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https://www.readbyqxmd.com/read/29222530/seizure-rates-in-enzalutamide-treated-men-with-metastatic-castration-resistant-prostate-cancer-and-risk-of-seizure-the-upward-study
#1
Susan Slovin, William Clark, Joan Carles, Andrew Krivoshik, Jung Wook Park, Fong Wang, Daniel George
Importance: The androgen receptor inhibitor enzalutamide prolongs survival in men with metastatic castration-resistant prostate cancer (mCRPC). In controlled clinical studies, 0.5% (10 of 2051) of patients experienced seizure, but patients with a history of or risk factors for seizure were excluded. Men with mCRPC and seizure risk factors have an estimated seizure rate of 2.8 per 100 patient-years without enzalutamide exposure. Objective: To assess seizure incidence in patients with seizure risk factors who were receiving enzalutamide for mCRPC...
December 7, 2017: JAMA Oncology
https://www.readbyqxmd.com/read/29222242/treatment-of-inherited-bone-marrow-failure-syndromes-beyond-transplantation
#2
REVIEW
Rodrigo T Calado, Diego V Clé
Despite significant progress in transplantation by the addition of alternative hematopoietic stem cell sources, many patients with inherited bone marrow failure syndromes are still not eligible for a transplant. In addition, the availability of sequencing panels has significantly improved diagnosis by identifying cryptic inherited cases. Androgens are the main nontransplant therapy for bone marrow failure in dyskeratosis congenita and Fanconi anemia, reaching responses in up to 80% of cases. Danazol and oxymetholone are more commonly used, but virilization and liver toxicity are major adverse events...
December 8, 2017: Hematology—the Education Program of the American Society of Hematology
https://www.readbyqxmd.com/read/29220539/significance-and-mechanism-of-androgen-receptor-ar-overexpression-and-ar-mtor-crosstalk-in-hepatocellular-carcinoma
#3
Hong Zhang, Xiaoxing Li, Yang Yang, Yanjie Zhang, Hui-Yun Wang, X F Steven Zheng
Hepatocellular carcinoma (HCC) is a male-dominant cancer and androgen receptor (AR) has been linked to the pathogenesis of HCC. However, AR expression and its precise role in HCC remain controversial. Moreover, previous anti-androgen and -AR clinical trials in HCC failed to demonstrate clinical benefits. In this study, we found that AR is overexpressed in the nucleus of approximately 37% HCC tumors, which is significantly associated with advanced disease stage and poor survival. AR overexpression in HCC cells markedly alters AR-dependent transcriptome, stimulates oncogenic growth and determines therapeutic response to enzalutamide, a second generation of AR antagonist...
December 8, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29216878/adaptive-phenotype-drives-resistance-to-androgen-deprivation-therapy-in-prostate-cancer
#4
Nicoletta Ferrari, Ilaria Granata, Matteo Capaia, Marina Piccirillo, Mario Rosario Guarracino, Roberta Venè, Antonella Brizzolara, Andrea Petretto, Elvira Inglese, Martina Morini, Simonetta Astigiano, Adriana Agnese Amaro, Francesco Boccardo, Cecilia Balbi, Paola Barboro
BACKGROUND: Prostate cancer (PCa), the second most common cancer affecting men worldwide, shows a broad spectrum of biological and clinical behaviour representing the epiphenomenon of an extreme heterogeneity. Androgen deprivation therapy is the mainstay of treatment for advanced forms but after few years the majority of patients progress to castration-resistant prostate cancer (CRPC), a lethal form that poses considerable therapeutic challenges. METHODS: Western blotting, immunocytochemistry, invasion and reporter assays, and in vivo studies were performed to characterize androgen resistant sublines phenotype in comparison to the parental cell line LNCaP...
December 8, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/29216311/amelioration-of-sexual-behavior-and-motor-activity-deficits-in-a-castrated-rodent-model-with-a-selective-androgen-receptor-modulator-sarm-2f
#5
Megumi Morimoto, Yuichiro Amano, Masahiro Oka, Ayako Harada, Hisashi Fujita, Yukiko Hikichi, Ryuichi Tozawa, Masuo Yamaoka, Takahito Hara
Sarcopenia and cachexia present characteristic features of a decrease in skeletal muscle mass and strength, anorexia, and lack of motivation. Treatments for these diseases have not yet been established, although selective androgen receptor modulators (SARMs) are considered as therapeutic targets. We previously reported that a novel SARM compound, SARM-2f, exhibits anabolic effect on muscles, with less stimulatory effect on prostate weight compared with testosterone, in rat Hershberger assays and cancer cachexia models...
