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Proceedings of the National Academy of... Jul 1987Fifty-five ovarian cancer patients receiving platinum drug-based chemotherapy have been studied prospectively to determine the extent of formation of the bidentate... (Comparative Study)
Comparative Study
Fifty-five ovarian cancer patients receiving platinum drug-based chemotherapy have been studied prospectively to determine the extent of formation of the bidentate intrastrand adducts of diammineplatinum covalently attached to the N7 positions of adenosine and/or guanosine in leukocyte DNA. Data for clinical response, obtained from medical records, were then correlated with the adduct values. Patients were treated with platinum-based single-agent or combination chemotherapy containing cis-diamminedichloroplatinum (II) or diamminecyclobutane-dicarboxylatoplatinum on approved experimental protocols. Adduct measurements were performed by ELISA, and disease response to therapy was assessed by standard oncologic criteria. This study comprises a total of 101 blood samples obtained after intravenous cis-diamminedichloroplatinum (II) or diamminecyclobutane-dicarboxylatoplatinum infusion from 55 individuals, and in each case the highest (or "peak") adduct level for each patient was chosen for statistical analysis. Values for median adduct levels in patients grouped by complete response, partial response, and no response were 212, 193, and 62 amol of adduct per microgram of DNA, respectively. Analysis of these data by Jonckheere's test (an extension of the Mann-Whitney test) shows that higher levels of adduct formation correlates with disease response with a two-sided P value of 0.030. Of eight patients on single-agent therapy whose buffy-coat samples did not have measurable adduct levels, none responded to therapy. Analysis of these data using the exact test for trend shows that the formation of adduct at a level of 160 amol/micrograms of DNA or greater correlates with disease response with a two-sided P value of 0.032. Thus in ovarian cancer patients, the formation of the intrastrand diammineplatinum adducts in leukocyte DNA is associated with favorable disease response to cis-diamminedichloroplatinum (II) or diamminecyclobutane-dicarboxylatoplatinum chemotherapy.
Topics: Adult; Aged; Altretamine; Antineoplastic Agents; Antineoplastic Combined Chemotherapy Protocols; Carboplatin; Cisplatin; Combined Modality Therapy; Cyclophosphamide; DNA Damage; DNA, Neoplasm; Drug Evaluation; Female; Humans; Middle Aged; Misonidazole; Organoplatinum Compounds; Ovarian Neoplasms
PubMed: 3110781
DOI: 10.1073/pnas.84.14.5024 -
Zhongguo Yao Li Xue Bao = Acta... Dec 1983
Topics: Altretamine; Animals; Antineoplastic Agents; Biotransformation; Female; Male; Mice; Neoplasms, Experimental; Rats; Structure-Activity Relationship; Triazines
PubMed: 6230876
DOI: No ID Found -
British Journal of Cancer Aug 1982A hypothesis is proposed that tumour lysis may be an important factor affecting blood levels of CEA. This has been explored in an experimental study with a model tumour...
A hypothesis is proposed that tumour lysis may be an important factor affecting blood levels of CEA. This has been explored in an experimental study with a model tumour system, consisting of immune-deprived mice bearing human CEA-producing tumours. Using agents such as irradiation, chemotherapeutic drugs, diphtheria toxin and techniques such as cryosurgery, it has been shown that tumour lysis is important when it is both rapid and extensive. The extent to which this may occur in patients remains uncertain, except in rare instances of dramatic response of malignant disease to treatment.
Topics: Altretamine; Animals; Breast Neoplasms; Carcinoembryonic Antigen; Cell Line; Colonic Neoplasms; Cyclophosphamide; Diphtheria Toxin; Humans; Lung Neoplasms; Mice; Necrosis; Neoplasm Transplantation; Neoplasms, Experimental; Time Factors
PubMed: 6817775
DOI: 10.1038/bjc.1982.186 -
The Journal of Investigative Dermatology Jul 1952
Topics: Altretamine; Antineoplastic Combined Chemotherapy Protocols; Atmospheric Pressure; Cisplatin; Cyclophosphamide; Doxorubicin; Humans; Humidity; Skin
PubMed: 14946439
DOI: 10.1038/jid.1952.61 -
American Journal of Public Health and... Mar 1960
Topics: Altretamine; Carmustine; Data Collection; Histoplasmin; Tuberculin; Tuberculin Test
PubMed: 13820348
DOI: 10.2105/ajph.50.3_pt_1.368 -
British Journal of Cancer Apr 1980The cytotoxicity of hexamethylmelamine (HMM) and its metabolites pentamethylmelamine (PMM), N,2,2,4,6-tetramethylmelamine (TMM) and hydroxymethylpentamethylmelamine...
