{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,2]],"date-time":"2025-11-02T09:49:26Z","timestamp":1762076966385,"version":"build-2065373602"},"reference-count":24,"publisher":"MDPI AG","issue":"22","license":[{"start":{"date-parts":[[2022,11,19]],"date-time":"2022-11-19T00:00:00Z","timestamp":1668816000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"ELKUS Foundation","award":["5U54CA118948 to UM","R21 CA216789 to NSB"],"award-info":[{"award-number":["5U54CA118948 to UM","R21 CA216789 to NSB"]}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["5U54CA118948 to UM","R21 CA216789 to NSB"],"award-info":[{"award-number":["5U54CA118948 to UM","R21 CA216789 to NSB"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["5U54CA118948 to UM","R21 CA216789 to NSB"],"award-info":[{"award-number":["5U54CA118948 to UM","R21 CA216789 to NSB"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Reliable preclinical models are needed for screening new cancer drugs. Thus, we developed an improved 3D tumor organoid model termed \u201corganoid raft cultures\u201d (ORCs). Development of ORCs involved culturing tumors ex vivo on collagen beds (boats) with grid supports to maintain their morphological structure. The ORCs were developed from patient-derived xenografts (PDXs) of colon cancers excised from immune-deficient mice (NOD\/SCID\/IL2Rgammanull). We utilized these new models to evaluate the efficacy of an investigational drug, Navitoclax (ABT-263). We tested the efficacy of ABT-263, an inhibitor of BCL-2 family proteins, in these ORCs derived from a PDX that showed high expression of antiapoptotic BCL2 family proteins (BCL-2, BCL-XL, and BCL-W). Hematoxylin and eosin staining evaluation of PDXs and corresponding ORCs indicated the retention of morphological and other histological integrity of ORCs. ORCs treated with ABT-263 showed decreased expression of antiapoptotic proteins (BCL2, BCL-XL and BCL-W) and increased proapoptotic proteins (BAX and PUMA), with concomitant activation of caspase 3. These studies support the usefulness of the ORCs, developed from PDXs, as an alternative to PDXs and as faster screening models.<\/jats:p>","DOI":"10.3390\/ijms232214392","type":"journal-article","created":{"date-parts":[[2022,11,21]],"date-time":"2022-11-21T03:05:11Z","timestamp":1668999911000},"page":"14392","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Developing 3D Organoid Raft Cultures from Patient-Derived Xenografts as Rapid Models to Screen Efficacy of Experimental Therapeutics"],"prefix":"10.3390","volume":"23","author":[{"given":"Prachi","family":"Bajpai","sequence":"first","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9180-0323","authenticated-orcid":false,"given":"Nilam Sanjib","family":"Banerjee","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dianne W.","family":"Moore","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Molecular Genetics, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyung-Gyoon","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farrukh","family":"Afaq","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carlo M.","family":"Contreras","sequence":"additional","affiliation":[{"name":"Department of Surgery, Ohio State University, Columbus, OH 43210, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martin J.","family":"Heslin","sequence":"additional","affiliation":[{"name":"Mitchell Cancer Institute, University of South Alabama, Mobile, AL 36688, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vishnu B.","family":"Reddy","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"},{"name":"O\u2019Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shajan","family":"Peter","sequence":"additional","affiliation":[{"name":"O\u2019Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA"},{"name":"Division of Gastroenterology, Department of Medicine, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sooryanarayana","family":"Varambally","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"},{"name":"O\u2019Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3095-4089","authenticated-orcid":false,"given":"Sameer","family":"Al Diffalha","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"},{"name":"O\u2019Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Upender","family":"Manne","sequence":"additional","affiliation":[{"name":"Department of Pathology, University of Alabama at Birmingham, Birmingham, AL 35233, USA"},{"name":"O\u2019Neal Comprehensive Cancer Center, University of Alabama at Birmingham, Birmingham, AL 35233, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2022,11,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1038\/s41568-018-0007-6","article-title":"Organoids in cancer research","volume":"18","author":"Drost","year":"2018","journal-title":"Nat. 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