ABSTRACT
BACKGROUND/AIMS: Thiazolidinediones, which are synthetic insulin sensitizers, are known activators of peroxisome proliferator-activated receptor gamma (PPARgamma). PPARgamma ligands, including endogenous 15-deoxy-delta12,14-prostaglandin J2 (15d-PGJ2), are thought to elicit antineoplastic effects in various cancer cells. In this study, the antineoplastic effects of PPARgamma ligands against hepatocellular carcinoma (HCC) cells were investigated. METHODS: HepG2, Hep3B, and PLC/PRF5 cells were cultured with troglitazone (TGZ), pioglitazone (PGZ), rosiglitazone (RGZ), or 15d-PGJ2 at concentrations of 20-100 micrometer. Cell viability, cell cycle arrest, apoptosis, and caspase activity were measured using the MTT assay, flow cytometry, enzyme-linked immunosorbent assay (ELISA), and colorimetric assays, respectively. The effects of various caspase inhibitors were also measured using a cell death detection ELISA. RESULTS: All three cell lines expressed the PPARgamma gene. TGZ and 15d-PGJ2 strongly inhibited growth in HepG2, Hep3B, and PLC/PRF5 cells. In contrast, PGZ and RGZ showed a much weaker effect in all cell lines. In terms of cell cycle arrest and apoptosis, TGZ induced G0/G1 arrest in HepG2 cells and increased the apoptotic fraction in Hep3B and PLC/PRF5 cells. In contrast, 15d-PGJ2 induced apoptosis only in HepG2 and Hep3B cells. TGZ and 15d-PGJ2 increased caspase-3 activity significantly and increased caspase-9 activity slightly. TGZ- and 15d-PGJ2-induced apoptoses were inhibited by a pancaspase inhibitor (Z-VAD-FMK) and a caspase-3 specific inhibitor (Z-DEVD-FMK) in a dose-dependent manner. CONCLUSIONS: TGZ and 15d-PGJ2 elicit antineoplastic effects in various HCC cells via caspase-dependent apoptotic induction. Their differential effects on similar cell types suggest that another antineoplastic mechanism, most likely a PPARgamma-independent pathway, is involved.
Subject(s)
Antineoplastic Agents , Apoptosis , Carcinoma, Hepatocellular , Caspase 3 , Caspase 9 , Caspase Inhibitors , Cell Cycle Checkpoints , Cell Death , Cell Line , Cell Survival , Chromans , Enzyme-Linked Immunosorbent Assay , Flow Cytometry , Hep G2 Cells , Insulin , Ligands , Peroxisomes , PPAR gamma , Prostaglandin D2 , ThiazolidinedionesABSTRACT
An acute myocardial infarction caused by a septic coronary embolism is a known complication of infective endocarditis and usually carries a fatal prognosis. We experienced a case of a 27-year-old man with an acute myocardial infarction caused by a coronary embolism due to bacterial endocarditis. An echocardiogram demonstrated mitral valve regurgitation with highly mobile multiple vegetations. Because of the high risk of systemic embolization and congestive heart failure, the patient underwent emergency surgery. Mitral valve replacement and an embolectomy were performed successfully without any surgical complications.
Subject(s)
Adult , Humans , Embolectomy , Embolism , Emergencies , Endocarditis , Endocarditis, Bacterial , Heart Failure , Mitral Valve , Mitral Valve Insufficiency , Myocardial Infarction , PrognosisABSTRACT
Cardiovascular disease is the most frequent cause of death in patients with acromegaly. Recently, long-term treatment with a somatostatin analogue (Sandostatin LAR) has been shown to be effective in controlling growth hormone (GH) and insulin like growth factor-1 (IGF-1) hypersecretion in most patients with acromegaly. Along with the effectiveness in the hormone profile, Sandostatin LAR has been reported to be effective for tumor mass shrinkage and clinical symptom improvement. We have encountered a female acromeglic patient with severe dilated cardiomyopathy and the patient was treated with Sandostatin LAR After treatment for 12 months, as seen by follow up echocardiography, the overall cardiac function was significantly improved. We report the case with a review of the literature.