In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2018-12

AUTHORS

Andrea R. Mazzocchi, Shiny A. P. Rajan, Konstantinos I. Votanopoulos, Adam R. Hall, Aleksander Skardal

ABSTRACT

Variability in patient response to anti-cancer drugs is currently addressed by relating genetic mutations to chemotherapy through precision medicine. However, practical benefits of precision medicine to therapy design are less clear. Even after identification of mutations, oncologists are often left with several drug options, and for some patients there is no definitive treatment solution. There is a need for model systems to help predict personalized responses to chemotherapeutics. We have microengineered 3D tumor organoids directly from fresh tumor biopsies to provide patient-specific models with which treatment optimization can be performed before initiation of therapy. We demonstrate the initial implementation of this platform using tumor biospecimens surgically removed from two mesothelioma patients. First, we show the ability to biofabricate and maintain viable 3D tumor constructs within a tumor-on-a-chip microfluidic device. Second, we demonstrate that results of on-chip chemotherapy screening mimic those observed in subjects themselves. Finally, we demonstrate mutation-specific drug testing by considering the results of precision medicine genetic screening and confirming the effectiveness of the non-standard compound 3-deazaneplanocin A for an identified mutation. This patient-derived tumor organoid strategy is adaptable to a wide variety of cancers and may provide a framework with which to improve efforts in precision medicine oncology. More... »

PAGES

2886

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s41598-018-21200-8

DOI

http://dx.doi.org/10.1038/s41598-018-21200-8

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1100901821

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/29440675


Indexing Status Check whether this publication has been indexed by Scopus and Web Of Science using the SN Indexing Status Tool
Incoming Citations Browse incoming citations for this publication using opencitations.net

JSON-LD is the canonical representation for SciGraph data.

TIP: You can open this SciGraph record using an external JSON-LD service: JSON-LD Playground Google SDTT

