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Y Carpentier

Publications and source records attributed to Y Carpentier.

At least 37 records · Page 2Linked to original sources

Evaluation of a method for detection of cells with reduced drug retention in solid tumours.

A method for detection of cells with reduced drug retention was evaluated in solid tumours. After a 1 h incubation with daunorubicin (DNR), the right angle scatter (RAS), forward angle scatter (FAS), and specific fluorescence (Fluo) were measured in sensitive and resistant cells; only Fluo was related qualitatively, but not quantitatively, to resistance. Various incubation conditions were examined. When the pH of the incubation medium increased, the DNR retention increased in sensitive and resistant cells. In contrast, when the cell concentration increased, the DNR retention decreased. Using sensitive and resistant cell lines, a proportion of resistant cells lower than 10% can be detected in a mixture. To analyse cells from solid tumours, the cells were dissociated by repeated fine needle aspirations. Tumours from 22 patients have been processed with this technique; 8 samples were classified as S (sensitive); 2 as R (resistant); and 12 as I (intermediate). Further experiments were run to study and improve the method. Another method of detection of dead cells was tested. The intra-assay variability of the technique was found to be less than 10%. When the study was performed with different fragments of the same tumour, the variation, corresponding to the tumour heterogeneity, rose to 21 to 36%. The inter-assay reproducibility was too bad, so a variant of this technique has been adapted, using verapamil or cyclosporin A, which is able to block DNR efflux; this new method allows tumour cells to be used as their own controls.

ATP Binding Cassette Transporter, Subfamily B, Mem↗

Alterations of growth fraction and DNA content in K562 cells by differentiating agents.

The growth fraction, estimated by the monoclonal antibody Ki-67 labeling, and DNA content, assessed by ethidium bromide staining, were determined simultaneously in K562 leukemic cells by flow cytometry. A multiparametric analysis enabled the fraction of the cell population with G1, S, and G2 + M contents in Ki-67-positive and Ki-67-negative cells to be evaluated. Butyric acid (BUT) was used as positive control. The fraction of Ki-positive cells decreased with the BUT concentration, while the proportion of cells with G1 DNA content increased only in the Ki-negative cells. Adriamycin, aclacinomycin A, and fagaronine induced differentiation, as assessed by benzidine staining and glycophorin A expression. These drugs decreased the fraction of Ki-positive cells by more than 50% for both anthracyclines and by 25% for fagaronine. Following treatment, Ki-negative cells displayed a G1, but also a G2 and a S DNA content in different proportions, indicating that induction of quiescent cells by differentiating agents is not a uniform process and is worthy of interest.

Aclarubicin↗

[Induction of quiescence by differentiating agents].

The growth fraction of cancer cells, estimated by the monoclonal antibody Ki-67 labelling, and DNA content were determined simultaneously en K562 human leukemic cells by flow cytometry. Adriamycin, aclacinomycin A and fagaronine induced differentiation, as assessed by benzidine staining and glycophorin A expression. These drugs decreases the fraction of Ki-67 positive cells, Ki-67 negative cells displayed a G1, but also a G2 and a S DNA content in different proportions, indicating that induction of quiescent cells by differentiating agents is not a uniform process and is worthy of interest.

Aclarubicin↗

Comparative effects of fagaronine, adriamycin and aclacinomycin on K562 cell sensitivity to natural-killer-mediated lysis. Lack of agreement between alteration of transferrin receptor and CD15 antigen expressions and induction of resistance to natural killer.

Little is known about membrane target antigens for natural killer (NK) cells. Transferrin receptor and CD15 antigen might be two of these target structures. A novel antileukemic alkaloid, fagaronine, is able to induce hemoglobin synthesis in the K562 cell line. Numerous reports suggest relations between the expression of natural killer target structures and the differentiation stage of malignant cells. Effects of fagaronine on the expression of glycophorin A, transferrin receptor and CD15 antigen and susceptibility to NK-mediated lysis have been investigated in K562 cells and compared to those of two anthracyclines (Adriamycin and aclacinomycin A) known to be erythroid-differentiation inducers. When comparing the balance of differentiating effect and toxicity, the dose and time-dependent effects of the drugs, fagaronine and aclacinomycin, are equivalent on K562 cells. In experimental conditions where fagaronine (3500 nM), Adriamycin (40 nM) and aclacinomycin (15 nM) recruit the same percentage of hemoglobin-containing cells (40%-50%), glycophorin A expression increases and transferrin receptor expression decreases. Only Adriamycin treatment decreases CD15 antigen expression. In addition, Adriamycin and aclacinomycin, but not fagaronine, induce resistance to NK-mediated lysis. These data suggest that (a) it is unlikely that CD15 antigen and transferrin receptor, separately considered, can be unique target structures for NK cells; and (b) fagaronine is a potent erythroid inducer which, in our system, has similar effects to aclacinomycin without induced resistance to NK attack.

