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Daniel C Danila, Aliaksandra Samoila, Chintan Patel, Nicole Schreiber, Amrita Herkal, Aseem Anand, Diogo Bastos, Glenn Heller, Martin Fleisher, Howard I Scher
Circulating tumor cell (CTC) number measured with the CellSearch assay is prognostic for survival in metastatic castration-resistant prostate cancer before and after therapy. Using a standard operating protocol for sample collection, processing, and analysis, we compared detection rates of CellSearch performed using US Food and Drug Administration-cleared methodology with a second positive selection assay, AdnaTest, and a nonselection polymerase chain reaction (PCR)-based (direct detection PCR [DDPCR]) assay in 55 blood samples from 47 men with progressive metastatic castration-resistant prostate cancer...
September 2016: Cancer Journal
Takahide Hayano, Hiroshi Matsui, Hirofumi Nakaoka, Nobuaki Ohtake, Kazuyoshi Hosomichi, Kazuhiro Suzuki, Ituro Inoue
Prostate cancer (PC) is the second most common cancer in men. Family history is the major risk factor for PC. Only two susceptibility genes were identified in PC, BRCA2 and HOXB13. A comprehensive search of germline variants for patients with PC has not been reported in Japanese families. In this study, we conducted exome sequencing followed by Sanger sequencing to explore responsible germline variants in 140 Japanese patients with PC from 66 families. In addition to known susceptibility genes, BRCA2 and HOXB13, we identified TRRAP variants in a mutually exclusive manner in seven large PC families (three or four patients per family)...
2016: PloS One
Jianzhong Zhang, Li Xiao, Zhiqiang Qin, Aiming Xu, Kai Zhao, Chao Liang, Chenkui Miao, Jundong Zhu, Wei Chen, Yibo Hua, Yiyang Liu, Chao Zhang, Yajie Yu, Shifeng Su, Zengjun Wang
Germline HOXB13 G84E mutation (rs138213197) has been described associated with prostate cancer (PCa) susceptibility but results of different studies are inconsistent. We conducted this meta-analysis to evaluate the specific role of this mutation. Relevant available studies were identified by searching the databases Pubmed, Embase and Web of Science. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to measure the strength of the association. Subgroup analysis were performed to evaluate the specific role of rs138213197 in disease aggressiveness, diagnostic age and family history...
September 10, 2016: Oncotarget
Kathleen A Cooney, Jennifer L Beebe-Dimmer
No abstract text is available yet for this article.
October 2016: BJU International
Hannah Brechka, Erin M McAuley, Sophia M Lamperis, Gladell P Paner, Donald J Vander Griend
A fundamental understanding of prostate development and tissue homeostasis has the high potential to reveal mechanisms for prostate disease initiation and identify novel therapeutic approaches for disease prevention and treatment. Our current understanding of prostate lineage specification stems from the use of developmental model systems that rely upon the embryonic preprostatic urogenital sinus mesenchyme to induce the formation of mature prostate epithelial cells. It is unclear, however, how the urogenital sinus epithelium can derive both adult urethral glands and prostate epithelia...
October 4, 2016: Stem Cells and Development
Erik Bovinder Ylitalo, Elin Thysell, Emma Jernberg, Marie Lundholm, Sead Crnalic, Lars Egevad, Pär Stattin, Anders Widmark, Anders Bergh, Pernilla Wikström
BACKGROUND: Novel therapies for men with castration-resistant prostate cancer (CRPC) are needed, particularly for cancers not driven by androgen receptor (AR) activation. OBJECTIVES: To identify molecular subgroups of PC bone metastases of relevance for therapy. DESIGN, SETTING, AND PARTICIPANTS: Fresh-frozen bone metastasis samples from men with CRPC (n=40), treatment-naïve PC (n=8), or other malignancies (n=12) were characterized using whole-genome expression profiling, multivariate principal component analysis (PCA), and functional enrichment analysis...
August 3, 2016: European Urology
Tilman Todenhöfer, Arun Azad, Craig Stewart, Jian Gao, Bernhard J Eigl, Martin E Gleave, Anthony M Joshua, Peter C Black, Kim N Chi
PURPOSE: The expression of AR-V7 (androgen receptor splice variant) 7 in circulating tumor cells has been associated with resistance to abiraterone and enzalutamide in patients with metastatic castration resistant prostate cancer. We used a sensitive, whole blood reverse transcriptase-polymerase chain reaction assay that does not require circulating tumor cell enrichment to correlate outcomes of abiraterone with whole blood expression of AR-V7 and other prostate cancer associated transcripts...
