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Enhanced Survival with Implantable Scaffolds That Capture Metastatic Breast Cancer Cells In Vivo

dc.contributor.authorRao, Shreyas S.
dc.contributor.authorBushnell, Grace G.
dc.contributor.authorAzarin, Samira M.
dc.contributor.authorSpicer, Graham
dc.contributor.authorAguado, Brian A.
dc.contributor.authorStoehr, Jenna R.
dc.contributor.authorJiang, Eric J.
dc.contributor.authorBackman, Vadim
dc.contributor.authorShea, Lonnie D.
dc.contributor.authorJeruss, Jacqueline S.
dc.contributor.otherUniversity of Alabama Tuscaloosa
dc.contributor.otherUniversity of Michigan
dc.contributor.otherUniversity of Minnesota Twin Cities
dc.contributor.otherNorthwestern University
dc.contributor.otherUniversity of Colorado Boulder
dc.date.accessioned2023-09-28T19:04:29Z
dc.date.available2023-09-28T19:04:29Z
dc.date.issued2016
dc.description.abstractThe onset of distant organ metastasis from primary breast cancer marks the transition to a stage IV diagnosis. Standard imaging modalities often detect distant metastasis when the burden of disease is high, underscoring the need for improved methods of detection to allow for interventions that would impede disease progression. Here, microporous poly(e-caprolactone) scaffolds were developed that capture early metastatic cells and thus serve as a sentinel for early detection. These scaffolds were used to characterize the dynamic immune response to the implant spanning the acute and chronic foreign body response. The immune cell composition had stabilized at the scaffold after approximately 1 month and changed dramatically within days to weeks after tumor inoculation, with CD11b(+)Gr1(hi)Ly6C(-) cells having the greatest increase in abundance. Implanted scaffolds recruited metastatic cancer cells that were inoculated into the mammary fat pad in vivo, which also significantly reduced tumor burden in the liver and brain. Additionally, cancer cells could be detected using a label-free imaging modality termed inverse spectroscopic optical coherence tomography, and we tested the hypothesis that subsequent removal of the primary tumor after early detection would enhance survival. Surgical removal of the primary tumor following cancer cell detection in the scaffold significantly improved disease-specific survival. The enhanced disease-specific survival was associated with a systemic reduction in the CD11b(+)Gr1(hi)Ly6C(-) cells as a consequence of the implant, which was further supported by Gr-1 depletion studies. Implementation of the scaffold may provide diagnostic and therapeutic options for cancer patients in both the high-risk and adjuvant treatment settings. (C) 2016 AACR.en_US
dc.format.mediumelectronic
dc.format.mimetypeapplication/pdf
dc.identifier.citationRao, S. S., Bushnell, G. G., Azarin, S. M., Spicer, G., Aguado, B. A., Stoehr, J. R., Jiang, E. J., Backman, V., Shea, L. D., & Jeruss, J. S. (2016). Enhanced Survival with Implantable Scaffolds That Capture Metastatic Breast Cancer Cells In Vivo. In Cancer Research (Vol. 76, Issue 18, pp. 5209–5218). American Association for Cancer Research (AACR). https://doi.org/10.1158/0008-5472.can-15-2106
dc.identifier.doi10.1158/0008-5472.CAN-15-2106
dc.identifier.orcidhttps://orcid.org/0000-0001-7649-0171
dc.identifier.orcidhttps://orcid.org/0000-0002-8891-803X
dc.identifier.orcidhttps://orcid.org/0000-0002-2152-2233
dc.identifier.urihttps://ir.ua.edu/handle/123456789/10795
dc.languageEnglish
dc.language.isoen_US
dc.publisherAmerican Association of Cancer Research
dc.subjectCIRCULATING TUMOR-CELLS
dc.subjectTISSUE-ENGINEERED BONE
dc.subjectSUPPRESSOR-CELLS
dc.subjectPREMETASTATIC NICHE
dc.subjectBIOLOGICAL TISSUE
dc.subjectMYELOID CELLS
dc.subjectGROWTH
dc.subjectSOIL
dc.subjectRECRUITMENT
dc.subjectEXPRESSION
dc.subjectOncology
dc.titleEnhanced Survival with Implantable Scaffolds That Capture Metastatic Breast Cancer Cells In Vivoen_US
dc.typeArticle
dc.typetext

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