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Articles by J. S Lee
Total Records ( 8 ) for J. S Lee
  J. S Lee , P Buzkova , H. A Fink , J Vu , L Carbone , Z Chen , J Cauley , D. C Bauer , A. R Cappola and J. Robbins
 

Background  Subclinical thyroid dysfunction is common in older adults and affects bone metabolism, but its effects on fracture risk have not been reported. We sought to determine prospectively whether older men and women with subclinical hyperthyroidism or hypothyroidism have an increased risk of hip fracture.

Methods  Prospective cohort of 3567 US community-dwelling adults, 65 years or older, with biochemically defined subclinical thyroid dysfunction or euthyroidism was enrolled from June 10, 1989, through May 30, 1990, and followed up through 2004. Main outcome measures included incidence and hazard ratios (HRs), with 95% confidence intervals (CIs), of confirmed incident hip fractures for groups with subclinical hypothyroidism, subclinical hyperthyroidism, and euthyroidism as defined at baseline.

Results  During 39 952 person-years (median follow-up, 13 years), hip fracture incidence (per 1000 men-years) was 13.65 in men with subclinical hyperthyroidism (n = 29) and 10.27 in men with subclinical hypothyroidism (n = 184), both greater than 5.0 in men with euthyroidism (n = 1159). Men with subclinical hypothyroidism had a multivariable-adjusted HR of 2.31 (95% CI, 1.25-4.27); those with subclinical hyperthyroidism, 3.27 (0.99-11.30). After excluding those with baseline use of thyroid-altering medications, men with endogenous subclinical hyperthyroidism had a higher HR of 4.91 (95% CI, 1.13-21.27), as did men with endogenous subclinical hypothyroidism (2.45, 1.27-4.73). Hip fracture incidence (per 1000 women-years) was 8.93 in women with subclinical hypothyroidism (n = 359) and 10.90 in women with subclinical hyperthyroidism (n = 142) compared with 10.18 in women with euthyroidism (n = 1694). No clear association between subclinical dysfunction and fracture was observed in women.

Conclusions  Older men with subclinical hyperthyroidism or hypothyroidism are at increased risk for hip fracture. Whether treatment of the subclinical syndrome reduces this risk is unknown.

  Y. J Kim , J. S Lee , K. S Hong , J. W Chung , J. H Kim and K. B. Hahm
 

Colitis-associated cancers arise in the setting of chronic inflammation wherein an "inflammation-dysplasia-carcinoma" sequence prevails. Based on our previous findings in which the proton pump inhibitor could impose significant levels of anti-inflammatory, antiangiogenic, and selective apoptosis induction beyond gastric acid suppression, we investigated whether omeprazole could prevent the development of colitis-associated cancer in a mouse model induced by repeated bouts of colitis. Omeprazole, 10 mg/kg, was given i.p. all through the experimental periods for colitis-associated carcinogenesis. Molecular changes regarding inflammation and carcinogenesis were compared between control groups and colitis-associated cancer groups treated with omeprazole in addition to chemopreventive outcome. Nine of 12 (75.0%) mice in the control group developed multiple colorectal tumors, whereas tumors were noted in only 3 of 12 (25.0%) mice treated with daily injections of omeprazole. The cancer-preventive results of omeprazole treatment was based on significant decreases in the levels of nitric oxide, thiobarbituric acid–reactive substance, and interleukin-6 accompanied with attenuated expressions of tumor necrosis factor-, inducible nitric oxide synthase, and cyclooxygenase-2. The expressions of matrix metalloproteinase (MMP)-9, MMP-11, and MT1-MMMP were significantly decreased in mice treated with omeprazole in accordance with significant decreases in the number of β-catenin–accumulated crypts. A significant induction of apoptosis was observed in tumor tissue treated with omeprazole. Omeprazole could block the trophic effect of gastrin in colon epithelial cells. The significant anti-inflammatory, antioxidative, and antimutagenic activities of omeprazole played a cancer-preventive role against colitis-induced carcinogenesis, and our novel in vivo evidence is suggestive of chemopreventive action independent of gastric acid suppression. Cancer Prev Res; 3(8); 963–74. ©2010 AACR.

  W. M Wolf , H. A Vlachos , O. C Marroquin , J. S Lee , C Smith , W. D Anderson , J. T Schindler , E. M Holper , J. D Abbott , D. O Williams , W. K Laskey , K. E Kip , S. F Kelsey and S. R. Mulukutla
 

Background— Diabetes is a powerful predictor of adverse events in patients undergoing percutaneous coronary intervention. Drug-eluting stents reduce restenosis rates compared with bare metal stents; however, controversy remains regarding which drug-eluting stents provides greater benefit in patients with diabetes. Accordingly, we compared the safety and efficacy of sirolimus-eluting stents (SES) with paclitaxel-eluting stents (PES) among diabetic patients in a contemporary registry.

Methods and Results— Using the National Heart, Lung, and Blood Institute Dynamic Registry, we evaluated 2-year outcomes of diabetic patients undergoing percutaneous coronary interventions with SES (n=677) and PES (n=328). Clinical and demographic characteristics, including age, body mass index, insulin use, left ventricular function, and aspirin/clopidogrel use postprocedure, did not differ significantly between the groups except that PES-treated patients had a greater frequency of hypertension and hyperlipidemia. At the 2-year follow-up, no significant differences were observed between PES and SES with regard to safety or efficacy end points. PES- and SES-treated patients had similar rates of death (10.7% versus 8.2%, P=0.20), death and myocardial infarction (14.9% versus 13.6%, P=0.55), repeat revascularization (14.8% versus 17.8%, P=0.36), and stent thrombosis (1.3% versus 1.3%, P=0.95). After adjustment, no significant differences between the 2 stent types in any outcome were observed.

