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...
Saved in:
Published in | Pancreas Vol. 45; no. 6; p. 863 |
---|---|
Main Authors | , , , , |
Format | Journal Article |
Language | English |
Published |
United States
01.07.2016
|
Subjects | |
Online Access | Get more information |
Cover
Loading…
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. |
---|---|
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 |
BookMark | eNpNUNtKxDAUDKK4F_0DkfxA1yRtk-2jVNdd2GVF9Hk5SU5rZJuWpBX8Ab_b4gWclznMDHNgZuTUtx4JueJswVmhbpoOFuw_8iw9IVOepzLJlmI5IbMY3xjjKs2LczIRMityVcgp-dx3vTNwpJsGaudr2lb0Lgx1svF2MGjpDnvQ7dHFhpav4GuM1Hm6G4LzSMFbuh4a8PQRvAkIYxctxxMD3YcafOtspE_4jnCMdI09hrZGj-0Qv7-MVuxaH_GCnFVjBC9_eU5eVvfP5TrZ7h825e02MZnK-gS0VtYowyBfWtDA8qqQFRhjmVVSsKxSgms5StoyaUUKyLkRGdMm1TlKMSfXP73doBu0hy64BsLH4W8Q8QVCGmbN |
CitedBy_id | crossref_primary_10_1146_annurev_bioeng_110220_123503 crossref_primary_10_1186_s40364_022_00356_6 crossref_primary_10_1016_j_bbcan_2021_188527 crossref_primary_10_3390_cancers13194991 crossref_primary_10_1007_s11864_020_00737_9 crossref_primary_10_1016_j_gendis_2018_09_002 crossref_primary_10_3390_cancers12102765 crossref_primary_10_3389_fphar_2019_01438 crossref_primary_10_2967_jnumed_117_192534 crossref_primary_10_1016_j_gde_2019_02_003 crossref_primary_10_1097_MPA_0000000000002084 crossref_primary_10_3390_cancers13081873 crossref_primary_10_1371_journal_pone_0283692 crossref_primary_10_3390_biomedicines11041058 crossref_primary_10_1007_s13361_017_1851_4 crossref_primary_10_1016_j_drudis_2021_11_007 crossref_primary_10_1016_j_joca_2019_08_004 crossref_primary_10_1088_1361_6528_abc208 crossref_primary_10_1007_s11892_019_1261_z crossref_primary_10_3390_organoids1010008 crossref_primary_10_1038_s41551_020_0592_z crossref_primary_10_31857_S0026898423060186 crossref_primary_10_1016_j_jcmgh_2017_12_004 crossref_primary_10_1158_1535_7163_MCT_18_0510 crossref_primary_10_1007_s11523_018_0609_7 crossref_primary_10_1088_2050_6120_ab4ed8 crossref_primary_10_1186_s12974_021_02305_w crossref_primary_10_1016_j_isci_2024_110289 crossref_primary_10_18632_oncotarget_24425 crossref_primary_10_3390_ijms23136956 crossref_primary_10_3390_cancers12102750 crossref_primary_10_1088_1758_5090_ac6d11 crossref_primary_10_1007_s13402_021_00585_1 crossref_primary_10_1038_s41596_018_0022_9 crossref_primary_10_1016_j_lfs_2024_122758 crossref_primary_10_1172_jci_insight_135544 crossref_primary_10_34133_bmef_0005 crossref_primary_10_1002_ppsc_201700222 crossref_primary_10_3389_fonc_2023_1164535 crossref_primary_10_1038_s42003_021_02938_w crossref_primary_10_1364_BOE_7_004364 crossref_primary_10_3390_cancers14030525 crossref_primary_10_1038_s41525_022_00342_9 crossref_primary_10_3389_fonc_2020_00553 crossref_primary_10_1186_s13045_018_0662_9 crossref_primary_10_1364_BOE_8_001911 crossref_primary_10_1016_j_gendis_2023_02_052 crossref_primary_10_3389_fimmu_2024_1341079 crossref_primary_10_3390_cancers12040811 crossref_primary_10_1002_cyto_a_24534 crossref_primary_10_1016_j_compbiomed_2024_108846 crossref_primary_10_1038_s42003_023_05368_y crossref_primary_10_15252_msb_20177697 crossref_primary_10_3390_biomedicines11030890 crossref_primary_10_3390_ijms20112766 crossref_primary_10_1016_j_lfs_2020_117784 crossref_primary_10_3390_cancers13194979 crossref_primary_10_1016_j_jneumeth_2024_110171 crossref_primary_10_1146_annurev_cancerbio_030419_033333 