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https://www.readbyqxmd.com/read/29930715/leinal-polypeptide-promotes-nk-cells-to-suppress-pca-survival-in-vitro
#1
Qun Rao, Huiping Zhang, Cuantai Zhang, Qianyuan Zhuang, Guanghui Du, Shaogang Wang, Zhangqun Ye, Yuan Chen
As an important component in the innate immune system, natural killer (NK) cells have been demonstrated to be clinically associated with prostate cancer (PCa) progression and castration resistance. Therefore, the development of novel agents that may enhance the cytotoxicity of NK cells possesses promising therapeutic applications. In the present study, leinal polypeptide (LP) solution was supplemented into a co-culture system of NK and PCa cells, as it was previously demonstrated that LP are able to activate NK cells, which kill PCa cells based on an MTT cell viability assay...
July 2018: Oncology Letters
https://www.readbyqxmd.com/read/29925281/alkaline-phosphatase-in-metastatic-castration-resistant-prostate-cancer-reassessment-of-an-older-biomarker
#2
Daniel Heinrich, Øyvind Bruland, Theresa A Guise, Hiroyoshi Suzuki, Oliver Sartor
Since most patients with metastatic castration-resistant prostate cancer (mCRPC) have bone metastases, it is important to understand the potential impact of therapies on prognostic biomarkers, such as ALP. Clinical studies involving mCRPC life-prolonging agents (i.e., sipuleucel-T, abiraterone, enzalutamide, docetaxel, cabazitaxel, and radium-223) have shown that baseline ALP level is prognostic for overall survival, and may be a better prognostic marker for overall survival than prostate-specific antigen in patients with bone-dominant mCRPC...
June 21, 2018: Future Oncology
https://www.readbyqxmd.com/read/29923504/comparison-of-microdosimetry-based-absorbed-doses-to-control-tumours-and-clinically-obtained-tumour-absorbed-doses-in-treatments-with-sup-223-sup-ra
#3
Pablo Minguez Gabina, John C Roeske, Ricardo Mínguez, Alfonso Gomez de Iturriaga, Emilia Rodeño
We performed Monte Carlo simulations in order to determine by means of microdosimetry calculations the average number of hits to the cell nucleus required to reach a tumour control probability (TCP) of 0.9, 〈n<sub>0.9</sub> 〉, for the source geometry of a nucleus embedded in a homogeneous distribution of <sup>223</sup>Ra atoms. From the results obtained and following the MIRD methodology, we determined the values of lesion absorbed doses needed to reach a TCP of 0...
June 20, 2018: Physics in Medicine and Biology
https://www.readbyqxmd.com/read/29921838/patient-derived-organoids-to-model-rare-prostate-cancer-phenotypes
#4
Loredana Puca, Rohan Bareja, Davide Prandi, Reid Shaw, Matteo Benelli, Wouter R Karthaus, Judy Hess, Michael Sigouros, Adam Donoghue, Myriam Kossai, Dong Gao, Joanna Cyrta, Verena Sailer, Aram Vosoughi, Chantal Pauli, Yelena Churakova, Cynthia Cheung, Lesa Dayal Deonarine, Terra J McNary, Rachele Rosati, Scott T Tagawa, David M Nanus, Juan Miguel Mosquera, Charles L Sawyers, Yu Chen, Giorgio Inghirami, Rema A Rao, Carla Grandori, Olivier Elemento, Andrea Sboner, Francesca Demichelis, Mark A Rubin, Himisha Beltran
A major hurdle in the study of rare tumors is a lack of existing preclinical models. Neuroendocrine prostate cancer is an uncommon and aggressive histologic variant of prostate cancer that may arise de novo or as a mechanism of treatment resistance in patients with pre-existing castration-resistant prostate cancer. There are few available models to study neuroendocrine prostate cancer. Here, we report the generation and characterization of tumor organoids derived from needle biopsies of metastatic lesions from four patients...
