{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:07Z","timestamp":1760146867130,"version":"build-2065373602"},"reference-count":62,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T00:00:00Z","timestamp":1734048000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Medullary thyroid carcinoma (MTC), a rare neuroendocrine tumor comprising 3\u20135% of thyroid cancers, arises from calcitonin-producing parafollicular C cells. Despite aggressive behavior, surgery remains the primary curative treatment, with limited efficacy reported for radiotherapy and chemotherapy. Recent efforts have explored the pathogenetic mechanisms of MTC, identifying it as a highly vascularized neoplasm overexpressing pro-angiogenic factors. Building on the established benefits of zebrafish embryos, we previously created an in vivo MTC xenograft platform that allows real-time observation of tumor-induced angiogenesis and evaluation of the anti-angiogenic effects of tyrosine kinase inhibitors. In this study, we present a method using selective plane illumination microscopy (SPIM) to characterize vascular permeability in these xenografted embryos. Taking advantage of dextran injections into the blood flow of zebrafish embryos, we found that the diffusion coefficient in embryos grafted with MTC cells was about tenfold lower compared with the same parameter in controls. The results demonstrate the potential of our approach to estimate diffusion parameters, providing valuable insights into vascular permeability changes in MTC-implanted zebrafish embryos compared with controls. Our study sheds light on the intricate vascular biology of MTC, offering a promising tool for future investigations into tumor-induced angiogenesis and therapeutic strategies in diverse neoplasms.<\/jats:p>","DOI":"10.3390\/ijms252413392","type":"journal-article","created":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T08:10:47Z","timestamp":1734077447000},"page":"13392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["How Tumors Affect Hemodynamics: A Diffusion Study on the Zebrafish Transplantable Model of Medullary Thyroid Carcinoma by Selective Plane Illumination Microscopy"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9321-9508","authenticated-orcid":false,"given":"Silvia","family":"Carra","sequence":"first","affiliation":[{"name":"Laboratory of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Germano","family":"Gaudenzi","sequence":"additional","affiliation":[{"name":"Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS Istituto Auxologico Italiano, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgia","family":"Franceschetti","sequence":"additional","affiliation":[{"name":"Department of Physics \u201cG. Occhialini\u201d, Universit\u00e0 degli Studi di Milano-Bicocca, Piazza Della Scienza 3, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6240-0216","authenticated-orcid":false,"given":"Maddalena","family":"Collini","sequence":"additional","affiliation":[{"name":"Department of Physics \u201cG. Occhialini\u201d, Universit\u00e0 degli Studi di Milano-Bicocca, Piazza Della Scienza 3, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6638-7709","authenticated-orcid":false,"given":"Laura","family":"Sironi","sequence":"additional","affiliation":[{"name":"Department of Physics \u201cG. Occhialini\u201d, Universit\u00e0 degli Studi di Milano-Bicocca, Piazza Della Scienza 3, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaux","family":"Bouzin","sequence":"additional","affiliation":[{"name":"Department of Physics \u201cG. Occhialini\u201d, Universit\u00e0 degli Studi di Milano-Bicocca, Piazza Della Scienza 3, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2068-9581","authenticated-orcid":false,"given":"Luca","family":"Persani","sequence":"additional","affiliation":[{"name":"Laboratory of Endocrine and Metabolic Research, IRCCS Istituto Auxologico Italiano, 20100 Milan, Italy"},{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6578-6460","authenticated-orcid":false,"given":"Giuseppe","family":"Chirico","sequence":"additional","affiliation":[{"name":"Department of Physics \u201cG. Occhialini\u201d, Universit\u00e0 degli Studi di Milano-Bicocca, Piazza Della Scienza 3, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2478-683X","authenticated-orcid":false,"given":"Giovanni","family":"Vitale","sequence":"additional","affiliation":[{"name":"Laboratory