Suchergebnisse

To evaluate the protective effect of thalidomide, a potent anti-inflammatory drug, on the development of diabetic cardiomyopathy (DMCMP). We induced type 1 diabetes using streptozocin in 8-week-old Sprague-Dawley rats, divided them into two groups-a thalidomide treatment group (DM-T, n = 15) and a non-treatment group (DM-N, n = 15)-and compared them with a normal control (n = 10). Ten weeks after diabetes induction, heart and lung mass indices were higher in the DM-N group compared with the control group. In the DM-T group, increases in heart and lung mass indices were attenuated compared with the DM-N group. On echocardiographic examination, systolic and diastolic mitral annulus velocities were impaired in the DM-N group, but they remained normal in the DM-T group. On haemodynamic analyses, left ventricular (LV) systolic function, represented by end-systolic elastance (0.35 +/- 0.14 vs. 0.18 +/- 0.07 mmHg/mu l, P < 0.001) and preload-recruitable stroke work (90.5 +/- 24.3 vs. 51.8 +/- 22.0 mmHg, P < 0.001), was preserved in the DM-T group compared with the DM-N group. Likewise, deterioration of LV diastolic function was attenuated in the DM-T group. Increases in serum levels of TNF-alpha were attenuated in the DM-T group compared with the DM-N group. On histological analysis, thalidomide treatment lowered total myocardial collagen content and the expression of TNF-alpha, IL-1 beta, ICAM-1, and VCAM-1. In an animal model of DMCMP, deterioration of LV systolic and diastolic function was partially prevented by thalidomide treatment. ; This study was supported by the Korea Research Foundation Grant funded by the Korean Government (KRF-2007-313-E00217). ; PEREZ AV, 2009, INT J CARDIOL ; Dunlay SM, 2008, CIRCULATION, V118, P625, DOI 10.1161/CIRCULATIONAHA.107.759191 ; Pacher P, 2008, NAT PROTOC, V3, P1422, DOI 10.1038/nprot.2008.138 ; Westermann D, 2007, DIABETES, V56, P1834, DOI 10.2337/db06-1662 ; Boudina S, 2007, CIRCULATION, V115, P3213, DOI 10.1161/CIRCULATIONAHA.106.679597 ; Loh HK, 2007, BASIC CLIN PHARMACOL, V100, P233 ; Sun M, 2007, CIRCULATION, V115, P1398, DOI 10.1161/CIRCULATIONAHA.106.643585 ; Westermann D, 2007, DIABETES, V56, P641, DOI 10.2337/db06-1163 ; Yndestad A, 2006, EUR J HEART FAIL, V8, P790, DOI 10.1016/j.ejheart.2006.02.007 ; Westermann D, 2006, DIABETOLOGIA, V49, P2507, DOI 10.1007/s00125-006-0385-2 ; Arroba AI, 2006, J ENDOCRINOL, V191, P55, DOI 10.1677/joe.1.06908 ; Leichman JG, 2006, AM J CLIN NUTR, V84, P336 ; Chong LW, 2006, J BIOMED SCI, V13, P403, DOI 10.1007/s11373-006-9079-5 ; Sjoholm A, 2006, DIABETES-METAB RES, V22, P4, DOI 10.1002/dmrr.568 ; Lv P, 2006, MEDIAT INFLAMM, DOI 10.1155/MI/2006/93253 ; Gullestad L, 2005, CIRCULATION, V112, P3408, DOI 10.1161/CIRCULATIONHA.105.564971 ; Nguyen MTA, 2005, J BIOL CHEM, V280, P35361, DOI 10.1074/jbc.M504611200 ; Tschope C, 2005, FASEB J, V19, P2057, DOI 10.1096/fj.05-4095fje ; Yoon YS, 2005, CIRCULATION, V111, P2073, DOI 10.1161/01.CIR.0000162472.52990.36 ; Tschope C, 2004, FASEB J, V18, P1967, DOI 10.1096/fj.04-1614fje ; Nian M, 2004, CIRC RES, V94, P1543, DOI 10.1161/01.RES.0000130526.20854.fa ; Tsutamoto T, 2004, EUR J HEART FAIL, V6, P173, DOI 10.1016/j.ejheart.2003.10.004 ; Hasselbaink DM, 2003, BIOCHEM J, V371, P753 ; Poirier P, 2001, DIABETES CARE, V24, P5 ; Adlard JW, 2000, ANTI-CANCER DRUG, V11, P787 ; JACOBSON JM, 2000, EXPERT OPIN PHARMACO, V1, P849 ; Raje N, 1999, NEW ENGL J MED, V341, P1606 ; Tschope C, 1999, IMMUNOPHARMACOLOGY, V44, P35 ; Georgakopoulos D, 1998, AM J PHYSIOL-HEART C, V274, pH1416 ; Rodrigues B, 1998, MOL CELL BIOCHEM, V180, P53 ; Meldrum DR, 1998, AM J PHYSIOL-REG I, V274, pR577 ; Yokoyama T, 1997, CIRCULATION, V95, P1247 ; MALKUSCH W, 1995, EXP LUNG RES, V21, P67 ; KANNEL WB, 1979, JAMA-J AM MED ASSOC, V241, P2035 ; WEISS JL, 1976, J CLIN INVEST, V58, P751 ; 0

