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Strahlentherapie und Onkologie
Published in: Strahlentherapie und Onkologie 7/2012

01-07-2012 | Original article

Intra- and intertumor heterogeneities in total, chronic, and acute hypoxia in xenografted squamous cell carcinomas

Detection and quantification using (immuno-)fluorescence techniques

Authors: C.-A. Maftei, C. Bayer, Ph.D., K. Shi, P. Vaupel

Published in: Strahlentherapie und Onkologie | Issue 7/2012

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Abstract

Background

Heterogeneously distributed hypoxia is a major characteristic of solid tumors. (Immuno-)fluorescence detection of hypoxia in experimental tumors is frequently assessed in a single central section; however, this may not necessarily be representative of the whole tumor. In order to determine whether analysis of one central section is exemplary of the whole tumor and whether different volumes have an impact on tumor oxygenation, we assessed the fractions of total (TH), chronic (CH), and acute hypoxia (AH) throughout different layers of tumors of varying volumes.

Materials and methods

Xenografted FaDu human squamous cell carcinomas of different volumes were investigated for intra- and intertumor heterogeneities. Tissue blocks located at the apical, central, and basal layer were sliced from individual tumors. Four serial cryosections were analyzed from each tissue block. Vital tumor tissue was explored for the distribution of Hoechst 33342 (perfusion), pimonidazole (hypoxia), and CD31 (endothelium) to assess TH, CH, and AH.

Results

Fractions of TH, CH, and AH were consistently similar in the serial sections of individual tissue blocks. However, significant differences were found between the apical, central, and basal blocks that were even opposite depending on the tumor volume. Pooled data from all three tissue blocks revealed significantly higher fractions of hypoxia in the large tumors than in the small tumors.

Conclusion

FaDu tumors exhibit a heterogeneous and volume-dependent oxygenation status. Assessing the average fractions of TH, CH, and AH from central blocks corresponds best to the average of the entire tumor. However, information on intratumor heterogeneities is lost, especially when considering tumors of substantially different volumes.
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Metadata
Title
Intra- and intertumor heterogeneities in total, chronic, and acute hypoxia in xenografted squamous cell carcinomas
Detection and quantification using (immuno-)fluorescence techniques
Authors
C.-A. Maftei
C. Bayer, Ph.D.
K. Shi
P. Vaupel
Publication date
01-07-2012
Publisher
Springer-Verlag
Published in
Strahlentherapie und Onkologie / Issue 7/2012
Print ISSN: 0179-7158
Electronic ISSN: 1439-099X
DOI
https://doi.org/10.1007/s00066-012-0105-4

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