ArticleFertility and sterility2024
Therapeutic effects of in vivo administration of an inhibitor of tryptophan 2,3-dioxygenase (680c91) for the treatment of fibroids: a preclinical study.
Article in Fertility and sterility, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 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.
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Who cites it
11 citing papers in PubMed, 12 citations in OpenAlex.
- Tryptophan metabolism in tumor microenvironment and therapeutic implications.Journal of advanced research · 2026Review
- In vivo inhibition of TDO2 in fibroids results in widespread alteration in the tumor transcriptome.Clinical science (London, England : 1979) · 2026Article
- Transcriptomic and functional analysis of fibroid extracellular vesicles.Clinical science (London, England : 1979) · 2026Article
- Comparative Analysis of Differentially Expressed Long Non-Coding RNA in Pre- and Postmenopausal Fibroids.International journal of molecular sciences · 2025Article
- Role of Kynurenine and Its Derivatives in Liver Diseases: Recent Advances and Future Clinical Perspectives.International journal of molecular sciences · 2025Review
- Review
- The in vivo effects of knockdown of long non-coding RNA XIST on fibroid growth and gene expression.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2024Article
- Observational
- In Vivo Effects of Bay 11-7082 on Fibroid Growth and Gene Expression: A Preclinical Study.Cells · 2024Article
- Targeting the long non-coding RNA MIAT for the treatment of fibroids in an animal model.Clinical science (London, England : 1979) · 2024Article
- The Effect of Race/Ethnicity and MED12 Mutation on the Expression of Long Non-Coding RNAs in Uterine Leiomyoma and Myometrium.International journal of molecular sciences · 2024Article
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
objectiveFibroids are characterized by marked overexpression of tryptophan 2,3 dioxygenase (TDO2). The objective of this study was to determine the effectiveness of in vivo administration of an inhibitor of TDO2 (680C91) on fibroid size and gene expression.
designAnimal and ex vivo human study.
settingAcademic Research Institution. SUBJECTS: Severe combined immunodeficiency mice bearing human fibroid xenografts treated with vehicle and TDO2 inhibitor.
interventionDaily intraperitoneal administration of 680C91 or vehicle for 2 months and in vitro studies with fibroid explants.
main outcome measuresTumor weight and gene expression profile of xenografts and in vitro mechanistic experiments using fibroid explants.
resultsCompound 680C91 was well-tolerated with no effects on blood chemistry and body weight. Treatment of mice with 680C91 resulted in 30% reduction in the weight of fibroid xenografts after 2 months of treatment and as expected lower levels of kynurenine, the byproduct of tryptophan degradation and an endogenous ligand of aryl hydrocarbon receptor (AhR) in the xenografts. The expression of cytochrome P450 family 1 subfamily B member 1 (CYP1B1), transforming growth factor β3 (TGF-β3), fibronectin (FN1), cyclin-dependent kinase 2 (CDK2), E2F transcription factor 1 (E2F1), interleukin 8 (IL-8) and secreted protein acidic and cysteine rich (SPARC) mRNA were lower in the xenografts of mice treated with 680C91 compared with vehicle controls. Similarly, the protein abundance of collagen, FN1, CYP1B1, and SPARC were lower in the xenografts of 680C9- treated mice compared with vehicle controls. Immunohistochemical analysis of xenografts indicated decreased expression of collagen, Ki67 and E2F1 but no significant changes in cleaved caspase 3 expression in mice treated with 680C91. The levels of kynurenine in the xenografts showed a direct correlation with the tumor weight and FN1 levels. In vitro studies with fibroid explants showed a significant induction of CYP1B1, TGF-β3, FN1, CDK2, E2F1, IL8, and SPARC mRNA by tryptophan, which could be blocked by cotreatment with 680C91 and the AhR antagonist CH-223191.
conclusionThe results indicate that correction of aberrant tryptophan catabolism in fibroids could be an effective treatment through its effect to reduce cell proliferation and extracellular matrix accumulation.
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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.