Identification of APEX2 as an oncogene in liver cancer.

BACKGROUND: DNA damage is one of the critical contributors to the occurrence and development of some cancers. APEX1 and APEX2 are the most important molecules in the DNA damage, and APEX1 has been identified as a diagnostic and prognostic biomarker in liver hepatocellular carcinoma (LIHC). However, the expression of APEX2 and its functional mechanisms in LIHC are still unclear. AIM: To examine the expression of APEX2 and the potential mechanism network in LIHC. METHODS: We conducted a pan-cancer analysis of the expression of APEX1 and APEX2 using the interactive TIMER tool. GEO datasets, including GSE14520, GSE22058, and GSE64041, were used to compare the APEX2 expression level in tumor tissues and adjacent non-tumor tissues. Then, we calculated the 5-year survival rate according to the web-based Kaplan-Meier analysis. We included the TCGA liver cancer database in GSEA analysis based on the high and low APEX2 expression, showing the potential mechanisms of APEX2 in LIHC. After that, we conducted Pearson correlation analysis using GEPIA2. Next, we performed quantitative polymerase chain reaction (qPCR) assay to examine the APEX2 levels in normal liver cell line LO2 and several liver cancer cell lines, including HepG2, Huh7, SMMC7721, and HCCLM3. APEX2 in HCCLM3 cells was knocked down using small interfering RNA. The role of APEX2 in cell viability was confirmed using CCK-8. Dual-luciferase reporter assay was performed to examine the promoter activity of CCNB1 and MYC. RESULTS: APEX1 and APEX2 are both highly expressed in the tumor tissues of BLCA, BRCA, CHOL, COAD, ESCA, HNSC, LIHC, LUAD, LUSC, READ, and STAD. APEX2 overexpression in LIHC was validated using GSE14520, GSE22058, and GSE64041 datasets. The survival analysis showed that LIHC patients with high expression of APEX2 had a lower overall survival rate, even in the AJCC T1 patients. High level of APEX2 could indicate a lower overall survival rate in patients with or without viral hepatitis. The GSEA analysis identified that kinetochore and spindle microtubules are the two main cellular components of APEX2 in GO Ontology. APEX2 was also positively associated with molecular function regulation of chromosome segregation and DNA replication. The results of KEGG analysis indicated that APEX2 expression was positively correlated with cell cycle pathway and pro-oncogenic MYC signaling. Pearson correlation analysis showed that APEX2 had a significant positive correlation with CCNB1 and MYC. APEX2 level was higher in liver cancer cell lines than in normal liver LO2 cells. Small interfering RNA could knock down the APEX2 expression in HCCLM3 cells. Knockdown of APEX2 resulted in a decrease in the viability of HCCLM3 cells as well as the expression and promoter activity of CCNB1 and MYC. CONCLUSION: APEX2 is overexpressed in LIHC, and the higher APEX2 level is associated with a worse prognosis in overall survival. APEX2 is closely involved in the biological processes of chromosome segregation and DNA replication. APEX2 expression is positively correlated with the pro-oncogenic pathways. Knockdown of APEX2 could inhibit the cell viability and CCNB1 and MYC pathways, suggesting that APEX2 is an oncogene in LIHC, which could be a potential pharmaceutic target in the anti-tumor therapy.

Is ERAS effective and safe in laparoscopic gastrectomy for gastric carcinoma? A meta-analysis.

BACKGROUND: It is still unclear whether enhanced recovery after surgery is effective and safe in laparoscopic gastrectomy for gastric carcinoma. METHODS: Cochrane library databases, Medline, Embase, and Pubmed were searched from January 1, 1986, to December 31, 2016. Randomized controlled trials (RCTs) comparing fast-track recovery with conventional recovery strategies in laparoscopic radical gastrectomy for gastric carcinoma were included. The main outcomes measured were postoperative hospital stay, time to first flatus, hospital charge, and overall complication rate. RESULTS: Six RCTs with 400 patients were included in this study. Fast-track surgery has shorter postoperative hospital stays (weighted mean difference (WMD) - 2.65; 95% CI, - 4.01 to - 1.29, z = 3.82, P < 0.01) and less hospitalization expenditure (WMD - 523.43; 95% CI, - 799.79 to - 247.06, z = 3.71, P < 0.01) than conventional recovery strategies. There was no significant difference with respect to duration to first flatus (WMD - 17.72; 95% CI, - 39.46-4.02, z = 1.60, P = 0.11) and complication rate (OR 1.57; 95% CI, 0.82-2.98, z = 1.37, P = 0.17). CONCLUSIONS: Enhanced recovery after surgery is effective and safe and is thus recommended in laparoscopic radical gastrectomy for gastric carcinoma.

Pitavastatin suppressed liver cancer cells in vitro and in vivo.

