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Castrate resistant prostate cancer

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https://www.readbyqxmd.com/read/28107595/chromogranin-a-and-neurone-specific-enolase-variations-during-the-first-three-months-of-abiraterone-therapy-predict-outcomes-in-patients-with-metastatic-castration-resistant-prostate-cancer
#1
Liancheng Fan, Yanqing Wang, Chi Chenfei, Jiahua Pan, Xun Shangguan, Zhixiang Xin, Jianian Hu, Zhou Lixin, Baijun Dong, Wei Xue
OBJECTIVE: To determine the prognostic factors of circulating chromogranin A (CgA) and neurone-specific enolase (NSE) variations during the first 3 months of abiraterone Acetate (AA) treatment in metastatic castration-resistant prostate cancer (mCRPC) patients. PATIENTS AND METHODS: The serum levels of CgA, NSE were measured at baseline and after 3 months of AA treatments in 40 mCRPC patients. Outcome measures were PSA progression-free survival (PSA-PFS), radiographic PFS (rPFS) and overall survival (OS)...
January 20, 2017: BJU International
https://www.readbyqxmd.com/read/28105499/cx4945-suppresses-the-growth-of-castration-resistant-prostate-cancer-cells-by-reducing-ar-v7-expression
#2
Chuangzhong Deng, Jieping Chen, Shengjie Guo, Yanjun Wang, Qianghua Zhou, Zaishang Li, Xingping Yang, Xingsu Yu, Zhenfeng Zhang, Fangjian Zhou, Hui Han, Kai Yao
PURPOSE: The aberrant expression of casein kinase 2 (CK2) has been reported to be involved in the tumorigenesis and progression of prostate cancer. The inhibition of CK2 activity represses androgen-dependent prostate cancer cells by attenuating the androgen receptor (AR) signaling pathway. In this study, we examined the effect of CK2 inhibition in castration-resistant prostate cancer (CRPC) cells, in which AR variants (ARVs) play a predominant role. METHODS: A newly synthetic CK2 selective inhibitor CX4945 was utilized to study the effect of CK2 inhibition in CRPC cells by CCK8 assay and colony formation assay...
January 19, 2017: World Journal of Urology
https://www.readbyqxmd.com/read/28104311/comprehensive-profiling-of-the-androgen-receptor-in-liquid-biopsies-from-castration-resistant-prostate-cancer-reveals-novel-intra-ar-structural-variation-and-splice-variant-expression-patterns
#3
Bram De Laere, Pieter-Jan van Dam, Tom Whitington, Markus Mayrhofer, Emanuela Henao Diaz, Gert Van den Eynden, Jean Vandebroek, Jurgen Del-Favero, Steven Van Laere, Luc Dirix, Henrik Grönberg, Johan Lindberg
BACKGROUND: Expression of the androgen receptor splice variant 7 (AR-V7) is associated with poor response to second-line endocrine therapy in castration-resistant prostate cancer (CRPC). However, a large fraction of nonresponding patients are AR-V7-negative. OBJECTIVE: To investigate if a comprehensive liquid biopsy-based AR profile may improve patient stratification in the context of second-line endocrine therapy. DESIGN, SETTING, AND PARTICIPANTS: Peripheral blood was collected from patients with CRPC (n=30) before initiation of a new line of systemic therapy...
January 16, 2017: European Urology
https://www.readbyqxmd.com/read/28103659/-a-case-of-giant-prostate-carcinoma-effectively-treated-with-external-beam-radiation-therapy
#4
Sohei Kanda, Shintaro Narita, Naoki Komine, Seiichi Kitajima, Misa Yamauchi, Akihiro Sugita, Yutaka Saito, Tomonori Habuchi
We present a case of gigantic prostate tumor in a patient with castration-resistant prostate cancer with successful local control by external-beam radiation therapy. A 71-year-old man was shown to have a prostate specific antigen (PSA)level of 24.5 ng/ml, Gleason 9, cT2N1M1a, prostate adenocarcinoma with an estimated prostate volume of 26.9 g. He achieved a PSA nadir at 4 months after the initial androgen deprivation therapy and was diagnosed with castration-resistant prostate cancer three years later. Eight months after the diagnosis of castration-resistant prostate cancer, he visited our hospital due to urinary retention...
