Using Biological Markers to Predict Risk of Radiation Injury

Fleckenstein, Katharina; Gauter-Fleckenstein, Benjamin; Jackson, Isabel L.; Rabbani, Zahid N.; Anscher, Mitchell S.; Vujašković, Željko

doi:10.1016/j.semradonc.2006.11.004

Cited by 109 publications

(95 citation statements)

References 59 publications

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“…Oxidative stress, inflammatory cell recruitment and cytokine production following radiation to the lung has been examined in many studies and postulated to play a major role in the development of functional lung damage [169]. It was thought that genistein would be an ideal agent to treat radiation-induced lung damage as it has both anti-oxidant and anti-inflammatory properties (blocks activation of NFκB).…”

Section: Control Dietmentioning

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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Section: Control Dietmentioning

confidence: 99%

Effects of genistein following fractionated lung irradiation in mice

Para¹,

Bezjak²,

Yeung³

et al. 2009

Radiotherapy and Oncology

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“…Unfortunately, during conventional radiotherapy or stereotactic body radiotherapy, lung complications such as pneumonitis and fibrosis can cause significant morbidity in cancer survivors. Radiation-induced pulmonary fibrosis (RIPF) triggers physiologic abnormalities (1)(2)(3). Despite the pressing medical need, little progress has been made to mitigate the radiation-induced pneumonitis.…”

Section: Introductionmentioning

confidence: 99%

A Hypoxia-Induced Vascular Endothelial-to-Mesenchymal Transition in Development of Radiation-Induced Pulmonary Fibrosis

Choi

Hong

Nam

et al. 2015

Clinical Cancer Research

134

128

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Purpose: Radiation-induced pulmonary fibrosis (RIPF) is a late side effect of thoracic radiotherapy. The purpose of our study was to gain further insight into the development of RIPF.Experimental Design/Results: Here, we observed that irradiation of mouse lungs induced collagen deposition, particularly around blood vessels, in the early phase of RIPF. Such deposition subsequently became evident throughout the irradiated tissues. Accompanied by the collagen deposition, vascular EndMT (endothelial-to-mesenchymal transition) began to develop in the early phase of RIPF, before the appearance of EMT (epithelial-tomesenchymal transition) of alveolar epithelial (AE) II cells in the substantive fibrotic phase. Concomitant with the EndMT, we detected vascular endothelial cell (EC)-specific hypoxic damage in the irradiated lung tissues. In human pulmonary artery endothelial cells (HPAEC), the radiation-induced EndMT via activation of TGFb-R1/Smad signaling was dependent on HIF1a expression. A novel HIF1a inhibitor, 2-methoxyestradiol (2-ME), inhibited the irradiation-induced EndMT via downregulation of HIF1a-dependent Smad signaling. In vivo, 2-ME inhibited the vascular EndMT, and decreased the collagen deposition associated with RIPF. Furthermore, HIF1a-related EndMT was observed also in human RIPF tissues.Conclusions: We provide the first evidence that an EndMT occurs in RIPF development and that the EndMT may be effectively inhibited by modulating vascular EC-specific hypoxic damage.

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“…Recent insights into the mechanism of radiation-induced lung injury [5][6][7] have opened new opportunities for therapeutic intervention. A new therapeutic approach is targeted against the continuous production of reactive oxygen/reactive nitrogen species (ROS/RNS) in an ongoing process that perpetuates lung injury [5].…”

Section: Introductionmentioning

confidence: 99%

Comparison of two Mn porphyrin-based mimics of superoxide dismutase in pulmonary radioprotection

Gauter-Fleckenstein

Fleckenstein

Owzar

et al. 2008

Free Radical Biology and Medicine

Self Cite

110

131

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Development of radiation (RT) induced lung injury is associated with chronic production of reactive oxygen and nitrogen species (ROS/RNS). MnTE-2-PyP 5+ is a catalytic Mn porphyrin (MnP) mimic of SOD, already shown to protect lungs from RT induced injury by scavenging ROS/RNS. The purpose of this study was to compare MnTE-2-PyP 5+ with the newly synthesized MnTnHex-2-PyP 5+ which is expected to be a more effective radioprotector due to its lipophilic properties. This study shows that Fischer rats which were irradiated to their right hemithorax (28 Gy) have less pulmonary injury as measured with breathing frequencies when treated with daily subcutaneous injections of MnTE-2-PyP 5+ (3 and 6 mg/kg) or MnTnHex-2-PyP 5+ (0.3 -0.6 -1.0 mg/kg) for 2 weeks after RT. However, at 16 weeks post RT, only MnTE-2-PyP 5+ at a dose of 6 mg/kg is able to ameliorate oxidative damage, block activation of HIF-1α and TGF-β and impair upregulation of CA-IX and VEGF. MnTnHex-2-PyP 5+ at a dose of 0.3 mg/kg is effective only in reducing RT-induced TGF-β and CA-IX expression. Significant loss in bodyweight was observed in animals receiving MnTnHex-2-PyP 5+ (0.3 and 0.6 mg/kg). MnTnHex-2-PyP 5+ has the ability to dissolve lipid membranes causing local irritations/necrosis at injection sites if given at doses of 1 mg/kg or higher. In conclusion, both compounds show ability to ameliorate lung damage as measured with breathing frequencies and histopathologic evaluation. However, MnTE-2-PyP 5+ at 6 mg/kg proved to be more effective in reducing expression of key molecular factors known to play an important role in radiation-induced lung injury.

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Using Biological Markers to Predict Risk of Radiation Injury

Cited by 109 publications

References 59 publications

Effects of genistein following fractionated lung irradiation in mice

Effects of genistein following fractionated lung irradiation in mice

A Hypoxia-Induced Vascular Endothelial-to-Mesenchymal Transition in Development of Radiation-Induced Pulmonary Fibrosis

Comparison of two Mn porphyrin-based mimics of superoxide dismutase in pulmonary radioprotection

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