Expression of C-Kit & PDGFRα and correlation with chemotherapy resistance in ovarian serous carcinomas:a clinical study

Objective： To investigate the expression of C-Kit and PDGFRa and their correlation with chemotherapy resistance in ovarian serous carcinoma. Methods： We undertook SP immunohistochemical technique to examine the expression of C-Kit and PDGFRa in 59 cases with ovarian serous carcinomas, using archival paraffin-embedded specimens. Then we observed the correlation with chemotherapy resistance. Results： C-Kit and PDGFRa immunostainings were observed posi- tively expressed in 57.63% and 66.10% cases. C-Kit expression was statistically correlated with the progression of disease after first-line chemotherapy （P 〈 0.05）, but PDGFRa was not statistically significant （P 〉 0.05）. There were great difference between of C-Kit and PDGFRa expressions in samples of different differentiated and clinical stages of ovarian serous carcinomas （P 〈 0.01 or P 〈 0.05）. Conclusion： C-Kit is statistically correlated with chemotherapy resistance, while PDGFRa is not correlated.

Primary Ovarian Small Cell Carcinoma of Pulmonary Type: Analysis of 6 Cases and Review of 31 Cases in the Literatures

Objective Primary ovarian small cell carcinoma of pulmonary type(SCCOPT)is a rare ovarian tumor with a poor prognosis.The platinum-based chemotherapy is the standard treatment.However,there is little research on the clinical characteristics of SCCOPT and the potential benefits of other treatments due to its low incidence.The study aims to investigate clinicopathological characteristics and treatment of SCCOPT.Methods We summarized the clinical,imaging,laboratorical and pathological characteristics of 37 SCCOPT cases,in which 6 cases were admitted to the Gansu Provincial Hospital from the year of 2008 to 2022 and 31 cases reported in 17 English and 3 Chinese literatures.Results The median age of the studied SCCOPT cases(n=37)was 56.00(range,22-80)years.Almost 80%of them had a stageⅢorⅣtumor.All patients underwent an operation and postoperative chemotherapy.Nevertheless,all cases had a poor prognosis,with a median overall survival time of 12 months.Immunohistochemical y,the SCCOPT of all patients showed positive expressions of epithelial markers,such as CD56 and sex-determining region of Y chromosome-related high-mobility-group box 2(SOX-2),and negative expressions of estrogen receptor,progesterone receptor,vimentin,Leu-7,and somatostatin receptor 2.The tumor of above 80%cases expressed synaptophysin.Only a few cases expressed neuron-specific enolase,chromogranin A,and thyroid transcription factor-1.Conclusions SCCOPT had a poor prognosis.SOX-2 could be a biomarker to be used to diagnose SCCOPT.

Related Study on the Nm23-H1 Gene Expression in the Model of Ovarian Carcinoma Cell Lines with High Frequent Metastasis

Objective: To select the ovarian carcinoma cell lines with high frequent metastasis and study the association between nm23-H1 gene expression and metastasis of ovarian carcinoma. Methods: Each ovarian cancer cell line was transplanted subcutaneously into the flank of nude mice, and the metastatic behavior was evaluated by counting lung tumor foci at different time points. The metastatic tumors were cultured in vitro, then substrain was established and transplanted subcutaneously three times. The RNA level of nm23 in 8 human ovarian cancer cell lines were examined by northern-blot. Results: Of the 8 human ovarian cancer cell lines, 4 had high requent metastatic potentiality. The expression of nm23 RNA in human ovarian cancer cells was inversely related to metastatic behavior in the experimental animals (r=0.96, P=0.0001). Conclusion: The difference of the tendency of metastasis which was determined by genetic and molecular levels was significant among different type of cell lines and subtypes. The expression of nm23 mRNA in human ovarian carcinomas was correlated closely with the reduced metastatic behavior in experimental animals and may serve as a sensitive prognostic indicator for ovarian cancer.

