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https://www.readbyqxmd.com/read/28346424/skp2-deficiency-restricts-the-progression-and-stem-cell-features-of-castration-resistant-prostate-cancer-by-destabilizing-twist
#1
D Ruan, J He, C-F Li, H-J Lee, J Liu, H-K Lin, C-H Chan
Castration-resistant prostate cancer (CRPC) remains a major clinical challenge because of the lack of effective targeted therapy for its treatment. The mechanism underlying how CRPC gains resistance toward hormone depletion and other forms of chemotherapy is poorly understood. Research on understanding the factors that drive these processes is desperately needed to generate new therapies to cure the disease. Here, we discovered a fundamental role of S-phase protein kinase 2 (Skp2) in the formation and progression of CRPC...
March 27, 2017: Oncogene
https://www.readbyqxmd.com/read/28345444/budgetary-impact-of-cabazitaxel-use-after-docetaxel-treatment-for-metastatic-castration-resistant-prostate-cancer
#2
Kyle Flannery, Ed Drea, Louis Hudspeth, Shelby Corman, Xin Gao, Mei Xue, Raymond Miao
BACKGROUND: With the approval of several new treatments for metastatic castration-resistant prostate cancer (mCRPC), budgetary impact is a concern for health plan decision makers. Budget impact models (BIMs) are becoming a requirement in many countries as part of formulary approval or reimbursement decisions. Cabazitaxel is a second-generation taxane developed to overcome resistance to docetaxel and is approved for the treatment of patients with mCRPC previously treated with a docetaxel-containing regimen...
April 2017: Journal of Managed Care & Specialty Pharmacy
https://www.readbyqxmd.com/read/28344102/effect-of-visceral-disease-site-on-outcomes-in-patients-with-metastatic-castration-resistant-prostate-cancer-treated-with-enzalutamide-in-the-prevail-trial
#3
Joshi J Alumkal, Simon Chowdhury, Yohann Loriot, Cora N Sternberg, Johann S de Bono, Bertrand Tombal, Joan Carles, Thomas W Flaig, Tanya B Dorff, De Phung, David Forer, Sarah B Noonberg, Hank Mansbach, Tomasz M Beer, Celestia S Higano
BACKGROUND: The Multinational Phase 3, Randomized, Double-Blind, Placebo-Controlled Efficacy and Safety Study of Oral MDV3100 in Chemotherapy-Naive Patients With Progressive Metastatic Prostate Cancer Who Have Failed Androgen Deprivation Therapy (PREVAIL) trial was unique as it included patients with visceral disease. This analysis was designed to describe outcomes for the subgroup of men from PREVAIL with specific sites of visceral disease to help clinicians understand how these patients responded to enzalutamide prior to chemotherapy...
March 3, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28342996/induction-of-neuroendocrine-differentiation-in-prostate-cancer-cells-by-dovitinib-tki-258-and-its-therapeutic-implications
#4
Shalini S Yadav, Jinyi Li, Jennifer A Stockert, Bryan Herzog, James O'Connor, Luis Garzon-Manco, Ramon Parsons, Ashutosh K Tewari, Kamlesh K Yadav
Prostate cancer (PCa) remains the second-leading cause of cancer-related deaths in American men with an estimated mortality of more than 26,000 in 2016 alone. Aggressive and metastatic tumors are treated with androgen deprivation therapies (ADT); however, the tumors acquire resistance and develop into lethal castration resistant prostate cancer (CRPC). With the advent of better therapeutics, the incidences of a more aggressive neuroendocrine prostate cancer (NEPC) variant continue to emerge. Although de novo occurrences of NEPC are rare, more than 25% of the therapy-resistant patients on highly potent new-generation anti-androgen therapies end up with NEPC...
March 23, 2017: Translational Oncology
https://www.readbyqxmd.com/read/28337641/inhibition-of-proliferation-of-prostate-cancer-cell-line-du-145-in-vitro-and-in-vivo-using-salvia-miltiorrhiza-bunge
#5
Woong Jin Bae, Jin Bong Choi, Kang Sup Kim, U Syn Ha, Sung Hoo Hong, Ji Youl Lee, Tae-Kon Hwang, Sung Yeoun Hwang, Zhi-Ping Wang, Sae Woong Kim
OBJECTIVE: To investigate the antiproliferative activity of Salvia miltiorrhiza Bunge. (SM) on the castration-resistant prostate cancer (CRPC) cell line DU-145, in vitro and in vivo. METHODS: Prostate cancer cell line (DU-145) and normal prostate cell line (RWPE-1) were treated with SM at different concentrations (3.125, 12.5, 25 and 50 μg/mL) to investigate the antiproliferative effects. DNA laddering analysis was performed to investigate the apoptosis of DU-145 cells...
