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https://www.readbyqxmd.com/read/28644302/the-role-of-bone-targeted-therapies-for-prostate-cancer-in-2017
#1
Samer L Traboulsi, Fred Saad
PURPOSE OF REVIEW: Bone-targeted agents (BTAs), such as zoledronic acid and denosumab, delay the occurrence of skeletal-related events (SREs) in metastatic prostate cancer (PCa) patients. Recently, several agents, such as abiraterone acetate, enzalutamide and radium-223, were approved for the treatment of metastatic castration-resistant PCa (mCRPC). These agents resulted in improved overall survival (OS), pain control and had positive effects on bone health. Combining BTAs to the newly approved agents demonstrates additional benefits that warrant a review of available evidence looking at appropriate combination therapies and timing of BTAs for optimizing the management of advanced and metastatic PCa...
July 20, 2017: Current Opinion in Supportive and Palliative Care
https://www.readbyqxmd.com/read/28642484/mir-100-5p-inhibition-induces-apoptosis-in-dormant-prostate-cancer-cells-and-prevents-the-emergence-of-castration-resistant-prostate-cancer
#2
Noushin Nabavi, Nur Ridzwan Nur Saidy, Erik Venalainen, Anne Haegert, Abhijit Parolia, Hui Xue, Yuwei Wang, Rebecca Wu, Xin Dong, Colin Collins, Francesco Crea, Yuzhuo Wang
Carcinoma of the prostate is the most common cancer in men. Treatment of aggressive prostate cancer involves a regiment of radical prostectomy, radiation therapy, chemotherapy and hormonal therapy. Despite significant improvements in the last decade, the treatment of prostate cancer remains unsatisfactory, because a significant fraction of prostate cancers develop resistance to multiple treatments and become incurable. This prompts an urgent need to investigate the molecular mechanisms underlying the evolution of therapy-induced resistance of prostate cancer either in the form of castration-resistant prostate cancer (CRPC) or transdifferentiated neuroendocrine prostate cancer (NEPC)...
June 22, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28641939/low-molecular-weight-protein-tyrosine-phosphatase-expression-as-a-prognostic-factor-for-men-with-metastatic-hormone-na%C3%A3-ve-prostate-cancer
#3
Mari Ohtaka, Yasuhide Miyoshi, Takashi Kawahara, Shinji Ohtake, Masato Yasui, Koichi Uemura, Shuko Yoneyama, Yusuke Hattori, Jun-Ichi Teranishi, Yumiko Yokomizo, Hiroji Uemura, Hiroshi Miyamoto, Masahiro Yao
OBJECTIVES: Recent studies have demonstrated that up-front docetaxel combined with androgen deprivation therapy (ADT) prolongs survival in some patients with metastatic hormone-naïve prostate cancer (mHNPC). However, new biomarkers for selecting personalized treatment strategies for mHNPC are warranted. We evaluated the value of low-molecular-weight protein tyrosine phosphatase (LMW-PTP) expression as a prognosticator in men with mHNPC. METHODS AND MATERIALS: A total of 48 men with mHNPC diagnosed from 2003 to 2009 were enrolled in this study...
June 19, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28641312/impact-of-novel-mir-145-3p-regulatory-networks-on-survival-in-patients-with-castration-resistant-prostate-cancer
#4
Yusuke Goto, Akira Kurozumi, Takayuki Arai, Nijiro Nohata, Satoko Kojima, Atsushi Okato, Mayuko Kato, Kazuto Yamazaki, Yasuo Ishida, Yukio Naya, Tomohiko Ichikawa, Naohiko Seki
BACKGROUND: Despite recent advancements, metastatic castration-resistant prostate cancer (CRPC) is not considered curative. Novel approaches for identification of therapeutic targets of CRPC are needed. METHODS: Next-generation sequencing revealed 945-1248 miRNAs from each lethal mCRPC sample. We constructed miRNA expression signatures of CRPC by comparing the expression of miRNAs between CRPC and normal prostate tissue or hormone-sensitive prostate cancer (HSPC)...
