{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T02:48:47Z","timestamp":1787021327490,"version":"build-2736575974"},"reference-count":66,"publisher":"The Company of Biologists","issue":"5","license":[{"start":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T00:00:00Z","timestamp":1684368000000},"content-version":"vor","delay-in-days":3,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"DOI":"10.13039\/501100000770","name":"University of Manchester","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000770","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/100010269","name":"Wellcome Trust","doi-asserted-by":"crossref","award":["NU-009842"],"award-info":[{"award-number":["NU-009842"]}],"id":[{"id":"10.13039\/100010269","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000774","name":"Newcastle University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100000774","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100000691","name":"Academy of Medical Sciences","doi-asserted-by":"crossref","award":["NIF\/R5A\/0027"],"award-info":[{"award-number":["NIF\/R5A\/0027"]}],"id":[{"id":"10.13039\/501100000691","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,5,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Head and neck cancer (HNC) differs at anatomical sites and hypopharyngeal cancer (HPC) is a type of HNC. The non-surgical treatment option for advanced cases of HPC is radiotherapy (RT) with or without chemotherapy but survival is poor. Thus, new treatment approaches in combination with RT are essential. Yet, obtaining post-RT treated tumour specimens and lack of animal models with identical anatomical sites are the major translational research barriers. To overcome these barriers, for the first time, we have developed a tumour-stroma based in vitro three-dimensional (3D)-tumouroid co-culture model of HPC by growing FaDu and HS-5 cells together to mimic the complex tumour-microenvironment in a Petri dish. Before growing the cells together, imaging flow cytometry revealed distinct epithelial and non-epithelial characteristics of the cells. Growth rate of the 3D-tumouroid co-culture was significantly higher compared to the tumouroid monoculture of FaDu. Histology and morphometric analysis were done for the characterisation as well as the development of hypoxia was measured by CAIX immunostaining in this 3D-tumouroid co-culture. Taken together, this innovative in vitro 3D model of HPC resembles many features of the original tumour. The wider application of this pre-clinical research tool is in understanding newer combination (e.g. immunotherapy) treatment approaches with RT in HPC and beyond.<\/jats:p>","DOI":"10.1242\/bio.059949","type":"journal-article","created":{"date-parts":[[2023,5,17]],"date-time":"2023-05-17T07:28:26Z","timestamp":1684308506000},"source":"Crossref","is-referenced-by-count":6,"title":["Bioengineering of a tumour-stroma 3D-tumouroid co-culture model of hypopharyngeal cancer"],"prefix":"10.1242","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0416-0688","authenticated-orcid":false,"given":"Santu","family":"Saha","sequence":"first","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Leukaemia Research Cytogenetics Group, Wolfson Childhood Cancer Research Centre, Level 6, Herschel Building, Brewery Lane, Faculty of Medical Sciences, Newcastle University 1 , Newcastle upon Tyne, NE1 7RU , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel","family":"Howarth","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Paul O'Gorman Building, Faculty of Medical Sciences, Newcastle University 2 , Newcastle upon Tyne, NE2 4HH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sweta","family":"Sharma-Saha","sequence":"additional","affiliation":[{"name":"Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Paul O'Gorman Building, Faculty of Medical Sciences, Newcastle University 2 , Newcastle upon Tyne, NE2 4HH , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles","family":"Kelly","sequence":"additional","affiliation":[{"name":"Department of Clinical Oncology, Northern Centre for Cancer Care, Freeman Hospital 3 , Newcastle upon Tyne, NE7 7DN , UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","published-online":{"date-parts":[[2023,5,17]]},"reference":[{"key":"2023051814023917800_BIO059949C1","doi-asserted-by":"publisher","first-page":"584232","DOI":"10.3389\/fcell.2020.584232","article-title":"HS-5 and HS-27A stromal cell lines to study bone marrow mesenchymal stromal cell-mediated support to cancer development","volume":"8","author":"Adamo","year":"2020","journal-title":"Front. Cell Dev. Biol."