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Biomedical subjects

G Mathé

Publications and source records attributed to G Mathé.

At least 343 records · Page 19Linked to original sources
PubMed1977

Effectiveness of murine leukemia chemotherapy according to the immune state: reconsideration of correlations between chemotherapy, tumour cell killing, and survival time.

Cyclophosphamide (CPM) chemotherapy (134 mg/kg) of L1210 leukemia is less efficient in mice previously immunodepressed by antithymocyte serum (ATS) than in non-ATS pretreated mice. On the other hand, administration of a higher dose of CPM (403 mg/kg), which kills a greater number of leukemic cells but induces an immunodepression, according to the skin graft test, results in a shorter survival time than does the administration of a lower dose of CPM (134 mg/kg), capable of killing fewer leukemic cells but not inducing such an immunodepression. Thus, it appears that: (1) the antileukemic effect of the same dose of a chemotherapeutic drug is less efficient in immunodepressed than in nonimmunodepressed hosts, and (2) calculation of the number of neoplastic cells killed by a given chemotherapy by extrapolation from the survival time may lead to erroneous conclusions.

Animals↗
PubMed1977

Treatment of malignant gliomas and brain metastases in adults using a combination of adriamycine, VM 26, and CCNU. Results of a type II trial.

Forty-three patients with inoperable and/or recurring malignant gliomas and 30 patients with multiple recurring brain metastases were treated with a combination of adriamycine (45 mg/m 2 and 4-dimethyl-epipodophyllotoxin D-thenylidene (VM 26) (60 mg/m 2 for 2 days) and 1-(2-chloroethyl)-3-cyclohexyl-1-nitroso-urea (CCNU) (60 mg/m 2 for 2 days). These cycles of treatment were repeated as soon as the hematologic restoration was complete. The treatment was well-tolerated and the clinical condition of 31 out of 43 glioblastoma patients improved during the 2 months after the beginning of the treatment. Six out of eight patients with breast cancer metastases, one out of 13 with bronchial cancer metastases, and three out of nine with other types of cancer metastases also benefitted from the treatment. Examination of the results reveals the following characteristics: 1. A low degree of efficiency of this combination in the treatment of brain metastases, except for breast cancer metastases. 2. Absence of complete correlation between the clinical results observed and the cinegammagraphic developments 3. Similarity of the results independent of the initial localization 4. Establishment of a 6-month median survival period, with ten patients at present in a state of apparently complete remission, 180-506 days after beginning of the treatment.

Adult↗
PubMed1977

Treatment of murine EAkR lymphosarcoma by surgery combined with systemic or local active BCG immunotherapy applied repeatedly.

A combined treatment modality imcorporating surgery plus BCG immunotherapy was administered to (C57Bl/6 X DBA/2)F1 mice grafted with EAkR lymphosarcoma. A single preoperative local or postoperative systemic BCG administration cured 20-30% of the animals, but did not prolong the survival time of these groups. Repeated s.c. injections of BCG resulted in a significant increase in survival time compared to the group submitted to surgery alone. In contrast, multiple i.v. injections of BCG before and after surgery were no more effective than surgery alone and were less effective than a single postsurgical i.v. injection in producing cures. We have concluded that for local BCG therapy, multiple injections before and after surgery are more effective than a single injection. However, for systemic therapy, multiple injections are less effective than a single injection applied postoperatively.

Animals↗
PubMed1977

Cellular and humoral immunity to leukemia cells in BCG-induced growth control of a murine leukemia.

The antitumor effects of weekly iv injections of 1.0 mg BCG and/or sc injections of 10(7) irradiated leukemia cells were studied in an isogeneic, transplantable lymphoid leukemia in the C57BL/6 mouse. The injections were started at day 1 after ip inoculation of 10(5) leukemia cells. BCG prolonged the survival time of most animals and cured 22%. BCG plus irradiated cells cured only about 10% of the mice, and irradiated cells alone had no curative effect. Individual tumor-bearing mice in the various experimental groups were examined with respect to ascites tumor cell number; complement-dependent cytotoxic antibodies in sera; direct and antibody-dependent cytotoxicity to tumor cells of lymphoid cells from peritoneal fluid, the spleen, and peripheral lymph nodes; and the cytology of ascites, the spleen, and lymph nodes. Only the antibody-dependent lymphocyte-mediated cytotoxicity (ADLMC) was correlated with the ascites tumor cell number, since the ADLMC was high only in mice with a tumor cell number less than that of the controls. Furthermore, since mice with a low tumor cell number had predominantly only lymphocytes as the nonmalignant cell type in their peritoneal fluid, ADLMC may have had an important role in BCG-induced control of tumor growth.

Animals↗
PubMed1977

[Treatment of inoperable glioblastomas using a combination of adriamycin, VM 26 and CCNU].

46 non resectable malignant gliomas adult patients were treated with a combination protocol of chemotherapy with administration of adriamycin, VM 26 and CCNU. The tolerance to this treatment was good except for the delayed hematological toxicity related to cumulative doses of CCNU, which limited after 5 courses of chemotherapy the possibility of further treatment with the same combination. As far as the neurological responses are concerned, 66 per 100 patients were good responders, but we found a poor relation (50%) between the degree of clinical response and regression of tumour volume in brain scan. The median survival of this group of patients was 9 months and 11 patients/46 are still alive in good state 14 months after they entered into this trial. According to these data we discuss the introduction of chemotherapy at the early stage of the disease.

Adult↗
PubMed1977

Follow-up of the first (1962) pilot study of active immunotherapy of acute lymphoid leukaemia: a critical discussion.