June 19, 2018: Nature Communications
https://www.readbyqxmd.com/read/29921690/neoadjuvant-intensive-androgen-deprivation-therapy-selects-for-prostate-tumor-foci-with-diverse-subclonal-oncogenic-alterations
#5
Adam G Sowalsky, Huihui Ye, Manoj Bhasin, Eliezer M Van Allen, Massimo Loda, Rosina T Lis, Laleh Montaser-Kouhsari, Carla Calagua, Fen Ma, Joshua W Russo, Rachel J Schaefer, Olga S Voznesensky, Zhenwei Zhang, Glenn J Bubley, Bruce Montgomery, Elahe A Mostaghel, Peter S Nelson, Mary-Ellen Taplin, Steven P Balk
Primary prostate cancer (PCa) can have extensive microheterogeneity, but its contribution to the later emergence of metastatic castration-resistant PCa (mCRPC) remains unclear. In this study, we microdissected residual PCa foci in radical prostatectomies from 18 men treated with neoadjuvant intensive androgen deprivation therapy (leuprolide, abiraterone acetate, and prednisone) and analyzed them for resistance mechanisms. Transcriptome profiling showed reduced but persistent androgen receptor (AR) activity in residual tumors with no increase in neuroendocrine differentiation...
June 19, 2018: Cancer Research
https://www.readbyqxmd.com/read/29914450/concurrent-regulation-of-lkb1-and-camkk2-in-the-activation-of-ampk-in-castrate-resistant-prostate-cancer-by-a-well-defined-polyherbal-mixture-with-anticancer-properties
#6
Amber F MacDonald, Ahmed Bettaieb, Dallas R Donohoe, Dina S Alani, Anna Han, Yi Zhao, Jay Whelan
BACKGROUND: Zyflamend, a blend of herbal extracts, effectively inhibits tumor growth using preclinical models of castrate-resistant prostate cancer mediated in part by 5'-adenosine monophosphate-activated protein kinase (AMPK), a master energy sensor of the cell. Clinically, treatment with Zyflamend and/or metformin (activators of AMPK) had benefits in castrate-resistant prostate cancer patients who no longer responded to treatment. Two predominant upstream kinases are known to activate AMPK: liver kinase B1 (LKB1), a tumor suppressor, and calcium-calmodulin kinase kinase-2 (CaMKK2), a tumor promotor over-expressed in many cancers...
June 18, 2018: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/29914436/treatment-in-the-stampede-era-for-castrate-resistant-prostate-cancer-in-the-uk-ongoing-challenges-and-underappreciated-clinical-problems
#7
Rosa U Greasley, Rebecca Turner, Karen Collins, Janet Brown, Liam Bourke, Derek J Rosario
BACKGROUND: This study aimed to explore the opinions of healthcare professionals regarding the management of men with advanced prostate cancer with particular emphasis on treatment timing and sequencing; treatment adverse-effects and exercise a supportive therapy. METHODS: Semi-structured interviews with a purposively selected group of healthcare professionals involved in prostate cancer care within the NHS, conducted over the phone or face to face. A total of 37 healthcare professionals participated in the interviews including urologists, clinical oncologists, medical oncologists, clinical nurse specialists, general practitioners, physiotherapists, exercise specialists, service managers, clinical commissioners and primary care physicians...
June 19, 2018: BMC Cancer
https://www.readbyqxmd.com/read/29912284/epcr-an-r-package-for-survival-and-time-to-event-prediction-in-advanced-prostate-cancer-applied-to-real-world-patient-cohorts
#8
Teemu D Laajala, Mika Murtojärvi, Arho Virkki, Tero Aittokallio
Motivation: Prognostic models are widely used in clinical decision-making, such as risk stratification and tailoring treatment strategies, with the aim to improve patient outcomes while reducing overall healthcare costs. While prognostic models have been adopted into clinical use, benchmarking their performance has been difficult due to lack of open clinical datasets. The recent DREAM 9.5 Prostate Cancer Challenge carried out an extensive benchmarking of prognostic models for metastatic Castration-Resistant Prostate Cancer (mCRPC), based on multiple cohorts of open clinical trial data...
