PubMed Health⌕ Search

Biomedical subjects

G Mathé

Publications and source records attributed to G Mathé.

At least 235 records · Page 13Linked to original sources
PubMed1983

Reversal of immunological tolerance by aclacinomycin through inhibition of suppressor cell activity.

The elimination of suppressor cells by aclacinomycin, which could be the mechanism by which immune responses are enhanced after its administration, was studied in mice in which tolerance had been induced by the injection of high doses of sheep red blood cells (SRBC). We observed that tolerance could not be induced in aclacinomycin-treated mice, and that aclacinomycin inhibited the expression of tolerance to SRBC. This drug also diminished the capacity of spleen cells from SRBC-tolerant mice to inhibit the response of normal animals upon adoptive transfer, indicating that suppressor cells had been eliminated from the tolerant spleen cell population. The efficiency of the elimination of suppressor cells for DTH reactions appears greater than that of suppressor cells for plaque-forming cell responses.

Aclarubicin↗
PubMed1983

Comparative analysis of the immunopharmacological properties of three new nitrosourea analogues: RPCNU, RFCNU and Chlorozotocin.

Three sugar derivatives of chloroethyl nitrosoureas: RPCNU, RFCNU and Chlorozotocin (CLZ) were examined for their effect on the immune system in mice when administered at the minimal antineoplastic therapeutic dose. When the drugs were administered 4 days prior to antigenic stimulation, a potentiation of DTH to oxazolone was observed whereas the antibody response to SRBC was markedly decreased. When injected 24 h after immunization, the nitrosourea analogues did not modify the intensity of DTH reaction and of allograft rejection and only RFCNU depressed the antibody response. The proliferative response of spleen cells to T or B cell mitogens was strongly depressed after in vivo treatment with either of the three analogues. Concomitantly, peritoneal macrophages became strongly cytostatic for tumor cells and also displayed an enhanced chemiluminescence upon phagocytosis. An augmentation of antibody-dependent cellular cytotoxicity of spleen cells was observed only after CLZ administration which also resulted in an increase of NK activity of peritoneal cells but in an inhibition of spleen cell cytotoxicity. This study demonstrates that the nitrosourea analogues act as immunomodulating agents and reinforces their interest as antineoplastic drugs since they can stimulate nonspecific effector mechanisms known to play a role in resistance against tumors.

Animals↗
PubMed1983

[Japanese-French cooperation in tumor pharmacotherapy: 1970-1990].

Since 1970, we have carried out cancer chemotherapy and immunotherapy in cooperation with Japanese scientists, particularly Prof. H. Umezawa, who has generously supplied bleomycin, peplomycin, acalcinomycin A (ACM), THP-adriamycin (THP), neothramycin and bestatin. Malignant tumors curable by pharmacotherapy are polycythemia vera (CR 100%), acute lymphoid leukemia (ALL) (CR 80%), Burkitt tumor (CR 80 or 50%), Hodgkin disease (CR 80%), chorioepithelioma (CR 80%), testicular cancer (CR 80%), ovary cancer of children (CR 80%), Wilms renal cancer (CR 60%), rhabdomyosarcoma (CR 75%), osteosarcoma (CR 60%), Ewing tumor (CR 60%), brain tumor of children (CR greater than 50%), testicular embryonal cancer of children (CR greater than 50%), acute myeloid leukemia (AML) (CR 50%), non-Hodgkin lymphoma (NHL) (CR 50%), ovary cancer of adults (CR 40%), small cell lung cancer (CR 20%) and breast cancer. Our experimental and/or clinical experience with ACM, THP, methoxy-9-ellipticine lactate, navelbine, 4-demethyl-epipodophyllotoxin-beta-d-ethyledene glucoside, bestatin and interferon is presented. ACM is effective against AML, ALL, NHL, Burkitt tumor, breast cancer. We have comparatively investigated cardiac and dermal toxicity of 12 kinds of anthracycline antibiotics and mitoxantrone, using golden hamsters. Of the drugs examined, ACM, THP, AD-32 and AD-143 cause much less cardiomyopathy and alopecia than the other agents. The results have been confirmed by electron microscopic studies. Bestatin is an immunorestorator, which recovers immunological functions decreased in aged animals. We hope that cancer chemotherapy and immunotherapy will progress in future and contribute to cure of neoplasms. Japanese scientists have been making a great contribution in the field of cancer pharmacotherapy, and we are eager to cooperate with Japanese scientists in cancer treatment studies.

