No abstract

Scheme 1Optically active biaryls represented by 1,1'-binaphthyls have found extensive use in chiral auxiliaries for a variety of synthetic asymmetric reactions including catalytic ones,1•2 and considerable attention has been paid to their preparation by asymmetric

The chaperonin-containing t-complex polypeptide 1 (CCT) is a hetero-oligomeric molecular chaperone that assists in the folding of actin, tubulin, and other cytosolic proteins. We recently reported that the expression level of CCT is closely correlated with growth rates of mammalian cultured cells. Here we examine the levels of CCT subunits and other molecular chaperones in tumor tissues of patients with hepatocelluar and colonic carcinoma, and compare them with nontumor tissues in the same patients. Expression levels of CCTbeta in tumor tissues was significantly higher than in nontumor tissues in all patients with hepatocellular carcinoma (n = 15) and 83% of patients with colonic carcinoma (n = 17). The increased level of CCT expression in colonic cancer cells was confirmed by immunohistochemistry with anti-CCTbeta antibody. The levels of CCTbeta were highly correlated (r = 0.606) with those of the proliferating cell nuclear antigen (PCNA), which was used as an indicator of cell growth. CCTalpha gave similar results, although the correlation with PCNA levels was weaker. Other cytosolic and endoplasmic reticulum chaperones also showed higher expression in significant numbers of tumor tissues but less frequently than that observed with CCT. These results suggest that CCT is up-regulated in rapidly proliferating tumor cells in vivo to effectively produce proteins required for growth, and may serve as a useful tumor marker because it is widely distributed in the cytosol.

To examine the role of the loss of heterozygosity (LOH) in hepatitis-related carcinogenesis, we performed a genomewide scan of LOH in 44 tumors of hepatocellular carcinoma (HCC) using 216 microsatellite markers throughout all human chromosomes. A high frequency of LOH (G30% of informative cases) was observed at 33 loci on chromosome arms 4q, 6q, 8p, 8q, 9p, 9q, 13q, 16p, 16q, 17p, and 19p. LOH on 19p has not yet been reported, and that appears to be a new candidate in the search for tumor suppressor genes. High rates of LOH are correlated with hepatitis B virus (HBV) positivity, poorly differentiated tumors, vascular invasion, and intrahepatic metastasis (P F .0001). LOH on 13q and 16q occurred more frequently in HBV(؉) patients (P F .0001), and LOH on 6q occurred more frequently in virus-negative patients (P F .001). The frequency of LOH on 4q and 13q was significantly lower in well-differentiated tumors than in moderately and poorly differentiated tumors (P F .01). In contrast, LOH on 6q was frequently detected in well-differentiated tumors compared with other histological subclasses (P F .001). Our results suggest that LOH on 6q may play an important role in the early stage of hepatocarcinogenesis in virus-negative patients, but different mechanisms might underlie the initial step to carcinogenesis in HBV ( Primary hepatocellular carcinoma (HCC) is one of the most common causes of death from cancer in many countries of the world, especially in Asia and Africa. Among risk factors such as hepatitis virus infection, exposure to aflatoxin B1, heavy alcohol consumption, and several genetic diseases, epidemiological studies have shown that the hepatitis B virus (HBV) plays a major role in the carcinogenesis of HCC. [1][2][3] Histological findings suggest that the development of HCC is a multistep process involving qualitative and quantitative changes in expressed genes. 4 The molecular genetic approach has shown that multiple carcinogenic steps correspond to the accumulation of sequentially occurring genetic aberrations such as the activation of oncogenes and the inactivation of tumor suppressor genes. 5 Although the multistep mechanism of carcinogenesis is well defined in colorectal cancer, the detailed mechanism for HCC remains unidentified.In Japan, more than 70% of patients with HCC are hepatitis C virus (HCV) positive, 10% to 20% are HBV positive, and the rest are virus negative. 6,7 HCC can be induced in HBx transgenic mice and HCV core protein transgenic mice, indicating that both HBV and HCV could play a direct role in hepatocarcinogenesis. 8,9 However, no clinical evidence exists to show that the pathway to HCC differs among HBVpositive, HCV-positive, and virus-negative patients.Only a limited number of studies on the activation of proto-oncogenes in HCC have been reported. These include amplifications of the cyclin D1 gene and the c-myc gene in some HCCs. 10,11 These studies suggest that inactivation of tumor suppressor genes is imperative for hepatocarcinogenesis. The frequent loss of heterozygosity (LOH...

Tyrosinase inhibitory and antioxidant activity of gallic acid and its series of alkyl chain esters were investigated. All inhibited the oxidation of L-3,4-dihydroxyphenylalanine (L-DOPA) catalyzed by mushroom tyrosinase. However, gallic acid and its short alkyl chain esters were oxidized as substrates yielding the colored oxidation products. In contrast, the long alkyl chain esters inhibited the enzyme activity without being oxidized. This indicates that the carbon chain length is associated with their tyrosinase inhibitory activity, presumably by interacting with the hydrophobic protein pocket in the enzyme. On the other hand, the esters, regardless their carbon chain length, showed potent scavenging activity on the autoxidation of linoleic acid and 1,1-diphenyl-2-p-picryhydrazyl (DPPH) radical, suggesting that the alkyl chain length is not related to the activity. The effects of side-chain length of gallates in relation to their antibrowning activity are studied.