The concentration of interleukin-2 and interleukin-2 soluble receptors in peritoneal fluid of patients with unexplained infertility

OBJECTIVES: We measured the concentration of interleukin-2 (IL-2) and interleukin-2 soluble receptor (sIL-2R) in peritoneal fluid (PF) of patients with unexplained infertility. MATERIALS AND METHODS: PF was obtained during laparoscopy from 7 women with unexplained infertility (UI) and 11 women with benign noninflammatory ovarian tumors. All laparoscopies were performed in follicular phase of the cycle. IL-2 and sIL-2R concentrations were measured in PF supernate stored in -70 degrees C until analysis using ELISA method (ENDOGEN). RESULTS: We found significantly (p = 0.009) lower concentration of sIL-2R in PF from patients with UI (303.844 U/ml) than in reference group (556.385 U/ml). The level of IL-2 was not detectable in 2 cases from women with UI and 5 cases from reference group. The concentration of IL-2 in PF did not differ (p = 0.135) between patients with UI (2.346 pg/ml) and those from reference group (1.064 pg/ml). CONCLUSIONS: The concentration of sIL-2R in PF of patients with UI was lower than in those from reference group. This may be the factor responsible for insufficient local immunosuppression, affecting reproduction.     

Prognostic significance of vascular endothelial growth factor expression in ovarian cancer patients: a long-term follow-up

Abstract.   Rudlowski C, Pickart A-K, Fuhljahn C, Friepoertner T, Schlehe B, Biesterfeld S, Schroeder W. Prognostic significance of vascular endothelial growth factor VEGF expression in ovarian cancer patients: a long-term follow-up. Int J Gynecol Cancer 2006; 16(Suppl. 1): 183–189.
The purpose of the study was to determine vascular endothelial growth factor (VEGF) concentrations in ascites from ovarian cancer and to correlate these data with VEGF expression in ovarian tumors, serum VEGF concentrations, and clinicopathologic characteristics. Ascites, serum, and tumor tissue from 65 ovarian carcinomas and eight borderline tumors were collected. VEGF concentration in peritoneal fluids and sera was determined using enzyme immunoassay. VEGF tumor expression was evaluated immunohistochemically. Significantly higher VEGF concentrations were found in ascites from malignant tumors (median, 2575 pg mL⁻¹) compared with borderline tumors (median 181.9 pg mL⁻¹) and benign peritoneal fluid (184.5 pg mL⁻¹). Both VEGF ascites concentration and tumor expression correlated with advanced tumor stages and ascites volume. Elevated VEGF ascites levels were negatively correlated to patient survival. No differences between VEGF serum levels could be observed between ovarian cancer patients and patients with benign cysts. This study showed for the first time the clinical significance of elevated VEGF ascites level in ovarian carcinomas. VEGF is expressed by ovarian tumor cells and locally released in the malignant peritoneal fluid but is not increased in the serum of preoperative ovarian cancer patients. The enhanced VEGF level support novel therapeutic perspectives by VEGF inhibition.     

Ovarian carcinoma cells and IL-1beta-activated human peritoneal mesothelial cells are possible sources of vascular endothelial growth factor in inflammatory and malignant peritoneal effusions