},{"key":"2023051814023917800_BIO059949C2","doi-asserted-by":"publisher","first-page":"480","DOI":"10.1186\/s12885-021-08222-8","article-title":"Clinical significance of tumor-stroma ratio in head and neck cancer: a systematic review and meta-analysis","volume":"21","author":"Almangush","year":"2021","journal-title":"BMC Cancer"},{"key":"2023051814023917800_BIO059949C3","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1016\/j.clinbiochem.2004.05.009","article-title":"Clinical utility of cytokeratins as tumor markers","volume":"37","author":"Barak","year":"2004","journal-title":"Clin. Biochem."},{"key":"2023051814023917800_BIO059949C4","doi-asserted-by":"publisher","first-page":"707","DOI":"10.3324\/haematol.2017.167486","article-title":"Modeling multiple myeloma-bone marrow interactions and response to drugs in a 3D surrogate microenvironment","volume":"103","author":"Belloni","year":"2018","journal-title":"Haematologica"},{"key":"2023051814023917800_BIO059949C5","doi-asserted-by":"publisher","first-page":"846","DOI":"10.1016\/j.semcancer.2022.02.011","article-title":"Radiotherapy-induced remodeling of the tumor microenvironment by stromal cells","volume":"86","author":"Berg","year":"2022","journal-title":"Semin. Cancer Biol."},{"key":"2023051814023917800_BIO059949C6","doi-asserted-by":"publisher","first-page":"E8","DOI":"10.1002\/lary.24933","article-title":"Prognostic value of hypoxia-associated markers in advanced larynx and hypopharynx squamous cell carcinoma","volume":"125","author":"Bernstein","year":"2015","journal-title":"Laryngoscope"},{"key":"2023051814023917800_BIO059949C7","author":"Board","year":"2021"},{"key":"2023051814023917800_BIO059949C8","doi-asserted-by":"publisher","first-page":"103724","DOI":"10.1016\/j.critrevonc.2022.103724","article-title":"Models of head and neck squamous cell carcinoma using bioengineering approaches","volume":"175","author":"Bonartsev","year":"2022","journal-title":"Crit. Rev. Oncol. Hematol."},{"key":"2023051814023917800_BIO059949C9","doi-asserted-by":"publisher","first-page":"603640","DOI":"10.3389\/fimmu.2020.603640","article-title":"3D tumor models and their use for the testing of immunotherapies","volume":"11","author":"Boucherit","year":"2020","journal-title":"Front. Immunol."},{"key":"2023051814023917800_BIO059949C10","doi-asserted-by":"publisher","first-page":"1237","DOI":"10.3390\/jcm12031237","article-title":"Current therapeutic strategies for patients with hypopharyngeal carcinoma: oncologic and functional outcomes","volume":"12","author":"Bozec","year":"2023","journal-title":"J. Clin. Med."},{"key":"2023051814023917800_BIO059949C11","doi-asserted-by":"publisher","first-page":"e240","DOI":"10.1016\/S1470-2045(18)30096-2","article-title":"Combining precision radiotherapy with molecular targeting and immunomodulatory agents: a guideline by the American Society for Radiation Oncology","volume":"19","author":"Bristow","year":"2018","journal-title":"Lancet Oncol."},{"key":"2023051814023917800_BIO059949C12","doi-asserted-by":"publisher","first-page":"171","DOI":"10.1016\/S0140-6736(21)00233-6","article-title":"Contemporary radiotherapy: present and future","volume":"398","author":"Chandra","year":"2021","journal-title":"Lancet"},{"key":"2023051814023917800_BIO059949C13","doi-asserted-by":"publisher","first-page":"124","DOI":"10.1038\/s41577-021-00568-1","article-title":"Immunomodulation by radiotherapy in tumour control and normal tissue toxicity","volume":"22","author":"Cytlak","year":"2022","journal-title":"Nat. Rev. Immunol."},{"key":"2023051814023917800_BIO059949C14","doi-asserted-by":"publisher","first-page":"235","DOI":"10.1590\/S1806-83242011000300008","article-title":"Vimentin expression and the influence of Matrigel in cell lines of head and neck squamous cell carcinoma","volume":"25","author":"Dal Vechio","year":"2011","journal-title":"Braz. Oral Res."