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 repo...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.展开更多
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 ...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.展开更多
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...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.展开更多
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 obtain...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.展开更多
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: Sixtee...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.展开更多
<strong>Introduction: </strong><span style="font-family:""><span style="font-family:Verdana;">Epithelial Ovarian Carcinoma (EOC) comprises the vast majority (almost 90%...<strong>Introduction: </strong><span style="font-family:""><span style="font-family:Verdana;">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. </span><b><span style="font-family:Verdana;">Patient and Method: </span></b><span style="font-family:Verdana;">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. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">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). </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">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.</span></span>展开更多
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 pro...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.展开更多
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 advance...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.展开更多
Objective:To study the manifestation,pathohistologic type,stage of disease,treatment andoutcome of epithelial ovarian carcinoma in women under the age of 30 years.Methods:The 21 cases of epithelial ovarian carcinoma i...Objective:To study the manifestation,pathohistologic type,stage of disease,treatment andoutcome of epithelial ovarian carcinoma in women under the age of 30 years.Methods:The 21 cases of epithelial ovarian carcinoma in women aged below 30 years betweenJan,1986 and Mar,2002 were analyzed retrospectively.Results:The median age at the time of diagnosis was 24 years(range,16-29 years).All car-cinomas occurred after menarche.The most common symptoms were abdominal pain(50%),fol-lowed by tympanites(25%)and menstrual disorders(19%).The initial diagnosis was usuallymade by physical examination,ultrasonography and serum CA125.The mean maximal tumor di-ameter was 17.6 cm.Ten patients had Stage Ⅰ disease(5 Ⅰa,5 Ⅰc),five had Stage Ⅲ disease,andthe other six were unknown during staging operation.There were nine mucinous tumors,six se-rous tumors.Most tumors were well-differentiated and classified as Grade1 in 11 cases,Grade2 in2 cases,Grade3 in 2 cases,unknown in 6 cases.Optimal and suboptimal cytoreduction wasachieved in 14 patients in primary treatment and 5 in recurrent treatment.8 patients were treatedwith conservative surgery.18 patients were treated with chemotherapy and 7 patients had experi-enced six or more than six courses of chemotherapy.The median follow-up was 50 months(range,2-192 months).There were 6 deaths,2 alive with tumor,11 alive without the disease,2losing follow-up.The 3-year survival rate was 89%,and 5-year survival rate was 76%.Conclusion:Young patients with epithelial ovarian carcinoma appeared to have a less aggres-sive form of the disease and a more favorable prognosis.展开更多
Purpose: HLA-G binds to the inhibitory receptors of uterine NK cells and plays an important role in protection of fetal cells from maternal NK lysis. HLA-G also mediates tumor escape, but the immunosuppressive role is...Purpose: HLA-G binds to the inhibitory receptors of uterine NK cells and plays an important role in protection of fetal cells from maternal NK lysis. HLA-G also mediates tumor escape, but the immunosuppressive role is often neglected. These studies have focused on the examination of HLA-G expression in human breast and ovarian carcinoma and HLA-G immunosuppressive role in NK cytolysis. Methods: We examined HLA-G expression in breast and ovarian carcinoma cell lines by real time PCR, ELISA and immunofluorescent staining, and in frozen breast and ovarian carcinoma tissues by immunohistochemistry (IHC). We treated the breast cancer cell lines with anti-human HLA-G antibody or progesterone. Then, NK cytolysis was measured by using MTT assay. Results: We find breast and ovarian cancer cell lines increase the expression of HLA-G mRNA and protein, compared to normal cells. IHC shows that 100% of frozen breast and ovarian carcinoma tissues overexpress HLA-G protein. HLA-G IHC scores of breast and ovarian