Tetraidothyroacetic Acid (Tetrac) and Tetrac Nanoparticles Inhibit Growth of Human Renal Cell Carcinoma Xenografts

Renal cell carcinoma is the most lethal of the common urologic malignancies, with no available effective therapeutics. Tetrac (tetraiodothyroacetic acid) is a deaminated analogue of L-thyroxine (T 4 ) that blocks the pro-angiogenesis actions of T 4 and 3, 5, 3′-triiodo-L-thyronine as well as other...

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Bibliographic Details
Published in:Anticancer research 2009-10, Vol.29 (10), p.3825-3831
Main Authors: YALCIN, M, BHARALI, D. J, LANSING, L, DYSKIN, E, MOUSA, S. S, HERCBERGS, A, DAVIS, F. B, DAVIS, P. J, MOUSA, S. A
Format: Article
Language:English
Subjects:
Animals
Biological and medical sciences
Carcinoma, Renal Cell - blood supply
Carcinoma, Renal Cell - drug therapy
Carcinoma, Renal Cell - pathology
Cell Growth Processes - drug effects
Cell Line, Tumor
Chick Embryo
Chorioallantoic Membrane - blood supply
Chorioallantoic Membrane - drug effects
Humans
Kidney Neoplasms - blood supply
Kidney Neoplasms - drug therapy
Kidney Neoplasms - pathology
Kidneys
Lactic Acid - administration & dosage
Lactic Acid - chemistry
Lactic Acid - pharmacokinetics
Medical sciences
Mice
Nanoparticles - administration & dosage
Nanoparticles - chemistry
Neovascularization, Pathologic - drug therapy
Neovascularization, Pathologic - pathology
Nephrology. Urinary tract diseases
Polyglycolic Acid - administration & dosage
Polyglycolic Acid - chemistry
Polyglycolic Acid - pharmacokinetics
Thyroxine - administration & dosage
Thyroxine - analogs & derivatives
Thyroxine - chemistry
Thyroxine - pharmacokinetics
Tumors
Tumors of the urinary system
Xenograft Model Antitumor Assays
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Summary:Renal cell carcinoma is the most lethal of the common urologic malignancies, with no available effective therapeutics. Tetrac (tetraiodothyroacetic acid) is a deaminated analogue of L-thyroxine (T 4 ) that blocks the pro-angiogenesis actions of T 4 and 3, 5, 3′-triiodo-L-thyronine as well as other growth factors at the cell surface receptor for thyroid hormone on integrin αvβ3. Since this integrin is expressed on cancer cells and also on endothelial and vascular smooth cells, the possibility exists that Tetrac may act on both cell types to block the proliferative effects of thyroid hormone on tumor growth and tumor-related angiogenesis. To test this hypothesis, we determined the effect of Tetrac on tumor cell proliferation and on related angiogenesis of human renal cell carcinoma (RCC). We used two models: tumor cell implants in the chick chorioallantoic membrane (CAM) system and xenografts in nude mice. To determine the relative contribution of the nuclear versus the plasma membrane action of Tetrac, we compared the effects of unmodified Tetrac to Tetrac covalently linked to poly (lactide-co-glycolide) as a nanoparticle (Tetrac NP) that acts exclusively at the cell surface through the integrin receptor. In the CAM model, Tetrac and Tetrac NP (both at 1 μg/CAM) arrested tumor-related angiogenesis and tumor growth. In the mouse xenograft model, Tetrac and Tetrac NP promptly reduced tumor volume (p
ISSN:0250-7005
1791-7530