This Article Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Services 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 Vaupel, P. Articles by Höckel, M. Search for Related Content PubMed PubMed Citation Articles by Vaupel, P. Articles by Höckel, M.

Oxygenation of Human Tumors: Evaluation of Tissue Oxygen Distribution in Breast Cancers by Computerized O₂ Tension Measurements¹

Institute of Physiology and Pathophysiology [P. V., K. S.] and Department of Gynecology and Obstetrics [C. K., M. H.], University of Mainz, D-6500 Mainz, Germany

Direct oxygen partial pressure (pO₂) readings in breast cancers, in fibrocystic disease, and in the normal breast have been obtained using a novel technique which allows for the systematic evaluation of the oxygenation status as a function of pathological staging and histological grading. Measurements were performed in awake pre- and postmenopausal patients with well-defined arterial blood gas status.

The measuring procedure encompasses a computerized electrode movement in the tissue which avoids significant compression artifacts and allows routine measurement in human tumors before, during, and after treatment. Using this reliable technique, pO₂ measurements in the normal breast and in fibrocystic disease resulted in oxygenation patterns which were characteristic for normal, adequately supplied tissues. The median pO₂ values were 65 and 67 mm Hg, respectively, with no pO₂ readings below 12.5 mm Hg in the normal breast, and 5 mm Hg in fibrocystic disease, respectively. In contrast, in breast cancers the median pO₂ value was 30 mm Hg (pooled data for pathological stages T₁-T₄). To date, 6 of 15 breast cancers exhibited pO₂ values between zero and 2.5 mm Hg, i.e., tissue areas with less than half-maximum radiosensitivity. The oxygenation pattern in breast cancers and the occurrence of hypoxia and/or anoxia did not correlate with either the pathological stages and histological grades or with a series of clinically relevant parameters. No significant differences were found between pre- and postmenopausal tumors and between lobular and ductal carcinomas. Tumor-to-tumor variability in the oxygenation pattern was more pronounced than intratumor heterogeneity. pO₂ variations within a tumor cannot be predicted, e.g., as a function of the measuring site (tumor center versus periphery).

¹ Dedicated to Dr. med. h.c. Erwin Braun, an untiring sponsor of biomedical research, on the occasion of his 70th birthday.

² To whom requests for reprints should be addressed, at Institute of Physiology and Pathophysiology, University of Mainz, D-6500 Mainz, Germany.

Received 12/19/90. Accepted 4/ 3/91.

This article has been cited by other articles:

				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]

				K. A. Krohn, J. M. Link, and R. P. Mason Molecular Imaging of Hypoxia J. Nucl. Med., June 1, 2008; 49(Suppl_2): 129S - 148S. [Abstract] [Full Text] [PDF]

				Z. Xiao, S. Halls, D. Dickey, J. Tulip, and R. B. Moore Fractionated versus Standard Continuous Light Delivery in Interstitial Photodynamic Therapy of Dunning Prostate Carcinomas Clin. Cancer Res., December 15, 2007; 13(24): 7496 - 7505. [Abstract] [Full Text] [PDF]

				X.-F. Li, S. Carlin, M. Urano, J. Russell, C. C. Ling, and J. A. O'Donoghue Visualization of Hypoxia in Microscopic Tumors by Immunofluorescent Microscopy Cancer Res., August 15, 2007; 67(16): 7646 - 7653. [Abstract] [Full Text] [PDF]

				H. J. Kang, H. J. Kim, J.-K. Rih, T. L. Mattson, K. W. Kim, C.-H. Cho, J. S. Isaacs, and I. Bae BRCA1 Plays a Role in the Hypoxic Response by Regulating HIF-1{alpha} Stability and by Modulating Vascular Endothelial Growth Factor Expression J. Biol. Chem., May 12, 2006; 281(19): 13047 - 13056. [Abstract] [Full Text] [PDF]

