Highly effective and reversible control of the rocking rates of rotaxanes by changes to the size of stimulus-responsive ring components.

We have designed and synthesized rotaxanes whose rates of rocking motion (pendular motion) were switched reversibly through changes to the size of the ring component in response to external stimuli. The ring molecules of the rotaxanes incorporate a metaphenylene unit, which swings like a pendulum, and a dianthrylethane unit, which undergoes reversible isomerization in response to photo- and thermal stimuli and changes the size of the ring component. The rocking rates were estimated quantitatively by variable-temperature (VT) NMR spectroscopy and saturation transfer experiments, which revealed substantial changes in the rates between the open and closed forms, particularly in the case of rotaxanes with an isopropoxy group attached to a phenylene unit.

A shuttling molecular machine with reversible brake function.

Design, synthesis, and demonstration of a prototype of a shuttling molecular machine with a reversible brake function are reported. It is a photochemically and thermally reactive rotaxane composed of a dianthrylethane-based macrocycle as the ring component and a dumbbell shaped molecular unit with two, secondary ammonium stations separated by a phenylene spacer as the axle component. The rate of shuttling motion was shown to be reduced to less than 1 % (from 340 to <2.5 s(-1)) by reducing the size of the ring component from 30-crown-8 to 24-crown-8 macrocycles upon photoirradiation. The ring component was turned back to 30-crown-8 by thermal ring opening, thus establishing a reversible brake function that works in response to photochemical and thermal stimuli.

An anthracene-based photochromic macrocycle as a key ring component to switch a frequency of threading motion.

A concept and demonstration of a switching in frequencies of molecular motions are described using a pseudorotaxane system. The setup consists of dibenzylammonium hexafluorophosphate and a photochromic dianthrylethane-based [24]crown-8-type macrocycle, which we designed as a key ring component for the pseudorotaxane system having photocontrollable threading functionality by changing the size of ring component due to the action of light.

Outcome of patients with hepatitis C virus-related single, small hepatocellular carcinoma.

To clarify the cumulative recurrence-free interval and survival rate with hepatitis C virus (HCV)-related single, small hepatocellular carcinoma (HCC), we studied 32 patients with surgical resection, 61 with ablation therapy and 28 with transcatheter chemoembolization (TACE). A log-rank test revealed that there were no significant differences in the recurrence-free interval (p = 0.08) and survival (p = 0.279) between the resection and the ablation groups. Univariate analysis using the Cox proportional hazards regression model showed initial treatment (p = 0.0051) was associated with recurrence-free interval. Platelet count (p = 0.009), indocianine green retention rate at 15 minutes (p = 0.003), Child-Pugh classification (p = 0.001), serum albumin level (p = 0.0012) and serum total bililubin (p = 0.015) were associated with survival. Hence patients with HCV-related single, small HCC should be treated according to their hepatic reserve.

Aspirin induces hepatoma-derived cell apoptosis via a hydrogen peroxide-dependent pathway.

Here we studied whether aspirin (ASA) has any influence on viability of human hepatoma-derived SKHep-1 cells and whether hydrogen peroxide (H(2)O(2)) has any relation with this effect. ASA inhibited SKHep-1 cell proliferation dose- and time-dependently. Intracellular H(2)O(2) increased as early as 15 min after ASA supplementation. Cellular apoptosis correlated with an increase in intracellular H(2)O(2) level. Moreover, in the presence of a catalase inhibitor-aminotriazol, ASA showed more apoptotic effect on SKHep-1 cells with increasing intracellular H(2)O(2) level. In conclusion, the present results shows that ASA induced SKHep-1 cell apoptosis has a relation with an early increase in intracellular H(2)O(2) level and catalase inhibitor synergizes to induce this process.

Risk factors for local recurrence of small hepatocellular carcinoma tumors after a single session, single application of percutaneous radiofrequency ablation.

BACKGROUND: The objectives of this study were to clarify risk factors for local tumor recurrence and to determine which patients with hepatocellular carcinoma (HCC) are most suitable for a single session, single application of percutaneous radiofrequency (RF) ablation. METHODS: Fifty-six consecutive patients with 65 HCC tumors measuring 2 cm (risk ratio [RR], 4.9; 95%CI, 1.3-16.4; P = 0.019) and subcapsular location (RR, 5.2; 95%CI, 1.7-16.6; P = 0.005) were associated independently with local recurrence. The other four factors were not associated with local recurrence in this study. CONCLUSIONS: A single session, single application of RF ablation produced favorable local control. Patients who have nonsubcapsular HCC tumors measuring

Inhibition by arsenic trioxide of human hepatoma cell growth.

Arsenic trioxide (As(2)O(3)) has been shown to be effective for treatment of patients with refractory or relapsed acute promyelocytic leukemia and a variety of other malignant hematopoetic disorders. We studied the effect of this agent on proliferation of human hepatoma-derived cell lines (SK-Hep-1, HepG2, and HuH7). In HuH7 cells, As(2)O(3) reduced proliferation time- and dose-dependently at 1 and 2 microM, while in SK-Hep-1 and HepG2 cells, As(2)O(3) inhibited proliferation at 2 and 4 microM respectively. Cell cycle analysis by flow cytometry showed that As(2)O(3) induced apoptosis in these hepatoma-derived cells as confirmed by appearance of sub-G(1) cells. Sensitivity of hepatoma-derived cells to As(2)O(3) was inversely related to their intracellular glutathione (GSH) and intensity of GSH synthesis. Arsenic sensitivity was restored to relatively resistant cell lines when GSH was depleted by L-buthionine sulfoximine (BSO). These results indicate that As(2)O(3) may have therapeutic potential for treatment of hepatocellular carcinoma.

Outcome of patients with hepatitis C virus-related hepatocellular carcinoma occurring after interferon therapy.

To determine whether previous IFN therapy for chronic hepatitis C (HCV) infection influences the outcome of patients with hepatocellular carcinoma (HCC), 143 patients were enrolled in this study. Of 143 patients, 48 had received previous IFN therapy (IFN group) and the remaining 95 had not (untreated group). We estimated distant intrahepatic recurrence-free intervals and disease-specific survivals of the two groups by the Kaplan-Meier method and analyzed the difference by the log-rank test. Factors determining distant intrahepatic recurrence-free interval and disease-specific survival were studied by univariate and multivariate analysis using Cox proportional hazards regression model. The proportion of patients with single tumors was significantly higher in the IFN group (p = 0.026). The IFN group showed a significantly higher distant intrahepatic recurrence-free interval (p = 0.001) and disease-specific survival (p = 0.003). Moreover, multivariate analysis indicated that previous IFN therapy for chronic HCV infection was a significant independent factor for distant intrahepatic recurrence-free interval and disease-specific survival. These results indicate that previous IFN therapy reduces multicentric hepatocarcinogenesis of HCV-related HCC and improves the patients' survival.