Aclarubicin↗
PubMed1983

Kinetics and metabolism of a new fluoropyrimidine, 5'-deoxy-5-fluorouridine, in humans.

5'-Deoxy-5-fluorouridine (5'-dFUrd) is a new antineoplastic agent which possesses a higher therapeutic index in several experimental tumors compared to other fluoropyrimidines. During a Phase I trial, 5'-dFUrd, 1 to 15 g/sq m/week, was administered to patients as a 25- to 35-min i.v. infusion. Plasma kinetics and metabolism of 5'-dFUrd were investigated. The unmetabolized drug was measured by a high-performance liquid chromatography assay. 5-Fluorouracil and 5,6-dihydrofluorouracil, the two detected plasma metabolites, were quantitated by a gas chromatography-mass spectrometry methodology with a detection limit of 0.07 microM for both metabolites. The disposition of 5'-dFUrd in humans at therapeutic doses followed a nonlinear kinetic process. Plasma concentrations of 5-fluorouracil generated in vivo represented approximately 6% of 5'-dFUrd concentrations and the 5-fluorouracil half-life ranged from 8.8 to 27.1 min. High plasma values of 5,6-dihydrofluorouracil (14.5 to 30 microM) were observed in patients, indicating the importance of this pathway in humans.

Colonic Neoplasms↗
PubMed1983

[AIDS and its association with human tumors and viruses. A viral and/or immunogenetic cause?].

This paper is an editorial review of the relationship between the AIDS, Kaposi sarcoma, adult-T-lymphoma, other neoplasias, HTLV, ATLV and other viruses, amyl-nitrite and immunosuppressive drugs and the possible immunogenetic mechanism related to the immunity suppressor branch due to Ia antigen allogenic reaction similar to that of graft versus host reaction which may also induce angiosarcomas.

Acquired Immunodeficiency Syndrome↗
PubMed1983

Interleukins and immunosuppressive factors: a regulatory system?

On exogenous stimulus immunocompetent leucocytes produce antigen-specific factors, which essentially determine the magnitude and duration of T-lymphocyte dependent immunoreactions. Interleukin 1 (IL-1, monokin) and interleukin 2 (IL-2, lymphokine) form a bimodal amplification system which may operate in vivo at the level of peripheral lymphoid organs, which interleukin 3 (IL 3, lymphokine) may function as a positive feed-back signal at the level of multipotential stem cells. The physiological IL-2 has wider importance, since the permanent expression of Il-2 gene due to the insertion of the viral promoter sequence (HTLV in human) led to uncontrolled proliferation of T-cells and to the development of lymphomas and leukemias of mature T-cell phenotype. On the afferent arc of immunoreactions endogenous factors mediate T-cell proliferation inhibitory effect probably via interaction with the interleukin system. Some practical aspects of these two antagonistic group of factors are presented and discussed.

Animals↗
PubMed1983

Phase II clinical evaluation of 4'-epi-doxorubicin.

4'-Epi-doxorubicin (4'e-Dx) was used as a single agent in a broad phase II study involving a variety of advanced metastatic tumors. A total of 115 patients were treated, of whom 93 were evaluable. The dosage was 75 mg/m2/cycle repeated every 21 days, with a maximal cumulative dose of 550 mg/m2. Nine responses were achieved in a total of 28 patients with breast cancer (32%). The response rate was 54% in breast cancer patients receiving 4'e-Dx as first-line treatment, 25% in patients previously given chemotherapy without doxorubicin, and 11% in patients previously given chemotherapy with doxorubicin. Some therapeutic activity was also detected in endometrial carcinoma, epidermoid carcinoma of the cervix, non-Hodgkin's lymphoma, melanoma, and skin epidermoid tumor, but the number of patients entered in the study with these various tumors was too limited to allow any statement on efficacy of 4'e-Dx. No treatment schedule with 4'e-Dx had to be interrupted because of toxicity. In a total of 373 evaluable cycles, only three acute reversible ECG abnormalities were recorded. In 16 of 109 evaluable patients there was some minor or moderate alteration of one or more of the three major blood cell parameters following 4'e-Dx therapy, requiring a postponement of the next cycle by less than or equal to 10 days.

