Search results for: Androgen Receptor (Phospho-Ser650) Antibody
#34681642 2021/10/12 To Up
Hijacking Sexual Immuno-Privilege in GBM-An Immuno-Evasion Strategy.Regulatory T-cells (Tregs) are immunosuppressive T-cells, which arrest immune responses to 'Self' tissues. Some immunosuppressive Tregs that recognize seminal epitopes suppress immune responses to the proteins in semen, in both men and women. We postulated that GBMs express reproductive-associated proteins to manipulate reproductive Tregs and to gain immune privilege. We analyzed four GBM transcriptome databases representing â900 tumors for hypoxia-responsive Tregs, steroidogenic pathways, and sperm/testicular and placenta-specific genes, stratifying tumors by expression. In silico analysis suggested that the presence of reproductive-associated Tregs in GBM tumors was associated with worse patient outcomes. These tumors have an androgenic signature, express male-specific antigens, and attract reproductive-associated Related Orphan Receptor C (RORC)-Treg immunosuppressive cells. GBM patient sera were interrogated for the presence of anti-sperm/testicular antibodies, along with age-matched controls, utilizing monkey testicle sections. GBM patient serum contained anti-sperm/testicular antibodies at levels > six-fold that of controls. Myeloid-derived suppressor cells (MDSCs) and tumor-associated macrophages (TAMs) are associated with estrogenic tumors which appear to mimic placental tissue. We demonstrate that RORC-Tregs drive poor patient outcome, and Treg infiltration correlates strongly with androgen levels. Androgens support GBM expression of sperm/testicular proteins allowing Tregs from the patient's reproductive system to infiltrate the tumor. In contrast, estrogen appears responsible for MDSC/TAM immunosuppression.
Martyn A Sharpe, David S Baskin, Amanda V Jenson, Alexandra M Baskin0.1ml (1mg/ml)0.1ml (1mg/ml)1l25ml100ml50ml200ml10ml5ml1l
#34629314 2021/09/17 To Up
Molecular Classification of Triple Negative Breast Cancer and the Emergence of Targeted Therapies.Triple negative breast cancer (TNBC) represents 15% to 20% of all primary breast cancers and is the most aggressive subtype of breast cancer. There has been rapid progress in targeted therapy and biomarker development to identify the optimal treatments for TNBC. To update recent developments, this article comprehensively reviews molecular classification and biomarkers of TNBC and targeted therapy developments in immunotherapy, PARP and AKT pathway inhibitors, antibody-drug conjugates and androgen receptor blockade. The treatment of TNBC has dramatically evolved beyond basic cytotoxic chemotherapy into an expanding domain of targeted therapies tailored to the heterogeneity of this complex and aggressive disease. Progress will continue through the sustained and devoted efforts of our investigators and the patients who dedicatedly enroll in clinical trials. Through a daring persistence to challenge the status quo we now have the opportunity to offer our patients with TNBC a new sense of hope.
Elizabeth Sakach, Ruth O'Regan, Jane Meisel, Xiaoxian Li
1947 related Products with: Molecular Classification of Triple Negative Breast Cancer and the Emergence of Targeted Therapies.100ul96T
#34628475 2021/10/09 To Up
Treatment with abiraterone or enzalutamide does not impair immunological response to COVID-19 vaccination in prostate cancer patients.Data regarding the safety and efficacy of COVID-10 vaccines among cancer patients are lacking. Factors such as age, underlying disease and antineoplastic treatment confer negatively to the immune response due to vaccination. The degree of immunosuppression though may be lessen by targeted treatments like the androgen receptor-targeted agents (ARTA) that are commonly used in patients with metastatic prostate cancer. Herein, we report our data on 25 patients with prostate cancer under treatment with ARTA who were vaccinated for COVID-19. Our data suggest that these patients develop neutralizing antibodies against SARS-CoV-2 similarly to healthy volunteers. No safety issues were noted.