Clinical characteristics and survival of patients with normal-sized ovarian carcinoma syndrome: Retrospective analysis of a single institution 10-year experiment

BACKGROUND Normal size ovarian cancer syndrome(NOCS)is a challenge for clinicians regarding timely diagnosis and management due to atypical clinical and imaging features.It is extremely rare with only a few cases reported in the literature.More data are needed to clarify its biological behavior and compare the differences with abnormal size ovarian cancer.AIM To assess the clinical and pathological features of NOCS patients treated in our institution in the last 10 years and to explore risk factors for relapse and survival.METHODS Patients who were pathologically diagnosed with NOCS between 2008 and 2018 were included.Papillary serous ovarian carcinoma(PSOC)patients were initially randomly recruited as the control group.Demographics,tumor characteristics,treatment procedures,and clinical follow-up were retrospectively collected.Risk factors for progression-free survival and overall survival were assessed.RESULTS A total of 110 NOCS patients were included;80(72.7%)had primary adnexal carcinoma,two(1.8%)had mesotheliomas,18(16.4%)had extraovarian peritoneal serous papillary carcinoma,and eight(7.3%)had metastatic tumors.Carbohydrate antigen(CA)125 and ascites quantity were lower in the NOCS cohort than in the PSOC group.The only statistically significant risk factors for worse overall survival(P<0.05)were the levels of CA199 and having fewer than six chemotherapy cycles.The 1-year,3-year,and 5-year survival rates were 75.5%,27.7%,and 13.8%,respectively.CONCLUSION The clinical symptoms of the NOCS group are atypical,and the misdiagnosis rate is high.Ascites cytology and laparoscopic exploration are valuable in the early diagnosis to avoid a misdiagnosis.The level of CA199 is the most important predictor of overall survival,and more than six cycles of chemotherapy contributes to the increased survival rates of NOCS patients.

THE ASSOCIATION OF THE EXPRESSION OF MTA1, NM23H1 WITH THE INVASION, METASTASIS OF OVARIAN CARCINOMA

Objective. To understanding the molecular mechanisms in invasion andmetastasis of the ovarian carcinoma, we investigate a novel candidate metastasis―associated gene (MTA1) and nm23Hl mRNA expression and mutation in ovarian carcinoma. Methods. Twenty primary ovariancarcinoma specimens, 20 corresponding lymph nodes and 8 normal ovarian was examined for mRNAexpression and mutation of MTA1 and nm23Hl genes by reverse-transcription ploymerase chain reaction(RT―PCR) and RT―PCR―SSCP analysis. The level of the expression was determined by the relativeoptic desity (ROD) of the PCR products. Results. The frequency of MAT1 overexpression was 100% (7/7)in primary ovarian carcinoma with metastasis but only 38.5% (5/13) in those without metastasis(P=0.0103). Overexpression of MAT1 was observed in 87.5% (6/7) of lymph nodes with metastasis butonly 23% (3/13). of lymph nodes without metastasis (P=0.0118). In contrast with MAT1, low expressionof nm23H1 mRNA was seen in 7 of 7 o-varian carcinoma with metastasis but only in 4 of 13(30%) ofthose without metastassis (P=0.0043). Low nm23H1 expression was also seen in 7 of 7 lymph nodes withmetastasis but only in 5 of 13 (38.5%) nonmetastatic lymph nodes (P=0.0102). The ROD ratio of MAT1to nm23Hl increased with the development of metastasis. No mutation of MAT1 and nm23H1 genes wasfound by SSCP analysis. Conclusion. The mRNA expression of MTA1 and nm23H1 is positively andnegatively correlated with lymph node metastasis, respectively. Expression abnormalities but notmutation of the two genes are frequent events related to lymph node metastasis of ovarian cancer.

