Neuroblastoma SH-SY5Y cell-derived exosomes stimulate dendrite-like outgrowths and modify the differentiation of A375 melanoma cells.

The identification of small vesicles released by many cell types as tools of intercellular communication is proposed. Here, we identify SH-SY5Y neuroblastoma-derived exosomes comprised of major histocompatibility complex II (MHC II), Hsp90 and flotillin-1. Our data also suggest that, when applied extracellularly, exosomes released from neuronal cells stimulate dendrite-like outgrowth and melanogenesis of A375 melanoma cells through the mitogen-activated protein kinase (MAP kinase), extracellular signal-regulated kinase 1 (ERK1) activation. These results suggest a modification of differentiation of melanocyte by the treatment of neuronal cell exosomes. Since exosomes from neuronal cells have the capacity to affect melanoma cells, they could be generally implicated in intercellular communication between different types of cells.

Postmarketing surveillance study of the efficacy and safety of phentermine in patients with obesity.

BACKGROUND: Obesity is a complex problem that is now considered a chronic metabolic disease. In Korea, phentermine has been widely used for the treatment of obesity in the primary care setting since 2004. However, there have been very few studies on the safety and efficacy of phentermine. To investigate the safety and efficacy of this drug, a postmarketing surveillance study was performed. METHODS: A total of 795 patients with obesity (body mass index ≥ 25 kg/m(2)) were enrolled from 30 primary care centers in Korea from September 2006 to November 2007. Patients were examined to ascertain safety and efficacy at 4-, 8-, and 12-week intervals. The criterion for efficacy was defined as a weight loss ≥ 5% of body weight. RESULTS: Of the 795 enrolled patients, 735 (92.5%) were evaluated in safety assessments and 711 (89.4%) was included in efficacy assessments. A total of 266 adverse events (AEs) were reported by 218 patients (30.6%), and no serious AEs were reported. Among 711 patients, 324 patients (45.6%) lost ≥ 5% of their body weight. The mean weight loss was 3.8 ± 4.0 kg. CONCLUSION: AEs are commonly associated with phentermine, even though phentermine is effective for weight loss and relatively well-tolerated.

Proteomic analysis reveals upregulation of RKIP in S-180 implanted BALB/C mouse after treatment with ascorbic acid.

Tumor cells have an invasive and metastatic phenotype that is the main cause of death for cancer patients. Tumor establishment and penetration consists of a series of complex processes involving multiple changes in gene expression. In this study, intraperitoneal administration of a high concentration of ascorbic acid inhibited tumor establishment and increased survival of BALB/C mice implanted with S-180 sarcoma cancer cells. To identify proteins involved in the ascorbic acid-mediated inhibition of tumor progression, changes in the liver proteome associated with ascorbic acid treatment of BALB/C mice implanted with S-180 were investigated using two-dimensional gel electrophoresis and mass spectrometry. Eleven protein spots were identified whose expression was different between control and ascorbic acid treatment groups. In particular, Raf kinase inhibitory protein (RKIP) and annexin A5 expression were quantitatively up-regulated. The increase in RKIP protein level was detected in the tumor tissue and accompanied by an increase in mRNA level. Our results suggest a possibility that these proteins are related to the ascorbic acid-mediated suppression of tumor formation.

Pregabalin and gabapentin inhibit substance P-induced NF-kappaB activation in neuroblastoma and glioma cells.

Pregabalin and gabapentin are lipophilic amino acid derivatives of gamma-amino butyric acid that show anticonvulsant and analgesic activity against neuropathic pain. In this study, we investigated their actions on substance P-induced NF-kappaB activation in human neuroblastoma and rat glioma cells. Pregabalin and gabapentin decreased substance P-induced NF-kappaB activation in these cells. These drugs also inhibited NF-kappaB activation in rat spinal dorsal root ganglia cells pre-treated in vitro with substance P. These results suggest a previously undefined role of pregabalin and gabapentin in the regulation of inflammation-related intracellular signaling in both neuronal and glial cells.