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https://www.readbyqxmd.com/read/28549433/js-k-a-nitric-oxide-pro-drug-regulates-growth-and-apoptosis-through-the-ubiquitin-proteasome-pathway-in-prostate-cancer-cells
#1
Guobin Tan, Mingning Qiu, Lieqian Chen, Sai Zhang, Longzhi Ke, Jianjun Liu
BACKGROUND: In view of the fact that JS-K might regulate ubiquitin E3 ligase and that ubiquitin E3 ligase plays an important role in the mechanism of CRPC formation, the goal was to investigate the probable mechanism by which JS-K regulates prostate cancer cells. METHODS: Proliferation inhibition by JS-K on prostate cancer cells was examined usingCCK-8 assays. Caspase 3/7 activity assays and flow cytometry were performed to examine whether JS-K induced apoptosis in prostate cancer cells...
May 26, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28539888/safety-and-immunogenicity-of-a-human-epidermal-growth-factor-receptor-1-her1-based-vaccine-in-prostate-castration-resistant-carcinoma-patients-a-dose-escalation-phase-i-study-trial
#2
Iraida Caballero, Lazaro E Aira, Anabel Lavastida, Xitlally Popa, Javier Rivero, Joaquín González, Mónica Mesa, Narjara González, Kelly Coba, Patricia Lorenzo-Luaces, Barbara Wilkinson, Yuliannis Santiesteban, Yanela Santiesteban, Mayelin Troche, Eduardo Suarez, Tania Crombet, Belinda Sánchez, Angel Casacó, Amparo Macías, Zaima Mazorra
Metastatic castration-resistant prostate cancer (CRPC) remains incurable due to the lack of effective therapies. Activation of the human epidermal growth factor receptor 1 (HER1) in prostate cancer contributes to metastatic progression as well as to disease relapse. Here, we determined the toxicity and immunogenicity of a HER1-based cancer vaccine in CRPC patients included in a phase I clinical trial. CRPC patients (n = 24) were intramuscularly vaccinated with HER1 vaccine consisting of the extracellular domain of HER1 molecule (ECD) and very small size proteoliposome from Neisseria meningitidis (VSSP) and Montanide ISA-51 VG as adjuvants...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/28536297/androgen-receptor-inhibitor-induced-brcaness-and-parp-inhibition-are-synthetically-lethal-for-castration-resistant-prostate-cancer
#3
Likun Li, Styliani Karanika, Guang Yang, Jiangxiang Wang, Sanghee Park, Bradley M Broom, Ganiraju C Manyam, Wenhui Wu, Yong Luo, Spyridon Basourakos, Jian H Song, Gary E Gallick, Theodoros Karantanos, Dimitrios Korentzelos, Abul Kalam Azad, Jeri Kim, Paul G Corn, Ana M Aparicio, Christopher J Logothetis, Patricia Troncoso, Timothy Heffernan, Carlo Toniatti, Hyun-Sung Lee, Ju-Seog Lee, Xuemei Zuo, Wenjun Chang, Jianhua Yin, Timothy C Thompson
Cancers with loss-of-function mutations in BRCA1 or BRCA2 are deficient in the DNA damage repair pathway called homologous recombination (HR), rendering these cancers exquisitely vulnerable to poly(ADP-ribose) polymerase (PARP) inhibitors. This functional state and therapeutic sensitivity is referred to as "BRCAness" and is most commonly associated with some breast cancer types. Pharmaceutical induction of BRCAness could expand the use of PARP inhibitors to other tumor types. For example, BRCA mutations are present in only ~20% of prostate cancer patients...
May 23, 2017: Science Signaling
https://www.readbyqxmd.com/read/28536143/aurora-kinase-a-promotes-ar-degradation-via-the-e3-ligase-chip
#4
James M Larner, Sukumar Sarkar, David L Brautigan
Reducing the levels of the androgen receptor (AR) is one of the most viable approaches to combat castration-resistant prostate cancer (CRPC). Previously, we observed that proteasomal-dependent degradation of AR in response to 2-methoxyestradiol (2-ME) depends primarily on the E3 ligase C-terminus of HSP70-interacting protein (STUB1/CHIP). Here, 2-ME stimulation activates CHIP by phosphorylation via Aurora kinase A (AURKA). Aurora A kinase inhibitors and RNAi knockdown of Aurora A transcript selectively blocked CHIP phosphorylation and AR degradation...
