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Accession Number ADA570818
Title Understanding the Effects of Cytotoxic Chemotherapeutics on the Innate Immune System.
Publication Date Mar 2012
Media Count 36p
Personal Author E. S. Nakasone
Abstract In breast cancer, myeloid cells recruitment into tumors following radiation therapy and chemotherapy is frequently observed in pre-clinical models. We therefore sought to determine the significance of myeloid cell recruitment following chemotherapy treatment and their role in therapeutic resistance. Using intravital imaging of tumors in live mice, we observed that the tumors of the polyoma middle T antigen (PyMT) mouse model of luminal breast cancer show a stage-dependent sensitivity to treatment with doxorubicin. Doxorubicin treatment recruits CCR2+Gr1+7/4+CD11b+ immature myeloid cells with monocytic morphology. Inhibition of this recruitment via orthotopic transplantation of Ccr2+/+ cancer cells from PyMT mice into Ccr2-/- mice enhances the response to doxorubicin. Furthermore, changes in tumor vasculature and tumor grade accompany this improved response, indicating that CCR2 signaling may play important roles in tumor proliferation and differentiation, angiogenesis, in addition to therapeutic response. The data herein presented show that antagonism of CCR2 signaling in combination with cytotoxic chemotherapy treatment may be a potentially powerful therapeutic strategy for the treatment of breast cancer.
Keywords Angiogenesis
Antigens
Bone marrow
Breast cancer
Cells(Biology)
Chemokines
Chemoresistance
Chemotherapy
Cytotoxins
Doxorubicin
Immune system
Inhibition
Intravital imaging
Myeloid cell infiltration
Neoplasms
Tumor microenvironments


 
Source Agency Non Paid ADAS
NTIS Subject Category 57E - Clinical Medicine
57Q - Pharmacology & Pharmacological Chemistry
Corporate Author Cold Spring Harbor Lab., New York.
Document Type Technical report
Title Note Annual summary rept. 1 Jan 2011-29 Feb 2012.
NTIS Issue Number 1315
Contract Number W81XWH-11-1-0036

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