Amplification found in a number of cyclin genes, especially in cyclin D and E, is an important event process that takes place in cancers, including hepatocellular carcinoma (HCC). The activities of a wide range of cell cycle-related kinases remain obscure in HCC. The purpose of the present study is to determine the cyclins and kinase activities of HCC in Long-Evans Cinnamon (LEC) rats. Cyclin D1, E, A, H, Cdk1(cyclin-dependent kinase; Cdc2), Cdk4, and Cdk6 protein levels were determined by Western blot analysis at different pathologic stages of liver tissues exhibiting HCC. Enzymatic activities of cyclin D1, E, A, Cdk4, Cdk6, Cdc2, Cdk7, and Wee1 kinase were measured by in-gel kinase assay. Protein levels and kinase activities of cyclin D1, E, Cdk4, cyclin A, and Wee1 increased proportionally with the development of HCC, especially in the transition process from chronic hepatitis to HCC. Although Cdc2 kinase activity was found to increase slightly from normal liver to chronic hepatitis, its activity remained unchanged in the process from chronic hepatitis to HCC. Cdk6 and Cdk7 activities remained unchanged in the process from normal liver to HCC. These data suggest that the increase in Cdc2 kinase may play a role in the process from normal liver to chronic hepatitis, whereas the predominant increase in cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 suggests involvement not only in the process from normal liver to chronic hepatitis, but also during transition into HCC. (HEPATOLOGY 2000;32:711-720.)The inbred strain of Long-Evans Cinnamon (LEC) rats was established from the closed colony of Long Evans rats. 1 These rats exhibit severe acute liver damage with jaundice spontaneously at the age of 4 to 5 months, leading to fulminant hepatic failure in more than 50%. The rats usually survive chronic hepatitis and within a year develop cholangiofibrosis and hepatocellular carcinoma (HCC). [2][3][4][5] Because the natural history of liver disease in LEC rats resembles that of human liver disease in which HCC follows persistent chronic liver disease, LEC rats are regarded as one of the most useful animal models of HCC. 3 Hitherto, little is known about the mechanism that leads to the progression of HCC. Recently, it has been known that changes do occur that alter the cell cycle of related proteins during the malignant transformation process. [6][7][8][9] Because cyclins are prime cell regulating events leading to proliferation in animal cells, the deranged expression of different cyclins may also be the key to carcinogenesis in LEC rats.We have previously reported on the importance of protein phosphorylation in signal transduction in relation to proliferation, differentiation, and carcinogenesis of hepatocytes. [10][11][12][13] Most cell cycle-related proteins show phosphorylation enzymatic activity contributing to cell cycle transition. 6,14-16 Cyclins and their catalytic subunit, the cell-dependent kinases, play key roles in the regulation of animal cell cycle events. 14 Progress of cells through the cycle is governed b...

New π-extended pentalene derivatives bearing two thiophene rings are synthesized from 3-bromo-4-ethynylthiopenes as stable orange crystals by using a nickel complex. The observed electronic properties and molecular structure clearly indicate low contribution of the pentalene π system as predicted by the TD-DFT calculations.

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A point mutation of the N-ras gene is one of the known genetic alterations identified in patients with acute lymphoblastic leukemia (ALL), but its clinical importance is still controversial. Using polymerase chain reactions, we examined codons 12, 13 and 61 of this gene in 125 Japanese childhood ALL patients (64 common-ALL, 22 pre-B-ALL, 33 T-ALL, 2 B-ALL, 3 undifferentiated ALL, and 1 unclassified ALL) including 9 relapsed patients. An N-ras point mutation was observed in 14 (11%) patients (9 common-ALL, 3 T-ALL, and 2 undifferentiated ALL; 13 patients at diagnosis and 1 at relapse). The patients with undifferentiated ALL harbored an N-ras mutation at a significantly higher rate. However, no correlation was found between the presence of an N-ras mutation and sex, age, or white blood count. There was no significant difference in the event-free survival rate between 13 fresh patients with an N-ras mutation and 103 patients with a wild-type configuration. The N-ras mutation was present in about 10% of childhood ALL cases but it did not have a prognostic impact. The sequence analyses revealed that the majority of the patients (13/14) had an N-ras mutation of a G to A transition. This finding was consistent with previous reports on N-ras mutations in acute leukemias in which the incidence of a G to A mutation was significantly higher in ALL than in myeloid malignancies.

The synthesis of several new 2-(2-thieny1)aziridines and an examination of their cycloaddition with olefinic and acetylenic dipolarophiles is described.