July 17, 2016: Journal of Urology
Jingjing Liu, Wendy J C Prager-van der Smissen, Marjanka K Schmidt, J Margriet Collée, Sten Cornelissen, Roy Lamping, Anja Nieuwlaat, John A Foekens, Maartje J Hooning, Senno Verhoef, Ans M W van den Ouweland, Frans B L Hogervorst, John W M Martens, Antoinette Hollestelle
The HOXB13 p.G84E mutation has been firmly established as a prostate cancer susceptibility allele. Although HOXB13 also plays a role in breast tumor progression, the association of HOXB13 p.G84E with breast cancer risk is less evident. Therefore, we comprehensively interrogated the entire HOXB13 coding sequence for mutations in 1,250 non-BRCA1/2 familial breast cancer cases and 800 controls. We identified two predicted deleterious missense mutations, p.G84E and p.R217C, that were recurrent among breast cancer cases and further evaluated their association with breast cancer risk in a larger study...
2016: Scientific Reports
Patrick G Pilie, Veda N Giri, Kathleen A Cooney
No abstract text is available yet for this article.
July 2016: Asian Journal of Andrology
Huan Tong, Jie-Qi Ke, Fei-Zhou Jiang, Xiao-Jun Wang, Fang-Yuan Wang, Yi-Ran Li, Wen Lu, Xiao-Ping Wan
PURPOSE: To elucidate the role of tumor-associated macrophage (TAM) in the loss of ERα in endometrial cancer (EC) and the underlying mechanism. MATERIALS AND METHODS: Tissue microarrays and immunohistochemistry assays were performed using endometrial cancer tissue along with coculture, immunofluorescence, invasion assays and ChIP-qPCR using a human endometrial cancer cell line. RESULTS: Compared with normal tissue, an increased number of TAM was found in EC tissue (34...
June 28, 2016: Cancer Letters
Qiang Hao, Dong Wei, Yaoguang Zhang, Xin Chen, Fan Yang, Ze Yang, Xiaoquan Zhu, Jianye Wang
In the past twenty-five years, over 700 case-control association studies on the risk of prostate cancer have been published worldwide, but their results were largely inconsistent. To facilitate following and explaining these findings, we performed a systematic meta-analysis using allelic contrasts for gene-specific SNVs from at least three independent population-based case-control studies, which were published in the field of prostate cancer between August 1, 1990 and August 1, 2015. Across 66 meta-analyses, a total of 20 genetic variants involving 584,100 subjects in 19 different genes (KLK3, IGFBP3, ESR1, SOD2, CAT, CYP1B1, VDR, RFX6, HNF1B, SRD5A2, FGFR4, LEP, HOXB13, FAS, FOXP4, SLC22A3, LMTK2, EHBP1 and MSMB) exhibited significant association with prostate cancer...
April 19, 2016: Oncotarget
Chang-Hyun Lee, Chun Kee Chung, Jung Hun Ohn, Chi Heon Kim
Ependymomas occur in both the brain and spine. The prognosis of these tumors sometimes differs for different locations. The genetic landscape of ependymoma is very heterogeneous despite the similarity of histopathologic findings. In this review, we describe the genetic differences between spinal ependymomas and their intracranial counterparts to better understand their prognosis. From the literature review, many studies have reported that spinal cord ependymoma might be associated with NF2 mutation, NEFL overexpression, Merlin loss, and 9q gain...
March 2016: Journal of Korean Neurosurgical Society
Thomas Whitington, Ping Gao, Wei Song, Helen Ross-Adams, Alastair D Lamb, Yuehong Yang, Ilaria Svezia, Daniel Klevebring, Ian G Mills, Robert Karlsson, Silvia Halim, Mark J Dunning, Lars Egevad, Anne Y Warren, David E Neal, Henrik Grönberg, Johan Lindberg, Gong-Hong Wei, Fredrik Wiklund
Molecular characterization of genome-wide association study (GWAS) loci can uncover key genes and biological mechanisms underpinning complex traits and diseases. Here we present deep, high-throughput characterization of gene regulatory mechanisms underlying prostate cancer risk loci. Our methodology integrates data from 295 prostate cancer chromatin immunoprecipitation and sequencing experiments with genotype and gene expression data from 602 prostate tumor samples. The analysis identifies new gene regulatory mechanisms affected by risk locus SNPs, including widespread disruption of ternary androgen receptor (AR)-FOXA1 and AR-HOXB13 complexes and competitive binding mechanisms...
April 2016: Nature Genetics
Justine Varinot, Adéline Furudoï, Sarah Drouin, Véronique Phe, Raphaele Renard Penna, Morgan Roupret, Marc-Olivier Bitker, Olivier Cussenot, Eva Compérat
The HOXB13 gene is a member of the homeobox gene family, and prostate development depends on HOXB13 function. HOXB13 is a very sensitive and specific marker of prostate tissue and prostate cancer. When the origin of a tumor in a resection specimen or in biopsy material is unclear, it allows determining the prostate as the primary. Our aim was to determine whether HOXB13 has similar sensitivity for determining prostate origin of lymph node and bone metastases. We retrieved cases of lymph node and bone metastases of histologically confirmed prostate cancer (PCa) and selected lymph node metastases of urothelial carcinoma (UCa)...
