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https://www.readbyqxmd.com/read/28930697/overexpression-of-muc1-and-genomic-alterations-in-its-network-associate-with-prostate-cancer-progression
#1
Xiaozeng Lin, Yan Gu, Anil Kapoor, Fengxiang Wei, Tariq Aziz, Diane Ojo, Yanzhi Jiang, Michael Bonert, Bobby Shayegan, Huixiang Yang, Khalid Al-Nedawi, Pierre Major, Damu Tang
We investigate the association of MUC1 with castration-resistant prostate cancer (CRPC), bone metastasis, and PC recurrence. MUC1 expression was studied in patient-derived bone metastasis and CRPCs produced by prostate-specific PTEN(-/-) mice and LNCaP xenografts. Elevations in MUC1 expression occur in CRPC. Among nine patients with hormone-naïve bone metastasis, eight express MUC1 in 61% to 100% of PC cells. Utilizing cBioPortal PC genomic data, we organized a training (n=300), testing (n=185), and validation (n=194) cohort...
September 17, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28930600/line-1-as-a-therapeutic-target-for-castration-resistant-prostate-cancer
#2
Nadine Houede, Pier Vincenzo Piazza, Philippe Pourquier
Prostate cancer is the third leading cause of death by cancer in men. Surgery or hormone deprivation usually contains the progression of the local forms of the disease. In metastatic situations, chemotherapy or second generation hormone therapies are used with an overall survival that never exceeds 36 months when tumors become resistant to castration. In the search for new alternatives, clinical trials with various classes of anticancer drugs have been performed, including chemotherapies, targeted therapies with kinase inhibitors, radium-223, or immunotherapies with somehow limited efficacy...
January 1, 2018: Frontiers in Bioscience (Landmark Edition)
https://www.readbyqxmd.com/read/28928853/the-influence-of-prednisone-on-the-efficacy-of-cabazitaxel-in-men-with-metastatic-castration-resistant-prostate-cancer
#3
Carlo Buonerba, Guru Sonpavde, Francesca Vitrone, Davide Bosso, Livio Puglia, Michela Izzo, Simona Iaccarino, Luca Scafuri, Margherita Muratore, Francesca Foschini, Brigitta Mucci, Vincenzo Tortora, Martina Pagliuca, Dario Ribera, Vittorio Riccio, Rocco Morra, Mirta Mosca, Nicola Cesarano, Ileana Di Costanzo, Sabino De Placido, Giuseppe Di Lorenzo
Background: Cabazitaxel is a second-generation taxane that is approved for use with concomitant low dose daily prednisone in metastatic castration resistant prostate cancer (mCRPC) after docetaxel failure. Since the role of daily corticosteroids in improving cabazitaxel efficacy or ameliorating its safety profile has not been adequately investigated so far, we compared outcomes of patients receiving cabazitaxel with or without daily corticosteroids in a retrospective single-Institution cohort of mCRPC patients...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28928839/analysis-of-resistance-associated-gene-expression-in-docetaxel-resistant-prostate-cancer-cells
#4
Sangchul Lee, Kwangtaek Kim, Jin-Nyoung Ho, Hyunjin Jin, Seok-Soo Byun, Eunsik Lee
Docetaxel-based chemotherapy is the standard treatment for metastatic castration-resistant prostate cancer (CRPC). However, a number of patients with metastatic CRPC are refractory to docetaxel or develop docetaxel resistance. The underlying molecular mechanisms of docetaxel resistance remain unclear, which is a significant burden to the management of metastatic prostate cancer. In the present study, the differential gene expression between docetaxel-sensitive (PC3) and docetaxel-resistant (PC3DR2) prostate cancer cells was identified using DNA microarrays, western blot analysis and reverse transcription-quantitative polymerase chain reaction...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928235/testosterone-protects-high-fat-low-carbohydrate-diet-induced-non-alcoholic-fatty-liver-disease-in-castrated-male-rats-mainly-via-modulating-er-stress
#5
Yue Jia, Jennifer Kuang Yee, Christina Wang, Liana Nikolaenko, Maruja Diaz-Arjonilla, Joshua N Cohen, Samuel W French, Peter Y Liu, YanHe Lue, Wai-Nang Paul Lee, Ronald S Swerdloff
We previously showed that testosterone (T) deficiency enhanced high-fat diet (HFD) induced hepatic steatosis in rats that was independent of insulin resistance, and that T replacement reduced hepatic macrovesicular fat accumulation and inflammation. The present report explores the mechanism of T-protective effects on HFD-induced steatohepatitis. Adult male rats were randomized into four treatment groups for 15 weeks (intact rats on regular chow diet or HFD, and castrated rats on HFD with/without T replacement)...
