An Organoid-Based Preclinical Model of Human Gastric CancerSummary
Background & Aims: Our goal was to develop an initial study for the proof of concept whereby gastric cancer organoids are used as an approach to predict the tumor response in individual patients. Methods: Organoids were derived from resected gastric cancer tumors (huTGOs) or normal stomach tissu...
| Main Authors: | , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2019-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X18301309 |
| _version_ | 1818323928339185664 |
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| author | Nina G. Steele Jayati Chakrabarti Jiang Wang Jacek Biesiada Loryn Holokai Julie Chang Lauren M. Nowacki Jennifer Hawkins Maxime Mahe Nambirajan Sundaram Noah Shroyer Mario Medvedovic Michael Helmrath Syed Ahmad Yana Zavros |
| author_facet | Nina G. Steele Jayati Chakrabarti Jiang Wang Jacek Biesiada Loryn Holokai Julie Chang Lauren M. Nowacki Jennifer Hawkins Maxime Mahe Nambirajan Sundaram Noah Shroyer Mario Medvedovic Michael Helmrath Syed Ahmad Yana Zavros |
| author_sort | Nina G. Steele |
| collection | DOAJ |
| description | Background & Aims: Our goal was to develop an initial study for the proof of concept whereby gastric cancer organoids are used as an approach to predict the tumor response in individual patients. Methods: Organoids were derived from resected gastric cancer tumors (huTGOs) or normal stomach tissue collected from sleeve gastrectomies (huFGOs). Organoid cultures were treated with standard-of-care chemotherapeutic drugs corresponding to patient treatment: epirubicin, oxaliplatin, and 5-fluorouracil. Organoid response to chemotherapeutic treatment was correlated with the tumor response in each patient from whom the huTGOs were derived. HuTGOs were orthotopically transplanted into the gastric mucosa of NOD scid gamma mice. Results: Whereas huFGOs exhibited a half maximal inhibitory concentration that was similar among organoid lines, divergent responses and varying half maximal inhibitory concentration values among the huTGO lines were observed in response to chemotherapeutic drugs. HuTGOs that were sensitive to treatment were derived from a patient with a near complete tumor response to chemotherapy. However, organoids resistant to treatment were derived from patients who exhibited no response to chemotherapy. Orthotropic transplantation of organoids resulted in the engraftment and development of human adenocarcinoma. RNA sequencing revealed that huTGOs closely resembled the patient's native tumor tissue and not commonly used gastric cancer cell lines and cell lines derived from the organoid cultures. Conclusions: The treatment of patient-derived organoids alongside patients from whom cultures were derived will ultimately test their usefulness to predict individual therapy response and patient outcome. Keywords: Stomach, Organoids, Gastroids, Chemotherapy |
| first_indexed | 2024-12-13T11:20:29Z |
| format | Article |
| id | doaj.art-0b3344e92de44f69ab10a3fbb7d5b624 |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-12-13T11:20:29Z |
| publishDate | 2019-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-0b3344e92de44f69ab10a3fbb7d5b6242022-12-21T23:48:28ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2019-01-0171161184An Organoid-Based Preclinical Model of Human Gastric CancerSummaryNina G. Steele0Jayati Chakrabarti1Jiang Wang2Jacek Biesiada3Loryn Holokai4Julie Chang5Lauren M. Nowacki6Jennifer Hawkins7Maxime Mahe8Nambirajan Sundaram9Noah Shroyer10Mario Medvedovic11Michael Helmrath12Syed Ahmad13Yana Zavros14Department of Cell and Developmental Biology, University of Michigan, Ann Arbor, MichiganDepartment of Pharmacology and Systems Physiology, University of Cincinnati, Cincinnati, OhioDepartment of Pathology and Lab Medicine, University of Cincinnati College of Medicine, Cincinnati, OhioDepartment of Environmental Health, Division of Biostatistics and Bioinformatics, University of Cincinnati College of Medicine, Cincinnati, OhioDepartment of Molecular Genetics, Biochemistry, and