Molecular and immunologycal basis of a novel therapeutic formulation: Oligoelements Zn, Se and Mn plus Lachesis Muta venom (O-LM).

CRESCENTI ERNESTO; CROCI MAXIMO; CREMASCHI GARCIELA; GENARO ANA; MOHAMAD NORA; SAMBUCO LORENA; MEDINA VANINA; BERGOC ROSA; RIVERA ELENA

June 2-6, 2006. Atlanta, Georgia, USA.

Congreso; 42nd Annual Meeting of the American Society of Clinical Oncology ASCO.; 2006

http://www.asco.org/portal/site/ASCO Home > Abstracts & Research > Abstracts > 2006 ASCO Annual Meeting   Molecular and immunologycal basis of a novel therapeutic formulation: Oligoelements Zn, Se and Mn plus Lachesis Muta venom (O-LM). Sub-category:  Other Novel Agents  Category:  Developmental Therapeutics: Molecular Therapeutics  Meeting:  2006 ASCO Annual Meeting    Abstract No: 13158 Citation: Journal of Clinical Oncology, 2006 ASCO Annual Meeting Proceedings Part I. Vol 24, No. 18S (June 20 Supplement), 2006: 13158 Author(s): E. J. Crescenti, M. Croci, G. Cremaschi, A. Genaro, N. Mohamad, L. Sambuco, V. Medina, R. Bergoc, E. S. Rivera Abstract: Background: We have previously reported that O-LM inhibited malignant cell proliferation in vitro and in vivo, increasing survival in rodent tumor models. We also demonstrated a protective action of O-LM against undesirable effects of chemotherapy and ionizing radiation, enhancing their therapeutic action. Furthermore, O-LM applied to patients with advanced breast, colon and pancreatic cancer resulted in increased survival and better quality of life with no side effects. In this work we further investigated the mechanisms involved in O-LM therapeutic effect. Methods: Two groups of Nude mice, control and O-LM (Zn, Se, Mn 4µ g/ml each; L. Muta 4 ng/ml) treated (0.1 ml/day, sc) were inoculated with PANC-1 cells to evaluate tumor development. PCNA, P53, antioxidant enzymes, apoptosis, microvessels and immune cell markers were studied by immunohistochemistry. In control and O-LM treated BALB/c mice we determined in vitro responses to T and B selective mitogens. Results: O-LM treated tumors showed significant lower growing rate, smaller mass (3,77±0,95 vs 9,75±2,30 cm3) and an important peritumoral lymphoid infiltrate. Apoptotic cells and P53 expression were increased while PCNA was negative and microvessels counts were lower than controls. O-LM produced a 3-fold increase in Superoxide Dismutase activity. The infiltrates showed an important number of CD11 bearing cells and B220 positive but CD3 and CD19 negative cells, suggesting the presence of NK cells. In BALB/c mice T selective mitogen Con A, but not B selective mitogens responses were enhanced, with a maximum after 60 days of O-LM treatment. A 4-fold increase in IFNγ release was observed in cell-free supernatants from lymph node culture stimulated with Con A obtained from 60-days treated mice. Conclusions: Present data demonstrate the capacity of O-LM to modulate free radical production, the expression of tumor markers and suggest an important up-regulation of innate and T-cell mediated immunity induced by in vivo treatment with O-LM. These results reinforce the hypothesis that the effective therapeutic action of O-LM is based on its ability of targeting simultaneously multiple pathways involved in cancer development with the additional advantage of the total absence of adverse effects.