{"id":{"repo_id":"utmb","oai_identifier":"oai:utmb-ir.tdl.org:2152.3/810"},"canonical_url":"https://search.dev.ndltd.org/etd/utmb/oai:utmb-ir.tdl.org:2152.3/810","repository":{"repo_id":"utmb","name":"University of Texas Medical Branch","base_url":"https://utmb-ir.tdl.org/server/oai/request"},"display":{"title":"Growth Factors Up-Regulate Epithelial Stem Cells: Treatment Strategies for Colorectal Cancers","abstract":"Colorectal-cancer is a leading cause of cancer deaths in United States. Accumulating evidence suggests that elevated progastrins (PG) increase the risk of colon carcinogenesis, however mechnaims involved remain ill-defined. Recently, cell-surface AnnexinA2 (CS-ANXA2) was discovered as a non-conventional receptor for progastrin. Therefore, the first goal was to examine whether ANXA2 expression is required to mediate proliferative/anti-apoptotic effects of progastrin on target cells. The studies in chapter 2, conclude that ANXA2 mediates growth effects of PG on target cells (including colonic-epithelial-cells), in vitro and in vivo, associated with up-regulation of stem/progenitor cell markers. Surprisingly, overexpression of autocrine PG in HEK-293 cells, imparted tumorigenic/metastatic potential to the cells (chapter 3). Based on these data, the second goal was to investigate the phenotypic differences between non-transformed and transformed stem cell using non-tumorigenic (HEK-C) and tumorigenic (HEK-mGAS) isogenic cells. The studies in chapter 3, conclude that transformed stem cells, unlike normal stem cells, co-express CS-ANXA2 with stem-cell-markers DCAMKL-1/CD44. Interestingly, CS-ANXA2 dictates morphology/growth characteristics of spheroidal growths, in vitro. The third goal was to identify cancer stem cell (CSC) marker(s), for developing targeted therapies against colon cancers. Since both DCAMKL-1/LGR5 have been reported as colonic CSC markers, the possible phenotypic/proliferative differences between DCAMKL-1+ve and LGR5+ve human colon CSCs was examined. Results in chapter 4 suggest that DCAMKL-1+ve cells are significantly more proliferative than either DCAMKL-1-ve or LGR5+ve stem cells. Thus targeting DCAMKL-1+ve cells may be more effective in treating/eradicating colon-cancers; this possibility was examined as part of my fourth goal. Although several therapies are currently available for treating cancers, recurrence remains a challenge. It is believed that CSCs are resistant to radiation and chemotherapeutic treatments, and are the likely cause of cancer relapse. It is therefore important to develop novel therapies which are relatively non-toxic and specifically target CSCs. Therefore the fourth goal was to examine the inhibitory efficacy of non-toxic dietary agent (Curcumin) ± RNAi against DCAMKL-1. The results in chapter 5 suggest that combination of curcumin+siRNA-DCAMKL-1 effectively attenuates growth of colon-cancer-cells in vitro and in vivo, by synergistically augmenting autophagic/apoptotic cell-death mechanisms. It is hypothesized that the combinatorial treatment will significantly reduce the risk of relapse.","abstract_html":"Colorectal-cancer is a leading cause of cancer deaths in United States. Accumulating evidence suggests that elevated progastrins (PG) increase the risk of colon carcinogenesis, however mechnaims involved remain ill-defined. Recently, cell-surface AnnexinA2 (CS-ANXA2) was discovered as a non-conventional receptor for progastrin. Therefore, the first goal was to examine whether ANXA2 expression is required to mediate proliferative/anti-apoptotic effects of progastrin on target cells. The studies in chapter 2, conclude that ANXA2 mediates growth effects of PG on target cells (including colonic-epithelial-cells), in vitro and in vivo, associated with up-regulation of stem/progenitor cell markers. Surprisingly, overexpression of autocrine PG in HEK-293 cells, imparted tumorigenic/metastatic potential to the cells (chapter 3). Based on these data, the second goal was to investigate the phenotypic differences between non-transformed and transformed stem cell using non-tumorigenic (HEK-C) and tumorigenic (HEK-mGAS) isogenic cells. The studies in chapter 3, conclude that transformed stem cells, unlike normal stem cells, co-express CS-ANXA2 with stem-cell-markers DCAMKL-1/CD44. Interestingly, CS-ANXA2 dictates morphology/growth characteristics of spheroidal growths, in vitro. The third goal was to identify cancer stem cell (CSC) marker(s), for developing targeted therapies against colon cancers. Since both DCAMKL-1/LGR5 have been reported as colonic CSC markers, the possible phenotypic/proliferative differences between DCAMKL-1+ve and LGR5+ve human colon CSCs was examined. Results in chapter 4 suggest that DCAMKL-1+ve cells