Microbiology, University of Cincinnati, Cincinnati, OhioDepartment of Biomedical Engineering, University of Cincinnati, Cincinnati, OhioDepartment of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TexasDepartment of Pediatric Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OhioDepartment of Pediatric Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OhioDepartment of Pediatric Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OhioDepartment of Medicine, Section of Gastroenterology and Hepatology, Baylor College of Medicine, Houston, TexasDepartment of Environmental Health, Division of Biostatistics and Bioinformatics, University of Cincinnati College of Medicine, Cincinnati, OhioDepartment of Pediatric Surgery, Cincinnati Children’s Hospital Medical Center, Cincinnati, OhioDepartment of Surgery, University of Cincinnati Cancer Institute, Cincinnati, OhioDepartment of Pathology and Lab Medicine, University of Cincinnati College of Medicine, Cincinnati, Ohio; Correspondence Address correspondence to: Yana Zavros, PhD, University of Cincinnati College of Medicine, Department of Pharmacology and Systems Physiology, 231 Albert B. Sabin Way, Room 4255 MSB, Cincinnati, Ohio 45267-0576. fax: (513) 558-3756.Background & Aims: Our goal was to develop an initial study for the proof of concept whereby gastric cancer organoids are used as an approach to predict the tumor response in individual patients. Methods: Organoids were derived from resected gastric cancer tumors (huTGOs) or normal stomach tissue collected from sleeve gastrectomies (huFGOs). Organoid cultures were treated with standard-of-care chemotherapeutic drugs corresponding to patient treatment: epirubicin, oxaliplatin, and 5-fluorouracil. Organoid response to chemotherapeutic treatment was correlated with the tumor response in each patient from whom the huTGOs were derived. HuTGOs were orthotopically transplanted into the gastric mucosa of NOD scid gamma mice. Results: Whereas huFGOs exhibited a half maximal inhibitory concentration that was similar among organoid lines, divergent responses and varying half maximal inhibitory concentration values among the huTGO lines were observed in response to chemotherapeutic drugs. HuTGOs that were sensitive to treatment were derived from a patient with a near complete tumor response to chemotherapy. However, organoids resistant to treatment were derived from patients who exhibited no response to chemotherapy. Orthotropic transplantation of organoids resulted in the engraftment and development of human adenocarcinoma. RNA sequencing revealed that huTGOs closely resembled the patient's native tumor tissue and not commonly used gastric cancer cell lines and cell lines derived from the organoid cultures. Conclusions: The treatment of patient-derived organoids alongside patients from whom cultures were derived will ultimately test their usefulness to predict individual therapy response and patient outcome. Keywords: Stomach, Organoids, Gastroids, Chemotherapyhttp://www.sciencedirect.com/science/article/pii/S2352345X18301309 |
| spellingShingle | Nina G. Steele Jayati Chakrabarti Jiang Wang Jacek Biesiada Loryn Holokai Julie Chang Lauren M. Nowacki Jennifer Hawkins Maxime Mahe Nambirajan Sundaram Noah Shroyer Mario Medvedovic Michael Helmrath Syed Ahmad Yana Zavros An Organoid-Based Preclinical Model of Human Gastric CancerSummary Cellular and Molecular Gastroenterology and Hepatology |
| title | An Organoid-Based Preclinical Model of Human Gastric CancerSummary |
| title_full | An Organoid-Based Preclinical Model of Human Gastric CancerSummary |
| title_fullStr | An Organoid-Based Preclinical Model of Human Gastric CancerSummary |
| title_full_unstemmed | An Organoid-Based Preclinical Model of Human Gastric CancerSummary |
| title_short | An Organoid-Based Preclinical Model of Human Gastric CancerSummary |
| title_sort | organoid based preclinical model of human gastric cancersummary |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X18301309 |
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