June 15, 2018: Bioinformatics
https://www.readbyqxmd.com/read/29911685/docetaxel-treatment-in-pten-and-erg-aberrant-metastatic-prostate-cancers
#9
Pasquale Rescigno, David Lorente, David Dolling, Roberta Ferraldeschi, Daniel Nava Rodrigues, Ruth Riisnaes, Susana Miranda, Diletta Bianchini, Zafeiris Zafeiriou, Spyridon Sideris, Ana Ferreira, Ines Figueiredo, Semini Sumanasuriya, Joaquin Mateo, Raquel Perez-Lopez, Adam Sharp, Nina Tunariu, Johann S de Bono
Background: Loss of PTEN is a common genomic aberration in castration-resistant prostate cancer (CRPC) and is frequently concurrent with ERG rearrangements, causing resistance to next-generation hormonal treatment (NGHT) including abiraterone. The relationship between PTEN loss and docetaxel sensitivity remains uncertain. Objective: To study the antitumor activity of docetaxel in metastatic CRPC in relation to PTEN and ERG aberrations. Design setting and participants: Single-centre, retrospective analysis of PTEN loss and ERG expression using a previously described immunohistochemistry (IHC) binary classification system...
May 2018: European urology oncology
https://www.readbyqxmd.com/read/29911070/mechanisms-and-approaches-for-overcoming-enzalutamide-resistance-in-prostate-cancer
#10
REVIEW
Alexandra Vander Ark, Jingchen Cao, Xiaohong Li
Enzalutamide, a second-generation small-molecule inhibitor of the androgen receptor (AR), has been approved for patients who failed with androgen deprivation therapy and have developed castration-resistant prostate cancer. More than 80% of these patients develop bone metastases. The binding of enzalutamide to the AR prevents the nuclear translocation of the receptor, thus inactivating androgen signaling. However, prostate cancer cells eventually develop resistance to enzalutamide treatment. Studies have found resistance both in patients and in laboratory models...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/29909985/structural-alterations-driving-castration-resistant-prostate-cancer-revealed-by-linked-read-genome-sequencing
#11
Srinivas R Viswanathan, Gavin Ha, Andreas M Hoff, Jeremiah A Wala, Jian Carrot-Zhang, Christopher W Whelan, Nicholas J Haradhvala, Samuel S Freeman, Sarah C Reed, Justin Rhoades, Paz Polak, Michelle Cipicchio, Stephanie A Wankowicz, Alicia Wong, Tushar Kamath, Zhenwei Zhang, Gregory J Gydush, Denisse Rotem, J Christopher Love, Gad Getz, Stacey Gabriel, Cheng-Zhong Zhang, Scott M Dehm, Peter S Nelson, Eliezer M Van Allen, Atish D Choudhury, Viktor A Adalsteinsson, Rameen Beroukhim, Mary-Ellen Taplin, Matthew Meyerson
Nearly all prostate cancer deaths are from metastatic castration-resistant prostate cancer (mCRPC), but there have been few whole-genome sequencing (WGS) studies of this disease state. We performed linked-read WGS on 23 mCRPC biopsy specimens and analyzed cell-free DNA sequencing data from 86 patients with mCRPC. In addition to frequent rearrangements affecting known prostate cancer genes, we observed complex rearrangements of the AR locus in most cases. Unexpectedly, these rearrangements include highly recurrent tandem duplications involving an upstream enhancer of AR in 70%-87% of cases compared with <2% of primary prostate cancers...