[
  {
    "@context": "https://springernature.github.io/scigraph/jsonld/sgcontext.json", 
    "about": [
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/1112", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Oncology and Carcinogenesis", 
        "type": "DefinedTerm"
      }, 
      {
        "id": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/11", 
        "inDefinedTermSet": "http://purl.org/au-research/vocabulary/anzsrc-for/2008/", 
        "name": "Medical and Health Sciences", 
        "type": "DefinedTerm"
      }
    ], 
    "author": [
      {
        "affiliation": {
          "alternateName": "Wake Forest University", 
          "id": "https://www.grid.ac/institutes/grid.241167.7", 
          "name": [
            "Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center, 27101, Winston-Salem, NC, USA", 
            "Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Medical Center Boulevard, 27157, Winston-Salem, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Mazzocchi", 
        "givenName": "Andrea R.", 
        "id": "sg:person.07672654660.06", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07672654660.06"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Wake Forest University", 
          "id": "https://www.grid.ac/institutes/grid.241167.7", 
          "name": [
            "Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center, 27101, Winston-Salem, NC, USA", 
            "Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Medical Center Boulevard, 27157, Winston-Salem, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Rajan", 
        "givenName": "Shiny A. P.", 
        "id": "sg:person.01273515354.52", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01273515354.52"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Wake Forest Baptist Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.412860.9", 
          "name": [
            "Department of Surgery-Surgical Oncology, Wake Forest Baptist Medical Center, Medical Center Boulevard, 27157, Winston-Salem, NC, USA", 
            "Comprehensive Cancer Center at Wake Forest Baptist Medical, Medical Center Boulevard, 27157, Winston-Salem, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Votanopoulos", 
        "givenName": "Konstantinos I.", 
        "id": "sg:person.01155643513.53", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01155643513.53"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Wake Forest Baptist Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.412860.9", 
          "name": [
            "Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center, 27101, Winston-Salem, NC, USA", 
            "Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Medical Center Boulevard, 27157, Winston-Salem, NC, USA", 
            "Comprehensive Cancer Center at Wake Forest Baptist Medical, Medical Center Boulevard, 27157, Winston-Salem, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Hall", 
        "givenName": "Adam R.", 
        "id": "sg:person.01051262074.86", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01051262074.86"
        ], 
        "type": "Person"
      }, 
      {
        "affiliation": {
          "alternateName": "Wake Forest Baptist Medical Center", 
          "id": "https://www.grid.ac/institutes/grid.412860.9", 
          "name": [
            "Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center, 27101, Winston-Salem, NC, USA", 
            "Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Medical Center Boulevard, 27157, Winston-Salem, NC, USA", 
            "Comprehensive Cancer Center at Wake Forest Baptist Medical, Medical Center Boulevard, 27157, Winston-Salem, NC, USA", 
            "Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, 27157, Winston-Salem, NC, USA"
          ], 
          "type": "Organization"
        }, 
        "familyName": "Skardal", 
        "givenName": "Aleksander", 
        "id": "sg:person.01033434737.72", 
        "sameAs": [
          "https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01033434737.72"
        ], 
        "type": "Person"
      }
    ], 
    "citation": [
      {
        "id": "https://doi.org/10.1016/j.biomaterials.2012.03.034", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001413490"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.actbio.2015.07.030", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1001763644"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1517/17460441.2014.886562", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1003259885"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13073-015-0158-y", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005318614", 
          "https://doi.org/10.1186/s13073-015-0158-y"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1186/s13073-015-0158-y", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1005318614", 
          "https://doi.org/10.1186/s13073-015-0158-y"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2559.1998.00349.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010095112"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1046/j.1365-2559.1998.00349.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1010095112"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev-genom-090413-025552", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1012620595"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.tcb.2011.09.005", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1015131685"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.advenzreg.2006.12.012", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017553917"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm.3947", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017703944", 
          "https://doi.org/10.1038/nm.3947"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/nm.3947", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1017703944", 
          "https://doi.org/10.1038/nm.3947"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/1758834015591952", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018195640"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/1758834015591952", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018195640"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jbm.b.33736", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1018279418"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/annonc/mdu478", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1021148509"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/biot.201100290", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1024464451"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1039/c4lc00173g", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1025676724"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1088/1758-5090/7/3/031001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027066739"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1053/j.seminoncol.2015.07.013", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027156493"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ymeth.2008.01.010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027843922"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.ymeth.2008.01.010", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1027843922"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/1087057104265040", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028028391"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1177/1087057104265040", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028028391"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1007/s10439-015-1298-3", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1028453148", 
