Objective: To study the cell effects of raloxifene on uterine and leiomyoma tissue in postmenopausal women. Design: Prospective, randomized, double-blind, placebo-controlled study. Setting: Department of Obstetrics an...Objective: To study the cell effects of raloxifene on uterine and leiomyoma tissue in postmenopausal women. Design: Prospective, randomized, double-blind, placebo-controlled study. Setting: Department of Obstetrics and Gynecology, University “ Magna Graecia” of Catanzaro, Italy. Patient(s): Forty postmenopausal women affected by uterine leiomyomas and selected for hysterectomy. Intervention(s): Treatment for three cycles of 28 days with raloxifene at a dose of 180 mg/day orally (raloxifene group) or placebo tablets (3 tablets/day orally)-(placebo group). Main Outcome Measure(s): Uterine and leiomyoma dimensions were measured in each subject at entry and before surgery. On leiomyomas and homologous myometrium the proliferating cell nuclear antigen (PCNA)--positive cells/total cells (PCNA/TC) and the Bcl-2-positive cells/Bax-positive cells (Bcl-2/Bax) ratios (% ), as proliferation and apoptotic indexes, respectively, were measured. Result(s): After treatment, uterine and leiomyoma sizes were significantly changed in comparison with baseline and the placebo group. PCNA/TC and Bcl-2/Bax ratios were significantly higher in leiomyomas than in homologous myometrium. A significant difference was detected in PCNA/TC between the myometrium of the raloxifene and control groups, whereas no difference was observed in the Bcl-2/Bax ratio. A significant difference in PCNA/TC and Bcl-2/Bax ratios was detected in leiomyoma tissue between the raloxifene group and controls. Conclusion(s): In postmenopausal women, raloxifene administration reduces uterine leiomyomas by exerting a cell antiproliferative and proapoptotic action.展开更多
Objective: To study the effect of estrogen and tamoxifen on chemotherapeutic sensitivity in ER(+) endometrial carcinoma cells.Methods: DNA fragmentation as the criteria for apoptotic cell death was used to evaluate th...Objective: To study the effect of estrogen and tamoxifen on chemotherapeutic sensitivity in ER(+) endometrial carcinoma cells.Methods: DNA fragmentation as the criteria for apoptotic cell death was used to evaluate the value of estrogen, tamoxifen and adriamycin in ER(+) endometrial carcinoma cells. DNA fragmentation was measured with the cell death ELISA.Results: Adriamycin and tamoxifen could induce apoptosis in ER(+) endometrial carcinoma cell. The cell apoptosis level was decreased with the increasing of 17-β-estradiol concentration (P<0.001) and was inversely proportional to 17-β-estradiol concentration (IgM) (P<0.01). The cell apoptosis level was increased with the increasing of tamoxifen concentration (P<0.01) and was also directly proportional to tamoxifen concentration (IgM). Furthermore, the cell apoptosis level was increased significantly after treated with both tamoxifen and adriamycin.Conclusion: Estrogen may block apoptosis induced by adriamycin in ER(+) endometrial carcinoma cell. Tamoxifen can increase the sensitivity of endometrial carcinoma cell to adriamycin. Tamoxifen combined with chemotherapeutic drug may be of significant therapeutic benefit in ER(+) endometrial carcinoma. Key words endometrial carcinoma - estrogen - tamoxifen - adriamycin - cell apoptosis展开更多
Objective： To investigate a possible mechanism responsible for anti-apoptotic effects of melatonin and provide theoretical evidences for clinical therapy. Methods： lschemia-reperfusion mediated neuronal cell injury ...Objective： To investigate a possible mechanism responsible for anti-apoptotic effects of melatonin and provide theoretical evidences for clinical therapy. Methods： lschemia-reperfusion mediated neuronal cell injury model was constructed in cerebellar granule neurons （CGNs） by deprivation of glucose, serum and oxygen in media. After ischemia, melatonin was added to the test groups to reach differential concentration during reperfusion. DNA fragmentation, mitochondrial transmembrane potential, mitochondrial cytochrome c release and caspase-3 activity were observed after subjecting cerebellar granule neurons to oxygen-glucose deprivation （OGD）. Results： The results showed that OGD induced typical cell apoptosis change, DNA ladder and apoptosis-related alterations in mitochondrial functions including depression of mitochondrial transmembrane potential （its maximal protection ratio was 73.26%） and release of cytochrome c （its maximal inhibition ratio was 42.52%） and the subsequent activation of caspase-3 （its maximal protection ratio was 59.32%） in cytoplasm. Melatonin reduced DNA damage and inhibited release of mitochondrial cytochrome c and activation of caspase-3. Melatonin can strongly prevent the OGD-induced loss of the mitochondria membrane potential. Conclusion： Our findings suggested that the direct inhibition of mitochondrial pathway might essentially contribute to its anti-apoptotic effects in neuronal ischemia-reperfiusion.展开更多
