ArticleProceedings of the National Academy of Sciences of the United States of America2011
Targeting zebrafish and murine pituitary corticotroph tumors with a cyclin-dependent kinase (CDK) inhibitor.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Cited by 64 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.
Treatment of Pituitary Cushing Disease With a Selective CDK Inhibitor, R-roscovitine
A Phase 2 Multicenter Study of Seliciclib (R-roscovitine) for Cushing Disease
Who cites it
64 citing papers in PubMed, 133 citations in OpenAlex.
- INHAND: Non-proliferative and proliferative lesions of fish - Chapter 4. Fish endocrine system.Journal of toxicologic pathology · 2026Article
- Review
- Cushing's Disease in the Animal Kingdom: Translational Insights for Human Medicine.International journal of molecular sciences · 2025Review
- Genetic models of Cushing's disease : From cells, in vivo transgenic models to human pituitary organoids.Pituitary · 2025Review
- Cyclin-dependent protein kinases and cell cycle regulation in biology and disease.Signal transduction and targeted therapy · 2025Review
- Advances in pharmacological treatment of CushingZhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2024Review
- Seliciclib: A New Treatment for Cushing's Disease?TouchREVIEWS in endocrinology · 2024Article
- Current and Emerging Pharmacological Therapies for Cushing's Disease.Current pharmaceutical design · 2024Review
- Article
- Article
- Treatment of Cushing Disease With Pituitary-Targeting Seliciclib.The Journal of clinical endocrinology and metabolism · 2023Article
- Review
- Gene Mutations in Cushing's Syndrome.Molecular syndromology · 2023Review
- Preclinical Models of Neuroendocrine Neoplasia.Cancers · 2022Review
- The Expression of Cell Cycle-Related Genes inCancers · 2022Article
- Current and Emerging Medical Therapies in Pituitary Tumors.Journal of clinical medicine · 2022Review
- EmCyclinD-EmCDK4/6 complex is involved in the host EGF-mediated proliferation ofFrontiers in microbiology · 2022Article
- Cushing's Disease Management: Glimpse Into 2051.Frontiers in endocrinology · 2022Article
- Exploration of novel heterofused 1,2,4-triazine derivative in colorectal cancer.Journal of enzyme inhibition and medicinal chemistry · 2021Article
- Modeling human brain tumors in flies, worms, and zebrafish: From proof of principle to novel therapeutic targets.Neuro-oncology · 2021Review
4 more citing papers are in PubMed but not listed here.
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 3 institutions in 1 country.
Funding
Abstract
Cushing disease caused by adrenocorticotropin (ACTH)-secreting pituitary adenomas leads to hypercortisolemia predisposing to diabetes, hypertension, osteoporosis, central obesity, cardiovascular morbidity, and increased mortality. There is no effective pituitary targeted pharmacotherapy for Cushing disease. Here, we generated germline transgenic zebrafish with overexpression of pituitary tumor transforming gene (PTTG/securin) targeted to the adenohypophyseal proopiomelanocortin (POMC) lineage, which recapitulated early features pathognomonic of corticotroph adenomas, including corticotroph expansion and partial glucocorticoid resistance. Adult Tg:Pomc-Pttg fish develop neoplastic coticotrophs and pituitary cyclin E up-regulation, as well as metabolic disturbances mimicking hypercortisolism caused by Cushing disease. Early development of corticotroph pathologies in Tg:Pomc-Pttg embryos facilitated drug testing in vivo. We identified a pharmacologic CDK2/cyclin E inhibitor, R-roscovitine (seliciclib; CYC202), which specifically reversed corticotroph expansion in live Tg:Pomc-Pttg embryos. We further validated that orally administered R-roscovitine suppresses ACTH and corticosterone levels, and also restrained tumor growth in a mouse model of ACTH-secreting pituitary adenomas. Molecular analyses in vitro and in vivo showed that R-roscovitine suppresses ACTH expression, induces corticotroph tumor cell senescence and cell cycle exit by up-regulating p27, p21 and p57, and downregulates cyclin E expression. The results suggest that use of selective CDK inhibitors could effectively target corticotroph tumor growth and hormone secretion.
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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.