PubMed Health⌕ Search

Biomedical subjects

M F Poupon

Publications and source records attributed to M F Poupon.

At least 91 records · Page 5Linked to original sources
PubMed1992

[The role of gastrin releasing peptide as a lung growth factor].

The proliferation of the bronchial epithelium and tumors associated with this tissue is controlled by various growth factors. The main factor is Gastrin Releasing Peptide (GRP), the human counterpart of the amphibian bombesin. These neuropeptides also act as neuromediators and gut hormones. All peptides of this family share a conserved C terminal sequence which is required for biological activity. The determination of this sequence has provided the basis for the design of specific agonist and antagonist peptides and for the generation of monoclonal antibodies (Mab). GRP interacts with a receptor coupled to a G protein and the signalling process leads to the activation of phospholipase C and kinases, and the mobilization of calcium. GRP promotes the proliferation of foetal and adult bronchial epithelium and of small cell lung cancer (SCLC) cells. GRP is also an autocrine growth factor for some SCLC cell lines. The growth of these lines is reduced in vitro and in vivo by MAb and specific antagonists. Hyperplasia of GRP producing cells has been shown in various lung diseases in adults and children. Pharmacological data on GRP suggest that its antagonists could be used in the treatment of SCLC (in addition to chemotherapy) and of interstitial lung disease. The cloning of the GRP receptor should facilitate the design of specific and potent antagonists of the peptide.

Adult↗
PubMed1991

Preclinical antitumor activity of a new Vinca alkaloid derivative, S 12363.

S 12363 is a new Vinca alkaloid derivative obtained by appending an optically active alpha-aminophosphonate at the C23 position of O4-deacetyl vinblastine. S 12363 was evaluated for cytotoxic and antitumor activity against a spectrum of murine and human tumors. This compound was, respectively, on average, 72- and 36-fold more cytotoxic than were vincristine and vinblastine, when tested on a panel of 2 murine and 37 human tumor cell lines using the microculture tetrazolium assay. S 12363 exhibited significant antitumor activity against murine transplantable tumors (i.p. and s.c. P388 leukemia, i.p. L1210 leukemia, i.p. and i.v. B16 melanoma, i.p. M5076 sarcoma, and s.c. colon adenocarcinoma 38), while no activity was observed on s.c. Lewis lung carcinoma. S 12363, when administered i.p., showed moderate activity on human NCI-H460 lung and PANC-1 pancreas tumor xenografts in nude mice. However, when it was administered i.v., it exerted a significant activity against human HT-29 colon, NCI-H460 lung, NCI-H125 lung, PANC-1 pancreas, and A-431 vulvar tumor xenografts. S 12363 was also active in vivo against a P388 leukemia subline resistant to vincristine. On the in vivo panel of tumors used in this study, S 12363 was at least as active as reference compounds, while its optimal dosage was 10- to 40-fold lower than that of vinblastine, depending on the models studied. The effects of schedule and route of administration on the antitumor activity of S 12363 were studied in both i.p. inoculated P388 leukemia and B16 melanoma, in which the activity was improved by single and intermittent treatment (Days 1, 8, and 15) and i.p. route. S 12363, which differs only by the configuration of the asymmetric carbon atom of the side chain, was 300-fold less cytotoxic and 1000-fold less potent in vivo than was S 12363. These results suggest that S 12363 could present a therapeutic advantage over its congeners and deserves further pharmacological evaluations.

Animals↗
PubMed1991

Liver tumors in cirrhosis: experimental study with SPIO-enhanced MR imaging.

The influence of cirrhosis on superparamagnetic iron oxide (SPIO)-enhanced magnetic resonance (MR) imaging of the liver was studied in 31 rats. Experimental models included carbon tetrachloride-induced cirrhosis and liver engrafting of rhabdomyosarcoma S4T cells. Hepatic uptake of SPIO measured with relaxometry decreased dramatically with histologic grade, while splenic uptake increased; the same results were achieved by calculating K values. Imaging of 13 tumorous cirrhotic rats confirmed these results by showing a muted decrease in liver signal intensity on spin-echo images after injection of SPIO. Nevertheless, all intrahepatic tumors could be visualized, as confirmed by postmortem examination. On gradient-echo images, postinjection contrast between the tumor and the liver was not affected by cirrhosis. Thus, despite strong impairment of hepatic uptake in cirrhosis, the diagnostic efficacy of MR imaging with SPIO did not seem to be significantly affected.

