scholarly journals Role of Alternative Splicing in Prostate Cancer Aggressiveness and Drug Resistance in African Americans

2019 ◽  
pp. 119-139
Author(s):  
Jacqueline Olender ◽  
Norman H. Lee
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Alternative Splicing ◽  
African Americans ◽  
Cancer Aggressiveness

scholarly journals The Emerging Role of Extracellular Vesicle-Mediated Drug Resistance in Cancers: Implications in Advanced Prostate Cancer

2015 ◽  
Vol 2015 ◽  
pp. 1-13 ◽  
Author(s):  
Carolina Soekmadji ◽  
Colleen C. Nelson
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Multidrug Resistance ◽  
Advanced Prostate Cancer ◽  
Control Cell ◽  
Extracellular Vesicle ◽  
Multidrug Resistance Proteins ◽  
Acquired Drug Resistance ◽  
Resistance Proteins

Emerging evidence has shown that the extracellular vesicles (EVs) regulate various biological processes and can control cell proliferation and survival, as well as being involved in normal cell development and diseases such as cancers. In cancer treatment, development of acquired drug resistance phenotype is a serious issue. Recently it has been shown that the presence of multidrug resistance proteins such as Pgp-1 and enrichment of the lipid ceramide in EVs could have a role in mediating drug resistance. EVs could also mediate multidrug resistance through uptake of drugs in vesicles and thus limit the bioavailability of drugs to treat cancer cells. In this review, we discussed the emerging evidence of the role EVs play in mediating drug resistance in cancers and in particular the role of EVs mediating drug resistance in advanced prostate cancer. The role of EV-associated multidrug resistance proteins, miRNA, mRNA, and lipid as well as the potential interaction(s) among these factors was probed. Lastly, we provide an overview of the current available treatments for advanced prostate cancer, considering where EVs may mediate the development of resistance against these drugs.

Abstract 471: High expression of miR-182 promotes prostate cancer aggressiveness in African-Americans compared to Caucasians

2018 ◽  
Author(s):  
Marisa Shiina ◽  
Yutaka Hashimoto ◽  
Guoren Deng ◽  
Varahram Shahryari ◽  
Majid Shahana ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African Americans ◽  
High Expression ◽  
Cancer Aggressiveness

Abstract A78: The role of tumor microenvironment in prostate cancer of African Americans

2015 ◽  
Author(s):  
Farah Rahmatpanah ◽  
Tracy Luu ◽  
Pardis Zaeri ◽  
Xin Chen ◽  
Yuanjie Hu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
African Americans ◽  
Tumor Microenvironment

Abstract PO-128: Interrogating the role of race-related alternative splicing of SEMA3C in prostate cancer

2020 ◽  
Author(s):  
Tyler A. Allen ◽  
Jay Chandar ◽  
Bonnie L. Lacroix ◽  
Steven R. Patierno ◽  
Daniel J. George ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Alternative Splicing

scholarly journals Dysregulated Alternative Splicing Landscape Identifies Intron Retention as a Hallmark and Spliceosome as a Therapeutic Vulnerability in Aggressive Prostate Cancer

2019 ◽  
Author(s):  
Dingxiao Zhang ◽  
Qiang Hu ◽  
Yibing Ji ◽  
Hsueh-Ping Chao ◽  
Amanda Tracz ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Transcriptional Regulation ◽  
Alternative Splicing ◽  
Hematological Malignancies ◽  
Intron Retention ◽  
Therapy Resistance ◽  
Copy Number Variations ◽  
Castration Resistant ◽  
Cancer Aggressiveness ◽  
Transcriptional Alterations

ABSTRACTDysregulation of mRNA alternative splicing (AS) has been implicated in development and progression of hematological malignancies. Here we describe the first comprehensive AS landscape in the spectrum of human prostate cancer (PCa) development, progression and therapy resistance. We find that the severity of splicing dysregulation correlates with disease progression and establish intron retention (IR) as a hallmark of PCa stemness and aggressiveness. Systematic interrogation of 274 splicing-regulatory genes (SRGs) uncovers prevalent SRG mutations associated with, mainly, copy number variations leading to mis-expression of ~68% of SRGs during PCa evolution. Consequently, we identify many SRGs as prognostic markers associated with splicing disruption and patient outcome. Interestingly, androgen receptor (AR) controls a splicing program distinct from its transcriptional regulation. The spliceosome modulator, E7107, reverses cancer aggressiveness and abolishes the growth of castration-resistant PCa (CRPC) models. Altogether, we establish aberrant AS landscape caused by dysregulated SRGs as a novel therapeutic vulnerability for CRPC.Statement of significanceWe present the first comprehensive AS landscape during PCa evolution and link genomic and transcriptional alterations in SRGs to global splicing dysregulation. AR regulates splicing in pri-PCa and CRPC distinct from its transcriptional regulation. Intron retention is a hallmark for and spliceosome represents a therapeutic vulnerability in aggressive PCa.