of Geriatric and Oncologic Neuroendocrinology Research, IRCCS Istituto Auxologico Italiano, 20100 Milan, Italy"},{"name":"Department of Medical Biotechnology and Translational Medicine, University of Milan, 20100 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7378-4462","authenticated-orcid":false,"given":"Laura","family":"D\u2019Alfonso","sequence":"additional","affiliation":[{"name":"Department of Physics \u201cG. Occhialini\u201d, Universit\u00e0 degli Studi di Milano-Bicocca, Piazza Della Scienza 3, 20126 Milan, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2024,12,13]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2307","DOI":"10.1056\/NEJMra1501993","article-title":"Biologic and Clinical Perspectives on Thyroid Cancer","volume":"375","author":"Fagin","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"933","DOI":"10.1210\/js.2018-00178","article-title":"Update on Multiple Endocrine Neoplasia Type 2: Focus on Medullary Thyroid Carcinoma","volume":"2","author":"Raue","year":"2018","journal-title":"J. Endocr. Soc."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1002\/jso.20690","article-title":"Current approaches to medullary thyroid carcinoma, sporadic and familial","volume":"94","author":"Fialkowski","year":"2006","journal-title":"J. Surg. Oncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1046\/j.1365-2265.1998.00392.x","article-title":"Prognostic factors for survival and for biochemical cure in medullary thyroid carcinoma: Results in 899 patients. The GETC Study Group. Groupe d\u2019etude des tumeurs a calcitonine","volume":"48","author":"Modigliani","year":"1998","journal-title":"Clin. Endocrinol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1797","DOI":"10.1002\/1097-0142(20010501)91:9<1797::AID-CNCR1199>3.0.CO;2-P","article-title":"Current approaches and perspectives in the therapy of medullary thyroid carcinoma","volume":"91","author":"Vitale","year":"2001","journal-title":"Cancer"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1114","DOI":"10.1002\/(SICI)1097-0142(19960901)78:5<1114::AID-CNCR23>3.0.CO;2-4","article-title":"Treatment of advanced medullary thyroid carcinoma with a combination of recombinant interferon alpha-2b and octreotide","volume":"78","author":"Lupoli","year":"1996","journal-title":"Cancer"},{"key":"ref_7","first-page":"983","article-title":"Slow release lanreotide in combination with interferon-alpha2b in the treatment of symptomatic advanced medullary thyroid carcinoma","volume":"85","author":"Vitale","year":"2000","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1579","DOI":"10.1073\/pnas.91.4.1579","article-title":"Single missense mutation in the tyrosine kinase catalytic domain of the RET protooncogene is associated with multiple endocrine neoplasia type 2B","volume":"91","author":"Carlson","year":"1994","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1038\/367375a0","article-title":"A mutation in the RET proto-oncogene associated with multiple endocrine neoplasia type 2B and sporadic medullary thyroid carcinoma","volume":"367","author":"Hofstra","year":"1994","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1046\/j.1365-2265.1996.681503.x","article-title":"Somatic mutations in the RET proto-oncogene in sporadic medullary thyroid carcinoma","volume":"44","author":"Marsh","year":"1996","journal-title":"Clin. Endocrinol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"458","DOI":"10.1038\/363458a0","article-title":"Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A","volume":"363","author":"Mulligan","year":"1993","journal-title":"Nature"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"3149","DOI":"10.1210\/jc.2013-1204","article-title":"Multiple endocrine neoplasia type 2 and familial medullary thyroid carcinoma: An update","volume":"98","author":"Wells","year":"2013","journal-title":"J. Clin. Endocrinol. Metab."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1002\/med.21409","article-title":"Approved and Experimental Small-Molecule Oncology Kinase Inhibitor Drugs: A Mid-2016 Overview","volume":"37","author":"Fischer","year":"2017","journal-title":"Med. Res. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"285","DOI":"10.1016\/j.ecl.2018.11.006","article-title":"Management of Medullary Thyroid Cancer","volume":"48","author":"Viola","year":"2019","journal-title":"Endocrinol. Metab. Clin. N. Am."