OBJECTIVE: Inflammatory or malignant peritoneal diseases are associated with high levels of ascitic vascular endothelial growth factor (VEGF). We compared the VEGF secretion by human peritoneal mesothelial cells (HPMC) and ovarian carcinoma (OVCA) cells and its regulation by pro-inflammatory cytokines. MATERIALS AND METHODS: VEGF secretion in cultured HPMC, established human OVCA cell lines, and inflammatory or OVCA-associated ascites was determined by enzyme linked immunosorbent assay. RESULTS: HPMC constitutively produced VEGF at median levels of 43 +/- 7 pg/10(5) cells. Treatment of HPMC with 1 ng/ml IL-1beta (567 +/- 213 pg/10(5) cells) or TNF-alpha (89 +/- 1 pg/10(5) cells) resulted in a 13-fold (P < 0.01) or 2-fold (P < 0.05) elevation of the VEGF secretion. In OVCA, the constitutive VEGF expression was 8-fold higher than VEGF levels in HPMC (364 +/- 185 pg/10(5) cells; P < 0.001). VEGF secretion in OVCA cells was also increased by IL-1beta (514 +/- 105 pg/10(5) cells; P < 0.01) or TNF-alpha (458 +/- 168 pg/10(5) cells; P < 0.01) reaching similar levels as in IL-1beta-activated HPMC. Median VEGF levels in malignant ascites (2761 +/- 1549 pg/ml) were 11-fold higher compared with levels in inflammatory fluids (244 +/- 170 pg/ml; P < 0.01). VEGF levels in both inflammatory- and OVCA-associated fluids correlated with ascitic IL-1beta levels (P < 0.05). CONCLUSION: We identified ovarian cancer cells and/or IL-1beta-activated peritoneal mesothelial cells as important sources of ascitic VEGF. The present data indicate that IL-1beta-triggered VEGF production by neoplastic and normal cells is a common pathomechanism for ascites formation in both inflammatory and malignant conditions.     

卵巢上皮性癌中Claudin-3和MT1-MMP基因的表达及其意义

目的:探讨Claudin-3和MT1-MMP在卵巢上皮性癌组织中的表达及其与预后的关系。方法:用免疫组化法测定卵巢上皮性癌72例、上皮性卵巢肿瘤20例和正常卵巢组织10例中Claudin-3和MT1-MMP的表达。结果:Claudin-3和MT1-MMP在正常卵巢组织中未见表达,在癌组织中的表达高于良性囊腺瘤的表达,卵巢上皮性癌中、低分化组的Claudin-3表达显著高于高分化组(P=0.001),有淋巴结转移组的Claudin-3表达显著高于无淋巴结转移组(P=0.001);MT1-MMP在晚期卵巢上皮性癌中的表达显著高于早期癌(P=0.011)。单因素分析,Claudin-3和MT1-MMP高表达组患者的平均生存时间显著低于低表达组(P=0.029)。结论:Claudin-3和MT1-MMP在卵巢上皮性癌的转移和浸润中起着重要作用,其高表达与不良预后有关。     

卵巢浆液性癌B7-H4的表达及临床病理意义

目的:探讨B7-H4在卵巢上皮性肿瘤浆液性癌中的表达及其临床病理意义。方法:用逆转录聚合酶链反应(RT-PCR)技术及免疫组织化学染色的方法检测6例良性卵巢上皮性肿瘤、10例交界性卵巢上皮性肿瘤、41例卵巢浆液性癌、5例内膜样癌、2例透明细胞癌和10例粘液性癌标本中B7-H4 mRNA及蛋白表达,并结合临床病理资料对其中41例卵巢浆液性癌中B7-H4蛋白的表达进行分析。结果:B7-H4 mRNA在74例卵巢上皮性肿瘤中均有表达,B7-H4蛋白在良性卵巢上皮性肿瘤、交界性卵巢上皮性肿瘤、恶性卵巢上皮性肿瘤中的表达阳性比例分别为2/6、6/10、52/58,恶性标本阳性率明显高于非恶性标本,差异有统计学意义(P<0.05);58例恶性卵巢上皮性癌标本中浆液性癌、内膜样癌、透明细胞癌、黏液性癌的B7-H4蛋白阳性比例分别为41/41、5/5、2/2、4/10,前三种病理类型B7-H4蛋白阳性率明显高于最后一种,且差异有统计学意义(P<0.05);41例卵巢浆液性癌标本中B7-H4蛋白阳性细胞比例在<10%,>10%~50%,>50~80%,>80~100%4组中的分布差异无显著性(P>0.05),且其蛋白表达与临床分期及病理分级有关(P<0.05),而与患者年龄、腹水细胞学、淋巴结转移无关(P>0.05)。结论:B7-H4在卵巢浆液性癌的高表达及其与临床分级分期的关系,提示其可能与肿瘤发生发展有关,可为卵巢恶性肿瘤诊断及治疗提供靶位点。     

