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Deprecated: Implicit conversion from float 209.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 Horm+Cancer 2017 ; 8 (3): 157-65 Nephropedia Template TP
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Nanoparticulate Tetrac Inhibits Growth and Vascularity of Glioblastoma Xenografts #MMPMID28396979
Sudha T; Bharali DJ; Sell S; Darwish NHE; Davis PJ; Mousa SA
Horm Cancer 2017[Jun]; 8 (3): 157-65 PMID28396979show ga
Thyroid hormone as L-thyroxine (T4) stimulates proliferation of glioma cells in vitro and medical induction of hypothyroidism slows clinical growth of glioblastoma multiforme (GBM). The proliferative action of T4 on glioma cells is initiated nongenomically at a cell surface receptor for thyroid hormone on the extracellular domain of integrin ?v?3. Tetraiodothyroacetic acid (tetrac) is a thyroid hormone derivative that blocks T4 action at ?v?3 and has anticancer and anti-angiogenic activity. Tetrac has been covalently bonded via a linker to a nanoparticle (Nanotetrac, Nano-diamino-tetrac, NDAT) that increases the potency of tetrac and broadens the anticancer properties of the drug. In the present studies of human GBM xenografts in immunodeficient mice, NDAT administered daily for 10 days subcutaneously as 1 mg tetrac equivalent/kg reduced tumor xenograft weight at animal sacrifice by 50%, compared to untreated control lesions (p < 0.01). Histopathological analysis of tumors revealed a 95% loss of the vascularity of treated tumors compared to controls at 10 days (p < 0.001), without intratumoral hemorrhage. Up to 80% of tumor cells were necrotic in various microscopic fields (p < 0.001 vs. control tumors), an effect attributable to devascularization. There was substantial evidence of apoptosis in other fields (p < 0.001 vs. control tumors). Induction of apoptosis in cancer cells is a well-described quality of NDAT. In summary, systemic NDAT has been shown to be effective by multiple mechanisms in treatment of GBM xenografts.Electronic supplementary material: The online version of this article (doi:10.1007/s12672-017-0293-6) contains supplementary material, which is available to authorized users.