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Biomedical subjects

E Bonmassar

Publications and source records attributed to E Bonmassar.

At least 145 records · Page 8Linked to original sources
PubMed1980

Chemotherapy immunogenicity.

A number of studies have demonstrated that a moderate immune reaction may augment the response to chemotherapy. Two approaches are examined in the current report: (a) chemoimmunotherapy with viable L1210 cells that were antigenically altered by treatment with DTIC (L1210/DTCI), and (b) chemotherapy plus treatment with lymphocytes from mice immunized against L1210/DTCI. Treatment of the parental leukemias L1210 Ha and L1210 Cr with BCNU or cyclophosphamide in combination with viable antigenically altered tumor cells and with lymphocytes immunized against the antigenically altered tumor cells resulted in marked therapeutic responses. The observations suggest that these combined therapeutic modalities are worthy of investigation employing human tumors.

Animals↗
PubMed1980

Drug-mediated antigenic changes in murine leukemia cells: antagonistic effects of quinacrine, an antimutagenic compound.

Because the antigenic changes occurring after in vivo treatment of murine lymphoma cells with 5-(3,3-dimethyl-1-triazenyl)-1H-imidazole-4-carboxamide (DTIC) were suggested to result from DTIC-induced somatic mutation(s), quinacrine dihydrochloride, an antimutagenic compound, was tested for possible antagonistic activity related to this phenomenon. The increased immunogenicity of L1210Ha leukemia occurring at the first transplant generation of DTIC-treated histocompatible (BALB/cCr x DBA/2Cr)F1 male mice or the appearance of strong lymphoma-associated transplantation antigens at transplant generation 6 was prevented by simultaneous administration of quinacrine. However, the compound did not modify the antitumor or immunodepressive activity of DTIC in the mouse. We concluded that the selective antagonistic effect of quinacrine on DTIC-mediated immunogenic changes (DMIC) supported the hypothesis that the molecular mechanism of DMIC could be related to somatic mutation(s).

Animals↗
PubMed1980

In vivo or in vitro modulating effects of vincristine on the generation of allogeneic cytotoxic lymphocytes in vitro.

Cytotoxic lymphocytes carrying the H-2(i5) haplotype were generated in vitro against alloantigens specified by the IC-S-G-D regions of H-2. Responder lymphocytes were collected from donors B10.A(5R) non-treated or treated with 3 or 0.6 mg/Kg, ip of Vincristinee (VCR) and incubated with irradiated B10 spleen cells. High doses of VCR produced depression of the cytotoxic response (CR), whereas 0.6 mg/Kg of the drug produced substantial increase of the response. Further experiments were conducted adding VCR in vitro to the tissue culture during the generation of cytotoxic lymphocytes. Depression of CR occurred following treatment with high concentrations of VCR. On the other hand, marked increase of CR was found using responder lymphocytes treated in vitro with low concentrations (i.e. 0.016 - 0.0032 microgram/ml) of the drug. The mechanism of VCR-induced enhancement of CR has not been elucidated. However, the present data show the possibility of increasing host immune responses by treatment of donor mice or of responder lymphocytes with VCR at selected doses or concentrations.

Animals↗
PubMed1980

Differential graft resistance of C3H mice pretreated with antitumor drugs against BALB/c bone marrow or lymphoma cells.

Sequential treatment of mice with 5-(3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC) and Cyclophosphamide (Cy) produced long-term inhibition of endogenous cells proliferation in the spleen and impairment of classical allograft response, similar to that obtainable with lethal total body irradiation. The growth of BALB/c bone marrow or of virus-induced LSTRA leukemia of BALB/c origin, was studied comparatively in drug-treated or irradiated histocompatible (BALB/c x DBA/2)F1 or allogeneic C3H/HeN hosts. No splenic resistance of Hh type against bone-marrow cells was detected in C3H recipients, either irradiated or drug-treated, confirming previous studies on the Hh susceptibility of C3H strain. In contrast, strong transplantation resistance was detected in the spleen, liver and lung of the same hosts, irradiated or drug-treated, and challenged with LSTRA cells. It follows that Hh-susceptible mice are competent for mounting a localized radioresistant and drug-resistant response, directed against a virus-induced lymphoma.

Animals↗
PubMed1979

Augmentation of natural killer activity by pyran copolymer in mice.

Treatment of older mice with pyran copolymer, a known interferon-inducer, was found to result in a rapid boosting of cell-mediated cytolytic activity against YAC-1 tumor target cells. The effector cells were characterized as being non-adherent and were presumed to be natural killer (NK) cells. Augmentation occurred in various lymphoid organs and was detectable 2-3 days after drug treatment. Differences in the levels of boosted activity among the lymphoid organs resulted when the route of administration was varied. The degree of augmentation was largely independent of the dose of pyran, but did vary among different strains of mice. Augmentation, moreover, was followed by a rapid decline by 5-7 days.

Adjuvants, Immunologic↗
PubMed1979

Adriamycin-induced antitumor response in lethally irradiated mice.

