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      The avian chorioallantoic membrane as an alternative tool to study medullary thyroid cancer

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          Abstract

          Preclinical trials of medullary thyroid cancer (MTC) therapeutics require both in vitro and in vivo analyses. Human tumour xenografted rodent models, which are considered the ‘gold standard’ to study and validate the efficacy and toxicity of lead compounds before translation to clinical trials, are very expensive, subject to organismal variability and ethical controversies. The avian chorioallantoic membrane (CAM) assay provides an alternative versatile, cost-effective and ethically less objectionable short-term, in vivo model for reliable screening of drugs. In this work, we grafted two MTC cell lines and patient-derived MTC tumour samples onto the avian CAM and characterised the resulted tumours histologically and immunohistochemically. Our findings provide the evidence that the CAM assay is a suitable model for studying the pathophysiology of MTC and can even be used as in vivo system for drug testing.

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          Most cited references16

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          A critical analysis of current in vitro and in vivo angiogenesis assays.

          The study of angiogenesis has grown exponentially over the past 40 years with the recognition that angiogenesis is essential for numerous pathologies and, more recently, with the advent of successful drugs to inhibit angiogenesis in tumours. The main problem with angiogenesis research remains the choice of appropriate assays to evaluate the efficacy of potential new drugs and to identify potential targets within the angiogenic process. This selection is made more complex by the recognition that heterogeneity occurs, not only within the endothelial cells themselves, but also within the specific microenvironment to be studied. Thus, it is essential to choose the assay conditions and cell types that most closely resemble the angiogenic disease being studied. This is especially important when aiming to translate data from in vitro to in vivo and from preclinical to the clinic. Here we critically review and highlight recent advances in the principle assays in common use including those for endothelial cell proliferation, migration, differentiation and co-culture with fibroblasts and mural cells in vitro, vessel outgrowth from organ cultures and in vivo assays such as chick chorioallantoic membrane (CAM), zebrafish, sponge implantation, corneal, dorsal air sac, chamber and tumour angiogenesis models. Finally, we briefly discuss the direction likely to be taken in future studies, which include the use of increasingly sophisticated imaging analysis systems for data acquisition.
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            The chick embryo chorioallantoic membrane (CAM). A multifaceted experimental model

            During avian development the mesodermal layers of the allantois and chorion fuse to form the chorioallantoic membrane (CAM). This structure rapidly expands generating a rich vascular network that provides an interface for gas and waste exchange. The CAM allows to study tissue grafts, tumor growth and metastasis, wound healing, drugs delivery and toxicologic analysis, and angiogenic and anti-angiogenic molecules. The CAM is relatively simple, quick, and low-cost model that allows screening of a large number of pharmacological samples in a short time; does not require administrative procedures for obtaining ethics committee approval for animal experimentation. Moreover, being naturally immunodeficient, the chick embryo may receive transplantations from different tissues and species, without immune responses.
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              The chick embryo chorioallantoic membrane as a model for tumor biology.

              Among the in vivo models, the chick embryo chorioallantoic membrane (CAM) has been used to implant several tumor types as well as malignant cell lines to study their growth rate, angiogenic potential and metastatic capability. This review article is focused on the major compelling literature data on the use of the CAM to investigate tumor growth and the metastatic process.
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                Author and article information

                Journal
                Endocr Connect
                Endocr Connect
                EC
                Endocrine Connections
                Bioscientifica Ltd (Bristol )
                2049-3614
                May 2019
                26 March 2019
                : 8
                : 5
                : 462-467
                Affiliations
                [1]Otto Loewi Research Center – Immunology and Pathophysiology , Medical University of Graz, Graz, Austria
                Author notes
                Correspondence should be addressed to N Ghaffari-Tabrizi-Wizsy: nassim.ghaffari@ 123456medunigraz.at

                *(N Ghaffari-Tabrizi-Wizsy and C A Passegger contributed equally to this work)

                Article
                EC-18-0431
                10.1530/EC-18-0431
                6479196
                30913539
                2b3949b1-43e5-4503-b257-5756dbb7a000
                © 2019 The authors

                This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.

                History
                : 14 January 2019
                : 26 March 2019
                Categories
                Research

                medullary thyroid carcinoma,endocrine cancers,precilinal trials,3r

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