Characterizing the Microvascular Phenotype of Mouse Models of Glioblastoma and Anaplastic Thyroid Cancer
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CitationShrivastav, Shruti. 2019. Characterizing the Microvascular Phenotype of Mouse Models of Glioblastoma and Anaplastic Thyroid Cancer. Master's thesis, Harvard Medical School.
AbstractThere are almost 8.2 million cancer related deaths worldwide and although the dawn of immune-oncology therapeutic solutions has revolutionized the way scientists think about cancer research, only a few tumor types have been susceptible to immunotherapy. Solid tumors like glioblastomas are some of the most aggressive cancers with no improvement in the standard of care for almost twenty years. Glioblastoma is unique in that it has the ability to manipulate normal brain cells to stimulate angiogenesis and co-opt existing vasculature. Both innate and adaptive immune cells play essential roles in glioma growth, specifically macrophages that accumulate around blood vessels and produce pro-angiogenic chemokines. Intravascular leukocyte recruitment is restricted to postcapillary and collecting venules. The lab generated a monoclonal antibody to recognize surface expressed DARC and observed restriction to post-capillary venules. Using the DARC antibody, I have characterized the neovascularization in a syngeneic mouse model of glioblastoma, GL261, and have initially found that the tumoral and peri-tumoral compartments contain more DARC positive post capillary venules than healthy mouse brain. Additionally, imaging of resected tumor and peri-tumoral tissue using two-photon microscopy reveals the presence of DARC positive vasculature in the peri-tumoral and tumor tissue. In contrast, I have observed the opposite effect in a mouse model of anaplastic thyroid cancer, another solid tumor with poor prognosis in a tissue that is highly vascularized.
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