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Biomedical subjects

D Thevenin

Publications and source records attributed to D Thevenin.

27 records · Page 2Linked to original sources
PubMed1987

Prognostic value of clonogenic assay for induction and duration of complete remission in acute myelogenous leukemia.

The validity of an in vitro clonogenic drug sensitivity assay to predict the induction and the duration of complete remission was evaluated in a group of 81 patients with acute myelogenous leukemia treated with chemotherapy including an anthracycline drug (daunorubicin or adriamycin) and cytosine arabinoside (Ara-C). The inhibition of bone marrow clonogenic leukemic cells by in vitro exposure to anthracyclines 10(-5) and 10(-6) M, Ara-C 10(-5) M, and daunorubicin 10(-6) M + Ara-C 10(-7) M was significantly correlated with the achievement of a complete remission, but not with the duration of remission. A high second plating efficiency was correlated with short duration of complete remission, reflecting the poor prognosis of a high self-renewal capacity.

Adolescent↗
PubMed1986

[In vitro inhibition of granulopoiesis by beta-lactam antibiotics. Comparison of piperacillin, mezlocillin, ceftriaxone and ceftazidime].

The mechanism of neutropenia induced by beta-lactam antibiotics was explored by studying the action of these drugs on granulopoiesis in vitro. Normal bone marrows were cultivated in the presence of increasing concentrations of piperacillin (10 marrows), mezlocillin, ceftriaxone and ceftazidime (5 marrows each) in order to find out whether these antibiotics exhibited toxicity to granulocyte-monocyte precursors. A dose-dependent inhibition of granulopoiesis was found in all cases. When the doses used were equivalent to maximum plasma concentrations in vivo, inhibition was minimal with piperacillin and mezlocillin and much more pronounced with the cephalosporins. This dose-dependent inhibition suggests that toxicity is involved in the mechanism of neutropenia induced by beta-lactam antibiotics.

Anti-Bacterial Agents↗
PubMed1985

DNA ligases in human leukemia.

Following partial purification on sucrose gradient and/or phosphocellulose chromatography, DNA ligase was tested in peripheral white blood and bone marrow cells of nearly 100 patients with various kinds of leukemias, mainly acute leukemias. Terminal deoxynucleotidyl transferase (TdT) was tested in parallel. DNA ligase of acute myeloblastic leukemia (AML) was extracted with the same sedimentation coefficient (5.5S) on sucrose gradient, and eluted with the same KCl molarity (0.3 M) than the one extracted from normal lymphocytes. Acute lymphoblastic leukemias (ALL) were characterized by no detectable DNA ligase activity--in most T or non T-non B-ALL, or a low activity in pre-B and B (Burkitt type) ALL, with levels similar to the one observed in chronic lymphocytic leukemia (CLL). An inverse relationship was observed between DNA-ligase and TdT in ALL, ligase being undetectable in cells positive for TdT and being present in some T or non T-non B, and in all pre-B and B-ALL negative for TdT. AML and chronic myelocytic leukemia (CML) were characterized by a markedly higher DNA-ligase activity. This activity was higher in the most differentiated subtypes--M2, M3 and M4 subtypes of FAB classification--and in CML. Moreover a high degree of correlation was observed in AML between the DNA ligase activity and the S phase fraction measured by 3 H-thymidine autoradiography or flow cytophotometry on the total cell sampling. Besides their clinical interest, these results are discussed in relation with the role of DNA-ligase in DNA replication and repair.

Adolescent↗
PubMed1985

In vitro sensitivity of leukemic clonogenic cells to four anthracyclines (adriamycin, daunorubicin, rubidazone and aclacinomycin) in human acute myeloid leukemia.

We used an in vitro clonogenic assay in semi-solid medium to test the sensitivity of human leukemic progenitors to different anthracyclines. Bone marrow leukemic cells of 19 patients with acute myeloid leukemia were plated after exposure to adriamycin (ADR), daunorubicin (DNR), rubidazone (RDZ) and aclacinomycin (ACLA). We obtained a dose-dependent response curve with all anthracyclines, with wide response curve with all anthracyclines, with wide patient to patient variations. In 9 out of 19 cases, in vitro sensitivity to the four drugs correlated (4 sensitive and 5 resistant cases), but in 10 patients the results were discordant, with 8 conflicting results between ADR and the other three anthracyclines, raising the possibility of the absence of cross-resistance between these drugs.

Aclarubicin↗
PubMed1983

In vitro culture of clonogenic leukaemic cells in acute myeloid leukaemia: growth pattern and drug sensitivity.

Bone marrow from 43 of 45 AML patients grew leukaemic colonies in culture with a technique using methyl-cellulose semi-solid medium and stimulation with PHA-leucocyte conditioned medium. Plating efficiency was significantly greater in M4FAB subtypes than in M1 or M2. The presence of Auer rods in cultured cells and the existence of cytogenetic abnormalities in both fresh and cultured blast cells in one patient confirmed the leukaemic origin of these colonies. These clonogenic cells were closely related to the growth fraction, as demonstrated by a high suicide index and a linear correlation between percentage of bone marrow blasts in S phase and plating efficiency. In vitro CFU-L sensitivity to cytosine-arabinoside (ARA-C) and to adriamycin (ADR) was tested in 22 patients treated with these two drugs. In the group sensitive in vitro to ARA-C (10 patients), 70% entered complete remission. In the resistant group (12 patients), only 25% had complete remission while 75% had resistant disease. Eight of 14 patients sensitive to ADR in vitro achieved complete remission, while five were resistant to chemotherapy. On the other hand, six of eight patients resistant in vitro were resistant in vivo. When drug sensitivities to ARA-C and ADR were cumulated, an excellent in vitro to in vivo correlation was found when the patient was sensitive or resistant to both drugs in vitro.

Bone Marrow↗
PubMed1982

PHA-induced blast colonies and kinetic parameters in acute myeloid leukemia.

The in vitro leukemic colony-forming ability of 30 acute myeloid leukemias tested after PHA stimulation was analyzed by comparing the CFU-GM growth pattern, the myeloblast [3H]thymidine index and the response to treatment. PHA-induced leukemic colonies were obtained in 15 out of 30 cases. No correlation was found between the FAB classification, the CFU-GM growth pattern and the PHA-induced colony growth. A significant correlation was observed between PHA-induced colony growth and [3H]thymidine labeling index (p less than 0.001). A correction was also noted between the presence of leukemic growth and the failure of the induction treatment (p less than 0.02). The proliferation of the clonogenic blastic subpopulation selected by this technique seems to be linked to a poor prognosis.

Cell Division↗