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Biomedical subjects

F Spreafico

Publications and source records attributed to F Spreafico.

At least 91 records · Page 5Linked to original sources

Effects on in vitro tumor growth of macrophages isolated from human ascitic ovarian tumors.

Macrophages were isolated from 22 human ascitic ovarian epithelial tumors and their growth-inhibitory capacity was tested using as targets the following in vitro tumor cell lines: murine TLX9 lymphoma and FS6 sarcoma; human myeloid K562 leukemia and human E cell line derived from an ovarian carcinoma. Macrophage preparations were heterogeneous in their interaction with tumor target cells, and assay conditions, such as the type of target cell, incubation time, and attacker to target cell (A:T) ratio critically affected the evaluation of the cytotoxic potential of tumor-associated macrophages. At an A:T ratio of 7:1 no cytostatic activity on TLX9 and K562 cells was ever observed, but in the presence of specific antibody 8 out of 12 macrophage preparations tested showed significant antibody-dependent cytotoxicity on TLX9 lymphoma cells. Macrophage preparations from two patients significantly inhibited growth of the FS6 sarcoma and a cytostatic activity on E cells was observed in five additional patients. Significant stimulation of the proliferative capacity of at least one of the target cell lines was observed in 11 subjects at an A:T ratio of 7:1. In 12 patients, macrophage cytostatic activity on E cells was also tested at an A:T ratio of 35:1; eight out of 12 preparations showed significant cytotoxicity under these conditions. When the same subject was repeatedly tested at short intervals the same pattern of inhibition or stimulation of tumor growth was observed.

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In vitro generation of nonspecific suppressor cells and their characterization.

In vitro preculture of C3H/He splenocytes for 48 to 96 hr induces aspecific suppressor cells evaluated by their ability to reduce 3H-TdR uptake by fresh syngeneic splenocytes stimulated by different amounts of Concanavalin A (Con A) in vitro. This suppressive activity is obtained in medium containing 10% heat-inactivated fetal calf serum (FCS) or similar amounts of heat-inactivated bovine serum, syngeneic, or allogeneic murine sera but not by unheated FCS. Suppressive activity is resistant to mitomycin C and radiation up to 5,000 R. Exposure of precultured cells to carbonyl iron or plastic adherence, but not to anti-Thy 1.2 serum plus complement, results in removal of the suppressive activity.

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Effect of chemotherapeutic agents on natural cell-mediated cytotoxicity in mice.

Spleen natural killer (NK) activity was investigated in cells from C57BL/6J mice treated with various chemotherapeutic agents; 51Cr-labeled YAC-1 lymphoma cells were used as targets. Treatment with azathioprine (a single injection of 100-400 mg/kg ip or 5 daily doses of 80 mg/kg lp) and cyclophosphamide (a single injection of 50--200 mg/kg ip or 5 daily doses of 25 mg/kg ip) resulted in a marked dose-dependent inhibition of NK activity 2 days later. NK cells recovered rapidly from drug-induced suppression; by 7 days after drug treatment, no difference from control values was observed. Dimethyltriazenoimidazole carboxamide (20--200 mg/kg ip) and adriamycin (10--15 mg/kg iv) did not impair natural cytotoxicity per unit number of lymphoid cells, daunomycin (10 mg/kg iv) caused borderline impairment of NK acitivity, and N-trifluoroacetyl-adriamycin-14-valerate (80 mg/kg iv) markedly suppressed natural cytotoxicity. These results are discussed in light of the known effects of these agents on T-cells, B-cells, and K-cells and on hematopoietic histocompatibility-type reactions.

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Some examples of interactions between drugs in cancer chemotherapy.

Drug combinations in cancer treatment are widely utilized because they frequently result in better therapeutic activity than the single treatments. The mechanism(s) by which this can be achieved may reside in an enhanced chemotherapeutic effect or in reduced toxicity, it being difficult to dissociate the two aspects. To underline this difficulty, experimental studies will be reported. A first example illustrates the interaction between phenobarbital and cyclophosphamide. Depending on the schedule of administration, different effects can be obtained. These effects cannot always be explained by pharmacokinetic data. A second example deals with the combination of anthracycline antibiotics (daunomycin and adriamycin) with immunostimulant treatment (C. parvum). Both in vitro and in vivo adriamycin was less toxic than daunomycin for macrophages. As predicted on the basis of this finding, adriamycin resulted in a synergistic antitumoral effect when combined with macrophage activators.

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Suppression of mitogen responses and graft-versus-host reaction by splenocytes from mice bearing Lewis lung carcinoma.

The presence of suppressor cells in the spleens of C57BL/6 mice bearing Lewis lung carcinoma was investigated with the use of the in vitro lymphoproliferative response to mitogens and the graft-versus-host reaction (GVHR) as test systems. Splenocytes from tumor-bearing mice showed a lower response to mitogens when obtained 15-27 days after tumor transplant. In parallel, these cells were capable of suppressing the response of normal spleen cells to mitogens and their capacity to mount a GVHR in allogeneic hosts. Treatments with procedures known to remove adherent phagocytes, but not treatments with anti-Thy 1.2 serum plus complement, removed the suppressive activity observed.

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Comparative antineoplastic activity of adriamycin and N-trifluoroacetyladriamycin-14-valerate.

A comparative investigation of the antineoplastic activity of adriamycin and its derivative, N-trifluoroacetyladriamycin-14-valerate (AD 32), was conducted in murine tumor models employing different treatment schedules and injection routes. In all conditions tested, ie, ascitic and disseminated L1210 leukemia, ascitic LSTRA lymphoma, and advanced Lewis lung carcinoma, AD 32 was significantly more effective in terms of lifespan prolongation and induction of cures than optimal adriamycin treatments. As with adriamycin, AD 32 was ineffective on ic transplanted L1210 leukemia.

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Preliminary characterization in mice of the effect of isoprinosine on the immune system.

A preliminary characterization of the immunomodulatory activity of isoprinosine in mice was conducted in both normal and tumor-bearing mice. Under the experimental conditions employed, isoprinosine given ip and orally was found to possess some immunomodulatory capacity in various model systems. The compound appeared to preferentially influence T- but not B-cell responses; it did not apparently influence the functional capacity of macrophages, K cells, and NK cells.

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