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Results for “Lomustine”

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At least 1,333 records · Page 74Linked to original sources
PubMed1991

Release of 7-alkylguanines from N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea-modified DNA by 3-methyladenine DNA glycosylase II.

Purified bacterial 3-methyladenine DNA glycosylase II releases four 7-alkylguanines from [3H]N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea-modified DNA: 7-(2-hydroxyethyl)guanine,1,2-bis(7-guanyl)ethane, 7-(2-chloroethyl)guanine, and 7-(2-ethoxyethyl)guanine. 7-(2-Ethoxyethyl)guanine, a new compound, is formed as a result of an interaction with ethanol, a common solvent for the 2-haloethylnitrosoureas. Of the four 7-alkylguanines which are released from [3H]N-(2-chloroethyl)-N'-cyclohexyl-N-nitrosourea-modified DNA, 7-(2-hydroxyethyl)guanine is released at a rate very much slower than the other three. As shown by a study of the spontaneous decomposition of the corresponding 7-alkyl-deoxyguanines, differences in chemical stability do not appear to explain the slow release of 7-(2-hydroxyethyl)guanine. In view of previous results showing a difference in the distribution of alkylation products between sensitive and resistant glial cell lines, the broad specificity of this enzyme suggests that glycosylase activity could play a role in cellular resistance to 2-haloethylnitrosoureas.

Alkylation↗
PubMed1977

Role of radiation therapy in combination with chemotherapy in extensive oat cell cancer of the lung: a randomized study.

After 3 months of chemotherapy with procarbazine, vincristine, cyclophosphamide, and CCNU, patients with extensive oat cell carcinoma of the lung were randomly allocated to receive 3000 rads of involved-field irradiation and further chemotherapy or to continue with chemotherapy only. In addition, all patients received 3000 rads of prophylactic whole-brain irradiation. The addition of involved-field radiation, as given in this trial, not only failed to improve survival but was unable to alter the pattern of sites of initial relapse. There were no cases of extension to the brain in 31 consecutive patients who received prophylactic whole-brain irradiation. This was in strong contrast to a preceding trial in which six cases of brain extension occurred among 19 patients who did not receive prophylactic whole-brain irradiation.

Aged↗
PubMedDate not supplied

Synthesis and cytotoxic activity of a new alkylating derivative of dipyridamole.

Synthesis of 2,6-Bis[bis(2-chloroethyl) amino]-4,8-dipiperidinopyrimido[5,4-d] pyrimidine, a derivative of dipyridamole, was carried out by treating dipyridamole with thionyl chloride. Cytotoxic activity of this compound was assessed using cultured P388 leukaemia cells and HeLa cells. The compound inhibited the colony-forming ability of HeLa cells and showed a cytotoxicity on P388 cells comparable to that of other alkylating drugs (chlorambucil and CCNU).

Alkylating Agents↗
PubMed1990

Adjuvant chemotherapy for medulloblastoma: the first multi-centre control trial of the International Society of Paediatric Oncology (SIOP I).

Two hundred and eighty-six patients with medulloblastoma from 46 centres in 15 countries were treated in a prospective randomized trial designed to assess the value of adjuvant chemotherapy. All patients were treated by craniospinal irradiation. Those randomly allocated to receive adjuvant chemotherapy were given vincristine during irradiation and maintenance CCNU and vincristine, given in 6-weekly cycles, for 1 year. The overall survival was 53% at 5 years and 45% at 10 years. At the close of the trial in 1979, the difference between the disease-free survival rate for the chemotherapy and control groups was statistically significant (P = 0.005). Since then, late relapses have occurred in the chemotherapy arm and the statistically significant difference between the two groups has been lost. Although there is now no statistical difference between the two arms of the trial, a benefit for chemotherapy persists in a number of sub-groups; partial or sub-total surgery (P = 0.007), brainstem involvement (P = 0.001), and stage T3 and T4 disease (P = 0.002). A number of prognostic factors for medulloblastoma have emerged; sub-total resection, extent of disease and being male sex carry a poor prognosis.

