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Articles by S. Kim
Total Records ( 3 ) for S. Kim
  J. W Choi , J. Y Um , J. K Kundu , Y. J Surh and S. Kim
 

Aminoacyl-transfer ribonucleic acid (tRNA) synthetases-interacting multifunctional protein (AIMP) 2 is a factor associated with the macromolecular protein synthesis machinery consisting of nine different aminoacyl-tRNA synthetases and three non-enzymatic factors. However, it was shown to work as a multifaceted regulator through the versatile interactions with diverse signal mediators. For instance, it can mediate pro-apoptotic response to DNA damage and tumor necrosis factor- (TNF-) stimulus and growth-arresting signal by transforming growth factor (TGF)-β. Considering that these pathways are critically implicated in the control of tumorigenesis, AIMP2 is expected to work as a potent tumor suppressor with broad coverage against different cancer types. Here we investigated whether AIMP2 would give gene dosage effect on its pro-apoptotic and anti-proliferative activities using the wild-type, hetero- and homozygous AIMP2 cells and whether AIMP2 would be critical in preventing tumorigenesis using different in vivo tumor models. Both the apoptotic responses to DNA damage and TNF- and sensitivity to growth arresting TGF-β signal were reduced in AIMP2 hetero- and homozygous cells compared with the wild-type cells in dose-dependent manner. In all the in vivo carcinogenesis experiments, reduction of AIMP2 level in heterozygous AIMP2 mice provided higher susceptibility to tumor formation. Thus, this work proves the functional significance of AIMP2 in determination of cell proliferation and death, and as a haploinsufficient tumor suppressor.

  S. J Hwang , Y. H Jeong , I. S Kim , K. S Park , M. K Kang , J. S Koh , J. R Park , Y Park , E. H Koh , C. H Kwak , J. Y Hwang and S. Kim
  Background—

Among patients treated with clopidogrel, carriers of the cytochrome P450 (CYP) 2C19 loss-of-function allele have shown increased platelet reactivity and higher rates of ischemic events. Although adjunctive cilostazol to dual antiplatelet therapy (or "triple antiplatelet therapy") intensifies platelet inhibition, it remains unknown whether triple antiplatelet therapy after percutaneous coronary intervention can achieve adequate platelet inhibition in patients with the CYP2C19 mutant allele.

Methods and Results—

CYP2C19 genotyping for *1, *2, and *3 was performed in 134 high-risk patients undergoing elective percutaneous coronary intervention. After measurement of preprocedural platelet reactivity, patients were randomly assigned to receive either adjunctive cilostazol 100 mg twice daily (triple group; n=69) or high maintenance-dose (MD) clopidogrel of 150 mg daily (high-MD group; n=65). Using light transmittance aggregometry and the VerifyNow P2Y12 assay, platelet reactivity was assessed before the index procedure and at 30-day follow-up. The primary end point was absolute change in maximal platelet aggregation (Aggmax) according to CYP2C19 genotyping. High posttreatment platelet reactivity was defined as 5 µmol/L ADP–induced maximal platelet aggregation >50%. In noncarriers of the CYP2C19*2/*3 mutant allele, Aggmax values after 5 and 20 µmol/L ADP stimuli did not differ significantly between the triple (n=22) versus the high-MD group (n=22) (23.6±21.6% versus 16.6±15.4%, P=0.224 and 26.4±22.2% versus 18.6±14.9%, P=0.174, respectively). Absolute changes in late platelet aggregation and P2Y12 reaction unit were not different between the groups. The rate of high posttreatment platelet reactivity at 30-day follow-up also was comparable between the triple versus the high-MD group (4.5% versus 13.6%, P=0.607). In carriers of at least 1 CYP2C19*2/*3 mutant allele, the triple group (n=47) showed greater values of Aggmax after addition of 5 µmol/L (25.8±16.8% versus 11.1±19.8%, P<0.001) and 20 µmol/L ADP (26.3±16.0% versus 11.5±16.3%, P<0.001) compared with the high-MD group (n=43). Likewise, absolute changes in late platelet aggregation and P2Y12 reaction unit were consistently greater in the triple versus the high-MD group. Fewer patients in the triple group met the criteria of high posttreatment platelet reactivity at 30-day follow-up compared with the high-MD group (6.4% versus 37.2%, P<0.001).

Conclusions—

Among high-risk patients undergoing elective percutaneous coronary intervention, adjunctive cilostazol can achieve consistently intensified platelet inhibition and reduce the risk of high posttreatment platelet reactivity irrespective of CYP2C19 genotyping.

Clinical Trial Registration—

URL: http://www.clinicaltrials.gov. Unique identifier: NCT01012193.

  M. Ferwana , B. Firwana , R. Hasan , M. H. Al-Mallah , S. Kim , V. M. Montori and M. H. Murad
 

Aims

Pioglitazone, a thiazolidinedione, was approved for treatment of Type 2 diabetes. However, several observational studies suggest an association of pioglitazone with an increased risk of bladder cancer in patients with diabetes. Therefore, we sought to perform a systematic review and meta-analysis to evaluate the magnitude of this association and the quality of the supporting evidence.

Methods

Electronic databases were queried to identify controlled studies of pioglitazone that measured the risk of bladder cancer.

Results

Six studies involving 215 142 patients using pioglitazone were included, with a median period of follow-up of 44 months. The hazard of developing bladder cancer was significantly higher in patients using pioglitazone (hazard ratio 1.23; 95% CI 1.09-1.39; I2 = 0%) compared with control groups. The risk of bias was moderate across the six studies. Considering an incidence rate of 20.8 per 100 000 person years, the number needed to harm was five additional cases of bladder cancer per 100 000 person years.

Conclusions

Patients treated with pioglitazone have a slight increased risk of bladder cancer compared to general population. Patient involvement and weighing treatment benefits versus risks should be discussed with patient toward shared decision. Patients with type 2 diabetes with risk factors, such as family history, smoking, or exposure to certain forms of chemotherapy may need to consider other anti-hyperglycemic agents. Also, pioglitazone should be discontinued in type 2 diabetes patients with newly diagnosed bladder cancer.

 
 
 
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