Melatonin Protects Against Hyperoxia-Induced Apoptosis in Alveolar Epithelial type II Cells by Activating the MT2/PI3K/AKT/ETS1 Signaling Pathway.

PURPOSE: Hyperoxia-induced apoptosis in alveolar epithelial type II cells (AECIIs) plays a critical role in the development of bronchopulmonary dysplasia (BPD). Melatonin has been shown to improve BPD. However, the protective effect of melatonin on hyperoxia-induced apoptosis in AECIIs and the precise mechanisms involved remain unclear. METHODS: Human alveolar epithelial type II A549 cells were treated with hyperoxia as an in vitro model to investigate the antiapoptotic mechanism of melatonin. CCK-8 assays were performed to investigate the viability of A549 cells. Hoechst 33,258 staining was carried out to quantify apoptosis in A549 cells. The protein expression levels of E26 oncogene homolog 1 (ETS1), Bcl-2, Bax, Bim, Wnt, ß-catenin, AKT and phosphorylated AKT were measured by western blotting. LY294002, SC79 and the downregulation of ETS1, melatonin receptor 1 (MT1) and MT2 with specific siRNAs were used to investigate the role of the PI3K/AKT pathway, ETS1, MT1 and MT2 in hyperoxia-induced apoptosis in A549 cells. RESULTS: Melatonin prevented hyperoxia-induced apoptosis in A549 cells, and the upregulation of E26 oncogene homolog 1 (ETS1) contributed to the antiapoptotic effect of melatonin. Melatonin activated the PI3K/AKT axis, which led to ETS1 upregulation and inhibited apoptosis in hyperoxia-exposed A549 cells. Furthermore, melatonin-induced activation of the PI3K/AKT axis, upregulation of ETS1 and inhibition of apoptosis were reversed by melatonin receptor 2 (MT2) siRNA in hyperoxia-exposed A549 cells. CONCLUSION: Melatonin prevents hyperoxia-induced apoptosis by activating the MT2/PI3K/AKT/ETS1 axis in alveolar epithelial cells.

Perioperative safety analysis of transcatheter arterial chemoembolization for hepatocellular carcinoma patients with preprocedural leukopenia or thrombocytopenia.

Patients with hepatocellular carcinoma (HCC) exhibit a high incidence of concomitant cirrhosis with leukopenia and/or thrombocytopenia. In the present study, perioperative changes in the white blood cell (WBC) and platelet (PLT) counts and associated complications were investigated to assess the safety of transcatheter arterial chemoembolization (TACE) for HCC patients with preprocedural leukopenia or thrombocytopenia. The records of 1,461 HCC patients who received TACE between January 2012 and December 2013 were retrospectively reviewed. The incidence of complications during the perioperative period and changes in the WBC and PLT counts were recorded. A Chi-squared test was used to evaluate the associations between postoperative infection and preprocedural WBC count and between bleeding at the puncture site and preprocedural PLT count. The WBC count of the majority of the patients increased within 3 days and returned to the preprocedural level within 30 days after TACE. The PLT count decreased within 3 days and returned to the preprocedural level within 30 days after TACE. The major complications were liver decompensation (n=66), puncture site bleeding (n=45), infection (n=33), severe thrombocytopenia (n=8), upper gastrointestinal bleeding (n=6), tumor bleeding (n=4) and agranulocytosis (n=3). A Chi-squared test revealed that postoperative infection was not associated with preprocedural WBC count and puncture site bleeding was not associated with decreased PLT count due to hypersplenism. Therefore, TACE was found to be safe for HCC patients with preprocedural thrombocytopenia or leukopenia due to hypersplenism, with a low incidence of major complications during the perioperative period.

Acquired amegakaryocytic thrombocytopenic purpura induced by percutaneous ethanol injection during treatment of hepatocellular carcinoma: A case report.

Percutaneous ethanol injection is an important localized treatment method for patients presenting with hepatocellular carcinoma (HCC). Among the advantages of percutaneous ethanol injection are its minimal invasiveness, simplicity, low cost and low risk of complications. However, the increasing popularity of percutaneous ethanol injection has resulted in serious adverse effects attributed to individual variations. The present study describes the case of a patient who exhibited acquired amegakaryocytic thrombocytopenic purpura, caused by percutaneous ethanol injection treatment for HCC. This complication was promptly identified, and platelet transfusion and injection of recombinant human interleukin-11 resulted in a rapid recovery of the patient's platelet count. Attention should be given to this rare complication in patients administered percutaneous ethanol injection treatment for HCC.

Enhanced therapeutic efficacy of combined use of sorafenib and transcatheter arterial chemoembolization for treatment of advanced hepatocellular carcinoma.

OBJECTIVE: Clinical trials suggest that combining transcatheter arterial chemoembolization with sorafenib in patients with advanced hepatocellular carcinoma shows a superior safety and tolerability profile. Our study aimed to retrospectively analyze the utility and prognostic factors of this combined therapy in these patients. METHODS: Patients with advanced hepatocellular carcinoma, treated by transcatheter arterial chemoembolization and sorafenib subsequently, between February 2010 and September 2012 in our hospital, were retrospectively analyzed. After sorafenib treatment for 12 weeks, abdominal enhanced computed tomography or magnetic resonance imaging was used to evaluate short-term outcomes and clinical benefit rate. Overall survival and adverse events were recorded during follow-up. Univariate and multivariate analyses were used to identify relationships between baseline characteristics and overall survival. RESULTS: Fifty-one advanced hepatocellular carcinoma patients were included. Common adverse events for sorafenib were hand-foot skin reaction, alopecia, diarrhea, anorexia and fatigue. The clinical benefit rate was 64% and the median survival time was 7.5 months. Median survival of patients with and without portal vein tumor thrombi was 6.0 months and 10.3 months (P < 0.001), respectively. Median survival of patients with cholinesterase ≥5000 U/l and < 5000 U/l was 10.6 months and 6.1 months (P < 0.001), respectively. Multivariate analysis identified the presence of portal vein tumor thrombi and low cholinesterase level as independent negative predictors of survival. CONCLUSIONS: Combining sorafenib and transcatheter arterial chemoembolization was safe and effective for advanced hepatocellular carcinoma patients with extrahepatic spread but without portal vein tumor thrombi. Portal vein tumor thrombi and cholinesterase level are independent predictors of prognosis following this combined therapy.