Biomaterial Database

Anti-glioma therapy with temozolomide and status of the DNA-repair gene MGMT. 2009

Tsuyoshi Fukushima, and Hideo Takeshima, and Hiroaki Kataoka

Department of Pathology, University of Miyazaki, Kiyotake, Miyazaki 889-1692, Japan. fukuchan@med.miyazaki-u.ac.jp

The prognosis of patients with glioblastoma is extremely poor despite multimodal treatments including surgery, chemotherapy and radiotherapy. Recently, the alkylating agent, temozolomide (TMZ) has been shown to improve survival in patients with malignant gliomas, including those with glioblastoma in some clinical studies, and has become one of the standard modalities for treatment of newly diagnosed and recurrent malignant gliomas. The epigenetic silencing of the DNA repair enzyme O(6)-methylguanine-DNA-methyltransferase (MGMT) is the strongest predictive marker for favorable outcome in patients treated with TMZ. However, it remains to be determined how patients with tumors lacking MGMT promoter methylation should be treated. Moreover, even patients with TMZ-sensitive glioblastoma cannot avoid eventual recurrence. In this article, we review the mechanism of the effect of TMZ on tumor cells and resistance to TMZ, and provide an overview of the current management and trials for patients with glioblastoma.

UI	MeSH Term	Description	Entries
D001932	Brain Neoplasms	Neoplasms of the intracranial components of the central nervous system, including the cerebral hemispheres, basal ganglia, hypothalamus, thalamus, brain stem, and cerebellum. Brain neoplasms are subdivided into primary (originating from brain tissue) and secondary (i.e., metastatic) forms. Primary neoplasms are subdivided into benign and malignant forms. In general, brain tumors may also be classified by age of onset, histologic type, or presenting location in the brain.	Brain Cancer,Brain Metastases,Brain Tumors,Cancer of Brain,Malignant Primary Brain Tumors,Neoplasms, Intracranial,Benign Neoplasms, Brain,Brain Neoplasm, Primary,Brain Neoplasms, Benign,Brain Neoplasms, Malignant,Brain Neoplasms, Malignant, Primary,Brain Neoplasms, Primary Malignant,Brain Tumor, Primary,Brain Tumor, Recurrent,Cancer of the Brain,Intracranial Neoplasms,Malignant Neoplasms, Brain,Malignant Primary Brain Neoplasms,Neoplasms, Brain,Neoplasms, Brain, Benign,Neoplasms, Brain, Malignant,Neoplasms, Brain, Primary,Primary Brain Neoplasms,Primary Malignant Brain Neoplasms,Primary Malignant Brain Tumors,Benign Brain Neoplasm,Benign Brain Neoplasms,Benign Neoplasm, Brain,Brain Benign Neoplasm,Brain Benign Neoplasms,Brain Cancers,Brain Malignant Neoplasm,Brain Malignant Neoplasms,Brain Metastase,Brain Neoplasm,Brain Neoplasm, Benign,Brain Neoplasm, Malignant,Brain Neoplasms, Primary,Brain Tumor,Brain Tumors, Recurrent,Cancer, Brain,Intracranial Neoplasm,Malignant Brain Neoplasm,Malignant Brain Neoplasms,Malignant Neoplasm, Brain,Neoplasm, Brain,Neoplasm, Intracranial,Primary Brain Neoplasm,Primary Brain Tumor,Primary Brain Tumors,Recurrent Brain Tumor,Recurrent Brain Tumors,Tumor, Brain
D003606	Dacarbazine	An antineoplastic agent. It has significant activity against melanomas. (from Martindale, The Extra Pharmacopoeia, 31st ed, p564)	DTIC,5-(3,3-Dimethyl-1-triazeno)imidazole-4-carboxamide,Biocarbazine,DIC,DTIC-Dome,Decarbazine,Deticene,Dimethyl Imidazole Carboxamide,Dimethyl Triazeno Imidazole Carboxamide,ICDT,NSC-45388,Carboxamide, Dimethyl Imidazole,DTIC Dome,DTICDome,Imidazole Carboxamide, Dimethyl,NSC 45388,NSC45388
D004260	DNA Repair	The removal of DNA LESIONS and/or restoration of intact DNA strands without BASE PAIR MISMATCHES, intrastrand or interstrand crosslinks, or discontinuities in the DNA sugar-phosphate backbones.	DNA Damage Response
D005909	Glioblastoma	A malignant form of astrocytoma histologically characterized by pleomorphism of cells, nuclear atypia, microhemorrhage, and necrosis. They may arise in any region of the central nervous system, with a predilection for the cerebral hemispheres, basal ganglia, and commissural pathways. Clinical presentation most frequently occurs in the fifth or sixth decade of life with focal neurologic signs or seizures.	Astrocytoma, Grade IV,Giant Cell Glioblastoma,Glioblastoma Multiforme,Astrocytomas, Grade IV,Giant Cell Glioblastomas,Glioblastoma, Giant Cell,Glioblastomas,Glioblastomas, Giant Cell,Grade IV Astrocytoma,Grade IV Astrocytomas
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000077204	Temozolomide	A dacarbazine derivative that is used as an alkylating antineoplastic agent for the treatment of MALIGNANT GLIOMA and MALIGNANT MELANOMA.	8-Carbamoyl-3-methylimidazo(5,1-d)-1,2,3,5-tetrazin-4(3H)-one,CCRG 81045,CCRG-81045,M&B 39831,M&B-39831,Methazolastone,NSC 362856,NSC-362856,TMZ-Bioshuttle,TMZA-HE,Temodal,Temodar,Temozolomide Hexyl Ester,CCRG81045,M&B39831,NSC362856,TMZ Bioshuttle
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D018906	Antineoplastic Agents, Alkylating	A class of drugs that differs from other alkylating agents used clinically in that they are monofunctional and thus unable to cross-link cellular macromolecules. Among their common properties are a requirement for metabolic activation to intermediates with antitumor efficacy and the presence in their chemical structures of N-methyl groups, that after metabolism, can covalently modify cellular DNA. The precise mechanisms by which each of these drugs acts to kill tumor cells are not completely understood. (From AMA, Drug Evaluations Annual, 1994, p2026)	Alkylating Agents, Antineoplastic,Alkylating Antineoplastic Agents,Alkylating Antineoplastic Drugs,Alkylating Antineoplastics,Alkylating Drugs, Antineoplastic,Antineoplastic Alkylating Agents,Antineoplastic Drugs, Alkylating,Antineoplastics, Alkylating,Antineoplastic Alkylating Drugs,Drugs, Antineoplastic Alkylating
D019853	O(6)-Methylguanine-DNA Methyltransferase	An enzyme that transfers methyl groups from O(6)-methylguanine, and other methylated moieties of DNA, to a cysteine residue in itself, thus repairing alkylated DNA in a single-step reaction. EC 2.1.1.63.	Methylated-DNA-Protein-Cysteine S-Methyltransferase,O(6)-AGT,O(6)-Methylguanine Methyltransferase,DNA Repair Methyltransferase I,DNA Repair Methyltransferase II,Guanine-O(6)-Alkyltransferase,O(6)-Alkylguanine-DNA Alkyltransferase,O(6)-MeG-DNA Methyltransferase,O(6)-Methylguanine DNA Transmethylase,Methylated DNA Protein Cysteine S Methyltransferase,S-Methyltransferase, Methylated-DNA-Protein-Cysteine