Expression of c-Met in Primary and Recurrent Hepatocellular Carcinoma.

BACKGROUND: The clinical course of hepatocellular carcinoma (HCC) is complicated, because it often recurs and shows multiple lesions, some of which progress to a more malignant form, shortening the life of the patient. The hepatocyte growth factor receptor c-Met has been shown to play an important role in the pathogenesis of HCC, but the influence of c-Met expression on the clinical course of HCC remains to be fully elucidated. METHODS: We randomly selected and included 600 tumor specimens obtained from the primary and recurrent lesions of 319 HCC cases between 1995 and 2007. The expression of c-Met was determined by immunohistochemistry using archived formalin-fixed paraffin-embedded samples. We analyzed the correlation between c-Met expression and clinical parameters, including survival. In addition, we examined c-Met expression in the malignant transition of HCC in all cases including recurrent lesions. RESULTS: Survival analysis using the multivariate Cox proportional-regression model revealed that the prognosis was significantly better in the primary cases with high c-Met expression than in those with low c-Met expression (hazard ratio 0.159, 95% confidence interval 0.065-0.391; p < 0.001). During the course of recurrence, some cases with high c-Met expression returned to low c-Met expression. Among 40 cases with high c-Met expression, 29 survived more than 2 years after detecting the high c-Met expression. CONCLUSION: High expression of c-Met may be a prognostic factor for a good, rather than a poor, HCC prognosis. The involvement of c-Met expression in the malignant transition of recurrent HCC is obscure.

Efficacy and safety of saxagliptin in combination with insulin in Japanese patients with type 2 diabetes mellitus: a 16-week double-blind randomized controlled trial with a 36-week open-label extension.

BACKGROUND: We examined the efficacy and safety of saxagliptin as an add-on to insulin in Japanese patients with type 2 diabetes mellitus. RESEARCH DESIGN AND METHODS: We randomized 240 patients with type 2 diabetes mellitus on insulin monotherapy to 5-mg saxagliptin or placebo as add-on therapy for a 16-week, double-blind period. All patients received 5-mg saxagliptin and insulin for an additional 36 weeks (open-label extension). Change in hemoglobin A1c (HbA1c) at Week 16 was the main endpoint. RESULTS: At Week 16, the adjusted change in HbA1c from baseline increased by 0.51% with placebo and decreased by 0.40% with saxagliptin (difference -0.92% [95% confidence interval -1.07%, -0.76%; p < 0.001]). In patients receiving saxagliptin, reductions in HbA1c at Week 16 were maintained to Week 52, while switching from placebo to saxagliptin resulted in a similar reduction in HbA1c. The incidence of hypoglycemia was not markedly increased with saxagliptin versus placebo in the double-blind period and did not increase substantially during the open-label extension period. The efficacy and safety of saxagliptin was similar between the elderly and non-elderly patient groups. CONCLUSIONS: Adding saxagliptin to ongoing insulin therapy improved glycemic control and was well tolerated in Japanese patients with type 2 diabetes.