Modeling of non-steroidal anti-inflammatory drug effect within signaling pathways and miRNA-regulation pathways.

To date, it is widely recognized that Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) can exert considerable anti-tumor effects regarding many types of cancers. The prolonged use of NSAIDs is highly associated with diverse side effects. Therefore, tailoring down the NSAID application onto individual...

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Autores principales:	Jian Li, Ulrich R Mansmann
Formato:	article
Lenguaje:	EN
Publicado:	Public Library of Science (PLoS) 2013
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/28ecfa3b0045487fafd0e7f6df3dcaae
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spelling	oai:doaj.org-article:28ecfa3b0045487fafd0e7f6df3dcaae2021-11-18T08:59:37ZModeling of non-steroidal anti-inflammatory drug effect within signaling pathways and miRNA-regulation pathways.1932-620310.1371/journal.pone.0072477https://doaj.org/article/28ecfa3b0045487fafd0e7f6df3dcaae2013-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23967306/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203To date, it is widely recognized that Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) can exert considerable anti-tumor effects regarding many types of cancers. The prolonged use of NSAIDs is highly associated with diverse side effects. Therefore, tailoring down the NSAID application onto individual patients has become a necessary and relevant step towards personalized medicine. This study conducts the systemsbiological approach to construct a molecular model (NSAID model) containing a cyclooxygenase (COX)-pathway and its related signaling pathways. Four cancer hallmarks are integrated into the model to reflect different developmental aspects of tumorigenesis. In addition, a Flux-Comparative-Analysis (FCA) based on Petri net is developed to transfer the dynamic properties (including drug responsiveness) of individual cellular system into the model. The gene expression profiles of different tumor-types with available drug-response information are applied to validate the predictive ability of the NSAID model. Moreover, two therapeutic developmental strategies, synthetic lethality and microRNA (miRNA) biomarker discovery, are investigated based on the COX-pathway. In conclusion, the result of this study demonstrates that the NSAID model involving gene expression, gene regulation, signal transduction, protein interaction and other cellular processes, is able to predict the individual cellular responses for different therapeutic interventions (such as NS-398 and COX-2 specific siRNA inhibition). This strongly indicates that this type of model is able to reflect the physiological, developmental and pathological processes of an individual. The approach of miRNA biomarker discovery is demonstrated for identifying miRNAs with oncogenic and tumor suppressive functions for individual cell lines of breast-, colon- and lung-tumor. The achieved results are in line with different independent studies that investigated miRNA biomarker related to diagnostics of cancer treatments, therefore it might shed light on the development of biomarker discovery at individual level. Particular results of this study might contribute to step further towards personalized medicine with the systemsbiological approach.Jian LiUlrich R MansmannPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 8, Iss 8, p e72477 (2013)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Jian Li Ulrich R Mansmann Modeling of non-steroidal anti-inflammatory drug effect within signaling pathways and miRNA-regulation pathways.
description	To date, it is widely recognized that Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) can exert considerable anti-tumor effects regarding many types of cancers. The prolonged use of NSAIDs is highly associated with diverse side effects. Therefore, tailoring down the NSAID application onto individual patients has become a necessary and relevant step towards personalized medicine. This study conducts the systemsbiological approach to construct a molecular model (NSAID model) containing a cyclooxygenase (COX)-pathway and its related signaling pathways. Four cancer hallmarks are integrated into the model to reflect different developmental aspects of tumorigenesis. In addition, a Flux-Comparative-Analysis (FCA) based on Petri net is developed to transfer the dynamic properties (including drug responsiveness) of individual cellular system into the model. The gene expression profiles of different tumor-types with available drug-response information are applied to validate the predictive ability of the NSAID model. Moreover, two therapeutic developmental strategies, synthetic lethality and microRNA (miRNA) biomarker discovery, are investigated based on the COX-pathway. In conclusion, the result of this study demonstrates that the NSAID model involving gene expression, gene regulation, signal transduction, protein interaction and other cellular processes, is able to predict the individual cellular responses for different therapeutic interventions (such as NS-398 and COX-2 specific siRNA inhibition). This strongly indicates that this type of model is able to reflect the physiological, developmental and pathological processes of an individual. The approach of miRNA biomarker discovery is demonstrated for identifying miRNAs with oncogenic and tumor suppressive functions for individual cell lines of breast-, colon- and lung-tumor. The achieved results are in line with different independent studies that investigated miRNA biomarker related to diagnostics of cancer treatments, therefore it might shed light on the development of biomarker discovery at individual level. Particular results of this study might contribute to step further towards personalized medicine with the systemsbiological approach.
format	article
author	Jian Li Ulrich R Mansmann
author_facet	Jian Li Ulrich R Mansmann
author_sort	Jian Li
title	Modeling of non-steroidal anti-inflammatory drug effect within signaling pathways and miRNA-regulation pathways.
title_short	Modeling of non-steroidal anti-inflammatory drug effect within signaling pathways and miRNA-regulation pathways.
title_full	Modeling of non-steroidal anti-inflammatory drug effect within signaling pathways and miRNA-regulation pathways.
title_fullStr	Modeling of non-steroidal anti-inflammatory drug effect within signaling pathways and miRNA-regulation pathways.
title_full_unstemmed	Modeling of non-steroidal anti-inflammatory drug effect within signaling pathways and miRNA-regulation pathways.
title_sort	modeling of non-steroidal anti-inflammatory drug effect within signaling pathways and mirna-regulation pathways.
publisher	Public Library of Science (PLoS)
publishDate	2013
url	https://doaj.org/article/28ecfa3b0045487fafd0e7f6df3dcaae
work_keys_str_mv	AT jianli modelingofnonsteroidalantiinflammatorydrugeffectwithinsignalingpathwaysandmirnaregulationpathways AT ulrichrmansmann modelingofnonsteroidalantiinflammatorydrugeffectwithinsignalingpathwaysandmirnaregulationpathways
_version_	1718421070717911040

Modeling of non-steroidal anti-inflammatory drug effect within signaling pathways and miRNA-regulation pathways.

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