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The Expression And The Significance Of VEGF And Flt-1 In The Tissues,Blood Serum And Ascites Of The Ovarian Cancer Patients

Posted on:2009-12-01Degree:MasterType:Thesis
Country:ChinaCandidate:H X LiFull Text:PDF
GTID:2144360242481111Subject:Clinical Medicine
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The ovarian cancer has become a serious threat to women's lives and health, because of difficulties in early detection, early diagnosis and particularly resistant to conventional chemotherapy drugs, and so on. Vascular endothelial growth factor (VEGF) is a kind of protein that can specifically promote vascular endothelial cell growth and increase vascular permeability, which plays an important role in a variety of solid tumors in their occurrence and development. VEGF will play its biological effects when it binds with its specificity and high affinity receptors .So far there are three kinds specific receptors found. Flt-1 (VEGFR-1) , combining to VEGF, mainly regulates the relationship between the vascular endothelial cells and the interaction of the vascular endothelial cells and stromal cells besides its fundamental effects, and shows the effect of cavity promotion and vascular permeability. Previously studies adopted serology, immunohistochemical and Westen-blot method, had shown that VEGF binding to its receptor may play a variety of complex biological effects, participate in the growth of ovarian cancer cells, the formation of ascites, abdominal pots and distant metastasis and other clinical pathological process. But there is lack of experimental evidence whether VEGF can be used as a diagnosis of ovarian cancer detection factor, and the mechanism of promoting ascites, lymph nodes,abdominal and basin transformation are not clear. Our study in ovarian cancer by detecting expression of VEGF and its receptor Flt-1 protein and peritoneum of angiogenesis in ovarian cancer tissues , expression of VEGF in serum,ascites and precipitation ascites cells, is to reveal the possible effect of VEGF in ovarian cancer clinical pathological process, and to provide experimental basis for the usage of VEGF in ovarian cancer diagnosis and treatment . [Materials and methods]Choose hospitalization patients in second hospital of Jilin University from January 2006 to January 2008: 43 cases of patients with ovarian cancer; 18 cases of benign ovarian tumor 16 cases of patients with normal ovarian tissue. Take the serum of venous blood of all patients in the first hospitalization before surgery, store in -20℃. And collect ovarian tumor tissues, or normal ovarian tissue,omentum and peritoneal tissue, stored inside formalin- fixed. The tissues are used to detect the expression of VEGF, Flt-1 protein and angiogenesis by immune SP Detection. Meannwhile collect 20 ml ascites , anticoagulated. Stored the supernatant in -20℃. Detect the VEGF protein in the supernatants of by ELISA; Detect the immune fluorescence intensity in the precipitation cells of ascites by flow cytometry within 24 hours. Collect patients with non-malignant pelvic fluid as the control group, including the 5 cases of tuberculosis, 5 cases of benign ovarian tumors, and 5 cases pelvic inflammatory effusion.[Results]:1. The comparison of the positive expression rate of VEGF and its receptor Flt-1 among groups classed accordance with ovarian cancer clinical pathological characteristics: In ovarian cancer, the patients stage III-IV get higher rate of positive expression of VEGF and its receptor Flt-1 than stage I-II (P <0.05); The patients whose ascites is above 500 ml is higher than that is below 500 ml (P <0.05); The patients that have pots of peritoneal metastasis is higher than those without pots peritoneal metastasis (P <0.05), there are no difference between age groups, different histological types and different histological types . The comparison of the positive expression rate of VEGF and its receptor Flt-1 among patients with ovarian cancer, benign ovarian tumor patients and the control group of patients: patients with ovarian cancer, the positive rate of expression of VEGF and Flt-1 higher than that of benign tumors and the control group of patients in ovarian tissue (P< 0.05). benign ovarian tumor patients and the control group showed no significant difference (P> 0.05). In ovarian cancer patients's ovarian tissue, cancer cells, vascular endothelial cells and lymphocytes express VEGF, but in benign ovarian tumors and normal ovarian tissue of ovarian control group, the expression cells of VEGF are vascular endothelial cells. In all ovarian tissue, vascular endothelial cells mainly express Flt-1 and some ovarian cancer cells also express Flt-1. The microvascular density (MVD) of ovarian tissue in ovarian cancer Patients and VEGF expression in lymphocytes are different between patients who have pots of peritoneal metastasis and haven't: patients who have pots of peritoneal metastasis, the microvessel density are higher than those without metastasis of ovarian cancer patients (P <0.05); So are the positive expression rates of VEGF lymphocytes (P <0.05);2. The comparison of the positive expression rate of VEGF and its receptor Flt-1 in omentum and peritoneal tissues between groups classed according to whether exist cancer metastasis: Both omentum and peritoneal tissues, the positive expression rate in those exist cancer metastasis are higher than those without cancer metastases (P <0.05) (P <0.05). .3. The comparison of levels of VEGF protein in the supernatant of ascites and serum among groups of ovarian cancer, benign ovarian tumors and control group patients :About ovarian cancer patients, the level of VEGF protein in the supernatant of ascites is higher than that in serum (P <0.05),so is it in benign ovarian tumors patients (P <0.05), but have no significant difference in the supernatant of ascites and in serum of the control group patients(P> 0.05). The level of VEGF protein of ovarian cancer is higher than benign ovarian tumor and control group in the supernatant of ascites, and so is it in serum (P <0.05); The level of VEGF protein of benign ovarian tumor is higher than the control group patients in the supernatant of ascites(P <0.05), but have no significant difference in serum (P> 0.05).4. The comparison of ovarian cancer diagnostic significance among VEGF in Serum, VEGF in the supernatant of ascites and CA125 in serum: The sensitivity and specificity of CA125 in Serum in the diagnosis of ovarian cancer are as follows: 83.9%, 90.9%. in Serum are 90.6% 39.3%,and are 77.3% and 93.9% in the supernatant of ascites. When put the three methods together the diagnosis sensitivity and specificity of ovarian cancer are improved upto 96.5%, 93.9% .5. VEGF expression in precipitation cells of ascites of ovarian cancer patients and non-malignant ascites: The immune fluorescence intensity of precipitation cells of ovarian cancer ascites is higher than that of non-malignant ascites (P <0.05).[Conclusion]:1. Besides ascites exfoliated cells detection, to make the multiple indicator joint detection including VEGF at the same time, , will be beneficial to increasing ovarian cancer preoperative diagnosis rate, especially for exfoliated cells negative cases .VEGF detection of ascites also can identify benign and malignant tumors. When VEGF in Serum, VEGF in the supernatant of ascites and CA125 in serum are detected at the same time ,diagnostic sensitivity and specificity of ovarian cancer will be significantly improved.2. Ovarian cancer cells, vascular endothelial cells and lymphocytes of ovarian cancer patients may express VEGF. VEGF secretion ovarian cancer cells, on one hand can influent the cells around the tumor, and on the other hand achieve the local ovarian cancer invasion,metastasis and proliferation . VEGF is secreted to serum and ascites, and promotes cancer angiogenesis,forms a massive ascites, and results in abdominal pots and distant metastasis.3.High expression of VEGF may indicate poor prognosis. Monitoring VEGF in serum will be conducive to tumor recurrence and evaluate the prognosis of the patients.
Keywords/Search Tags:vascular endothelial growth factor, ovarian tumor, flow cytometry, enzyme-linked immunosorbent assay, ascites
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