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Castrate resistent

Ru-Jun Mo, Zhao-Dong Han, Ying-Ke Liang, Jian-Heng Ye, Shu-Lin Wu, Sharron X Lin, Yan-Qiong Zhang, Sheng-Da Song, Fu-Neng Jiang, Wei-De Zhong, Chin-Lee Wu
To investigate immune profile consisting of stromal PD-L1 expression, inhibitory or non-T-cell inflamed tumor microenvironment that may predict response to anti-PD-L1/PD-1 immunotherapy in prostate cancer, we validated the specificity of a PD-L1 monoclonal antibody (E1L3N) and identified PD-L1 specific expression in prostatic stromal nerve cells. PD-L1 expression was analyzed in 73 primary prostate cancers and 7 castration-resistant prostate cancers (CRPC) by IHC and resulting data from primary prostate cancers were correlated with tumor-associated lymphocytes (TALs), clinicopathological characteristics and clinical outcome...
December 11, 2018: International Journal of Cancer. Journal International du Cancer
Yun-Jie Yang, Yun-Yi Kong, Gao-Xiang Li, Yue Wang, Ding-Wei Ye, Bo Dai
OBJECTIVES: To identify biomarkers that predict the response to standard androgen deprivation therapy (ADT) of patients newly diagnosed with metastatic castration-sensitive prostate cancer (CSPC) to improve therapeutic decision-making. We investigated whether the characterization of baseline circulating tumor cells (CTCs) predicted the effective period of standard ADT. MATERIALS AND METHODS: The study included 108 patients newly diagnosed with high-volume metastatic CSPC...
December 7, 2018: BJU International
B You, K-C Zhang
OBJECTIVE: MicroRNA-144-3p (miR-144-3p) has been implicated in the tumorigenesis of multiple types of cancer. However, its role in castration-resistant prostate cancer (CRPC) remains largely unknown. This study aimed to explore the biological role of miR-144-3p in the development of CRPC. MATERIALS AND METHODS: RT-qPCR was performed to measure the expression levels of miR-144-3p in CRPC tissues. CRPC cells were transfected with miR-144-3p or NC. MTT and colony formation assays were used to determine cell growth; flow cytometry was used to measure apoptosis; a luciferase reporter assay was used to predict the target genes regulated by miR-144-3p...
November 2018: European Review for Medical and Pharmacological Sciences
Harsh Shah, Ulka Vaishampayan
With the decrease in PSA screening based on the 2011 United States Preventive Services Task Force guidelines and the potential approval of highly sensitive imaging techniques over the next few years, we are likely to see an increasing trend of metastatic prostate cancer diagnosis. Traditional therapy for nonmetastatic prostate cancer (nmPC) has consisted of androgen deprivation therapy (ADT) followed by other hormonal therapy maneuvers, such as anti-androgen withdrawal, herbal preparations, low dose steroids, or ketoconazole...
December 7, 2018: Targeted Oncology
Chunhua Wang, Chaoying Hu, Dan Gao, Zirun Zhao, Xiaoping Chen, Xiao Hu, Shili Gong, Lin Li, Lan Zhang
PURPOSE: Abiraterone acetate is a highly variable drug and has been approved for the treatment of patients with metastatic castration-resistant prostate cancer in many countries. This study was conducted to compare the pharmacokinetic profile between the test product (abiraterone acetate tablet) and reference product ZYTIGA® (250 mg) mainly. METHODS: To overcome the high intra-subject variability of abiraterone, a two-sequence and four-period crossover study was designed to assess bioequivalence between the two products in 32 healthy male Chinese subjects under fasting conditions...
December 10, 2018: Cancer Chemotherapy and Pharmacology
Lesley J Scott
Oral enzalutamide (Xtandi® ), a second generation androgen receptor inhibitor, is indicated for the treatment of castration-resistant prostate cancer (CRPC) in numerous countries worldwide, with specific indications in this patient population varying between individual countries. Based on extensive experience in the clinical trial and/or real-world settings, oral enzalutamide 160 mg once daily is an effective and generally well tolerated treatment in a broad spectrum of patients with CRPC, including in nonmetastatic and metastatic disease and in chemotherapy-naive and -experienced metastatic CRPC...
December 8, 2018: Drugs
Chung C W Lee, Ravi Shashi Nayana Munuganti, James W Peacock, Kush Dalal, Ivy Z F Jiao, Ashley Shepherd, Liangliang Liu, Kevin J Tam, Colin G Sedgwick, Satyam Bhasin, Kevin C K Lee, Luke Gooding, Benjamin Vanderkruk, Tabitha Tombe, Yifan Gong, Martin E Gleave, Artem Cherkasov, Christopher J Ong
Despite the amenability of early-stage prostate cancer to surgery and radiation therapy, locally advanced and metastatic prostate cancer is clinically problematic. Chemical castration is often used as a first-line therapy for advanced disease, but progression to the castration-resistant prostate cancer phase occurs with dependable frequency, largely through mutations to the androgen receptor (AR), aberrant AR signaling, and AR-independent mechanisms, among other causes. Semaphorin 3C (SEMA3C) is a secreted signaling protein that is essential for cardiac and neuronal development and has been shown to be regulated by the AR, to drive epithelial-to-mesenchymal transition and stem features in prostate cells, to activate receptor tyrosine kinases, and to promote cancer progression...
