{"@context":"http://iiif.io/api/presentation/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/manifest.json","@type":"sc:Manifest","label":"Efforts towards Development of New Generation Taxoids: SAR Study, Combination Treatment, and Gold Nanoparticle Drug Delivery System","metadata":[{"label":"dc.description.sponsorship","value":"This work is sponsored by the Stony Brook University Graduate School in compliance with the requirements for completion of degree"},{"label":"dc.format","value":"Monograph"},{"label":"dc.format.medium","value":"Electronic Resource"},{"label":"dc.identifier.uri","value":"http://hdl.handle.net/11401/78210"},{"label":"dc.language.iso","value":"en_US"},{"label":"dcterms.abstract","value":"According to the National Cancer Institute, the number of people living with cancer is expected to rise to 19 million by 2024. While significant advancements have been made in chemotherapy, combating drug resistance and cancer stem cells have remained a major challenge. Therapeutic effectiveness of first generation taxoids, i.e., paclitaxel, is limited in melanoma, pancreatic, gastric, brain and renal cancers. Therefore, it is essential to develop new taxoid anticancer agents with superior pharmacological properties and improved potency against various tumors, particularly against drug-resistant cancers and cancer stem cells. Building upon our extensive SAR studies on taxoids, new -05 and -06 series of third-generation taxoids, bearing a m-OCF3 or m-OCF2H group at the C2-benzoate position, respectively, were designed and synthesized using the ?-lactam synthon method. These taxoids were evaluated against various drug-sensitive and drug-resistant cancer cell lines, as well as patient-derived cancer stem cells PPT2. These taxoids exhibited 1?2 orders of magnitude higher potency than paclitaxel against various cancer cell lines. In order to minimize the amount of SB-T-1214 used in the treatment, and maximize its efficacy against tumor metastasis, the combination of SB-T-1214 with epigallocatechin gallate (EGCG), CMC2.24 (a curcumin analogue) or SB-M-104 (a MMP-9 inhibitor) against various cancer cell lines, including breast, ovarian, colon and pancreatic cancer cell lines has been investigated. The combination treatment exhibited strong synergistic effects depending on the dosage and the cancer type. SB-T-1214 and biotin functionalized gold nanoparticle was developed as a drug delivery system. Biotin serves as a tumor targeting molecule, and SB-T-1214 serves as a highly potent drug. Gold nanoparticle serves as a tumor homing vehicle to deliver drug to the tumor tissue. A self-immolative disulfide linker was applied to facilitate the rapid drug release, and polyethylene glycol spacers were used to improve the solubility."},{"label":"dcterms.available","value":"2018-03-22T22:39:19Z"},{"label":"dcterms.contributor","value":"Ngai, Ming-Yu"},{"label":"dcterms.creator","value":"Wang, Xin"},{"label":"dcterms.dateAccepted","value":"2018-03-22T22:39:19Z"},{"label":"dcterms.dateSubmitted","value":"2018-03-22T22:39:19Z"},{"label":"dcterms.description","value":"Department of Chemistry."},{"label":"dcterms.extent","value":"370 pg."},{"label":"dcterms.format","value":"Monograph"},{"label":"dcterms.identifier","value":"http://hdl.handle.net/11401/78210"},{"label":"dcterms.issued","value":"2017-08-01"},{"label":"dcterms.language","value":"en_US"},{"label":"dcterms.provenance","value":"Made available in DSpace on 2018-03-22T22:39:19Z (GMT). No. of bitstreams: 1\nWang_grad.sunysb_0771E_13466.pdf: 18738081 bytes, checksum: 40368a7f7d9765b5ff6e4b04f4034625 (MD5)\n Previous issue date: 2017-08-01"},{"label":"dcterms.subject","value":"combination treatment"},{"label":"dcterms.title","value":"Efforts towards Development of New Generation Taxoids: SAR Study, Combination Treatment, and Gold Nanoparticle Drug Delivery System"},{"label":"dcterms.type","value":"Dissertation"},{"label":"dc.type","value":"Dissertation"}],"description":"This manifest was generated dynamically","viewingDirection":"left-to-right","sequences":[{"@type":"sc:Sequence","canvases":[{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json","@type":"sc:Canvas","label":"Page 1","height":1650,"width":1275,"images":[{"@type":"oa:Annotation","motivation":"sc:painting","resource":{"@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/16%2F80%2F57%2F168057157707340633143846140077748692012/full/full/0/default.jpg","@type":"dctypes:Image","format":"image/jpeg","height":1650,"width":1275,"service":{"@context":"http://iiif.io/api/image/2/context.json","@id":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/16%2F80%2F57%2F168057157707340633143846140077748692012","profile":"http://iiif.io/api/image/2/level2.json"}},"on":"https://repo.library.stonybrook.edu/cantaloupe/iiif/2/canvas/page-1.json"}]}]}]}