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https://www.readbyqxmd.com/read/28819727/abiraterone-acetate-a-review-in-metastatic-castration-resistant-prostrate-cancer
#1
Lesley J Scott
Oral abiraterone acetate (Zytiga(®)) is a selective inhibitor of CYP17 and thereby inhibits androgen biosynthesis, with androgen signalling crucial in the progression from primary to metastatic prostate cancer (PC) and subsequently, in the development of metastatic castration-resistant PC (mCRPC). In large phase 3 trials and in the clinical practice setting, oral abiraterone acetate in combination with prednisone was an effective treatment and had an acceptable, manageable tolerability and safety profile in chemotherapy-naive and docetaxel-experienced men with mCRPC...
August 17, 2017: Drugs
https://www.readbyqxmd.com/read/28819719/activity-of-cabazitaxel-in-patients-with-metastatic-castration-resistant-prostate-cancer-after-treatment-with-single-or-dual-regimens-of-novel-androgen-receptor-targeting-agents
#2
Yukari Bando, Nobuyuki Hinata, Tomoaki Terakawa, Junya Furukawa, Ken-Ichi Harada, Yuzo Nakano, Masato Fujisawa
The purpose of this study was to evaluate the efficacy of cabazitaxel for patients with metastatic castration-resistant prostate cancer (mCRPC) after sequential therapy with docetaxel (DTX) and single or dual regimens of novel androgen receptor-axis-targeted (ARAT) agents. We retrospectively reviewed 84 consecutive patients treated with cabazitaxel at Kobe University Hospital and related hospitals from September 2014 to September 2016. The association of each prognostic parameter with progression-free survival (PFS) was evaluated, including the sequence of therapy...
August 17, 2017: Medical Oncology
https://www.readbyqxmd.com/read/28819028/padi2-mediated-citrullination-promotes-prostate-cancer-progression
#3
Lin Wang, Guanhua Song, Xiang Zhang, Tingting Feng, Jihong Pan, Weiwen Chen, Muyi Yang, Xinnuo Bai, Yu Pang, Jindan Yu, Jinxiang Han, Bo Han
Onset of castration-resistance prostate cancer (CRPC) after long-term androgen-deprivation therapy remains a major obstacle in the treatment of prostate cancer (PCa). The peptidylarginine deiminase PADI2 has been implicated in chronic inflammatory diseases and cancer. Here we show that PADI2 is an androgen-repressed gene and is upregulated in CRPC. PADI2 expression was required for survival and cell cycle progression of PCa cells, and PADI2 promoted proliferation of PCa cells under androgen-deprived or castration conditions in vitro and in vivo...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28819026/therapeutic-targeting-of-the-cbp-p300-bromodomain-blocks%C3%A2-the-growth-of-castration-resistant-prostate-cancer
#4
Lingyan Jin, Jesse Garcia, Emily Chan, Cecile de la Cruz, Ehud Segal, Mark Merchant, Samir Kharbanda, Ryan Raisner, Peter M Haverty, Zora Modrusan, Justin Ly, Edna Choo, Susan Kaufman, Maureen H Beresini, F Anthony Romero, Steven Magnuson, Karen E Gascoigne
Resistance invariably develops to anti-androgen therapies used to treat newly diagnosed prostate cancers, but effective treatments for castration-resistant disease remain elusive. Here we report that the transcriptional co-activator CBP/p300 is required to maintain the growth of castration-resistant prostate cancer. To exploit this vulnerability, we developed a novel small-molecule inhibitor of the CBP/p300 bromodomain that blocks prostate cancer growth in vitro and in vivo. Molecular dissection of the consequences of drug treatment revealed a critical role for CBP/p300 in histone acetylation required for the transcriptional activity of the androgen receptor and its target gene expression...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28819021/phenotypic-heterogeneity-of-circulating-tumor-cells-informs-clinical-decisions-between-ar-signaling-inhibitors-and-taxanes-in-metastatic-prostate-cancer
#5
Howard I Scher, Ryon P Graf, Nicole Schreiber, Brigit McLaughlin, Adam Jendrisak, Yipeng Wang, Jerry Lee, Stephanie Greene, Rachel Krupa, David Lu, Pascal Bamford, Jessica Louw, Lyndsey Dugan, Hebert Alberto Vargas, Martin Fleisher, Mark Landers, Glenn Heller, Ryan V Dittamore
The heterogeneity of an individual patient's tumor has been linked to treatment resistance, but quantitative biomarkers to rapidly and reproducibly evaluate heterogeneity in a clinical setting are currently lacking. Using established tools available in a CAP-accredited and CLIA-certified clinical laboratory, we quantified digital pathology features on 9,225 individual circulating tumor cells (CTCs) from 179 unique metastatic castration-resistant prostate cancer (mCRPC) patients to define phenotypically distinct cell types...