June 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28639950/reactive-oxygen-species-generation-and-increase-in-mitochondrial-copy-number-new-insight-into-the-potential-mechanism-of-cytotoxicity-induced-by-aurora-kinase-inhibitor-azd1152-hqpa
#5
Ali Zekri, Yashar Mesbahi, Samad Ghanizadeh-Vesali, Kamran Alimoghaddam, Ardeshir Ghavamzadeh, Seyed H Ghaffari
Aurora-B kinase overexpression plays important roles in the malignant progression of prostate cancer (PCa). AZD1152-HQPA, as an inhibitor of Aurora-B, has recently emerged as a promising agent for cancer treatment. In this study, we aimed to investigate the effects of AZD1152-HQPA on reactive oxygen species (ROS) generation and mitochondrial function in PCa. We used AZD1152-HQPA (Barasertib), a highly potent and selective inhibitor of Aurora-B kinase. The effects of AZD1152-HQPA on cell viability, DNA content, cell morphology, and ROS production were studied in the androgen-independent PC-3 PCa cell line...
June 21, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/28639228/role-of-20-hydroxyeicosatetraenoic-acid-20-hete-in-androgen-mediated-cell-viability-in-prostate-cancer-cells
#6
Cecilia Colombero, Daniela Papademetrio, Paula Sacca, Eduardo Mormandi, Elida Alvarez, Susana Nowicki
20-Hydroxyeicosatetraenoic acid (20-HETE) is generated intracellularly through the ω-hydroxylation of arachidonic acid by the cytochrome P450 (in humans, CYP4A11 and CYP4F2). 20-HETE induces mitogenic responses in different cancer cells. The aim of this study was to analyze how 20-HETE impacts cell survival, proliferation, and apoptosis in prostate cancer cells. Incubation of the human androgen-sensitive cells (LNCaP) with 1-10 μM HET0016 (a selective inhibitor of 20-HETE synthesis) reduced cell viability by 49*-64%* (*p < 0...
June 21, 2017: Hormones & Cancer
https://www.readbyqxmd.com/read/28638477/triptolide-inhibits-the-ar-signaling-pathway-to-suppress-the-proliferation-of-enzalutamide-resistant-prostate-cancer-cells
#7
Yangyang Han, Weiwei Huang, Jiakuan Liu, Dandan Liu, Yangyan Cui, Ruimin Huang, Jun Yan, Ming Lei
Enzalutamide is a second-generation androgen receptor (AR) antagonist for the treatment of metastatic castration-resistant prostate cancer (mCRPC). Unfortunately, AR dysfunction means that resistance to enzalutamide will eventually develop. Thus, novel agents are urgently needed to treat this devastating disease. Triptolide (TPL), a key active compound extracted from the Chinese herb Thunder God Vine (Tripterygium wilfordii Hook F.), possesses anti-cancer activity in human prostate cancer cells. However, the effects of TPL against CRPC cells and the underlying mechanism of any such effect are unknown...
2017: Theranostics
https://www.readbyqxmd.com/read/28638277/titanium-dioxide-nanoparticles-as-radiosensitisers-an-in-vitro-and-phantom-based-study
#8
Esho Qasho Youkhana, Bryce Feltis, Anton Blencowe, Moshi Geso
Objective: Radiosensitisation caused by titanium dioxide nanoparticles (TiO2-NPs) is investigated using phantoms (PRESAGE(®) dosimeters) and in vitro using two types of cell lines, cultured human keratinocyte (HaCaT) and prostate cancer (DU145) cells. Methods: Anatase TiO2-NPs were synthesised, characterised and functionalised to allow dispersion in culture-medium for in vitro studies and halocarbons (PRESAGE(®) chemical compositions). PRESAGE(®) dosimeters were scanned with spectrophotometer to determine the radiation dose enhancement...
2017: International Journal of Medical Sciences
https://www.readbyqxmd.com/read/28636142/clinical-development-of-immunotherapy-for-prostate-cancer
#9
REVIEW
Masanori Noguchi, Noriko Koga, Tsukasa Igawa, Kyogo Itoh
Prostate cancer is the most common cancer in men, and the second leading cause of cancer-related death in Western countries. Prostate cancer-related death occurs in patients with metastatic castration-resistant prostate cancer. Although several new drugs for castration-resistant prostate cancer have been approved, each of these has prolonged survival by just a few months. Consequently, new therapies are sorely needed. Recently, it has been recognized that immunotherapy is an effective treatment for prostate cancer patients...
