J Vrouvas | PubMed Health

PubMed2000

Increased G2 chromosomal radiosensitivity in cancer patients: the role of cdk1/cyclin-B activity level in the mechanisms involved.

PURPOSE: To test the hypothesis that deficient DNA repair as measured by increased G2 chromosomal radiosensitivity results from up-regulation of cdk1/cyclinB and cell cycle control mechanisms during the G2 to M transition. MATERIALS AND METHODS: A total of 185 cancer patients and 25 normal individuals were tested for G2 chromosomal radiosensitivity. The chromatid breaks were analysed in metaphase using the G2 assay or directly in G0 and G2 phase using premature chromosome condensation (PCC). The activity of cdk1/cyclinB, a key regulator of the G2 to M-phase transition, was measured by histone H1 kinase activity and correlated with the development of chromatid breaks after irradiation of cell lines in vitro. RESULTS: Based on the G2 assay, cancer patients on average showed increased chromosomal radiosensitivity above controls. When the analysis was carried out directly in G0 or G2 lymphocytes using PCC, no differences in the induction of chromosomal damage and its repair were observed between G2 assay-sensitive and G2-normal donors. Using the G2 assay to test G2 radiosensitivity in various cell lines, it was found that the higher the cdk1/cyclinB activity level of the cell line tested, the higher the yield of chromatid breaks scored. Furthermore, when mitotic cells from these cell lines were used for PCC induction in irradiated G2 lymphocytes it was observed that the higher the cdk1/cyclinB activity level of mitotic cells used, the higher was the induced yield of chromatid breaks. CONCLUSION: The cdk1/cyclin-B activity levels during the G2 to M transition impair DNA repair processes and play a major role in the yield of chromatid breaks induced after G2-irradiation. Regulation of cdk1/cyclinB complex activity rather than deficient repair enzymes of DNA damage may underlie the mechanisms of G2 radiosensitivity.

CDC2 Protein Kinase↗

PubMed1995

Extrapulmonary small cell cancer.

Extrapulmonary small cell cancer is rare, but it occurs in a wide variety of sites, where it has a behaviour quite different from the tumours normally found at those sites. Prognosis is generally poor, but combined modality treatment with combination chemotherapy can often achieve useful palliation and, occasionally, long term remission and cure.

Carcinoma, Small Cell↗

PubMed1995

Split course radiotherapy for bladder cancer in elderly unfit patients.

Between 1980 and 1987, 89 patients with T1-T4 carcinoma of the bladder were treated with a split course of external beam radiotherapy. All patients were felt to be unsuitable for a prolonged course of radical radiotherapy because of age and/or poor general health. The intention was to provide local control. The majority of patients were treated with 10-12 fractions, with a mean dose of 45 Gy (range 31.5-57.7), within a mean overall time of 48 days. Of the 89 patients only 62 were assessable with a median follow-up of 110 months (range 64-157). In the remainder, poor health, poor performance status, or early (< 3 months) death did not allow assessment of tumour control. Complete remission was achieved in 28/89 (31%) patients. This was highly dependent on T stage: 56% T1/T2, 30% T3a/T3b, 5% T4. Median survival for patients with Stage T1/T2, T3a/T3b and T4 disease was 22, 10 and 8 months respectively. Acute grade 1-2 radiation reactions occurred in 60% of these patients, and only 5/62 (8%) experienced grade 2-3 late complications, assessed according to the RTOG scoring system. No patient had more severe treatment related morbidity.

Adult↗