Pitavastatin classically functions as a blood cholesterol-lowering drug. Previously, it was discovered with antiglioma stem cell properties through drug screening. However, whether it can be used for liver cancer cell therapy has never been reported. In this study, the cell viability and colony formation assay were utilized to analyze the cytotoxicity of pitavastatin on liver cancer cells. The cell cycle alteration was checked after pitavastatin treatment. Apoptosis-related protein expression and the effect of caspase inhibitor were also checked. The in vivo inhibitory effect of pitavastatin on the growth of liver tumor was also tested. It was found that pitavastatin inhibited growth and colony formation of liver cancer Huh-7 cells and SMMC7721 cells. It induced arrest of liver cancer cells at the G1 phase. Increased proportion of sub-G1 cells was observed after pitavastatin treatment. Pitavastatin promoted caspase-9 cleavage and caspase-3 cleavage in liver cancer cells. Caspase inhibitor Z-VAD-FMK reversed the cleavage of cytotoxic effect of pitavastatin. Moreover, pitavastatin decreased the tumor growth and improved the survival of tumor-bearing mice. This study suggested the antiliver cancer effect of the old drug pitavastatin. It may be developed as a drug for liver cancer therapy.

Berberine modulates cisplatin sensitivity of human gastric cancer cells by upregulation of miR-203.

Chemotherapeutic resistance is the main reason of the failure in clinical treatment of gastric cancer. Berberine (BER) is the active compound of traditional Chinese medicine Huang Lian. The aim of this present study is to evaluate the effect of BER on cisplatin resistance in gastric cancer cells and to investigate its possible mechanism. Gastric cancer cell lines SGC-7901 and BGC-823 and their respective cisplatin-resistant variants SGC-7901/DDP and BGC-823/DDP were used in this study. We found that BER treatment significantly reversed cisplatin sensitivity and induced caspase-dependent apoptosis in SGC-7901/DDP and BGC-823/DDP cells; BER treatment induced miR-203 expression, and overexpression of miR-203 mimicked the cisplatin-sensitizing effect of BER. Importantly, we showed that miR-203 was able to target the 3'UTR of Bcl-w. Therefore, we conclude that BER treatment reduces cisplatin resistance of gastric cancer cells by modulating the miR-203/Bcl-w apoptotic axis. BER may be a novel agent to enhance chemotherapeutic responses in cisplatin-resistant gastric cancer patients.

Long-term oncologic outcomes of laparoscopic vs open surgery for stages II and III rectal cancer: A retrospective cohort study.

AIM: To evaluate the 5-year survival after laparoscopic surgery vs open surgery for stages II and III rectal cancer. METHODS: This study enrolled 406 consecutive patients who underwent curative resection for stages II and III rectal cancer between January 2000 and December 2009 [laparoscopic rectal resection (LRR), n = 152; open rectal resection (ORR), n = 254]. Clinical characteristics, operative outcomes, pathological outcomes, postoperative recovery, and 5-year survival outcomes were compared between the two groups. RESULTS: Most of the clinical characteristics were similar except age (59 years vs 55 years, P = 0.033) between the LRR group and ORR group. The proportion of anterior resection was higher in the LRR group than that in the ORR group (81.6% vs 66.1%, P = 0.001). The LRR group had less estimated blood loss (50 mL vs 200 mL, P < 0.001) and a lower rate of blood transfusion (4.6% vs 11.8%, P = 0.019) compared to the ORR group. The pathological outcomes of the two groups were comparable. The LRR group was associated with faster recovery of bowel function (2.8 d vs 3.7 d, P < 0.001) and shorter postoperative hospital stay (11.7 d vs 13.7 d, P < 0.001). The median follow-up time was 63 mo in the LRR group and 65 mo in the ORR group. As for the survival outcomes, the 5-year local recurrence rate (16.0% vs 16.4%, P = 0.753), 5-year disease-free survival (DFS) rate (63.0% vs 63.1%, P = 0.589), and 5-year overall survival (OS) rate (68.1% vs 63.5%, P = 0.682) were comparable between the LRR group and the ORR group. Stage by stage, there were also no statistical differences between the LRR group and the ORR group in terms of the 5-year local recurrence rate (stage II: 6.3% vs 8.7%, P = 0.623; stage III: 26.4% vs 23.2%, P = 0.747), 5-year DFS rate (stage II: 77.5% vs 77.6%, P = 0.462; stage III: 46.5% vs 50.9%, P = 0.738), and 5-year OS rate (stage II: 81.4% vs 74.3%, P = 0.242; stage III: 53.9% vs 54.1%, P = 0.459). CONCLUSION: LRR for stages II and III rectal cancer can yield comparable long-term survival while achieving short-term benefits compared to open surgery.

[The role of glucagon-like peptide-1 and its receptor in the mechanism of metabolic surgery].

