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.
References:
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.
Click here for full proposal
Click here for First Progress Report
Click here for Second Progress Report
Click here for Final Report
Click here for full proposal
Click here for First Progress Report
Click here for Second Progress Report
Click here for Final Report
1 comment:
Human FGF-b is a 17.2 kDa protein containing 154 amino acid residues. The Fibroblast Growth Factor-basic (FGF-b) is a heparin binding growth factor which stimulates the proliferation of a wide variety of cells including mesenchymal, neuroectodermal & endothelial cells. Basic Fibroblast Growth Factor, Human
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