 |
Journal articles
Lung Stereotactic Arc Therapy in Mice Development of Radiation Pneumopathy and Influence of HIF-1α Endothelial Deletion
Abstract : 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
Keywords :
Biological organs
Irradiation
Mammals
Radiotherapy
Tissue
Gene expression levels
Hypoxia inducible factor 1-alpha
Ipsilateral lungs
Local tumor control
Methods and materials
Radiation-induced
Research platforms
Radiation
chlordane
cre recombinase
hypoxia inducible factor 1alpha
vascular endothelial cadherin
integrase
animal tissue
Article
cell infiltration
comparative study
cone beam computed tomography
controlled study
endothelium
follow up
gene expression
genotype
lung disease
lung edema
major gene
mouse
neutrophil
nonhuman
priority journal
quantitative analysis
radiation dose
radiation exposure
radiation induced tissue damage
radiation injury
real time polymerase chain reaction
stereotactic body radiation therapy
tissue injury
treatment planning
adverse event
diagnostic imaging
disease model
epithelial mesenchymal transition
genetics
intensity modulated radiation therapy
lung alveolus
lung fibrosis
lung tumor
metabolism
pathology
physiology
procedures
radiation pneumonia
radiation response
Animals
Cone-Beam Computed Tomography
Disease Models
Animal
Epithelial-Mesenchymal Transition
Gene Deletion
Hybridization
Genetic
Hypoxia-Inducible Factor 1
alpha Subunit
Integrases
Lung
Lung Neoplasms
Mice
Organs at Risk
Phenotype
Pulmonary Alveoli
Pulmonary Edema
Pulmonary Fibrosis
Radiation Dosage
Radiation Pneumonitis
Radiosurgery
Intensity-Modulated
Running
Selective Breeding
https://hal-univ-evry.archives-ouvertes.fr/hal-02489958
Contributor : Univ Évry Hal <>
Submitted on : Monday, February 24, 2020 - 5:41:14 PM
Last modification on : Thursday, September 3, 2020 - 1:06:40 PM
Contributor : Univ Évry Hal <>
Submitted on : Monday, February 24, 2020 - 5:41:14 PM
Last modification on : Thursday, September 3, 2020 - 1:06:40 PM
