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DNA topoisomerase I (TOP1) levels of several human neoplasms are higher than those of normal tissues. TOP1 inhibitors are widely used in treating conventional therapy-resistant ovarian cancers. However, patients may develop resistance to TOP1 inhibitors, hampering chemotherapy success. In this study, we examined the mechanisms associated with the development of camptothecin (CPT) resistance in ovarian cancers and identified evodiamine (EVO), a natural product with TOP1 inhibiting activity that overcomes the resistance. The correlations among TOP1 levels, cancer staging, and overall survival (OS) were analyzed. The effect of EVO on CPT-resistant ovarian cancer was evaluated in vitro and in vivo. TOP1 was associated with poor prognosis in ovarian cancers (p = 0.024). EVO induced apoptosis that was detected using flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) assay. The tumor size decreased significantly in the EVO treatment group compared with the control group (p < 0.01) in a xenograft mouse model. Effects of drugs targeting TOP1 for prognosis and therapy in CPT-resistant ovarian cancer are anticipated. EVO with TOP1 can be developed as an antiproliferative agent for overcoming CPT resistance in ovarian cancers.

OBJECTIVE: Dyslipidemia with higher inflammatory states, disease activity, and longer disease duration in juvenile idiopathic arthritis (JIA) patients seemed to increase the risks of atherosclerosis. Tumor necrosis factor- α (TNF-α) receptor blocking agent etanercept has been proven to be effective in JIA. However, data about the correlation of anti-inflammatory treatment on lipid profiles and atherogenic index in JIA patients remains limited. This study aimed to investigate the longitudinal changes on lipid profiles and atherogenic index in JIA patients after etanercept treatment. METHODS: Twenty-three patients diagnosed with JIA (polyarticular type n = 7; oligoarticular type, n = 2; systemic type, n = 10, Enthesitis-related arthritis = 4) received treatment with etanercept during the period 2004-012 in a medical center. We measured their serum lipid profiles at baseline and 2, 4, 6, 12 months later, and determined whether there were differences in complete blood counts, inflammatory mediators, lipid levels and atherogenic indices between patients who had inactive disease (responders) and those who were poor responders (non-responders) to etanercept treatment. RESULTS: Analysis of dynamic change in total JIA patients before and after TNF inhibitor therapy showed modest increases in hemoglobin levels (P = 0.02) and decreases in WBC counts, Platelet and CRP levels progressively (p = 0.002, p = 0.006 and p = 0.006, respectively).Twelve of the 23 patients achieved inactive disease status (responders) after 12-months of treatment. In responders, compared to non-responders, total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C) increased significantly (P = 0.007,P = 0.044,P

PURPOSE: Heart failure (HF) had been reported with increased risk of hip fractures. However, the relationship between circulating biomarkers and bone mineral density (BMD) in chronic HF remained unclear. METHODS: This is a cross-sectional study which recruited stable chronic HF from registry of the Heart Failure Center of National Taiwan University Hospital. Patients underwent dual-energy x-ray absorptiometry (DEXA) measurements at hip and lumbar spines and biochemical assessments including B-type natriuretic peptide (BNP-32), myostatin, follistatin and osteoprotegerin (OPG). RESULTS: A total of 115 stable chronic HF individuals with left ventricular ejection fraction (EF)