2017: PloS One
https://www.readbyqxmd.com/read/29215767/exposure-to-levonorgestrel-increases-nest-acquisition-success-and-decreases-sperm-motility-in-the-male-fathead-minnow-pimephales-promelas
#6
Tyler Frankel, Lance Yonkos, Franklin Ampy, Jack Frankel
Progestins are utilized as a component of human contraceptives, and enter the environment via wastewater treatment plant effluent. Certain progestins activate fish androgen receptors and cause decreases in fecundity and masculinization of females. In this study, a nest acquisition assay and computer assisted sperm analysis (CASA) was used to examine the effects of levonorgestrel (LNG) on male fathead minnow (Pimephales promelas) reproductive fitness. Males were exposed to 0, 10, or 100ng/L LNG for 14d. Combinations of a control male and a male from one of the treatments were placed into a competitive nesting assay, and time each male spent holding the nest and time spent exhibiting aggressive behaviors were analyzed at 48hrs post-exposure...
December 7, 2017: Environmental Toxicology and Chemistry
https://www.readbyqxmd.com/read/29214797/high-throughput-in-vitro-data-to-inform-prioritization-of-ambient-water-monitoring-and-testing-for-endocrine-active-chemicals
#7
Wendy J Heiger-Bernays, Susanna Wegner, David Dix
The presence of industrial chemicals, consumer product chemicals, and pharmaceuticals is well documented in waters in the US and globally. Most of these chemicals lack health-protective guidelines and many have been shown to have endocrine bioactivity. There is currently no systematic or national prioritization for monitoring waters for chemicals with endocrine disrupting activity. We propose Ambient Water Bioactivity Concentrations (AWBCs) generated from high throughput data as a health-based screen for endocrine bioactivity of chemicals in water...
December 7, 2017: Environmental Science & Technology
https://www.readbyqxmd.com/read/29214142/molecular-mechanisms-of-enzalutamide-resistance-in-prostate-cancer
#8
REVIEW
Zoran Culig
Purpose of Review: Compensatory mechanisms leading to increased androgen receptor expression and activity after androgen ablation or anti-androgen treatment have been identified in prostate cancer. After hydroxyflutamide and bicalutamide were used in therapy of prostate cancer over many years, novel anti-androgen enzalutamide showed improved clinical activity. However, enzalutamide resistance develops over a certain time period, and molecular mechanisms responsible for this process are heterogeneous...
2017: Current Molecular Biology Reports
https://www.readbyqxmd.com/read/29212226/transcribed-ultraconserved-region-uc-63-promotes-resistance-to-docetaxel-through-regulation-of-androgen-receptor-signaling-in-prostate-cancer
#9
Yohei Sekino, Naoya Sakamoto, Keisuke Goto, Ririno Honma, Yoshinori Shigematsu, Kazuhiro Sentani, Naohide Oue, Jun Teishima, Akio Matsubara, Wataru Yasui
Docetaxel is the standard chemotherapy for metastatic castration-resistant prostate cancer (CRPC). However, nearly all patients ultimately become refractory due to the development of docetaxel resistance. The transcribed ultraconserved regions (T-UCRs) are a novel class of non-coding RNAs that are absolutely conserved across species and are involved in carcinogenesis including prostate cancer (PC). In this study, we investigated the transcriptional levels of 26 representative T-UCRs and determined the regions that were differentially expressed in PC...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29212159/lef1-tfe3-and-ar-are-putative-diagnostic-markers-of-solid-pseudopapillary-neoplasms
#10
Eun Kyung Kim, Mi Jang, Minhee Park, Hoguen Kim
The diagnosis of solid pseudopapillary neoplasms (SPNs) is challenging because some SPNs share many similar morphological and immunohistochemical features with other pancreatic neoplasms. In this study, we investigated potential diagnostic markers of SPN. Based on the SPN-specific upregulated genes from a previous DNA microarray and proteome study, we selected six immunohistochemical markers [beta-catenin, androgen receptor (AR), lymphoid enhancer-binding factor 1 (LEF1), transcription factor for immunoglobulin heavy-chain enhancer 3 (TFE3), fused in sarcoma (FUS), and WNT inhibitory factor 1 (WIF-1)]...
