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https://www.readbyqxmd.com/read/28820291/rationale-for-bipolar-androgen-therapy-bat-for-metastatic-prostate-cancer
#1
John T Isaacs, W Nathaniel Brennen, Samuel R Denmeade
No abstract text is available yet for this article.
August 18, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28752333/significance-of-long-chain-polyunsaturated-fatty-acids-in-human-health
#2
REVIEW
Rafael Zárate, Nabil El Jaber-Vazdekis, Noemi Tejera, José A Pérez, Covadonga Rodríguez
In the last decades, the development of new technologies applied to lipidomics has revitalized the analysis of lipid profile alterations and the understanding of the underlying molecular mechanisms of lipid metabolism, together with their involvement in the occurrence of human disease. Of particular interest is the study of omega-3 and omega-6 long chain polyunsaturated fatty acids (LC-PUFAs), notably EPA (eicosapentaenoic acid, 20:5n-3), DHA (docosahexaenoic acid, 22:6n-3), and ARA (arachidonic acid, 20:4n-6), and their transformation into bioactive lipid mediators...
December 2017: Clinical and Translational Medicine
https://www.readbyqxmd.com/read/28573914/treatment-strategies-for-dna-repair-deficient-prostate-cancer
#3
REVIEW
Benjamin A Teply, Emmanuel S Antonarakis
Common recurrent genetic alterations have been identified in prostate cancer through comprehensive sequencing efforts, and the prevalence of mutations in DNA repair pathway genes in patients with advanced and metastatic disease approaches 20-25%. Identification of these underlying DNA repair defects may present unique treatment opportunities for patients, both in terms of standard-of-care treatments and selected investigational agents. Areas covered: We review our current understanding of the genomic landscape of prostate cancer, with special attention to alterations in DNA repair pathway genes in metastatic castration-resistant disease...
August 2017: Expert Review of Clinical Pharmacology
https://www.readbyqxmd.com/read/28377935/gastrointestinal-bleeding-from-metastatic-prostate-adenocarcinoma-to-the-stomach
#4
Andree Koop, Bhaumik Brauhmbhatt, Jason Lewis, Michele D Lewis
We present a rare case of gastrointestinal (GI) bleeding associated with metastatic prostate adenocarcinoma to the stomach. Prostate cancer, which is the most common noncutaneous malignancy among men, rarely spreads to the stomach, with only 7 cases reported in the English literature. Symptoms may include abdominal pain, nausea, vomiting, and GI bleeding. Our patient was treated with epinephrine injection and bipolar cautery, but GI bleeding recurred 7 months later when he had worsening of his thrombocytopenia while using ibuprofen...
2017: ACG Case Reports Journal
https://www.readbyqxmd.com/read/28365160/bipolar-androgen-therapy-a-paradoxical-approach-for-the-treatment-of-castration-resistant-prostate-cancer
#5
EDITORIAL
Michael T Schweizer, Emmanuel S Antonarakis, Samuel R Denmeade
Bipolar androgen therapy (BAT) is a paradoxical treatment for castrate-resistant prostate cancer whereby testosterone levels are rapidly alternated between supraphysiologic and near-castrate concentrations. Initial studies demonstrated that BAT is safe and produces clinical responses. A trial comparing enzalutamide against BAT is ongoing.
March 29, 2017: European Urology
https://www.readbyqxmd.com/read/28334950/downstream-targets-of-gwas-detected-genes-for-breast-lung-and-prostate-and-colon-cancer-converge-to-g1-s-transition-pathway
#6
Olga Y Gorlova, Eugene I Demidenko, Christopher I Amos, Ivan P Gorlov
Genome-wide association studies (GWASs) identified over 500 single nucleotide polymorphisms (SNPs) influencing cancer risk. It is logical to expect the cancer-associated genes to cluster in pathways directly involved in carcinogenesis, e.g. cell cycle. Nevertheless, analyses of the GWAS-detected cancer risk genes usually show no or weak enrichment by known cancer genes.We hypothesized that GWAS-detected cancer risk-associated genes function as upstream regulators of the genes directly involved in carcinogenesis...
