Abstract
Intravital microscopy coupled with chronic animal window models has provided stunning insight into tumor pathophysiology, including gene expression, angiogenesis, cell adhesion and migration, vascular, interstitial and lymphatic transport, metabolic microenvironment and drug delivery. However, the findings to date have been limited to the tumor surface (< 150 μm). Here, we show that the multiphoton laser-scanning microscope can provide high three-dimensional resolution of gene expression and function in deeper regions of tumors. These insights could be critical to the development of novel therapeutics that target not only the tumor surface, but also internal regions.
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Acknowledgements
We thank S. Ramanujan, A. Kadambi, Y. Izumi, and D. Dolmans for assistance with tail-vein injections; S. Ramanujan, K. Burton, T. Padera, B. Stoll, C. Mouta-Carreira, and L. Munn for their comments on the manuscript (and T.P. for artwork); J. Kahn for dorsal skin-fold chamber preparations; and Brian Seed for VEGF-EGFP transgenic mice. This work was supported by an NIH fellowship to E.B.B./R.B.C. (T32CA73479) and an Outstanding Investigator Grant (R35CA56591), a Bioengineering Research Partnership Grant (R24 CA85140) and a Program Project Grant (P01CA80124) to R.K.J.
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Brown, E., Campbell, R., Tsuzuki, Y. et al. In vivo measurement of gene expression, angiogenesis and physiological function in tumors using multiphoton laser scanning microscopy. Nat Med 7, 864–868 (2001). https://doi.org/10.1038/89997
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DOI: https://doi.org/10.1038/89997
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