Radiation-induced lung injury

About: Radiation-induced lung injury is a research topic. Over the lifetime, 258 publications have been published within this topic receiving 6877 citations. The topic is also known as: Radiation Pneumonitis.

Sphingolipids as a Novel Therapeutic Target in Radiation-Induced Lung Injury.

Abstract: Radiation-induced lung injury (RILI) is a potential complication of thoracic radiotherapy that can result in pneumonitis or pulmonary fibrosis and is associated with significant morbidity and mortality. The pathobiology of RILI is complex and includes the generation of free radicals and DNA damage that precipitate oxidative stress, endothelial cell (EC), and epithelial cell injury and inflammation. While the cellular events involved continue to be elucidated and characterized, targeted and effective therapies for RILI remain elusive. Sphingolipids are known to mediate EC function including many of the cell signaling events associated with the elaboration of RILI. Sphingosine-1-phosphate (S1P) and S1P analogs enhance EC barrier function in vitro and have demonstrated significant protective effects in vivo in a variety of acute lung injury models including RILI. Similarly, statin drugs that have pleiotropic effects that include upregulation of EC S1P receptor 1 (S1PR1) have been found to be strongly protective in a small animal RILI model. Thus, targeting of EC sphingosine signaling, either directly or indirectly, to augment EC function and thereby attenuate EC permeability and inflammatory responses, represents a novel and promising therapeutic strategy for the prevention or treatment of RILI.

Ulinastatin enhances autophagy against radiation-induced lung injury in mice

Abstract: Background To investigate the enhancement of autophagy by ulinastatin for protecting against radiation-induced lung injury (RILI) in mice. Methods Forty C57BL/6 mice were equally divided into (I) control (C), (II) irradiation (R), (III) ulinastatin (U), (IV) 3-methyladenine (3-MA) (M), and (V) ulinastatin plus 3-MA (U+M) groups. Three mice in each group were infected with adeno-associated virus (AAV) carrying green fluorescent protein (GFP)-1A/1B-light chain 3 (GFP-LC3) in the lung for the marker of autophagy. All mice in R, U, M and U+M groups were given chest irradiation (1 Gy/min, 12 min), following injection with normal saline in C and U groups, ulinastatin (500,000 IU/kg·d, i.p., 7 d) in U group, 3-MA (10 mg/kg·d, i.p., 7 d) in M group, and ulinastatin plus 3-MA in U+M group. The effects of ulinastatin on lung injury and autophagy were evaluated by electron microscope (EM), immunohistochemistry, mRNA expression levels of collagen alpha-1 (COL1A1), collagen alpha-2 (COL1A2), α-smooth muscle actin (α-SMA) and transforming growth factor β1 (TGF-β1), and protein levels of LC3, α-SMA, COL1A2, TGF-β1, matrix metalloproteinase-2 (MMP-2) and MMP-9. Results EM observation revealed that the radiation caused the injury of type I and II alveolar epithelial cells, which was improved by ulinastatin treatment associated with increased the numbers of autophagosomes. GFP-LC3 signals was significantly enhanced by ulinastatin detected by immune histochemical tests. At transcriptional and/or translational levels, ulinastatin significantly enhanced the expression levels of TGF-β1 and LC3 but reduced COL1A1, COL1A2, α-SMA, MMP-2 and MMP-9 after radiation-induced RILI. Conclusions Ulinastatin reduces RILI by enhancing autophagy, which might be a potential therapeutic drug in the protection against RILI.

Abstract 3671: Anti-PD-1 treatment may potentiate the radiation-induced lung injury

