title: Low thyroid hormone levels improve survival in murine model for ocular melanoma.
abstract: 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 10(2) 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.
authors: Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Ido Didi
authors: ID
authors: Fabian
authors: Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Mordechai
authors: M
authors: Rosner
authors: Department of Cell and Developmental Biology, The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Ina
authors: I
authors: Fabian
authors: Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Vicktoria
authors: V
authors: Vishnevskia-Dai
authors: Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Ofira
authors: O
authors: Zloto
authors: Department of Human Molecular Genetics and Biochemistry, The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Elena
authors: E
authors: Shinderman Maman
authors: Department of Human Molecular Genetics and Biochemistry, The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Keren
authors: K
authors: Cohen
authors: Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Martin
authors: M
authors: Ellis
authors: Institute of Cancer Biology and Drug Discovery, School of Medical Technology, Taipei Medical University, Taipei, Taiwan.|Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.
authors: Hung-Yun
authors: HY
authors: Lin
authors: Department of Radiation Oncology, Cleveland Clinic, Cleveland, OH, USA.
authors: Aleck
authors: A
authors: Hercbergs
authors: Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Albany, NY, USA.|Department of Medicine, Albany Medical College, Albany, NY, USA.
authors: Paul J
authors: PJ
authors: Davis
authors: Department of Human Molecular Genetics and Biochemistry, The Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.|Translational Hemato-Oncology Laboratory, The Hematology Institute and Blood Bank, Meir Medical Center, Kfar-Saba, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors: Osnat
authors: O
authors: Ashur-Fabian
mesh_terms: D000818:Animals; D013956:Antithyroid Agents / Q000494:pharmacology*; D004195:Disease Models, Animal; D005134:Eye Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D006980:Hyperthyroidism / Q000139:chemically induced / Q000473:pathology*; D007037:Hypothyroidism / Q000139:chemically induced / Q000473:pathology*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000556:secondary; D008297:Male; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D011441:Propylthiouracil / Q000633:toxicity; D015996:Survival Rate; D013974:Thyroxine / Q000633:toxicity
chemical_list: D013956:Antithyroid Agents; D011441:Propylthiouracil; D013974:Thyroxine
keywords: integrin; thyroid; uveal melanoma