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D Lefevre

Publications and source records attributed to D Lefevre.

15 recordsLinked to original sources
PubMed1991

Study of molecular markers of resistance to m-AMSA in a human breast cancer cell line. Decrease of topoisomerase II and increase of both topoisomerase I and acidic glutathione S transferase.

Resistance to 0.8 microM 4'-(9-acridinylamino)methanesulphon-m-anisidide (m-AMSA) was induced by stepwise increases of drug concentration in the human tumor cell line CALc18 originating from a breast adenocarcinoma. The resistant cell line CALc18/AMSA exhibited a resistance index of 10 and a cross-resistance to other topoisomerase II inhibitors. A 3-fold decrease in the levels of topoisomerase II decatenating activity was found in CALc18/AMSA cells. By contrast, topoisomerase I activity was increased by about 3-fold in resistant cells. Interestingly this line was hypersensitive to camptothecin, a specific inhibitor of topoisomerase I. Restriction endonuclease patterns of the topoisomerase I and topoisomerase II loci were found to be identical in CALc18/AMSA and CALc18 with no evidence of gene amplification and rearrangements. Alkaline elution of m-AMSA-treated cells showed that DNA single strand breaks and DNA-protein crosslinks were decreased in CALc18/AMSA. The DNA lesions also obtained in m-AMSA-treated nuclei indicated that no drug uptake modification occurred in both cells. Moreover, the in vitro m-AMSA-induced DNA cleavage per unit of decatenating activity and the inhibitory effects of antitumoral drugs on decatenation were not found to be different with topoisomerase II from sensitive or resistant cells. However the specific cleavage induced by m-AMSA/per mg of crude protein from resistant cells was 2 to 3 times decreased. Multidrug resistance gene transcripts were not detected while levels of acidic glutathione S transferase mRNA were found to be 8 to 10-fold greater in resistant than in sensitive cell line with no amplification of the gene. In conclusion, the diminution of topoisomerase II activity and the increase of both topoisomerase I and acidic glutathione S transferase transcripts could contribute to the resistant phenotype of these breast cancer cells.

Adenocarcinoma↗
PubMed1989

Stimulation of the topoisomerase II induced DNA cleavage sites in the c-myc protooncogene by antitumor drugs is associated with gene expression.

The antitumor drugs mAMSA and VM26 were shown to stimulate the topoisomerase II (Topo II) cleavage activity on the c-myc protooncogene in several human tumor cell lines (N417, HL60, EJ, H146, CaSki, A431, IGROV1, and CAL18A) and human peripheral lymphocytes. The mAMSA-induced gene cleavage was found to increase with the steady-state levels of c-myc transcripts in cell lines while no cleavage could be evidenced in the other genes so far tested. In mAMSA-treated N417 cells, the overall genomic DNA cleavage detected by alkaline elution was found to be about 20 times lower than the c-myc gene cleavage. Topo II mRNA levels were associated with the nuclear Topo II decatenating activity in cell lines and increased with c-myc cleavage. Topo II decatenating activity was found to be 3 times lower in quiescent than in exponentially growing N417 cells, but the c-myc cleavage induced by mAMSA was found as intense in quiescent as in growing cells. Thus, our data seem to indicate that c-myc gene cleavage is not related to cellular Topo II content but rather to c-myc gene transcription. Therefore, we suggest that only a small fraction of the Topo II is able to react with drug on the c-myc gene in relation to its transcriptional accessibility. Since c-myc overexpression is frequently found to be related to human cancer progression, we suggest that this gene could be an important target for Topo II related antitumor drugs.

Amsacrine↗
PubMed1983

[Osteonecrosis in retransplated kidney patients resuming hemodialysis. Comparison with a hemodialysed population not having undergone transplantation. Discussion of the role and duration of corticotherapy as cause of aseptic osteonecrosis].

A systematic study in 5 hemodialysis centres was carried out for the incidence of aseptic osteonecrosis (AON) after two patients presented with this condition during hemodialysis after transplantation and rapid "retransplantation". The following observations were made after the assessment of similar cases and a comparison with a control population of hemodialysis patients not having undergone attempted renal transplantation. Ten patients had undergone "retransplantation". Four of these patients had one or more sites of AON. In 2 cases steroid therapy had been of short duration (29 and 43 days) but at massive doses. In the other two cases, steroid therapy had been prolonged for over one year. On the other hand, no cases of AON were found in the 156 patients not having undergone attempted transplantation on chronic hemodialysis therapy of known duration (p less than 0,00002). This study suggests that steroid therapy of very short duration may lead to irreversible early osteomedullary ischemia and to osteonecrosis. There was no significant difference in the duration of hemodialysis between the two groups of patients, with and without AON.

Adrenal Cortex Hormones↗
PubMed1983

Idiopathic disorders of fecal continence in children.

A group of 176 patients aged 2 to 15 years was investigated for idiopathic disorders of bowel function other than Hirschsprung's disease. Anorectal motility, as well as colorectal transit of radiopaque markers, were investigated. Before the end of the first month of life, 70 of the patients were constipated. Resting pressure was more unstable (P less than 0.001) and higher than normal in the rectal ampulla and upper anal canal (P less than 0.01). Retardation of markers occurred in the proximal and/or distal large bowel of 61% of the patients. The existence of functional abnormalities was demonstrated in the majority of children with idiopathic disorders of fecal continence.

Adolescent↗
PubMed1978

[Colonic occlusion].

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Colonic Diseases, Functional↗
PubMed1975

Passive avoidance behavior in rats after electroconvulsive shock: facilitative effect of response retardation.

Rats were trained in a one-trial passive avoidance task and then were submitted to electroconvulsive shock (ECS) or to sham ECS. Twenty-four hours later they were tested for retention, with the door opened either immediately or 30 sec after the beginning of the test. Rats initially forced to avoid for 30 sec continued to avoid for the entire test, but the others had the usual low step-through latencies seen with ECS-treated animals. Activity measures for those animals stepping through differentiated groups having received footshock from those not having footshock and ECS. A retest 5--10 min later showed "recovery" in the amnestic animals and continued avoidance behavior for those that avoided on the first test. Results are taken as evidence that ECS effects are not on memory storage but on the capacity of the animal to organize information effectively and quickly in order to produce an adaptive response.

Animals↗