To investigate the expression of P-glycoprotein (P-gp) and multidrug resistance- associated protein (MRP) and the relationship with cell cycle profiles in ovarian cancer SK-OV-3ip1 multicellular aggregates. Methods: Liquid overlay system was employed to obtain multicellular aggregates. Expression of P-gp and MRP was detected with flow cytometry (FCM). Outer, intermediate and inner cells from multicellular aggregates were collected by layer-trypsinized method. Cell cycle profiles were also analyzed by FCM. Results: Compared with control cells, no expression of P-gp and MRP was detected in monolyer cells (P=0.128 and P=0.604), but expression of P-gp and MRP in aggregate cells was significantly elevated (P<0.01). P-gp expression in every layer cells was also obviously increased (P<0.01). Furthermore, P-gp expression in every layer cells was also obviously increased (P=0.071). Tendency to increased G0-G1 phase and reduced S phase cells existed from outer through intermediate to inner layers in multicellular aggregates but with no statistical difference. Cell percentages in G2-M phase also had no difference. However, compared with monolayer cells, cells in G0-G1 phase increased and cells in S and G2-M phases lowered significantly in every layer and in the whole multicellular aggregates. Expression elevation of P-gp and MRP was consistent with increased G0-G1 percentage in aggregate cells. Conclusion: Expression of P-gp and MRP increases in cells of SK-OV-3ip1 multicellular aggregates and is consistent with increased G0-G1 percentage, which implies the possible relationship between them and the possible role in multicellular-mediated drug resistance.

Ovarian cancer is one of the most lethal malignant gynecological tumors. More than 70%of patients with ovarian cancer are diagnosed at advanced stage. The 5-year survival in patients with advanced ovarian cancer is less than 30%because of the lack of effective biomarkers for diagnosis, prognosis, and personalized treatment. MicroRNA (miR) is a class of small noncoding RNAs that negatively regulate gene expression primarily through post-transcriptional repression. Many studies on tissue miR in ovarian cancer have been carried out and show great potential in clinical practice. However, tissue samples are not easily available because sampling causes injury. Researchers have started to focus on plasma/serum miR, assuming that blood samples may replace tissue samples in miR research in the future. Plasma/serum miR research is still in its early stages. Studies on its function in the early diagnosis of ovarian cancer have achieved some progress, but plasma/serum miR profiling for prognosis and personalized treatment of ovarian cancer remains unknown. A thorough understanding of the function of plasma/serum miR in ovarian cancer will facilitate early diagnosis and improve treatment for ovarian cancer.

Objective:To identify differentially expressed long non-coding RNAs (lncRNAs) involved in the metastasis of epithelial ovarian cancer.
Methods:An in vitro invasion assay was performed to validate the invasive capability of SKOV3 and SKOV3.ip1 cell lines. Total RNA was then extracted, and microarray analysis was performed. Moreover, nine lncRNAs were selected for validation using RT-qPCR.
Results:Compared with the SKOV3 cells, the SKOV3.ip1 cells significantly improved in the in vitro invasive activity. Of the 4,956 lncRNAs detected in the microarray, 583 and 578 lncRNAs were upregulated and downregulated, respectively, in SKOV3.ip1 cells, compared with the parental SKOV3 cells. Seven of the analyzed lncRNAs (MALAT1, H19, UCA1, CCAT1, LOC645249, LOC100128881, and LOC100292680) confirmed the deregulation found by microarray analysis. Conclusion:LncRNAs clusters were differentially expressed in ovarian cancer cells with varying metastatic potentials. This result indicates that some lncRNAs might exert a partial or key role in epithelial ovarian cancer metastasis. Further studies should be conducted to determine the roles of these lncRNAs in ovarian cancer metastasis.

Objective:To study the diagnostic value of multiple tumor markers in malignant ovarian neoplasm.Methods:Sera obtained from 430 patients with ovarian masses (110 cases were malignant ovarian tumors,320 cases were benign ovarian tumors) before operation,and from 50 healthy women as control.Serologic examination of tumor markers included CA125,TSGF,SA,CEA,AFP,HCG and Fer.Results:The serum levels of CA125,TSGF,SA and Fer in patients with ovarian cancer were higher than those in patients with benign ovarian tumors (P<0.05),also in control group (P<0.05).In the diagnostic value of application for malignant ovarian neoplasm,CA125,TSGF and SA were better than the others.The sensitivity,specificity and accuracy in diagnosis of ovarian cancer were 86.4%,82.8%and 83.7% respectively for CA125 alone,78.2%,81.3%and 80.5% for TSGF alone,74.5%,81.9%and 80.0% for SA alone,whereas 95.5%,45.6%and 58.4% for multiple tumor markers combined in which 1 or more indices showed positive,93.6%,80.6%and 84.0% for that in which 2 or more indices showed positive,and 87.3%,90.3%and 89.5% for that in which 3 or more indices show positive.Conclusion:multiple tumor markers examination could improve the diagnosis of ovarian cancer,and examination of CA125,TSGF and SA combined is most ideal.