The cytotoxicity of hexamethylmelamine (HMM) and its metabolites pentamethylmelamine (PMM), N,2,2,4,6-tetramethylmelamine (TMM) and hydroxymethylpentamethylmelamine (HMPMM) and of the alkylating agent triethylenemelamine (TEM) were studied on a cell line derived from a human ovarian cancer, by measuring [3H]TdR uptake. After 24 h of incubation all the tested compounds inhibited [3H]TdR uptake, but only at a concentration of 100 micrograms/ml. However, after 120 h incubation, concentrations of 0.1--10 micrograms/ml resulted in highly significant cytotoxicity. HMPMM and TEM were the most active and their effect was not reversed 72 h after their removal. In our in vitro system no metabolism of HMM was observed.
Topics: Altretamine; Cell Line; Cells; Female; Humans; Ovarian Neoplasms; Thymidine; Time Factors; Triazines
PubMed: 6770884
DOI: 10.1038/bjc.1980.106 -
British Journal of Cancer May 1986Trimelamol (N2,N4,N6-trihydroxymethyl-N2,N4,N6-trimethylmelamine) is an analogue of pentamethylmelamine (PMM). In early clinical trials PMM failed to show significant...
Trimelamol (N2,N4,N6-trihydroxymethyl-N2,N4,N6-trimethylmelamine) is an analogue of pentamethylmelamine (PMM). In early clinical trials PMM failed to show significant anti-tumour activity in man which was attributed to poor metabolic activation. Trimelamol does not require activation and is therefore expected to be more active in man. PMM caused dose-limiting emesis and sedation whereas Trimelamol is much less neurotoxic in rodents. The relative penetration of PMM and Trimelamol into mouse brain has therefore been examined. Mice receiving PMM at 90 mg kg-1 i.p. were found to have high concentrations of the drug in the CNS compared to plasma (mean brain/plasma ratio 1.04) whereas animals receiving Trimelamol had consistently low CNS concentrations (mean brain/plasma ratio 0.08). This difference did not correlate with plasma protein binding which is greater for PMM (68.2%) than for Trimelamol (17.5%). However, it does appear to be related to lipophilicity. In Phase I clinical trial Trimelamol has proved much less emetic than PMM and causes no acute sedation. It is likely that this reduction in toxicity may be explained by the relatively poor ability of Trimelamol to enter the CNS.
Topics: Altretamine; Animals; Blood Proteins; Blood-Brain Barrier; Brain; Kinetics; Male; Mice; Mice, Inbred BALB C; Protein Binding; Triazines
PubMed: 3087399
DOI: 10.1038/bjc.1986.102 -
British Journal of Cancer Jul 1983Of 89 samples of cancer cells from ovarian cancer patients primary cultures representative of the cancer cell population could be established in 17. The clinical... (Comparative Study)
Comparative Study
Of 89 samples of cancer cells from ovarian cancer patients primary cultures representative of the cancer cell population could be established in 17. The clinical response to polychemotherapy was studied in relation to the inhibition of thymidine uptake by the cultured cells. Cultures of each patient's tumour were exposed to concentrations of the drugs the patients had been given for long enough to reproduce the area under the curve (AUC) of the plasma levels resulting from in vivo dosage. Full agreement was observed between the degree of thymidine uptake inhibition induced by at least one of the drugs administered to the cultured cells and the degree of clinical response. This approach may prove useful in pharmacological studies as a means of obtaining ovarian cancer cell populations representative of human tumours, even though the number of tumours that can be successfully evaluated in vitro is still too small to serve as a sound basis for prediction.
Topics: Adult; Aged; Altretamine; Antineoplastic Agents; Cell Survival; Cells, Cultured; Cisplatin; Cyclophosphamide; Dose-Response Relationship, Drug; Doxorubicin; Drug Therapy, Combination; Female; Fluorouracil; Humans; Middle Aged; Ovarian Neoplasms
PubMed: 6409137
DOI: 10.1038/bjc.1983.157 -
British Journal of Cancer Sep 1982
Topics: Altretamine; Animals; Antineoplastic Agents; Cell Line; Cisplatin; Cyclophosphamide; Hindlimb; Humans; Melphalan; Mice; Mice, Inbred CBA; Neoplasm Transplantation; Pancreatic Neoplasms; Semustine; Streptozocin; Transplantation, Heterologous; Vinblastine
PubMed: 6215052
DOI: 10.1038/bjc.1982.221