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. Author manuscript; available in PMC: 2011 Nov 1.
Published in final edited form as: Nat Rev Clin Oncol. 2010 Sep 14;7(11):653–664. doi: 10.1038/nrclinonc.2010.139

Figure 4.

Figure 4

Effect of vascular normalization. a | Tumor angiogenesis results from an imbalance between antiangiogenic and proangiogenic factors. Normalization aims to restore this balance and bring the tumor vasculature to a more normal phenotype. Permission obtained from the American Association for the Advancement of Science © Jain, R. K. Science 307, 58–62 (2005). b | Use of an anti-VEGF antibody, DC101, reduced IFP and had no effect on MVP. Permission obtained from the American Association of Cancer Research © Tong, R. T. et al. Cancer Res. 64, 3731–3736 (2004). c | Frozen sections of murine mammary adenocarcinoma (MCa IV) tumors with perfused biotinylated lectin to indentify functional vessels, and extravasated tetramethyl rhodamine isothiocyanate–BSA to study interstitial penetration. Vessels were identified using the ImageJ software and the average intensity of BSA was quantified as a function of distance from the blood vessel wall. Tumors treated with the antiangiogenic agent DC101 exhibited increased penetration of BSA in the tumor interstitial space. Permission obtained from the American Association of Cancer Research © Tong, R. T. et al. Cancer Res. 64, 3731–3736 (2004). d | Normalization by DC101 decreased hypoxia in brain tumors in mice. Hypoxia reached a minimum at day 5, and a partial relapse occurred at day 8. *P <0.05, compared with untreated control; +P <0.05, compared with rat IgG-treated control (day 2); #P <0.05, compared with day 2 after initiation of DC101 therapy. Permission obtained from Elsevier Ltd. © Winkler, F. et al. Cancer Cell 6, 553–563 (2004). Abbreviations: BSA, bovine serum albumin; IFP, interstitial fluid pressure; MVP, microvascular pressure.