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11.
Androgens control growth of prostate epithelial cells and androgen deprivation induces apoptosis, leading to prostate involution. We investigated the effects of surgical stress on prostate involution induced by androgen ablation and determined the underlying mechanisms. Androgen ablation in mice was induced by surgical castration and administration of the anti-androgenic drugs bicalutamide and MDV3100. Surgical stress was induced by sham castration under isoflurane anesthesia. Surgical stress delayed apoptosis and prostate involution induced by anti-androgenic drugs. These effects of stress were prevented by administering the selective beta2-adrenoreceptor antagonist ICI118,551 and were also blocked in BAD3SA/WT mice expressing phosphorylation-deficient mutant BAD3SA. These results indicate that apoptosis and prostate involution in response to androgen ablation therapy could be delayed by surgical stress via the beta2-adrenoreceptor/BAD signaling pathway. Thus, surgery could interfere with androgen ablation therapy, whereas administration of beta2-adrenoreceptor antagonists may enhance its efficacy. 相似文献
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Xu Zhang Wei Zhang Santosh L. Saraf Mehdi Nouraie Jin Han Michel Gowhari Johara Hassan Galina Miasnikova Adelina Sergueeva Sergei Nekhai Rick Kittles Roberto F. Machado Joe G. N. Garcia Mark T. Gladwin Martin H. Steinberg Paola Sebastiani Donald A. McClain Victor R. Gordeuk 《Human genetics》2015,134(8):895-904
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Geetha Nalairndran Ivy Chung Azad Hassan Abdul Razack Felicia Fei-Lei Chung Ling-Wei Hii Wei-Meng Lim Chin King Looi Chun-Wai Mai Chee-Onn Leong 《Journal of cellular and molecular medicine》2021,25(17):8187-8200
Prostate cancer (PCa) is the second most common malignancy and is the fifth leading cause of cancer mortality among men globally. Docetaxel-based therapy remains the first-line treatment for metastatic castration-resistant prostate cancer. However, dose-limiting toxicity including neutropenia, myelosuppression and neurotoxicity is the major reason for docetaxel dose reductions and fewer cycles administered, despite a recent study showing a clear survival benefit with increased total number of docetaxel cycles in PCa patients. Although previous studies have attempted to improve the efficacy and reduce docetaxel toxicity through drug combination, no drug has yet demonstrated improved overall survival in clinical trial, highlighting the challenges of improving the activity of docetaxel monotherapy in PCa. Herein, we identified 15 lethality hits for which inhibition could enhance docetaxel sensitivity in PCa cells via a high-throughput kinome-wide loss-of-function screen. Further drug-gene interactions analyses identified Janus kinase 1 (JAK1) as a viable druggable target with existing experimental inhibitors and FDA-approved drugs. We demonstrated that depletion of endogenous JAK1 enhanced docetaxel-induced apoptosis in PCa cells. Furthermore, inhibition of JAK1/2 by baricitinib and ruxolitinib synergizes docetaxel sensitivity in both androgen receptor (AR)–negative DU145 and PC3 cells, but not in the AR-positive LNCaP cells. In contrast, no synergistic effects were observed in cells treated with JAK2-specific inhibitor, fedratinib, suggesting that the synergistic effects are mainly mediated through JAK1 inhibition. In conclusion, the combination therapy with JAK1 inhibitors and docetaxel could be a useful therapeutic strategy in the treatment of prostate cancers. 相似文献
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Sonja Schmidt Birthe Gericke Giulio Fracasso Dunia Ramarli Marco Colombatti Hassan Y. Naim 《PloS one》2013,8(6)
Prostate-specific membrane antigen (PSMA) is a type-II membrane glycoprotein that was initially identified in LNCaP cells. It is expressed at elevated levels in prostate cancer. In view of the correlation between the expression levels of PSMA and disease grade and stage, PSMA is considered to be one of the most promising biomarkers in the diagnosis and treatment of prostate cancer. In LNCaP cells PSMA undergoes internalization via clathrin-coated pits followed by accumulation in the endosomes. PSMA associates with different types of detergent-resistant membranes (DRMs) along the secretory pathway. Its mature form is mainly insoluble in Lubrol WX, but does not associate with Triton X-100-DRMs. To understand the mechanism of PSMA internalization we investigated its association during internalization with DRMs. For this purpose, internalization was induced by antibody cross-linking. We demonstrate at the biochemical and cell biological levels