Tetrac Delayed the Onset of Ocular Melanoma in an Orthotopic Mouse Model

Ashur‐Fabian, Osnat; Zloto, Ofira; Fabian, Ina; Tsarfaty, Galya; Ellis, Martin; Steinberg, David M.; Hercbergs, Aleck; Davis, Paul J.; Fabian, Ido Didi

doi:10.3389/fendo.2018.00775

Cited by 8 publications

(7 citation statements)

References 51 publications

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“…The integrin αvβ3-mediated TH actions that are relevant to cancer biology can be regulated by the 3,3′,5,5′-tetraiodothyroacetic acid—a deaminated form of T4 known as tetrac—and its nanoparticulate analog—known as nano-diamino-tetrac (NDAT) or tetrac-NP [ 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 , 71 ]. Tetrac is a monocarboxylic acid carrying four iodo substituents at positions 3, 3′, 5 and 5′.…”

Section: Molecular Aspects Of the Actions Of Thmentioning

confidence: 99%

The Intriguing Thyroid Hormones–Lung Cancer Association as Exemplification of the Thyroid Hormones–Cancer Association: Three Decades of Evolving Research

Deligiorgi

Trafalis

2021

IJMS

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Exemplifying the long-pursued thyroid hormones (TH)–cancer association, the TH–lung cancer association is a compelling, yet elusive, issue. The present narrative review provides background knowledge on the molecular aspects of TH actions, with focus on the contribution of TH to hallmarks of cancer. Then, it provides a comprehensive overview of data pertinent to the TH–lung cancer association garnered over the last three decades and identifies obstacles that need to be overcome to enable harnessing this association in the clinical setting. TH contribute to all hallmarks of cancer through integration of diverse actions, currently classified according to molecular background. Despite the increasingly recognized implication of TH in lung cancer, three pending queries need to be resolved to empower a tailored approach: (1) How to stratify patients with TH-sensitive lung tumors? (2) How is determined whether TH promote or inhibit lung cancer progression? (3) How to mimic the antitumor and/or abrogate the tumor-promoting TH actions in lung cancer? To address these queries, research should prioritize the elucidation of the crosstalk between TH signaling and oncogenic signaling implicated in lung cancer initiation and progression, and the development of efficient, safe, and feasible strategies leveraging this crosstalk in therapeutics.

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Section: Molecular Aspects Of the Actions Of Thmentioning

confidence: 99%

The Intriguing Thyroid Hormones–Lung Cancer Association as Exemplification of the Thyroid Hormones–Cancer Association: Three Decades of Evolving Research

Deligiorgi

Trafalis

2021

IJMS

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“…Overexpression and activation of the protein renders tumor cells susceptible to actions of T4 to stimulate proliferation, to support cancer cell defense pathways such as anti-apoptosis (7) and radioresistance (8), and to enhance cancer-related angiogenesis (2,3,9,10). Preclinical studies have shown a variety of tumor cells to proliferate in response to physiological concentrations of T4 (11)(12)(13)(14). A derivative of T4, tetraiodothyroacetic acid (tetrac), blocks actions of T4 on tumor cell avb3 (3).…”

Section: Introductionmentioning

confidence: 99%

Actions of Thyroid Hormones on Thyroid Cancers

et al. 2021

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L-Thyroxine (T4) is the principal ligand of the thyroid hormone analogue receptor on the extracellular domain of integrin αvβ3. The integrin is overexpressed and activated in cancer cells, rapidly dividing endothelial cells, and platelets. The biologic result is that T4 at physiological concentration and without conversion to 3,3’,5-triiodo-L-thyronine (T3) may stimulate cancer cell proliferation and cancer-relevant angiogenesis and platelet coagulation. Pro-thrombotic activity of T4 on platelets is postulated to support cancer-linked blood clotting and to contribute to tumor cell metastasis. We examine some of these findings as they may relate to cancers of the thyroid. Differentiated thyroid cancer cells respond to physiological levels of T4 with increased proliferation. Thus, the possibility exists that in patients with differentiated thyroid carcinomas in whom T4 administration and consequent endogenous thyrotropin suppression have failed to arrest the disease, T4 treatment may be stimulating tumor cell proliferation. In vitro studies have shown that tetraiodothyroacetic acid (tetrac), a derivative of T4, acts via the integrin to block T4 support of thyroid cancer and other solid tumor cells. Actions of T4 and tetrac or chemically modified tetrac modulate gene expression in thyroid cancer cells. T4 induces radioresistance via induction of a conformational change in the integrin in various cancer cells, although not yet established in thyroid cancer cells. The thyroid hormone receptor on integrin αvβ3 mediates a number of actions of T4 on differentiated thyroid cancer cells that support the biology of the cancer. Additional studies are required to determine whether T4 acts on thyroid cancer cells.

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“…Given the promising capacity of luciferase-expressing melanoma cells to grow and to be quantified after grafting in zebrafish eyes, we decided to extend this assay to a well-established murine melanoma model suitable for investigating the mechanisms responsible for uveal melanoma liver tropism [ 30 , 31 , 32 ], immunologic and angiogenic aspects [ 33 ], and drug response [ 34 , 35 , 36 , 37 ]. On this basis, B16-LS9-luc + cells were injected in the zebrafish embryo eye, grafts were analyzed at t 0 and t 4 , and immunohistochemical analysis of cell grafts showed that tumor cells proliferate, as already observed for B16-BL6 tumors ( Figure 4 A).…”

Section: Resultsmentioning

confidence: 99%

An Orthotopic Model of Uveal Melanoma in Zebrafish Embryo: A Novel Platform for Drug Evaluation

et al. 2021

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Uveal melanoma is a highly metastatic tumor, representing the most common primary intraocular malignancy in adults. Tumor cell xenografts in zebrafish embryos may provide the opportunity to study in vivo different aspects of the neoplastic disease and its response to therapy. Here, we established an orthotopic model of uveal melanoma in zebrafish by injecting highly metastatic murine B16-BL6 and B16-LS9 melanoma cells, human A375M melanoma cells, and human 92.1 uveal melanoma cells into the eye of zebrafish embryos in the proximity of the developing choroidal vasculature. Immunohistochemical and immunofluorescence analyses showed that melanoma cells proliferate during the first four days after injection and move towards the eye surface. Moreover, bioluminescence analysis of luciferase-expressing human 92.1 uveal melanoma cells allowed the quantitative assessment of the antitumor activity exerted by the canonical chemotherapeutic drugs paclitaxel, panobinostat, and everolimus after their injection into the grafted eye. Altogether, our data demonstrate that the zebrafish embryo eye is a permissive environment for the growth of invasive cutaneous and uveal melanoma cells. In addition, we have established a new luciferase-based in vivo orthotopic model that allows the quantification of human uveal melanoma cells engrafted in the zebrafish embryo eye, and which may represent a suitable tool for the screening of novel drug candidates for uveal melanoma therapy.

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Tetrac Delayed the Onset of Ocular Melanoma in an Orthotopic Mouse Model

Cited by 8 publications

References 51 publications

The Intriguing Thyroid Hormones–Lung Cancer Association as Exemplification of the Thyroid Hormones–Cancer Association: Three Decades of Evolving Research

The Intriguing Thyroid Hormones–Lung Cancer Association as Exemplification of the Thyroid Hormones–Cancer Association: Three Decades of Evolving Research

Actions of Thyroid Hormones on Thyroid Cancers

An Orthotopic Model of Uveal Melanoma in Zebrafish Embryo: A Novel Platform for Drug Evaluation

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