Lung Stereotactic Arc Therapy in Mice Development of Radiation Pneumopathy and Influence of HIF-1α Endothelial Deletion
Autor: | Alexandra Suissa, M. Benadjaoud, Vincent Paget, Morgane Dos Santos, Laurence Mille-Hamard, Iman Momken, Fabien Milliat, Georges Tarlet, Olivier Guipaud, Jérémy Lavigne, Frédéric Soysouvanh, Agnès François, Nicolas Verger, Valérie Buard |
---|---|
Přispěvatelé: | Institut de Radioprotection et de Sûreté Nucléaire (IRSN), Unité de biologie intégrative des adaptations à l'exercice (UBIAE), Université d'Évry-Val-d'Essonne (UEVE)-Institut National de la Santé et de la Recherche Médicale (INSERM) |
Jazyk: | angličtina |
Rok vydání: | 2019 |
Předmět: |
treatment planning
Lung Neoplasms medicine.medical_treatment cell infiltration genotype epithelial mesenchymal transition adverse event radiation exposure stereotactic body radiation therapy Running Methods and materials Mice 0302 clinical medicine Intensity-Modulated genetics Lung comparative study Mammals Radiation quantitative analysis 3. Good health chlordane Oncology priority journal real time polymerase chain reaction 030220 oncology & carcinogenesis Hypoxia-Inducible Factor 1 radiation dose Endothelium endothelium radiation response diagnostic imaging Cre recombinase Pulmonary Edema alpha Subunit Radiation Dosage Radiosurgery Article animal tissue 03 medical and health sciences Genetic vascular endothelial cadherin procedures Radiation-induced mouse lung edema Tissue Integrases Animal Biological organs tissue injury intensity modulated radiation therapy Radiation therapy Hybridization Genetic integrase Gene Deletion Selective Breeding Organs at Risk Cancer Research lung disease Pulmonary Fibrosis [SDV]Life Sciences [q-bio] radiation induced tissue damage 030218 nuclear medicine & medical imaging lung tumor Gene expression levels major gene neutrophil Research platforms cone beam computed tomography Cone-Beam Computed Tomography Phenotype lung alveolus medicine.anatomical_structure Ipsilateral lungs Local tumor control Thoracic wall radiation injury Epithelial-Mesenchymal Transition medicine follow up Animals Radiology Nuclear Medicine and imaging controlled study Epithelial–mesenchymal transition Irradiation hypoxia inducible factor 1alpha Hypoxia inducible factor 1-alpha cre recombinase Hybridization radiation pneumonia nonhuman Radiotherapy business.industry disease model lung fibrosis Hypoxia-Inducible Factor 1 alpha Subunit Pulmonary Alveoli Radiation Pneumonitis Disease Models Animal physiology Disease Models Cancer research gene expression pathology Radiotherapy Intensity-Modulated business metabolism |
Zdroj: | International Journal of Radiation Oncology*Biology*Physics International Journal of Radiation Oncology*Biology*Physics, 2019, 104 (2), pp.279-290. ⟨10.1016/j.ijrobp.2019.01.081⟩ International Journal of Radiation Oncology, Biology, Physics International Journal of Radiation Oncology, Biology, Physics, 2019, 104 (2), pp.279-290. ⟨10.1016/j.ijrobp.2019.01.081⟩ |
ISSN: | 0360-3016 1879-355X |
Popis: | International audience; Purpose Stereotactic body radiation therapy offers good lung local tumor control by the administration of a high dose per fraction in small volumes. Stereotactic body radiation therapy preclinical modeling is now possible, and our aim was to develop a model of focal irradiation of the mouse lung and to investigate the impact of conditional hypoxia-inducible factor 1α (HIF-1α) deletion in the endothelium on radiation-induced tissue damage. Methods and Materials The Small Animal Radiation Research Platform was used to create a mouse model of focal irradiation of the lung using arc therapy. HIF-1α conditional deletion was obtained by crossing mice expressing Cre recombinase under the endothelial promoter VE-cadherin (VECad-Cre +/+ mice) with HIF-1α floxed mice. Results Lung stereotactic arc therapy allows thoracic wall sparing and long-term studies. However, isodose curves showed that neighboring organs received significant doses of radiation, as revealed by ipsilateral lung acute red hepatization and major gene expression level modifications. Conditional HIF-1α deletion reduced acute lung edema and tended to diminish neutrophil infiltrate, but it had no impact on long-term global tissue damage. Conclusions Arc therapy for focal high-dose irradiation of mouse lung is an efficient model for long-term studies. However, irradiation may have a strong impact on the structure and function of neighboring organs, which must be considered. HIF-1α conditional deletion has no beneficial impact on lung damage in this irradiation schedule. © 2019 |
Databáze: | OpenAIRE |
Externí odkaz: |