Kornek, Miroslaw Theodor: Does hepatic fibrosis accelerate orthotopic HCC tumor growth in a novel liver fibrosis model in the C3H/He mice?. - Bonn, 2008. - Dissertation, Rheinische Friedrich-Wilhelms-Universität Bonn.
Online-Ausgabe in bonndoc: https://nbn-resolving.org/urn:nbn:de:hbz:5N-13003
@phdthesis{handle:20.500.11811/3560,
urn: https://nbn-resolving.org/urn:nbn:de:hbz:5N-13003,
author = {{Miroslaw Theodor Kornek}},
title = {Does hepatic fibrosis accelerate orthotopic HCC tumor growth in a novel liver fibrosis model in the C3H/He mice?},
school = {Rheinische Friedrich-Wilhelms-Universität Bonn},
year = 2008,
note = {Treatment of HCC is challenging and improved animal models are needed for testing innovative therapies. In particular, a well characterized fibrosis tumor model is urgently needed. Here, a novel HCC tumor model was established based on the use of pre-fibrotic mice. Common methods such as CCL4 failed to induce fibrosis with a tolerable mortality rate in C3H/He mice. Instead, a combination of TAA (thioacetamide) i.p. and EtOH (ethanol) effectively induced liver fibrosis at lower mortality rate then CCL4. Fibrogenesis was characterized by typical histological changes besides protein level and steady state mRNA transcription measurement of alpha 1 procollagen (I), and quantification of hepatic MMP-2, sVEGF and sICAM-1 protein. All these biomarkers have been shown to be up regulated during fibrosis induction in rodents and human. This fibrosis model resembles critical aspects of human liver fibrosis, including haemodynamic microcirculation (HM) change manifesting in marked HM reduction in the fibrotic mouse liver.
For first time a marked intrahepatic HM was observed in mice as a result of induced fibrogenesis. Of great interest also was the second finding in this model: Pre-existing liver fibrosis was associated with advanced orthotopic hepatoma (Hepa129 tumor cells) and metastasis growth. In particular, intratumoral VEGF-A and VEGF-C and their VEGFR expression was increased, which might account for the observed rapid tumor development at the tumor cell implantation site and satellite formation. Thus, VEGF-C and its receptor could serve as a predictable marker for metastasis in HCC. MMP expression was increased as well, consistent with the fact that MMP-2 and MMP-9 are important HCC invasion factors.
In summary, this novel tumor model might serve as a valuable tool for future studies on HCC tumor development and formation of tumor and tumor satellites in liver fibrosis. It appears suitable for future tumor cell implantation experiments and further fibrosis studies. In addition, it will permit investigating the effect of fibrosis on HCC orthotopic tumor growth in vivo and testing innovative intervention studies aimed at treatment of HCC. Hopefully, these experimental studies can be helpful to improve treatment of human HCC patients with cirrhosis.},

url = {https://hdl.handle.net/20.500.11811/3560}
}

The following license files are associated with this item:

InCopyright