Inhibitory Effects of Anti-sense PTTG on Malignant Phenotype of Human Ovarian Carcinoma Cell Line SK-OV-3

To construct eukaryotic expression vector expressing full length anti-sense pituitary tumor transforming gene (PTTG) mRNA and observe its blocking effect on the potential invasion of human ovarian carcinoma cell line SK-OV-3. PCR primers containing designed enzyme cut sites were used for cloning full-length PTTG gene fragment, and the resulting PCR product was inserted into the eukaryotic vector pcDNA3.1 in the antisense direction. The recombinant vector was then transfected into SK-OV-3 by Lipofectamine. The positive cell clone was screened by G418, PTTG and bFGF at protein level expression were detected by Western blot. The biological behavior change of transfection positive cells was observed by colony formation in soft agar assay. Our results showed that SK-OV-3 clones stably expressing full-length recombinant pcDNA3.1-PTTGas were obtained. The expressions of PTTG and bFGF protein in transfected cells were decreased by 61.5 % and 52.3%, respectively as compared with non-transfected ones. The number of colony formation was reduced significantly in transfected cells as compared with empty vector transfected and non-transfected cells. It is concluded that the recombinant vector pcDNA3.1-PTTGas is a novel tool and provides an alternative anti-sense gene therapy targeted at PTTG in human carcinoma.

The Relationship between p38MAPK and Apoptosis during Paclitaxel Resistance of Ovarian Cancer Cells

To investigate the relationship between p38 mitogen-activated protein kinase （p38MAPK） and cell apoptosis during the paclitaxel resistance of ovarian carcinoma cell lines, flow cytometry （FCM） and PI staining were employed to determine the effect of p38MAPK inhibitor SB203580 on the apoptosis of A2780/Taxol cells, a drug-resistant human ovarian carcinoma cell line. p38MAPK protein expression in SB203580-treated cells was immunochemically measured. The 50% inhibition concentration （IC50） of paclitaxel on A2780/Taxol cells was determined by MTT assay. MDR-1 mRNA, and expression of p38MAPK and phospho-p53 protein were detected by RToPCR and Western blotting, respectively. The apoptosis rate of A2780/Taxol cells was （19.7±1.04）% 24 h after SB203580 treatment. A significant difference in apoptosis rate was found among experiment group, control group and untreated group （p〈0.05）. The relative reversal rate of A2780/Taxol cells to paclitaxel was （57.18±2.01）%. As compared with the control group and the untreated group, p38MAPK protein and MDR-1 mRNA in SB203580-treated cells was substantially decreased. The expression of p53 protein was significantly increased. It is concluded that p38MAPK pathway is related to paclitaxel resistance of ovarian carcinoma, and blockade of this pathway can promote the apoptosis of the drug-resistant cells and reverse the drug-resistance. Moreover, p38MAPK-mediated apoptosis in paclitaxel-resistant ovarian carcinoma cells depends on the activation of p53.

ROLE OF ERK1/2 KINASE IN CISPLATIN-INDUCED APOPTOSIS IN HUMAN OVARIAN CARCINOMA CELLS

Objective To investigate the role of extracellular regulated kinase (ERK1/2) pathway in cisplatin-induced apoptosis in human ovarian carcinoma cells. Methods Cisplatin-induced apoptosis were stained with DAPI and was assessed microscopically in human epithelial adenocarcinoma ovarian cell line SKOV3 cells. ERK activation was determined by Western blotting using an anti-phospho-ERK antibody to detect ERK activity. The effect of PD98059 on ERK activity induced by cisplatin was detected by MTT assay. Results Marked apoptosis of SKOV3 cells resulted from 48 hours treatment with 20 μg/mL cisplatin. Strong activation of ERK was led to by 15 μg/mL cisplatin. Dose response and time course of cisplatin induced apoptosis in SKOV3 cells. Cisplatin-induced ERK activation occurred at 12 hours and increased to highest induction at 24 hours by Western blotting. The effect of PD 98059 on ERK activity induced by cisplatin at the concentration of 100 μmol/L PD 98059. Statistically significant decreased in cell survival were observed with 100 μmol/L PD 98059 at 15 and 20 μg/mL cisplatin (P< 0.05). Conclusions Cisplatin activates the ERK signaling pathway in ovarian cancer cell line SKOV3. Inhibition of ERK acti-vity enhances sensitivity to cisplatin cytotoxity in ovarian cancer cell line SKOV3. Evaluation of ERK activity could be useful in predicting which ovarian cancer will response most favorably to cisplatin therapy.

