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Gastric cancer is common among the world, but genetic mechanisms of gastric carcinogenesis are not well understood. Gastric polypoid adenomas and flat dysplasias are regarded as precursor lesions. However, a detailed molecular study of these lesions has not been done to determine their role as precancerous lesions. We investigated mutations of the APC, beta-catenin, and K-ras genes, and microsatellite instability (MSI) status in 35 adenomas and 47 flat dysplasias without adenocarcinoma, 35 adenomas/dysplasias associated with adenocarcinomas, and 39 adenocarcinomas (20 diffuse type and 19 intestinal type). Somatic APC gene mutations were identified in 76% (59 of 78) of adenomas or flat dysplasias without associated adenocarcinoma, but in only 3% (1 of 30) of adenomas/dysplasias associated with adenocarcinoma, and in only 4% (3 of 69) of adenocarcinomas (P < 0.000001). No mutations of beta-catenin were found in adenocarcinomas, or adenomas/dysplasia without APC mutation. K-ras mutations were detected in 5% (4 of 82) of gastric adenomas/dysplasia without carcinoma, 3% (1 of 39) of adenocarcinomas without associated adenoma/dysplasia, and not in 32 adenocarcinomas with associated adenoma/dysplasia. High level of MSI (MSI-H) was more frequent in gastric adenoma/dysplasia associated with carcinoma (17%, 6 of 35) than in adenomas/dysplasia without carcinoma (3%, 2 of 75; P = 0.01). MSI-H was also more frequent in intestinal type adenocarcinoma (20%, 11 of 54) than in diffuse type (0%, 0 of 20; P = 0.03). APC gene mutations were present in six of nine (67%) of gastric adenomas/dysplasias with low level of MSI, but in none of the eight adenomas/dysplasia with MSI-H phenotype (P = 0.009). Our results indicate that somatic mutation of the APC gene plays an important role in the pathogenesis of gastric adenoma and dysplasia but has a limited role in neoplastic progression to adenocarcinoma. Gastric adenomas or dysplasias without APC mutations but with or without MSI may have a different biological behavior, and are precursors of intestinal-type of gastric adenocarcinomas.

Strong charge-spin coupling is found in a layered transition-metal trichalcogenide NiPS_{3}, a van der Waals antiferromagnet, from studies of the electronic structure using several experimental and theoretical tools: spectroscopic ellipsometry, x-ray absorption, photoemission spectroscopy, and density functional calculations. NiPS_{3} displays an anomalous shift in the optical spectral weight at the magnetic ordering temperature, reflecting strong coupling between the electronic and magnetic structures. X-ray absorption, photoemission, and optical spectra support a self-doped ground state in NiPS_{3}. Our work demonstrates that layered transition-metal trichalcogenide magnets are useful candidates for the study of correlated-electron physics in two-dimensional magnetic materials.

Background The present study was designed to investigate the effect and relationship of endothelial function and endothelial progenitor cells (EPCs) by green tea consumption in chronic smokers. The numbers of circulating EPCs have an inverse correlation with chronic smoking and endothelial dysfunction. Green tea catechin improved endothelial dysfunction in chronic smokers. Method and ResultsIn 20 young healthy smokers, endothelial functions, defined by flow-mediated endothelium dependent vasodilation (FMD) of the brachial artery via ultrasound as well as the number of EPCs isolated from peripheral blood, were determined at baseline and at 2 weeks after green tea consumption (8 g/day). Circulating EPCs were quantified by flow cytometry as CD45lowCD34 + KDR2+ cells and by acyl-low-density lipoprotein and fluorescein isotiocyanate-lectin double positive cells after culture for 7 days. Clinical characteristics and laboratory findings were not significantly different between the baseline and at 2 weeks after green tea intake. EPC levels were inversely correlated with the number of cigarettes smoked. Circulating EPCs by flow cytometry (78.6±72.6 vs 156.1±135.8 /ml, p<0.001) and cultured EPCs (118.2±35.7 vs 169.31±58.3/10 field, p<0.001) increased rapidly at 2 weeks after green tea consumption. FMD was significantly improved after 2 weeks (7.2±2.8 vs 9.3±2.4, p<0.001). The FMD correlated with EPC counts (r=0.67, p=0.003) before treatment and after 2 weeks (r=0.60, p=0.013). Conclusions A short-term administration of green tea consumption induces a rapid improvement of EPC levels and FMD. Green tea consumption may be effective to prevent future cardiovascular events in chronic smokers. (Circ J 2006; 70: 1052 -1057

In Korean epileptics, there was no significant relationship between three known SNPs in MDR1 and drug resistance. And there was no association of MDR1 haplotype based on above three sites with pharmacoresistance.

Loss of PTEN expression has been associated with advanced stages of tumor. Tumor angiogenesis is involved in tumor progression. In breast cancer, a high frequency of mutations of the PTEN locus has been reported. However, the prognostic importance of PTEN expression and its correlation with angiogenesis in breast cancer have not been well established. Formalin-fixed, paraffin-embedded tissues from 99 women with a primary diagnosis of invasive ductal carcinoma were evaluated for PTEN expression by immunohistochemical methods. The microvessel density (MVD) was also studied by immunohistochemical labeling of endothelial cells with CD34 antibody. Computerized image analysis was used to evaluate MVD. Reduced PTEN expression was seen in 27.3% of invasive ductal carcinoma. The MVD ranged from 22.0 to 197.0, with a median value of 58.5 (65.4 +/- 27.9). Reduced PTEN expression correlated with lymph node status (P < 0.01), tumor grade (P < 0.05), and tumor-node-metastasis (TNM) stage (P < 0.05). There was a statistically significant correlation between reduced PTEN expression and increased MVD (P < 0.05). The mean MVD was higher in reduced PTEN-expressive tumors, irrespective of stage, compared with normal PTEN-expressive tumors with the same stage. On multivariate analysis, only TNM stage and reduced PTEN expression correlated with survival. Our results suggest that reduced PTEN expression may be an independent prognostic indicator in patients with invasive ductal carcinoma. PTEN loss may be associated with increased tumor angiogenesis.

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Primary large cell neuroendocrine carcinomas (LCNEC) of the urinary bladder are rare. Reported herein is a case of a primary, pure LCNEC occurring in a man. The patient was a 32-year-old man who presented with hematuria of 1 week's duration. On cystoscopic examination, a solitary mass measuring 3 cm in diameter was detected protruding from the anterosuperior wall of the urinary bladder. Two months after the primary transurethral resection, significant regrowth of the remnant mass was noted on CT, and the patient underwent a partial cystectomy. A diagnosis of LCNEC was made based upon histological and immunohistochemical findings. Tumor cells were positive for synaptophysin, chromogranin A, CD56, epithelial membrane antigen, and cytokeratin. Histologically, the tumor penetrated the deep muscle and perivesical fat. In spite of three cycles of chemotherapy, the patient developed multiple metastases in the lung and liver 10 months postoperatively. LCNEC of the urinary bladder are uncommon entities, which have a possible fatal outcome.