{"id":{"repo_id":"nus","oai_identifier":"oai:scholarbank.nus.edu.sg:10635/30583"},"canonical_url":"https://search.dev.ndltd.org/etd/nus/oai:scholarbank.nus.edu.sg:10635/30583","repository":{"repo_id":"nus","name":"National University of Singapore","base_url":"https://scholarbank.nus.edu.sg/oai/request"},"display":{"title":"Connecting brain tumor stem cells with their primary tumor and exploring glycogen synthase kinase -3ß regulation of cell fate","abstract":"Malignant brain tumors such as gliomas can arise from a subpopulation of cells frequently called glioma stem cells (GSCs). These cells are often resistant to conventional therapies, hence are the likely culprits of tumor recurrence. Here, we describe the derivation of a human GSC line, NNI-8. Our method preserves the karyotypic integrity of the primary tumor, and our xenograft recapitulates the original patient histopathology. Furthermore, a stem cell signature derived from NNI-8 could stratify patients for survival in a clinical database. This infers that GSCs contribute to disease outcome and survival. In a small molecule screen targeting GSCs, we identified glycogen synthase kinase 3-beta (GSK3ß) inhibitors as likely candidates. We observed that pharmacological and genetic knockdown of GSK3 induced apoptosis and differentiation, preferentially in the CD133-expressing tumor-initiating fraction. In addition, GSC frequency was significantly reduced. Our data suggest that targeting GSK3 presents a viable treatment strategy in eradicating self-renewing GSCs.","abstract_html":"Malignant brain tumors such as gliomas can arise from a subpopulation of cells frequently called glioma stem cells (GSCs). These cells are often resistant to conventional therapies, hence are the likely culprits of tumor recurrence. Here, we describe the derivation of a human GSC line, NNI-8. Our method preserves the karyotypic integrity of the primary tumor, and our xenograft recapitulates the original patient histopathology. Furthermore, a stem cell signature derived from NNI-8 could stratify patients for survival in a clinical database. This infers that GSCs contribute to disease outcome and survival. In a small molecule screen targeting GSCs, we identified glycogen synthase kinase 3-beta (GSK3ß) inhibitors as likely candidates. We observed that pharmacological and genetic knockdown of GSK3 induced apoptosis and differentiation, preferentially in the CD133-expressing tumor-initiating fraction. In addition, GSC frequency was significantly reduced. Our data suggest that targeting GSK3 presents a viable treatment strategy in eradicating self-renewing GSCs.","abstract_has_math":false,"creators":["TING HUI LING, ESTHER"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["SOONG TUCK WAH","ANG BENG TI, CHRISTOPHER"],"committee_chairs":[],"committee_members":[],"year":2011,"date_issued":"2011-07-18","date_published":"2011-07-18","updated_at":"2026-08-21T16:47:23Z","subjects":["brain tumor, stem cells, GSK3ß, CD133, apoptosis, differentiation"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarbank.nus.edu.sg/handle/10635/30583","outbound_label":"Repository record","outbound_source":"dc:identifier.uri"},"source_record":{"url":"https://scholarbank.nus.edu.sg/oai/request?verb=GetRecord&metadataPrefix=dim&identifier=oai%3Ascholarbank.nus.edu.sg%3A10635%2F30583","prefix":"dim"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["PHYSIOLOGY"]},{"key":"dc:contributor.supervisor","label":"Supervisor","values":["SOONG TUCK WAH","ANG BENG TI, CHRISTOPHER"]},{"key":"dc:creator","label":"Author","values":["TING HUI LING, ESTHER"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2012-02-13T18:00:06Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2012-02-13T18:00:06Z"]},{"key":"dc:date.issued","label":"Date","values":["2011-07-18"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://scholarbank.nus.edu.sg/handle/10635/30583"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["brain