PT - JOURNAL ARTICLE AU - Sabrina Pacor AU - Sonia Zorzet AU - Moreno Cocchietto AU - Marina Bacac AU - Marta Vadori AU - Claudia Turrin AU - Barbara Gava AU - Anna Castellarin AU - Gianni Sava TI - Intratumoral NAMI-A Treatment Triggers Metastasis Reduction, Which Correlates to CD44 Regulation and Tumor Infiltrating Lymphocyte Recruitment AID - 10.1124/jpet.104.066175 DP - 2004 Aug 01 TA - Journal of Pharmacology and Experimental Therapeutics PG - 737--744 VI - 310 IP - 2 4099 - http://jpet.aspetjournals.org/content/310/2/737.short 4100 - http://jpet.aspetjournals.org/content/310/2/737.full SO - J Pharmacol Exp Ther2004 Aug 01; 310 AB - Intratumor (i.t.) injection of 35 mg/kg/day NAMI-A for six consecutive days to CBA mice bearing i.m. implants of MCa mammary carcinoma reduces primary tumor growth and particularly lung metastasis formation, causing 60% of animals to be free of macroscopically detectable metastases. The i.t. treatment allows study of the effects of NAMI-A on in vivo tumor cells exposed to millimolar concentrations for a relatively prolonged time. Under these conditions, NAMI-A reduces the number of CD44+ tumor cells and changes tumor cell phenotype to a lower aggressive behavior, as shown by scanning electron microscopy analysis. On primary tumor site, NAMI-A causes unbalance between 2n and aneuploid cells in favor of lymphocytes. Furthermore, in tumor tissue, nitric oxide production is increased and active matrix metalloproteinase 9 is decreased, and these effects are accompanied by a reduced hemoglobin concentration. These data are in agreement with the reduction of tumor invasion and metastasis and suggest the therapeutic usefulness of NAMI-A in neoadjuvant or tumor reduction treatments for preventing metastasis formation. These data further stress the usefulness of intratumor treatments as experimental preclinical model for studying in vivo the mechanism of tumor cell interactions after prolonged exposure to ruthenium-based compounds to be developed for metastasis inhibition. The American Society for Pharmacology and Experimental Therapeutics