{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,4]],"date-time":"2026-06-04T06:00:13Z","timestamp":1780552813525,"version":"3.54.1"},"update-to":[{"DOI":"10.12688\/f1000research.163596.1","type":"new_version","label":"New version","source":"publisher","updated":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000}}],"reference-count":41,"publisher":"F1000 Research Ltd","license":[{"start":{"date-parts":[[2025,8,14]],"date-time":"2025-08-14T00:00:00Z","timestamp":1755129600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010757","name":"National Centre for the Replacement Refinement and Reduction of Animals in Research","doi-asserted-by":"publisher","award":["NC\/T001631\/1"],"award-info":[{"award-number":["NC\/T001631\/1"]}],"id":[{"id":"10.13039\/501100010757","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000357","name":"North West Cancer Research","doi-asserted-by":"publisher","award":["TR2021.15"],"award-info":[{"award-number":["TR2021.15"]}],"id":[{"id":"10.13039\/501100000357","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["f1000research.com"],"crossmark-restriction":false},"short-container-title":["F1000Res"],"abstract":"<ns3:p>\n                    Background Pleural mesothelioma is a cancer of the lung lining associated with asbestos exposure. Platinum\/pemetrexed chemotherapy has been used for many years but provides little benefit and, despite recent immunotherapy advances, prognosis remains poor underpinning the need for development of novel therapeutics or drug repurposing. Fertilized hens\u2019 eggs provide a rapid and cost-effective alternative to murine models of pleural mesothelioma which are commonly used in preclinical studies, with chorioallantoic membrane (CAM) xenografts being a partial replacement for mouse flank xenografts. Here we describe methods to generate mesothelioma patient-derived xenografts on the CAM (CAM-PDX), and to subsequently assess these PDX nodules by preclinical imaging and histology. Methods Fragments of surplus mesothelioma tissue obtained from patient biopsies were implanted onto the CAM on embryonic day 7 (E7), fresh or following cryopreservation, with the established PDX dissected on E14 and fixed for histological\/immunohistochemical analysis. The optimal freezing method was determined by comparing tissue integrity and cellular content of cryopreserved tissue fragments with paired fresh samples via histological\/immunohistochemical analyses. [\n                    <ns3:sup>18<\/ns3:sup>\n                    F]-fluorodeoxyglucose positron emission tomography\/computed tomography (FDG-PET\/CT) was used to assess viability of PDXs\n                    <ns3:italic>in ovo.<\/ns3:italic>\n                    Results Methodologies for processing, cryopreservation, re-animation, and engraftment of mesothelioma tissue fragments were established. Cryopreservation of biopsy samples and parallel processing of contiguous sections allows for assessment of mesothelioma cellularity. CAM-PDXs, generated from fresh or slow-frozen tissue, were well vascularized whilst maintaining the architecture and cellular composition of the patient tissue. Furthermore, uptake of [\n                    <ns3:sup>18<\/ns3:sup>\n                    F]-FDG following intravenous injection could be visualized and quantified. Conclusions The CAM is a rapid platform for engrafting patient-derived tissue, maintaining elements of the tumor microenvironment and recapitulating heterogeneity observed in mesothelioma. Combining the CAM-PDX model and FDG-PET\/CT provides a quantitative\n                    <ns3:italic>in vivo<\/ns3:italic>\n                    platform for pre-screening of novel treatment strategies and drug combinations, with the potential for development of patient tumor avatars for predicting clinical response.\n                  <\/ns3:p>","DOI":"10.12688\/f1000research.163596.2","type":"journal-article","created":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T19:25:10Z","timestamp":1763666710000},"page":"481","update-policy":"https:\/\/doi.org\/10.12688\/f1000research.crossmark-policy","source":"Crossref","is-referenced-by-count":2,"title":["Methodology for generating chorioallantoic membrane patient-derived xenograft (CAM-PDX) models of pleural mesothelioma and performing preclinical imaging for the translation of cancer studies and drug screening."],"prefix":"10.12688","volume":"14","author":[{"given":"Jan","family":"Schulze","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3470-7528","authenticated-orcid":false,"given":"Sarah","family":"Barnett","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liam","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"Herrmann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harish","family":"Poptani","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Doris M","family":"Rassl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander","family":"Haragan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6494-9907","authenticated-orcid":false,"given":"Michael","family":"Shackcloth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2591-9796","authenticated-orcid":false,"given":"Joseph J","family":"Sacco","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2191-2001","authenticated-orcid":false,"given":"Judy M","family":"Coulson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"2560","published-online":{"date-parts":[[2025,8,14]]},"reference":[{"key":"ref16","doi-asserted-by":"publisher","first-page":"1184","DOI":"10.12688\/f1000research.15512.2","article-title":"Factors influencing malignant mesothelioma survival: a retrospective review of the National Mesothelioma Virtual Bank cohort.","volume":"7","author":"W Amin","year":"2018","journal-title":"F1000Res."