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  • Title: Tumor targeting by doxorubicin-RGD-4C peptide conjugate in an orthotopic mouse hepatoma model.
    Author: Kim JW, Lee HS.
    Journal: Int J Mol Med; 2004 Oct; 14(4):529-35. PubMed ID: 15375578.
    Abstract:
    Vascular targeting is a novel strategy that directs endothelial toxins at tumor vessels expressing specific markers and kills tumor cells by vascular occlusion. Integrin-binding RGD motif has been reported to have a homing property to experimental tumor vasculature. In the present study, we evaluated the effect of vascular targeting by doxorubicin-RGD-4C conjugate in an orthotopic murine hepatoma model. MTT assay showed that dox-RGD-4C conjugates had lower cytotoxicity against MH134 mouse hepatoma cells than free dox. When given intravenously to mice with implanted orthotopic hepatoma, however, the dox-RGD-4C suppressed the growth of hepatoma more effectively than free dox (mean tumor volumes 24 mm(3) vs. 67 mm(3), respectively; p=0.047). Histologic analysis of the hepatoma tissue revealed prominent tumor cell death in the dox-RGD-4C treated group and complete tumor cell necrosis in 40% of cases. Immunochemical staining showed expression of integrin alphav mainly around the tumor nodule. These results show that dox-RGD-4C conjugate has a better antitumor effect in an orthotopic mouse hepatoma model by tumor targeting. Integrin alphav of hepatoma feeding vessels is suggested to be targeted by the dox-RGD-4C conjugate.
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