RESUMO
Temozolomide (TMZ), an alkylating agent with a broad-spectrum antitumor activity, ability to cross blood-brain barrier (BBB), shown to be effective against malignant glioma. This study aims to investigate the effect of 1236C>T (rs1128503) single-nucleotide gene polymorphisms of ABCB1 (MDR1) in north-Indian patients diagnosed with glioma undergoing TMZ-based chemoradiotherapy. Genotyping was performed in 100 patients diagnosed with malignant glioma (50 anaplastic astrocytoma (AA) patients and 50 glioblastoma multiforme (GBM) patients) and 150 age and sex-matched controls by polymerase chain reaction-restriction fragment length polymorphisms (PCR-RFLP) method, followed by sanger sequencing. TMZ plasma levels were analyzed by reverse phase HPLC method. Glioma patient's survival time was analyzed by Kaplan-Meier's curve. Results of MDR1 gene 1236C>T polymorphism showed significant allelic and genotypic frequency association between glioma patients and controls. The plasma TMZ levels between metabolizers group in Grade III and Grade IV were found to be statistically significant (p < 0.05). The mutant genotype (TT) has less survival benefit compared with other genotypes (CT/CC) and the survival difference between AA and GBM was found to be statistically significant (p < 0.05). Though CT and TT polymorphisms have significant association with lower TMZ levels in both Grade III (AA) and IV (GBM) tumors, the survival difference seems to be mainly among patients with Grade III tumors. Our findings suggest that the MDR1 gene polymorphism plays a role in plasma TMZ levels and in survival time of glioma patients and, hence, TMZ therapy in malignant glioma can be predicted by genotyping MDR1 (1236C>T) gene polymorphism.
Assuntos
Membro 1 da Subfamília B de Cassetes de Ligação de ATP/genética , Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/genética , Glioma/genética , Polimorfismo de Nucleotídeo Único/genética , Temozolomida/uso terapêutico , Adulto , Idoso , Povo Asiático/genética , Neoplasias Encefálicas/tratamento farmacológico , Estudos de Casos e Controles , Quimiorradioterapia/métodos , Feminino , Genótipo , Glioblastoma/tratamento farmacológico , Glioblastoma/genética , Glioma/tratamento farmacológico , Humanos , Masculino , Pessoa de Meia-Idade , Farmacogenética/métodos , Adulto JovemRESUMO
Primary intracranial squamous cell carcinoma is extremely rare, with most cases arising from malignant transformation of dysembryogenetic lesions such as epidermoid and dermoid cysts. Intracranial squamous cell neoplasm arising de novo is even rarer and has been reported in only four patients to date. We herein describe a case of primary intracranial squamous cell carcinoma arising de novo in the right frontal lobe in a 35-year-old woman treated with a combination of surgery and postoperative conformal radiation. We have also shed light on the biology and the therapeutic options of this enigmatic tumour.