title: Ablative hypofractionated radiotherapy normalizes tumor vasculature in lewis lung carcinoma mice model.
abstract: Ablative hypofractionated radiotherapy (HFRT) significantly improves the overall survival of inoperable non-small cell lung cancer (NSCLC) patients compared with conventional radiation therapy. However, the radiobiological mechanisms of ablative HFRT remain largely unknown. The purpose of this study was to investigate the dynamic changes of tumor vessels and perfusion during and after ablative hypofractionated radiotherapy. Lewis lung carcinoma-bearing mice were treated with sham (control) and ablative hypofractionated radiotherapy of 12 Gy in 1 fraction (12 Gy/1F) and 36 Gy in 3 fractions (36 Gy/3F). Tumor microvessel density (MVD), morphology and function were examined at different times after irradiation. The results showed that, compared to the controls the MVD and hypoxia in ablative HFRT groups decreased, which were accompanied by an increase in the number of pericytes and their coverage of vessels. Functional tests revealed that tumor hypoxia and perfusion were improved, especially in the 36 Gy/3F group. Our results revealed that ablative hypofractionated radiotherapy not only repressed MVD and hypoxia, but also increased the vascular perfusion and the number of pericyte-covered vessels, suggesting that ablative HFRT normalized the tumor vasculature.
authors.affiliation: Department of Thoracic Oncology, Cancer Center and State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Lan
authors.forename: Xiao-Li
authors.initials: XL
authors.lastname: Wan
authors.forename: Lei
authors.initials: L
authors.lastname: Deng
authors.forename: Jian-Xin
authors.initials: JX
authors.lastname: Xue
authors.forename: Li-Shuai
authors.initials: LS
authors.lastname: Wang
authors.forename: Mao-Bin
authors.initials: MB
authors.lastname: Meng
authors.forename: Hua
authors.initials: H
authors.lastname: Ling
authors.forename: Xi
authors.initials: X
authors.lastname: Zhang
authors.forename: Xian-Ming
authors.initials: XM
authors.lastname: Mo
authors.forename: You
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000818:Animals; D018827:Carcinoma, Lewis Lung / Q000098:blood supply* / Q000532:radiotherapy*; D015687:Cell Hypoxia; D045744:Cell Line, Tumor; D019583:Dose Fractionation, Radiation; D005260:Female; D051379:Mice; D008810:Mice, Inbred C57BL; D019408:Platelet Endothelial Cell Adhesion Molecule-1 / Q000032:analysis
chemical_list: D019408:Platelet Endothelial Cell Adhesion Molecule-1