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Chemosensitivity Of Pancreatic Gemcitabine Cancer Animal Model And Application Of Proteomic Changes

Posted on:2013-02-11Degree:MasterType:Thesis
Country:ChinaCandidate:Q L YanFull Text:PDF
GTID:2214330371484970Subject:Surgery
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Background:The incidence of pancreatic cancer increased year by year, common malignancy in Europe and ranks4th in the country in the first nine cancer deaths. The initial diagnosis of pancreatic cancer, the mortality rate of80%within1year,3years was95%. Transfer the median survival time of patients3-6mo, locally advanced6-10mo. Mainly due to increased survival rates and surgical resection levels. Surgery is still the only promising measures to cure pancreatic cancer, but the lack of early diagnostic tools, only10%to20%of patients suitable for treatment when surgical resection, the overall resection rate was14%. By surgical resection, the overall5-year survival rate was18%, lymph node-negative patients was32%, and lymph nodes were negative margins can reach40%of patients.70%to80%of patients because the tumor can not be removed, must be non-surgical treatment to improve the quality of life and prolong survival. Even patients with tumor resection, previous randomized controlled studies have proved that long-term result is not satisfactory, most patients died of liver metastasis and local recurrence. So while the surgery with adjuvant chemotherapy, to achieve improved quality of life and prolong survival time purposes. And gemcitabine treatment of pancreatic cancer is still the drug of choice, but gemcitabine combined with other drugs there is no uniform standard program. Chemotherapy for pancreatic cancer is still not very satisfactory, although effects of gemcitabine on pancreatic cancer more precise, effective rate of25%. MDR (multidrug resistance, MDR) is one of the main failure of cancer chemotherapy. MDR refers to a cell resistance to toxic drug resistant cells, independent of the structure of many different mechanisms, or other produce cross-resistance to cytotoxic drugs, MDR genes by tumor cells caused by over-expression or amplification. But the mechanism is not clear, the development of proteomics research for finding new tumor markers provides a new way.Objective:(1) by analyzing the sensitivity to gemcitabine and non-sensitive protein spectrum in the expression of individual differences, to find the extent of the protein drug reactions peaks.(2) screening and verification of gemcitabine in pancreatic cancer chemotherapy and prognosis of tumor markers, giving the individual the most effective chemotherapy.Methods:To take100test established pancreatic cancer model in nude mice group given gemcitabine chemotherapy, the mice were killed to collect blood and lymph nodes and visceral lesions such as tissue samples, select a lymph node and distant metastasis in nude mice, tumor weight maximum control group of20cases, take no lymph node and distant metastasis in nude mice, the smallest of the20cases the tumor mass as the experimental group, the use of SELDI-TOF-MS protein chip technology and related serum protein fingerprint detection of nude mice, and the use of discriminant analysis bioinformatics data processing and screening markers to establish gemcitabine sensitivity evaluation system.Results:Three protein peaks (4295,3708,9475m/z) Portfolio Construction for the identification test group and control group model of pancreatic cancer chemotherapy sensitivity of95%(19/20), specificity95%(19/20), accurate95%(38/40).Conclusion:Protein spectrum in the pancreatic cancer diagnosis and evaluation of chemical treatment and so has some value, it is worth further study. Gemcitabine sensitivity by analyzing the individual cells in the protein expression differences between the peak to find the key to the degree of protein drug reactions peaks, is conducive to individual drugs. But ultimately also need to validated in clinical samples.
Keywords/Search Tags:Pancreatic cancer, proteomics, serum, gemcitabine, sensitivity
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