September 19, 2017: American Journal of Physiology. Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28928128/targeting-a-single-alternative-polyadenylation-site-coordinately-blocks-expression-of-androgen-receptor-mrna-splice-variants-in-prostate-cancer
#6
Jamie L Van Etten, Michael Nyquist, Yingming Li, Rendong Yang, Yeung Ho, Rachel 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/28925066/beyond-the-androgen-receptor-ii-new-approaches-to-understanding-and-treating-metastatic-prostate-cancer-report-from-the-2017-coffey-holden-prostate-cancer-academy-meeting
#7
REVIEW
Andrea K Miyahira, Heather H Cheng, Wassim Abida, Leigh Ellis, Lauren C Harshman, Daniel E Spratt, Jonathan W Simons, Kenneth J Pienta, Howard R Soule
INTRODUCTION: The 2017 Coffey-Holden Prostate Cancer Academy (CHPCA) Meeting, "Beyond the Androgen Receptor II: New Approaches to Understanding and Treating Metastatic Prostate Cancer," was held in Carlsbad, California from June 14-17, 2017. METHODS: The CHPCA is an annual scientific conference hosted by the Prostate Cancer Foundation (PCF) that is uniquely designed to produce extensive and constructive discussions on the most urgent and impactful topics concerning research into the biology and treatment of metastatic prostate cancer...
September 18, 2017: Prostate
https://www.readbyqxmd.com/read/28924064/circulating-steroid-hormone-variations-throughout-different-stages-of-prostate-cancer
#8
Gido Snaterse, Jenny A Visser, Wiebke Arlt, Johannes Hofland
Steroid hormones play a central role in the maintenance and progression of prostate cancer. The androgen receptor is the primary driver of tumor cell proliferation and is activated by the androgens testosterone and 5α-dihydrotestosterone. Inhibition of this pathway through medical or surgical castration improves survival in the majority of advanced prostate cancer patients. However, conversion of adrenal androgen precursors and alternative steroidogenic pathways have been found to contribute to tumor progression and resistance to treatment...
September 18, 2017: Endocrine-related Cancer
https://www.readbyqxmd.com/read/28923776/prostate-cancer-xenografts-and-hormone-induced-prostate-carcinogenesis
#9
REVIEW
Dalton T McLean, Douglas W Strand, William A Ricke
Despite the advancement of transgenic and gene knockout animal models in the prostate cancer research, there is still a need for utilizing xenograft models. Xenografts can be grown in multiple sites/organs within immunocompromised animals such as mice and rats. Although prostate xenografts have been derived from many species, human cells and tissues are the most commonly used due to their potential clinical significance. Xenograft models that progress from one state or stage to another are commonly used to address important scientific questions including malignant transformation, metastatic spread, and castration resistance...
September 8, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/28919714/radium-223-dichloride-for-prostate-cancer-treatment
#10
REVIEW
Emmanuel Deshayes, Mathieu Roumiguie, Constance Thibault, Philippe Beuzeboc, Florent Cachin, Christophe Hennequin, Damien Huglo, François Rozet, Diana Kassab-Chahmi, Xavier Rebillard, Nadine Houédé
Prostate cancer is the most common malignant disease in men. Several therapeutic agents have been approved during the last 10 years. Among them, radium-223 dichloride (Xofigo(®)) is a radioactive isotope that induces irreversible DNA double-strand breaks and consequently tumor cell death. Radium-223 dichloride is a calcium-mimetic agent that specifically targets bone lesions. Radium-223 dichloride has been approved for the treatment of metastatic castration-resistant prostate cancer with symptomatic bone metastases, without known visceral metastases...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28918838/inhibition-of-midkine-suppresses-prostate-cancer-cd133-stem-cell-growth-and-migration
#11
Suat Erdogan, Zeynep B Doganlar, Oguzhan Doganlar, Kader Turkekul, Riza Serttas
BACKGROUND: Midkine (MDK) is a tumor-promoting factor that is often overexpressed in various human carcinomas, and the role of MDK has not yet been fully investigated in prostate cancer stem cells. MATERIALS AND METHODS: Prostate cancer CD133(+) stem cells (PCSCs) were isolated from human castration-resistant PC3 cells. PCSCs were treated with different concentrations of MDK inhibitor, iMDK, for 24-72 hours. The IC50 values were determined by the MTT test. Endogenous MDK messenger RNA expression was knocked down by small interfering RNA...