August 17, 2017: Cancer Research
https://www.readbyqxmd.com/read/28818355/ar-v7-in-peripheral-whole-blood-of-patients-with-castration-resistant-prostate-cancer-association-with-treatment-specific-outcome-under-abiraterone-and-enzalutamide
#6
Anna Katharina Seitz, Silvia Thoene, Andreas Bietenbeck, Roman Nawroth, Robert Tauber, Mark Thalgott, Sebastian Schmid, Ramona Secci, Margitta Retz, Jürgen E Gschwend, Jürgen Ruland, Christof Winter, Matthias M Heck
BACKGROUND: It has been demonstrated that androgen receptor splice variant 7 (AR-V7) expression in circulating tumor cells (CTCs) predicts poor treatment response in metastatic castration-resistant prostate cancer (mCRPC) patients treated with abiraterone or enzalutamide. OBJECTIVE: To develop a practical and robust liquid profiling approach for direct quantification of AR-V7 in peripheral whole blood without the need for CTC capture and to determine its potential for predicting treatment response in mCRPC patients...
August 14, 2017: European Urology
https://www.readbyqxmd.com/read/28816284/-predictive-factor-analysis-of-time-to-progression-of-castration-resistant-prostate-cancer-after-androgen-deprivation-therapy
#7
G J Ji, C Huang, G Song, X S Li, Y Song, L Q Zhou
OBJECTIVE: To explore risk factors including prostate-specific antigen (PSA) kinetics for the prediction of castration-resistant prostate cancer (CRPC), and to build a practical model for predicting the progression to CRPC after androgen deprivation therapy (ADT) so as to facilitate clinicians in decision-making for prostate cancer patients receiving ADT. METHODS: A total of 185 patients with prostate cancer who had received ADT as the primary therapy in Department of Urology of Peking University First Hospital from 2003 to 2014 were enrolled retrospectively...
August 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28816267/-nuclear-export-signal-of-androgen-receptor-regulated-of-androgen-receptor-stability-in-prostate-cancer
#8
Y Q Gong, C J Zhang, S M He, X S Li, L Q Zhou, Y L Guo
OBJECTIVE: To investigate the mechanisms of nuclear export signal of androgen receptor (NES(AR)) in the regulation of androgen receptor (AR) protein expression and stability in prostate cancer. METHODS: The green fluorescent protein fusion protein expression vectors pEGFP-AR(1-918aa), pEGFP-NES(AR) (743-817aa), pEGFP-NAR (1-665aa) and pEGFP-NAR-NES(AR), and lysine mutants of NES(AR) pEGFP-NES(AR) K776R, pEGFP-NES(AR) K807R and pEGFP-NES(AR) K776R/K807R, were transiently transfected into prostate cancer cell line PC3...
August 18, 2017: Beijing da Xue Xue Bao. Yi Xue Ban, Journal of Peking University. Health Sciences
https://www.readbyqxmd.com/read/28814708/-a-case-of-pulmonary-tumor-thrombotic-microangiopathy-in-castration-resistant-prostate-cancer
#9
Kodai Hattahara, Akihiro Hamada, Rie Oyama, Kimihiko Masui, Yasumasa Shichiri
A man aged 83 years under treatment with enzalutamide for castration-resistant prostate cancer presented with general malaise and exertional dyspnea. The underlying cause could not be identified by further investigations. On the 5th hospital day, he died due to a sudden exacerbation of dyspnea. The results of an autopsy indicated tumor emboli and stenosis of small pulmonary arteries with the fibrocellular intimal thickening, and therefore our final diagnosis was pulmonary tumor thrombotic microangiopathy.
July 2017: Hinyokika Kiyo. Acta Urologica Japonica
https://www.readbyqxmd.com/read/28814281/impact-of-new-generation-hormone-therapy-on-cognitive-function-in-elderly-patients-treated-for-a-metastatic-prostate-cancer-cog-pro-trial-protocol
#10
Marie Lange, Heidi Laviec, Hélène Castel, Natacha Heutte, Alexandra Leconte, Isabelle Léger, Bénédicte Giffard, Aurélie Capel, Martine Dubois, Bénédicte Clarisse, Elodie Coquan, Frédéric Di Fiore, Sophie Gouérant, Philippe Bartélémy, Laure Pierard, Karim Fizazi, Florence Joly
BACKGROUND: New generation hormone-therapies (NGHT) targeting the androgen signalling pathway are nowadays proposed to elderly patients with metastatic castration-resistant prostate cancer (CRPCa). The impact of these treatments on cognitive function has never been evaluated whereas cognitive impairment may have an impact on the autonomy and the treatment adherence. The aim of this study is to prospectively assess the incidence of cognitive impairment in elderly men after treatment by NGHT for a metastatic CRPCa...
