The dual EGF/VEGF receptor tyrosine kinase inhibitor AEE788 inhibits growth of human hepatocellular carcinoma xenografts in nude mice.
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The dual EGF/VEGF receptor tyrosine kinase inhibitor AEE788 inhibits growth of human hepatocellular carcinoma xenografts in nude mice. / Okamoto, Kinya; Neureiter, Daniel; Alinger, Beate; Meissnitzer, Matthias; Sass, Gabriele; Schmitz, Volker; Pietro, Di Fazio; Wissniowski, Till; Gahr, Susanne; Hohenstein, Bernd; Kaufmann, Bernhard; Schlösser, Axel; Haus, Ulrike; Hahn, Eckhart G; Herold, Christoph; Ocker, Matthias.
In: INT J ONCOL, Vol. 33, No. 4, 4, 2008, p. 733-742.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - The dual EGF/VEGF receptor tyrosine kinase inhibitor AEE788 inhibits growth of human hepatocellular carcinoma xenografts in nude mice.
AU - Okamoto, Kinya
AU - Neureiter, Daniel
AU - Alinger, Beate
AU - Meissnitzer, Matthias
AU - Sass, Gabriele
AU - Schmitz, Volker
AU - Pietro, Di Fazio
AU - Wissniowski, Till
AU - Gahr, Susanne
AU - Hohenstein, Bernd
AU - Kaufmann, Bernhard
AU - Schlösser, Axel
AU - Haus, Ulrike
AU - Hahn, Eckhart G
AU - Herold, Christoph
AU - Ocker, Matthias
PY - 2008
Y1 - 2008
N2 - We investigated the effect of AEE788, a novel dual receptor tyrosine kinase inhibitor of the EGF and the VEGF receptor, for treatment of human HCC cell lines and in a subcutaneous xenograft model. Cell viability and apoptosis of HepG2 and Hep3B cells incubated with 0.1-100 microM AEE788 were quantified. In vivo, HepG2 cells were xenografted to NMRI mice and animals were treated orally with 50 mg/kg AEE788 3x/week. Immunohistochemistry and quantitative Western blotting was performed for pathway analysis in vitro and in vivo. AEE788 reduced growth and induced apoptosis of HCC cells by disrupting mitochondrial transmembrane potentials and inhibiting MAPK phosphorylation. In the xenografts, AEE788 lead to a reduced tumor growth by reducing proliferation and vascularisation. Except for a reversible skin reaction and weight loss, no signs of toxicity were observed. AEE788 is a promising new option for the treatment of HCC.
AB - We investigated the effect of AEE788, a novel dual receptor tyrosine kinase inhibitor of the EGF and the VEGF receptor, for treatment of human HCC cell lines and in a subcutaneous xenograft model. Cell viability and apoptosis of HepG2 and Hep3B cells incubated with 0.1-100 microM AEE788 were quantified. In vivo, HepG2 cells were xenografted to NMRI mice and animals were treated orally with 50 mg/kg AEE788 3x/week. Immunohistochemistry and quantitative Western blotting was performed for pathway analysis in vitro and in vivo. AEE788 reduced growth and induced apoptosis of HCC cells by disrupting mitochondrial transmembrane potentials and inhibiting MAPK phosphorylation. In the xenografts, AEE788 lead to a reduced tumor growth by reducing proliferation and vascularisation. Except for a reversible skin reaction and weight loss, no signs of toxicity were observed. AEE788 is a promising new option for the treatment of HCC.
M3 - SCORING: Zeitschriftenaufsatz
VL - 33
SP - 733
EP - 742
JO - INT J ONCOL
JF - INT J ONCOL
SN - 1019-6439
IS - 4
M1 - 4
ER -
