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https://www.readbyqxmd.com/read/29035540/targeted-clinical-nanoparticles-for-precision-cancer-therapy-based-on-disease-specific-molecular-inflection-points
#1
Charalambos Kaittanis, Alexander Bolaender, Barney Yoo, Nilesh Shah, Ouathek Ouerfelli, Jan Grimm
ional approaches based on clinical modular nanoplatforms are needed, in order to treat solid cancers according to their discrete molecular features. In the present study, we show that the clinical nanopharmaceutical Ferumoxytol, which consists of a glucose-based coat surrounding an iron oxide core, could identify molecular characteristics of prostate cancer, corresponding to unique phases of the disease continuum. By affixing a targeting probe for the prostate-specific membrane antigen on its surface, the nanopharmaceutical was able to assess the functional state of the androgen receptor pathway via MRI, guiding therapy and delivering it with the same clinical nanoparticle...
October 16, 2017: Nano Letters
https://www.readbyqxmd.com/read/29033586/targeting-the-androgen-receptor-in-triple-negative-breast-cancer-current-perspectives
#2
REVIEW
Alain Mina, Rachel Yoder, Priyanka Sharma
Triple-negative breast cancer (TNBC) is an aggressive subtype associated with frequent recurrence and metastasis. Unlike hormone receptor-positive subtypes, treatment of TNBC is currently limited by the lack of clinically available targeted therapies. Androgen signaling is necessary for normal breast development, and its dysregulation has been implicated in breast tumorigenesis. In recent years, gene expression studies have identified a subset of TNBC that is enriched for androgen receptor (AR) signaling. Interference with androgen signaling in TNBC is promising, and AR-inhibiting drugs have shown antitumorigenic activity in preclinical and proof of concept clinical studies...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/29032717/bet-inhibitors-in-metastatic-prostate-cancer-therapeutic-implications-and-rational-drug-combinations
#3
Mark C Markowski, Angelo M De Marzo, Emmanuel S Antonarakis
The bromodomain and extra-terminal (BET) family of proteins are epigenetic readers of acetylated histones regulating a vast network of protein expression across many different cancers. Therapeutic targeting of BET is an attractive area of clinical development for metastatic castration-resistant prostate cancer (mCRPC), particularly due to its putative effect on c-MYC expression and its interaction with the androgen receptor (AR). Areas Covered: We speculate that a combination approach using BET inhibition with other targeted therapies may be required to improve the therapeutic index of BET inhibition in the management of prostate cancer...
October 16, 2017: Expert Opinion on Investigational Drugs
https://www.readbyqxmd.com/read/29032351/testosterone-induced-modulation-of-peroxisomal-morphology-and-peroxisome-related-gene-expression-in-brown-trout-salmo-trutta-f-fario-primary-hepatocytes
#4
Célia Lopes, Fernanda Malhão, Cláudia Guimarães, Ivone Pinheiro, José F Gonçalves, L Filipe C Castro, Eduardo Rocha, Tânia V Madureira
Disruption of androgenic signaling has been linked to possible cross-modulation with other hormone-mediated pathways. Therefore, our objective was to explore effects caused by testosterone - T (1, 10 and 50μM) in peroxisomal signaling of brown trout hepatocytes. To study the underlying paths involved, several co-exposure conditions were tested, with flutamide - F (anti-androgen) and ICI 182,780 - ICI (anti-estrogen). Molecular and morphological approaches were both evaluated. Peroxisome proliferator-activated receptor alpha (PPARα), catalase and urate oxidase were the selected targets for gene expression analysis...
September 28, 2017: Aquatic Toxicology
https://www.readbyqxmd.com/read/29032082/effects-of-triclosan-on-hormones-and-reproductive-axis-in-female-yellow-river-carp-cyprinus-carpio-potential-mechanisms-underlying-estrogen-effect
#5
Fan Wang, Xiangmeng Guo, Wanguang Chen, Yaowen Sun, Chaojie Fan
Triclosan (TCS), a member of the class of compounds called pharmaceutical and personal care products (PPCPs), is a broad antibacterial and antifungal agent found in a lot of consumer products. However, TCS hormone effect mechanism in teleost female fish is not clear. Female Yellow River carp (Cyprinus carpio) were exposed to 1/20, 1/10 and 1/5 LC50 TCS (96h LC50 of TCS to carp) under semi-static conditions for 42days. Vitellogenin (Vtg), 17β-estradiol (E2), testosterone(T), estrogen receptor (Er), gonadotropin (GtH), and gonadotropin-releasing hormone (GnRH) levels were measured by enzyme-linked immunosorbent assay (ELISA)...