},{"key":"ref_15","first-page":"4645","article-title":"ZD6474 inhibits vascular endothelial growth factor signaling, angiogenesis, and tumor growth following oral administration","volume":"62","author":"Wedge","year":"2002","journal-title":"Cancer Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2298","DOI":"10.1158\/1535-7163.MCT-11-0264","article-title":"Cabozantinib (XL184), a novel MET and VEGFR2 inhibitor, simultaneously suppresses metastasis, angiogenesis, and tumor growth","volume":"10","author":"Yakes","year":"2011","journal-title":"Mol. Cancer Ther."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"e31681","DOI":"10.1016\/j.heliyon.2024.e31681","article-title":"Efficacy and safety of selpercatinib in treating RET-altered MTC: A single-arm meta-analysis","volume":"10","author":"Huang","year":"2024","journal-title":"Heliyon"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"825","DOI":"10.1056\/NEJMoa2005651","article-title":"Efficacy of Selpercatinib in RET-Altered Thyroid Cancers","volume":"383","author":"Wirth","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1089\/thy.2023.0363","article-title":"Pralsetinib in Patients with Advanced\/Metastatic Rearranged During Transfection (RET)-Altered Thyroid Cancer: Updated Efficacy and Safety Data from the ARROW Study","volume":"34","author":"Subbiah","year":"2024","journal-title":"Thyroid"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"491","DOI":"10.1016\/S2213-8587(21)00120-0","article-title":"Pralsetinib for patients with advanced or metastatic RET-altered thyroid cancer (ARROW): A multi-cohort, open-label, registrational, phase 1\/2 study","volume":"9","author":"Subbiah","year":"2021","journal-title":"Lancet Diabetes Endocrinol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"803171","DOI":"10.1155\/2013\/803171","article-title":"Cellular signaling pathway alterations and potential targeted therapies for medullary thyroid carcinoma","volume":"2013","author":"Giunti","year":"2013","journal-title":"Int. J. Endocrinol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1530\/ERC-12-0316","article-title":"Influence of RET mutations on the expression of tyrosine kinases in medullary thyroid carcinoma","volume":"20","author":"Mancikova","year":"2013","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1677\/ERC-08-0304","article-title":"Overexpression and activation of EGFR and VEGFR2 in medullary thyroid carcinomas is related to metastasis","volume":"17","author":"Pallares","year":"2010","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"665","DOI":"10.1530\/ERC-16-0132","article-title":"RET mutation and increased angiogenesis in medullary thyroid carcinomas","volume":"23","author":"Verrienti","year":"2016","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"298","DOI":"10.1038\/nature10144","article-title":"Molecular mechanisms and clinical applications of angiogenesis","volume":"473","author":"Carmeliet","year":"2011","journal-title":"Nature"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/S0092-8674(00)81683-9","article-title":"The hallmarks of cancer","volume":"100","author":"Hanahan","year":"2000","journal-title":"Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1219","DOI":"10.1038\/nm.1971","article-title":"Three-dimensional microscopy of the tumor microenvironment in vivo using optical frequency domain imaging","volume":"15","author":"Vakoc","year":"2009","journal-title":"Nat. Med."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"a006684","DOI":"10.1101\/cshperspect.a006684","article-title":"Vascular development in the zebrafish","volume":"2","author":"Gore","year":"2012","journal-title":"Cold Spring Harb Perspect. Med."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1006\/dbio.2000.9995","article-title":"The vascular anatomy of the developing zebrafish: An atlas of embryonic and early larval development","volume":"230","author":"Isogai","year":"2001","journal-title":"Dev. Biol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"781","DOI":"10.1038\/nature05577","article-title":"Notch signalling limits angiogenic cell behaviour in developing zebrafish arteries","volume":"445","author":"Siekmann","year":"2007","journal-title":"Nature"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1371","DOI":"10.1016\/j.bbadis.2013.01.016","article-title":"Zebrafish embryo as a tool to study tumor\/endothelial cell cross-talk","volume":"1832","author":"Tobia","year":"2013","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_32","doi-asserted-by":"crossref","unstructured":"Carra, S., Foglia, E., Cermenati, S., Bresciani, E., Giampietro, C., Lora Lamia, C., Dejana, E., Beltrame, M., and Cotelli, F. (2012). Ve-ptp modulates vascular integrity by promoting adherens junction maturation. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051245"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1016\/j.brainresbull.2007.10.043","article-title":"Functional and developmental analysis of the blood-brain barrier in zebrafish","volume":"75","author":"Jeong","year":"2008","journal-title":"Brain Res. Bull"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1143","DOI":"10.1038\/nm1195-1143","article-title":"Gridlock, a localized heritable vascular patterning defect in the zebrafish","volume":"1","author":"Weinstein","year":"1995","journal-title":"Nat. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"dev173757","DOI":"10.1242\/dev.173757","article-title":"Multi-sample SPIM image acquisition, processing and analysis of vascular growth in zebrafish","volume":"146","author":"Daetwyler","year":"2019","journal-title":"Development"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1126\/science.1100035","article-title":"Optical sectioning deep inside live embryos by selective plane illumination microscopy","volume":"305","author":"Huisken","year":"2004","journal-title":"Science"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Carra, S., Gaudenzi, G., Dicitore, A., Saronni, D., Cantone, M.C., Plebani, A., Ghilardi, A., Borghi, M.O., Hofland, L.J., and Persani, L. (2021). Vandetanib versus Cabozantinib in Medullary Thyroid Carcinoma: A Focus on Anti-Angiogenic Effects in Zebrafish Model. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22063031"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"R1","DOI":"10.1530\/ERC-16-0399","article-title":"Animal models of medullary thyroid cancer: State of the art and view to the future","volume":"24","author":"Vitale","year":"2017","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/S0145-305X(03)00103-4","article-title":"Development and maturation of the immune system in zebrafish, Danio rerio: A gene expression profiling, in situ hybridization and immunological study","volume":"28","author":"Lam","year":"2004","journal-title":"Dev. Comp. Immunol."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Carra, S., Gaudenzi, G., Dicitore, A., Cantone, M.C., Plebani, A., Saronni, D., Zappavigna, S., Caraglia, M., Candeo, A., and Bassi, A. (2022). Modeling Lung Carcinoids with Zebrafish Tumor Xenograft. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23158126"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Saronni, D., Gaudenzi, G., Dicitore, A., Carra, S., Cantone, M.C., Borghi, M.O., Barbieri, A., Mignani, L., Hofland, L.J., and Persani, L. (2022). Preclinical Evaluation of Novel Tyrosine-Kinase Inhibitors in Medullary Thyroid Cancer. Cancers, 14.","DOI":"10.3390\/cancers14184442"},{"key":"ref_42","first-page":"83","article-title":"Determination of agarose gel pore size: Absorbance measurements vis a vis other techniques","volume":"Volume 28","author":"Narayanan","year":"2006","journal-title":"International Conference on Materials for Advanced Technologies (Icmat 2005)"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"537","DOI":"10.1016\/j.jfoodeng.2012.03.024","article-title":"Investigation of the diffusion of dyes in agar gels","volume":"111","author":"Samprovalaki","year":"2012","journal-title":"J. Food Eng."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"1215","DOI":"10.1364\/OL.28.001215","article-title":"Measurement of dye diffusion in agar gel by use of low-coherence interferometry","volume":"28","author":"Storen","year":"2003","journal-title":"Opt. Lett."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2710","DOI":"10.1016\/S0006-3495(04)74325-8","article-title":"Size effects on diffusion processes within agarose gels","volume":"86","author":"Starchev","year":"2004","journal-title":"Biophys. J."