carcinoma are significantly higher than normal breast and ovarian tissues, respectively (both p < 0.01). Blocking HLA-G of the breast cancer cells by the antibody increases NK cytolysis. Progesterone upregulates HLA-G mRNA and protein of human breast cancer cell lines. The increased HLA-G expression by progesterone suppresses the NK cytolysis. Conclusion: Human breast and ovarian carcinoma overexpress HLA-G immunosuppressive molecules. Blocking HLA-G protein by antibody improves the cytolysis of NK cells against human breast cancer cell lines. In contrast, upregulation of HLA-G expression by progesterone impairs NK cytolytic function. Thus, HLA-G is a new immune checkpoint protein and potential cancer immunotherapeutic target.展开更多
Recent evidence suggests that the chemokine axis of CXC chemokine ligand-12 and its receptor CXC chemokine receptor-4(CXCL12/CXCR4) is highly expressed in gynecological tumors and the axis of CXC chemokine ligand-16 a...Recent evidence suggests that the chemokine axis of CXC chemokine ligand-12 and its receptor CXC chemokine receptor-4(CXCL12/CXCR4) is highly expressed in gynecological tumors and the axis of CXC chemokine ligand-16 and CXC chemokine receptor-6(CXCL16/CXCR6) is overexpressed in inflammation-associated tumors.This study aimed to determine the relationship between CXCL12/CXCR4,CXCL16/CXCR6 and ovarian carcinoma's clinicopathologic features and prognosis.Accordingly,the expression of these proteins in ovarian tissues was detected by tissue microarray and immunohistochemistry.The expressions of CXCL12/CXCR4 and CXCL16/CXCR6 were significantly higher in epithelial ovarian carcinomas than in normal epithelial ovarian tissues or benign epithelial ovarian tumors.The expression of chemokines CXCL12 and CXCL16 were positively correlated with their receptors CXCR4 and CXCR6 in ovarian carcinoma,respectively(r = 0.300,P < 0.05;r = 0.395,P < 0.05).Moreover,the expression of CXCL12 was related to the occurrence of ascites(χ2 = 4.76,P < 0.05),the expression of CXCR4 was significantly related to lymph node metastasis(χ2 = 4.37,P < 0.05),the expression of CXCR6 was significantly related to lymph node metastasis(χ2 = 7.43,P < 0.05) and histological type(χ2 = 33.48,P < 0.05).In univariate analysis,the expression of CXCR4 and CXCL16 significantly correlated with reduced median survival(χ2 = 4.67,P < 0.05;χ2 = 4.48,P < 0.05).Therefore,we conclude that the chemokine axes CXCL12/CXCR4 and CXCL16/CXCR6 may play important roles in the growth,proliferation,invasion,and metastasis of epithelial ovarian carcinoma.展开更多
Objective. To understanding the molecular mechanisms in invasion and metastasis of the ovarian car-cinoma, we investigate a novel candidate metastasis-associated gene (MTA1) and nm23H1 mRNA ex-pression and mutation in...Objective. To understanding the molecular mechanisms in invasion and metastasis of the ovarian car-cinoma, we investigate a novel candidate metastasis-associated gene (MTA1) and nm23H1 mRNA ex-pression and mutation in ovarian carcinoma.Methods. Twenty primary ovarian carcinoma specimens, 20 corresponding lymph nodes and 8 normalovarian was examined for mRNA expression and mutation of MTA1 and nm23H1 genes by revere-tran-scription ploymerase chain reaction(RT-PCR) and RT-PCR-SSCP analysis. The level of the expressionwas determined by the relative optic desity (ROD) of the PCR products.Results. The frequency of MAT1 overexpression was 100%(7/7) in primary ovarian carcinoma withmetastasis but only 38.5% (5/13) in those without metastasis (P=0.0103 ). Overexpression of MAT1 wasobserved in 87.5%(6/7) of lymph nodes with metastasis but only 23%(3/13) of lymph nodes withoutmetastasis (P=0.0118). In contrast with MAT1, low expression of nm23H1 mRNA was seen in 7 of 7 o-varian carcinoma with metastasis but only in 4 of 13(30%) of those without metastassis (P=0.0043). Lownm23H1 expression was also seen in 7 of 7 lymph nodes with metastasis but only in 5 of 13 (38.5%)nonmetastatic lymph nodes (P=0.0102). The ROD ratio of MAT1 to nm23H1 increased with the develop-ment of metastasis. No mutation of MAT1 and nm23H1 genes was found by SSCP analysis.Conclusion. The mRNA expression of MTA1 and nm23H1 is positively and negatively correlated withlymph node metastasis, respectively. Expression abnormalities but not mutation of the two genes are fre-quent events related to lymph node metastasis of ovarian cancer.展开更多
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 ...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.展开更多
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, pe...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.展开更多
