Epithelial ovarian cancer, which is one of the most lethal gynecological tumors, is also the biggest dififculty in the diagnosis and treatment of obstetrics and gynecology. In addition to the lack of early clinical symptoms and effective diagnostic methods, the reason includes the lack of accurate and comprehensive understanding of the development of epithelial ovarian cancer. Thus a lot of research aimed at better grasp of its pathogenesis, which is expected in the future progress of its diagnosis and treatment. Currently, three pathogenesis of epithelial ovarian cancer widely accepted are high gonadotropin theory, “dualism” hypothesis and stem cell hypothesis. This study discussed the theory above.

Objective To examine the expressions of glyoxalase Ⅰ (GLO-Ⅰ ) in endometrial cancer tissues and cell lines and to investigate the roles of GLO-Ⅰ on proliferation and apoptosis in endometrial cancer cells. Methods Immunohistochemistry, western blot and RT-PCR were used to investigate the expressions of GLO-Ⅰ protein and mRNA in endometrial cancer tissues and Ishikawa cell lines ;enzyme activity of GLO-Ⅰ in normal endometrium, endometrial cancer and paraneoplastic tissue samples was detected with spectrophotometer; proliferation and apoptosis of Ishikawa cell before and after RNA interference (RNAi) procedure were detected by the methyl thiazolyl tetrazolium (MTT) and flow cytometry, respectively. Results (1)There were significant differences of GLO-Ⅰ expression between normal endometrium (0/19) and endometrial cancer tissues ( 76%, 22/29 ); these were also significant differences of enzyme activity of GLO-Ⅰ among normal endometrium, paraneoplastic and endometrial cancer tissues( 1.1,0.8 vs 92.3 IU/mg; P <0.01 ). Enzyme activity of GLO-Ⅰ in fresh normal endometrium and paraneoplastic tissues was weak, while that of fresh endometrial cancer tissues was as high as 92. 3 IU/mg in average. (2)The expression of GLO-Ⅰ mRNA in Ishikawa cell transfected with GLO-Ⅰ siRNA was significantly lower than that in negative group (0.25 ± 0.06 vs 0.93 ± 0.10, P < 0.0l ), and the similar results that in the expression of GLO-Ⅰ protein (0.38 ±0.06 vs 0.94 ±0.13, P <0.01 ). (3) Proliferation in Ishikawa cell was significantly inhibited after silencing RNA expression of GLO-Ⅰ ( P = 0.028 ). The apoptosis rate of cells transfected with GLO- Ⅰ siRNA was significantly higher than that of negative control group and blank control group [ ( 6.7 ± 0.8 ) % vs ( 1.2 ± 0.4) %, ( 1.4 ± 0.4 ) %; P < 0.01 ]. Conclusion The expression and enzyme activity of GLO- Ⅰ is significantly increased in endometrial cancer, which could promote abnormal proliferation and inhibit apoptosis in endometrial cancer cells.

