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...

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Detalles Bibliográficos
Autores principales: Thurman, Morgan, van Doorn, Jacob, Danzer, Barbara, Webb, Thomas R, Stamm, Stefan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: SAGE Publications 2017
Materias:
Short Report
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5598794/
https://www.ncbi.nlm.nih.gov/pubmed/28932105
http://dx.doi.org/10.1177/1177271917730557
Descripción
Sumario: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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