December 2016: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28103574/68ga-psma-11-pet-ct-for-prostate-cancer-staging-and-risk-stratification-in-chinese-patients
#5
Shiming Zang, Guoqiang Shao, Can Cui, Tian-Nv Li, Yue Huang, Xiaochen Yao, Qiu Fan, Zejun Chen, Jin Du, Ruipeng Jia, Hongbin Sun, Zichun Hua, Jun Tang, Feng Wang
We evaluated the clinical utility of 68Ga-PSMA-11 PET/CT for staging and risk stratification of treatment-naïve prostate cancer (PCa) and metastatic castrate-resistant prostate cancer (mCRPC). Twenty-two consecutive patients with treatment-naïve PCa and 18 with mCRPC were enrolled. 68Ga-PSMA-11 PET/CT and magnetic resonance imaging (MRI) were performed for the evaluation of primary prostatic lesions, and bone scans were used for evaluation bone metastasis. Among the 40 patients, 37 (92.5% [22 treatment-naïve PCa, 15 mCRPC]) showed PSMA-avid lesions on 68Ga-PSMA-11 images...
January 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28101887/abiraterone-or-enzalutamide-in-advanced-castration-resistant-prostate-cancer-an-indirect-comparison
#6
Akhil Chopra, Mina Georgieva, Gilberto Lopes, Chong Ming Yeo, Benjamin Haaland
BACKGROUND: To perform a comparative effectiveness analyses between enzalutamide and abiraterone acetate in both the pre-docetaxel and post-docetaxel settings based on published phase III randomized trials. METHODS: The primary measure of efficacy was the posterior probability that enzalutamide outperforms abiraterone acetate (AA) with prednisone in terms of overall survival (OS) on average. Indirect meta-estimates were generated from four randomized studies in the context of a Bayesian hierarchical model with study-specific efficacy estimates meta-analyzed on the log scale...
January 19, 2017: Prostate
https://www.readbyqxmd.com/read/28099809/a-gemcitabine-based-peptide-conjugate-with-improved-metabolic-properties-and-dual-mode-of-efficacy
#7
Theodoros Karampelas, Eleni Skavatsou, Orestis Argyros, Demosthenes Fokas, Constantin Tamvakopoulos
Gemcitabine is a clinically established anticancer agent potent in various solid tumors but limited by its rapid metabolic inactivation and off-target toxicity. We have previously generated a metabolically superior to gemcitabine molecule (GSG) by conjugating gemcitabine to a gonadotropin releasing hormone receptor (GnRH-R) ligand peptide, and showed that GSG was efficacious in a castration resistant prostate cancer (CRPC) animal model. The current manuscript provides an in-depth metabolic and mechanistic study of GSG, coupled with toxicity assays that strengthen the potential role of GSG in the clinic...
January 18, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28097317/surrogate-end-points-for-all-cause-mortality-in-men-with-localized-unfavorable-risk-prostate-cancer-treated-with-radiation-therapy-vs-radiation-therapy-plus-androgen-deprivation-therapy-a-secondary-analysis-of-a-randomized-clinical-trial
#8
Trevor J Royce, Ming-Hui Chen, Jing Wu, Marian Loffredo, Andrew A Renshaw, Philip W Kantoff, Anthony V D'Amico
Importance: Several surrogates for prostate cancer-specific mortality satisfying the Prentice criteria exist, but whether these are surrogates for all-cause mortality, and how their performance compares, is unknown. Objective: To ascertain and compare the performance of 4 candidate surrogates (prostate-specific antigen [PSA] failure, PSA nadir >0.5 ng/mL, PSA doubling time <9 months, and interval to PSA failure <30 months) for all-cause mortality using the proportion of treatment-effect metric...
January 12, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/28096932/contemporary-agents-in-the-management-of-metastatic-castration-resistant-prostate-cancer
#9
REVIEW
Anil Kapoor, Christopher Wu, Bobby Shayegan, Adrian P Rybak
Docetaxel-based chemotherapy has been the standard of care for metastatic castration-resistant prostate cancer (mCRPC) since 2004. Over the past few years, there has been a significant paradigm shift in the treatment landscape of this disease. A deeper understanding of prostate cancer biology, along with the development of novel agents has created hope towards treating chemotherapy-naïve and resistant disease. Following the implementation of docetaxel as the first-line therapy for mCRPC, five novel therapies have demonstrated survival benefit in mCRPC...
November 2016: Canadian Urological Association Journal, Journal de L'Association des Urologues du Canada
https://www.readbyqxmd.com/read/28095710/the-evolving-role-of-chemotherapy-in-prostate-cancer
#10
Suliman Boulos, Danish Mazhar
Despite extensive clinical research of different chemotherapy agents for more than three decades, the role of chemotherapy in prostate cancer was only established in 2004, after demonstrating a survival benefit with docetaxel in metastatic castration-resistant prostate cancer. 6 years later, second-line chemotherapy using cabazitaxel, after disease progression on docetaxel, demonstrated an additional survival improvement. Recently, docetaxel given alongside standard hormonal therapy in newly diagnosed advanced prostate cancer was found to lead to significantly improved patient outcomes...
