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Incomplete Success of Angioinhibitor Therapy in Cancer: Estimation of Contribution of Pro-angiogenic Activity of Patient Thyroid Hormone

Abstract

Paul J Davis, Murat Yalcin, Hung-Yun Lin, Heng-Yuan Tang, Aleck Hercbergs, John T. Leith, Faith B Davis, Mary K Luidens and Shaker A Mousa

Despite the obvious promise of the strategy, pharmaceutical angioinhibition has had variable success in clinical cancer management. Thyroid hormone is a potent pro-angiogenic factor. Endogenous circulating levels of proangiogenic thyroid hormone in cancer patients treated with anti-angiogenic drugs may contribute to host resistance to angioinhibition and explain, at least in part, the variable cancer chemotherapeutic responses obtained with anti-angiogenic agents. The chick chorioallantoic membrane (CAM) angiogenesis assay accepts human tumor xenografts and is a system in which individual patient blood samples can be tested in xenograft vasculature for anti-angiogenic content—including thyroid hormone—in the presence of angioinhibitory drug dose escalation. The assay may also be used to screen individual patient tumor biopsy xenografts for susceptibility to angioinhibition.

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