Aclarubicin↗

Quantitative morphological aspects of granulocytic differentiation induced in HL-60 cells by dimethylsulfoxide and retinoic acid.

HL-60 cells differentiate to mature granulocytes when cultured with DMSO or retinoic acid. These two drugs can induce different expression of phenotypic or functional properties in these cells. The morphological characteristics of the differentiation sequences elicited by these two drugs have been therefore evaluated by a quantitative cytological analysis technique using a SAMBA 200 cell image processor. The maturation sequences induced by DMSO or retinoic acid differed mainly in nuclear geometry and cytoplasmic granules expression. Multivariate statistical analyses of data reveal that DMSO and retinoic acid elicited granulocytic maturation through two separate morphological pathways which can be individualized as early as 24 hr after differentiation induction. Image processing may therefore offer an interesting tool for studying new drugs with differentiation potential in chemotherapy.

Analysis of Variance↗

Association of adriamycin-induced resistance to NK-mediated lysis with sialic acid level and immunological reactivity of transferrin receptors and glycophorin A.

Adriamycin (ADM) can increase sialic acid content in K 562 cells and reduce their susceptibility to NK-mediated lysis. In this report, hypothetical relationship between this resistance and augmentation in sialylation has been investigated. Variations in the time of exposure to ADM showed that 12 hours were sufficient to cause maximal recruitment of benzidine-positive cells, growth inhibition and resistance to NK-mediated lysis. On the contrary, the membrane sialic acid density seemed stable and 24 hours of drug exposure were necessary to observe a clear rise in sialic acid. Neuraminidase treatment of control and ADM-treated K 562 cells was associated with an obvious enhancement in their susceptibility to NK-mediated lysis which can be explained by an increase in the target-effector binding ability as assessed by a direct conjugate-forming cell assay. However, the neuraminidase treatment did not modify the sensitivity difference to lysis between untreated and ADM-treated cells. As compared to control the reactivity of ADM-treated cells was higher with an antiglycophorin A (GPA) MAb and lower with an antitransferrin receptor (TFR) MAb. Kinetic studies suggested that GPA expression is a better index of ADM-induced resistance to NK-mediated lysis than TFR expression. In addition, neuraminidase treatment showed that TFR and GPA modulations induced by ADM can be correlated with sialylation alterations.

Cell Line↗

Effect of fagaronine on cell cycle progression of human erythroleukemia K562 cells.

Fagaronine (Fine) is a novel antileukemic drug extracted from Fagara xanthoxyloides Lam. (Rutaceae). In an attempt to know more about its mechanism of action we describe here its inhibitory activity on cell division, 3H-thymidine incorporation and on cell cycle progression. Fine inhibits cell proliferation of K562 cells by 50% at a concentration of 3 x 10(-6) mol/l at day 4. It stimulates incorporation of labelled macromolecular thymidine on day 1, but decreases incorporation on days 2, 3 and 4. Fine induces a cell accumulation in G2 and late-S phases. This accumulation (i) increases with Fine concentration, but a complete blockade is not observed, (ii) reaches a plateau after approximately 48 h, (iii) is reversible, whereas we have previously shown that cell growth inhibition and differentiation were not reversible.

Alkaloids↗

[Comparative analysis of serum levels of CA-50, CA-125, CA-19.9, enolase and CEA in bronchopulmonary cancer].

A serum assay of CA-50, CA-125, CA-19.9, ENOLASE (NSE) and CEA was performed in 65 patients with primary lung cancer, 63% of whom had visceral metastases, with the following histological distribution: squamous carcinoma (40), adenocarcinoma (9), large cell carcinoma (4), oat cell carcinoma (12). A raised CEA level was detected in 37% of cases, compared with 40.6% for CA-50, 44.6% for CA-19.9 and 40.6% for CA-125 and only 26.6% for NSE. Overall, at least one marker was positive in 83% of cases. Statistical analysis of the different markers (correlation analysis and principal component analysis) demonstrated the existence of a strict correlation between the levels of CA-50, CEA and CA-19.9 (p less than 0.01). ENOLASE was more frequently elevated in oat cell carcinomas (42%) than in non-oat cell carcinomas (30%), but the difference was not significant. In contrast, CA-125 appears to be a good marker for non-oat cell carcinomas (51%) (p less than 0.05). The authors also found a correlation between the presence of a raised level of CA-50 (p less than 0.05), CA-125 (p less than 0.02) and especially CEA (p less than 0.001) and the presence of visceral metastases. The initial survey of disseminated lung cancers should include the assay of at least 4 of these markers in order to obtain a reliable serum tracer in more than 2/3 of cases.