          "https://doi.org/10.1007/s10439-015-1298-3"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jjco/hyv144", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1029352136"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.biomaterials.2010.07.047", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030053928"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.drudis.2011.10.029", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1030164313"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/mop.0000000000000172", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036025462"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/mop.0000000000000172", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1036025462"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.apsb.2015.01.011", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1042106973"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0055119", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1044019994"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/his.13123", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046397210"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/his.13123", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1046397210"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1371/journal.pone.0020887", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1047829866"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1146/annurev-pathol-012414-040418", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048677889"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1349-7006.2010.01723.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048736591"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1111/j.1349-7006.2010.01723.x", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1048736591"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1201861", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049332185", 
          "https://doi.org/10.1038/sj.onc.1201861"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1201861", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049332185", 
          "https://doi.org/10.1038/sj.onc.1201861"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "sg:pub.10.1038/sj.onc.1201861", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049332185", 
          "https://doi.org/10.1038/sj.onc.1201861"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1309/ajcphsuj15neymip", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1049455458"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/jcb.21386", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052707975"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1016/j.cell.2014.08.016", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1052794984"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1002/bit.25950", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1053492530"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ar7000827", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055151640"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1021/ar7000827", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1055151640"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1093/jnci/djv332", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1059821588"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.1097/00000478-199609000-00001", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1060122134"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://doi.org/10.3791/53606", 
        "sameAs": [
          "https://app.dimensions.ai/details/publication/pub.1071425574"
        ], 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1075850344", 
        "type": "CreativeWork"
      }, 
      {
        "id": "https://app.dimensions.ai/details/publication/pub.1079143333", 
        "type": "CreativeWork"
      }
    ], 
    "datePublished": "2018-12", 
    "datePublishedReg": "2018-12-01", 
    "description": "Variability in patient response to anti-cancer drugs is currently addressed by relating genetic mutations to chemotherapy through precision medicine. However, practical benefits of precision medicine to therapy design are less clear. Even after identification of mutations, oncologists are often left with several drug options, and for some patients there is no definitive treatment solution. There is a need for model systems to help predict personalized responses to chemotherapeutics. We have microengineered 3D tumor organoids directly from fresh tumor biopsies to provide patient-specific models with which treatment optimization can be performed before initiation of therapy. We demonstrate the initial implementation of this platform using tumor biospecimens surgically removed from two mesothelioma patients. First, we show the ability to biofabricate and maintain viable 3D tumor constructs within a tumor-on-a-chip microfluidic device. Second, we demonstrate that results of on-chip chemotherapy screening mimic those observed in subjects themselves. Finally, we demonstrate mutation-specific drug testing by considering the results of precision medicine genetic screening and confirming the effectiveness of the non-standard compound 3-deazaneplanocin A for an identified mutation. This patient-derived tumor organoid strategy is adaptable to a wide variety of cancers and may provide a framework with which to improve efforts in precision medicine oncology.", 
    "genre": "research_article", 
    "id": "sg:pub.10.1038/s41598-018-21200-8", 
    "inLanguage": [
      "en"
    ], 
    "isAccessibleForFree": true, 
    "isFundedItemOf": [
      {
        "id": "sg:grant.2438796", 
        "type": "MonetaryGrant"
      }
    ], 
    "isPartOf": [
      {
        "id": "sg:journal.1045337", 
        "issn": [
          "2045-2322"
        ], 
        "name": "Scientific Reports", 
        "type": "Periodical"
      }, 
      {
        "issueNumber": "1", 
        "type": "PublicationIssue"
      }, 
      {
        "type": "PublicationVolume", 
        "volumeNumber": "8"
      }
    ], 
    "name": "In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening", 
    "pagination": "2886", 
    "productId": [
      {
        "name": "readcube_id", 
        "type": "PropertyValue", 
        "value": [
          "2ce5f1498676a1363723b4f1d812ea7c2aee4cbfdfda7ab06ee0c8881434132a"
        ]
      }, 
      {
        "name": "pubmed_id", 
        "type": "PropertyValue", 
        "value": [
          "29440675"
        ]
      }, 
      {
        "name": "nlm_unique_id", 
        "type": "PropertyValue", 
        "value": [
          "101563288"
        ]
      }, 
      {
        "name": "doi", 
        "type": "PropertyValue", 
        "value": [
          "10.1038/s41598-018-21200-8"
        ]
      }, 
      {
        "name": "dimensions_id", 
        "type": "PropertyValue", 
        "value": [
          "pub.1100901821"
        ]
      }
    ], 
    "sameAs": [
      "https://doi.org/10.1038/s41598-018-21200-8", 
      "https://app.dimensions.ai/details/publication/pub.1100901821"
    ], 
    "sdDataset": "articles", 
    "sdDatePublished": "2019-04-10T15:08", 
    "sdLicense": "https://scigraph.springernature.com/explorer/license/", 
    "sdPublisher": {
      "name": "Springer Nature - SN SciGraph project", 
      "type": "Organization"
    }, 
    "sdSource": "s3://com-uberresearch-data-dimensions-target-20181106-alternative/cleanup/v134/2549eaecd7973599484d7c17b260dba0a4ecb94b/merge/v9/a6c9fde33151104705d4d7ff012ea9563521a3ce/jats-lookup/v90/0000000001_0000000264/records_8663_00000552.jsonl", 
    "type": "ScholarlyArticle", 
    "url": "https://www.nature.com/articles/s41598-018-21200-8"
  }
]
 

