| LDR | | 00000nam u2200205 4500 |
| 001 | | 000000432341 |
| 005 | | 20200224121022 |
| 008 | | 200131s2019 ||||||||||||||||| ||eng d |
| 020 | |
▼a 9781085741491 |
| 035 | |
▼a (MiAaPQ)AAI13896560 |
| 040 | |
▼a MiAaPQ
▼c MiAaPQ
▼d 247004 |
| 082 | 0 |
▼a 615 |
| 100 | 1 |
▼a Fancher, Ashley Taylor. |
| 245 | 10 |
▼a Disrupting Androgen Receptor Transactivation Domains to Identify Lead Compounds with Potential to be Optimized and Developed into Prostate Cancer Therapeutics. |
| 260 | |
▼a [S.l.]:
▼b University of Pittsburgh.,
▼c 2019. |
| 260 | 1 |
▼a Ann Arbor:
▼b ProQuest Dissertations & Theses,
▼c 2019. |
| 300 | |
▼a 243 p. |
| 500 | |
▼a Source: Dissertations Abstracts International, Volume: 81-03, Section: B. |
| 500 | |
▼a Advisor: Johnston, Paul A. |
| 502 | 1 |
▼a Thesis (Ph.D.)--University of Pittsburgh, 2019. |
| 506 | |
▼a This item must not be sold to any third party vendors. |
| 506 | |
▼a This item must not be added to any third party search indexes. |
| 520 | |
▼a Prostate cancer (PCa) is the leading cause of cancer in men in the USA, with more than 160,000 new cases each year. PCa patients receiving standard of care androgen deprivation therapy (ADT) eventually acquire what's known as castration resistant prostate cancer (CRPC), and 20% of all PCa cases progress to this metastatic and incurable form of the disease. PCa is the second leading cause of cancer-related death in American men. Current FDA approved drugs for CRPC only provide a 2-5-month survival benefit due to the emergence of resistance to these therapies. Resistance involves continued androgen receptor (AR) signaling despite castrate serum levels of androgens. CRPC cells express elevated levels of both full-length AR (AR-FL), and constitutively active AR splice variants which lack the ligand binding domain (LBD) and display altered AR coactivator interactions, both of which contribute to persistent AR signaling. Overexpression of steroid-receptor coactivators are implicated in the progression of CRPC and amplify AR-mediated transcription by binding to either the activation function 2 (AF-2) surface formed by the AR-LBD, or the activation function 1 (AF-1) surface located in the amino-terminal domain of the receptor. Coactivator binding interactions enhance the recruitment of the basal transcriptional machinery and activate the transcription of AR target genes. Our lab has designed a screening paradigm to identify compounds with novel mechanisms of action to prevent or delay resistance. The screening paradigm uses a primary high content screening assay (HCS) designed to identify compounds that inhibit or disrupt protein-protein interactions (PPI's) between AR and one of its coactivators, transcriptional intermediary factor 2 (TIF2), together with panels of counter screens and characterization assays to prioritize hit compounds that inhibit or disrupt AF-2 and/or AF-1 transactivation. The ideal hit compound would prevent the transcription of both AR-FL and AR-V7 thereby providing a dual approach to preventing CRPC progression. |
| 590 | |
▼a School code: 0178. |
| 650 | 4 |
▼a Pharmaceutical sciences. |
| 690 | |
▼a 0572 |
| 710 | 20 |
▼a University of Pittsburgh.
▼b School of Pharmacy. |
| 773 | 0 |
▼t Dissertations Abstracts International
▼g 81-03B. |
| 773 | |
▼t Dissertation Abstract International |
| 790 | |
▼a 0178 |
| 791 | |
▼a Ph.D. |
| 792 | |
▼a 2019 |
| 793 | |
▼a English |
| 856 | 40 |
▼u http://www.riss.kr/pdu/ddodLink.do?id=T15491727
▼n KERIS
▼z 이 자료의 원문은 한국교육학술정보원에서 제공합니다. |
| 980 | |
▼a 202002
▼f 2020 |
| 990 | |
▼a ***1008102 |
| 991 | |
▼a E-BOOK |