tumor, stem cells, GSK3ß, CD133, apoptosis, differentiation"]}]},{"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":["https://scholarbank.nus.edu.sg/bitstreams/926d1688-d596-4ff9-b9cf-04dbfeae3a02/download","https://scholarbank.nus.edu.sg/handle/10635/30583"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Malignant brain tumors such as gliomas can arise from a subpopulation of cells frequently called glioma stem cells (GSCs). These cells are often resistant to conventional therapies, hence are the likely culprits of tumor recurrence. Here, we describe the derivation of a human GSC line, NNI-8. Our method preserves the karyotypic integrity of the primary tumor, and our xenograft recapitulates the original patient histopathology. Furthermore, a stem cell signature derived from NNI-8 could stratify patients for survival in a clinical database. This infers that GSCs contribute to disease outcome and survival. In a small molecule screen targeting GSCs, we identified glycogen synthase kinase 3-beta (GSK3ß) inhibitors as likely candidates. We observed that pharmacological and genetic knockdown of GSK3 induced apoptosis and differentiation, preferentially in the CD133-expressing tumor-initiating fraction. In addition, GSC frequency was significantly reduced. Our data suggest that targeting GSK3 presents a viable treatment strategy in eradicating self-renewing GSCs."]},{"key":"dc:description.degree","label":"Dc Description Degree","values":["Master's"]},{"key":"dc:format.checksum.md5","label":"Dc Format Checksum Md5","values":["c573eb96ada6d6a8912586a48270b765","04c44570d1b08cda1e105ac1701c8bee"]},{"key":"dc:title","label":"Title","values":["Connecting brain tumor stem cells with their primary tumor and exploring glycogen synthase kinase -3ß regulation of cell fate"]}]}],"canonical_facts":{"dc:contributor.other":["PHYSIOLOGY"],"dc:contributor.supervisor":["SOONG TUCK WAH","ANG BENG TI, CHRISTOPHER"],"dc:creator":["TING HUI LING, ESTHER"],"dc:date.accessioned":["2012-02-13T18:00:06Z"],"dc:date.available":["2012-02-13T18:00:06Z"],"dc:date.issued":["2011-07-18"],"dc:description.abstract":["Malignant brain tumors such as gliomas can arise from a subpopulation of cells frequently called glioma stem cells (GSCs). These cells are often resistant to conventional therapies, hence are the likely culprits of tumor recurrence. Here, we describe the derivation of a human GSC line, NNI-8. Our method preserves the karyotypic integrity of the primary tumor, and our xenograft recapitulates the original patient histopathology. Furthermore, a stem cell signature derived from NNI-8 could stratify patients for survival in a clinical database. This infers that GSCs contribute to disease outcome and survival. In a small molecule screen targeting GSCs, we identified glycogen synthase kinase 3-beta (GSK3ß) inhibitors as likely candidates. We observed that pharmacological and genetic knockdown of GSK3 induced apoptosis and differentiation, preferentially in the CD133-expressing tumor-initiating fraction. In addition, GSC frequency was significantly reduced. Our data suggest that targeting GSK3 presents a viable treatment strategy in eradicating self-renewing GSCs."],"dc:description.degree":["Master's"],"dc:format.checksum.md5":["c573eb96ada6d6a8912586a48270b765","04c44570d1b08cda1e105ac1701c8bee"],"dc:identifier.uri":["https://scholarbank.nus.edu.sg/bitstreams/926d1688-d596-4ff9-b9cf-04dbfeae3a02/download","https://scholarbank.nus.edu.sg/handle/10635/30583"],"dc:language.iso":["en"],"dc:relation.isreferencedby":["https://scholarbank.nus.edu.sg/handle/10635/30583"],"dc:subject":["brain tumor, stem cells, GSK3ß, CD133, apoptosis, differentiation"],"dc:title":["Connecting brain tumor stem cells with their primary tumor and exploring glycogen synthase kinase -3ß regulation of cell fate"],"dc:type":["Thesis"]},"updated_at":"2026-08-21T16:47:23Z"}