Abstract: Purpose: Combination of radiation therapy and anti-PD1 immunotherapy has been investigated both in the lab and in the clinic. Pneumonitis is a rare but potentially fatal toxicity of ant-programmed death-1 (PD-1) monoclonal antibodies (mAbs). The purpose of our study is to address whether anti-PD-1 mAbs will potentiate radiation-induced lung toxicity and mortality in a murine model using Small Animal Radiation Research Platform (SARRP) for lung-targeting irradiation (IR). Methods: Both lungs of male C57bl/6 mice were targeted for 20Gy using the SARRP. Mice were stratified into 4 treatment groups receiving IgG, anti-PD1, IR + IgG, or IR + anti-PD1. IgG or anti-PD-1 mAbs administrated via i.p. injection, with a dosage of 10mg/kg, twice per week for five doses. Acute lung injury was assessed by HE p Conclusions: Anti-PD-1 mAbs potentiates the radiation-induced pneumonitis, likely mediated by increased CD8+ cytotoxic T lymphocytes. Anti-PD-1 mAbs may increase the radiation-related mortality although it was not statistically significance at the day 120 following IR. Care should be taken for excessive lung toxicities in ongoing clinical trials of combining thoracic RT and anti-PD1 therapy. We will collaborate with NRG to further investigate clinical lung toxicities from combining thoracic radiotherapy with Nivo in the ongoing RTOG 3505 though analyzing the collected biospecimens. Note: This abstract was not presented at the meeting. Citation Format: Jianxin Xue, Shisuo Du, You Lu, Adam Dicker, Bo Lu. Anti-PD-1 treatment may potentiate the radiation-induced lung injury [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 3671. doi:10.1158/1538-7445.AM2017-3671

[Exploration of serum endothelin-1 as a marker of early radiation lung injury].

Abstract: AIM: To explore the possibility of endothelin-1(ET-1) as a serological marker of early diagnosis and progression of radiation induced lung injury. METHODS: One hundred and ninety female rats were randomly divided into control group (group C) and experimental groups, namely, radiation group (group R), fluvastatin treatment group (group Flu), retinoic acid treatment group (group Ra) and dexemethasone treatment group (group Dex). The chests of rats in experimental groups were exposed to radiation by linear accelerator after anesthesia. The radiation dose for each rat was 15Gy, 2Gy per minute, and radiation distance was 1 meter. The next day after radiation, fluvastatin (20 mg·kg~(-1)·d~(-1)) was administered orally in group Flu, retinoic acid (20 mg·kg~(-1)·d~(-1)) in group Ra and dexemethasone (3.33 mg·kg~(-1)·d~(-1)) in group Dex. The rats in group C and group R were medicated with the equal volume of normal saline. On the 5th, 15th, 30th, and 60th day after radiation, five rats were randomly chosen from each group respectively. The sera were harvested by decapitation or cardiopuncture and at the same time, lung tissues were cut off. The levels of serum ET-1 and LN were detected by radioimmunological assay(RIA). The pathologic changes of lung tissue were observed under light microscope. RESULTS: Compared to the control group, serum ET-1 level began to increase on the 5th day after exposure to radiation and reached the peak on the 60th day in group R. The levels of laminin and hyaluronic acid began to rise on the 30th day and the 60th day respectively. The elevation of serum ET-1 level in group R was obviously earlier than that in other groups and correlated to extent of lung injury. CONCLUSION: The serum ET-1 can be used as a marker of early diagnosis and dynamic changes of radiation lung injury.

TGF-β1-based CRISPR/Cas9 gene therapy attenuate Radiation-induced Lung Injury.

Abstract: Background Radiation-induced lung injury (RILI) is lacking effective therapeutic strategies. In this study, we conducted TGF-β1-based CRISPR/Cas9 gene therapy for RILI. Objectives Mouse lungs were irradiated with a single-dose of 20-Gy gamma rays followed by intravenous administration of Ad-CRISPR-TGF-β1 or Ad- CRISPR-Null. Methods Haematoxylin and eosin staining, as well as Masson staining were performed to observe lung morphology. Albumin and IgM concentrations in bronchoalveolar lavage fluid were measured by ELISA. Cytokine levels were measured using ELISA and/or real-time PCR with terminal deoxynucleotidyl transferase mediated nick-end labelling. Results Ad-CRISPR-TGFβ1 improved histopathological and biochemical markers of lung injury, reduced secretion and expression of inflammatory cytokines, and inhibited progression of fibrosis. Importantly, the SK1/S1P axis-which is known to play a key role via S1P1 in TGF-β1-dependent S1PR pattern remodelling-is responsible for promoting fibrosis. Conclusion Our results indicate novel insights for RILI therapy.