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 detect the activity of lactate dehydrogenase (LDH) and LDH isoenzyme, and to explore the relation between biological behavior ofpancreatic cancer and glycolysis. MethodsConsecutive 12 cases of pancreatic ductal adenocarcinoma and 12 benign lesions such as insulinoma from October 2006 to July 2008 were collected, as well as normal pancreatic tissues. The total activity of the LDH was detected by the LDH testing kits, and the iosenzyme pattern of LDH was inspected by the France Sebia hydrasys. ResultsCompared to the normal tissue, LDH activity ofpancreatic cancer and adjacent non-cancerous tissue was significantly higher (P＜0.05). LDH iosenzyme pattern in cancer tissue was also significantly different, the percentage of LDH4 and LDH5 increased obviously, and were greater than that innormal tissue (P＜0.05). ConclusionThe alteration of LDH activity and its isoenzyme pattern are possibly related to the pathogenesis of pancreatic cancer. Inhibit the LDH activity may be a new therapeutic strategy.
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.
ObjectiveTo summarize the therapeutic targets of pancreatic cancer (PC). MethodsThe related literatures about the therapeutic targets of PC were reviewed. ResultsPC was one of the most challenging tumor in worldwide, and was characterized as a highly aggressive disease with poor overall prognosis and a high mortality rate. The hallmark of PC was its poor response to radio-and chemo-therapy. Current chemotherapeutic regimens could not provide substantial survival benefit with a clear increase in overall survival. Recently, several new approaches which could significantly improve the clinical outcome of PC had been described, involving signal-transduction pathways, immune response, stroma reaction, and epigenetic changes. ConclusionsMany therapeutic targets are involved in the treatment of PC. As current therapies failed to significantly improve the progression and the survival of PC, new therapeutic approaches and clinical studies are strongly required.
【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.
【Abstract】Objective To investigate the possible mechanism of gemcitabine resistance in pancreatic cancer chemotherapy. Methods Recent literatures about the genes and signal pathways those play key roles in mediating gemcitabine chemotherapy resistance of pancreatic cancer were collected and reviewed.Results Oncogenes like c-Src and bcl-XL, inflammation pathway of NF-κB, cytokines like IL-1β and NO are closely related with the chemoresistance； the relationship between multiple drug resistance relevant genes like MDR1/P-gP and the resistance to gemcitabine remains to be clarified. Conclusion Genes and pathways like c-Src, bcl-XL, NF-κB, etc. might become new targets to increase the chemotherapeutic sensitivity of pancreatic cancer, however, the mechanism of pancreatic cancer chemotherapy resistance still needs further to be studied.
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.