				T. Nakano, Y. Suzuki, T. Ohno, S. Kato, M. Suzuki, S. Morita, S. Sato, K. Oka, and H. Tsujii Carbon beam therapy overcomes the radiation resistance of uterine cervical cancer originating from hypoxia. Clin. Cancer Res., April 1, 2006; 12(7): 2185 - 2190. [Abstract] [Full Text] [PDF]

				R. Cairns, I. Papandreou, and N. Denko Overcoming Physiologic Barriers to Cancer Treatment by Molecularly Targeting the Tumor Microenvironment Mol. Cancer Res., February 1, 2006; 4(2): 61 - 70. [Abstract] [Full Text] [PDF]

				J. H. Suh, B. Stea, A. Nabid, J. J. Kresl, A. Fortin, J.-P. Mercier, N. Senzer, E. L. Chang, A. P. Boyd, P. J. Cagnoni, et al. Phase III Study of Efaproxiral As an Adjunct to Whole-Brain Radiation Therapy for Brain Metastases J. Clin. Oncol., January 1, 2006; 24(1): 106 - 114. [Abstract] [Full Text] [PDF]

				R. Hase, M. Miyamoto, H. Uehara, M. Kadoya, Y. Ebihara, Y. Murakami, R. Takahashi, S. Mega, L. Li, T. Shichinohe, et al. Pigment Epithelium-Derived Factor Gene Therapy Inhibits Human Pancreatic Cancer in Mice Clin. Cancer Res., December 15, 2005; 11(24): 8737 - 8744. [Abstract] [Full Text] [PDF]

				H. Choy, A. Nabid, B. Stea, C. Scott, W. Roa, L. Kleinberg, J. Ayoub, C. Smith, L. Souhami, S. Hamburg, et al. Phase II Multicenter Study of Induction Chemotherapy Followed by Concurrent Efaproxiral (RSR13) and Thoracic Radiotherapy for Patients With Locally Advanced Non-Small-Cell Lung Cancer J. Clin. Oncol., September 1, 2005; 23(25): 5918 - 5928. [Abstract] [Full Text] [PDF]

				S. J. Kwon and Y. J. Lee Effect of Low Glutamine/Glucose on Hypoxia-Induced Elevation of Hypoxia-Inducible Factor-1{alpha} in Human Pancreatic Cancer MiaPaCa-2 and Human Prostatic Cancer DU-145 Cells Clin. Cancer Res., July 1, 2005; 11(13): 4694 - 4700. [Abstract] [Full Text] [PDF]

				R. C. Leonard, M. Untch, and F. Von Koch Management of anaemia in patients with breast cancer: role of epoetin Ann. Onc., May 1, 2005; 16(5): 817 - 824. [Abstract] [Full Text] [PDF]

				B. Yang and C. P. Reynolds Tirapazamine Cytotoxicity for Neuroblastoma Is p53 Dependent Clin. Cancer Res., April 1, 2005; 11(7): 2774 - 2780. [Abstract] [Full Text] [PDF]

				A. G. Taghian, R. Abi-Raad, S. I. Assaad, A. Casty, M. Ancukiewicz, E. Yeh, P. Molokhia, K. Attia, T. Sullivan, I. Kuter, et al. Paclitaxel Decreases the Interstitial Fluid Pressure and Improves Oxygenation in Breast Cancers in Patients Treated With Neoadjuvant Chemotherapy: Clinical Implications J. Clin. Oncol., March 20, 2005; 23(9): 1951 - 1961. [Abstract] [Full Text] [PDF]

				M M Vleugel, A E Greijer, A Shvarts, P van der Groep, M van Berkel, Y Aarbodem, H van Tinteren, A L Harris, P J van Diest, and E van der Wall Differential prognostic impact of hypoxia induced and diffuse HIF-1{alpha} expression in invasive breast cancer J. Clin. Pathol., February 1, 2005; 58(2): 172 - 177. [Abstract] [Full Text] [PDF]

