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M F Poupon

Publications and source records attributed to M F Poupon.

At least 127 records · Page 7Linked to original sources
PubMed1984

Amplified pulmonary metastases of a rat rhabdomyosarcoma in response to nitrosourea treatment.

Repeated observations in our laboratory show that the chloroethylnitrosourea of cysteamine ( CNCC ) induces slowed tumor growth rate and decreased lymph node metastasis in rats bearing a rhabdomyosarcoma but concomitantly enhances metastatic dissemination in the lung. Tumors obtained by sc graft of tumor cells, in syngeneic rats, gave a reproducible pattern of metastases at nodal and pulmonary sites after a 60-80-day period. CNCC was administered orally at a dose of 50 mg/kg once a week for 5 weeks beginning at the time of tumor appearance. Forty-five of 46 CNCC -treated rats had lung metastases with 95 (+/- 9.7) nodules; in the control group 29 of 41 rats had lung metastases with 7 (+/- 1.5) nodules. This amplifying effect was found after treatment with two other nitrosoureas (chlorozotocin and hydroxyethylchloroethylnitrosourea ) but not with cyclophosphamide and methotrexate. Lung metastatic amplification was also observed after treatment of the 13762 mammary adenocarcinoma in Fischer rats and treatment of nickel-induced soft tissue tumor. Several hypotheses have been proposed. The dissociated effect of nitrosourea on local tumor, lymph nodes, and pulmonary metastases does not support the concept of systemic immunosuppression as the main mechanism of this phenomenon, but a decrease of local immunological defenses exerted by NK cells, for example, could be possible. Alternatively, a direct effect of the drug on lung tissue, especially lesions of endothelial tissue, could be responsible for the observed effect. Nitrosourea treatment of rats after surgical excision of the tumor, as adjuvant chemotherapy, was responsible for an amplification effect in association with local recurrences. From this fact we hypothesized that nitrosourea treatment could modify the equilibrium of cell subpopulations in the tumor by selecting highly metastatic drug-resistant variants. Although the mechanism of the amplifying effect of nitrosoureas has not been elucidated, our study shows a possible risk in the use of these drugs for inductive or adjuvant chemotherapy.

Adenocarcinoma↗
PubMed1984

[Experimental study of cancer metastasis].

Chemotherapeutic assays, using nitrosoureas, performed on tumor bearing rats have shown a regression of local tumor, accompanied with an amplification of pulmonary metastases, demonstrating that the treatment of metastasis differs from the treatment of a local tumor. Cells organizing a tumor are heterogeneous for their drug resistance, and for a series of properties including their ability to form metastasis. Metastatic cells have to leave the tumoral tissue, to traverse biological barriers, to resist to immune system, to implant and growth in the target tissue. An experimental model has been used to characterize metastatic cells. Metastatic potential has been defined as the ability to invade lungs. Highly metastatic cloned cell lines, such as subline 6, were strongly stimulated to proliferate by EGF, expressed fibronectin, actively degraded the extracellular matrix, rapidly attached to endothelial vascular cells, and resisted to natural killer lymphocytes. Inversely, weakly metastatic lines, such as subline 8, were preferentially stimulated by FGF and EDGF, poorly expressed fibronectin, did not degrade extracellular matrix, slowly attached to vascular cells, and were killed by NK lymphocytes. Studies on a large series of clones showed a diversity between them, and that no one property was determinant. Modulation of these characters by growth factors, hormones and immune state of the host is discussed, and leads to conclude that the expression of metastatic potential of a tumor depends on genetically defined characters and also on influences excerted by the host.

Animals↗
PubMed1984

[Fibroblast cooperation in the graft of tumor cells in nude mice].

The occurrence and growth of xenogenic tumors in athymic Mice depend on å number of factors: the level of the immune response, the number of the injected tumor cells and the microenvironment of the tumor cells. We have demonstrated that the addition of cultivated fibroblasts to murine sarcoma cells was necessary for tumors to take. The addition of irradiated fibroblasts or of a medium conditioned by fibroblasts had the same effect. We therefore hypothesize an interaction between the fibroblasts which produce factors necessary for tumor cells and murine sarcoma cells which then initiate a tumor in the host. In vivo, tumor cells could induce host fibroblasts to produce growth factor(s) which in turn would help to initiate and maintain tumor growth.

