Effect of structured lipid-enriched total parenteral nutrition in rats bearing yoshida sarcoma

The efficacy of structured lipid, a triacylglycerol of medium and long chain fatty acids, as an element of nutritional support therapies in cancer cachexia was investigated. Using the Yoshida sarcoma to induce cachexia, male Sprague Dawley rats (90 g) were injected subcutaneously with tumor cells (n = 17) or sterile saline (n = 16). Seven days later, rats were randomized to two intravenous diets for 3 days at 220 kcal/kg body weight/d, including 2 g nitrogen/kg body weight/d and 39% of total calories as either structured lipid or long chain triglyceride. Nitrogen balance, tumor growth rate, energy metabolism, and plasma albumin and free fatty acid levels were measured, and whole-body protein kinetics and liver, muscle, and tumor fractional protein synthetic rates were evaluated by adding (14)C-leucine to the diet during the last 4 hours of feeding. Nitrogen balance improved (P < .05) in both tumor and control rats receiving structured lipid-enriched total parenteral nutrition, and was also greater in tumor rats compared with controls. There were no differences in tumor growth or protein kinetics between diet groups. Albumin was lower (P < .05) in tumor rats, but significantly higher in both tumor and control rats given structured lipid-enriched total parenteral nutrition. Free fatty acid was significantly higher in tumor rats versus controls. Whole-body protein kinetics were similar among the four groups. Liver weight, liver weight to body weight ratio, and liver protein synthetic rate were higher in tumor rats. Also, liver weight to body weight ratio was lower in tumor and control animals given structured lipid-enriched total parenteral nutrition. Muscle protein synthetic rate was significantly lower in tumor rats, but higher in tumor and control rats given long chain triglyceride-enriched total parenteral nutrition. The nutritional benefits of structured lipid-enriched total parenteral nutrition favor support of host tissue without promoting tumor growth.     

Two Hydrolase Resistant Analogues of Diadenosine 5′,5″′-P,P-Triphosphate for Studies with FHIT,The Human Fragile Histidine Triad Protein¶

Abstract

The design and synthesis of analogues of diadenosine 5′,5″′-P,P-triphosphate that are resistant to pyrophosphate hydrolysis is described in relation to their rôle in signalling and tumorigenesis involving the Fhit protein, the human fragile histidine triad protein, which is a novel Ap3A binding/cleaving protein.

     

Novel alkoxybenzamide inhibitors of poly(ADP-ribose) polymerase

We have previously described poly(ADP-ribose) polymerase-1 (PARP-1) inhibitors based on a substituted benzyl-phthalazinone scaffold. As an alternative chemical template, a novel series of alkoxybenzamides were developed with restricted conformation through intramolecular hydrogen bond formation; the compounds exhibit low nM enzyme and cellular activity as PARP-1 inhibitors.