January 18, 2017: Future Oncology
https://www.readbyqxmd.com/read/28093150/re-inhibition-of-the-hexosamine-biosynthetic-pathway-promotes-castration-resistant-prostate-cancer
#11
Anthony Atala
No abstract text is available yet for this article.
February 2017: Journal of Urology
https://www.readbyqxmd.com/read/28092670/neuropilin-1-is-upregulated-in-the-adaptive-response-of-prostate-tumors-to-androgen-targeted-therapies-and-is-prognostic-of-metastatic-progression-and-patient-mortality
#12
B W C Tse, M Volpert, E Ratther, N Stylianou, M Nouri, K McGowan, M L Lehman, S J McPherson, M Roshan-Moniri, M S Butler, J Caradec, C Y Gregory-Evans, J McGovern, R Das, M Takhar, N Erho, M Alshalafa, E Davicioni, E M Schaeffer, R B Jenkins, A E Ross, R J Karnes, R B Den, L Fazli, P A Gregory, M E Gleave, E D Williams, P S Rennie, R Buttyan, J H Gunter, L A Selth, P J Russell, C C Nelson, B G Hollier
Recent evidence has implicated the transmembrane co-receptor neuropilin-1 (NRP1) in cancer progression. Primarily known as a regulator of neuronal guidance and angiogenesis, NRP1 is also expressed in multiple human malignancies, where it promotes tumor angiogenesis. However, non-angiogenic roles of NRP1 in tumor progression remain poorly characterized. In this study, we define NRP1 as an androgen-repressed gene whose expression is elevated during the adaptation of prostate tumors to androgen-targeted therapies (ATTs), and subsequent progression to metastatic castration-resistant prostate cancer (mCRPC)...
January 16, 2017: Oncogene
https://www.readbyqxmd.com/read/28089304/management-of-prostate-cancer-in-elderly-patients-recommendations-of-a-task-force-of-the-international-society-of-geriatric-oncology
#13
REVIEW
Jean-Pierre Droz, Gilles Albrand, Silke Gillessen, Simon Hughes, Nicolas Mottet, Stéphane Oudard, Heather Payne, Martine Puts, Gilbert Zulian, Lodovico Balducci, Matti Aapro
CONTEXT: Prostate cancer is the most frequent male cancer. Since the median age of diagnosis is 66 yr, many patients require both geriatric and urologic evaluation if treatment is to be tailored to individual circumstances including comorbidities and frailty. OBJECTIVE: To update the 2014 International Society of Geriatric Oncology (SIOG) guidelines on prostate cancer in men aged >70 yr. The update includes new material on health status evaluation and the treatment of localised, advanced, and castrate-resistant disease...
January 11, 2017: European Urology
https://www.readbyqxmd.com/read/28088885/-androgen-receptor-mediated-processes-in-castrate-resistant-metastatic-prostate-cancer
#14
Zsófia Küronya, Krisztina Bíró, Fruzsina Gyergyay, Lajos Géczi
In the past six years, five new drugs have been approved by the FDA for the treatment of metastatic castrate-resistant prostate cancer. While the disease itself still remains incurable, the sequential use of these drugs can significantly prolong survival while maintaining good quality of life. Research from the past decade made it clear that androgen receptor-mediated processes play a central part in the progression of the disease. Hormonal mechanisms related to androgen-receptors can remain active until late stages of the disease...
January 2017: Orvosi Hetilap
https://www.readbyqxmd.com/read/28077788/androgen-receptor-splice-variants-and-prostate-cancer-from-bench-to-bedside
#15
REVIEW
Kristine M Wadosky, Shahriar Koochekpour
Therapeutic interventions for advanced prostate cancer (PCa) center on inhibiting androgen receptor (AR) and downstream signaling pathways. Resistance to androgen deprivation therapy and/or AR antagonists is inevitable and molecular mechanisms driving castration-resistant PCa (CR-PCa) primarily involve alterations in AR expression and activity. Detailed molecular biology work over the past decade, discussed at length in this review article, has revealed several AR transcripts that result from alternative splicing...
