Expression profiling of DNA methyl transferase I (DNMT1) and efficacy of a DNA-hypomethylating agent (decitabine) in combination with chemotherapy in osteosarcoma
© 2020 Background: Abnormality in the DNA methylation process is one of the hallmarks of cancer. Emerging evidence strongly supports the idea that defects in DNA methyl transferases (DNMTs) are involved in tumor development and progression. This alteration has major effects at the transcription leve...
Saved in:
Main Authors: | , , , , , , , |
---|---|
Format: | Journal |
Published: |
2020
|
Subjects: | |
Online Access: | https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85091985687&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/70742 |
Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
Institution: | Chiang Mai University |
id |
th-cmuir.6653943832-70742 |
---|---|
record_format |
dspace |
spelling |
th-cmuir.6653943832-707422020-10-14T08:40:38Z Expression profiling of DNA methyl transferase I (DNMT1) and efficacy of a DNA-hypomethylating agent (decitabine) in combination with chemotherapy in osteosarcoma Parunya Chaiyawat Nutnicha Sirikaew Piyaporn Budprom Jeerawan Klangjorhor Areerak Phanphaisarn Pimpisa Teeyakasem Jongkolnee Settakorn Dumnoensun Pruksakorn Medicine © 2020 Background: Abnormality in the DNA methylation process is one of the hallmarks of cancer. Emerging evidence strongly supports the idea that defects in DNA methyl transferases (DNMTs) are involved in tumor development and progression. This alteration has major effects at the transcription level of various cancer-associated genes. Methods: Expression profiles of DNMT1 were investigated in fresh frozen tissues, patient-derived cells, and formalin-fixed paraffin-embedded tissues using immunoblotting and immunohistochemistry analysis. We also examined an anti-tumor effect of single DNA-hypomethylating agent (decitabine) and a combination of decitabine and chemotherapy in osteosarcoma cell lines. Results: The results showed an overexpression of DNMT1 in most cases compared to normal cells and tissue samples. DNMT1 was also expressed at the same levels in paired primary cells derived from biopsy and post-chemotherapy tissues. Expression patterns of DNMT1 were examined in 77 osteosarcoma patients of whom 82% had positive DNMT1 with an IRS score > 0. Most of the cases expressed low to moderate levels of DNMT1 (IRS range 1–8, median = 2.0). Furthermore, we found that a combination of decitabine and chemotherapy had a synergistic effect in most of the tested osteosarcoma cells at a low dose therapeutic range of decitabine. Conclusions: Our study revealed DNMT1 expression patterns that indicated potential roles of DNMT1 in osteosarcoma transformation and progression. This finding also suggests the efficacy of a combination therapy of decitabine with chemotherapy for osteosarcoma treatment. 2020-10-14T08:40:38Z 2020-10-14T08:40:38Z 2020-12-01 Journal 22121374 2-s2.0-85091985687 10.1016/j.jbo.2020.100321 https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85091985687&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/70742 |
institution |
Chiang Mai University |
building |
Chiang Mai University Library |
continent |
Asia |
country |
Thailand Thailand |
content_provider |
Chiang Mai University Library |
collection |
CMU Intellectual Repository |
topic |
Medicine |
spellingShingle |
Medicine Parunya Chaiyawat Nutnicha Sirikaew Piyaporn Budprom Jeerawan Klangjorhor Areerak Phanphaisarn Pimpisa Teeyakasem Jongkolnee Settakorn Dumnoensun Pruksakorn Expression profiling of DNA methyl transferase I (DNMT1) and efficacy of a DNA-hypomethylating agent (decitabine) in combination with chemotherapy in osteosarcoma |
description |
© 2020 Background: Abnormality in the DNA methylation process is one of the hallmarks of cancer. Emerging evidence strongly supports the idea that defects in DNA methyl transferases (DNMTs) are involved in tumor development and progression. This alteration has major effects at the transcription level of various cancer-associated genes. Methods: Expression profiles of DNMT1 were investigated in fresh frozen tissues, patient-derived cells, and formalin-fixed paraffin-embedded tissues using immunoblotting and immunohistochemistry analysis. We also examined an anti-tumor effect of single DNA-hypomethylating agent (decitabine) and a combination of decitabine and chemotherapy in osteosarcoma cell lines. Results: The results showed an overexpression of DNMT1 in most cases compared to normal cells and tissue samples. DNMT1 was also expressed at the same levels in paired primary cells derived from biopsy and post-chemotherapy tissues. Expression patterns of DNMT1 were examined in 77 osteosarcoma patients of whom 82% had positive DNMT1 with an IRS score > 0. Most of the cases expressed low to moderate levels of DNMT1 (IRS range 1–8, median = 2.0). Furthermore, we found that a combination of decitabine and chemotherapy had a synergistic effect in most of the tested osteosarcoma cells at a low dose therapeutic range of decitabine. Conclusions: Our study revealed DNMT1 expression patterns that indicated potential roles of DNMT1 in osteosarcoma transformation and progression. This finding also suggests the efficacy of a combination therapy of decitabine with chemotherapy for osteosarcoma treatment. |
format |
Journal |
author |
Parunya Chaiyawat Nutnicha Sirikaew Piyaporn Budprom Jeerawan Klangjorhor Areerak Phanphaisarn Pimpisa Teeyakasem Jongkolnee Settakorn Dumnoensun Pruksakorn |
author_facet |
Parunya Chaiyawat Nutnicha Sirikaew Piyaporn Budprom Jeerawan Klangjorhor Areerak Phanphaisarn Pimpisa Teeyakasem Jongkolnee Settakorn Dumnoensun Pruksakorn |
author_sort |
Parunya Chaiyawat |
title |
Expression profiling of DNA methyl transferase I (DNMT1) and efficacy of a DNA-hypomethylating agent (decitabine) in combination with chemotherapy in osteosarcoma |
title_short |
Expression profiling of DNA methyl transferase I (DNMT1) and efficacy of a DNA-hypomethylating agent (decitabine) in combination with chemotherapy in osteosarcoma |
title_full |
Expression profiling of DNA methyl transferase I (DNMT1) and efficacy of a DNA-hypomethylating agent (decitabine) in combination with chemotherapy in osteosarcoma |
title_fullStr |
Expression profiling of DNA methyl transferase I (DNMT1) and efficacy of a DNA-hypomethylating agent (decitabine) in combination with chemotherapy in osteosarcoma |
title_full_unstemmed |
Expression profiling of DNA methyl transferase I (DNMT1) and efficacy of a DNA-hypomethylating agent (decitabine) in combination with chemotherapy in osteosarcoma |
title_sort |
expression profiling of dna methyl transferase i (dnmt1) and efficacy of a dna-hypomethylating agent (decitabine) in combination with chemotherapy in osteosarcoma |
publishDate |
2020 |
url |
https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85091985687&origin=inward http://cmuir.cmu.ac.th/jspui/handle/6653943832/70742 |
_version_ |
1681752958000168960 |