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F Joncourt

Publications and source records attributed to F Joncourt.

16 recordsLinked to original sources
PubMed1995

Patterns of drug resistance parameters in adult leukemia.

P-glycoprotein (Pgp), Glutathione (GSH), Glutathione S-Transferase (GST), and O6-Alkylguanine-DNA Alkyltransferase (ATase) were measured in parallel as putative indicators of drug resistance in adult leukemia. The patterns of resistance parameter expression of chronic and acute leukemia were different. In acute leukemia on average all parameters were increased as compared to normal bone marrow. In chronic leukemia GSH and GST were increased, whereas Atase, GPx and frequency of Pgp-expression were low. Treatment with cytostatic drugs did not influence median levels of expression/activity of the resistance parameters. Resistance parameter expression/activity of leukemic cells was also compared with various other tissue and tumor types. Generally the pattern of resistance parameter expression reflected the resistance status of the tissue, constitutively resistant tumor types and their corresponding normal tissue on average having higher levels than leukemic cells and other tissue and tumor types with acquired resistance. For individual patients with acute leukemia, however, none of the parameters was directly correlated with response to treatment.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1994

Parallel assessment of glutathione-based detoxifying enzymes, O6-alkylguanine-DNA alkyltransferase and P-glycoprotein as indicators of drug resistance in tumor and normal lung of patients with lung cancer.

The levels of several potential indicators of drug resistance were measured in tumor and corresponding normal tissue of 55 untreated patients with lung cancer. The resistance parameters include glutathione (GSH) level, activities of the enzymes glutathione transferase (GST), glutathione peroxidase (GPx) and O6-alkylguanine-DNA alkyltransferase (ATase), as well as expression of P-glycoprotein (Pgp). Median values of GSH, GST and GPx were significantly higher in tumor than in normal tissue of non-small-cell lung cancer (NSCLC) or of small-cell lung cancer (SCLC), whereas ATase was elevated in tumor tissue of NSCLC only. Pgp expression as determined by Western blotting was significantly lower in tumor than in normal tissue of NSCLC. Resistance-parameter expression did not correlate with stage of disease or age of the patients. We found a negative correlation between smoking intensity and GSH level in normal tissue. Our findings indicate that the fundamental differences in chemosensitivity between SCLC and NSCLC cannot be explained by differences in the GSH-system or in the expression of Pgp. However, the level of ATase activity may be one of the factors responsible for the difference in chemosensitivity.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1993

Cytostatic drug resistance: parallel assessment of glutathione-based detoxifying enzymes, O6-alkylguanine-DNA-alkyltransferase and P-glycoprotein in adult patients with leukaemia.

The levels of several potential indicators of resistance to cytostatic drugs were measured in leukaemic cells of a total of 64 adult patients with acute or chronic leukaemias before and during treatment and at relapse or recurrence of disease and compared with those of mononuclear cells from the bone marrow of healthy donors. The resistance factors included glutathione (GSH) and its associated enzymes glutathione-S-transferase (GST) and glutathione peroxidase (GPx) as well as O6-alkyguanine-DNA-alkyltransferase (ATase) and P-glycoprotein. Median values for most parameters were significantly higher in leukaemic cells than in those of normal donors although wide interindividual variation in the values of the various parameters, particularly GST, were seen. P-glycoprotein was measurable in 12.5% of untreated leukaemias but in none of the normal donors. The values of the parameters in untreated leukaemic patients were not statistically different from those at relapse or during disease progression. However, the median values for GSH, GST and GPx but not ATase in samples from untreated patients were significantly higher than those in samples taken during drug treatment. Patient response, disease-free survival or duration of remission did not correlate with the values of any of the parameters studied.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1991

Assessment of P-glycoprotein, glutathione-based detoxifying enzymes and O6-alkylguanine-DNA alkyltransferase as potential indicators of constitutive drug resistance in human colorectal tumors.

Drug resistance is a major problem in cancer chemotherapy. Treatment protocols generally include a number of different cytotoxic drugs given in combination. Therefore, drug resistance in the tumor is likely to result from the coexpression of several cellular activities able to prevent cell killing by any of the drugs used. In this study we have measured several potential drug resistance mechanisms consisting of the multidrug resistance gene product P-glycoprotein, glutathione, glutathione-transferase and -peroxidase, and the DNA repair enzyme O6-alkylguanine-DNA-alkyltransferase in samples of colon carcinoma and normal adjacent mucosa from 23 untreated patients. All of these, with the exception of P-glycoprotein, showed significant increases in tumor tissue levels when compared with normal tissue from the same patient. The significance was highest for glutathione peroxidase (P less than or equal to 0.0005). Individual patients, however, showed very different patterns, with none, several, or all monitored resistance mechanisms elevated in the tumor. The implications both in the choice of drugs and in the use of resistance modifying agents to improve therapy for the individual patient are discussed.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMed1985

Age-related changes in the formation of glucocorticoid and insulin receptors during lectin-induced activation of human peripheral blood lymphocytes.

