Atomoxetine and Fluoxetine Activate AMPK-ACC-CPT1 Pathway in Human SH-SY5Y and U-87 MG Cells

Objective@#Atomoxetine and fluoxetine are psychopharmacologic agents associated with loss of appetite and weight. Adenosine monophosphate-activated protein kinase (AMPK) is the cellular energy sensor that regulate metabolism and energy, being activated by fasting and inhibited by feeding in the hypothalamus. @*Methods@#Human brain cell lines (SH-SY5Y and U-87 MG cells) were used to study the outcome of atomoxetine and fluoxetine treatment in the activity of AMPK-acetyl-CoA carboxylase (ACC)- carnitine palmitoyl transferase 1 (CPT1) pathway and upstream regulation by calcium/calmodulin-dependent kinase kinase β (CaMKKβ) using immunoblotting and CPT1 enzymatic activity measures. @*Results@#Phosphorylation of AMPK and ACC increased significantly after atomoxetine and fluoxetine treatment in the first 30–60 minutes of treatment in the two cell lines. Activation of AMPK and inhibition of ACC was associated with an increase by 5-fold of mitochondrial CPT1 activity. Although the neuronal isoform CPT1C could be detected by immunoblotting, activity was not changed by the drug treatments. In addition, the increase in phospho-AMPK and phospho-ACC expression induced by atomoxetine was abolished by treatment with STO-609, a CaMKKβ inhibitor, indicating that AMPK-ACC-CPT1 pathway is activated through CaMKKβ phosphorylation. @*Conclusion@#These findings indicate that at the cellular level atomoxetine and fluoxetine treatments may activate AMPK-ACC-CPT1 pathways through CaMKKβ in human SH-SY5Y and U-87 MG cells.

Endoscopic Balloon Dilatation for Anastomotic Stricture Developed after Surgery for Colorectal Cancer

PURPOSE: This study was to evaluate the safety and efficacy of endoscopic balloon dilatation for anastomotic strictures that developed after colorectal cancer (CRC) operations. METHODS: Between Jan. 2001 and Dec. 2006, 18 patients (12 men, 6 women) who underwent endoscopic balloon dilatation for anastomotic strictures that developed after CRC operation at the Center for Colorectal Cancer, National Cancer Center, were enrolled, and their medical records were reviewed retrospectively. The median distance from the anal verge to the stricture was 10 cm (range, 3~40 cm). Dilatations were performed using through-the-scope balloons with diameters of 18 to 20 mm on inflation. RESULTS: The overall success rate of endoscopic balloon dilatation was 94.4% (17 patients). The mean number of treatment sessions per patient was 1.9 (range, 1~7). Of the 17 patients treated successfully, 11 patients (64.7%) required only one dilatation, 4 patients (23.2%) required 2 dilatations, and two patients (11.8%) required 7 dilatations. Failure of balloon dilatation occurred in one patient. No complications occurred. CONCLUSIONS: Endoscopic balloon dilatation of anastomotic strictures after a CRC operation is safe and efficient.

Immunohistochemical Expression of c-erbB-2 Protein in Breast Cancer

PURPOSE: A clinical trial that evaluated the efficacy of Herceptin(R) (anti-erbB2 antibody) as a first-line therapy for metastatic breast cancer was presented. It was demonstrated that 38% of the metastatic breast cancer patients benefited clinically from the Herceptin therapy. Recently, a trial of systemic chemotherapy was recommended as a first-line treatment for the patient with metastatic breast cancer refractory to Herceptin therapy. Therefore, it is necessary to evaluate c-erbB-2 protein expression in breast cancer prior to Herceptin treatment and the significance of c-erbB-2 protein as a prognostic predictor. METHODS: To evaluate c-erbB-2 protein as a prognostic predictor, we analyzed the expression of c-erbB-2 protein by the immunohistochemical method in comparison with other factors such as age, tumor size, stage, histologic grade, LN status, hormonal receptor status and DNA ploidy. Then we performed survival analysis. A total of 266 patients who underwent mastectomy between May 1998 and April 2000 were evaluated and statistical significance was determined by x2 test. RESULTS: In 146 of the 266 patients (54.9%) c-erbB-2 was positive in the tumor, and negative in the remaining 120. The overexpression of c-erbB-2 was positively correlated with tumor size and progesterone receptor positivity. The c-erbB-2 expression showed an association with a low recurrence-free survival probability in univariate analysis (P=0.0159). However, in multivariate analysis, c-erbB-2 expression was not an independent prognostic factor. CONCLUSION: The c-erbB-2 protein expression appears to have prognostic significance in breast cancer but long-term follow-up studies are necessary for confirmation.