are significantly more proliferative than either DCAMKL-1-ve or LGR5+ve stem cells. Thus targeting DCAMKL-1+ve cells may be more effective in treating/eradicating colon-cancers; this possibility was examined as part of my fourth goal. Although several therapies are currently available for treating cancers, recurrence remains a challenge. It is believed that CSCs are resistant to radiation and chemotherapeutic treatments, and are the likely cause of cancer relapse. It is therefore important to develop novel therapies which are relatively non-toxic and specifically target CSCs. Therefore the fourth goal was to examine the inhibitory efficacy of non-toxic dietary agent (Curcumin) ± RNAi against DCAMKL-1. The results in chapter 5 suggest that combination of curcumin+siRNA-DCAMKL-1 effectively attenuates growth of colon-cancer-cells in vitro and in vivo, by synergistically augmenting autophagic/apoptotic cell-death mechanisms. It is hypothesized that the combinatorial treatment will significantly reduce the risk of relapse.","abstract_has_math":false,"creators":["Kantara, Carla"],"institution":"The University of Texas Medical Branch at Galveston","degree_name":"Cell Biology (Doctoral)","degree_level":"Doctoral","degree_discipline":"Cancer Research","degree_department":null,"school":null,"contributors":[],"advisors":["Kayed, Rakez"],"committee_chairs":[],"committee_members":["Singh, Pomila","Ullrich, Robert","Carney, Darrell","Umar, Shahid"],"year":null,"date_issued":"","date_published":null,"updated_at":"2026-07-24T05:50:54Z","subjects":["Stem Cells","Colon Cancer","DCAMKL-1, LGR5, Curcumin, AnnexinA2."],"languages":[],"rights":[],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2152.3/810"],"render_values":[{"text":"http://hdl.handle.net/2152.3/810","href":"http://hdl.handle.net/2152.3/810","code":true}]}]},"links":{"outbound_url":"http://hdl.handle.net/2152.3/659","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Kayed, Rakez"]},{"key":"dc:contributor.committeemember","label":"Committee Member","values":["Singh, Pomila","Ullrich, Robert","Carney, Darrell","Umar, Shahid"]},{"key":"dc:creator","label":"Author","values":["Kantara, Carla"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2016-11-14T15:20:10Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2016-11-14T15:20:10Z"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]},{"key":"thesis:degree_discipline","label":"Discipline","values":["Cancer Research"]},{"key":"thesis:degree_level","label":"Degree Level","values":["Doctoral"]},{"key":"thesis:degree_name","label":"Degree Name","values":["Cell Biology (Doctoral)"]},{"key":"thesis:institution_name","label":"Thesis Institution Name","values":["The University of Texas Medical Branch at Galveston"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Stem Cells","Colon Cancer","DCAMKL-1, LGR5, Curcumin, AnnexinA2."]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/2152.3/659","http://hdl.handle.net/2152.3/810"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Colorectal-cancer is a leading cause of cancer deaths in United States. Accumulating evidence suggests that elevated progastrins (PG) increase the risk of colon carcinogenesis, however mechnaims involved remain ill-defined. Recently, cell-surface AnnexinA2 (CS-ANXA2) was discovered as a non-conventional receptor for progastrin. Therefore, the first goal was to examine whether ANXA2 expression is required to mediate proliferative/anti-apoptotic effects of progastrin on target cells. The studies in chapter 2, conclude that ANXA2 mediates growth effects of PG on target cells (including colonic-epithelial-cells), in vitro and in vivo, associated with up-regulation of stem/progenitor cell markers. Surprisingly, overexpression of autocrine PG in HEK-293 cells, imparted tumorigenic/metastatic potential to the cells (chapter 3). Based on these data, the second goal was to investigate the phenotypic differences between non-transformed and transformed stem cell using non-tumorigenic (HEK-C) and tumorigenic (HEK-mGAS) isogenic cells. The studies in chapter 3, conclude that transformed stem cells, unlike normal stem cells, co-express CS-ANXA2 with stem-cell-markers DCAMKL-1/CD44. Interestingly, CS-ANXA2 dictates morphology/growth characteristics of spheroidal growths, in vitro. The third goal was to identify cancer stem cell (CSC) marker(s), for developing targeted therapies against colon cancers. Since both DCAMKL-1/LGR5 have been reported as colonic CSC markers, the possible phenotypic/proliferative differences between DCAMKL-1+ve and LGR5+ve human colon CSCs was examined. Results in chapter 4 suggest that DCAMKL-1+ve cells are significantly more proliferative than either DCAMKL-1-ve or LGR5+ve stem