The influence of age on the number of receptors for insulin and glucocorticoids on human T cells was examined. The specific binding of 125I-insulin and 3H-dexamethasone to phytohemagglutinin-(PHA)-stimulated T cells was found to decrease with age. Populations of PHA-stimulated T cells, however, are heterogeneous with respect to cell cycle phases, and cells in different cell cycle phases have been shown to bear different numbers of receptors. Therefore, it was not clear whether the measured decrease in specific binding in cultures from aged donors was due to a decreased number of activated cells or to a decreased number of binding sites per cell. In parallel to measurements of receptors, performed at different times following stimulation (20 and 44 h), numbers of cells in the different early cell cycle phases G0, G1a and G1b were quantitated by flow cytometry. In this way the receptor number per cell in each phase of the cell cycle could be determined. Receptor numbers on resting cells and in the earliest phase of activation (G1a) were found not to be influenced by age. A decreased receptor density, however, was apparent on G1b cells from aged donors.

Adult↗
PubMed1984

Cell cycle-related changes in number of T-lymphocyte receptors for glucocorticoids and insulin.

Enriched human peripheral T-lymphocytes were stimulated with PHA and examined for variations in insulin and glucocorticoid (dexamethasone) receptor numbers during the early phases of the cell cycle. Cells in G0, G1a and G1b phases, where the G1a - G1b transition is an Interleukin 2 dependent event, were quantitated by flow cytometry. Few but significant numbers of glucocorticoid receptors (2700/cell) and no insulin receptors (-1/cell) were found in the resting (G0) phase. As cells entered the G1a phase the specific binding of dexamethasone increased and of insulin took place. Although the specific binding further increased as T-cells entered the G1b phase (as measured at 44 h of incubation and using hydroxyurea-treated cells), the major changes in the specific binding of dexamethasone took place during the period 16 - 20 h after stimulation. Based on these findings, it is concluded that both receptor types (cell membrane and cytoplasmic receptors) are being formed and increased at G1 phase prior to cell proliferation, indicating the importance of G1 phase in immunoregulation.

Adult↗
PubMed1983

Analysis of 3H-histamine interaction with lymphocytes: receptor binding or uptake?

The immunoregulatory role of histamine is presumably mediated by specific receptors on the plasma membrane of lymphocytes. However, using murine spleen cells and a whole cell assay commonly applied in hormone receptor studies, specific histamine receptors with an affinity higher than that of non-specific binding could not be identified. Nevertheless, approximately 30% of the totally bound histamine was undissociable over a range of added histamine concentrations (9 X 10(-6)-1 X 10(-2) M). Lectin stimulation of spleen cells caused an additional two-fold increase of undissociable histamine. The H1 receptor antagonist, diphenhydramine, blocked histamine uptake, whereas the H2 receptor antagonist, cimetidine, had no effect. Binding experiments carried out at 4 degrees C demonstrated that the amount of undissociable histamine was much reduced. Even at 4 degrees C, evidence for specific membrane associated histamine receptor could not be obtained. It was therefore concluded that lymphocytes take up histamine by an energy-dependent mechanism inhibitable by diphenhydramine but not cimetidine, and that the usual hormone receptor methodology did not allow the identification of specific membrane associated histamine receptors.

Animals↗
PubMed1982

Human lymphocyte proliferation. I. Correlation between activated and proliferating T-lymphocytes.

The response of human peripheral blood lymphocytes to Con A and PHA has been analyzed by [3H]thymidine incorporation and cytofluorometry. Using the latter method, it is possible to quantitate the number of cells in the G0 phase (normal RNA and DNA content) and in the G1 phase (elevated RNA, but normal DNA content). A very high correlation is found between numbers of Con A or PHA-induced G1 cells and [3H]thymidine incorporation in healthy donors. This high correlation is found when culture medium is enriched with 10% autologous plasma or 10% AB-serum. The use of a recently developed defined serum-free medium (RPMI 1640 with albumin, alanine, transferrin, sodium selenite and zinc chloride), however, suggest that donors can be divided into two groups according to different medium requirements for PHA-stimulated lymphocytes. Because several immunoregulatory mechanisms at the level of T-lymphocytes take place in the G1 phase, it can therefore be expected that cytofluorometric analyses of lymphocytes in the various cell cycle phases may improve the interpretation of altered lymphocyte response to lectins and antigens.

Cell Cycle↗
PubMed1982

Age-related changes in g0-g1 transition and proliferative capacity of mitogen-stimulated murine spleen cells.

The early kinetics of mitogen-stimulated of mitogen-stimulated spleen cells from young adult and aged NMRI mice were investigated. Using RNA synthesis as measured by cytofluorometry by cytofluorometry and 3H-leucine and 3H-thymidine incorporation as parameters, it was apparent that age-related changes occur at different levels during mitogen stimulation. First, in aged mice fewer cells per 10(6) spleen cells are being activated by mitogen, and, second, fewer of the activated lymphocytes will proliferate. However, the cells which initiate synthesis of RNA, protein, and DNA apparently behave in identical manners, chronologically, as cells from young adult mice.

