Glioblastoma Multiforme (GBM) is one of the most common brain lesions accounting for nearly half of all primary gliomas. Most gliomas are unresponsive to current cancer therapies due to the resistant nature of gliomas to radiation and chemotherapy. This resistance is hypothesized to be due in part to enhanced antioxidant enzyme activity. Catalase, an antioxidant enzyme that scavenges excess cellular hydrogen peroxides, is overexpressed in gliomas when compared to their normal cell counterpart, the astrocyte. Moreover, catalase expression has been found to correlate with increased resistance to oxidative stress. We hypothesize that inhibition of catalase using siRNA in gliomas will increase glioma sensitivity to radiation and anticancer agents. Radiation therapy, the major treatment modality for brain cancers, is limited by normal brain injury. We hypothesize that upregulation of catalase will protect normal brain cells from oxidative damage caused by radiation and chemotherapy agents. We will investigate the impact of catalase modulation in gliomas and normal brain cells to assess their impact on radiosensitization and radioprotection respectively.
| Smith-Pearson, Pameeka S; Kooshki, Mitra; Spitz, Douglas R et al. (2008) Decreasing peroxiredoxin II expression decreases glutathione, alters cell cycle distribution, and sensitizes glioma cells to ionizing radiation and H(2)O(2). Free Radic Biol Med 45:1178-89 |
| Smith, Pameeka S; Zhao, Weiling; Spitz, Douglas R et al. (2007) Inhibiting catalase activity sensitizes 36B10 rat glioma cells to oxidative stress. Free Radic Biol Med 42:787-97 |
