title: Increased basic fibroblast growth factor release and proliferation in             xenotransplanted squamous cell carcinoma after combined irradiation/anti-vascular             endothelial growth factor treatment.
abstract: Novel strategies of cancer therapy combine irradiation and anti-angiogenic             active compounds. However, little is known concerning the undesired cellular and             molecular effects caused by this novel treatment concept. We used a mouse squamous             cell carcinoma (SCC) xenotransplantation model to evaluate the potential undesired             effects which compromise the success of this therapeutic combination. SCCs were             subcutanously implanted in nude mice. Animals were treated with a fractionated             irradiation scheme (5x4 Gy) alone or in combination with daily injections of anti-vascular             endothelial growth factor (VEGF) antibodies. Controls remained untreated. Before             and after treatment, resonance imaging (MRI), ultrasound and near-infrared spectrometry             were used to evaluate tumor vessel integrity. Finally, tumors were explanted and             VEGF, basic fibroblast growth factor (bFGF), vessel density, proliferation and             apoptotic activity were analyzed by immunohistochemistry. Irradiation caused VEGF             release and we found evidence for VEGF-mediated vessel protection. In the tumors             derived from the combined treatment, blood volume was decreased, and apoptotic             indices were increased. Remarkably, bFGF levels and proliferative indices were             also increased. Combined irradiation/anti-VEGF treatment resulted in the desired             VEGF depletion and increased tumor cell apoptosis. Nonetheless, bFGF and proliferation             also increased, possibly suggesting a compensatory response. The application of             additional targeted drugs may help develop more effective SCC treatments.
authors.affiliation: Department of Otorhinolaryngology, Head and Neck Surgery, University                     Medical Center of the Johannes Gutenberg University Mainz, Mainz, Germany.
authors.forename: Kai
authors.initials: K
authors.lastname: Fruth
authors.forename: Stefan
authors.initials: S
authors.lastname: Weber
authors.forename: Yunus
authors.initials: Y
authors.lastname: Okcu
authors.forename: Ruediger
authors.initials: R
authors.lastname: Noppens
authors.forename: Klaus U
authors.initials: KU
authors.lastname: Klein
authors.forename: Eva
authors.initials: E
authors.lastname: Joest
authors.forename: Jana
authors.initials: J
authors.lastname: Hedrich
authors.forename: Sebastian
authors.initials: S
authors.lastname: Thilemann
authors.forename: Benjamin
authors.initials: B
authors.lastname: Pogorzelski
authors.forename: Dimitrios
authors.initials: D
authors.lastname: Koutsimpelas
authors.forename: Stefan
authors.initials: S
authors.lastname: Fischer
authors.forename: Kerstin
authors.initials: K
authors.lastname: Muennemann
authors.forename: Annette
authors.initials: A
authors.lastname: Affolter
authors.forename: Ulf R
authors.initials: UR
authors.lastname: Heinrich
authors.forename: Christoph
authors.initials: C
authors.lastname: Brochhausen
authors.forename: Irene
authors.initials: I
authors.lastname: Schmidtmann
authors.forename: Wolf J
authors.initials: WJ
authors.lastname: Mann
authors.forename: Heinz
authors.initials: H
authors.lastname: Schmidberger
authors.forename: Laura M
authors.initials: LM
authors.lastname: Schreiber
authors.forename: Juergen
authors.initials: J
authors.lastname: Brieger
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000378:metabolism* / Q000532:radiotherapy; D045744:Cell Line, Tumor; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism*; D006439:Hemodynamics; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2