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Articles by C. H Hsu
Total Records ( 4 ) for C. H Hsu
  P. A Thompson , C. H Hsu , S Green , A. T Stopeck , K Johnson , D. S Alberts and H H. S. Chow

Regular use of nonsteroidal anti-inflammatory drugs (NSAID) has been associated with reduced risk of breast cancer. Sulindac, a nonselective NSAID with both cyclooxygenase-2–dependent and –independent activities, is a candidate for breast chemoprevention. We conducted a phase Ib trial in 30 women at increased risk for breast cancer to evaluate the breast tissue distribution of sulindac at two dose levels (150 mg daily and 150 mg twice daily for 6 weeks), using nipple aspirate fluid (NAF) as a surrogate of breast tissue drug exposure. We also explored the effect of sulindac on drug-induced biomarkers in NAF. We show that sulindac and its metabolites partition to human breast as measured by NAF levels. Sulindac intervention did not decrease 13,14-dihydro-15-keto prostaglandin A2, a stable derivative of prostaglandin E2, in NAF, but exposure was associated with a significant trend towards higher levels of growth differentiation factor 15 in NAF in women receiving 150 mg twice daily (P = 0.038). These results are the first to show partitioning of sulindac and metabolites to human breast tissue and the first evidence for a potential dose-dependent effect of sulindac on growth differentiation factor 15 levels in NAF. Cancer Prev Res; 3(1); 101–7

  M. S Stratton , A. M Algotar , J Ranger Moore , S. P Stratton , E. H Slate , C. H Hsu , P. A Thompson , L. C Clark and F. R. Ahmann

The Nutritional Prevention of Cancer trial showed a 52% lower incidence of prostate cancer in men supplemented with selenium. As a result, our study was designed to assess whether selenium supplementation attenuates the progression of prostate cancer. A phase 2 randomized, double-blind, placebo-controlled clinical trial was conducted in men with localized nonmetastatic prostate cancer who had elected to forgo active treatment and be followed by active surveillance. A total of 140 men were randomized to placebo (n = 46), 200 µg/d (n = 47), or 800 µg/d (n = 47) selenium p.o. (as selenized yeast) and followed every 3 months for up to 5 years. Prostate-specific antigen (PSA) velocity was used as a marker of prostate cancer progression and was estimated using mixed-effects regression. Adjusting for age, body mass index, baseline selenium, smoking, baseline PSA, race, PSA method, and Gleason score, PSA velocities for the 200 µg/d and 800 µg/d treatment groups were not statistically significantly different from placebo (P = 0.32 and P = 0.61, respectively). In the highest quartile of baseline selenium, men supplemented with 800 µg selenium showed statistically significantly higher PSA velocity as compared with placebo (P = 0.018). Selenium supplementation did not show a protective effect on PSA velocity in subjects with localized prostate cancer. On the contrary, supplementation with high-dose selenium was observed to be a risk factor for increased PSA velocity in men with high baseline plasma selenium concentrations. Cancer Prev Res; 3(8); 1035–43. ©2010 AACR.

  J Shiue , C. S Chang , S. H Huang , C. H Hsu , J. S Tsai , W. H Chang , Y. M Wu , Y. C Lin , P. C Kuo , Y. S Huang , Y Hwu , J. J Kai , F. G Tseng and F. R. Chen

A Boersch electrostatic phase plate (BEPP) used in a transmission electron microscope (TEM) system can provide tuneable phase shifts and overcome the low contrast problem for biological imaging. Theoretically, a pure phase image with a high phase contrast can be obtained using a BEPP. However, a currently available TEM system utilizing a BEPP cannot achieve sufficiently high phase efficiency for biological imaging, owing to the practical conditions. The low phase efficiency is a result of the blocking of partial unscattered electrons by BEPP, and the contribution of absorption contrast. The fraction of blocked unscattered beam is related to BEPP dimensions and to divergence of the illumination system of the TEM. These practical issues are discussed in this paper. Phase images of biological samples (negatively stained ferritin) obtained by utilizing a BEPP are reported, and the phase contrast was found to be enhanced by a factor of ~1.5, based on the calculation using the Rose contrast criterion. The low gain in phase contrast is consistent with the expectation from the current TEM/BEPP system. A new generation of phase TEM utilizing BEPP and designed for biological imaging with a high phase efficiency is proposed.

  C. H Hsu , Y. R Pan , Y. D Liao , S. H Wu and C. Chen

The stability, structures and steric hindrances of recombinant RNases 2 and 4 expressed in bacteria were studied by circular dichroism (CD) and NMR techniques, and the results were compared with those of their authentic RNases extracted from oocytes of Rana catesbeiana. Although the overall structures of the recombinant and authentic proteins are almost identical, the extra N-terminal Met residue of the recombinant protein remarkably affects catalytic activity and stability. NMR chemical shift comparison of recombinant RNases and the authentic proteins indicated that the structural differences are mainly confined to the N-terminal helical and S2 anti-parallel β-sheet regions. Significant shift changes for the residues located on the S2 region indicate that the major influences on the structure around the N terminus is due to the loss of the hydrogen bond between Pyr1 and Val95(96) in recombinant RNases 2 and 4. We concluded the apparent steric hindrances of the extra Met to the binding pocket. As well, the affected conformational changes of active residues are attributed to the reduced activities of recombinant RNases. The structural integrity exerted by the N-terminal Pyr1 residue may be crucial for amphibian RNases and the greatest structural differences occur on the network of the Pyr1 residue and S2 β-sheet region.

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