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prostate cancer genomic

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https://www.readbyqxmd.com/read/29145505/spontaneous-development-of-epstein-barr-virus-associated-human-lymphomas-in-a-prostate-cancer-xenograft-program
#1
Alberto J Taurozzi, Ramprakash Beekharry, Michelle Wantoch, Marie-Christine Labarthe, Hannah F Walker, Robert I Seed, Matthew Simms, Greta Rodrigues, James Bradford, Geertje van der Horst, Gabri van der Pluijm, Anne T Collins
Prostate cancer research is hampered by the lack of in vivo preclinical models that accurately reflect patient tumour biology and the clinical heterogeneity of human prostate cancer. To overcome these limitations we propagated and characterised a new collection of patient-derived prostate cancer xenografts. Tumour fragments from 147 unsupervised, surgical prostate samples were implanted subcutaneously into immunodeficient Rag2-/-γC-/- mice within 24 hours of surgery. Histologic and molecular characterisation of xenografts was compared with patient characteristics, including androgen-deprivation therapy, and exome sequencing...
2017: PloS One
https://www.readbyqxmd.com/read/29144949/re-genomic-hallmarks-of-localized-non-indolent-prostate-cancer
#2
Anthony Atala
No abstract text is available yet for this article.
December 2017: Journal of Urology
https://www.readbyqxmd.com/read/29142311/a-standardized-herbal-extract-mitigates-tumor-inflammation-and-augments-chemotherapy-effect-of-docetaxel-in-prostate-cancer
#3
Chin-Hsien Tsai, Sheue-Fen Tzeng, Shih-Chuan Hsieh, Yu-Chih Yang, Yi-Wen Hsiao, Mong-Hsun Tsai, Pei-Wen Hsiao
Activation of the NFκB pathway is often associated with advanced cancer and has thus been regarded as a rational therapeutic target. Wedelia chinensis is rich in luteolin, apigenin, and wedelolactone that act synergistically to suppress androgen receptor activity in prostate cancer. Interestingly, our evaluation of a standardized Wedelia chinensis herbal extract (WCE) concluded its efficacy on hormone-refractory prostate cancer through systemic mechanisms. Oral administration of WCE significantly attenuated tumor growth and metastasis in orthotopic PC-3 and DU145 xenografts...
November 15, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29141559/new-histopathological-genetic-features-to-improve-active-surveillance-selection-for-low-risk-prostate-cancer
#4
Lih-Ming Wong, Kevin Chu, Niall Corcoran, Sam Norden
BACKGROUND: A recent surge in biomarkers to aid management of men with prostate cancer has occurred. Their applications are varied and not all tests are applicable to the active surveillance setting. OBJECTIVE: To review primary evidence on genetic and immunohistochemical biomarkers, and their role on patient selection and risk stratification for men on active surveillance for prostate cancer. EVIDENCE ACQUISITION: A PubMed electronic search using the terms (biomarker or genetic or histopathological) AND ("prostate cancer" AND "active surveillance") was performed from inception to April 2015...
November 13, 2017: Anti-cancer Agents in Medicinal Chemistry
https://www.readbyqxmd.com/read/29141455/methionine-adenosyltransferases-in-cancers-mechanisms-of-dysregulation-and-implications-for-therapy
#5
Lauren Y Maldonado, Diana Arsene, José M Mato, Shelly C Lu
Methionine adenosyltransferase genes encode enzymes responsible for the biosynthesis of S-adenosylmethionine, the principal biological methyl donor and precursor of polyamines and glutathione. Mammalian cells express three genes - MAT1A, MAT2A, and MAT2B - with distinct expression and functions. MAT1A is mainly expressed in the liver and maintains the differentiated states of both hepatocytes and bile duct epithelial cells. Conversely, MAT2A and MAT2B are widely distributed in non-parenchymal cells of the liver and extrahepatic tissues...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/29140415/apobec3a-b-deletion-polymorphism-and-cancer-risk
#6
Liv B Gansmo, Paal Romundstad, Kristian Hveem, Lars Vatten, Serena Nik-Zainal, Per Eystein Lønning, Stian Knappskog
Activity of the APOBEC enzymes has been linked to specific mutational processes in human cancer genomes. A germline APOBEC3A/B deletion polymorphism is associated with APOBEC-dependent mutational signatures, and the deletion allele has been reported to confer an elevated risk of some cancers in Asian populations, while the results in European populations, so far, have been conflicting. We genotyped the APOBEC3A/B deletion polymorphism in a large population based sample consisting of 11,106 Caucasian (Norwegian) individuals, including 7,279 incident cancer cases (1,769 breast- , 1,360 lung-, 1,585 colon-, and 2,565 prostate cancer) and a control group of 3,827 matched individuals without cancer (1,918 females and 1,909 males) from the same population...