April 15, 2017: Human Molecular Genetics
https://www.readbyqxmd.com/read/28246761/-antihormonal-therapy-in-prostate-cancer-side-effects
#7
C H Ohlmann, P Thelen
Androgen deprivation is still standard therapy for prostate cancer, either as primary androgen deprivation therapy or with the use of secondary hormonal drugs including abiraterone and enzalutamide. However, especially the clinically occult side effects like metabolic changes or cardiovascular complications and effects on the psyche of the patient are often not recognized in daily practice. Active monitoring of such side effects is essential for prevention and early intervention. In addition, the efficacy of androgen deprivation therapies is limited by primary and secondary resistance...
February 28, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28230171/impact-of-genetic-variation-on-human-camkk2-regulation-by-ca-2-calmodulin-and-multisite-phosphorylation
#8
Matthew T O'Brien, Jonathan S Oakhill, Naomi X Y Ling, Christopher G Langendorf, Ashfaqul Hoque, Toby A Dite, Anthony R Means, Bruce E Kemp, John W Scott
The Ca(2+)-calmodulin dependent protein kinase kinase-2 (CaMKK2) is a key regulator of neuronal function and whole-body energy metabolism. Elevated CaMKK2 activity is strongly associated with prostate and hepatic cancers, whereas reduced CaMKK2 activity has been linked to schizophrenia and bipolar disease in humans. Here we report the functional effects of nine rare-variant point mutations that were detected in large-scale human genetic studies and cancer tissues, all of which occur close to two regulatory phosphorylation sites and the catalytic site on human CaMKK2...
February 23, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28100850/molecular-characteristic-and-physiological-role-of-dopa-decarboxylase
#9
REVIEW
Joanna Guenter, Robert Lenartowski
The enzyme DOPA decarboxylase (aromatic-L-amino-acid decarboxylase, DDC) plays an important role in the dopaminergic system and participates in the uptake and decarboxylation of amine precursors in the peripheral tissues. Apart from catecholamines, DDC catalyses the biosynthesis of serotonin and trace amines. It has been shown that the DDC amino acid sequence is highly evolutionarily conserved across many species. The activity of holoenzyme is regulated by stimulation/blockade of membrane receptors, phosphorylation of serine residues, and DDC interaction with regulatory proteins...
December 31, 2016: Postȩpy Higieny i Medycyny Doświadczalnej
https://www.readbyqxmd.com/read/27749326/the-role-of-testosterone-in-the-treatment-of-castration-resistant-prostate-cancer
#10
Michael W Drazer, Walter M Stadler
Most men with metastatic prostate cancer who are treated with androgen deprivation therapy will eventually develop castration-resistant disease. In this review, we examine the molecular mechanisms that constitute castration resistance and how these processes may be exploited using testosterone-based therapies. We detail how the utilization of superphysiologic doses of testosterone at regular intervals, followed by a rapid clearance of testosterone through continued chemical castration, also known as bipolar androgen therapy, offers an especially promising therapeutic approach...
September 2016: Cancer Journal
https://www.readbyqxmd.com/read/27544575/prospective-randomized-trial-comparing-titanium-clips-to-bipolar-coagulation-in-sealing-lymphatic-vessels-during-pelvic-lymph-node-dissection-at-the-time-of-robot-assisted-radical-prostatectomy
#11
Pietro Grande, Giovanni Battista Di Pierro, Livio Mordasini, Matteo Ferrari, Christoph Würnschimmel, Hansjörg Danuser, Agostino Mattei
Lymphocele is the most common complication after pelvic lymph node dissection (PLND). Over the years, various techniques have been introduced to prevent lymphocele, but no final conclusion can be drawn regarding the superiority of one technique over another. In this prospective study, 220 patients undergoing robot-assisted radical prostatectomy between 2012 and 2015 were randomized to receive titanium clips (group A, n=110) or bipolar coagulation (group B, n=110) to seal lymphatic vessels at the level of the femoral canal during extended PLND (ePLND)...
