ArticleBMC women's health2012
Fibroid explants reveal a higher sensitivity against MDM2-inhibitor nutlin-3 than matching myometrium.
Article in BMC women's health, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
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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
4 citing papers in PubMed, 1 synthesis or guideline pooled it, 8 citations in OpenAlex.
- A Systematic Review of the Role of Senescent Cells in Uterine Leiomyomas: Deciphering Molecular Pathways and Exploring Therapeutic Prospects.Reproductive sciences (Thousand Oaks, Calif.) · 2026Pooled it
- Application of ex-vivo spheroid model system for the analysis of senescence and senolytic phenotypes in uterine leiomyoma.Laboratory investigation; a journal of technical methods and pathology · 2018Article
- p53 Expression in Lung Fibroblasts Is Linked to Mitigation of Fibrotic Lung Remodeling.The American journal of pathology · 2018Article
- Correlated expression of HMGA2 and PLAG1 in thyroid tumors, uterine leiomyomas and experimental models.PloS one · 2014Article
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Authors and funding
10 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundSpontaneous cessation of growth is a frequent finding in uterine fibroids. Increasing evidence suggests an important role of cellular senescence in this growth control. Deciphering the underlying mechanisms of growth control that can be expected not only to shed light on the biology of the tumors but also to identify novel therapeutic targets.
methodsWe have analyzed uterine leiomyomas and matching normal tissue for the expression of p14Arf and used explants to see if reducing the MDM2 activity using the small-molecule inhibitor nutlin-3 can induce p53 and activate genes involved in senescence and/or apoptosis. For these studies quantitative real-time RT-PCR, Western blots, and immunohistochemistry were used. Statistical analyses were performed using the student's t test.
resultsAn in depth analysis of 52 fibroids along with matching myometrium from 31 patients revealed in almost all cases a higher expression of p14Arf in the tumors than in the matching normal tissue. In tissue explants, treatment with the MDM2 inhibitor nutlin-3 induced apoptosis as well as senescence as revealed by a dose-dependent increase of the expression of BAX as well as of p21, respectively. Simultaneously, the expression of the proliferation marker Ki-67 drastically decreased. Western-blot analysis identified an increase of the p53 level as the most likely reason for the increased activity of its downstream markers BAX and p21. Because as a rule fibroids express much higher levels of p14Arf, a major negative regulator of MDM2, than matching myometrium it was then analyzed if fibroids are more sensitive against nutlin-3 treatment than matching myometrium. We were able to show that in most fibroids analyzed a higher sensibility than that of matching myometrium was noted with a corresponding increase of the p53 immunopositivity of the fibroid samples compared to those from myometrium.
conclusionsThe results show that uterine fibroids represent a cell population of advanced cellular age compared to matching myometrium. Moreover, the data point to members of the p53-network as to potential novel therapeutic targets for the treatment of uterine fibroids.
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