ArticleCell cycle (Georgetown, Tex.)2009
The cyclin dependent kinase inhibitor (R)-roscovitine prevents alloreactive T cell clonal expansion and protects against acute GvHD.
Article in Cell cycle (Georgetown, Tex.), 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 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
17 citing papers in PubMed, 29 citations in OpenAlex.
- Dissecting the regulatory network of transcription factors in T cell phenotype/functioning during GVHD and GVT.Frontiers in immunology · 2023Review
- Review
- Immunomodulatory Roles of Cell Cycle Regulators.Frontiers in cell and developmental biology · 2019Review
- Potent anti-leukemic activity of a specific cyclin-dependent kinase 9 inhibitor in mouse models of chronic lymphocytic leukemia.Oncotarget · 2018Article
- Dinaciclib induces immunogenic cell death and enhances anti-PD1-mediated tumor suppression.The Journal of clinical investigation · 2018Article
- Acute Graft-versus-Host Disease - Biologic Process, Prevention, and Therapy.The New England journal of medicine · 2017Review
- Article
- Modulating Innate and Adaptive Immunity by (R)-Roscovitine: Potential Therapeutic Opportunity in Cystic Fibrosis.Journal of innate immunity · 2016Review
- Roscovitine in cancer and other diseases.Annals of translational medicine · 2015Review
- Cyclin-dependent kinase 9 may as a novel target in downregulating the atherosclerosis inflammation (Review).Biomedical reports · 2014Article
- New roles for cyclin-dependent kinases in T cell biology: linking cell division and differentiation.Nature reviews. Immunology · 2014Review
- Foxp3 protein stability is regulated by cyclin-dependent kinase 2.The Journal of biological chemistry · 2013Article
- Cyclin-dependent kinase inhibitor therapy for hematologic malignancies.Expert opinion on investigational drugs · 2013Review
- Cyclin-dependent kinase 2 controls peripheral immune tolerance.Journal of immunology (Baltimore, Md. : 1950) · 2012Article
- Roscovitine blocks leukocyte extravasation by inhibition of cyclin-dependent kinases 5 and 9.British journal of pharmacology · 2011Article
- The Role of Pharmacokinetics and Pharmacodynamics in Early Drug Development with reference to the Cyclin-dependent Kinase (Cdk) Inhibitor - Roscovitine.Sultan Qaboos University medical journal · 2011Article
- The cyclin dependent kinase inhibitor (R)-roscovitine mediates selective suppression of alloreactive human T cells but preserves pathogen-specific and leukemia-specific effectors.Clinical immunology (Orlando, Fla.)Article
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5 authors at 4 institutions in 3 countries.
Funding
Abstract
Cell cycle re-entry of quiescent T lymphocytes regulated by cdk2 is required for antigen-specific clonal expansion and generation of productive T cell responses. Recently, we determined that induction of antigen-specific T cell tolerance results in impaired cdk2 activity leading to enhanced Smad3 transactivation, upregulation of p15 and blockade of cell cycle progression. Here we report that pharmacologic inhibition of cdk2 with (R)-roscovitine blocked expansion of alloreactive T cells in vitro and in vivo and protected from lethal acute GvHD. In addition to inhibiting alloreactive T cell responses, (R)-roscovitine prevented TNF-alpha-mediated activation of NF-kappa B pathway, which is involved in the inflammatory process leading to the development of GvHD. The combined anti-proliferative and anti-inflammatory properties of (R)-roscovitine make it an attractive treatment modality toward control of GvHD.
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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.