Adolescent↗
PubMed1990

[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].

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.

Astrocytoma↗
PubMed1979

Nitrosourea interaction with chromatin and effect on poly(adenosine diphosphate ribose) polymerase activity.

Poly(adenosine diphosphate ribose) polymerase, a chromatin-bound enzyme, was stimulated 150 to 200% after treatment of HeLa cells with methylnitrosourea (MNU). In contrast, a slight inhibitory effect on enzyme activity was observed after treatment of cells with various concentrations of chloroethylnitrosoureas. To define precisely the differential effects of nitrosoureas on the enzyme activity, their interactions with chromatin substructure were studied. A nonrandom, in vivo alkylation of chromatin DNA by equimolar concentrations of MNU and 1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea (CCNU) was revealed by digestion of nuclei from drug-treated cells with micrococcal nuclease and DNase I. [methyl-14C]MNU interacted preferentially with the more accessible regions of chromatin, the internucleosome linkers, whereas, the [chloroethyl-14C]CCNU alkylated the nucleosomal core DNA to a greater extent. These two drugs also differed in their extent of covalent modification of histone and nonhistone chromosomal protein. The binding of MNU to histones was greater than of CCNU. CCNU mainly affected nonhistone proteins. This difference in the reactivity of methyl and chloroethyl nitrosoureas with chromatin may relate to their differential effect on poly(adenosine diphosphate ribose) polymerase activity, as well as to their carcinogenic and antitumor properties.

Alkylation↗
PubMed1990

Nitrosourea derivatives for the treatment of Hodgkin's disease involving the central nervous system: a study of 23 cases.

This study deals with the effectiveness of nitrosourea derivatives (nitrosomethylurea and CCNU) used as single agents or in combination with vinca alkaloids, procarbazine and prednisolone in 23 patients suffering from Hodgkin's disease with spinal cord or intracranial involvement. Complete regression of neurologic symptoms was observed in 61% of patients with spinal cord compression and in 4 out of 5 cases of brain involvement. No relationship was found between type, degree and duration of symptoms, and treatment efficacy.

Adolescent↗
PubMed1979

Cyclic alternating combination chemotherapy for small cell bronchogenic carcinoma.

Sixty-one protocol-eligible patients with small cell bronchogenic carcinoma received cyclic alternating combination chemotherapy with two or three non-cross-resistant drug combinations. No chest or prophylactic brain radiation therapy was used. Twenty-eight months after starting treatment, disease-free survival was 23% for patients achieving a complete response (CR) and 13% overall. Initial treatment consisted of high-dose cyclophosphamide, methotrexate, and CCNU (CMC) for 6 weeks. Patients then received vincristine, adriamycin, and procarbazine (VAP) for 6 weeks. The addition of VAP increased the CR rate from 42% to 74% in limited-disease patients and from 24% to 36% in extensive-disease patients. Half of the patients were randomized to a third combination of VO-16-213 and ifosfamide. These patients were cycled at 6-week intervals through the three drug regimens while the remaining patients were cycled between CMC and VAP. The addition of VP-16-213 and ifosfamide did not increase the CR rate or prolong survival. Only complete responders survived beyond 24 months. Sequential use of non-cross-resistant drug combinations represents one method for increasing the CR rate.

Antineoplastic Agents↗
PubMed1990

[Effect of 2 different forms of chemotherapy on remission in patients with advanced ovarian cancer].

Results of combined treatment with two different drug combinations were compared in 82 patients with advanced ovarian carcinoma (stages III-IV). 41 patients received cyclophosphamide, methotrexate, vincristine (CMV) and the other 41 patients were treated with cyclophosphamide, adriamycin and cisplatin (CAP). 34 patients (82.9%) treated with the CAP-regimen and 20 patients (48.8%) treated with CMV had remissions following treatment. The average duration of remission was longer in the CAP group (18.1 months) compared to CMV treatment (11.6 months). The mean survival time 24.3 and 14.7 months respectively. It is concluded that three drug therapy is optimal in advanced ovarian carcinoma.

Antineoplastic Combined Chemotherapy Protocols↗