dose (4.5 ÎŒg mL-1) of irinotecan were studied on V79 cells using the comet assay, chromosome aberration assay, and micronucleus test. The cells were treated with irinotecan for 2 h or 24 h. The statistical signifi cance of the results was determined using the one-way ANOVA test and a nonparametric Mann Whitney U test. The comet assay did not show dose-dependent or time-dependent effects. The chromosome aberration analysis showed large DNA rearrangements, i.e.,
chromosome exchanges. Although the exposed cultures showed a signifi cant increase in micronucleated cells in respect to control, no dose-dependent relation was established among the treated cultures. Timedependent effect was also not observed.Irinotekan je citotoksiÄni lijek koji inhibira enzim DNA-topoizomerazu I. U ĆĄirokoj je primjeni u terapiji metastatskog karcinoma kolona i rektuma. U uvjetima in vitro primjenom komet-testa, analize kromosomskih aberacija i mikronukleus-testa na V79-stanicama istraĆŸili smo genotoksiÄni uÄinak maksimalne pojedinaÄne
doze (18 ÎŒg mL-1), preporuÄene monoterapijske doze (9 ÎŒg mL-1) i preporuÄene doze irinotekana za kombiniranu terapiju (4,5 ÎŒg mL-1). Kulture stanica bile su tretirane irinotekanom 2 h i 24 h. StatistiÄka
znaÄajnost odreÄivana je jednosmjernim ANOVA-testom i neparametrijskim Mann Whitneyevim U-testom.
Komet-testom nije utvrÄen uÄinak koncentracije i/ili vremena izloĆŸenosti. Analiza kromosomskih aberacija pokazala je prisutnost izmjena kromatida, tj. porast broja triradijusa i tetraradijusa. Iako je u kulturama stanica izloĆŸeni irinotekanu opaĆŸen znaÄajan porast broja mikronukleusa u odnosu na kontrolu, nije uoÄena ovisnost o dozi lijeka ni o vremenu izloĆŸenosti u opisanim eksperimentalnim uvjetima. Dobiveni rezultati upuÄuju na genotoksiÄnost irinotekana za V79-stanice. Nijednom od primijenjenih metoda nije utvrÄena ovisnost uÄinka irinotekana o vremenu ili dozi
IzloĆŸenost genotoksiÄnim agensima iz ĆŸivotnog okoliĆĄa tijekom prenatalnog razvoja i djetinjstva
Health disorders and diseases related to environmental exposure in children such as cancer and immunologic disturbances (asthma, allergies) are on the rise. However, complex transplacental and prepubertal genotoxicology is given very limited consideration, even though intrauterine development and early childhood may be critical for elucidating the cancer aetiology. The foetus is transplacentally exposed to contaminants in food and environment such as various chemicals, drugs, radiochemically contaminated water and air. Target organs of xenobiotic action may differ between the mother and the foetus due to specific stage of developmental physiology and enzyme distribution. This in turn may lead to different levels of clastogenic and aneugenic metabolites of the same xenobiotic in the mother and the foetus. Adultâs protective behaviour is not sufficient to isolate children from radioisotopes, pesticides, toxic metals and metalloids, environmental tobacco smoke, endocrine disrupting chemicals, and various food contaminants, which are just a part of the stressors present in a polluted environment. In order to improve legislation related to foetus and child exposure to genotoxic and possibly carcinogenic agents, oncologists, paediatricians, environmental health specialists, and genotoxicologists should work together much more closely to make a more effective use of accumulated scientific data, with the final aim to lower cancer incidence and mortality.UnatoÄ velikim naporima da se smanji okoliĆĄna izloĆŸenost u djece se dalje biljeĆŸi trend porasta pojavnosti karcinoma i imunosnih poremeÄaja (astma, alergije). Premda su intrauterini razvoj i rano djetinjstvo kritiÄno razdoblje za tumaÄenje etiologije nastanka karcinoma, transplacentalna i prepubertetna genotoksikologija
do danas su slabo istraĆŸene. Fetus je transplacentalno izloĆŸen brojnim fizikalnim i kemijskim Äimbenicima: kontaminantima iz hrane i okoliĆĄa, radiokemijski kontaminiranoj vodi, zraku te lijekovima. Ciljna tkiva za djelovanje ksenobiotika mogu biti razliÄita u majke i fetusa zbog razliÄitosti u razvojnoj fiziologiji i distribuciji enzima. Zbog toga u organizmu majke i fetusa mogu nastati razliÄite razine klastogenih i aneugenih metabolita istog ksenobiotika.
ZaĆĄtitna uloga odraslih u namjeri da sprijeÄe negativne utjecaje oneÄiĆĄÄenog okoliĆĄa na djetetovo zdravlje Äesto je ograniÄena jer su radioizotopi, olovo, PCB, pasivno puĆĄenje, ĆŸiva, endokrino aktivne tvari, pesticidi i kontaminanti prisutni u svim ĆŸivotnim podruÄjima tijekom razvoja i rasta djeteta. Kako bi se poboljĆĄalo zakonodavstvo vezano uz izloĆŸenost djece genotoksiÄnim i vjerojatno kancerogenim tvarima, tijekom razvoja potrebna je bolja suradnja onkologa, pedijatara, struÄnjaka zdravstvene ekologije i genotoksikologa.
