Evidence map›Paper›PMID 33649536›Full record

ArticleOncogene2021

Statins repress hedgehog signaling in medulloblastoma with no bone toxicities.

Qianhai Fan, Tingting Gong, Chaonan Zheng, Jessica M Y Ng, Jianquan Chen, Cynthia Myers, Harvey Hensley, Tom Curran, Zeng-Jie Yang

Abstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
1.6field-weighted citation impact, top 16% of its field
1 · What the graph read from it

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.

2 · The registry

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.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Review
  7. Review
  8. Article
  9. Article
  10. Review
  11. Statins: a repurposed drug to fight cancer.Journal of experimental & clinical cancer research : CR · 2021
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

9 authors at 3 institutions in 2 countries.

Qianhai FanPediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215007, China.
Tingting GongOrthopedic Institute, Medical College, Soochow University, Suzhou, Jiangsu, 215007, China.
Chaonan ZhengPediatric Cancer Center, College of Pharmaceutical Sciences, Soochow University, Suzhou, Jiangsu, 215007, China.
Jessica M Y NgChildren's Research Institute, Children's Mercy Kansas City, Kansas City, MO, USA.
Jianquan ChenOrthopedic Institute, Medical College, Soochow University, Suzhou, Jiangsu, 215007, China.
Cynthia MyersOrganic Synthesis Facility, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, USA.
Harvey HensleySmall Animal Imaging Facility, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, USA.
Tom CurranChildren's Research Institute, Children's Mercy Kansas City, Kansas City, MO, USA.ORCID http://orcid.org/0000-0003-1444-7551
Zeng-Jie YangCancer Biology Program, Fox Chase Cancer Center, Temple University Health System, Philadelphia, PA, USA. zengjie.yang@fccc.edu.ORCID http://orcid.org/0000-0003-1205-0964
Fox Chase Cancer Center · USSoochow University · CNMercy Research · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The Hedgehog (Hh) pathway plays an indispensable role in bone development and genetic activation of the pathway results in medulloblastoma (MB), the most common malignant brain tumor in children. Inhibitors of Hh pathway (such as vismodegib and sonedigib), which are used to treat MB, cause irreversible defects in bone growth in young children. Cholesterol is required for the activation of the Hh pathway, and statins, inhibitors of cholesterol biosynthesis, suppress MB growth by repressing Hh signaling in tumor cells. Here, we investigate the role of cholesterol biosynthesis in the proliferation and Hh signaling in chondrocytes, and examine the bone development in mice after statin treatment. Statins significantly inhibited MB growth in young mice, but caused no defects in bone development. Conditional deletion of NADP steroid dehydrogenase-like (NSDHL), an enzyme necessary for cholesterol biosynthesis, suppressed cholesterol synthesis in chondrocytes, and disrupted the growth plate in mouse femur and tibia, indicating the important function of intracellular cholesterol in bone development. Hh pathway activation and the proliferation of chondrocytes were inhibited by statin treatment in vitro; however, statins did not impair bone growth in vivo due to insufficient penetration into the bone. Our studies reveal a critical role of cholesterol in bone development, and support the utilization of statins for treatment of MB as well as other Hh pathway-associated malignancies.

Indexed as

3-Hydroxysteroid DehydrogenasesAnilidesAnimalsBone DevelopmentCell ProliferationCholesterolChondrocytesHedgehog ProteinsHumansHydroxymethylglutaryl-CoA Reductase InhibitorsLipogenesisMedulloblastomaMiceMice, KnockoutPyridinesSignal Transduction3-Hydroxysteroid DehydrogenasesAnilidesCholesterolHedgehog ProteinsHhAntag691Hydroxymethylglutaryl-CoA Reductase InhibitorsNsdhl protein, mousePyridines

Identifiers

PMID33649536
OpenAlexW3134970135

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.