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Search results for: Androgen Receptor

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#34847080   2021/11/30 To Up

Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice.

Functional gastrointestinal disorders (FGIDs) have prominent sex differences in incidence, symptoms, and treatment response that are not well understood. Androgens are steroid hormones present at much higher levels in males than females and could be involved in these differences. In adults with irritable bowel syndrome (IBS), a FGID that affects 5-10% of the population worldwide, we found that free testosterone levels were lower than those in healthy controls and inversely correlated with symptom severity. To determine how this diminished androgen signaling could contribute to bowel dysfunction, we depleted gonadal androgens in adult mice and found that this caused a profound deficit in gastrointestinal transit. Restoring a single androgen hormone was sufficient to rescue this deficit, suggesting that circulating androgens are essential for normal bowel motility in vivo. To determine the site of action, we probed androgen receptor expression in the intestine and discovered, unexpectedly, that a large subset of enteric neurons became androgen-responsive upon puberty. Androgen signaling to these neurons was required for normal colonic motility in adult mice. Taken together, these observations establish a role for gonadal androgens in the neural regulation of bowel function and link altered androgen levels with a common digestive disorder.
Daniella Rastelli, Ariel Robinson, Valentina N Lagomarsino, Lynley T Matthews, Rafla Hassan, Kristina Perez, William Dan, Peter D Yim, Madison Mixer, Aleksandra Prochera, Amy Shepherd, Liang Sun, Kathryn Hall, Sarah Ballou, Anthony Lembo, Judy Nee, Meenakshi Rao

2508 related Products with: Diminished androgen levels are linked to irritable bowel syndrome and cause bowel dysfunction in mice.

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#34844845   2021/11/26 To Up

Understanding and targeting prostate cancer cell heterogeneity and plasticity.

Prostate cancer (PCa) is a prevalent malignancy that occurs primarily in old males. Prostate tumors in different patients manifest significant inter-patient heterogeneity with respect to histo-morphological presentations and molecular architecture. An individual patient tumor also harbors genetically distinct clones in which PCa cells display intra-tumor heterogeneity in molecular features and phenotypic marker expression. This inherent PCa cell heterogeneity, e.g., in the expression of androgen receptor (AR), constitutes a barrier to the long-term therapeutic efficacy of AR-targeting therapies. Furthermore, tumor progression as well as therapeutic treatments induce PCa cell plasticity such that AR-positive PCa cells may turn into AR-negative cells and prostate tumors may switch lineage identity from adenocarcinomas to neuroendocrine-like tumors. This induced PCa cell plasticity similarly confers resistance to AR-targeting and other therapies. In this review, I first discuss PCa from the perspective of an abnormal organ development and deregulated cellular differentiation, and discuss the luminal progenitor cells as the likely cells of origin for PCa. I then focus on intrinsic PCa cell heterogeneity in treatment-naïve tumors with the presence of prostate cancer stem cells (PCSCs). I further elaborate on PCa cell plasticity induced by genetic alterations and therapeutic interventions, and present potential strategies to therapeutically tackle PCa cell heterogeneity and plasticity. My discussions will make it clear that, to achieve enduring clinical efficacy, both intrinsic PCa cell heterogeneity and induced PCa cell plasticity need to be targeted with novel combinatorial approaches.
Dean G Tang

2715 related Products with: Understanding and targeting prostate cancer cell heterogeneity and plasticity.

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#34843781   2021/11/26 To Up

In vitro profiling of toxic effects of environmental polycyclic aromatic hydrocarbons on nuclear receptor signaling, disruption of endogenous metabolism and induction of cellular stress.