May 23, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28534948/dual-strands-of-pre-mir%C3%A2-150-mir%C3%A2-150%C3%A2-5p-and-mir%C3%A2-150%C3%A2-3p-act-as-antitumor-mirnas-targeting-spock1-in-na%C3%A3-ve-and-castration-resistant-prostate-cancer
#5
Atsushi Okato, Takayuki Arai, Satoko Kojima, Keiichi Koshizuka, Yusaku Osako, Tetsuya Idichi, Akira Kurozumi, Yusuke Goto, Mayuko Kato, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki
Analysis of our microRNA (miRNA) expression signature in human cancers has shown that guide and passenger strands of pre-miR‑150, i.e., miR‑150‑5p and miR‑150‑3p, are significantly downregulated in cancer tissues. In miRNA biogenesis, the passenger strand of miRNA is degraded and is thought to have no functions. Thus, the aim of this study was to investigate the functional significance of miR‑150‑5p and miR‑150‑3p in naïve prostate cancer (PCa) and castration-resistant prostate cancer (CRPC)...
May 17, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/28532278/tackling-non-metastatic-castration-resistant-prostate-cancer-special-considerations-in-treatment
#6
Archana Anantharaman, Eric J Small
Prostate cancer (PCa) is currently the second most common cancer affecting men worldwide. Metastatic castration-resistant prostate cancer (mCRPC) is the incurable form of PCa, carrying the poorest prognosis, and can develop from non-metastatic CRPC (M0 CRPC). CRPC is defined as progression of the disease with castrate level testosterone levels, achieved with primary androgen deprivation therapy (ADT). M0 CRPC is a highly heterogeneous disease process lacking clear standard of care therapies. Areas covered: In this review, a broad literature search was undertaken to explore data available for therapeutic options and guidelines in the management of M0 CRPC...
May 23, 2017: Expert Review of Anticancer Therapy
https://www.readbyqxmd.com/read/28529549/abiraterone-acetate-and-prednisone-in-chemotherapy-na%C3%A3-ve-prostate-cancer-patients-rationale-evidence-and-clinical-utility
#7
REVIEW
E David Crawford, Neal D Shore, Daniel P Petrylak, Celestia S Higano, Charles J Ryan
Abiraterone acetate 1000 mg/day, combined with prednisone 5 mg PO twice daily, is indicated for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Abiraterone acetate is the oral prodrug of abiraterone, a specific CYP17 inhibitor that blocks androgen biosynthesis within the adrenal glands, testes and tumor microenvironment. In a phase III trial of men with asymptomatic or minimally symptomatic, chemotherapy-naïve mCRPC, treatment with oral abiraterone acetate plus prednisone led to a statistically significant improvement in the co-primary endpoints of overall survival and radiographic progression-free survival when compared with placebo plus prednisone...
May 2017: Therapeutic Advances in Medical Oncology
https://www.readbyqxmd.com/read/28529342/circulating-tumor-cells-and-serum-levels-of-mmp-2-mmp-9-and-vegf-as-markers-of-the-metastatic-process-in-patients-with-high-risk-of-metastatic-progression
#8
Marketa Skerenova, Veronika Mikulova, Otakar Capoun, Tomas Zima, Petra Tesarova
BACKGROUND AND AIMS: Metastases are a severe complication in cancer patients and biomarkers predicting their progression are still lacking for specific groups of patients. HER2 positive breast cancer (HER2 BC) patients on trastuzumab therapy are at risk of the development of unpredictable and often fatal central nervous system (CNS) metastases and castration resistant prostate cancer (CRPC) patients urgently need a marker of disease progression during therapy. Proposed metastatic markers: circulating tumor cells (CTC), serum levels of matrix metalloproteinase 2 (MMP-2), 9 (MMP-9) and vascular endothelial growth factor (VEGF) were prospectively studied to confirm their utility in these two narrowly defined groups of cancer patients...
