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Biomedical subjects

M Guigon

Publications and source records attributed to M Guigon.

At least 55 records · Page 3Linked to original sources
PubMed1990

Inhibition of human bone marrow progenitors by the synthetic tetrapeptide AcSDKP.

The purpose of this work was to study the effects of a tetrapeptide, acetyl-N-Ser-Asp-Lys-Pro (AcSDKP), an inhibitor of spleen colony-forming unit (CFU-S) entry into DNA synthesis, on human progenitor cells. Normal human mononuclear cells were incubated with concentrations of the synthetic tetrapeptide ranging from 10(-12) to 10(-7) M for 1.5 and 24 h and then plated in methylcellulose in the presence of human placenta-conditioned medium and recombinant human erythropoietin. The proportion of progenitors in DNA synthesis was determined by the thymidine suicide assay. Incubation with AcSDKP for 24 h leads to a significant inhibition of granulocyte-macrophage colony-forming unit (CFU-GM) and erythroid burst-forming unit (BFU-E) growth and in some cases of erythroid colony-forming unit (CFU-E) growth. The inhibition, which was never greater than 50%, was obtained with 10(-10)-10(-9) M AcSDKP, whereas no effect was seen at higher concentrations. The percentage of CFU-GM, BFU-E, and CFU-E in DNA synthesis was significantly reduced in five consecutive patients after incubation of cells for 24 h with inhibitory doses of the peptide, indicating that it is active on cycling cells. Therefore, these studies provide the first evidence that the tetrapeptide AcSDKP, originally obtained from bovine marrow and now chemically synthesized, is able to inhibit the in vitro growth of human progenitors and to decrease their proportion in cell cycle.

Amino Acid Sequence↗
PubMed1989

Long-term effects of high doses of cytosine arabinoside on pluripotent stem cells (CFU-S).

The purpose of this work was to investigate the long-term effects of high doses of cytosine arabinoside (Ara-C) on the pluripotent stem cell (spleen colony-forming units; CFU-S) compartment in mice. Studies were carried out on mice that survived the administration of repeated high doses of Ara-C (HDAra-C) with or without the injection of a partially purified CFU-S inhibitor or a bone marrow graft. The following features were examined 1, 1.5, and 5-7 months after treatment: CFU-S number, proliferative ability, and differentiation into different lineages. The results indicate that these parameters, which were severely disturbed soon after drug administration, returned to control levels within a month and remained unchanged as compared to age-matched controls for the following 6 months. Therefore, HDAra-C, given alone or with a CFU-S inhibitor or prior to bone marrow grafting, did not seem to induce long-lasting damage of the CFU-S compartment. However, our studies cannot eliminate the possibility of some residual stromal damage or some impairment of other properties of stem cells. It would be of importance to further clarify these points because HDAra-C are now used in the treatment of leukemias and prior to bone marrow transplantation.

Animals↗
PubMed1986

Differentiation pathways of pluripotent hemopoietic stem cells in long-term mouse bone marrow culture.

Differentiation pathways of CFU-S were examined in mouse bone marrow long-term culture system. E/G ratios of non-adherent CFU-S in this system increased from 2 to 7-9 by 2-3 weeks of culture and then fluctuated during the culture period. On the other hand, E/G ratios of adherent CFU-S were lower than that of non-adherent CFU-S, and always remained under 2. Some of the supernatants collected from culture flasks at weekly intervals increased E/G ratios of normal bone marrow CFU-S after 18-20 h of incubation. These results suggest that the differentiation of CFU-S is controlled by humoral factors, secreted from yet unknown cells in bone marrow, in this system.

Animals↗
PubMed1986

Pluripotent haemopoietic stem cell entry into DNA synthesis in vitro after stimulation by Ara-C treatment in vivo.

Non-cycling pluripotent bone marrow stem cells (CFU-S), taken 3 hrs after injection of 20 mg of Ara-C, have been shown to enter DNA synthesis at 1 to 3 hr after being cultured in alpha-medium. This phenomenon was observed when bone marrow was incubated as a plug, but not when incubated as a cell suspension in the present experimental conditions. These results suggest that a medullary structure is necessary in order to observe this effect and/or that accessory cells are destroyed during the process of single cell preparation.

Animals↗
PubMed1985

Cyclic AMP response to various haemopoietic regulators.

Diffusible inhibitors and stimulators are involved in the regulation of bone marrow pluripotent stem cell (CFU-S) proliferation. We have previously shown the existence of CFU-S inhibitors in foetal calf marrow and liver and have started their purification. The lack of a simple and time-saving test to determine the kinetic state of CFU-S and the activity of the inhibitors led us to explore the possibility of a biochemical proliferation marker that could be used for screening purpose. Since it was shown that cyclic AMP was implicated in the regulation of CFU-S proliferation, it was of interest to study the variations in cAMP levels after stimulation and inhibition of CFU-S entry into cycle. The results of in vitro experiments showed that the increase in cAMP levels observed in bone marrow cells after incubation with different haemopoietic stimulators was specific neither for bone marrow cells nor for the various haematopoietic regulators. In the in vivo experiments, an increased cAMP level was observed 8 hr after one injection of Ara-C at the time when CFU-S are recruited into S phase. However, no modification of cAMP levels has been observed after injection of CFU-S inhibitors in the Ara-C-treated mice. Although cAMP does not seem to be a suitable marker for testing the activity of inhibitory fractions during the purification process, this work has contributed to the study of CFU-S stimulators.

Animals↗
PubMed1984

A convenient source of CFU-s inhibitors: the fetal calf liver.