Download the RDF metadata as:  json-ld nt turtle xml License info

HOW TO GET THIS DATA PROGRAMMATICALLY:

JSON-LD is a popular format for linked data which is fully compatible with JSON.

curl -H 'Accept: application/ld+json' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-21200-8'

N-Triples is a line-based linked data format ideal for batch operations.

curl -H 'Accept: application/n-triples' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-21200-8'

Turtle is a human-readable linked data format.

curl -H 'Accept: text/turtle' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-21200-8'

RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/s41598-018-21200-8'


 

This table displays all metadata directly associated to this object as RDF triples.

228 TRIPLES      21 PREDICATES      69 URIs      21 LITERALS      9 BLANK NODES

Subject Predicate Object
1 sg:pub.10.1038/s41598-018-21200-8 schema:about anzsrc-for:11
2 anzsrc-for:1112
3 schema:author N4d56a2608b294c27afa7cb01a242bad8
4 schema:citation sg:pub.10.1007/s10439-015-1298-3
5 sg:pub.10.1038/nm.3947
6 sg:pub.10.1038/sj.onc.1201861
7 sg:pub.10.1186/s13073-015-0158-y
8 https://app.dimensions.ai/details/publication/pub.1075850344
9 https://app.dimensions.ai/details/publication/pub.1079143333
10 https://doi.org/10.1002/biot.201100290
11 https://doi.org/10.1002/bit.25950
12 https://doi.org/10.1002/jbm.b.33736
13 https://doi.org/10.1002/jcb.21386
14 https://doi.org/10.1016/j.actbio.2015.07.030
15 https://doi.org/10.1016/j.advenzreg.2006.12.012
16 https://doi.org/10.1016/j.apsb.2015.01.011
17 https://doi.org/10.1016/j.biomaterials.2010.07.047
18 https://doi.org/10.1016/j.biomaterials.2012.03.034
19 https://doi.org/10.1016/j.cell.2014.08.016
20 https://doi.org/10.1016/j.drudis.2011.10.029
21 https://doi.org/10.1016/j.tcb.2011.09.005
22 https://doi.org/10.1016/j.ymeth.2008.01.010
23 https://doi.org/10.1021/ar7000827
24 https://doi.org/10.1039/c4lc00173g
25 https://doi.org/10.1046/j.1365-2559.1998.00349.x
26 https://doi.org/10.1053/j.seminoncol.2015.07.013
27 https://doi.org/10.1088/1758-5090/7/3/031001
28 https://doi.org/10.1093/annonc/mdu478
29 https://doi.org/10.1093/jjco/hyv144
30 https://doi.org/10.1093/jnci/djv332
31 https://doi.org/10.1097/00000478-199609000-00001
32 https://doi.org/10.1097/mop.0000000000000172
33 https://doi.org/10.1111/his.13123
34 https://doi.org/10.1111/j.1349-7006.2010.01723.x
35 https://doi.org/10.1146/annurev-genom-090413-025552
36 https://doi.org/10.1146/annurev-pathol-012414-040418
37 https://doi.org/10.1177/1087057104265040
38 https://doi.org/10.1177/1758834015591952
39 https://doi.org/10.1309/ajcphsuj15neymip
40 https://doi.org/10.1371/journal.pone.0020887
41 https://doi.org/10.1371/journal.pone.0055119
42 https://doi.org/10.1517/17460441.2014.886562
43 https://doi.org/10.3791/53606
44 schema:datePublished 2018-12
45 schema:datePublishedReg 2018-12-01
46 schema:description Variability in patient response to anti-cancer drugs is currently addressed by relating genetic mutations to chemotherapy through precision medicine. However, practical benefits of precision medicine to therapy design are less clear. Even after identification of mutations, oncologists are often left with several drug options, and for some patients there is no definitive treatment solution. There is a need for model systems to help predict personalized responses to chemotherapeutics. We have microengineered 3D tumor organoids directly from fresh tumor biopsies to provide patient-specific models with which treatment optimization can be performed before initiation of therapy. We demonstrate the initial implementation of this platform using tumor biospecimens surgically removed from two mesothelioma patients. First, we show the ability to biofabricate and maintain viable 3D tumor constructs within a tumor-on-a-chip microfluidic device. Second, we demonstrate that results of on-chip chemotherapy screening mimic those observed in subjects themselves. Finally, we demonstrate mutation-specific drug testing by considering the results of precision medicine genetic screening and confirming the effectiveness of the non-standard compound 3-deazaneplanocin A for an identified mutation. This patient-derived tumor organoid strategy is adaptable to a wide variety of cancers and may provide a framework with which to improve efforts in precision medicine oncology.