Na taj naÄin ostvarilo bi se uspjeĆĄnije iskoriĆĄtavanje postojeÄih znanstvenih podataka u cilju smanjenja incidencije karcinoma i mortaliteta
A Novel Soluble Immune-Type Receptor (SITR) in Teleost Fish: Carp SITR Is Involved in the Nitric Oxide-Mediated Response to a Protozoan Parasite
Background- The innate immune system relies upon a wide range of germ-line encoded receptors including a large number of immunoglobulin superfamily (IgSF) receptors. Different Ig-like immune receptor families have been reported in mammals, birds, amphibians and fish. Most innate immune receptors of the IgSF are type I transmembrane proteins containing one or more extracellular Ig-like domains and their regulation of effector functions is mediated intracellularly by distinct stimulatory or inhibitory pathways. Methodology/Principal Findings - Carp SITR was found in a substracted cDNA repertoire from carp macrophages, enriched for genes up-regulated in response to the protozoan parasite Trypanoplasma borreli. Carp SITR is a type I protein with two extracellular Ig domains in a unique organisation of a N-proximal V/C2 (or I-) type and a C-proximal V-type Ig domain, devoid of a transmembrane domain or any intracytoplasmic signalling motif. The carp SITR C-proximal V-type Ig domain, in particular, has a close sequence similarity and conserved structural characteristics to the mammalian CD300 molecules. By generating an anti-SITR antibody we could show that SITR protein expression was restricted to cells of the myeloid lineage. Carp SITR is abundantly expressed in macrophages and is secreted upon in vitro stimulation with the protozoan parasite T. borreli. Secretion of SITR protein during in vivo T. borreli infection suggests a role for this IgSF receptor in the host response to this protozoan parasite. Overexpression of carp SITR in mouse macrophages and knock-down of SITR protein expression in carp macrophages, using morpholino antisense technology, provided evidence for the involvement of carp SITR in the parasite-induced NO production. Conclusion/Significance - We report the structural and functional characterization of a novel soluble immune-type receptor (SITR) in a teleost fish and propose a role for carp SITR in the NO-mediated response to a protozoan parasite
Identification of Novel Susceptibility Loci and Genes for Prostate Cancer Risk: A Transcriptome-Wide Association Study in over 140,000 European Descendants
Genome-wide association studyâidentified prostate cancer risk variants explain only a relatively small fraction of its familial relative risk, and the genes responsible for many of these identified associations remain unknown. To discover novel prostate cancer genetic loci and possible causal genes at previously identified risk loci, we performed a transcriptome-wide association study in 79,194 cases and 61,112 controls of European ancestry. Using data from the Genotype-Tissue Expression Project, we established genetic models to predict gene expression across the transcriptome for both prostate models and cross-tissue models and evaluated model performance using two independent datasets. We identified significant associations for 137 genes at P < 2.61 Ă 10â6, a Bonferroni-corrected threshold, including nine genes that remained significant at P < 2.61 Ă 10â6 after adjusting for all known prostate cancer risk variants in nearby regions. Of the 128 remaining associated genes, 94 have not yet been reported as potential target genes at known loci. We silenced 14 genes and many showed a consistent effect on viability and colony-forming efficiency in three cell lines. Our study provides substantial new information to advance our understanding of prostate cancer genetics and biology.
SIGNIFICANCE: This study identifies novel prostate cancer genetic loci and possible causal genes, advancing our understanding of the molecular mechanisms that drive prostate cancer
Association analyses identify 31 new risk loci for colorectal cancer susceptibility
Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention
Fine-mapping of prostate cancer susceptibility loci in a large meta-analysis identifies candidate causal variants
Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Prostate cancer is a polygenic disease with a large heritable component. A number of common, low-penetrance prostate cancer risk loci have been identified through GWAS. Here we apply the Bayesian multivariate variable selection algorithm JAM to fine-map 84 prostate cancer susceptibility loci, using summary data from a large European ancestry meta-analysis. We observe evidence for multiple independent signals at 12 regions and 99 risk signals overall. Only 15 original GWAS tag SNPs remain among the catalogue of candidate variants identified; the remainder are replaced by more likely candidates. Biological annotation of our credible set of variants indicates significant enrichment within promoter and enhancer elements, and transcription factor-binding sites, including AR, ERG and FOXA1. In 40 regions at least one variant is colocalised with an eQTL in prostate cancer tissue. The refined set of candidate variants substantially increase the proportion of familial relative risk explained by these known susceptibility regions, which highlights the importance of fine-mapping studies and has implications for clinical risk profiling. © 2018 The Author(s).Peer reviewe
- âŠ