Intestinal Absorption of Lipids Using a Pancreatic Enzyme-Free Nutritional Supplement in Patients with Cystic Fibrosis: A Randomized, Double-Blind, Crossover Pilot Trial.

Nutritional supplements for patients with exocrine pancreatic insufficiency (EPI) typically utilize pancreatic enzyme replacement therapy (PERT) which is associated with gastrointestinal side effects. We evaluated serum triglyceride levels in patients with cystic fibrosis following consumption of an enzyme-modified oil oral nutritional supplement (EMO-ONS) versus a standard triacylglycerol-based ONS product (TAG-ONS) used concomitantly with PERT and patient tolerability between the two approaches. Ten subjects with CF and EPI taking PERT were enrolled in a single-center, double-blind, cross-over proof of concept trial. Five subjects randomized to Arm 1 were administered a PERT placebo and EMO-ONS and 5 subjects in Arm 2 were administered TAG-ONS+PERT. After 4 to 14 days, subjects received the opposite ONS. Serum triglyceride levels were measured at baseline and hourly for 6 h. Following the above, subjects were randomly assigned to receive 2 daily servings of EMO-ONS+PERT placebo or TAG-ONS+PERT at home for 7-days, self-reporting gastrointestinal symptoms daily. Mean change in peak serum triglyceride levels were similar for both groups (EMO-ONS = 41.9 ± 46.7 mg/dL vs. TAG-ONS+PERT = 46.4 ± 44.1 mg/L; p = 0.85). There was no difference in mean ratio of the serum triglyceride AUC between the two groups (p = 0.58) or self-reported gastrointestinal tolerance. EMO-based products may provide a PERT-free alternative to traditional ONS products in patients with cystic fibrosis.

NS-398, a selective cyclooxygenase-2 inhibitor, reduces experimental bladder carcinoma outgrowth by inhibiting tumor cell proliferation.

OBJECTIVES: To evaluate the efficacy of the selective cyclooxygenase-2 (COX-2) inhibitor NS-398 in treating experimental T24 bladder carcinoma, and to assess its effect on tumor cell proliferation and survival and tumor vascularization. COX-2 overexpression is frequently observed in bladder carcinoma and has been correlated with an increased disease stage and with reduced patient survival. METHODS: NS-398 was used to inhibit COX-2 selectively in human T24 bladder carcinoma cells. Lentiviral transduction of the firefly luciferase gene allowed us to assess the effect of NS-398 on orthotopic bladder carcinoma growth over time in a noninvasive manner. Immunohistochemistry on bladder tissue sections was performed to determine the effect of NS-398 treatment on tumor cell proliferation (Ki-67), apoptosis (cleaved caspase-3), and angiogenesis (von Willebrand factor; CD31). RESULTS: T24 cells expressed COX-2 and secreted prostaglandin E2 (PGE2). Selective COX-2 inhibition using NS-398 abrogated PGE2 secretion and inhibited cell proliferation in vitro in a dose-dependent manner, without affecting cell viability. In vivo administration of NS-398 reduced the outgrowth of experimental orthotopic T24 bladder carcinoma. This was accompanied by a significant reduction in Ki-67-positive tumor cells but not by a reduction in tumor cell viability or tumor vascularization. CONCLUSIONS: Selective COX-2 inhibition by NS-398 reduces the outgrowth of T24 human bladder carcinoma in an orthotopic mouse model. The therapeutic activity was most likely caused by inhibition of tumor cell proliferation, rather than by inhibition of angiogenesis or tumor cell survival.