Tumor angiogenesis, tumor physiology, antiangiogenesis tumor therapy, noninvasive tumor imaging.
cancer, angiogenesis, experimental therapy.
Description of Research
The requirement during tumor growth for blood perfusion and a vasculature that supports it has led us to study vascular development in tumors, antiangiogenic approaches to cancer therapy, and the tumor metabolic and physiologic consequences of this therapy. Our studies have identified an ordered series of tumor vessel developmental and maturation events not unlike that described during physiologic angiogenesis. Tumor vessel maturation affects the response to antiangiogenic agents inasmuch as more mature vessels, characterized by pericyte coverage of the vascular endothelial cells, are relatively resistant to these agents while less mature vessels are relatively susceptible. The loss of vessels with therapy results in or worsens tumor ischemia and ischemic cell death, which is the mechanism underlying tumor growth control. These findings have led us to develop autochthonous murine tumor models that more closely recapitulate the vasculature in human cancers, which have a more mature vascular profile and may be more resistant to antiangiogenic therapy than commonly used transplanted mouse tumors. We are identifying signal transduction pathways activated in vascular endothelial cells in tumors that correlate with angiogenesis, vessel maturation and regression during therapy, so that we can assign molecular signatures to these vascular events. Finally, we are seeking noninvasive ways to evaluate events and outcomes of antivascular therapy. These efforts are in collaboration with laboratories using ultrasound, magnetic resonance, radionuclide and optical techniques to image hemodynamic, cellular and physiological events in tumors and have clinical implications and applications.
Please contact Dr. Lee for current rotation projects.
Gee MS, Procopio WN, Makonnen S, Feldman MD, Yeilding NM and Lee WMF : Tumor vessel development and maturation impose limits on the effectiveness of antivascular therapy Am. J. Pathol. 162: 183-193, 2003.
Gee MS and Lee WMF : The role of tumor oxygenation in vascular and clinical response to angiogenesis inhibition Adv. Exp. Med. Biol. 510: 1-5, 2003.
Kamotani Y, Lee WMF, Arger PH, Cary TW, Sehgal CM : Multigated contrast enhanced power Doppler to measure blood flow in mice tumors Ultrasound in Med. Biol. 29: 977-984, 2003.
Lee, W.M.F. and Yeilding, N.M..: Molecular Cell Biology In: Oxford Textbook of Medcicine (4th ed.) Warrell et al (eds.). Oxford University Press, Oxford, Great Britain, 2003.
Lee JC, Kim DC, Gee MS, Saunders HM, Sehgal CM, Feldman MD, Ross SR and Lee WMF : Interleukin-12 inhibits angiogenesis and growth of transplanted but not in situ mouse mammary tumor virus (MMTV)-induced mammary carcinomas Canc. Res. 62: 747-755, 2002.
Gee MS, Saunders HM, Lee JC, Sanzo JF, Jenkins WT, Evans SM, Trinchieri G, Sehgal CM, Feldman MD and Lee WMF : Doppler ultrasound imaging detects changes in tumor perfusion during antivascular therapy associated with vascular anatomic alterations Canc. Res. 61: 2974-2982, 2001.
Hunter CA, Yu D, Gee MS, Ngo CV, Sevignani C, Goldschmidt M, Golovkina TV, Evans S, Lee WMF and Thomas-Tikhonenko A : Cutting Edge: Systemic inhibition of angiogenesis underlies resistance to tumors during acute toxoplasmosis J. Immunol. 166: 5878-5881, 2001.
Umamheswar D, Poptani H, Feldman M, Nadal-Desbarats L, Gee MS, Lee WMF, Reddy R, Leigh JS and Glickson JD : Quantitative Magnetic Resonance Imaging of RIF-1 tumors in vivo: Detection of early response to cyclophosphamide therapy Canc. Res. 61: 7747-7753, 2001.
Gee, M.S., Koch, C.J., Evans, S.M., Jenkins, W.T.,Pletcher, C.H., Moore, J.S., Koblish, H.K., Lee, J., Lord, E.M., Trinchieri, G. and Lee, W.M.F. : Hypoxia-mediated apoptosis from angiogenesis inhibition underlies tumor control by recombinant IL-12 Canc. Res. 59: 4882-4889, 1999.
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Last updated: 03/18/2013
The Trustees of the University of Pennsylvania