Aptamer Selection against Fibroblast Growth Factor-8b for Therapeutic Uses in the Progression of Breast Cancer and Angiogenesis

Aptamer Selection against Fibroblast Growth Factor-8b for Therapeautic Uses in the Progression of Breast Cancer and Angiogenesis
Anisha Maheshwari, Fall 2013


Abstract:
                Although the medical field has undergone rapid growth within the past decade, much is still unknown about many life threatening diseases. Cancer, the uncontrolled growth of harmful cells, has proven to be one of the most fatal diseases known to man, accounting for millions of deaths around the world every year. Similar to cancer, angiogenesis, a cardiovascular disease involving the proliferation of abnormal blood vessels, is also known for its deleterious effects on the human body. Diseases such as cancer and angiogenesis have been a growing concern in modern medicine due to their biologically destructive nature. While much is still to be learned about these diseases and their harmful effects, vast efforts are being made to also generate innovative therapeutic and diagnostic techniques against them in order to inhibit the growth and effects of such abnormal and harmful cells.
                Recent research has led to a connection between cancer, specifically breast cancer, and angiogenesis in that a protein isoform known as Fibroblast Growth Factor-8b (FGF-8b) has been found to play a key role in both diseases and their growth in the body. FGF-8b belongs to a class of proteins that play a major part in processes of the body, such as mitogenic cell growth. It is a single-chain polypeptide that has been found to proliferate cancerous and tumor growth, as a result of its ability to propel rapid cell division. FGF-8b is specifically known for its high level of mitogenic involvement and activity in tumor and cancer growing cells, and has been researched extensively as it is the major isoform occurring in especially breast cancer (Nilsson et al., 2010). Due to its prevalence and transformation power in breast cancer, the FGF-8 gene is now categorized as an oncogene. Additionally, FGF-8b has not only shown to aid cancerous growth (Nilsson et al., 2010), but also multiply steroid regulated tumors, cause neovascularization, and therefore, trigger angiogenesis- one of the leading causes of rectum and colon cancer (Li et al., 2009). With such wide medical implications of FGF-8b, this project and its specific aims focus on the protein’s effects on the proliferation and progression of cancer.
           Specific Aim 1: The primary specific aim of this project focuses on generating a specific aptamer that can bind to FGF-8b.
           Specific Aim 2: The next specific aim is modifying the aptamer in order to inhibit the binding of FGF-8 and FGFR (Figure 1). As a result, this could prevent, reduce, or eliminate the protein’s effects on the progression and growth of abnormal cells in cancer and angiogenesis.

Figure 1. Primary Specific Aim of Aptamer Selection against FGF-8b (White, 2011):  Inhibition of FGF-8 through successful aptamer binding can prevent FGF-8 and FGFR binding, preventing a cascade of chemical reactions and pathways that may be harmful to the body in proliferating cancerous growth.


FGF-8b is currently available in lab (purified by Shawn Piasecki).

References:
Li, W.W., and R. E. Harris. (2009) “Angiogenesis inhibition in the prevention of colorectal cancer.”   The    Angiogenesis Foundation 7:1-23.
Nilsson, E.M., L.J.S. Brokken, and P.L. Harkonen. (2010) “Fibroblast growth factor 8 increases breast  cancer cell growth by promoting cell cycle progression and by protecting  against cell death.”  Experimental Cell Reseach 316(5):800-812.
White, Z. (2011) “Aptamer selection against FGF8.” The Aptamer Stream, Freshman  Research Initiative at  the University of Texas at Austin.

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Click here for First Progress Report

Click here for Second Progress Report

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