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https://www.readbyqxmd.com/read/28723513/the-natural-history-and-outcome-predictors-of-metastatic-castration-resistant-prostate-cancer
#1
REVIEW
Robert J van Soest, Jason A Efstathiou, Cora N Sternberg, Bertand Tombal
CONTEXT: Biomarkers for the treatment of metastatic castration-resistant prostate cancer (mCRPC) are urgently needed by clinicians to facilitate treatment decisions. OBJECTIVE: To review current prognostic and predictive biomarkers in mCRPC. EVIDENCE ACQUISITION: We performed a nonsystematic review of the literature from 2004 to August 2016 by searching in Medline. Cross-matching references were used to search for additional articles. We reviewed clinical research and review articles written in the English language...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28723508/targeting-adaptive-pathways-in-metastatic-treatment-resistant-prostate-cancer-update-on-the-stand-up-2-cancer-prostate-cancer-foundation-supported-west-coast-prostate-cancer-dream-team
#2
Rahul Aggarwal, Tomasz M Beer, Martin Gleave, Joshua M Stuart, Matthew Rettig, Christopher P Evans, Jack Youngren, Joshi J Alumkal, Jiaoti Huang, George Thomas, Owen Witte, Eric J Small
The Stand Up 2 Cancer/Prostate Cancer Foundation-funded West Coast Dream Team project is a prospective multi-institutional study focused on acquiring metastatic castration-resistant prostate cancer (mCRPC) biopsy tissue at the time of resistance to abiraterone or enzalutamide. It is the first large-scale study designed to analyze mCRPC tissue specifically in this patient population. Study accrual is on target, with 261 out of a planned 300 metastatic tumor biopsies performed by August 2016. Paired biopsies have been completed in 42 patients, with paired genomic data before and after therapy obtained in 26 cases...
December 2016: European Urology Focus
https://www.readbyqxmd.com/read/28721808/molecular-tests-for-the-choice-of-cancer-therapy
#3
Anna P Sokolenko, Evgeny N Imyanitov
There are over a dozen of approved cancer drugs, whose administration is tailored to predictive laboratory tests. The examples include estrogen and progesterone receptor status determination for the use of endocrine therapy, HER2 assessment for the administration of HER2-targeting agents, EGFR and ALK gene testing for lung cancer treatment, BRAF analysis in melanoma, etc. While first predictive tests relied on relatively easy laboratory procedures, more recent developments require rather sophisticated assays...
July 19, 2017: Current Pharmaceutical Design
https://www.readbyqxmd.com/read/28721070/association-of-estrogen-receptor-%C3%AE-pvuii-and-xbai-polymorphisms-with-prostate-cancer-susceptibility-and-risk-stratification-a-meta-analysis-from-case-control-studies
#4
Yining Zhao, Xi Zheng, Lijie Zhang, Qiang Hu, Yitian Guo, Hua Jiang, Shennan Shi, Xiang Zhang
BACKGROUND: Studies on the association between two single nucleotide polymorphisms (SNPs) in estrogen receptor α (ERα), PvuII (rs2234693 T>C) and XbaI (rs9340799 A>G), and the prostate cancer risk are inconsistent. Therefore, we performed a meta-analysis to derive a more accurate estimation of this relationship. METHODS: A literature search of PubMed, Embase, Web of Science databases until October 1, 2016, was conducted. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were calculated to assess the strength of this association...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28712484/relevance-of-dna-damage-repair-in-the-management-of-prostate-cancer
#5
Patricia Banks, Wen Xu, Declan Murphy, Paul James, Shahneen Sandhu
Recent insights into the genomic aberrations that underlie and drive prostate cancer have redoubled efforts to molecularly stratify treatments based on predictive markers. Approximately 23% of patients with metastatic castration-resistant prostate cancer exhibit somatic or germline aberrations in genes implicated in DNA repair, such as BRCA2, BRCA1, ATM, CHEK2, and PALB2, as well as mismatch repair genes. At least 10% of men with advanced disease have germline mutations in DNA-repair genes (DRG). The enrichment of DRG defects in metastatic disease compared with localized, primary tumors suggests a possible role in carcinogenesis, disease progression, and potentially accounts for a more aggressive phenotype...
