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Research Program–
This research program of the Keck Center utilizes both cell-based and in vivo studies to investigate the relationships between hemostasis proteins, inflammation proteins, and regulation of the multistage development of cancer. Colorectal cancer is the third most common carcinoma in men and women in the U.S. and Canada. One in 18 people will develop colorectal cancer in their lifetime and the American Cancer Society estimates that approximately 150,000 new cases of colorectal cancer will be diagnosed this year. The Keck Center utilizes an inflammatory model of colon cancer in mice to identify mechanisms by which proteins of hemostasis and inflammation influence the pathologies associated with colorectal cancer. Additional studies of the Center focus on vascular development of cancers utilizing cell-based studies of primary endothelial cells and in vivo models in which genetic mutations are introduced into a gene to study functional domain requirements of a protein in regulating angiogenesis. Research Program Investigators
Recent Publications Guillen-Ahlers H, Buechler SA, Suckow MA, Castellino FJ, Ploplis VA. (2008). Sulindac treatment alters collagen and matrilysin expression in adenomas of ApcMin/+ mice. Carcinogenesis 29:1421-1427. Ploplis VA, Tipton H, Menchen H, Castellino FJ. (2007). A urokinase-type plasminogen activator deficiency diminishes the frequency of intestinal adenomas in Apc Min/+ mice. J. Pathol. 213:266-274. Balsara R, Castellino FJ, Ploplis VA. (2006). A novel function of plasminogen activator inhibitor-1 in modulation of the Akt pathway in wild-type and plasminogen activator inhibitor-1 deficient endothelial cells. J. Biol. Chem. 281:22527-22536.
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An association between the gene products associated with blood coagulation (hemostasis), and tumor development, growth, and metastasis has been reported as early as 1911. Since that time, additional studies have indicated that the hemostasis-inflammation crosstalk plays a role in carcinogenesis, and that chronic inflammation, e,g., colitis, prostatitis, is a contributing factor to the pathological events leading to cancer. Further research supports a role for hemostasis proteins in the development of the vascular network within tumors (angiogenesis), which is vital to the survival of the tumor. Therefore, hemostasis proteins regulate cancer progression at all stages of development.