Lethally irradiated mice pretreated with a wide range of Adriamycin (ADM) doses were tested for their in vivo antitumor response against transplanted lymphoma cells. Tumor growth, as assessed by 125IUdR uptake, was markedly impaired by treatment with ADM by a variety of different administration schedules. This ADM-induced antitumor response was largely dose-dependent, occurred regardless of route of administration, and was detectable as late as 15-30 days following drug treatment. No genetic restriction could be found to regulate the development of this response, since tumor growth inhibition occurred in syngeneic as well as allogeneic tumor-host combinations. ADM-induced antitumor response did not appear to be due to direct antitumor action by the drug, but rather to some interaction with host immune mechanisms. Antimacrophage agents, such as silica or carrageenan, abrogated the response. The possible implication of different cells as effectors of this response is discussed.

Animals↗
PubMed1979

In vitro generation of primary cytotoxic lymphocytes against L5178Y leukemia antigenically altered by 5-(3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide in vivo.

Drug-mediated tumor antigens (DMTA), which appear after in vivo treatment of murine lymphomas with 5-(3,3'-dimethyl-1-triazeno)-imidazole-4-carboxamide (DTIC), are shown to elicit strong primary cell-mediated responses in vitro. Specific cytotoxic response is obtained using CD2F1 (H-2d/H-2d) spleen cells cocultured in vitro for 5 days with inactivated histocompatible L5178Y/DTIC lymphoma cells in a one-way mixed lymphocyte tumor culture. Sensitized lymphoid cells are markedly cytotoxic for L5178Y/DTIC targets and are minimally or not active against the parental lymphoma. Marginal or no cross-reactivity is found between L5178Y/DTIC lymphoma and other untreated or DTIC-treated tumor or normal cells. Cytotoxic activity is T dependent, since it is abrogated by treatment in vitro with anti-serum and complement and is not elicited by spleen cells of athymic (nude) donors.

Animals↗
PubMed1977

Radioresistant inhibition of lymphoma growth in congenitally athymic (nude) mice.

Several murine tumors were used to determine whether the phenomenon of tumor inhibition in athymic "nude" mice reported previously could be extended to other tumor systems in nude as well as conventional mice. The results with the L5MF-22 tumor line were confirmed, and similar data were obtained with the K36 leukemia of AKR mice and the LAF-17 leukemia of B10.A origin. This phenomenon of tumor inhibition has been called, tentatively, radioresistant inhibition of tumor and may be explained by one of several possibilities. The immunological origin of such tumor inhibition is supported by various observations. The data on tumor cell proliferation in spleens and liver of lethally irradiated mice were similar to previous findings on hemopoietic histocompatibility-incompatible lymphomas. Additionally, the nude mice were stronger responders against lymphoma cells than were conventional hosts. Another explanation is that the tumor inhibition is due to natural cytotoxicity.

Animals↗
PubMed1976

Antigenic changes of L5178Y lymphoma after treatment with 5-(3,3-dimethyl-1-triazeno) imidazole-4-carboxamide in vivo.

Immunologic alteration of the L5178Y lymphoma was obtained in vivo after treatment with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DIC). A single dose of 1,3-bis(2-chlorethyl)-1-nitrosourea (BCNU) "CURED" MICE CHALLENGED WITH L5178Y cells that had been treated with DIC (L5178Y/DIC) for four transplant generations; BCNU did not cure mice bearing the parent tumor. The L5178Y/DIC, treated in vivo for five transplant generations, id not grow in syngeneic mice. L5178Y/OIC cell growth and incidences of death were similar to those of parent cells when inoculated into heavily immunosuppressed mice. Adoptive transfer of lymphocytes from spleens of mice sensitized to the drug-altered tumor specifically protected immunosuppressed mice bearing the L5178Y/DIC tumor. Little protection was afforded by lymphocytes immune to the parent L5178Y tumor, whereas nonimmune lymphocytes or lymphocytes immune against unrelated tumors were completely ineffective. Anti-L5178Y/DIC lymphocytes did not cure mice challenged with the parent L5178Y tumor. Irradiated (400 R) mice previously sensitized to L5178Y/DIC cells rejected 10(2)-10(7) inocula of L5178Y/DIC cells and died when the parent L5178Y was used for challenge. It was concluded that antigeni( alterations of L5178Y cells occurred in (BALB/ctcr X DBA/2Cr)F1 mice after treatment with DIC in vivo.

Animals↗
PubMed1976

Drug-mediated immunogenic changes of virus-induced leukemia in vivo.

LSTRA and RBL-5 lymphomas induced by Moloney and Rauscher leukemia viruses, respectively, were used to determine whether antigenically altered tumors induced by 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamide in vivo would retain their original antigenic properties and/or have new antigenic properties. The tumors became highly immunogenic in the syngeneic hosts after 4 to 8 transplant generations with drug treatment. Syngeneic mice could be protected against challenge with the parental tumor by presensitization with the drug-altered sublines while unrelated tumor lines were incapable of protecting them. The drug-altered subline of LSTRA was used for treatment of the LSTRA in conjunction with chemotherapy, and this immunochemotherapy produced significant increases in number of survivors and increases in median survival time compared to either treatment alone. Tolerance studies indicated that there are novel antigens and parental tumor antigens associated with the drug-treated sublines.

Animals↗