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prostate cancer genomic

Leena Latonen, Ebrahim Afyounian, Antti Jylhä, Janika Nättinen, Ulla Aapola, Matti Annala, Kati K Kivinummi, Teuvo T L Tammela, Roger W Beuerman, Hannu Uusitalo, Matti Nykter, Tapio Visakorpi
To understand functional consequences of genetic and transcriptional aberrations in prostate cancer, the proteomic changes during disease formation and progression need to be revealed. Here we report high-throughput mass spectrometry on clinical tissue samples of benign prostatic hyperplasia (BPH), untreated primary prostate cancer (PC) and castration resistant prostate cancer (CRPC). Each sample group shows a distinct protein profile. By integrative analysis we show that, especially in CRPC, gene copy number, DNA methylation, and RNA expression levels do not reliably predict proteomic changes...
March 21, 2018: Nature Communications
Salpie Nowinski, Aida Santaolalla, Ben O'Leary, Massimo Loda, Ayesha Mirchandani, Mark Emberton, Mieke Van Hemelrijck, Anita Grigoriadis
Novel approaches for classification, including molecular features, are needed to direct therapy for men with low-grade prostate cancer (PCa), especially men on active surveillance. Risk alleles identified from genome-wide association studies (GWAS) could improve prognostication. Those risk alleles that coincided with genes and somatic copy number aberrations associated with progression of PCa were selected as the most relevant for prognostication. In a systematic literature review, a total of 698 studies were collated...
February 27, 2018: Oncotarget
Li Gao, Li-Jie Zhang, Sheng-Hua Li, Li-Li Wei, Bin Luo, Rong-Quan He, Shuang Xia
BACKGROUND: MiR-452-5p has been reported to be down-regulated in prostate cancer, affecting the development of this type of cancer. However, the molecular mechanism of miR-452-5p in prostate cancer remains unclear. Therefore, we investigated the network of target genes of miR-452-5p in prostate cancer using bioinformatics analyses. MATERIALS AND METHODS: We first analyzed the expression profiles and prognostic value of miR-452-5p in prostate cancer tissues from a public database...
March 6, 2018: Pathology, Research and Practice
Ding Qian-Shan, Zhang Li, Wang Bi-Cheng, Zeng Zhi, Zou Xian-Qiong, Cao Peng-Bo, M S Zhou Guang-Ming, Tang Meng, Wu Lu, B S Wu Lian-Lian, Yu Hong-Gang, Guo Yong, Zhou Fu-Xiang
Microrchidia 2 (MORC2) plays important roles in DNA damage repair and lipogenesis, but the clinical and functional role of MORC2 in cancer remains largely unexplored. In this study, we showed that MORC2 was widely expressed in human tissues while significantly up-regulated in most cancer types employing immunohistochemical staining and analysis of mRNA expression profile of more than 2000 human tissue samples from 15 different organs (lung, prostate, liver, breast, brain, stomach, colon/rectum, pancreas, ovary, endometrium, skin, nasopharynx, kidney, oesophagus and bladder)...
March 16, 2018: Human Pathology
J M Cozar, I Robles-Fernandez, L J Martinez-Gonzalez, M Pascual-Geler, Alba Rodriguez-Martinez, M J Serrano, J A Lorente, M J Alvarez-Cubero
Prostate cancer (PC) is one of the most common cancers worldwide. The observed variability in progression and responses to the same treatment between patients underlie the genetic heterogeneity of the disease. Nowadays, screening and follow-up biomarkers in PC are still having a deep lack of information, which makes difficult the cancer diagnosis, prognosis and the selection of the most suitable therapies. This is making that currently unnecessary biopsies, over-treatments and hormonoresistances have high rates of prevalence among patients...
January 2018: Mutation Research
Theodore Gourdin
PURPOSE OF REVIEW: Summarizes recent advances in the treatment of metastatic castration-sensitive and castration-resistant prostate cancer. RECENT FINDINGS: New randomized data suggest a survival advantage to early abiraterone in castration-sensitive metastatic prostate cancer. Prospective and retrospective studies are examining sequencing of existing cytotoxic and androgen-receptor-targeted therapies in both castration-sensitive and castration-resistant disease...
March 16, 2018: Current Opinion in Oncology
Feilun Cui, Jianpeng Hu, Yu Fan, Jian Tan, Huaming Tang
Prostate cancer (PCa) is the most frequently diagnosed type of cancer in Chinese males. Cell-cycle aberration is a hallmark of cancer. Spindle pole body component 25 homolog (SPC25), a component of the Ndc80 complex, serves an important role in regulating mitotic chromosome segregation. However, the functional roles of SPC25 in PCa remain poorly understood. To the best of our knowledge, the present study was the first to demonstrate that SPC25 is significantly upregulated in PCa. In order to investigate the molecular roles of SPC25, a loss of function assay was performed, revealing that SPC25 knockdown inhibited cell proliferation, and induced a decrease in the number of cells in the S phase and an increase in the number of cells in the G2/M phase...
