ArticleOncotarget2015
Molecular targeting of protein arginine deiminases to suppress colitis and prevent colon cancer.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 38 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.
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Who cites it
38 citing papers in PubMed, 56 citations in OpenAlex.
- PAD4 deletion in synovial macrophages exacerbates pathology in inflammatory arthritis.Research square · 2026Article
- Neutrophil extracellular traps in colorectal cancer: a paradoxical nexus of tumor defense and disease progression.Frontiers in immunology · 2026Review
- Roles of peptidylarginine deiminase (PAD) and protein citrullination in viral infections.Frontiers in microbiology · 2026Review
- How histone modifications influence cellular radiosensitivity: Pharmaceutically targeting epigenetic regulators as a promising avenue to overcome radioresistance.Acta pharmaceutica Sinica. B · 2025Review
- Citrullination in tumor immunity and therapy.The Journal of clinical investigation · 2025Review
- Exploring metabolic pathways in gastrointestinal cancer: new evidence of causality.Discover oncology · 2025Article
- Biombalance™, an Oligomeric Procyanidins-Enriched Grape Seed Extract, Prevents Inflammation and Microbiota Dysbiosis in a Mice Colitis Model.Antioxidants (Basel, Switzerland) · 2025Article
- A cyclic peptide toolkit reveals mechanistic principles of peptidylarginine deiminase IV regulation.Nature communications · 2024Article
- Crossing epigenetic frontiers: the intersection of novel histone modifications and diseases.Signal transduction and targeted therapy · 2024Review
- Understanding the matrix: collagen modifications in tumors and their implications for immunotherapy.Journal of translational medicine · 2024Review
- Protein citrullination: inhibition, identification and insertion.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2023Review
- Role of non-canonical post-translational modifications in gastrointestinal tumors.Cancer cell international · 2023Review
- Development of LB244, an Irreversible STING Antagonist.Journal of the American Chemical Society · 2023Article
- Cl-amidine attenuates lipopolysaccharide-induced inflammation in human gingival fibroblasts via the JNK/MAPK, NF-κB, and Nrf2 signalling pathways.Human cell · 2023Article
- Review
- Intrinsic function of the peptidylarginine deiminase PADI4 is dispensable for normal haematopoiesis.Biology open · 2022Article
- Neutrophils and polymorphonuclear myeloid-derived suppressor cells: an emerging battleground in cancer therapy.Oncogenesis · 2022Review
- Inhibition of NETosis for treatment purposes: friend or foe?Molecular and cellular biochemistry · 2022Review
- The Citrullination-Neutrophil Extracellular Trap Axis in Chronic Diseases.Journal of innate immunity · 2022Review
- A Review of Neutrophil Extracellular Traps (NETs) in Disease: Potential Anti-NETs Therapeutics.Clinical reviews in allergy & immunology · 2021Review
Corrections and comments
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Ulcerative colitis (UC) is a chronic disease, in which the lining of the colon becomes inflamed and develops ulcers leading to abdominal pain, diarrhea, and rectal bleeding. The extent of these symptoms depends on disease severity. The protein arginine deiminase (PAD) family of enzymes converts peptidyl-Arginine to peptidyl-Citrulline through citrullination. PADs are dysregulated, with abnormal citrullination in many diseases, including UC and colorectal cancer (CRC). We have developed the small molecule, pan-PAD inhibitor, Chlor-amidine (Cl-amidine), with multiple goals, including treating UC and preventing CRC. Building off our recent results showing that: 1) Cl-amidine suppresses colitis in vivo in a dextran sulfate sodium (DSS) mouse model; and 2) Cl-amidine induces microRNA (miR)-16 in vitro causing cell cycle arrest, we tested the hypothesis that Cl-amidine can prevent tumorigenesis and that miR-16 induction, by Cl-amidine, may be involved in vivo. Consistent with our hypothesis, we present evidence that Cl-amidine, delivered in the drinking water, prevents colon tumorigenesis in our mouse model of colitis-associated CRC where mice are given carcinogenic azoxymethane (AOM), followed by multiple cycles of 2% DSS to induce colitis. To begin identifying mechanisms, we examined the effects of Cl-amidine on miR-16. Results show miR-16 suppression during the colitis-to-cancer sequence in colon epithelial cells, which was rescued by drinking Cl-amidine. Likewise, Ki67 and cellular proliferation targets of miR-16 (Cyclins D1 and E1) were suppressed by Cl-amidine. The decrease in cell proliferation markers and increase in tumor suppressor miRNA expression potentially define a mechanism of how Cl-amidine is suppressing tumorigenesis in vivo.
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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.