ArticleOncoscience2015
A quasi-quantitative dual multiplexed immunoblot method to simultaneously analyze ATM and H2AX Phosphorylation in human peripheral blood mononuclear cells.
Article in Oncoscience, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
14 citing papers in PubMed, 18 citations in OpenAlex.
- Article
- Improving rigor and reproducibility in western blot experiments with the blotRig analysis.Scientific reports · 2024Article
- Mouse models ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Entrapment and Delivery of Doxorubicin: Employing a Permeable Lipopeptide-Based Hydrogel as an Efficient Cationic Binder.Applied biochemistry and biotechnology · 2023Article
- Mouse models ofbioRxiv : the preprint server for biology · 2023Article
- Article
- Antibody validation for Western blot: By the user, for the user.The Journal of biological chemistry · 2020Article
- Dormant origin signaling during unperturbed replication.DNA repair · 2019Review
- Quantitative analysis of ATM phosphorylation in lymphocytes.DNA repair · 2019Article
- pRAD50: a novel and clinically applicable pharmacodynamic biomarker of both ATM and ATR inhibition identified using mass spectrometry and immunohistochemistry.British journal of cancer · 2018Article
- LMTK3 confers chemo-resistance in breast cancer.Oncogene · 2018Article
- Phase I study of veliparib in combination with gemcitabine.Cancer chemotherapy and pharmacology · 2017Article
- The downregulation of the RNA-binding protein Staufen2 in response to DNA damage promotes apoptosis.Nucleic acids research · 2016Article
- ATM serine-1981 phosphorylation is a plausible biomarker.Cell cycle (Georgetown, Tex.) · 2015Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Pharmacologic inhibition of DNA repair may increase the efficacy of many cytotoxic cancer agents. Inhibitors of DNA repair enzymes including APE1, ATM, ATR, DNA-PK and PARP have been developed and the PARP inhibitor olaparib is the first-in-class approved in Europe and the USA for the treatment of advanced BRCA-mutated ovarian cancer. Sensitive pharmacodynamic (PD) biomarkers are needed to further evaluate the efficacy of inhibitors of DNA repair enzymes in clinical trials. ATM is a protein kinase that mediates cell-cycle checkpoint activation and DNA double-strand break repair. ATM kinase activation at DNA double-strand breaks (DSBs) is associated with intermolecular autophosphorylation on serine-1981. Exquisite sensitivity and high stoichiometry as well as facile extraction suggest that ATM serine-1981 phosphorylation may be a highly dynamic PD biomarker for both ATM kinase inhibitors and radiation- and chemotherapy-induced DSBs. Here we report the pre-clinical analytical validation and fit-for-purpose biomarker method validation of a quasi-quantitative dual multiplexed immunoblot method to simultaneously analyze ATM and H2AX phosphorylation in human peripheral blood mononuclear cells (PBMCs). We explore the dynamics of these phosphorylations in PBMCs exposed to chemotherapeutic agents and DNA repair inhibitors in vitro, and show that ATM serine-1981 phosphorylation is increased in PBMCs in sarcoma patients treated with DNA damaging chemotherapy.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.