June 27, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/28700989/doritool-a-bioinformatics-integrative-tool-for-post-association-functional-annotation
#6
Isabel Martín-Antoniano, Lola Alonso, Miguel Madrid, Evangelina López de Maturana, Núria Malats
The emergence of high-throughput data in biology has increased the need for functional in silico analysis and prompted the development of integrative bioinformatics tools to facilitate the obtainment of biologically meaningful data. In this paper, we present DoriTool, a comprehensive, easy, and friendly pipeline integrating biological data from different functional tools. The tool was designed with the aim to maximize reproducibility and reduce the working time of the researchers, especially of those with limited bioinformatics skills, and to help them with the interpretation of the results...
July 13, 2017: Public Health Genomics
https://www.readbyqxmd.com/read/28700469/microarray-analysis-of-copy-number-variations-and-gene-expression-profiles-in-prostate-cancer
#7
Yuping Han, Xuefei Jin, Hongyan Li, Kaichen Wang, Ji Gao, Lide Song, Yanting Lv
BACKGROUND: This study aimed to identify potential prostate cancer (PC)-related variations in gene expression profiles. METHODS: Microarray data from the GSE21032 dataset that contained the whole-transcript and exon-level expression profile (GSE21034) and Agilent 244K array-comparative genomic hybridization data (GSE21035) were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) and copy-number variations (CNVs) were identified between PC and normal tissue samples...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28698647/identification-of-fbxl4-as-a-metastasis-associated-gene-in-prostate-cancer
#8
Elzbieta Stankiewicz, Xueying Mao, D Chas Mangham, Lei Xu, Marc Yeste-Velasco, Gabrielle Fisher, Bernard North, Tracy Chaplin, Bryan Young, Yuqin Wang, Jasmin Kaur Bansal, Sakunthala Kudahetti, Lucy Spencer, Christopher S Foster, Henrik Møller, Peter Scardino, R Tim Oliver, Jonathan Shamash, Jack Cuzick, Colin S Cooper, Daniel M Berney, Yong-Jie Lu
Prostate cancer is the most common cancer among western men, with a significant mortality and morbidity reported for advanced metastatic disease. Current understanding of metastatic disease is limited due to difficulty of sampling as prostate cancer mainly metastasizes to bone. By analysing prostate cancer bone metastases using high density microarrays, we found a common genomic copy number loss at 6q16.1-16.2, containing the FBXL4 gene, which was confirmed in larger series of bone metastases by fluorescence in situ hybridisation (FISH)...
July 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28697756/proteomic-characterization-of-paired-non-malignant-and-malignant-african-american-prostate-epithelial-cell-lines-distinguishes-them-by-structural-proteins
#9
Jennifer S Myers, Karin A Vallega, Jason White, Kaixian Yu, Clayton C Yates, Qing-Xiang Amy Sang
BACKGROUND: While many factors may contribute to the higher prostate cancer incidence and mortality experienced by African-American men compared to their counterparts, the contribution of tumor biology is underexplored due to inadequate availability of African-American patient-derived cell lines and specimens. Here, we characterize the proteomes of non-malignant RC-77 N/E and malignant RC-77 T/E prostate epithelial cell lines previously established from prostate specimens from the same African-American patient with early stage primary prostate cancer...
July 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28694034/insertion-and-deletion-derived-tumour-specific-neoantigens-and-the-immunogenic-phenotype-a-pan-cancer-analysis
#10
Samra Turajlic, Kevin Litchfield, Hang Xu, Rachel Rosenthal, Nicholas McGranahan, James L Reading, Yien Ning S Wong, Andrew Rowan, Nnennaya Kanu, Maise Al Bakir, Tim Chambers, Roberto Salgado, Peter Savas, Sherene Loi, Nicolai J Birkbak, Laurent Sansregret, Martin Gore, James Larkin, Sergio A Quezada, Charles Swanton
BACKGROUND: The focus of tumour-specific antigen analyses has been on single nucleotide variants (SNVs), with the contribution of small insertions and deletions (indels) less well characterised. We investigated whether the frameshift nature of indel mutations, which create novel open reading frames and a large quantity of mutagenic peptides highly distinct from self, might contribute to the immunogenic phenotype. METHODS: We analysed whole-exome sequencing data from 5777 solid tumours, spanning 19 cancer types from The Cancer Genome Atlas...
