상세정보
Export to Refworks부가기능
Data-driven HTS Strategies for Selection of Drug Combinations and 3D Models for Physiologically Relevant Drug Discovery
상세 프로파일
| 자료유형 | 학위논문 |
|---|---|
| 서명/저자사항 | Data-driven HTS Strategies for Selection of Drug Combinations and 3D Models for Physiologically Relevant Drug Discovery. |
| 개인저자 | Kochanek, Stanton Joseph. |
| 단체저자명 | University of Pittsburgh. School of Pharmacy. |
| 발행사항 | [S.l.]: University of Pittsburgh., 2019. |
| 발행사항 | Ann Arbor: ProQuest Dissertations & Theses, 2019. |
| 형태사항 | 229 p. |
| 기본자료 저록 | Dissertations Abstracts International 81-04B. Dissertation Abstract International |
| ISBN | 9781088383391 |
| 학위논문주기 | Thesis (Ph.D.)--University of Pittsburgh, 2019. |
| 일반주기 |
Source: Dissertations Abstracts International, Volume: 81-04, Section: B.
Advisor: Johnston, Paul A. |
| 이용제한사항 | This item must not be sold to any third party vendors. |
| 요약 | Currently, the approval rate for cancer drugs is dismal, where only ~ 5% of candidates that enter phase I clinical trials become therapies. To address this, it is necessary to improve our preclinical strategies. In particular, the leading clinical observation for patient treatment is that drug combinations more consistently provide better therapeutic outcomes and reduce or delay the emergence of drug resistance as opposed to monotherapy alone. What's more, models that better recapitulate tumor biology are more likely to be predictive of therapeutic success. Therefore, it was necessary for our laboratory to use data-driven high-throughput / content screening strategies to confirm synergistic drug-drug interactions and optimize cell culture conditions in 3D for drug discovery, to address these preclinical limitations. Specifically, we developed a strategy to confirm and evaluate the synergistic interaction between DCs identified in a pilot screen of 20 drugs performed in pairwise combinations. We were able to both confirm synergism across 4 DCs and develop a mechanism of synergistic action. We also characterized 11 head and neck squamous cell carcinoma cell lines as multicellular tumor spheroids (MCTSs) looking at changes in cellular viability and spheroid diameter over time as well as other microenvironmental characteristics of a solid tumor. Lastly, we applied our MCTSs to screen 19 FDA approved drugs to determine drug sensitivity in both 2D and 3D models. We observed that 2D was consistently more sensitive than 3D and that it was necessary to implement several metrics to adequately evaluate drug effect in 3D. |
| 일반주제명 | Pharmaceutical sciences. |
| 언어 | 영어 |
| 바로가기 | 
: 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