June 11, 2018: Cell
https://www.readbyqxmd.com/read/29906643/the-efficacy-and-safety-comparison-of-docetaxel-cabazitaxel-estramustine-and-mitoxantrone-for-castration-resistant-prostate-cancer-a-network-meta-analysis
#12
Pan Song, Chuiguo Huang, Yan Wang
AIMS: The aim of this study was to compare the efficacy and safety of docetaxel, cabazitaxel, docetaxel + estramustine, mitoxantrone in the management of castration-resistant prostate cancer (CRPC). METHODS: Electronic databases including PubMed, Cochrance Library and Embase were searched for studies published from when the databases were established to January 1 s t, 2018. Randomized controlled trials (RCTs) that compared docetaxel + prednisone (DP), cabazitaxel + prednisone (CP), docetaxel + estramustine + prednisone (DEP), and mitoxantrone + cabazitaxel prednisone (MP) for CRPC treatment were identified...
June 12, 2018: International Journal of Surgery
https://www.readbyqxmd.com/read/29906450/inactivation-of-cdk12-delineates-a-distinct-immunogenic-class-of-advanced-prostate-cancer
#13
Yi-Mi Wu, Marcin Cieślik, Robert J Lonigro, Pankaj Vats, Melissa A Reimers, Xuhong Cao, Yu Ning, Lisha Wang, Lakshmi P Kunju, Navonil de Sarkar, Elisabeth I Heath, Jonathan Chou, Felix Y Feng, Peter S Nelson, Johann S de Bono, Weiping Zou, Bruce Montgomery, Ajjai Alva, Dan R Robinson, Arul M Chinnaiyan
Using integrative genomic analysis of 360 metastatic castration-resistant prostate cancer (mCRPC) samples, we identified a novel subtype of prostate cancer typified by biallelic loss of CDK12 that is mutually exclusive with tumors driven by DNA repair deficiency, ETS fusions, and SPOP mutations. CDK12 loss is enriched in mCRPC relative to clinically localized disease and characterized by focal tandem duplications (FTDs) that lead to increased gene fusions and marked differential gene expression. FTDs associated with CDK12 loss result in highly recurrent gains at loci of genes involved in the cell cycle and DNA replication...
June 14, 2018: Cell
https://www.readbyqxmd.com/read/29906246/o-glycosylation-mediated-signaling-circuit-drives-metastatic-castration-resistant-prostate-cancer
#14
Sheue-Fen Tzeng, Chin-Hsien Tsai, Tai-Kuang Chao, Yu-Ching Chou, Yu-Chih Yang, Mong-Hsun Tsai, Tai-Lung Cha, Pei-Wen Hsiao
Disseminated castration-resistant prostate cancer (CRPC) is a common disease in men that is characterized by limited survival and resistance to androgen-deprivation therapy. The increase in human epidermal growth factor receptor 2 (HER2) signaling contributes to androgen receptor activity in a subset of patients with CRPC; however, enigmatically, HER2-targeted therapies have demonstrated a lack of efficacy in patients with CRPC. Aberrant glycosylation is a hallmark of cancer and involves key processes that support cancer progression...
June 15, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/29905090/narrative-medicine-in-metastatic-prostate-cancer-reveals-ways-to-improve-patient-awareness-quality-of-care
#15
Giuseppe De Vincentis, Fabio Monari, Sergio Baldari, Matteo Salgarello, Viviana Frantellizzi, Elisabetta Salvi, Luigi Reale, Silvia Napolitano, Giario Conti, Enrico Cortesi
AIM: To describe the journey of patients with metastatic castration-resistant prostate cancer (mCRPC) in treatment with radium-223. METHODS: A multiperspective analysis was performed using narrative medicine in four Italian centers. RESULTS: The substantial impact of mCRPC on quality of life through all phases of the disease was described. After an initial lack of awareness of the disease or denial of its effects, symptoms of pain, fatigue and side effects often led to sadness, fear and loneliness...
