UICC World Cancer Congress 2006

Objective: A number of cytokines (TNF-apha, IL-1,IL-6, interferon-gamma) and proteolysis-inducing factor (PIF) have been proposed as mediators in cachexia. Dolichyl Phosphate (Dol-P) plays an essential role in cytokine synthesis and protein processing. This study was carried out to present evidence that Dol-P is rate limiting factor in pathogenesis of cachexia using a “urinary dolichol test” and polyprenol (PP) supplement in nutrition. Methods: Urinary dolichol (Dol) concentrations were studied in 64 patients with cachexia with good performance status and life expectancy >1 to 2 months, treated with megestrol acetate >480 mg/day (group 1), 48 patients with poor performance status and short life expectancy, treated with prednisolone 50mg/day (group 2). Nutrition of 30 and 25 patients in both groups contained PP 2 mg/day. Results: Mean urinary Dol concentration in patients from group 1 (45,9 + 4,8 mkg/mmol) as well as in group 2 (62,3 + 9,5 mkg/mmol) was significantly higher (p<0,001) than that observed in patients without weight loss (19,8 + 2,2 mkg/mmol). Urinary Dol increase was shown to be correlated with weight loss in cachexia: 2 mkg/mmol = 1 kg. PP in nutrition caused a significant fall in production of IL-1 in group 1 (from mean 74,8 pg/ml to 26,3 pg/ml, p<0,001) and a fall in the proportion of patients excreting PIF (from 90% to 27%, p<0,001). Dol-P dependent disorders in cachexia are established as a new mechanism of weight loss and target for therapy. Modulating effect of Dol-P substitute polyprenol on IL-1and PIF opens up possibilities for cachexia management.