Theses and Dissertations from UMD

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New submissions to the thesis/dissertation collections are added automatically as they are received from the Graduate School. Currently, the Graduate School deposits all theses and dissertations from a given semester after the official graduation date. This means that there may be up to a 4 month delay in the appearance of a give thesis/dissertation in DRUM

More information is available at Theses and Dissertations at University of Maryland Libraries.

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Subject: search.filters.subject.Colon cancer

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    The effect of folic acid and its metabolites on human colorectal cancer cells
    (2016) Leahy, Elizabeth; Lee, Seong-Ho; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    In the United States, colorectal cancer (CRC) is the third leading cause of death from cancer. Promising research has shown the chemopreventive effects of folic acid (FA) on CRC. Folate is a water-soluble B vitamin that is essential in the transfer of one-carbon necessary for DNA synthesis and methylation reactions. Because folate is essential in DNA replication, a deficiency can predispose cells to neoplastic transformation. While folate depletion in normal tissues can predispose them to becoming cancerous, researchers discovered that folate depletion in colon cancer cells might suppress the progression of current neoplasms, decreasing cell proliferation. The current study investigated the role of FA and its metabolites on CRC cell proliferation, apoptosis, cell cycle regulation and metastasis. We demonstrated that FA did not regulate proliferation in several different colon cancer cell lines. FA did not influence cell cycle regulation, apoptosis or metastasis in HCT116 cells. In addition, we observed that FA decreased expression of proteins involved in epithelial-mesenchymal transition (EMT) in A549 lung cancer cells. Metabolites of FA, including dihydrofolic acid (DHF) and tetrahydrofolic acid (THF), did not significantly affect HCT116 cell proliferation or cell cycle regulation. This study suggests that FA and its metabolites do not regulate colon cancer. Further studies are warranted to investigate the potential role of FA in lung cancer EMT.
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    ANTICANCER MECHANISM OF TOLFENAMIC ACID IN COLORECTAL CANCER
    (2016) Lou, Zhiyuan; Lee, Seong-Ho; Nutrition; Digital Repository at the University of Maryland; University of Maryland (College Park, Md.)
    Colorectal cancer (CRC) is the third leading cause of cancer-related death in the United States. Chemopreventive therapies could be effective way to treat CRC. Tolfenamic acid, one of the NSAIDs, shows anti-cancer activities in several types of cancer. Aberrant Wnt/β-catenin regulation pathway is a major mechanism of colon tumorigenesis. Here, we sought to better define the mechanism by which tolfenamic acid suppresses colorectal tumorigenesis focusing on regulation of β-catenin pathway. Treatment of tolfenamic acid led to a down-regulation of β-catenin expression in dose dependent manner in human colon cancer cell lines without changing mRNA. MG132 inhibited tolfenamic acid-induced downregulation of β-catenin and exogenously overexpression β-catenin was stabilized in the presence of tolfenamic acid. Tolfenamic acid induced an ubiquitin-mediated proteasomal degradation of β-catenin. In addition, tolfenamic acid treatment decreased transcriptional activity of β-catenin and expression of Smad2 and Smad3 while overexpression of Smad 2 inhibited tolfenamic acid-stimulated transcriptional activity of β-catenin. Moreover, tolfenamic acid decreased β-catenin target gene such as vascular endothelial growth factor (VEGF) and cyclin D1. In summary, tolfenamic acid is a promising therapeutic drug targeting Smad 2-mediated downregulation of β-catenin in CRC.