June 15, 2018: Future Oncology
https://www.readbyqxmd.com/read/29904891/%C3%AE-viniferin-activates-autophagic-apoptosis-and-cell-death-by-reducing-glucocorticoid-receptor-expression-in-castration-resistant-prostate-cancer-cells
#16
Kejun Cheng, Xi Liu, Lu Chen, Jian-Min Lv, Fa-Jun Qu, Xiu-Wu Pan, Lin Li, Xin-Gang Cui, Yi Gao, Dan-Feng Xu
Prostate cancer (PCa) is one of the most commonly diagnosed urological malignancies. However, there are limited therapies for PCa patients who develop biochemical recurrence after androgen deprivation therapy (ADT). In the present study, we investigated the therapeutic efficacy and mechanism of α-Viniferin (KCV), an oligostilbene of trimeric resveratrol, against human PCa cells and found that it markedly inhibited the proliferation of LNCaP, DU145, and PC-3 cancer cells in a time- and dose-dependent manner, and had a strong cytotoxicity in non-androgen-dependent PCa cells...
June 15, 2018: Medical Oncology
https://www.readbyqxmd.com/read/29904592/prostate-specific-antigen-psa-kinetic-as-a-prognostic-factor-in-metastatic-prostate-cancer-receiving-androgen-deprivation-therapy-systematic-review-and-meta-analysis
#17
Andika Afriansyah, Agus Rizal Ardy Hariandy Hamid, Chaidir Arif Mochtar, Rainy Umbas
Aim: Metastatic prostate cancer (mPCa) has a poor outcome with median survival of two to five years. The use of androgen deprivation therapy (ADT) is a gold standard in management of this stage.  Aim of this study is to analyze the prognostic value of PSA kinetics of patient treated with hormonal therapy related to survival from several published studies Method: Systematic review and meta-analysis was performed using literature searching in the electronic databases of MEDLINE, Science Direct, and Cochrane Library...
2018: F1000Research
https://www.readbyqxmd.com/read/29900882/impact-of-taxanes-on-androgen-receptor-signaling
#18
REVIEW
Shanshan Bai, Bryan Y Zhang, Yan Dong
The development and progression of metastatic castration-resistant prostate cancer is the major challenge in the treatment of advanced prostate cancer. The androgen receptor signaling pathway remains active in metastatic castration-resistant prostate cancer. Docetaxel and cabazitaxel are the first- and second-line chemotherapy, respectively, for patients with metastatic castration-resistant prostate cancer. These two taxanes, in general, function by (i) inhibiting mitosis and inducing apoptosis and (ii) preventing microtubule-dependent cargo trafficking...
June 12, 2018: Asian Journal of Andrology
https://www.readbyqxmd.com/read/29896275/mycophenolate-mofetil-induces-c-jun-n-terminal-kinase-expression-in-22rv1-cells-an-impact-on-androgen-receptor-signaling
#19
Ondrej Zenata, Zdenek Dvorak, Radim Vrzal
Mycophenolate Mofetil (MYC) is a transplant drug used to prevent rejection in heart and kidneys transplant patients. Inosine monophosphate dehydrogenase (IMPDH), an enzyme involved in de novo synthesis of guanosine nucleotides, was considered as a primary target for MYC. Recently, we described that MYC was activates aryl hydrocarbon receptor and it antagonizes glucocorticoid receptor. Here we describe an androgen receptor (AR) as another off-target for MYC. We found that MYC increased basal and dihydrotestosterone (DHT)-inducible AR-dependent luciferase activity in AIZ-AR cells...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29895265/reintroducing-testosterone-in-the-db-db-mouse-partially-restores-normal-glucose-metabolism-and-insulin-resistance-in-a-leptin-independent-manner
#20
Koichi Yabiku, Keiko Nakamoto, Akihiro Tokushige
BACKGROUND: Testosterone signals through the androgen receptor (AR) and AR knockout mice develop obesity, suggesting a functional association between AR and leptin signaling. Furthermore, physiological blood concentrations of testosterone have been found to inhibit the development of arteriosclerosis, obesity and diabetes. However, these findings have not been verified by testosterone replacement in animal models and whether or not testosterone acts directly by activating AR to enhance leptin signaling, or indirectly by its conversion into estrogen remains unclear...
June 13, 2018: BMC Endocrine Disorders
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