Increase of tumour infiltrating lymphocytes in mice treated with antimetastatic doses of NAMI-A.
NAMI-A is a novel antitumour agent, based on ruthenium, which has proved effectiveness against lung metastases of solid mouse tumours. The study focuses on the effects of NAMI-A on leukocyte infiltration into the primary tumour of MCa mammary carcinoma, implanted subcutaneously (s.c.) or intramuscularly (i.m.) into CBA mice. NAMI-A, given with a cycle of daily treatments for six consecutive days on advanced tumours at 35 mg/kg/day, markedly reduces lung metastasis independently of the tumour type (Lewis lung carcinoma, MCa mammary carcinoma or TS/A adenocarcinoma) being treated and of the site of tumour implantation (s.c. or i.m.). The analysis of leukocyte infiltration of the primary tumour, performed on a single cell suspension of cells isolated from a Ficoll gradient on which a raw suspension of primary tumour cells was layered, showed NAMI-A to significantly increase tumour infiltrating lymphocytes. These lymphocytes are almost all CD3+ cells with a significant increase of the CD8+ over the CD4+ subpopulation that reduces the helper/suppressor ratio from 2.8 to 2.1. These data indicated the absence of toxicity of NAMI-A for tumour infiltrating lymphocytes and suggested that this compound might even synergize in combined treatments with cancer immunotherapy.
Magnarin
M
M
Callerio Foundation Onlus, Trieste, Italy.
Bergamo
A
A
Carotenuto
M E
ME
Zorzet
S
S
Sava
G
G
D000230:Adenocarcinoma / Q000188:drug therapy / Q000276:immunology*; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D018827:Carcinoma, Lewis Lung / Q000188:drug therapy / Q000276:immunology*; D004121:Dimethyl Sulfoxide / Q000031:analogs & derivatives* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000517:prevention & control / Q000556:secondary*; D016246:Lymphocytes, Tumor-Infiltrating / Q000276:immunology*; D008325:Mammary Neoplasms, Experimental / Q000188:drug therapy / Q000276:immunology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008808:Mice, Inbred CBA; D009942:Organometallic Compounds / Q000627:therapeutic use*; D017975:Ruthenium Compounds; D013601:T-Lymphocytes / Q000145:classification / Q000276:immunology*
D000970:Antineoplastic Agents; D009942:Organometallic Compounds; D017975:Ruthenium Compounds; C113661:imidazolium-bis(imidazole)dimethylsulfoxideimidazotetrachlororuthenate(III); D004121:Dimethyl Sulfoxide