November 13, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29137428/pten-loss-is-associated-with-prostate-cancer-recurrence-and-alterations-in-tumor-dna-methylation-profiles
#7
Milan S Geybels, Min Fang, Jonathan L Wright, Xiaoyu Qu, Marina Bibikova, Brandy Klotzle, Jian-Bing Fan, Ziding Feng, Elaine A Ostrander, Peter S Nelson, Janet L Stanford
Background: Prostate cancer (PCa) with loss of the tumor suppressor gene PTEN has an unfavorable prognosis. DNA methylation profiles associated with PTEN loss may provide further insights into the mechanisms underlying these more aggressive, clinically relevant tumors. Methods: The cohort included patients with clinically localized PCa. Samples taken from the primary tumor were used to determine PTEN genomic deletions using FISH, and to analyze epigenome-wide DNA methylation profiles...
October 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/29137223/hormone-induced-dna-damage-response-and-repair-mediated-by-cyclin-d1-in-breast-and-prostate-cancer
#8
REVIEW
Gabriele Di Sante, Agnese Di Rocco, Claudia Pupo, Mathew C Casimiro, Richard G Pestell
Cell cycle control proteins govern events that leads to the production of two identical daughter cells. Distinct sequential temporal phases, Gap 1 (G1), Gap 0 (G0), Synthesis (S), Gap 2 (G2) and Mitosis (M) are negotiated through a series of check points during which the favorability of the local cellular environment is assessed, prior to replicating DNA [1]. Cyclin D1 has been characterized as a key regulatory subunit of the holoenzyme that promotes the G1/S-phase transition through phosphorylating the pRB protein...
October 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/29134670/altered-mitochondrial-genome-content-signals-worse-pathology-and-prognosis-in-prostate-cancer
#9
Anton M F Kalsbeek, Eva K F Chan, Judith Grogan, Desiree C Petersen, Weerachai Jaratlerdsiri, Ruta Gupta, Ruth J Lyons, Anne-Maree Haynes, Lisa G Horvath, James G Kench, Phillip D Stricker, Vanessa M Hayes
BACKGROUND: Mitochondrial genome (mtDNA) content is depleted in many cancers. In prostate cancer, there is intra-glandular as well as inter-patient mtDNA copy number variation. In this study, we determine if mtDNA content can be used as a predictor for prostate cancer staging and outcomes. METHODS: Fresh prostate cancer biopsies from 115 patients were obtained at time of surgery. All cores underwent pathological review, followed by isolation of cancer and normal tissue...
November 14, 2017: Prostate
https://www.readbyqxmd.com/read/29129398/genomic-markers-in-prostate-cancer-decision-making
#10
REVIEW
Vito Cucchiara, Matthew R Cooperberg, Marc Dall'Era, Daniel W Lin, Francesco Montorsi, Jack A Schalken, Christopher P Evans
CONTEXT: Although the widespread use of prostate-specific antigen (PSA) has led to an early detection of prostate cancer (PCa) and a reduction of metastatic disease at diagnosis, PSA remains one of the most controversial biomarkers due to its limited specificity. As part of emerging efforts to improve both detection and management decision making, a number of new genomic tools have recently been developed. OBJECTIVE: This review summarizes the ability of genomic biomarkers to recognize men at high risk of developing PCa, discriminate clinically insignificant and aggressive tumors, and facilitate the selection of therapies in patients with advanced disease...
November 9, 2017: European Urology
https://www.readbyqxmd.com/read/29127096/retention-of-interstitial-genes-between-tmprss2-and-erg-is-associated-with-low-risk-prostate-cancer
#11
Stephen J Murphy, Farhad Kosari, R Jeffrey Karnes, Aqsa Nasir, Sarah H Johnson, Athanasios G Gaitatzes, James B Smadbeck, Laureano J Rangel, George Vasmatzis, John C Cheville
TMPRSS2-ERG gene fusions occur in over 50% of prostate cancers, but their impact on clinical outcomes is not well understood. Retention of interstitial genes between TMPRSS2 and ERG has been reported to influence tumor progression in an animal model. In this study, we analyzed the status of TMPRSS2-ERG fusion genes and interstitial genes in tumors from a large cohort of men treated surgically for prostate cancer, associating alterations with biochemical progression. Through whole-genome mate pair sequencing, we mapped and classified rearrangements driving ETS family gene fusions in 133 cases of very low-, low-, intermediate-, and high-risk prostate cancer from radical prostatectomy specimens...
