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Quantitative Analysis Of Heparanase Gene Expression And Correlativity Of Metastasis Or Recurrence In Pancreatic Carcinoma

Posted on:2008-06-12Degree:MasterType:Thesis
Country:ChinaCandidate:C LeiFull Text:PDF
GTID:2144360218454232Subject:Surgery
Abstract/Summary:PDF Full Text Request
Primary pancreatic carcinoma(PPC) as a common malignant tumor in alimentary is a clinical symptom to hide ,it make progress quickly, and its prognosis is very bad and the existence rate of PPC is very low.Its biology characteristics: easily invasion nerve and blood vessel, the rate of lymphometastasis is high, and the anatomy position of PPC is deep, and lack the particularity toumor marker and the clinical manifestations in early grade, etc.As the same time, the postoperative recurrence or metastasis of PPC is easy occurrence. 75% of the accurate clinical diagnosis of PPC or more is already belong to the medium or later period, the surgical operation excision rate of PPC is low, and its not sensitive to the chemotherapy and radiotherapy. The existence rate of 5 years is still 5%.After the comprehensive treatment , it is predicting the tumor to relapse and metastasis, evaluating the prognosis of PPC that is a key place to raise the existence rate.To solve this problem must build up the particularity index that can predict the postoperative recurrence or metastasis and further evaluate the treatment result.Currently those original studies are concentrat on early diagnosis and the therapy, but not studies to evaluate its prognosis through finding the tumor marker , the research on recurrence or metastasis of PPC is less .At home and abroad currently ,its research still just the start stage, the beginning see the clues.Heparanase is a mammalian endo-glucuronidase that includes the Hpa1 and Hpa2 responsible for heparan sulfate degradation.Heparan sulfate is a major constituent of the extracellular matrix(ECM) and heparan sulfate–degrading activity is thought to play a decisive role in fundamental biological processes associated with remodeling of the ECM, such as angiogenesis and cancer metastasis. Heparanase activity has long been correlated with the metastatic potential of tumor-derived cells. heparan sulfate–degrading activity promote the postoperative recurrence or metastasis of tumor though raising blood vesseland, lymphatic vessel density assistance or associated with PA, , matrix metalloproteinases( MMPs), bEFG, VEGF, etc. Heparanase has been correlated with the postoperative recurrence or metastasis of tumor.In this research, expression the Hpa1 in 37 cases Primary pancreatic carcinoma by various methods to explore the relationship of hap1 and its clinicopathologic characters, Correlativity of expression the Hpa1 Among LVD, MVD, invasion, recurrence, metastasis in PPC were statistically analyzed.To provide the new theories of the postoperative recurrence or metastasis, further explore to find index sign to predict the recurrence or metastasis and prognosis. Objective:Through real time RT- PCR , Western- Blotting, Immunohisto-chemistry staining, the expression of Hpa1mRNA and Hpa1potein is Quantitativly detected in 37 pancreatic cancer tissues, peri-carcinomatous tissues and nontumoral tissues. Synchronous content of Hpa1 in Serum of those pancreas cancer was detected by ELISA(Enzyme-linked immunoadsordent assay) . the quantitative analysis Correlativity of expression the Hpa1 Among dissimilarity organization, LVD ,MVD ,invasion, recurrence , metastasis in PPC Thus to evaluate Hpa1 value in recurrence , metastasis ascpet and to provide experimental theories to predict the recurrence or metastasis and prognosis.Methods:(1)Real-Time RT-PCR assay:To observe the expression of hap1 mRNA in pancreatic cancer tissues, peri-carcinomatous tissues and nontumoral tissues.(2) Immunohisto-chemistry staining assay: To detected the expression of Hpa1,MVD,LVDin Primary pancreatic carcinoma.(3) Western-Blotting assay: To analyse Quantitativly the expression of Hpa1 potein in Primary pancreatic carcinoma .(4)ELISA assay: To observe chang of Hpa1 protein in Serum of Primary pancreatic carcinoma.Results:(1)The expression amounts of heparanase1mRNA in pancreatic cancer tissues were calculated 23.53±s 4.13.its expression amounts is 5.76±s 2.28 time in a normal pancreas.and 1.39±0.54 in peri-carcinomatous tissues ( p<0.05). Among pancreatic cancer tissues, peri-carcinomatous tissues and nontumoral tissues,the expression of Hpa1 potein were detected 1.76±0.28, 1.21±0.37,0.36±0.14 (p<0.05). The expression rate of Hpa11 is 64.9%(24/37) in PPC and it was declining among tissues.(2)The expression of Hpa1 was associated with lymph node metastasis,TNM grade and Invasion to nerves or vascellum, Peplos of pancreatic tumor separately.But no relationship among hisological differentiation , age, gend, the tumor size.(3)The positive expression of Hpa1 was associated with the postoperative recurrence or metastasis of PPC ,it may pass to promote MVD,LVD of PPC that lead to the postoperative recurrence or metastasis of PPC gradually.(4)Serum Hpa1 levels were significantly higher in patients with Hpa1-positive tumors compared with those with Hpa1-negative tumors.and the pancreatic carcinoma clinical pathology and the postoperative recurrence or metastasis is relationship with Serum Hpa1 levels. Conclusions:(1)Hpa1 has significantly higher relationship with the arising and development of pancreatic cancer ,also with its the clinicopathologic stages, Invasion to nerves or vascellum, Peplos of pancreatic tumor, lymphatic metastasis.while they may be target proteins in the antilymphatic therapy for pancreatic cancer.(2)This suggests that Hpa1 may contribute to the highly invasive , early metastatic behavior, the postoperative recurrence of pancreatic cancer.it leads to the postoperative recurrence or metastasis of PPC gradually through promoting MVD,LVD.(3)Hpa1 is acted as molecular markers to predictions of survival rate and the postoperative recurrence or metastasis in pancreatic cancer...
Keywords/Search Tags:pancreatic neoplasm, Heparanase, metastasis, recurrence, RT-PCR
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