The predictive role of plasma TGF-β1 during radiation therapy for radiation-induced lung toxicity deserves further study in patients with non-small cell lung cancer

Zhao, Lujun; Sheldon, Kerby; Chen, Ming; Yin, Moli S.; Hayman, James A.; Kalemkerian, Gregory P.; Arenberg, Douglas A.; Lyons, Susan E.; Curtis, Jeffrey L.; Davis, Mary A.; Cease, Kemp B.; Brenner, Dean E.; Anscher, Mitchell S.; Lawrence, Theodore S.; Kong, Feng-Ming

doi:10.1016/j.lungcan.2007.08.010

Cited by 86 publications

(48 citation statements)

References 51 publications

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“…Following activation, myofibroblasts themselves begin to secrete TGFβ1 and are thereby able to sustain their own activation through a self-stimulatory mechanism, which facilitates the auto-perpetuating process characteristic of fibrosis. In addition, TGFβ1 is a potent stimulus for the production of ECM components, such as collagen (22), and elevation of TGFβ1 levels in the plasma of patients during the 4th week of radiotherapy is significantly predictive of RILI (23). In the present study, the continuous increase in the TGFβ1 protein expression in the irradiated lungs of minipigs further indicates the key function served by TGFβ1 in the pathogenesis of RILI.…”

supporting

confidence: 59%

Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs

Yue

Liu

et al. 2015

Experimental and Therapeutic Medicine

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Abstract. Radiation-induced lung injury (RILI) is a common complication associated with thoracic radiotherapy. The aim of the present study was to investigate the effects of a single 15-Gy dose of right-thoracic lung irradiation on the expression levels of matrix metalloproteinases (MMPs) and other proteins in the alveolar epithelial type II (AE2) cells of Bama minipigs. All minipigs received either right-thoracic irradiation or sham irradiation under anesthesia, and were sacrificed at 4, 8, 12 or 24 weeks after irradiation. Collagen deposition was measured using Masson's trichrome staining. Surfactant protein A (SP-A), transforming growth factor β1 (TGFβ1), MMP2, MMP9, vimentin and E-cadherin protein expression levels were evaluated using western blot analysis, and the MMP2 and MMP9 gelatinase activities were tested using gelatin zymography. SP-A and α-smooth muscle actin (α-SMA) co-localization was visualized using double immunofluorescence staining. At each time-point following irradiation, a significant increase in TGFβ1, α-SMA, MMP2, MMP9 and vimentin protein expression levels and MMP2 and MMP9 gelatinase activity were observed in the irradiated lungs compared with the sham-irradiated controls. By contrast, SP-A and E-cadherin protein expression levels decreased in a time-dependent manner post-irradiation. SP-A and α-SMA co-localization was observed in irradiated alveolar epithelial cells. These data demonstrate that E-cadherin, SP-A, MMP2 and MMP9 may function as sensitive predictors of RILI. Epithelial-mesenchymal transition (EMT) occurs in the irradiated lungs of Bama minipigs, and MMP2 and MMP9 may contribute to EMT in AE2 cells by regulating TGFβ1. Therefore, EMT may serve a crucial function in the development of RILI.

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supporting

confidence: 59%

Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs

Yue

Liu

et al. 2015

Experimental and Therapeutic Medicine

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“…Blocking the proinflammatory cytokine's ability to bind to its receptor prevented further signal transduction and generation of late tissue damage. In addition, plasma TGF-β1 of patients has been shown to be significantly predictive of radiation-induced lung toxicity, thus further implicating TGF-β1 as an important factor in lung radiation response [137].…”

Section: Rosmentioning

confidence: 99%

“…In thoracic radiotherapy, dose escalation is limited by the normal tissue complication probability (NTCP). Using current treatment protocols, the risk of radiation pneumonitis is of most concern as it has considerable impact on patient morbidity and mortality [16,137,[152][153][154][155].…”

Section: Introductionmentioning

confidence: 99%

Effects of genistein following fractionated lung irradiation in mice

Para¹,

Bezjak²,

Yeung³

et al. 2009

Radiotherapy and Oncology

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Radiation therapy for lung cancer and cancers of the upper thorax is limited by side effects to normal tissue of the lung. An understanding of mechanisms leading to radiation induced lung damage is essential to developing protective agents. In this thesis an anti-oxidant and anti-inflammatory agent Genistein was investigated for its potential to affect DNA damage, tissue inflammation, functional deficits and survival. We hypothesized that chronic oxidative stress and the subsequent inflammatory response play a key role in the development of major lung complications, radiation pneumonitis and fibrosis. If side effects of radiation could be reduced, then larger doses could be delivered to the tumor with a better chance of eradicating the disease.ii Acknowledgements

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“…These genes include the cytokine TGFb-1 that can be activated by IR probably as a response to oxidative stress and inflammation, 2 and gives rise to fibrosis 35,36 and other cytokines such as those from the cytocrome P450 family including CYP2D6. 37 The 509 C>T SNP in TGFb-1 has been identified as a potential candidate biomarker for predicting the development of fibrosis after radiotherapy in breast and prostate cancer.…”

Section: Snps Associated With Ionizing Radiation Toxicitymentioning

confidence: 99%

Molecular markers for prediction of risk of radiation-related injury to normal tissue

Ghilotti

Pierotti

Gariboldi

2010

J Nucleic Acids Invest

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The predictive role of plasma TGF-β1 during radiation therapy for radiation-induced lung toxicity deserves further study in patients with non-small cell lung cancer

Cited by 86 publications

References 51 publications

Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs

Role of matrix metalloproteinases in radiation-induced lung injury in alveolar epithelial cells of Bama minipigs

Effects of genistein following fractionated lung irradiation in mice

Molecular markers for prediction of risk of radiation-related injury to normal tissue

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