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Biomedical subjects

C Riccardi

Publications and source records attributed to C Riccardi.

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

Transplantation resistance of drug-treated hybrid or allogeneic mice against murine lymphomas. I. Immunopharmacology studies.

Sequential treatment of mice with non-lethal doses of 5(3,3'-dimethyl-l-triazeno)-imidazole-4-carboxamide (DTIC) and cyclophosphamide (Cy) was found to produce long-term inhibition of endogenous cell proliferation in the spleen and profound impairment of classical allograft responses, similar to that detectable in lethally irradiated mice. Studies were carried out with drug-treated (i.e. treated with DTIC + Cy) conventional or nude mice inoculated with lymphoma cells homozygous for the H-2b or H-2d haplotype. Transplantation resistance in various tumour-host combinations was studied in terms of survival times after tumor challenge or lymphoma cell proliferation in spleen and liver, measured by the uptake of DNA precursor 125I-labelled 5-iodo-2'-deoxyuridine ([125I]dUrd). The results of in vivo transplantation immunity tests or in vitro tests of generation of cytotoxic lymphocytes confirmed that classical T-dependent allograft responses were abrogated by drug treatment of H-2-incompatible hosts. However, localized resistance against lymphoma graft, mainly at spleen level, was found in drug-treated hybrid mice, or conventional and "nude" allogeneic recipients, as judged by [123I]dUrd uptake inhibition. Resistance presumably regulated, at least in part by the Hh (hemopoietic histocompatibility) system, was abrogated by pretreatment with carrageenan, an antimacrophage agent. In addition, treatment with DTIC + Cy did not abrogate NK activity of mice when the in vitro cytotoxicity test was conducted 5 h after Cy administration, i.e. at the time used for tumor challenge in vivo. It was concluded that selected immunological functions (i.e., antilymphoma natural resistance insensitive to DTIC + Cy, called drug-resistant inhibition of tumors, DRIT) possibly of non-T origin, similar to those detectable in lethally-irradiated mice, can be retained by hosts subjected to high doses of certain anti-tumor agents.

Animals↗
PubMed1980

Suppression of activity of mouse natural killer (NK) cells by activated macrophages from mice treated with pyran copolymer.

Treatment of young mice with pyran copolymer caused a substantial decrease in natural killer (NK) cell activity at 7 days. The decrease in cytotoxicity was associated with the presence of splenic suppressor cells, capable of inhibiting in vitro the NK activity of spleen cells from normal mice. The suppressor cells appeared to be macrophages, being plastic-adherent, phagocytic and radioresistant, and lacking demonstrable Thy 1.2 antigen. Sonicates or culture supernatants of adherent spleen cells from pyran-treated mice were also able to inhibit NK activity, suggesting that suppressor cells act by release of soluble factors.

Animals↗
PubMed1980

Cytotoxic effector cells with the characteristics of natural killer cells in the lungs of mice.

Cells with in vitro cytotoxicity against tumor targets in a short-term 51Cr release assay have been recovered from the lungs of mice that were either untreated or injected with biological or synthetic agents 1--3 days earlier. The cytotoxic effector cells were non-adherent, non-phagocytgic and shared many characteristics with splenic natural killer (NK) cells. This finding is discussed with particular regard to our previous observations on the rapid in vivo elimination from the lungs of intravenously injected, radiolabelled tumor cells.

Adjuvants, Immunologic↗
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

Effects of adriamycin on the activity of mouse natural killer cells.

Adriamycin, a widely employed anti-neoplastic agent, was found to have either inhibitory or stimulatory effects on NK activity, depending on the site examined. A single i.p. administration of ADM resulted in a rapid increase of cytolytic activity by PEC of various mouse strains. The effector cells appeared to be NK cells, being nonadherent and nonphagocytic; they expressed low amounts of Thy 1.2 antigen and had the same pattern of specificity as splenic NK cells. In contrast to the stimulatory effects of NK activity of PEC, ADM caused a transient dose-dependent depression of NK activity in the spleen, with a peak reduction at day 3 and recovery within a few days thereafter. The depressed NK activity could be reversed by removal of adherent cells by passage through a nylon column. Moreover, ADM induced cytostatic activity against tumor cells by macrophages, suggesting that activated macrophages may be responsible for suppression of splenic NK activity. The possible modulation of the levels of NK activity by ADM-induced macrophages was supported by mixture experiments, in which plastic adherent spleen cells from ADM-treated mice, but not from normal mice, inhibited the NK activity of normal spleen cells.

