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The prognosis of gioblastoma, the standard chemotherapy agent for which is temozolomide (TMZ), remains poor despite recent advances in multimodal treatments. Therefore, it is necessary to identify and develop novel therapeutics for this malignant disease. Ribavirin, an anti‑viral agent which is one of the standard agents for treatment of chronic hepatitis C in combination with interferon (IFN), was recently revealed to have an antitumor potential towards various tumor cells, including malignant glioma cells. The aim of the present study was to examine the antitumor effect of ribavirin in combination with TMZ and IFN‑β on glioma cells and to evaluate the possibility that such combinations might represent a novel candidate for glioblastoma therapy. The combination of ribavirin with TMZ and IFN‑β displayed a significant cell growth inhibitory effect with a ribavirin dose‑dependency, including a relatively low concentration of ribavirin, on not only TMZ‑sensitive but also TMZ‑resistant malignant glioma cells. The antitumor efficacy of such a combination further indicated a synergistic interaction when assessed by the Chou‑Talalay method. Furthermore, flow cytometry analysis suggested that apoptosis induction was one of the possible biological processes underlying the synergistic antitumor effect of these triple combination treatments. Therefore, such combinations may be potentially important in the clinical setting for glioblastoma treatment, although further detailed studies, e.g. on the adverse effects, are required. [ABSTRACT FROM AUTHOR]

Abstract  The deep-sea yeastCryptococcus liquefaciensstrain N6 possesses high superoxide dismutase (SOD) activity and a high tolerance toward metal ions. To clarify the relationship between metal tolerance and SOD activity in this strain, we cloned the Cu/Zn SOD gene. This gene (Cl-SOD1) consists of 471 bp encoding 157 amino acids; the associated protein had 59.9–76.7% identity with Cu/Zn SOD proteins of other yeast species. The highest identity corresponded toCryptococcus gattii(76.7%).Cl-SOD1expression in thesod1mutant ofSaccharomyces cerevisiaerevealed that this SOD protein was functional inS. cerevisiae. TheCl-SOD1 protein possessed approximately fourfold greater activity thanS. cerevisiaeSOD1 (Sc-SOD1) at 30?C. The amount ofCl-SOD1 mRNA in strain N6 increased in the presence of copper ion. However, the level of this transcript was not dependent on an increase in copper ion concentration and did not correlate well with changes in the amount of Cu/Zn SOD protein. This result suggests that strain N6 possesses other Cu/Zn SOD genes induced in a manner different fromCl-SOD1as found inCandida albicans, or that theCl-SOD1gene undergoes posttranscriptional regulation upon increase of copper ion. [ABSTRACT FROM AUTHOR]