Compartmental responses after thoracic irradiation of mice: Strain differences

Chiang, Chi-Shiun; Liu, Wei-Chung; Jung, Shih‐Ming; Chen, Fang-Hsin; Wu, Chi-Rong; McBride, William H.; Lee, Chung-Chi; Hong, Ji-Hong

doi:10.1016/j.ijrobp.2005.02.037

Cited by 95 publications

(90 citation statements)

References 37 publications

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“…These findings support earlier reports about delayed death or impairment of resident epithelial and/or endothelial cells leading to a loss of barrier function in the irradiated lung tissue [5,16,17]. Interestingly, increased apoptosis was observed in both, the irradiated and the shielded lung tissue.…”

Section: Discussionsupporting

confidence: 91%

“…The appearance of foamy macrophages in the BALF of irradiated C57BL/6 mice has already been observed in an earlier study [17]. However, here we show for the first time that radiation-induced formation of lipid droplets is not restricted to BALF-macrophages but is also found in tissue macrophages as well as in resident endothelial cells.…”

Section: Discussionsupporting

confidence: 88%

“…We speculate that as biomarkers for radiation-induced pneumopathy in patients [18,19]. Moreover, a time-dependent increase in tissue levels of TGF-ß, tumor necrosis factor-α, IL-1ß, and IL-6 mRNA as well as of MCP-1 and 3 and MIP-1γ proteins levels has been described in irradiated mice [13,17,20].…”

Section: Discussionmentioning

confidence: 81%

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New insights into the molecular pathology of radiation-induced pneumopathy

Cappuccini¹,

Eldh

Bruder

et al. 2011

Radiotherapy and Oncology

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Section: Discussionsupporting

confidence: 91%

Section: Discussionsupporting

confidence: 88%

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New insights into the molecular pathology of radiation-induced pneumopathy

Cappuccini¹,

Eldh

Bruder

et al. 2011

Radiotherapy and Oncology

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“…Inbred C3H/HeN mice manifest pulmonary injury patterns similar to those of humans when irradiated [15,16]. The animals were exposed to either sham irradiation or a single fraction of 10 Gy whole body irradiation, and sacrificed 2 h, 6 h, and 24 h after irradiation.…”

Section: Results Comparison Of the Anti-oxidant Defense Systems Of Lunmentioning

confidence: 99%

“…Because lung tissue cannot be obtained from these patients, we used red blood cells (RBC) as a surrogate to assess the anti-oxidant capacity of the patient. This was based on the results we obtained using radiation pneumonitissensitive inbred mice (C3H/HeN) [15,16] as an experimental model. We first demonstrated that oxidative stress response in the lung correlates with that in RBC in irradiated mice.…”

Section: Introductionmentioning

confidence: 99%

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Park

Ramnath

Yang

et al. 2007

Free Radical Biology and Medicine

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Radiation pneumonitis is an unpredictable complication of radiotherapy for lung cancer and a condition which can cause significant morbidity. The ability to identify patients at a high risk of developing pneumonitis is critical, since it will enable the individualization of the treatment plan. Because the cytotoxic effect of radiation is propagated through ROS and ROS-driven oxidative stress, the role of anti-oxidant defense systems in radiation pneumonitis was investigated. Using the pneumonitis-sensitive C3H/HeN mice as a model, we demonstrated that the anti-oxidant response of the lung correlated well with that of RBC. We then proceeded to test whether differences of RBC anti-oxidant response would predict the pneumonitis development in patients. SOD, GPX, CAT activities and glutathione in RBC were measured at baseline and then weekly for 6 weeks of treatment in fifteen eligible patients receiving concurrent chemo-radiotherapy for unresectable stage III NSCLC. Striking differences were found in the anti-oxidant activities of RBC with respect to the pneumonitis development. Those who developed pneumonitis showed higher SOD and lower GPX activities at baseline compared to those who did not (3.7 vs. 6.8 unit/mg for median SOD, 16.5 vs. 10.7 nmol/min/mg for median GPX). The functional imbalance of SOD and GPX was displayed consistently throughout the treatment period. The sensitivity and specificity of pneumonitis prediction were further increased when the GPX/SOD ratio was analyzed (pre-treatment P = 0.0046). Our results provide a strong rationale to monitor SOD and GPX activities of RBC to identify patients who are at risk of developing pneumonitis, and to implement a strategy of increasing the GPX/SOD ratio in order to lower the risk.

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Modeling and multiscale characterization of the quantitative imaging based fibrosis index reveals pathophysiological, transcriptome and proteomic correlates of lung fibrosis induced by fractionated irradiation

Zhou

Moustafa

Cao

et al. 2019

Intl Journal of Cancer

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Pulmonary fibrosis represents a leading cause of morbidity and mortality worldwide. Therapy induced lung fibrosis constitutes a pivotal dose‐limiting side effect of radiotherapy and other anticancer agents. We aimed to develop objective criteria for assessment of fibrosis and discover pathophysiological and molecular correlates of lung fibrosis as a function of fractionated whole thoracic irradiation. Dose–response series of fractionated irradiation was utilized to develop a non‐invasive and quantitative measure for the degree of fibrosis – the fibrosis index (FI). The correlation of FI with histopathology, blood‐gas, transcriptome and proteome responses of the lung tissue was analyzed. Macrophages infiltration and polarization was assessed by immunohistochemistry. Fibrosis development followed a slow kinetic with maximum lung fibrosis levels detected at 24‐week post radiation insult. FI favorably correlated with radiation dose and surrogates of lung fibrosis i.e., enhanced pro‐inflammatory response, tissue remodeling and extracellular matrix deposition. The loss of lung architecture correlated with decreased epithelial marker, loss of microvascular integrity with decreased endothelial and elevated mesenchymal markers. Lung fibrosis was further attributed to a switch of the inflammatory state toward a macrophage/T‐helper cell type 2‐like (M2/Th2) polarized phenotype. Together, the multiscale characterization of FI in radiation‐induced lung fibrosis (RILF) model identified pathophysiological, transcriptional and proteomic correlates of fibrosis. Pathological immune response and endothelial/epithelial to mesenchymal transition were discovered as critical events governing lung tissue remodeling. FI will be instrumental for deciphering the molecular mechanisms governing lung fibrosis and discovery of novel targets for treatment of this devastating disease with an unmet medical need.

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Compartmental responses after thoracic irradiation of mice: Strain differences

Cited by 95 publications

References 37 publications

New insights into the molecular pathology of radiation-induced pneumopathy

New insights into the molecular pathology of radiation-induced pneumopathy

High superoxide dismutase and low glutathione peroxidase activities in red blood cells predict susceptibility of lung cancer patients to radiation pneumonitis

Modeling and multiscale characterization of the quantitative imaging based fibrosis index reveals pathophysiological, transcriptome and proteomic correlates of lung fibrosis induced by fractionated irradiation

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