Objective:To investigate the role of mitochondria in sodium butyrate-induced apoptosis of ovarian carcinoma cells in vitro.Methods:Human ovarian epithelial cancer 3AO cells were cultured in vitro and treated with sodium butyrate of different concentration for different time. The characters of apoptosis were assessed through light microscopy and DNA ladder analysis. The morphological changes of mitochondria were detected through electron and epifluorescence microscopy. The functional changes of mitochondria and the expression of Bcl-2/Bax protein were analyzed by flow cytometry.Results:As the concentration of sodium butyrate rose to 4mmol/L, the morphologic characters of apoptosis were found by light microscopy, DNA ladder was observed. Under epifluorescence microscope the fluorescence of the control group was stronger than that of the experimental group. Under electron microscope swelled mitochondria was detected. Flow cytometry analysis showed mitochondria transmembrane potentials decreased and there were down-regulate of Bcl-2 protein and up-regulate of the Bax protein(P＜0.05).Conclusion:Sodium butyrate can induce apoptosis of 3AO cells in a time-dose dependent manner. Mitochondrion may play a key role in the procedure of apoptosis of ovarian cancer cells.

Objective: To investigate the cellular immunity response in vitro and the tumorigenecities in vivo of mB7-1 gene transfected murine ovarian cancer cell line. Methods: mB7-1 gene was transfected into the NuTu-19 cell line by retrovirus vector, and the expression of mB7-1 gene was confirmed by flow cytometry(FCM).NuTu-19/neo and NuTu-19/mB7-1 cells were injected subcutaneously into syngeneic Fischer 344 rats respectively, and their tumorigenecities were recorded. Proliferation indices of lymphocyte were assayed after syngenieic mixed tumor-lymphocyte cultures(MTLCs). The lysis activity of CTL toward tumor cells was determined using methyl thiazolyl tetrazolium(MTT) assay. Results: Successful transfection of mB7-1 gene into NuTu-19 cell line was comfirmed with FCM. In vitro study showed that there was no obvious changes in cell growth of gene transfected cell line, compared with the cell line NuTu-19. NuTu-19/mB7-1 cells could induce more effective proliferation of effector lymphocytes( P ＜ 0.05). The lysis activity of CTL activated by NuTu-19/mB7-1 was stronger than that of NuTu-19/neo ( P ＜ 0.01). Tumor sizes were smaller in the NuTu-19/mB7-1 receptance syngeneic Fischer 344 rats compared with those in the control group. Conclusion: mB7-1 genetically modified ovarian cancer cells could induce the cellular immunity response in vitro and the tumorigenecitiy of NuTu-19 cells was decreased after inoculation with the experimental vaccine.

Objective: To compare the pharmacokinetics of the routine intraperitonealchemotherapy (RIP) and continuous washing intraperitoneal chemotherapy (CWIP) of cisplatin(CDDP) in 38 patients with ovarian cancer. Methods: The patients had a performance status ofⅡ -Ⅳ on the FIGO scale.38 patients were randomized into CWIP group (16 patients) and RIP group(22 patients). CDDP was used as intraperitoneal chemotherapy (IP) with 70mg/m2. In 72h, thesamples from serum, ascites and urine were collected respectively and their platinum density weredetermined with electrochemistry polarographic analysis. On the third day and one month after IP,liver and kidney function and blood routine were examined. Results: The maximum concentration(Cmax) of plasma in CWIP and RIP groups were 3.84μg/ml and 1.27μg/ml respectively;the Cmaxof ascites were 7.04μg/ml and 4.43μg/ml respectively in the two groups. The area under the plas-ma concentration-time curve(AUC) in CWIP and RIP groups were 1067.77μg. h/ml and 191.72μg.h/ml respectively,and 1299.02μg. h/ml and 584.43μg. h/ml in ascites,their statistics dif-ference were significant ( P ＜ 0.05). Conclusion: CWIP is better than the RIP in the pharmacoki-netics, while its side-effects is not increased. The new methods may be used on the patients.

Objective:The histological types of ovarian tumors were investigated and analyzed in China in order to compare with those in other countries,which will benefit to the prevention and treatment of ovarian cancer.Methods:The pathological data from 42 197 cases of ovarian tumors in ten years during 1980 to 1989 were registered according to the WHO classification for ovarian tumors. Some indefinite cases pathologically in the first diagnosis should bereconfirmed according to the WHO classification.Results: Forty-two thousand one hundred and ninety seven cases ofovarian tumors were selected from all tumors in 21 provinces and 3 major regional cities in China.There were 10 288(24.4%) malignant tumors in all cases.They were composed by 5 650(54.9%) cases of epithelial tumors,1 871(18.2%) cases of germ cell tumors,837(8.5%) cases of sex cord tumors,1 003(9.7%) cases of secondarytumors,and 891(8.7%) cases of other tumors.The malignant tumors constituent ratios were 58.5% and 50.9% respectively in the north and south of the Yangtze River..The histological types of ovarian tumors were about the same ratios,but the malignant tumors were different in Chinese six major administrative region andalso in the region both north and south of the Yangtzy River.The ratio of borderline epithelial ovarian tumors to epithelial tumors was 1:5.9.Borderlineserous cystadenocarcnoma appeared to be similar to borderline mucinous cystadenocarcinoma in frequency.Serous cystadenocarcinoma was found to be the most frequent one in malignant epithelial tumors.Conclusion:Compared with reports abroad,the different types of malignant ovarian tumors inChina represent a different distributive pattern.The malignant epithelial ovarian tumors were lower than that in other countries (55% vs 80%-90%),while the malignant germ cell tumors and sex cord stromal tumors were 6 and 3 times higher thanthose abroad,the main metastasizing tumors come from gastroenteric carcinoma,while the metastasizing tumors from breast cancer were only 2.5%.