Objective To investigate natural spontaneous menopausal age , menstruation span and their relationship with menarche age and parity in Pudong district of Shanghai. Methods From Jan 2007 to Jul 2008, 15 083 spontaneous menopause women undergoing cervical cancer screening were enrolled in this study. The questionnaire included menarche age, parity, spontaneous menopausal age and menstruation span. Those women were divided into four groups based on age, which were group of 56 -60, 61 -65, 66 -70 and more than 70. Analysis of variance (ANOVA) was used for comparing difference between menopausal age and menstruation span. Multiple factor regressions was used to analyze the relationship between menarche age, parity and menopausal age and menstruation span. Results (1) Spontaneous menopausal age: the minimum was 29 years old, the maximum was 61 years old, and the mean age was (50.6 ±3.7)years old. The mean spontaneous menopause age were (50.9 ± 3.4), ( 50.7 ± 3.7 ), (50.0 ± 4.1 ), (49.6 ±4.0) years in groups of 56 -60, 61 -65, 66 -70 and more than 70 years. With the increasing age range in four groups, the increasing trends of menopausal age were observed, which the difference of 1.36 year was shown between groups of 56 - 60 and more than 70 years. (2) Menstruation span: the mean of menstruation span was (34.3 ± 4.1 ) years, which the minimal age of 12 years and maximal age of 48 years were recorded. (34.6 ± 3.8), (34.3 ± 4.1 ), (33.9 ± 4.6), (33.2 ± 4. 5) were observed in groups of 56 - 60,61 -65, 66 -70 and more than 70 years. With the increasing age range in four groups, the increasing trends of menstruation span were observed, which the difference of 1.41 year was shown between groups of 56 –60 and more than 70 years. (3)The impact of menarche age on menopausal age and menstruation span: there was no correlation between menarche age and menopausal age ( r = 0.02); however, menstruation span was found to be negatively correlated with the menarche age ( r = - 0.43 ). (4) The impact of parity on menopausal age and menstruation span: the mean menopausal age of women who had 1 -2 deliveries was significantly higher than those had no delivery or more than 3 deliveries ( P < 0.05 ). However, there was no difference in menopausal age between women with 1 and 2 deliveries or between women without delivery and more than 3 deliveries (P > 0.05). Menstruation span of women with 1 delivery was significantly longer that those with more than 1 delivery( P < 0.05 ), similarly, women with 2 deliveries had longer menstruation span than women without delivery or more than 3 deliveries(P < 0.05 ). There were no difference in menstruation span between women with more than 3 deliveries and without delivery ( P >0.05 ). (5) Multifactor regression analysis for menstruation span: menarche age was correlated with menstruation span negatively ( r = - 0.97,P <0.001 ). There was significantly different menstruation span between group of 61 -65, 66 -70 or more than 70 years and group of 56-60 (r= -0. 18, P=0.020; r= -0.78,P <0.001 and r= - 1.23,P<0.001). Menstruation span in women with 1 -2 deliveries was significantly longer than that of women without delivery or more than 3 deliveries. (6)Multifactor logistic analysis of menopausal age: there was no association between menarche age and menopausal age, however, significant differences were found in mean menopausal age between different groups, which show that menopausal age of group 56 - 60 years was significant higher than the other groups, including age-group 61 -65 years ,66 -70 years and over 70 years ( r = - 0.18, P = 0.020; r = - 0.78,P < 0.001; r = - 1.23, P < 0.001 ). Menopausal age in women with 1 - 2 deliveries was significantly higher than those of women without delivery or with more than 3 deliveries,however, no difference between women with 1 and 2 deliveries or between women without deliveries and more than 3 deliveries was observed. Conclusion (1) Menopausal age and menstruation span exhibited increasing trends in Pudong district of Shanghai. (2) Menarche age and parity were the important factors influencing menopausal age and menstruation span. (3) With younger age of menarche, the menstruation span become longer. (4) Deliveries of 1 -2 times can significantly delay the menopause and prolong menstruation span, however, the multiple deliveries ( ≥ 3 times) had no significant impact on menopausal age and menstruation span.

Objective:To compare the therapeutic and toxic profile of topotecan given intraperitoneally with intravenously in human ovarian cancer xenografted into athymic nude mice.Methods: Eighty female Balb-c/nu-nu mice were randomized assigned into eight groups (n=10). Xeneografts resulted from intramesentery injection of cultured human ovarian cancer cells SKOV3 in athymic mice. Onset of intraperitoneal treatment with either topotecan or cisplatin (7.5 mg/kg) was on day 7. Animals scheduled for topotecan i.p. received intraperitoneal application of topotecan (1.5 mg/kg×2, 3.0 mg/kg×2, 6.0 mg/kg×2 or 10.0 mg/kg×1). Animals scheduled for topotecan i.v. received intravenous administration of topotecan (6.0 mg/kg×2 or 10.0 mg/kg×1). Two weeks after drug application animals were killed. Tumor growth inhibition were assessed and compared with untreated mice and cisplatin intraperitoneally administered mice. Acute toxicity was determined by loss of body weight. Cell cycle division and apoptosis after drug administration was determined by flow cytometric analysis.Results: In a panel of ten tumour xenografts, intraperitoneal topotecan was significantly more effective than intravenous administration. The toxicity profile suggested a better tolerability in terms of weight loss after intraperitoneal administration than cisplatin control. Topotecan 10.0 mg/kg i.p. per day (1 day) schedule was an optimal treatment for ovarian cancer and well tolerated by mice with no signs of acute toxicity. Topotecan and cisplatin induce cells G0-G1 arrest and apparent apoptosis. No significant difference among mice treated with topotecan intraperitoneally or intravenously or cisplatin was observed in term of apoptosis and cell cycle perturbation.Conclusion:The results may have implications for the future design of clinical studies on intraperitoneal application of topotecan. It suggests that apoptosis and cell cycle perturbation play an limited role in the mechanism of topotecan administration.

