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Biomedical subjects

M D'Incalci

Publications and source records attributed to M D'Incalci.

At least 289 records · Page 16Linked to original sources
PubMed1981

Dose-dependent pharmacokinetics of PMM in the rat.

Concentrations of pentamethylmelamine (PMM) and some metabolites were determined in plasma of rats treated with 10 and 50 mg PMM/kg IV. The areas under the plasma levels curve after these doses were 241 and 1,827 mu g/ml X min; plasma clearances were 0.042 and 0.027 l . kg(-1) . min(-1), respectively. These data suggest that PMM pharmacokinetics is dose-dependent in the rat. The N-demethylated metabolite levels were not proportional to the administered dose.

Altretamine↗
PubMed1980

Low-dose cyclophosphamide versus adriamycin plus cyclophosphamide in advanced ovarian cancer. A randomized clinical study.

After intensive staging 74 ovarian cancer patients were randomized to two arms balanced for stage and post-surgery residual tumor. The two regimens were CTX 100 mg/day continuously and ADM 50 mg/m2 IV every 4 weeks plus CTX 100 mg/day. The response rates were respectively 42% and 52%. Median survival times were 13 and 14 months. The incidence of side effects was significantly higher in the combination-treatment arm. No other statistical differences were found.

Adult↗
PubMed1980

Time dependence of the in vitro cytotoxicity of hexamethylmelamine and its metabolites.

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.

Altretamine↗
PubMed1980

Pharmacokinetic approach to in vitro testing of ovarian cancer cell sensitivity.

Cell populations obtained from ovarian cancer specimens were seeded in primary culture and morphologically identified as cancer cells. Methotrexate, cytosine arabinoside, 5-fluorouracil, antinomycin D, melphalan, and adriamycin were added to the culture medium at different concentrations and for various periods of time. The results are discussed in relation to the pharmacokinetic availability of drugs in the plasma compartment of patients treated by different therapuetic regimens. Totally inactive drugs can be identified by comparing plasma levels with active concentrations while for drugs active in vitro at concentrations in the range of pharmacokinetic levels, the percentage of responders among patients might be explained by the intrinsic variability of cancer cells.

Antineoplastic Agents↗
PubMed1979

Pharmacokinetics of cyclophosphamide after prolonged low dose treatment in ovarian cancer patients.

We have studied Cyclophosphamide (Cy) pharmacokinetics in 9 patients after their first intravenous dose of 100 mg, and in 9 patients after 6--13 months of continual treatment with the same dose every day. The half-life of Cy was shorter (p less than 0.05) in the latter group, the Co was greater (less than 0.01) and the Vd was clearly less (p less than 0.01). The AUC was unchanged.

Cyclophosphamide↗
PubMed1979

Hexamethylmelamine in ovarian cancer resistant to cyclophosphamide and adriamycin.

Thirty-four patients resistant to cyclophosphamide and Adriamycin received hexamethylmelamine at one of two dose regimens: 6 mg/kg/day orally for 21 days every 4 weeks or 8 mg/kg/day orally for 21 days every 6 weeks. Only five patients responded. Tolerance to the drug was, however, satisfactory; nausea, pyrosis, and vomiting were the only frequent side effects. Myelosuppression occurred in only one case.

Adult↗
PubMed1978

Variable oral absorption of hexamethylmelamine in man.

Plasma levels of hexamethylmelamine were measured by a sensitive and specific gas chromatographic assay in 11 patients after they received oral doses ranging from 120 to 300 mg/m2. Peak levels were reached in 0.5--3 hours and ranged from 0.2 to 20.8 micrograms/ml. The area under the curve ranged from 70.2 to 3606.6 micrograms/ml x minute. The half-life of the beta-phase of elimination also showed considerable variability, ranging between 4.66 and 10.2 hours. These parameters were not related to the dose administered. No plasma accumulation of the drug was observed after daily treatment with hexamethylmelamine for 14--21 days.

Absorption↗
PubMedDate not supplied

Driving p53 response to Bax activation greatly enhances sensitivity to taxol by inducing massive apoptosis.

The proapoptotic gene bax is one of the downstream effectors of p53. The p53 binding site in the bax promoter is less responsive to p53 than the one in the growth arrest mediating gene p21. We introduced the bax gene under the control of 13 copies of a strong p53 responsive element into two ovarian cancer cell lines. The clones expressing bax under the control of p53 obtained from the wild-type (wt) p53-expressing cell line A2780 were much more sensitive (500- to 1000-fold) to the anticancer agent taxol than the parent cell line, with a higher percentage of cells undergoing apoptosis after drug treatment that was clearly p53-dependent and bax-mediated. Xenografts established in nude mice from one selected clone (A2780/C3) were more responsive to taxol than the parental line and the apoptotic response of A2780/C3 tumors was also increased after treatment. Introduction of the same plasmid into the p53 null SKOV3 cell line did not alter the sensitivity to taxol or the induction of apoptosis. In conclusion, driving the p53 response (after taxol treatment) by activating the bax gene rather than the p21 gene results in induction of massive apoptosis, in vitro and in vivo, and greatly enhances sensitivity to the drug.

Animals↗