【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.
Objective To summarize the domestic and abroad articles related to the research on the relation between microRNA （miRNA） and pancreatic cancer，and explore the important effects of miRNA expression patterns in diagnosis of pancreatic cancer. Methods “microRNA and pancreatic cancer” were searched as key words by PubMed and CNKI series full-text database retrieval systems from 2000 to 2012. Totally 60 English papers and 15 Chinese papers were obtained. Choice criteria：the basic research of miRNA and pancreatic cancer，the clinical research of miRNA and pancreatic cancer， and the prospect of miRNA in pancreatic cancer diagnosis and treatment. According to the choice criteria，31 papers were finally analyzed. Results The miRNA expression spectrum and specific miRNA expression such as miR-21，miR-34，miR-217，miR-196a，miR-10a，miR-155，miR-221，miR-222，miR-181a，miR-181b，miR-181d， and the family members of miR-200 and let-7 might be used as tumor markers to differentiate pancreatic cancer from normal pancreas，chronic pancreatitis or pancreatic endocrine tumors，and might be used as prognostic factor to predict the outcome. Conclusions miRNA expression spectrum are not only related to diagnosis of pancreatic cancer， but also have provided a new research direction and method for gene therapy of pancreatic cancer．
ObjectiveTo investigate the expression of ubiquitin-specific protease 9X (USP9X) in pancreatic cancer, and to evaluate the correlation of USP9X with the survival of patients with pancreatic cancer.
MethodThe expression of USP9X was detected in 55 pieces of surgically resected primary pancreatic cancer tissues and adjacent nontumorous pancreatic tissues by streptavidin-perosidase immunohistochemical method.
ResultsThe rate of USP9X high expression in the 55 pieces of the primary pancreatic cancer tissues was 58.2% (32/55), which in the adjacent nontumorous pancreatic tissues was zero. The expression of USP9X was not correlated with the gender, age, tumor position, or tumor size (P > 0.05), while which was significantly correlated with the differentiation degree, lymph node metastasis, or TNM stage (P < 0.05). By using Cox proportional hazard model, the multivariable analysis revealed that the differentiation degree, lymph node metastasis, and USP9X expression were the independent risk factors. Survival of the patient with USP9X high expression was significantly shorter than that with USP9X low expression (P < 0.05), and there was the same result in the patients with stageⅡ, with lymph node negative, or intermediate differentiation degree (P < 0.05).
ConclusionThe results indicate that USP9X might play an important role in the pathogenesis and prognosis of pancreatic cancer.
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.
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.
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.
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.
【 Abstract 】 Objective Overexpressions of epidermal growth factor (EGF) and EGF receptor have been associated with progression and invasive phenotype of pancreatic cancer. However, the underlying molecular mechanism by which EGF worked in pancreatic cancer cells has not been completely understood. In this study, effect of EGF on the invasion and metastasis of pancreatic cancer cells and its regulatory mechanism were investigated. Methods The effects of EGF on the proliferation, adhesion and invasion of pancreatic cancer cells were detected by WST-1 proliferation assay, adhesion assay and invasive assay, respectively. The activity and expression of MMP-2 and MMP-9 were examined by zymography, Western blot and RT-PCR, respectively. The activity of NF- κ B was examined by EMSA. Results EGF could significantly promote the invasiveness of pancreatic cancer cells but did not affect cell proliferation or adhesion. The expressions of NF- κ B and MMP-9 were significantly increased by EGF, but EGF did not affect the activity and expression of MMP-2. Furthermore, EGF stimulated the NF- κ B binding activity. Pretreatment with NF- κ B inhibitors, pyrrolidine dithiocarbamate (PDTC), could significantly inhibit the activity of NF- κ B induced by EGF. Meanwhile, the EGF-induced expression and activity of MMP-9, as well as cell invasiveness were also inhibited by NF- κ B inhibitor. Conclusion EGF could increase the expression and promote the invasiveness of MMP-9 via the activation of NF- κ B in pancreatic cancer cells, which implies that NF- κ B inhibitant, such as PDTC, may diminish the invasiveness of pancreatic cancer cells.
Objective To summary the principle of magnetic resonance spectroscopy imaging and its application progress in diagnosis and differential diagnosis of pancreatic cancer. Methods The newest related literatures of home and abroad were collected and reviewed. Results Magnetic resonance spectroscopy imaging was a technology using the magnetic resonance phenomena and chemical shift phenomena to measure molecular organization. The spectroscopy most commonly used in clinical and scientific research includes 1H， 31P， and 23Na. Conclusion Magnetic resonance spectroscopy as the only approach to noninvasive quantitative provding biochemical information in vivo， has an important significance to the diagnosis and differential diagnosis of pancreatic cancer.
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.