EFFECTS OF RETINOIC ACID ON PROLIFERATION AND DIFFEREN-TIATION OF A HUMAN OVARIAN CARCINOMA CELL LINE:3AO

Objective To observe the effects of retinoic acid (RA) on the proliferation and differentiation of a human ovarian carcino-ma cell line: 3AO cells. Methods 3AO cell proliferation was evaluated by viable cell count, percentage of cells in each cycle phase were analyzed by flow cytometric analysis, alkaline phosphatase (AKP) activity was determined as described , and CA125 expression was measured by ELISA. Results RA could inhibit the proliferation of 3AO cells accompanied with morphological changes in a dose-dependent manner. Cell cycle analysis indicated that RA inhibition of 3AO cells growth occurred through induction of G1 arrest with a concomitant reduction in the proportion of cells in S phase, AKP activity increased significantly after treatment with RA(0.1 μmol/L) for 1-5 days. Dose-response studies revealed that the AKP activity increased to a different extent as a function of RA concentrations. Furthermore, RA could suppress the expression of CA125 tumor marker in 3AO cells.Conclusion RA could markedly inhibit the proliferation and induce the differentiation of 3AO cells. for 1-5 days. Dose

Targeting of p38 Mitogen-activated Protein Kinases to Early Growth Response gene 1 (EGR-1) in the Human Paclitaxel-resistance Ovarian Carcinoma Cells

To investigate the relationship between the expression of early growth response gene 1 （EGR-1） and p38MAPK pathway in the paclitaxel resistance of ovarian carcinoma cells, the effect of p38MAPK inhibitor SB203580 on cell apoptosis was examined by using Hoechst 33258 staining. The intracellular Rh123 （Rhodamine 123） accumulation was detected by the flow cytometry （FCM）. The 50% inhibition concentration （IC50） of paclitaxel for A2780/Taxol cells was determined by MTT method. Electrophoretic motility shift assay （EMSA） was employed to examine the EGR-1DNA binding activity. MDR1 and EGR-1 mRNA were assessed by RT-PCR. The expressed of p-gp, phos- phorylated p53 and p38 were detected by Western blotting. SB203580 could remarkably promote the apoptosis of A2780/Taxol cells, and the cell apoptosis was in a time-dependent manner. Cellular Rh123 accumulation was increased, and the IC50 of paclitaxel for A2780/Taxol cells was decreased significantly. A2780/Taxol cell line after SB203580 treatment was shown to have a significantly higher level of EGR-1 DNA binding activity. SB203580 down-regulated the activity of p38MAPK pathway, but up-regulated EGR-1 expression. SB203580 significantly increased the level of cellular phosphorylated p53 protein, but decreased the p-gp protein level and MDR1 mRNA level in A2780/Taxol cells. There existed a close relationship between p38MAPK pathway and the paclitaxel resistance of ovarian carcinoma cells. The expression of EGR-1 mediated by p38MAPK pathway plays a critical role in paclitaxel resistance of ovarian carcinoma cells.

SEVEN CASES OF EPITHELIAL OVARIAN CARCINOMA WITH BRAIN METASTASIS

Objective To summarize the clinical characteristics, treatment, and prognosis of brain metastasis in patients with epithelial ovarian carcinoma. Metbods Retrospective analysis was conducted in 7 cases of brain metastases of epithelial ovarian carcinoma from January 1986 to March 2007 in Peking Union Medical College Hospital for summarizing therapy results and prognosisaffecting factors. Results Incidence of brain metastases of epithelial ovarian carcinoma was about 0. 66% （7/1 055 ）. Serous adenocarcinoma was the predominant pathological type in 4 cases and the subsequent was adenocarcinoma in 3 cases. All the patients were diagnosed at late stage, 6 cases with the International Federation of Gynecology and Obstetrics （HGO） stage Ⅲc and 1 with FIGO stage IV. The mean duration from diagnosis of ovarian carcinoma to brain metastasis was 32.7 ± 20. 0 months （range, 23-73 months）. Single metastasis focus occurred in 43% of cases and multiple metastases in 57% of cases. Fifty-seven percent of patients presented extracranial metastasis. Serum CA125 played a role in monitoring reoccur- rence and brain metastases. The average survival time was about 12 months. Better treatment with prolonged survival could be achieved by combination of operation and chemotherapy or combination of radiotherapy with chemotherapy. Concltusions As a rare condition, brain metastasis of epithelial ovarian carcinoma is rising in incidence with improved treatment of ovarian carcinoma and prolonged survival. However, brain metastasis indicates bad prognosis which can be improved by combined therapy.

