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Inhibitory Effects of Antagonists of Growth Hormone-Releasing Hormone (GHRH) in Thyroid Cancer.

Inhibitory Effects of Antagonists of Growth Hormone-Releasing Hormone (GHRH) in Thyroid Cancer.
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Pópulo H, Nunes B, Sampaio C, Batista R, Pinto MT, Gaspar TB, Miranda-Alves L, Cai RZ, Zhang XY, Schally AV, Sobrinho-Simões M, Soares P,


Pópulo H, Nunes B, Sampaio C, Batista R, Pinto MT, Gaspar TB, Miranda-Alves L, Cai RZ, Zhang XY, Schally AV, Sobrinho-Simões M, Soares P, (click to view)

Pópulo H, Nunes B, Sampaio C, Batista R, Pinto MT, Gaspar TB, Miranda-Alves L, Cai RZ, Zhang XY, Schally AV, Sobrinho-Simões M, Soares P,

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Hormones & cancer 2017 09 188(5-6) 314-324 doi 10.1007/s12672-017-0307-4

Abstract

Growth hormone-releasing hormone (GHRH) is a peptide hormone secreted by the hypothalamus that regulates the synthesis and secretion of growth hormone (GH) in the pituitary. The extra-hypothalamic GHRH and its cognate receptors (GHRHR and splice variants) play a mitogenic role by stimulating cell proliferation and preventing apoptotic cell death. It is well established that GHRH antagonists inhibit the growth, tumorigenicity, and metastasis of various human malignancies. In this work, we studied the effect of two new GHRH antagonists, MIA602 and MIA690, on thyroid cancer. We studied the effect of MIA602 and MIA690 on thyroid cancer in vitro, using human thyroid cancer cell lines, and in vivo, using chicken embryo chorioallantoic membrane (CAM) assays. We found that mRNA for GHRH and GHRH receptor is expressed in thyroid cell lines and in samples of thyroid tumors. Immunohistochemistry confirmed the expression of GHRHR protein in specimens of thyroid tumor. We observed that GHRH antagonists inhibited the growth and increased apoptosis of thyroid cancer cells. In vivo, the antagonists inhibited growth and angiogenesis of engrafted thyroid tumors. Our results suggest that GHRH expression may play a role in growth of thyroid cancer and that GHRH antagonists can be a therapeutic option for thyroid cancer patients.

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