January 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28074331/a-retrospective-analysis-of-the-first-41-mcrpc-patients-with-bone-pain-treated-with-radium-223-at-the-national-institute-of-oncology-in-hungary
#16
Zs Küronya, I Sinkovics, P Ágoston, K Bíró, I Bodrogi, I Böde, M Dank, F Gyergyay, T Vajdics, Zs Kolonics, K Nagyiványi, Á Rúzsa, L Géczi
Radium-223 dichloride is an alpha-emitting radiopharmaceutical which significantly prolongs overall survival in patients with castration-resistant prostate cancer (CRPC) and symptomatic bone metastases. This was a retrospective analysis of the efficacy and safety of Radium-223 in the first 41 patients treated at a single center in Hungary. Radium-223 was given at a dose of 50 kBq/kg intravenously every 4 weeks for up to 6 cycles. Between 23rd July 2014 and 23rd February 2016, 41 patients were treated. Patient demographics, laboratory values, treatment outcomes and adverse events were collected from medical records...
January 10, 2017: Pathology Oncology Research: POR
https://www.readbyqxmd.com/read/28074210/diagnostic-value-of-additional-68-ga-psma-pet-before-223-ra-dichloride-therapy-in-patients-with-metastatic-prostate-carcinoma
#17
Axel Bräuer, Kambiz Rahbar, Julia Konnert, Martin Bögemann, Lars Stegger
PURPOSE: Medical imaging plays an important role in selecting patients with metastatic castration-resistant prostate cancer for (223)Ra-dichloride therapy of bone metastases. The purpose of this study was to investigate whether (68)Ga-PSMA-PET has incremental value over conventional imaging for selecting patients suitable for (223)Ra-dichloride therapy. METHODS: In 27 consecutive patients referred for (223)Ra-dichloride therapy additional (68)Ga-PSMA-PET/CT was performed and tracer distribution was evaluated systematically with respect to the detection of visceral metastases and bone metastases with inadequate uptake on bone scintigraphy...
January 11, 2017: Nuklearmedizin. Nuclear Medicine
https://www.readbyqxmd.com/read/28069876/targeting-plk1-to-enhance-efficacy-of-olaparib-in-castration-resistant-prostate-cancer
#18
Xiaoqi Liu, Jie Li, Ruixin Wang, Yifan Kong, Meaghan M Broman, Colin Carlock, Long Chen, Zhiguo Li, Elia Farah, Timothy L Ratliff
Olaparib is a FDA-approved PARP inhibitor (PARPi) that has shown promise as a synthetic lethal treatment approach for BRCA-mutant castration-resistant prostate cancer (CRPC) in clinical use. However, emerging data has also shown that even BRCA-mutant cells may be resistant to PARPi. The mechanistic basis for these drug resistances is poorly understood. Polo-like kinase 1 (Plk1), a critical regulator of many cell cycle events, is significantly elevated upon castration of mice carrying xenograft prostate tumors...
January 9, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28069826/endostatin-inhibits-androgen-independent-prostate-cancer-growth-by-suppressing-nuclear-receptor-mediated-oxidative-stress
#19
Joo Hyoung Lee, Minsung Kang, Hong Wang, Gurudatta Naik, James A Mobley, Guru Sonpavde, W Timothy Garvey, Victor M Darley-Usmar, Selvarangan Ponnazhagan
Androgen-deprivation therapy has been identified to induce oxidative stress in prostate cancer (PCa), leading to reactivation of androgen receptor (AR) signaling in a hormone-refractory manner. Thus, antioxidant therapies have gained attention as adjuvants for castration-resistant PCa. Here, we report for the first time that human endostatin (ES) prevents androgen-independent growth phenotype in PCa cells through its molecular targeting of AR and glucocorticoid receptor (GR) and downstream pro-oxidant signaling...
January 9, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28068321/analysis-of-dna-methylation-in-single-circulating-tumor-cells
#20
C F Pixberg, K Raba, F Müller, B Behrens, E Honisch, D Niederacher, H Neubauer, T Fehm, W Goering, W A Schulz, P Flohr, G Boysen, M Lambros, J S De Bono, W T Knoefel, C Sproll, N H Stoecklein, R P L Neves
Direct analysis of circulating tumor cells (CTCs) can inform on molecular mechanisms underlying systemic spread. Here we investigated promoter methylation of three genes regulating epithelial-to-mesenchymal transition (EMT), a key mechanism enabling epithelial tumor cells to disseminate and metastasize. For this, we developed a single-cell protocol based on agarose-embedded bisulfite treatment, which allows investigating DNA methylation of multiple loci via a multiplex PCR (multiplexed-scAEBS). We established our assay for the simultaneous analysis of three EMT-associated genes miR-200c/141, miR-200b/a/429 and CDH1 in single cells...
January 9, 2017: Oncogene
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