November 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/29211901/corrigendum-for-low-dose-dihydrotestosterone-drives-metabolic-dysfunction-via-cytosolic-and-nuclear-hepatic-androgen-receptor-mechanisms
#11
(no author information available yet)
No abstract text is available yet for this article.
December 1, 2017: Endocrinology
https://www.readbyqxmd.com/read/29211833/a-prospective-phase-ii-study-of-combined-androgen-blockade-in-patients-with-androgen-receptor-positive-metastatic-or-locally-advanced-unresectable-salivary-gland-carcinoma
#12
C Fushimi, Y Tada, H Takahashi, T Nagao, H Ojiri, T Masubuchi, T Matsuki, K Miura, D Kawakita, H Hirai, E Hoshino, S Kamata, T Saotome
Background: There is no standard first-line chemotherapy for recurrent/metastatic or unresectable locally advanced salivary gland carcinoma (SGC). Patients and methods: We conducted a single institution, open-label, single arm, phase II trial of combined androgen blockade (CAB) for androgen receptor (AR)-positive SGC. Leuprorelin acetate was administered subcutaneously at a dose of 3.75 mg every 4 weeks. Bicalutamide was administered orally at a daily dose of 80 mg...
December 1, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/29210989/supraphysiologic-testosterone-therapy-in-the-treatment-of-prostate-cancer-models-mechanisms-and-questions
#13
REVIEW
Osama S Mohammad, Michael D Nyquist, Michael T Schweizer, Stephen P Balk, Eva Corey, Stephen Plymate, Peter S Nelson, Elahe A Mostaghel
Since Huggins defined the androgen-sensitive nature of prostate cancer (PCa), suppression of systemic testosterone (T) has remained the most effective initial therapy for advanced disease although progression inevitably occurs. From the inception of clinical efforts to suppress androgen receptor (AR) signaling by reducing AR ligands, it was also recognized that administration of T in men with castration-resistant prostate cancer (CRPC) could result in substantial clinical responses. Data from preclinical models have reproducibly shown biphasic responses to T administration, with proliferation at low androgen concentrations and growth inhibition at supraphysiological T concentrations...
December 6, 2017: Cancers
https://www.readbyqxmd.com/read/29210800/molecular-modifiers-of-hormone-receptor-action-decreased-androgen-receptor-expression-in-mismatch-repair-deficient-endometrial-endometrioid-adenocarcinoma
#14
Qiong Gan, Suzanne Crumley, Russell R Broaddus
Endometrial endometrioid carcinoma is related to estrogen excess and expression of estrogen and progesterone receptors. Epidemiological evidence suggests that exposure to elevated androgens, as in polycystic ovarian syndrome, increases the risk of endometrial cancer. Factors impacting androgen receptor (AR) expression are not well studied. Mismatch repair (MMR) deficiency due to MLH1 gene methylation is one of the most common molecular alterations in endometrial cancer, occurring in 15% to 20% of cases. MLH1 methylation can be associated with decreased expression of other genes, so we examined the effect of MMR status on AR expression...
November 28, 2017: International Journal of Gynecological Pathology
https://www.readbyqxmd.com/read/29209770/androgen-and-estrogen-sensitivity-of-bird-song-a-comparative-view-on-gene-regulatory-levels
#15
REVIEW
Carolina Frankl-Vilches, Manfred Gahr
Singing of songbirds is sensitive to testosterone and its androgenic and estrogenic metabolites in a species-specific way. The hormonal effects on song pattern are likely mediated by androgen receptors (AR) and estrogen receptor alpha (ERα), ligand activated transcription factors that are expressed in neurons of various areas of the songbirds' vocal control circuit. The distribution of AR in this circuit is rather similar between species while that of ERα is species variant and concerns a key vocal control area, the HVC (proper name)...
