ABSTRACT
PURPOSE: Tropomyosin-related kinase (Trk) receptors play critical roles in tumor development and are considered attractive targets for cancer therapy. We investigated correlations of the expression of TrkA, TrkB, and TrkC with clinicopathological features and outcomes in gastric cancer. METHODS: Tumor samples were obtained from 221 patients with gastric cancer who underwent gastrectomy between 2003 and 2007. The expression of TrkA, TrkB, and TrkC was analyzed using immunohistochemical staining. The relationship of their expression to clinicopathological factors and outcomes was assessed. RESULTS: High expression of TrkA, TrkB, or TrkC was significantly associated with histopathology (p = 0.022, p < 0.001, and p < 0.001). High expression of TrkA was significantly correlated with variables related to tumor progression, including lymph node metastasis (p = 0.024) and distant metastasis or recurrence (p < 0.001). Distant metastasis or recurrence was found in a significantly higher proportion of patients with high expression of TrkC than in those with low expression (p = 0.036). High expression of TrkA was significantly associated with poorer relapse-free survival (RFS) in univariate analysis (p = 0.001). High expression of TrkA or TrkC was significantly associated with poorer disease-specific survival (DSS) in univariate analysis (p < 0.001 and p = 0.008). In multivariate analysis, TrkA was an independent predictor of RFS [hazard ratio (HR), 2.294; 95 % confidence interval (CI), 1.309-4.032; p = 0.004] and DSS (HR, 2.146; 95 % CI, 1.195-3.861; p = 0.011). Expression of TrkB was not associated with RFS or DSS in univariate analysis. CONCLUSIONS: Our results demonstrated that TrkA expression was associated with tumor progression and poor survival, and was an independent predictor of poor outcomes in gastric cancer patients.
Subject(s)
Membrane Glycoproteins/biosynthesis , Protein-Tyrosine Kinases/biosynthesis , Receptor, trkA/biosynthesis , Receptor, trkC/biosynthesis , Stomach Neoplasms/enzymology , Adult , Aged , Disease-Free Survival , Female , Humans , Immunohistochemistry , Kaplan-Meier Estimate , Male , Membrane Glycoproteins/analysis , Middle Aged , Polymerase Chain Reaction , Prognosis , Proportional Hazards Models , Protein-Tyrosine Kinases/analysis , Receptor, trkA/analysis , Receptor, trkB , Receptor, trkC/analysis , Stomach Neoplasms/mortalityABSTRACT
We studied the pathogenesis of cyclosporine-induced hypomagnesemia in five patients with nephrosis. Serum magnesium concentrations and urinary excretion of magnesium were reduced by the therapy. In contrast, the magnesium concentrations in mononuclear blood cells were increased. We conclude that short-term use of cyclosporine induces an intracellular shift of magnesium and causes hypomagnesemia.