PubMed Health⌕ Search

Biomedical subjects

S Ménard

Publications and source records attributed to S Ménard.

At least 181 records · Page 10Linked to original sources

Comparison of the natural humoral antitumor reactivity of different strains of mice.

Normal serum from C3Hf mice showed a complement-dependent cytotoxic reactivity against EL4 lymphoma cells, starting from 2 to 3 months of age, whereas normal serum from BALB/c and C57BL/6J mice became reactive only at a later age. The cytotoxins of normal sera of the 3 strains, as well as of a C57BL antiembryo antiserum studied in parallel, belong to the IgM class. When absorption were performed, using a variety of absorbing cells, marked differences were found among the sera, which according to their behavior could be divided in two groups: one group comprises the BALB/c and the C57BL sera, the other group the C3Hf serum from both young and old mice and the antiembryo antiserum. The reactivity of the 3 latter sera seems to be directed against specifities related to an ecotropic N-tropic virus, which on the contrary did not seem to be involved in the reactivity of BALB/c and C57BL sera. The C57BL antiembryo antiserum obtained by immunization with C3Hf embryos behaved differently from the C57BL normal serum and similarly to the C3Hf normal serum.

Animals↗

Natural antilymphoma antibodies in C3Hf mice serum: lack of identity with autoimmune and anti murine leukemia virus antibodies.

Absorption experiments on C3Hf normal mouse sera followed by cytotoxic tests on EL4 lymphoma cells were done to investigate a possible identity between natural antilymphoma antibodies (NAA) and various types of autoantibodies known to be present in normal mouse sera. Single C3Hf normal sera were also tested both by cytotoxicity on EL4 cells and by radioimmune precipitation assay (RIP) on 125I-labelled AKR ecotropic virus to ascertain whether or not viral antigen are the target structures of the NAA activity. The study provides evidence that NAA coexist with autoanticorpal and antiviral activities although they are distinct entities.

Animals↗

Natural anti-tumor serum reactivity in BALB/c mice. I. Characterization and interference with tumor growth.

A natural cytotoxic reactivity directed against syngeneic or allogeneic tumor cells was demonstrated in serum of BALB/c mice by an in vitro cytotoxicity test using rabbit serum as the source of complement. The reactivity, studied on syngeneic fibrosarcoma cells, was found to be minimal in mice less than 10 weeks old and to increase progressively with age. T-deprivation determined an increase of reactivity in young mice to levels reached spontaneously only by the serum of 40-week-old mice. The BALB/c serum also revealed natural anti-thymus antibodies. Non-identity between anti-tumor and anti-thymus antibodies was demonstrated by direct cytotoxicity and absorption tests. An inoculum of syngeneic fibrosarcoma cells increased the level of anti-tumor serum reactivity in both normal and T-deprived young mice. The natural anti-tumor cytotoxicity revelaed in vitro seemed to exert a specific in vivo protection as suggested by the indirect correlation found between the level of the natural anti-tumor reactivity and the grwoth of a transplanted fibrosarcoma.

Age Factors↗

Natural anti-tumor serum reactivity in BALB/c mice. II. Control by regulator T-cells.

By a complement-dependent cytotoxicity test, 37 sera from 1- to 18-month-old BALB/c mice were tested for natural anti-tumor and anti-thymus immune reactivity. The level of anti-tumor and anti-thymus antibodies increased with age, and a high individual variability, particularly evident in the older animals, was found. The appearance of the spontaneous antibodies was correlated to the T-cell status of mice. Animals with the higher spleen T-cell content were those with the higher anti-thymus and the lower anti-tumor natural antibody level, and vice versa. In T-deprived mice the anti-tumor response increased, whereas the anti-thymus response was not influenced. An inoculum of T cells from young to older syngeneic mice yielded a decrease of the anti-tumor response and an increase of the anti-thymus response. Homeostatic immunologic mechanisms, in which the cellular and the humoral system alternate in the tumor cell control, are suggested.

Age Factors↗

Relationship between antigenicity and morphology of murine lung adenomata.