Significance of serum and peritoneal fluid lactate dehydrogenase levels in ovarian cancer

We investigated prospectively whether the detection of serum lactate dehydrogenase (LDH) and/or peritoneal fluid LDH levels may serve as a reliable biochemical marker in discriminating ovarian carcinoma from benign ovarian tumors. In this series, postoperatively 20 of 50 patients had a diagnosis of ovarian cancer while the remaining 30 patients had benign ovarian tumor. No significant difference in peritoneal fluid LDH levels was observed between patients with ovarian cancer and benign ovarian tumor (p > 0.05). Serum LDH levels in ovarian cancer patients were significantly higher than those in patients with benign ovarian tumor (p < 0.05). Statistically significant differences were not observed in LDH levels of different histological types of ovarian cancer and different stages of the disease. Serum LDH levels presented diagnostic accuracy with high specificity and may have a potential use as a biochemical marker.     

Correlation between soluble Fas level and apoptosis of T cells in ovarian carcinoma

OBJECTIVES: The objectives were to examine the correlation between soluble Fas (sFas) level and apoptosis of T cells in peripheral blood and peritoneal fluid of patients with ovarian carcinoma and to investigate the possible sFas effect on T cell apoptosis. STUDY DESIGN: Patients with stages I-II ovarian carcinoma (n=10) and patients with stages III-IV ovarian carcinoma (n=22), as well as ovarian benign tumors (n=8), were enrolled in the study. Apoptosis of and Fas expression on T cells from peripheral blood and peritoneal fluids were assessed by flow cytometry. Soluble Fas level was assayed using an ELISA kit. The effects of peritoneal fluid on Jurkat cell apoptosis with or without depletion of sFas were evaluated and compared in vitro. RESULTS: The sFas level and apoptosis of T cells in peripheral blood and peritoneal fluid from stages III-IV ovarian carcinoma were significantly higher than those from stages I-II ovarian carcinoma (p<0.01 in all instances) and benign ovarian tumor (p<0.01 in all instances). In peritoneal fluid, the sFas level and apoptosis of T cells from stages I-II ovarian carcinoma were significantly higher than those from benign ovarian tumor (p<0.01 in all instances), and the Fas expression on T cells from ovarian carcinoma were higher than those from benign ovarian tumor (p<0.05 in all instances). There was a positive correlation between the sFas level and the apoptosis of T cells in peritoneal fluids from stages III-IV ovarian carcinoma (r=0.647, p=0.001). Peritoneal fluid of ovarian carcinoma could induce significant Jurkat cell apoptosis. The blocking of Fas expression on the Jurkat cell surface, but not the deletion of sFas, may remarkably restrain the apoptosis level. CONCLUSIONS: Elevated sFas is correlated with apoptosis of T cells in peripheral blood and peritoneal fluid from ovarian carcinoma. Soluble Fas evidently does not affect T cell apoptosis, which is probably due to elevated Fas expression on T cells.     