November 10, 2017: Cancer Research
https://www.readbyqxmd.com/read/29126443/ubiquitin-c-terminal-hydrolase-isozyme-l1-is-associated-with-shelterin-complex-at-interstitial-telomeric-sites
#12
Aleksandar Ilic, Sumin Lu, Vikram Bhatia, Farhana Begum, Thomas Klonisch, Prasoon Agarwal, Wayne Xu, James R Davie
BACKGROUND: Ubiquitin C-terminal hydrolase isozyme L1 (UCHL1) is primarily expressed in neuronal cells and neuroendocrine cells and has been associated with various diseases, including many cancers. It is a multifunctional protein involved in deubiquitination, ubiquitination and ubiquitin homeostasis, but its specific roles are disputed and still generally undetermined. RESULTS: Herein, we demonstrate that UCHL1 is associated with genomic DNA in certain prostate cancer cell lines, including DU 145 cells derived from a brain metastatic site, and in HEK293T embryonic kidney cells with a neuronal lineage...
November 10, 2017: Epigenetics & Chromatin
https://www.readbyqxmd.com/read/29122834/liquid-biopsy-in-prostate-cancer-a-case-for-comprehensive-genomic-characterization-of-circulating-tumor-cells
#13
EDITORIAL
Debasish Boral, Dario Marchetti
No abstract text is available yet for this article.
November 9, 2017: Clinical Chemistry
https://www.readbyqxmd.com/read/29121062/loss-of-function-jak1-mutations-occur-at-high-frequency-in-cancers-with-microsatellite-instability-and-are-suggestive-of-immune-evasion
#14
Lee A Albacker, Jeremy Wu, Peter Smith, Markus Warmuth, Philip J Stephens, Ping Zhu, Lihua Yu, Juliann Chmielecki
Immune evasion is a well-recognized hallmark of cancer and recent studies with immunotherapy agents have suggested that tumors with increased numbers of neoantigens elicit greater immune responses. We hypothesized that the immune system presents a common selective pressure on high mutation burden tumors and therefore immune evasion mutations would be enriched in high mutation burden tumors. The JAK family of kinases is required for the signaling of a host of immune modulators in tumor, stromal, and immune cells...
2017: PloS One
https://www.readbyqxmd.com/read/29119376/regulatory-effects-of-antitumor-agent-matrine-on-foxo-and-pi3k-akt-pathway-in-castration-resistant-prostate-cancer-cells
#15
Qi Li, Hai Huang, Zheng He, Yi Sun, Yufeng Tang, Xiaohong Shang, Chengbin Wang
We previously demonstrated that matrine could inhibit the proliferating, migrating, as well as invading processes of both PC-3 and DU145 cells. However, the underlying molecular mechanisms have not yet been clearly defined. In this study, using various techniques such as high throughput sequencing technology, bioinformatics, quantitative real-time PCR, and immunoblot analysis, we aimed to understand whether matrine serves as a novel regulator of FOXO and PI3K-AKT signaling pathway. DU145 and PC-3 cell lines were cultured for 24 h in vitro...
November 7, 2017: Science China. Life Sciences
https://www.readbyqxmd.com/read/29117387/two-novel-susceptibility-loci-for-prostate-cancer-in-men-of-african-ancestry
#16
David V Conti, Kan Wang, Xin Sheng, Jeannette T Bensen, Dennis J Hazelett, Michael B Cook, Sue A Ingles, Rick A Kittles, Sara S Strom, Benjamin A Rybicki, Barbara Nemesure, William B Isaacs, Janet L Stanford, Wei Zheng, Maureen Sanderson, Esther M John, Jong Y Park, Jianfeng Xu, Victoria L Stevens, Sonja I Berndt, Christopher A Haiman
Prostate cancer incidence is 1.6-fold higher in African Americans than in other populations. The risk factors that drive this disparity are unknown and potentially consist of social, environmental, and genetic influences. To investigate the genetic basis of prostate cancer in men of African ancestry, we performed a genome-wide association meta-analysis using two-sided statistical tests in 10 202 case subjects and 10 810 control subjects. We identified novel signals on chromosomes 13q34 and 22q12, with the risk-associated alleles found only in men of African ancestry (13q34: rs75823044, risk allele frequency = 2...
