ArticleEndocrinology2018
The AKT/BCL-2 Axis Mediates Survival of Uterine Leiomyoma in a Novel 3D Spheroid Model.
Article in Endocrinology, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
15 citing papers in PubMed, 25 citations in OpenAlex.
- Human Myometrial Cell Fate under Chronic Oxidative Stress for Leiomyomagenesis.Research square · 2026Article
- Compressive force induces differential gene and protein expression in uterine fibroids.F&S science · 2025Article
- UTERINE FIBROIDS.Physiological reviews · 2025Review
- Establishment of 3D Cultures of Myometrium, Leiomyoma, and Leiomyosarcoma Cells: Advantages and Disadvantages of Two Different Models.Reproductive sciences (Thousand Oaks, Calif.) · 2024Article
- Engineered uterine primary myometrial cells with high-mobility group AT-hook 2 overexpression display a leiomyoma-like transcriptional and epigenomic phenotype.F&S science · 2024Article
- Functional, patient-derived 3D tri-culture models of the uterine wall in a microfluidic array.Human reproduction (Oxford, England) · 2024Article
- The Functional Role of the Long Non-Coding RNA LINCMD1 in Leiomyoma Pathogenesis.International journal of molecular sciences · 2024Article
- Myometrial oxidative stress drives MED12 mutations in leiomyoma.Cell & bioscience · 2022Article
- Uterine Fibroids: Hiding in Plain Sight.Physiology (Bethesda, Md.) · 2022Review
- Wnt/β-catenin signaling pathway in uterine leiomyoma: role in tumor biology and targeting opportunities.Molecular and cellular biochemistry · 2021Review
- Activation of protein kinase B by WNT4 as a regulator of uterine leiomyoma stem cell function.Fertility and sterility · 2020Article
- An engineered chimeric toxin that cleaves activated mutant and wild-type RAS inhibits tumor growth.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Down-regulation of miR-543 expression increases the sensitivity of colorectal cancer cells to 5-Fluorouracil through the PTEN/PI3K/AKT pathway.Bioscience reports · 2019Article
- 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
- Establishment of a 3D spheroid culture system to evaluate the responsiveness of uterine leiomyoma cells to female hormones.Reproductive medicine and biologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
A deeper understanding of the pathways that drive uterine leiomyoma (ULM) growth and survival requires model systems that more closely mimic the in vivo tumors. This would provide new insights into developing effective therapeutic strategies for these common benign tumors of childbearing-aged women. In this study, we examined the role of BCL-2 in mediating ULM survival in the context of increased protein kinase B (AKT) and oxidative stress using a three-dimensional (3D), spheroid-based model that more closely resembles the native ULM tumor microenvironment. Human primary cells from matched myometrium (MM) and ULM tissues were used to establish spheroid cultures in vitro. Histological and immunohistochemical methods were used to assess the spheroid architecture and characteristics. Viability assays for 3D cultures were used to evaluate their response to BH3 mimetics and the superoxide inducer, paraquat (PQ). Primary MM and ULM cells formed spheroids in culture. Notably, ULM spheroids exhibited low proliferation, increased oxidative stress, and secretion of interstitial collagen. Knockdown studies revealed that AKT sustained BCL-2 expression in ULM. The targeting of BCL-2 with BH3 mimetics effectively reduced viability and induced apoptosis in a subset of ULM spheroids. ULM spheroids that did not respond to BH3 mimetics alone responded to combination treatment with PQ. In conclusion, BCL-2 mediates AKT survival of ULM, providing compelling evidence for further evaluation of BH3 mimetics for ULM treatment. ULM spheroids recapitulated intrinsic features of the native ULM tumor microenvironment and can be used as a model for preclinical testing of potential therapeutic options for ULM.
Indexed as
Identifiers
What OpenQuestion holds
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.