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The Expression And Clinical Significance Of RKIP In Patients With Cholangiocarcinoma

Posted on:2013-10-09Degree:MasterType:Thesis
Country:ChinaCandidate:L J ChengFull Text:PDF
GTID:2234330374958687Subject:Internal Medicine
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The cholangiocarcinoma (CC) is a malignant tumor derived from the biliaryepithelium, common in old people, men slightly more than women, and thatlack of specificity early clinical manifestation. It was15%~40%of the5years survival of radical resection, while easily relapse and metastasis. Thecholangiocarcinoma form often more than a step, many factors which worktogether, including cancer gene and tumor-suppressor genes. The relativebalance is broken, and some growth factor, receptor, signaling pathwaysdownstream factors may all involved in the bile duct carcinoma formation.Raf kinase inhibitor protein (RKIP) that a part of phospha-tidylethanolalmine binding proteins, is a soluble basic protein which has beenpurified from bovine brain. It is constituted by a single polypeptide chain witha molecular weight of about21-23kD and an isoelectric point of about8.6. Itis that existing widely in the evolution of the highly conservative smallmolecular cytoplasm protein, mainly located in the organization of thecytoplasm and the plasma membrane. It is found that RKIP involved a varietyof signal transduction pathways regulation. It can inhibit MAP kinase(Raf-MEK-ERK), G protein-coupled receptor (GPCR) kinase and NF-κBsignaling cascades, involving several kinds of cell behavior such as cellgrowth, development, proliferation and differentiation, and neuraldevelopment, sperm happen, etc. The expression disorders can lead somepathophysiology process, such as tumor.The research in recent years indicates that RKIP has a close relationshipwith tumor participating in occurrence and development of tumor. RKIP caninhibit tumor cells to transfer. The first evidence derived from cell lines ofmetastatic prostate cancer Furthermore, over-expression of RKIP-1inmetastatic cancer cells can decrease their invasiveness. Treatment of breast and prostate cancer cells with chemotherapeutic agents induces RKIP-1over-expression and predisposes these cancer cells to apoptotic. Recently, ithas been proposed that the level of RKIP-1in the blood can be used as aprognostic marker for prostate cancer patients. There is another report thatRKIP can inhibit the gene let-7which also inhibits the transference of breastcancer to some extent. Besides, RKIP has a low expression on squamous cellcarcinoma of the lung, breast cancer, bladder cancer, nasopharyngealcarcinoma, cervical cancer. The decrease of expression is associated with thedegree of tumor metastasis. So RKIP is considered as transference-inhibitedfactor, which is very important in occurrence and development of malignanttumor. While it is also reported that the expression in non-small-cell lungcarcinoma is the same as primary tumors and metastatic lesions, in contrast,p-RKIP has a conspicuous low expression in cancer tissue which can beregarded as prognosis index. Thereby, the research on RKIP and p-RKIPestablish a new direction into the treatment to tumor. Then, RKIP and p-RKIPin formation and development of the cholangiocarcinoma exactly what effectdid, is worth further discussing, to open up new direction of the bile ductcancer treatmentObjective: Our object is to mainly study the expression of RKIP andp-RKIP proteins on cholangiocarcinoma, which discussed the relationshipbetween expression and clinical pathological index and the meaning of thepatients who has an operation on cancer of bile duct.Method:1We will take30cases of paraffin wax what are cholangiocarcinomapatients’ surgical specimens, cholangiocarcinoma tissue and peritumoralnormal bile duct tissue (about2cm lesions outside organization).2The pathological type of cholangiocarcinoma is determined with HE staining,and observation results in optical microscope. It is used by the CK19monoclonal antibodies to mark organization specimens with immunohistoche-mistry.3Then measure the expression of RKIP and p-RKIP in cholangiocarcinoma tissue and peritumoral normal bile duct tissue with immunohistochemistry.Two chips per tissue: cholangiocarcinoma tissue (A) and peritumoral normalbile duct tissue (B), separately set up negative comparison to immunohistochemistry.4Take each section express positive regional as five pictures, withimage-pro-plus software processing images. The expression of cancer tissueand peritumoral normal tissue will be detected to in the area of the positiveaverage light density values (mean density). Deal with the statistical differenceof mean density in each group by statistic software SPSS17.0.5The test for patients with follow-up, through the telephone and the returnvisit clear survival time and cause of death of postoperative.Results:1Qualitation of tissue types:30examples with HE staining arecholangiocarcinoma tissue and normal epithelium of bile duct tissue, have ahigh expression marked by CK19.2RKIP has a low expression in cholangiocarcinoma tissue, which meandensity is0.016±0.024and that has a high expression in peritumoral normaltissue with0.166±0.038. The comparison between them has statisticalsignificance (P<0.05). The mean density of p-RKIP in cancer tissue andperitumoral normal tissue respectively is0.044±0.028and0.047±0.029, wherehas no statistical significance.3The expression of RKIP is related with lymph nodes and transference, andcorrelated with live time after operation, while has no immediate relationshipwith age, gender, pathological classification and cell differentiation.Conclusion: The expression of RKIP in the cholangiocarcinoma tissue islower than that in normal epithelium of bile duct. The decrease is a significantprognosis index with the patient of cholangiocarcinoma. But the p-RKIPexpression in cholangiocarcinoma tissue is the same as in normal tissue.
Keywords/Search Tags:RKIP, p-RKIP, cholangiocarcinoma, immunohistochemistry, metastasis
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