April 2018: Oncology Letters
Rong-Quan He, Xia Yang, Liang Liang, Gang Chen, Jie Ma
The present study aimed to explore the potential clinical significance of microRNA (miR)-124-3p expression in the hepatocarcinogenesis and development of hepatocellular carcinoma (HCC), as well as the potential target genes of functional HCC pathways. Reverse transcription-quantitative polymerase chain reaction was performed to evaluate the expression of miR-124-3p in 101 HCC and adjacent non-cancerous tissue samples. Additionally, the association between miR-124-3p expression and clinical parameters was also analyzed...
April 2018: Oncology Letters
Krishna B Singh, Eun-Ryeong Hahm, Lora H Rigatti, Daniel P Normolle, Jian-Min Yuan, Shivendra V Singh
We have shown previously that dietary administration of phenethyl isothiocyanate (PEITC), a small molecule from edible cruciferous vegetables, significantly decreases the incidence of poorly-differentiated prostate cancer in Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) mice without any side effects. In this study, we investigated the role of c-Myc-regulated glycolysis in prostate cancer chemoprevention by PEITC. Exposure of LNCaP (androgen-responsive) and 22Rv1 (castration-resistant) human prostate cancer cells to PEITC resulted in suppression of expression as well as transcriptional activity of c-Myc...
March 15, 2018: Cancer Prevention Research
(no author information available yet)
The Metastatic Prostate Cancer Project aims to gather genomic and phenotypic data from large numbers of men with prostate cancer, creating a database that scientists can use in their own research efforts. Any man with advanced disease who wants to participate may do so.
March 14, 2018: Cancer Discovery
Margaret M Centenera, Luke A Selth, Esmaeil Ebrahimie, Lisa M Butler, Wayne D Tilley
Recent genomic analyses of metastatic prostate cancer have provided important insight into adaptive changes in androgen receptor (AR) signaling that underpin resistance to androgen deprivation therapies. Novel strategies are required to circumvent these AR-mediated resistance mechanisms and thereby improve prostate cancer survival. In this review, we present a summary of AR structure and function and discuss mechanisms of AR-mediated therapy resistance that represent important areas of focus for the development of new therapies...
March 12, 2018: Cold Spring Harbor Perspectives in Medicine
Wei Sun, Paul Bunn, Chong Jin, Paul Little, Vasyl Zhabotynsky, Charles M Perou, David Neil Hayes, Mengjie Chen, Dan-Yu Lin
We systematically studied the association between somatic copy number aberration (SCNA), DNA methylation and gene expression using -omic data from The Cancer Genome Atlas (TCGA) on six cancer types: breast cancer, colon cancer, glioblastoma, leukemia, lower-grade glioma and prostate cancer. A major challenge for such integrated study is that the association between DNA methylation and gene expression is severely confounded by tumor purity and cell type composition, which are often unobserved and difficult to estimate...
February 26, 2018: Nucleic Acids Research
Veronica L Cox, Anas A Saeed Bamashmos, Wai Chin Foo, Shiva Gupta, Sireesha Yedururi, Naveen Garg, Hyunseon Christine Kang
Lynch syndrome is the most common hereditary cancer syndrome, the most common cause of heritable colorectal cancer, and the only known heritable cause of endometrial cancer. Other cancers associated with Lynch syndrome include cancers of the ovary, stomach, urothelial tract, and small bowel, and less frequently, cancers of the brain, biliary tract, pancreas, and prostate. The oncogenic tendency of Lynch syndrome stems from a set of genomic alterations of mismatch repair proteins. Defunct mismatch repair proteins cause unusually high instability of regions of the genome called microsatellites...
March 2018: Radiographics: a Review Publication of the Radiological Society of North America, Inc
Amirali Salmasi, Jonathan Said, Alan W Shindel, Pooria Khoshnoodi, Ely R Felker, Anthony E Sisk, Tristan Grogan, Debbie McCullough, John Bennett, Helen Bailey, H Jeffrey Lawrence, David A Elashoff, Leonard S Marks, Steven S Raman, Phillip G Febbo, Robert E Reiter
PURPOSE: Multiparametric MRI (mpMRI) and biopsy-based molecular tests such as the 17-gene Oncotype DX® Genomic Prostate Score™ (GPS) assay are increasingly used to improve risk stratification in men with clinically localized prostate cancer (PCa). The GPS assay was previously shown to be a significant independent predictor of adverse pathology (AP) at radical prostatectomy (RP) in men diagnosed with systematic biopsies only. We therefore investigated the ability of GPS to predict AP in the setting of MRI-guided prostate biopsy...
