Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:2.1.1.37 (DNA methyltransferase)
 4,983 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A 23-year-old man presented with a brain stem glioma manifesting as a 6-month history of right hemiparesis and diplopia. Serial magnetic resonance imaging showed an intrinsic diffuse brain stem glioma that gradually localized to the left cerebral peduncle after initial adjuvant therapy. Surgery was performed through a left subtemporal transtentorial approach under motor-evoked potential (MEP) mapping by direct peduncular stimulation. The lateral aspect of the midbrain was exposed, a train of five bipolar 25 mA pulses was applied, and MEPs recorded from the extremities. MEPs were only recorded from the left extremities even with left cerebral peduncular stimulation. Partial resection of the tumor was safely performed, with slight temporary neurological worsening. The histological diagnosis was anaplastic astrocytoma. Individual adjuvant therapy based on the results of real-time reverse transcription-polymerase chain reaction of O6-methylguanine-deoxyribonucleic acid methyltransferase achieved an almost complete tumor response. Surgery under pyramidal tract mapping and intensive postoperative adjuvant therapy resulted in a good outcome despite the presence of a generally intractable intrinsic brain stem glioma.
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PMID:Biopsy of brain stem glioma using motor-evoked potential mapping by direct peduncular stimulation and individual adjuvant therapy. Case report. 1569 22

Temozolomide (TMZ) is an alkylating agent earlier approved for recurrent anaplastic astrocytoma and approved for the treatment of newly diagnosed glioblastoma in the USA and Europe in 2005. TMZ shows good blood-brain barrier penetration and exhibits a favorable side effect profile. Its key mode of action appears to be methylation at N(7) and O(6)-positions of guanine. The level of expression and activity of the DNA repair enzyme O(6)-methylguanine DNA methyltransferase is thought to be a major predictor of response to TMZ. The demonstration of prolonged survival when TMZ was added to radiotherapy in the European Organisation for Research and Treatment of Cancer 26981/22981/NCIC CE.3 trial has been a breakthrough in the treatment of newly diagnosed glioblastoma. The early preliminary evidence for activity in recurrent malignant gliomas further resulted in a broad evaluation of TMZ for other tumors in neuro-oncology, mainly low-grade gliomas, brain metastases and primary cerebral lymphomas.
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PMID:Temozolomide: a milestone in the pharmacotherapy of brain tumors. 1655 52