47 schema:genre research_article
48 schema:inLanguage en
49 schema:isAccessibleForFree true
50 schema:isPartOf Nc9ecb178d0a34520a536135f2ebe4ad9
51 Nf8914997766c4193b10be878fa6b7733
52 sg:journal.1045337
53 schema:name In vitro patient-derived 3D mesothelioma tumor organoids facilitate patient-centric therapeutic screening
54 schema:pagination 2886
55 schema:productId N16f04148fba24a7a8b4f8daab9c31db8
56 N1fb0bd72dd834ea38ef0b2b792da04a8
57 N96b8343440664f2c8fbe5f6b03ff2004
58 Naac8df6580204403b9eacbcf8c1bc375
59 Nce593d3e19b14711a25d587116028743
60 schema:sameAs https://app.dimensions.ai/details/publication/pub.1100901821
61 https://doi.org/10.1038/s41598-018-21200-8
62 schema:sdDatePublished 2019-04-10T15:08
63 schema:sdLicense https://scigraph.springernature.com/explorer/license/
64 schema:sdPublisher N197deed4978e4c3a8e9d82acdf08bc8b
65 schema:url https://www.nature.com/articles/s41598-018-21200-8
66 sgo:license sg:explorer/license/
67 sgo:sdDataset articles
68 rdf:type schema:ScholarlyArticle
69 N05abb8ac926a4e3e891b03f637c6715d rdf:first sg:person.01033434737.72
70 rdf:rest rdf:nil
71 N16f04148fba24a7a8b4f8daab9c31db8 schema:name doi
72 schema:value 10.1038/s41598-018-21200-8
73 rdf:type schema:PropertyValue
74 N197deed4978e4c3a8e9d82acdf08bc8b schema:name Springer Nature - SN SciGraph project
75 rdf:type schema:Organization
76 N1fb0bd72dd834ea38ef0b2b792da04a8 schema:name dimensions_id
77 schema:value pub.1100901821
78 rdf:type schema:PropertyValue
79 N430a41c06870422b8cfad3a7e69d720b rdf:first sg:person.01155643513.53
80 rdf:rest N899c3b03cc4a434f87bddc25e1c8a48f
81 N4d56a2608b294c27afa7cb01a242bad8 rdf:first sg:person.07672654660.06
82 rdf:rest N52465b27c8af490ea1d7e313138d22df
83 N52465b27c8af490ea1d7e313138d22df rdf:first sg:person.01273515354.52
84 rdf:rest N430a41c06870422b8cfad3a7e69d720b
85 N899c3b03cc4a434f87bddc25e1c8a48f rdf:first sg:person.01051262074.86
86 rdf:rest N05abb8ac926a4e3e891b03f637c6715d
87 N96b8343440664f2c8fbe5f6b03ff2004 schema:name readcube_id
88 schema:value 2ce5f1498676a1363723b4f1d812ea7c2aee4cbfdfda7ab06ee0c8881434132a
89 rdf:type schema:PropertyValue
90 Naac8df6580204403b9eacbcf8c1bc375 schema:name pubmed_id
91 schema:value 29440675
92 rdf:type schema:PropertyValue
93 Nc9ecb178d0a34520a536135f2ebe4ad9 schema:volumeNumber 8
94 rdf:type schema:PublicationVolume
95 Nce593d3e19b14711a25d587116028743 schema:name nlm_unique_id
96 schema:value 101563288
97 rdf:type schema:PropertyValue
98 Nf8914997766c4193b10be878fa6b7733 schema:issueNumber 1
99 rdf:type schema:PublicationIssue
100 anzsrc-for:11 schema:inDefinedTermSet anzsrc-for:
101 schema:name Medical and Health Sciences
102 rdf:type schema:DefinedTerm
103 anzsrc-for:1112 schema:inDefinedTermSet anzsrc-for:
104 schema:name Oncology and Carcinogenesis
105 rdf:type schema:DefinedTerm
106 sg:grant.2438796 http://pending.schema.org/fundedItem sg:pub.10.1038/s41598-018-21200-8
107 rdf:type schema:MonetaryGrant
108 sg:journal.1045337 schema:issn 2045-2322
109 schema:name Scientific Reports
110 rdf:type schema:Periodical
111 sg:person.01033434737.72 schema:affiliation https://www.grid.ac/institutes/grid.412860.9
112 schema:familyName Skardal
113 schema:givenName Aleksander
114 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01033434737.72
115 rdf:type schema:Person
116 sg:person.01051262074.86 schema:affiliation https://www.grid.ac/institutes/grid.412860.9
117 schema:familyName Hall
118 schema:givenName Adam R.
119 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01051262074.86
120 rdf:type schema:Person
121 sg:person.01155643513.53 schema:affiliation https://www.grid.ac/institutes/grid.412860.9