that: [i] exclusively homodimers of PSMA are associated with Lubrol WX-DRMs, [ii] antibody-induced cross-linking of PSMA molecules results in a time-dependent partitioning into another DRMs type, namely Triton X-100-DRMs, and [iii] concomitant with its association with Triton-X-100-DRMs internalization of PSMA occurs along tubulin filaments. In a previous work (Colombatti et al. (2009) PLoS One 4: e4608) we demonstrated that the small GTPases RAS and RAC1 and the MAPKs p38 and ERK1/2 are activated during antibody cross-linking. As downstream effects of this activation we observed a strong induction of NF-kB associated with an increased expression of IL-6 and CCL5 genes and that IL-6 and CCL5 enhanced the proliferative potential of LNCaP cells synergistically. These observations together with findings reported here hypothesize a fundamental role of DRMs during activation of PSMA as platforms for trafficking, endocytosis and signalling. Understanding these mechanisms constitutes an essential prerequisite for utilization of PSMA as a therapeutically suitable target in prostate cancer. 相似文献
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Heydar Valizadeh Habib Abbasipour Hassan Askary Vahid Reza Moniri 《Archives Of Phytopathology And Plant Protection》2013,46(10):1162-1169
Dericorys albidula Serville (Orthoptera: Dericorythidae) is a major pest of Haloxylon ammodendron and other saxaul plant species in the Qom province, Iran. Using fungal insecticides can be an alternative method for chemical insecticides. Effect of insecticide fungi, Metarhizium anisopliae var. acridum, on the various nymphs of D. albidula was studied in the field through 2005 and 2006. Fixed concentrations of fungi (106, 107, 108, 109, 1010 and 1013 spore mL?1) were prepared as gasoline formulation and were sprayed on the locusts on H. ammodendron trees, and mortality percentage was recorded 15 days after treatment. The results showed that various concentrations significantly affected on the second, third, fourth and fifth nymphal instars of D. albidula compared to control in 2006, although this effect was lower in 2005 on nymphs. Mortality of the highest concentration (1013 spore mL?1) was higher (17.6–24%) than other concentrations in all tests, but these values were not notable. The results of this study showed that using M. anisopliae var. acridum diluted in gasoline can be effective on nymphal instars of locust, D. albidula, in two continuous years. 相似文献
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C.S. Fagnant-Sperati Y. Ren N.A. Zhou E. Komen B. Mwangi J. Hassan A. Chepkurui R. Nzunza J. Nyangao W.B. van Zyl M. Wolfaardt P.N. Matsapola F.B. Ngwana S. Jeffries-Miles A. Coulliette-Salmond S. Peñaranda E. Vega J.H. Shirai A.L. Kossik N.K. Beck D.S. Boyle C.C. Burns M.B. Taylor P. Borus J.S. Meschke 《Journal of applied microbiology》2021,130(3):971-981
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The foraging strategies for both food or hosts of three trichogrammatid species: Trichogramma evanescens, Trichogramma cacoecia and Trichogramma dendrolimi were compared using artificial patches of Sitotroga cerealella eggs. In all experiments, inexperienced and newly emerged wasps of < 1 h old were singly tested. When the females were allowed to land upon the hosts, the decision-making process for initial acceptance or rejection was species-dependent. The initial search in T. evanescens was for food, whereas T. dendrolimi or T. cacoeciae start to oviposit immediately after their emergence. When honey-deprived or undeprived females were each exposed to single patches for 20 or 60 min, variations in mean number of probing females 'drilling and ovipositing' were also species-dependent. Acceptance of host eggs by honey-deprived females and subsequent egg deposition were higher in both T. cacoeciae and T. dendrolimi than in T. evanescens . For all species, the probing of honey-undeprived females was higher than that of deprived ones. When the exposure period was prolonged to 24 or 48 h and the number of patches per female increased to three, most of the honey-deprived or undeprived T. evanescens females attacked one patch, and only a few of them attacked two patches. Foraging activity of honey-deprived females of T. cacoeciae was restricted to single patches, whereas most undeprived ones attacked more than one patch. In contrast, honey-deprived or undeprived T. dendrolimi females attacked more than one patch. The experiments showed that T. dendrolimi females have more powerful ovipositing urges than looking for food and that the opposite was the case for T. evanescens , with T. cacoeciae being intermediate. 相似文献
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