				B. Chen, B. W. Pogue, X. Zhou, J. A. O'Hara, N. Solban, E. Demidenko, P. J. Hoopes, and T. Hasan Effect of Tumor Host Microenvironment on Photodynamic Therapy in a Rat Prostate Tumor Model Clin. Cancer Res., January 15, 2005; 11(2): 720 - 727. [Abstract] [Full Text] [PDF]

				P. Vaupel and L. Harrison Tumor Hypoxia: Causative Factors, Compensatory Mechanisms, and Cellular Response Oncologist, November 1, 2004; 9(suppl_5): 4 - 9. [Abstract] [Full Text] [PDF]

				R. S. Bindra, P. J. Schaffer, A. Meng, J. Woo, K. Maseide, M. E. Roth, P. Lizardi, D. W. Hedley, R. G. Bristow, and P. M. Glazer Down-Regulation of Rad51 and Decreased Homologous Recombination in Hypoxic Cancer Cells Mol. Cell. Biol., October 1, 2004; 24(19): 8504 - 8518. [Abstract] [Full Text] [PDF]

				B. Clavo, J. L. Perez, L. Lopez, G. Suarez, M. Lloret, V. Rodriguez, D. Macias, M. Santana, M. A. Hernandez, R. Martin-Oliva, et al. Ozone Therapy for Tumor Oxygenation: a Pilot Study Evid. Based Complement. Altern. Med., June 1, 2004; 1(1): 93 - 98. [Abstract] [Full Text] [PDF]

				M. J. Grimshaw, T. Hagemann, A. Ayhan, C. E. Gillett, C. Binder, and F. R. Balkwill A Role for Endothelin-2 and Its Receptors in Breast Tumor Cell Invasion Cancer Res., April 1, 2004; 64(7): 2461 - 2468. [Abstract] [Full Text] [PDF]

				G. Hopfl, O. Ogunshola, and M. Gassmann HIFs and tumors--causes and consequences Am J Physiol Regulatory Integrative Comp Physiol, April 1, 2004; 286(4): R608 - R623. [Abstract] [Full Text] [PDF]

				J. G. Rajendran, D. A. Mankoff, F. O'Sullivan, L. M. Peterson, D. L. Schwartz, E. U. Conrad, A. M. Spence, M. Muzi, D. G. Farwell, and K. A. Krohn Hypoxia and Glucose Metabolism in Malignant Tumors: Evaluation by [18F]Fluoromisonidazole and [18F]Fluorodeoxyglucose Positron Emission Tomography Imaging Clin. Cancer Res., April 1, 2004; 10(7): 2245 - 2252. [Abstract] [Full Text] [PDF]

				R. A. Cairns and R. P. Hill Acute Hypoxia Enhances Spontaneous Lymph Node Metastasis in an Orthotopic Murine Model of Human Cervical Carcinoma Cancer Res., March 15, 2004; 64(6): 2054 - 2061. [Abstract] [Full Text] [PDF]

				E. Kikuchi, S. Menendez, M. Ohori, C. Cordon-Cardo, N. Kasahara, and B. H. Bochner Inhibition of Orthotopic Human Bladder Tumor Growth by Lentiviral Gene Transfer of Endostatin Clin. Cancer Res., March 1, 2004; 10(5): 1835 - 1842. [Abstract] [Full Text] [PDF]

				R. L. Cowen, K. J. Williams, E. C. Chinje, M. Jaffar, F. C. D. Sheppard, B. A. Telfer, N. S. Wind, and I. J. Stratford Hypoxia Targeted Gene Therapy to Increase the Efficacy of Tirapazamine as an Adjuvant to Radiotherapy: Reversing Tumor Radioresistance and Effecting Cure Cancer Res., February 15, 2004; 64(4): 1396 - 1402. [Abstract] [Full Text] [PDF]

