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Nucleoside transporter proteins are specialized proteins that mediate the transport of nucleosides and nucleoside analog drugs across the plasma membrane. The human equilibrative nucleoside transporter 1 (hENT1) is a member of these proteins and mediates cellular entry of gemcitabine, cytarabine, and fludarabine. The hENT1 expression has been demonstrated to be related with prognosis and activity of gemcitabine-based therapy in breast, ampullary, lung, and pancreatic cancer. We investigated the immunohistochemical expression of hENT in tumor samples from 111 patients with resected gastric adenocarcinoma, correlating these data with clinical parameters and disease outcomes. None of the patients received chemotherapy or radiation therapy before or after surgery as a part of an adjuvant or neoadjuvant program. On univariate survival analysis, the hENT1 expression was associated with overall survival (OS) and disease free survival (DFS). Specifically, those patients with overexpression of hENT1 showed a shorter OS (P = 0.021) and a shorter DFS (P = 0.033). Considering only the node positive patients, higher hENT levels were associated with significantly shorter median DFS (21.7 months; 95% CI 11.1–32.4) compared with patients with low expression of hENT1. The hENT1 expression was defined, in the lymph-node positive patients, as an independent prognostic factor (P = 0.019). Furthermore, considering only patients with diffuse or mixed tumors and lymph-node positive, the expression of hENT1 was strongly related with DFS and OS. Immunohistochemistry for the hENT1 protein carries prognostic information in patients with resected gastric cancer and holds promise as a predictive factor in chemotherapy decisions. J. Cell. Physiol. 223: 384–388, 2010. © 2010 Wiley-Liss, Inc. [ABSTRACT FROM AUTHOR]

Abstract: We investigated the clinical significance of tumour-infiltrating FOXP3-positive regulatory T cells (Tregs) in radically resected (R0) gastric cancer. From a single-institution database, tumors of 110 patients who underwent R0 resection for stage II–III disease were studied for FOXP3-positive Tregs by immunohistochemistry. The observed median number of FOXP3-positive Tregs was used as the cut-point in analyses (<6 versus ⩾6 count). Tregs were significantly higher in gastric carcinomas than in normal tissue (P =0.0001). Tregs count ⩾6 was significantly associated with vascular/lymphatic/perineural invasion (VELIPI) in the tumour (P =0.03). Multivariate analysis showed association between adverse relapse-free survival and grading 3, stage III, VELIPI and Tregs count ⩾6 (P =0.02). Adverse overall survival was associated with grading 3, stage III, VELIPI and Tregs count ⩾6 (P =0.006). FOXP3-positive Tregs may be a novel marker for identifying high-risk gastric cancer patients. Present findings deserve additional investigation as Tregs may also represent an innovative therapeutic target. [Copyright &y& Elsevier]