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Anti-tumor effect of combined treatment with thymosin alpha 1 and interleukin-2 after 5-fluorouracil in liver metastases from colorectal cancer in rats

✍ Scribed by Guido Rasi; Gianfranco Silecchia; Paola Sinibaldi-Vallebona; Erasmo Spaziani; Pasquale Pierimarchi; Mariliana Sivilia; Salvatore Tremiterra; Enrico Garaci


Publisher
John Wiley and Sons
Year
1994
Tongue
French
Weight
625 KB
Volume
57
Category
Article
ISSN
0020-7136

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✦ Synopsis


We studied the effect of combined chemo-immunotherapy, 5-FU followed by thymosin al (Toll) and interleukin-2 (IL-2) at low doses, on liver metastases from colorectal cancer, induced by splenic injection of DHD/KIZ cells (I ,2-dimethylhydrazineinduced 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/Tal /IL-2. 5-FU was administered i.v. as a continuous infusion for 7 days by an osmotic device implanted surgically. Toll and IL-2 were administered for 4 days and repeated after I I days. Combined chemo-immunotherapy was shown both to significantly reduce the growth of liver metastases and to prevent extra-hepatic spread. 5-FU/TaI / IL-2 also improved survival rate. Combined immunotherapy after 5-FU restored NK activity of the peripheral-bloodmononuclear-cell (PBMC) in tumor and/or 5-FU immunodepressed rats and enhanced PBMC cytotoxic activity against the DHD/KI2 autologous cell line. This model was devised to mimic the clinical situation of unresectable liver metastases.