Pharmacologic Inhibition of HIF-1 alpha Attenuates Radiation-Induced Pulmonary Fibrosis in a Preclinical Image Guided Radiation Therapy
DC Field | Value | Language |
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dc.contributor.author | Nam, Jae-Kyung | - |
dc.contributor.author | Kim, A-Ram | - |
dc.contributor.author | Choi, Seo-Hyun | - |
dc.contributor.author | Kim, Ji-Hee | - |
dc.contributor.author | Han, Su Chul | - |
dc.contributor.author | Park, Seungwoo | - |
dc.contributor.author | Lee, Yong Jin | - |
dc.contributor.author | Kim, Joon | - |
dc.contributor.author | Cho, Jaeho | - |
dc.contributor.author | Lee, Hae-June | - |
dc.contributor.author | Lee, Yoon-Jin | - |
dc.date.accessioned | 2021-08-30T02:16:13Z | - |
dc.date.available | 2021-08-30T02:16:13Z | - |
dc.date.created | 2021-06-18 | - |
dc.date.issued | 2021-02-01 | - |
dc.identifier.issn | 0360-3016 | - |
dc.identifier.uri | https://scholar.korea.ac.kr/handle/2021.sw.korea/49362 | - |
dc.description.abstract | Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a long-term side effect of thoracic radiation therapy. Hypoxia-induced vascular endothelial mesenchymal transition (EndMT) can occur during the development of RIPF. Here, we examined the direct contribution of endothelial HIF-1 alpha (EC-HIF1 alpha) on RIPF. Methods and Materials: An inducible Cre-lox-mediated endothelial Hif1a deletion mouse line was used to evaluate the potential of HIF-1 alpha inhibition to suppress RIPF. To evaluate the effects of a pharmacologic HIF-1 alpha inhibitor on RIPF after image guided radiation therapy (IGRT) for spontaneous lung adenocarcinoma, we generated conditional tdTomato; K-Ras(G12D); and p53 (flox/flox) mice to facilitate tracking of tumor cells expressing tdTomato. Results: We found that vascular endothelial-specific HIF-1 alpha deletion shortly before radiation therapy inhibited the progression of RIPF along with reduced EndMT, whereas prolonged deletion of endothelial HIF-1 alpha before irradiation did not. Moreover, we revealed that postirradiation treatment with the novel HIF-1 alpha inhibitor, 2-methoxyestradiol (2-ME) could efficiently inhibit RIPF and EndMT. In addition, IGRT using primary mouse models of non-small cell lung cancer showed that combined treatment of 2-ME with ablative high-dose radiation therapy efficiently inhibited RIPF and the growth of both multifocal and single tumors, concomitantly reducing radiation-induced EndMT of normal as well as tumor regions. Conclusion: These results suggest that a negative regulator of HIF-1 alpha-mediated EndMT, such as 2-ME, may serve as a promising inhibitor of RIPF in radiation therapy. (C) 2020 The Author(s). Published by Elsevier Inc. | - |
dc.language | English | - |
dc.language.iso | en | - |
dc.publisher | ELSEVIER SCIENCE INC | - |
dc.subject | STEREOTACTIC BODY RADIOTHERAPY | - |
dc.subject | TO-MESENCHYMAL TRANSITION | - |
dc.subject | LUNG-CANCER | - |
dc.subject | TUMOR-GROWTH | - |
dc.subject | TGF-BETA | - |
dc.subject | HYPOXIA | - |
dc.subject | 2-METHOXYESTRADIOL | - |
dc.subject | ANGIOGENESIS | - |
dc.subject | PNEUMONITIS | - |
dc.subject | MECHANISMS | - |
dc.title | Pharmacologic Inhibition of HIF-1 alpha Attenuates Radiation-Induced Pulmonary Fibrosis in a Preclinical Image Guided Radiation Therapy | - |
dc.type | Article | - |
dc.contributor.affiliatedAuthor | Kim, Joon | - |
dc.identifier.doi | 10.1016/j.ijrobp.2020.09.006 | - |
dc.identifier.scopusid | 2-s2.0-85092622834 | - |
dc.identifier.wosid | 000607368300030 | - |
dc.identifier.bibliographicCitation | INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS, v.109, no.2, pp.553 - 566 | - |
dc.relation.isPartOf | INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | - |
dc.citation.title | INTERNATIONAL JOURNAL OF RADIATION ONCOLOGY BIOLOGY PHYSICS | - |
dc.citation.volume | 109 | - |
dc.citation.number | 2 | - |
dc.citation.startPage | 553 | - |
dc.citation.endPage | 566 | - |
dc.type.rims | ART | - |
dc.type.docType | Article | - |
dc.description.journalClass | 1 | - |
dc.description.journalRegisteredClass | scie | - |
dc.description.journalRegisteredClass | scopus | - |
dc.relation.journalResearchArea | Oncology | - |
dc.relation.journalResearchArea | Radiology, Nuclear Medicine & Medical Imaging | - |
dc.relation.journalWebOfScienceCategory | Oncology | - |
dc.relation.journalWebOfScienceCategory | Radiology, Nuclear Medicine & Medical Imaging | - |
dc.subject.keywordPlus | STEREOTACTIC BODY RADIOTHERAPY | - |
dc.subject.keywordPlus | TO-MESENCHYMAL TRANSITION | - |
dc.subject.keywordPlus | LUNG-CANCER | - |
dc.subject.keywordPlus | TUMOR-GROWTH | - |
dc.subject.keywordPlus | TGF-BETA | - |
dc.subject.keywordPlus | HYPOXIA | - |
dc.subject.keywordPlus | 2-METHOXYESTRADIOL | - |
dc.subject.keywordPlus | ANGIOGENESIS | - |
dc.subject.keywordPlus | PNEUMONITIS | - |
dc.subject.keywordPlus | MECHANISMS | - |
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