Hypoxia is important in the biology and aggression of human glial brain tumors

Sydney M. Evans, Kevin D. Judy, Isolde Dunphy, W. Timothy Jenkins, Wei Ting Hwang, Peter T. Nelson, Robert A. Lustig, Kevin Jenkins, Deirdre P. Magarelli, Stephen M. Hahn, Ruth A. Collins, Sean Grady, Cameron J. Koch

Research output: Contribution to journalArticlepeer-review

269 Scopus citations

Abstract

We investigated whether increasing levels of tissue hypoxia, measured by the binding of EF5 [2-(2-nitro-1-H-imidazol-1-yl)-N-(2,2,3,3,3- pentafluoropropyl) acetamide] or by Eppendorf needle electrodes, were associated with tumor aggressiveness in patients with previously untreated glial brain tumors. We hypothesized that more extensive and severe hypoxia would be present in tumor cells from patients bearing more clinically aggressive tumors. Hypoxia was measured with the 2-nitroimidazole imaging agent EF5 in 18 patients with supratentorial glial neoplasms. In 12 patients, needle electrode measurements were made intraoperatively. Time to recurrence was used as an indicator of tumor aggression and was analyzed as a function of EF5 binding, electrode values and recursive partitioning analysis (RPA) classification. On the basis of EF5 binding, WHO grade 2 tumors were characterized by modest cellular hypoxia (pO2s ≈ 10%) and grade 3 tumors by modest-to-moderate hypoxia (pO2s ≈ 10%- 2.5%). Severe hypoxia (≈0.1% oxygen) was present in 5 of 12 grade 4 tumors. A correlation between more rapid tumor recurrence and hypoxia was demonstrated with EF5 binding, but this relationship was not predicted by Eppendorf measurements.

Original languageEnglish
Pages (from-to)8177-8184
Number of pages8
JournalClinical Cancer Research
Volume10
Issue number24
DOIs
StatePublished - Dec 15 2004

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

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