propylthiouracil and Lung-Neoplasms

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.

Topics: Animals; Antithyroid Agents; Disease Models, Animal; Eye Neoplasms; Hyperthyroidism; Hypothyroidism; Lung Neoplasms; Male; Melanoma; Mice; Mice, Inbred C57BL; Propylthiouracil; Survival Rate; Thyroxine

Topics: Antithyroid Agents; Humans; Hypothyroidism; Insulin-Like Growth Factor I; Lung Neoplasms; Propylthiouracil; Survival Rate

In order to investigate whether goitrogens and liver enzyme-inducers modify the tumorigenesis in the liver or lung, 6-week old male F344 rats were given single subcutaneous injection of DHPN, and starting one week later received water containing goitrogens, namely sulfadimethoxine (SDM), propylthiouracil (PTU) and potassium thiocyanate (KSCN), or an enzyme-inducer, phenobarbital (PB), for 19 weeks ad libitum. Although the number of GST-P positive foci in the liver was significantly increased in the PB group as compared to the control group, there were no significant fluctuations in the SDM, PTU and PB groups. With respect to the lung, it is suggested that SDM, KSCN and PB may enhance the lung tumorigenesis, since the multiplicities of hyperplasias of alveolar epithelia were increased in groups treated with these compounds.

Topics: Animals; Antithyroid Agents; Liver Neoplasms, Experimental; Lung Neoplasms; Male; Nitrosamines; Phenobarbital; Propylthiouracil; Rats; Rats, Inbred F344; Sulfadimethoxine; Thiocyanates

The local growth rate of Morris Hepatoma 44 (generation time, 6 months) was inhibited by 66 to 87%, and host survival was prolonged by 36 to 78% after the induction of hypothyroidism within 2 weeks of tumor implantation by propylthiouracil (0.1% in Purina chow), 131I(1 mCi/100 g body weight i.p.), or surgical thyroidectomy. In additional experiments, we studied the effects of inducing hypothyroidism (131I) at different stages in the natural history of Morris Hepatoma 44 on local and metastatic growth as well as on host survival. Induction of hypothyroidism within 2 weeks of tumor implantation (Group I) reduced local tumor growth as well as the number and size of pulmonary metastases, and prolonged survival by 70 to 80%. Induction of hypothyroidism at 6 weeks postimplantation when tumors were palpable (Group II) inhibited local growth by 39%, reduced the number and size of pulmonary metastases by approximately 80%, and prolonged host survival by 35%. Initiation of 131I treatment at 11 weeks when microscopic pulmonary emboli were present in most animals (Group III) reduced local growth by 19% and the number and size of pulmonary metastases by 72 and 50%, respectively. In this case, survival was prolonged by 17%. We conclude from these results that the local and metastatic growth of Morris hepatoma 44 as well as host survival are thyroid hormone-dependent processes. The mechanisms responsible for these observations remain to be explained.

Topics: Animals; Hypothyroidism; Liver Neoplasms, Experimental; Lung Neoplasms; Male; Neoplasm Metastasis; Propylthiouracil; Rats; Thyroidectomy