				F. Denis, P. Garaud, E. Bardet, M. Alfonsi, C. Sire, T. Germain, P. Bergerot, B. Rhein, J. Tortochaux, and G. Calais Final Results of the 94-01 French Head and Neck Oncology and Radiotherapy Group Randomized Trial Comparing Radiotherapy Alone With Concomitant Radiochemotherapy in Advanced-Stage Oropharynx Carcinoma J. Clin. Oncol., January 1, 2004; 22(1): 69 - 76. [Abstract] [Full Text] [PDF]

				L. B. Gardner, F. Li, X. Yang, and C. V. Dang Anoxic Fibroblasts Activate a Replication Checkpoint That Is Bypassed By E1a Mol. Cell. Biol., December 15, 2003; 23(24): 9032 - 9045. [Abstract] [Full Text] [PDF]

				B M Seddon and P Workman The role of functional and molecular imaging in cancer drug discovery and development Br. J. Radiol., December 1, 2003; 76(suppl_2): S128 - S138. [Abstract] [Full Text] [PDF]

				P. Vaupel, A. Mayer, S. Briest, and M. Hockel Oxygenation Gain Factor: A Novel Parameter Characterizing the Association between Hemoglobin Level and the Oxygenation Status of Breast Cancers Cancer Res., November 15, 2003; 63(22): 7634 - 7637. [Abstract] [Full Text] [PDF]

				M. Demasi, L. G. Cleland, R. J. Cook-Johnson, G. E. Caughey, and M. J. James Effects of Hypoxia on Monocyte Inflammatory Mediator Production: DISSOCIATION BETWEEN CHANGES IN CYCLOOXYGENASE-2 EXPRESSION AND EICOSANOID SYNTHESIS J. Biol. Chem., October 3, 2003; 278(40): 38607 - 38616. [Abstract] [Full Text] [PDF]

				F. Denis, P. Bougnoux, L. Paon, O. le Floch, and F. Tranquart Radiosensitivity of Rat Mammary Tumors Correlates With Early Vessel Changes Assessed by Power Doppler Sonography J. Ultrasound Med., September 1, 2003; 22(9): 921 - 929. [Abstract] [Full Text] [PDF]

				E. Shaw, C. Scott, J. Suh, S. Kadish, B. Stea, J. Hackman, A. Pearlman, K. Murray, L. Gaspar, M. Mehta, et al. RSR13 Plus Cranial Radiation Therapy in Patients With Brain Metastases: Comparison With the Radiation Therapy Oncology Group Recursive Partitioning Analysis Brain Metastases Database J. Clin. Oncol., June 15, 2003; 21(12): 2364 - 2371. [Abstract] [Full Text] [PDF]

				G. Acs, P. J. Zhang, C. M. McGrath, P. Acs, J. McBroom, A. Mohyeldin, S. Liu, H. Lu, and A. Verma Hypoxia-Inducible Erythropoietin Signaling in Squamous Dysplasia and Squamous Cell Carcinoma of the Uterine Cervix and Its Potential Role in Cervical Carcinogenesis and Tumor Progression Am. J. Pathol., June 1, 2003; 162(6): 1789 - 1806. [Abstract] [Full Text] [PDF]

				B. Yang, N. Keshelava, C. P. Anderson, and C. P. Reynolds Antagonism of Buthionine Sulfoximine Cytotoxicity for Human Neuroblastoma Cell Lines by Hypoxia Is Reversed by the Bioreductive Agent Tirapazamine Cancer Res., April 1, 2003; 63(7): 1520 - 1526. [Abstract] [Full Text] [PDF]

				C. Koumenis, C. Naczki, M. Koritzinsky, S. Rastani, A. Diehl, N. Sonenberg, A. Koromilas, and B. G. Wouters Regulation of Protein Synthesis by Hypoxia via Activation of the Endoplasmic Reticulum Kinase PERK and Phosphorylation of the Translation Initiation Factor eIF2{alpha} Mol. Cell. Biol., November 1, 2002; 22(21): 7405 - 7416. [Abstract] [Full Text] [PDF]