},{"key":"2023051814023917800_BIO059949C15","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s13046-019-1086-2","article-title":"3D models in the new era of immune oncology: focus on T cells, CAF and ECM","volume":"38","author":"Di Modugno","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"2023051814023917800_BIO059949C16","doi-asserted-by":"publisher","first-page":"2765","DOI":"10.3390\/cancers12102765","article-title":"Three-dimensional cell culture systems in radiopharmaceutical cancer research","volume":"12","author":"Doctor","year":"2020","journal-title":"Cancers"},{"key":"2023051814023917800_BIO059949C17","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1016\/j.canlet.2020.12.045","article-title":"Radiotherapy, immunotherapy, and the tumour microenvironment: Turning an immunosuppressive milieu into a therapeutic opportunity","volume":"502","author":"Donlon","year":"2021","journal-title":"Cancer Lett."},{"key":"2023051814023917800_BIO059949C18","doi-asserted-by":"publisher","first-page":"47","DOI":"10.1159\/000492308","article-title":"Treatment options for hypopharyngeal cancer","volume":"83","author":"Eckel","year":"2019","journal-title":"Adv. Otorhinolaryngol."},{"key":"2023051814023917800_BIO059949C19","doi-asserted-by":"publisher","first-page":"19","DOI":"10.1038\/icb.2012.56","article-title":"Mechanisms of mesenchymal stromal cell immunomodulation","volume":"91","author":"English","year":"2013","journal-title":"Immunol. Cell Biol."},{"key":"2023051814023917800_BIO059949C20","doi-asserted-by":"crossref","first-page":"205","DOI":"10.14712\/fb2014060050205","article-title":"Towards dissecting molecular routes of intercellular communication in the tumour microenvironment: phenotypic plasticity of stem cell-associated markers in co-culture (carcinoma cell\/fibroblast) systems","volume":"60","author":"F\u00edk","year":"2014","journal-title":"Folia Biol."},{"key":"2023051814023917800_BIO059949C21","doi-asserted-by":"publisher","first-page":"56","DOI":"10.3390\/cancers13010056","article-title":"3D culture systems for exploring cancer immunology","volume":"13","author":"Fitzgerald","year":"2020","journal-title":"Cancers"},{"key":"2023051814023917800_BIO059949C22","doi-asserted-by":"publisher","first-page":"238","DOI":"10.1038\/bjc.2014.610","article-title":"Imaging tumour hypoxia with positron emission tomography","volume":"112","author":"Fleming","year":"2015","journal-title":"Br. J. Cancer"},{"key":"2023051814023917800_BIO059949C23","doi-asserted-by":"publisher","first-page":"698","DOI":"10.1038\/bjc.2017.430","article-title":"The hypoxia marker CAIX is prognostic in the UK phase III VorteX-Biobank cohort: an important resource for translational research in soft tissue sarcoma","volume":"118","author":"Forker","year":"2018","journal-title":"Br. J. Cancer"},{"key":"2023051814023917800_BIO059949C24","doi-asserted-by":"publisher","first-page":"849","DOI":"10.1080\/09553000701727531","article-title":"Experimental anti-tumor therapy in 3-D: spheroids--old hat or new challenge?","volume":"83","author":"Friedrich","year":"2007","journal-title":"Int. J. Radiat. Biol."},{"key":"2023051814023917800_BIO059949C25","doi-asserted-by":"publisher","first-page":"1006","DOI":"10.3390\/cells10051006","article-title":"Tumour hypoxia-mediated immunosuppression: mechanisms and therapeutic approaches to improve cancer immunotherapy","volume":"10","author":"Fu","year":"2021","journal-title":"Cells"},{"key":"2023051814023917800_BIO059949C26","doi-asserted-by":"publisher","first-page":"448","DOI":"10.1016\/S0301-472X(01)00612-9","article-title":"Acute myeloid leukemia cells are protected from spontaneous and drug-induced apoptosis by direct contact with a human bone marrow stromal cell line (HS-5)","volume":"29","author":"Garrido","year":"2001","journal-title":"Exp. Hematol."},{"key":"2023051814023917800_BIO059949C27","doi-asserted-by":"publisher","first-page":"3549","DOI":"10.3892\/ol.2016.5076","article-title":"Differences in tumor stroma derived from irradiated versus non-irradiated fibroblasts in a co-culture model with head and neck squamous cell carcinoma","volume":"12","author":"Gehrke","year":"2016","journal-title":"Oncol. Lett."},{"key":"2023051814023917800_BIO059949C28","doi-asserted-by":"publisher","first-page":"277","DOI":"10.1016\/j.clon.2014.02.002","article-title":"The meaning, measurement and modification of hypoxia in the laboratory and the clinic","volume":"26","author":"Hammond","year":"2014","journal-title":"Clin. Oncol."