The presence of a bone-marrow stem-cell inhibitor able to prevent CFU-s entry into DNA synthesis after cytosine arabinoside (Ara-C) treatment has been detected in 7-month-old fetal calf liver. The inhibitory fraction was obtained through ultrafiltration of a delipidated tissue extract powder and purified by BioGel-P-2 chromatography. The elution pattern on Sephadex G10 is similar to that of the bone-marrow inhibitory extract previously obtained from fetal calf bone marrow. It corresponds to a low-molecular-weight molecule (MW less than 2000), devoid of species specificity and having no inhibitory effect on GM-CFC proliferation.

Animals↗
PubMed1983

Further purification of a CFU-S inhibitor: in vivo effects after cytosine arabinoside treatment.

This paper describes a large scale extraction procedure which allows the preparation of a stable CFU-S inhibitor from fetal calf bone marrow. The use of BioGel P-2 gels results in an increase of the specific activity of the inhibitor as well as in the yield of the preparation. When injected into mice, the inhibitory fraction (Ve/Vo 1.17-1.8) prevent CFU-S entry into cycle after cytosine arabinoside at a dose of 4 micrograms per mouse. When administered during lethal protocols of Ara-C treatment, it significantly increases the percentage of surviving animals. Thus, this low molecular weight factor (below 2,000 D), devoid of species-specificity, enhances the tolerance of animals to high doses of chemotherapy and might be of interest in cancer treatment.

Animals↗
PubMed1982

Protection of mice against lethal doses of 1 beta-D-arabinofuranosylcytosine by pluripotent stem cell inhibitors.

The aim of this work was to study whether an inhibitor of pluripotent stem cell (CFU-S) recruitment, which we have shown previously to be able to increase the number of CFU-S after a fractionated treatment with 1-beta-D-arabinofuranosylcytosine, could increase the survival of mice given injections of lethal doses of the same drug. Two protocols of 1-beta-D-arabinofuranosylcytosine treatment were used in two different mouse strains, which both killed the mice within a week. An inhibitor of CFU-S was prepared by dialysis from fetal calf marrow, and a first step of purification was made by chromatography on Sephadex G-10. When given injections 2 hr before the drug, the number of surviving mice was increased significantly with the dialysate; fractions separated by chromatography appeared to be more effective to increase the animal survival. These preliminary results indicate that a factor of low molecular weight (below M.W. 3500) extracted from fetal calf marrow is able to protect animals during 1-beta-D-arabinofuranosylcytosine treatment. The inhibitor seems to be specific for CFU-S, without any inhibiting effect on tumor cell kinetics in vitro. If the absence of species specificity found for higher to lower species is confirmed for the lower to the higher species, then this inhibitor could be an effective tool during cancer chemotherapy.

Animals↗
PubMed1981

[Inhibitors of bone marrow stem cells proliferation. Possible applications during chemotherapy (author's transl)].

An inhibitor of bone marrow stem cell (CFU-S) proliferation, prepared from fetal calf marrow, was administered to mice during sequential treatments with Cytosine Arabinoside. Results show that the percentage of CFU-S survival is significantly increased when the inhibitor is given simultaneously with the drug. A purified fraction of the inhibitor obtained by chromatography permitted survival of mice receiving lethal doses of Cytosine Arabinoside. The inhibit seems to be specific for CFU-S and has no effect on EMT6 tumor cells in vitro. Since it is not specific for the animal species, its clinical use could be envisaged to protect bone marrow during chemotherapy.

Animals↗
PubMed1978

Stimulating factors and cell recruitment in murine bone marrow stem cells and EMT6 tumours.

The role of a stimulating factor in cell recruitment and the kinetics of its secretion were investigated by in vivo and in vitro techniques. The association of these two methods made it possible to demonstrate that a non-cycling population liberates a factor which in turn stimulates quiescent bone marrow stem cells into DNA synthesis. Moreover, it seems that undamaged cells are capable of secreting this factor. A stimulating factor responsible for cell recruitment was also demonstrated in an experimental EMT6 tumour and the kinetics of its secretion reported.

Animals↗
PubMed1978

Inhibition of CFU-S entry into cell cycle after irradiation and drug treatment.

The cell cycle inhibition of pluripotent bone marrow stem cells (CFU-S) by a fetal calf bone marrow extract (BME) was studied. The normally quiescent cells were made to enter cell cycle by treatment with either irradiation or the phase specific drug cytosine arabinoside (Ara-C). Using the vitro-vivo system of Frindel et al., we have shown that when the BME was added to the incubation medium, no triggering of CFU-S into cycle could be observed. The inhibitory effect was also demonstrated when the BME was injected simultaneously with the drug. The possible relationships of BME with stimulating factors controlling CFU-S entry into cycle are discussed.

Animals↗
PubMed1976

Study of an inhibiting factor of epidermal proliferation in plucked skin and various tumours of mice.

The aim of our research was to investigate, by autoradiographic methods, the presence of an inhibitory factor (IF) in normal skin, in plucked skin and in five experimental skin tumors of the mouse, capable of inhibiting epidermal proliferation. The experimental model used was that of Bullough & Laurence (1960), i.e. a wound in the ear of a mouse. After tritiated thymidine administration the measurement of the labelling index confirmed the existence of an inhibitory substance in normal skin. The plucked skin had no inhibitory effect when it was taken 24 h after plucking, but after 4 days its effect had returned to normal. The skin tumours, whether epithelial or mesenchymal, showed the same inhibitory effect as normal skin whereas a non-cutaneous tumour tested had no inhibitory effect.

Animals↗