Mostrar el registro sencillo del ítem
dc.contributor.author
Rosemblit, Cinthia
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.contributor.author
Datta, Jashodeep
dc.contributor.author
Lowenfeld, Lea
dc.contributor.author
Xu, Shuwen
dc.contributor.author
Basu, Amrita
dc.contributor.author
Kodumudi, Krithika
dc.contributor.author
Wiener, Doris
dc.contributor.author
Czerniecki, Brian J.
dc.date.available
2020-04-24T19:41:58Z
dc.date.issued
2018-04
dc.identifier.citation
Rosemblit, Cinthia; Datta, Jashodeep; Lowenfeld, Lea; Xu, Shuwen; Basu, Amrita; et al.; Oncodriver inhibition and CD4+ Th1 cytokines cooperate through Stat1 activation to induce tumor senescence and apoptosis in HER2+ and triple negative breast cancer: implications for combining immune and targeted therapies; Impact Journals; Oncotarget; 9; 33; 4-2018; 23058-23077
dc.identifier.issn
1949-2553
dc.identifier.uri
http://hdl.handle.net/11336/103583
dc.description.abstract
In patients with HER2-expressing breast cancer many develop resistance to HER2 targeted therapies. We show that high and intermediate HER2-expressing cancer cell lines are driven toward apoptosis and tumor senescence when treated with either CD4+ Th1 cells, or Th1 cytokines TNF-α and IFN-γ, in a dose dependent manner. Depletion of HER2 activity by either siRNA or trastuzumab and pertuzumab, and subsequent treatment with either anti-HER2 Th1 cells or TNF-α and IFN-γ resulted in synergistic increased tumor senescence and apoptosis in cells both sensitive and cells resistant to trastuzumab which was inhibited by neutralizing anti-TNF-α and IFN-γ. Th1 cytokines induced minimal senescence or apoptosis in triple negative breast cancer cells (TNBC); however, inhibition of EGFR in combination with Th1 cytokines sensitized those cells causing both senescence and apoptosis. TNF-α and IFN-γ led to increased Stat1 phosphorylation through serine and tyrosine sites and a compensatory reduction in Stat3 activation. Single agent IFN-γ enhanced Stat1 phosphorylation on tyrosine 701 and similar effects were observed in combination with TNF-α and EGFR inhibition. These results demonstrate Th1 cytokines and antioncodriver blockade cooperate in causing tumor senescence and apoptosis in TNBC and HER2-expressing breast cancer, suggesting these combinations could be explored as non-cross-reactive therapy preventing recurrence in breast cancer.
dc.format
application/pdf
dc.language.iso
eng
dc.publisher
Impact Journals
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.rights
info:eu-repo/semantics/openAccess
dc.rights.uri
https://creativecommons.org/licenses/by/2.5/ar/
dc.subject
CD4+ T-HELPER IMMUNITY
dc.subject
HER2/NEU
dc.subject
TRIPLE NEGATIVE
dc.subject
BREAST CANCER
dc.subject.classification
Bioquímica y Biología Molecular
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
Ciencias Biológicas
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.subject.classification
CIENCIAS NATURALES Y EXACTAS
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.title
Oncodriver inhibition and CD4+ Th1 cytokines cooperate through Stat1 activation to induce tumor senescence and apoptosis in HER2+ and triple negative breast cancer: implications for combining immune and targeted therapies
dc.type
info:eu-repo/semantics/article
dc.type
info:ar-repo/semantics/artículo
dc.type
info:eu-repo/semantics/publishedVersion
dc.date.updated
2020-03-10T12:27:05Z
dc.journal.volume
9
dc.journal.number
33
dc.journal.pagination
23058-23077
dc.journal.pais
Estados Unidos
![Se ha confirmado la validez de este valor de autoridad por un usuario](/themes/CONICETDigital/images/authority_control/invisible.gif)
dc.journal.ciudad
Albany
dc.description.fil
Fil: Rosemblit, Cinthia. H. Lee Moffitt Cancer Center; Estados Unidos. University of Pennsylvania; Estados Unidos. Consejo Nacional de Investigaciones Científicas y Técnicas; Argentina
dc.description.fil
Fil: Datta, Jashodeep. University of Pennsylvania; Estados Unidos
dc.description.fil
Fil: Lowenfeld, Lea. University of Pennsylvania; Estados Unidos
dc.description.fil
Fil: Xu, Shuwen. University of Pennsylvania; Estados Unidos
dc.description.fil
Fil: Basu, Amrita. H. Lee Moffitt Cancer Center; Estados Unidos
dc.description.fil
Fil: Kodumudi, Krithika. H. Lee Moffitt Cancer Center; Estados Unidos
dc.description.fil
Fil: Wiener, Doris. H. Lee Moffitt Cancer Center; Estados Unidos
dc.description.fil
Fil: Czerniecki, Brian J.. H. Lee Moffitt Cancer Center; Estados Unidos. University of Pennsylvania; Estados Unidos
dc.journal.title
Oncotarget
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.ncbi.nlm.nih.gov/pubmed/29796172
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/doi/http://dx.doi.org/10.18632/oncotarget.25208
dc.relation.alternativeid
info:eu-repo/semantics/altIdentifier/url/https://www.oncotarget.com/article/25208/text/
Archivos asociados