122 schema:familyName Votanopoulos
123 schema:givenName Konstantinos I.
124 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01155643513.53
125 rdf:type schema:Person
126 sg:person.01273515354.52 schema:affiliation https://www.grid.ac/institutes/grid.241167.7
127 schema:familyName Rajan
128 schema:givenName Shiny A. P.
129 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.01273515354.52
130 rdf:type schema:Person
131 sg:person.07672654660.06 schema:affiliation https://www.grid.ac/institutes/grid.241167.7
132 schema:familyName Mazzocchi
133 schema:givenName Andrea R.
134 schema:sameAs https://app.dimensions.ai/discover/publication?and_facet_researcher=ur.07672654660.06
135 rdf:type schema:Person
136 sg:pub.10.1007/s10439-015-1298-3 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028453148
137 https://doi.org/10.1007/s10439-015-1298-3
138 rdf:type schema:CreativeWork
139 sg:pub.10.1038/nm.3947 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017703944
140 https://doi.org/10.1038/nm.3947
141 rdf:type schema:CreativeWork
142 sg:pub.10.1038/sj.onc.1201861 schema:sameAs https://app.dimensions.ai/details/publication/pub.1049332185
143 https://doi.org/10.1038/sj.onc.1201861
144 rdf:type schema:CreativeWork
145 sg:pub.10.1186/s13073-015-0158-y schema:sameAs https://app.dimensions.ai/details/publication/pub.1005318614
146 https://doi.org/10.1186/s13073-015-0158-y
147 rdf:type schema:CreativeWork
148 https://app.dimensions.ai/details/publication/pub.1075850344 schema:CreativeWork
149 https://app.dimensions.ai/details/publication/pub.1079143333 schema:CreativeWork
150 https://doi.org/10.1002/biot.201100290 schema:sameAs https://app.dimensions.ai/details/publication/pub.1024464451
151 rdf:type schema:CreativeWork
152 https://doi.org/10.1002/bit.25950 schema:sameAs https://app.dimensions.ai/details/publication/pub.1053492530
153 rdf:type schema:CreativeWork
154 https://doi.org/10.1002/jbm.b.33736 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018279418
155 rdf:type schema:CreativeWork
156 https://doi.org/10.1002/jcb.21386 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052707975
157 rdf:type schema:CreativeWork
158 https://doi.org/10.1016/j.actbio.2015.07.030 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001763644
159 rdf:type schema:CreativeWork
160 https://doi.org/10.1016/j.advenzreg.2006.12.012 schema:sameAs https://app.dimensions.ai/details/publication/pub.1017553917
161 rdf:type schema:CreativeWork
162 https://doi.org/10.1016/j.apsb.2015.01.011 schema:sameAs https://app.dimensions.ai/details/publication/pub.1042106973
163 rdf:type schema:CreativeWork
164 https://doi.org/10.1016/j.biomaterials.2010.07.047 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030053928
165 rdf:type schema:CreativeWork
166 https://doi.org/10.1016/j.biomaterials.2012.03.034 schema:sameAs https://app.dimensions.ai/details/publication/pub.1001413490
167 rdf:type schema:CreativeWork
168 https://doi.org/10.1016/j.cell.2014.08.016 schema:sameAs https://app.dimensions.ai/details/publication/pub.1052794984
169 rdf:type schema:CreativeWork
170 https://doi.org/10.1016/j.drudis.2011.10.029 schema:sameAs https://app.dimensions.ai/details/publication/pub.1030164313
171 rdf:type schema:CreativeWork
172 https://doi.org/10.1016/j.tcb.2011.09.005 schema:sameAs https://app.dimensions.ai/details/publication/pub.1015131685
173 rdf:type schema:CreativeWork
174 https://doi.org/10.1016/j.ymeth.2008.01.010 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027843922
175 rdf:type schema:CreativeWork
176 https://doi.org/10.1021/ar7000827 schema:sameAs https://app.dimensions.ai/details/publication/pub.1055151640
177 rdf:type schema:CreativeWork
178 https://doi.org/10.1039/c4lc00173g schema:sameAs https://app.dimensions.ai/details/publication/pub.1025676724
179 rdf:type schema:CreativeWork
180 https://doi.org/10.1046/j.1365-2559.1998.00349.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1010095112
181 rdf:type schema:CreativeWork