June 21, 2017: International Journal of Urology: Official Journal of the Japanese Urological Association
https://www.readbyqxmd.com/read/28632486/randomized-noncomparative-phase-ii-trial-of-early-switch-from-docetaxel-to-cabazitaxel-or-vice-versa-with-integrated-biomarker-analysis-in-men-with-chemotherapy-na%C3%A3-ve-metastatic-castration-resistant-prostate-cancer
#10
Emmanuel S Antonarakis, Scott T Tagawa, Giuseppe Galletti, Daniel Worroll, Karla Ballman, Marie Vanhuyse, Guru Sonpavde, Scott North, Costantine Albany, Che-Kai Tsao, John Stewart, Atef Zaher, Ted Szatrowski, Wei Zhou, Ada Gjyrezi, Shinsuke Tasaki, Luigi Portella, Yang Bai, Timothy B Lannin, Shalu Suri, Conor N Gruber, Erica D Pratt, Brian J Kirby, Mario A Eisenberger, David M Nanus, Fred Saad, Paraskevi Giannakakou
Purpose The TAXYNERGY trial ( ClinicalTrials.gov identifier: NCT01718353) evaluated clinical benefit from early taxane switch and circulating tumor cell (CTC) biomarkers to interrogate mechanisms of sensitivity or resistance to taxanes in men with chemotherapy-naïve, metastatic, castration-resistant prostate cancer. Patients and Methods Patients were randomly assigned 2:1 to docetaxel or cabazitaxel. Men who did not achieve ≥ 30% prostate-specific antigen (PSA) decline by cycle 4 (C4) switched taxane. The primary clinical endpoint was confirmed ≥ 50% PSA decline versus historical control (TAX327)...
June 20, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28631600/inhibition-of-carbonic-anhydrase-ix-by-ureidosulfonamide-inhibitor-u104-reduces-prostate-cancer-cell-growth-but-does-not-modulate-daunorubicin-or-cisplatin-cytotoxicity
#11
Anne Riemann, Antje Güttler, Verena Haupt, Henri Wichmann, Sarah Reime, Matthias Bache, Dirk Vordermark, Oliver Thews
Carbonic anhydrase IX has emerged as a promising target for cancer therapy. It is highly up-regulated in hypoxic regions and mediates pH regulation critical for tumor cell survival as well as extracellular acidification of the tumor microenvironment which promotes tumor aggressiveness via various mechanisms, such as augmenting metastatic potential. Therefore, the aim of this study was to analyze the complex interdependency between CA IX and the tumor microenvironment in prostate tumor cells in concern of potential therapeutic implications...
June 19, 2017: Oncology Research
https://www.readbyqxmd.com/read/28631332/inhibition-of-microrna-500-has-anti-cancer-effect-through-its-conditional-downstream-target-of-tfpi-in-human-prostate-cancer
#12
Bing Cai, Wei Chen, Yue Pan, Hongde Chen, Yirong Zhang, Zhiliang Weng, Yeping Li
PURPOSE: We investigated the prognostic potential and regulatory mechanism of microRNA-500 (miR-500), and human gene of tissue factor pathway inhibitor (TFPI) in prostate cancer. METHODS: MiR-500 expression was assessed by qRT-PCR in prostate cancer cell lines and primary tumors. Cancer patients' clinicopathological factors and overall survival were analyzed according to endogenous miR-500 level. MiR-500 was downregulated in DU145 and VCaP cells. Its effect on prostate cancer proliferation, invasion in vitro, and tumorigenicity in vivo, were probed...
