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Interferon regulatory factor gene messenger ribonucleic acid expression and response to interferon-beta in gliomas

Interferon regulatory factor gene messenger ribonucleic acid expression and response to interferon-beta in gliomas

International Journal of Immunotherapy 17(1): 9-19

ISSN/ISBN: 0255-9625

To predict the sensitivity of gliomas to interferon-beta (IFN-beta), the direct effect of IFN-beta on human glioma cells was investigated. Reverse transcription-polymerase chain reaction (RT-PCR) was performed on total RNA extracted from the U87IR human glioma cell line, an IFN-resistant cell line derived from U87MG via a continuing culture with escalating doses of IFN-beta. RT-PCR was also performed on U87MG, and 114 frozen human neuroectodermal tumor tissue samples from glioma patients treated with IFN-beta and primers specific to the interferon receptor (IFNR) and interleukin-1 beta converting enzyme (ICE, caspase-1) and common to interferon regulatory factor (IRF)-1 and IRF-2. Discrimination between IRF-1 and IRF-2 was achieved by digestion with the restriction enzyme EcoT221. Defective IFNR and ICE messenger RNA (mRNA) expression and the IRF-1/IRF-2 (IRF-1/2) ratio in U87IR were less than those in U87MG. In the 114 patients treated with IFN-beta, prognostic factors included IFNR-mRNA, ICE-mRNA and the IRF-1/IRF-2 ratio. The IRF-1/IRF-2 ratio examined to determine the efficacy of the initial therapy among 78 patients who were treated with IFN-beta and who showed favorable therapeutic results was significantly higher than that among 32 patients who showed poor response (p<0.0001, Mann-Whitney U-test). The patients with IRF-1/IRF-2 ratio gtoreq1 recorded significantly better therapeutic results in the effect of the initial therapy than those with IRF-1/IRF-2 <1 (p=0.0007, Mann-Whitney U-test). IRF-1 and IRF-2 mRNA expression seem to be the most important factors in the sensitivity of gliomas to IFN.

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Accession: 010865978

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