Effect of carbogen breathing on the radiation response of a human glioblastoma xenograft: analysis of hypoxia and vascular parameters of regrowing tumors.
OBJECTIVE
The aim of these experiments was to study the relationship between the previously demonstrated efficacy of carbogen breathing on tumor oxygenation status and the response to radiation assessed by a growth delay assay. This study was also developed to investigate the microenvironmental changes caused by combined treatment compared to irradiation only in regrowing tumors.


METHODS
A human glioblastoma xenograft tumor line was implanted in nude mice. Irradiations consisted of 10 Gy or 20 Gy with and without carbogen breathing. Several microenvironmental parameters (tumor cell hypoxia, tumor blood perfusion, vascular volume, and microvascular density) were analyzed after immunohistochemical staining. Tumor growth delay was monitored for up to 120 days after treatment.


RESULTS
In general, there was no benefit of combined treatment. However, a small subgroup with good response to combined radiation and carbogen treatment was identified showing little hypoxia and mainly necrosis in the regrowing tumors. These microenvironmental characteristics were not seen in tumors of the other treatment groups.


CONCLUSIONS
The observations suggest that a subgroup of patients, who could potentially benefit from the combined carbogen and radiation treatment, might be identified. However, the heterogeneous response to treatment illustrates the need for selection of patients before start of treatment.
Schuuring
Janneke
J
Department of Neurology, Radboud University, Nijmegen Medical Center, Nijmegen, The Netherlands. J.Schuuring@hccnet.nl
Bussink
Johan
J
Bernsen
Hans J J A
HJ
Peeters
Wenny
W
van der Kogel
Albert J
AJ
D000818:Animals; D002245:Carbon Dioxide / Q000494:pharmacology*; D005909:Glioblastoma / Q000378:metabolism / Q000473:pathology / Q000532:radiotherapy / Q000628:therapy*; D006801:Humans; D000860:Hypoxia / Q000378:metabolism*; D007150:Immunohistochemistry; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D010100:Oxygen / Q000494:pharmacology*; D011838:Radiation-Sensitizing Agents / Q000494:pharmacology*; D014183:Transplantation, Heterologous
D011838:Radiation-Sensitizing Agents; D002245:Carbon Dioxide; C011700:carbogen; D010100:Oxygen