October 12, 2017: Toxicology and Applied Pharmacology
https://www.readbyqxmd.com/read/29031189/renal-subcapsular-xenografing-of-human-fetal-external-genital-tissue-a-new-model-for-investigating-urethral-development
#6
Dylan Isaacson, Joel Shen, Mei Cao, Adriane Sinclair, Xuan Yue, Gerald Cunha, Laurence Baskin
In this paper, we introduce our novel renal subcapsular xenograft model for the study of human penile urethral and clitoral development. We grafted fifteen intact fetal penes and clitorides 8-11 weeks fetal age under the renal capsules of gonadectomized athymic mice. The mice were treated with a subcutaneous pellet of dihydrotestosterone (DHT), diethylstilbestrol (DES) or untreated with hormones. Xenografts were harvested after fourteen days of growth and analyzed via serial histologic sectioning and immunostaining for Ki-67, cytokeratins 6, 7 and 10, uroplakin and the androgen receptor...
September 22, 2017: Differentiation; Research in Biological Diversity
https://www.readbyqxmd.com/read/29030639/androgen-receptor-increases-hematogenous-metastasis-yet-decreases-lymphatic-metastasis-of-renal-cell-carcinoma
#7
Qingbo Huang, Yin Sun, Xin Ma, Yu Gao, Xintao Li, Yuanjie Niu, Xu Zhang, Chawnshang Chang
Clear cell renal cell carcinoma (ccRCC) is a gender-biased tumor. Here we report that there is also a gender difference between pulmonary metastasis and lymph node metastasis showing that the androgen receptor (AR)-positive ccRCC may prefer to metastasize to lung rather than to lymph nodes. A higher AR expression increases ccRCC hematogenous metastasis yet decreases ccRCC lymphatic metastases. Mechanism dissection indicates that AR enhances miR-185-5p expression via binding to the androgen response elements located on the promoter of miR-185-5p, which suppresses VEGF-C expression via binding to its 3' UTR...
October 13, 2017: Nature Communications
https://www.readbyqxmd.com/read/29030409/clinical-relevance-of-androgen-receptor-alterations-in-prostate-cancer
#8
REVIEW
Emma Jernberg, Anders Bergh, Pernilla Wikström
Prostate cancer (PC) remains a leading cause of cancer-related deaths among men worldwide, despite continuously improved treatment strategies. Patients with metastatic disease are treated by androgen deprivation therapy (ADT) that with time results in the development of castration-resistant prostate cancer (CRPC) usually established as metastases within bone tissue. The androgen receptor (AR) transcription factor is the main driver of CRPC development and of acquired resistance to drugs given for treatment of CRPC, while a minority of patients have CRPC that is non-AR driven...
November 2017: Endocrine Connections
https://www.readbyqxmd.com/read/29029032/foxa1-expression-is-a-strong-independent-predictor-of-early-psa-recurrence-in-erg-negative-prostate-cancers-treated-by-radical-prostatectomy
#9
Maria Christina Tsourlakis, Agapi Eleftheriadou, Annegret Stender, Philipp Weigand, Katharina Grupp, Claudia Hube-Magg, Martina Kluth, Cornelia Schroeder, Stefan Steurer, Andrea Hinsch, Andreas Luebke, Alexander Angerer, Corinna Wittmer, Emily Friedrich, Cosima Göbel, Franziska Büscheck, Hans Heinzer, Markus Graefen, Ronald Simon, Guido Sauter, Waldemar Wilczak, Sarah Minner, Thorsten Schlomm, Frank Jacobsen
FOXA1 is a transcription factor involved in androgen signaling with relevance for lineage specific gene expression of the prostate. The expression was analyzed by immunohistochemistry on a tissue microarray containing 11,152 prostate cancer specimens. Results were compared to tumor phenotype, biochemical recurrence, androgen receptor expression, ERG status and other recurrent genomic alterations. FOXA1 expression was detectable in 97.6% of 8,227 interpretable cancers and considered strong in 28.5%, moderate in 46...
September 26, 2017: Carcinogenesis
https://www.readbyqxmd.com/read/29027610/risk-factors-for-and-incidence-of-seizures-in-metastatic-castration-resistant-prostate-cancer-a-real-world-retrospective-cohort-study
#10
Charles Dharmani, Machaon Bonafede, Andrew Krivoshik
BACKGROUND AND OBJECTIVE: This real-world study assessed the prevalence, risk factors for, and incidence of seizures in patients with metastatic castration-resistant prostate cancer (mCRPC). METHODS: Patients with mCRPC were selected from MarketScan Commercial and Medicare Supplemental Databases between 1 January 2009 and 31 July 2012. Prevalence of seizure risk factors were described separately and in combination with other risk factors. Seizure incidence was calculated overall and for each risk factor group...