Thirty-six lung adenomata induced in mice by urethane followed or not by cortisone, all had an adenomatous morphology at first s.c. transplant in syngeneic hosts. Seventeen of them acquired a sarcomatous structure within a few s.c. transplant generations whilst the other 19 remained adenomatous for as long as tested, i.e. at least 10 transplant generations. The change of morphology was not dependent on s.c. growth, since tumours also transformed when allowed to grow in the lung, and was not correlated to the capacity of a tumour for growth or metastasis. The 2 types of tumours were antigenically different, since only tumours that after few transplants changed their morphology were found at the first s.c. transplant to possess tumour-associated membrane antigens as revealed by an in vitro test. In addition, only the tumours which acquired a sarcomatous morphology were found gs-positive. The majority of antigenic primary tumours arose in mice belonging to the groups of treatment which induced the strongest immunodepression. It is suggested that a predisposition to sarcoma progression is related to an immunological control, at the time of adenoma induction, of an oncornavirus, responsible for the superimposed sarcomatous change.

Adenoma↗

Embryonic antigens shared between chemically induced lymphosarcomas and fibrosarcomas of the mouse.

An antiserum obtained by the immunization of C57BL/HeDp mice with a pool of C3HF/Dp 7,12-dimethylbenz[alpha]anthracene (DMBA)-induced fibrosarcomas exerted a specific cytotoxic activity in vitro on C57BL/HeDp chemically induced lymphosarcomas. Conversely, C57BL/HeDp spleen cells sensitized against C3Hf/Dp chemically induced lymphosarcomas or embryo cells were cytotoxic for plated cells of syngeneic DMBA-induced fibrosarcomas. Absorption studies with antiembryo and antilymphoma antisera showed that embryonic antigens were shared between lymphosarcomas and fibrosarcomas and that all serologically defined antigens present on lymphoma cells, including virus-related antigens, were also on fibrosarcoma cells.

Animals↗

Embryonic antigens and growth of murine fibrosarcomata.

The amount of embryonic antigens (EA) was estimated in 13 BALB/c fibrosarcomata by in vitro cell mediated cytotoxicity of anti-embryo spleen cells and by quantitative absorption of an anti-embryo antiserum. A direct relationship between amount of EA and tumour growing capacity was found. EA were detected also on fast dividing testicular cells. It is suggested that EA expression on tumour cells is related to a cell membrane function controlling mitosis rather than to a function specifically related to the neoplastic status. Tumour take of low doses of 2 EA-bearing sarcomata was found to be enhanced in anti-embryo immune BALB/c mice in comparison with that in normal and anti-fibroblast immune mice.

Animals↗

Immunogenicity and immunosensitivity of urethane-induced murine lung adenomata, in relation to the immunological impairment of the primary tumour host.

The depression of the immunological status of BALB/c mice treated during infancy with two different doses of urethane, alone or combined with cortisone, was evaluated by counting the number of plaque forming cells at 30 or 50 days of age. The incidence of lung adenomatous nodules was directly related to the degree of immunological impairment at 50 days of age. Twenty-seven lung adenomata were tested in an in vitro system involving spleen cells immune against the same single tumour used as target cell. Eighty-six per cent of tumours in the most immunodepressed group of mice were positive compared with 20-40% in the less immunodepressed groups. Syngeneic cross-reaction tests showed that non-immunogenic tumours were immunosensitive since 66% positive tests were obtained when target cells belonging to the less immunodepressed groups were tested with spleen cells of mice immunized with immunogenic adenomata.

Adenoma↗

Incidence, growth and antigenicity of fibrosarcomas induced by Teflon disc in mice.

Subcutaneous sarcomas were induced in BALB/c, C3Hf/Dp, and C57BL/He female mice by implantation of a Teflon disc or by injection of 7,12-dimethylbenz (a) anthracene (DMBA). The incidence of DMBA tumors was homogeneously high (60-86%) in the 3 strains, and the latency varied from 16 to 26 weeks from treatment. Teflon-induced tumors developed, in the BALB/c, C3Hf/Dp, C57BL/He mice, in 44, 94, and 30%, with a mean latency of 78, 61, and 82 weeks respectively. Evaluation of the growing capacity of 4 DMBA-induced and 14 Teflon-induced fibrosarcomas at the first and second transplant passage showed that Teflon tumors grew faster and needed a smaller cell dose to take than the DMBA tumors. Transplantation type antigens were detected only on the chemically induced tumors. Cross-reacting antigens were detected on 3 of the 5 Teflon-induced tumors by an in vitro assay for cell-mediated cytotoxicity.

9,10-Dimethyl-1,2-benzanthracene↗

Analysis of rabbit and guinea pig complement efficiency in cytotoxicity tests against fibrosarcoma and lymphosarcoma cells.