August 16, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28814252/bone-imaging-in-metastatic-castration-resistant-prostate-cancer-where-do-we-stand
#11
Petros Sountoulides, Linda Metaxa
We are witnessing an era of increased clinical interest in metastatic castration-resistant prostate cancer, both in terms of treatment and also in terms of imaging options. This surge in interest is attributed to the recent developments in treatments for metastatic prostate cancer that are able to confer a significant survival advantage. We are therefore anticipating an increase in the number of patients that we will need to treat at this disease stage. Imaging is undoubtedly crucial in monitoring disease response to treatment and progression...
August 16, 2017: Current Radiopharmaceuticals
https://www.readbyqxmd.com/read/28812304/management-of-castration-resistant-taxane-resistant-prostate-cancer
#12
Tomasz M Beer
Metastatic castration-resistant prostate cancer that is progressing despite docetaxel chemotherapy is difficult to treat and often aggressive. If not previously used, modern androgen signaling inhibitors have established clinical activity in this setting. Cabazitaxel and radium-223 have also been shown to extend survival in appropriately selected patients. Carboplatin-containing chemotherapy regimens have not been studied in randomized trials with a survival endpoint, but they have demonstrated activity in phase II trials and are occasionally considered in the post-docetaxel setting...
August 15, 2017: Oncology (Williston Park, NY)
https://www.readbyqxmd.com/read/28811771/predictive-value-of-stathmin-1-and-osteopontin-expression-for-taxan-resistance-in-metastatic-castrate-resistant-prostate-cancer
#13
Asude Aksoy, Gokhan Artas, Omur Gokmen Sevindik
OBJECTIVE: Several pathways are known to be activated during metastasis and treatment of cancer. We investigated the role of osteopontin (OPN) and stathmin-1 (STHMN1) in metastatic castrate-resistant (mCRPC). METHODS: We included 30 patients who received at least 6 cycles of taxane regimen for metastatic mPC in the present study. For this study retrospective data was taken from Firat University, Faculty of Medicine, Medical Oncology Department between 2009 and 2015...
May 2017: Pakistan Journal of Medical Sciences Quarterly
https://www.readbyqxmd.com/read/28811384/loss-of-spdef-and-gain-of-tgfbi-activity-after-androgen-deprivation-therapy-promote-emt-and-bone-metastasis-of-prostate-cancer
#14
Wei-Yu Chen, Yuan-Chin Tsai, Hsiu-Lien Yeh, Florent Suau, Kuo-Ching Jiang, Ai-Ning Shao, Jiaoti Huang, Yen-Nien Liu
Androgen deprivation therapy (ADT) targeting the androgen receptor (AR) is a standard therapeutic regimen for treating prostate cancer. However, most tumors progress to metastatic castration-resistant prostate cancer after ADT. We identified the type 1, 2, and 4 collagen-binding protein transforming growth factor-β (TGFβ)-induced protein (TGFBI) as an important factor in the epithelial-to-mesenchymal transition (EMT) and malignant progression of prostate cancer. In prostate cancer cell lines, AR signaling stimulated the activity of the transcription factor SPDEF, which repressed the expression of TGFBI ADT, AR antagonism, or overexpression of TGFBI inhibited the activity of SPDEF and enhanced the proliferation rates of prostate cancer cells...
August 15, 2017: Science Signaling
https://www.readbyqxmd.com/read/28811363/targeting-ar-variant-coactivator-interactions-to-exploit-prostate-cancer-vulnerabilities
#15
Fiorella Magani, Stephanie O Peacock, Meghan A Rice, Maria J Martinez, Ann M Greene, Pablo S Magani, Rolando Lyles, Jonathan R Weitz, Kerry L Burnstein
Castration-resistant prostate cancer (CRPC) progresses rapidly and is incurable. Constitutively active androgen receptor splice variants (AR-Vs) represent a well-established mechanism of therapeutic resistance and disease progression. These variants lack the AR ligand-binding domain and, as such, are not inhibited by androgen deprivation therapy (ADT), which is the standard systemic approach for advanced PC. Signaling by AR-Vs, including the clinically relevant AR-V7, is augmented by Vav3, an established AR coactivator in CRPC...