},{"key":"2023051814023917800_BIO059949C29","doi-asserted-by":"publisher","first-page":"466","DOI":"10.1038\/nature23470","article-title":"Mitotic progression following DNA damage enables pattern recognition within micronuclei","volume":"548","author":"Harding","year":"2017","journal-title":"Nature"},{"key":"2023051814023917800_BIO059949C30","doi-asserted-by":"publisher","first-page":"40","DOI":"10.1016\/j.ctro.2022.06.004","article-title":"Hypoxia in relationship to tumor volume using hypoxia PET-imaging in head & neck cancer - A scoping review","volume":"36","author":"Hildingsson","year":"2022","journal-title":"Clin. Transl. Radiat. Oncol."},{"key":"2023051814023917800_BIO059949C31","doi-asserted-by":"publisher","first-page":"e404","DOI":"10.1016\/S1470-2045(19)30306-7","article-title":"Radioimmunotherapy for the treatment of head and neck cancer","volume":"20","author":"Karam","year":"2019","journal-title":"Lancet Oncol."},{"key":"2023051814023917800_BIO059949C32","doi-asserted-by":"publisher","first-page":"738","DOI":"10.1111\/boc.201200018","article-title":"Upregulation of IL-6, IL-8 and CXCL-1 production in dermal fibroblasts by normal\/malignant epithelial cells in vitro: Immunohistochemical and transcriptomic analyses","volume":"104","author":"Kolar","year":"2012","journal-title":"Biol. Cell"},{"key":"2023051814023917800_BIO059949C33","doi-asserted-by":"publisher","first-page":"1408","DOI":"10.1038\/leu.2011.108","article-title":"Mesenchymal stromal cell \u2018licensing\u2019: a multistep process","volume":"25","author":"Krampera","year":"2011","journal-title":"Leukemia"},{"key":"2023051814023917800_BIO059949C34","doi-asserted-by":"publisher","first-page":"2916","DOI":"10.3390\/cancers12102916","article-title":"Tumor microenvironment as a regulator of radiation therapy: new insights into stromal-mediated radioresistance","volume":"12","author":"Krisnawan","year":"2020","journal-title":"Cancers"},{"key":"2023051814023917800_BIO059949C35","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1007\/978-3-319-26666-4_10","article-title":"Methods: Using Three-Dimensional Culture (Spheroids) as an In Vitro Model of Tumour Hypoxia","volume":"899","author":"Leek","year":"2016","journal-title":"Adv. Exp. Med. Biol."},{"key":"2023051814023917800_BIO059949C36","doi-asserted-by":"publisher","first-page":"3532","DOI":"10.1093\/bioinformatics\/btw413","article-title":"MorphoLibJ: integrated library and plugins for mathematical morphology with ImageJ","volume":"32","author":"Legland","year":"2016","journal-title":"Bioinformatics"},{"key":"2023051814023917800_BIO059949C37","doi-asserted-by":"publisher","first-page":"1591","DOI":"10.3389\/fimmu.2018.01591","article-title":"Hypoxia-driven immunosuppressive metabolites in the tumor microenvironment: new approaches for combinational immunotherapy","volume":"9","author":"Li","year":"2018","journal-title":"Front. Immunol."},{"key":"2023051814023917800_BIO059949C38","doi-asserted-by":"publisher","first-page":"817","DOI":"10.1177\/2472555219860446","article-title":"Three-dimensional leukemia co-culture system for in vitro high-content metabolomics screening","volume":"24","author":"Lu","year":"2019","journal-title":"SLAS Discov."},{"key":"2023051814023917800_BIO059949C39","doi-asserted-by":"publisher","first-page":"30","DOI":"10.1200\/JCO.20.00290","article-title":"Randomized phase II trial of nivolumab with stereotactic body radiotherapy versus nivolumab alone in metastatic head and neck squamous cell carcinoma","volume":"39","author":"Mcbride","year":"2021","journal-title":"J. Clin. Oncol."},{"key":"2023051814023917800_BIO059949C40","doi-asserted-by":"publisher","first-page":"3100","DOI":"10.1158\/1078-0432.CCR-11-1877","article-title":"Carbonic anhydrase IX promotes tumor growth and necrosis in vivo and inhibition enhances anti-VEGF therapy","volume":"18","author":"Mcintyre","year":"2012","journal-title":"Clin. Cancer Res."},{"key":"2023051814023917800_BIO059949C41","doi-asserted-by":"publisher","first-page":"203","DOI":"10.1038\/s41568-020-0246-1","article-title":"Inflammatory microenvironment remodelling by tumour cells after radiotherapy","volume":"20","author":"Mclaughlin","year":"2020","journal-title":"Nat. Rev. Cancer"},{"key":"2023051814023917800_BIO059949C42","doi-asserted-by":"publisher","first-page":"193","DOI":"10.3389\/fimmu.2019.00193","article-title":"Role of radiation therapy in modulation of the tumor stroma and microenvironment","volume":"10","author":"Menon","year":"2019","journal-title":"Front. Immunol."