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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Animals, Apoptosis, Carcinoma, Hepatocellular, Cell Movement, Cell Survival, Drug Therapy, Combination, Humans, Immunosuppressive Agents, Indazoles, Liver Neoplasms, Mice, Mice, SCID, Neovascularization, Pathologic, Phenylurea Compounds, Platelet-Derived Growth Factor, Protein Kinases, Receptor Protein-Tyrosine Kinases, Sirolimus, Subcutaneous Fat, TOR Serine-Threonine Kinases, Vascular Endothelial Growth Factor A, Xenograft Model Antitumor Assays.
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Is aBT-869 , a multi-targeted tyrosine kinase inhibitor , in combination with rapamycin effective for subcutaneous hepatocellular carcinoma xenograft? Context: Receptor tyrosine kinase inhibitors (RTKIs) and mTOR inhibitors are potential novel anticancer therapies for HCC. We hypothesized that combination targeted on distinctive signal pathways would provide synergistic therapeutics. ABT-869, a novel RTKI, and rapamycin were investigated in HCC pre-clinical models. Rapamycin, but not ABT-869, inhibited in vitro growth of Huh7 and SK-HEP-1 HCC cells in a dose dependant manner. However, in subcutaneous Huh7 and SK-HEP-1 xenograft models, either ABT-869 or rapamycin can significantly reduce tumor burden. Combination treatment reduced the tumors to the lowest volume (95+/-20mm(3)), and was significantly better than single agent treatment (p<0.05). Immunohistochemical staining of tumor shows that ABT-869 potently inhibits VEGF in HCC in vivo. In addition, the MAPK signaling pathway has been inhibited by significant inhibition of phosphorylation of p44/42 MAP kinase by ABT-869 in vivo. Rapamycin inhibits phosphorylation of p70 S6 kinase and 4E-BP-1, downstream targets of mTOR, and decreases VEGF. Combination treatment showed synergistic effect on expression levels of p27 in vivo. Dramatic inhibition of neo-angiogenesis by ABT-869 was also demonstrated.
assistant
HCC could potentially be treated with the combination treatment of ABT-869 and rapamycin. Clinical trials on combination therapy are warranted. Final Decision: yes