[The long coding RNA GSTM3TV2 acts an oncogene to promote chemoresistance in pancreatic cancer].

Objectives: To examine the expression of the long coding RNA GSTM3TV2 in pancreatic cancer tissues and to examine its role and mechanism in chemoresistance of pancreatic cancer cells. Methods: The expression of lncRNA GSTM3TV2 in 15 pancreatic cancer specimens and corresponding adjacent to cancer tissue samples diagnosed by Department of Pathology, Peking Union Medical College Hospital was detected by real-time PCR.And the expressions of GSTM3TV2 in pancreatic cancer cell AsPC-1, BxPC-3, MIAPaCa-2, PanC-1, SU86.86, T3M4, and chemoresistant cells AsPC-1/GR and MIAPaCa-2/GR, and human pancreatic nestin-expressing cells hTERT-HPNE were detected. Pancreatic cancer cell lines were transfected with GSTM3TV2-pcDNA3.1(+)in order to get cells with GSTM3TV2 overexpression.GSTM3TV2-siRNA was transfected into pancreatic cancer cells to knock down GSTM3TV2. The cell chemoresistance was measured by CCK-8 and flow cytometry assay when incubated with nab-paclitaxel. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of GSTM3TV2 on chemoresistance of tumor growth in nude mice.Western blot assay was also performed to detect the molecular mechanism of chemoresistance of GSTM3TV2. Results: Comparing toadjacent tissues(0.084±0.019), GSTM3TV2 expression was significantly upregulated in the pancreatic cancer tissues(0.493±0.084) (t=5.146, P<0.05). GSTM3TV2 expression were higher in the chemotherapy resistance pancreatic cancer cells AsPC-1/GR(210.799±19.788) and MIAPaCa-2/GR(122.408±23.419) than that in the AsPC-1(3.793±0.615) and the MIAPaCa-2(5.179±1.095)(t=21.800,P<0.05;t=-18.490,P<0.05). The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing GSTM3TV2 group ((1 059.609±102.498)mm(3)) was significantly larger than that in the control group((566.414±81.087) mm(3)) by treated with nab-paclitaxel(t=4.230,P<0.05).Meanwhile, GSTM3TV2 could promote the expression of Cyclin D1, CDK6, Cyclin E1, Vimentin, N-cadherin, ZEB1, Snail and Slug; but decrease cleaved caspase-3, cleaved PARP in pancreatic cancer cells. Conclusions: The expression level of GSTM3TV2 in pancreatic canceris higher than that in paired adjacent tissues. GSTM3TV2 may act as an oncogene to promote chemoresistance in pancreatic cancer through regulation of cell proliferation, apoptosis, and epithelial-mesenchymal transition.

[The expression of KLK7 in pancreatic cancer and the effects on the biological behavior of pancreatic cancer cells].

Objective: To investigate the expression of KLK7 in pancreatic cancer and its clinical significance. Methods: Immunohistochemistry was used to detect the expression of KLK7 protein in pancreatic cancer tissue microarray with 92 samples. Statistical analysis of the relationship between KLK7 and clinicopathological characteristics was finished. Pancreatic cancer cell lines were infected with lentiviuses in order to get cells with KLK7 stable overexpression.KLK7-siRNA was transfected into pancreatic cancer cells to knock down KLK7.Cell proliferation and chemosensitivity were detected by CCK-8 assay; Cell invasion and migration abilities were detected by Transwell assay. At the same time, subcutaneous xenograft tumor models were established in nude mice to observe the effect of KLK7 on tumor growth in nude mice. Data were statistically analyzed by rank sum test, χ(2) test and Logistic regression analysis. Results: The expression level of KLK7 in pancreatic cancer tissues was higher than that in paired adjacent tissues (P<0.05). KLK7 expression was correlated with vascular invasion(χ(2)=7.535, P<0.05). Further univariate and multivariate analysis showed that KLK7 expression was an independent risk factor for vascular invasion of pancreatic cancer(χ(2)=7.535, P<0.05). The overexpression of KLK7 in pancreatic cancer cell lines BxPC-3 and CFPAC can increase their proliferation abilities, reduce the chemosensitivity and promote their migration and invasion behaviour; The results of in vivo experiments showed that the volume of subcutaneously transplanted tumors in the overexpressing KLK7 group was significantly larger than that in the control group (t=4.479, P<0.05). The group of overexpressing KLK7 showed greater tumor weight than the control group(t=2.831, P<0.05). Conclusions: The expression level of KLK7 in pancreatic ductal adenocarcinoma was higher than that in paired adjacent tissues and it is an independent risk factor for vascular invasion of pancreatic cancer.KLK7 can promote the proliferation of pancreatic cancer cells, reduce the chemosensitivity and increase the invasion and migration of pancreatic cancer cells.