October 13, 2017: Clinical Drug Investigation
https://www.readbyqxmd.com/read/29024781/the-role-of-androgen-receptors-in-atherosclerosis
#11
REVIEW
Kaloyan Takov, Junxi Wu, Martin A Denvir, Lee B Smith, Patrick W F Hadoke
Male disadvantage in cardiovascular health is well recognised. However, the influence of androgens on atherosclerosis, one of the major causes of many life-threatening cardiovascular events, is not well understood. With the dramatic increase in clinical prescription of testosterone in the past decade, concerns about the cardiovascular side-effects of androgen supplementation or androgen deprivation therapy are increasing. Potential atheroprotective effects of testosterone could be secondary to (aromatase-mediated) conversion into oestradiol or, alternatively, to direct activation of androgen receptors (AR)...
October 9, 2017: Molecular and Cellular Endocrinology
https://www.readbyqxmd.com/read/29024132/expression-of-isotocin-is-male-specifically-upregulated-by-gonadal-androgen-in-the-medaka-brain
#12
Junpei Yamashita, Yukika Kawabata, Kataaki Okubo
Oxytocin, a mammalian neuropeptide primarily synthesized in the supraoptic and paraventricular nuclei of the hypothalamus, mediates a variety of physiological and behavioral processes ranging from parturition and lactation to affiliation and prosociality. Multiple studies in rodents have shown that the expression of the oxytocin gene (Oxt) is stimulated by estrogen, while androgen has no apparent effect. However, this finding is not consistent across all studies, and no study has examined sex steroid regulation of Oxt or its orthologs in other animals...
October 10, 2017: Journal of Neuroendocrinology
https://www.readbyqxmd.com/read/29023530/allele-specific-expression-at-the-androgen-receptor-alpha-gene-in-a-hybrid-unisexual-fish-the-amazon-molly-poecilia-formosa
#13
Fangjun Zhu, Ingo Schlupp, Ralph Tiedemann
The all-female Amazon molly (Poecilia formosa) is the result of a hybridization of the Atlantic molly (P. mexicana) and the sailfin molly (P. latipinna) approximately 120,000 years ago. As a gynogenetic species, P. formosa needs to copulate with heterospecific males including males from one of its bisexual ancestral species. However, the sperm only triggers embryogenesis of the diploid eggs. The genetic information of the sperm donor typically will not contribute to the next generation of P. formosa. Hence, P...
2017: PloS One
https://www.readbyqxmd.com/read/29023247/mir-449a-a-potential-therapeutic-agent-for-cancer
#14
He Yong-Ming, Ji Ai-Jun, Xu Xiao-Yue, Lu Jian-Wei, Yu Chen, Chen Ye
MicroRNAs (miRNAs) have been reported to be associated with cancer progression and carcinogenesis. They are small, highly conserved, noncoding RNA molecules consisting of 19-25 nucleotides. By binding to complementary binding sites within the 3'-untranslated region of target mRNAs, miRNAs inhibit the translation of mRNAs or promote their degradation. miRNAs play critical roles in cancer initiation and development by functioning either as oncogenes or as tumor suppressors. Similarly, several studies have shown that miRNAs are involved in regulating various biological processes, including apoptosis, proliferation, cellular differentiation, signal transduction, and carcinogenesis...
October 11, 2017: Anti-cancer Drugs
https://www.readbyqxmd.com/read/29022906/increasing-ar-by-hif-2%C3%AE-inhibitor-pt-2385-overcomes-the-side-effects-of-sorafenib-by-suppressing-hepatocellular-carcinoma-invasion-via-alteration-of-pstat3-pakt-and-perk-signals
#15
Junjie Xu, Longbo Zheng, Jiang Chen, Yin Sun, Hui Lin, Ren-An Jin, Minyue Tang, Xiao Liang, Xiujun Cai
Although sorafenib is currently used as a standard treatment for advanced hepatocellular carcinoma, low response rate, transient and limited efficacy, primary and acquired resistance and negative side-effects gain increasing attentions, suggesting the need for better efficacious combination therapy. Here, we demonstrated that the sorafenib-induced or hypoxia-induced hypoxia inducible factor (HIF)-2α could bind to an hypoxia responsive element within 500 bp region of androgen receptor (AR) promoter and thus transcriptionally suppress AR...
