Low thyroid hormone levels improve survival in murine model for ocular melanoma

Ido Didi Fabian, Mordechai Rosner, Ina Fabian, Vicktoria Vishnevskia-Dai, Ofira Zloto, Elena Shinderman Maman, Keren Cohen, Martin Ellis, Hung Yun Lin, Aleck Hercbergs, Paul J. Davis, Osnat Ashur-Fabian

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27 引文 斯高帕斯(Scopus)

摘要

Uveal melanoma is highly metastatic, prognosis is poor and there are no effective treatments to extend survival. Accumulating evidence suggests that thyroid hormones have a mitogenic effect via binding to αvβ3 integrin. We aimed to examine the impact of thyroid status on survival in a murine B16F10 model for ocular melanoma, highly expressing the integrin. In two independent experiments oral propylthiouracil (PTU) was used to induce hypothyroidism (n=9), thyroxine to induce hyperthyroidism (n=11) and mice given plain water served as control (n=8). At day 21, the subretinal space was inoculated with 102 B16F10 cells. In non-inoculated mice (n=6 of each group) serum free T4 (FT4) levels were measured and additional non-inoculated mice (3 given PTU and 4 given thyroxine or water) served as internal control to demonstrate the impact of the dissolved substance. The PTU-inoculated mice showed clinical evidence of intraocular tumor growth significantly later than the thyroxine mice (P=0.003) and survival time was significantly longer (P<0.001). FT4 levels differed significantly between groups (P<0.001) and with no signs of illness in the internal control group. Our findings suggest that hyperthyroidism shortens survival, whereas relative hypothyroidism may have a protective role in metastatic ocular melanoma.
原文英語
頁(從 - 到)11038-11046
頁數9
期刊Oncotarget
6
發行號13
出版狀態已發佈 - 2015

ASJC Scopus subject areas

  • 腫瘤科

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