Michalis Liontos, Evangelos Terpos, Elena Kunadis, Flora Zagouri, Alexandros Briasoulis, Efi Skafida, Oraianthi Fiste, Christos Markellos, Angeliki Andrikopoulou, Sentiljana Gumeni, Maria Kaparelou, Konstantinos Koutsoukos, Maria Gavriatopoulou, Efstathios Kastritis, Ioannis P Trougakos, Meletios- Athanasios Dimopoulos
1968 related Products with: Treatment with abiraterone or enzalutamide does not impair immunological response to COVID-19 vaccination in prostate cancer patients.
#34568716 2021/09/16 To Up
Metastatic Castration-Resistant Prostate Cancer Remains Dependent on Oncogenic Drivers Found in Primary Tumors.Metastatic prostate cancer is initially sensitive to androgen receptor inhibition, but eventually becomes castration-resistant prostate cancer (mCRPC). Early use of more intensive therapies targeting androgen receptor and other oncogenic drivers in treatment-naÃ¯ve primary prostate cancer (PC) may be more effective than that in advanced mCRPC. However, analysis of primary tumors may not reveal targetable metastatic drivers that are subclonal in the primary tumor or acquired at metastatic sites.
David J Einstein, Seiji Arai, Carla Calagua, Fang Xie, Olga Voznesensky, Brian J Capaldo, Christina Luffman, Jonathan L Hecht, Steven P Balk, Adam G Sowalsky, Joshua W Russo
1475 related Products with: Metastatic Castration-Resistant Prostate Cancer Remains Dependent on Oncogenic Drivers Found in Primary Tumors.
#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 5Î±-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
1683 related Products with: Androgen receptor transactivates KSHV noncoding RNA PAN to promote lytic replication-mediated oncogenesis: A mechanism of sex disparity in KS.5mg100ug Lyophilized2 Pieces/Box200 100ug Lyophilized10mg100ug50 ug 100 μg100 μg
#34505421 2021/07/23 To Up
Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3Î²-hydroxysteroid dehydrogenase, 17-20Î±-hydroxylase, 17Î²-hydroxysteroid dehydrogenase and 5Î±-reductase.Glioblastoma (GB) is the mostÂ commonÂ and aggressive primary brain tumour in adult humans. Therapeutic resistance and tumour recurrence after surgical removalÂ contribute toÂ poor prognosisÂ for glioblastoma patients.Â 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 explanationÂ for this finding. Studies indicate thatÂ the metabolism and proliferation ofÂ GB-derived cellsÂ are increasedÂ by sex steroids,Â theÂ expression ofÂ androgen receptors (ARs)Â andÂ theÂ synthesis ofÂ androgensÂ and oestrogens, suggesting thatÂ these hormonesÂ have a role in the tumour pathogenesis.Â The expression of aromatase,Â theÂ enzyme that converts androgens to oestrogens, hasÂ beenÂ reported in glial cells and GBÂ cell lines. Thus, itÂ wasÂ necessaryÂ toÂ test whetherÂ the steroidogenic enzymes involved in androgen synthesis are expressed in GB cells.Â Therefore,Â here,Â weÂ investigated the expression of fourÂ key enzymes involved in androgen synthesis in human-derived GBÂ cells.Â U87 cells were cultured inÂ Dulbecco'sÂ modified EagleÂ mediumÂ plusÂ foetal bovine serumÂ and antibiotics on slides for immunocytochemistry or immunofluorescence. U87, LN229 and C6 cells were also cultured in multi-wellÂ chambersÂ to obtain proteins for WesternÂ blotting.Â WeÂ usedÂ primary antibodies againstÂ 3Î²-hydroxysteroid dehydrogenase (3Î²-HSD), 17Î±-hydroxilase/17,20-lyase (P450c17),Â 17Î²-hydroxysteroid dehydrogenase (17Î²-HSD)Â and 5Î±-reductase.Â Immunocytochemistry, andÂ immunofluorescenceÂ results revealed thatÂ glioblastomaÂ cellsÂ express 3Î²-HSD, P450c17, 17Î²-HSD and 5Î±-reductaseÂ proteins in their cytoplasm. Moreover, WesternÂ blot analyses revealed bands corresponding to theÂ molecular weightÂ of theseÂ four enzymes in the three GB cell lines.Â Thus, glioblastoma cells haveÂ the key enzymatic machinery necessary to synthesize androgens,Â and these enzymesÂ mightÂ beÂ usefulÂ targetsÂ for newÂ therapeuticÂ approaches.
