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Author Jendreyko, Nina ♦ Mcgavern, Dorian B. ♦ Rader, Christoph
Source CiteSeerX
Content type Text
File Format PDF
Subject Domain (in DDC) Computer science, information & general works ♦ Data processing & computer science
Subject Keyword Tumor Angiogenesis ♦ Adenovirus-delivered Anti-tie-2 Intrabody Mikhail Popkov ♦ Important Role ♦ Control-treated Tumor ♦ Histopathol-ogic Analysis ♦ Vascular Endothelium ♦ Antitumor Effect ♦ Slk Sarcoma ♦ Sw1222 Colon Carcinoma Xenograft Growth ♦ Tie-2 Receptor Pathway ♦ Endothelial Cell Specific Receptor Kinase ♦ Human Tie-2-monospecific Pad-1s05 Intrabody ♦ Cancer Therapy ♦ Murine Model ♦ Human Colon Carcinoma ♦ Antiangiogenic Agent ♦ Tumor Model ♦ Pad-gfp Control-treated Tumor ♦ Human Tie-2 Surface Expression ♦ Tie-2 Receptor-interaction Pathway ♦ Tumor Angio-genesis ♦ Cancer Re ♦ Marked Decrease ♦ Human Kaposi Sarcoma ♦ Vessel Density ♦ Adenoviral Vector ♦ Present Study ♦ Potential Utility ♦ Endothelium-specific Receptor Tie-2 ♦ Promising Approach ♦ Therapeutic Potential ♦ Well-established Primary Tumor ♦ Genetic Deletion
Abstract Inhibition of tumor angiogenesis is a promising approach for cancer therapy. As an endothelial cell–specific receptor kinase expressed almost exclusively on the surface of vascular endothelium, Tie-2 has an important role in tumor angio-genesis. To explore the therapeutic potential of blocking Tie-2 receptor-interaction pathway, an adenoviral vector was used to deliver a recombinant single-chain antibody fragment rabbit intrabody (pAd-2S03) capable of inhibition of both mouse and human Tie-2 surface expression. pAd-2S03 was given to mice with well-established primary tumors, either a human Kaposi’s sarcoma (SLK) or a human colon carcinoma (SW1222). The intrabody significantly inhibited growth of both tumors (75 % and 63%, respectively) when compared with pAd-GFP control-treated tumors (P < 0.01). Histopathol-ogic analysis of cryosections taken from mice treated with pAd-2S03 revealed a marked decrease in vessel density, which was reduced by>87 % in both tumor models when compared with control-treated tumors (P < 0.01). In contrast, human Tie-2-monospecific pAd-1S05 intrabody did not affect the growth of tumors, indicating that the antitumor effect of pAd-2S03 was due to the inhibition of tumor angiogenesis in these murine models. Our results show that the Tie-2 receptor pathway is essential for both SLK sarcoma and SW1222 colon carcinoma xenograft growth. The present study shows the potential utility of antiangiogenic agents that target the endothelium-specific receptor Tie-2 for down-regulation or genetic deletion. (Cancer Res 2005; 65(3): 972-81)
Educational Role Student ♦ Teacher
Age Range above 22 year
Educational Use Research
Education Level UG and PG ♦ Career/Technical Study