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E Monti

Publications and source records attributed to E Monti.

83 records · Page 5Linked to original sources
PubMedDate not supplied

Endocannabinoids in the immune system and cancer.

The present review focuses on the role of the endogenous cannabinoid system in the modulation of immune response and control of cancer cell proliferation. The involvement of cannabinoid receptors, endogenous ligands and enzymes for their biosynthesis and degradation, as well as of cannabinoid receptor-independent events is discussed. The picture arising from the recent literature appears very complex, indicating that the effects elicited by the stimulation of the endocannabinoid system are strictly dependent on the specific compounds and cell types considered. Both the endocannabinoid anandamide and its congener palmitoylethanolamide, exert a negative action in the onset of a variety of parameters of the immune response. However, 2-arachidonoylglycerol appears to be the true endogenous ligand for peripheral cannabinoid receptors, although its action as an immunomodulatory molecule requires further characterization. Modulation of the endocannabinoid system interferes with cancer cell proliferation either by inhibiting mitogenic autocrine/paracrine loops or by directly inducing apoptosis; however, the proapoptotic effect of anandamide is not shared by other endocannabinoids and suggests the involvement of non-cannabinoid receptors, namely the VR1 class of vanilloid receptors. In conclusion, further investigations are needed to elucidate the function of endocannabinoids as immunosuppressant and antiproliferative/cytotoxic agents. The experimental evidence reviewed in this article argues in favor of the therapeutic potential of these compounds in immune disorders and cancer.

Animals↗
PubMedDate not supplied

Effect of trimetazidine on early and delayed doxorubicin myocardial toxicity.

The influence of the administration of trimetazidine on the myocardial toxicity induced by doxorubicin was studied on an in vivo model in the rat. Trimetazidine was chosen due to its ability to act as a scavenger of oxygen-derived free radicals, which have been implicated in both early and delayed cardiotoxic manifestations after doxorubicin treatment. In the present study, doxorubicin was administered as 4 weekly i.v. injections of 3 mg/kg. The cardiotoxic effects were evaluated by measuring predictive ECG parameters (QT and ST intervals) as well as the contractile performance of atria isolated from treated animals. Heart preparations were also examined by light microscopy. Trimetazidine, 2.5 mg/kg/day i.p. for 3 days before doxorubicin administration plus 2.5 mg/kg/day p.o. for 10 weeks, was unable to prevent the development of doxorubicin-induced long-term cardiotoxicity. However, a significant improvement of the early cardiotoxic signs was observed in trimetazidine-treated rats, as reported in previous investigations. The present findings suggest that different target structures may be involved in the early and delayed free radical-mediated effects of doxorubicin.

Animals↗
PubMedDate not supplied

Trifluoperazine does not affect doxorubicin cardiotoxicity in the rat.

Sprague Dawley rats received doxorubicin (DXR) at a dose of 3 mg/kg i.v. every third day for a total of three administrations, according to an acute and delayed cardiotoxicity experimental model previously described. DXR was found to induce significant ECG alterations (Qat and Sat prolongation) and typical morphologic lesions in the left ventricle. Trifluoperazine (TFP), administered at the doses of 0.2 of 2 mg/kg i.p., 5 days a week for 4 weeks, starting 1 day before DXR, was ineffective in preventing the electrocardiographic and morphologic alterations induced by DXR.

Animals↗
PubMedDate not supplied

Free radical-dependent DNA lesions are involved in the delayed cardiotoxicity induced by adriamycin in the rat.

The role of free radicals in the genesis of adriamycin (ADR)-induced delayed cardiotoxicity and the cardioprotective effects of the spin trap N-tert-butyl-alpha-phenylnitrone (PBN) were investigated in an in vivo rat model. As ADR and free radicals are no longer present in the myocardium by the time the delayed effects of the drug become apparent, ADR has been proposed to act by causing early radical-dependent DNA lesions, resulting in impaired synthesis of critical target proteins. DNA lesions were detected 10 days after ADR treatment (3X3 mg/kg i.v.) and were still present at the time of onset of the delayed cardiomyopathy. PBN, administered by a slow-release osmotic pump to maintain constant plasma levels throughout the time of persistence of ADR in the myocardium (approximately 2 weeks), prevented the development of DNA lesions, as well as the late contractile and electrical impairment induced by the anthracycline, thus supporting the hypothesis that free radicals play a causal role in both phenomena.

Animals↗
PubMedDate not supplied

Antiproliferative effect of genistein and adriamycin against estrogen-dependent and -independent human breast carcinoma cell lines.

The effects of the combination of genistein, a tyrosine kinase inhibitor, and adriamycin, an anthracycline anticancer drug, were studied in three human breast carcinoma cell lines (MCF-7/WT, MCF-7/ADR(R) and MDA-231) differing in estrogen receptor status and adriamycin sensitivity. Genistein inhibited cell proliferation in all three cell lines (IC50 between 7.0 and 37.0 microM). The combination produced additive to synergistic effects; epidermal growth factor receptor modulation by adriamycin does not seem to be involved in this interaction. The possible therapeutic advantage of this drug combination, especially on hormone-independent and multidrug resistant tumor cells, deserves further investigation.

Breast Neoplasms↗