Young Youn Cho,1,2 Su Jong Yu,1 Hye Won Lee,3 Do Young Kim,3 Wonseok Kang,4 Yong-Han Paik,4 Pil Soo Sung,5 Si Hyun Bae,6 Su Cheol Park,7 Young Seok Doh,8,9 Kang Mo Kim,9 Eun Sun Jang,10 In Hee Kim,11 Won Kim,12 Yoon Jun Kim1 1Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea; 2Department of Internal Medicine, Chung-Ang University Hospital, Seoul, Korea; 3Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea; 4Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 5Department of Internal Medicine, Seoul St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea; 6Department of Internal Medicine, Eunpyeong St. Mary's Hospital, The Catholic University of Korea College of Medicine, Seoul, Korea; 7Department of Internal Medicine, Korea Cancer Center Hospital, Korea Institute of Radiological and Medical Sciences, Seoul, Korea; 8Department of Internal Medicine, Eulji University Hospital, Daejeon, Korea; 9Department of Gastroenterology, Asan Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 10Departments of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul, Korea; 11Department of Internal Medicine, Chonbuk National University Hospital, Chonbuk National University Medical School, Cheongju-si, Korea; 12Department of Internal Medicine, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, KoreaCorrespondence: Yoon Jun KimDepartment of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, 101 Daehak-no, Jongno-gu, Seoul, 03080 (110-744), KoreaTel +82-2-2072-3081Fax +82-2-743-6701Email yoonjun@snu.ac.krBackground/Aim: Sorafenib is the first systemic therapy for the treatment of advanced-stage hepatocellular carcinoma (HCC) and progressive HCC after locoregional therapy. The aim of this study was to evaluate the prognostic factors of long-term survivors after sorafenib treatment.Methods: This multicenter, retrospective, cohort study included 1,566 unresectable HCC patients who received sorafenib treatment between 2007 and 2014 in nine tertiary centers in Korea. The patients were classified into a long-term survivor group (survival more than two years, n = 257) or a control group (n = 1309). The primary outcomes were the prognostic factors affecting long-term survival. Secondary endpoints included time-to-progression and other safety profiles.Results: The patients were predominantly men (83.8%) with chronic hepatitis B (77.3%) and Barcelona clinic of liver cancer-stage C (BCLC-C) (78.3%). The median overall survival was 9.0 months. After treatment, eight patients (0.4%) achieved complete response and 139 patients (8.8%) achieved partial response according to the mRECIST criteria. The prognostic factors predicting long-term survival were metformin use (adjusted hazard ratio [aHR] = 3.464; P 1,000 ng/mL; HR = 0.361; P < 0.001).Conclusion: This large, multicenter, retrospective study showed an objective response rate of 9.1% and a proportion of long-term survivors of 16.4% in Korean patients. The prognostic factors derived in our study can be used in clinical practice during sorafenib treatment.Keywords: sorafenib, hepatocellular carcinoma, prognosis, survival