【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 study the effect of tumor associated neutrophil (TAN) releasing a proliferation-inducing ligand (APRIL) on the proliferation of pancreatic cancer cells in microenvironment.Methods① The expressions of APRIL in neutrophils (differentiated by HL-60 cell) and TAN cells were detected by use ELISA. ② The expressions of APRIL receptors B cell maturation antigen (BCMA) and trans-membrane activator and CAML interactor (TACI) in pancreatic cancer cell line PANC-1 were confirmed by use Western blotting. ③ Pancreatic cancer PANC-1 cells were co-cultured with TAN, and divided into a PANC-1 control group (referred to as the control group), a PANC-1+TAN treatment group (referred to as the PANC-1+TAN group), PANC-1+TAN+APRIL antibody treatment group (referred to as PANC-1+TAN+APRIL group), and PANC-1+rtificial recombinant APRIL protein (rAPRIL) treatment group (referred to as PANC-1+rAPRIL group). The CCK8 method was used to determine TAN release of APRIL on PANC-1 effect of cell proliferation activity.Results① The APRIL content in the culture medium of TAN cell group was higher than that of neutrophil group [(556.20±84.38) pg/mL vs. (377.17±57.07) pg/mL, P=0.038]. ② PANC-1 cells express the receptors BCMA and TACI of APRIL. ③ PANC-1 cell activity of PANC-1+TAN group and PANC-1+rAPRIL group [(126.80±1.42)%, (168.95±12.54)%] were significantly higher than the control group [(100 ± 0.00)%, P<0.05, P<0.001], the activity of PANC-1 cells in the PANC-1+TAN group was significantly higher than that in the PANC-1+TAN+APRIL group [(86.29 ± 12.20)%, P=0.003] and significantly lower than that of PANC-1+rAPRIL group (P=0.002), the activity of PANC-1 cells in PANC-1+rAPRIL group was significantly higher than that in PANC-1+TAN+APRIL antibody group (P<0.001).ConclusionIn the microenvironment of pancreatic cancer, the release of APRIL from TAN increases, which promotes the proliferative activity of PANC-1 in pancreatic cancer cells, which provides a new idea for the mechanism research and treatment of pancreatic cancer progression.
On the basis of established JF305 cell line from human pancreatic cancer at this university, cell clone technique, cell electrophoresis, flower cytometer, and cancer orthotopically implanted nude mice technique were used to establish the sublines with different metastatic potential from human pancreatic cancer line-JF305 and the nude mice model implanted orthotopically with human pancreatic cancer monoclonal sublines with different metastatic potential. The results showed that the monoclonal cell sublines with different metastatic potential from human pancreatic caner-JF305 and the nude mice model implanted orthotopically with the sublines, would provided a useful method to study the metastatic mechanism of human pancreatic cancer.
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 evaluate the predictive value of the geriatric nutritional risk index (GNRI) for postoperative overall and severe complications after pancreaticoduodenectomy (PD) in the elderly patients with pancreatic cancer. MethodsThe clinical data of the elderly (65 years old or more) patients with pancreatic cancer underwent PD were retrospectively collected, who were admitted to the Fifth Affiliated Hospital of Xinjiang Medical University from January 2017 to October 2021. The incidences of postoperative overall and severe complications (Clavien-Dindo grade Ⅲ–Ⅴ was defined as severe complications) were summarized. The univariate and multivariate logistic regression models were used to analyze whether GNRI was a risk factor for overall and severe complications after PD. The area under the receiver operating characteristic curve (AUC) was used to evaluate the ability of GNRI to distinguish whether overall or severe complications occurred after PD and to confirm the optimal threshold. Then the patients were assigned into a high nutritional risk group (greater than the optimal threshold) and low nutritional risk group (the optimal threshold or less) based on this. Simultaneously, the clinical outcomes of the two groups were compared. ResultsIn this study, 190 elderly patients with pancreatic cancer were enrolled, 95(50.0%) of whom developed complications, including 28(29.5%) cases of serious complications. The results of multivariate logistic regression model analysis showed that the decreased GNRI was a risk factor for the occurrence of overall and severe complications after PD for the elderly patients [OR(95%CI)=0.361(0.154, 0.848), P=0.019; OR(95%CI)=0.906(0.834, 0.983), P=0.018]. The AUC of GNRI for assessing the occurrence of overall and severe complications was 0.765 and 0.715, respectively, with the optimal critical values of 98 and 96, respectively. Compared with the low nutritional risk group, the high nutritional risk group had higher postoperative total hospitalization costs (Z=–2.37, P=0.019), higher occurrences of overall complications (χ2=44.61, P<0.001) and severe complications (χ2=29.39, P＜0.001). ConclusionsIn elderly patients with pancreatic cancer underwent PD, incidence of serious complications is not lower. GNRI has a good discriminative value in terms of postoperative overall and severe complications. When preoperative GNRI is 98 or less and GNRI is 96 or less, patients should be given early preoperative nutritional support treatment in time.
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.
ObjectiveTo summarize the research progress of correlation between pancreatic cancer and diabetes mellitus.MethodsRecent studies on the association between pancreatic cancer and diabetes mellitus were extensively reviewed, and relevant research results on the association between pancreatic cancer and diabetes mellitus were reviewed.ResultsPancreatic cancer had a particular association with diabetes. Patients with pancreatic cancer may develop new diabetes or worsen existing diabetes mellitus. About 50% of patients with pancreatic cancer had diabetes mellitus before diagnosis, suggesting a “dual causal relationship” between pancreatic cancer and diabetes mellitus. Long-term type 2 diabetes mellitus (T2DM) was one of the high risk factors for the occurrence and development of pancreatic cancer. T2DM may also increase the risk of pancreatic cancer due to hyperinsulinemia, adipokine, and other factors. Pancreatic cancer was one of the cause of diabetes mellitus at the same time, but its mechanism was not yet known, also needed to get a lot of information to understand the impact of long-term diabetes mellitus on the development of pancreatic cancer, as well as the reason of pancreatic cancer related to diabetes mellitus mechanism.ConclusionThe clear relationship between pancreatic cancer and diabetes mellitus has not been proved, and further research is needed to clarify the relationship between them.
ObjectiveTo explore the significance of mesenchymal epithelial transition factor (MET) as a clinical prognostic evaluation index for patients with pancreatic cancer based on bioinformatics analysis.MethodsThe GSE28735 and GSE62452 gene chips from GEO database were downloaded and the difference of MET gene expression between cancer and adjacent cancerous tissues were analyzed by bioinformatics. We downloaded pancreatic cancer gene chip from TCGA database to analyze the correlation between MET gene expression and clinicopathological features of pancreatic cancer patients and prognosis risk. Finally, the possible molecular mechanism of MET involved in pancreatic carcinogenesis was analyzed by GO and KEGG enrichment analysis.ResultsThe expression level of MET gene in pancreatic cancer tissues was significantly higher than that in adjacent cancerous tissues (P<0.001). The overall survival and disease-free survival of pancreatic cancer patients in the high MET gene expression group were lower than those in the low expression group (P<0.001). The expression level of MET gene was related to the age of pancreatic cancer patients, T stage, and histological grading of tumors (P<0.05), and high MET gene expression, age >65 years, and N1 stage were independent risk factors affecting the prognosis of pancreatic cancer patients. KEGG enrichment analysis showed that MET was mainly related to PI3K/AKT signaling pathway, FAK signaling pathway, and cancer transcription dysregulation and so on.ConclusionMET may be a valuable tumor marker for pancreatic cancer and can predict the poor prognosis of patients with pancreatic cancer.