June 20, 2017: Prostate
https://www.readbyqxmd.com/read/28630216/fractionated-dosing-improves-preclinical-therapeutic-index-of-pyrrolobenzodiazepine-containing-antibody-drug-conjugates
#13
Mary Jane Hinrichs, Pauline M Ryan, Bo Zheng, Shameen Afif-Rider, Xiang-Qing Yu, Michele Gunsior, Haihong Zhong, Jay Harper, Binyam Bezabeh, Kapil Vashisht, Marlon Rebelatto, Molly Reed, Patricia C Ryan, Shannon Breen, Neki Patel, Cui Chen, Luke A Masterson, Arnaud Tiberghien, Philip W Howard, Nazzareno Dimasi, Rakesh Dixit
                Purpose:  To use preclinical models to identify a dosing schedule that improves tolerability of highly potent pyrrolobenzodiazepine dimers (PBD) antibody drug conjugates (ADCs) without compromising anti-tumor activity.  <p>                Experimental design:   A series of dose-fractionation studies were conducted to investigate the pharmacokinetic drivers of safety and efficacy of PBD ADCs in animal models.  The exposure-activity relationship was investigated in mouse xenograft models of human prostate cancer, breast and gastric cancer by comparing anti-tumor activity after single and fractionated dosing with tumor-targeting ADCs conjugated to SG3249, a potent PBD dimer...
June 19, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28629213/la-sopravvivenza-dei-pazienti-oncologici-in-italia
#14
Vincenzo Coviello, Carlotta Buzzoni, Mario Fusco, Alessandro Barchielli, Francesco Cuccaro, Roberta De Angelis, Adriano Giacomin, Stefano Luminari, Giorgia Randi, Lucia Mangone
OBJECTIVES: Population-based survival statistics are fundamental to assess the efficacy of services offered to improve cancer patients' prognosis. This study aims to update cancer survival estimates for the Italian population, as well as provide new measures, such as the crude probability of death, which takes into account the possibility of dying from causes other than cancer, and the change in life expectancy after a cancer diagnosis, to properly address various questions. RESULTS: The study includes 1,932,450 cancer cases detected by the Network of Italian Cancer Registries (AIRTUM) from 1994 to 2011 and provides estimates for 38 cancer sites and for allsites cancer...
March 2017: Epidemiologia e Prevenzione
https://www.readbyqxmd.com/read/28628624/heterogeneity-of-mirna-expression-in-localized-prostate-cancer-with-clinicopathological-correlations
#15
Ahmed Hussein Zedan, Søren Garm Blavnsfeldt, Torben Frøstrup Hansen, Boye Schnack Nielsen, Niels Marcussen, Mindaugas Pleckaitis, Palle Jörn Sloth Osther, Flemming Brandt Sørensen
INTRODUCTION: In the last decade microRNAs (miRNAs) have been widely investigated in prostate cancer (PCa) and have shown to be promising biomarkers in diagnostic, prognostic and predictive settings. However, tumor heterogeneity may influence miRNA expression. The aims of this study were to assess the impact of tumor heterogeneity, as demonstrated by a panel of selected miRNAs in PCa, and to correlate miRNA expression with risk profile and patient outcome. MATERIAL AND METHODS: Prostatectomy specimens and matched, preoperative needle biopsies from a retrospective cohort of 49 patients, who underwent curatively intended surgery for localized PCa, were investigated with a panel of 6 miRNAs (miRNA-21, miRNA-34a, miRNA-125b, miRNA-126, miRNA-143, and miRNA-145) using tissue micro-array (TMA) and in situ hybridization (ISH)...
2017: PloS One
https://www.readbyqxmd.com/read/28627814/prognostic-role-of-circulating-soluble-upar-in-various-cancers-a-systematic-review-and-meta-analysis
#16
REVIEW
K L Liu, J H Fan, Jing Wu
BACKGROUND: Soluble uPAR (suPAR) is a soluble fraction of uPAR which is an important cell surface receptor. Recent evidence suggests that circulating suPAR levels are elevated in multiple malignancies and associated with prognosis of patients, although the results are not consistent. This study aimed to analyze the effect of suPAR on the prognosis in various carcinomas through a systematic review and meta-analysis. METHODS: Eligible studies were searched in PubMed and EMBASE...
