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Biomedical subjects

F Cavallo

Publications and source records attributed to F Cavallo.

18 recordsLinked to original sources

Role of neutrophils and CD4+ T lymphocytes in the primary and memory response to nonimmunogenic murine mammary adenocarcinoma made immunogenic by IL-2 gene.

TS/A is a spontaneous adenocarcinoma, apparently not immunogenic in BALB/cnAnCr mice. TS/A cells are unable to stimulate a syngeneic antitumor response either in vitro or in vivo. To evaluate the immunogenic potential of IL-2-releasing neoplastic cells, we used an expression vector to introduce the cDNA coding for murine IL-2 into TS/A cells. Six clones releasing between 30 and 6800 U of IL-2/10(5) cells/ml/48 h have been isolated. Both low (30 U, B1.30) and high (6000 U, B4.6000) IL-2-releasing clone are capable of stimulating a proliferative and cytotoxic response in syngeneic cultures. While the B1.30 clone grows in 60% of syngeneic mice with a delayed pattern, the five clones that release higher levels of IL-2 are promptly rejected. Rejection is associated with neutrophil infiltration, the intensity of which is directly proportional to the amount of IL-2 released. NK cells and CD4+ lymphocytes are uninfluential, whereas CD8+ lymphocytes play only a minor role. This neutrophil-dominated rejection leaves a long-lasting, tumor-specific, T lymphocyte-mediated immune memory. For its induction, CD4+ lymphocytes are required. Their specific activation appears to depend on both the amount of IL-2 released and the granulocyte-mediated reaction that may lead to a more efficient presentation of tumor-associated Ag. These data support the notion that, after transduction of IL-2 gene, cancer cells may elicit an immune antitumor response, and stress the potential use of IL-2 as a component of new tumor vaccines.

Adenocarcinoma

Growth and spread of human malignant T lymphoblasts in immunosuppressed nude mice: a model for meningeal leukemia.

Previous work has shown that nude (nu/nu) mice additionally immunosuppressed by splenectomy, sublethal irradiation, and treatment with antiasialo GM1 antiserum (SIA-nu/nu mice) have no detectable natural killer activity and allow the growth of human malignant lymphoblasts. We show here that all SIA-nu/nu mice engrafted intravenously with 5 x 10(6) malignant lymphoblasts originally derived from a child with a T-cell acute lymphoblastic leukemia (PF382) and from a boy with a T-cell lymphoma (ST-4) develop lethal meningeal leukemia and die within 35 days. Histologic examination of moribund SIA-nu/nu mice showed that vertebral and skull bone marrow was always replaced by proliferating human T lymphoblasts. From the spinal canal, lymphoblasts spread to the meninges, causing hind leg paralysis. Leaving the skull, they permeated the meninges and then invaded the nervous parenchyma. This efficient and reproducible experimental model may be suitable for experimental studies on the pathogenesis of meningeal leukemia.

Animals

A novel transforming protein (SHC) with an SH2 domain is implicated in mitogenic signal transduction.

A new SH2-containing sequence, SHC, was isolated by screening cDNA libraries with SH2 representative DNA probes. The SHC cDNA is predicted to encode overlapping proteins of 46.8 and 51.7 kd that contain a single C-terminal SH2 domain, and an adjacent glycine/proline-rich motif with regions of homology with the alpha 1 chain of collagen, but no identifiable catalytic domain. Anti-SHC antibodies recognized three proteins of 46, 52, and 66 kd in a wide range of mammalian cell lines. These SHC proteins complexed with and were phosphorylated by activated epidermal growth factor receptor. The physical association of SHC proteins with activated receptors was recreated in vitro by using a bacterially expressed SHC SH2 domain. NIH 3T3 mouse fibroblasts that constitutively overexpressed SHC acquired a transformed phenotype in culture and formed tumors in nude mice. These results suggest that the SHC gene products couple activated growth factor receptors to a signaling pathway that regulates the proliferation of mammalian cells.

3T3 Cells

In vitro and in vivo immunomodulatory activity of ST 789 on two human lymphoblastic T cell lines.

The immunomodulatory activity of the synthetic derivative, N-alpha-5(1,6-dihydro-6-oxo-9-purinyl) pentyloxy-carbonyl-L-arginine (ST 789) has been evaluated by using two human T-cell lines stabilized in our laboratory from the pleural effusion fluid of a patient with acute T lymphoblastic leukemia and from the lymph node biopsy of a child with convoluted T-cell lymphoma, respectively. In vitro, ST 789 did not substantially modify the expression of membrane antigens and the proliferation of both lines, whereas their growth in immunosuppressed nude mice was hampered by the local injection of 0.1 microgram/mouse ST 789 for ten days. The combined administration of ST 789 with human peripheral blood polymorphonuclear cells completely inhibited the in vivo tumorigenicity of the T lymphoma. These in vivo findings show that the antitumor action displayed by ST 789 is probably due to its boosting of natural mechanisms.