},{"key":"ref3","doi-asserted-by":"publisher","first-page":"375-386","DOI":"10.1016\/S0140-6736(20)32714-8","article-title":"First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial.","volume":"397","author":"P Baas","year":"2021","journal-title":"Lancet."},{"key":"ref27","doi-asserted-by":"publisher","first-page":"16878","DOI":"10.1038\/s41598-017-17204-5","article-title":"QuPath: Open source software for digital pathology image analysis.","volume":"7","author":"P Bankhead","year":"2017","journal-title":"Sci. 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Cancer Res."}],"container-title":["F1000Research"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/f1000research.com\/articles\/14-481\/v2\/xml","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-481\/v2\/pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/f1000research.com\/articles\/14-481\/v2\/iparadigms","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,11,20]],"date-time":"2025-11-20T19:25:20Z","timestamp":1763666720000},"score":1,"resource":{"primary":{"URL":"https:\/\/f1000research.com\/articles\/14-481\/v2"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,8,14]]},"references-count":41,"URL":"https:\/\/doi.org\/10.12688\/f1000research.163596.2","relation":{"has-version":[{"id-type":"doi","id":"10.12688\/f1000research.163596.1","asserted-by":"subject"}]},"ISSN":["2046-1402"],"issn-type":[{"value":"2046-1402","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,8,14]]},"assertion":[{"value":"Indexed","URL":"https:\/\/f1000research.com\/articles\/14-481\/v2#article-reports","order":0,"name":"referee-status","label":"Referee status","group":{"name":"current-referee-status","label":"Current Referee Status"}},{"value":"10.5256\/f1000research.179975.r386165, Ulrich Jarry, Unit\u00e9 de Pharmacologie Pr\u00e9clinique, Rennes, 24 Jun 2025, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/14-481\/v1#referee-response-386165","order":0,"name":"referee-response-386165","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Sarah Barnett<\/b>; \n<i>Posted: 08 Aug 2025<\/i>;  \n<i>In relation to the animal experiment statistics from the UK Home Office, the reviewer makes a fair point. Since mice can be immunodeficient due to genetic modification but others due to a random mutation and subsequent selective breeding, it is not actually clear which group(s) immunodeficient mice would be classified under by the Home Office, and therefore, we have updated the text accordingly.&nbsp;<\/i> \n<i>We agree with the reviewer that the chicken\u2019s immune system is developing and not fully functional at these stages. However, when we refer to immune cells in the PDX models, the assumption is that these cells are human-derived and were transplanted in from the patient. We have updated the text to make it clear that we are referring to patient-derived immune cells that have been transplanted with the PDX, not host-derived immune cells.<\/i> \n<i>The CAM-PDX scoring criteria are outlined in the methods section. Xenografts were scored (yes\/no) for the presence of radial vessels (top view image) and feeder vessels (bottom view image). An example of both is shown in Figure 3. We have also updated the text to clarify.<\/i>","URL":"https:\/\/f1000research.com\/articles\/14-481\/v2#referee-comment-14334","order":1,"name":"referee-comment-14334","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"10.5256\/f1000research.179975.r386170, Stuart A. Clayton, West Virginia University, Morgantown, 24 Jun 2025, version 1, indexed","URL":"https:\/\/f1000research.com\/articles\/14-481\/v1#referee-response-386170","order":2,"name":"referee-response-386170","label":"Referee Report","group":{"name":"article-reports","label":"Article Reports"}},{"value":"<b>Sarah Barnett<\/b>; \n<i>Posted: 08 Aug 2025<\/i>;  \n<i>We have amended the typographical error in the introduction (first paragraph, line 3).<\/i> \n<i>We have updated the terminology from sterilized to disinfected in relation to the use of 70% ethanol for cleaning purposes. \u201cUV-sterilisation\u201d is commonly used and widely understood terminology however we have added \u201cgermicidal irradiation\u201d for clarity.<\/i> \n<i>We have created videos of the windowing and implanting procedure. These resources have been uploaded to Figshare and referenced in the text.<\/i> \n<i>We agree that it would be useful to monitor genetic changes, and this is something we are doing in an ongoing project, but it is beyond the scope of this methods article.<\/i>","URL":"https:\/\/f1000research.com\/articles\/14-481\/v2#referee-comment-14335","order":3,"name":"referee-comment-14335","label":"Referee Comment","group":{"name":"article-reports","label":"Article Reports"}},{"value":"This research was funded by a NC3Rs (National Centre for the Replacement, Refinement & Reduction of Animals in Research) project grant, reference NC\/T001631\/1, and a North West Cancer Research project grant, reference TR2021.15. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.","order":4,"name":"grant-information","label":"Grant Information"},{"value":"This is an open access article distributed under the terms of the Creative Commons Attribution Licence, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.","order":0,"name":"copyright-info","label":"Copyright"}]}}