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1038\/sj.bjc.6604929","article-title":"Why are tumour blood vessels abnormal and why is it important to know?","volume":"100","author":"Nagy","year":"2009","journal-title":"Br. J. Cancer"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1039","DOI":"10.1107\/S1600577517008372","article-title":"Analysis of the microvascular morphology and hemodynamics of breast cancer in mice using SPring-8 synchrotron radiation microangiography","volume":"24","author":"Torii","year":"2017","journal-title":"J. Synchrotron. Radiat."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3109\/03009734.2015.1064501","article-title":"Vascular permeability--the essentials","volume":"120","year":"2015","journal-title":"Ups. J. Med. Sci."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"874","DOI":"10.1593\/neo.09554","article-title":"Tumor interstitial fluid pressure as an early-response marker for anticancer therapeutics","volume":"11","author":"Ferretti","year":"2009","journal-title":"Neoplasia"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1038\/nrc1456","article-title":"High interstitial fluid pressure\u2014an obstacle in cancer therapy","volume":"4","author":"Heldin","year":"2004","journal-title":"Nat. Rev. Cancer"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1038\/scientificamerican0794-58","article-title":"Barriers to drug delivery in solid tumors","volume":"271","author":"Jain","year":"1994","journal-title":"Sci. Am."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1146\/annurev-bioeng-071813-105259","article-title":"The role of mechanical forces in tumor growth and therapy","volume":"16","author":"Jain","year":"2014","journal-title":"Annu. Rev. Biomed. Eng."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1038\/nrc1893","article-title":"Drug penetration in solid tumours","volume":"6","author":"Minchinton","year":"2006","journal-title":"Nat. Rev. Cancer"},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Welter, M., and Rieger, H. (2013). Interstitial fluid flow and drug delivery in vascularized tumors: A computational model. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070395"},{"key":"ref_55","doi-asserted-by":"crossref","unstructured":"Simonsen, T.G., Gaustad, J.V., Leinaas, M.N., and Rofstad, E.K. (2012). High interstitial fluid pressure is associated with tumor-line specific vascular abnormalities in human melanoma xenografts. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0040006"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1038\/nmeth.2019","article-title":"Fiji: An open-source platform for biological-image analysis","volume":"9","author":"Schindelin","year":"2012","journal-title":"Nat. Methods"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1002\/aja.1002030302","article-title":"Stages of embryonic development of the zebrafish","volume":"203","author":"Kimmel","year":"1995","journal-title":"Dev. Dyn."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1006\/dbio.2002.0711","article-title":"In vivo imaging of embryonic vascular development using transgenic zebrafish","volume":"248","author":"Lawson","year":"2002","journal-title":"Dev. Biol."},{"key":"ref_59","unstructured":"Westerfield, M. (1993). The Zebrafish Book: A Guide for the Laboratory Use of Zebrafish (Brachydanio Rerio), University of Oregon Press."},{"key":"ref_60","first-page":"283","article-title":"Characterisation of thyroid medullary carcinoma TT cell line","volume":"12","author":"Zabel","year":"1997","journal-title":"Histol. Histopathol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"R67","DOI":"10.1530\/ERC-13-0388","article-title":"Zebrafish as an innovative model for neuroendocrine tumors","volume":"21","author":"Vitale","year":"2014","journal-title":"Endocr. Relat. Cancer"},{"key":"ref_62","unstructured":"Tikhonov, A.N., and Samarskii, A.A. (2000). Equations of Mathematical Physics, Dover Publications, INC."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13392\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T16:54:36Z","timestamp":1760115276000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/25\/24\/13392"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,13]]},"references-count":62,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2024,12]]}},"alternative-id":["ijms252413392"],"URL":"https:\/\/doi.org\/10.3390\/ijms252413392","relation":{},"ISSN":["1422-0067"],"issn-type":[{"type":"electronic","value":"1422-0067"}],"subject":[],"published":{"date-parts":[[2024,12,13]]}}}