Advances in Molecular Mechanisms and Treatment of Radiation-Induced Pulmonary Fibrosis

Chen, Zhongjie; Wu, Zhiqiang; Ning, Wen

doi:10.1016/j.tranon.2018.09.009

Cited by 72 publications

(72 citation statements)

References 103 publications

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“…After IR exposure, the expression of Th2-related cytokines increased, and the expression of Th1-related cytokines decreased. Thereafter, alveolar macrophage accumulation in the irradiated tissue increased, and TGF-β was dramatically expressed [ 36 ]. Macrophages can be divided into two subsets according to their distinct functions [ 37 , 38 , 39 ].…”

Section: Characteristics Of Ripfmentioning

confidence: 99%

“…In addition, administration of amifostine before IR also reduced macrophage accumulation and TGF-β1 expression in lung tissue [ 86 ]. Superoxide dismutase (SOD) is a metalloprotease that protects against oxidative damage [ 36 ]. Recombinant SOD-TAT (Superoxide dismutase fusion of TAT) protein protected against RILI in mice.…”

Section: Therapeutic Targets and Their Inhibitors In Ripfmentioning

confidence: 99%

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Radiation-Induced Lung Fibrosis: Preclinical Animal Models and Therapeutic Strategies

Jin

Yoo

Kim

et al. 2020

Cancers

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Radiation-induced lung injury (RILI), including acute radiation pneumonitis and chronic radiation-induced lung fibrosis, is the most common side effect of radiation therapy. RILI is a complicated process that causes the accumulation, proliferation, and differentiation of fibroblasts and, finally, results in excessive extracellular matrix deposition. Currently, there are no approved treatment options for patients with radiation-induced pulmonary fibrosis (RIPF) partly due to the absence of effective targets. Current research advances include the development of small animal models reflecting modern radiotherapy, an understanding of the molecular basis of RIPF, and the identification of candidate drugs for prevention and treatment. Insights provided by this research have resulted in increased interest in disease progression and prognosis, the development of novel anti-fibrotic agents, and a more targeted approach to the treatment of RIPF.

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Section: Characteristics Of Ripfmentioning

confidence: 99%

Section: Therapeutic Targets and Their Inhibitors In Ripfmentioning

confidence: 99%

Radiation-Induced Lung Fibrosis: Preclinical Animal Models and Therapeutic Strategies

Jin

Yoo

Kim

et al. 2020

Cancers

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“…RIPF is a late effect of radiation on the lungs. 8 It develops in the third phase of RT-induced lung tissue damage. The first phase is asymptomatic.…”

Section: Ripfmentioning

confidence: 99%

Cellular senescence and radiation-induced pulmonary fibrosis

Thummuri

Zheng

et al. 2019

Translational Research

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Radiation-induced pulmonary fibrosis (RIPF) is a serious treatment complication that affects about 9-30% cancer patients receiving radiotherapy for thoracic tumors. RIPF is characterized by progressive and irreversible destruction of lung tissues and deterioration of lung function, which can compromise quality of life and eventually lead to respiratory failure and death. Unfortunately, the mechanisms by which radiation causes RIPF have not been well established nor has an effective treatment for RIPF been developed. Recently, an increasing body of evidence suggests that induction of senescence by radiation may play an important role in RIPF and clearance of senescent cells (SnCs) with a senolytic agent, small molecule that can selectively kill SnCs, has the potential to be developed as a novel therapeutic strategy for RIPF. This review discusses some of these new findings to promote further study on the role of cellular senescence in RIPF and the development of senolytic therapeutics for RIPF.

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“…However, the ideals prove to be far from realistic with 35% of thoracic irradiation patients at risk to develop lung injury. 4–6 Therefore, it is necessary to examine radiation injury to thoracic organs and tissue through pre-clinical models in mice.…”

Section: Introductionmentioning

confidence: 99%

Murine Radiation-Induced Stomach Pathology from Whole Thoracic Irradiation

McIlrath

Pérez-Torres

2020

Preprint

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PurposeRadiation-induced lung injury is a common side effect in the treatment of lung and breast cancers. There is a large focus in the field on leveraging mouse models of radiation-induced lung injury to find novel treatments for the condition. While attempting to irradiate mouse lungs for purposes of creating a radiation-induced pulmonary fibrosis model, noticeable declines in health were observed at much earlier time points than recorded for lung pathology. This was later attributed to stomach pathology observed in CT images and ex vivo dissection.MethodsFor this study, we used longitudinal microCT to characterize male C57Bl/6 mice irradiated with a single dose of 20 Gy to the whole thoracic area delivered by an X-Rad cabinet irradiator. CT was performed with respiratory gating at 2 to 4 week timepoints to construct a timeline of pathology leading up to fibrosis and quantify severity of fibrosis afterwards. However, a mouse imaged at the 10 week timepoint showed evidence of stomach distention. These mice were sacrificed and their stomachs removed. Histology was performed on the stomachs using H&E staining.ResultsOn the CT images, we observed a large, spherical volume of hypointense signal, caudal to the lungs (Figure 1). This correlated with a distended stomach caused by constipation and gas build-up within the stomach. Statistical analysis showed 81% of mice (n=105) died prematurely after irradiation and before significant development of pulmonary fibrosis. Mice sacrificed and dissected showed unpassed bolus as contents of the stomach, and histology showed cell necrosis of the stomach walls.ConclusionThe histology indicated an inability for food to be digested and moved into the small intestine. This lead to a blockage and ensuing stomach distention. Given the severity of the pathology’s consequences, it lead to the mouse’s imminent mortality inhibiting the efficacy of the study. Future studies need to consider careful placement of shields or any beam contouring devices to ensure protection of the stomach given its higher radiosensitivity in contrast to the lungs.

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Advances in Molecular Mechanisms and Treatment of Radiation-Induced Pulmonary Fibrosis

Cited by 72 publications

References 103 publications

Radiation-Induced Lung Fibrosis: Preclinical Animal Models and Therapeutic Strategies

Radiation-Induced Lung Fibrosis: Preclinical Animal Models and Therapeutic Strategies

Cellular senescence and radiation-induced pulmonary fibrosis

Murine Radiation-Induced Stomach Pathology from Whole Thoracic Irradiation

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