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Lung Cancer |

Expression of TGF-β-1 Alterations in Radiation-Induced Lung Injury by Halofuginone

Mustafa Calik; Guler Yavas; Saniye Calik; Cagdas Yavas; Zeliha Celik; Hidir Esme
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Department of Thoracic Surgery, Konya Education and Research Hospital, Konya, Turkey


Chest. 2014;146(4_MeetingAbstracts):585A. doi:10.1378/chest.1993728
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Abstract

SESSION TITLE: Lung Cancer Posters I

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Wednesday, October 29, 2014 at 01:30 PM - 02:30 PM

PURPOSE: To evaluate the expression of TGF-β-1 Alterations in radiation-induced lung injury (RILI) by Halofuginone (H).

METHODS: Wistar-Albino rats were treated with 12 Gy of thoracic irradiation. H was applied intraperitoneally with daily doses of either 2.5 or 5 μg. At 6th and 16th weeks of radiotherapy (RT), 5 rats from each group were sacrificed. The lung tissues were dissected for conventional light microscopy.

RESULTS: The inflammation, fibrosis and transforming growth factor (TGF)-β scores of all study groups were significantly different at 6th and 16th week of RT (p< 0.001 for all). H, either used with lower or higher doses ameliorated the radiation-induced pulmonary fibrosis at 6th and 16th week of RT (p< 0.001 for all). In parallel to this finding, the differences between the TGF- β scores of RT only and RT+H groups’ 6th and 16th week of RT were significantly different (p< 0.001 for all). The inflammation, fibrosis and TGF- β scores of RT only group were deteriorated at 16th week of RT when compared to 6th week findings (p< 0.001 for all). On the other hand only the TFG- β scores of RT+2.5 μg H group (p<0.001), and the fibrosis scores of RT+5 μg H group were significantly different at 6th and 16th weeks of RT.

CONCLUSIONS: H either used in lower or higher doses may ameliorate the RILI. The most prominent improvement was observed in higher group after long term follow-up.

CLINICAL IMPLICATIONS: The lung is one of the most sensitive organs to ionizing radiation, and damage to normal lung tissue remains a major dose limiting factor for patients receiving radiation to the thorax.Halofuginone has been shown to protect against radiation induced soft tissue fibrosis by virtue of inhibiting various members of TFG- β signaling pathway. By the light of these findings, Halofuginone can be effective for ameliorating radiation-induced lung fibrosis by decreasing TGF- β induced collagen synthesis. This issue warrants further studies.

DISCLOSURE: The following authors have nothing to disclose: Mustafa Calik, Guler Yavas, Saniye Calik, Cagdas Yavas, Zeliha Celik, Hidir Esme

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