Dyskin, EvgenyLansing, Lawrence S.Bharali, Dhruba JyotiMousa, Shaymaa S.Bridoux, AlexandreHercbergs, Aleck A.Lin, HungyungDavis, Faith B.Glinsky, Gennadi VictorGlinskii, Anna B.Ma, J.Davis, Paul J.Mousa, S. A.2022-03-302022-03-302010-04Yalçın, M. vd. (2010). "Tetraiodothyroacetic acid (Tetrac) and nanoparticulate tetrac arrest growth of medullary carcinoma of the thyroid". Journal of Clinical Endocrinology and Metabolism, 95(4), 1972-1980.0021-972X1945-7197https://doi.org/10.1210/jc.2009-1926https://academic.oup.com/jcem/article/95/4/1972/2597596?login=truehttp://hdl.handle.net/11452/25463Context: Tetraiodothyroacetic acid (tetrac) blocks angiogenic and tumor cell proliferation actions of thyroid hormone initiated at the cell surface hormone receptor on integrin alpha v beta 3. Tetrac also inhibits angiogenesis initiated by vascular endothelial growth factor and basic fibroblast growth factor. Objective: We tested antiangiogenic and antiproliferative efficacy of tetrac and tetrac nanoparticles (tetrac NP) against human medullary thyroid carcinoma (h-MTC) implants in the chick chorioallantoic membrane (CAM) and h-MTC xenografts in the nude mouse. Design: h-MTCcells were implanted in the CAM model (n = 8 per group); effects of tetrac and tetrac NP at 1 mu g/CAM were determined on tumor angiogenesis and tumor growth after 8 d. h-MTC cells were also implanted sc in nude mice (n = 6 animals per group), and actions on established tumor growth of unmodified tetrac and tetrac NP ip were determined. Results: In the CAM, tetrac and tetrac NP inhibited tumor growth and tumor-associated angiogenesis. In the nude mouse xenograft model, established 450-500 mm(3) h-MTC tumors were reduced in size over 21 d by both tetrac formulations to less than the initial cell mass (100 mm(3)). Tumor tissue hemoglobin content of xenografts decreased by 66% over the course of administration of each drug. RNA microarray and quantitative real-time PCR of tumor cell mRNAs revealed that both tetrac formulations significantly induced antiangiogenic thrombospondin 1 and apoptosis activator gene expression. Conclusions: Acting via a cell surface receptor, tetrac and tetrac NP inhibit growth of h-MTC cells and associated angiogenesis in CAM and mouse xenograft models.eninfo:eu-repo/semantics/openAccessActivated protein-kinaseCell-surface receptorAlpha-cateninProangiogenic actionMicroarray analysisGamma-cateninE-cadherinHormoneExpressionIntegrinEndocrinology & metabolismAnimaliaMus musculusAnimalsAntineoplastic agentsBody weightCarcinoma, medullaryCells, culturedChick embryoChorioallantoic membraneExcipientsFemaleHemoglobinsHumansLactic acidMiceMice, nudeNanoparticlesNeovascularization, pathologicOligonucleotide array sequence analysisPolyglycolic acidReverse transcriptase polymerase chain reactionRNA, neoplasmThyroid neoplasmsThyroxineXenograft model antitumor assaysArticle0002764023000602-s2.0-779516307901972198095420133461Endocrinology & metabolismIntegrin; Thyroid Hormones; Nano-Diamino-TetracAlpha cateninAngiogenesis inhibitorCaspase 2Caspase 8 associated protein 2DFFA proteinFas antigenGlyceraldehyde 3 phosphate dehydrogenaseHemoglobinMessenger RNANanoparticleProteinTetraiodothyroacetic acidThrombospondin 1Unclassified drugVasculotropin AAntineoplastic agentDrug derivativeExcipientHemoglobinLactic acidNanoparticlePolyglycolic acidPolylactic acid polyglycolic acid copolymerPolylactic acid-polyglycolic acid copolymerRNATetraiodothyroacetic acidThyroxineAnimal experimentAnimal tissueAntiangiogenic activityArticleCancer cell cultureCancer inhibitionCancer sizeCell cycle arrestChorioallantoisControlled studyDrug distributionDrug effectDrug efficacyFemaleGene expressionHumanHuman cellHuman cell cultureMicroarray analysisMouseNonhumanPriority journalReal time polymerase chain reactionThyroid medullary carcinomaTissue levelAnimalBiosynthesisBody weightCell cultureChick embryoDNA microarrayDrug screeningGeneticsMedullary carcinomaMetabolismNeovascularization (pathology)Nude mousePathologyReverse transcription polymerase chain reactionThyroid tumor