July 7, 2017: Lancet Oncology
https://www.readbyqxmd.com/read/28693295/germline-dna-copy-number-variations-as-potential-prognostic-markers-for-non-muscle-invasive-bladder-cancer-progression
#11
Yoshiaki Yamamoto, Yutaka Suehiro, Atomu Suzuki, Ryosuke Nawata, Yoshihisa Kawai, Ryo Inoue, Hiroshi Hirata, Hiroaki Matsumoto, Takahiro Yamasaki, Kohsuke Sasaki, Hideyasu Matsuyama
Accumulating evidence has suggested that germline DNA copy number variations (CNVs) affect various disorders, including human malignancies. However, the significance of CNVs in non-muscle invasive bladder cancer (NMIBC) remains unclear. The purpose of the present study was to identify the role of CNVs in NMIBC. Array comparative genomic hybridization (CGH) analysis was performed to search for candidate CNVs associated with NMIBC susceptibility. Quantitative polymerase chain reaction was carried out to evaluate CNVs associated with patient outcome in 189 NMIBC cases...
July 2017: Oncology Letters
https://www.readbyqxmd.com/read/28679531/transcriptional-regulation-of-nkx3-1-in-prostate-luminal-stem-cell-specification-and-cancer-initiation-via-its-3-genomic-region
#12
Qing Xie, Zhu A Wang
Nkx3.1, a transcription factor expressed in the prostate epithelium, is crucial for maintaining prostate cell fate and suppressing tumor initiation. Nkx3.1 is ubiquitously expressed in luminal cells of hormonally-intact prostate, but upon androgen deprivation, exclusively labels a type of luminal stem cells named castration-resistant Nkx3.1-expressing cells (CARNs). During prostate cancer initiation, Nkx3.1 expression is frequently lost in both humans and mouse models. Therefore, investigating how Nkx3.1 expression is regulated in vivo is important for understanding the mechanisms of prostate stem cell specification and cancer initiation...
July 5, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28677795/ctbp2-is-associated-with-angiogenesis-and-regulates-the-apoptosis-of-prostate-cancer-cells
#13
Qiang Xuan, Xiaoge Zhong, Weidong Li, Zengnan Mo, Yuanjie Huang, Yanling Hu
Angiogenesis is associated with prostate cancer (PCa) development and progression. Aberrant expression of C-terminal binding protein (CtBP)2 has been observed in PCa, but whether its change in expression plays a significant role in angiogenesis has not been completely characterized. we attempted to integrate and analyze the genome-wide association study (GWAS) of follicle stimulating hormone receptor (FSHR) and CtBP2, the Cancer Genome Atlas (TCGA) data and CtBP2 binding data in CistromeMap (18) to explore the mechanism of CtBP2 in PCa, and performed pathway enrichment analysis...
June 28, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28676700/the-multifaceted-roles-of-parp1-in-dna-repair-and-chromatin-remodelling
#14
REVIEW
Arnab Ray Chaudhuri, André Nussenzweig
Cells are exposed to various endogenous and exogenous insults that induce DNA damage, which, if unrepaired, impairs genome integrity and leads to the development of various diseases, including cancer. Recent evidence has implicated poly(ADP-ribose) polymerase 1 (PARP1) in various DNA repair pathways and in the maintenance of genomic stability. The inhibition of PARP1 is therefore being exploited clinically for the treatment of various cancers, which include DNA repair-deficient ovarian, breast and prostate cancers...
July 5, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28675175/telomeres-and-telomerase-in-prostate-cancer-development-and-therapy
#15
REVIEW
Mindy Kim Graham, Alan Meeker
Aberrations in telomere biology are among the earliest events in prostate cancer tumorigenesis and continue during tumour progression. Substantial telomere shortening occurs in prostate cancer cells and high-grade prostatic intraepithelial neoplasia. Not all mechanisms of telomere shortening are understood, but oxidative stress from local inflammation might accelerate prostatic telomere loss. Critically short telomeres can drive the accumulation of tumour-promoting genomic alterations; however, continued telomere erosion is unsustainable and must be mitigated to ensure cancer cell survival and unlimited replication potential...
July 4, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28667915/knockdown-of-tnf-receptor-associated-factor-2-traf2-modulates-in-vitro-growth-of-trail-treated-prostate-cancer-cells
#16
Bingbing Wei, Jun Ruan, Yuanyuan Mi, Jimeng Hu, Jian Zhang, Zhirong Wang, Qiang Hu, Haowen Jiang, Qiang Ding
TNF receptor-associated factor 2 (TRAF2) is documented to regulate tumor development and progression. Currently, the effect of TRAF2 on growth of androgen-refractory prostate cancer in response to TRAIL and the molecular mechanisms are not well understood. Here, we aim to investigate the effect of TRAF2 on in vitro growth of human androgen-insensitive prostate cancer DU-145 cells in the presence of TRAIL. Bioinformatics analysis of the Cancer Genome Atlas (TCGA) data was performed to examine TRAF2 expression and the prognostic value in prostate cancer...