February 2017: European Urology
https://www.readbyqxmd.com/read/27473672/growth-inhibition-by-testosterone-in-an-androgen-receptor-splice-variant-driven-prostate-cancer-model
#12
Daisuke Nakata, Kazuhide Nakayama, Tsuneo Masaki, Akira Tanaka, Masami Kusaka, Tatsuya Watanabe
BACKGROUND: Castration resistance creates a significant problem in the treatment of prostate cancer. Constitutively active splice variants of androgen receptor (AR) have emerged as drivers for resistance to androgen deprivation therapy, including the next-generation androgen-AR axis inhibitors abiraterone and enzalutamide. In this study, we describe the characteristics of a novel castration-resistant prostate cancer (CRPC) model, designated JDCaP-hr (hormone refractory). METHODS: JDCaP-hr was established from an androgen-dependent JDCaP xenograft model after surgical castration...
December 2016: Prostate
https://www.readbyqxmd.com/read/27338150/bipolar-androgen-therapy-for-men-with-androgen-ablation-na%C3%A3-ve-prostate-cancer-results-from-the-phase-ii-batman-study
#13
Michael T Schweizer, Hao Wang, Brandon Luber, Rosa Nadal, Avery Spitz, D Marc Rosen, Haiyi Cao, Emmanuel S Antonarakis, Mario A Eisenberger, Michael A Carducci, Channing Paller, Samuel R Denmeade
BACKGROUND: We have previously documented a paradoxical anti-tumor effect when castration-resistant prostate cancer patients were treated with intermittent, high-dose testosterone (i.e., Bipolar Androgen Therapy; BAT). Because, an adaptive increase in androgen receptor expression following chronic androgen deprivation therapy (ADT) may underlie this effect, we tested whether men with hormone-sensitive (HS) prostate cancer (PC) would also respond to BAT if given following a 6-month ADT lead-in...
September 2016: Prostate
https://www.readbyqxmd.com/read/27271795/characterization-of-fibroblast-free-cwr-r1ca-castration-recurrent-prostate-cancer-cell-line
#14
Mojgan Shourideh, Adam DePriest, James L Mohler, Elizabeth M Wilson, Shahriar Koochekpour
BACKGROUND: The previously established CWR-R1 cell line has been used as an in vitro model representing castration-recurrent prostate cancer. Microscopic observation of subconfluent cells demonstrated two distinct cellular morphologies: polygonal closely aggregated epithelial cells surrounded by bipolar fibroblastic cells with long processes. This study sought to establish and characterize a fibroblast-free derivative of the CWR-R1 cell line. METHODS: The CWR-R1ca cell line was established from CWR-R1 cells by removing fibroblasts using multiple cycles of short-term trypsinization, cloning, and pooling single-cell colonies...
September 2016: Prostate
https://www.readbyqxmd.com/read/27166396/testosterone-in-androgen-receptor-signaling-and-dna-repair-enemy-or-frenemy
#15
Melvin Lee Kiang Chua, Robert G Bristow
Androgen suppression mediates transcriptional downregulation of DNA repair genes. Stimulation with supraphysiologic levels of dihydrotestosterone induces formation of lethal DNA breaks through recruitment of topoisomerase II enzymes to fragile DNA sites. Bipolar castration and stimulation that contributes to increasing DNA damage represents a novel strategy of sensitizing prostate cancer to cytotoxic therapies, including radiotherapy. Clin Cancer Res; 22(13); 3124-6. ©2016 AACRSee related article by Hedayati et al...
