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Biomedical subjects

F Spreafico

Publications and source records attributed to F Spreafico.

At least 55 records · Page 3Linked to original sources
PubMed1986

Metastatic growth of a murine tumor: evidence of dissemination to the lungs in the absence of subcutaneous growth.

Growth of MCA-38/B colon adenocarcinoma was detectable 30-33 days after subcutaneous (s.c.) tumor cell inoculation in mice. Seventy percent of the mice receiving 10(7) tumor cells, 50% of those receiving 10(6), and 15% of the mice given 10(5) cells developed s.c. tumors (mean of 4 experiments, total of 80 mice per group). Metastases in the presence of a primary tumor were observed in 11% of 10(7) and in 10% of 10(6) tumor-cell injected animals. Lung metastases were detected in the absence of tumor growth at the site of s.c. cell injection in 19% of 10(7), in 8% of 10(6) and in 5% of 10(5) and 10(4) tumor-cell inoculated mice. In parallel experiments an intravenous (i.v.) inoculum of tumor cells produced lung colonies in 40% of 10(6) and in 14% of 10(5) tumor-cell injected animals. Smaller inocula did not give rise to lung colonies, thus making it unlikely that accidental i.v. inoculations of tumor cells during the s.c. injections caused the observed metastatic dissemination to the lungs.

Adenocarcinoma↗
PubMed1986

The effect of Biostim (RU 41.740) on natural killer activity in different mouse organs.

The effect of Biostim, a mixture of two glycoproteins extracted from K. pneumoniae, on NK activity in lung, blood and spleen was investigated in mice. Marked increases in NK-cytotoxicity for YAC-1 targets were found after single or repeated administrations of this compound by the i.p. or the oral route in the absence of increases of serum IFN. The highest increases in NK activity were found in lymphoid cells recovered from the lung, active treatments with Biostim significantly increasing the proportion of both target-binding cells and lytic conjugate-forming NK cells. In addition to increasing the rate of clearance from lung and spleen of in vivo-injected radiolabelled YAC-1 cells, short (3 h) exposures to Biostim in vitro augmented the NK-cytotoxicity of murine and human cells. By showing that NK cells can also be a target of Biostim, these results can contribute to a better understanding of the mode of action of this immunomodulator.

Adjuvants, Immunologic↗
PubMed1986

A preliminary analysis of the effects of elliptinium on immune reactivities in mice.

The immune effects of Elliptinium (2-methyl-9-hydroxyellipticinium, 9-HME), a chemical recently shown to possess clinical antineoplastic activity, were investigated in mice. Primary antibody responses to T-dependent and T-independent antigens, DTH reactivity and responsiveness to mitogens were significantly depressed only by post treatment with single drug doses of at least 5 mg/kg i.v., i.e. doses clearly above those known to exert full antitumoral effectiveness and to induce lymphoid cell depletion in the same species. Only drug doses in the LD50 range (i.e. 10 mg/kg) reduced the capacity of NK cells and of activated macrophages to express non-specific cytotoxicity towards tumor target cells. When repeated dose regimens were used, significant immune depression was again seen at doses above those displaying chemotherapeutic activity. Data obtained suggest that at chemotherapeutically effective dosages 9-HME possesses in mice a comparatively low immunodepressive potential and that immune cells mediating natural host defence mechanisms appear especially resistant to this drug.

Alkaloids↗
PubMed1985

Relationship between large granular lymphocytes and NK-1.2+ cells from normal and poly(inosinic:cytidylic acid) (poly(I:C]-treated mice.

The present work analyzes the relationship between large granular lymphocytes (LGL), NK-1.2+ cells, and natural killer (NK) activity of C3H/HeN mice. Different hematic cell fractions were obtained according to their nylon-wool adherence and density on Percoll gradients. NK-1.2+ cells (8% of nucleated cells) were more numerous than LGL (3% of nucleated cells) in the input blood population. Eighty-five percent of LGL were recovered from the sorted NK-1.2+ cell fraction. After incubation on nylon-wool column, 63% of LGL and 36% of NK-1.2+ were eluted in the nonadherent fraction. Eighteen percent of NK-1.2+ cells were recovered from the most adherent elutable cell fraction. After the discontinuous Percoll gradient most LGL were present in the low-density fractions while 20% of NK-1.2+ cells were recovered from the highest-density fraction. NK activity was significant both in the nylon-wool-nonadherent and -adherent fractions. After the Percoll gradient most NK activity was present in the low-density fractions. In the present experimental conditions treatment poly(inosinic:cytidylic acid) (poly(I:C] did not increase the numbers of LGL and NK-1.2+ cells either in the blood or in the spleen. However it increased significantly the NK activity of the input cell populations and of the nonadherent and low-density fractions. Similarly, exposure of specific pathogen-free (SPF) mice to non-SPF conditions stimulated NK cytotoxicity but did not alter the percentage of LGL in the blood or in the spleen. Poly(I:C) treatment induced a shift of LGL and NK-1.2+ cells toward the low-density fractions. In poly(I:C)-treated mice images of granule secretion from LGL were detected. Taken together, the present results indicate that LGL and NK-1.2+ cell populations do not totally overlap. Moreover subpopulations of LGL and NK-1.2+ cells can differ in NK activity, morphology, density, adherence to nylon wool, and response to poly(I:C).