June 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28665395/alternative-splicing-promotes-tumour-aggressiveness-and-drug-resistance-in-african-american-prostate-cancer
#17
Bi-Dar Wang, Kristin Ceniccola, SuJin Hwang, Ramez Andrawis, Anelia Horvath, Jennifer A Freedman, Jacqueline Olender, Stefan Knapp, Travers Ching, Lana Garmire, Vyomesh Patel, Mariano A Garcia-Blanco, Steven R Patierno, Norman H Lee
Clinical challenges exist in reducing prostate cancer (PCa) disparities. The RNA splicing landscape of PCa across racial populations has not been fully explored as a potential molecular mechanism contributing to race-related tumour aggressiveness. Here, we identify novel genome-wide, race-specific RNA splicing events as critical drivers of PCa aggressiveness and therapeutic resistance in African American (AA) men. AA-enriched splice variants of PIK3CD, FGFR3, TSC2 and RASGRP2 contribute to greater oncogenic potential compared with corresponding European American (EA)-expressing variants...
June 30, 2017: Nature Communications
https://www.readbyqxmd.com/read/28664150/coexpression-and-expression-quantitative-trait-loci-analyses-of-the-angiogenesis-gene-gene-interaction-network-in-prostate-cancer
#18
Hui-Yi Lin, Chia-Ho Cheng, Dung-Tsa Chen, Y Ann Chen, Jong Y Park
BACKGROUND: Prostate cancer (PCa) shows a substantial clinical heterogeneity. The existing risk classification for PCa prognosis based on clinical factors is not sufficient. Although some biomarkers for PCa aggressiveness have been identified, their underlying functional mechanisms are still unclear. We previously reported a gene-gene interaction network associated with PCa aggressiveness based on single nucleotide polymorphism (SNP)-SNP interactions in the angiogenesis pathway. The goal of this study is to investigate potential functional evidence of the involvement of the genes in this gene-gene interaction network...
October 2016: Translational Cancer Research
https://www.readbyqxmd.com/read/28663546/inherited-determinants-of-early-recurrent-somatic-mutations-in-prostate-cancer
#19
Alessandro Romanel, Sonia Garritano, Blerta Stringa, Mirjam Blattner, Davide Dalfovo, Dimple Chakravarty, David Soong, Kellie A Cotter, Gianluca Petris, Priyanka Dhingra, Paola Gasperini, Anna Cereseto, Olivier Elemento, Andrea Sboner, Ekta Khurana, Alberto Inga, Mark A Rubin, Francesca Demichelis
Prostate cancer is a highly heritable molecularly and clinically heterogeneous disease. To discover germline events involved in prostate cancer predisposition, we develop a computational approach to nominate heritable facilitators of somatic genomic events in the context of the androgen receptor signaling. Here, we use a ranking score and benign prostate transcriptomes to identify a non-coding polymorphic regulatory element at 7p14.3 that associates with DNA repair and hormone-regulated transcript levels and with an early recurrent prostate cancer-specific somatic mutation in the Speckle-Type POZ protein (SPOP) gene...
June 29, 2017: Nature Communications
https://www.readbyqxmd.com/read/28662213/verification-and-characterization-of-an-alternative-low-density-lipoprotein-receptor-related-protein-1-splice-variant
#20
Marlen Kolb, Susanne Kurz, Angelika Schäfer, Klaus Huse, Andreas Dietz, Gunnar Wichmann, Gerd Birkenmeier
BACKGROUND: Low density lipoprotein (LDL) receptor-related protein 1 (LRP1) is a ubiquitously expressed multi-ligand endocytosis receptor implicated in a wide range of signalling, among others in tumour biology. Tumour-associated genomic mutations of the LRP1 gene are described, but nothing is known about cancer-associated expression of LRP1 splice variants Therefore, the focus of this study was on an annotated truncated LRP1 splice variant (BC072015.1; NCBI GenBank), referred to as smLRP1, which was initially identified in prostate and lung carcinoma...
2017: PloS One
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