Background:Hepatocellular carcinoma (HCC) is the third leading cause of cancer deaths worldwide. We tested megestrol acetate (MA) against placebo in the treatment of advanced HCC.Methods:From 2002 through 2007, this randomised double-blind trial enrolled 204 patients with treatment-naive advanced HCC (Eastern Cooperative Oncology Group (ECOG) performance rating of 0-3) from specialist care centres in six Asia-Pacific nations. Patients received placebo or MA (320 mg day−1). End points were overall survival (OS) and quality of life.Results:An adverse but not statistically significant difference in OS was found for MA vs placebo: median values 1.88 and 2.14 months, respectively (hazard ratio (HR)=1.25, 95% CI=0.92–1.71, P=0.16). However, OS was similar among patients of good functional status (Child-Pugh A and ECOG 0, 1 or 2) (44.3%) in both treatment groups, with the adverse effect of MA confined to those of poor status. Megestrol acetate patients had a worse global health status (not statistically significant) but reduced levels of appetite loss and nausea/vomiting.Conclusion:Megestrol acetate has no role in prolonging OS in advanced treatment-naive HCC. Overall survival with placebo differed markedly from that in similar trials conducted elsewhere, suggesting therapeutic outcomes may be strongly dependent on ECOG status and Child-Pugh score.

The incidence of inflammatory bowel disease, a relapsing intestinal condition whose precise etiology is still unclear, has continually increased over recent years. Metabolic profiling is an effective method with high sample throughput that can detect and identify potential biomarkers, and thus may be useful in investigating the pathogenesis of inflammatory bowel disease. In this study, using a metabonomics approach, a pilot study based on ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) was performed to characterize the metabolic profile of plasma and urine samples of rats with experimental colitis induced by 2,4,6-trinitrobenzene sulfonic acid. Acquired metabolic profile data were processed by multivariate data analysis for differentiation and screening of potential biomarkers. Five metabolites were identified in urine: two tryptophan metabolites [4-(2-aminophenyl)-2,4-dioxobutanoic acid and 4,6-cihydroxyquinoline], two gut microbial metabolites (phenyl-acetylglycine and p-cresol glucuronide), and the bile acid 12a-hydroxy-3-oxocholadienic acid. Seven metabolites were identified in plasma: three members of the bile acid ⁄ alcohol group (cholic acid, 12a-hydroxy-3-oxocholadienic acid and cholestane-3,7,12,24,25-pentol) and four lysophosphatidylcholines [LysoPC(20:4), LysoPC(16:0), LysoPC(18:1) and LysoPC(18:0)]. These metabolites are associated with damage of the intestinal barrier function, microbiota homeostasis, immune modulation and the inflammatory response, and play important roles in the pathogenesis of inflammatory bowel disease. Our results positively support application of the metabonomic approach in study of the pathophysiological mechanism of inflammatory bowel disease.Abbreviations 5-HT, serotonin; DSS, dextran sodium sulfate; IBD, inflammatory bowel disease; LysoPC, lysophosphatidylcholine; MPO, myeloperoxidase; OPLS-DA, orthogonal projections to latent structures discriminant analysis; PCA, principal components analysis; TNBS, 2,4,6-trinitrobenzene sulfonic acid; UPLC-ESI-QTOF-MS, ultra-performance liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry; VIP, variable importance in projection.

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