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¹ßÇ¥Çü½Ä : Á¢¼ö¹øÈ£ - 890055    HNOP-41 
Effect of Perioperative Treatment with A Hypoxia-Inducible Factor-1- Alpha Inhibitor in an Orthotopic Surgical Mouse Model of Thyroid Cancer
Dept. of Otorhinolaryngology Head and Neck Surgery1, Biomedical Research Institute2, Pusan National Univ. Hosp., Busan, Korea, Dept. of Otorhinolaryngology Head and Neck Surgery3, Seoul National Univ. Bundang Hosp.,Seongnam, Korea Seoul National Univ. College of Medicine4, Seoul, Korea
Wonjae CHA, Wonjae CHA1,2, Dong-Wook KIM3, Sung Dong KIM3, Eun-Hui JEON 3, Woo-Jin JEONG 3, Soon-Hyun AHN 3,4
¸ñÀû: Despite an excellent prognosis, some patients with thyroid cancer suffer from locally invasive disease that cannot be controlled by conventional therapy. Our previous study suggested that hypoxia inducible factor-1-alpha (HIF1¥á) might be an important marker for the identification of and a target for treatment of intractable thyroid cancer. Therefore, in the present study, we established an orthotopic mouse surgical model of thyroid cancer that mimics the clinical setting, and evaluated the effect of perioperative treatment with a HIF1¥á inhibitor. ¹æ¹ý:Seven thyroid cancer cell lines (SNU-790, BCPAP, KTC1, TPC1, TPC1-M, KTC2, and FRO) and four HIF1¥á inhibitors (echinomycin, LAQ824, temsirolimus, and vorinostat) were used in this study. Expression of HIF1¥á and related proteins was evaluated in the cell lines immunoblotting and cell proliferation assays were conducted and echinomycin was validated in an orthotopic surgical mouse model. °á°ú:Nuclear expression of HIF1¥á increased in the tumorigenic cell lines. HIF1¥á inhibitors inhibited proliferation and colony formation in all the cell lines. In the orthotopic surgical model, the group treated with surgery and echinomycin treatment group showed a highly significant survival gain (p=0.001) compared to the control group. °á·Ð:The highly significant survival gain resulting from their use in perioperative adjuvant treatment in vivo and their anticancer effect in vitro suggest that HIF1¥á inhibitors might be candidates perioperative adjuvant chemotherapeutic agents for thyroid cancer. Combining adjuvant HIF1¥á inhibitor chemotherapy with surgery might be an effective therapeutic strategy for thyroid cancer that is refractory to conventional treatments.


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