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Expression And Clinical Applications Of Prostate-specific Membrane Antigen In Pancreatic Cancer

Posted on:2015-09-17Degree:MasterType:Thesis
Country:ChinaCandidate:H ZhangFull Text:PDF
GTID:2284330431475203Subject:Oncology
Abstract/Summary:PDF Full Text Request
Objective:Pancreatic cancer is one of the highly malignant tumor of the digestive system, at home and abroad in recent years, the incidence of pancreatic cancer showed a strong upward trend, early diagnosis is often difficult, because of its poor prognosis, characterized by highly aggressive and high transfer rate, five-year survival rate of only3%. Despite surgery and chemotherapy has been greatly improved, but the past20years the prognosis of patients with pancreatic cancer has not improved significantly, the survival rate of patients surgical resection remains low. Therefore, a more in-depth understanding of the pathogenesis of pancreatic cancer, early diagnosis of pancreatic cancer and effectively explore effective therapeutic targets is crucial to improve the level of treatment of pancreatic cancer.PSMA is present in prostate epithelial cell membrane of an n-type intrinsic membrane protein11’. Its gene is located on11P11a12, there is a homologous gene is located on11q14, eDN^about2.65Kb. PSMA contains750amino acids with a molecular weight IOOKD, the amino terminal located within the cell membrane, the membrane containing the19amino acid segment, comprising24amino acid transmembrane segment, the outer segment membrane comprising707amino acids, the membrane section and the outer section of the film containing up epitopes may be combined with a variety of monoclonal antibodies, in particular, and an outer segment membrane monoclonal antibody binds to an epitope with greater diagnostic and therapeutic value.Recent studies have found, PSMA can be expressed in a variety of solid tumor vascular endothelial cells. In1998,27cases of non-prostate cancer study found that all tumor neovascular endothelial cells can express PSMA, but can not express PSMA normal endothelial cells, which means that in addition to prostate-specific PSMA, but also may have tumor vascular endothelial cell-specific. Chang et124, also a large number of cancer research organizations, including renal cell carcinoma, bladder transitional cell carcinoma of skin, testis embryonal carcinoma, malignant glioma and other highly expression of PSMA malignancy, immunohistochemical methods they use to study the five different PSMA monoclonal antibody, found all of them can be combined with tumor-associated vasculature endothelial newborn, but in non-cancerous tissue and benign vascular tissue vasculature express negative. On the other hand, in prostate cancer tissues, very few endothelial cells express PSMA, a number of vascular tumors such as hemangioma, angiosarcoma, endothelial cells into tumor endothelial cells did not express PSMA, indicating that the expression of PSMA and learn about the nature of the tumor tissue by regulating tumor cell-matrix interactions, may be the expression of PSMA endothelial cells are stimulated tumor cells secrete a number of growth factors. PSMA expression of growth factors relationship needs further study. To all the growth and metastasis of solid tumors, angiogenesis must have, and is capable of expressing PSMA nascent vasculature. PSMA is more specific and is selectively expressed in tumors arising in neonatal vasculature. PSMA can be used as an ideal target factor, but also to avoid the treatment of antibody-dependent matrix must pass through before entering the vascular system and the shortcomings of cancer cells. Angiogenesis in tumor formation and spread an important role in the process has been fully discussed, in vivo anti-angiogenic good strategic outlook. Studies have shown that, PSMA PSMA gene promoter must contain reverse transcriptase promoter, the region started PSMA selectively transcribed, but only in tumor-associated vasculature newborn Expression control by separating the neonatal vasculature endothelial cell specific promoter region of the PSMA gene, gene therapy can develop specific anti-angiogenesis.This study aimed to investigate the protein levels in patients with pancreatic cancer tissue PSMA expression; expression in pancreatic cancer tissue RNA levels; relationship PSMA levels and prognosis; relationship PSMA levels and clinical stage and grade. Methods:一、 PSMA protein expression in patients with pancreatic cancerComplete clinical data collected pancreatic tissue paraffin sections using immunohistochemical staining expression in pancreatic cancer tissues and normal pa、ncreatic tissue control protein levels.二PSMA mRNA expression in patients with pancreatic cancerRNA was extracted from pancreatic cancer tissue, the expression of anti-transcribed into cDNA, real-time quantitative PCR technique to detect pancreatic cancer and normal pancreatic tissue control mRNA levels三、PSMA levels and prognosisPancreatic cancer patients will be divided into two groups:PSMA high expression group and the low expression group. Kaplan-Meier survival analysis applied its relationship with prognosis四、PSMA levels and clinical featuresSpearman’s correlation analysis application PSMA levels with age, tumor size, histological grade, lymph node metastasis, TNM stage relationship-Results:Pancreatic cancer cells not only at the protein and mRNA levels were expressed. PSMA levels and prognosis of pancreatic ductal adenocarcinomas patients PSMA expression is significantly lower than the survival of patients with low expression of PSMA. PSMA levels and histological grade and TNM stage.Conclusions:PSMA involved in the development of the pancreas, which may be a potential therapeutic target for pancreatic cancer...
Keywords/Search Tags:PSMA, Pancreatic cancer, Expression, Prognosis, Clinical pathology
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