May 16, 2017: Biomedical Papers of the Medical Faculty of the University Palacký, Olomouc, Czechoslovakia
https://www.readbyqxmd.com/read/28498618/phase-i-clinical-trial-of-cell-division-associated-1-cdca1-peptide-vaccination-for-castration-resistant-prostate-cancer
#9
Wataru Obara, Fuminori Sato, Kazuyoshi Takeda, Renpei Kato, Yoichiro Kato, Mitsugu Kanehira, Ryo Takata, Hiromitsu Mimata, Tamotsu Sugai, Yusuke Nakamura, Tomoaki Fujioka
We screened cell division associated 1 (CDCA1) as an oncogene that is overexpressed on several cancers, including prostate cancer. We also identified a highly immunogenic HLA-A*2402-restricted epitope peptide corresponding to part of the CDCA1 protein. We conducted a phase I clinical trial for patients with castration resistant prostate cancer (CRPC) using a CDCA1 peptide vaccination. Twelve patients having HLA-A*2402 with CRPC after failure of docetaxel chemotherapy were enrolled. They received subcutaneous administration of the CDCA1 peptide as an emulsion with Montanide ISA51VG once a week in a dose-escalation manner (doses of 1...
May 12, 2017: Cancer Science
https://www.readbyqxmd.com/read/28498452/calpain-and-ar-v7-two-potential-therapeutic-targets-to-overcome-acquired-docetaxel-resistance-in-castration-resistant-prostate-cancer-cells
#10
Lei Liu, Ning Lou, Xiang Li, Guanghua Xu, Hailong Ruan, Wen Xiao, Bin Qiu, Lin Bao, Changfei Yuan, Xinmian Huang, Keshan Wang, Qi Cao, Ke Chen, Hongmei Yang, Xiaoping Zhang
Docetaxel-based chemotherapy has been widely used as the first-line treatment for castration-resistant prostate cancer (CRPC) patients. However, the mechanisms of docetaxel-resistance remain unclear. In the present study with the establishment of 2 in vitro models of docetaxel-resistant CRPC cell sublines, we firstly reported that activation of calpain may play a promotional role in the resistance of docetaxel in prostate cancer, meanwhile using the calpain inhibitor combined with docetaxel improved the efficiency of docetaxel in docetaxel-resistant cell sublines...
May 4, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28497777/phase-i-ii-clinical-trial-to-assess-safety-and-efficacy-of-intratumoral-and-subcutaneous-injection-of-hvj-e-in-castration-resistant-prostate-cancer-patients
#11
K Fujita, Y Nakai, A Kawashima, T Ujike, A Nagahara, T Nakajima, T Inoue, C M Lee, M Uemura, Y Miyagawa, Y Kaneda, N Nonomura
Inactivated Sendai virus particles (hemagglutinating virus of Japan envelope (HVJ-E)) have a novel antitumor effect: HVJ-E fused to prostate cancer cells via cell surface receptor causes apoptosis of prostate cancer cells in vitro and in vivo. HVJ-E also induces antitumor immunity by activating natural killer (NK) cells and cytotoxic T cells and suppressing regulatory T cells in vivo. We conducted an open-label, single-arm, phase I/II clinical trial in patients with castration-resistant prostate cancer (CRPC) to determine the safety and efficacy of intratumoral and subcutaneous injection of HVJ-E...
May 12, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28490267/darolutamide-odm-201-for-the-treatment-of-prostate-cancer
#12
Neal D Shore
Androgen deprivation therapy (ADT) is a mainstay initial treatment for advanced hormone-sensitive prostate cancer (HSPC), but disease progression to castration-resistant prostate cancer (CRPC) invariably occurs when patients do not succumb to another disease or comorbidity. Recognition that the androgen receptor (AR) axis continues to drive disease progression has led to the development of several AR-directed approved agents, including abiraterone acetate and enzalutamide. An investigational agent, darolutamide (ODM-201, BAY-1841788), has completed early-phase clinical trials, and two global phase III trials are currently accruing patients...
