ObjectiveTo analyze the effects of miR-451a on the proliferation and apoptosis of human pancreatic cancer BxPc3 cells, and to explore its molecular mechanisms.MethodsThe liposome transfection mimics of miR-451a were established in the BxPc3 cells, which were used as the research objects, and different concentrations (25, 50, 100 and 200 μmol/L) of miR-451a and blank control group were set up respectively. The expression of miR-451a mRNA in the BxPc3 cells after the transfection was detected by the qRT-PCR method. The effects of miR-451a at different concentrations on the proliferation, cell clone number, cell cycle and apoptosis, and the expressions of the macrophage migration inhibitory factor (MIF), calcium binding protein 39 (CAB39), phosphorylated phosphatidylinositol-3-kinase (p-PI3K) and phosphorylated protein kinase B (p-AKT) proteins in the BxPc3 cells were detected by the MTT assay, plate cloning assay, flow cytometry, and Western blot, respectively.ResultsThe expressions of miR-451a mRNA in the transfected BxPc3 cells were significantly higher than in the blank control BxPc3 cells (P<0.050). The miR-451a could inhibit the proliferation of BxPc3 cells in a time- and concentration-dependent manner significantly (P<0.050), block the differentiation of BxPc3 cells in the G0/G1 phase, and induce the apoptosis with a concentration-dependent manner (P<0.050). The expressions of MIF, CAB39, p-PI3K, and p-AKT proteins in the BxPc3 cells were down-regulated with a concentration-dependent manner (P<0.050).ConclusionFrom results of this study, miR-451a could inhibit proliferation and induce apoptosis of BxPc3 cells in a concentration-dependent manner, and its mechanisms might be related to inhibition of PI3K/AKT signaling pathway.
ObjectiveTo analyze the expression of Hsa-miR-29c in gastric cancer and its mechanism of action, and to explore its relationship with clinicopathological characteristics and prognosis of gastric cancer patients.MethodsTheoverexpression of Hsa-miR-29c in gastric cancer cell lines of MKN28 and MKN45 were established by lentivirus transfection (transfection group), and the control group of empty lentivirus (negative control group) was established. The expressions of Hsa-miR-29c in cells of the two groups after transfection were detected by real time polymerase chain reaction (qRT-PCR), and the proliferation and clonogenesis of cells in the two groups were detected by CCK-8 and plate cloning. The expression of extracellular matrix protein 1 (ECM1), type Ⅰ collagen (Col Ⅰ), smooth muscle actin(α-SMA), matrix metalloproteinase-2 (MMP-2), and tissue inhibitor of metalloproteinase-1 (TIMP-1) in the two groups were detected by Western blot. qRT-PCR and immunohistochemistry were used to detect the expression of Hsa-miR-29c in 70 gastric cancer tissues and adjacent tissues respectively, and then analyzed its relationship with the clinicopathological features and prognosis of gastric cancer.ResultsThe stable expression of Hsa-miR-29c gastric cancer cell line was successfully constructed in this research, the expression of Hsa-miR-29c in the transfection group was significantly higher than that in the negative control group (P<0.05). The proliferation and clone forming ability of MKN28 and MKN45 cells in the transfection group were significantly lower than those in the negative control group (P<0.05). Compared with the negative control group, the expression of Col Ⅰ and TIMP-1 in MKN28 and MKN45 cells were increased after transfection, while the expression levels of ECM1, α-SMA, and MMP-2 were significantly decreased, with significant differences between the two groups (P<0.05). The expression level of Hsa-miR-29c in gastric cancer tissues was significantly lower than that of adjacent tissues (P<0.05), and the positive expression rate was not related to age, sex, and pathological type (P>0.05), but related to tumor size, TNM stage, tumor differentiation, and lymph node metastasis (P<0.05). The mean survival time (MST) of patients with negative expression of Hsa-miR-29c was significantly shorter than that of patients with positive expression (P=0.029).ConclusionsHsa-miR-29c is down expressed in gastric cancer, and is related to the clinical characteristics and prognosis of it. The overexpression of Hsa-miR-29c can inhibit the proliferation of gastric cancer cells, and the mechanism may be related to the inhibition of extracellular matrix (ECM) signaling pathway.
ObjectiveTo investigate the expression level and the clinical significance of Traf-2 and Nck-interacting protein kinase (TNIK) in gastric cancer tissues.MethodsWe retrospectively collected 78 cases of gastric cancer and its adjacent tissues which were diagnosed by surgery and pathology, all the patients received surgery in the Department of General Surgery in Luoyang Central Hospital Affiliated to Zhengzhou University, from July 2014 to December 2017, as well as 42 cases of gastric ulcer tissues in the same period. The expression of TNIK protein was detected by using immunohistochemical method and Western blot method in 78 cases of human gastric cancer tissues, corresponding adjacent normal tissues, and 42 cases of gastric ulcer tissues, the relationship between expression of TNIK protein and clinicopathologial features of gastric cancer was explored.ResultsThe positive expression rate of TNIK protein in gastric cancer tissues was 66.67% (52/78), and adjacent cancer tissues showed low expression rate of 11.54% (9/78), while it was 21.43% (9/42) in gastric ulcer tissues. On the positive expression rate of TNIK protein, gastric cancer tissues compared with adjacent cancer tissues and gastric ulcer tissues, the difference was statistically significant (P<0.05), however, there was no statistically significant difference between adjacent cancer tissues and gastric ulcer tissues (P>0.05). Western blot method showed that the expression level of TNIK protein in gastric cancer tissues was all significantly higher than that in adjacent cancer tissues and gastric ulcer tissues, the differences were statistically significant (P<0.05), but the difference was not significant when compared the adjacent cancer tissues and gastric ulcer tissues (P=0.772). The expression of TNIK protein was irrelevent to sexual distinction, CEA value, tumor diameter, and pathological type (P>0.05), while it was closely related to patients’ age, TNM stage, differentiation grade, distant metastasis, and lymph node metastasis (P<0.05). The prognosis of patients with positive expression of TNIK protein was worse than that of patients with negative expression of TNIK protein (P<0.05).ConclusionTNIK protein is highly expressed in gastric cancer tissues, which is associated with poorly prognostic factors and poor prognosis, and it may be a therapeutic target in patients with gastric cancer.
