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Lin Cao - One of the best experts on this subject based on the ideXlab platform.

  • Gestrinone inhibits growth of human uterine leiomyoma may relate to activity regulation of erα src and p38 mapk
    Biomedicine & Pharmacotherapy, 2012
    Co-Authors: Yan Zhu, Tingting Zhang, Shuwu Xie, Yang Cao, Xiangjie Guo, Jieyun Zhou, Xianying Zhou, Lin Cao
    Abstract:

    The study was to investigate the effect of Gestrinone on the growth of human uterine leiomyoma cells and on the levels and activity of p38, Src and estrogen receptor alpha (ERα). Human uterine leiomyoma cells were cultured and treated with dimethylsulfoxide (DMSO) or a Gestrinone concentration gradient. Morphological changes were observed and apoptosis was evaluated. Levels of p38 and phosphorylated-p38 (pp38) were assayed by enzyme-linked immunosorbent assay (ELISA). Levels of ERα and Src were analyzed using real-time RT-PCR and Western blotting. The result showed that Gestrinone significantly inhibited the growth of cultured human uterine leiomyoma cells in a concentration- and time-dependent manner, with a 50% inhibitory concentration (IC(50)) value and corresponding 95% confidence intervals (CI) of 43.67 (23.46∼81.32), 27.78 (12.51∼61.68) and 15.25 (7.17∼32.43) μmol/L at 20, 40 and 60h, respectively. Compared with control-treated leiomyoma cells, Gestrinone significantly reduced both the expression of ERα (P 0.05) in response to the tested concentrations of 0.1 to 3.0μmol/L. As a conclusion, Gestrinone suppresses the proliferation of uterine leiomyoma cells mainly by regulating the activity of ERα/Src/p38 MAPK in a concentration-dependent manner at a low concentration of 0.1∼3.0μM, but not significantly regulating apoptosis. Gestrinone opposes the growth of uterine leiomyoma through multiple genes.

  • effects of Gestrinone on uterine leiomyoma and expression of c src in a guinea pig model
    Acta Pharmacologica Sinica, 2007
    Co-Authors: Yan Zhu, Xiaoyan Qiu, Lei Wang, Guiming Liu, Xiurong Jiang, Zuyue Sun, Lin Cao
    Abstract:

    Aim: To investigate the effect of Gestrinone on uterine leiomyomas and the expression of c-Src, estradiol receptors (ER), and progesterone receptors (PR) in a guinea pig model. Methods: After being oophorectomized, the guinea pigs were allocated into random groups. The model group was treated with estradiol benzoate (E 2 ) for 16 weeks. In the Gestrinone-treated groups, the animals were treated with E 2 for 6 weeks in advance, and then in combination with Gestrinone for 10 weeks. Histological examination was performed to evaluate whether there were leiomyoma features in the animals. The protein levels of c-Src, phospho- 416 Src, ER, and PR were assayed by Western blotting and an immunohistochemical method. Results: Morphological changes were observed in the myometrium of the guinea pig model, including an increase of uterine weights, proliferation of uterine smooth muscles, and the formation of nodules. High protein levels of c-Src, phospho- 416 Src, ER, and PR were observed in the myometrium of the guinea pig model. In the Gestrinone-treated group, there were no nodules observed. The histological features of the myometrium were similar to that of the control group. Low protein levels of c-Src, phospho- 416 Src, ER, and PR were observed in the Gestrinone-treated group. Conclusion: The upregulation of c-Src and phospho- 416 Src indicated that the activity of c-Src is augmented in the uterine leiomyoma model. c-Src was associated with the formation of uterine leiomyomas in the model, and Gestrinone markedly suppressed the growth of uterine leiomyomas in the model. Gestrinone inhibited not only the protein expression of ER and PR, but also c-Src and the autophosphorylation of c-Src in the guinea pig leiomyoma model.

Yan Zhu - One of the best experts on this subject based on the ideXlab platform.

  • Gestrinone inhibits growth of human uterine leiomyoma may relate to activity regulation of erα src and p38 mapk
    Biomedicine & Pharmacotherapy, 2012
    Co-Authors: Yan Zhu, Tingting Zhang, Shuwu Xie, Yang Cao, Xiangjie Guo, Jieyun Zhou, Xianying Zhou, Lin Cao
    Abstract:

    The study was to investigate the effect of Gestrinone on the growth of human uterine leiomyoma cells and on the levels and activity of p38, Src and estrogen receptor alpha (ERα). Human uterine leiomyoma cells were cultured and treated with dimethylsulfoxide (DMSO) or a Gestrinone concentration gradient. Morphological changes were observed and apoptosis was evaluated. Levels of p38 and phosphorylated-p38 (pp38) were assayed by enzyme-linked immunosorbent assay (ELISA). Levels of ERα and Src were analyzed using real-time RT-PCR and Western blotting. The result showed that Gestrinone significantly inhibited the growth of cultured human uterine leiomyoma cells in a concentration- and time-dependent manner, with a 50% inhibitory concentration (IC(50)) value and corresponding 95% confidence intervals (CI) of 43.67 (23.46∼81.32), 27.78 (12.51∼61.68) and 15.25 (7.17∼32.43) μmol/L at 20, 40 and 60h, respectively. Compared with control-treated leiomyoma cells, Gestrinone significantly reduced both the expression of ERα (P 0.05) in response to the tested concentrations of 0.1 to 3.0μmol/L. As a conclusion, Gestrinone suppresses the proliferation of uterine leiomyoma cells mainly by regulating the activity of ERα/Src/p38 MAPK in a concentration-dependent manner at a low concentration of 0.1∼3.0μM, but not significantly regulating apoptosis. Gestrinone opposes the growth of uterine leiomyoma through multiple genes.