In a complement-dependent 51Cr cytotoxicity assay, using as target murine fibrosarcoma or lymphosarcoma cells, the rabbit complement (RC) was more efficient than guinea pig complement (GPC) when tested either with strong antisera, such as antihistocompatibility sera, or with weak sera, such as wera from normal mice shown previously to posses a natural antitumor response. The high efficiency of RC was not due to activation by antibodies of a different class or specificity than those activating GPC. In fact, both 2-mercaptoethanol (2-Me)-sensitive or-resistant immunoglobulins could activate both RC and GPC, and the results of absorption tests indicated that the antibodies detected using either of the 2 complements were directed against the same specificities. In addition, the results of tests searching for cooperative antibodies excluded that a cooperative effect might be responsible for the high efficiency of RC. With weak antisera, sera of different rabbits were found to have different complement activity.

Animals↗

Onco-embryonic antigens on murine normal adult cells.

Normal adult C57BL/6J fibroblasts, cultured to saturation density and therefore in resting phase, were harvested by EDTA, treated with trypsin at various concentrations for different lengths of time and then tested for absorbing capacity of a C57BL/He anti-embryo serum, the residual cytotoxic activity being measured by a 51Cr release assay on a C57BL/He lymphosarcoma known to carry embryonic antigens. A weak proteolytic treatment (0.05-0.25% trypsin for 5-10 min) uncovered structures which absorbed over 40% activity of the anti-embryo serum. The treated fibroblasts partially retained the absorbing capacity for an antihistocompatibility serum. Higher doses or longer exposure to trypsin progressively inactivated the absorbing capacity of fibroblasts for both antisera. Trypsin treatment of fibrosarcoma cells, which when untreated completely absorbed the anti-embryo serum, decreased their absorbing capacity. Additionally, normal untreated fibroblasts in growing phase were found to absorb the anti-embryo serum.

Animals↗

In vivo resistance and in vitro cellular reactivity against lymphosarcoma cells in immunized mice.

In an earlier report we have shown that an allogeneic but not a syngeneic immunization of mice with lymphoma cells evoked a humoral complement-dependent cytotoxic response against lymphoma cells syngeneic with the serum. Here we report the results of an investigation, using the same experimental model, on the cellular antitumor response in vitro and the in vivo tumor resistance. Both the allogeneic and the syngeneic antitumor immunizations induced a cellular immune response that was detectable in vitro and that not inhibited by the correspondent antiserum that was obtained with the same type of immunization. The humoral and cellular immune responses evoked in our system seem, therefore, directed against different antigenic determinants. In the in vivo experiments the maximal antitumor protection was obtained in mice immunized syngeneically, whereas the allogeneic immunization gave a protection that was similar to that obtained in mice immunized with normal allogeneic thymus cells. However, mitomycin-C-blocked thymus cells were unable to induce any protection against the tumor challenge, whereas blocked allogeneic tumor cells conferred the same degree of protection as that obtained with untreated cells. The in vivo transfer in untreated mice of sera obtained with syngeneic or allogeneic antitumor immunization did not give any protection against the tumor challenge.

Animals↗

Two novel monoclonal antibodies against the MUC4 tandem repeat reacting with an antigen overexpressed by lung cancer.

In this study we investigated the immunochemical and cytochemical reactivity of two monoclonal antibodies against the 16-amino acid tandem repeat of MUC4 to demonstrate a possible variation of the mucin core peptide expression related to lung cancer. The immunocytochemical anti-MUC4 reactivity was analyzed in four lung cancer cell lines (Calu-1, Calu-3, H460, SKMES) and in other tumor cell lines, as well as in frozen materials from 21 lung adenocarcinomas (ACs), including five bronchioloalveolar carcinomas (BACs), and 11 squamous cell lung carcinomas (SqCCs). A weak fluorescence anti-MUC4 positivity (range: 10.3-16.2) was observed only in acetone-fixed lung cancer cell lines Calu-1, Calu-3 and H460. These three lung cancer cell lines also showed a cytoplasmic immunoperoxidase reactivity. The immunostaining in lung cancer tissues showed a granular cytoplasmic reactivity: 15/21 (71%) and 17/21 (80%) ACs were positive with BC-LuC18.2 and BC-LuCF12, respectively. All BACs were positive. Moderate to strong reactivity was present in well-differentiated ACs. In the normal lung parenchyma counterparts weak reactivity was found only in bronchiolar cells. All SqCCs were negative. Anti-MUC4 reactivity was also observed in the alveolar mucus. In conclusion, our anti-MUC4 MAbs detect a secretion product present in mucus and this product is elaborated by lung cancer cells and overexpressed in well-differentiated lung ACs.

Adenocarcinoma↗