ArticleScience translational medicine2010
An integrated genomic and epigenomic approach predicts therapeutic response to zebularine in human liver cancer.
Article in Science translational medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers, 2 of them syntheses that pooled it.
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
50 citing papers in PubMed, 2 syntheses or guidelines pooled it, 92 citations in OpenAlex.
- Incorporating DNA Methyltransferase Inhibitors (DNMTis) in the Treatment of Genitourinary Malignancies: A Systematic Review.Targeted oncology · 2018Pooled it
- Role of RASSF1A promoter methylation in the pathogenesis of hepatocellular carcinoma: a meta-analysis of 21 cohort studies.Molecular biology reports · 2014Pooled it
- Article
- Epigenetic upregulation of TET2 is an independent poor prognostic factor for intrahepatic cholangiocarcinoma.Virchows Archiv : an international journal of pathology · 2022Article
- Epigenetic mechanisms of liver tumor resistance to immunotherapy.World journal of hepatology · 2021Review
- Epigenetic modifications precede molecular alterations and drive human hepatocarcinogenesis.JCI insight · 2021Article
- Epigenetics in hepatocellular carcinoma development and therapy: The tip of the iceberg.JHEP reports : innovation in hepatology · 2020Review
- Article
- Effect of Zebularine on p16INK4a, p14ARF, p15INK4b, and DNA Methyltransferase 1 Gene Expression, Cell Growth Inhibition, and Apoptosis Induction in Human Hepatocellular Carcinoma PLC/PRF5 and Pancreatic Cancer PA-TU-8902 Cell Lines.Iranian journal of pharmaceutical research : IJPR · 2020Article
- The mitochondrial type IB topoisomerase drives mitochondrial translation and carcinogenesis.Nature communications · 2019Article
- Genome-wide discovery and validation of diagnostic DNA methylation-based biomarkers for hepatocellular cancer detection in circulating cell free DNA.Theranostics · 2019Article
- LINE-1 hypomethylation in human hepatocellular carcinomas correlates with shorter overall survival and CIMP phenotype.PloS one · 2019Article
- The immune contexture of hepatocellular carcinoma predicts clinical outcome.Scientific reports · 2018Article
- Ginkgo biloba induces different gene expression signatures and oncogenic pathways in malignant and non-malignant cells of the liver.PloS one · 2018Article
- Zebularine Promotes Hepatic Differentiation of Rabbit Bone Marrow Mesenchymal Stem Cells by Interfering with p38 MAPK Signaling.Stem cells international · 2018Article
- The relationship between DNA methylation andOncotarget · 2017Article
- RNA-seq reveals distinctive RNA profiles of small extracellular vesicles from different human liver cancer cell lines.Oncotarget · 2017Article
- Adverse genomic alterations and stemness features are induced by field cancerization in the microenvironment of hepatocellular carcinomas.Oncotarget · 2017Article
- Zebularine upregulates expression of CYP genes through inhibition of DNMT1 and PKR in HepG2 cells.Scientific reports · 2017Article
- New Insights into the Epigenetics of Hepatocellular Carcinoma.BioMed research international · 2017Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Epigenomic changes such as aberrant hypermethylation and subsequent atypical gene silencing are characteristic features of human cancer. Here, we report a comprehensive characterization of epigenomic modulation caused by zebularine, an effective DNA methylation inhibitor, in human liver cancer. Using transcriptomic and epigenomic profiling, we identified a zebularine response signature that classified liver cancer cell lines into two major subtypes with different drug responses. In drug-sensitive cell lines, zebularine caused inhibition of proliferation coupled with increased apoptosis, whereas drug-resistant cell lines showed up-regulation of oncogenic networks (for example, E2F1, MYC, and TNF) that drive liver cancer growth in vitro and in preclinical mouse models. Assessment of zebularine-based therapy in xenograft mouse models demonstrated potent therapeutic effects against tumors established from zebularine-sensitive but not zebularine-resistant liver cancer cells, leading to increased survival and decreased pulmonary metastasis. Integration of the zebularine gene expression and demethylation response signatures allowed differentiation of patients with hepatocellular carcinoma according to their survival and disease recurrence. This integrated signature identified a subclass of patients within the poor-survivor group that is likely to benefit from therapeutic agents that target the cancer epigenome.
Indexed as
Identifiers
What OpenQuestion holds
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.