Animals↗
PubMed1991

[Metastatic dissemination of cancer cells].

During the natural history of a tumor, cancer cells become more and more aggressive and their increasing malignancy leads usually to the patient's death. The expression of malignant properties by tumor cells is manifested by the occurrence of metastases and is the result of an overexpression of molecules that are normally or barely non expressed by the normal cell progenitors. These molecules can be involved in cell attachment (receptor to the extracellular matrix), in proteolysis (collagenases), in angiogenesis (b FGF), in adhesion to endothelial cells, in resistance to the immune system. The genetic instability of tumor cells favors the amplification, mutation and gene translocation events, resulting in the activation of some genes or/and oncogenes which might direct the expression of the malignant properties. Finally, metastatic cells have been shown to have a growth advantage over non metastatic cells, so that metastatic cell population becomes ultimately numerously dominant in the primary tumor. The current knowledge about the malignant cell properties allow us to begin to understand how a cancer cell becomes metastatic and how the metastatic dissemination is usually an ineluctable process.

Animals↗
PubMed1991

[Vectorisation of doxorubicin in nanospheres and reversion of pleiotropic resistance of tumor cells].

A multidrug resistance human cell line (Dox-R-MCF7), originating from mammary adenocarcinoma was compared to the drug sensitive parent line (MCF7) to determine whether or not the use of doxorubicin-loaded biodegradable nanospheres (NS-Dox) could circumvent drug resistance. The Dox-R-MCF7 line was shown to resist free doxorubicin (Dox) as the 50% lethal dose for them was 150 times higher than for the sensitive cell-line. Isohexylcyanoacrylate nanospheres, porous matrices of biodegradable innocuous polymer, diameter 300 nm, were loaded with doxorubicin. Free Dox, NS-Dox and Dox-free polymer (NS) were added to the culture medium for 6 hrs. In terms of 50% lethal dose, NS-Dox were cytotoxic for the resistant cell line to an identical extent as for the sensitive parent line. Dox-free nanospheres alone or mixed with free-Dox were noncytotoxic for the resistant line. Drug targetting could be of main importance to overcome multidrug resistance.

Breast Neoplasms↗
PubMed1991

Heparin-binding sites of rat rhabdomyosarcoma cells with low and high metastatic capacity.

Proteins able to bind the iduronate containing glycosaminoglycans: heparin, heparan sulfate and dermatan sulfate, were detected in strongly (RMS 0) and weakly (RMS 8) metastatic rat rhabdomyosarcoma cell lines. The 35S-methionine-labeled proteins solubilized from the cell membranes were chromatographed on Heparin-Ultrogel affinity column. The main retained protein migrated with an apparent molecular size of 19 kDa on polyacrylamide gel electrophoresis from both cell lines. The 19 kDa protein exhibited a higher affinity for iduronate containing glycosaminoglycans than for the glucuronate containing chondroitin sulfates. It was immunologically distinct from acid and basic fibroblast growth factors. The membranes of the RMS 8 cells contained about a two times higher amount of labeled 19 kDa protein than the membranes of the RMS 0 cells. The decreased amount of the labeled heparin-binding proteins in the highly metastatic cell line is in agreement with the previously evidenced decreased receptor-mediated binding of the iduronate containing glycosaminoglycans by these cells.

Animals↗
PubMed1990

Methionine dependency of malignant tumors: a possible approach for therapy.

