Effect of a fluorinated pyrimidine on cachexia and tumour growth in murinecachexia models: relationship with a proteolysis inducing factor

The fluorinated pyrimidine nucleoside, 5'-deoxy-5-fluorouridine (5'-dFUrd) has been shown to effectively attenuate the progress of cachexia in the mur ine adenocarcinomas MAC16 and colon 26 as well as in the human uterine cerv ical carcinoma xenograft, Yumoto. Although concomitant inhibition of tumour growth was observed in all three models this was not sufficient to account for the preservation of body weight. An attempt has been made to correlate the anti-cachectic activity of 5'-dFUrd with the presence of a tumour prod uced proteolysis-inducing factor (PIF), thought to be responsible for the d evelopment of cachexia in the MAC16 model. Two variants of colon 26 adenoca rcinoma were employed, clone 20 which produces profound cachexia, and clone 5 which produces no change in body weight in recipient animals. Mice beari ng the colon 26, clone 20 variant showed evidence for the presence of PIF i n tumour, serum and urine, while there was no evidence for the presence of PIF in tumour or body fluids of mice bearing the clone 5 tumours. Treatment of animals bearing the clone 20 variant with 5'-dFUrd led to the disappear ance of PIF from the tumour, serum and urine concomitant with the attenuati on of the development of cachexia. The human cervical carcinoma, Yumoto, wh ich also induced cachexia in recipiant animals. showed expression of PIF in tumour, serum and urine in control and vehicle-treated mice. but was absen t in mice treated with 5'-dFUrd. Thus in these experimental models cachexia appears to be correlated with the presence of PIF. (C) 2000 Cancer Researc h Campaign.