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Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy

BACKGROUND: Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro. This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients' tumours. METHODS: The...

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Autores principales: Glaysher, S, Gabriel, F G, Johnson, P, Polak, M, Knight, L A, Parker, K, Poole, M, Narayanan, A, Cree, I A
Formato: Texto
Lenguaje:English
Publicado: Nature Publishing Group 2010
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938260/
https://www.ncbi.nlm.nih.gov/pubmed/20700122
http://dx.doi.org/10.1038/sj.bjc.6605817
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author Glaysher, S
Gabriel, F G
Johnson, P
Polak, M
Knight, L A
Parker, K
Poole, M
Narayanan, A
Cree, I A
author_facet Glaysher, S
Gabriel, F G
Johnson, P
Polak, M
Knight, L A
Parker, K
Poole, M
Narayanan, A
Cree, I A
author_sort Glaysher, S
collection PubMed
description BACKGROUND: Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro. This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients' tumours. METHODS: The chemosensitivity of a series of 31 ovarian tumours, all previously treated with platinum-based chemotherapy, was assessed using the ATP-based tumour chemosensitivity assay (ATP-TCA) and correlated with resistance gene expression measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) in a TaqMan Array following extraction of mRNA from formalin-fixed paraffin-embedded tissue. The results were standardised against a housekeeping gene (PBGD), and assessed by multiple linear regression. RESULTS: Predictive multiple linear regression models were derived for four single agents (cisplatin, gemcitabine, topotecan, and treosulfan), and for the combinations of cisplatin+gemcitabine and treosulfan+gemcitabine. Particularly strong correlations were obtained for cisplatin, gemcitabine, topotecan, and treosulfan+gemcitabine. No individual gene expression showed direct correlation with activity in the ATP-TCA. Genes involved in DNA repair and apoptosis were strongly represented, with some drug pumps also involved. CONCLUSION: The chemosensitivity of ovarian cancer to drugs is related to the expression of genes involved in sensitivity and resistance mechanisms.
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spelling pubmed-29382602011-08-24 Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy Glaysher, S Gabriel, F G Johnson, P Polak, M Knight, L A Parker, K Poole, M Narayanan, A Cree, I A Br J Cancer Translational Therapeutics BACKGROUND: Ovarian cancer shows considerable heterogeneity in its sensitivity to chemotherapy both clinically and in vitro. This study tested the hypothesis that the molecular basis of this difference lies within the known resistance mechanisms inherent to these patients' tumours. METHODS: The chemosensitivity of a series of 31 ovarian tumours, all previously treated with platinum-based chemotherapy, was assessed using the ATP-based tumour chemosensitivity assay (ATP-TCA) and correlated with resistance gene expression measured by quantitative reverse-transcriptase polymerase chain reaction (qRT-PCR) in a TaqMan Array following extraction of mRNA from formalin-fixed paraffin-embedded tissue. The results were standardised against a housekeeping gene (PBGD), and assessed by multiple linear regression. RESULTS: Predictive multiple linear regression models were derived for four single agents (cisplatin, gemcitabine, topotecan, and treosulfan), and for the combinations of cisplatin+gemcitabine and treosulfan+gemcitabine. Particularly strong correlations were obtained for cisplatin, gemcitabine, topotecan, and treosulfan+gemcitabine. No individual gene expression showed direct correlation with activity in the ATP-TCA. Genes involved in DNA repair and apoptosis were strongly represented, with some drug pumps also involved. CONCLUSION: The chemosensitivity of ovarian cancer to drugs is related to the expression of genes involved in sensitivity and resistance mechanisms. Nature Publishing Group 2010-08-24 2010-08-10 /pmc/articles/PMC2938260/ /pubmed/20700122 http://dx.doi.org/10.1038/sj.bjc.6605817 Text en Copyright © 2010 Cancer Research UK https://creativecommons.org/licenses/by/4.0/This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made.The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material.If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit https://creativecommons.org/licenses/by/4.0/.
spellingShingle Translational Therapeutics
Glaysher, S
Gabriel, F G
Johnson, P
Polak, M
Knight, L A
Parker, K
Poole, M
Narayanan, A
Cree, I A
Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy
title Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy
title_full Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy
title_fullStr Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy
title_full_unstemmed Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy
title_short Molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy
title_sort molecular basis of chemosensitivity of platinum pre-treated ovarian cancer to chemotherapy
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2938260/
https://www.ncbi.nlm.nih.gov/pubmed/20700122
http://dx.doi.org/10.1038/sj.bjc.6605817
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