cells. Thus targeting DCAMKL-1+ve cells may be more effective in treating/eradicating colon-cancers; this possibility was examined as part of my fourth goal. Although several therapies are currently available for treating cancers, recurrence remains a challenge. It is believed that CSCs are resistant to radiation and chemotherapeutic treatments, and are the likely cause of cancer relapse. It is therefore important to develop novel therapies which are relatively non-toxic and specifically target CSCs. Therefore the fourth goal was to examine the inhibitory efficacy of non-toxic dietary agent (Curcumin) ± RNAi against DCAMKL-1. The results in chapter 5 suggest that combination of curcumin+siRNA-DCAMKL-1 effectively attenuates growth of colon-cancer-cells in vitro and in vivo, by synergistically augmenting autophagic/apoptotic cell-death mechanisms. It is hypothesized that the combinatorial treatment will significantly reduce the risk of relapse."]},{"key":"dc:format.mimetype","label":"Dc Format Mimetype","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Growth Factors Up-Regulate Epithelial Stem Cells: Treatment Strategies for Colorectal Cancers"]}]}],"canonical_facts":{"dc:contributor.advisor":["Kayed, Rakez"],"dc:contributor.committeemember":["Singh, Pomila","Ullrich, Robert","Carney, Darrell","Umar, Shahid"],"dc:creator":["Kantara, Carla"],"dc:date.accessioned":["2016-11-14T15:20:10Z"],"dc:date.available":["2016-11-14T15:20:10Z"],"dc:description.abstract":["Colorectal-cancer is a leading cause of cancer deaths in United States. Accumulating evidence suggests that elevated progastrins (PG) increase the risk of colon carcinogenesis, however mechnaims involved remain ill-defined. Recently, cell-surface AnnexinA2 (CS-ANXA2) was discovered as a non-conventional receptor for progastrin. Therefore, the first goal was to examine whether ANXA2 expression is required to mediate proliferative/anti-apoptotic effects of progastrin on target cells. The studies in chapter 2, conclude that ANXA2 mediates growth effects of PG on target cells (including colonic-epithelial-cells), in vitro and in vivo, associated with up-regulation of stem/progenitor cell markers. Surprisingly, overexpression of autocrine PG in HEK-293 cells, imparted tumorigenic/metastatic potential to the cells (chapter 3). Based on these data, the second goal was to investigate the phenotypic differences between non-transformed and transformed stem cell using non-tumorigenic (HEK-C) and tumorigenic (HEK-mGAS) isogenic cells. The studies in chapter 3, conclude that transformed stem cells, unlike normal stem cells, co-express CS-ANXA2 with stem-cell-markers DCAMKL-1/CD44. Interestingly, CS-ANXA2 dictates morphology/growth characteristics of spheroidal growths, in vitro. The third goal was to identify cancer stem cell (CSC) marker(s), for developing targeted therapies against colon cancers. Since both DCAMKL-1/LGR5 have been reported as colonic CSC markers, the possible phenotypic/proliferative differences between DCAMKL-1+ve and LGR5+ve human colon CSCs was examined. Results in chapter 4 suggest that DCAMKL-1+ve cells are significantly more proliferative than either DCAMKL-1-ve or LGR5+ve stem cells. Thus targeting DCAMKL-1+ve cells may be more effective in treating/eradicating colon-cancers; this possibility was examined as part of my fourth goal. Although several therapies are currently available for treating cancers, recurrence remains a challenge. It is believed that CSCs are resistant to radiation and chemotherapeutic treatments, and are the likely cause of cancer relapse. It is therefore important to develop novel therapies which are relatively non-toxic and specifically target CSCs. Therefore the fourth goal was to examine the inhibitory efficacy of non-toxic dietary agent (Curcumin) ± RNAi against DCAMKL-1. The results in chapter 5 suggest that combination of curcumin+siRNA-DCAMKL-1 effectively attenuates growth of colon-cancer-cells in vitro and in vivo, by synergistically augmenting autophagic/apoptotic cell-death mechanisms. It is hypothesized that the combinatorial treatment will significantly reduce the risk of relapse."],"dc:format.mimetype":["application/pdf"],"dc:identifier.uri":["http://hdl.handle.net/2152.3/659","http://hdl.handle.net/2152.3/810"],"dc:subject":["Stem Cells","Colon Cancer","DCAMKL-1, LGR5, Curcumin, AnnexinA2."],"dc:title":["Growth Factors Up-Regulate Epithelial Stem Cells: Treatment Strategies for Colorectal Cancers"],"dc:type":["Thesis"],"thesis:degree_discipline":["Cancer Research"],"thesis:degree_level":["Doctoral"],"thesis:degree_name":["Cell Biology (Doctoral)"],"thesis:institution_name":["The University of Texas Medical Branch at Galveston"]},"updated_at":"2026-07-24T05:50:54Z"}