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Biomedical subjects

F Spreafico

Publications and source records attributed to F Spreafico.

At least 73 records · Page 4Linked to original sources
PubMed1981

Inhibition of human natural killer activity by cyclosporin A.

The effect of in vitro exposure to cyclosporin A on human natural killer (NK) activity was investigated using peripheral blood lymphocytes as effectors and 51Cr-labeled K562 cells as targets. After preincubation of the effectors with the drug for 20 hr, a dose-dependent reduction of NK activity was observed at concentrations ranging from 0.1 to 10 micrograms/ml. Exposure to the drug during the 20-hr preincubation and the 4-hr 51Cr-release assay resulted in greater impairment of NK cytotoxicity than preincubation alone, whereas the drug, present only during the assay, had no effect on cytolytic activity. Inhibition of NK activity required a minimal exposure time to the drug of 8 hr. The inhibitory effect of cyclosporin A on NK activity was rapidly reversible as, after a 20-hr incubation with 19 micrograms/ml, complete recovery of cytotoxicity was already observed after a further 4-hr culture in medium. Partially purified human fibroblast interferon augmented NK activity even in the presence of high concentrations (10 micrograms/ml) of cyclosporin A.

Cells, Cultured↗
PubMed1980

Divergent effects of macrophage toxins on growth of primary tumors and lung metastases in mice.

The effects of silica and carrageenan on primary tumor growth and metastases were evaluated in c57bl/6 and BALB/c mice transplanted with the poorly immunogenic Lewis lung (3ll) carcinoma, mFS6 sarcoma and Madison 109 carcinoma spontaneously metastasizing to the lungs. Silica and carrageenan significantly enhanced lung metastases and decreased primary tumor weight in all three experimental models. A similar augmentation of lung secondaries was found after i.v. inoculation of 3LL tumor cells. The effects of carrageenan on primary 3LL tumor growth and metastases were observed also in thymus-deprived animals. The effect of macrophage toxins was studied also in C57BL/6 mice transplanted with the M5076/73A ovarian carcinoma. This tumor spontaneously metastasizes to various abdominal organs, but not to the lung. After treatment with carrageenan, lung metastases were observed, but no effect on secondaries at other anatomical sites or on the primary tumor was detectable. It is suggested that host defense mechanisms impaired by silica and carrageenan may have divergent effects in the regulation of growth of some primary tumors and spontaneous lung metastases.

Animals↗
PubMed1980

The effect of acute administration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) on humoral antibody production and cell-mediated activities in mice.

The effect of single doses of TCDD (1.2, 6 or 30 gamma/kg) on several immune parameters has been investigated in young adult C57B1/6 mice. TCDD profoundly suppressed the primary and secondary humoral response to T-dependent (sheep erythrocytes, SRBC) and T-independent (Type III pneumococcal polysaccharide, S III) antigens. In vitro lymphoproliferative responses to Concanavallin A (Con A) and bacterial lypopolysaccharide (LPS), and macrophage and natural killer (NK) cell-mediated cytotoxicity were not significantly affected per unit number of lymphoid cells. Moreover, the ability of splenocytes from TCDD treated animals to mediate a graft versus host (GVH) reaction was not impaired.

Animals↗
PubMed1980

The heterogeneity of the interaction between cancer chemotherapeutic agents and host resistance mechanisms.

Employing adriamycin and daunomycin as model drugs, evidence is presented that a differential effect on host defense mechanisms can be important in determining the therapeutic efficacy of antitumorals. The heterogeneity of these and other cancer chemotherapeutic agents in immunocyte populations such as macrophages, suppressor cells, and natural-killer cells is examined, and discussed is the possible relevance of this heterogeneity in understanding the mode of action and in better use of antitumorals in combined approaches.

Animals↗
PubMed1980

A characterization of the activity of alpha-1,3,5-triglycidyl-s-triazinetrione, a novel antineoplastic compound.

To extend initial results on the antineoplastic activity of alpha-1,3,5-triglycidyl-s-triazinetrione (TGT, NSC 296934), a novel triepoxidic derivative, this compound was tested in a series of murine transplantable tumors. Repeated daily treatments with well-tolerated systemic doses of this chemical produced substantial retardation in tumor growth and significant prolongation of survival in the line 16 mammary, M5067 ovarian, and Madison 109 lung carcinomas and in mFS6 fibrosarcoma. Very marked activity was also seen in the P815 mastocytoma, B16 melanoma, line 38 colon carcinoma, and an intracerebrally transplanted ependymoblastoma, with high proportions of cures after one or two injections in IP transplanted SL2 lymphoma and line 26 colon carcinoma. It is concluded that the high level of antineoplastic effectiveness and the wide spectrum of TGT activity together with its novel structural characteristics could be of clinical significance.

Adenocarcinoma↗
PubMed1980

Effect of chemotherapeutic agents on natural and BCG-stimulated macrophage cytotoxicity in mice.