March 23, 2017: Chinese Journal of Integrative Medicine
https://www.readbyqxmd.com/read/28337529/the-impact-of-repeated-cycles-of-radioligand-therapy-using-177-lu-lu-psma-617-on-renal-function-in-patients-with-hormone-refractory-metastatic-prostate-cancer
#6
Anna Yordanova, Anja Becker, Elisabeth Eppard, Stefan Kürpig, Christian Fisang, Georg Feldmann, Markus Essler, Hojjat Ahmadzadehfar
BACKGROUND: [(177)Lu]Lu-PSMA-617 is a well-tolerated therapy for the treatment of metastatic prostate cancer. However, because of the mainly renal excretion of the tracer, the kidneys are one of the most limiting organs. The purpose of this study was to examine the post-therapeutic changes in renal function over time and to identify risk factors for developing renal toxicity. We also tested the reliability of markers for renal function monitoring. METHODS: Fifty-five patients with castrate-resistant metastatic prostate cancer treated with at least three cycles of [(177)Lu]Lu-PSMA-617 were investigated...
March 23, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28334734/multinucleated-polyploidy-drives-resistance-to-docetaxel-chemotherapy-in-prostate-cancer
#7
Karuna Mittal, Shashi Donthamsetty, Ramneet Kaur, Chunhua Yang, Meenakshi V Gupta, Michelle D Reid, Da Hoon Choi, Padmashree C G Rida, Ritu Aneja
BACKGROUND: Docetaxel is the only FDA-approved first-line treatment for castration-resistant prostate cancer (CRPC) patients. Docetaxel treatment inevitably leads to tumour recurrence after an initial therapeutic response with generation of multinucleated polyploid (MP) cells. Here we investigated role of MP cells in clinical relapse of CRPC. METHODS: Prostate cancer (PC-3) cells were treated with docetaxel (5 nM) for 3 days followed by a washout and samples were collected at close intervals over 35 days post drug washout...
March 23, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28324007/aberrant-tgf-%C3%AE-signaling-drives-castration-resistant-prostate-cancer-in-a-male-mouse-model-of-prostate-tumorigenesis
#8
Hong Pu, Diane Begemann, Natasha Kyprianou
The androgen receptor (AR) plays a critical role as a driver of castration-resistant-prostate cancer (CRPC). Our previous studies demonstrated that disruption of transforming growth factor-β (TGF-β) signaling via introduction of dominant-negative TGF-β type II receptor (DNTGF-RβII) in the prostate epithelium of transgenic adenocarcinoma of the prostate (TRAMP) mice accelerated tumor. This study investigated the consequences of disrupted TGF-β signaling on prostate tumor growth under conditions of castration-induced androgen deprivation (ADT) in the pre-clinical model DNTGFβRII...
March 16, 2017: Endocrinology
https://www.readbyqxmd.com/read/28323036/targeting-androgen-receptor-versus-targeting-androgens-to-suppress-castration-resistant-prostate-cancer
#9
Changcheng Guo, Shuyuan Yeh, Yuanjie Niu, Gonghui Li, Junhua Zheng, Lei Li, Chawnshang Chang
Prostate cancer (PCa) is the 2nd leading cause of cancer-related death among men in the United States and its progression is tightly associated with the androgen/androgen receptor (AR) signals. Men castrated before puberty (eunuchs) or men with inherited deficiency of type II 5α-reductase (with failure to convert testosterone to the more potent dihydrotestosterone) (DHT) do not develop PCa. To date, androgen deprivation therapy (ADT) with anti-androgen treatments to reduce or prevent androgens from binding to the AR remains the main therapeutic option for advanced PCa since its discovery by Huggins and Hodges in 1941...
March 18, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28321130/effective-combinatorial-immunotherapy-for-castration-resistant-prostate-cancer
#10
Xin Lu, James W Horner, Erin Paul, Xiaoying Shang, Patricia Troncoso, Pingna Deng, Shan Jiang, Qing Chang, Denise J Spring, Padmanee Sharma, John A Zebala, Dean Y Maeda, Y Alan Wang, Ronald A DePinho
A significant fraction of patients with advanced prostate cancer treated with androgen deprivation therapy experience relapse with relentless progression to lethal metastatic castration-resistant prostate cancer (mCRPC). Immune checkpoint blockade using antibodies against cytotoxic-T-lymphocyte-associated protein 4 (CTLA4) or programmed cell death 1/programmed cell death 1 ligand 1 (PD1/PD-L1) generates durable therapeutic responses in a significant subset of patients across a variety of cancer types. However, mCRPC showed overwhelming de novo resistance to immune checkpoint blockade, motivating a search for targeted therapies that overcome this resistance...