Adjuvants, Immunologic

Zinc and copper in breast cancer. A joint study in northern Italy and southern France.

The relationship between breast cancer and two trace elements, zinc (Zn) and copper (Cu), was investigated by means of an hospital based case-control study at Milan (Italy) and Montpellier (France). Variables concerning dietary intake of Zn and Cu (in Milan) and their blood levels (both in Milan and Montpellier) were measured. Dietary intake, evaluated through a questionnaire of the dietary history type, and blood levels of Zn and Cu were measured in 261 cases and 261 controls. Cu blood level showed a contradictory tendency in the two samples (higher in controls in Milan, higher in cases in Montpellier), which tended to lessen after adjustment for related variables. No odds ratios (OR) in the different quantiles, nor X2 for trend reached statistical significance. A sharp difference was evidenced on the opposite with regard to Zn blood values in cases and controls. In both samples Zn mean values are significantly higher in cases than in controls, and the difference remains significant in the two samples even after adjustment for related variables. The pooled OR computed from the two samples, after adjustment for known risk factors and related variables, reaches in the fourth quartile a value of 9.5 (CI: 4.9-18.2). Dietary intake of the two minerals (measured only in Milan sample) showed no difference between cases and controls, but a stronger relationship between dietary and blood Zn was evidenced in cases with respect to controls. The authors suggest that the higher Zn level in cases might be related with an higher incorporation of Zn in cancer cases and that the same mineral might play a possible role in tumor growth promotion.

Adult

Growth and dissemination of human malignant lymphoblasts in immunosuppressed nu/nu mice.

Athymic nu/nu mice are commonly employed for the heterotransplantation of solid human tumors. Leukemias, however, have consistently proved difficult to transplant and, to enhance their take, recipient nu/nu mice have been variously immunosuppressed. In this study, the natural reactivity against human malignant T lymphoblast (PF382) of splenectomized nu/nu mice (S-nu/nu), nu/nu mice splenectomized and treated with polyinosinic-polycytidylic acid (SIC-nu/nu), and nu/nu mice splenectomized, irradiated and repeatedly injected with antiasialo GM1 antiserum (SIA-nu/nu) has been correlated with the in vivo growth of subcutaneous and intravenous PF382 cell challenges. SIC-nu/nu mice display a marked natural killer (NK) activity, quickly clear 125I-Urd-labelled PF382 cells injected intravenously and do not allow the growth of subcutaneous nor intravenous PF382 cell challenges. S-nu/nu mice display a slightly lower NK activity and slower clearance of 125I-Urd-labelled PF382 cells. Moreover, an intravenous PF382 cell challenge kills 56% of S-nu/nu mice. SIA-nu/nu mice have no NK activity, slowly clear 125I-Urd-labelled PF382 cells and always allow the growth of PF382 cells injected either subcutaneously or intravenously with a consistent pattern. Following the intravenous challenge, PF382 cells first metastasize to liver and kideny, then focal or diffuse infiltrations of the bone marrow and menings become evident. SIA-nu/nu mice thus offer an interesting experimental model for study of the pathogenesis of leukemic infiltration of the meninges, and the exploration of possible therapeutic approaches.

Animals

The role of diet history and biologic assays in the study of "diet and breast cancer".

Nutritional factors related to breast cancer were investigated by means of a hospital-based case-control study in Milan (Italy) and Montpellier (France). Liposoluble vitamins, cholesterol and triglycerides were measured in blood samples taken from interviewed subjects (319 cases and 344 controls). In addition serum zinc and copper was assessed in the Italian samples and serum fatty acids and malonyl-di-aldehyde in the French samples. A significant difference was found between cases and controls in total fat and cholesterol intake in both populations, and in saturated fatty acid and mono-unsaturated fatty acid consumption in the French samples. No difference emerged in liposoluble vitamin consumption in both populations nor in zinc and copper consumption in the Italian samples. A statistically significant higher serum level of cholesterol and plasma level of vitamin E was observed in cases compared to controls in both populations. The difference in plasma vitamin E was confirmed after adjustment on total cholesterol and triglycerides. Similarly, zinc serum level was higher in Italian cases than in Italian controls, while malonyl-di-aldehyde was lower in French cases than French controls. A multivariate analysis was performed after classification of cases and controls according to quantile distribution of controls. Nutrient consumption and relevant blood markers were directly or partially correlated in both populations. All known risk factors plus age, serum total cholesterol and triglycerides were used as covariates. The odds ratio values for the highest quantiles are: Dietary cholesterol, OR = 1.9 (1.1-3.4); total dietary lipids, OR = 1.9 (1.0-3.4); plasma vitamin E, OR = 4.2 (1.9-9.0); serum zinc, OR = 12.2 (5.4-27.7); serum malonyl-di-aldehyde, OR = 0.56 (0.33-0.97).

Breast Neoplasms

Liposoluble vitamins and lipid parameters in breast cancer. A joint study in northern Italy and southern France.