转化生长因子β_1、白细胞介素2、7与卵巢上皮性癌患者腹腔局部免疫功能的关系

目的:探讨转化生长因子β1(TGFβ1)和白细胞介素-2(IL-2)、白细胞介素-7(IL-7)与卵巢上皮性癌腹腔局部免疫功能的关系。方法:采用酶联免疫吸附试验(ELISA)法,测定49例卵巢上皮性癌,18例卵巢良性上皮性肿瘤患者血清、腹腔液中TGFβ1和IL-2、IL-7水平,比较两组之间各细胞因子水平的差异性及其相互关系。结果:卵巢上皮性癌患者血清中TGFβ1、IL-2水平与良性对照组差异无显著性(P>0.05),IL-7水平则高于对照组(P<0.05);腹腔液中TGFβ1水平明显高于对照组(P<0.01),IL-2水平明显低于对照组(P<0.05),IL-7水平则与对照组相比差异无显著性(P>0.05)。Ⅲ期患者腹腔液中TGFβ1水平明显高于Ⅰ、Ⅱ期(P<0.01)。卵巢上皮性癌患者血清与腹腔液中TGFβ1、IL-2相关性不显著,而IL-7水平存在正相关;卵巢上皮性癌患者血清中TGFβ1;、IL-2和IL-7水平两两之间均无明显相关性;但腹腔液中TGFβ1与IL-2、IL-7水平均存在显著的负相关,IL-2与IL-7水平则无明显相关性。结论:卵巢癌存在腹腔局部免疫缺陷,腹腔液中TGFβ1、IL-2和IL-7参与这一过程,且3者之间可能存在一定的关系。     

Secretion of vascular endothelial growth factor in ovarian cancer.

Vascular endothelial growth factor (VEGF) is an important regulator of vascular endothelial cell function during vasculogenesis and tumor growth and is believed to play a major role in peritoneal fluid accumulation in ascites tumors. High VEGF production from primary tumors has been reported to correlate with increased metastatic spreading and worse prognosis compared to low VEGF secreting tumors. In addition, VEGF secretion has recently been proposed as one of the major factors responsible for defective immune function in cancer patients. In order to evaluate whether ovarian carcinomas actively secrete VEGF, in this study we have analyzed and quantified VEGF secretion in several fresh and established human ovarian carcinoma cell lines in vitro using a sensitive enzyme-linked immunosorbent assay (ELISA). In addition, VEGF levels were also evaluated in the ascitic fluids and plasma of six ovarian cancer patients. All fresh tumors secreted high levels of VEGF (mean = 5,046, range between 1,760 and 7,780 pg/ml/10(5) cells/48 hr) when compared to established ovarian carcinoma cell lines (mean = 493, range between 160 to 1,120 pg/ml/10(5) cells/48 hr) (p <0.02). Importantly, high grade malignancies were found to secrete larger amounts of VEGF (mean = 6,660 pg/ml) when compared to lower grade tumors (mean = 1,820 pg/ml) (p <0.01). Ascitic fluids from all patients were rich in VEGF (mean = 5,483, range between 1,300 and 11,200 pg/ml) and plasma levels of VEGF in ovarian cancer patients were significantly higher (mean = 408, range between 160 and 810 pg/ml) when compared with healthy individuals (mean = 46, range between 35 and 60 pg/ml) (p <0.01). Taken together, these data demonstrate that ovarian cancers secrete large amounts of VEGF in vitro and in vivo. This findings therefore suggest that this factor may play a crucial role in the genesis of ascitic fluid accumulation, angiogenesis and tumor induced immunosuppression in ovarian cancer patients. The design of anti-angiogenic treatment directed at blocking the action of VEGF may be a reasonable novel therapeutic approach in the treatment of ovarian cancer.     

P53-status in primary ovarian carcinomas, ovarian metastases of neoplasms in other sites and benign ovarian tumors: predictive value in comparison to histopathological parameters

OBJECTIVE: The purpose of this study was to determine whether the tumor suppressor gene p53 can be used as a prognosis factor to assess individual patient risk in primary ovarian carcinoma. MATERIALS AND METHODS: The concentration of the mutated, as well as the wild type p53 was examined in 98 cases of ovarian carcinoma. Among 98 ovarian tumors examined, 77 were primary carcinomas, 14 tumors were metastasis of foreign tumors, and 7 were benign ovarian tumors. The pan-53 ELISA from Fa. Dianova was used to test for the p53 protein. RESULTS: The p53 protein concentration exhibited a wide range in the different tissue samples. Benign tumors contained significantly lower p53 concentrations than malignant tumors. After the data was analyzed using Kaplan-Meier, a p53 concentration of 507.1 pg/ml was established as cut-off point for assessing cancer prognosis as good or poor. Patients exhibiting p53 concentrations over 507.1 pg/ml had a median life expectancy of 20 months, and patients exhibiting lower tumor concentrations of p53 had a life expectancy of over 70 months. A significant relationship between patient life expectancy could also be shown for tumor stage and type, whereas not for tumor grading. CONCLUSIONS: Based on the results of this study, the routine measurement of p53 may allow for a better prognostic assessment of life expectancy of patients with primary ovarian carcinoma.     

