Objective:To elucidate the role of ERK1/2 MAPKs signal transduction in the protective effects of ischemic preconditioning during liver transplantation. Methods: Twenty-four rats were equally randomized into 4 groups: sham control (group A); liver transplantation (group B); ischemic preconditioning+liver transplantation (group C), and MEK inhibitor intervention+ischemic preconditioning+liver transplantation (group D). Serum AST and ALT were detected after operation and cellular ultrastructures were observed by transmission electron microscopy. Liver tissue ERK1/2 MAPKs phosphorylation activities were evaluated through determining ERK-1 protein phosphorylation by Western blotting. Results: Serum ALT and AST activity in group B and group D was significantly higher than those in group A, and remained normal in group C. Liver tissue ERK1/2 MAPKs phosphorylation activity increased significantly in group C, and the activation effect was inhibited in group B and D. Cellular ultrastructure was obviously damaged in group B and group D, and the damage was prevented in group C.Conclusion: Ischemic preconditioning has a protective effect on transplanted liver cells in which ERK1/2 MAPKs pathway plays a pivotal role.

BACKGROUND AND OBJECTIVEAccumulating data indicate that docetaxel plus cisplatin and 5-fluorouracil has certain effect on advanced gastric or gastro-oesophageal junction adenocarcinoma. This study was to evaluate the efficacy and toxicity of docetaxel plus nedaplatin and 5-fluorouracil (DNF regimen) in treating advanced esophageal carcinoma.

METHODSForty-three patients with pathologically confirmed advanced esophageal carcinoma treated by DNF regimen: intravenous infusion of docetaxel (75 mg/m(2)) over 1 h, intravenous infusion of nedaplatin (100 mg/m(2)) over 3 h, intravenous infusion of leucovorin (CF, 200 mg/m(2)) over 2 h, intravenous injection of 5-fluorouracil (375 mg/m(2)) over 10 min, followed by a 46-hour infusion of 5-fluorouracil (2.6 g/m(2)). The cycle was repeated every three weeks. Treatment efficacy was evaluated every two weeks according to the WHO standards. All patients received at least two cycles of chemotherapy.

RESULTSPatients received a total of 144 cycles of treatment, and all were evaluable for efficacy and toxicity. Of the 43 patients, 2 (4.65%) achieved complete response (CR), 25 (58.14%) achieved partial response (PR), 9 (20.93%) had stable disease (SD), and 7 (16.28%) had progressive disease (PD). The overall response rate was 62.8%. The median time-to-progression (TTP) was 201 days and the median survival time (MST) was 310 days. Grade III/IV adverse events mainly included neutropenia (20.93%), febrile neutropenia (4.65%), thrombocytopenia (6.98%) and vomiting (9.30%). One patient died of grade IV thrombocytopenia.

CONCLUSIONDNF regimen is effective for and well tolerated by patients with advanced esophageal carcinoma.

Adenocarcinoma ; drug therapy ; pathology ; secondary ; Adult ; Aged ; Antineoplastic Combined Chemotherapy Protocols ; adverse effects ; therapeutic use ; Carcinoma, Squamous Cell ; drug therapy ; pathology ; secondary ; Esophageal Neoplasms ; drug therapy ; pathology ; Female ; Fluorouracil ; administration & dosage ; adverse effects ; Humans ; Liver Neoplasms ; drug therapy ; secondary ; Lung Neoplasms ; drug therapy ; secondary ; Lymphatic Metastasis ; Male ; Middle Aged ; Neoplasm Staging ; Neutropenia ; chemically induced ; Organoplatinum Compounds ; administration & dosage ; adverse effects ; Remission Induction ; Survival Rate ; Taxoids ; administration & dosage ; adverse effects ; Thrombocytopenia ; chemically induced

Objective To investigate the relationship between X-ray injury cross-complementing protein 1 (XRCC1) gene polymorphism and prognosis in patients with triple-negative breast cancer (TNBC). Methods Patients with primary triple-negative breast cancer (TNBC) diagnosed in the Ninth People′s Hospital, Shanghai Jiaotong University School of Medicine from January 2013 to January 2015 were selected. Patients were selected for genotyping (XRCC1 gene Arg280His, Arg399Gln and Arg194Trp) and divided into survival group and death group according to the prognosis of patients. Logistic regression was used to analyze the relationship between XRCC1 genotype and prognosis. Results A total of 130 patients were enrolled in the study, with an average age of (50.4 ± 6.3) years. The mean follow-up time was (45 ± 13) months, including 62 patients with breast cancer-related deaths and 68 patients with survival. The patients in death group was older than those in the survival group [(52.6 ± 6.7) years vs. (48.3 ± 5.2) years, P < 0.01), and and the lymph node metastasis rate was higher [88.7%(55/62) vs.73.5%(50/68), P＝0.028]. The frequency of XRCC1 gene Arg399Gln genotype in the survival and death group was GG: 61.8% vs. 38.7%; GA: 32.4% vs. 41.5%; AA: 5.9% vs. 19.4%, P＝0.011.There were also statistical differences between the two groups in the frequency of allele, and the frequency of A allele was significantly higher in the death group than in the survival group (40.4% vs. 22.0%, P<0.01). For the additive model of the Arg399Gln polymorphism A allele, for each additional copy of the A allele, the risk was 1.443 times that before the increase (95% CI 1.174-1.793, P<0.01). After adjusting for age and lymph node metastasis, the A allele still significantly increased the risk of death ( OR＝1.533, 95% CI 1.254-1.903, P < 0.01). Conclusions The XRCC1 gene Arg399Gln polymorphism is associated with the prognosis of TNBC, and patients with the A allele have a poor prognosis.