June 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28488028/overall-survival-and-response-pattern-of-castration-resistant-metastatic-prostate-cancer-to-multiple-cycles-of-radioligand-therapy-using-177-lu-lu-psma-617
#13
Hojjat Ahmadzadehfar, Simone Wegen, Anna Yordanova, Rolf Fimmers, Stefan Kürpig, Elisabeth Eppard, Xiao Wei, Carl Schlenkhoff, Stefan Hauser, Markus Essler
PURPOSE: Up to 30% of patients with castration-resistant prostate cancer (CRPC) do not show any response to the first cycle of radioligand therapy (RLT) with [(177)Lu]Lu-PSMA-617 (Lu-PSMA). We evaluated patient response to the second and third cycles of RLT in patients that underwent at least three cycles. The second aim of this study was to calculate the median overall survival (OS) of responders and non-responders after the first cycle and after all three cycles of RLT. METHODS: CRPC patients were treated with Lu-PSMA, with a median interval of 8 weeks between each cycle...
May 9, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28487115/lncrna-hoxd-as1-regulates-proliferation-and-chemo-resistance-of-castration-resistant-prostate-cancer-via-recruiting-wdr5
#14
Peng Gu, Xu Chen, Ruihui Xie, Jinli Han, Weibin Xie, Bo Wang, Wen Dong, Changhao Chen, Meihua Yang, Junyi Jiang, Ziyue Chen, Jian Huang, Tianxin Lin
Castration-resistant prostate cancer (CRPC) that occurs after the failure of androgen deprivation therapy is the leading cause of deaths in prostate cancer patients. Thus, there is an obvious and urgent need to fully understand the mechanism of CRPC and discover novel therapeutic targets. Long noncoding RNAs (lncRNAs) are crucial regulators in many human cancers, yet their potential roles and molecular mechanisms in CRPC are poorly understood. In this study, we discovered that an lncRNA HOXD-AS1 is highly expressed in CRPC cells and correlated closely with Gleason score, T stage, lymph nodes metastasis, and progression-free survival...
May 6, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28485785/study-on-the-influence-of-metformin-on-castration-resistant-prostate-cancer-pc-3-cell-line-biological-behavior-by-its-inhibition-on-plc%C3%AE%C2%B5-gene-mediated-notch1-hes-and-androgen-receptor-signaling-pathway
#15
Y Yang, X-H Wu
OBJECTIVE: To study the regulation of metformin on the biological behaviors of the castration-resistant prostate cancer (CRPC) PC-3 cell such as proliferation, invasion, apoptosis through influencing Notch1/Hes and androgen receptor (AR) signaling pathway activity by its inhibition on the expression of PLCε gene. MATERIALS AND METHODS: Human prostate cancer-3 (PC-3) cell line was divided into PC-3 cell line (group A), PC-3 cell line + metformin (10 mM) (group B), PC-3 cell line + metformin (20 mM) (group C), PLCε gene knockout cell line (group D), PLCε knockout cell line + metformin (10 mM)_ (group E) and PLCε knockout cell line + metformin (20 mM) (group F), which were respectively tested at 24 h, 48 h and 72 h, and five duplicate wells were set at each time point in each group...
April 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/28485104/microrna-181a-promotes-docetaxel-resistance-in-prostate-cancer-cells
#16
Cameron M Armstrong, Chengfei Liu, Wei Lou, Alan P Lombard, Christopher P Evans, Allen C Gao
BACKGROUND: Docetaxel is one of the primary drugs used for treating castration resistant prostate cancer (CRPC). Unfortunately, over time patients invariably develop resistance to docetaxel therapy and their disease will continue to progress. The mechanisms by which resistance develops are still incompletely understood. This study seeks to determine the involvement of miRNAs, specifically miR-181a, in docetaxel resistance in CRPC. METHODS: Real-time PCR was used to measure miR-181a expression in parental and docetaxel resistant C4-2B and DU145 cells (TaxR and DU145-DTXR)...