At present, surgery has become one of the treatments for type 2 diabetes, but it is still unclear about the therapeutic mechanism. Many experiments has proved that the anatomical and physiological structure has been altered leading to significant changes related to the secretion of gastrointestinal hormones and neuropeptides. These molecular are related to the metabolism of glucose, functions of islet cells and sensitivity of insulin. Intensive studies of glucagon-like peptide-1 (GLP-1) play an important role in the surgical treatment of diabetes and now it has gained increasing recognition. However, GLP-1 must be combined with GLP-1 receptor (GLP-1R) to execute its function. In this paper we reviewed the role of GLP-1 and its receptor in the mechanism of metabolic surgery.

[Duodenojejunal bypass in treatment for 7 cases with non-severe obese type 2 diabetes mellitus].

OBJECTIVE: To investigate the efficacy and feasibility of duodenojejunal bypass(DJB)on non-severe obese patients with type 2 diabetes mellitus(T2DM). METHODS: The body mass index (BMI), fasting plasma glucose(FPG), 2h-postprandial plasma glucose(2hPG), fasting insulin(F-ins), fasting c-peptide(F-CP), glycated hemoglobin and hypoglycemic agents dose changes were tested in 7 patients with non-severe obese T2DM undergoing DJB, preoperatively and within 24 weeks after surgery during the follow-up. Data were collected and the clinical outcomes of T2DM were analyzed. RESULTS: In 7 cases of non-obese T2DM who underwent DJB, one patient was weaned off hypoglycemic agents with normal FPG, 2hPG and HbA1c postoperatively. Five required significantly lower dosage. No significant improvement in 1 case. Complete remission rate of hyperglycemia was 1/7, effective rate was 6/7, and effective rate of HbA1c was 5/7. No significant changes in BMI were observed between the preoperative and postoperative phases. CONCLUSION: Plasma glucose level can be markedly reduced by duodenojejunal bypass in non-obese T2DM, independent of weight loss, and the mechanism remains unclear.

Laparoscopic vs open left hepatectomy for hepatolithiasis.

AIM: To explore the feasibility and therapeutic effect of total laparoscopic left hepatectomy (LLH) for hepatolithiasis. METHODS: From June 2006 to October 2009, 61 consecutive patients with hepatolithiasis who met the inclusion criteria for LLH were treated in our institute. Of the 61 patients with hepatolithiasis, 28 underwent LLH (LLH group) and 33 underwent open left hepatectomy (OLH group). Clinical data including operation time, intraoperative blood loss, postoperative complication rate, postoperative hospital stay time, stone clearance and recurrence rate were retrospectively analyzed and compared between the two groups. RESULTS: LLH was successfully performed in 28 patients. The operation time of LLH group was longer than that of OLH group (158 +/- 43 min vs 132 +/- 39 min, P < 0.05) and the hospital stay time of LLH group was shorter than that of OLH group (6.8 +/- 2.8 d vs 10.2 +/- 3.4 d, P < 0.01). No difference was found in intraoperative blood loss (180 +/- 56 mL vs 184 +/- 50 mL), postoperative complication rate (14.2% vs 15.2%), and stone residual rate (intermediate rate 17.9% vs 12.1% and final rate 0% vs 0%) between the two groups. No perioperative death occurred in either group. Fifty-seven patients (93.4%) were followed up for 2-40 mo (mean 17 mo), including 27 in LLH group and 30 in OLH group. Stone recurrence occurred in 1 patient of each group. CONCLUSION: LLH for hepatolithiasis is feasible and safe in selected patients with an equal therapeutic effect to that of traditional open hepatectomy.

[Factors influencing the long-term survival in pancreatic carcinoma patients after radical resection].

OBJECTIVE: To investigate the factors influencing the long-term survival of pancreatic carcinoma patients after radical resection. METHODS: The data of 184 pancreatic carcinoma patients with radical resection were analyzed retrospectively. Analysis of the prognostic factors influencing the long-term survival was performed using Cox proportional hazard regression model. RESULTS: The overall 1-, 3- and 5-year survival rates in this group were 61.7%, 29.0% and 14.3%, respectively. They were 78.0%, 38.4% and 25.7%, respectively, for the patients with a tumor < 3 cm in diameter, significantly better than those with a tumor >or= 3 cm (52.8%, 22.7% and 7.2%, respectively, P < 0.05). Moreover, the 1-, 3- and 5-year survival rates were 67.6%, 30.5% and 17.4%, respectively, in the patients without lymph node involvement, much longer than that in those with lymph node metastasis (37.1%, 20.6% and 0, respectively, P < 0.05). Multivariate analysis by Cox proportional hazard regression model revealed that the tumor size (P < 0.05) and lymph node metastasis (P < 0.01) significantly influenced the long-term survival of the patients. CONCLUSION: Tumor size and lymph node metastasis are significant factors influencing the long-term survival of pancreatic carcinoma patients with radical resection. Therefore, early diagnosis and radical resection are the key points to improve treatment outcome.