Changes in tumor hypoxia induced by mild temperature hyperthermia as assessed by dual-tracer immunohistochemistry Journal Article


Authors: Sun, X.; Li, X. F. ; Russell, J.; Xing, L.; Urano, M.; Li, G. C.; Humm, J. L.; Ling, C. C.
Article Title: Changes in tumor hypoxia induced by mild temperature hyperthermia as assessed by dual-tracer immunohistochemistry
Abstract: Purpose: To study the changes in hypoxia resulting from mild temperature hyperthermia (MTH) in a subcutaneous xenograft model using dual-tracer immunohistochemical techniques. Materials and methods: HT29 tumors were locally heated at 41 °C. Changes in tumor hypoxia were investigated by pimonidazole and EF5. Pimonidazole was given 1 h preheating, EF5 at various times during or after treatment, 1 h later the animals were sacrificed. Blood vessels were identified by CD31 staining, and perfusion by Hoechst 33342 injected 1 min pre-sacrifice. Results: The overall hypoxic fraction was significantly decreased by MTH during and immediately after heating. However, MTH induced both increases and decreases in tumor hypoxia in different parts of the tumor. Specifically, MTH decreased hypoxia in the regions with relatively well-perfused blood vessels, but increased hypoxia in regions that were poorly perfused. At 24-h post heating, newly formed hypoxic regions surrounded previously-hypoxic foci, which in turn surrounded pimonidazole-stained debris. Quantitative analysis did not evince changes in tumor oxygenation due to MTH at 24 h post-treatment. Conclusion: In this xenograft model, the effect of MTH on tumor oxygenation was variable, both spatially and kinetically. Overall tumor oxygenation was improved during and after heating, but the effect was short-lived. © 2008 Elsevier Ireland Ltd. All rights reserved.
Keywords: immunohistochemistry; controlled study; human cell; nonhuman; colorectal cancer; adenocarcinoma; animal cell; mouse; animals; mice; animal tissue; oxygen; animal experiment; animal model; cancer cell culture; hypoxia; colorectal neoplasms; drug distribution; quantitative analysis; staining; transplantation, heterologous; blood vessel; pimonidazole; cell hypoxia; hyperthermia; hyperthermia, induced; blood flow; analysis of variance; radiation-sensitizing agents; drug binding; nitroimidazoles; tissue oxygenation; cd31 antigen; ef5; 2 (2 nitro 1h imidazol 1 yl) n (2,2,3,3,3 pentafluoropropyl)acetamide; etanidazole; hydrocarbons, fluorinated; tissue perfusion; heating; mild temperature hyperthermia
Journal Title: Radiotherapy and Oncology
Volume: 88
Issue: 2
ISSN: 0167-8140
Publisher: Elsevier Inc.  
Date Published: 2008-08-01
Start Page: 269
End Page: 276
Language: English
DOI: 10.1016/j.radonc.2008.05.015
PUBMED: 18538874
PROVIDER: scopus
PMCID: PMC2612785
DOI/URL:
Notes: --- - "Cited By (since 1996): 8" - "Export Date: 17 November 2011" - "CODEN: RAOND" - "Source: Scopus"
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MSK Authors
  1. Gloria C Li
    132 Li
  2. Xiao-Feng Li
    11 Li
  3. Ligang Xing
    15 Xing
  4. Xiaorong Sun
    19 Sun
  5. John Laurence Humm
    433 Humm
  6. James Russell
    41 Russell
  7. C Clifton Ling
    331 Ling
  8. Moneyasu Urano
    23 Urano