Animals↗
PubMed1983

Localization of gallium in tumor cells. Electron microscopy, electron probe microanalysis and analytical ion microscopy.

The incorporation of gallium in tumor cells in vitro and in solid tumors was studied with electron microscopy and two microanalytical techniques. It was thus possible (1) to directly prove that gallium is concentrated in lysosomes of tumor cells; (2) to demonstrate that in these lysosomes, gallium is precipitated with phosphorus; and (3) to propose a mechanism of gallium concentration in tumor cells; in this mechanism, the accumulation of gallium as phosphate salts in lysosomes is directly related to the acid phosphatase activity of these organelles.

Animals↗
PubMed1983

Variable susceptibility to NK activity of cloned cell lines derived from a primary rat rhabdomyosarcoma: relationship to metastatic potential.

In vitro cloned lines derived from a primary nickel-induced rat rhabdomyosarcoma exhibited diverse levels of susceptibility to spontaneous NK activity. The presence of NK target structures was revealed by competition assays on all cloned cell lines, and the NK susceptibility of the tumour lines varied according to their osmotic fragility. Tumour cell lines derived from metastatic lung nodules presented similar NK susceptibilities to cells originating from the primary tumour. However, cloned cell lines differed in their capacity to form lung colonies after i.v. injection, and in their potential for invading lungs after s.c. primary tumour development. No correlation was found between lung colonization potential and NK resistance. Studies of the correlation between metastatic potential and NK sensitivity revealed that (1) all the NK resistant tumour cells were highly metastatic; (2) NK susceptible tumour cells could be either highly or weakly metastatic. Therefore, highly metastatic tumour cells could be either resistant or susceptible to NK lysis. We conclude that the property of resistance to NK contributes to a high metastatic potential. However, other properties could counterbalance and finally prevail over NK susceptibility thus enabling NK susceptible cell lines to be also highly metastatic.

Animals↗
PubMed1983

Alphafoetoprotein uptake by cloned cell lines derived from a nickel-induced rat rhabdomyosarcoma.

Rat, mouse, pig and chicken alphafoetoproteins (AFP), rat serum albumin and egg albumin, or their fluoresceinated conjugates were added to cultures of several cloned cell lines isolated from a nickel-induced rat rhabdomyosarcoma. The intracellular uptake of assayed proteins was revealed by the indirect immunoperoxidase technique and/or by direct fluorescence microscopy. All the clones examined bound AFP, and all but one internalized the protein. The protein localized in the membrane and the cytoplasm, as well as along straight processes interconnecting cells. Nuclei were always AFP negative. The protein uptake of fluoresceinated conjugates of AFP and serumalbumin was already visible 15 min after incubation and progressed with time to reach a plateau 4-5 h later. Ultrastructural radioautographs of cells incubated with [3H]-AFP (rat) showed protein accumulation in several organelles and particularly in lipid droplets. Parallel to these observations, the intracellular presence of AFP within myofibrillar structures was demonstrated in tongue sections of rat foetuses and neonates. The results presented here provide experimental evidence of the reappearance in cloned cell lines derived from a primary rhabdomyosarcoma of a property pertaining to foetal striated muscle.

Animals↗
PubMed1983

Growth, metastasis, immunogenicity, and chromosomal content of a nickel-induced rhabdomyosarcoma and subsequent cloned cell lines in rats.

Karyotype patterns, growth, metastasis, and immunogenicity were compared in a rhabdomyosarcoma induced by a single injection of metallic nickel with those in subsequent tumor-cloned cell lines. The primary tumor was induced in a male WAG rat by im injection of 20 mg nickel powder. The parental cell line (9-4/0) and 8 cell subpopulations (J 9-4) isolated from a primary tumor by cloning on agarose were examined. The tumor cell dose inducing tumors in 50% of the animals after sc injection (TD50) and the in vitro growth characteristics showed a marked heterogeneity between parental and cloned tumor cell lines. In vitro doubling times and saturation densities were also heterogeneous without showing a discernible relationship with TD50. Chromosome patterns of the cell lines exhibited very similar modal numbers, whereas chromosome numbers were somewhat different; neither of these exhibited any correlation with tumorigenicity. Parental cell line 9-4/0 expressed a significant degree of immunogenicity, but it did not protect against pulmonary metastasis in immunized rats. Among 6 clones studied, only clone J 9-4/2 appeared to be immunogenic and reduced metastatic spread. The relevance of the comparison between the different characteristics is discussed.

