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Author Choi, Seo-Hyun ♦ Nam, Jae-Kyung ♦ Jang, Junho ♦ Lee, Hae-June ♦ Lee, Yoon-Jin
Source United States Department of Energy Office of Scientific and Technical Information
Content type Text
Language English
Subject Keyword APPLIED LIFE SCIENCES ♦ CARCINOMAS ♦ CHEMOTHERAPY ♦ COLLAGEN ♦ COMBINED THERAPY ♦ COMPARATIVE EVALUATIONS ♦ DENSITY ♦ DEPOSITION ♦ DEPOSITS ♦ FIBROBLASTS ♦ GROWTH FACTORS ♦ INHIBITION ♦ IRRADIATION ♦ LUNGS ♦ PLANT GROWTH ♦ RADIOSENSITIVITY ♦ RADIOTHERAPY
Abstract Radiotherapy is a widely used treatment for many tumors. Combination therapy using anti-angiogenic agents and radiation has shown promise; however, these combined therapies are reported to have many limitations in clinical trials. Here, we show that radiation transformed tumor endothelial cells (ECs) to fibroblasts, resulting in reduced vascular endothelial growth factor (VEGF) response and increased Snail1, Twist1, Type I collagen, and transforming growth factor (TGF)-β release. Irradiation of radioresistant Lewis lung carcinoma (LLC) tumors greater than 250 mm{sup 3} increased collagen levels, particularly in large tumor vessels. Furthermore, concomitant sunitinib therapy did not show a significant difference in tumor inhibition versus radiation alone. Thus, we evaluated multimodal therapy that combined pirfenidone, an inhibitor of TGF-induced collagen production, with radiation and sunitinib treatment. This trimodal therapy significantly reduced tumor growth, as compared to radiation alone. Immunohistochemical analysis revealed that radiation-induced collagen deposition and tumor microvessel density were significantly reduced with trimodal therapy, as compared to radiation alone. These data suggest that combined therapy using pirfenidone may modulate the radiation-altered tumor microenvironment, thereby enhancing the efficacy of radiation therapy and concurrent chemotherapy. - Highlights: • Radiation changes tumor endothelial cells to fibroblasts. • Radio-resistant tumors contain collagen deposits, especially in tumor vessels. • Pirfenidone enhances the efficacy of combined radiation and sunitinib therapy. • Pirfenidone reduces radiation-induced collagen deposits in tumors.
ISSN 0006291X
Educational Use Research
Learning Resource Type Article
Publisher Date 2015-06-26
Publisher Place United States
Journal Biochemical and Biophysical Research Communications
Volume Number 462
Issue Number 2


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