Comparison of the effects of the antimetastatic compound ImH[trans-RuCl4(DMSO)Im] (NAMI-A) on the arthritic rat and on MCa mammary carcinoma in mice.
The effects of the new molecule ImH[trans-RuCl4(DMSO)Im] (NAMI-A), administered orally or intraperitoneally to adjuvant-arthritic rats or orally to mice bearing s.c. or i.m. implants of MCa mammary carcinoma, were studied. NAMI-A was not able to modify the progression of chronic inflammation in the complete Freund-adjuvant injected animals. Histology indicated a significant worsening of the inflammatory process, characterised by an increased infiltration of inflammatory cells, as well as by a remarkable deposition of connective tissue fibres around the blood vessels and alveolar walls. NAMI-A had no effect on primary i.m. implanted MCa mammary carcinoma growth and its lung metastasis formation, but significantly interfered with the cell cycle of primary tumor cells following bolus oral administration. On the contrary, NAMI-A caused a significant inhibition of lung metastasis accompanied by a dramatic deposition of connective tissue fibres around the primary tumor mass, when given as medicated food to mice implanted s.c. with MCa tumor. These data indicated that NAMI-A is well absorbed after oral administration although there is no connection between lung concentration and the antimetastatic activity. Conversely, the marked deposition of connective tissues in NAMI-A treated animals is in agreement with the reported effects of the compound on extracellular matrix and tumor blood vessels.
Sava
G
G
Callerio Foundation, Institutes of Biological Research, Trieste, Italy. GSAVA@FC.UNIV.TRIESTE.IT
Gagliardi
R
R
Cocchietto
M
M
Clerici
K
K
Capozzi
I
I
Marrella
M
M
Alessio
E
E
Mestroni
G
G
Milanino
R
R
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D000970:Antineoplastic Agents / Q000008:administration & dosage*; D001168:Arthritis / Q000188:drug therapy*; D004121:Dimethyl Sulfoxide / Q000008:administration & dosage / Q000031:analogs & derivatives*; D005260:Female; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000556:secondary*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy* / Q000473:pathology*; D051379:Mice; D009362:Neoplasm Metastasis; D009942:Organometallic Compounds / Q000008:administration & dosage*; D051381:Rats; D017975:Ruthenium Compounds / Q000008:administration & dosage*
D000893:Anti-Inflammatory Agents; D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D004121:Dimethyl Sulfoxide