Gastric metastasis from ovarian carcinoma: A case report and literature review

An isolated parenchymal gastric metastasis from ovarian carcinoma without any other sites of recurrence is extremely rare. Only two cases have been reported, both of which were symptomatic. We herein report such a case without any symptoms. A 61-year-old woman presented with a high cancer antigen-125 level without any other clinical manifestation. A subsequent 18 F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography scan revealed a submucosal mass with hypermetabolism of 18F-FDG (standardized uptake value:5.36) in the gastric antrum. The final pathology after gastric antrectomy showed a metastatic gastric tumor from a primary ovarian carcinoma. We also performed an extensive literature review about gastric metastasis from ovarian carcinoma published until recently, and this is the first case of an isolated parenchymal gastric metastasis from ovarian carcinoma without any symptoms.

P16 GENE EXPRESSION IN OVARIAN EPITHELIAL CYSTADENOCARCINOMA

P16 gene expression was measured by immnohistochemical method in poor differentiated serous cystadenocarcinoma cell line, xenograft of highly metastasizing human ovarian carcinoma in nude mice and paramn embedded tissues from 69 patients with ovarian carcinoma. The result showed that P16 gene was positive expression in HO-8910 cell of mother line,HO8910PM cell line and xenograft of highly mcatstasizing human ovarian carcinoma in nude mice. However, P16gene in the metastatic cell had a weaker expression. P16gene positive expression were also found in sl cases of 69cases (73.9%) in the ovarian epithelial carcinoma paramn embedded tissues. Comparative studies showed that the positive rate of P16 gene expression markedly reduced with the increase of pathologic grade and clinical stage,metastasis in the lymph node and decrease of 5-year survival (P<0.05, p<0.01).P16 gene is not only a controller of cytokerastic cycle, but also a key member of tumorigenic suppresser:its absence and expression degree are also correlated with the ovarian carcinoma genesis and development,especially with the metastasis of the ovarian cancer.

Construction of Three-dimensional In Vitro Culture Model of Ovarian Carcinoma and the Study of Its Multicellular Drug Resistance

To explore the role and possible mechanism of apoptosis and caspase-3 activity in the development of multicellular drug resistance of ovary cancer. Ovarian cancer cell A2780 multicellular spheroids （MCS） were obtained from three-dimensional culture. Drug sensitivity of monolayer cells （MC） and MCS were respectively tested by MTT staining and cytometry. The apoptosis of MC and MCS were determined by the flow cytometry （FCM）. The expression of bcl-2 and caspase-3 in A2780/MC and A2780/MCS were detected by using Western blot and caspase-3 assay kit, A2780/MC was compacted into mass after 2 days in three-dimensional cell culture model, and MCS had more than two layers of cells growing within 5 days. Compared with A2780/MC, A2780/MCS were more resistant to the anticancer drug, and the apoptosis rate was significantly lower than those of A2780/MC, The activity of caspase-3 in A2780/MCS was significantly lower than the A2780/MC. But the expression of bcl-2 in A2780/MCS was significantly higher than that in A2780/MC. It was suggested that the drug resistance of MCS might be associated with the overexpression of anti-apoptosis protein bcl-2 and the down-regulation of caspase-3 activity.