December 6, 2017: Journal of Comparative Physiology. A, Neuroethology, Sensory, Neural, and Behavioral Physiology
https://www.readbyqxmd.com/read/29209210/critical-role-of-hepatic-cyp450s-in-the-testis-specific-toxicity-of-5r-5-hydroxytriptolide-in-c57bl-6-mice
#16
Cunzhi Yu, Yu Li, Mingxia Liu, Man Gao, Chenggang Li, Hong Yan, Chunzhu Li, Lihan Sun, Liying Mo, Chunyong Wu, Xinming Qi, Jin Ren
Low solubility, tissue accumulation, and toxicity are chief obstacles to developing triptolide derivatives, so a better understanding of the pharmacokinetics and toxicity of triptolide derivatives will help with these limitations. To address this, we studied pharmacokinetics and toxicity of (5R)-5-hydroxytriptolide (LLDT-8), a novel triptolide derivative immunosuppressant in a conditional knockout (KO) mouse model with liver-specific deletion of CYP450 reductase. Compared to wild type (WT) mice, after LLDT-8 treatment, KO mice suffered severe testicular toxicity (decreased testicular weight, spermatocytes apoptosis) unlike WT mice...
2017: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/29207642/crosstalk-in-competing-endogenous-rna-network-reveals-the-complex-molecular-mechanism-underlying-lung-cancer
#17
Xiang Jin, Yinghui Guan, Hui Sheng, Yang Liu
We investigated the transcriptional mechanism underlying lung cancer development. RNA sequencing analysis was performed on blood samples from lung cancer cases and healthy controls. Differentially expressed microRNAs (miRNAs), circular RNAs (circRNAs), mRNAs (genes), and long non-coding RNAs (lncRNA) were identified, followed by pathway enrichment analysis. Based on miRNA target interactions, a competing endogenous network was established and significant nodes were screened. Differentially expressed transcriptional factors were retrieved from the TRRUST database and the transcriptional factor regulatory network was constructed...
October 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/29207253/influence-of-postnatal-prolactin-modulation-on-the-development-and-maturation-of-ventral-prostate-in-young-rats
#18
Ana C L Camargo, Flávia B Constantino, Sérgio A A Santos, Ketlin T Colombelli, Maeli Dal-Pai-Silva, Sérgio L Felisbino, Luis A Justulin
Besides androgenic dependence, other hormones also influence the prostate biology. Prolactin has been described as an important hormone associated with maintenance of prostatic morphophysiology; however, there is a lack of information on the involvement of prolactin during prostate development and growth. This study aimed to evaluate whether perinatal prolactin modulation interferes with rat ventral prostate (VP) development and maturation. Therefore, prolactin or bromocriptine (an inhibitor of prolactin release from the pituitary) were administered to Sprague Dawley rats from postnatal Day (PND) 12 to PND 21 or 35...
December 6, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/29207031/prl%C3%A2-3-increases-the-aggressive-phenotype-of-prostate-cancer-cells-in%C3%A2-vitro-and-its-expression-correlates-with-high-grade-prostate-tumors-in-patients
#19
Donna R Edwards, Krzysztof Moroz, Haitao Zhang, David Mulholland, Asim B Abdel-Mageed, Debasis Mondal
The increased expression of phosphatase of regenerating liver-3 (PRL‑3) has been shown to be associated with the aggressive and metastatic phenotype of different solid tumors. However, it is not known whether PRL‑3 plays a similar role in the progression of prostate cancer (PCa). In this study, immunoblot analysis of androgen receptor (AR)-positive PCa lines (LNCaP and LNCaP‑SF) revealed the constitutive cytoplasmic expression of PRL‑3, and stimulation with R1881 (AR agonist) rapidly increased the nuclear translocation of PRL‑3...
November 20, 2017: International Journal of Oncology
https://www.readbyqxmd.com/read/29206494/prenatal-diagnosis-of-twin-fetuses-with-a-novel-ar-gene-mutation-in-a-chinese-family-of-complete-androgen-insensitivity-syndrome
#20
Weiqing Wu, Qian Geng, Yang Liu, Zhiyong Xu, Peining Li, Jiansheng Xie
INTRODUCTION AND AIMS: Androgen insensitivity syndrome (AIS) is an X-linked recessive genetic disorder caused by mutations in the androgen receptor (AR) gene. Only a few cases of AIS with AR gene mutations have been diagnosed prenatally. This study aimed to investigate the gene mutation in a Chinese complete androgen insensitivity syndrome family and perform prenatal diagnosis for twin fetuses. CASE REPORT: We evaluated the AR gene of the child proband in a Chinese CAIS family, and detected a novel mutation c...
December 5, 2017: Fetal and Pediatric Pathology
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