August 15, 2017: Molecular Cancer Research: MCR
https://www.readbyqxmd.com/read/28811331/targeting-a-single-alternative-polyadenylation-site-coordinately-blocks-expression-of-androgen-receptor-mrna-splice-variants-in-prostate%C3%A2-cancer
#16
Jamie L Van Etten, Michael Nyquist, Yingming Li, Rendong Yang, Yeung Ho, Rachel M Johnson, Olivia Ondigi, Daniel F Voytas, Christine Henzler, Scott M Dehm
Prostate cancer is the second leading cause of male cancer deaths due to disease progression to castration resistant prostate cancer (CRPC). Androgen receptor (AR) splice variants including AR-V7 function as constitutively active transcription factors in CRPC cells, thereby promoting resistance to AR-targeted therapies. To date, there are no AR variant specific treatments for CRPC. Here we report that the splicing of AR variants AR-V7 as well as AR-V1 and AR-V9 is regulated coordinately by a single polyadenylation signal in AR intron 3...
August 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28809610/phase-iii-study-comparing-a-reduced-dose-of-cabazitaxel-20-mg-m-2-and-the-currently-approved-dose-25-mg-m-2-in-postdocetaxel-patients-with-metastatic-castration-resistant-prostate-cancer-proselica
#17
Mario Eisenberger, Anne-Claire Hardy-Bessard, Choung Soo Kim, Lajos Géczi, Daniel Ford, Loïc Mourey, Joan Carles, Phillip Parente, Albert Font, Gabriel Kacso, Mustapha Chadjaa, Wenping Zhang, John Bernard, Johann de Bono
Purpose Cabazitaxel 25 mg/m(2) (C25) significantly improved overall survival (OS) versus mitoxantrone ( P < .001) in postdocetaxel patients with metastatic castration-resistant prostate cancer (mCRPC) in the phase III TROPIC study. The phase III PROSELICA study ( ClinicalTrials.gov identifier: NCT01308580) assessed the noninferiority of cabazitaxel 20 mg/m(2) (C20) versus C25 in postdocetaxel patients with mCRPC. Methods Patients were stratified by Eastern Cooperative Oncology Group performance status, measurability of disease per Response Evaluation Criteria in Solid Tumors (RECIST), and region, and randomly assigned to receive C20 or C25...
August 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28809609/the-who-what-and-how-of-cabazitaxel-treatment-in-metastatic-castration-resistant-prostate-cancer
#18
Tian Zhang, Andrew J Armstrong
No abstract text is available yet for this article.
August 15, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28808045/fighting-tubulin-targeting-anticancer-drug-toxicity-and-resistance
#19
REVIEW
Roberta Visconti, Domenico Grieco
Tubulin-targeting drugs, like taxanes and vinca alkaloids, are among the most effective anticancer therapeutics used in the clinic today. Specifically, anti-microtubule cancer drugs (AMCDs) have proven to be effective in the treatment of castration-resistant prostate cancer and triple-negative breast cancer. AMCDs, however, have limiting toxicities that include neutropenia and neurotoxicity, and, in addition, tumor cells can become resistant to the drugs after long-term use. Co-targeting mitotic progression/slippage with inhibition of the protein kinases WEE1 and MYT1 that regulate CDK1 kinase activity may improve AMCD efficacy, reducing the acquisition of resistance by the tumor and side effects from the drug and/or its vehicle...
September 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28806246/response-assessment-of-223ra-treatment-should-a-fluorocholine-pet-ct-be-performed
#20
Ana María García Vicente, Ángel Soriano Castrejón, Ruth Alvarez Cabellos, Belén Sanchez Gil, Nicolás Mohedano Mohedano
We present 3 cases of patients with castration-resistant prostate cancer and bone metastases treated with Ra, belonging to our prospective and multicenter ChoPET-Rad study. All patients underwent clinical, hematological, and biochemical monitoring between each Ra administration. Initial and follow-up F-fluorocholine PET/CT and Tc-biphosphonate bone scintigraphy were performed previously and after the third Ra administration. Both techniques correctly established the response to treatment, in agreement to the biochemical response, although differences in the disease expression (concordant and discordant patterns) were found because of the different radiotracer biodistribution and molecular information derived from them...
August 12, 2017: Clinical Nuclear Medicine
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