Changes in Alternative Splicing as Pharmacodynamic Markers for Sudemycin D6
Objective: The aim of the study was to define pharmacodynamic markers for sudemycin D6, an experimental cancer drug that changes alternative splicing in human blood. Methods: Blood samples from 12 donors were incubated with sudemycin D6 for up to 24 hours, and at several time points total RNA from l...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
SAGE Publishing
2017-09-01
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| Series: | Biomarker Insights |
| Online Access: | https://doi.org/10.1177/1177271917730557 |
| Summary: | Objective: The aim of the study was to define pharmacodynamic markers for sudemycin D6, an experimental cancer drug that changes alternative splicing in human blood. Methods: Blood samples from 12 donors were incubated with sudemycin D6 for up to 24 hours, and at several time points total RNA from lymphocytes was prepared and the pre-messenger RNA (mRNA) splicing patterns were analyzed with reverse transcription-polymerase chain reaction. Results: Similar to immortalized cells, blood lymphocytes change alternative splicing due to sudemycin D6 treatment. However, lymphocytes in blood respond slower than immortalized cultured cells. Conclusions: Exon skipping in the DUSP11 and SRRM1 pre-mRNAs are pharmacodynamic markers for sudemycin D6 treatment and show effects beginning at 9 hours after treatment. |
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| ISSN: | 1177-2719 |