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The Relative Factors Affecting The Survival In Pancreatic Cancer,Value Of MIC-1 In Pancreatic Cancer And It's Expression In P.pastoris

Posted on:2008-08-23Degree:DoctorType:Dissertation
Country:ChinaCandidate:Y WangFull Text:PDF
GTID:1114360218955987Subject:Oncology
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Part one:The relative factors affecting the survival in pancreatic cancerObjective: To analysis relative factors affecting the survival in pancreatic cancer.Methods: Statistical analysis of prognostic factors of pancreatic cancer with different clinicopathological factors and treatments,the cumulative curve was dipicted using the Kaplan-Meier method.Results:①From January 2001 to December 2005, 233 patients with the diagnosis of pancreatic cancer by pathological and cytology were analysis. The median survival of the whole collective were 8.67 months,the 1-year survival rate was 29.6%, the 2-year survival rate was 13.7%,the 3-year survival rate was 10.1%,and the 5-year survival rate was 4.5 %.②Survival in pancreatic cancer wre associated with weightloss, back pain,CA19-9, TNM stage and treatment.③Patients are grouped as radical surgery group, cancer-directed treatment goup(including intraoperative Iodine-125 seed interstitial brachytherapy, 5-FU interstitial chemotherapy, radiotherapy, chemotherapy, transcatheter arterial infusion chemotherapy), no cancer-directed treatment goup(including cases who only received biopsies or bypass), median survival of the three groups were 14 months, 8.3 months and 6.6 months respectively. 1-year survival rate were 53.5 %, 22.5% and 11.8 %, 3-year survival rate were 20.5%, 6.3%, 3.9%, 5-year survival rate were 5.8%, 0%, 0%, respectively.Conclusions: Early diagnosis and raiseing radical resection rate are key measure to improve the survival of pancreatic cancer. Part two:The value of serum MIC-lin the diagnosis of pancreatic cancerObjective: To investigate the the value of serum macrophage inhibitory cytokine-1 (MIC-1) in the diagnosis of pancreatic cancer.Methods: Serum MIC-1 levels were determined by ELISA in 171 patients with pancreatic adenocarcinomas, in 17 patients with ampullary carcinomas, in 27 patients with benign pancreatic tumors, and in 47 healthy control subjects. The diagnostic performance of serum MIC-1 as a marker of pancreatic cancer was compared with that of serum CA19-9, CA242 and CEA.Results:①Serum MIC-1 levels were significantly higher in patients with pancreatic cancer (1547.28±1241.14 pg/mL) and in patients with ampullary (1847.22±821.99 pg/mL) than in those with benign pancreatic neoplasms (371.51±261.63 pg/mL), or in healthy controls (295.46±160.12 pg/mL).②Serum MIC-1 levels were significantly higher in male than in female, or in jaundice patients than in no jaundice patients. MIC-1 elevations were independent of patient's age, TNM stage, or tumor size.③An elevated serum MIC-1 (defined as 2 SD above the mean for healthy controls) performed as well as CA19-9 (sensitivity, 83.6% and 76.6%, respectively), and the combination of MIC-1 and CA19-9 significantly improved the diagnosis (sensitivity, 95.3%) than the combination of CA19-9, CA242, CEA (sensitivity, 81.9%).Conclusions: Serum MIC-1 measurement can aid in the diagnosis of pancreatic adenocarcinoma. Part three:The optimizing expression of human MIC-1 in Picha pastorisObjective: To construct codon optimized expression vector of the human microphage inhibitory cytokine-1 (MIC-1), and to obtain highly expressing yeast strain.Methods: MIC-1 cDNA gene fragments were obtained from human placenta by RT-PCR. The seven poor biased usage codon of 5′terminal was mutated by site-directed mutagenesis as the Pichia pastories preferred codons to raise MIC-1 expression level. Pichia pastories expression vector pPIC9k was constructed. The recombinant plamid was transformed to GS115, and the highly expressing strain was selected.Results: MIC-1 recombinant protein expressing vector with the Pichia pastories preferred codons was constructed, and the highly expressing yeast strain was obtained.Conelusious: We obtained the stable recombinant GS115 strain which can highly expressing MIC-1. And it has laid the foundation for studying the function of the MIC-1 or preparing the antibody of MIC-1 for clinical useage.
Keywords/Search Tags:pancreatic cancer, prognostic factors, survival, MIC-1, Diagnosis, Pancreatic cancer, Pichia pastories
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