title: Gene expression profiles predicting the response to IFN-β and a combination of temozolomide and IFN-β in malignant gliomas.
abstract: Temozolomide (TMZ) is an alkylating agent that has yielded significant benefits and is a current standard agent in the treatment of malignant gliomas. However, its survival benefit remains unsatisfactory. Recently, a synergistic antitumor effect between TMZ and interferon-β (IFN-β) was reported in malignant glioma cells. The Japan Clinical Oncology Group (JCOG) brain tumor study group has recently began a randomized phase II study to evaluate the clinical effectiveness of combination therapy with TMZ and IFN-β in glioblastomas. However, it is not sufficient just to evaluate the mechanisms and establish an experimental basis for rational clinical therapy with IFN-β and TMZ. The precise mechanisms governing the direct effects of IFN-β and a combination of IFN-β and TMZ in gliomas are not yet fully understood. To gain insight into the mechanisms of sensitivity/resistance involving IFN-β and combination therapy with IFN-β and TMZ, and further to identify new marker(s) that could be used clinically to predict the response to such therapy and new target gene(s) for therapies related to malignant glioma patho-genesis, we evaluated the gene expression profiles of human malignant glioma cell lines employing a high-density oligo-nucleotide DNA array, GeneChip. We present a list of the most highly upregulated and downregulated genes which may be involved in conferring a response to IFN-β and synergistic effect between IFN-β and TMZ in malignant gliomas. Although the present study has several limitations, our reported candidate genes could represent not only potential molecular markers but also chemotherapy targets for improving the treatment outcome by devising strategies that are able to circumvent primary drug resistance in malignant gliomas.
authors.affiliation: Department of Neurological Surgery, Nihon University School of Medicine, 30-1 Oyaguchi-Kamimachi, Itabashi-ku, Tokyo 173-8610, Japan. ayoshino@med.nihon-u.ac.jp
authors.forename: Atsuo
authors.initials: A
authors.lastname: Yoshino
authors.forename: Shinya
authors.initials: S
authors.lastname: Tashiro
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Ogino
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yachi
authors.forename: Takashi
authors.initials: T
authors.lastname: Ohta
authors.forename: Takao
authors.initials: T
authors.lastname: Fukushima
authors.forename: Takao
authors.initials: T
authors.lastname: Watanabe
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Katayama
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Okamoto
authors.forename: Emiko
authors.initials: E
authors.lastname: Sano
authors.forename: Kouhei
authors.initials: K
authors.lastname: Tsumoto
mesh_terms: D015088:2',5'-Oligoadenylate Synthetase / Q000096:biosynthesis / Q000378:metabolism; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D003606:Dacarbazine / Q000008:administration & dosage / Q000031:analogs & derivatives; D015536:Down-Regulation; D004790:Enzyme Induction / Q000187:drug effects; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics* / Q000473:pathology; D006801:Humans; D016899:Interferon-beta / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D000077204:Temozolomide
chemical_list: D016899:Interferon-beta; D003606:Dacarbazine; D015088:2',5'-Oligoadenylate Synthetase; D000077204:Temozolomide