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http://hdl.handle.net/11375/15318
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DC Field | Value | Language |
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dc.contributor.advisor | Wallace, John L. | en_US |
dc.contributor.author | Elsheikh, Wagdi K. | en_US |
dc.date.accessioned | 2014-06-18T21:13:37Z | - |
dc.date.created | 2013-12-15 | en_US |
dc.date.issued | 2014-04 | en_US |
dc.identifier.other | opendissertations/8628 | en_US |
dc.identifier.other | 9704 | en_US |
dc.identifier.other | 4925588 | en_US |
dc.identifier.uri | http://hdl.handle.net/11375/15318 | - |
dc.description.abstract | <p>Colorectal cancer leads to more than 600,000 deaths worldwide per year. An abundance of research has shown that several non-steroidal anti-inflammatory drugs (NSAIDs) can exert chemotherapeutic and chemo-preventative effects in colorectal cancer patients. It is important to note, that use of many different NSAIDs carries a significant risk for cardiovascular and gastrointestinal (GI) complications. A recently developed group of NSAIDs, which release hydrogen sulfide (H<sub>2</sub>S), has been shown to have greatly reduced these side effects as compared to conventional NSAIDs. This is likely attributable to the ability of H<sub>2</sub>S to increase the resistance of the GI mucosa to injury, as well as to accelerate repair of injury when it occurs. Moreover, H<sub>2</sub>S has been shown to be a vasodilator, and therefore may offset some of the hypertensive effects of NSAIDs.</p> <p>We assessed the chemotherapeutic actions of two of these newly developed NSAIDs. ATB-346 is an H<sub>2</sub>S-releasing derivative of naproxen and ATB-352 is an H<sub>2</sub>S-releasing derivative of ketoprofen. These drugs were tested in the azoxymethane mouse model and in the APC<sup>Min/+ </sup>mouse model of Colorectal cancer.</p> <p>In the azoxymethane model of colorectal cancer ATB-346 caused a significant reduction in number aberrant crypt foci (ACF), which are pre-neoplastic lesions used as markers of colorectal cancer. The reduction was superior to naproxen at all doses tested. ATB-352 also caused a significant reduction in the number of ACF, however the reduction was not superior to that produced by ketoprofen. In APC<sup>Min/+ </sup>mice treated with ATB-346 for 14 days (14.5 mg/kg) we observed a complete inhibition of the formation of colonic polyps/tumours and a 97.5% reduction in total polyp score. Shorter treatment with ATB-346 also produced similar reduction in total polyp score. We found that ATB-346-treated mice had lower levels of b-catenin and cmyc without significant changes in APC or p53 levels. <strong></strong></p> <p>These results demonstrate ATB-346 can exert superior chemo-preventative effects in mice models of colon cancer while leading to no gastric or intestinal damage.</p> | en_US |
dc.subject | Colorectal Cancer | en_US |
dc.subject | NSAIDs | en_US |
dc.subject | Neoplasms | en_US |
dc.subject | Gastrointestinal Disease | en_US |
dc.subject | Chemo-prevention | en_US |
dc.subject | Hydrogen Sulfide | en_US |
dc.subject | Digestive System Diseases | en_US |
dc.subject | Medical Pharmacology | en_US |
dc.subject | Neoplasms | en_US |
dc.subject | Pharmaceutics and Drug Design | en_US |
dc.subject | Digestive System Diseases | en_US |
dc.title | CHEMO-PREVENTATIVE EFFECTS OF HYDROGEN SULFIDE-RELEASING NSAIDS IN MURINE COLORECTAL CANCER | en_US |
dc.type | thesis | en_US |
dc.contributor.department | Medical Sciences (Division of Physiology/Pharmacology) | en_US |
dc.date.embargo | 2014-12-12 | - |
dc.description.degree | Master of Science (MSc) | en_US |
dc.date.embargoset | 2014-12-12 | en_US |
Appears in Collections: | Open Access Dissertations and Theses |
Files in This Item:
File | Size | Format | |
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fulltext.pdf | 2.53 MB | Adobe PDF | View/Open |
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