March 20, 2017: Nature
https://www.readbyqxmd.com/read/28319807/targeting-nf-kappa-b-signaling-by-artesunate-restores-sensitivity-of-castrate-resistant-prostate-cancer-cells-to-antiandrogens
#11
Jessica J Nunes, Swaroop K Pandey, Anjali Yadav, Sakshi Goel, Bushra Ateeq
Androgen deprivation therapy (ADT) is the most preferred treatment for men with metastatic prostate cancer (PCa). However, the disease eventually progresses and develops resistance to ADT in majority of the patients, leading to the emergence of metastatic castration-resistant prostate cancer (mCRPC). Here, we assessed artesunate (AS), an artemisinin derivative, for its anticancer properties and ability to alleviate resistance to androgen receptor (AR) antagonists. We have shown AS in combination with bicalutamide (Bic) attenuates the oncogenic properties of the castrate-resistant (PC3, 22RV1) and androgen-responsive (LNCaP) PCa cells...
March 16, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28319070/foxa1-inhibits-prostate-cancer-neuroendocrine-differentiation
#12
J Kim, H Jin, J C Zhao, Y A Yang, Y Li, X Yang, X Dong, J Yu
Neuroendocrine prostate cancer (NEPC) has increasingly become a clinical challenge. The mechanisms by which neuroendocrine (NE) cells arises from prostate adenocarcinoma cells are poorly understood. FOXA1 is a transcription factor of the forkhead family that is required for prostate epithelial differentiation. In this study, we demonstrated that FOXA1 loss drives NE differentiation, demarcated by phenotypical changes and NEPC marker expressions. Mechanistically, this is mediated by FOXA1 binding to the promoter of interleukin 8 (IL-8), a chemokine previously shown elevated in NEPC, to directly inhibit its expression...
March 20, 2017: Oncogene
https://www.readbyqxmd.com/read/28318331/docetaxel-chemotherapy-in-metastatic-castration-resistant-prostate-cancer-cost-of-care-in-medicare-and-commercial-populations
#13
A Armstrong, C Bui, K Fitch, T Goss Sawhney, B Brown, S Flanders, M Balk, J Deangelis, J Chambers
OBJECTIVE: To estimate the healthcare costs and characteristics of docetaxel chemotherapy episodes of care for men with metastatic castration-resistant prostate cancer (mCRPC). METHODS: We used Medicare 5% sample and MarketScan® Commercial (2010 - 2013) claims data sets to identify men with mCRPC and initial episodes of docetaxel treatment. Docetaxel episodes included docetaxel claim costs from the first claim until 30 days after the last claim, with earlier termination for death, insurance disenrollment, or the end of a 24-month look-forward period from initial docetaxel index date...
March 20, 2017: Current Medical Research and Opinion
https://www.readbyqxmd.com/read/28315704/interleukin-6-and-prostate-cancer-current-developments-and-unsolved-questions
#14
Zoran Culig, Martin Puhr
Interleukin (IL)-6 is a pro-inflammatory cytokine that is expressed in prostate tumors and in the stromal tumor micro-enviroment. It is known to regulate proliferation, apoptosis, angiogenesis, and differentiation. The signaling pathway of Janus kinase and signal transducer and activator of transcription (STAT)3, which is activated by IL-6, is in the focus of scientific investigations for improved treatment approaches. Different effects of IL-6 and/or STAT3 on tumor cell growth have been observed in human and murine prostate cancer (PCa) models...
March 16, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28314838/a-phase-i-study-of-abiraterone-acetate-combined-with-bez235-a-dual-pi3k-mtor-inhibitor-in-metastatic-castration-resistant-prostate-cancer
#15
Xiao X Wei, Andrew C Hsieh, Won Kim, Terence Friedlander, Amy M Lin, Mirela Louttit, Charles J Ryan
LESSONS LEARNED: The combination of standard dose abiraterone acetate and BEZ235, a pan-class I PI3K and mTORC1/2 inhibitor, was poorly tolerated in men with progressive mCRPC.Although the clinical development of BEZ235 has been discontinued in prostate cancer, agents that more selectively target PI3K-AKT-mTOR signaling may have a more favorable therapeutic index and should continue to be explored. BACKGROUND: Androgen receptor (AR) and phosphatidylinositol-3 kinase (PI3K) signaling are two commonly perturbed pathways in prostate cancer...
