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Biomedical subjects

G Mathé

Publications and source records attributed to G Mathé.

At least 271 records · Page 15Linked to original sources
PubMed1981

Prevention of spontaneous tumors of aged mice by immunopharmacologic manipulation: study of immune antitumor mechanisms.

Effects produced by long-term application of three immune modifiers (azimexon, retinoic acid, and tuftsin) on the depressed immune systems of 18-month-old inbred C57BL/6 female mice were investigated. The effect of each agent was examined on four cell types (cytotoxic T-cells, K-cells, NK cells, and macrophages) possibly involved in antitumor defenses and on the spontaneous tumor development that accompanied advancing age. Three substances chosen for this study appeared able to alter immune parameters, and each one displayed its own pattern of activity. Common to all three agents were an increase of age-depressed tumoricidal activity of peritoneal macrophages and no effect on the depressed NK activity of spleen cells. Retinoic acid increased splenic K-cell activity, already elevated in aged mice and unaffected by the other two agents. Cytotoxic T-cell activity, diminished by age, was stimulated considerably by retinoic acid and by tuftsin but only slightly by azimexon. Histopathologic studies revealed a decrease in the incidence of spontaneous tumors in the 3 treated groups. This decrease was statistically significant in the retinoic acid- and tuftsin-treated groups when compared with the incidence in untreated mice of the same age. Correlation of drug-induced modifications of the immune system with tumor incidence in aged mice was attempted.

Adjuvants, Immunologic↗
PubMed1981

Cellular blood fluorescence polarization: a possible prognostic tool in human acute lymphatic leukemia.

We measured the fluorescence polarization of 1-6 diphenyl hexatriene in mononucleated cells from the peripheral blood of 49 acute lymphoid leukemic patients in complete hematological remission with an Elscint MV-1 microviscosimeter. The measurements of fluorescence polarization were made at various times after the remission was achieved. Our results represent two years of this prospective study. We found that lymphoid leukemic patients in remission could be separated into two groups according to the lowest value of fluorescence polarization of their blood cells. 1) The first group of 26 patients showed values superior to 3.44 poises, in all samples, corresponding to the lowest value of normal controls. 2) The second group showed at least one value of blood fluorescence polarization lower than 3.44 poises. This second group had a significantly lower median duration of remission and survival compared to the first. We have subdivided these two groups according to other established prognostic parameters such as cytological subtype and initial volume of the disease: we found that cellular fluorescence polarization could give additional prognostic information. These data suggest that fluorescence polarization measurements have a prognostic value to follow acute lymphoid leukemia patients in complete remission: when a low value is found there is a significant risk of relapse.

Adolescent↗
PubMed1980

[The management of ovarian adenocarcinoma. "Second look" surgical operation after chemotherapy (author's transl)].

Forty patients with adenocarcinoma of the ovary (including 34 in stages III and IV) underwent a "second look" surgical operation after a first course of chemotherapy. The operation, which carried negligible morbidity, demonstrated complete remission in 27,5% of the cases; whenever necessary and possible achieved complete remission by surgical excision; and helped in establishing a second course of chemotherapy or chemo-immunotherapy. This therapeutic strategy seems to have had overall favourable repercussions on the patients' short- and mid-term survical. Long-term results cannot yet be assessed, but the knowledge of late failures suggests that applying intensive chemotherapy or, preferably, chemo-immunotherapy after the "second look", or even reserving potent cytostatic drugs for that period, could be beneficial. From the very favourable survival rate in patients found on second look to have complete remission, one may conclude that surgically confirmed remission should be considered as the primary target of the initial treatment.

Adenocarcinoma↗
PubMed1980

Vindesine: a new vinca alkaloid.

Vindesine (VDS) is an analogue of the vinca alkaloids. Its spectrum of antitumoral activity is similar to that of vincristine (VCR), but with milder experimental neurotoxicity, and it inhibits the polymerization of tubulin. Its terminal half-life is 24 h and its plasma clearance is intermediate between those of vinblastine (VLB) and VCR. The maximal tolerated dose is 4-5 mg/m2/week, the dose-limiting toxicity being myelosuppression (nadir by days 7-8 and recovery by days 11-13). It has already been demonstrated as efficient in childhood acute lymphoid leukemia (ALL), non-Hodgkin's lymphoma, blastic crisis of chronic myeloid leukemia, and esophageal carcinoma. It has also shown activity in Hodgkin's disease, breast and germ cell carcinomas, and melanoma. Intolerance is mainly neurologic, with paresthesias, without motor impairment, or hematologic, with leukopenia, and sometimes alopecia, asthenia, and muscle pains. The results are better if the patients have not been treated previously; continuous infusion could be of interest and there appears to be no cross-resistance with its parent VCR, as documented in ALL.

Animals↗
PubMed1980

Cisplatinumdiamminodichloride (CPDD) in chemotherapy of cancers: a phase II therapeutic trial.

We have conducted a phase II trial of cisplatinumdiamminodichloride (CPDD) which not only demonstrated its remarkable activity in embryonic carcinoma of the testes, but also in ovarian carcinoma, in melanoma, and in epidermoid carcinoma, especially of the head and of the uterus cervix. Its toxicity, manifested mainly in the digestive and renal tracts, confines its administration to hospitalized patients only. This compound is now indicated in combination therapy for the above-mentioned tumors.

