O6-alkylguanine-DNA alkyltransferase activity in human brain tumors.

The O6-alkylguanine-DNA alkyltransferase (AT) activity in different kinds of human brain tumors was investigated. Twenty-seven brain tumors were analysed. Twenty-five of them showed proficient AT activity with values ranging between 20 and 722 fmol AT/mg protein. The two AT-deficient tumors observed were an oligodendroglioma and an astrocytoma. The relationship between the different histological kinds of tumor, with respect to the AT activity was: meningeomas greater than sarcomas greater than glioblastomas greater than astrocytomas greater than oligodendrogliomas greater than neurinomas greater than lymphomas. The proposal of Kohn (DNA filter elution methods in anticancer drug development. In: Concepts, Clinical Developments, and Therapeutic Advances in Cancer Chemotherapy. Editor: F.M. Muggia. Martinus Nijhoff Publishers, Boston) to confine treatments with alkylating antineoplastic agents to AT-deficient tumors, is discussed.

Study on aneuploidy and p53 mutations in astrocytomas.

To determine whether a correlation exists between aneuploidy and p53 status in astrocytic tumors we analyzed 48 astrocytomas with different grades of malignancy for the presence of p53 mutations and aneuploidy of chromosomes 10 and 17 (Ch10, Ch17), known to be particularly involved with this type of tumor. We used polymerase chain reaction (PCR)-based denaturing gradient gel electrophoresis (DGGE) analysis on exons 5-8 of the p53 gene, and fluorescence in situ hybridization (FISH) analysis on interphase nuclei using chromosome specific pericentromeric probes, respectively. Our results showed that Ch10/Ch17 aneuploidy is a common early event in astrocytomas (90% of low grade tumors are aneuploid). p53 mutations and Ch17 aneuploidy are early events, but their incidence is not dependent on tumor grade. Loss of Ch10 is the only alteration that significantly correlates with tumor progression. No significant correlation between the presence of Ch10/Ch17 aneuploidy and p53 mutations was found. However, the coexistence of p53 mutations and aneuploidy, was observed in a subset of cases. The presence of p53 mutations appeared to be a significant predictor of a poor prognosis. In conclusion, genomic instability may or may not be associated with p53 mutations in astrocytomas, thus suggesting that other cellular determinants can also be responsible for the aneuploidy observed.

Radiation treatment plus CCNU plus the radiosensitizer lonidamine in malignant gliomas operated.

From June 1988 to January 1990, 28 patients with primary brain tumours were operated and treated with radiotherapy (RT) (50 Gy whole brain + 10 Gy boost to tumour bed) + cyclohexylnitrosourea (CCNU) 130 mg/msq p.o. every 6 weeks + the radiosensitizer Lonidamine (LND) (150 mg T.I.D. for the whole duration of treatment). Myelotoxicity of this regimen was acceptable, with two cases of grade IV leukopenia and thrombocytopenia requiring discontinuation of treatment. LND was discontinued in 6 patients for major toxicity (myalgias and/or testicular pain), and 3 additional patients required dose reduction of this drug. The median follow-up time of the patients on study was 12 months. The median survival time (MST) was 5 months for grade IV astrocytomas (n = 8) and 16 months for grade III lesions (= 20). No correlation was seen between survival of patients and DNA content, measured by flow cytometry, or levels of O6- alkylguanine-DNA alkyltransferase, an enzyme that repairs the CCNU-induced DNA damage.

Acute intracranial epidural haematoma in a basketball player: a case report.

A 35-year-old basketball player suffered a serious double head injury during a match. An acute left temporal epidural haematoma, which necessitated surgical drainage, developed. The exceptional circumstances of the trauma are discussed and the literature concerning basketball-related injuries is reviewed.

[Possible role of 06-methylguanine-DNA-transferase in the response of patients with primary tumor of the brain to chemotherapy using chloro-ethyl-nitroso-urea: results of a current study]. / Possible ruolo della 06-metilguanina-DNA-Transferasi nella risposta di pazienti con tumori cerebrali primitivi alla chemioterapia con Cloro-Etil-Nitroso-Uree: risultati di uno studio in corso.

We have started a study to measure the MT activity in surgical specimens from high grade human malignant gliomas, with the dual aim to (i), know whether lack of activity can be demonstrated in these tumors, and (ii), relate the measured levels of MT to the histology of the tumors and to the response of patients to chemotherapy with 1-(2-Chloroethyl)-3-Cyclohexyl-1-Nitrosourea (CCNU). To date, 12 Gliomas have been assayed. In 11 tumors, MT activities ranging from 30 to 150 fmoles/mg protein have been measured. The only negative specimen derived from a patient who had received radiotherapy before surgery. At the present stage of the study, therefore, we have no unequivocal evidence for the existence of MT-deficient Gliomas.