MEK inhibitor enhances sensitivity to chemotherapeutic drugs in multidrug resistant hepatocellular carcinoma cells.

The aim of the present study was to investigate the association between the mitogen-activated protein kinase (MAPK) signal transduction pathway and multidrug resistance in hepatocellular carcinoma cells. A Cell Counting Kit-8 assay was used to determine the drug sensitivity of HepG2 and HepG2/ADM hepatocellular carcinoma cell lines in combination with the MAPK/extracellular-signal-regulated kinase kinase (MEK) inhibitor U0126. Flow cytometry was used to analyze the rate of apoptosis. The reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to determine P-glycoprotein (P-gp) and multidrug resistance-associated protein 1 (MRP1) mRNA expression following treatment with various concentrations of U0126. P-gp and MRP1 expression levels were measured using Western blot analysis. The half-maximal inhibitory concentration was markedly decreased in combination with U0126. RT-qPCR results demonstrated that the expression of multidrug resistance 1 (MDR1) and MRP1 in HepG2/ADM cells was increased 5.37- and 6-14-fold compared with that in HepG2 cells. Furthermore, the expression levels in HepG2/ADM cells were decreased following U0126 treatment in a dose-dependent manner. The expression of P-gp and MRP1 in HepG2/ADM cells was increased 2.68- and 2.76-fold compared with that in HepG2 cells. Furthermore, the expression levels in HepG/ADM cells were decreased following U0126 treatment in a dose-dependent manner. The results of the present study indicate that the MEK inhibitor U0126 enhances sensitivity to chemotherapeutic drugs by downregulating P-gp and MRP1 expression in resistant hepatocellular carcinoma cells. The combination of MEK inhibitor and conventional chemotherapeutic drugs may provide novel therapeutic prospects for the treatment of drug-resistant hepatocellular carcinoma.

Recent perspectives of management of breast cancer metastasis - an update.

Breast cancer is the leading cause of cancer related deaths in women and one of the most common cancers globally. The major obstacle in the management of breast cancer, especially at advanced stages, is metastasis. Metastasis in the advanced stages of breast cancer could decrease survival to approximately 5 years. The reasons could include lack of targeted receptors or chemotherapeutic agents for the management of advanced-stage breast cancer metastasis. The new emerging avenues for the management of this deadly pathological state include local manipulations like radiofrequency ablation (RFA), microwave thermotherapy, cryosurgery (cryotherapy), chemoembolization, radioembolization, breast surgery, or metastasectomy. Few single-institution reports showed improved survival in selected patients like those with oligometastatic stage IV breast cancer. The present review article focused on these emerging new multimodality treatment approaches for a possible efficient management.

Laparoscopic jejunoileal side-to-side anastomosis for the treatment of type 2 diabetes mellitus in Chinese patients with a body mass index of 24-32 kg/m2.

OBJECTIVE: Laparoscopic jejunoileal side-to-side anastomosis (LJISSA) is an upcoming procedure that offers good metabolic improvement without causing significant malabsorption. The objective of this study was to evaluate the results of this novel procedure for the control of type 2 diabetes mellitus (T2DM) in patients with a body mass index (BMI) of 24-32 kg/m 2. MATERIALS AND METHODS: Fifty-seven patients with T2DM who underwent LJISSA between February 2010 and May 2013 were recruited in this study. Data collected included fasting blood glucose (FBG), 2 h postprandial blood glucose (2 h PBG), 1 h postprandial C peptide (1 h C-P), and glycosylated hemoglobin (HbA1c). RESULTS: Postoperatively, glycemic parameters (FBG and 2 h PBG, HbA1c and 1 h C-P) improved in all 57 patients. At 12 months, 34 patients had a remission of diabetes, and the remaining 23 patients showed a significantly decreased requirement for oral hypoglycemic agents. The patients with a BMI of 28-32 kg/m 2 had significant weight loss of between 7.8% and 20% (P < 0.05), whereas weight loss was not significant in those with a BMI of 24-28 kg/m 2. The group achieving remission had a higher BMI (28-32 kg/m 2), shorter duration of diabetes (<10 years), and higher stimulated C-P (>4 ng/mL). These three factors may be the predictors of diabetes resolution at 12 months. CONCLUSION: LJISSA seems to be a promising procedure for the control of T2DM. A multicenter study with a larger number of patients and a longer follow-up period is needed to substantiate our preliminary findings.

[Feasibility of terminal intestinal exteriorization in laparoscopic anterior resection for anterior cancer].

OBJECTIVE: To discuss the feasibility of terminal intestinal exteriorization (exteriorization without ileostomy) in laparoscopic anterior resection for rectal cancer. METHODS: Clinicopathological data of 77 patients undergoing laparoscopic anterior resection for low rectal cancer in our department from January 2011 to December 2013 were retrospectively analyzed. After laparoscopic rectal resection, 32 patients received terminal intestinal exteriorization (exteriorization group) and 45 patients received preventive ileostomy (ileostomy group). Anastomosis-related, stoma-related and intestinal stoma closure-related morbidity was compared between the two groups. RESULTS: There were no significant differences in operative time, blood loss and overall hospital stay between the two groups (all P>0.05). The total hospital cost was (5.39±1.74)×10(4) yuan in the exteriorization group, and (6.98±1.37)×10(4) yuan in the ileostomy group(P<0.01). The incidences of postoperative anastomotic fistula was not significantly different between the two groups(P>0.05). Three patients(9.4%) developed anastomotic leak in the exteriorization group and 2(4.4%) in the ileostomy group. The anastomotic leak was managed by opening the external intestinal wall and maturating an ileostomy under local anaesthesia. All these 5 patients were cured with nutritional support, antibiotics, continuous local drainage. In the exteriorization group, 5 patients had complications related to stoma and intestinal stoma closure operation(15.6%), which was lower than(42.2%) in the ileostomy group(P=0.013). CONCLUSION: Terminal intestinal exteriorization in laparoscopic anterior resection is a safe and feasible surgical procedure with little trauma and less hospital cost, which can be an alternative as a prophylactic treatment for patients with high risk of anastomotic leak.