Growth promoting properties of cell free malignant ascites and benign peritoneal fluid on epithelial ovarian carcinoma cells in culture

van Geene P, Kehoe S, Luesley D, Ward K. Growth promoting properties of cell free malignant ascites and benign peritoneal fluid on epithelial ovarian carcinoma cells in culture. Int J Gynecol Cancer 1998; 8 : 197–202.
The growth of epithelial ovarian carcinoma is regulated by a number of cytokines, some of which are stimulatory and some inhibitory. The cells of origin of these cytokines are known in only a few cases but include tumor cells, lymphocytes, macrophages, other components of the immune system, and mesothelial cells. Malignant ascites and non-malignant peritoneal fluid contain varying quantities of cytokines dependent on the cell populations present and therefore the relative importance of any individual cytokine in the stimulation of tumor cells may vary between patients. Because of the potential for cytokines to act in synergy or in short paracrine loops it is proposed that the overall growth regulating effect of ascites is of clinical importance to the patient with ovarian carcinoma. We have measured the overall stimulatory effect of 38 malignant and 26 benign, cell free, peritoneal fluids on the growth of epithelial ovarian carcinoma cells cultured in vitro . In all cases, peritoneal fluid increased the growth of ovarian carcinoma cells in vitro when compared to standard growth media. There was no significant difference in stimulation between peritoneal fluid obtained from benign ovarian tumors and other benign gynecologic conditions, but fluid obtained from patients with ovarian carcinoma had a significantly greater growth stimulatory effect ( P = 0.0132).     

Expression and localization of aquaporin-5 in the epithelial ovarian tumors

OBJECTIVE: To investigate the expression and localization of aquaporin-5 (AQP5) in epithelial ovarian tumors and its clinic significance. METHODS: The expression of AQP5 protein and mRNA in 65 cases epithelial ovarian tumors and 13 cases normal tissue were measured by immunohistochemical technique, Western blotting and RT-PCR, respectively. RESULTS: AQP5 is mainly localized in the basolateral membranes of benign tumor cells, the apical and basolateral membrane of borderline cells and scattered in the membrane of malignant cells and almost no or weak staining in normal ovarian epithelium. The AQP5 expression in ovarian malignant and borderline tumors was significantly higher than that of benign tumors (P < 0.05) and normal tissue (P < 0.05). Of all the epithelial ovarian malignant tumors, the AQP5 expression in cases with ascites volume more than 1000 ml was higher than that of ascites volume less than 500 ml (P < 0.05). Increased AQP5 protein level was associated with lymph node metastasis (P < 0.05). There is a positive correlation between ascites amount and the expression of AQP5 protein and mRNA (P < 0.05), as well as lymph node metastasis and the expression of AQP5 protein and mRNA (P < 0.05). The AQP5 expression was not related with FIGO stage, grade and histological type (P > 0.05). CONCLUSION: The data suggest that overexpression of AQP5 play an important role in tumorigenesis of epithelial ovarian tumors, which may be related to the ascites formation of ovarian carcinoma.     

