We report the first case of single port laparoscopic right hemicolectomy for advanced colon cancer. An abdominal 3 cm length incision was made via the umbilicus. A small wound retractor and a surgical glove were used as a single port. All soft tissue anterior to the superior mesenteric vein was completely removed and D3 lymph node dissection was achieved. The total operative time was 180 min with minimal blood loss (< 50 mL). The size of the tumor was 5 cm x 3 cm and its tumor stage was T3N0. Sixty-nine lymph nodes were harvested and none were positive. We believe that single port surgery for colon cancer is a feasible and safe procedure with surgical results comparable to conventional laparoscopic procedures.

Purpose: PRKCDBP is a putative tumor suppressor in which alteration has been observed in several human cancers. We investigated expression and function of PRKCDBP in colorectal cells and tissues to explore its candidacy as a suppressor in colorectal tumorigenesis.Experimental Design: Expression and methylation status of PRKCDBP and its effect on tumor growth were evaluated. Transcriptional regulation by NF-kB signaling was defined by luciferase reporter and chromatin immunoprecipitation assays.Results: PRKCDBP expression was hardly detectable in 29 of 80 (36%) primary tumors and 11 of 19 (58%) cell lines, and its alteration correlated with tumor stage and grade. Promoter hypermethylation was commonly found in cancers. PRKCDBP expression induced the G 1 cell-cycle arrest and increased cellular sensitivity to various apoptotic stresses. PRKCDBP was induced by TNFa, and its level correlated with tumor cell sensitivity to TNFa-induced apoptosis. PRKCDBP induction by TNFa was disrupted by blocking NF-kB signaling while it was enhanced by RelA transfection. The PRKCDBP promoter activity was increased in response to TNFa, and this response was abolished by disruption of a kB site in the promoter. PRKCDBP delayed the formation and growth of xenograft tumors and improved tumor response to TNFa-induced apoptosis.Conclusions: PRKCDBP is a proapoptotic tumor suppressor which is commonly altered in colorectal cancer by promoter hypermethylation, and its gene transcription is directly activated by NF-kB in response to TNFa. This suggests that PRKCDBP inactivation may contribute to tumor progression by reducing cellular sensitivity to TNFa and other stresses, particularly under chronic inflammatory microenvironment. Clin Cancer Res; 17(24); 7551-62. Ó2011 AACR.

Interaction between the receptor for advanced glycation end products (RAGE) and its ligands amplifies the proinflammatory response. N-Linked glycosylation of RAGE plays an important role in the regulation of ligand binding. The receptor for advanced glycation end products (RAGE) 2 is a multiligand receptor that binds to carboxymethyl lysineand AGE-modified proteins and lipids but also to more autonomous ligands including high mobility group box 1 protein (HMGB1), members of the S100/Calgranulin protein family, amyloid ␤-peptide and Mac-1 (1-7). Binding of ligands to RAGE is mediated by an extracellular region of the receptor comprising an N-terminal variable (V)-domain and two constant (C)-immunoglobulin domains (2,8,9). Interaction between RAGE and ligands recruits diverse signal transduction pathways involving NF-B and MAP kinase activation and consequently the expression of proinflammatory genes (10 -14). RAGE also acts as an endothelial adhesion receptor promoting leukocyte recruitment during inflammation via a direct interaction with the ␤2-integrins Mac-1 or p150,95 expressed by leukocytes (15,16). RAGE contains two potential N-linked glycosylation sites at Asn 25 and Asn 81 (1). It is now well established that RAGE is N-link glycosylated and that some of the added N-glycan is further modified, resulting in an anionic nonsialylated carboxylated N-glycan (17-20). The nonsialylated carboxylated Nglycan is essential for binding of RAGE to HMGB1, S100A8/A9, and S100A12 in particular, indicating that N-linked glycosylation and/or the modification of the added N-glycan play important roles in the regulation of RAGE-ligand binding (18,21,22).A naturally occurring polymorphism has been identified that results in a glycine-to-serine substitution at position 82 within the V-domain. This polymorphism occurs with relatively high incidence compared with other RAGE polymorphisms that have been identified (23,24). The G82S mutant RAGE displays enhanced ligand binding to S100A12 and AGE ligands (25,26). Consequently, this RAGE variant is associated with increased NF-B activation and inflammatory gene expression (25,26). In addition, the G82S polymorphism is associated with reduced levels of soluble RAGE (sRAGE) that in a number of diseases magnifies the contribution from RAGE toward inflammation (27-31). How ligand binding and sRAGE levels are altered by the G82S polymorphism is unknown. The G82S substitution occurs within one of the potential N-linked glycosylation consensus sites, involving Asn 81 . On this basis, we hypothesized that the G82S substitution may influence the glycosylation pattern of RAGE, with consequences for ligand binding and proinflammatory signaling. Here, we describe detailed analysis of the glycosylation of RAGE and identify enhanced glycosylation induced by the G82S polymorphism.

SPLS for colon cancer is feasible and can be performed by following oncologic principles. However, surgeons should be aware of the potential for unexpected adjacent organ injury ( ClinicalTrial.gov identifier: NCT01203969).