May 2016: Virchows Archiv: An International Journal of Pathology
Young-Rang Kim, Taek Won Kang, Phuong Kim To, Nguyen Thi Xuan Nguyen, Young Seok Cho, Chaeyong Jung, Min Soo Kim
Many prostate cancer (PCa) patients die of recurrent disease due to the emergence of hormone-independent cancer cells of which the mechanism is not fully understood. Our previous studies demonstrated that most castration- resistant prostate cancers (CRPC) overexpress the HOXB13 transcription factor to confer positive growth signals. Since HOXB13 also suppresses p21WAF1/CIP1 (p21) expression, we studied the correlation between HOXB13 and p21 in selected samples of PCa. While there was no statistically significant correlation between expression of HOXB13 and p21, HOXB13-deficient tumors had three times higher odds for expressing p21 than HOXB13-positive tumors...
April 2016: Oncology Reports
Tine M Storebjerg, Søren Høyer, Pia Kirkegaard, Flemming Bro, Torben F Ørntoft, Michael Borre, Karina D Sørensen
OBJECTIVES: To determine the prevalence of the HOXB13 G84E mutation (rs138213197) in Danish men with or without prostate cancer (PCa) and to investigate possible correlations between HOXB13 mutation status and clinicopathological characteristics associated with tumour aggressiveness. MATERIALS AND METHODS: We conducted a case-control study including 995 men with PCa (cases) who underwent radical prostatectomy (RP) between 1997 and 2011 at the Department of Urology, Aarhus University Hospital, Denmark...
October 2016: BJU International
Allal Ouhtit, Mohammed N Al-Kindi, Parvathy R Kumar, Ishita Gupta, Somya Shanmuganathan, Yahya Tamimi
HOXB13, a member of the homeobox proteins family, is a key regulator of the epithelial differentiation in the prostate gland. HOXB13 is overexpressed during malignant progression of the prostatic tissue and suspected to contribute in the pathogenesis of the prostate gland. In androgen deprived conditions, HOXB13 is thought to act through inhibition of the tumour suppressor protein p21. Since HOXB13 has a multifaceted role in ventral prostate development, its critical partners in the cascade need to be elucidated for a further understanding of its role in prostate malignancy...
2016: Frontiers in Bioscience (Elite Edition)
Henry T Lynch, Omofolasade Kosoko-Lasaki, Stephen W Leslie, Marc Rendell, Trudy Shaw, Carrie Snyder, Anthony V D'Amico, Sarah Buxbaum, William B Isaacs, Stacy Loeb, Judd W Moul, Isaac Powell
Prostate cancer (PC) has the highest degree of genetic transmission of any form of malignancy. In some families, the hereditary pattern is so strong as to mimic an autosomal dominance trait. We reviewed the known predisposing genetic markers to assess possible strategies for screening of families at risk. We carried out a systematic literature search using the Pubmed service of the National Center for Biotechnology Information (NCBI) and several gene libraries, including the NCBI SNP Library, the Online Mendelian Inheritance in Man® Catalog of Human Genes and Genetic Disorders (OMIM) and SNPedia to obtain known gene loci, SNPs and satellite markers associated with PC...
June 1, 2016: International Journal of Cancer. Journal International du Cancer
Gretchen K Hubbard, Laura N Mutton, May Khalili, Ryan P McMullin, Jessica L Hicks, Daniella Bianchi-Frias, Lucas A Horn, Ibrahim Kulac, Michael S Moubarek, Peter S Nelson, Srinivasan Yegnasubramanian, Angelo M De Marzo, Charles J Bieberich
Genetic instability, a hallmark feature of human cancers including prostatic adenocarcinomas, is considered a driver of metastasis. Somatic copy number alterations (CNA) are found in most aggressive primary human prostate cancers, and the overall number of such changes is increased in metastases. Chromosome 10q23 deletions, encompassing PTEN, and amplification of 8q24, harboring MYC, are frequently observed, and the presence of both together portends a high risk of prostate cancer-specific mortality. In extant genetically engineered mouse prostate cancer models (GEMM), isolated MYC overexpression or targeted Pten loss can each produce early prostate adenocarcinomas, but are not sufficient to induce genetic instability or metastases with high penetrance...
January 15, 2016: Cancer Research
Mark M Pomerantz, Fugen Li, David Y Takeda, Romina Lenci, Apurva Chonkar, Matthew Chabot, Paloma Cejas, Francisca Vazquez, Jennifer Cook, Ramesh A Shivdasani, Michaela Bowden, Rosina Lis, William C Hahn, Philip W Kantoff, Myles Brown, Massimo Loda, Henry W Long, Matthew L Freedman
Master transcription factors interact with DNA to establish cell type identity and to regulate gene expression in mammalian cells. The genome-wide map of these transcription factor binding sites has been termed the cistrome. Here we show that the androgen receptor (AR) cistrome undergoes extensive reprogramming during prostate epithelial transformation in man. Using human prostate tissue, we observed a core set of AR binding sites that are consistently reprogrammed in tumors. FOXA1 and HOXB13 colocalized at the reprogrammed AR binding sites in human tumor tissue...
November 2015: Nature Genetics
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