December 1, 2018: Journal of the Endocrine Society
Mohamed Islam Delma
Prostate cancer is a prevalent malignant disease. Castration-resistant prostate cancer (CRPC) is a poor prognosis form that develops upon resistance to first-line androgen deprivation therapy. Intensive research is ongoing to find efficient therapeutics for this refractory state. Actually, the combination of PI3K/Akt inhibitors with new-generation antiandrogens is among the most promising therapeutic schemes, although not yet at the optimal level. Metformin effects on prostate cancer, notably its therapeutic targets shared with antiandrogens and/or PI3K/Akt inhibitors, are reviewed in this article...
October 2, 2018: Curēus
Elahe A Mostaghel
Castration resistant prostate cancer is characterized by loss of the androgen inactivation enzyme HSD17B2, emphasizing the importance of intratumoral androgens in tumor progression. Inactive isoforms generated by alternative splicing destabilize the wild-type enzyme, adding steroidogenesis to other prostate cancer drivers that undergo oncogenic splicing, highlighting aberrant splicing as a therapeutic target.
December 10, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
(no author information available yet)
The transcription factor ONECUT2 is a core regulator of metastatic castration-resistant prostate cancer.
December 7, 2018: Cancer Discovery
Kelly Khai-Li Yap, William Wong, Lingyun Ji, Susan Groshen, David I Quinn, Alan H Bryce, Tanya B Dorff
BACKGROUND: Skeletal-related events cause significant morbidity in patients with metastatic castration-resistant prostate cancer. In the ALSYMPCA study, radium-223 (Ra223) was found to provide pain palliation in addition to prolonged survival and reduced skeletal-related events (SREs). Given previous evidence that bisphosphonates impacted pain relief from the radiopharmaceutical samarium-153, we evaluated whether the timing of bone supportive therapy (BST) such as zoledronic acid or denosumab affected pain palliation from Ra223...
November 10, 2018: Cancer Treatment and Research Communications
India Anderson-Carter, Natasza Posielski, Jinn-Ing Liou, Tariq A Khemees, Tracy M Downs, E Jason Abel, David F Jarrard, Kyle A Richards
BACKGROUND: Statins are thought to possess antineoplastic properties related to their effect on cell proliferation and steroidogenesis. Progression to castrate resistant prostate cancer (CaP) includes de-regulation of androgen synthesis suggesting a role for statins in this setting. Our goal was to assess the role of statin use on oncologic outcomes in patients with advanced CaP being treated with androgen deprivation therapy (ADT). METHODS: The national VA database was used to identify all men diagnosed with CaP who were treated with ADT for at least 6 months between 2000 and 2008 with follow-up through May 2016...
December 7, 2018: Urologic Oncology
Ethan M Basch, Mark Scholz, Johann S de Bono, Nicholas Vogelzang, Paul de Souza, Gavin Marx, Ulka Vaishampayan, Saby George, James K Schwarz, Emmanuel S Antonarakis, Joseph M O'Sullivan, Arash Rezazadeh Kalebasty, Kim N Chi, Robert Dreicer, Thomas E Hutson, Amylou C Dueck, Antonia V Bennett, Erica Dayan, Milan Mangeshkar, Jaymes Holland, Aaron L Weitzman, Howard I Scher
BACKGROUND: Bone metastases in patients with metastatic castration-resistant prostate cancer (mCRPC) are associated with debilitating pain and functional compromise. OBJECTIVE: To compare pain palliation as the primary endpoint for cabozantinib versus mitoxantrone-prednisone in men with mCRPC and symptomatic bone metastases using patient-reported outcome measures. DESIGN, SETTING, AND PARTICIPANTS: A randomized, double-blind phase 3 trial (COMET-2; NCT01522443) in men with mCRPC and narcotic-dependent pain from bone metastases who had progressed after treatment with docetaxel and either abiraterone or enzalutamide...
December 4, 2018: European Urology
Dong-Jin Hwang, Yali He, Suriyan Ponnusamy, Michael L Mohler, Thirumagal Thiyagarajan, Iain J McEwan, Ramesh Narayanan, Duane D Miller
In our effort to find small molecule treatments of advanced prostate cancers (PCs), the novel series of indolyl and indolinyl propanamides (series II and III) were discovered as selective androgen receptor degraders (SARDs). Initial studies of androgen receptor (AR) antagonist (1) and agonist (2) propanamides yielded a tertiary aniline (3) with novel SARD activity but poor metabolic stability. Cyclization to II and III produced sub-micromolar AR antagonism and protein degradation selective to AR and AR splice variant (AR SV)...