Spontaneous or Bacillus Calmette Guérin (BCG)-stimulated macrophage cytotoxicity was investigated in the peritoneal cavity of BALB/c x DBA/2 treated with various chemotherapeutic agents. The SV40-transformed mKSA TU5 (TU5) line and the mFS6 sarcoma were used as targets. Cytolytic activity of macrophages from individual mice (4-6 per experimental group) was measured as release of [3H methyl]thymidine from prelabelled target cells. Treatment with azathioprine (a single injection 100-400 mg/kg or 5 daily doses of 10-80 mg/kg s.c.) and dimethyltriazenoimidazole carboxamide (a single injection of 45-180 mg/kg or 5 daily doses of 3-30 mg/kg i.v.) resulted in marked dose-dependent inhibition of spontaneous macrophage cytotoxicity against TU5 tumor cells 2 days later. By 7 days after drug treatment spontaneous cytotoxicity of macrophages had returned to normal levels. In contrast adriamycin (a single dose of 5-10 mg/kg or 5 daily doses of 0.6-2.5 mg/kg i.v.) and cyclophosphamide (a single dose of 50-200 mg/kg or 5 daily doses of 6-25 mg/kg i.v.) did not affect spontaneous cytolytic activity of murine macrophages. BCG-stimulated macrophage cytotoxicity was investigated using mFS6 target cells which were relatively resistant to the spontaneous levels of macrophage-mediated cytolysis; the same pattern of effects was observed, azathioprine and dimethyltriazenoimidazole carboxamide inhibiting cytolytic activity levels in contrast to adriamycin and cyclophosphamide. These results are discussed in terms of the known effects of these agents on other functions of mononuclear phagocytes and on other immune reactivities.

Aminoimidazole Carboxamide↗
PubMed1980

In vitro effects of saccharin on cell-mediated host defence mechanisms.

In vitro exposure to saccharin (0.1-2 mg/ml) did not affect the tumoricidal activity of macrophages and natural killer (NK) cells from mice and rats. In contrast saccharin at doses of 0.5-2 mg/ml significantly and consistently depressed the blastogenic response of rat lymph node cells to phytohemagglutinin (PHA). Similarly mouse splenocytes showed impaired responsiveness to PHA and bacterial lipopolysaccharides n the presence of 2 mg/ml saccharin. Compared with murine lymphoid cells, human peripheral blood lymphocytes were relatively resistant to the immunodepressive activity of saccharin, a low but significant, depression (21%) of the response to PHA being observed only at the highest concentration (2 mg/ml) in 1 of 3 normal healthy donors tested.

Animals↗
PubMed1980

Metastasizing capacity of tumour cells from spontaneous metastases of transplanted murine tumours.

We investigated the metastasizing capacity of spontaneous lung metastases from the MN/MCA1 and mFS6 sarcoma, the B16 melanoma and colon 26 carcinoma. Spontaneous metastases at other visceral organs (liver, spleen, kidney, ovary, uterus) from the M5076/73A (M5) ovarian carcinoma and colon 26 carcinoma were also studied. Tumour cells from individual spontaneous metastases were used immediately after isolation from the normal parenchyma (mFS6, M5 and colon 26) and/or after 1 s.c. passage in syngeneic mice (MN/MCA1, mFS6, B16 and M5). Spontaneous metastases were examined for all tumours and their secondaries after i.m. or s.c. inoculation of tumour cells; artificial lung colonies were measured after i.v. injection only of cells from the primary mFS6 and MN/MCA1 and B16 or their spontaneous metastases. Individual spontaneous metastases were to some extent heterogeneous in their metastatic potential, a minority of the secondaries having greater or lesser metastatic capacity than the appropriate primary. Overall, tumour cells from spontaneous metastases did not show greater metastasizing capacity than primary neoplasms, nor was there evidence that metastases from specific organs (e.g. spleen and kidney) tended to home to the specific anatomical sites from which they were originally isolated. These observations in a series of murine tumours of different histology, transplantation history and pattern of metastasis, do not support the hypothesis that metastases are the ultimate expression of strong selection of variant cells with greater intrinsic metastatic potential, pre-existing within the primary tumour.

Animals↗
PubMed1980

Heterogeneity of the interaction of anticancer agents with the immune system and its possible relevance in chemoimmunotherapy.

The heterogeneity existing among cancer chemotherapeutic agents, even when structurally closely related, in their quantitative and qualitative interaction with the various cellular components of host defence mechanisms involved in cancer control is reviewed. In addition to being a possible determinant of antineoplastic drugs in vivo efficacy, this heterogeneity can be of importance also in the development of less empirical and more effective approaches to the design of combinations to be used in cancer chemoimmunotherapy. Non-specific immunomodulatory agents are in fact also heterogenous in their mode of action on the various components of the immune complex. Examples of chemoimmunotherapeutic combinations based on drugs acting at complementary levels on host defences are presented and the mechanistic basis for their in vivo synergistic activity discussed.

Animals↗
PubMed1980

Effect of 2,3,7,8-tetrachlorodibenzo-p-dioxin on macrophage and natural killer cell-mediated cytotoxicity in mice.

C57Bl/6 J mice (6-8 weeks old) were given single i. p. doses (1, 2, 6 and 30 micrograms/kg) of 2,3,7,8-tetrachloro-dibenzo-p-dioxin (TCDD) and macrophage-mediated and natural killer (NK) cell-mediated cytotoxicity was evaluated at different times after treatment. Peritoneal macrophage cytolytic activity was measured as 3H-thymidine release from prelabelled mKSATU5 target cells in a 48 hours assay; macrophage-mediated cytostasis was assessed in terms of inhibitions of 3H-thymidine uptake by SL2 lymphoma cells. Spleen NK activity was measured using 51Cr-labelled YAC-1 lymphoma cells as targets. TCDD did not modify spontaneous macrophage-mediated and NK cell-mediated cytotoxicity per unit number of effector cells nor did it affect the macrophages' capacity to express increased cytolytic and cytostatic activity in the presence of endotoxin. Lower numbers of peritoneal macrophages and splenocytes were recovered from TCDD treated mice. Thus the total numbers of lytic units recovered from animals exposed to TCDD were lower than controls. Impairment of these cellular effector mechanisms, due to cell loss rather than inhibition of function, might play a role in the lowered resistance to bacterial infection of mice given TCDD and in the carcinogenic and cocarcinogenic activity of this chemical.

Animals↗