ArticleLeukemia2005
Synergistic interactions between MEK1/2 and histone deacetylase inhibitors in BCR/ABL+ human leukemia cells.
Article in Leukemia, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It has been retracted, and should not be counted. Cited by 26 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
26 citing papers in PubMed, 70 citations in OpenAlex.
- Article
- Histone Deacetylase Inhibition Enhances the Antitumor Activity of a MEK Inhibitor in Lung Cancer Cells HarboringMolecular cancer therapeutics · 2018Article
- Integrated Drug Expression Analysis for leukemia: an integrated in silico and in vivo approach to drug discovery.The pharmacogenomics journal · 2017Article
- Sorafenib and DE605, a novel c-Met inhibitor, synergistically suppress hepatocellular carcinoma.Oncotarget · 2015Article
- The histone deacetylase inhibitor SAHA sensitizes acute myeloid leukemia cells to a combination of nucleoside analogs and the DNA-alkylating agent busulfan.Leukemia & lymphoma · 2014Article
- SAHA and S116836, a novel tyrosine kinase inhibitor, synergistically induce apoptosis in imatinib-resistant chronic myelogenous leukemia cells.Cancer biology & therapy · 2014Article
- Histone deacetylase inhibitors in glioblastoma: pre-clinical and clinical experience.Medical oncology (Northwood, London, England) · 2014Review
- Synergistic interaction between the HDAC inhibitor, MPT0E028, and sorafenib in liver cancer cells in vitro and in vivo.Clinical cancer research : an official journal of the American Association for Cancer Research · 2014Article
- MEK inhibitors as a chemotherapeutic intervention in multiple myeloma.Blood cancer journal · 2013Article
- Preclinical activity of the rational combination of selumetinib (AZD6244) in combination with vorinostat in KRAS-mutant colorectal cancer models.Clinical cancer research : an official journal of the American Association for Cancer Research · 2012Article
- Preclinical evaluation of dual PI3K-mTOR inhibitors and histone deacetylase inhibitors in head and neck squamous cell carcinoma.British journal of cancer · 2012Article
- Deactylase inhibition in myeloproliferative neoplasms.Investigational new drugs · 2010Review
- Activating Transcription Factor 3 regulates in part the enhanced tumour cell cytotoxicity of the histone deacetylase inhibitor M344 and cisplatin in combination.Cancer cell international · 2010Article
- Article
- MEK inhibitors potentiate dexamethasone lethality in acute lymphoblastic leukemia cells through the pro-apoptotic molecule BIM.Leukemia · 2009Article
- Abrogation of mitogen-activated protein kinase and Akt signaling by vandetanib synergistically potentiates histone deacetylase inhibitor-induced apoptosis in human glioma cells.The Journal of pharmacology and experimental therapeutics · 2009Article
- Inhibitors of deacetylases suppress oncogenic KIT signaling, acetylate HSP90, and induce apoptosis in gastrointestinal stromal tumors.Cancer research · 2009Article
- Article
- Sorafenib and vorinostat kill colon cancer cells by CD95-dependent and -independent mechanisms.Molecular pharmacology · 2009Article
- Histone deacetylase inhibitors trichostatin A and valproic acid circumvent apoptosis in human leukemic cells expressing the RUNX1 chimera.Cancer science · 2008Article
Corrections and comments
- Retraction · 2016-06-01Falsification/Fabrication of Data · False/Forged Authorship · Investigation by ORI · Misconduct - Official Investigation(s) and/or Finding(s) · Misconduct by Author ·
- Commented on by
- Commented on by
- Retracted
Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Interactions between the histone deacetylase inhibitor SAHA and the pharmacologic MEK1/2 inhibitor PD184352 were examined in Bcr/Abl+ human leukemia cells. Coadministration of minimally toxic concentrations of SAHA (or sodium butyrate) and PD184352 (or U0126) resulted in a synergistic increase in mitochondrial damage, caspase activation, and apoptosis in K562 and LAMA 84 cells. Similar interactions were observed in CD34+ cells from two patients with CML and in imatinib mesylate-resistant K562 cells but not in normal human CD34+ bone marrow cells. These events were associated with a marked increase in ROS generation, inactivation of ERK and Akt, downregulation of p21CIP1, Bcr/Abl, and cyclin D1, and activation of JNK. Of these events, ROS generation, ERK inactivation, and cytochrome c/AIF release were largely caspase-independent, whereas the other phenomena displayed varying degrees of caspase-dependence. Using pharmacologic and genetic approaches, generation of ROS, p21CIP1 downregulation, and inactivation of Akt and MEK were found to play significant functional roles in SAHA/PD184352-mediated lethality, whereas JNK activation and Raf-1 downregulation were determined to represent secondary events. These findings indicate that interruption of the MEK/ERK pathway substantially lowers the threshold for HDAC inhibitor-mediated oxidative injury, mitochondrial dysfunction, and apoptosis, suggesting that this approach warrants further examination in Bcr/Abl+-related malignancies.
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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.