Radical Gastrectomy Combined with Modified Gastric Bypass Surgery for Gastric Cancer Patients with Type 2 Diabetes.

The aim of the study is to explore the effectiveness of radical gastrectomy with modified gastric bypass surgery in treating gastric cancer patients with type 2 diabetes mellitus (T2DM). A total of 93 patients with gastric cancer and T2DM were treated in our hospital and enrolled in this study. Patients in group A (n = 30) had a body mass index (BMI) of >28 kg/m(2). Radical total gastrectomy and modified esophagojejunal Roux-en-y anastomosis were performed on 13 patients, and radical distal subtotal gastrectomy and gastric remnant jejunal Roux-en-y anastomosis were performed on 17 patients. The data from groups B, C, and D were derived from 63 patients with gastric cancer and diabetes who were admitted to our hospital from January 2005 to July 2012. All patients underwent radical gastrectomy (including 21 cases of gastric cancer surgery with Billroth I anastomosis, 25 cases of radical gastrectomy with Roux-en-Y anastomosis and BMI >28 kg/m(2), and 17 cases with BMI <28 kg/m(2)). The BMI, fasting blood glucose (FBG), meal after the 2-hour glucose (2 h PBG), C-peptide (C-P), and glycosylated hemoglobin (HbAIC) data were collected before and 6 and 12 months after surgery. In groups A and D, BMI, FBG, 2 h PBG, C-P, and HbAIC at the 6th and 12th post-operative months were significantly lower than those before the surgery. In group B, BMI, FBG, 2 h PBG, C-P, and HbAIC at the 6th and 12th post-operative months did not decrease significantly, when compared with the pre-operative levels. In group C, BMI, FBG, 2 h PBG, C-P, and HbAIC at the 6th and 12th post-operative months decreased but showed no statistical significance. However, in comparison, groups A C showed significant differences after the surgeries. Radical gastrectomy combined with modified gastric bypass surgery is effective in treating patients with gastric cancer with type 2 diabetes, although this requires further investigation.

ZnPP reduces autophagy and induces apoptosis, thus aggravating liver ischemia/reperfusion injury in vitro.

There is growing evidence indicating that autophagy plays a protective role in liver ischemia/reperfusion (IR) injury. Heme oxygenase-1 (HO-1) can also prevent liver IR injury by limiting inflammation and inducing an anti-apoptotic response. Autophagy also plays a crucial role in liver IR injury. The aim of the present study was to investigate the role of HO-1 in liver IR injury and the association between HO-1, autophagy and apoptotic pathways. IR simulation was performed using buffalo rat liver (BRL) cells, and HO-1 activity was either induced by hemin (HIR group) or inhibited by zinc protoporphyrin (ZnPP) (ZIR group). In the HIR and ZIR group, the expression of HO-1 and autophagy-related genes [light chain 3-Ⅱ (LC3-Ⅱ)] was assessed by RT-qPCR and the protein expression of caspases, autophagy-related genes and genes associated with apoptotic pathways (Bax) was detected by western blot anlaysis. The results of RT-PCR revealed the genetically decreased expression of HO-1 and autophagy-related genes in the ZIR group. Similar results were obtained by western blot analysis and immunofluorescence. An ultrastructural analysis revealed a lower number of autophagosomes in the ZIR group; in the HIR group, the number of autophagosomes was increased. The expression of Bax and cytosolic cytochrome c was increased, while that of Bcl-2 was decreased following treatment of the cells with ZnPP prior to IR simulation; the oppostie occurred in the HIR group. Cleaved caspase-3, caspase-9 and poly(ADP-ribose) polymerase (PARP) protein were activated in the IR and ZIR groups. The disruption of mitochondrial membrane potential was also observed in the ZIR group. In general, the downregulation of HO-1 reduced autophagy and activated the mitochondrial apoptotic pathway.

The clinical value of Fufangkushen injection in the treatment of stomach cancer: a meta-analysis.

OBJECTIVE: The purpose of this meta-analysis was to evaluate the effects of Fufangkushen injection combined with chemotherapy in the treatment of stomach cancer. MATERIALS AND METHODS: The relevant clinical trials about Fufangkushen injection combined with chemotherapy in the treatment of stomach cancer were search in the data bases of Pubmed, EMBASE, Cochran and CNKI. The data related to objective response rate, Karnofsky (KPS) score and toxicity were extracted and pooled using the Stata 11.0 software. Dichotomous data was presented as risk ratio (RR) and its 95% confidence interval (95% CI). RESULTS: Thirteen relevant trials were included in this meta-analysis. Heterogeneity test indicated there was no statistical heterogeneity among the studies, thus the fixed effects mode was used to calculat the results. Pooled results indicated that the objective response rate (ORR) and KPS score improvement in Fufangkushen chemotherapy group was significant higher than that of control group (RR = 1.24, P < 0.05). Synthesis data also demonstrated the Fufangkushen injection can significantly decrease the risk of developing granulocytopenia in stomach cancer patients treated with chemotherapy (RR = 0.67,P < 0.05). CONCLUSION: Fufangkushen injection combined with chemotherapy can increase the objective response rate, improve the quality of life and decrease the risk of developing granulocytopenia in patients with stomach cancer.