Luteinizing hormone in peritoneal and ovarian cyst fluids: a predictor of ovarian carcinoma

Objective: The aim of this study was to define the role of luteinizing hormone (LH) as a tumor marker, specific for ovarian cancer. Methods: The study included 34 women with functional and benign ovarian cysts, 11 women with borderline ovarian tumors, 22 patients with advanced ovarian cancer and 15 patients with non-ovarian intraperitoneal malignancies. Serum, peritoneal fluid and ovarian cyst aspirates were obtained intraoperatively (laparoscopy or laparotomy) and were subjected to the LH analysis. Results: Peritoneal fluid LH levels were significantly increased in patients with ovarian cancer and those with borderline ovarian tumors as compared to patients with functional and benign ovarian cysts (P=0.005 and P=0.007, respectively). The patients with non-ovarian malignancies demonstrated the same peritoneal fluid LH levels as patients with benign ovarian tumors. There was no significant difference in the level of peritoneal fluid LH between ovarian cancer patients with and without ascites. The patients with functional and benign ovarian cysts demonstrated also significantly lower cyst fluid LH levels as compared to patients with malignant and borderline ovarian cysts (P=0.01 and P=0.03, respectively). Peritoneal and ovarian cyst fluid levels of LH were significantly increased in patients with fibrothecomas as compared to patients with other benign ovarian cysts. There were no significant differences in the serum LH levels comparing patients from all study groups. Conclusion: LH, detectable in peritoneal and ovarian cyst fluids, can be used as a tumor marker for identification of patients with borderline and malignant ovarian tumors.     

Comparison between serum CA 125 and CA 19-9 assays and tissular OC 125 and 1116NS 19-9 reactivity in malignant and benign ovarian tumors.

This preliminary study included 25 patients with primary epithelial ovarian cancer (EOC) (18 serous, 3 serous-mucinous, 1 endometrioid, 2 undifferentiated carcinomas and 1 malignant Brenner carcinoma); 2 patients with borderline ovarian tumors and 20 patients with benign ovarian tumors (9 benign cystic teratomas, 6 serous cystoadenomas and 5 mucinous cystoadenomas). Blood samples for the measurement of CA 125 and CA 19-9 were drawn from all patients before surgery. Serum CA 125 (Reference Value-RV = 65 U/ml) and CA 19-9 (RV = 40 U/ml) were measured with IRMAs using the monoclonal antibodies (MoAbs) OC 125 and 1116NS 19-9. The same antigens were detected on paraffin-embedded tissue sections by immunocytochemistry with the avidin-biotin complex method employing the same MoAbs used for serum IRMAs. Among the 25 patients with EOC serum CA 125 levels were elevated in 20: tissular OC 125 reactivity was observed in 15 (75%) of them. Of the 5 EOC patients with normal CA 125 levels, 4 showed OC 125 reactivity. Only 2 of the 25 EOC patients had elevated serum CA 19-9 levels: one of them had tissular 1116 NS 19-9 reactivity. Among the 23 patients with normal serum CA 19-9 levels only 5 had immunocytochemical reactivity for this antigen. The 2 patients with borderline ovarian tumors had negative serum CA 125 and CA 19-9 assay: tissular OC 125 reactivity was observed in both patients, while 1116 NS 19-9 reactivity was detected in only one.(ABSTRACT TRUNCATED AT 250 WORDS)     

Concentrations of follicle stimulating hormone are increased in ovarian tumor fluid: implications for the management of ovarian cancer

PURPOSE OF INVESTIGATION: Significant progress has been made in recent years in the understanding of the mechanisms postulated by the gonadotropin theory of ovarian carcinogenesis. In the present study we compare FSH concentrations between serum and fluid from cysts or the rectouterine pouch of patients with epithelial tumors and non-neoplastic lesions. METHODS: We enrolled 277 patients. They were divided into five groups: I (n = 44)--ovarian cancer patients, II (n = 16)--borderline tumors, III (n = 40)--benign epithelial cystadenomas, IV (n = 137)--non-neoplastic lesions and V (n = 22)--admitted for "second-look" laparoscopy. RESULTS: There were any significant differences between FSH concentrations in serum and tumor fluid in patients with ovarian cancer (36.46 vs 28.11 mIU/ml) and borderline epithelial tumors (31.5 vs 22.7 mIU/ml). For benign cystadenomas the respective concentrations were 28.96 mIU/ml in serum and 6.93 mIU/ml in tumor fluid in these groups p < 0.0000001. The same highly significant differences were found in non-neoplastic lesions (24.97 vs 4.77 mIU/ml), p < 0.0000001. Patients who underwent "second-look" laparoscopy demonstrated significant differences (p < 0.05) as FSH concentration in serum and peritoneal fluid when neoplastic cells were not disclosed, but the difference was not significant (p = 0.752) when fluid from the rectouterine pouch was positive for carcinoma cells. CONCLUSIONS: The results of our study can reflect an ineffective tumor: blood barrier and easy diffusion of gonadotropins into the tumor tissue. Local reduction of FSH levels through administration of GnRH analogs may in some clinical situations produce clear therapeutic benefits for the management of ovarian malignancies.     