December 7, 2018: Journal of Medicinal Chemistry
Xin Chen, Zhixiong Chen, Bin Zheng, Wei Tang
Castration-resistant prostate cancer (CRPC) lacks effective treatment, and studies have shown that PARPi inhibitors, such as Olaparib, are somewhat effective; however, the efficacy of Olaparib in CRPC still needs to be further improved. Nitrogen permease regulator-like 2 (NPRL2) is reported to be a tumor suppressor candidate gene and is closely related to the DNA repair pathway, which can affect the sensitivity of many chemotherapeutic drugs. However, there is no research on whether NPRL2 is associated with sensitivity to Olaparib...
December 3, 2018: Biochemical and Biophysical Research Communications
Yangzhou Liu, Shankun Zhao, Jiamin Wang, Zhiguo Zhu, Lianmin Luo, Ermao Li, Fucai Tang, Zhigang Zhao
PURPOSE: To evaluate whether serum neuroendocrine markers could effectively predict treatment outcomes in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: The PubMed, Cochrane Library and Embase databases were sought to identify eligible studies concerning serum neuroendocrine markers and the prognosis of post-treatment mCRPC from inception to April 2018. The association between serum neuroendocrine markers, that is, chromogranin A (CgA) and neurone-specific enolase (NSE), levels and the prognosis of post-treatment mCRPC were summarized using a random-effects model and hazard ratio (HR) with 95% CI Sensitivity analyses were conducted to assess potential bias...
December 5, 2018: Urologia Internationalis
Thomas Grochtdreis, Hans-Helmut König, Alexander Dobruschkin, Gunhild von Amsberg, Judith Dams
BACKGROUND: Treatment of metastatic prostate cancer is associated with high personal and economic burden. Recently, new treatment options for castration-resistant prostate cancer became available with promising survival advantages. However, cost-effectiveness of those new treatment options is sometimes ambiguous or given only under certain circumstances. The aim of this study was to systematically review studies on the cost-effectiveness of treatments and costs of castration-resistant prostate cancer (CRPC) and metastasizing castration-resistant prostate cancer (mCRPC) on their methodological quality and the risk of bias...
2018: PloS One
Xue-Fei Ding, Tian-Bao Huang, Ying Gao, Sheng-Ming Lu, Hua-Zhi Tao, Jia-Nan Xu, Yao-Zong Xu, Fei Wang, Yu-Quan Zhou, Guang-Chen Zhou, Yang Luan
OBJECTIVE: To evaluate the clinical significance of permanent 125 I prostate brachytherapy in patients with castration-resistant prostate cancer. METHODS: A retrospective study of 45 patients with castration-resistant prostate cancer from the Clinical Medical College, Yangzhou University, Yangzhou, Jiangsu, China was carried out. Patients were divided into two groups according to different treatments: 21 patients received endocrine therapy alone (control group), and 24 patients underwent brachytherapy combined with endocrine therapy (treatment group)...
December 4, 2018: International Journal of Urology: Official Journal of the Japanese Urological Association
Fatima Karzai, David VanderWeele, Ravi A Madan, Helen Owens, Lisa M Cordes, Amy Hankin, Anna Couvillon, Erin Nichols, Marijo Bilusic, Michael L Beshiri, Kathleen Kelly, Venkatesh Krishnasamy, Sunmin Lee, Min-Jung Lee, Akira Yuno, Jane B Trepel, Maria J Merino, Ryan Dittamore, Jennifer Marté, Renee N Donahue, Jeffrey Schlom, Keith J Killian, Paul S Meltzer, Seth M Steinberg, James L Gulley, Jung-Min Lee, William L Dahut
BACKGROUND: Checkpoint inhibitors have not been effective for prostate cancer as single agents. Durvalumab is a human IgG1-K monoclonal antibody that targets programmed death ligand 1 and is approved by the U.S. Food and Drug Administration for locally advanced or metastatic urothelial cancer and locally advanced, unresectable stage 3 non-small cell lung cancer. Olaparib, a poly (ADP-ribose) polymerase inhibitor, has demonstrated an improvement in median progression-free survival (PFS) in select patients with metastatic castration-resistant prostate cancer (mCRPC)...
December 4, 2018: Journal for Immunotherapy of Cancer
Zhiping Cai, Yapei Wu, Yao Li, Jizhong Ren, Linhui Wang
Long non-coding RNAs (lncRNAs) have been found essential for tumorigenesis of prostate cancer (PC), but its role in the regulation of castration-resistant prostate cancer (CRPC) is poorly identified. Here, we showed that a lncRNA, Breast-Cancer Anti-Estrogen Resistance 4 (BCAR4), which plays a pivotal role in the tamoxifen-resistance of breast cancer, was significantly upregulated in CRPC, but not in castration-sensitive prostate cancer (CSPC), compared to normal prostate tissue. High BCAR4 levels in CRPC were correlated with poor patients' overall survival...
December 4, 2018: Aging
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