文摘Objective: To study the cell effects of raloxifene on uterine and leiomyoma tissue in postmenopausal women. Design: Prospective, randomized, double-blind, placebo-controlled study. Setting: Department of Obstetrics and Gynecology, University “ Magna Graecia” of Catanzaro, Italy. Patient(s): Forty postmenopausal women affected by uterine leiomyomas and selected for hysterectomy. Intervention(s): Treatment for three cycles of 28 days with raloxifene at a dose of 180 mg/day orally (raloxifene group) or placebo tablets (3 tablets/day orally)-(placebo group). Main Outcome Measure(s): Uterine and leiomyoma dimensions were measured in each subject at entry and before surgery. On leiomyomas and homologous myometrium the proliferating cell nuclear antigen (PCNA)--positive cells/total cells (PCNA/TC) and the Bcl-2-positive cells/Bax-positive cells (Bcl-2/Bax) ratios (% ), as proliferation and apoptotic indexes, respectively, were measured. Result(s): After treatment, uterine and leiomyoma sizes were significantly changed in comparison with baseline and the placebo group. PCNA/TC and Bcl-2/Bax ratios were significantly higher in leiomyomas than in homologous myometrium. A significant difference was detected in PCNA/TC between the myometrium of the raloxifene and control groups, whereas no difference was observed in the Bcl-2/Bax ratio. A significant difference in PCNA/TC and Bcl-2/Bax ratios was detected in leiomyoma tissue between the raloxifene group and controls. Conclusion(s): In postmenopausal women, raloxifene administration reduces uterine leiomyomas by exerting a cell antiproliferative and proapoptotic action.
文摘Objective: To study the effect of estrogen and tamoxifen on chemotherapeutic sensitivity in ER(+) endometrial carcinoma cells.Methods: DNA fragmentation as the criteria for apoptotic cell death was used to evaluate the value of estrogen, tamoxifen and adriamycin in ER(+) endometrial carcinoma cells. DNA fragmentation was measured with the cell death ELISA.Results: Adriamycin and tamoxifen could induce apoptosis in ER(+) endometrial carcinoma cell. The cell apoptosis level was decreased with the increasing of 17-β-estradiol concentration (P<0.001) and was inversely proportional to 17-β-estradiol concentration (IgM) (P<0.01). The cell apoptosis level was increased with the increasing of tamoxifen concentration (P<0.01) and was also directly proportional to tamoxifen concentration (IgM). Furthermore, the cell apoptosis level was increased significantly after treated with both tamoxifen and adriamycin.Conclusion: Estrogen may block apoptosis induced by adriamycin in ER(+) endometrial carcinoma cell. Tamoxifen can increase the sensitivity of endometrial carcinoma cell to adriamycin. Tamoxifen combined with chemotherapeutic drug may be of significant therapeutic benefit in ER(+) endometrial carcinoma. Key words endometrial carcinoma - estrogen - tamoxifen - adriamycin - cell apoptosis
文摘Objective： To investigate a possible mechanism responsible for anti-apoptotic effects of melatonin and provide theoretical evidences for clinical therapy. Methods： lschemia-reperfusion mediated neuronal cell injury model was constructed in cerebellar granule neurons （CGNs） by deprivation of glucose, serum and oxygen in media. After ischemia, melatonin was added to the test groups to reach differential concentration during reperfusion. DNA fragmentation, mitochondrial transmembrane potential, mitochondrial cytochrome c release and caspase-3 activity were observed after subjecting cerebellar granule neurons to oxygen-glucose deprivation （OGD）. Results： The results showed that OGD induced typical cell apoptosis change, DNA ladder and apoptosis-related alterations in mitochondrial functions including depression of mitochondrial transmembrane potential （its maximal protection ratio was 73.26%） and release of cytochrome c （its maximal inhibition ratio was 42.52%） and the subsequent activation of caspase-3 （its maximal protection ratio was 59.32%） in cytoplasm. Melatonin reduced DNA damage and inhibited release of mitochondrial cytochrome c and activation of caspase-3. Melatonin can strongly prevent the OGD-induced loss of the mitochondria membrane potential. Conclusion： Our findings suggested that the direct inhibition of mitochondrial pathway might essentially contribute to its anti-apoptotic effects in neuronal ischemia-reperfiusion.