Aging↗
PubMed1982

Aging and immunity: decrease in interleukin-2 production and interleukin-2-dependent RNA-synthesis in lectin-stimulated and murine spleen cells.

The RNA-content of G1 cells in lectin-stimulated spleen cell cultures of young and aged NMRI mice was determined by flow cytometry. In spleen cells of aged mice a preferential decrease of G1 cells with a high RNA-content, so-called G1b cells, was found. Since, as shown in a previous report, only cells with a high RNA-content are able to proliferate and the passage of low (G1a) to high (G1b) RNA-content is interleukin-2(IL-2)-dependent, the ability of young and old spleen cells to produce IL-2 was tested. In old spleen cells a diminished production of IL-2 was found. Addition of external IL-2, however, did not increase the proliferative capacity of old spleen cells, nor did it induce more G1b cells. Thus spleens of aged mice contain cells, which can be activated by lectin, but then fail to respond to IL-2. Both decrease in IL-2 production and receptivity for IL-2 may contribute to the diminishing immune response in aging individuals.

Aging↗
PubMed1981

Age-related changes of mitogen responsiveness in different lymphoid organs from outbred NMRI mice.

Lymphocytes from spleen, thymus and lymph nodes from individual young adult (3--4 months) and aged (26--30 months) NMRI mice were stimulated with the mitogens Con A, PHA and LPS. 24 hours later, the number of cell with increased RNA-content (G1 cells) was determined by cytofluorometry. In parallel the 3H-thymidine incorporation after 48 hours was measured for the same cell samples. Aged animals in average produced less G1 cells and incorporated less 3H-thymidine as compared to young adults. By calculating the 3H-thymidine incorporation per G1 cell, the proliferative capacity of mitogen-induced G1 cells can be estimated. These ratios are lower in aged mice as compared to young adult, suggesting that in these animals not only less cells can be activated as measured by cytofluorometry, but also from these activated cells again fewer continue the cell cycle by initiating DNA-synthesis. In response to Con A and PHA, aged mice in average produce less G1 cells in all of the three lymphoid organs tested. In response to LPS, however, the young adult produced only few G1 cells in lymph nodes and practically none in thymus, whereas in aged animals a considerable number of G1 cells was found in both organs. Corresponding results were found for the 3H-thymidine incorporation. These results indicate that in addition to the reduction of the mitogen-response an age-related change in the distribution of mitogen-responsive cells in the different lymphoid organs takes place.

Aging↗
PubMed1981

The influence of serum on lymphocyte cultures. II. Cell cycle specificity of serum action in spleen cells.

Serum exerts several effects in lymphocyte cultures, one of them being manifested very early. The presence of fetal calf serum (FCS) results in a markedly higher thymidine uptake within a few minutes, as compared with serum-free cultures. On the other hand, the uptake of uridine and other purine bases seem to be little influences by serum. Experiments comparing the uptake of thymidine into the cytoplasm or into trichloroacetic acid-precipitable material suggested that the intracellular thymidine pool increases in size when FCS is added. Using a Lineweaver--Burk plot for thymidine and uridine uptake over a 4-h period, no changes in uridine uptake were observed in the presence of FCS; on the contrary, serum induced an increased Vmax for thymidine, whereas Km remained constant. Cytofluorographic quantitation of G0 and G1 cells indicated that cells disappear more rapidly from the G1 phase in the presence of FCS. The addition of hydroxyurea to the cultures prevented this disappearance. The results taken together strongly suggest that serum contains a factor promoting the shift of G1 cells into the S phase. When a 4-h culture period was used, all sera from different species tested at low concentrations appeared to contain this activity.

Aging↗
PubMed1981

Ageing and immunity in outbred NMRI mice: lack of correlation between age-related decline of the response to T cell mitogens, the antibody response to a T-dependent antigen and lifespan in outbred NMRI mice.

Responses to different mitogens and the primary in vitro antibody response to a T-dependent antigen (SRBC) were tested in individual mice of various ages from an outbred strain (NMRI). Comparing mean values, an age-related decrease was found only for the responses to Con A and PHA but not for LPS nor for the primary in vitro antibody response to SRBC. The magnitude of the responses obtained in individual mice of the same age varied greatly. Some of the young as well as aged animals could respond very well to antigen, mitogen or both and there was a complete lack of correlation between the magnitude of individual responses to mitogen and the number of PFC produced in the in vitro antibody response to SRBC. Additionally, we investigated whether the magnitude of the immune responses measured in individual mice had any influence on their lifespan. The mitogen response and the in vitro PFC production of spleen cells from individual semi-splenectomized mice were therefore compared with their lifespan. The lifespan did not appear to be influenced by any of the immune responses measured.

Aging↗