Downregulating testosterone levels enhance immunotherapy efficiency.
Ontology highlight
ABSTRACT:
SUBMITTER: Wang L
PROVIDER: S-EPMC8477942 | biostudies-literature | 2021
REPOSITORIES: biostudies-literature
Publications
Downregulating testosterone levels enhance immunotherapy efficiency.
Wang Luoyang L Jiang Guoqiang G Jing Nan N Liu Xuerun X Zhuang Huiren H Zeng Wenfeng W Liang Wei W Liu Zheng Z
Oncoimmunology 20210927 1
Low response rates to certain tumor types remain a major challenge for immune checkpoint blockade therapy. In this study, we first conducted an integrated biomarker evaluation of bladder cancer patients from confirmatory cohorts (IMvigor210) and found that no significant differences exist between sexes before acceptance of anti-PD-L1 treatment, whereas male patients showed a better response. Thus, we then focused on sex-related changes post anti-PD-L1 treatment and found no obvious impact on the ...[more]
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Project description:Abstract Background The mechanism of erectile dysfunction (ED) caused by a low androgen level is still not clear. Aim To explore the influence of the low testosterone state on G protein–coupled receptor kinase interactor 1 (GIT1) and its contact to erectile function. Methods Thirty male Sprague-Dawley rats aged 8 weeks were distributed at random into 5 groups: control (sham operated), castration, testosterone supplement after castration, castration + vacant lentiviral transfection, and castration + lentiviral transfection. The testis and epididymis were removed through a scrotal incision to develop castrated rats. Four weeks after castration, a lentivirus carrying the GIT1 gene was injected into the middle of rat penile corpus cavernosum. One week after transfection, maximum intracavernous pressure/mean arterial pressure (ICPmax/MAP), serum testosterone, nitric oxide, GIT1, endothelial nitric oxide synthase (eNOS), phospho-eNOS (p-eNOS), p-eNOS/eNOS, and the interaction between eNOS and GIT1 were assessed in the rats. Outcomes The levels of GIT1 in the penile cavernous tissue of castrated rats are significantly lower than that of controls. Results GIT1 was expressed in the cytoplasm and cell membrane of vascular endothelial cells and smooth muscle cells in rat penile tissue. In comparison with normal rats, the castrated rats showed lower levels of GIT1 expression, GIT1 and eNOS interaction, p-eNOS/eNOS, nitric oxide, and ICPmax/MAP (P < .01). Overexpression of GIT1 can intensively enhance the expression level of GIT1, the interaction between GIT1 and eNOS, p-eNOS/eNOS, nitric oxide, and ICPmax/MAP in rats (P < .01). Clinical Translation Modulating the interaction between eNOS and GIT1 might be a novel method of treating ED caused by a low androgen level. Strengths and Limitations The impact of GIT1 phosphorylation on the activity of eNOS and its possible mechanisms affecting erectile function require further study. Conclusion A low testosterone state inhibits erectile function in rats by reducing the expression of GIT1 and the protein interaction between GIT1 and eNOS.
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