Animals↗
PubMed1985

Large granular lymphocytes from murine blood and intestinal epithelium: comparison of surface antigens, natural killer activity, and morphology.

Large granular lymphocytes obtained from murine blood (B-LGL) and intestinal epithelium (IE-LGL) are cells associated with natural killer (NK) activity and thought to be a first line of defense against tumors and/or infectious organisms. Since B-LGL and IE-LGL represent circulating and mucosal NK effectors, respectively, we compared their surface markers, NK activity and morphology to define possible differences between NK cells in different anatomical compartments. B-LGL and IE-LGL were purified by Percoll gradient centrifugation from nude, normal, and beige C57BL/6 mice. We have defined the following surface phenotypes. B-LGL: In nude mice most of them expressed T-200 (89%), asialo-GM1 (71%), and NK-1.1 (72%); 15% possessed the Thy-1.2 antigen, few cells expressed Ly-2, and none showed Ly-1 positivity. Beige mouse B-LGL were positive for T-200 and NK-1.1. IE-LGL; Nude IE-LGL compared to nude B-LGL showed a similar expression of T-200 and Thy-1.2. Ly-1+ and Ly-2+ cells were more numerous than in B-LGL, whereas NK-1.1+ and asialo-GM1+ cells were less numerous. Interestingly, Ly-2+ IE-LGL were at least partially Thy-1.2-. In euthymic mice IE-LGL had a phenotype comparable to that of nude IE-LGL. The NK activity of B-LGL from nude and normal mice was considerably higher than that of IE-LGL from the corresponding mice. IE-LGL from nude mice possessed larger cytoplasms, and more numerous and bigger azurophilic granules than B-LGL. Similar findings were obtained in normal mice. In beige mice 95% of B-LGL showed a single granule whereas 80% of IE-LGL contained multiple granules (mean 3/cell). Giant granules were frequently found in beige IE-LGL while they were rare in beige B-LGL. Thus, clear differences exist between B-LGL and IE-LGL and they may reflect either different homing patterns of subpopulations of LGL or different stages of maturation of the same lineage of cells.

Animals↗
PubMed1985

The immunological activity of plant toxins used in the preparation of immunotoxins--II. The immunodepressive activity of gelonin.

The immunological activity of Gelonin, a 30,000 dalton plant protein possessing close similarity to Ricin chain A as a protein synthesis inhibitor which may be of interest for the preparation of antibody-toxin conjugates, was studied in mice. At in vitro concentrations not affecting baseline radioactivity uptake, this substance reduced mitogen responses with the following order of sensitivity PHA less than ConA less than LPS. In microgram/ml concentrations it also markedly reduced macrophage-dependent cytotoxicity while not affecting NK activity. Macrophagic (but not NK) cytotoxicity and mitogen responses were similarly depressed after in vivo treatment. When given before (but not after) stimulus, Gelonin also reduced the primary responses to a T-dependent and, although to a lower degree, to a T-independent antigen, and decreased resistance to allogeneic tumor grafts and L. monocytogenes challenges. The immunopharmacological activity of this and similar substances should be considered in the design of antibody-toxin conjugates and in the evaluation of their therapeutic activity.

Animals↗
PubMed1985

[Different clinical and prognostic aspects of angina pectoris in unstable phase].

The purpose of this study was to focus on the clinical and angiographic characteristics of 113 patients with crescendo angina (Group I) as compared to 187 patients with angina of new onset (Group II), selected from a series of 474 consecutive subjects, admitted to our clinic between January 1976 and July 1983 because of recurrent episodes of spontaneous angina, who underwent cardiac catheterization and coronary angiography within one month of hospitalization. Group I patients showed a greater incidence of prior transmural myocardial infarction (p less than 0.01), arterial hypertension (p less than 0.01), multivessel disease (p less than 0.01) and a lower value of left ventricular ejection fraction (p less than 0.01) than Group II patients. In the latter group of patients anginal episodes were more frequently associated with S-T segment elevation than with S-T segment depression (p less than 0.001), while the opposite was found in patients with crescendo angina. Survival curves up to five years showed that medically treated patients with crescendo angina had a worse long-term prognosis than patients with unstable angina of new onset (p less than 0.01). On the contrary no difference was found between the surgically treated patients of the two groups. Our data suggest that the more diffuse involvement of the coronary tree associated with a more depressed left ventricular function may result in an unfavorable long-term prognosis in patients with crescendo angina as compared to those with unstable angina of new onset. Such a difference between the two groups was abolished by surgical treatment.

Angina Pectoris↗
PubMed1984

Enhanced xanthine oxidase activity in mice treated with interferon and interferon inducers.

