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#34543357   2021/09/20 To Up

Androgen receptor transactivates KSHV noncoding RNA PAN to promote lytic replication-mediated oncogenesis: A mechanism of sex disparity in KS.

Kaposi's sarcoma-associated herpesvirus (KSHV) preferentially infects and causes Kaposi's sarcoma (KS) in male patients. However, the biological mechanisms are largely unknown. This study was novel in confirming the extensive nuclear distribution of the androgen receptor (AR) and its co-localization with viral oncoprotein of latency-associated nuclear antigen in KS lesions, indicating a transcription way of AR in KS pathogenesis. The endogenous AR was also remarkably higher in KSHV-positive B cells than in KSHV-negative cells and responded to the ligand treatment of 5α-dihydrotestosterone (DHT), the agonist of AR. Then, the anti-AR antibody-based chromatin immunoprecipitation (ChIP)-associated sequencing was used to identify the target viral genes of AR, revealing that the AR bound to multiple regions of lytic genes in the KSHV genome. The highest peak was enriched in the core promoter sequence of polyadenylated nuclear RNA (PAN), and the physical interaction was verified by ChIP-polymerase chain reaction (PCR) and the electrophoretic mobility shift assay (EMSA). Consistently, male steroid treatment significantly transactivated the promoter activity of PAN in luciferase reporter assay, consequently leading to extensive lytic gene expression and KSHV production as determined by real-time quantitative PCR, and the deletion of nuclear localization signals of AR resulted in the loss of nuclear transport and transcriptional activity in the presence of androgen and thus impaired the expression of PAN RNA. Oncogenically, this study identified that the AR was a functional prerequisite for cell invasion, especially under the context of KSHV reactivation, through hijacking the PAN as a critical effector. Taken together, a novel mechanism from male sex steroids to viral noncoding RNA was identified, which might provide a clue to understanding the male propensity in KS.
Mingzhu Ding, Jinfeng Wu, Rui Sun, Lijun Yan, Lei Bai, Jiajian Shi, Hua Feng, Yuqi Zhang, Ke Lan, Xing Wang

1435 related Products with: Androgen receptor transactivates KSHV noncoding RNA PAN to promote lytic replication-mediated oncogenesis: A mechanism of sex disparity in KS.

5mg10mg100ug50 ug 100 μg100 μg100ug Lyophilized2 Pieces/Box200 100ug Lyophilized

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#34505421   2021/07/23 To Up

Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β-hydroxysteroid dehydrogenase, 17-20α-hydroxylase, 17β-hydroxysteroid dehydrogenase and 5α-reductase.

Glioblastoma (GB) is the most common and aggressive primary brain tumour in adult humans. Therapeutic resistance and tumour recurrence after surgical removal contribute to poor prognosis for glioblastoma patients. Men are known to be more likely than women to develop an aggressive form of GB, and differences in sex steroids have emerged as a leading explanation for this finding. Studies indicate that the metabolism and proliferation of GB-derived cells are increased by sex steroids, the expression of androgen receptors (ARs) and the synthesis of androgens and oestrogens, suggesting that these hormones have a role in the tumour pathogenesis. The expression of aromatase, the enzyme that converts androgens to oestrogens, has been reported in glial cells and GB cell lines. Thus, it was necessary to test whether the steroidogenic enzymes involved in androgen synthesis are expressed in GB cells. Therefore, here, we investigated the expression of four key enzymes involved in androgen synthesis in human-derived GB cells. U87 cells were cultured in Dulbecco's modified Eagle medium plus foetal bovine serum and antibiotics on slides for immunocytochemistry or immunofluorescence. U87, LN229 and C6 cells were also cultured in multi-well chambers to obtain proteins for Western blotting. We used primary antibodies against 3β-hydroxysteroid dehydrogenase (3β-HSD), 17α-hydroxilase/17,20-lyase (P450c17), 17β-hydroxysteroid dehydrogenase (17β-HSD) and 5α-reductase. Immunocytochemistry, and immunofluorescence results revealed that glioblastoma cells express 3β-HSD, P450c17, 17β-HSD and 5α-reductase proteins in their cytoplasm. Moreover, Western blot analyses revealed bands corresponding to the molecular weight of these four enzymes in the three GB cell lines. Thus, glioblastoma cells have the key enzymatic machinery necessary to synthesize androgens, and these enzymes might be useful targets for new therapeutic approaches.
Jose Antonio Mondragón, Yesenia Serrano, Andrea Torres, Martin Orozco, Jose Segovia, Gabriel Manjarrez, Marta Catalina Romano

2828 related Products with: Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3β-hydroxysteroid dehydrogenase, 17-20α-hydroxylase, 17β-hydroxysteroid dehydrogenase and 5α-reductase.

96 wells1.00 flask96 tests100ul100ug1.00 flask100 μl1 mg10 1 ml1 ml250ul

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#34469608   2021/09/01 To Up

The 27th Annual Prostate Cancer Foundation Scientific Retreat Report.

The 27th Annual Prostate Cancer Foundation (PCF) Scientific Retreat was held virtually from October 20 to 23, 2020.
Andrea K Miyahira, Howard R Soule

1066 related Products with: The 27th Annual Prostate Cancer Foundation Scientific Retreat Report.

