{"id":{"repo_id":"nus","oai_identifier":"oai:scholarbank.nus.edu.sg:10635/28135"},"canonical_url":"https://search.dev.ndltd.org/etd/nus/oai:scholarbank.nus.edu.sg:10635/28135","repository":{"repo_id":"nus","name":"National University of Singapore","base_url":"https://scholarbank.nus.edu.sg/oai/request"},"display":{"title":"Arsenic trioxide in ovarian cancer","abstract":"Arsenic trioxide (As2O3) has shown anti-tumour activity against a variety of solid tumours in vitro. However, the mechanisms responsible for its cytotoxicity against ovarian carcinoma remain elusive. In this thesis, the molecular determinants of its effects and factors mediating its chemoresistance in ovarian cancer cells were investigated. It was found that As2O3 treatment caused both apoptosis induction and caspase-independent cell death involving mitochondrial dysfunction. This was accompanied by endoplasmic reticulum stress induction and an increase in intracellular glutathione (GSH) level. The latter was in turn prevented by the concurrent use of GSH modulator, buthionine sulfoximine but not ascorbic acid. Gene expression analysis of arsenic-resistant OVCAR-3 (OVCAR-3/AsR) cells showed the involvement of multiple factors mediating its chemoresistance. Of particular interest, a genetic hub involving elevated interleukin 1A signalling was identified. This could consecutively modulate the expression of other genes, thus promoting and ensuing the continual growth and survival of OVCAR-3/AsR cells.","abstract_html":"Arsenic trioxide (As2O3) has shown anti-tumour activity against a variety of solid tumours in vitro. However, the mechanisms responsible for its cytotoxicity against ovarian carcinoma remain elusive. In this thesis, the molecular determinants of its effects and factors mediating its chemoresistance in ovarian cancer cells were investigated. It was found that As2O3 treatment caused both apoptosis induction and caspase-independent cell death involving mitochondrial dysfunction. This was accompanied by endoplasmic reticulum stress induction and an increase in intracellular glutathione (GSH) level. The latter was in turn prevented by the concurrent use of GSH modulator, buthionine sulfoximine but not ascorbic acid. Gene expression analysis of arsenic-resistant OVCAR-3 (OVCAR-3/AsR) cells showed the involvement of multiple factors mediating its chemoresistance. Of particular interest, a genetic hub involving elevated interleukin 1A signalling was identified. This could consecutively modulate the expression of other genes, thus promoting and ensuing the continual growth and survival of OVCAR-3/AsR cells.","abstract_has_math":false,"creators":["ONG PEI SHI"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["HO CHI LUI, PAUL","CHAN SUI YUNG"],"committee_chairs":[],"committee_members":[],"year":2008,"date_issued":"2008-09-14","date_published":"2008-09-14","updated_at":"2026-08-21T16:47:23Z","subjects":["Arsenic Trioxide; Ovarian cancer; Mitochondrial dysfunction; Caspase-independent cell death; Endoplasmic reticulum stress; glutathione"],"languages":["en"],"rights":[],"rights_urls":[],"identifier_entries":[]},"links":{"outbound_url":"https://scholarbank.nus.edu.sg/handle/10635/28135","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%2F28135","prefix":"dim"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["PHARMACY"]},{"key":"dc:contributor.supervisor","label":"Supervisor","values":["HO CHI LUI, PAUL","CHAN SUI YUNG"]},{"key":"dc:creator","label":"Author","values":["ONG PEI SHI"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2011-11-08T18:00:34Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2011-11-08T18:00:34Z"]},{"key":"dc:date.issued","label":"Date","values":["2008-09-14"]},{"key":"dc:relation.isreferencedby","label":"Dc Relation Isreferencedby","values":["https://scholarbank.nus.edu.sg/handle/10635/28135"]},{"key":"dc:type","label":"Dc Type","values":["Thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["Arsenic Trioxide; Ovarian cancer; Mitochondrial dysfunction; Caspase-independent cell death; Endoplasmic reticulum stress; glutathione"]}]},{"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/8a2e7593-aeac-471a-be2a-f0b70175aab6/download","https://scholarbank.nus.edu.sg/handle/10635/28135"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Arsenic trioxide (As2O3) has shown anti-tumour activity against a variety of solid tumours in vitro. 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