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Male Sexual Function
Published in Anthony R. Mundy, John M. Fitzpatrick, David E. Neal, Nicholas J. R. George, The Scientific Basis of Urology, 2010
Giulio Garaffa, Suks Minhas, David J. Ralph
Testicular descent can be subdivided in two separate phases, an intra-abdominal and inguino-scrotal phase. The first phase is initiated at about 10 to 14 weeks of gestation and lasts to about week 20 to 23. This phase is mediated by ILF3 factor, that is, structurally closely related to relaxin and that stimulates gubernaculum mesenchymal cells. However, androgens don not play any role during the phase of intraabdominal descent (5). The second phase of descent is usually completed by week 35 in the human and is mediated by the action of androgens on the gubernaculum and the cranial suspensory ligament of the testis. Above all, the androgen-mediated regression of the cranial suspensory ligament is a condition sine qua non for a complete testicular descent. The androgens also affect the second phase of the testicular descent by inducing the masculinization of the sensory nucleus of the genitofemoral nerve. Furthermore, the sensory branch of this nerve, when adequately stimulated by androgens, acts via the calcitonin gene related transmitter inducing the migration of the gubernaculums testis and transection of this nerve causes ipsilateral cryptorchisdism (6).
Effects of YM155 on the proliferation and apoptosis of pulmonary artery smooth muscle cells in a rat model of high pulmonary blood flow-induced pulmonary arterial hypertension
Published in Clinical and Experimental Hypertension, 2022
Bingbing Ye, Xiaofei Peng, Danyan Su, Dongli Liu, Yanyun Huang, Yuqin Huang, Yusheng Pang
YM155 is a novel, small-molecule antitumor drug that functions as a suppressor of SVV. As a transcription suppressor of the SVV promoter, YM155 inhibits the alternative transcription of SVV through DNA damage induction (25). Studies have demonstrated that YM155 selectively inhibits the expression of SVV in different cancer cell lines, such as colon cancer and cervical cancer (26,27). YM155 has also been unveiled to suppress the expression of SVV by binding to interleukin enhancer-binding factor 3 (ILF3), which is involved in the transcription of SVV (28). In vitro studies have shown that YM155, as a means of molecular therapy, has a strong effect on the targeted inhibition of SVV (25,28). Moreover, in-vivo application of YM155 as an inhibitor of SVV can down-regulate mRNA and protein levels of SVV in PASMCs of rats with chronic hypoxic PAH, as well as up-regulate the expression and activity of Kv, further supporting the therapeutic potential of YM155 (22,23).
Survivin as a biological biomarker for diagnosis and therapy
Published in Expert Opinion on Biological Therapy, 2021
Yuming Li, Wenshu Lu, Jiarun Yang, Mark Edwards, Shisong Jiang
Overexpression of interleukin enhancer-binding factor 3 (ILF3/NF110) enhances the promoter for the SVN gene(BIRC5). This effect makes ILF3 an additional SVN target. Small molecules targeting the above-mentioned genes and their products have been studied both in vitro and in clinical trials. Sepantronium bromide (YM155), a small molecule inhibitor of SVN, exerts its effect by direct binding to ILF3/NF110, attenuating SVN gene transcription in a concentration-dependent manner [81]. YM155 downregulates SVN expression and induces apoptosis in human hormone-refractory prostate cancer (HRPC) cell lines [82] and non-small-cell lung cancer (NSCLC) cell lines in nude mice [83]. The safety and efficacy of YM155 when combined with carboplatin (C) and paclitaxel (P) was examined in patients with advanced NSCLC in a phase I/II study (NCT01100931). The triple combination exhibited a favorable safety profile but failed to demonstrate an improvement in the response rate [84]. Another phase I study was conducted to evaluate the safety and pharmacokinetics of YM155 in combination with the tyrosine kinase inhibitor erlotinib in patients with EGFR TKI refractory advanced NSCLC. The results suggest that inhibiting SVN is a potential therapeutic target in this defined group of patients [85].