Objective To explore the clinical value of preoperative neoadjuvant chemotherapy (NAC) combined with laparoscopic pancreatoduodenectomy (LPD) with multiple surgical approaches in the treatment of borderline resectable pancreatic head cancer. Methods The clinicopathologic data of 35 patients with critical resectable pancreatic head carcinoma admitted to the Department of Hepatobiliary and Pancreatic Surgery of Luoyang Central Hospital Affiliated to Zhengzhou University and the Department of Hepatobiliary and Pancreatic Surgery of the Fifth Affiliated Hospital of Zhengzhou University from January 2017 to June 2022 were retrospectively analyzed. All patients received NAC before operation (AG protocol). At the end of the course of treatment, according to the type of borderline resectable pancreatic cancer (BRPC) [venous invasion type (BRPC-V type) and arterial invasion type (BRPC-A type)], take the individualized surgical approach for LPD (BRPC-V type: inferior mesenteric vein approach; BRPC-A type: left posterior approach, medial uncinate process approach, anterior approach, or lower mesocolon approach). The intraoperative condition, R0/R1 resection rate, lymph node dissection, postoperative complications, average hospital stay, recovery, follow-up and survival were recorded. Results① Efficacy evaluation of NAC: 13 patients were partially relieved , 17 patients were stable and 5 patients were progressive after 4 weeks of treatment. Five progressive patients continued to receive comprehensive internal medicine treatment, and the remaining 30 patients underwent LPD. ② Intraoperative situation: LPD were successfully completed in 30 patients, 2 patients underwent extended pancreaticoduodenectomy combined with superior mesenteric vein (or) portal vein reconstruction among them. Among the 30 patients with LPD, there were 10 cases of inferior mesenteric vein approach, 10 cases of left posterior approach, 6 cases of medial uncinate process approach, 1 case of left posterior approach+medial uncinate process approach, 2 cases of anterior approach, and 1 case of inferior mesocolon approach. The mean operative time was (379.4±77.3) min, the intraoperative blood loss was (436.9±95.1) mL. ③ Postoperative situation: The incidence rate of postoperative surgery-related complications was 33.3% (10/30), including 4 cases of Clavien-Dindo grade Ⅰ [biliary fistula in 1 case (3.3%), A-grade pancreatic fistula in 1 case (3.3%), gastric draining dysfunction in 1 case (3.3%), diarrhea in 1 case (3.3%)], 5 cases of grade Ⅱ [pulmonary infection in 2 cases (6.6%), B-grade pancreatic fistula in 2 cases (6.6%), abdominal infection in 1 case (3.3%)], and 1 case of grade Ⅲ [gastroduodenal artery stump bleeding (3.3%)]. Among the 10 patients with complications, 9 cases recovered after symptomatic treatment, and 1 case died, with a fatality rate of 3.3% (1/30). The mean postoperative hospital stay was (17.3±5.5) days. ④ Excision rate and pathological results: R0 resection rate was 90.0% (9/10) in 10 patients with BR-PV type LPD, and R1 resection was performed in 1 patient. R0 resection rate was 75.0% (15/20) in 20 patients with BR-A type, and R1 resection was performed in 5 patients (2 patients with medial uncinate process approach; Left posterior approach in 2 cases; Submesocolon approach was used in 1 case). In 30 patients with LPD, the total R0 removal rate was 80.0% (24/30), the number of lymph nodes dissected was (11±5). Pathological type: There were 26 cases (86.7%) of ductal adenocarcinoma in 30 patients, 1 case of adeno-squamous carcinoma (3.3%), 1 case of mucinous carcinoma (3.3%), 2 cases of acinocytic cell carcinoma (6.7%). 23 cases (76.7%) of medium-high differentiation and 5 cases (16.6%) of low differentiation, two cases (6.7%) were undifferentiated. ⑤ Postoperative follow-up and survival: 30 patients were completely followed-up for 6-39 months, with a median follow-up time of 17 months. The median survival time of BRPC-V and BRPC-A patients was 24.0 months and 17.0 months, respectively. The overall survival rates of 30 patients at 1, 2 and 3 years after operation were 77.3%、46.5% and 13.7%, respectively. Conclusion The selection of preoperative NAC combined with individualized surgical approach for patients with borderline resectable pancreatic head cancer is beneficial to improve the radical resection rate and clinical therapeutic effect, and has good clinical application value.