[Clavien-Dindo classification and influencing factors analysis of complications after laparoscopic pancreaticoduodenectomy].

Objective: To semi-quantify the postoperative complications occurred after laparoscopic pancreaticoduodenectomy(LPD) using Clavien-Dindo score, thereafter exploring its impact factors. Methods: In this retrospective cohort study, the clinical data of 124 patients who had undergone LPD for periampullary tumor from June 2016 to June 2017 at Department of Biliary Pancreatic Surgery, Affiliated Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology were collected.Malignancy was confirmed based on postoperative pathological reports.Postoperative complications were semi-quantitated using Clavien-Dindo score.Multivariable logistic regression model was applied to explore the factors related to severe complications(Clavien-Dindo Ⅲb-Ⅴ). Results: Of the 124 patients, there were 64 males(51.6%) and 60 females(48.4%), with age of 57 years(range, 23-82 years). In total, postoperative complications occurred in 30 patients(24.2%). Among the 30 patients, 4 patients suffered Clavien-Dindo grade Ⅰ, 18 patients(14.5%) suffered Clavien-Dindo grade Ⅱ, 6 patients(4.8%) suffered Clavien-Dindo grade Ⅲa, 1 patient(0.1%) suffered Clavien-Dindo grade Ⅳb, and 1 patient(0.1%) suffered Clavien-Dindo grade Ⅴ.Intraabdominal hemorrhage occurred in 8 patients, pancreatic fistula was found in 10 patients(7 patients had biochemical leakage and 3 of them had grade B pancreatic fistula), both biliary fistula and gastrointestinal fistula were found in 1 patient.Abdominal infection occurred in 10 patients, both liver failure and renal failure occurred in one patient.Moreover, arrhythmia was found in two patients, and mortality occurred in one patient.Five patients suffered multiple complications.Univariable analysis showed that postoperative complications were associated with body mass index, American Society of Anesthesiologists(ASA) score, intraoperative blood transfusion, and pancreatic texture(P<0.05). In multivariable logistic regression, ASA grade Ⅲ, intraoperative blood transfusion, and pancreatic softness were independently related to postoperative complications after LPD(P<0.05). Conclusions: Clavien-Dindo score is feasible to be applied in management of patients with LPD.ASA score, texture of pancreas, and intraoperative blood transfusion were independently associated with postoperative complications.

MicroRNA-219-5p functions as a tumor suppressor partially by targeting platelet-derived growth factor receptor alpha in colorectal cancer.

Platelet-derived growth factor receptor (PDGFR) signaling pathway was involved in the progress of colorectal cancer (CRC). By using the bioinformatic system online, we found that PDGFRα is a potential target of miR-219-5p. However, the expression pattern and underlying mechanisms of miR-219-5p had not been elucidated in CRC. Herein, we first evaluated the expression of miR-219-5p in tumor tissues by real-time polymerase chain reaction. Next, we confirmed that PDGFRα is the target of miR-219-5p by using luciferase report. And then, we investigated the biological functions of miR-219-5p in vitro in cell proliferation and apoptosis as well as cell cycle by gain and loss of function strategies. Data shown that miR-219-5p is down-regulated in CRC tissues compared with the corresponding matched normal tissues. PDGFRα was a direct target of miR-219-5p. Overexpression of miR-219-5p could inhibit cell proliferation, promote cell apoptosis and induce cell cycle arrest at the G1 phase. Furthermore, miR-219-5p suppressed the activation of the phosphatidylinositol 3-kinase/Akt signaling pathway and downregulated G1 cell-cycle-related protein cyclin D1, cyclin-dependent kinase (CDK) 4, and CDK6. Taken together, our results demonstrate that miR-219-5p functions as a tumor suppressor partially by targeting PDGFRα in colorectal cancer.