The follow-up of the first active immunotherapy (AI) controlled pilot study on acute lymphoid leukaemia (ALL), started in 1962, is reported: seven patients out of 20 are still in first remission and eight of the AI group are still alive between 10 and 13 years later, while all ten controls have relapsed and died. The methodology of this pilot study is discussed, as well as the results of the later AI trials conducted on ALL. In the light of a critical discussion and of the further trials conducted by the authors or published in the literature, the authors conclude that A1 is efficient in ALL and that its use is indicated as, in several trials, it has been as active as maintenance chemotherapy, as it has induced no deaths in 300 patients contrary to maintenance chemotherapy, which has been responsible for 4 to 28% of deaths in patients in complete remission, and as the authors have registered no late relapses after three years in the AI trials, while such relapses appear in most maintenance chemotherapy trials.

BCG Vaccine↗
PubMed1977

A cytokinetic analysis of bacillus calmette-guérin-induced growth control of a murine leukemia.

The cytokinetics of an isogeneic, transplantable, lymphoid leukemia, growing as an ascitic tumor in the C57BL/6 mouse, has been investigated during normal growth and during regression induced by weekly injections i.v. of 1.0 mg Bacillus Calmette-Guérin (BCG). Survival was significantly prolonged in the BCG-treated group, and 27% of the mice were apparently cured. The tumor growth curves showed, furthermore, that BCG-rreated mice could be divided into two groups according to whether the ascitic tumor cell number was at control level or below that of the controls. By methods such as stathmokinetics, tritiated thymidine autoradiography, and cytophotometry, it was demonstrated that the proliferative activity was higher in BCG mice with a low tumor mass as compared to controls and BCG mice with a tumor mass similar to that of controls. The cytokinetic characteristics of BCG mice with a low ascitic tumor cell number were especially expressed by high mitotic activity, high initial labeling indices, short potential tumor doubling time, and a low number of G0-G1 cells. Furthermore the ascitic tumor cell loss rate was increased in these mice during the whole experimental period. It was deduced from the various parameters and especially from the cytophotometric and autoradiographic results that BCG induces a preferential kill of tumor cells in G0-G1 and the first part of the S phase. In addition, the cytological aspects of the ascitic tumor were found to be related to the cell kinetic pattern as the amount of small and large tumor cells increased and decreased, respectively, with accumulation of tumor cells in G0-G1.

Animals↗
PubMed1977

Human models for cancer active immunotherapy.

In this editorial, the author considers the human models for research on cancer immunotherapy. He distinguishes between trials which have given a direct demonstration of the action of immunotherapy, in which the effect of this treatment has been compared to therapeutic abstention, and those which have shown an indirect proof of its action and in which immunotherapy is compared to chemotherapy of which the effect is known, or in which the combination of chemotherapy and immunotherapy is compared with the same chemotherapy applied alone. The author concludes with methodological and ethical considerations about clinical trials applied to active immunotherapy.

Clinical Trials as Topic↗
PubMed1977

Preliminary results of phase I and II clinical trials of RFCNU, a new nitrosourea sugar derivative, in digestive tract tumours.

RFCNU or (chloro-2-ethyl)-l-(ribofuranosyl-isopropylidene-2', 3' paranitrobenzoate-5')-3 nitrosourea, a new synthetic nitrosourea derivative, which has been shown to have, in mice, among all nitrosourea derivatives tested, the longest maximallly efficient dose interval (MEDI) and which is not immunosuppressive at the smallest dose of MEDI, gave in a phase II trial on digestive tract tumours (at the dose of 400 mg/m2 per month determined by the phase I trial), 30% objective remissions among which 13% were greater than 50%.

Adolescent↗
PubMed1977

Comparison of the restoration effect of Pseudomonas aeruginosa, BCG and poly I: poly C on cancer patients non responsive to recall antigen delayed hypersensitivity.

A preparation of 10 serotypes of Pseudomonas aeruginosa has restored skin delayed hypersensitivity reactions to recall antigens in about fifty per cent of cancer patients not previously immunodepressed by radiotherapy or chemotherapy, but anergic. This proportion is similar to that obtained by given modalities of administration of BCG, C. parvum or levamisole, while other modalities of application of BCG or administration of poly I: poly C do not induce such an immuno-restoration in a significant number of patients.

BCG Vaccine↗
PubMed1977

Heat-killed Pseudomonas aeruginosa as a systemic adjuvant in cancer immunotherapy.

The effect of heat-killed Pseudomonas aeruginosa (10 serotypes) on antibody formation, macrophage activation and leukemia growth was investigated in relation to the dose injected and to the time and the route of administration. It appeared that intravenous administration of the preparation (10(9) bacteria per ml) was the most efficient at the dose of 0.1 ml since: 1) it increased the number of PFC against SRBC when injected 10 days before the antigen (higher doses and shorter time intervals resulted either in no modification or an significant inhibition of the PFC response; 2) it induced a slight activation of peritoneal macrophages as measured by their cytostatic activity for tumor cells in vitro, when injected 3 or 7 days before testing whereas higher doses were ineffective; 3) it increased the survival time of leukemic mice when administered 2.5 days before the injection of L1210 tumor cells, and higher doses were also effective in this immunoprophylaxis assay. When the subcutaneous route was used, large doses appeared to be the most effective: 1) potentiation of the PFC response was obtained only when 0.5 or 0.2 ml were given 10 days before the antigen; 2) macrophage activation was demonstrated 7 and 10 days after 0.5 ml; 3) leukemia growth was retared when 0.5 or 0.2 ml was injected 2.5 days prior to L1210 tumor cell inoculation and also when 0.2 and 0.1 ml were injected 7 days before tumor cells. No correlation between macrophage activation and the inhibition of tumor growth could be found.

Animals↗