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

Fabian ID, Rosner M, Fabian I, Vishnevskia-Dai V, Zloto O, Shinderman Maman E, Cohen K, Ellis M, Lin HY, Hercbergs A, Davis PJ, Ashur-Fabian O - Oncotarget (2015)

Bottom Line: We aimed to examine the impact of thyroid status on survival in a murine B16F10 model for ocular melanoma, highly expressing the integrin.At day 21, the subretinal space was inoculated with 10(2) B16F10 cells.FT4 levels differed significantly between groups (P<0.001) and with no signs of illness in the internal control group.

View Article: PubMed Central - PubMed

Affiliation: Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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.

No MeSH data available.


Related in: MedlinePlus

(A) Differences in time from inoculation to clinical evidence of intraocular tumor growth, (B) tumor growth to death and (C) inoculation to death (survival time) between the PTU (n=8), thyroxine (n=11) and control (n=9) groups. Data are presented as mean ± standard deviation. PTU – propylthiouracil.
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Figure 4: (A) Differences in time from inoculation to clinical evidence of intraocular tumor growth, (B) tumor growth to death and (C) inoculation to death (survival time) between the PTU (n=8), thyroxine (n=11) and control (n=9) groups. Data are presented as mean ± standard deviation. PTU – propylthiouracil.

Mentions: Figure 4 shows the differences in time from inoculation to clinical evidence of intraocular tumor growth (Figure 4A), tumor growth to death (Figure 4B) and the survival time from the day of inoculation till death (Figure 4C) of the different experimental groups. The PTU group had a significantly longer inoculation-to-tumor time (Figure 4A) than the control group (p = 0.019), whereas there were no significant differences between the control and thyroxine groups (p = 0.626). Of note, intraocular tumors were diagnosed significantly earlier in the thyroxine group compared to the PTU group (p = 0.003).


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

Fabian ID, Rosner M, Fabian I, Vishnevskia-Dai V, Zloto O, Shinderman Maman E, Cohen K, Ellis M, Lin HY, Hercbergs A, Davis PJ, Ashur-Fabian O - Oncotarget (2015)

(A) Differences in time from inoculation to clinical evidence of intraocular tumor growth, (B) tumor growth to death and (C) inoculation to death (survival time) between the PTU (n=8), thyroxine (n=11) and control (n=9) groups. Data are presented as mean ± standard deviation. PTU – propylthiouracil.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4484437&req=5

Figure 4: (A) Differences in time from inoculation to clinical evidence of intraocular tumor growth, (B) tumor growth to death and (C) inoculation to death (survival time) between the PTU (n=8), thyroxine (n=11) and control (n=9) groups. Data are presented as mean ± standard deviation. PTU – propylthiouracil.
Mentions: Figure 4 shows the differences in time from inoculation to clinical evidence of intraocular tumor growth (Figure 4A), tumor growth to death (Figure 4B) and the survival time from the day of inoculation till death (Figure 4C) of the different experimental groups. The PTU group had a significantly longer inoculation-to-tumor time (Figure 4A) than the control group (p = 0.019), whereas there were no significant differences between the control and thyroxine groups (p = 0.626). Of note, intraocular tumors were diagnosed significantly earlier in the thyroxine group compared to the PTU group (p = 0.003).

Bottom Line: We aimed to examine the impact of thyroid status on survival in a murine B16F10 model for ocular melanoma, highly expressing the integrin.At day 21, the subretinal space was inoculated with 10(2) B16F10 cells.FT4 levels differed significantly between groups (P<0.001) and with no signs of illness in the internal control group.

View Article: PubMed Central - PubMed

Affiliation: Goldschleger Eye Institute, Sheba Medical Center, Tel Hashomer, affiliated to Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.

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.

No MeSH data available.


Related in: MedlinePlus