ESTABLISHMENT OF INTRAPERITONEAL TRANSPLANTATION MODEL OF CISPLATIN-RESISTANT OVARIAN CARCINOMA CELL IN SCID MICE

Objective： to develop an intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP cell in severe combined immunodeficiency （SCID） mouse and to study its biologic characteristics. Methods： Sixteen qualified C.B 17/SCID mouse were divided into two groups randomly. Human ovarian carcinoma SKOV3 or SKOV3/CDDP cells were injected intraperitoneally into the SCID mouse at the amount of 1×10^7 cells （0.5 mL） per mouse. The behaviors of mice, tumor growth and morphology were analyzed. The expression of cancer antigen 125 （CA125）, GST-π and Topo-Ⅱ were examined by immunohistochemical method. Results： In this experimental study, transplanted tumors are formed in 100% SCID mice in the two groups. The morphology, growth pattern and CA125 secretion of SKOV3/CDDP group were as same as those of SKOV3 group. It shows that the tumors of the two groups kept the characteristics of ovaries serosity papillary adenocarcinoma. Compared with SKOV3 group, the expression of GST-π and Topo-Ⅱ gene in SKOV3/CDDP group were significantly higher （P〈0.05）. Conclusion： An intraperitoneal transplantation model of human ovarian carcinoma SKOV3/CDDP in SCID mice has been developed successfully. It may be an ideal animal model for biotherapy research of ovarian carcinoma as it can simulate the biological behavior of peritoneal metastasis of human ovarian carcinoma and the drug tolerance is maintained.

Three Weeks Carboplatin/Paclitaxel versus Weekly Regimen in Egyptian Women Cohort Treated for Ovarian Carcinoma

Introduction: Epithelial Ovarian Carcinoma (EOC) comprises the vast majority (almost 90%) of ovarian carcinomas. Chemotherapy is the main treatment in ovarian cancers. The standard of care in the chemotherapeutic is the combination of a platinum (carboplatin or cisplatin) and a taxane (paclitaxel or docetaxel). Studies were done to determine whether this combination to be given weekly or every 3 weeks. Patient and Method: Inclusion criteria: 1) Female patients between the ages of 17 - 78 years. 2) Baseline hematological, renal and liver laboratory profiles were within accepted ranges. 3) Performance status of the patients was 0-II. 4) Patients were pathologically proven ovarian cancer. 5) A follow-up period for at least 6 months was required. Exclusion criteria: 1) Patients who had double malignancy were excluded. 2) Performance status more than II. 3) Other comorbidity. Results: We reviewed 69 female patients with EOC, with 60% received every three weeks regimen. Mean age was 53.22 years. At a median follow up of 45.9 months, there was no significant different between the two protocols in terms of mean PFS, 62.35 months (95% CI: 50.08 - 74.63 months) for the three-weekly cohort, and 69.25 months (95% CI: 55.24 - 83.26 months) for weekly protocol (p = 0.613). The three weekly regimen patients had a higher incidence of hospital admission (40% vs 18.5% for the weekly protocol patients), but it didn’t reach a statistical significance (p = 0.063). The three weekly protocol had a significantly higher incidence of causing a neutropenic fever (p = 0.003). Conclusion: In our cohort of Egyptian women with EOC, no significant difference in PFS was found when compared the weekly Carboplatin/paclitaxel when compared to the classic three weeks, although the weekly protocol may be causing less febrile neutropenia and fewer hospital admissions.

