ArticleBMC cancer2005
A phase I study of hydralazine to demethylate and reactivate the expression of tumor suppressor genes.
Article in BMC cancer, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02446652 (Phase III Clinical Trial), which is not on this map. Cited by 57 papers.
What it found
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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.
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.
Phase III Clinical Trial: "Evaluation of the Combination of TRANSKRIP ® Plus Carboplatin and Paclitaxel as First Line Chemotherapy on Survival of Patients With Recurrent - Persistent Cervical Cancer
Who cites it
57 citing papers in PubMed, 150 citations in OpenAlex.
- A double-blind, placebo-controlled, randomized phase III trial of chemotherapy plus epigenetic therapy with hydralazine valproate for advanced cervical cancer. Preliminary results.Medical oncology (Northwood, London, England) · 2011Trial
- A proof-of-principle study of epigenetic therapy added to neoadjuvant doxorubicin cyclophosphamide for locally advanced breast cancer.PloS one · 2006Trial
- Phthalazine as a medically versatile polyheterocyclic core with underexplored anticancer potential.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- DNMT Enzymes and Their Impact on Cervical Cancer: A State-of-the-Art Review.International journal of molecular sciences · 2025Review
- Combination of hydralazine and all-trans retinoic acid targeting breast cancer cells.BMC cancer · 2025Article
- Fragment-based discovery of new potential DNMT1 inhibitors integrating multiple pharmacophore modeling, 3D-QSAR, virtual screening, molecular docking, ADME, and molecular dynamics simulation approaches.Molecular diversity · 2025Article
- Review
- The inhibitory and transcriptional effects of the epigenetic repurposed drugs hydralazine and valproate in lymphoma cells.American journal of cancer research · 2024Article
- New insights for gynecological cancer therapies: from molecular mechanisms and clinical evidence to future directions.Cancer metastasis reviews · 2023Review
- Design, synthesis, and biological evaluation of novel carbazole derivatives as potent DNMT1 inhibitors with reasonable PK properties.Journal of enzyme inhibition and medicinal chemistry · 2022Article
- Effect of epigenetic treatment on SSTClinical and translational medicine · 2022Article
- Targeting Epigenetic Regulatory Enzymes for Cancer Therapeutics: Novel Small-Molecule Epidrug Development.Frontiers in oncology · 2022Review
- Hydralazine and Panobinostat Attenuate Malignant Properties of Prostate Cancer Cell Lines.Pharmaceuticals (Basel, Switzerland) · 2021Article
- Pre-Operative Decitabine in Colon Cancer Patients: Analyses on WNT Target Methylation and Expression.Cancers · 2021Article
- Low-dose hydralazine during gestation reduces renal fibrosis in rodent offspring exposed to maternal high fat diet.PloS one · 2021Article
- Epigallocatechin gallate inhibits HeLa cells by modulation of epigenetics and signaling pathways.3 Biotech · 2020Article
- Making it or breaking it: DNA methylation and genome integrity.Essays in biochemistry · 2020Review
- Reversal of increased mammary tumorigenesis by valproic acid and hydralazine in offspring of dams fed high fat diet during pregnancy.Scientific reports · 2019Article
- Molecular mechanisms in progression of HPV-associated cervical carcinogenesis.Journal of biomedical science · 2019Review
- Substituted anthraquinones represent a potential scaffold for DNA methyltransferase 1-specific inhibitors.PloS one · 2019Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundThe antihypertensive compound hydralazine is a known demethylating agent. This phase I study evaluated the tolerability and its effects upon DNA methylation and gene reactivation in patients with untreated cervical cancer.
methodsHydralazine was administered to cohorts of 4 patients at the following dose levels: I) 50 mg/day, II) 75 mg/day, III) 100 mg/day and IV) 150 mg/day. Tumor biopsies and peripheral blood samples were taken the day before and after treatment. The genes APC, MGMT; ER, GSTP1, DAPK, RARbeta, FHIT and p16 were evaluated pre and post-treatment for DNA promoter methylation and gene expression by MSP (Methylation-Specific PCR) and RT-PCR respectively in each of the tumor samples. Methylation of the imprinted H19 gene and the "normally methylated" sequence clone 1.2 was also analyzed. Global DNA methylation was analyzed by capillary electrophoresis and cytosine extension assay. Toxicity was evaluated using the NCI Common Toxicity Criteria.
resultsHydralazine was well tolerated. Toxicities were mild being the most common nausea, dizziness, fatigue, headache and palpitations. Overall, 70% of the pretreatment samples and all the patients had at least one methylated gene. Rates of demethylation at the different dose levels were as follows: 50 mg/day, 40%; 75 mg/day, 52%, 100 mg/day, 43%, and 150 mg/day, 32%. Gene expression analysis showed only 12 informative cases, of these 9 (75%) re-expressed the gene. There was neither change in the methylation status of H19 and clone 1.2 nor changes in global DNA methylation.
conclusionHydralazine at doses between 50 and 150 mg/day is well tolerated and effective to demethylate and reactivate the expression of tumor suppressor genes without affecting global DNA methylation.
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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.