¹ßÇ¥Çü½Ä :
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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
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¸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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