Irradiation combined with SU5416: microvascular changes and growth delay in a human xenograft glioblastoma tumor line.
OBJECTIVE
The combination of irradiation and the antiangiogenic compound SU5416 was tested and compared with irradiation alone in a human glioblastoma tumor line xenografted in nude mice. The aim of this study was to monitor microenvironmental changes and growth delay.


METHODS
A human glioblastoma xenograft tumor line was implanted in nude mice. Irradiations consisted of 10 Gy or 20 Gy with and without SU5416. Several microenvironmental parameters (tumor cell hypoxia, tumor blood perfusion, vascular volume, and microvascular density) were analyzed after imunohistochemical staining. Tumor growth delay was monitored for up to 200 days after treatment.


RESULTS
SU5416, when combined with irradiation, has an additive effect over treatment with irradiation alone. Analysis of the tumor microenvironment showed a decreased vascular density during treatment with SU5416. In tumors regrowing after reaching only a partial remission, vascular characteristics normalized shortly after cessation of SU5416. However, in tumors regrowing after reaching a complete remission, permanent microenvironmental changes and an increase of tumor necrosis with a subsequent slower tumor regrowth was found.


CONCLUSIONS
Permanent vascular changes were seen after combined treatment resulting in complete remission. Antiangiogenic treatment with SU5416 when combined with irradiation has an additive effect over treatment with irradiation or antiangiogenic treatment alone.
Schuuring
Janneke
J
Department of Neurology, University Medical Center, Nijmegen, The Netherlands.
Bussink
Johan
J
Bernsen
Hans J J A
HJ
Peeters
Wenny
W
van Der Kogel
Albert J
AJ
D020533:Angiogenesis Inhibitors / Q000627:therapeutic use*; D000818:Animals; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004307:Dose-Response Relationship, Radiation; D004354:Drug Screening Assays, Antitumor; D005909:Glioblastoma / Q000098:blood supply / Q000188:drug therapy* / Q000473:pathology / Q000532:radiotherapy*; D006801:Humans; D007211:Indoles / Q000627:therapeutic use*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008833:Microcirculation / Q000187:drug effects / Q000528:radiation effects; D009336:Necrosis; D011758:Pyrroles / Q000627:therapeutic use*; D012008:Recurrence; D012074:Remission Induction; D014183:Transplantation, Heterologous
D020533:Angiogenesis Inhibitors; D007211:Indoles; D011758:Pyrroles; C116890:Semaxinib