When methionine (Met), an essential amino acid, was substituted for by its precursor homocysteine (Hcy) in the culture medium, normal cells such as fibroblasts proliferated normally. In contrast, many tumor cells failed to grow or grew at a lower rate. Met dependency is acquired simultaneously with cell transformation, as observed with HBL 100, a human mammary epithelial cell line that acquired increased malignancy as a function of in vitro passage number, and NIH/3T3 (J10), a mouse fibroblast line transformed by transfection with the human HRAS oncogene. A relationship was observed between Met dependency and metastatic potential of the RMS-21, RMS-S4T, and RMS-J1 sublines derived from RMS-0, a rat rhabdomyosarcoma cell line: the higher the metastatic potential of the cell line, the higher the concentration of Met required to maintain its proliferation. Met-independent cells derived from the RMS-0 line, obtained by a progressive decrease of Met in the culture medium lost their tumorigenicity when injected into rats fed with Met-deprived diets. In addition, the in vitro motility of RMS-S4T tumor cells, a marker of metastatic capability, decreased in Met-free Hcy-complemented (Met- Hcy+) medium. Similarly, RMS-0 tumor cells, preincubated in a Met- Hcy+ culture medium for 24 hours, evidenced a decreased capacity to form lung colonies when injected into syngeneic rats: the median number of lung colonies was 27 and 3 (P less than .05) for cells cultivated in Met+ Hcy- and Met- Hcy+ media, respectively. An amino acid-defined mixture reproducing casein composition was used as a protein source in the diets fed to RMS-J1 tumor-bearing rats. Dietary substitution of Hcy for Met (i.e., met deprivation) resulted in decreased tumor growth (from 44.4 +/- 1.0 to 40.6 +/- 1.4; P less than .05) and prevention of metastatic spread (from 37 to 0; P less than .05). In conclusion, exogenous Met can be substituted for Hcy to maintain the survival of normal cells but is essential for tumor cell growth in vivo as well as in vitro. Therefore, this defect of cancerous versus normal cells could be used for a therapeutic purpose.

Adenocarcinoma↗
PubMed1989

Binding and internalization of exogenous glycosaminoglycans in weakly and highly metastatic rhabdomyosarcoma cells.

The fate of exogenous glycosaminoglycans in cultures of strongly (RMS 0) and weakly (RMS 8) metastatic rat rhabdomyosarcoma cells was studied. The time course and concentration dependence of binding and internalization of the radiolabeled sulfated glycosaminoglycans were determined. Weakly metastatic cells took up heparin, heparan and dermatan sulfates into their pericellular compartment at a higher rate than the strongly metastatic RMS 0 cells. The RMS 8 cells exhibited about two times more binding sites for these iduronic acid containing glycosaminoglycans, and internalized higher amounts of them than the RMS 0 cells. The uptake of the chondroitin sulfate into the peri- and intracellular compartments of both cell types was about 5-15% of that of the other glycosaminoglycans studied. The specificity of displacement of the pericellular heparin and dermatan sulfate by the unlabeled glycosaminoglycans indicates the involvement of specific structural features of the polysaccharide chains in the interactions of glycosaminoglycans with the surface of rhabdomyosarcoma cells, beside ionic forces due to the polyanionic character of the glycosaminoglycans. Heparin and heparan sulfate degradation products, mainly large oligosaccharides, were recovered from the surface of RMS 0 cells but were absent on the surface of the RMS 8 cells. About 30% of the internalized heparin and heparan sulfate was present in the partially degraded form in both cell types. Oligosaccharides derived from glycosaminoglycans were not released into the medium. The decrease in the amount of iduronic acid containing glycosaminoglycans internalized by the highly invasive cells seems to be correlated with an increased cell-associated degradation and with an apparent loss of glycosaminoglycan binding sites on the cell surface.

Animals↗
PubMed1989

Promotion of micrometastasis proliferation in a rat rhabdomyosarcoma model by epidermal growth factor.

Using a rat rhabdomyosarcoma 9-4/0, we investigated the role of epidermal growth factor (EGF) in tumor dissemination. In vitro, we detected high-affinity EGF receptors on tumor cells and stimulation of their proliferation by EGF. When injected iv, EGF-pretreated cells demonstrated an increased capacity to form lung colonies and to invade lymphatic tissue. In vivo, EGF treatment led to increased metastatic spread of subcutaneous tumors. When primary tumors were ablated, and the treatment was given from the time of graft until ablation (seeding step), no effect on metastatic spread was noticed. When treatment was given from the time of ablation until death (growth step), EGF increased the number of lung metastases and of invaded lymph node sites.

