Purpose: Despite continual efforts to develop a prognostic model of gastric cancer by using clinical and pathologic parameters, a clinical test that can discriminate patients with good outcomes from those with poor outcomes after gastric cancer surgery has not been established. We aim to develop practical biomarker-based risk score that can predict relapse of gastric cancer after surgical treatment.Experimental Design: Microarray technologies were used to generate and analyze gene expression profiling data from 65 gastric cancer patients to identify biomarker genes associated with relapse. The association of expression patterns of identified genes with relapse and overall survival was validated in independent gastric cancer patients.Results: We uncovered two subgroups of gastric cancer that were strongly associated with the prognosis. For the easy translation of our findings into practice, we developed a scoring system based on the expression of six genes that predicted the likelihood of relapse after curative resection. In multivariate analysis, the risk score was an independent predictor of relapse in a cohort of 96 patients. We were able to validate the robustness of the six-gene signature in an additional independent cohort.Conclusions: The risk score derived from the six-gene set successfully prognosticated the relapse of gastric cancer patients after gastrectomy.

Protein O-phosphorylation often occurs reciprocally with O-GlcNAc modification and represents a regulatory principle for proteins. O-phosphorylation of serine by glycogen synthase kinase-3b on Snail1, a transcriptional repressor of E-cadherin and a key regulator of the epithelial-mesenchymal transition (EMT) programme, results in its proteasomal degradation. We show that by suppressing O-phosphorylation-mediated degradation, O-GlcNAc at serine112 stabilizes Snail1 and thus increases its repressor function, which in turn attenuates E-cadherin mRNA expression. Hyperglycaemic condition enhances O-GlcNAc modification and initiates EMT by transcriptional suppression of E-cadherin through Snail1. Thus, dynamic reciprocal O-phosphorylation and OGlcNAc modification of Snail1 constitute a molecular link between cellular glucose metabolism and the control of EMT.

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Progressive renal injury in diabetes mellitus leads to major morbidity and mortality. The manifestations of diabetic nephropathy may be a consequence of the actions of certain cytokines and growth factors. Prominent among these is transforming growth factor-beta (TGF-beta) because it promotes renal cell hypertrophy and stimulates extracellular matrix accumulation, the two hallmarks of diabetic renal disease. In cell culture, high ambient glucose increases TGF-beta mRNA and protein in proximal tubular, glomerular epithelial, and mesangial cells. Neutralizing anti-TGF-beta antibodies prevent the hypertrophic and matrix stimulatory effects of high glucose in these cells. In experimental and human diabetes mellitus, several reports describe overexpression of TGF-beta in the glomeruli and tubulointerstitium. We demonstrate that short-term treatment of diabetic mice with neutralizing monoclonal antibodies against TGF-beta significantly reduces kidney weight and glomerular hypertrophy and attenuates the increase in extracellular matrix mRNAs. Long-term treatment of diabetic mice further improves the renal pathology and also ameliorates the functional abnormalities of diabetic nephropathy. Finally, we provide evidence that the renal TGF-beta system is significantly up-regulated in human diabetes. The kidney of a diabetic patient actually elaborates TGF-beta1 protein into the circulation whereas the kidney of a non-diabetic subject extracts TGF-beta1 from the circulation. The data we review here strongly support the hypothesis that elevated production or activity of the TGF-beta system mediates diabetic renal hypertrophy and extracellular matrix expansion.

Objective. The purpose of this study was to assess the role of known suspicious sonographic findings and to find other additional sonographic findings to differentiate benign and malignant thyroid nodules with "eggshell" calcifications. Methods. Our Institutional Review Board approved this retrospective study, and informed consent was not required. We reviewed sonographic findings of thyroid nodules in 795 patients who underwent thyroid surgery in our institution between August 2006 and February 2007. Ninety-three thyroid nodules with eggshell calcifications in 92 patients were included in this study. Each lesion was evaluated for known suspicious sonographic criteria, including marked hypoechogenicity, irregular or microlobulated margins, and a taller-than-wide shape, as well as 2 additional sonographic findings: a hypoechoic halo and disruption of eggshell calcifications (halo and disrupted calcification rim). The sensitivity and specificity based on the sonographic criteria were calculated and compared among the 2 types of criteria. Results. Among the 93 thyroid nodules, 59 were malignant and 34 were benign. The halo and disrupted calcification rim showed higher sensitivity (62.7% and 76.3%, respectively) than any of the known suspicious sonographic criteria (40.7%, 35.6%, and 55.9%). The combination of both the halo and the disrupted calcification rim showed significantly higher sensitivity (93.2%) than the combination of the known suspicious sonographic criteria (78%; P < .05), although both had the same specificity (64.7%). Conclusions. In thyroid nodules with eggshell calcifications but no other calcifications, the findings of a peripheral halo and disruption of the eggshell calcifications may be more useful sonographic predictors of malignancy than hypo echogenicity, microlobulated margins, and a taller-than-wide shape.

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The follicular variant of papillary thyroid carcinoma tends to have relatively benign sonographic features, such as hypoechogenicity, well-defined margins, an oval shape, and no microcalcifications, but most lesions were correctly classified as malignant by both sonography and FNAB. The possibility of FVPTC should be considered when thyroid nodules with a relatively benign sonographic appearance have suspicious or malignant FNAB results.

Despite remarkable progress in understanding and treating gastrointestinal stromal tumors (GISTs) during the past two decades, the pathological characteristics of GISTs have not been made clear yet. Furthermore, concrete diagnostic criteria of malignant GISTs are still uncertain. We collected pathology reports of 1,227 GISTs from 38 hospitals in Korea between 2003 and 2004 and evaluated the efficacy of the NIH and AFIP classification schemes as well as the prognostic factors among pathologic findings. The incidence of GISTs in Korea is about 1.6 to 2.2 patients per 100,000. Extra-gastrointestinal GISTs (10.1%) are more common in Korea than in Western countries. In univariate analysis, gender, age, tumor location, size, mitosis, tumor necrosis, vascular and mucosal invasions, histologic type, CD34 and s-100 protein expression, and classifications by the NIH and AFIP criteria were found to be significantly correlated with patient's survival. However, the primary tumor location, stage and classification of the AFIP criteria were prognostically significant in predicting patient's survival in multivariate analysis. The GIST classification based on original tumor location, size, and mitosis is more efficient than the NIH criteria in predicting patient's survival, but the mechanism still needs to be clarified through future studies.