{"id":{"repo_id":"wfu","oai_identifier":"oai:wakespace.lib.wfu.edu:10339/86346"},"canonical_url":"https://search.dev.ndltd.org/etd/wfu/oai:wakespace.lib.wfu.edu:10339/86346","repository":{"repo_id":"wfu","name":"Wake Forest University","base_url":"https://wakespace.lib.wfu.edu/oai/request"},"display":{"title":"Novel Oligomeric Fluoropyrimidines and Their Efficacy for the Treatment of Colorectal Carcinoma Independent of p53 Mutation","abstract":"The treatment of advanced stage colorectal carcinoma (CRC) is rarely achieved with today’s standard of care, including 5-fluorouracil (5-FU). Resistance to 5-FU is unfortunately frequent in CRC partially due to the dependency 5-FU displays towards normal p53 function, a tumor suppressor protein that is commonly mutated in advanced CRC. In addition to the relatively low success rate of 5-FU in aggressive CRC, 5-FU treatment also causes systemic toxicity, particularly to the GI-tract. The presented studies aimed to demonstrate that our novel oligomeric fluoropyrimidines are able to overcome these limitations of 5-FU in vivo. The results indicate that F10 and other fluoropyrimidines showed little-to-no p53 dependency in in vivo xenografts. While F10 displayed the same p53 independency in vitro when assessing cell viability and caspase activation, 5-FU showed a dependency on normal p53 function in vitro while further studies are needed to conclude in vivo p53-dependency. The results also indicate that these fluoropyrimidines are viable treatments for CRC by showing tumor suppression in xenograft models and in a more realistic orthotopic model. Systemic toxicity was not seen during novel fluoropyrimidine treatment in terms of GI-tract villi or crypt shortening, whereas 5-FU caused major toxicity, both short-term and long-term. These findings indicate that the limitations of 5-FU are eliminated by our fluoropyrimidines in a mouse model and may possibly transition to the clinical setting.","abstract_html":"The treatment of advanced stage colorectal carcinoma (CRC) is rarely achieved with today’s standard of care, including 5-fluorouracil (5-FU). Resistance to 5-FU is unfortunately frequent in CRC partially due to the dependency 5-FU displays towards normal p53 function, a tumor suppressor protein that is commonly mutated in advanced CRC. In addition to the relatively low success rate of 5-FU in aggressive CRC, 5-FU treatment also causes systemic toxicity, particularly to the GI-tract. The presented studies aimed to demonstrate that our novel oligomeric fluoropyrimidines are able to overcome these limitations of 5-FU in vivo. The results indicate that F10 and other fluoropyrimidines showed little-to-no p53 dependency in in vivo xenografts. While F10 displayed the same p53 independency in vitro when assessing cell viability and caspase activation, 5-FU showed a dependency on normal p53 function in vitro while further studies are needed to conclude in vivo p53-dependency. The results also indicate that these fluoropyrimidines are viable treatments for CRC by showing tumor suppression in xenograft models and in a more realistic orthotopic model. Systemic toxicity was not seen during novel fluoropyrimidine treatment in terms of GI-tract villi or crypt shortening, whereas 5-FU caused major toxicity, both short-term and long-term. These findings indicate that the limitations of 5-FU are eliminated by our fluoropyrimidines in a mouse model and may possibly transition to the clinical setting.","abstract_has_math":false,"creators":["Dominijanni, Anthony"],"institution":"Wake Forest University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2017,"date_issued":"2017","date_published":"2017","updated_at":"2026-07-27T22:02:17Z","subjects":["colorectal carcinoma"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10339/86346","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:creator","label":"Author","values":["Dominijanni, Anthony"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2017-08-22T08:35:25Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2019-08-18T08:30:11Z"]},{"key":"dc:date.issued","label":"Date","values":["2017"]},{"key":"dc:publisher","label":"Institution","values":["Wake Forest University"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["colorectal carcinoma"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["en"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10339/86346"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["The treatment of advanced stage colorectal carcinoma (CRC) is rarely achieved with today’s standard of care, including 5-fluorouracil (5-FU). Resistance to 5-FU is unfortunately frequent in CRC partially due to the dependency 5-FU displays towards normal p53 function, a tumor suppressor protein that is commonly mutated in advanced CRC. In addition to the relatively low success rate of 5-FU in aggressive CRC, 5-FU treatment also causes systemic toxicity, particularly to the GI-tract. The presented studies aimed to demonstrate that our novel oligomeric fluoropyrimidines are able to overcome these limitations of 5-FU in vivo. The results indicate that F10 and other fluoropyrimidines showed little-to-no p53 dependency in in vivo xenografts. While F10 displayed the same p53 independency in vitro when assessing cell viability and caspase activation, 5-FU showed a dependency on normal p53 function in vitro while further studies are needed to conclude in vivo p53-dependency. The results also indicate that these fluoropyrimidines are viable treatments for CRC by showing tumor suppression in xenograft models and in a more realistic orthotopic model. Systemic toxicity was not seen during novel fluoropyrimidine treatment in terms of GI-tract villi or crypt shortening, whereas 5-FU caused major toxicity, both short-term and long-term. These findings indicate that the limitations of 5-FU are eliminated by our fluoropyrimidines in a mouse model and may possibly transition to the clinical setting."]},{"key":"dc:title","label":"Title","values":["Novel Oligomeric Fluoropyrimidines and Their Efficacy for the Treatment of Colorectal Carcinoma Independent of p53 Mutation"]}]}],"canonical_facts":{"dc:creator":["Dominijanni, Anthony"],"dc:date.accessioned":["2017-08-22T08:35:25Z"],"dc:date.available":["2019-08-18T08:30:11Z"],"dc:date.issued":["2017"],"dc:description.abstract":["The treatment of advanced stage colorectal carcinoma (CRC) is rarely achieved with today’s standard of care, including 5-fluorouracil (5-FU). Resistance to 5-FU is unfortunately frequent in CRC partially due to the dependency 5-FU displays towards normal p53 function, a tumor suppressor protein that is commonly mutated in advanced CRC. In addition to the relatively low success rate of 5-FU in aggressive CRC, 5-FU treatment also causes systemic toxicity, particularly to the GI-tract. The presented studies aimed to demonstrate that our novel oligomeric fluoropyrimidines are able to overcome these limitations of 5-FU in vivo. The results indicate that F10 and other fluoropyrimidines showed little-to-no p53 dependency in in vivo xenografts. While F10 displayed the same p53 independency in vitro when assessing cell viability and caspase activation, 5-FU showed a dependency on normal p53 function in vitro while further studies are needed to conclude in vivo p53-dependency. The results also indicate that these fluoropyrimidines are viable treatments for CRC by showing tumor suppression in xenograft models and in a more realistic orthotopic model. Systemic toxicity was not seen during novel fluoropyrimidine treatment in terms of GI-tract villi or crypt shortening, whereas 5-FU caused major toxicity, both short-term and long-term. These findings indicate that the limitations of 5-FU are eliminated by our fluoropyrimidines in a mouse model and may possibly transition to the clinical setting."],"dc:identifier.uri":["http://hdl.handle.net/10339/86346"],"dc:language.iso":["en"],"dc:publisher":["Wake Forest University"],"dc:subject":["colorectal carcinoma"],"dc:title":["Novel Oligomeric Fluoropyrimidines and Their Efficacy for the Treatment of Colorectal Carcinoma Independent of p53 Mutation"],"dc:type":["Thesis"]},"updated_at":"2026-07-27T22:02:17Z"}