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https://www.readbyqxmd.com/read/28527407/mechanisms-of-resistance-to-systemic-therapy-in-metastatic-castration-resistant-prostate-cancer
#1
REVIEW
Giuseppe Galletti, Benjamin I Leach, Linda Lam, Scott T Tagawa
Patients with metastatic castration-resistant prostate cancer (mCPRC) now have an unprecedented number of approved treatment options, including chemotherapies (docetaxel, cabazitaxel), androgen receptor (AR)-targeted therapies (enzalutamide, abiraterone), a radioisotope (radium-223) and a cancer vaccine (sipuleucel-T). However, the optimal treatment sequencing pathway is unknown, and this problem is exacerbated by the issues of primary and acquired resistance. This review focuses on mechanisms of resistance to AR-targeted therapies and taxane-based chemotherapy...
May 8, 2017: Cancer Treatment Reviews
https://www.readbyqxmd.com/read/28526418/prevalence-of-measurable-disease-in-metastatic-castration-resistant-prostate-cancer
#2
Guru Sonpavde, Ankit Madan, Mary K Baker, Jori E May, Gurudatta Naik, Sejong Bae
BACKGROUND: Because of the low historical prevalence of measurable disease in metastatic castration-resistant prostate cancer (mCRPC), phase II trials have used prostate-specific antigen (PSA) and bone scan changes as primary end points. Frequent whole-body imaging and improved computed tomography technology currently identify measurable disease more frequently, warranting consideration of objective response as a major end point. PATIENTS AND METHODS: Data from reported phase III trials of mCRPC were analyzed...
April 26, 2017: Clinical Genitourinary Cancer
https://www.readbyqxmd.com/read/28525684/223ra-dichloride-response-in-a-patient-with-paget-disease-and-bone-metastases-secondary-to-castration-resistant-prostate-cancer
#3
Lina García Cañamaque, Cristina Rioja Parada, Paloma García De la Peña
PURPOSE: Paget disease is commonly asymptomatic and discovered when an imaging test is performed for another clinical indication or when elevated serum alkaline phosphatase is found. Bone pain usually appears late in the disease process and is only present in a minority of patients. For diagnosis, X-ray and bone scan are the most recommended imaging methods; radionuclide imaging of the skeleton has become the standard, since it is the most sensitive test for detecting increased bone activity...
May 18, 2017: Tumori
https://www.readbyqxmd.com/read/28522737/why-targeting-psma-is-a-valuable-addition-in-the-management-of-castration-resistant-prostate-cancer-the-urologists-point-of-view
#4
Boris Hadaschik, Martin Boegemann
No abstract text is available yet for this article.
May 18, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28522124/-prostate-cancer-histoseminar-update-of-the-2016-who-classification%C3%A2-%C3%A2-case-n-o-6-castration-resistant-prostate-cancer-with-partial-neuroendocrin-differenciation
#5
https://www.readbyqxmd.com/read/28521303/emt-circulating-tumor-cells-detected-by-cell-surface-vimentin-are-associated-with-prostate-cancer-progression
#6
Arun Satelli, Izhar Batth, Zachary Brownlee, Abhishek Mitra, Shouhao Zhou, Hyangsoon Noh, Christina R Rojas, Heming Li, Qing H Meng, Shulin Li
Recent advances in the field of circulating tumor cells (CTC) have shown promise in this liquid biopsy-based prognosis of patient outcome. However, not all of the circulating cells are tumor cells, as evidenced by a lack of tumor-specific markers. The current FDA standard for capturing CTCs (CellSearch) relies on an epithelial marker and cells captured via CellSearch cannot be considered to have undergone EMT. Therefore, it is difficult to ascertain the presence and relevance of any mesenchymal or EMT-like CTCs...
May 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28515055/exome-sequencing-of-african-american-prostate-cancer-reveals-loss-of-function-erf-mutations
#7
Franklin W Huang, Juan Miguel Mosquera, Andrea Garofalo, Coyin Oh, Maria Baco, Ali Amin-Mansour, Bokang Rabasha, Samira Bahl, Stephanie A Mullane, Brian D Robinson, Saud Aldubayan, Francesca Khani, Beerinder Karir, Eejung Kim, Jeremy Chimene-Weiss, Matan Hofree, Alessandro Romanel, Joseph R Osborne, Jong Wook Kim, Gissou Azabdaftari, Anna Woloszynska-Read, Karen Sfanos, Angelo M De Marzo, Francesca Demichelis, Stacey Gabriel, Eliezer M Van Allen, Jill Mesirov, Pablo Tamayo, Mark A Rubin, Isaac J Powell, Levi A Garraway
African-American men have the highest incidence and mortality from prostate cancer. Whether a biological basis exists for this disparity remains unclear. Exome sequencing (n=102) and targeted validation (n = 90) of localized primary hormone-naïve prostate cancer in African-American men identified several gene mutations not previously observed in this context, including recurrent loss-of-function mutations in ERF, an ETS transcriptional repressor, in 5% of cases. Analysis of existing prostate cancer cohorts revealed ERF deletions in 3% of primary prostate cancers and mutations or deletions in ERF in 3-5% of lethal castration-resistant prostate cancers...
May 17, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28505901/re-activation-of-notch1-synergizes-with-multiple-pathways-in-promoting%C3%A2-castration-resistant-prostate-cancer
#8
Anthony Atala
No abstract text is available yet for this article.
