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Combined inhibitors of angiogenesis and histone deacetylase:Efficacy in rat hepatoma

World Journal of Gastroenterology 2011年第31期17卷 3623-3629页

作者： Marion Ganslmayer Annette Zimmermann Steffen Zopf christoph herold Medical Department 1 University hospital Erlangen-Nuernberg Department of Otolaryngology University of Marburg

AIM:To evaluate the antitumoral effect of combined inhibitors of angiogenesis and histone deacetylases in an experimental rat hepatoma ***:MH7777A hepatoma cells were injected into the liver of male Buffalo *** 7 d treatment with the vascular endothelial growth factor receptor antagonist PTK787/ZK222584(PTK/ZK),the histone deacetylase inhibitor MS-275,tamoxifen(TAM) and/or retinoic acid was initiated(n ≥ 8 animals/group).Natural tumor development was shown in untreated control groups(control 1 with n = 12,control 2 with n = 8).The control groups were initiated at different time points to demonstrate the stability of the hepatoma *** documentation of possible side effects,we documented any change in body weight,loss of fur and *** 21 d treatment,the rats were *** target parameters were tumor size and metastasis ***,immunohistochemistry for the proliferating cell nuclear antigen(PCNA) and TdT-mediated dUTP-biotin nick end labeling(TUNEL) assay were ***:The control groups developed large tumor nodules with extrahepatic tumor burden in the lung and abdominal organs(control 1:6.18 cm3 ± 4.14 cm3 and control 2:8.0 cm3 ± 4.44 cm3 28 d after tumor cell injection).The tumor volume did not differ significantly in the control groups(P = 0.13).As single agents MS-275 and PTK/ZK reduced tumor volume by 58.6% ± 2.6% and 48.7% ± 3.2% vs control group 1,which was significant only for MS-275(P = 0.025).The combination of MS-275 and PTK/ZK induced a nearly complete and highly significant tumor shrinkage by 90.3% ± 1%(P = 0.005).Addition of TAM showed no further efficacy,while quadruple therapy with retinoic acid increased antitumoral efficacy(tumor reduction by 93 ± 1%) and side *** positive cells were not significantly reduced by the single agents,while dual therapy(MS-275 and PTK/ZK) and quadruple therapy reduced the PCNA-positive cell fraction significantly by 9.1 and 20.6% vs control 1(P < 0.05).Th

关键词： PTK787 ZK222584 MS-275 Hepatocellular carcinoma Histone deacetylase inhibitor

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Improvement of quantitative testing of liver function in patients with chronic hepatitis C after installment of antiviral therapy

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World Journal of Gastroenterology 2005年第35期11卷 5521-5524页

作者： Matthias Ocker Marion Ganslmayer Steffen Zopf Susanne Gahr christopher Janson Eckhart G. Hahn christoph herold Department of Medicine I University Erlangen-Nuernberg Ulmenweg 18 Erlangen 91054 Germany

MM： To investigate if and to what extent antiviral therapy influenced a broad panel of quantitative testing of liver function （QTLF）. METHODS： Fifty patients with chronic hepatitis C were either treated with interferon （n = 8）, interferon/ribavirin （n = 19） or peg-interferon/ribavirin （n = 23）. Quantitative testing of liver function, including aminopyrine breath test （ABT）, galactose elimination capacity （GEC）, sorbitol clearance （SCI） and indocyanine green clearance （ICG） was performed before and 3 mo after initiation of antiviral therapy. RESULTS： After 3 mo of antiviral treatment, 36 patients showed normal transaminases and were negative for HCVRNA, 14 patients did not respond to therapy. ABT and GEC as parameters of microsomal and cytosolic liver function were reduced in all patients before therapy initiation and returned to normal values in the 36 therapy responders after 3 too. Parameters of liver perfusion （SCl and ICG） were not affected by antiviral therapy. In the 14 non-responders, no changes in QTLF values were observed during the treatment period. CONCLUSION： ICG and SCI remained unaffected in patients with chronic hepatitis C, while ABT and GEC were significantly compromised. ABT and GEC normalized in responders to antiviral therapy. Early determination of ABT and GEC may differentiate responders from non-responders to antiviral treatment in hepatitis C.

关键词： Aminopyrine breath test Galactose eliminationcapacity Indocyanine green clearance Sorbitol clearance Hepatitis C Interferon Ribavirin

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