Triple angiokinase inhibition, tumour hypoxia and radiation response of FaDu human squamous cell carcinomas
| Autor: | Frank Hilberg, Katja Le, Xuanjing Zhou, Annegret Dörfler, Peter Geyer, Michael Baumann, Wolfgang Eicheler, Ala Yaromina, Daniel Zips |
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| Rok vydání: | 2008 |
| Předmět: |
Male
Pathology medicine.medical_specialty Indoles Angiogenesis Cell Survival Cell Mice Nude Radiation Tolerance Receptor tyrosine kinase Mice Random Allocation Radiation sensitivity Reference Values medicine Animals Radiology Nuclear Medicine and imaging Laryngeal Neoplasms Probability biology Dose-Response Relationship Drug Neovascularization Pathologic Chemistry Histology Dose-Response Relationship Radiation Hematology Hypoxia (medical) Immunohistochemistry Cell Hypoxia Disease Models Animal medicine.anatomical_structure Oncology biology.protein Carcinoma Squamous Cell Female Dose Fractionation Radiation medicine.symptom Stem cell Perfusion Neoplasm Transplantation |
| Zdroj: | Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology. 92(3) |
| ISSN: | 1879-0887 |
| Popis: | Background and purpose: To test the effect of BIBF 1120, a novel small molecule inhibitor of multiple angiogenic receptor tyrosine kinases, on the hypoxia and radiation response of tumours. Materials and methods: Poorly differentiated human squamous cell carcinoma FaDu growing in nude mice was treated with BIBF 1120 and investigated by functional histology. To test the effect of BIBF 1120 on the radiobiological hypoxic fraction (rHF), the number and intrinsic radiation sensitivity of tumour stem cells and the outcome after fractionated irradiation, a series of local tumour control assays were performed. Results: BIBF 1120 significantly reduced the vessel area, vessel area with a perfusion signal and tumour growth rate but did not affect tumour hypoxia or the number and intrinsic radiation sensitivity of tumour stem cells. Concurrent BIBF 1120 had no effect on local tumour control after fractionated irradiation. Conclusion: Triple angiokinase inhibition resulted in a clear-cut decrease of angiogenesis, vessel area with a perfusion signal and tumour growth but did not change tumour hypoxia or radiation response of tumour stem cells. Further experiments into mechanisms of interaction between anti-angiogenic strategies and irradiation appear to be necessary to better define and exploit the potential of this strategy to improve local tumour control after fractionated radiotherapy. |
| Databáze: | OpenAIRE |
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