Jose Antonio MondragÃ³n, Yesenia Serrano, Andrea Torres, Martin Orozco, Jose Segovia, Gabriel Manjarrez, Marta Catalina Romano
1366 related Products with: Glioblastoma cells express crucial enzymes involved in androgen synthesis: 3Î²-hydroxysteroid dehydrogenase, 17-20Î±-hydroxylase, 17Î²-hydroxysteroid dehydrogenase and 5Î±-reductase.96 wells1.00 flask96 tests100 μl100ul100ug1.00 flask10 ug100 μg1 mg10 1 ml
#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 SouleEach
#34399825 2021/08/16 To Up
SELP Asp603Asn and severe thrombosis in COVID-19 males.Thromboembolism is a frequent cause of severity and mortality in COVID-19. However, the etiology of this phenomenon is not well understood. A cohort of 1186 subjects, from the GEN-COVID consortium, infected by SARS-CoV-2 with different severity was stratified by sex and adjusted by age. Then, common coding variants from whole exome sequencing were mined by LASSO logistic regression. The homozygosity of the cell adhesion molecule P-selectin gene (SELP) rs6127 (c.1807Gâ>âA; p.Asp603Asn) which has been already associated with thrombotic risk is found to be associated with severity in the male subcohort of 513 subjects (odds ratioâ=â2.27, 95% Confidence Interval 1.54-3.36). As the SELP gene is downregulated by testosterone, the odd ratio is increased in males older than 50 (OR 2.42, 95% CI 1.53-3.82). Asn/Asn homozygotes have increased D-dimers values especially when associated with poly Qââ¥â23 in the androgen receptor (OR 3.26, 95% CI 1.41-7.52). These results provide a rationale for the repurposing of antibodies against P-selectin as adjuvant therapy in rs6127 male homozygotes especially if older than 50 or with an impaired androgen receptor.
Chiara Fallerini, Sergio Daga, Elisa Benetti, Nicola Picchiotti, Kristina Zguro, Francesca Catapano, Virginia Baroni, Simone Lanini, Alessandro Bucalossi, Giuseppe Marotta, Francesca Colombo, Margherita Baldassarri, Francesca Fava, Giada Beligni, Laura Di Sarno, Diana Alaverdian, Maria Palmieri, Susanna Croci, Andrea M Isidori, Simone Furini, Elisa Frullanti, , Alessandra Renieri, Francesca Mari5 mg100 ug100 assays96 wells (1 kit)1 pce 5 G96 wells (1 kit)50 mg100 μg
#34265880 2021/07/16 To Up
Association of antimullerian hormone with the size of the appendix testis, the androgen and estrogen receptors and their expression in the appendix testis, in congenital cryptorchidism.Antimullerian hormone (AMH) causes regression of the mullerian ducts in the male fetus. The appendix testis (AT) is a vestigial remnant of mullerian duct origin, containing both androgen (AR) and estrogen (ER) receptors. The role of both AMH and AT in testicular descent is yet to be studied. We investigated the possible association of AMH with AT size, the AR and ER, and their expression in the AT, in congenital cryptorchidism.
Xenophon Sinopidis, Eirini Kostopoulou, Andrea Paola Rojas-Gil, Antonios Panagidis, Eleni Kourea, Spyros Skiadopoulos, George Georgiou, Bessie E Spiliotis
1490 related Products with: Association of antimullerian hormone with the size of the appendix testis, the androgen and estrogen receptors and their expression in the appendix testis, in congenital cryptorchidism.1500 Units1mg
#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
2613 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 G0.1 mg100 mg96 Tests5 g250 mg 100 G0.1 ml
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