  • effects of Gestrinone on uterine leiomyoma and expression of c src in a guinea pig model
    Acta Pharmacologica Sinica, 2007
    Co-Authors: Yan Zhu, Xiaoyan Qiu, Lei Wang, Guiming Liu, Xiurong Jiang, Zuyue Sun, Lin Cao
    Abstract:

    Aim: To investigate the effect of Gestrinone on uterine leiomyomas and the expression of c-Src, estradiol receptors (ER), and progesterone receptors (PR) in a guinea pig model. Methods: After being oophorectomized, the guinea pigs were allocated into random groups. The model group was treated with estradiol benzoate (E 2 ) for 16 weeks. In the Gestrinone-treated groups, the animals were treated with E 2 for 6 weeks in advance, and then in combination with Gestrinone for 10 weeks. Histological examination was performed to evaluate whether there were leiomyoma features in the animals. The protein levels of c-Src, phospho- 416 Src, ER, and PR were assayed by Western blotting and an immunohistochemical method. Results: Morphological changes were observed in the myometrium of the guinea pig model, including an increase of uterine weights, proliferation of uterine smooth muscles, and the formation of nodules. High protein levels of c-Src, phospho- 416 Src, ER, and PR were observed in the myometrium of the guinea pig model. In the Gestrinone-treated group, there were no nodules observed. The histological features of the myometrium were similar to that of the control group. Low protein levels of c-Src, phospho- 416 Src, ER, and PR were observed in the Gestrinone-treated group. Conclusion: The upregulation of c-Src and phospho- 416 Src indicated that the activity of c-Src is augmented in the uterine leiomyoma model. c-Src was associated with the formation of uterine leiomyomas in the model, and Gestrinone markedly suppressed the growth of uterine leiomyomas in the model. Gestrinone inhibited not only the protein expression of ER and PR, but also c-Src and the autophosphorylation of c-Src in the guinea pig leiomyoma model.

Paolo Vercellini - One of the best experts on this subject based on the ideXlab platform.

  • endometrial patterns during therapy with danazol or Gestrinone for endometriosis structural and ultrastructural study
    Human Pathology, 1992
    Co-Authors: Maurizio Marchini, Luigi Fedele, Stefano Bianchi, Giuliana Di Nola, Simona Nava, Paolo Vercellini
    Abstract:

    We treated 36 women with laparoscopically proven endometriosis with danazol 600 mg/d (n = 17) or Gestrinone 5.0 mg/wk (n = 19) for 6 months. Endometrial samples were obtained before and at 3 and 6 months of treatment and were studied by light, scanning, and transmission electron microscopy. At 3 months of treatment, the endometria of the danazol-treated patients were more atrophic than those of the women who received Gestrinone. Some cell organelle involution was evident in patients of both treatment groups. After 6 months of treatment, marked endometrial atrophy was observed in all the patients, including those in whom spotting had occurred. The ultrastructural investigation demonstrated complete involution of the cytoplasmic organelles with cytoplasmic collapse in glandular cells of patients treated with danazol, whereas in the Gestrinone group degeneration phenomena were observed in both nucleus and cytoplasm. Irregular secretory transformation was seen in the endometria of patients in both groups. Long-term treatment with danazol caused endometrial atrophy similar to that induced by Gestrinone, but it appeared earlier; thus, the former drug seems preferable in short-term treatment.

Frances J Thomas - One of the best experts on this subject based on the ideXlab platform.

  • tissue and endocrine responses to Gestrinone and danazol in the treatment of endometriosis
    Reproduction Fertility and Development, 1993
    Co-Authors: Kevin L Forbes, Frances J Thomas
    Abstract:

    An open comparative study of Gestrinone and danazol in the treatment of endometriosis demonstrated a similar decrease in the extent of active endometriotic deposits, assessed visually following therapy. Biochemical endocrinological changes during therapy with Gestrinone showed that basal concentrations of gonadotrophin remained unchanged, oestradiol concentrations varied and the free fraction of testosterone increased. A similar range of side effects was reported in both treatment groups, consisting predominantly of 'androgenic' effects in 10 of 15 women treated with Gestrinone and 5 of 12 treated with danazol. The results suggest that Gestrinone is an effective alternative agent for the treatment of endometriosis.

Valerio M Jasonni - One of the best experts on this subject based on the ideXlab platform.