Date of Award

12-2016

Document Type

Thesis

Degree Name

Master of Science (MS)

Legacy Department

Bioengineering

Committee Member

Dr. Brian Booth, PhD, Committee Chair

Committee Member

Dr. Sarah Harcum, PhD

Committee Member

Dr. Guigen Zhang, PhD

Abstract

Breast cancer is the most commonly diagnosed cancer among women in the United States, affecting about 12 percent of women nationally (Ma and Jemal, 2013). The American Cancer Society estimates that 246,600 new cases of invasive breast cancer will be diagnosed in women in 2016 (American Cancer Society, 2016 b). Breast cancer accounts for almost 30% of new cancer diagnoses and is one of the leading causes of cancer related deaths among women in developed countries. In addition, breast cancer is becoming a worldwide problem with incidence and mortality rates increasing steadily over the past 20 years in developing countries (Ma and Jemal, 2013). Current treatment options for breast cancer include surgery, chemotherapy, and radiation; however, there are many negative side effects associated with these treatments, and these treatments are not always suitable for every patient. In addition, there is a risk of local breast cancer recurrence, particularly in patients who undergo a lumpectomy. Up to 20% of breast cancer patients experience recurrence, and of these recurrences, around 70% are defined as local (Zimmerman and Mehr, 2014). Therefore, there is a need for the development of a therapeutic agent specifically designed to target the surgical site and minimize the risk of locally recurrent breast cancer. The overall goal of this research was to develop an injectable soft tissue regeneration matrix for the prevention of local HER2+ breast cancer recurrence. Collagen type I beads were crosslinked with tannic acid (TA) to form the basis for the injectable therapy. The collagen beads were seeded with human adipocytes. The adipocytes attach and grow on the collagen beads, thus remodeling the beads and releasing the tannic acid to the surrounding environment. The tannic acid acts as an anticancer therapeutic agent by inducing apoptosis in HER2+ breast cancer cells via caspase pathways. In order to prove the viability of this therapeutic option, several studies were conducted. LIVE/DEAD assays were used to prove successful seeding of the human adipocytes onto the collagen beads. Cell viability studies were conducted to assess the effect of tannic acid on human adipocytes and HER2+ breast cancer cells. In addition, the Folin-Ciocalteu assay was used to analyze the release profile of tannic acid. RNA was isolated from both the human adipocytes and HER2+ breast cancer cells, and Real Time-PCR was conducted to determine the activated pathways involved in cell apoptosis as a result of exposure to tannic acid. Western blotting was used to identify expression of caspases from proteins isolated from the HER2+ breast cancer cell line and normal human breast epithelial cell line.

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