Radiation and the lung: A reevaluation of the mechanisms mediating pulmonary injury

Morgan, Graeme; Breit, Samuel N.

doi:10.1016/0360-3016(94)00477-3

Cited by 245 publications

(123 citation statements)

References 52 publications

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“…Moreover, increased numbers of activated T-lymphocytes in the BALF were found to correlate with the onset of radiation-induced pneumonitis [23]. Here we show for the first time that CD4 + CD25 + IL-17 + and CD4 + CD25 + Foxp3 + expressing cells are recruited to the lung tissue of irradiated mice.…”

Section: Discussionsupporting

confidence: 52%

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: 52%

New insights into the molecular pathology of radiation-induced pneumopathy

Cappuccini¹,

Eldh

Bruder

et al. 2011

Radiotherapy and Oncology

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“…The histopathological changes to the irradiated lung have been well described (18,20,21). The inflammatory phase is generally characterized by alveolar cell depletion and inflammatory cell accumulation (4,22). This process initiated the activation of specific leukocyte subsets to produce important biological mediators, including cytokines, growth factors and chemokines, which participate in the majority of the aspects of the inflammatory response (4).…”

Section: A B Cmentioning

confidence: 99%

Radiation-induced pulmonary injury accelerated pulmonary metastasis in a mouse model of breast cancer

Gong

et al. 2015

Oncology Letters

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Abstract. The aim of the present study was to investigate the acceleration of pulmonary metastasis due to pulmonary injury caused by radiation treatment in a mouse model of breast cancer, in addition to determining the associated mechanism. The passive metastatic breast cancer model was used in radiation-treated BALB/c mice. In total, 24 mice were randomly separated into two groups, with 12 mice per group, and the groups were treated with or without pulmonary radiation. The survival time and variation of the weights of the lungs, spleen and liver were recorded. Lung metastasis was also evaluated, and chemokine (C-X-C motif) ligand 12 (CXCL12)/chemokine (C-X-C motif) receptor 4 (CXCR4) expression was determined. The results revealed that the group with radiation-induced pulmonary injury exhibited an increased incidence of pulmonary metastasis and shorter survival time compared with the mice without pulmonary radiation. The radiation-treated group possessed an increased number of metastatic nodules in the lungs, but metastasis was not evident in the liver and spleen. The CXCL12/CXCR4 axis was markedly expressed and the expression was significantly increased subsequent to radiation compared with the expression in normal lung tissues. The present study demonstrated that radiation-induced pulmonary injury may accelerate metastatic tumor growth and decrease the overall survival rate of the mice following in situ injection of tumor cells. Tumor localization and growth may have been favored by metastatic conditioning in the lung subsequent to radiotherapy. The CXCL12/CXCR4 axis may affect key elements in the multistep process of metastasis induced by radiation injury.

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“…1), which may eventually severely compromise tissue function. Factors that play a role in remodeling of the ECM include structural ECM proteins, inhibitors of ECM breakdown, and cytokines influencing transcription of profibrotic genes (2).…”

mentioning

confidence: 99%

Radiation and Transforming Growth Factor-β Cooperate in Transcriptional Activation of the Profibrotic Plasminogen Activator Inhibitor-1 Gene

Hageman¹,

Eggen

Rozema³

et al. 2005

Clinical Cancer Research

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Radiation-induced fibrosis is an important side effect in the treatment of cancer. Profibrotic proteins, such as plasminogen activator inhibitor-1 (PAI-1), transforming growth factor-h (TGF-h), and tissue type inhibitor of metalloproteinases-1 (Timp-1), are thought to play major roles in the development of fibrosis via the modulation of extracellular matrix integrity.We did a detailed analysis of transcriptional activation of these profibrotic genes by radiation and TGF-h. Irradiation of HepG2 cells led to a high increase in PAI-1mRNA levels and a mild increase in Timp-1mRNA levels. In contrast,TGF-h1and Smad7 were not increased. Radiation and TGF-h showed strong cooperative effects in transcription of the PAI-1 gene. The TGF-b1 gene showed a mild cooperative activation, whereas Timp-1and Smad7 were not cooperatively activated by radiation and TGF-h. Analysis using the proximal 800 bp of the human PAI-1 promoter revealed a dose-dependent increase of PAI-1levels between 2 and 32 Gy g-rays that was independent of latent TGF-h activation. Subsequent site-directed mutagenesis of the PAI-1 promoter revealed that mutation of a p53-binding element abolished radiation-induced PAI-1 transcription. In line with this, PAI-1 was not activated in p53-null Hep3B cells, indicating that p53 underlies the radiation-induced PAI-1activation and the cooperativity with theTGF-h/Smad pathway. Together, these data show that radiation and TGF-h activate PAI-1 via partially nonoverlapping signaling cascades that in concert synergize on PAI-1 transcription. This may play a role in patient-to-patient variations in susceptibility toward fibrosis after radiotherapy.

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Radiation and the lung: A reevaluation of the mechanisms mediating pulmonary injury

Cited by 245 publications

References 52 publications

New insights into the molecular pathology of radiation-induced pneumopathy

New insights into the molecular pathology of radiation-induced pneumopathy

Radiation-induced pulmonary injury accelerated pulmonary metastasis in a mouse model of breast cancer

Radiation and Transforming Growth Factor-β Cooperate in Transcriptional Activation of the Profibrotic Plasminogen Activator Inhibitor-1 Gene

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