Objective To summarize the clinical characteristics,treatment,and prognosis of brain metastasis in patients with epithelial ovarian carcinoma.Methods Retrospective analysis was conducted in 7 cases of brain metastases...Objective To summarize the clinical characteristics,treatment,and prognosis of brain metastasis in patients with epithelial ovarian carcinoma.Methods 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 prognosis-affecting factors.Results Incidence of brain metastases of epithelial ovarian carcinoma was about 0.66%(7/1055).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(FIGO)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 reoccurrence 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.Conclusions 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.展开更多
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 cas...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.展开更多
Objective To investigate the mechanism of low-dose fractionated radiation on reversing cisplatin resistance in ovarian carcinoma via vascular endothelial growth factor(VEGF) and mammalian target of rapamycin(mTOR) in ...Objective To investigate the mechanism of low-dose fractionated radiation on reversing cisplatin resistance in ovarian carcinoma via vascular endothelial growth factor(VEGF) and mammalian target of rapamycin(mTOR) in vivo.Methods Human cisplatin-resistant ovarian carcinoma cells(SKOV3/DDP) were injected into nude mice to establish ovarian cancer xenografts. The mice were randomly divided into three groups: a control group, a low-dose fractionated radiation(LDRFT) group, and a conventional-dose radiation group. Each group was exposed to 0 cGy, 50 cGy, and 200 cGy radiation, respectively, for 4 weeks, up to a total of 8.0 Gy. Mice in the LDFRT group were irradiated twice daily with 6 hour intermissions on day 1 and 2 of every week for a total of 4 weeks. Conventional-dose group mice were given a single 200 cGy radiation dose on the first day each week for a total of 4 weeks. Maximum horizontal and vertical diameters of the tumors were measured every other day and used to create a tumor growth curve. After 4 weeks of irradiation, we dissected the tumor tissue and calculated the tumor inhibition rate. RT-PCR detected the expression of VEGF and m TOR, and Western blots detected the expression of corresponding proteins.Results Both LDRFT and conventional-dose radiation inhibited the growth of tumor cells, and growth of tumors in the two radiation groups compared with growth in the control group were significantly different(P < 0.05). The rate of tumor inhibition in the LDFRT group(37.5603%) was lower than in the conventionaldose group(47.4446%), but there was no significant difference(P 0.05). Compared with the other two groups, the m RNA expression of VEGF was significantly lower in the LDFRT group(P < 0.05), but there was no obvious difference between the conventional-dose and control groups. There was no obvious difference in the m RNA expression of m TOR among the three groups, but the expression of the protein p-m TOR was lower in the LDFRT group(P < 0.05), as confirmed by Western blotting.Conclusion LDFRT is as effective at inhibiting the growth of tumor cells as conventional-dose radiation. In addition, LDFRT could deregulate the expression of VEGF and p-m TOR, and may therefore play a vital role in reversing cisplatin resistance in ovarian cancer.展开更多
Objective.To investigate the relationship between mdrl gene expression and multidrug-resistance in o- varian carcinoma. Design. We established tumor-bearing mice model of ovarian carcinoma,compared the anticancer drug...Objective.To investigate the relationship between mdrl gene expression and multidrug-resistance in o- varian carcinoma. Design. We established tumor-bearing mice model of ovarian carcinoma,compared the anticancer drug sensitivity of OC/mdr-cell and OC/mdr+ cell in vitro, investigated the effect of cyclosporin A on reversing the multidrug resistance both in vitro and in the tumor-bearing mice model,detected the mdrl gene expre- sion in human ovarian carcinoma specimens. Main outcome measures. Anticancer drug sensitivity of both OC/mdr-cell and OC/mdr+ cell is mea- sured by the methods of MTT assays. mdrl gene expression is detected by the methods of RT-PCR. Results. Using MTT assay,OC/mdr+ cell is 4. 1 - 15. 5 times more resistant to VP-16,VCR,DNR, and DOX than OC/mdr-cell in vitro.2 μg/ml cyclosporine A(CsA)reduced the resistance of OC/mdr+ cell to DOX,from 0. 324±0. 072μg/ml to 0. 088±0. 