October 12, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/29022712/predictive-structure-based-toxicology-approaches-to-assess-the-androgenic-potential-of-chemicals
#16
Daniela Trisciuzzi, Domenico Alberga, Kamel Mansouri, Richard S Judson, Ettore Novellino, Giuseppe Felice Mangiatordi, Orazio Nicolotti
We present a practical and easy-to-run in silico workflow exploiting a structure-based strategy making use of docking simulations to derive highly predictive classification models of the androgenic potential of chemicals. Models were trained on a high-quality chemical collection comprising 1689 curated compounds made available within CoMPARA consortium from the US Environmental Protection Agency and were integrated with a two-step applicability domain whose implementation had the effect of improving both the confidence in prediction and statistics by reducing the number of false negatives...
October 12, 2017: Journal of Chemical Information and Modeling
https://www.readbyqxmd.com/read/29022558/klinefelter-syndrome-in-childhood-variability-in-clinical-and-molecular-findings
#17
Neşe Akcan, Şükran Poyrazoğlu, Firdevs Baş, Rüveyde Bundak, Feyza Darendeliler
OBJECTIVE: Klinefelter syndrome (KS) is the most common (1/500-1/1000) chromosomal disorder in males, but only 10% of cases are identified in childhood. This study aimed to review the data of the children with KS to assess the age and reason for diagnosis, clinical and laboratory findings, as well as the presence of comorbidities. METHODS: Twenty-three KS patients were analyzed retrospectively. Age at admission, presenting symptoms, comorbid problems, height, weight, pubertal status, biochemical findings, hormone profiles, bone mineral density, and karyotype were evaluated...
October 12, 2017: Journal of Clinical Research in Pediatric Endocrinology
https://www.readbyqxmd.com/read/29017493/enzalutamide-versus-abiraterone-as-a-first-line-endocrine-therapy-for-castration-resistant-prostate-cancer-enable-study-for-pca-a-study-protocol-for-a-multicenter-randomized-phase-iii-trial
#18
Kouji Izumi, Atsushi Mizokami, Mikio Namiki, Shogo Inoue, Nobumichi Tanaka, Yuko Yoshio, Kei Ishibashi, Manabu Kamiyama, Noriyasu Kawai, Hideki Enokida, Takashi Shima, Shizuko Takahara
BACKGROUND: Both enzalutamide and abiraterone have demonstrated improved radiographic progression-free and overall survival for castration-resistant prostate cancer (CRPC) compared with placebo controls before docetaxel treatment in phase III studies. These oral agents target androgen and androgen receptor signaling and are thought to be less toxic than chemotherapy. Cross-resistance to these agents was recently reported because of their similar mechanism of action, and it is important to assess which agent is more effective to use initially for CRPC...
October 10, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29017058/androgen-receptor-pathway-independent-prostate-cancer-is-sustained-through-fgf-signaling
#19
Eric G Bluemn, Ilsa M Coleman, Jared M Lucas, Roger T Coleman, Susana Hernandez-Lopez, Robin Tharakan, Daniella Bianchi-Frias, Ruth F Dumpit, Arja Kaipainen, Alexandra N Corella, Yu Chi Yang, Michael D Nyquist, Elahe Mostaghel, Andrew C Hsieh, Xiaotun Zhang, Eva Corey, Lisha G Brown, Holly M Nguyen, Kenneth Pienta, Michael Ittmann, Michael Schweizer, Lawrence D True, David Wise, Paul S Rennie, Robert L Vessella, Colm Morrissey, Peter S Nelson
Androgen receptor (AR) signaling is a distinctive feature of prostate carcinoma (PC) and represents the major therapeutic target for treating metastatic prostate cancer (mPC). Though highly effective, AR antagonism can produce tumors that bypass a functional requirement for AR, often through neuroendocrine (NE) transdifferentiation. Through the molecular assessment of mPCs over two decades, we find a phenotypic shift has occurred in mPC with the emergence of an AR-null NE-null phenotype. These "double-negative" PCs are notable for elevated FGF and MAPK pathway activity, which can bypass AR dependence...
October 9, 2017: Cancer Cell
https://www.readbyqxmd.com/read/29017052/cellular-origin-of-androgen-receptor-pathway-independent-prostate-cancer-and-implications-for-therapy
#20
W Nathaniel Brennen, John T Isaacs
In this issue of Cancer Cell, Bluemn et al. report that ∼20% of metastatic castration-resistant prostate cancers express neither AR nor neuroendocrine genes and show AR pathway-independent growth, driven instead by a FGFR/MAPK/ID1 signaling cascade. These results provide a strong rationale for co-targeting AR bypass pathways with initial AR antagonism.
October 9, 2017: Cancer Cell
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