July 1, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/26954621/phase-i-and-ii-therapies-targeting-the-androgen-receptor-for-the-treatment-of-castration-resistant-prostate-cancer
#16
REVIEW
Athanasios Dellis, Athanasios G Papatsoris
INTRODUCTION: Prostate cancer is the most common cancer in elderly males. Regardless of the initial hormonal treatment in metastatic disease, a significant proportion of patients develop castration resistant prostate cancer (CRPC). A better understanding of the molecular mechanisms behind castration resistance has led to the approval of oral medications such as abiraterone acetate and enzalutamide. Relevant research is accelerated with numerous agents being tested for the management of CRPC...
June 2016: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/26872373/darpp-32-from-neurotransmission-to-cancer
#17
REVIEW
Abbes Belkhiri, Shoumin Zhu, Wael El-Rifai
Dopamine and cAMP-regulated phosphoprotein Mr 32,000 (DARPP-32), also known as phosphoprotein phosphatase-1 regulatory subunit 1B (PPP1R1B), was initially discovered as a substrate of dopamine-activated protein kinase A (PKA) in the neostriatum in the brain. While phosphorylation at Thr-34 by PKA converts DARPP-32 into a potent inhibitor of protein phosphatase 1 (PP1), phosphorylation at Thr-75 transforms DARPP-32 into an inhibitor of PKA. Through regulation of DARPP-32 phosphorylation and modulation of protein phosphatase and kinase activities, DARPP-32 plays a critical role in mediating the biochemical, electrophysiological, and behavioral effects controlled by dopamine and other neurotransmitters in response to drugs of abuse and psychostimulants...
April 5, 2016: Oncotarget
https://www.readbyqxmd.com/read/26793880/-the-mechanisms-of-prostate-cancer-progression-through-androgen-receptor
#18
Yusuke Goto, Shinichi Sakamoto, Tomohiko Ichikawa
Androgen receptor(AR) has a critical role in prostate cancer(PCa) progression and targeting AR axis signaling by androgen deprivation therapy is a standard treatment for advanced PCa. Recently, the role of AR even in castration-resistant PCa(CRPC) is well recognized and emerging evidence suggests survival advantages of treatment by targeting AR in CRPC. This review outlines AR functions that contribute to PCa progression, AR structural alterations and AR activation via intracrine, co-factors, and kinase pathways in CRPC...
January 2016: Nihon Rinsho. Japanese Journal of Clinical Medicine
https://www.readbyqxmd.com/read/26622483/bipolar-button-electrode-plasma-vaporization-of-the-prostate-an-effective-option-for-patients-with-post-brachytherapy-retention
#19
Yiwei Lin, Ben Liu, Liping Xie
Urinary retention is a common urinary complication following brachytherapy for prostate cancer. When conservative therapy has failed, surgical intervention, such as transurethral resection of the prostate (TURP), is performed. In the present case, it was found that conventional bipolar TURP was an inappropriate choice of therapy, since the electrical loop could easily rupture and discharge sparks when encountering the seeds intraoperatively; however, bipolar button-electrode plasma vaporization of the prostate was proven to be a much safer technique...
October 2015: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/26567111/tumor-associated-endo180-requires-stromal-derived-lox-to-promote-metastatic-prostate-cancer-cell-migration-on-human-ecm-surfaces
#20
Matthew P Caley, Helen King, Neel Shah, Kai Wang, Mercedes Rodriguez-Teja, Julian H Gronau, Jonathan Waxman, Justin Sturge
The diverse composition and structure of extracellular matrix (ECM) interfaces encountered by tumor cells at secondary tissue sites can influence metastatic progression. Extensive in vitro and in vivo data has confirmed that metastasizing tumor cells can adopt different migratory modes in response to their microenvironment. Here we present a model that uses human stromal cell-derived matrices to demonstrate that plasticity in tumor cell movement is controlled by the tumor-associated collagen receptor Endo180 (CD280, CLEC13E, KIAA0709, MRC2, TEM9, uPARAP) and the crosslinking of collagen fibers by stromal-derived lysyl oxidase (LOX)...
February 2016: Clinical & Experimental Metastasis
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