				L. Kleinberg, S.A. Grossman, K. Carson, G. Lesser, A. O'Neill, J. Pearlman, P. Phillips, T. Herman, and M. Gerber Survival of Patients With Newly Diagnosed Glioblastoma Multiforme Treated With RSR13 and Radiotherapy: Results of a Phase II New Approaches to Brain Tumor Therapy CNS Consortium Safety and Efficacy Study J. Clin. Oncol., July 15, 2002; 20(14): 3149 - 3155. [Abstract] [Full Text] [PDF]

				B. M. Seddon, R. J. Maxwell, D. J. Honess, R. Grimshaw, F. Raynaud, G. M. Tozer, and P. Workman Validation of the Fluorinated 2-Nitroimidazole SR-4554 as a Noninvasive Hypoxia Marker Detected by Magnetic Resonance Spectroscopy Clin. Cancer Res., July 1, 2002; 8(7): 2323 - 2335. [Abstract] [Full Text] [PDF]

				M. C. Krishna, S. English, K. Yamada, J. Yoo, R. Murugesan, N. Devasahayam, J. A. Cook, K. Golman, J. H. Ardenkjaer-Larsen, S. Subramanian, et al. Overhauser enhanced magnetic resonance imaging for tumor oximetry: Coregistration of tumor anatomy and tissue oxygen concentration PNAS, February 19, 2002; 99(4): 2216 - 2221. [Abstract] [Full Text] [PDF]

				H. Nishi, K. H. Nishi, and A. C. Johnson Early Growth Response-1 Gene Mediates Up-Regulation of Epidermal Growth Factor Receptor Expression during Hypoxia Cancer Res., February 1, 2002; 62(3): 827 - 834. [Abstract] [Full Text] [PDF]

				N. E. Matthews, M. A. Adams, L. R. Maxwell, T. E. Gofton, and C. H. Graham Nitric Oxide-Mediated Regulation of Chemosensitivity in Cancer Cells J Natl Cancer Inst, December 19, 2001; 93(24): 1879 - 1885. [Abstract] [Full Text] [PDF]

				R. A. Cairns, T. Kalliomaki, and R. P. Hill Acute (Cyclic) Hypoxia Enhances Spontaneous Metastasis of KHT Murine Tumors Cancer Res., December 1, 2001; 61(24): 8903 - 8908. [Abstract] [Full Text] [PDF]

				M. Crowther, N. J. Brown, E. T. Bishop, and C. E. Lewis Microenvironmental influence on macrophage regulation of angiogenesis in wounds and malignant tumors J. Leukoc. Biol., October 1, 2001; 70(4): 478 - 490. [Abstract] [Full Text] [PDF]

				R. Airley, J. Loncaster, S. Davidson, M. Bromley, S. Roberts, A. Patterson, R. Hunter, I. Stratford, and C. West Glucose Transporter Glut-1 Expression Correlates with Tumor Hypoxia and Predicts Metastasis-free Survival in Advanced Carcinoma of the Cervix Clin. Cancer Res., April 1, 2001; 7(4): 928 - 934. [Abstract] [Full Text]

				M. Hockel and P. Vaupel Tumor Hypoxia: Definitions and Current Clinical, Biologic, and Molecular Aspects J Natl Cancer Inst, February 21, 2001; 93(4): 266 - 276. [Abstract] [Full Text] [PDF]

				S. L. Green, R. A. Freiberg, and A. J. Giaccia p21Cip1 and p27Kip1 Regulate Cell Cycle Reentry after Hypoxic Stress but Are Not Necessary for Hypoxia-Induced Arrest Mol. Cell. Biol., February 15, 2001; 21(4): 1196 - 1206. [Abstract] [Full Text]

				R. V. Iyer, P. T. Haynes, R. F. Schneider, B. Movsas, and J. D. Chapman Marking Hypoxia in Rat Prostate Carcinomas with {beta}-D-[125I]Azomycin Galactopyranoside and [99mTc]HL-91: Correlation with Microelectrode Measurements J. Nucl. Med., February 1, 2001; 42(2): 337 - 344. [Abstract] [Full Text]