The relationship between breast cancer, liposoluble vitamins, cholesterol and triglycerides was investigated by means of a hospital-based case-control study conducted at Milan (Italy) and Montpellier (France). These parameters were measured in blood samples taken from 319 cases and 344 controls. The interview included an evaluation of dietary intake of liposoluble vitamins. No difference emerged in liposoluble vitamin consumption, whereas a statistically significantly higher serum level of cholesterol and plasma level of vitamin E existed in cases compared to controls. The difference in plasma vitamin E was confirmed after adjustment for total cholesterol and triglycerides. In contrast, vitamin A variations appear to follow triglyceride trends. A multivariate analysis of the vitamin E plasma level was performed after classification of cases and controls according to quintile distribution of controls. All known risk factors plus age, serum total cholesterol and triglycerides were used as covariates. The odds ratio value for the highest quintile of plasma vitamin E is: 4.2 (1.9-9.0).

Adult

The relationship of dietary intake and serum levels of retinol and beta-carotene with breast cancer. Results of a case-control study.

The possible association between the risk of breast cancer, blood level, and dietary intake of preformed Vitamin A (retinol) and beta-carotene was investigated in a case-control study carried out from May 1982 to June 1985. The patients studied were 214 previously untreated individuals with T1-2, N0-1, M0 breast cancer admitted to the National Cancer Institute of Milan and 215 controls admitted for conditions other than neoplastic or metabolic disorders. Both cases and controls were selected from an age group ranging from 30 to 65 years old. Plasma levels of retinol and beta-carotene were tested from blood samples drawn during the first day after admission to the hospital. A questionnaire about diet was used to estimate the mean intake of 69 food items from which a daily dietary index of retinol and beta-carotene intake was computed. Information relating to the woman's history, socioeconomic status, and known risk factors for breast cancer was also collected. No association was found between beta-carotene (in the diet or blood) or dietary retinol and the risk of breast cancer. As for blood retinol, our data show a significant trend of increasing risk with higher levels; multivariate relative risk for subsequent serum levels based on the control quintiles, are 1, 1.5, 1.8, 1.7; (test for linear trend: chi-square = 8.26). Thus, these findings, together with the results of other studies, suggest that retinol and beta-carotene are unlikely to be related to the risk of breast cancer.

Adult

[Validity of retrograde peripheral phlebography (author's transl)].

The Authors present and discuss the results obtained in phlebographic exploration by a particular method, namely retrograde peripheral phlebography. After describing the technicalities of this procedure, they evaluated its advantages and disadvantages, and conclude by recommending a more widespread use of this examination.

Female

[Blood levels of lead and erythrocyte ALA-dehydrase in 200 employees of a Turin metallurgical plant. Analysis of variables connected with alcohol drinking and smoking habits].

The relationships between blood value of Pb and activity of Ala-dehydrase erythrocyte enzyme were studied in relation to the following variables: age, activity, residence, smoking habits, drinking habits. 200 adults, subdividable into occupationally exposed were examined. The data obtained showed a relationship between smoking and Aladehydrase; a relationship was also found to exist between alcohol and blood Pb and inhibition of Ala-dehydrase activity.

Adult

[Analysis of some hematological parameters and variables connected with drinking and smoking in relation to subclinical blood lead values].

Long-term investigation of the mechanisms involved in the uptake of lead and its effect on the body is referred to. The relation between smoking, drinking and some blood parameters and blood lead and Ala-dehydrase is examined. A close connection between blood lead and alcohol, but not smoking, was noted, whereas both variables led to marked inhibition of Aladehydrase. A model for the relation between alcohol and blood lead was sought. There was a significant relation between Ala-dehydrase activity and the red cell count; this was corroborated by further statistical analysis and observation of increased globular values.

Alcohol Drinking

[Introduction to new research on correlations between manic-depressive psychosis and adult obesity-linked diabetes].

The problem of the association between adult diabetes, obesity and manic-depressive psychosis is examined in the light of new endocrinological and psychopharmacological findings. After a critical review of the vast old and recent literature on the matter, a physiopathological interpretation of the clinical association is put forward on the basis of mental, nervous and endocrine correlations in carbohydrate metabolism, with special reference to manic-depressive psychosis. The insulin-like effect of lithium on carbohydrate metabolism and correlated ions (phosphates, calcium, magnesium, potassium) at cell membrane level is then discussed. Theoretical and practical conclusions are drawn on the basis of these data. The former propose an essentially "structural" or "intersection" hypothesis of the association and suggest depth study of the insulin function especially in the "normal" phase of manic-depressive psychosis. The latter show the possibility of a clinical trial with lithium and other anti-depressant drugs in obese diabetics, with a close cooperation between psychiatrist and diabetologist.

Adult

[Lead. Environmental diffusion and biological aspects].

The problems raised by ambient lead are examined with reference to its uptake, absorption and metabolism in man, animal metabolism and toxicology, sub-clinical effects, and health aspects. The existing research picture of this very complex field is surveyed.

Animals