Animals↗
PubMed1979

Activation of mouse macrophages by pyran copolymer and role in augmentation of natural killer activity.

Inoculation of mice with pyran copolymer resulted in activation of natural killer (NK) cells as well as macrophages. Conditions optimal for the boosting of NK activity seemed to differ from those optimal for macrophage activation as assessed by cytostasis of tumor target cells. Peak levels of macrophage cytostatic reactivity were found at about 7 days after drug injection and were only achieved by the highest doses of pyran tested. Macrophage activation was consistently higher in the peritoneal cavity than in the spleen, regardless of route of administration, in contrast to the failure of i.v. pyran to induce high NK reactivity in peritoneal exudate cells. At 2-3 days after pyran treatment of older mice, NK augmentation reached peak levels, but only minimal macrophage activation was found. Despite these differences, macrophages played a role in regulating NK activity in pyran-treated mice. Functional macrophages appeared to be required for augmentation of NK activity by pyran, since boosting was impaired by prior in vivo inoculation of silica. Macrophages also appeared able to inhibit NK activity. In younger mice that exhibited high spontaneous levels of NK activity, pyran treatment produced a substantial reduction in NK activity to levels below those of untreated mice. This depression coincided with the time of peak levels of macrophage cytostasis. Furthermore, removal of adherent cells from the spleen cells of these pyran-treated mice resulted in levels of NK activity almost as high as those of untreated mice. The possibility that the depression of NK activity in young mice by pyran copolymer is due to suppressor cells is discussed.

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

Rapid in vivo assay of mouse natural killer cell activity.

A rapid elimination of tumor cells from some organs was detected in mice following iv injection of tumor cells labeld in vitro with [125I]5-iodo-2'-deoxyuridine. Recovery of radioactivity in different organs (spleen, liver, and lungs) was reduced in mice with high natural killer (NK) cell reactivity in their spleens, as measured in vitro by concomitant short-term 51Cr release assay. Considerable parallelism between in vitro and in vivo reactivities against two mouse lymphomas and a human myeloid cell line was found in mice of different strains and ages. Similarly, various immunophamacologic treatments had comparable effects on in vitro and in vivo reactivities. These findings are consistent with the hypothesis that rapid cytolysis of tumor cells occurred in vivo and that NK cells played a major role in their elimination.

Age Factors↗
PubMed1978

Growth and rejection patterns of murine lymphoma cells antigenically altered following drug treatment in vivo.

Murine leukemia cells transformed by in vivo treatment with 5-(3,3-dimethyl-1-triazeno)imidazole-4-carboxamide (DTIC) are rejected by histocompatible recipients following inocula of 10(7) cells i.p. Progressive tumor growth or tumor growth and regression was monitored measuring the extent of DNA synthesis in the peritoneal cavity of mice using the [125I]5-iodo-2'-deoxyuridine uptake method. In addition, the results were confirmed by cell count and mortality data. Comparable growth rate was found initially in both DTIC and parental lines in histocompatible hosts. Later, mice challenged with parental lines died, whereas hosts inoculated with DTIC-treated sublines rejected the tumor. On the other hand, lethal growth occurred in mice inoculated with DTIC-treated sublines when immunodepressed by cyclophosphamide given before tumor challenge, or by methotrexate given after challenge of a methotrexate-resistant DTIC-treated subline. The similarity between the growth rate of the parental and DTIC-treated lines in histocompatible hosts does not support the hypothesis of impaired "oncogenic potential" of such DTIC-treated lines. Furthermore, the growth and rejection pattern of a parental line in H-2-incompatible hosts was similar to that observed for DTIC-treated lines in histocompatible hosts, suggesting that comparable immune mechanisms were involved in both cases.

Animals↗