September 2017: American Journal of the Medical Sciences
https://www.readbyqxmd.com/read/28917268/targeting-androgen-independent-pathways-new-chances-for-patients-with-prostate-cancer
#12
REVIEW
C Cattrini, E Zanardi, G Vallome, A Cavo, L Cerbone, A Di Meglio, C Fabbroni, M M Latocca, F Rizzo, C Messina, A Rubagotti, P Barboro, F Boccardo
Androgen deprivation therapy (ADT) is the mainstay treatment for advanced prostate cancer (PC). Most patients eventually progress to a condition known as castration-resistant prostate cancer (CRPC), characterized by lack of response to ADT. Although new androgen receptor signaling (ARS) inhibitors and chemotherapeutic agents have been introduced to overcome resistance to ADT, many patients progress because of primary or acquired resistance to these agents. This comprehensive review aims at exploring the mechanisms of resistance and progression of PC, with specific focus on alterations which lead to the activation of androgen receptor (AR)-independent pathways of survival...
October 2017: Critical Reviews in Oncology/hematology
https://www.readbyqxmd.com/read/28916652/lsd1-mediated-epigenetic-reprogramming-drives-cenpe-expression-and-prostate-cancer-progression
#13
Yi Liang, Musaddeque Ahmed, Haiyang Guo, Fraser Soares, Junjie T Hua, Shuai Gao, Catherine Lu, Christine Poon, Wanting Han, Jens Langstein, Muhammad B Ekram, Brian Li, Elai Davicioni, Mandeep Takhar, Nicholas Erho, R Jeffrey Karnes, Dianne Chadwick, Theodorus van der Kwast, Paul C Boutros, Cheryl H Arrowsmith, Felix Y Feng, Anthony Michael Joshua, Amina Zoubeidi, Changmeng Cai, Housheng H He
Androgen receptor (AR) signaling is a key driver of prostate cancer (PCa), and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant PCa (CRPC). Here we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell cycle genes including CENPE, a centromere binding protein and mitotic kinesin...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28915573/lipid-catabolism-inhibition-sensitizes-prostate-cancer-cells-to-antiandrogen-blockade
#14
Thomas W Flaig, Maren Salzmann-Sullivan, Lih-Jen Su, Zhiyong Zhang, Molishree Joshi, Miguel A Gijón, Jihye Kim, John J Arcaroli, Adrie Van Bokhoven, M Scott Lucia, Francisco G La Rosa, Isabel R Schlaepfer
Prostate cancer (PCa) is the most common malignancy among Western men and the second leading-cause of cancer related deaths. For men who develop metastatic castration resistant PCa (mCRPC), survival is limited, making the identification of novel therapies for mCRPC critical. We have found that deficient lipid oxidation via carnitine palmitoyltransferase (CPT1) results in decreased growth and invasion, underscoring the role of lipid oxidation to fuel PCa growth. Using immunohistochemistry we have found that the CPT1A isoform is abundant in PCa compared to benign tissue (n=39, p<0...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28913790/delivery-of-hsp90-inhibitor-using-water-soluble-polymeric-conjugates-with-high-drug-payload
#15
Jose A Suárez Del Pino, Rohit Kolhatkar
PURPOSE: HSP90 (Heat shock protein 90kD) has been validated as a therapeutic target in Castrate Resistant Prostate Cancer. Unfortunately, HSP90 inhibitors suffer from dose-limiting toxicities that hinder their clinical applications. Previously developed polymeric delivery systems for HSP90 inhibitors had either low drug content or low biological activity suggesting the need for better delivery system for HSP90 inhibitors. METHODS: We developed a simplified synthetic strategy to prepare polyethylene glycol based water-soluble polymeric system for model HSP90 inhibitor geldanamycin (GDM)...
September 14, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28910332/concurrent-treatment-with-simvastatin-and-nf-%C3%AE%C2%BAb-inhibitor-in-human-castration-resistant-prostate-cancer-cells-exerts-synergistic-anti-cancer-effects-via-control-of-the-nf-%C3%AE%C2%BAb-lin28-let-7-mirna-signaling-pathway
#16
Minyong Kang, Kyoung-Hwa Lee, Hye Sun Lee, Chang Wook Jeong, Ja Hyeon Ku, Hyeon Hoe Kim, Cheol Kwak
We examined the anti-cancer effects and molecular mechanism of simvastatin in human castration-resistant prostate cancer (CRPC) cells, particularly focused on LIN28B and its target molecule, let-7 microRNA (miRNA) among the various target genes of NF-κB. A human CRPC cell line (PC3) was used in the current study. Gene expression patterns were evaluated using real time-PCR and western blot analysis. CCK-8 assay was used for assessing cell viability and proliferation, and a clonogenic assay was adopted to evaluate clonal proliferative capabilities...