With the emergence of new concepts, methods and techniques in modern medicine, the basic research and clinical treatment for gynecological oncology has rapidly developed in the past couple of years. Evidence-based medicine, individualized therapy and microinvasive therapy give us more opportunities to treat the patient. Nowadays, it is possible for the clinic to implement new approaches to improve the outcome and the quality of life for the patients with minimal side effects at the same time. There has been a lot of reports from in vitro studies suggesting that gonadotrophin may play an important role in tumorigenesis, estrogen may promote tumor cell proliferation through PAX2 gene. Survivin, a protein serving as an apoptosis inhibitor, may be crucial for the regulation of tumor cell proliferation and apoptosis.

Background and purpose:Choriocarcinoma is a highly malignant tumor,which metastasis could occur at early stage,the molecular mechanism is still under investigation.DLX4 is a member of homeodomain transcriptional factors,and its abnormal expression has a close correlation with mammary cancer,colon caner and so on.Based on our previous study that DLX4 was highly expressed in choriocarcinoma JEG-3 cell lines,we used RNAi to knock down the expression of DLX4,and aimed to explore the effect of DLX4 on the adhesion,movement and invasion ability of choriocarcinoma cells.Methods:DLX4 siRNA and control siRNA plasmid were constructed and transfected into choriocarcinoma cell line JEG-3 cells with LipofectamineTM2000.JEG-3 cells that expressed high level of DLX4 siRNA and control siRNA plasmid were selected and maintained with G418.The effect of RNAi was detected by western blot,and then the adhesion,movement and invasion ability of JEG-3 cells were investigated by cell-ECM adhesion assay,Transwell chamber and Transwell-Matrigel model,respectively.Results:DLX4 RNAi inhibited DLX4 protein expression specifically and effectively.The adhesion rate of the cells in JEG-3 siDLX4 group was(30.6?4.2)%,which was significantly less than(57.2?4.0)% in JEG-3 without transfenction and(51.6?3.9)% in JEG-3 scDLX4 groups(P0.05).Conclusions:The knock-down of DLX4 by RNAi could prevent the adhesion and invasion ability of choriocarcinoma cells,which provides a new thought for further research in invasion and metastasis of choriocarcinoma.

OBJECTIVETo identify an effective auxiliary therapy for epithelial ovarian cancer.

METHODSProgesterone acetate given at 250 mg intramuscularly twice a week for 1 month followed by increased administration to 500 mg intramuscularly every two weeks for 3 years was used in combination with platinum based chemotherapy to treat patients with epithelial ovarian cancer as a first-line therapy. Prognoses of the patients receiving progesterone combined with chemotherapy (progesterone group) and those receiving chemotherapy only (control group) were compared.

RESULTSThree-year recurrence and survival conditions of the progesterone and control groups were as follows. Stage Ia: no patient relapsed or died in either group. Stage Ib-Ic: three-year recurrence rates were 14.2% and 37.5%, respectively (P = 0.2845); three-year survival rates were 92.3% and 87.5% (P = 0.7221). Stage II: 1 patient relapsed and died among the 3 patients in the progesterone group; among the 4 patients in the control group, 1 patient relapsed, none died. Stage III: three-year recurrence rates were 30.8% and 64.3%, respectively (P = 0.1170); three-year survival rates were 85.7% and 42.9%, respectively (P = 0.005). Stage IV: 4 patients relapsed and 1 patient died among the 7 patients in the progesterone group; both the patients in the control group relapsed and died.

CONCLUSIONSThe results indicated that progesterone combined with platinum based chemotherapy as a first-line therapy may improve the prognosis of advanced epithelial ovarian cancer, but would not change the prognosis of early stage epithelial ovarian cancer.

Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; administration & dosage ; Female ; Humans ; Middle Aged ; Neoplasm Recurrence, Local ; Neoplasm Staging ; Neoplasms, Glandular and Epithelial ; drug therapy ; mortality ; pathology ; Ovarian Neoplasms ; drug therapy ; mortality ; pathology ; Progesterone ; administration & dosage ; Survival Rate

Objective To assess the efficacy of ultrasound contrast agent Levovist in evaluating vascularization of ovarian tumors.Methods Nineteen ovarian lesions (seven benign ovarian tumors,twelve malignant ovarian tumors) were submitted to color Doppler flow imaging (CDFI) before and after i.v.Levovist for examining their vascularization,including the number of blood vessel,vessel torsion and Doppler signal enhancement. And then receiver operator characteristic(ROC) curves were established.Results Compared to benign tumors',after contrast color Doppler signals in malignant tumors enhanced obviously and character characteristic vessel morphologies were observed.Vessel numbers and tortuosity increased obviously.Doppler signal enhancement appeared earlier,arrival to peak enhancement was quicker,and duration longer.ROC showed time to commencement for the enhancement ≤50 s,time to peak ≤100 s and enhancement duration ≥400 s,at which the sensitivity and specificity were the highest.Conclusions Levovist,as a contrast agent, increases the intensity of color Doppler signals obviously,and allows a more complete display of the vascular patterns of ovarian tumor.It improves markedly the role of CDFI in the diagnosis and differentiation of ovarian tumors.

OBJECTIVETo investigate the effects of sulindac metabolites on proliferation and apoptosis in the human umbilical vein endothelial cell line ECV304 in vitro.

METHODSThe proliferation profile of ECV304 was determined by methyl thiazolyl tetrazolium (MTT) method. Cell cycle distribution, apoptosis and the ultrastructure of ECV304 were detected by flow cytometry (FCM) and electron microscopy, respectively.

RESULTSMTT assay showed that the sulfide inhibited the proliferation of ECV304 and its effect was dose-dependent; the IC(50) was 200 micromol/L. FCM showed that the sulfide changed cell cycle distribution. The cell cycle distribution was as follows: G(1) phase (control group 77.74% +/- 1.58%; sulfone group 75.63% +/- 2.12%; sulfide group 46.12% +/- 1.60%); S phase (control group 13.64% +/- 1.22%; sulfone group 16.40 +/- 2.30%; sulfide group 27.26% +/- 2.08%); G(2)-M phase (control group 8.61% +/- 0.67%; sulfone group 7.98% +/- 0.49%; sulfide group 26.62% +/- 3.54%). The apoptosis rates in the control group, sulfone group and sulfide group were 6.08% +/- 3.39%, 4.81% +/- 2.14% and 51.90% +/- 5.67%, respectively. Sulfide reduced the proportion of G(1) phase, increased the proportion of S phase, G(2)-M phase and the apoptosis rate significantly (P < 0.01, vs control). In the sulfide-treated cells, there were nuclear fragmentation and chromosomal condensation, shrinkage of the cell and loss of contact with neighboring cells. Apoptotic bodies were observed. Sulfone showed no effect on cell proliferation, cell cycle distribution or cell morphology.

CONCLUSIONSSulfide can significantly reduce the proliferation of ECV304, change the cell cycle distribution and arrest cells in G(2)-M phase where apoptosis may be induced. Sulfone has no such effects on this cell line.

Angiogenesis Inhibitors ; pharmacology ; Anti-Inflammatory Agents, Non-Steroidal ; pharmacology ; Apoptosis ; drug effects ; Cell Cycle ; drug effects ; Cell Division ; drug effects ; Cell Line ; Dose-Response Relationship, Drug ; Endothelium, Vascular ; cytology ; drug effects ; ultrastructure ; Humans ; Microscopy, Electron ; Sulindac ; analogs & derivatives ; pharmacology ; Umbilical Veins

Purpose:Our study is to find out the inhibitory action of recombinant human TNF-related apoptosis-inducing ligand(TRAIL) on ovarian cancer cell line cultured in vitro. Methods:MTT was applied to assay the inhibiting action of various concentration of TRAIL on two ovarian cancer cell lines of 3AO and HO-8910.The apoptosis rates were measured by flow cytometry. Results:The growth of human ovarian cancer cells was effectively inhibited by TRAIL. A clear dose- and time-dependent correlation between TRAIL concentration and the degree of apoptosis induction was observed with up to 43.20% apoptotic cells after 24 h of incubation with 50 ng/ml TRAIL. The cells assumed typical cell apoptosis configuration. Conclusions:TRAIL can effectively inhibit the growth of ovarian cancer cells and induce apoptosis of the cells.