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2.
Br J Cancer ; 106(2): 262-8, 2012 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-22146522

RESUMO

BACKGROUND: Severe early and late radiation reaction to radiotherapy is extremely rare in breast cancer patients. Such a reaction prompted an investigation into a 44-year-old mother (patient A-T213). METHODS: A neurological examination was performed and blood lymphocytes and skin fibroblasts were assessed for radiosensitivity chromosomally and by colony-forming assay. The ATM gene was sequenced and ATM mutations modelled by site-directed mutagenesis. The ATM kinase activity was also assessed. RESULTS: Patient A-T213 was normally ambulant with no ataxia and minimal other neurological features. T lymphocytes and skin fibroblasts were unusually radiosensitive, although less sensitive than in classical ataxia telangiectasia (A-T). A lymphoblastoid cell line and skin fibroblasts expressed ATM protein with some retained kinase activity. One missense ATM mutation c.8672G>A (p.Gly2891Asp) and a c.1A>G substitution were identified. In the modelling system, the p.Gly2891Asp mutant protein was expressed and shown to have residual ATM kinase activity. CONCLUSION: Patient A-T213 has a milder form of A-T with biallelic ATM mutations, which may have contributed to breast cancer development, and certainly caused the severe radiation reaction. Ataxia telangiectasia should be investigated as a potential cause of untoward severe early and late radiation reactions in breast cancer patients.


Assuntos
Ataxia Telangiectasia/diagnóstico , Neoplasias da Mama/radioterapia , Ataxia Telangiectasia/complicações , Ataxia Telangiectasia/genética , Proteínas Mutadas de Ataxia Telangiectasia , Neoplasias da Mama/complicações , Neoplasias da Mama/genética , Proteínas de Ciclo Celular/genética , Proteínas de Ligação a DNA/genética , Feminino , Humanos , Pessoa de Meia-Idade , Mutação , Proteínas Serina-Treonina Quinases/genética , Tolerância a Radiação , Proteínas Supressoras de Tumor/genética
4.
Br J Cancer ; 90(4): 781-6, 2004 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-14970853

RESUMO

Assessment of low-grade glioma treatment response remains as much of a challenge as the treatment itself. Proton magnetic resonance spectroscopy ((1)H-MRS) and imaging were incorporated into a study of patients receiving temozolomide therapy for low-grade glioma in order to evaluate and monitor tumour metabolite and volume changes during treatment. Patients (n=12) received oral temozolomide (200 mg m(-2) day(-1)) over 5 days on a 28-day cycle for 12 cycles. Response assessment included baseline and three-monthly magnetic resonance imaging studies (pretreatment, 3, 6, 9 and 12 months) assessing the tumour size. Short (TE (echo time)=20 ms) and long (TE=135 ms) echo time single voxel spectroscopy was performed in parallel to determine metabolite profiles. The mean tumour volume change at the end of treatment was -33% (s.d.=20). The dominant metabolite in long echo time spectra was choline. At 12 months, a significant reduction in the mean choline signal was observed compared with the pretreatment (P=0.035) and 3-month scan (P=0.021). The reduction in the tumour choline/water signal paralleled tumour volume change and may reflect the therapeutic effect of temozolomide.


Assuntos
Antineoplásicos Alquilantes/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Glioma/tratamento farmacológico , Glioma/metabolismo , Espectroscopia de Ressonância Magnética , Administração Oral , Adulto , Antineoplásicos Alquilantes/administração & dosagem , Colina/metabolismo , Dacarbazina/administração & dosagem , Feminino , Humanos , Masculino , Temozolomida , Resultado do Tratamento , Água/análise
5.
Ann Oncol ; 14(12): 1715-21, 2003 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-14630674

RESUMO

BACKGROUND: The aim of this study was to assess the efficacy of temozolomide in patients with World Health Organisation (WHO) grade II gliomas treated with surgery alone using imaging and clinical criteria. PATIENTS AND METHODS: Thirty patients with histologically verified WHO grade II gliomas (17 astrocytoma, 11 oligodendroglioma, two mixed oligoastrocytoma) following surgery 2-104 months (median 23 months) after initial diagnosis received temozolomide 200 mg/m(2)/day for 5 days, on a 28-day cycle, for a maximum of 12 cycles or until tumour progression. Median age was 40 years (range 25-68 years). Median follow-up from entry into the study was 3 years [range 23-47 months (for patients alive)]. Objective response was assessed by 3-monthly magnetic resonance imaging and monthly health-related quality of life (HQoL) and clinical assessment. Tumour size was measured as the high signal intensity area on fluid attenuated inversion recovery sequences. Responses were assessed using change in the product of two perpendicular diameters as complete response (CR), partial response (PR), minimal response (MR), stable disease (SD) and progressive disease (PD). RESULTS: Twenty-nine of 30 patients entered into the study were evaluable for response. Three patients had a PR, 14 MR, 11 SD and one PD. Twenty-four patients received 12 cycles of chemotherapy. Of 29 evaluable patients, three discontinued after four, five and six cycles and two after 10 cycles. Nine patients progressed (three during chemotherapy-one PD and two initial SD-and six after completion of chemotherapy); five had evidence of transformation. The 3-year progression-free survival was 66%. Five patients died; the actuarial 3-year survival was 82%. Ninety-six per cent of patients with impaired HQoL had improvement in at least one HQoL domain. There was improvement in 115 of the 207 domains (56%). Fifteen of 28 patients (54%) with epilepsy had reduction in seizure frequency, of whom six became seizure free. Six patients had transient grade III/IV haematological toxicity (11 episodes; 3.5%). CONCLUSIONS: Temozolomide has single-agent activity in patients with WHO grade II cerebral glioma, with modest improvement in quality of life and improvement in epilepsy control. On present evidence, temozolomide cannot be considered as primary therapy without formal comparison with other treatment modalities.


Assuntos
Antineoplásicos/uso terapêutico , Neoplasias Encefálicas/tratamento farmacológico , Dacarbazina/análogos & derivados , Dacarbazina/uso terapêutico , Glioma/tratamento farmacológico , Administração Oral , Adulto , Antineoplásicos/administração & dosagem , Neoplasias Encefálicas/patologia , Neoplasias Encefálicas/cirurgia , Dacarbazina/administração & dosagem , Progressão da Doença , Intervalo Livre de Doença , Feminino , Glioma/patologia , Glioma/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Convulsões/etiologia , Convulsões/prevenção & controle , Temozolomida , Resultado do Tratamento
6.
Br J Radiol ; 73(866): 121-2, 2000 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-10884722
8.
S Afr Med J ; 60(2): 47-8, 1981 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-7017966

RESUMO

A double-blind within-patient study was carried out on Zimbabwean Blacks to investigate the effect of once-daily atenolol on hypertension in doses of 100 and 200 mg/d. Atenolol 200 mg produced significant changes in diastolic pressure readings taken in the supine and standing positions and after exercise; with atenolol 100 mg modest but non-significant changes occurred. These findings are less impressive than those previously reported in White subjects. We conclude that beta-adrenoceptor blocking agents should not be used as drugs of first choice for hypertension in our Black population.


Assuntos
Atenolol/administração & dosagem , Negro ou Afro-Americano , Hipertensão/tratamento farmacológico , Propanolaminas/administração & dosagem , Adulto , Idoso , População Negra , Pressão Sanguínea/efeitos dos fármacos , Ensaios Clínicos como Assunto , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pulso Arterial/efeitos dos fármacos , Zimbábue
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