				B. J. Maurer, L. Melton, C. Billups, M. C. Cabot, and C. P. Reynolds Synergistic Cytotoxicity in Solid Tumor Cell Lines Between N-(4-Hydroxyphenyl)retinamide and Modulators of Ceramide Metabolism J Natl Cancer Inst, December 6, 2000; 92(23): 1897 - 1909. [Abstract] [Full Text] [PDF]

				C. Blancher, J. W. Moore, K. L. Talks, S. Houlbrook, and A. L. Harris Relationship of Hypoxia-inducible Factor (HIF)-1{{alpha}} and HIF-2{{alpha}} Expression to Vascular Endothelial Growth Factor Induction and Hypoxia Survival in Human Breast Cancer Cell Lines Cancer Res., December 1, 2000; 60(24): 7106 - 7113. [Abstract] [Full Text]

				M. Lopez de Heredia, J. M. Izquierdo, and J. M. Cuezva A Conserved Mechanism for Controlling the Translation of beta -F1-ATPase mRNA between the Fetal Liver and Cancer Cells J. Biol. Chem., March 15, 2000; 275(10): 7430 - 7437. [Abstract] [Full Text] [PDF]

				B. W. Henderson, T. M. Busch, L. A. Vaughan, N. P. Frawley, D. Babich, T. A. Sosa, J. D. Zollo, A. S. Dee, M. T. Cooper, D. A. Bellnier, et al. Photofrin Photodynamic Therapy Can Significantly Deplete or Preserve Oxygenation in Human Basal Cell Carcinomas during Treatment, Depending on Fluence Rate Cancer Res., February 1, 2000; 60(3): 525 - 529. [Abstract] [Full Text]

				J. M. Star-Lack, E. Adalsteinsson, M. F. Adam, D. J. Terris, H. A. Pinto, J. M. Brown, and D. M. Spielman In Vivo 1H MR Spectroscopy of Human Head and Neck Lymph Node Metastasis and Comparison with Oxygen Tension Measurements AJNR Am. J. Neuroradiol., January 1, 2000; 21(1): 183 - 193. [Abstract] [Full Text] [PDF]

				J. M. Brown The Hypoxic Cell: A Target for Selective Cancer Therapy--Eighteenth Bruce F. Cain Memorial Award Lecture Cancer Res., December 1, 1999; 59(23): 5863 - 5870. [Abstract] [Full Text] [PDF]

				L. Kleinberg, S. A. Grossman, S. Piantadosi, J. Pearlman, H. Engelhard, G. Lesser, J. Ruffer, and M. Gerber Phase I Trial to Determine the Safety, Pharmacodynamics, and Pharmacokinetics of RSR13, a Novel Radioenhancer, in Newly Diagnosed Glioblastoma Multiforme J. Clin. Oncol., August 1, 1999; 17(8): 2593 - 2593. [Abstract] [Full Text] [PDF]

				R. D. Braun, J. L. Lanzen, and M. W. Dewhirst Fourier analysis of fluctuations of oxygen tension and blood flow in R3230Ac tumors and muscle in rats Am J Physiol Heart Circ Physiol, August 1, 1999; 277(2): H551 - H568. [Abstract] [Full Text] [PDF]

				B. J. Maurer, L. S. Metelitsa, R. C. Seeger, M. C. Cabot, and C. P. Reynolds Increase of Ceramide and Induction of Mixed Apoptosis/Necrosis by N-(4-Hydroxyphenyl)- retinamide in Neuroblastoma Cell Lines J Natl Cancer Inst, July 7, 1999; 91(13): 1138 - 1146. [Abstract] [Full Text] [PDF]

				C. Schmaltz, P. H. Hardenbergh, A. Wells, and D. E. Fisher Regulation of Proliferation-Survival Decisions during Tumor Cell Hypoxia Mol. Cell. Biol., May 1, 1998; 18(5): 2845 - 2854. [Abstract] [Full Text]