March 17, 2017: Oncologist
https://www.readbyqxmd.com/read/28314611/clinical-outcomes-from-androgen-signaling-directed-therapy-after-treatment-with-abiraterone-acetate-and-prednisone-in-patients-with-metastatic-castration-resistant-prostate-cancer-post-hoc-analysis-of-cou-aa-302
#16
Matthew R Smith, Fred Saad, Dana E Rathkopf, Peter F A Mulders, Johann S de Bono, Eric J Small, Neal D Shore, Karim Fizazi, Thian Kheoh, Jinhui Li, Peter De Porre, Mary B Todd, Margaret K Yu, Charles J Ryan
In the COU-AA-302 trial, abiraterone acetate plus prednisone significantly increased overall survival for patients with chemotherapy-naïve metastatic castration-resistant prostate cancer (mCRPC). Limited information exists regarding response to subsequent androgen signaling-directed therapies following abiraterone acetate plus prednisone in patients with mCRPC. We investigated clinical outcomes associated with subsequent abiraterone acetate plus prednisone (55 patients) and enzalutamide (33 patients) in a post hoc analysis of COU-AA-302...
March 14, 2017: European Urology
https://www.readbyqxmd.com/read/28314571/erratum-to-predictors-of-time-to-metastasis-in-castration-resistant-prostate-cancer
#17
(no author information available yet)
No abstract text is available yet for this article.
March 14, 2017: Urology
https://www.readbyqxmd.com/read/28314320/the-clinical-efficacy-of-enzalutamide-in-metastatic-prostate-cancer-prospective-single-center-study
#18
Giuseppe Cicero, Rossella DE Luca, Patrizia Dorangricchia, Francesco Dieli
BACKGROUND/AIM: To evaluate the effectiveness of enzalutamide in Italian patients with hormone-refractory metastatic castration-resistant prostate cancer, progressing after chemotherapy with docetaxel plus prednisone. PATIENTS AND METHODS: A total of 60 patients were enrolled. Reduction in serum prostate-specific antigen (PSA) was assessed as the primary endpoint, while reduction in pain, safety, progression-free survival and overall survival represented secondary endpoints...
March 2017: Anticancer Research
https://www.readbyqxmd.com/read/28302679/disrupting-androgen-receptor-signaling-induces-snail-mediated-epithelial-mesenchymal-plasticity-in-prostate-cancer
#19
Lu Miao, Lin Yang, Rui Li, Daniel Nava Rodrigues, Mateus Crespo, Jer-Tsong Hsieh, Wayne D Tilley, Johann S de Bono, Luke A Selth, Ganesh V Raj
Epithelial to mesenchymal plasticity (EMP) has been linked to metastasis, stemness, and drug resistance. In prostate cancer (PCa), EMP has been associated with both suppression and activation of androgen receptor (AR) signaling. Here we investigated the effect of the potent AR antagonist enzalutamide on EMP in multiple preclinical models of PCa and patient tissues. Enzalutamide treatment significantly enhanced the expression of EMP drivers (ZEB1, ZEB2, Snail, Twist, and FOXC2) and mesenchymal markers (N-cadherin, fibronectin, and vimentin) in PCa cells, enhanced PCa cell migration, and induced PCa transformation to a spindle, fibroblast-like morphology...
March 16, 2017: Cancer Research
https://www.readbyqxmd.com/read/28302580/the-role-of-therapeutic-layering-in-optimizing-treatment-for-patients-with-castration-resistant-prostate-cancer-radar-ii
#20
E David Crawford, Daniel P Petrylak, Neal Shore, Fred Saad, Susan F Slovin, Nicholas J Vogelzang, Thomas E Keane, Phillip J Koo, Leonard G Gomella, Joe M O'Sullivan, Bertrand Tombal, Raoul S Concepcion, Paul Sieber, Nelson N Stone, Steven E Finkelstein, Evan Y Yu
OBJECTIVE: To offer recommendations on identification of disease progression, treatment management strategies, and suggestions on timing of initiating and discontinuing specific CRPC treatments. MATERIALS AND METHODS: The RADAR II [Prostate Cancer Radiographic Assessments for Detection of Advanced Recurrence] Working Group convened to provide guidance on sequencing, combination, or layering of approved treatments for mCRPC based on available data and clinical experience...
March 13, 2017: Urology
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