March 7, 2018: Journal of Urology
Constantinos Roufas, Dimitrios Chasiotis, Anestis Makris, Christodoulos Efstathiades, Christos Dimopoulos, Apostolos Zaravinos
Background: Recently, immune-checkpoint blockade has shown striking clinical results in different cancer patients. However, a significant inter-individual and inter-tumor variability exists among different cancers. The expression of the toxins granzyme A (GZMA) and perforin 1 (PRF1), secreted by effector cytotoxic T cells and natural killer (NK) cells, were recently used as a denominator of the intratumoral immune cytolytic activity (CYT). These levels are significantly elevated upon CD8+ T-cell activation as well as during a productive clinical response against immune-checkpoint blockade therapies...
2018: Frontiers in Oncology
A M Rose, A Krishan, C F Chakarova, L Moya, S Chambers, M Hollands, J C Illingworth, S M G Williams, H E James, A Z Shah, C N A Palmer, A Chakravarti, J N Berg, J Batra, S S Bhattacharya
Background: MSR1 repeats are a 36-38bp minisatellite element that have recently been implicated in the regulation of gene expression, through copy number variation (CNV). Patients and methods: Bioinformatic and experimental methods were used to assess the distribution of MSR1 across the genome, evaluate the regulatory potential of such elements and explore the role of MSR1 elements in cancer, particularly non-familial breast cancer and prostate cancer. Results: MSR1s are predominately located at chromosome 19 and are functionally enriched in regulatory regions of the genome, particularly regions implicated in short-range regulatory activities (H3K27ac, H3K4me1, and H3K4me3)...
March 2, 2018: Annals of Oncology: Official Journal of the European Society for Medical Oncology
Peng Zhang, Yarong Song, Yadong Sun, Xuechao Li, Lifeng Chen, Likun Yang, Yifei Xing
Prostate cancer (PCa) represents one of the most common solid neoplasms, and metastasis is the second leading cause of death in adult males. Anoikis is a programmed cell death that is induced upon cell detachment from the extracellular matrix (ECM), which behaves as a critical protective mechanism for anchorage-independent cell growth and metastasis formation. However, in the absence of ECM attachment, shift of metabolic pattern and tolerance to anoikis facilitate the survival of aggressive cancer cells in the circulatory system as well as their metastasis to distant sites...
March 5, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
Johnny R Ramroop, Mark N Stein, Justin M Drake
Prostate cancer is the most common malignancy in men in the United States. While androgen deprivation therapy results in tumor responses initially, there is relapse and progression to metastatic castration-resistant prostate cancer. Currently, all prostate cancer patients receive essentially the same treatment, and there is a need for clinically applicable technologies to provide predictive biomarkers toward personalized therapies. Genomic analyses of tumors are used for clinical applications, but with a paucity of obvious driver mutations in metastatic castration-resistant prostate cancer, other applications, such as phosphoproteomics, may complement this approach...
2018: Frontiers in Oncology
Sangkyu Lee, Sarah Kerns, Harry Ostrer, Barry Rosenstein, Joseph O Deasy, Jung Hun Oh
PURPOSE: Late genitourinary (GU) toxicity after radiation therapy limits the quality of life of prostate cancer survivors; however, efforts to explain GU toxicity using patient and dose information have remained unsuccessful. We identified patients with a greater congenital GU toxicity risk by identifying and integrating patterns in genome-wide single nucleotide polymorphisms (SNPs). METHODS AND MATERIALS: We applied a preconditioned random forest regression method for predicting risk from the genome-wide data to combine the effects of multiple SNPs and overcome the statistical power limitations of single-SNP analysis...
January 31, 2018: International Journal of Radiation Oncology, Biology, Physics
W Y Mansour, P Tennstedt, J Volquardsen, C Oing, M Kluth, C Hube-Magg, K Borgmann, R Simon, C Petersen, E Dikomey, K Rothkamm
Here we report that PTEN contributes to DNA double-strand break (DSB) repair via homologous recombination (HR), as evidenced by (i) inhibition of HR in a reporter plasmid assay, (ii) enhanced sensitivity to mitomycin-C or olaparib and (iii) reduced RAD51 loading at IR-induced DSBs upon PTEN knockdown. No association was observed between PTEN-status and RAD51 expression either in-vitro or in-vivo in a tissue microarray of 1500 PTEN-deficient prostate cancer (PC) samples. PTEN depletion and sustained activation of AKT sequestered CHK1 in the cytoplasm, thus impairing the G2/M-checkpoint after irradiation...
March 2, 2018: Scientific Reports
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