Polycyclic aromatic hydrocarbons (PAHs) may interact with multiple intracellular receptors and related signaling pathways. We comprehensively evaluated the toxicity profiles of six environmentally relevant PAHs differing in structure, genotoxicity and their ability to activate the aryl hydrocarbon receptor (AhR). We focused particularly on their impact on intracellular hormone-, xenobiotic- and lipid-sensing receptors, as well as on cellular stress markers, combining a battery of human reporter gene assays and qRT-PCR evaluation of endogenous gene expression in human hepatocyte-like HepaRG cells, with LC/MS-MS analysis of cellular sphingolipids. The effects of PAHs included: activation of estrogen receptor α (in case of fluoranthene (Fla), pyrene (Pyr), benz[a]anthracene (BaA), benzo[a]pyrene (BaP)), suppression of androgen receptor activity (Fla, BaA, BaP and benzo[k]fluoranthene (BkF)), enhancement of dexamethasone-induced glucocorticoid receptor activity (chrysene (Chry), BaA, and BaP), or potentiation of triiodothyronine-induced thyroid receptor α activity (all tested PAHs). PAHs also induced transcription of endogenous gene targets of constitutive androstane receptor (Fla, Pyr), or repression of target genes of pregnane X receptor and peroxisome proliferator-activated receptor α (in case of the AhR-activating PAHs - Chry, BaA, BaP, and BkF) in HepaRG cells. In the same cell model, the AhR agonists reduced the expression of glucose metabolism genes (PCK1, G6PC and PDK4), and they up-regulated levels of glucosylceramides, together with a concomitant induction of expression of UGCG, glucosylceramide synthesis enzyme. Finally, both BaP and BkF were found to induce expression of early stress and genotoxicity markers: ATF3, EGR1, GDF15, CDKN1A/p21, and GADD45A mRNAs, while BaP alone increased levels of IL-6 mRNA. Overall, whereas low-molecular-weight PAHs exerted significant effects on nuclear receptors (with CYP2B6 induction observed already at nanomolar concentrations), the AhR activation by 4-ring and 5-ring PAHs appeared to be a key mechanism underlying their impact on nuclear receptor signaling, endogenous metabolism and induction of early stress and genotoxicity markers.
Pavlína Šimečková, Kateřina Pěnčíková, Ondrej Kováč, Josef Slavík, Martina Pařenicová, Jan Vondráček, Miroslav Machala

1920 related Products with: In vitro profiling of toxic effects of environmental polycyclic aromatic hydrocarbons on nuclear receptor signaling, disruption of endogenous metabolism and induction of cellular stress.

5 G2 Pieces/Box50 ug2 Pieces/Box2 Pieces/Box100ug5mg100ul100ug Lyophilized

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#34843630   2021/11/29 To Up

Combination therapy with novel androgen receptor antagonists and statin for castration-resistant prostate cancer.

One of the growth mechanisms of castration-resistant prostate cancer (CRPC) is de novo androgen synthesis from intracellular cholesterol, and statins may be able to inhibit this mechanism. In addition, statins have been reported to suppress the expression of androgen receptors (ARs) in prostate cancer cell lines. In this study, we investigated a combination therapy of novel AR antagonists and statin, simvastatin, for CRPC.
Hiroshi Nakayama, Yoshitaka Sekine, Daisuke Oka, Yoshiyuki Miyazawa, Seiji Arai, Hidekazu Koike, Hiroshi Matsui, Yasuhiro Shibata, Kazuhiro Suzuki

1701 related Products with: Combination therapy with novel androgen receptor antagonists and statin for castration-resistant prostate cancer.

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#34843005   2021/11/29 To Up

A phase 1 study to assess the safety, pharmacokinetics, and anti-tumor activity of the androgen receptor n-terminal domain inhibitor epi-506 in patients with metastatic castration-resistant prostate cancer.

EPI-506 is the first of a new class of drugs targeting the N-terminal domain (NTD) of the androgen receptor (AR), potentially overcoming known resistance mechanisms to androgen receptor pathway inhibitors (ARPIs) among men with metastatic castration resistant prostate cancer (mCRPC).
Corinne Maurice-Dror, Ronan Le Moigne, Ulka Vaishampayan, Robert B Montgomery, Michael S Gordon, Nan Hyung Hong, Leah DiMascio, Frank Perabo, Kim N Chi

1682 related Products with: A phase 1 study to assess the safety, pharmacokinetics, and anti-tumor activity of the androgen receptor n-terminal domain inhibitor epi-506 in patients with metastatic castration-resistant prostate cancer.

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#34838672   2021/11/24 To Up

Protective effect of the association of curcumin with piperine on prostatic lesions: New perspectives on BPA-induced carcinogenesis.