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#34225789   2021/07/05 To Up

Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial.

Therapeutic targeting of host-cell factors required for SARS-CoV-2 entry is an alternative strategy to ameliorate COVID-19 severity. SARS-CoV-2 entry into lung epithelium requires the TMPRSS2 cell surface protease. Pre-clinical and correlative data in humans suggest that anti-androgenic therapies can reduce the expression of TMPRSS2 on lung epithelium. Accordingly, we hypothesize that therapeutic targeting of androgen receptor signaling via degarelix, a luteinizing hormone-releasing hormone (LHRH) antagonist, will suppress COVID-19 infection and ameliorate symptom severity.
Nicholas G Nickols, Matthew B Goetz, Christopher J Graber, Debika Bhattacharya, Guy Soo Hoo, Matthew Might, David B Goldstein, Xinchen Wang, Rachel Ramoni, Kenute Myrie, Samantha Tran, Leila Ghayouri, Sonny Tsai, Michelle Geelhoed, Danil Makarov, Daniel J Becker, Jun-Chieh Tsay, Melissa Diamond, Asha George, Mohammad Al-Ajam, Pooja Belligund, R Bruce Montgomery, Elahe A Mostaghel, Carlie Sulpizio, Zhibao Mi, Ellen Dematt, Joseph Tadalan, Leslie E Norman, Daniel Briones, Christina E Clise, Zachary W Taylor, Jeffrey R Huminik, Kousick Biswas, Matthew B Rettig

1870 related Products with: Hormonal intervention for the treatment of veterans with COVID-19 requiring hospitalization (HITCH): a multicenter, phase 2 randomized controlled trial of best supportive care vs best supportive care plus degarelix: study protocol for a randomized controlled trial.

250 mg 1 G 1 G96 Tests100 mg250 mg0.1 mg5 g100ug

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#34167925   2021/06/21 To Up

Prostate-specific Membrane Antigen Biology in Lethal Prostate Cancer and its Therapeutic Implications.

Prostate-specific membrane antigen (PSMA) is a promising, novel theranostic target in advanced prostate cancer (PCa). Multiple PSMA-targeted therapies are currently in clinical development, with some agents showing impressive antitumour activity, although optimal patient selection and therapeutic resistance remain ongoing challenges.
Beshara Sheehan, Christina Guo, Antje Neeb, Alec Paschalis, Shahneen Sandhu, Johann S de Bono

2113 related Products with: Prostate-specific Membrane Antigen Biology in Lethal Prostate Cancer and its Therapeutic Implications.

100 25 ml Ready-to-use 1 kit(96 Wells)

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#34035067   2021/05/25 To Up

Darolutamide Potentiates the Antitumor Efficacy of a PSMA-targeted Thorium-227 Conjugate by a Dual Mode of Action in Prostate Cancer Models.

Androgen receptor (AR) inhibitors are well established in the treatment of castration-resistant prostate cancer and have recently shown efficacy also in castration-sensitive prostate cancer. Although most patients respond well to initial therapy, resistance eventually develops, and thus, more effective therapeutic approaches are needed. Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and presents an attractive target for radionuclide therapy. Here, we evaluated the efficacy and explored the mode of action of the PSMA-targeted thorium-227 conjugate (PSMA-TTC) BAY 2315497, an antibody-based targeted alpha-therapy, in combination with the AR inhibitor darolutamide.
Stefanie Hammer, Andreas Schlicker, Sabine Zitzmann-Kolbe, Simon Baumgart, Urs B Hagemann, Arne Scholz, Bernard Haendler, Pascale Lejeune, Jenny Karlsson, Christine Ellingsen, Hartwig Hennekes, Carsten H Nielsen, Mark U Juul, Dominik Mumberg, Christoph A Schatz

2715 related Products with: Darolutamide Potentiates the Antitumor Efficacy of a PSMA-targeted Thorium-227 Conjugate by a Dual Mode of Action in Prostate Cancer Models.



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#33971182   2021/05/07 To Up

Glucocorticoids and Androgens Protect From Gastric Metaplasia by Suppressing Group 2 Innate Lymphoid Cell Activation.

The immune compartment is critical for maintaining tissue homeostasis. A weak immune response increases susceptibility to infection, but immune hyperactivation causes tissue damage, and chronic inflammation may lead to cancer development. In the stomach, inflammation damages the gastric glands and drives the development of potentially preneoplastic metaplasia. Glucocorticoids are potent anti-inflammatory steroid hormones that are required to suppress gastric inflammation and metaplasia. However, these hormones function differently in males and females. Here, we investigate the impact of sex on the regulation of gastric inflammation.
Jonathan T Busada, Kylie N Peterson, Stuti Khadka, Xiaojiang Xu, Robert H Oakley, Donald N Cook, John A Cidlowski

1655 related Products with: Glucocorticoids and Androgens Protect From Gastric Metaplasia by Suppressing Group 2 Innate Lymphoid Cell Activation.

2500 assays200ug500 ml96T100ug Lyophilized25ml5 x 200ul/Unit10 lt200ug25ml

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