RELATIONSHIP AMONG COX-2 PROTEIN EXPRESSION,PGs LEVELS AND BIOLOGIC BEHAVIOR IN OVARIAN CARCINOMA TISSUES

Objective: To study the relationship among cyclooxygenase-2 (COX-2) protein expression, prostaglandins levels and biologic behavior in ovarian carcinoma tissues. Methods: The expression of COX-2 protein, levels of prostaglandin (PG)E2, 6-keto-PGF1α and thromboxane (TX)B2 in 54 biopsy specimens from patients with ovarian serous tumors which included three groups: 33 samples of ovarian serous carcinoma; 10 samples of borderline ovarian serous tumors and 11 samples of benign ovarian serous tumors and 10 samples of normal ovarian tissues were detected by Western blot analysis and radioimmunoassay to investigate their clinical significance. Results: The expression of COX-2 protein (82%, 27/33) and its relative content (20.08±3.53) in ovarian serous carcinoma tissues were statistically higher than those in benign ovarian serous tumor tissues and normal ovary tissues i.e., 0 and (15.04±0.12), 0 and (15.33±0.60) (P<0.05). The expression of COX-2 protein in borderline ovarian serous tumor tissues (90%, 9/10) and relative content (20.61±3.03) were statistically greater than those in benign ovarian serous tumor and normal ovary tissues (P<0.05). The expression of COX-2 protein and its relative content showed no significant differences in ovarian carcinoma tissues of different clinical stages (I to II and III to IV), different histological grades, with or without ascites and lymph metastasis. The levels of PGE2, 6-keto-PGF1 and TXB2 α in ovarian serous carcinoma tissues were statistically higher than in borderline ovarian serous tumor, benign ovarian serous tumor or normal ovarian tissues (P<0.05). No significant differences of the levels were found among borderline tissues, benign tissues and normal ovarian tissues (P>0.05). The levels of PGE2, 6-keto-PGF1 α and TXB2 showed no significant differences in ovarian carcinoma tissues with different clinical stages (I to II and III to IV), different histological grades, with or without ascites and lymph metastasis. COX-2 expression was correlated with the levels of PGE2, 6-KETO-PGF1 α and TXB2 (P<0.01). Conclusion: Our data suggest that COX-2 overexpression leads to increased PGE2, 6-KETA-PGF1 α and TXB2 biosynthesis, which may be mechanisms underlying the contribution of COX-2 to the development of ovarian serous carcinoma. BGF2, 6-keto-PGF1 and TXB2 may be helpful parameters of α diagnosis and differentiate diagnosis in ovarian serous carcinoma.

Morphological and molecular basis of ovarian serous carcinoma

Serous carcinoma is the most common type of epithelial ovarian cancer. In this review, we provide a com- prehensive picture of ovarian serous cancers from multiple aspects： the first part of this review summarizes the morphological, histological, and immunological signatures of ovarian serous carcinoma; subsequently, we review the history of the evolvement of different grading systems used in ovarian serous cancer; in the end, we focus on characterizing the genetics that underlie the 2-tiered pathways through which ovarian serous cancers are believed to arise： the low-grade and the high-grade pathways.

IMMUNOLOGIC CHARACTER OF TUMOR INFILTRATING LYMPHOCYTES IN OVARIAN CARCINOMA

Objective: To study immunologic character of tumor-infiltrating lymphocytes (TIL) on postin vitro expansion in ovarian carcinoma, and evaluate the prospects by adopting TIL treatment of ovarian carcinoma at an advanced stage. Methods: Cellular phenotype changes in TIL were analyzed by flow cytometry. By means of molecular biology and immunologic methods, ability to secrete cytokines and anti-tumor activities of in TIL was studied. Results: Difference of cellular phenotypes in TIL was probably related to the type, feature and resource of the tumor. TIL obtained from phoroplast and parenchyma was dominant in CD3+CD4+. TIL obtained from tumor tissues, around microvessels and ascitic fluid was dominant in CD3+CD8 Concentration of rIL-2in vitro played a significant role in immunologic character of TIL. By means of rIL-2 expansionin vitro, TIL has apparently been improved in competence of secreting some cytokines, such as IL-2, TNF-α, IFN-γ, and anti-tumor activities. The activated TIL was more stimulated by further adding anti-CD3 or PHA (suitable concentration), which significantly increased its ability to secrete cytokines. Treatment with TIL+CTX or TIL+ rIL-2, could apparently improve phenotypes in peripheral blood of patients, with definitive effects. Conclusion: Immunologic activities of TILin vitro are apparently improved by rIL2 expansion. Regression of tumor, by means of infusion TIL, is not largely attributed to direct cytotoxicity to tumor cells, but indirectly and partly augmenting cellular activities and abilities of immunomodulation in patients with ovarian carcinoma being dependent on secreting multiple cytokines.

Ovarian carcinoma in two patients with chronic liver disease

Ascites is a common and debilitating complication of cirrhosis. However, patients with chronic liver disease are not spared from other causes of ascites and physicians should be careful not to miss an underlying malignancy. Ovarian cancer is an insidious disease, which is difficult to diagnose and it ranks first in mortality among all gynecological cancers. Here, we present two cases of patients with chronic liver disease that developed ascites not： simply because of drrhosis but as a manifestation of ovarian cancer. We would like to emphasize that the causes of ascites, other than the liver itself, should not be overlooked in patients with chronic liver disease.