},{"key":"2023051814023917800_BIO059949C66","doi-asserted-by":"crossref","first-page":"2289","DOI":"10.1016\/S0140-6736(21)01550-6","article-title":"Head and neck cancer","volume":"398","author":"Mody","year":"2021","journal-title":"Lancet"},{"key":"2023051814023917800_BIO059949C43","doi-asserted-by":"publisher","first-page":"1972","DOI":"10.1016\/j.cell.2018.11.021","article-title":"Organoid modeling of the tumor immune microenvironment","volume":"175","author":"Neal","year":"2018","journal-title":"Cell"},{"key":"2023051814023917800_BIO059949C44","doi-asserted-by":"publisher","first-page":"986","DOI":"10.1038\/sj.bjc.6603651","article-title":"Quantitative evaluation of vimentin expression in tumour stroma of colorectal cancer","volume":"96","author":"Ngan","year":"2007","journal-title":"Br. J. Cancer"},{"key":"2023051814023917800_BIO059949C45","doi-asserted-by":"publisher","first-page":"S66","DOI":"10.1017\/S0022215116000463","article-title":"Radiotherapy in head and neck cancer management: United Kingdom National Multidisciplinary Guidelines","volume":"130","author":"Nutting","year":"2016","journal-title":"J. Laryngol. Otol."},{"key":"2023051814023917800_BIO059949C46","doi-asserted-by":"publisher","first-page":"929","DOI":"10.1002\/cyto.a.23580","article-title":"Characteristics of live parameters of the HS-5 human bone marrow stromal cell line cocultured with the leukemia cells in hypoxia, for the studies of leukemia-stroma cross-talk","volume":"93","author":"Podszywalow-Bartnicka","year":"2018","journal-title":"Cytometry A"},{"key":"2023051814023917800_BIO059949C47","doi-asserted-by":"publisher","first-page":"254","DOI":"10.1053\/j.seminoncol.2019.07.003","article-title":"Ionizing radiation effects on the tumor microenvironment","volume":"46","author":"Portella","year":"2019","journal-title":"Semin. Oncol."},{"key":"2023051814023917800_BIO059949C48","doi-asserted-by":"publisher","first-page":"S104","DOI":"10.1017\/S0022215116000529","article-title":"Hypopharyngeal cancer: United Kingdom National Multidisciplinary Guidelines","volume":"130","author":"Pracy","year":"2016","journal-title":"J. Laryngol. Otol."},{"key":"2023051814023917800_BIO059949C49","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1002\/1097-0142(197201)29:1&lt;117::AID-CNCR2820290119&gt;3.0.CO;2-R","article-title":"A new human cell line (FaDu) from a hypopharyngeal carcinoma","volume":"29","author":"Rangan","year":"1972","journal-title":"Cancer"},{"key":"2023051814023917800_BIO059949C50","doi-asserted-by":"publisher","first-page":"21","DOI":"10.1016\/j.molcel.2020.07.026","article-title":"DNA Damage and Cancer Immunotherapy: A STING in the Tale","volume":"80","author":"Reislander","year":"2020","journal-title":"Mol. Cell"},{"key":"2023051814023917800_BIO059949C51","doi-asserted-by":"publisher","first-page":"7689","DOI":"10.3390\/ijms23147689","article-title":"Human mesenchymal stromal cells do not cause radioprotection of head-and-neck squamous cell carcinoma","volume":"23","author":"Ruhle","year":"2022","journal-title":"Int. J. Mol. Sci."},{"key":"2023051814023917800_BIO059949C52","doi-asserted-by":"publisher","first-page":"1751","DOI":"10.1038\/s41467-017-01883-9","article-title":"DNA double-strand break repair pathway regulates PD-L1 expression in cancer cells","volume":"8","author":"Sato","year":"2017","journal-title":"Nat. Commun."},{"key":"2023051814023917800_BIO059949C53","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1158\/2159-8290.CD-20-1680","article-title":"The next decade of immune checkpoint therapy","volume":"11","author":"Sharma","year":"2021","journal-title":"Cancer Discov."},{"key":"2023051814023917800_BIO059949C54","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1007\/s11307-015-0885-x","article-title":"Evaluation of CAIX and CAXII expression in breast cancer at varied O2 levels: CAIX is the superior surrogate imaging biomarker of tumor hypoxia","volume":"18","author":"Tafreshi","year":"2016","journal-title":"Mol. Imaging Biol."