Adolescent↗
PubMed1980

Preclinical and phase I studies of malonatoplatinum.

After preclinical toxicologic study in baboons, we are conducting a phase I trial of malonatoplatinum, starting with 3 mg/kg and now reaching 1 mg/kg. Toxicity, mainly hematologic, was mild and our study was mainly limited by poor solubility. Regressions, which have been rare in the advanced-tumor patients, have been observed in three patients considered as clinically resistant to cisdichlorodiammino-platinum (DDP). Malonatoplatinum pharmacokinetics appeared similar to those of DDP as far as total platinum is concerned.

Adolescent↗
PubMed1980

Ultrastructural study of the cardiotoxicity and light-microscopic findings of the skin after treatment of golden hamsters with seven different anthracyclines.

Golden hamsters were administered seven anthracyclines: adriamycin (ADM), detorubicin (DTR), daunorubicin (DNR), 4'-epi-adriamycin (eADM), rubidazone (RBZ), aclacinomycin (ACM), and N-trifluoroacetyladriamycin-14-valerate (AD-32), three times a week during 4 weeks, at doses equivalent to 3/4 of those which are optimally oncostatic on murine L1210 leukemia. We examined their myocardia by electron microscopy (EM) and their skin by light microscopy (LM), and report here the findings of these two examinations. The mortality was very high for the groups of hamsters treated with ADM, DTR, DRB, eADM, and RBZ (all treated hamsters died before the end of the fourth week) and very low for those treated with ACM and AD-32 (for each drug, only one of the 21 treated animals died after 4 weeks of treatment). After the first week of treatment and chiefly after the second week, all treated hamsters, except those treated with ACM, showed very severe EM alterations of their myocardia. EM detected almost no early myocardial lesions in ACM-treated hamsters but, after 4 weeks of treatment, severe cardiac lesions also appeared which, like those after AD-32, were nonlethal and reversible. LM of the skin detected degenerative lesions with atrophy of all epidermic layers and a loss of the hair (alopecia) in all treated hamsters except those treated with ACM and AD-32; the skin in these two groups preserved its normal histologic structure. These observations agree with phase I-II clinical ACM studies in which the rate of ECG abnormalities was 4.5% and the rate of alopecia 0%, and with an early AD-32 clinical study conducted by Blum [3].

Animals↗
PubMed1980

Correction of immunodeficiency in aged mice by levamisole and bestatin administration.

An attempt to correct the impaired immune functions of aged mice was made by injecting repeatedly (over a 6-month period) two chemically defined immunostimulating agents, levamisole and bestatin, into 12- to 16-month-old hybrid mice. Continuous treatment with levamisole restored T-cell-dependent functions (delayed-type hypersensitivity reaction and antibody response to T-dependent antigens) and prevented the appearance of suppressor cells induced by aging. In aged animals, this treatment led to macrophage activation and to a significant reduction of ADCC activity near the baseline value of young animals. Weekly injections of bestatin resulted in varying effects, depending on the dose administered. Small doses (10 microgram/injection) were more effective in restoring humoral response to SRBC rather than delayed-type hypersensitivity reaction, whereas large doses (100 microgram/injection) had the opposite effect. Macrophage activation was obtained only after the administration of the high dose of bestatin. Continuous treatment with bestatin did not eliminate suppressor cell activity, but decreased the ADCC normally elevated in aged animals. A significant reduction of spontaneous tumors and prolongation of median survival was observed in mice given repeated injections of levamisole and of 100 microgram bestatin, compared with untreated aged mice and with mice given low doses of bestatin.

Adjuvants, Immunologic↗
PubMed1980

In vivo immunomodulating properties of two synthetic agents: azimexon and tuftsin.

Mice were submitted to various immunologic tests at different times after a single intravenous (IV) injection of azimexon or tuftsin in order to determine the mode of action of these chemically defined immunomodulators. Azimexon, (BM 12,531) an aziridine derivative, potentiated antibody responses to both thymus-dependent (TNP-KLH) and thymus-independent (TNP-LPS) antigens and DTH reaction to oxazolone when injected at least 1 day before the antigen. It activated macrophages, rendering them cytostatic for tumor cells, but depressed ADCC activity of spleen cells directed against antibody-coated CRBC. Tuftsin, a basic tetrapeptide, potentiated antibody response to TNP-KLH when injected at least 3 days before the antigen. The response to TNP-LPS was stimulated on days 1 and 3, but was slightly depressed on day 7. It rendered macrophages highly cytostatic for tumor cells but, as observed with azimexon, the activation process required 7 days to develop. ADCC was enhanced throughout the period of observation.

Adjuvants, Immunologic↗
PubMed1980

Tumor-necrotizing serum production by administration of BCG + Pseudomonas: its application in treatment of fibrosarcoma in mice.

A Pseudomonas aeruginosa (i.v.) treatment (10(8) killed organisms) has shown the capacity to induce the release of tumor-necrotizing factor in the serum of BCG-pretreated mice to the same extent as an LPS treatment. Lower doses of P. aeruginosa (10(7) killed organisms) were applied in BCG-pretreated mice (1 mg given IV 7 days prior to or 1 day after tumor graft) bearing a methylcholanthrene-induced fibrosarcoma. In both cases this combined treatment significantly delayed tumor growth without a toxic side effect.

Animals↗