182 https://doi.org/10.1053/j.seminoncol.2015.07.013 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027156493
183 rdf:type schema:CreativeWork
184 https://doi.org/10.1088/1758-5090/7/3/031001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1027066739
185 rdf:type schema:CreativeWork
186 https://doi.org/10.1093/annonc/mdu478 schema:sameAs https://app.dimensions.ai/details/publication/pub.1021148509
187 rdf:type schema:CreativeWork
188 https://doi.org/10.1093/jjco/hyv144 schema:sameAs https://app.dimensions.ai/details/publication/pub.1029352136
189 rdf:type schema:CreativeWork
190 https://doi.org/10.1093/jnci/djv332 schema:sameAs https://app.dimensions.ai/details/publication/pub.1059821588
191 rdf:type schema:CreativeWork
192 https://doi.org/10.1097/00000478-199609000-00001 schema:sameAs https://app.dimensions.ai/details/publication/pub.1060122134
193 rdf:type schema:CreativeWork
194 https://doi.org/10.1097/mop.0000000000000172 schema:sameAs https://app.dimensions.ai/details/publication/pub.1036025462
195 rdf:type schema:CreativeWork
196 https://doi.org/10.1111/his.13123 schema:sameAs https://app.dimensions.ai/details/publication/pub.1046397210
197 rdf:type schema:CreativeWork
198 https://doi.org/10.1111/j.1349-7006.2010.01723.x schema:sameAs https://app.dimensions.ai/details/publication/pub.1048736591
199 rdf:type schema:CreativeWork
200 https://doi.org/10.1146/annurev-genom-090413-025552 schema:sameAs https://app.dimensions.ai/details/publication/pub.1012620595
201 rdf:type schema:CreativeWork
202 https://doi.org/10.1146/annurev-pathol-012414-040418 schema:sameAs https://app.dimensions.ai/details/publication/pub.1048677889
203 rdf:type schema:CreativeWork
204 https://doi.org/10.1177/1087057104265040 schema:sameAs https://app.dimensions.ai/details/publication/pub.1028028391
205 rdf:type schema:CreativeWork
206 https://doi.org/10.1177/1758834015591952 schema:sameAs https://app.dimensions.ai/details/publication/pub.1018195640
207 rdf:type schema:CreativeWork
208 https://doi.org/10.1309/ajcphsuj15neymip schema:sameAs https://app.dimensions.ai/details/publication/pub.1049455458
209 rdf:type schema:CreativeWork
210 https://doi.org/10.1371/journal.pone.0020887 schema:sameAs https://app.dimensions.ai/details/publication/pub.1047829866
211 rdf:type schema:CreativeWork
212 https://doi.org/10.1371/journal.pone.0055119 schema:sameAs https://app.dimensions.ai/details/publication/pub.1044019994
213 rdf:type schema:CreativeWork
214 https://doi.org/10.1517/17460441.2014.886562 schema:sameAs https://app.dimensions.ai/details/publication/pub.1003259885
215 rdf:type schema:CreativeWork
216 https://doi.org/10.3791/53606 schema:sameAs https://app.dimensions.ai/details/publication/pub.1071425574
217 rdf:type schema:CreativeWork
218 https://www.grid.ac/institutes/grid.241167.7 schema:alternateName Wake Forest University
219 schema:name Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Medical Center Boulevard, 27157, Winston-Salem, NC, USA
220 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center, 27101, Winston-Salem, NC, USA
221 rdf:type schema:Organization
222 https://www.grid.ac/institutes/grid.412860.9 schema:alternateName Wake Forest Baptist Medical Center
223 schema:name Comprehensive Cancer Center at Wake Forest Baptist Medical, Medical Center Boulevard, 27157, Winston-Salem, NC, USA
224 Department of Cancer Biology, Wake Forest School of Medicine, Medical Center Boulevard, 27157, Winston-Salem, NC, USA
225 Department of Surgery-Surgical Oncology, Wake Forest Baptist Medical Center, Medical Center Boulevard, 27157, Winston-Salem, NC, USA
226 Virginia Tech-Wake Forest School of Biomedical Engineering and Sciences, Wake Forest School of Medicine, Medical Center Boulevard, 27157, Winston-Salem, NC, USA
227 Wake Forest Institute for Regenerative Medicine, Wake Forest School of Medicine, Medical Center, 27101, Winston-Salem, NC, USA
228 rdf:type schema:Organization
 




Preview window. Press ESC to close (or click here)


...