June 2017: Journal of Urology
https://www.readbyqxmd.com/read/28502694/phase-ii-trial-of-the-pi3-kinase-inhibitor-buparlisib-bkm-120-with-or-without-enzalutamide-in-men-with-metastatic-castration-resistant-prostate-cancer
#9
Andrew J Armstrong, Susan Halabi, Patrick Healy, Joshi J Alumkal, Carolyn Winters, Julie Kephart, Rhonda L Bitting, Carey Hobbs, Colleen F Soleau, Tomasz M Beer, Rachel Slottke, Kelly Mundy, Evan Y Yu, Daniel J George
BACKGROUND: Phosphatidylinositol-3-kinase (PI3K) and androgen receptor pathway activation is common in metastatic castration resistant prostate cancer (mCRPC). Buparlisib is an oral, pan-class I PI3 kinase inhibitor. METHODS: This was a multisite single arm phase II trial of buparlisib 100 mg ± enzalutamide daily in men with mCRPC whose disease progressed on or who were not candidates for docetaxel. The primary end-point was the rate of radiographic/clinical progression-free survival (PFS) at 6 months...
May 11, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28501574/androgen-production-in-pediatric-adrenocortical-tumors-may-occur-via-both-the-classic-and-or-the-alternative-backdoor-pathway
#10
Nesa Marti, Jana Malikova, José A Galván, Maude Aebischer, Marco Janner, Zdenek Sumnik, Barbora Obermannova, Genevieve Escher, Aurel Perren, Christa E Flück
Children with adrenocortical tumors (ACTs) often present with virilization due to high tumoral androgen production, with dihydrotestosterone (DHT) as most potent androgen. Recent work revealed two pathways for DHT biosynthesis, the classic and the backdoor pathway. Usage of alternate routes for DHT production has been reported in castration-resistant prostate cancer, CAH and PCOS. To assess whether the backdoor pathway may contribute to the virilization of pediatric ACTs, we investigated seven children suffering from androgen producing tumors using steroid profiling and immunohistochemical expression studies...
May 10, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/28498618/phase-i-clinical-trial-of-cell-division-associated-1-cdca1-peptide-vaccination-for-castration-resistant-prostate-cancer
#11
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
#12
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
#13
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/28493842/mesenchymal-stem-cell-infiltration-during-neoplastic-transformation-of-the-human-prostate
#14
W Nathaniel Brennen, Baohui Zhang, Ibrahim Kulac, L Nelleke Kisteman, Lizamma Antony, Hao Wang, Alan K Meeker, Angelo M De Marzo, Isla P Garraway, Samuel R Denmeade, John T Isaacs
Mesenchymal Stem Cells (MSCs) have been identified in prostate cancer, raising the critical question of their physical and temporal source. Therefore, MSCs were quantified and characterized in benign and malignant prostate tissue representing different disease states and a wide range of age groups from fetal development through adult death using analytical and functional methodologies. In contrast to lineage-restricted Mesenchymal Progenitor Cells (MPCs) found in normal prostate tissue, MSCs with tri-lineage differentiation potential (adipogenesis, osteogenesis, and chondrogenesis) are identified in prostate tissue from a subset of men with prostate cancer, consistent with an influx of more stem-like progenitors (i...
April 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28490267/darolutamide-odm-201-for-the-treatment-of-prostate-cancer
#15
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...
May 11, 2017: Expert Opinion on Pharmacotherapy
https://www.readbyqxmd.com/read/28490047/development-and-validation-of-an-lc-ms-ms-method-for-the-simultaneous-quantification-of-abiraterone-enzalutamide-and-their-major-metabolites-in-human-plasma
#16
Merel van Nuland, M J X Hillebrand, H Rosing, J H M Schellens, J H Beijnen
BACKGROUND: Abiraterone acetate and enzalutamide are 2 novel drugs for the treatment of metastatic castration-resistant prostate cancer. The metabolism of these drugs is extensive. Major metabolites are N-desmethyl enzalutamide, enzalutamide carboxylic acid, abiraterone N-oxide sulfate, and abiraterone sulfate; of which N-desmethyl enzalutamide is reported to possess antiandrogen capacities. A liquid chromatography-tandem mass spectrometry method for simultaneous quantification of abiraterone, enzalutamide, and the main metabolites has been developed and validated to support therapeutic drug monitoring...
June 2017: Therapeutic Drug Monitoring
https://www.readbyqxmd.com/read/28488360/cabazitaxel-in-patients-with-metastatic-castration-resistant-prostate-cancer-safety-and-quality-of-life-data-from-the-australian-early-access-program
#17
Phillip Parente, Siobhan Ng, Francis Parnis, Alex Guminski, Howard Gurney
AIM: Cabazitaxel is a next generation taxane that has been shown to improve overall survival in patients with metastatic castration-resistant prostate cancer (mCRPC) whose disease progressed during or after docetaxel-based therapy. A worldwide early access program (EAP) study was established to provide access to cabazitaxel ahead of commercial availability and to evaluate its safety and tolerability. The Australian EAP included patient-reported outcomes to evaluate the impact of cabazitaxel on quality of life (QoL)...
May 10, 2017: Asia-Pacific Journal of Clinical Oncology
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
#18
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
#19
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
#20
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
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