024μg/ml. To OC/mdr-cell,CsA did not significantly in- crease its sensitivity to DOX.Tumor-bearing mice with positive mdrl gene expression showed non-respon- siveness to DOX chemotherapy. When combined with intraperitoneal injection of CsA, the growth rate of tumor cells decreased significantly (P<0. 01 ). Only 4 of 23(17. 39% )tumors from patients who had not received chemotherapy exhibited positive mdrl gene expreession, while 6 of 9 (66. 67%)treated patients showed positive mdrl gene expression (Fisher exact test: P<0. 05 ). After cytoreductive surgery and chemotherapy, 14 of 19 untreated patients with negative mdrl gene expression had partial or complete re- sponse, while in patients with positive mdrl gene expression, 8 of 10 showed poor prognosis(Fisher exact test: P<0. 05 ). Conclusion. The expression of mdrl gene is associated with previous chemotherapy. CsA can reverse the resistance of mdr+ cells to indr-associated drs both in vitro and in vivo’ For the patients with ovarian carcinoma., the percentage of nonresponsiveness to the chemotherapy was found to be significantly higher among patients with positive mdrl gene expression than those with negative mdrl gene expression. mdrl gene expression can be detected to predict the clinical prognosis of patients with ovarian carcinoma.展开更多
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 malig...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 cirrhosis 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.展开更多
Objective:To determine expressions of HLA class I and CD80 in humanepithelial ovarian carcinomas(EOC) and the clinical significance.Methods:Expression of HLA class I was detected by immunohistochemical technique. Expr...Objective:To determine expressions of HLA class I and CD80 in humanepithelial ovarian carcinomas(EOC) and the clinical significance.Methods:Expression of HLA class I was detected by immunohistochemical technique. Expression of CD80 mRNA was examined by reverse transcriptions-polymerase chain reaction(RT-PCR).Results:The positive rate of HLA classⅠ was 59.09%.CD80 mRNA was expressed on 9.09% of all 44 EOC tissues.HLA classⅠ expression rate in stage Ⅲ-Ⅳ was lower than that in stage Ⅰ-Ⅱ;in tumors of node-positive patients was lower than that of node-negative patients(P<0.05).In patiens with tumors expressing HLA class Ⅰ antigens,recurrence rate was lower than that in patients with tumors deficient in HLA class Ⅰ(P<0.01).In four patients with tumors expressing CD80 mRNA,recurrence did not occur,in contrast to patients with tumors lacking CD80 mRNA,in whom tumor relapse rate was 57.5%(P<0.05).Relapse ratein tumors deficient both HLA class Ⅰ and CD80 was significantly higher than that of tumors coexpression the two molecules.Conclusions:EOC cells may escapefrom the immune surveillance of the host through downregulating expressions ofHLA class Ⅰ and CD80.Evaluation of expressions of these surface immunoregulatory molecules may be helpful for judging prognoses of EOC patients and guiding immunotherapy.展开更多
基金Supported by National Key Technology R&D Program of China,No.2019YFC1005200,and No.2019YFC1005202National Natural Science Foundation of China,No.81501530,No.81802896,and No.81701530+1 种基金Natural Science Foundation of Hubei Province,No.2017CFB800Hubei Province Health and Family Planning Scientific Research Project,No.WJ2017Z013,and No.WJ2019M127.
文摘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.
文摘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.
基金R&D program of Heilongjiang Province (No. GB05C402-11)
文摘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.
文摘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.
基金This work was supported by a grant from the Science & Technology Research Project, Public Health Department of Hebei Province (No. 2003/03086)
文摘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.
文摘<strong>Introduction: </strong><span style="font-family:""><span style="font-family:Verdana;">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. </span><b><span style="font-family:Verdana;">Patient and Method: </span></b><span style="font-family:Verdana;">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. </span><b><span style="font-family:Verdana;">Results: </span></b><span style="font-family:Verdana;">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). </span><b><span style="font-family:Verdana;">Conclusion: </span></b><span style="font-family:Verdana;">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.</span></span>
文摘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.
基金the National Natural Science Foundation of China (No.39370706).
文摘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.
