The CDKN2A and CDKN2B genes, encoding p16 and p15 respectively, are located on chromosome 9p21, a locus at which frequent homozygous and heterozygous deletions occur in many primary human tumors, including esophageal carcinoma. CDKN2A and CDKN2B inhibit cyclin dependent kinase 4 (CDK4) and CDK6 and control cellular proliferation by preventing entry into the S phase of the cell cycle. Their inactivation may contribute to uncontrolled growth in human cancer. We previously described CDKN2A exon 2 mutations in a pilot study of 43 esophageal cancers. In order to determine whether CDKN2A and CDKN2B are frequent targets of 9p21 deletion in esophageal carcinogenesis, we have now analyzed 60 primary esophageal cancers for mutations in both exons 1 and 2 of CDKN2A and CDKN2B by direct sequencing of PCR amplified genomic DNAs. In conjunction with our previously published data, we have identified a total of eight nucleic acid substitutions among 60 esophageal carcinomas; here, we describe one new CDKN2B nonsense mutation and one new silent CDKN2B mutation that occurred somatically. Taken together, these results suggest that intragenic mutations in CDKN2A and CDKN2B occur in esophageal cancer, but that they are infrequent events. In view of the known high frequency of loss of heterozygosity at the chromosome 9p21 locus in esophageal cancers, the current data suggest that intragenic mutation is not the predominant mode of inactivation of CDKN2A and CDKN2B or that other genes are targets of deletion at this locus in these cancers.

The effects of tea water extracts (TWE), crude tea polysaccharides (CTP), and a tea polysaccharide fraction (TPF) were tested on hyperglycemic diabetic mice. Results indicated that TWE, CTP, and TPF could significantly decrease fasting blood glucose (FBG) and glucosylated serum protein (GSP) in alloxan-induced diabetic mice compared to the control group. In vitro antioxidant activities of TWE, CTP, and TPF for scavenging hydroxyl radicals and superoxide radicals decreased with the degree of purification and were lowest for TPF. High-performance gel permeation chromatography (HPGPC) and component analysis revealed the molecular mass distribution and constituents of TWE, CTP, and TPF, indicating that a 100-120 kDa fraction contained the hypoglycemic activity. This fraction was essentially composed of polysaccharides (approximately 90%) with substantial amounts of arabinogalactan proteins. The second-derivative IR spectra of TWE, CTP, and TPF with peak intensity around 1075 and 1045 cm(-1), which characterize galactopyranose in the backbone and arabinofuranose units in side branches, respectively, further substantiated the importance of the arabinogalactan proteins. Taken together, the results indicate that a soluble tea polysaccharide is the major hypoglycemic factor in tea and that this polysaccharide may be developed to a potential natural hypoglycemic functional ingredient.

No abstract

No abstract

No abstract