This study was designed to investigate the mode of action of trabectedin in myelomonocytic leukemia cells by applying systems biology approaches to mine gene expression profiling data and pharmacological assessment of the cellular effects. Significant enrichment was found in regulons of target genes inferred for specific transcription factors, among which MAFB was the most upregulated after treatment and was central in the transcriptional network likely to be relevant for the specific therapeutic effects of trabectedin against myelomonocytic cells. Using the Connectivity Map, similarity among transcriptional signatures elicited by treatment with different compounds was investigated, showing a high degree of similarity between transcriptional signatures of trabectedin and those of the topoisomerase I inhibitor, irinotecan, and an anti-dopaminergic antagonist, thioridazine. The study highlights the potential importance of systems biology approaches to generate new hypotheses that are experimentally testable to define the specificity of the mechanism of action of drugs.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5817395 | PMC |
| http://dx.doi.org/10.1038/tpj.2016.76 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Biomechanical and Functional Features of the Carrier Erythrocytes Prolonging Circulation Time of Biotherapeutic Targeted to Glycophorin A.
Bioconjug Chem
January 2025
Department of Pharmacology, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104-5127, United States.
Red blood cells (RBCs) serve as natural transporters and can be modified to enhance the pharmacokinetics and pharmacodynamics of a protein cargo. Affinity targeting of Factor IX (FIX) to the RBC membrane is a promising approach to improve the (pro)enzyme's pharmacokinetics. For RBC targeting, purified human FIX was conjugated to the anti-mouse glycophorin A monoclonal antibody Ter119.
View Article and Find Full Text PDFDo the Shuffle: Expanding the Synthetic Biology Toolkit for Shufflon-like Recombination Systems.
ACS Synth Biol
January 2025
Department of Life Sciences, Imperial College London, London SW7 2AZ, U.K.
Naturally occurring DNA inversion systems play an important role in the generation of genetic variation and adaptation in prokaryotes. Shufflon invertase (SI) from plasmid R64, recognizing asymmetric sites, has been adopted as a tool for synthetic biology. However, the availability of a single enzyme with moderate rates of recombination has hampered the more widespread use of SIs.
View Article and Find Full Text PDFCoordinated neuron-glia regeneration through Notch signaling in planarians.
PLoS Genet
January 2025
Howard Hughes Medical Institute, Massachusetts Institute of Technology, Cambridge, Massachusetts, United States of America.
Some animals can regenerate large missing regions of their nervous system, requiring mechanisms to restore the pattern, numbers, and wiring of diverse neuron classes. Because injuries are unpredictable, regeneration must be accomplished from an unlimited number of starting points. Coordinated regeneration of neuron-glia architecture is thus a major challenge and remains poorly understood.
View Article and Find Full Text PDFEnhanced silk production and pupal weight in Bombyx mori through CRISPR/Cas9-mediated circadian Clock gene disruption.
PLoS One
January 2025
Department of Biology, University of Padova, Padova, Italy.
The domesticated silkworm, Bombyx mori, is crucial for global silk production, which is a significant economic activity supporting millions of livelihoods worldwide. Beyond traditional silk production, the growing demand for insect larvae in cosmetics, biomedical products, and animal feed underscores the need to enhance B. mori productivity.
View Article and Find Full Text PDFMechanism of Radix Bupleuri and Hedysarum Multijugum Maxim drug pairs on liver fibrosis based on network pharmacology, bioinformatics and molecular dynamics simulation.
PLoS One
January 2025
School of Public Health, Anhui University of Science and Technology, Hefei, China.
A number of studies demonstrate the therapeutic effectiveness of Radix Bupleuri (RB) and Hedysarum Multijugum Maxim (HMM) in treating liver fibrosis, but the exact molecular mechanisms remain unclear. This study aims to explore the mechanism of RB-HMM drug pairs in treating liver fibrosis by using network pharmacology, bioinformatics, molecular docking, molecular dynamics simulation technology and in vitro experiments. Totally, 155 intersection targets between RB-HMM and liver fibrosis were identified.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!