Animals↗
PubMed1982

Heterogeneity of the growth and metastatic behavior of cloned cell lines derived from a primary rhabdomyosarcoma.

In order to study the heterogeneity of the metastatic and tumorigenic behaviors of malignant neoplasms, we have isolated a series of cloned cell lines from a primary nickel-induced rat rhabdomyosarcoma. The growth characteristics in vitro and in vivo and metastatic capacity following s.c. or i.v. injection of cells were compared to those of the parental cell line. Differences between the cloned cell lines themselves and between the clones and the parental cells were found in the number of metastases provoked by both i.v. and s.c. injections, in the number of cells required to induce s.c. tumors, and in the growth rate of those tumors. In vitro, the doubling times and saturation densities of the different cell lines varied greatly. A direct correlation was observed between the 50% tumoral dose and the initial tumor growth phase. We found that there was a tendency for lines which were highly metastatic after s.c. injection to have a low metastatic capacity after i.v. injection and inversely. The two types of metastasis (spontaneous and experimental) appear therefore to depend on different characteristics of the cells used.

Animals↗
PubMed1981

Adoptive transfer of immunity induced by semi-allogeneic hybrid cells, against a murine fibrosarcoma.

Semi-allogeneic somatic hybrid cells derived from the fusion of a C57BL/6 fibrosarcoma (MCB6-1) and A9 cells (C3H origin) were used to immunize C57BL/6 mice against the parental tumor cells. These hybrid cells expressed H-2 histocompatibility antigen of both parental cells (H-2b and H-2k), and failed to produce tumors in normal C57BL/6 mice. A single i.p. injection of hybrid cells induced anti-tumor immunity which could be transferred to normal C57BL/6 recipient mice by immune spleen or peritoneal cells; the efficient cells were T cells, as this activity was completely abrogated by treatment with anti-Thy-1-2 antiserum and complement. Among immune splenic T cells, only the light-density T cells, obtained after fractionation on Percoll gradient, were effective in the transfer of immunity. Immunity induced by the hybrid cells was specific for MCB6-1 parental tumor cells. This immunity could be transferred during two brief periods, 7 to 12 days, and 40 to 50 days, after hybrid cell injection; there appeared to be an intermediate period, 12 to 40 days after immunization, during which no immunity could be transferred. These results suggest a suppressive mechanism implicated during hybrid cell immunization and interacting with the anti-tumor immune response.

Animals↗
PubMed1981

Adoption of tumor immunity: role of the major histocompatibility complex.

T cells from spleens of mice immunized against a chemically induced tumor were able, when transferred to normal syngeneic mice together with tumor cells, to protect adoptively against tumor growth. The inability of such cells to identically protect pangenic nude mice and F1 hybrid mice, and the incompetence of T cells alone in the in vitro tests indicated that the T cells by themselves were unable to kill the tumor cells. We hypothesized that the protection transmitted by spleen T cells results from an interaction with the recipient mouse and that this interaction is controlled by the major histocompatibility complex (MHC). Analysis of the lack of protection at the level of the MHC subregion demonstrated that in the transfer of immune spleen T cells from parent mice to F1 recipient mice, an identity of the KIA subregion permitted a complete transfer of protection. In the transfer of immune spleen T cells from F1 mice to parent recipients, a semi-identity of the KIA subregion was sufficient but a complete identity of the H2D subregion was necessary. The use of such a model, requiring the transfer of parental cells to F1 hybrid mice, necessitated the analysis of the possible role of the hybrid resistance gene. We have demonstrated the absence of correlation between the hybrid resistance and the adoptive protection. At the present stage of this work, the adoptive neutralization test allows us to conclude that the immunologic rejection of a chemically induced tumor is the result of interaction between 2 cells, a T cell and a radioresistant non-T cell.

Animals↗
PubMed1979

Cytostatic effect of spleen cells of cyclophosphamide-treated mice on tumor cells.

Spleen cells of mice receiving an i.p. injection of a sublethal dose of cyclophosphamide (CY) have the ability to inhibit tumor growth in vitro. This effect is dose dependent and is maximal at the peak of the spleen regeneration which follows the phase of atrophy due to CY toxicity. This cytostasis is neither tumor-specific nor strain-restricted and the cells responsible for this inhibition of tumor cell multiplication have the characteristics of macrophages: they lack the Thy 1-2 antigenic marker, appear in CY treated nude mice, stick on plastic vessels, and are retained by adherence columns (nylon wool or Sephadex G10); their activity is greatly reduced when a specific macrohpage toxic reagent such as carrageenan is added to the cultures. The effector cells are similar to those which are able to suppress the response of normal splenocytes to T and B mitogens, and which appear in the same conditions of induction, after CY injection.