Adenocarcinoma↗

[Serum enzymes and triglycerides in mice with a mammary tumor (Ca-755 adenocarcinoma)].

Investigations on mice inoculated with Ca-755 mammary adenocarcinoma have shown that the levels of serum LDH (especially isozymes resulting from the B sub-unit), TGO and TG are higher than those found in normal mice, while PAL (only bone isozyme) and TGP are lower. Comparisons were made with tumour age (exponential and plateau-growth phases), which appeared to be important for LDH and PAL bone isozyme, since LDH increased and PAL decreased with increasing age of the tumour. For the PAL and TG alterations, there could be assumed an effect of cachectin (TNF: tumour necrosis factor).

Adenocarcinoma↗

Effects of a new antitumor compound, mopidamol, on thymidine and 2-deoxyglucose transport in leukaemic L 1210 cells.

The effects of 2,2',2",2"'-[(4-piperidinopyrimido[5,4-d]pyrimidine-2,6- diyl)dinitrilo]-tetraethanol (mopidamol, RA-233), a drug with antitumour properties, have been studied on membrane transports of L 1210 cells grown in culture. The results show that mopidamol is an inhibitor of thymidine and 2-deoxyglucose transport at concentrations less than or equal to 10(-4) mol/l. The inhibitory effect on cancer cells occurs as soon as 20 s after contact with the drug. Lineweaver and Burk's plots demonstrate a non-competitive type inhibitory effect on membrane transports. In addition, thymidine incorporation in DNA is decreased in the presence of mopidamol.

Animals↗

Phase I study of SOAz.

SOAz, an inorganic cyclic derivative, was given as a single iv injection through one cycle in a phase I trial. Dose-limiting toxic effects noted were neutropenia and thrombocytopenia occurring at doses greater than or equal to 220 mg/M2 in patients with prior myelosuppressive treatment. The time to nadir for blood cell counts was long, as well as the time to recovery, so cumulative toxicity could be suspected. No other significant toxicity was noted. In patients with measurable volume, no significant antitumor responses were seen. For further study, the dose of 220 mg/m2 every 6-8 weeks according to hematologic restoration is recommended.

Adult↗

[Effect of methotrexate on oxygen consumption of L1210 cells and their isolated mitochondria].

Methotrexate, at doses inhibiting cell growth without any lethal effect, alters oxygen consumption in L 1210 cells as soon as 3 hrs. after culture. After a 24 hrs. treatment with methotrexate, there is a close relationship between cellular oxygen uptake and growth inhibition. These two effects are reversible. With mitochondria from treated cells, an inhibition of respiration is observed in the presence of glutamate-malate. No effect occurs with succinate. These results in vitro are compatible with concentrations used in patients.

Animals↗

Methotrexate induced alteration of glycolysis in L1210 cells in vitro.

Methotrexate, in non-lethal doses, greatly enhances anaerobic glycolysis in L1210 cells. Lactate/glucose ratio remains constant but intracellular levels of glycolytic enzymes are increased. ATP accumulating in the cells seems to reflect an alteration of regulation of the glycolysis.

Animals↗

Colonic mucosal atrophy induced by a liquid elemental diet in rats.

The weight, the total crypt cell population, and the proliferation parameters of the colon were estimated in rats during a 4-week administration of a liquid elemental diet (Vivonex standard). Both mitotic and DNA synthesis activity were decreased (P less than 0.01) in the colonic mucosa during the administration of the diet. The weight of the colon was electively decreased (P less than 0.01) from the first week of the treatment. After four weeks, a 75% decrease in the cell population of mucosal glands was observed. This showed that considerable atrophy of the colonic mucosa occurred under the effect of feeding the elemental diet. This atrophy was probably mediated by a reduction in the proliferative activity of the stem cells in the mucosal glands.

Animal Nutritional Physiological Phenomena↗