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High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines
Head and neck squamous cell carcinoma (HNSCC) is a common cancer diagnosis worldwide. Despite advances in treatment, HNSCC has very poor survival outcomes, emphasizing an ongoing need for development of improved therapeutic options. The distinct tumor characteristics of human papillomavirus (HPV)-po...
Autores principales: | , , , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995257/ https://www.ncbi.nlm.nih.gov/pubmed/29899842 http://dx.doi.org/10.18632/oncotarget.25436 |
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author | Ghasemi, Farhad Black, Morgan Sun, Ren X. Vizeacoumar, Frederick Pinto, Nicole Ruicci, Kara M. Yoo, John Fung, Kevin MacNeil, Danielle Palma, David A. Winquist, Eric Mymryk, Joe S. Ailles, Laurie A. Datti, Alessandro Barrett, John W. Boutros, Paul C. Nichols, Anthony C. |
author_facet | Ghasemi, Farhad Black, Morgan Sun, Ren X. Vizeacoumar, Frederick Pinto, Nicole Ruicci, Kara M. Yoo, John Fung, Kevin MacNeil, Danielle Palma, David A. Winquist, Eric Mymryk, Joe S. Ailles, Laurie A. Datti, Alessandro Barrett, John W. Boutros, Paul C. Nichols, Anthony C. |
author_sort | Ghasemi, Farhad |
collection | PubMed |
description | Head and neck squamous cell carcinoma (HNSCC) is a common cancer diagnosis worldwide. Despite advances in treatment, HNSCC has very poor survival outcomes, emphasizing an ongoing need for development of improved therapeutic options. The distinct tumor characteristics of human papillomavirus (HPV)-positive vs. HPV-negative disease necessitate development of treatment strategies tailored to tumor HPV-status. High-throughput robotic screening of 1,433 biologically and pharmacologically relevant compounds at a single dose (4 μM) was carried out against 6 HPV-positive and 20 HPV-negative HNSCC cell lines for preliminary identification of therapeutically relevant compounds. Statistical analysis was further carried out to differentiate compounds with preferential activity against cell lines stratified by the HPV-status. These analyses yielded 57 compounds with higher activity in HPV-negative cell lines, and 34 with higher-activity in HPV-positive ones. Multi-point dose-response curves were generated for six of these compounds (Ryuvidine, MK-1775, SNS-032, Flavopiridol, AZD-7762 and ARP-101), confirming Ryuvidine to have preferential potency against HPV-negative cell lines, and MK-1775 to have preferential potency against HPV-positive cell lines. These data comprise a valuable resource for further investigation of compounds with therapeutic potential in the HNSCC. |
format | Online Article Text |
id | pubmed-5995257 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-59952572018-06-13 High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines Ghasemi, Farhad Black, Morgan Sun, Ren X. Vizeacoumar, Frederick Pinto, Nicole Ruicci, Kara M. Yoo, John Fung, Kevin MacNeil, Danielle Palma, David A. Winquist, Eric Mymryk, Joe S. Ailles, Laurie A. Datti, Alessandro Barrett, John W. Boutros, Paul C. Nichols, Anthony C. Oncotarget Research Paper Head and neck squamous cell carcinoma (HNSCC) is a common cancer diagnosis worldwide. Despite advances in treatment, HNSCC has very poor survival outcomes, emphasizing an ongoing need for development of improved therapeutic options. The distinct tumor characteristics of human papillomavirus (HPV)-positive vs. HPV-negative disease necessitate development of treatment strategies tailored to tumor HPV-status. High-throughput robotic screening of 1,433 biologically and pharmacologically relevant compounds at a single dose (4 μM) was carried out against 6 HPV-positive and 20 HPV-negative HNSCC cell lines for preliminary identification of therapeutically relevant compounds. Statistical analysis was further carried out to differentiate compounds with preferential activity against cell lines stratified by the HPV-status. These analyses yielded 57 compounds with higher activity in HPV-negative cell lines, and 34 with higher-activity in HPV-positive ones. Multi-point dose-response curves were generated for six of these compounds (Ryuvidine, MK-1775, SNS-032, Flavopiridol, AZD-7762 and ARP-101), confirming Ryuvidine to have preferential potency against HPV-negative cell lines, and MK-1775 to have preferential potency against HPV-positive cell lines. These data comprise a valuable resource for further investigation of compounds with therapeutic potential in the HNSCC. Impact Journals LLC 2018-05-25 /pmc/articles/PMC5995257/ /pubmed/29899842 http://dx.doi.org/10.18632/oncotarget.25436 Text en Copyright: © 2018 Ghasemi et al. http://creativecommons.org/licenses/by/3.0/ This article is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0/) (CC-BY), which permits unrestricted use and redistribution provided that the original author and source are credited. |
spellingShingle | Research Paper Ghasemi, Farhad Black, Morgan Sun, Ren X. Vizeacoumar, Frederick Pinto, Nicole Ruicci, Kara M. Yoo, John Fung, Kevin MacNeil, Danielle Palma, David A. Winquist, Eric Mymryk, Joe S. Ailles, Laurie A. Datti, Alessandro Barrett, John W. Boutros, Paul C. Nichols, Anthony C. High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines |
title | High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines |
title_full | High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines |
title_fullStr | High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines |
title_full_unstemmed | High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines |
title_short | High-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines |
title_sort | high-throughput testing in head and neck squamous cell carcinoma identifies agents with preferential activity in human papillomavirus-positive or negative cell lines |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5995257/ https://www.ncbi.nlm.nih.gov/pubmed/29899842 http://dx.doi.org/10.18632/oncotarget.25436 |
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