Animals↗
PubMed1979

Immunity to a 3-methylcholanthrene-induced fibrosarcoma in the C57BL/6 mouse: in vivo analysis by the adoptive tumor neutralization test.

Analyses of the adoptive tumor neutralization test (modified Winn test) in C57BL/6 mice made immune to a 3-methylcholantheene-induced fibrosarcoma showed that the reaction was mediated by a thymus-derived lymphocyte, it was tumor-specific, and the resistance of the immunized donor mouse to the challenge was strongly correlated with the protection of the recipient mouse. Proliferation of immune cells and close contact between tumor cells and immune T-cells were required. The hypothesis of a participation of the recipient in the reaction was considered because of the lack of adoptive protection of pangenic nude mice.

Animals↗
PubMed1978

Active suppression of in vitro reactivity of spleen cells after BCG treatment.

It was found that spleen cells from mice injected i.v. with large doses of BCG respond to PHA stimulation less intensely than do normal spleen cells. We were able to show that nylon wool column purified BCG treated T cells also had a low PHA reactivity. Unfractionated spleen cells, adherent cells or T-enriched populations from BCG treated mice, when added to normal T cells lowered their PHA reactivity. When the same BCG treated cell populations were added to tumor cells in vitro, they inhibited their growth.

Animals↗
PubMed1977

Splenic modifications induced by cyclophosphamide in C3H/He, nude, and "B" mice.

The spleen cell population of adult C3H/He mice injected with a single sublethal dose of cyclophosphamide (CY) has been analyzed. An initial phase of spleen atrophy is followed by a considerable hypertrophy, and a progressive return to normal. During the phase of spleen atrophy, both B and T cell compartments are depleted, as estimated by the percentages of cells killed by anti-Thy 1-2 and anti-Ig antisera plus complement. During the stage of regeneration, the percentage of Ig + cells increases rapidly, and at the peak of splenomegaly, the percentage of Ig + cells is high whereas almost no Thy 1-2 + cells are detectable. Progresively, the spleen cell content returns to the original values. In thymo-deprived mice (nude mice and B mice) the percentage of null cells increases during the stage of regeneration, and B mice develop a large number of Ig +-bearing cells. Histologic examination shows that follicles (B-dependent areas) disappear 1 to 2 days before periarteriolar sheaths (T-dependent areas). At the peak of splenomegaly the architecture of the spleen is destroyed, and the interstitial tissue is composed of a dense and uniform layer of lymphoid cells. Progressively, the architecture returns to normal. In nude mice, the disappearance of follicles, and the appearance of a homogenous layer of lymphocytes has been observed. When analyzed for their pattern of electrophoretic mobilities (E.M.), spleen cells from untreated mice reveal two peaks of E.M. 0.80 and 1.15 micron x s-1 x V-1 x cm-1. After CY treatment, during the step of splenic hypertrophy, these two peaks disappear, and a single peak of intermediate mobility appears. In T-deprived mice, a single peak of the same mobility is detected at this stage. The nature and origin of cells which appear during the phase of regeneration are unclear, but their appearance in T-deprived mice argues against thymo dependence. These spleen cells have the ability to suppress the response of normal spleen lymphocytes to T and B cell mitogens.

Animals↗
PubMed1977

Cytostatic effect of spleen cells of tumor-bearing mice on syngenetic tumor cells.

Spleen cell suspensions of methylcholanthrene-induced tumor-bearing mice were tested for their ability to inhibit tumor growth in vitro. The level of cytostasis was correlated with tumor growth and disappeared rapidly after surgical removal of the tumor. Pretreatment by anti-Thy 1-2 antiserum and complement, or by carbonyl iron and a magnet, showed that adherent, non-T-cells were the main effector cells of the cytostatic antitumor effect. Thymus cells suspensions from tubor-bearing mice were not effective in inhibiting tumor growth. This cytostatic effect was not tumor specific, inasmuch as the same spleen cell suspension inhibited growth of tumor cells of different origin.

Animals↗