Objective To investigate the inhibitory effects of RNA interference (RNAi) expression vector on the expression of survivin in pancreatic cancer cell PANC-1. Methods The protein and mRNA expressions of survivin were examined with immunofluorescence and RT-PCR. The survivin gene was cloned into the T-vector and sequenced. The RNAi expression vectors targeting survivin, named si-svv-1 and si-svv-2 respectively according to whether they harbored a mutation or no mutation, were constructed and transfected into PANC-1 cells with liposome. The expression of survivin mRNA was detected with RT-PCR. Apoptosis of PANC-1 cells was analyzed with DNA ladder and FACS. Results There was a high degree expression of survivin in PANC-1 cells. The expression of survivin was not inhibited by RNAi expression vectors si-svv-1, but inhibited about (72.43±8.04)% by si-svv-2 and the apoptosis rate of PANC-1 cells increased to （12.36±1.44）% after 72 h. Conclusion The RNAi expression vector can effectively inhibit the expression of survivin in pancreatic cancer cell PANC-1 cells and induce the apoptosis in PANC-1 cells.
Objective To search for the significant gene indicators in the diagnosis of pancreatic cancer. Methods Literatures about genetic diagnosis of pancreatic cancer were collected and reviewed. Results K-ras, p53, DPC4 and telomerase genes were considered to play important roles in the diagnosis of pancreatic cancer. Conclusion Detection of the genes related to pancreatic cancer may be of helpful in early diagnosis of pancreatic cancer.
ObjectiveTo systematically review the expression of E-cadherin protein and the risk of pancreatic cancer. MethodsWe searched PubMed, EMbase, The Cochrane Library, CNKI, VIP, CBM and WanFang Data from inception to October 2016 to collect case-control studies about the correlation between E-cadherin protein expression and the risk of pancreatic cancer. Two reviewers independently screened the literature, extracted data and assessed the risk of bias of included studies. Then meta-analysis was performed using RevMan 5.2 software and Stata 12.0 software. ResultsSeventeen studies (986 cases in pancreatic cancer group and 433 cases in normal pancreatic tissue group) were finally included. The results of meta-analysis showed that: the expression of E-cadherin protein in the pancreatic cancer group was lower than normal tissue group (OR=0.04, 95%CI 0.01 to 0.23, P=0.000 2), poor differentiation group was lower than high or middle differentiation group (OR=0.44, 95%CI 0.26 to 0.76, P=0.003), lymph node metastasis group was lower than without lymph node metastasis group (OR=0.50, 95% CI 0.31 to 0.81, P=0.005), and the difference was statistically significant. However, there was no significant difference between the clinical stageⅠ-Ⅱ group and Ⅲ-Ⅳ group (OR=0.63, 95%CI 0.25 to 1.59, P=0.33), pancreatic head cancer group and pancreatic body and tail cancer group (OR=1.22, 95%CI 0.72 to 2.07, P=0.46), pancreatic cancer with nerve invasion group and without nerve invasion group (OR=1.45, 95%CI 0.81 to 2.62, P=0.21), pancreatic cancer with vascular invasion group and without vascular invasion group (OR=0.55, 95%CI 0.13 to 2.22, P=0.40). ConclusionLower expression of E-cadherin protein is significantly associated with the risk of pancreatic cancer. Due to the limited quality and quanity of includied studies, the above conclusion should be approved by more studies.
ObjectiveTo evaluate the quality of pancreatic cancer guidelines using evidence-based methods based on the global burden of pancreatic cancer, so as to explore its status, region distribution, characteristics of coverage themes, and difference of therapies recommended by the guidelines of various quality, and to provide references for clinical decisionmaking. MethodsPubMed, The Cochrane Library (Issue 11, 2013), CBM, CNKI, and VIP, as well as the website of National Guidelines Clearinghouse (NGC), Guidelines International Network (GIN), and National Institute for Clinical Excellence (NICE) were systematically searched for pancreatic cancer treatment guidelines. The Appraisal of Guidelines for Research and Evaluation (AGREE Ⅲ) was applied to assess methodological quality of included guidelines. ResultsA total of 14 relevant guidelines (including five evidence-based guidelines) were included involving seven countries of four continents (Asia, Europe, North America and Oceania) and four international academic organizations. There were only two domains, namely "scope and purpose" and "clarity of presentations" which got high average scores (more than 60%) among all 14 guidelines. The mean AGREE domain scores in guidelines varied with areas, and the quality of five evidence-based guidelines was superior to that established by consensus. According to the outcomes of AGREE Ⅲ, 11 guidelines were weakly recommended, while 3 were not recommended due to poor methodological quality. The subjects of 14 guidelines covered six treatment categories, including chemotherapy, surgery, radiotherapy, support therapy, radiotherapy, and interventional therapy. ConclusionThe overall methodological quality of pancreatic cancer guidelines is not high among different countries or regions. The quality of evidence-based guidelines is superior to that established by consensus. Chemotherapy, surgery, radiotherapy and support therapy were reccommended as predominant choice by these guidelines.