文摘Objective:To study the manifestation,pathohistologic type,stage of disease,treatment andoutcome of epithelial ovarian carcinoma in women under the age of 30 years.Methods:The 21 cases of epithelial ovarian carcinoma in women aged below 30 years betweenJan,1986 and Mar,2002 were analyzed retrospectively.Results:The median age at the time of diagnosis was 24 years(range,16-29 years).All car-cinomas occurred after menarche.The most common symptoms were abdominal pain(50%),fol-lowed by tympanites(25%)and menstrual disorders(19%).The initial diagnosis was usuallymade by physical examination,ultrasonography and serum CA125.The mean maximal tumor di-ameter was 17.6 cm.Ten patients had Stage Ⅰ disease(5 Ⅰa,5 Ⅰc),five had Stage Ⅲ disease,andthe other six were unknown during staging operation.There were nine mucinous tumors,six se-rous tumors.Most tumors were well-differentiated and classified as Grade1 in 11 cases,Grade2 in2 cases,Grade3 in 2 cases,unknown in 6 cases.Optimal and suboptimal cytoreduction wasachieved in 14 patients in primary treatment and 5 in recurrent treatment.8 patients were treatedwith conservative surgery.18 patients were treated with chemotherapy and 7 patients had experi-enced six or more than six courses of chemotherapy.The median follow-up was 50 months(range,2-192 months).There were 6 deaths,2 alive with tumor,11 alive without the disease,2losing follow-up.The 3-year survival rate was 89%,and 5-year survival rate was 76%.Conclusion:Young patients with epithelial ovarian carcinoma appeared to have a less aggres-sive form of the disease and a more favorable prognosis.
文摘Purpose: HLA-G binds to the inhibitory receptors of uterine NK cells and plays an important role in protection of fetal cells from maternal NK lysis. HLA-G also mediates tumor escape, but the immunosuppressive role is often neglected. These studies have focused on the examination of HLA-G expression in human breast and ovarian carcinoma and HLA-G immunosuppressive role in NK cytolysis. Methods: We examined HLA-G expression in breast and ovarian carcinoma cell lines by real time PCR, ELISA and immunofluorescent staining, and in frozen breast and ovarian carcinoma tissues by immunohistochemistry (IHC). We treated the breast cancer cell lines with anti-human HLA-G antibody or progesterone. Then, NK cytolysis was measured by using MTT assay. Results: We find breast and ovarian cancer cell lines increase the expression of HLA-G mRNA and protein, compared to normal cells. IHC shows that 100% of frozen breast and ovarian carcinoma tissues overexpress HLA-G protein. HLA-G IHC scores of breast and ovarian carcinoma are significantly higher than normal breast and ovarian tissues, respectively (both p < 0.01). Blocking HLA-G of the breast cancer cells by the antibody increases NK cytolysis. Progesterone upregulates HLA-G mRNA and protein of human breast cancer cell lines. The increased HLA-G expression by progesterone suppresses the NK cytolysis. Conclusion: Human breast and ovarian carcinoma overexpress HLA-G immunosuppressive molecules. Blocking HLA-G protein by antibody improves the cytolysis of NK cells against human breast cancer cell lines. In contrast, upregulation of HLA-G expression by progesterone impairs NK cytolytic function. Thus, HLA-G is a new immune checkpoint protein and potential cancer immunotherapeutic target.
基金supported by grants from NationalNatural Science Foundation for Young Scholars of China(No. 30700763)Promotive Research Foundation forExcellent Young and Middle-aged Scientists of Shandong(No. BS2009SW002)
文摘Recent evidence suggests that the chemokine axis of CXC chemokine ligand-12 and its receptor CXC chemokine receptor-4(CXCL12/CXCR4) is highly expressed in gynecological tumors and the axis of CXC chemokine ligand-16 and CXC chemokine receptor-6(CXCL16/CXCR6) is overexpressed in inflammation-associated tumors.This study aimed to determine the relationship between CXCL12/CXCR4,CXCL16/CXCR6 and ovarian carcinoma's clinicopathologic features and prognosis.Accordingly,the expression of these proteins in ovarian tissues was detected by tissue microarray and immunohistochemistry.The expressions of CXCL12/CXCR4 and CXCL16/CXCR6 were significantly higher in epithelial ovarian carcinomas than in normal epithelial ovarian tissues or benign epithelial ovarian tumors.The expression of chemokines CXCL12 and CXCL16 were positively correlated with their receptors CXCR4 and CXCR6 in ovarian carcinoma,respectively(r = 0.300,P < 0.05;r = 0.395,P < 0.05).Moreover,the expression of CXCL12 was related to the occurrence of ascites(χ2 = 4.76,P < 0.05),the expression of CXCR4 was significantly related to lymph node metastasis(χ2 = 4.37,P < 0.05),the expression of CXCR6 was significantly related to lymph node metastasis(χ2 = 7.43,P < 0.05) and histological type(χ2 = 33.48,P < 0.05).In univariate analysis,the expression of CXCR4 and CXCL16 significantly correlated with reduced median survival(χ2 = 4.67,P < 0.05;χ2 = 4.48,P < 0.05).Therefore,we conclude that the chemokine axes CXCL12/CXCR4 and CXCL16/CXCR6 may play important roles in the growth,proliferation,invasion,and metastasis of epithelial ovarian carcinoma.
