Cytosine deaminase/5-fluorocytosine exposure induces bystander and radiosensitization effects in hypoxic glioblastoma cells in vitro.

Purpose: Treatment of glioblastoma (GBM) is limited by therapeutic ratio; therefore, successful therapy must be specifically cytotoxic to cancer cells. Hypoxic cells are ubiquitous in GBM, and resistant to radiation and chemotherapy, and, thus, are logical targets for gene therapy. In this study, we investigated whether cytosine deaminase (CD)/5-fluorocytosine (5-FC) enzyme/prodrug treatment induced a bystander effect (BE) and/or radiosensitization in hypoxic GBM cells.

Response of intracerebral human glioblastoma xenografts to multifraction radiation exposures.

Purpose: We investigated the effects of fractionated radiation treatments on the life spans of athymic rats bearing intracerebral brain tumors.

Methods And Materials: U-251 MG or U-87 MG human glioblastoma cells were implanted into the brains of athymic rats, and the resulting tumors were irradiated once daily with various doses of ionizing radiation for 5 consecutive days or for 10 days with a 2-day break after Day 5.

Results: Five daily doses of 1 and 1.

Hypoxia-induced BAX overexpression and radiation killing of hypoxic glioblastoma cells.

One major challenge in treating glioblastoma multiforme (GBM) has been the presence of radiation-resistant hypoxic cells. The pro-apoptosis protein BAX has been reported to be a possible radiation sensitizer of cancer cells; however, to our knowledge, no studies have reported on the effects of BAX on radiation sensitivity under hypoxic conditions. Therefore, in this study, we specifically overexpressed murine Bax in hypoxic cells in an attempt to enhance radiation-induced cell killing.

Antitumor effects of specific telomerase inhibitor GRN163 in human glioblastoma xenografts.

Telomerase is a ribonucleoprotein complex that elongates telomeric DNA and appears to play an important role in cellular immortalization of cancers. Because telomerase is expressed in the vast majority of malignant gliomas but not in normal brain tissues, it is a logical target for gliomaspecific therapy. The telomerase inhibitor GRN163, a 13-mer oligonucleotide N3'-->P5' thio-phosphoramidate (Geron Corporation, Menlo Park, Calif.

Growth of human glioblastomas as xenografts in the brains of athymic rats.

Background: We have developed xenografts of human glioblastoma (GBM) and established the baseline growth parameters and histopathological features of these tumors.

Materials-methods: Cells from 4 different human GBM cell lines were injected into the right caudate-putamen of brain in athymic rats. We measured tumor weights and the estimated survival time of each rat.