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dc.contributor.author
Robl, Bernhard
dc.contributor.author
Botter, Sander Martijn
dc.contributor.author
Boro, Aleksandar
dc.contributor.author
Meier, Daniela
dc.contributor.author
Neri, Dario
dc.contributor.author
Fuchs, Bruno
dc.date.accessioned
2017-11-23T09:41:25Z
dc.date.available
2017-10-06T02:25:27Z
dc.date.available
2017-11-23T09:41:25Z
dc.date.issued
2017-06
dc.identifier.other
10.1016/j.tranon.2017.02.005
en_US
dc.identifier.uri
http://hdl.handle.net/20.500.11850/190750
dc.identifier.doi
10.3929/ethz-b-000190750
dc.description.abstract
The targeted delivery of tumor necrosis factor-α (TNF-α) with antibodies specific to splice isoforms of fibronectin [e.g., F8-TNF, specific to the extra-domain A (EDA) domain of fibronectin] has already shown efficacy against experimental sarcomas but has not yet been investigated in orthotopic sarcomas. Here, we investigated F8-TNF in a syngeneic K7 M2–derived orthotopic model of osteosarcoma as a treatment against pulmonary metastases, the most frequent cause of osteosarcoma-related death. Immunofluorescence on human osteosarcoma tissue confirmed the presence of EDA in primary tumors (PTs) as well as metastases. In mice, the efficacy of F8-TNF against PTs and early pulmonary metastases was evaluated. Intratibial PT growth was not affected by F8-TNF, yet early micrometastases were reduced possibly due to an F8-TNF–dependent attraction of pulmonary CD4+, CD8+, and natural killer cells. Furthermore, immunofluorescence revealed stronger expression of EDA in early pulmonary metastases compared with PT tissue. To study progressing pulmonary metastases, a hind limb amputation model was established, and the efficacy of F8-TNF, alone or combined with doxorubicin, was investigated. Despite the presence of EDA in metastases, no inhibition of progressive metastatic growth was detected. No significant differences in numbers of CD4+ or CD8+ cells or F4/80+ and Ly6G+ myeloid-derived cells were observed, although a strong association between metastatic growth and presence of pulmonary Ly6G+ myeloid-derived cells was detected. In summary, these findings demonstrate the potential of F8-TNF in activating the immune system and reducing early metastatic growth yet suggest a lack of efficacy of F8-TNF alone or combined with doxorubicin against progressing osteosarcoma metastases.
en_US
dc.format
application/pdf
dc.language.iso
en
en_US
dc.publisher
Elsevier
en_US
dc.rights.uri
http://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title
Evaluation of F8-TNF-alpha in Models of Early and Progressive Metastatic Osteosarcoma
en_US
dc.type
Journal Article
dc.rights.license
Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International
dc.date.published
2017-04-25
ethz.journal.title
TRANSLATIONAL ONCOLOGY
ethz.journal.volume
10
en_US
ethz.journal.issue
3
en_US
ethz.pages.start
419
en_US
ethz.pages.end
430
en_US
ethz.version.deposit
publishedVersion
en_US
ethz.identifier.wos
ethz.identifier.scopus
ethz.publication.place
s.l.
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03463 - Neri, Dario / Neri, Dario
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02020 - Dep. Chemie und Angewandte Biowiss. / Dep. of Chemistry and Applied Biosc.::02534 - Institut für Pharmazeutische Wiss. / Institute of Pharmaceutical Sciences::03463 - Neri, Dario / Neri, Dario
ethz.date.deposited
2017-10-06T02:25:35Z
ethz.source
WOS
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-11-23T09:41:27Z
ethz.rosetta.lastUpdated
2019-02-02T13:36:10Z
ethz.rosetta.exportRequired
true
ethz.rosetta.versionExported
true
ethz.COinS
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