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Life Science : Ascochlorin activates p53 in a manner distinct from DNA damaging agents
( Ji Hak Jeong ),( Hiroo Nakajima ),( Junji Magae ),( Chiharu Furukawa ),( Keiko Taki ),( Kensuke Otsuka ),( Masanori Tomita ),( In Seon Lee ),( Cheorl Ho Kim ),( Hyeun Wook Chang ),( Kwan Sik Min ),( 영남대학교 약품개발연구소 2009 영남대학교 약품개발연구소 연구업적집 Vol.19 No.-
Ascochlorin activates p53 in a manner distinct from DNA damaging agents
Jeong, Ji-Hak,Nakajima, Hiroo,Magae, Junji,Furukawa, Chiharu,Taki, Keiko,Otsuka, Kensuke,Tomita, Masanori,Lee, In-Seon,Kim, Cheorl-Ho,Chang, Hyeun-Wook,Min, Kwan-Sik,Park, Kwang-Kyun,Park, Kwan-Kyu,Ch Wiley Subscription Services, Inc., A Wiley Company 2009 International journal of cancer: Journal internati Vol.124 No.12
<P>Ascochlorin, a prenylphenol antitumor antibiotic, profoundly increases the expression of endogenous p53 by increasing protein stability in the human osteosarcoma cells and human colon cancer cells. Ascochlorin also increases DNA binding activity to the p53 consensus sequence in nuclear extract and enhances transcription of p53 downstream targets. Ascochlorin specifically induces p53 phosphorylation at ser 392 without affecting ser 15 or 20, whereas DNA damaging agents typically phosphorylate these serines. Moreover, ascochlorin does not induce phosphorylation of ATM and CHK1, an established substrate of ATR that is activated by genotoxins, nor does it increase DNA strand break, as confirmed by comet assay. The structure-activity relationship suggests that p53 activation by ascochlorin is related to inhibition of mitochondrial respiration, which is further supported by the observation that respiratory inhibitors activate p53 in a manner similar to ascochlorin. These results suggest that ascochlorin, through the inhibition of mitochondrial respiration, activates p53 through a mechanism distinct from genotoxins. © 2009 UICC</P>
Single-Stage Endoscopic Stone Extraction and Cholecystectomy during the Same Hospitalization
Toshiaki Terauchi,Hiroharu Shinozaki,Satoshi Shinozaki,Yuichi Sasakura,Masaru Kimata,Junji Furukawa,Alan Kawarai Lefor,Yoshiro Ogata,Kenji Kobayashi 대한소화기내시경학회 2019 Clinical Endoscopy Vol.52 No.1
Background/Aims: The clinical impact of single-stage endoscopic stone extraction by endoscopic retrograde cholangiopancreatography(ERCP) and cholecystectomy during the same hospitalization remains elusive. This study aimed to determine the effcacy and safety ofsingle-stage ERCP and cholecystectomy during the same hospitalization in patients with cholangitis. Methods: We retrospectively reviewed the medical records of 166 patients who underwent ERCP for mild to moderate cholangitis dueto choledocholithiasis secondary to cholecystolithiasis from 2012 to 2016. Results: Complete stone extraction was accomplished in 92% of patients (152/166) at the first ERCP. Among 152 patients whounderwent complete stone extraction, cholecystectomy was scheduled for 119 patients (78%). Cholecystectomy was performed duringthe same hospitalization in 89% of patients (106/119). We compared two groups of patients: those who underwent cholecystectomyduring the same hospitalization (n=106) and those who underwent cholecystectomy during a subsequent hospitalization (n=13). In thedelayed group, cholecystectomy was performed about three months after the first ERCP. There were no significant differences betweenthe groups in terms of operative time, rate of postoperative complications, and interval from cholecystectomy to discharge. Conclusions: Single-stage endoscopic stone extraction is recommended in patients with mild to moderate acute cholangitis due tocholedocholithiasis. The combination of endoscopic stone extraction and cholecystectomy during the same hospitalization is safe andfeasible.