June 2017: Prostate
https://www.readbyqxmd.com/read/28484088/radium-223-for-primary-bone-metastases-in-patients-with-hormone-sensitive-prostate-cancer-after-radical-prostatectomy
#17
Vera Wenter, Annika Herlemann, Wolfgang P Fendler, Harun Ilhan, Natalia Tirichter, Peter Bartenstein, Christian G Stief, Christian la Fougère, Nathalie L Albert, Axel Rominger, Christian Gratzke
Radium-223 dichloride (Ra-223) is the first bone-targeting agent showing improvement in overall survival in patients with castration-resistant prostate cancer (CRPC) and bone metastases. We aimed to assess feasibility of Ra-223 treatment in patients with metastatic hormone-sensitive prostate cancer (mHSPC). Ten patients with primary bone metastases received Ra-223 following radical prostatectomy (RP). Changes in alkaline phosphatase (ALP) and prostate-specific antigen (PSA) were recorded, while pain intensity was evaluated using the self-reporting Brief Pain Inventory (BPI) questionnaire...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28473535/androgen-receptor-variant-ar-v9-is-co-expressed-with-ar-v7-in-prostate-cancer-metastases-and-predicts-abiraterone-resistance
#18
Manish Kohli, Yeung Ho, David W Hillman, Jamie L Van Etten, Christine Henzler, Rendong Yang, Jame M Sperger, Yingming Li, Elizabeth Tseng, Ting Hon, Tyson Clark, Winston Tan, Rachel E Carlson, Liguo Wang, Hugues Sicotte, Ho Thai, Rafael Jimenez, Haojie Huang, Peter T Vedell, Bruce W Eckloff, J Fernando Quevedo, Henry C Pitot, Brian Costello, Jin Jen, Eric D Wieben, Kevin A T Silverstein, Joshua M Lang, Liewei Wang, Scott M Dehm
Purpose: Androgen receptor (AR) variant AR-V7 is a ligand-independent transcription factor that promotes prostate cancer resistance to AR-targeted therapies.  Accordingly, efforts are underway to develop strategies for monitoring and inhibiting AR-V7 in castration-resistant prostate cancer (CRPC).  The purpose of this study was to understand whether other AR variants may be co-expressed with AR-V7 and promote resistance to AR-targeted therapies.<br /><br /> Experimental Design:  We utilized complementary short- and long-read sequencing of intact AR mRNA isoforms to characterize AR expression in CRPC models...
May 4, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28472637/lipid-oligonucleotide-conjugates-improve-cellular-uptake-and-efficiency-of-tctp-antisense-in-castration-resistant-prostate-cancer
#19
Sara Karaki, Sebastien Benizri, Raquel Mejías, Virginie Baylot, Nicolas Branger, Tan Nguyen, Brune Vialet, Khalid Oumzil, Philippe Barthélémy, Palma Rocchi
Translationally controlled tumor protein (TCTP) has been implicated in a plethora of important cellular processes related to cell growth, cell cycle progression, malignant transformation and inhibition of apoptosis. Therefore, TCTP is now recognized as a potential therapeutic target in several cancers including prostate, breast and lung cancers. We previously showed that TCTP is overexpressed in castration-resistant prostate cancer (CRPC), and it has been implicated resistance to treatment. Recently, we developed TCTP antisense oligonucleotides (ASOs) to inhibit TCTP expression...
May 1, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28472366/androgen-receptor-gene-status-in-plasma-dna-associates-with-worse-outcome-on-enzalutamide-or-abiraterone-for-castration-resistant-prostate-cancer-a-multi-institution-correlative-biomarker-study
#20
V Conteduca, D Wetterskog, M T A Sharabiani, E Grande, M P Fernandez-Perez, A Jayaram, S Salvi, D Castellano, A Romanel, C Lolli, V Casadio, G Gurioli, D Amadori, A Font, S Vazquez-Estevez, A González Del Alba, B Mellado, O Fernandez-Calvo, M J Méndez-Vidal, M A Climent, I Duran, E Gallardo, A Rodriguez, C Santander, M I Sáez, J Puente, D Gasi Tandefelt, A Wingate, D Dearnaley, F Demichelis, U De Giorgi, E Gonzalez-Billalabeitia, G Attard
Background: There is an urgent need to identify biomarkers to guide personalized therapy in castration-resistant prostate cancer (CRPC). We aimed to clinically qualify androgen receptor (AR) gene status measurement in plasma DNA using multiplex droplet digital PCR (ddPCR) in pre- and post-chemotherapy CRPC. Methods: We optimized ddPCR assays for AR copy number and mutations and retrospectively analyzed plasma DNA from patients recruited to one of the three biomarker protocols with prospectively collected clinical data...
May 3, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
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