crossref_primary_10_1364_BOE_389164 crossref_primary_10_1371_journal_pone_0216564 crossref_primary_10_1016_j_ctrv_2019_101926 crossref_primary_10_1002_cpsc_109 crossref_primary_10_1080_19382014_2021_1941555 crossref_primary_10_1002_adhm_202303350 crossref_primary_10_3390_ijms21165656 crossref_primary_10_3390_jcm8091399 crossref_primary_10_18632_oncotarget_26780 crossref_primary_10_1002_jms_4452 crossref_primary_10_1016_j_xcrm_2020_100017 crossref_primary_10_1038_s41388_022_02448_x crossref_primary_10_1177_2472555220915830 crossref_primary_10_1134_S002689332306016X crossref_primary_10_1016_j_biotechadv_2021_107883 crossref_primary_10_1158_1078_0432_CCR_18_3590 crossref_primary_10_1002_jbio_201600276 crossref_primary_10_3390_cancers15184601 crossref_primary_10_1186_s12935_021_02044_1 crossref_primary_10_1016_j_neo_2019_04_004 crossref_primary_10_1016_j_semcancer_2018_06_005 crossref_primary_10_1089_ars_2017_7451 |
ContentType | Journal Article |
DBID | CGR CUY CVF ECM EIF NPM |
DOI | 10.1097/mpa.0000000000000543 |
DatabaseName | Medline MEDLINE MEDLINE (Ovid) MEDLINE MEDLINE PubMed |
DatabaseTitle | MEDLINE Medline Complete MEDLINE with Full Text PubMed MEDLINE (Ovid) |
DatabaseTitleList | MEDLINE |
Database_xml | – sequence: 1 dbid: NPM name: PubMed url: https://proxy.k.utb.cz/login?url=http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=PubMed sourceTypes: Index Database – sequence: 2 dbid: EIF name: MEDLINE url: https://proxy.k.utb.cz/login?url=https://www.webofscience.com/wos/medline/basic-search sourceTypes: Index Database |
DeliveryMethod | no_fulltext_linktorsrc |
Discipline | Medicine |
EISSN | 1536-4828 |
ExternalDocumentID | 26495796 |
Genre | Journal Article Research Support, N.I.H., Extramural |
GrantInformation_xml | – fundername: NCI NIH HHS grantid: R01 CA185747 – fundername: NCI NIH HHS grantid: R01 CA161976 |
GroupedDBID | --- .-D .55 .GJ .XZ .Z2 0R~ 123 4Q1 4Q2 4Q3 53G 5RE 5VS 8L- AAAAV AAHPQ AAIQE AAJCS AAMTA AARTV AASCR AAYEP ABASU ABBUW ABDIG ABJNI ABOCM ABVCZ ABXVJ ABZAD ACCJW ACDDN ACEWG ACGFO ACGFS ACILI ACWDW ACWRI ACXJB ACXNZ ADFPA ADGGA ADHPY ADNKB AE3 AE6 AEBDS AEETU AENEX AFDTB AFEXH AFUWQ AHQNM AHRYX AHVBC AINUH AJIOK AJNWD AJNYG AJZMW ALMA_UNASSIGNED_HOLDINGS ALMTX AMJPA AMKUR AMNEI AOHHW AWKKM BQLVK BS7 C45 CGR CS3 CUY CVF DIWNM DU5 DUNZO E.X EBS ECM EEVPB EIF EJD EX3 F2K F2L F5P FCALG FL- GNXGY GQDEL H0~ HLJTE HZ~ IKREB IN~ JF9 JG8 JK3 JK8 K8S KD2 KMI L-C N9A NPM N~M O9- OAG OAH OCUKA ODA ODMTH OHYEH OJAPA OL1 OLG OLV OLW OLZ OPUJH ORVUJ OUVQU OVD OVDNE OWU OWV OWW OWX OWY OWZ OXXIT P-K P2P R58 RLZ S4R S4S T8P TEORI TSPGW V2I VVN W3M WOQ WOW X3V X3W X7M XXN XYM YFH ZFV ZXP ZZMQN |
ID | FETCH-LOGICAL-c474t-abb7dc7c0a58daba05f96faccd0d76204f721b66fabd06d23ae11c240bc3b5e62 |
IngestDate | Sat Sep 28 07:57:52 EDT 2024 |
IsDoiOpenAccess | false |
IsOpenAccess | true |
IsPeerReviewed | true |
IsScholarly | true |
Issue | 6 |
Language | English |
LinkModel | OpenURL |
MergedId | FETCHMERGED-LOGICAL-c474t-abb7dc7c0a58daba05f96faccd0d76204f721b66fabd06d23ae11c240bc3b5e62 |
OpenAccessLink | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874911 |
PMID | 26495796 |
ParticipantIDs | pubmed_primary_26495796 |
PublicationCentury | 2000 |
PublicationDate | 2016-07-01 |
PublicationDateYYYYMMDD | 2016-07-01 |
PublicationDate_xml | – month: 07 year: 2016 text: 2016-07-01 day: 01 |