August 1, 2017: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29115469/microrna%C3%A2-512%C3%A2-3p-is-upregulated-and-promotes-proliferation-and-cell-cycle-progression-in-prostate-cancer-cells
#17
Zhigang Rao, Ziqi He, Yi He, Zonghua Guo, Dongbo Kong, Jufang Liu
Prostate cancer (PCa) is the most commonly diagnosed cancer in males worldwide. MicroRNAs (miRNAs/miRs) are small non‑coding RNAs that participate in the regulation of various biological processes by regulating post‑transcriptional gene expression. However, whether dysregulation of miRNA expression may be associated with the carcinogenesis of PCa remains to be elucidated. The present study identified differentially expressed miRNAs in PCa by analyzing two publicly available gene expression datasets, GSE14857 and GSE21036...
October 20, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29113170/screening-of-potential-therapy-targets-for-prostate-cancer-using-integrated-analysis-of-two-gene-expression-profiles
#18
Rui Zhao, Yao Wang, Muchun Zhang, Xinquan Gu, Weihua Wang, Jiufeng Tan, Xin Wei, Ning Jin
The aim of the present study was to analyze potential therapy targets for prostate cancer using integrated analysis of two gene expression profiles. First, gene expression profiles GSE38241 and GSE3933 were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between prostate cancer and normal control samples were identified using the Linear Models for Microarray Data package. Pathway enrichment analysis of DEGs was performed using Gene Ontology and the Kyoto Encyclopedia of Genes and Genomes...
November 2017: Oncology Letters
https://www.readbyqxmd.com/read/29111351/chemoprevention-with-isothiocyanates-from-bench-to-bedside
#19
Carsten Gründemann, Roman Huber
Isothiocyanates (ITCs) are naturally occurring hydrolization products from glucosinolates (GLSs) in brassicaceae and in epidemiological studies their intake has been weakly to moderately inversely correlated with the risk of colorectal cancer, prostate cancer and lung cancer. Numerous preclinical studies demonstrate chemopreventive mode of actions of ITCs, mainly related to a.) detoxification (induction of phase II enzymes), b.) anti-inflammatory properties by down-regulation of NFkappaB activity, c.) cyclin-mediated cell cycle arrest and d...
October 27, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29109393/scalable-whole-exome-sequencing-of-cell-free-dna-reveals-high-concordance-with-metastatic-tumors
#20
Viktor A Adalsteinsson, Gavin Ha, Samuel S Freeman, Atish D Choudhury, Daniel G Stover, Heather A Parsons, Gregory Gydush, Sarah C Reed, Denisse Rotem, Justin Rhoades, Denis Loginov, Dimitri Livitz, Daniel Rosebrock, Ignaty Leshchiner, Jaegil Kim, Chip Stewart, Mara Rosenberg, Joshua M Francis, Cheng-Zhong Zhang, Ofir Cohen, Coyin Oh, Huiming Ding, Paz Polak, Max Lloyd, Sairah Mahmud, Karla Helvie, Margaret S Merrill, Rebecca A Santiago, Edward P O'Connor, Seong H Jeong, Rachel Leeson, Rachel M Barry, Joseph F Kramkowski, Zhenwei Zhang, Laura Polacek, Jens G Lohr, Molly Schleicher, Emily Lipscomb, Andrea Saltzman, Nelly M Oliver, Lori Marini, Adrienne G Waks, Lauren C Harshman, Sara M Tolaney, Eliezer M Van Allen, Eric P Winer, Nancy U Lin, Mari Nakabayashi, Mary-Ellen Taplin, Cory M Johannessen, Levi A Garraway, Todd R Golub, Jesse S Boehm, Nikhil Wagle, Gad Getz, J Christopher Love, Matthew Meyerson
Whole-exome sequencing of cell-free DNA (cfDNA) could enable comprehensive profiling of tumors from blood but the genome-wide concordance between cfDNA and tumor biopsies is uncertain. Here we report ichorCNA, software that quantifies tumor content in cfDNA from 0.1× coverage whole-genome sequencing data without prior knowledge of tumor mutations. We apply ichorCNA to 1439 blood samples from 520 patients with metastatic prostate or breast cancers. In the earliest tested sample for each patient, 34% of patients have ≥10% tumor-derived cfDNA, sufficient for standard coverage whole-exome sequencing...
November 6, 2017: Nature Communications
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