文摘Objective. To understanding the molecular mechanisms in invasion and metastasis of the ovarian car-cinoma, we investigate a novel candidate metastasis-associated gene (MTA1) and nm23H1 mRNA ex-pression and mutation in ovarian carcinoma.Methods. Twenty primary ovarian carcinoma specimens, 20 corresponding lymph nodes and 8 normalovarian was examined for mRNA expression and mutation of MTA1 and nm23H1 genes by revere-tran-scription ploymerase chain reaction(RT-PCR) and RT-PCR-SSCP analysis. The level of the expressionwas determined by the relative optic desity (ROD) of the PCR products.Results. The frequency of MAT1 overexpression was 100%(7/7) in primary ovarian carcinoma withmetastasis but only 38.5% (5/13) in those without metastasis (P=0.0103 ). Overexpression of MAT1 wasobserved in 87.5%(6/7) of lymph nodes with metastasis but only 23%(3/13) of lymph nodes withoutmetastasis (P=0.0118). In contrast with MAT1, low expression of nm23H1 mRNA was seen in 7 of 7 o-varian carcinoma with metastasis but only in 4 of 13(30%) of those without metastassis (P=0.0043). Lownm23H1 expression was also seen in 7 of 7 lymph nodes with metastasis but only in 5 of 13 (38.5%)nonmetastatic lymph nodes (P=0.0102). The ROD ratio of MAT1 to nm23H1 increased with the develop-ment of metastasis. No mutation of MAT1 and nm23H1 genes was found by SSCP analysis.Conclusion. The mRNA expression of MTA1 and nm23H1 is positively and negatively correlated withlymph node metastasis, respectively. Expression abnormalities but not mutation of the two genes are fre-quent events related to lymph node metastasis of ovarian cancer.
基金Supported by Heilongjiang Province Natural Science Funds (D03-55) and Heilongjiang Province Sanitary Bureau Science Funds (2003-003)
文摘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.
文摘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.
文摘Objective To summarize the clinical characteristics,treatment,and prognosis of brain metastasis in patients with epithelial ovarian carcinoma.Methods 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 prognosis-affecting factors.Results Incidence of brain metastases of epithelial ovarian carcinoma was about 0.66%(7/1055).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(FIGO)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 reoccurrence 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.Conclusions 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.
文摘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.
基金Supported by a grant from the Province Natural Sciences Foundation of Shandong(No.ZR2016040034)
文摘Objective To investigate the mechanism of low-dose fractionated radiation on reversing cisplatin resistance in ovarian carcinoma via vascular endothelial growth factor(VEGF) and mammalian target of rapamycin(mTOR) in vivo.Methods Human cisplatin-resistant ovarian carcinoma cells(SKOV3/DDP) were injected into nude mice to establish ovarian cancer xenografts. The mice were randomly divided into three groups: a control group, a low-dose fractionated radiation(LDRFT) group, and a conventional-dose radiation group. Each group was exposed to 0 cGy, 50 cGy, and 200 cGy radiation, respectively, for 4 weeks, up to a total of 8.0 Gy. Mice in the LDFRT group were irradiated twice daily with 6 hour intermissions on day 1 and 2 of every week for a total of 4 weeks. Conventional-dose group mice were given a single 200 cGy radiation dose on the first day each week for a total of 4 weeks. Maximum horizontal and vertical diameters of the tumors were measured every other day and used to create a tumor growth curve. After 4 weeks of irradiation, we dissected the tumor tissue and calculated the tumor inhibition rate. RT-PCR detected the expression of VEGF and m TOR, and Western blots detected the expression of corresponding proteins.Results Both LDRFT and conventional-dose radiation inhibited the growth of tumor cells, and growth of tumors in the two radiation groups compared with growth in the control group were significantly different(P < 0.05). The rate of tumor inhibition in the LDFRT group(37.5603%) was lower than in the conventionaldose group(47.4446%), but there was no significant difference(P 0.05). Compared with the other two groups, the m RNA expression of VEGF was significantly lower in the LDFRT group(P < 0.05), but there was no obvious difference between the conventional-dose and control groups. There was no obvious difference in the m RNA expression of m TOR among the three groups, but the expression of the protein p-m TOR was lower in the LDFRT group(P < 0.05), as confirmed by Western blotting.Conclusion LDFRT is as effective at inhibiting the growth of tumor cells as conventional-dose radiation. In addition, LDFRT could deregulate the expression of VEGF and p-m TOR, and may therefore play a vital role in reversing cisplatin resistance in ovarian cancer.