2017: PloS One
https://www.readbyqxmd.com/read/28906339/multiparametric-magnetic-resonance-imaging-of-prostate-cancer-bone-disease-correlation-with-bone-biopsy-histological-and-molecular-features
#17
Raquel Perez-Lopez, Daniel Nava Rodrigues, Ines Figueiredo, Joaquin Mateo, David J Collins, Dow-Mu Koh, Johann S de Bono, Nina Tunariu
OBJECTIVES: The aim of this study was to correlate magnetic resonance imaging (MRI) of castration-resistant prostate cancer (CRPC) bone metastases with histological and molecular features of bone metastases. MATERIALS AND METHODS: Forty-three bone marrow biopsies from 33 metastatic CRPC (mCRPC) patients with multiparametric MRI and documented bone metastases were evaluated. A second cohort included 10 CRPC patients with no bone metastases. Associations of apparent diffusion coefficient (ADC), normalized b900 diffusion-weighted imaging (nDWI) signal, and signal-weighted fat fraction (swFF) with bone marrow biopsy histological parameters were evaluated using Mann-Whitney U test and Spearman correlations...
September 12, 2017: Investigative Radiology
https://www.readbyqxmd.com/read/28905815/psa-time-to-nadir-as-a-prognostic-factor-of-first-line-docetaxel-treatment-in-castration-resistant-prostate-cancer-evidence-from-patients-in-northwestern-china
#18
Kai-Jie Wu, Xin-Qi Pei, Ge Tian, Da-Peng Wu, Jin-Hai Fan, Yu-Mei Jiang, Da-Lin He
Docetaxel-based chemotherapy remains the first-line treatment for patients with metastatic castration-resistant prostate cancer (mCRPC) in China; however, the prognostic factors associated with effects in these patients are still controversial. In this study, we retrospectively reviewed the data from 71 eligible Chinese patients who received docetaxel chemotherapy from 2009 to 2016 in our hospital and experienced a reduction of prostate-specific antigen (PSA) level ≥50% during the treatment and investigated the potential role of time to nadir (TTN) of PSA...
September 12, 2017: Asian Journal of Andrology
https://www.readbyqxmd.com/read/28903443/radioligand-therapy-of-metastatic-prostate-cancer-using-177-lu-psma-617-after-radiation-exposure-to-223-ra-dichloride
#19
Hojjat Ahmadzadehfar, Stefanie Zimbelmann, Anna Yordanova, Rolf Fimmers, Stefan Kürpig, Elisabeth Eppard, Florian C Gaertner, Xiao Wei, Stefan Hauser, Markus Essler
Radioligand therapy with (177)Lu-PSMA-617 is an innovative and effective therapy for castrate-resistant metastatic prostate cancer patients. For patients with symptomatic bone metastases without visceral metastases, the guidelines recommend radionuclide therapy with (223)Ra-dichloride as a single therapeutic agent or in combination with hormone therapy. The aim of this study was to evaluate the safety of repeated cycles of (177)Lu-PSMA-617 after exposure to more cycles of (223)Ra. Forty-nine patients were treated with three cycles of Lu-PSMA-617 divided into two groups subjected to a history of therapy with (223)Ra...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903426/the-prognostic-implication-of-intraductal-carcinoma-of-the-prostate-in-metastatic-castration-resistant-prostate-cancer-and-its-potential-predictive-value-in-those-treated-with-docetaxel-or-abiraterone-as-first-line-therapy
#20
Jinge Zhao, Pengfei Shen, Guangxi Sun, Ni Chen, Jiandong Liu, Xin Tang, Rui Huang, Diming Cai, Jing Gong, Xingming Zhang, Zhibin Chen, Xiang Li, Qiang Wei, Peng Zhang, Zhenhua Liu, Jiyan Liu, Hao Zeng
Intraductal carcinoma of the prostate (IDC-P) is recognized as a newly pathological entity in 2016 WHO classification. It's role in metastatic castration-resistant prostate cancer (CRPC) remains obscure. We aimed to explore the association of IDC-P with clinical outcome and to further identify its potential predictive role in making first-line treatment decisions for mCRPC. We retrospectively analyzed data of 131 mCRPC patients. IDC-P was diagnosed by re-biopsy at the time of mCRPC. Among total patients, 45 and 41 received abiraterone or docetaxel as first-line therapies, respectively...
August 15, 2017: Oncotarget
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