Role of the MDR-1-Encoded Multiple Drug Resistance Phenotype in Prostate Cancer Cell Lines

1993 ◽  
Vol 150 (5 Part 1) ◽  
pp. 1544-1547 ◽  
Author(s):  
Gerhard Theyer ◽  
Marion Schirmböck ◽  
Therese Thalhammer ◽  
Edward R. Sherwood ◽  
Gerhard Baumgartner ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Drug Resistance ◽  
Cell Lines ◽  
Cancer Cell ◽  
Prostate Cancer Cell ◽  
Multiple Drug Resistance ◽  
Multiple Drug ◽  
Prostate Cancer Cell Lines ◽  
Mdr 1

Effect of chronic treatment of combined statins and aspirin on the risk of prostate cancer detection.

2012 ◽  
Vol 30 (5_suppl) ◽  
pp. 185-185
Author(s):  
Cristina Suarez ◽  
Rafael Morales ◽  
Jose Placer ◽  
Isaac Nunez ◽  
Jacques Planas ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Multivariate Analysis ◽  
Chronic Treatment ◽  
Univariate Analysis ◽  
Combined Treatment ◽  
Adult Men ◽  
Cancer Aggressiveness ◽  
Increased Risk ◽  
The Impact

185 Background: The role of chronic treatment (ChT) with statins and aspirin on prostate cancer (PC) carcinogenesis is controversial. Both drugs are frequently used in adult men who are at risk of PC, and many of them receive both drugs simultaneously. The impact of the combined treatment (CT) with statins and aspirin on PC risk has never been reported. We proposed to explore the influence of ChT with statins and aspirin in the PC risk detection and their aggressiveness. Methods: 2408 men were consecutively biopsied for cause: PSA > 4 ng/mL (64.4%), abnormal DRE (9%) or both (26.6%). ChT with statins and aspirin (>1 year) was controlled. Median age was 68 years (46–86) and median PSA 7.0 ng/mL (0.7-1279). At least 10 cores, plus 1 to 8 additional cores, were obtained. The PC detection rate was 35.2% and the Gleason score was < 7 in 20.8%, 7 in 50.9% and > 7 (HGPC) in 28.3%. Multivariate and univariate analysis were done and OR calculated to analyze the strength of the relationships. Results: 440 men (18.3%) were receiving statins alone (SA), 160 (6.6%) aspirin alone (AA), and 304 (12.6%) both drugs simultaneously. Multivariate analysis showed that CT was the only independent predictor of a reduced risk of PC detection, p=0.025, (OR 0.589, 95%CI 0.370-0-936). PC was detected in 552 of 1502 men (36.7%) not receiving statins or aspirin, 34.5% (152/440) receiving SA, 40% (64/160) receiving AA, and in 26.3% (80/304) receiving statins and aspirin simultaneously. Related to cancer aggressiveness, multivariate analysis showed that combined treatment predicted significantly an increased risk of HGPC, p=0.013, (OR 2.672, 95%CI 1.226-5.825). HGPC was detected in 136 of 552 (24.6%) PCs detected in men not receiving statins or aspirin, in 40 of 152 (26.3%) PCs detected in men receiving SA, in 24 of 64 (37.7%) PCs detected in men receiving AA, and in 40 of 80 (50%) PCs detected in men receiving statins and aspirin simultaneously. Conclusions: This study suggests that ChT with the combination of statins and aspirin reduce significantly the risk of PC detection in men subjected to prostate biopsy for cause. However, this reduction of PC detection is accompanied by a significant increase of PC aggressiveness.

scholarly journals The role of GATA2 in lethal prostate cancer aggressiveness

2016 ◽  
Vol 14 (1) ◽  
pp. 38-48 ◽  
Author(s):  
Veronica Rodriguez-Bravo ◽  
Marc Carceles-Cordon ◽  
Yujin Hoshida ◽  
Carlos Cordon-Cardo ◽  
Matthew D. Galsky ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Aggressiveness ◽  
Lethal Prostate Cancer
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