文摘Objective.To investigate the relationship between mdrl gene expression and multidrug-resistance in o- varian carcinoma. Design. We established tumor-bearing mice model of ovarian carcinoma,compared the anticancer drug sensitivity of OC/mdr-cell and OC/mdr+ cell in vitro, investigated the effect of cyclosporin A on reversing the multidrug resistance both in vitro and in the tumor-bearing mice model,detected the mdrl gene expre- sion in human ovarian carcinoma specimens. Main outcome measures. Anticancer drug sensitivity of both OC/mdr-cell and OC/mdr+ cell is mea- sured by the methods of MTT assays. mdrl gene expression is detected by the methods of RT-PCR. Results. Using MTT assay,OC/mdr+ cell is 4. 1 - 15. 5 times more resistant to VP-16,VCR,DNR, and DOX than OC/mdr-cell in vitro.2 μg/ml cyclosporine A(CsA)reduced the resistance of OC/mdr+ cell to DOX,from 0. 324±0. 072μg/ml to 0. 088±0. 024μg/ml. To OC/mdr-cell,CsA did not significantly in- crease its sensitivity to DOX.Tumor-bearing mice with positive mdrl gene expression showed non-respon- siveness to DOX chemotherapy. When combined with intraperitoneal injection of CsA, the growth rate of tumor cells decreased significantly (P<0. 01 ). Only 4 of 23(17. 39% )tumors from patients who had not received chemotherapy exhibited positive mdrl gene expreession, while 6 of 9 (66. 67%)treated patients showed positive mdrl gene expression (Fisher exact test: P<0. 05 ). After cytoreductive surgery and chemotherapy, 14 of 19 untreated patients with negative mdrl gene expression had partial or complete re- sponse, while in patients with positive mdrl gene expression, 8 of 10 showed poor prognosis(Fisher exact test: P<0. 05 ). Conclusion. The expression of mdrl gene is associated with previous chemotherapy. CsA can reverse the resistance of mdr+ cells to indr-associated drs both in vitro and in vivo’ For the patients with ovarian carcinoma., the percentage of nonresponsiveness to the chemotherapy was found to be significantly higher among patients with positive mdrl gene expression than those with negative mdrl gene expression. mdrl gene expression can be detected to predict the clinical prognosis of patients with ovarian carcinoma.
文摘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 cirrhosis 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.
文摘Objective:To determine expressions of HLA class I and CD80 in humanepithelial ovarian carcinomas(EOC) and the clinical significance.Methods:Expression of HLA class I was detected by immunohistochemical technique. Expression of CD80 mRNA was examined by reverse transcriptions-polymerase chain reaction(RT-PCR).Results:The positive rate of HLA classⅠ was 59.09%.CD80 mRNA was expressed on 9.09% of all 44 EOC tissues.HLA classⅠ expression rate in stage Ⅲ-Ⅳ was lower than that in stage Ⅰ-Ⅱ;in tumors of node-positive patients was lower than that of node-negative patients(P<0.05).In patiens with tumors expressing HLA class Ⅰ antigens,recurrence rate was lower than that in patients with tumors deficient in HLA class Ⅰ(P<0.01).In four patients with tumors expressing CD80 mRNA,recurrence did not occur,in contrast to patients with tumors lacking CD80 mRNA,in whom tumor relapse rate was 57.5%(P<0.05).Relapse ratein tumors deficient both HLA class Ⅰ and CD80 was significantly higher than that of tumors coexpression the two molecules.Conclusions:EOC cells may escapefrom the immune surveillance of the host through downregulating expressions ofHLA class Ⅰ and CD80.Evaluation of expressions of these surface immunoregulatory molecules may be helpful for judging prognoses of EOC patients and guiding immunotherapy.