Optical Imaging of Drug-Induced Metabolism Changes in Murine and Human Pancreatic Cancer Organoids Reveals Heterogeneous Drug Response
Three-dimensional organoids derived from primary pancreatic ductal adenocarcinomas are an attractive platform for testing potential anticancer drugs on patient-specific tissue. Optical metabolic imaging (OMI) is a novel tool used to assess drug-induced changes in cellular metabolism, and its quantit...
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| Published in | Pancreas Vol. 45; no. 6; p. 863 |
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| Main Authors | , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
01.07.2016
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| Subjects | |
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| Abstract | Three-dimensional organoids derived from primary pancreatic ductal adenocarcinomas are an attractive platform for testing potential anticancer drugs on patient-specific tissue. Optical metabolic imaging (OMI) is a novel tool used to assess drug-induced changes in cellular metabolism, and its quantitative end point, the OMI index, is evaluated as a biomarker of drug response in pancreatic cancer organoids.
Optical metabolic imaging is used to assess both malignant cell and fibroblast drug response within primary murine and human pancreatic cancer organoids.
Anticancer drugs induce significant reductions in the OMI index of murine and human pancreatic cancer organoids. Subpopulation analysis of OMI data revealed heterogeneous drug response and elucidated responding and nonresponding cell populations for a 7-day time course. Optical metabolic imaging index significantly correlates with immunofluorescence detection of cell proliferation and cell death.
Optical metabolic imaging of primary pancreatic ductal adenocarcinoma organoids is highly sensitive to drug-induced metabolic changes, provides a nondestructive method for monitoring dynamic drug response, and presents a novel platform for patient-specific drug testing and drug development. |
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| AbstractList | Three-dimensional organoids derived from primary pancreatic ductal adenocarcinomas are an attractive platform for testing potential anticancer drugs on patient-specific tissue. Optical metabolic imaging (OMI) is a novel tool used to assess drug-induced changes in cellular metabolism, and its quantitative end point, the OMI index, is evaluated as a biomarker of drug response in pancreatic cancer organoids.
Optical metabolic imaging is used to assess both malignant cell and fibroblast drug response within primary murine and human pancreatic cancer organoids.
Anticancer drugs induce significant reductions in the OMI index of murine and human pancreatic cancer organoids. Subpopulation analysis of OMI data revealed heterogeneous drug response and elucidated responding and nonresponding cell populations for a 7-day time course. Optical metabolic imaging index significantly correlates with immunofluorescence detection of cell proliferation and cell death.
Optical metabolic imaging of primary pancreatic ductal adenocarcinoma organoids is highly sensitive to drug-induced metabolic changes, provides a nondestructive method for monitoring dynamic drug response, and presents a novel platform for patient-specific drug testing and drug development. |
| Author | Castellanos, Jason A Skala, Melissa C Merchant, Nipun B Nagathihalli, Nagaraj S Walsh, Alex J |
| Author_xml | – sequence: 1 givenname: Alex J surname: Walsh fullname: Walsh, Alex J organization: From the Department of Biomedical Engineering, Vanderbilt University; and †Department of Surgery, Vanderbilt University School of Medicine, Nashville, TN; ‡Sylvester Comprehensive Cancer Center, University of Miami; and §Division of Surgical Oncology and ∥Department of Surgery, University of Miami Miller School of Medicine, Miami, FL – sequence: 2 givenname: Jason A surname: Castellanos fullname: Castellanos, Jason A – sequence: 3 givenname: Nagaraj S surname: Nagathihalli fullname: Nagathihalli, Nagaraj S – sequence: 4 givenname: Nipun B surname: Merchant fullname: Merchant, Nipun B – sequence: 5 givenname: Melissa C surname: Skala fullname: Skala, Melissa C |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/26495796$$D View this record in MEDLINE/PubMed |
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| SubjectTerms | Animals Antineoplastic Agents - pharmacology Carcinoma, Pancreatic Ductal - diagnostic imaging Carcinoma, Pancreatic Ductal - drug therapy Carcinoma, Pancreatic Ductal - metabolism Cell Proliferation - drug effects Cell Survival - drug effects Humans Mice, Knockout Microscopy, Fluorescence, Multiphoton - methods Optical Imaging - methods Organoids - diagnostic imaging Organoids - drug effects Organoids - metabolism Pancreatic Neoplasms - diagnostic imaging Pancreatic Neoplasms - drug therapy Pancreatic Neoplasms - metabolism Reproducibility of Results Sensitivity and Specificity Time Factors |
| Title | Optical Imaging of Drug-Induced Metabolism Changes in Murine and Human Pancreatic Cancer Organoids Reveals Heterogeneous Drug Response |
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