Conclusions— PES and SES are equally efficacious and have similar safety profiles in diabetic patients undergoing percutaneous coronary interventions in clinical practice.

  R Agarwal , A. M Gonzalez Angulo , S Myhre , M Carey , J. S Lee , J Overgaard , J Alsner , K Stemke Hale , A Lluch , R. M Neve , W. L Kuo , T Sorlie , A Sahin , V Valero , K Keyomarsi , J. W Gray , A. L Borresen Dale , G. B Mills and B. T. Hennessy
 

Purpose: We studied the expression levels of cyclins B1, D1, and E1 and the implications of cyclin overexpression for patient outcomes in distinct breast cancer subtypes defined by clinical variables and transcriptional profiling.

Experimental Design: The expression levels of cyclins B1, D1, and E1 were quantified in 779 breast tumors and 53 cell lines using reverse phase protein arrays and/or transcriptional profiling.

Results: Whereas cyclin E1 overexpression was a specific marker of triple-negative and basal-like tumors, cyclin B1 overexpression occurred in poor prognosis hormone receptor–positive, luminal B and basal-like breast cancers. Cyclin D1 overexpression occurred in luminal and normal-like cancers. Breast cancer subgroups defined by integrated expression of cyclins B1, D1, and E1 correlated significantly (P < 0.000001) with tumor subtypes defined by transcriptional profiling and clinical criteria. Across three hormone receptor–positive data sets, cyclin B1 was the dominant cyclin associated with poor prognosis in univariate and multivariate analyses. Although CCNE1 was present in significantly higher copy numbers in basal-like versus other subtypes (ANOVA P < 0.001), CCNB1 gene copy number did not show gain in breast cancer. Instead, cyclin B1 expression was increased in tumors with co-occurrence of TP53 mutations and MYC amplification, a combination that seems to characterize basal-like and luminal B tumors. CCNB1 gene expression was significantly correlated with PLK, CENPE, and AURKB gene expression.

Conclusion: Cyclins B1, D1, and E1 have distinct expressions in different breast cancer subtypes. Novel PLK, CENPE, and AURKB inhibitors should be assessed for therapeutic utility in poor prognosis cyclin B1–overexpressing breast cancers.

  C Yoo , J. E Kim , J. L Lee , J. H Ahn , D. H Lee , J. S Lee , S Na , C. S Kim , J. H Hong , B Hong , C Song and H. Ahn
  Objective

The effects of sunitinib in a broad patient population, especially those of Asian ethnicity, have been rarely investigated. Here, we assessed the efficacy and safety of sunitinib in Korean patients with advanced renal cell carcinoma.

Methods

Between April 2006 and August 2008, 77 Korean patients with advanced renal cell carcinoma were treated with sunitinib. We performed retrospective analysis for efficacy in terms of survival outcomes and response rate. Toxicity profiles were also assessed.

Results

A total of 65 patients, including 39 (60%) patients without previous cytotoxic or immunotherapy, were eligible for the analysis. In 53 patients with measurable lesions, the objective response rate was 43% and disease control was achieved in 46 (86%) patients. The median time to treatment failure, time to progression and overall survival were 7.0, 11.8 and 22.8 months, respectively, with a median follow-up of 26.8 months in surviving patients. The most common treatment-related adverse events were fatigue (81%) and stomatitis (60%). The most common Grade 3 or 4 adverse events were hand–foot syndrome (16%), thrombocytopenia (16%) and stomatitis (10%). Dose reduction was required in 46% of patients.

Conclusions

The efficacy was similar to a previous Phase III trial and a safety profile of sunitinib was manageable in Korean patients with advanced renal cell carcinoma, although the incidence of dose reduction and Grade 3 or 4 adverse events were higher than those of western reports. Future studies should investigate the ethnic differences in toxicity profiles of sunitinib.

  J. S Lee , Y. H Kim , S. J Yoon and B. C. Kang
 

This study assessed the reference dose levels for dental panoramic radiography in Gwangju city, South Korea based on the dose width product (DWP) and compared them with those already established elsewhere. A total of 44 panoramic dental radiographic sets (36 digital and 8 analogue panoramic sets) in 41 dental clinics in Gwangju city were chosen. The third quartile DWP was determined from 429 surface dose measurements of the adult surface dose in panoramic dental radiography. The third quartile DWP for panoramic radiography was 60.1 mGy mm. The proposed DWP reference levels of 60.1 mGy mm were less than or equal to those previously reported in other countries, such as Italy and UK, and acceptable for panoramic radiography in Gwangju, South Korea.

  S Nakanishi , J. S Lee , K. E Gardner , J. M Gardner , Y. h Takahashi , M. B Chandrasekharan , Z. W Sun , M. A Osley , B. D Strahl , S. L Jaspersen and A. Shilatifard
 

Histone H2B monoubiquitination by Rad6/Bre1 is required for the trimethylation of both histone H3K4 and H3K79 by COMPASS and Dot1 methyltransferases, respectively. The dependency of methylation at H3K4 and H3K79 on the monoubiquitination of H2BK123 was recently challenged, and extragenic mutations in the strain background used for previous studies or epitope-tagged proteins were suggested to be the sources of this discrepancy. In this study, we show that H3K4 and H3K79 methylation is solely dependent on H2B monoubiquitination regardless of any additional alteration to the H2B sequence or genome. Furthermore, we report that Y131, one of the yeast histone H2A/H2B shuffle strains widely used for the last decade in the field of chromatin and transcription biology, carries a wild-type copy of each of the HTA2 and HTB2 genes under the GAL1/10 promoter on chromosome II. Therefore, we generated the entire histone H2A and H2B alanine-scanning mutant strains in another background, which does not express wild-type histones.

 
 
 
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