Increasing evidence has indicated that perturbation of cyclins is one of the major factors leading to cancer. The aim of this study was not only to investigate various cell cycle-related kinase activities in hepatocellular carcinoma (HCC), but also to analyze the difference of cell cycle-related kinase activity levels between hepatitis C virus (HCV)-induced HCC and HCVinduced cirrhosis. The protein levels of cyclins D1, E, A, and H, and of cyclin dependent kinase 1 (Cdk1), Cdk2, Cdk4, Cdk6, and Cdk7 in HCC and in surrounding nontumorous cirrhosis were determined by Western blot. The enzymatic activities of cyclins D1, E, A, Cdk1, Cdk4, Cdk6, Cdk7, and Wee1 were measured using in vitro kinase assays. Protein levels and kinase activities of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 were significantly elevated in HCC compared with surrounding cirrhotic tissues. The enhanced cyclin D1-related kinase activity in HCC was accompanied by the up-regulation of Cdk4 activity, but not Cdk6 activity. The kinase activities of Cdk6, Cdk7, and Cdk1 did not differ between HCC and surrounding cirrhotic tissues. In addition, the protein levels and kinase activities of cyclin D1, Cdk4, and cyclin E were higher in poorly differentiated HCC and advanced HCC. In conclusion, the increases of cyclin D1, Cdk4, cyclin E, cyclin A, and Wee1 play an important role in the development of HCC from cirrhosis. Cyclin D1, Cdk4, and cyclin E activation may be closely related to the histopathologic grade and progression of HCC. R ecent studies, including our research, have revealed that the deranged expression of cell cyclerelated proteins is one of the major factors contributing to hepatocellular carcinoma (HCC) development. 1-6 Here we investigated biochemical differences of various cell cycle-related kinase activities and protein levels in cirrhosis and HCC.Specific cyclin/cyclin-dependent kinase (Cdk) complexes are activated at different intervals during the cell cycle. 7-15 Cyclin D1/Cdk4 and cyclin D1/Cdk6 are activated in mid-G1 (Fig. 1, phase 1), whereas cyclin E/Cdk2 complexes are required for the G1/S transition (Fig. 1, phase 2), cyclin A/Cdk2 for the progression of DNA synthesis (Fig. 1, phase 3), and cyclin A-B/Cdk1 for the G2/M transition (Fig. 1, phase 4) of mitosis. The activation of cyclin D1/Cdk4 and cyclin D1/Cdk6 complexes at mid-G1 is responsible for the phosphorylation of retinoblastoma protein (pRb), and 2 Rb related proteins, p107, and p130. Members of the pRb family form complexes with transcription factors of the E2F family. 16 This interaction with pRb family members blocks the transcriptional activity of E2Fs; the complexes formed also function as active transcriptional repressor complexes at the promoters of some cell cycle genes. Phosphorylation of the pRb family inhibits the interaction with E2F family transcription factor and permits the expression of genes necessary for S-phase entry (cyclin A, proliferating cell nuclear antigen, and so on). 17 The expression of cyclins E and A at mid-to late-G1 permits the form...

Endoscopic papillary balloon dilation is a safe and effective technique for the treatment of common bile duct stones, even in high-risk patients.

ESD using the SBK can be carried out with greater ease and safety for colorectal neoplasia.

No abstract

We performed a randomized prospective trial to compare unsedated endoscopy via transnasal and transoral routes using a small-caliber endoscope. Two hundred patients referred for diagnostic esophagogastroduodenoscopy (EGD) were randomly allocated to two groups: those undergoing transnasal (TN) and transoral (TO) endoscopy. We examined the insertion rate, examination duration, nasal pain, pharyngeal pain, number of occurrences of pharyngeal reflex, severity of discomfort throughout the examination, and rate of adverse events. Patients were asked to rate the severity of their pain or discomfort on a 10-cm visual analog scale (VAS). We identified statistically significant differences between the TN and TO groups in rate of insertion (95% versus 100%, respectively, P < 0.05) and examination duration (9.7 +/- 3.0 min versus 8.4 +/- 2.7 min, respectively, P < 0.005). Severity of discomfort throughout the examination was comparable in the TN and TO groups (3.0 +/- 1.8 versus 2.9 +/- 2.3, NS). Nasal bleeding occurred as an adverse event in 4.1% of patients in the TN group. Patients in the TO group were more likely than those in the TN group to prefer the present method in the subsequent endoscopic examination (99.0% versus 82.1%, P < 0.00005). These results indicated that transoral insertion is superior to transnasal insertion in endoscopy procedures performed with small-caliber endoscope.