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Metastasis: Hematogeneous Several interdependent mechanisms influence the metastatic cascade, and despite the impressive rate of publication in this area (> 10,000 hits on Medline from 2000 to 2006), we still know little about the key steps in the process. An outstanding question in the field of metastasis is whether cancer cells need to actively adhere to and migrate out of blood vessels at the secondary site in order to colonize. On the one hand, we know that cancer cells express endothelial adhesion receptors, similar to leukocytes, that allow them to roll on and adhere to endothelium. But other studies have found clumps of cancer cells surviving and growing within the lumen of blood vessels at the secondary site. |
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Blood circulating endothelial cells and circulating progenitor cells as biomarkers of antiangiogenic therapy in cancer patients Due to spectacular successes in clinical trials, the use of antiangiogenic agents in cancer patients is rapidly becoming part of clinical practice in the USA and elsewhere. But targeting angiogenic vessels requires new and adequate methods for the assessment of the biologic effect of various agents developed to control cancer progression. Traditionally, tumor angiogenesis has been evaluated by measuring microvessel density in biopsy specimens using immunohistochemistry. |
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Studies of bone marrow-derived endothelial cells incorporation into perfused blood vessels in tumors Synopsis Recent studies have demonstrated that the cellular contribution of the bone marrow to tumor neovascularization is highly complex. In this context, the extent to which bone marrow-derived cells incorporate as bona fide endothelial (non-hematopoietic) cells into perfused tumor vessels, or any new vessels formed postnatally (vasculogenesis), is unclear. To this end, we developed models to characterize local vessel-derived and bone marrow-derived endothelial cells (BMDECs). Then, we characterized the BMD-ECs based on a set of endothelial markers and morphology. |
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The goals of this project are to understand the mechanisms underlying the temporal and spatial heterogeneities in tumor vasculature by studying angiogenesis, vascular collapse, intermittent flow, and maturation of vascular network; to quantify parameters that govern tumor angiogenesis and blood flow; and finally, to develop strategies for manipulating these parameters to increase or decrease angiogenesis and blood flow reproducibly. |
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