Identification of the inhibitory p40 subunit of interleukin 12 from the ascitic fluid of patients with advanced carcinoma of the ovary

DeCesare SL, Gamero A, Becker J, Barton D, Bomalaski J, Fiorica J, Arango H, Hoffman M, Djeu J. Identification of the inhibitory p40 subunit of interleukin 12 from the ascitic fluid of patients with advanced carcinoma of the ovary. Int J Gynecol Cancer 1988; 8 : 133–137.
Objective: To determine the levels of interleukin 12 (IL-12) in the ascites from patients diagnosed with advanced epithelial ovarian cancer.
Methods: Ascites samples from advanced ovarian cancer patients and peritoneal fluid from normal controls and endometriosis patients were tested for the presence of IL-12 by ELISA. Two different IL-12 ELISA kits were used. One ELISA kit detected the bioactive heterodimeric form of the IL-12 cytokine composed of the p40 and p35 subunits, while the second kit detected both the bioactive form and the p40 subunit of IL-12.
Results: The first ELISA, which tested for only the bioactive heterodimer of IL-12, was negative in all 28 ovarian cancer patients. The second ELISA assay, which reacts with both the p40 subunit monomer and the heterodimer of IL-12, showed detectable levels of IL-12 in all 28 cancer patients and all 29 benign patients. Since no IL-12 heterodimer was detected in the first assay, these results represented the p40 monomer levels. A significantly higher median level of IL-12 monomer was found in malignant ascites compared to all benign control groups ( P < 0.05).
Conclusions: Ascites from advanced ovarian cancer patients contains significantly higher levels of the IL-12 p40 subunit than peritoneal fluid from normal patients, but contains no measurable bioactive IL-12 heterodimer. The secreted p40 subunit has been shown to inhibit IL-12 mediated activation of T and natural killer cells in vitro. In vivo suppression of lymphocytes by IL-12 p40 in ovarian cancer patients has not yet been demonstrated.     

IGF1、IGF1R及IGFBP3在卵巢上皮性肿瘤的表达及临床病理意义

目的:探讨胰岛素样生长因子1(IGF1)及其受体(IGF1R)、胰岛素样生长因子结合蛋白质3(IGFBP3)在卵巢上皮性肿瘤的表达及在原发性卵巢上皮性癌(EOC)中的临床病理意义。方法:用免疫组化法检测10例正常卵巢组织、13例良性卵巢上皮性肿瘤、12例交界性卵巢上皮性肿瘤、50例EOC手术病理标本中IGF1、IGF1R、IGFBP3的表达,分析三者表达与EOC临床病理特征的相关性。结果:(1)IGF1、IGF1R、IGFBP3在正常卵巢组织、良性卵巢上皮性肿瘤、交界性卵巢上皮性肿瘤、EOC的表达依次增强,IGF1阳性表达率分别为20.00%,23.08%,25.00%,80.00%;IGF1R阳性表达率分别为20.00%,30.77%,33.33%,84.00%;IGFBP3阳性表达率分别为30.00%,38.46%,41.67%,86.00%,三者在EOC组的阳性表达率均明显高于交界性卵巢上皮性肿瘤组(P<0.01)。(2)IGF1R在EOC中的表达阳性程度与病理学分级、临床分期、腹水/腹腔冲洗液阳性之间呈显著正相关(P<0.05);IGFBP3表达的阳性程度与临床分期呈显著的负相关(P<0.05)。(3)IGF1R在EOC中的表达程度与IGF1表达程度间呈显著的正相关(P<0.05)。结论:卵巢上皮性癌中存在IGF1、IGF1R、IGFBP3的过表达,三者共同参与了EOC的发生发展过程;IGF1R与EOC不良预后的重要临床病理指标间呈显著的正相关,IGF1R可作为卵巢上皮性癌基因靶向治疗的新靶点。     

