Anti-tumor effect of combined treatment with thymosin alpha 1 and interleukin-2 after 5-fluorouracil in liver metastases from colorectal cancer in rats.
We studied the effect of combined chemo-immunotherapy, 5-FU followed by thymosin alpha 1 (T alpha 1) and interleukin-2 (IL-2) at low doses, on liver metastases from colorectal cancer, induced by splenic injection of DHD/K12 cells (1,2-dimethylhydrazine-induced colon adenocarcinoma) in syngeneic BDIX rats. The presence of liver metastases was checked by laparotomy 14 days after tumor-cell injection. Evaluable rats were assigned randomly to 5 experimental groups designated as control, 5-FU, IL-2, 5-FU/IL-2 and 5-FU/T alpha 1/IL-2. 5-FU was administered i.v. as a continuous infusion for 7 days by an osmotic device implanted surgically. T alpha 1 and IL-2 were administered for 4 days and repeated after 11 days. Combined chemo-immunotherapy was shown both to significantly reduce the growth of liver metastases and to prevent extra-hepatic spread. 5-FU/T alpha 1/IL-2 also improved survival rate. Combined immunotherapy after 5-FU restored NK activity of the peripheral-blood-mononuclear-cell (PBMC) in tumor and/or 5-FU immunodepressed rats and enhanced PBMC cytotoxic activity against the DHD/K12 autologous cell line. This model was devised to mimic the clinical situation of unresectable liver metastases.
Rasi
G
G
Istituto di Medicina Sperimentale, Consiglio Nazionale delle Ricerche (CNR), Rome, Italy.
Silecchia
G
G
Sinibaldi-Vallebona
P
P
Spaziani
E
E
Pierimarchi
P
P
Sivilia
M
M
Tremiterra
S
S
Garaci
E
E
D000818:Animals; D002277:Carcinoma / Q000188:drug therapy*; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003131:Combined Modality Therapy; D003602:Cytotoxicity, Immunologic; D005472:Fluorouracil / Q000008:administration & dosage; D007167:Immunotherapy; D007376:Interleukin-2 / Q000008:administration & dosage*; D007694:Killer Cells, Natural / Q000276:immunology; D008113:Liver Neoplasms / Q000556:secondary*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D016019:Survival Analysis; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology; D000077596:Thymalfasin; D013947:Thymosin / Q000008:administration & dosage / Q000031:analogs & derivatives*
D007376:Interleukin-2; D013947:Thymosin; D005472:Fluorouracil; D000077596:Thymalfasin