Jae Hyuk Choi

Seoul National University, Sŏul, Seoul, South Korea

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Publications (3)11.86 Total impact

  • [show abstract] [hide abstract]
    ABSTRACT: In this study, we show that atraxia telangiectasia mutated kinase (ATM) activity is generally upregulated by different apoptotic stimuli, i.e. TNF-α, TRAIL, paclitaxel, or UV. Apoptotic progression is markedly attenuated by siATM-RNA through down regulation of caspase-8 and caspase-9 in parallel with decreases in FLIP-S (short form of cellular FLICE inhibitory protein) protein levels and Bid cleavage. In addition, ATM activity is upregulated through t-Cdc6 while caspase-8 and caspase-9 activities increase. Taken together, we suggest that ATM regulates caspase-8 activation by influencing levels of FLIP-S, ATM kinase activity is upregulated by t-Cdc6, and increased ATM activity plays an essential role in the amplification of apoptosis in TNF-α-stimulated HeLa cells.
    FEBS letters 02/2014; · 3.54 Impact Factor
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    ABSTRACT: BACKGROUND: The use of self-expandable metal stents (SEMS) for the treatment of malignant colorectal obstruction is increasing. However, results of risk factors for its complications are inconsistent. This study aimed to examine the clinical effectiveness of the procedure as well as the complications and risk factors associated with the complications. METHODS: Medical records of patients with malignant colorectal obstruction who underwent endoscopic placement of covered or uncovered SEMS were reviewed retrospectively. The procedure was performed by two endoscopists with experience in pancreatobiliary endoscopy. RESULTS: A total of 152 patients were included (102 men; mean age, 70 ± 12.5 years). The procedure was performed for palliative management in 83 patients and performed as a bridge to surgery in 69 patients. There were 111 uncovered stents and 41 covered stents. The technical success rate was 100 % and the clinical success rate 94.1 %. Overall complications were observed in 49 patients (32.2 %) during the follow-up period (median, 98 days; interquartile range, 19-302 days). Obstruction (17.1 %), migration (7.9 %), perforation (5.2 %), bleeding (1.3 %), and tenesmus (0.7 %) were the causes of the complications. Stage IV disease, carcinomatosis peritonei, complete obstruction of the colon, palliative intention, and covered stents increased the complications based on the univariate analysis. Multivariate analysis revealed that complete obstruction of the colon and covered stents were significantly independent risk factors for complications. In the palliative group, Kaplan-Meier analysis showed significantly shorter median duration to the onset of complications in the covered stent group than in the uncovered stent group. CONCLUSIONS: Although SEMS in patients with malignant colorectal obstruction is effective both as palliative therapy and as a bridge to surgery, one-third of patients experienced complications. Severity of obstruction and stent type can influence outcomes.
    Surgical Endoscopy 03/2013; · 3.43 Impact Factor
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    ABSTRACT: The Cdc6 protein, a key DNA replication initiation factor, contributes to the long-term maintenance of the S-phase checkpoint by anchoring the Rad3-Rad26 complex to chromatin. Here, we demonstrate that ATR (AT mutated and Rad3 related) activity is essential for maintaining high chromatin levels of the Cdc6 protein, thereby delaying entry into mitosis during hydroxyurea (HU)-induced S-phase arrest of HeLa cells. Downregulation of ATR (AT mutated and Rad3 related) (i.e., using ATR-siRNA) reduced the protein levels of chromatin Cdc6 and significantly increased the cellular levels of phospho-histone H3 (Ser 10), an index of mitosis. Downregulation of Cdc6 was completely restored by pretreatment with MG132, a proteasome inhibitor. Moreover, mitotic entry of MG132-pretreated cells was significantly downregulated. Our results also show that ATR (AT mutated and Rad3 related) kinase phosphorylates Cdc6 at serine residue 6. Thus, this ATR (AT mutated and Rad3 related)-mediated phosphorylation of Cdc6 is likely associated with stabilization of Cdc6 protein, thereby maintaining high levels of chromatin Cdc6 and delaying premature mitotic entry. This novel mechanism likely contributes to the functional regulation of chromatin Cdc6, which delays the cell cycle of hydroxyurea-induced cells to enter mitosis at the S-phase checkpoint.
    The international journal of biochemistry & cell biology 01/2009; 41(6):1410-20. · 4.89 Impact Factor