卵巢上皮性癌组织中水通道1蛋白和mRNA的表达及其临床意义

目的探讨水通道1(AQP1)蛋白和mRNA在卵巢上皮性癌组织中的表达及其临床意义。方法采用免疫组化法、蛋白印迹法和RT-PCR技术检测35例卵巢上皮性癌、15例卵巢交界性上皮性肿瘤、15例卵巢良性上皮性肿瘤组织中AQP1蛋白和mRNA的表达,并以13例正常卵巢组织为对照。结果AQP1蛋白主要表达于卵巢上皮性肿瘤和正常卵巢组织的毛细血管及小血管内皮细胞膜,卵巢上皮性癌和卵巢交界性上皮性肿瘤组织中AQP1蛋白表达水平分别为0.39±0.12和0.43±0.21,AQP1mRNA表达水平分别为0.93±0.51和0.95±0.34,均明显高于卵巢良性上皮性肿瘤和正常卵巢组织(AQP1蛋白表达水平分别为0.27±0.13和0.24±0.13,AQP1mRNA表达水平分别为0.51±0.41和0.34±0.29;P<0.05)。卵巢上皮性癌患者腹水量≥1000ml者其癌组织中AQP1蛋白表达水平为0.46±0.13、AQP1mRNA表达水平为1.25±0.57,明显高于腹水量为1～499ml者(AQP1蛋白表达水平为0.35±0.11,AQP1mRNA表达水平为0.75±0.45;P<0.05);卵巢上皮性癌组织中AQP1蛋白和mRNA表达与其手术病理分期、病理类型、病理分级和有无淋巴结转移无关(P>0.05)。结论AQP1蛋白和mRNA过度表达在卵巢上皮性癌发生、发展中起一定的作用,是其腹水形成的原因之一。     

RU486对OHSS模型大鼠血管内皮生长因子产生的作用

目的:探讨RU486对卵巢过度刺激综合征(OHSS)模型大鼠血管内皮生长因子(VEGF)产生的作用。方法:30只22日龄雌性大鼠,从22日龄起每天皮下注射10IUPMSG连续4d,26日龄时皮下注射100IUhCG,建立OHSS模型。在27日龄将上述大鼠随机分成5组,每组6只。其中4组(A-D组)为实验组,分别皮下注射不同剂量(1mg/kg、5mg/kg、10mg/kg、20mg/kg)的RU486;另一组为对照组不给药。RU486注射48h后,采用酶联免疫吸附试验方法测定血清和腹腔冲洗液中VEGF水平;采用免疫组织化学法和逆转录聚合酶链反应技术检测卵巢组织VEGF蛋白质和mRNA的表达。结果:B组和C组的血清VEGF水平分别为55.00±14.13pg/ml和49.67±17.44pg/ml,均显著低于对照组(76.17±18.19pg/ml)(P<0.05)。同样,B组和C组的腹腔VEGF水平分别为10.43±6.80pg/ml、10.30±5.82pg/ml,也均显著低于对照组(17.12±1.71pg/ml)(P<0.05)。B组和C组的卵巢组织VEGF蛋白质和mRNA的表达显著低于对照组(P<0.05)。结论:适当剂量的RU486能够降低OHSS模型大鼠VEGF的产生。