Administration to mice of either interferon (IFN) or IFN inducers resulted in a marked increase of xanthine oxidase (XO) activity in different organs. Dose response studies revealed that serum XO was increased by administration of polyinosylic-polycyticylic acid (poly I-C) at doses as low as 0.1 mg/kg. In view of the well known ability of XO to generate superoxide radicals it is suggested that its induction might play a role in several biological effects of IFN.

Animals↗
PubMed1984

On the immunopharmacology of cancer chemotherapeutics.

This paper discusses a number of aspects having possible clinical relevance regarding the immunopharmacology of the chemical agents commonly employed in anticancer treatment. After describing results obtained examining the effects exerted by such drugs on cells such as NK, macrophages and suppressor elements, the following conclusions are discussed: a) that cancer chemotherapeutics even when having similar modes of cytotoxic action and possessing close structural analogies, can markedly vary in their immunological activity; b) that immunocytes exhibit an at least operational hierarchy in their sensitivity to the effect of a given drug. Experimental data on the possibility that anticancer chemicals may differentially affect given types of immune cell when present in various anatomical districts are also presented. Examples of the possible practical implications of such findings on the immunomodulatory activity of cancer chemotherapy agents are lastly discussed.

Adjuvants, Immunologic↗
PubMed1984

Chemotherapy-increased antineoplastic effects of antibody-toxin conjugates.

A model, employing murine L1210 leukemia to which the artificial determinant TNP was bound in vitro and an anti-DNP antibody-ricin A-chain conjugate, was used to explore the in vivo therapeutic potential of combined immunotoxin-chemotherapy treatment. Under conditions in which immunotoxin and chemotherapy as single therapies had only marginal therapeutic activity, their combined use was markedly effective.

Animals↗
PubMed1983

The immunomodulatory activity of the plant proteins Momordica charantia inhibitor and pokeweed antiviral protein.

The immunological activity of Momordica Charantia inhibitor (MCI) and of Pokeweed antiviral protein (PAP-S), 30,000 daltons plant proteins possessing close similarity to Ricin A chain as inhibitor of protein synthesis, was investigated in mice. In vivo, single nontoxic injections of microgram amount of these substances delayed H2-incompatible skin allograft rejection, splenocyte responsiveness to ConA and PHA, but not to LPS, and abrogated the PFC response to a T-dependent (SRBC) antigen while totally sparing that to a T-independent (S III) stimulus. Injection of these substances could also reduce NK cell activity while increasing macrophage-mediated spontaneous cytotoxicity. In vitro, MCI and PAP-S at non-cytotoxic concentrations inhibited lymphoid cell responsiveness to PHA and ConA, but not to LPS, and markedly enhanced macrophage-dependent cytotoxicity.

Animals↗
PubMed1982

Metastatic potential of metastases, tumor cell heterogeneity, and therapeutic implications.

The metastasizing capacity of spontaneous metastases of several murine tumors of different histology, origin, and disseminative pattern was investigated to test the hypothesis that metastases originate from various subpopulations within the primary tumor. Overall, tumor cells from individual metastases did not show greater metastasizing capacity than the cells of the original tumor, although a degree of heterogeneity was seen. Differences in the immunologic profile among metastases of the same tumor were also observed. The possible therapeutic implications of these findings are discussed.

Animals↗
PubMed1982

Effect of medroxyprogesterone acetate on DMBA-induced rat mammary carcinoma and on immunological reactivity.

The antineoplastic activity of medroxyprogesterone acetate (MPA) was investigated in rats bearing DMBA-induced mammary carcinomas, a classical model of hormone-dependent tumor. Using a repeated injection schedule of relatively short duration, MPA was markedly effective (80% CR + PR) not only on relatively small (1-1.5 cm) tumors but also on advanced (4.5-5.5 cm) neoplasms. MPA effectiveness was comparable to that of a frankly toxic adriamycin regimen. In antitumorally effective schedules MPA was incapable of significantly affecting in either direction cellular and humoral immunological reactivities in rodents.

9,10-Dimethyl-1,2-benzanthracene↗
PubMed1982

In vitro and in vivo cytotoxicity of 6 amino-5-formyl-methylamino-1,3-dimethyl uracil, a uracilic metabolite of caffeine.

The in vitro cytotoxicity of 6 amino-5 formylmethylamino-1,3 dimethyluracil (ADMU) a major metabolite of caffeine in rats was studied by cell counts or [3H]thymidine incorporation in the murine Lewis lung carcinoma (3LL) and L929 fibroblast cells and in the human E cell line derived from an ovarian carcinoma. Unlike 5-fluorouracil (5FU) which was markedly cytotoxic, ADMU concentrations up to 60 micrograms/ml were devoid appreciable cytocidal action. Similarly, 1-10 micrograms 5FU markedly inhibited the blastogenic response of rat lymphocytes to PHA, whereas lymphoproliferation was not affected at ADMU concentrations up to 100 micrograms/ml. In vivo administration of ADMU (40 mg/kg, twice a day on day 1 to 3) to L1210 leukaemia-bearing mice caused a transient short-lasting reduction of tumour cell numbers only on day 6 after leukaemia inoculation.U

Animals↗