【Abstract】Objective To analyze the function of BAG3 in antiapoptosis and chemotherapy resistance induction process of pancreatic cancer.Methods The expressions of BAG-3 in pancreatic cancerous tissues of patients with chemotherapy and those without chemotherapy before resection were determined by immunohistochemistry. The expression difference of BAG-3 protein 18 hours after cultured with chemotherapy drugs (concentration of drugs: 5-FU 50 μg/ml, MMC 0.5 μg/ml, EADM 1.5 μg/ml) of 3 pancreatic cancer cell lines （MIACaPa-2, PANC-1, SW1990） was measured through Western blotting method.Results The median positive rate of pancreatic cancer tissue from patients accepted chemotherapy before resection was higher than those not accepted chemotherapy, but there wasn’t significant difference. Eighteen hours after cultured with drugs, the level of BAG-3 of this three cell lines had significant increased compared with control group (P＜0.05). Conclusion Chemotherapy induces elevation of BAG-3 expression of pancreatic cancer. The upregulate of BAG-3 may associate with the chemotherapy resistance induced by drugs.
ObjectiveTo investigate the indications and clinical effect of pancreatoduodenectomy with extended lymphadenectomy for pancreatic head carcinoma. MethodsThe clinical data of 21 patients with pancreatic head carcinoma that performed pancreatoduodenectomy with extended lymphadenectomy between June 2010 to June 2011 in Union Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology were retrospective analyzed. The 21 patients included 15 men and 6 women with an age range of 36-57 years and an average age of 47.8 years. ResultsThere were 3 cases(14.3%), 9 cases(42.9%), 8 cases(38.1%), and 1 case(4.8%) in stageⅠ, ⅡA, ⅡB, andⅢ, respectively. Eighteen cases had a R0 resection(85.7%) and 3 cases had a R1 resection. The total number of resected lymph nodes were 14-43 with an average of 27.4. Lymph node invasion occurred in 10 cases(47.6%). The average operative time was 6.8 h(5-8.5 h) and the average amount of blood transfusion was 5.6 U(3-8 U). There was no death in this group and 5 cases(23.8%) had postoperative complications. Tree cases(14.3%) developed pancreatic fistula, 1 case(4.8%) developed bile leakage, 1 case(4.8%) developed abdominal hemorrhage, 1 case(4.8%) developed gastrointestinal bleeding, and 2 cases(9.5%) developed intractable diarrhea. Postoperative pathological results in high, medium, and low differentiated adenocarcinoma was 6 cases(28.6%), 10 cases(47.6%), and 5 cases(23.8%), respec-tively. Twenty one cases were followed-up, the follow-up time ranged from 5 to 40 months with a median time of 19 months. 1-, 2-, and 3-year cumulative survival rates was 66.7%, 38.1%, and 19%, respectively. ConclusionSelective application of pancreatoduodenectomy with extended lymphadenectomy in resectable pancreatic head carcinoma is conducive to increase the proportion of the radical resection and improve the prognosis, but the postoperative complications is higher.
ObjectiveTo summarize current patient-derived organoids as preclinical cancer models, and its potential clinical application prospects. MethodsCurrent patient-derived organoids as preclinical cancer models were reviewed according to the results searched from PubMed database. In addition, how cancer-derived human tumor organoids of pancreatic cancer could facilitate the precision cancer medicine were discussed. ResultsThe cancer-derived human tumor organoids show great promise as a tool for precision medicine of pancreatic cancer, with potential applications for oncogene modeling, gene discovery and chemosensitivity studies. ConclusionThe cancer-derived human tumor organoids can be used as a tool for precision medicine of pancreatic cancer.
