Evidence map›Paper›PMID 24287465›Full record

ArticlePharmaceuticals (Basel, Switzerland)2013

Hedgehog pathway blockade inhibits melanoma cell growth in vitro and in vivo.

Kathryn E O'Reilly, Eleazar Vega-Saenz de Miera, Miguel F Segura, Erica Friedman, Laura Poliseno, Sung Won Han, Judy Zhong, Jiri Zavadil, Anna Pavlick, Eva Hernando and 1 more

Open access · goldAbstract read
In one paragraph

Article in Pharmaceuticals (Basel, Switzerland), 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
34citing papers in PubMed, 1 pooled it
1.6field-weighted citation impact, top 17% 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

34 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Tumor-derived GLI1 promotes remodeling of the immune tumor microenvironment in melanoma.Journal of experimental & clinical cancer research : CR · 2024
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  8. Review
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  19. UVB Irradiation Induced Cell Damage and Early Onset ofAnimals : an open access journal from MDPI · 2020
    Article
  20. Article
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

11 authors at 3 institutions in 3 countries.

Kathryn E O'ReillyDepartment of Dermatology, New York University School of Medicine, New York, NY 10016, USA. Iman.Osman@nyumc.org.
Eleazar Vega-Saenz de Miera
Miguel F Segura
Erica Friedman
Laura Poliseno
Sung Won Han
Judy Zhong
Jiri Zavadil
Anna Pavlick
Eva Hernando
Iman Osman
New York University · USNYU Langone Health · USVall d'Hebron Institut de Recerca · ES

Funding

Vaccine FacilityP30CA016087 · NCI · NEW YORK UNIVERSITY SCHOOL OF MEDICINE · PI ADRIANA HEGUY · 1985 to 2026
$83.1M
NCI NIH HHS P30 CA016087
6 · The paper itself

Abstract

Previous reports have demonstrated a role for hedgehog signaling in melanoma progression, prompting us to explore the therapeutic benefit of targeting this pathway in melanoma. We profiled a panel of human melanoma cell lines and control melanocytes for altered expression of hedgehog pathway members and determined the consequences of both genetic and pharmacological inhibition of the hedgehog pathway activator Smoothened (SMO) in melanoma, both in vitro and in vivo. We also examined the relationship between altered expression of hedgehog pathway mediators and survival in a well-characterized cohort of metastatic melanoma patients with prospectively collected follow up information. Studies revealed that over 40% of the melanoma cell lines examined harbored significantly elevated levels of the hedgehog pathway mediators SMO, GLI2, and PTCH1 compared to melanocytes (p < 0.05). SMO inhibition using siRNA and the small molecule inhibitor, NVP-LDE-225, suppressed melanoma growth in vitro, particularly in those cell lines with moderate SMO and GLI2 expression. NVP-LDE-225 also induced apoptosis in vitro and inhibited melanoma growth in a xenograft model. Gene expression data also revealed evidence of compensatory up-regulation of two other developmental pathways, Notch and WNT, in response to hedgehog pathway inhibition. Pharmacological and genetic SMO inhibition also downregulated genes involved in human embryonic stem cell pluripotency. Finally, increased SMO expression and decreased expression of the hedgehog pathway repressor GLI3 correlated with shorter post recurrence survival in metastatic melanoma patients. Our data demonstrate that hedgehog pathway inhibition might be a promising targeted therapy in appropriately selected metastatic melanoma patients.

Identifiers

PMID24287465
PMCPMC3854019
OpenAlexW1989859296

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.