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Yasuaki Fukuda,Masahiro Kanbe,Manami Watanabe,Katsuaki Dan,Keiichi Matsuzaki,Susumu Kitanaka,Shohei Miyata 대한약학회 2013 Archives of Pharmacal Research Vol.36 No.8
We have previously reported that many ingenolcompounds derived from Euphorbia kansui exhibit topoisomerase(topo) II inhibitory activity. Of these compounds,3EZ,20Ac-ingenol inhibited topo I activity. Camptothecin,which inhibits the religation activity of topo I withoutinterfering with the binding of topo I to DNA and inducestopo I-mediated DNA cleavage, was used as a positivecontrol. In this study, we found that 3EZ,20Ac-ingenol didnot hamper the binding of topo I to DNA in the samemanner as camptothecin but affected the inhibition ofcleavage of one DNA strand. 3EZ,20Ac-ingenol inhibitedcell proliferation by blocking cell cycle progression in theG2/M phase. To define the mechanism of inhibition ofDT40 cell proliferation, the change in Akt activity wasobserved because Akt activity is regulated in response toDNA damage. Western blot analysis revealed that3EZ,20Ac-ingenol downregulated the expression of p-Akt,and apoptosis was detected by the presence of DNA double-strand breaks and caspase 3 activation.
Keiji Yokoyama,Ryo Yamauchi,Kumiko Shibata,Hiromi Fukuda,Hideo Kunimoto,Kazuhide Takata,Takashi Tanaka,Shinjiro Inomata,Daisuke Morihara,Yasuaki Takeyama,Satoshi Shakado,Shotaro Sakisaka 대한간학회 2019 Clinical and Molecular Hepatology(대한간학회지) Vol.25 No.2
Background/Aims: There is a controversy about the availability of invasive treatment for esophageal/gastric varices in patients with Child-Pugh class C (CP-C) end-stage liver cirrhosis (LC). We have evaluated the validity of invasive treatment with CP-C end-stage LC patients. Methods: The study enrolled 51 patients with CP-C end-stage LC who had undergone invasive treatment. The treatment modalities included endoscopic variceal ligation in 22 patients, endoscopic injection sclerotherapy in 17 patients, and balloon-occluded retrograde transvenous obliteration (BRTO) in 12 patients. We have investigated the overall survival (OS) rates and risk factors that contributed to death within one year after treatment. Results: The OS rate in all patients at one, three, and five years was 72.6%, 30.2%, and 15.1%, respectively. The OS rate in patients who received endoscopic treatment and the BRTO group at one, three, and five years was 67.6%, 28.2% and 14.1% and 90.0%, 36.0% and 18.0%, respectively. The average of Child-Pugh scores (CPS) from before treatment to one month after variceal treatment significantly improved from 10.53 to 10.02 (P=0.003). Three significant factors that contributed to death within one year after treatment included the presence of bleeding varices, high CPS (≥11), and high serum total bilirubin levels (≥4.0 mg/dL). Conclusions: The study demonstrated that patients with a CPS of up to 10 and less than 4.0 mg/dL of serum total bilirubin levels may not have a negative impact on prognosis after invasive treatment for esophageal/gastric varices despite their CP-C end-stage LC.
Manabu Tsukamoto,Toshiharu Mori,Eiichiro Nakamura,Yasuaki Okada,Hokuto Fukuda,Yoshiaki Yamanaka,Ken Sabanai,Ke-Yong Wang,Takeshi Hanagiri,Satoshi Kuboi,Kazuhiro Yatera,Akinori Sakai 대한골다공증학회 2020 Osteoporosis and Sarcopenia Vol.6 No.4
Objectives: Chronic obstructive pulmonary disease (COPD) is a risk factor for osteoporosis. Nevertheless, much remains unclear regarding the bone metabolism dynamics associated with COPD. The present study focuses on the associations between the COPD severity and serum bone metabolism biomarkers. Methods: We enrolled 40 patients who visited the orthopedics departments at our institutions and underwent dual-energy X-ray absorptiometry between September 2015 and December 2017. Only male osteoporosis patients over 45 years of age were included, and 5 patients were excluded due to disease or use of internal medicines affecting bone metabolism. All subjects underwent lung function testing, spine radiography, and blood tests. We measured percent forced expiratory volume in 1 second (%FEV1), which reflects COPD severity, and we examined the relationships between %FEV1 and serum levels of bone metabolism biomarkers. Results: All subjects were diagnosed with osteoporosis based on T-scores. %FEV1 correlated with body weight, body mass index (BMI), and Z-score/T-scores. %FEV1 moderately correlated with serum levels of alkaline phosphatase (ALP), procollagen type 1 N-terminal propeptide (P1NP), and tartrate-resistant acid phosphatase 5b in the partial correlation analysis adjusted for BMI or T-score in the lumbar vertebrae. We performed a hierarchical multiple regression analysis to identify that serum ALP and P1NP were the independent explanatory variables to %FEV1 independent of other factors. Conclusions: The data suggest that the COPD severity in middle-aged and older men with osteoporosis associates with decreased bone formation. COPD patients may exhibit bone metabolism dynamics characterized by low bone turnover with osteogenesis dysfunction as COPD becomes severe.