Bisphenol A (BPA) is a chemical agent which can exert detrimental effects on the male reproductive system, especially the prostate gland. In this study we described the efficacy of the dietary agent curcumin, alone or combined with piperine, to suppress the impact of BPA on the prostate. Adult gerbils were divided into nine experimental groups (n = 7 each group), regarding control (water and oil), exposed to BPA (50 μg/kg/day in water) or curcumin (100 mg/kg) and/or piperine (20 mg/kg). To evaluate the effects of the phytotherapic agents, the other groups received oral doses every two days, BPA plus curcumin (BCm), piperine (BP), and curcumin + piperine (BCmP). BPA promoted prostatic inflammation and morphological lesions in ventral and dorsolateral prostate lobes, associated with an increase in androgen receptor-positive cells and nuclear atypia, mainly in the ventral lobe. Curcumin and piperine helped to minimize these effects. BPA plus piperine or curcumin showed a reduction in nuclear atypical phenotype, indicating a beneficial effect of phytochemicals. Thus, these phytochemicals minimize the deleterious action of BPA in prostatic lobes, especially when administered in association. The protective action of curcumin and piperine consumption is associated with weight loss, anti-inflammatory potential, and control of prostate epithelial cell homeostasis.
Camila Helena Facina, Silvana Gisele Pegorin Campos, Thalles Fernando Rocha Ruiz, Rejane Maira Góes, Patrícia Simone Leite Vilamaior, Sebastião Roberto Taboga

2419 related Products with: Protective effect of the association of curcumin with piperine on prostatic lesions: New perspectives on BPA-induced carcinogenesis.

2 ml Ready-to-use 2 25 ml Ready-to-use 25 MG 6 ml 2 ml Ready-to-use 1 mg0.2 mg 6 ml Ready-to-use 100.00 ug 25 ml Ready-to-use 2 ml Ready-to-use

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#34838638   2021/11/24 To Up

Regulatory role of dihydrotestosterone on BMP-6 receptors in granular cells of sheep antral follicles.

Bone morphogenetic protein-6 (BMP-6) and dihydrotestosterone (DHT) affect steroid synthesis in follicles and regulate cell proliferation in the ovaries of female animals. However, little is known about granular cells (GCs) in sheep. We identified the key BMP-6 receptors, activin receptor-like kinase(ALK-6), and bone morphogenetic protein receptor type 2 (BMPRII) in sheep follicles using immunohistochemistry (IHC) and immunofluorescence (IF). Both ALK-6 and BMPRII were expressed in the GC layer, GC membranes, and cytoplasm. We evaluated ALK-6 and BMPRII expression at the follicular development stage using quantitative real-time PCR and western blotting to detect sheep GCs from large, medium, and small follicles (diameters of ≥ 5, 2-5, and ≤ 2 mm, respectively). The mRNA abundance and protein expression of ALK-6 and BMPRII were significantly higher in GCs from large follicles compared to those in GCs from small follicles (P < 0.05) and were the lowest in GCs from medium follicles. To assess whether DHT affects ALK-6 and BMPRII expression in sheep GCs, we cultured GCs from large follicles in vitro then incubated them with DHT (10, 10, 10 M). We found that 10-M DHT significantly inhibited ALK-6 and BMPRII mRNA and protein (P < 0.05). We further explored whether DHT regulates ALK-6 and BMPRII through the nuclear androgen receptor (AR) pathway and found that 10-M flutamide, a non-selective androgen inhibitor, partially relieved the inhibitory effect of 10M DHT on ALK-6 and BMPRII expression. Thus, GCs in sheep antral follicles differentially expressed ALK-6 and BMPRII at various stages, indicating that BMP-6 plays different roles to some extent during the development of antral follicles, and that high concentrations of DHT can inhibit the expression of ALK-6 and BMPRII via the androgen receptor pathway in sheep GCs. The present study aimed to determine the expression of the main BMP-6-related main receptors, namely, ALK-6 and BMPRII, during the development of GCs in sheep antral follicles and a potential mechanism of DHT regulation in sheep GCs. Our findings lay a foundation for the further exploration of the effects of ovarian BMP-6 expression on follicular development.
Jianshu Lv, Wenbo Ge, Ziqiang Ding, Jianlin Zeng, Wenjuan Wang, Hongwei Duan, Yong Zhang, Xingxu Zhao, Junjie Hu

1226 related Products with: Regulatory role of dihydrotestosterone on BMP-6 receptors in granular cells of sheep antral follicles.