Objective To observe the expression of Galectin-3 and Galectin-1 in pancreatic cancer and explore the relationship between the expression and pathological grading. Methods Forty specimens of pancreatic carcinoma tissue and thirty-one specimens of normal pancreas tissue were selected, which were confirmed by surgical resection and pathology from 2002 to 2009. The expression of Galectin-3 mRNA and Galectin-1 mRNA in pancreatic cancer cell lines SW1990, PANC-1 and ASPC -1 was detected by means of reverse transcriptase-polymerase chain reaction; the expression of Galectin-3 protein and Galectin-1 protein in SW1990, PANC-1 and ASPC-1 was detected by means of immunocytochemistry; the expression of Galectin-3 protein and Galectin-1 protein in pancreatic cancer and normal pancreatic tissue was detected by means of immunohistochemistry. Results In SW1990, PANC-1 and ASPC-1, Galectin-3 mRNA signal and protein were detected, but no Galectin-1 mRNA signal or protein was detected. There was no expression of Galectin-3 protein or Galectin-1 protein in the 31 specimens of normal pancrease tissue, while there were Galectin-3 protein and Galectin-1 protein expressed in the 40 specimens of pancreatic cancer tissue. In the 40 specimens of pancreatic cancer tissue, the expression of Galectin-3 protein was observed in pancreatic cancer cells, but not in fibroblasts or matrix cells around the cancer mass; while the expression of Galectin-1 protein was observed in fibroblasts and matrix cells around the cancer mass, but not observed in pancreatic cancer cells. There was no significant association between the expression of Galectin-3 protein in pancreatic cancer and pathological grading (P>0.05); while the expression of Galectin-1 protein in pancreatic cancer was related to the pathological grading, and the expression of Galectin-1 protein was significant higher in poorly differentiated tumors than that in well/moderately differentiated tumors (P<0.05). Conclusions Galectin-3 or Galectin-1 is not expressed in normal pancreases; Galectin-3 is expressed in pancreatic cancer cells; Galectin-1 is expressed in fibroblasts and matrix cells around the cancer mass. The expression of Galectin-1 is related with the differentiation of pancreatic cancer.
【Abstract】 Objective To explore the features of Ki-ras mutations at codon 12 in Chinese patients of pancreatic cancer and to compare these features with those in Western countries. Methods Fifty-nine samples were collected during operations for pancreatic adenocarcinoma in our hospital from December 1989 to November 1997. The patients, age ranged from 30 to 73 years 〔(55.5±10.4) years〕,with 38 males and 21 female. TNM staging of the patients: stage Ⅰ(n=4); stage Ⅱ(n=8), stage Ⅲ(n=42),stage Ⅳ(n=5). PCR was used to amplify target gene and Dot blot hybridization for detecting Ki-ras mutations at codon 12 was performed in fifty-nine specimens of Chinese pancreatic cancer. The data of Ki-ras mutations at codon 12 from Western countries were gotten by Medline system. Results Ki-ras mutation at codon 12 was detected in 76.3% of the patients in this group. The frequency of double mutation of Ki-ras at codon 12 in this group (15.6%) was highest than that in western countries. Our results were compared with those reported in Western countries. The results suggested that there were the significant differences in the substitution of Ki-ras mutations at codon 12 and in the ratio of transition to transversion in pancreatic cancer among various countries. Conclusion Ki-ras mutations at codon 12 is frequent in Chinese pancreatic cancer, and a gene component to pancreatic cancer may be different among various countries. In addition, the effect of Ki-ras mutations at codon 12 on prognosis of patients with pancreatic cancer is different in various countries.
Objective To investigate the expressions of CXCR4 and β-catenin in pancreatic cancer, explore the relationship between them, and explore the possible biomarkers about invasion and metastasis of pancreatic cancer. Methods Forty-eight samples of pancreatic cancer and 20 samples of normal pancreas tissues were selected. The expressions of CXCR4 and β-catenin were examined by the immunohistological technique. Spearman, Chi-square， and rank test were used to analyze the relation between the protein expressions and clinical characteristics. Survival analysis was evaluated by Kaplan-Meier product limit method and Log-rank test. Variables were evaluated by Cox proportional hazards analysis. The size of test was 0.05. Results The positive expression rates of CXCR4 and β-catenin in pancreatic cancer tissues were 85.4% (41/48) and 75.0% (36/48), respectively. Co-expression rate of CXCR4 and β-catenin was 70.8% (34/48). There were significant differences between various CXCR4 staining and lymph node metastasis and TNM stage (P=0.012, 0.005, respectively). β-catenin positive expression was associated with lymph node metastasis (P=0.047). However, abnormal β-catenin positive expression could not determine the clinical survival. Kaplan-Meier estimated curves suggested that clinical prognosis was poor for patients with CXCR4 expression. Multivariate analysis showed that CXCR4, late TNM stage, and lymph node metastasis were independent prognostic factors for pancreatic cancer. Conclusions Both CXCR4 and β-catenin abnormally express in pancreatic cancer. CXCR4 may be an important marker for pancreatic cancer progression.