PublicationDecade | 2010 |
PublicationPlace | United States |
PublicationPlace_xml | – name: United States |
PublicationTitle | Pancreas |
PublicationTitleAlternate | Pancreas |
PublicationYear | 2016 |
References | 23117810 - J Biomed Opt. 2012 Nov;17(11):116015 18042710 - Proc Natl Acad Sci U S A. 2007 Dec 4;104(49):19494-9 25557080 - Cell. 2015 Jan 15;160(1-2):324-38 24686167 - Cancer Res. 2014 Jun 1;74(11):3067-75 24641346 - Mol Pharm. 2014 Jul 7;11(7):2071-81 22439937 - Cancer Cell. 2012 Mar 20;21(3):418-29 25780745 - Biomed Opt Express. 2015 Jan 15;6(2):559-73 22607264 - Annu Rev Biomed Eng. 2012;14:351-67 22254170 - Biomed Opt Express. 2012 Jan 1;3(1):75-85 17477729 - J Biomed Opt. 2007 Mar-Apr;12(2):024014 24130112 - Cancer Res. 2013 Oct 15;73(20):6164-74 220260 - J Biol Chem. 1979 Jun 10;254(11):4764-71 11864371 - Genome Biol. 2002;3(2):RESEARCH0009 25100563 - Cancer Res. 2014 Sep 15;74(18):5184-94 2569889 - Biochemistry. 1989 May 16;28(10):4259-62 1741380 - Proc Natl Acad Sci U S A. 1992 Feb 15;89(4):1271-5 24332913 - Cell. 2013 Dec 19;155(7):1639-51 11964266 - Biophys J. 2002 May;82(5):2811-25 26255562 - Gastroenterology. 2015 Dec;149(7):1932-1943.e9 16299584 - Biol Proced Online. 2005;7:144-61 6487734 - Biophys J. 1984 Sep;46(3):343-8 |
References_xml | |
SSID | ssj0017359 |
Score | 2.5108998 |
Snippet | Three-dimensional organoids derived from primary pancreatic ductal adenocarcinomas are an attractive platform for testing potential anticancer drugs on... |
SourceID | pubmed |
SourceType | Index Database |
StartPage | 863 |
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 |
URI | https://www.ncbi.nlm.nih.gov/pubmed/26495796 |
Volume | 45 |
hasFullText | |
inHoldings | 1 |
isFullTextHit | |
isPrint | |
link | http://utb.summon.serialssolutions.com/2.0.0/link/0/eLvHCXMwnV1Lb9NAEF6lICEuqLyhBe2BW7VgO17v-ohCUajkwKEVvVX7DKmoE6VJD_wAfg8_kRnv2k5KEY8crGjXXj_m03g8880MIa-E1qVJLWc655zl2g6ZzIxk3vrElL7MdFO7s5oU45P86JSfDgY_NlhL65V-bb7dmFfyP1KFMZArZsn-g2S7RWEA_oN8YQsShu1fyfjjIniiP1zEXkP-4N1yPWXYjwPj-pVbgYy_Yh-MkEXQkF8rdLCHqEFw4X8CyTe2ozkYIQiWIUNzPrOYRHLlsMLyGGkzc7gSh5xZPAt6_pFeu8Ulikt1hvpnOPZLm0jTh6BG6hKzV1Qk-R0p7IPYYWmipsiJxDYvs_AGmKqlOu-9tJXDCk-hYsJktljXsXd09F6kRcd0hZdPq3ELlsuYIR5VcqgwGaG3qV9l0Ia_6P1QTxgUaKhH2f54vrU7SG9x0WABzECMTxZ_nr1Wjbud2iE7QqJGnaB3KEatxJCXbXpmKd7cdDlYfDouce1DpjFojnfJvfglQt8GWN0nA1c_IHeqyLV4SL5HdNGILjr3dBNdtEcXjeiis5oGdFFAF23QRXt00YAu2qGLRnTRLXQ1Z6Etuh6Rk_eHx6Mxi107mMlFvmJKa2GNMIni0iqtEu7LwitjbGIFdj_wIkt1AUPaJoXNhsqlqQHDUpuh5q7IHpNb9bx2TwkthZTOiFIYDYamSlUmfO4zaZT0OVhWz8iT8ATPFqE0y1n7bJ__dmaP3O1xuE9ue7hL9wIMy5V-2UjzJ7cPe90 |
link.rule.ids | 786 |
linkProvider | National Library of Medicine |
openUrl | ctx_ver=Z39.88-2004&ctx_enc=info%3Aofi%2Fenc%3AUTF-8&rfr_id=info%3Asid%2Fsummon.serialssolutions.com&rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&rft.genre=article&rft.atitle=Optical+Imaging+of+Drug-Induced+Metabolism+Changes+in+Murine+and+Human+Pancreatic+Cancer+Organoids+Reveals+Heterogeneous+Drug+Response&rft.jtitle=Pancreas&rft.au=Walsh%2C+Alex+J&rft.au=Castellanos%2C+Jason+A&rft.au=Nagathihalli%2C+Nagaraj+S&rft.au=Merchant%2C+Nipun+B&rft.date=2016-07-01&rft.eissn=1536-4828&rft.volume=45&rft.issue=6&rft.spage=863&rft_id=info:doi/10.1097%2Fmpa.0000000000000543&rft_id=info%3Apmid%2F26495796&rft_id=info%3Apmid%2F26495796&rft.externalDocID=26495796 |