},{"key":"2023051814023917800_BIO059949C55","doi-asserted-by":"publisher","first-page":"114018","DOI":"10.1016\/j.addr.2021.114018","article-title":"In-vitro 3D modelling for charged particle therapy - Uncertainties and opportunities","volume":"179","author":"Thiagarajan","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"2023051814023917800_BIO059949C56","doi-asserted-by":"publisher","first-page":"113791","DOI":"10.1016\/j.addr.2021.05.001","article-title":"Hot or cold: Bioengineering immune contextures into in vitro patient-derived tumor models","volume":"175","author":"Too","year":"2021","journal-title":"Adv. Drug Deliv. Rev."},{"key":"2023051814023917800_BIO059949C57","doi-asserted-by":"publisher","first-page":"669","DOI":"10.1038\/nri3902","article-title":"Immunological hallmarks of stromal cells in the tumour microenvironment","volume":"15","author":"Turley","year":"2015","journal-title":"Nat. Rev. Immunol."},{"key":"2023051814023917800_BIO059949C58","doi-asserted-by":"publisher","first-page":"1248","DOI":"10.1002\/bit.24400","article-title":"Co-culture of stromal and erythroleukemia cells in a perfused hollow fiber bioreactor system as an in vitro bone marrow model for myeloid leukemia","volume":"109","author":"Usuludin","year":"2012","journal-title":"Biotechnol. Bioeng."},{"key":"2023051814023917800_BIO059949C59","doi-asserted-by":"publisher","first-page":"2236","DOI":"10.3390\/nano10112236","article-title":"From 2D to 3D cancer cell models-the enigmas of drug delivery research","volume":"10","author":"Van Zundert","year":"2020","journal-title":"Nanomaterials"},{"key":"2023051814023917800_BIO059949C60","doi-asserted-by":"publisher","first-page":"992","DOI":"10.3390\/cells9040992","article-title":"Hypoxia-driven immune escape in the tumor microenvironment","volume":"9","author":"Vito","year":"2020","journal-title":"Cells"},{"key":"2023051814023917800_BIO059949C61","doi-asserted-by":"publisher","first-page":"1045","DOI":"10.1007\/s00432-021-03854-6","article-title":"Ex vivo propagation in a novel 3D high-throughput co-culture system for multiple myeloma","volume":"148","author":"Waldschmidt","year":"2022","journal-title":"J. Cancer Res. Clin. Oncol."},{"key":"2023051814023917800_BIO059949C62","doi-asserted-by":"publisher","first-page":"112","DOI":"10.1186\/1476-4598-12-112","article-title":"Bone-stromal cells up-regulate tumourigenic markers in a tumour-stromal 3D model of prostate cancer","volume":"12","author":"Windus","year":"2014","journal-title":"Mol. Cancer"},{"key":"2023051814023917800_BIO059949C63","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.3390\/jcm8101686","article-title":"Stroma-rich co-culture multicellular tumor spheroids as a tool for photoactive drugs screening","volume":"8","author":"Yakavets","year":"2019","journal-title":"J. Clin. Med"},{"key":"2023051814023917800_BIO059949C64","doi-asserted-by":"publisher","first-page":"2473974X211059429","DOI":"10.1177\/2473974X211059429","article-title":"Times to diagnosis, staging, and treatment of head and neck cancer before and during COVID-19","volume":"5","author":"Yao","year":"2021","journal-title":"OTO Open"},{"key":"2023051814023917800_BIO059949C65","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.biomaterials.2018.01.038","article-title":"A TRACER 3D co-culture tumour model for head and neck cancer","volume":"164","author":"Young","year":"2018","journal-title":"Biomaterials"}],"container-title":["Biology Open"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.logists.com\/bio\/bio\/article-pdf\/doi\/10.1242\/bio.059949\/2864513\/bio059949.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/journals.logists.com\/bio\/bio\/article-pdf\/doi\/10.1242\/bio.059949\/2864513\/bio059949.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,10,20]],"date-time":"2024-10-20T11:14:22Z","timestamp":1729422862000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.biologists.com\/bio\/article\/12\/5\/bio059949\/310415\/Bioengineering-of-a-tumour-stroma-3D-tumouroid-co"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,5,15]]},"references-count":66,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2023,5,15]]}},"URL":"https:\/\/doi.org\/10.1242\/bio.059949","relation":{},"ISSN":["2046-6390"],"issn-type":[{"value":"2046-6390","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,5,15]]},"article-number":"bio059949"}}