May 1, 2017: Clinical Laboratory
https://www.readbyqxmd.com/read/28625507/contemporary-patterns-of-care-and-outcomes-of-men-found-to-have-lymph-node-metastases-at-the-time-of-radical-prostatectomy
#17
Piotr Zareba, James Eastham, Peter T Scardino, Karim Touijer
PURPOSE: A thorough understanding of the natural history and consensus regarding the optimal management of pathologic lymph node-positive (pN1) prostate cancer are lacking. Our objective was to describe patterns of care and outcomes of a contemporary cohort of men with pN1 prostate cancer. MATERIALS AND METHODS: The National Cancer Data Base (NCDB) was used to identify 7,791 men who were found to have LN metastases at the time of radical prostatectomy (RP). Multinomial logistic regression and Cox proportional hazards regression were used to identify patient, tumor and facility characteristics associated with choice of post-RP management strategy and overall survival (OS), respectively...
June 15, 2017: Journal of Urology
https://www.readbyqxmd.com/read/28624848/-177-lu-psma-617-radioligand-therapy-and-outcome-in-patients-with-metastasized-castration-resistant-prostate-cancer
#18
Axel Bräuer, Lena Sophie Grubert, Wolfgang Roll, Andres Jan Schrader, Michael Schäfers, Martin Bögemann, Kambiz Rahbar
PURPOSE: Radioligand therapies targeting prostate-specific membrane antigen (PSMA) have been established for the treatment of metastasized castration-resistant prostate cancer (mCRPC) in the last decade and show promising response rates and a favourable toxicity profile. The aim of this study was to evaluate the overall survival (OS) and to identify parameters predicting outcome in mCRPC patients treated with (177)Lu-PSMA-617. METHODS: Between December 2014 and January 2017, 59 consecutive patients (median age 72 years; interquartile range, (IQR, 66-76 years) with mCRPC, who had been treated with at least one next-generation antihormonal drug as well as chemotherapy, were included in this study...
June 17, 2017: European Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/28624527/significantly-altered-expression-of-mir-511-3p-and-its-target-akt3-has-negative-prognostic-value-in-human-prostate-cancer
#19
Fan Zhang, Zhongjun Wu
PURPOSE: In this study, we assessed the expression and functions of microRNA-511-3p (miR-511-3p) in human prostate cancer (CaP). METHODS: Gene expressions of miR-511-3p in CaP cells and human CaP tumors were assessed by qPCR. In VCaP and PC3 cells, miR-511-3p was overexpressed by lentivirus. The functions of miR-511-3p upregulation in regulating in vitro cancer proliferation, migration and in vivo cancer growth were assessed by MTT, transwell and transplantation assays, respectively...
June 14, 2017: Biochimie
https://www.readbyqxmd.com/read/28623636/eleven-year-management-of-prostate-cancer-patients-on-active-surveillance-what-have-we-learned
#20
Cristina Marenghi, Maria Francesca Alvisi, Federica Palorini, Barbara Avuzzi, Fabio Badenchini, Nice Bedini, Lara Bellardita, Davide Biasoni, Davide Bosetti, Alessandra Casale, Mario Catanzaro, Maurizio Colecchia, Letizia De Luca, Simona Donegani, Paola Dordoni, Rodolfo Lanocita, Massimo Maffezzini, Tiziana Magnani, Julia Menichetti, Antonella Messina, Sara Morlino, Biagio Paolini, Tiziana Rancati, Silvia Stagni, Antonio Tesone, Tullio Torelli, Edoardo Tulli Baldoin, Marta Vaiani, Sergio Villa, Silvia Villa, Nadia Zaffaroni, Nicola Nicolai, Roberto Salvioni, Riccardo Valdagni
PURPOSE: To evaluate the outcomes of active surveillance (AS) on patients with low-risk prostate cancer (PCa) and to identify predictors of disease reclassification. METHODS: In 2005, we defined an institutional AS protocol (Sorveglianza Attiva Istituto Nazionale Tumori [SAINT]), and we joined the Prostate Cancer Research International: Active Surveillance (PRIAS) study in 2007. Eligibility criteria included clinical stage ≤T2a, initial prostate-specific antigen (PSA) <10 ng/mL, and Gleason Pattern Score (GPS) ≤3 + 3 (both protocols); ≤25% positive cores with a maximum core length containing cancer ≤50% (SAINT); and ≤2 positive cores and PSA density <0...
June 14, 2017: Tumori
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