Adolescent↗
PubMed1983

The common acute lymphoid leukemia antigen on b cells of chronic lymphoid leukemia and non-Hodgkin's lymphoma.

Fourteen out of 21 non-Hodgkin lymphoma (NHL) and 3/11 chronic lymphoid leukemia cells (CLL) had the common acute lymphoid leukemia antigen (CALLA) All 32 patients had monoclonal B-cell proliferation. The CLL patients had 90% CALLA positive cells while the proportion of their leukemic elements was superior. Lymph-nodes or bone marrow invaded by a B monoclonal tumor cell population of NHL had significantly more CALLA positive cells (42.1 +/- 32.5%) than non-invaded tissues (11.4 +/- 10.3%). In NHL tissues with monoclonal B-cells, lymph-nodes had significantly more CALLA positive cells (56.0 +/- 29.9%) than marrow (23.5 +/- 27.7%). It is well known that the (CALLA) is not specific for ALL. It has been believed to be a differentiation antigen on pre B-cells. The present study confirms that it also occurs on B-cells (2,4,6,7,8,9,10,11).

Antigens, Neoplasm↗
PubMed1983

Efficacy of and errors in randomized multicenter trials. A review of 230 clinical trials.

An attempt was made to study the efficacy in and one of the errors of randomized multicenter clinical trials. Efficacy was defined for the present purpose as a statistically significant clinical difference between at least 2 of the treatment arms studied. The error studied was defined here as non-excluded protocol deviations found during a systematic record review. The nature (multicenter randomized trial or un-controlled pilot study) of 8 so-called "breakthrough" studies which seemed particularly important for future cancer treatment was also established. The number of yearly randomized trials seems to have increased by a factor of 10 between 1969 and 1981, as judged by the abstracts published by the American Society of Clinical Oncology. 23% yielded statistically significant results, which is 18% over the 5% expected chance significances. Of 174 papers and abstracts published by one group, only 18 were reviewable original studies. The corresponding figures for another group was 6 of 22. This explains why only 8 scientifically new statistical significances were found in one series of 76 original articles. The mean dose of cytostatics actually given to 192 breast cancer patients varied, as judged by a record review, between 71 and 93% of the protocol doses. These figures agree with the 15-30% of nonexcluded protocol deviations found previously. Of the 8 "breakthrough" studies, 7 were single center pilot studies without randomized controls, and only 1 was a randomized multicenter study. It is suggested that more relevant questions can be asked in multicenter randomized clinical trials if they are based on promising single center pilot results, and that record reviews should be performed so that protocol deviations can regularly be reported.

Antineoplastic Agents↗
PubMed1982

[Treatment of acute myeloid leukemia with a protocol combining intensive induction chemotherapy, early consolidation treatment, splenectomy and long-term maintenance chemotherapy. Preliminary study].

Twenty-seven patients aged from 10 to 60 years (mean 34.4 +/- 13 years) in the first perceptible phase of acute myeloid leukemia were subjected to intensive induction chemotherapy consisting of adriamycin (ADM), vincristin (VCR) and cytosine arabinoside (ARA-C). Twenty-four patients (89%) attained complete remission (CR) after 1 to 3 cycles and were then given an early consolidation treatment with one of the previous cycles. This was followed by long-term continuous maintenance chemotherapy with 6-mercaptopurine (6-MP) and methotrexate (MTX) alternatively and 3-monthly reinforcement courses of donaurubicin (DNR) and VCR. Twenty of these 24 patients were splenectomized soon after the consolidation treatment. None of the spleens were enlarged, and histological sections of the spleens, liver biopsies and mesenteric lymph-nodes stained with routine dyes and by the naphthol AS-D chloroacetate esterase method revealed mature granulocytes but no demonstrable leukaemic cells. In the group of splenectomized patients, the probabilities of staying in complete remission at 27 and 44 months were 70 +/- 12.6% and 52 +/- 18.5% respectively, and the probabilities of remaining alive at 32 and 55 months were 79 +/- 11% and 57 +/- 19% respectively. Age over 40 and evidence of extramedullary infiltration at presentation appeared to leave little hope of disease-free survival. The rationale for the present therapeutic study is discussed.

Adolescent↗