Animals↗
PubMed1988

Correlation between reversion of a dedifferentiated rat hepatoma line and the recovery of tumorigenicity.

The injection into athymic nude mice of well-differentiated cells of the H4IIEC3 rat hepatoma line leads to tumor take and growth. Animals given injections of cells of a "dedifferentiated" variant subclone, however, do not develop tumors, whereas revertant clones are malignant. Nevertheless, tumors are obtained by increasing the number of injected dedifferentiated cells, and the cells from these tumors do express liver-specific messenger RNAs. Finally, the differentiated state of these tumor cells is stable in vitro. This correlation between the differentiated state of the cells and tumorigenicity is also observed in somatic hybrids between the variant cells and the differentiated ancestors. These hybrids express the hepatic functions and give rise to tumors. The only in vitro character of transformation which distinguishes the two types of cells is anchorage independence of growth. Since two other independent variants develop tumors, it is established that the nonmalignant state is not simply due to the lack of expression of liver-specific traits. There is strong evidence that different mechanisms are responsible for the dedifferentiated state of the two classes of variants, and this supports the hypothesis that the correlation between the dedifferentiated state of the nonmalignant variant and its nontumorigenic phenotype relies on the level of regulation specifically affected in this clone.

Animals↗
PubMed1988

In vivo emergence of a highly metastatic tumour cell line from a rat rhabdomyosarcoma after treatment with an alkylating agent.

Rats bearing a transplanted nickel-induced rhabdomyosarcoma (RMS 9-4/0), treated with chlorozotocin (CZT), an alkylating agent, showed an amplified metastatic invasion of the lung (median of 165 lung tumour nodules, compared to 3 for untreated controls). A higher level of metastatic invasion (200 nodules) was reached spontaneously after the grafting of the S4T line, which was obtained by successive in vivo passages of RMS 9-4/0 cells in CZT treated rats. S4T tumour cells also invaded the liver and a considerable proportion of the lymph nodes. The NT4T line, obtained by successive in vivo passages in untreated rats, showed a lesser degree of enhancement of metastatic capacity (57 nodules). Both derived lines proved to be more aggressive than the parental, proliferated more rapidly, and were resistant to CZT toxicity. Only the non-treated lineage became more resistant to NK lysis. The S4T line lost its myogenic differentiation and was best described as a fibrohistiosarcoma, whereas NT4T did not. Chromosome analysis demonstrated a reduced range of chromosome number per cell in both lines. We conclude that both S4T and NT4T tumours became more metastatic than RMS 9-4/0 as the result of tumour progression through in vivo passages, and that in addition S4T acquired a spontaneously higher metastatic potential, similar to that which occurred in rats grafted with RMS 9-4/0 or NT4T tumours and treated by CZT. This suggests an inheritable mutation in the S4T line.

Animals↗
PubMed1988

[Recent progress in the biology of small cell bronchial carcinoma].

Progress achieved in the understanding of small cell lung cancer (SCLC) include: the establishment and characterization of cell lines with the identification of a variant type with poor prognosis; the use of non-specific biochemical markers such as neuron specific enolase (NSE) and calcitonin; the generation of monoclonal antibodies (MoAbs) directed against SCLC antigens; growth factors including GRP and IGF. GRP or human bombesin produced by the tumor cells favours their own growths; in cytogenetics, with the observation of a characteristic chromosomal abnormality: the deletion of the short arm of chromosome 3 (3p 14-23). The region deleted is currently under study to identify the genes potentially involved in the oncogenesis of SCLC. the activation of several oncogenes: C-myc, N-myc, L-myc, Myb, Raf-1. The amplification of C-myc favors the tumor cell progression and is related to a bad prognosis. This biological approach has confirmed the neuroendocrine origin of these tumor cells (as a result of protein studies of the cytoskeleton and of MoAbs); it has allowed the use of tumor markers in the diagnosis and work-up of SCLC and the consideration of new therapeutic approaches. Current studies concern the deletion of 3p- and the integration of the cytogenetic data, growth factors and oncogenes in a coherent model of the genesis of SCLC.

Biomarkers, Tumor↗