This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Lanzen, J. Articles by Dewhirst, M. W. Search for Related Content PubMed PubMed Citation Articles by Lanzen, J. Articles by Dewhirst, M. W.

Direct Demonstration of Instabilities in Oxygen Concentrations within the Extravascular Compartment of an Experimental Tumor

Departments of ¹ Radiation Oncology, ² Biomedical Engineering, and ³ Kenan Plastic Surgery Research Labs and Biomedical Engineering, Duke University Medical Center, Durham, North Carolina; ⁴ Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit Michigan; and ⁵ Department of Physiology, University of Arizona, Tucson, Arizona

Requests for reprints: Mark W. Dewhirst, Research Drive, Room 201 MSRB, Box 3455 DUMC, Durham, NC 27710. Phone: 919-684-4180; Fax: 919-684-8718; E-mail: dewhirst{at}radonc.duke.edu.

To test the hypothesis that temporal variations in microvessel red cell flux cause unstable oxygen levels in tumor interstitium, extravascular oxygenation of R3230Ac mammary tumors grown in skin-fold window chambers was measured using recessed tip polarographic microelectrodes. Red cell fluxes in microvessels surrounding pO₂ measurement locations were measured using fluorescently labeled red cells. Temporal pO₂ instability was observed in all experiments. Median pO₂ was inversely related to radial distance from microvessels. Transient fluctuations above and below 10 mm Hg were consistently seen, except in one experiment near the oxygen diffusion distance limit (140 µm) where pO₂ fluctuations were <2 mm Hg and median pO₂ was <5 mm Hg. Vascular stasis was not seen in these experiments. These results show that fluctuations in red cell flux, as opposed to vascular stasis, can cause temporal variations in pO₂ that extend from perivascular regions to the maximum oxygen diffusion distance. (Cancer Res 2006; 66(4): 2219-23)

This article has been cited by other articles:

				S. Matsumoto, H. Yasui, S. Batra, Y. Kinoshita, M. Bernardo, J. P. Munasinghe, H. Utsumi, R. Choudhuri, N. Devasahayam, S. Subramanian, et al. Simultaneous imaging of tumor oxygenation and microvascular permeability using Overhauser enhanced MRI PNAS, October 20, 2009; 106(42): 17898 - 17903. [Abstract] [Full Text] [PDF]

				L. I. Cardenas-Navia, D. Mace, R. A. Richardson, D. F. Wilson, S. Shan, and M. W. Dewhirst The Pervasive Presence of Fluctuating Oxygenation in Tumors Cancer Res., July 15, 2008; 68(14): 5812 - 5819. [Abstract] [Full Text] [PDF]

				W. R Wilson, K. O Hicks, F. B Pruijn, and A. V Patterson Targeting Tumor Hypoxia with Prodrugs: Challenges and Opportunities Am. Assoc. Cancer Res. Educ. Book, April 12, 2008; 2008(1): 293 - 310. [Abstract] [Full Text] [PDF]

				C. R. Cox and M. S. Gilmore Native Microbial Colonization of Drosophila melanogaster and Its Use as a Model of Enterococcus faecalis Pathogenesis Infect. Immun., April 1, 2007; 75(4): 1565 - 1576. [Abstract] [Full Text] [PDF]

				N. Chaudary and R. P. Hill Hypoxia and Metastasis Clin. Cancer Res., April 1, 2007; 13(7): 1947 - 1949. [Full Text] [PDF]

				E. K. Rofstad, K. Galappathi, B. Mathiesen, and E.-B. M. Ruud Fluctuating and Diffusion-Limited Hypoxia in Hypoxia-Induced Metastasis Clin. Cancer Res., April 1, 2007; 13(7): 1971 - 1978. [Abstract] [Full Text] [PDF]

				M. W. Dewhirst Intermittent Hypoxia Furthers the Rationale for Hypoxia-Inducible Factor-1 Targeting Cancer Res., February 1, 2007; 67(3): 854 - 855. [Abstract] [Full Text] [PDF]

				P. Martinive, F. Defresne, C. Bouzin, J. Saliez, F. Lair, V. Gregoire, C. Michiels, C. Dessy, and O. Feron Preconditioning of the Tumor Vasculature and Tumor Cells by Intermittent Hypoxia: Implications for Anticancer Therapies Cancer Res., December 15, 2006; 66(24): 11736 - 11744. [Abstract] [Full Text] [PDF]

				Y. F. Zhou, M. Bosch-Marce, H. Okuyama, B. Krishnamachary, H. Kimura, L. Zhang, D. L. Huso, and G. L. Semenza Spontaneous Transformation of Cultured Mouse Bone Marrow-Derived Stromal Cells. Cancer Res., November 15, 2006; 66(22): 10849 - 10854. [Abstract] [Full Text] [PDF]

				V. Raman, D. Artemov, A. P. Pathak, P. T. Winnard Jr., S. McNutt, A. Yudina, A. Bogdanov Jr., and Z. M. Bhujwalla Characterizing Vascular Parameters in Hypoxic Regions: A Combined Magnetic Resonance and Optical Imaging Study of a Human Prostate Cancer Model. Cancer Res., October 15, 2006; 66(20): 9929 - 9936. [Abstract] [Full Text] [PDF]

				C. Koumenis and B. G. Wouters "Translating" Tumor Hypoxia: Unfolded Protein Response (UPR)-Dependent and UPR-Independent Pathways Mol. Cancer Res., July 1, 2006; 4(7): 423 - 436. [Abstract] [Full Text] [PDF]