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The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer

BACKGROUND: Repair of various types of DNA damages is critical for genomic stability. DNA-dependent protein kinase (DNA-PK) has an important role in DNA double-strand break repair. We examined whether there may be a correlation between DNA-PK activity in peripheral blood lymphocytes (PBLs) and survi...

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Autores principales: Someya, M, Sakata, K-i, Matsumoto, Y, Kamdar, R P, Kai, M, Toyota, M, Hareyama, M
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111168/
https://www.ncbi.nlm.nih.gov/pubmed/21559021
http://dx.doi.org/10.1038/bjc.2011.158
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author Someya, M
Sakata, K-i
Matsumoto, Y
Kamdar, R P
Kai, M
Toyota, M
Hareyama, M
author_facet Someya, M
Sakata, K-i
Matsumoto, Y
Kamdar, R P
Kai, M
Toyota, M
Hareyama, M
author_sort Someya, M
collection PubMed
description BACKGROUND: Repair of various types of DNA damages is critical for genomic stability. DNA-dependent protein kinase (DNA-PK) has an important role in DNA double-strand break repair. We examined whether there may be a correlation between DNA-PK activity in peripheral blood lymphocytes (PBLs) and survival percentages in various cancer patients. We also investigated the changes of DNA-PK activity in PBLs after radiotherapy. METHODS: A total of 167 of untreated cancer patients participated in this study. Peripheral blood was collected, separated, and centrifuged. DNA-PK activity was measured by DNA-pull-down assay. Chromosomal aberrations were examined by cytogenetic methods. RESULTS: DNA-PK activity of PBLs in advanced cancer patients was significantly lower than that in early stage. The patients with lower DNA-PK activity in PBLs tended to have the lower disease-specific survivals and distant metastasis-free survivals than those with higher DNA-PK activity in advanced stages. There was also a tendency of inverse correlation between DNA-PK activity and excess fragments. The DNA-PK activity of PBLs in most patients decreased in response to radiation as the equivalent whole-body dose increased. CONCLUSION: Cancer patients in advanced stage, with lower DNA-PK activity of PBLs might have higher distant metastasis and exhibit poorer prognosis. Therefore, DNA-PK activity in PBLs could be used as a marker to predict the chromosomal instability and poorer prognosis.
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spelling pubmed-31111682012-05-24 The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer Someya, M Sakata, K-i Matsumoto, Y Kamdar, R P Kai, M Toyota, M Hareyama, M Br J Cancer Translational Therapeutics BACKGROUND: Repair of various types of DNA damages is critical for genomic stability. DNA-dependent protein kinase (DNA-PK) has an important role in DNA double-strand break repair. We examined whether there may be a correlation between DNA-PK activity in peripheral blood lymphocytes (PBLs) and survival percentages in various cancer patients. We also investigated the changes of DNA-PK activity in PBLs after radiotherapy. METHODS: A total of 167 of untreated cancer patients participated in this study. Peripheral blood was collected, separated, and centrifuged. DNA-PK activity was measured by DNA-pull-down assay. Chromosomal aberrations were examined by cytogenetic methods. RESULTS: DNA-PK activity of PBLs in advanced cancer patients was significantly lower than that in early stage. The patients with lower DNA-PK activity in PBLs tended to have the lower disease-specific survivals and distant metastasis-free survivals than those with higher DNA-PK activity in advanced stages. There was also a tendency of inverse correlation between DNA-PK activity and excess fragments. The DNA-PK activity of PBLs in most patients decreased in response to radiation as the equivalent whole-body dose increased. CONCLUSION: Cancer patients in advanced stage, with lower DNA-PK activity of PBLs might have higher distant metastasis and exhibit poorer prognosis. Therefore, DNA-PK activity in PBLs could be used as a marker to predict the chromosomal instability and poorer prognosis. Nature Publishing Group 2011-05-24 2011-05-10 /pmc/articles/PMC3111168/ /pubmed/21559021 http://dx.doi.org/10.1038/bjc.2011.158 Text en Copyright © 2011 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
Someya, M
Sakata, K-i
Matsumoto, Y
Kamdar, R P
Kai, M
Toyota, M
Hareyama, M
The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer
title The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer
title_full The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer
title_fullStr The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer
title_full_unstemmed The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer
title_short The association of DNA-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer
title_sort association of dna-dependent protein kinase activity of peripheral blood lymphocytes with prognosis of cancer
topic Translational Therapeutics
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3111168/
https://www.ncbi.nlm.nih.gov/pubmed/21559021
http://dx.doi.org/10.1038/bjc.2011.158
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