Evidence map›Paper›PMID 20814245›Full record

ArticleCancer biology & therapy2010

Gli3 mediates cell survival and sensitivity to cyclopamine in pancreatic cancer.

Adam Steg, Hope M Amm, Zdenek Novak, Andra R Frost, Martin R Johnson

Open access · bronzeAbstract read
In one paragraph

Article in Cancer biology & therapy, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.

0numbers the graph read from it
0cells of the map it votes in
23citing papers in PubMed
0.8field-weighted citation impact, top 29% 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

23 citing papers in PubMed, 35 citations in OpenAlex.

  1. Review
  2. Review
  3. Article
  4. Chemistry and bioactivities of natural steroidal alkaloids.Natural products and bioprospecting · 2022
    Review
  5. Article
  6. Review
  7. GLI3: a mediator of genetic diseases, development and cancer.Cell communication and signaling : CCS · 2020
    Review
  8. Attenuation of hedgehog/GLI signaling by NT1721 extends survival in pancreatic cancer.Journal of experimental & clinical cancer research : CR · 2019
    Article
  9. Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
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  17. Article
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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

5 authors at 1 institution in 1 country.

Adam StegDepartment of Pharmacology and Toxicology, University of Alabama at Birmingham, Birmingham, Alabama, USA.
Hope M Amm
Zdenek Novak
Andra R Frost
Martin R Johnson
University of Alabama at Birmingham · US

Funding

RTOG Foreign AccrualU10CA021661 · NCI · AMERICAN COLLEGE OF RADIOLOGY · PI CURRAN, WALTER J. · 1985 to 2013
$150.3M
RADIATION THERAPY ONCOLOGY GROUP-STATISTICAL UNIT GRANTU10CA032115 · NCI · AMERICAN COLLEGE OF RADIOLOGY · PI SADEK, RAMSES · 1985 to 2008
$9.4M
NCI NIH HHS P20-CA10195NCI NIH HHS U10 CA021661NCI NIH HHS U10 CA032115
6 · The paper itself

Abstract

Activation of the hedgehog (HH) pathway plays a critical role in the development and continued growth of pancreatic adenocarcinoma (PAC). Cyclopamine, a HH pathway inhibitor, has been shown to suppress PAC cell proliferation in vitro and in vivo. However, the molecular basis of response to cyclopamine has not been fully elucidated nor have genes that predict sensitivity to this compound been identified. To better understand these features of HH pathway inhibition, we evaluated the biological and molecular effects of cyclopamine in vitro. The viability of 9 human PAC cell lines following cyclopamine exposure was determined using MTS assay. Proliferation and induction of apoptosis in treated cells were examined by bromo-deoxyuridine incorporation, caspase activation, and mitochondrial membrane potential. Gene expression before and after cyclopamine treatment was determined using Taqman real-time quantitative polymerase chain reaction (RTQ-PCR) and Taqman low-density array (TLDA). Among the cell lines examined, cyclopamine IC50 values ranged from 8.79 to >30 µM. Response to cyclopamine included reduced cell proliferation and induction of apoptosis with and without mitochondrial membrane depolarization. Regression analysis revealed that GLI3 expression significantly correlated with cyclopamine resistance (r = 0.80; p = 0.0102). Knockdown of GLI3 using siRNAs increased sensitivity to cyclopamine. In addition, GLI3 siRNAs decreased PAC cell viability and reduced expression of genes involved in HH signaling (Patched 1 and GLI1) and cell proliferation, similar to cyclopamine. These effects were not observed in PAC cells with undetectable GLI3 expression. These data suggest that Gli3 mediates cell survival and sensitivity to cyclopamine in pancreatic cancer.

Indexed as

Cell SurvivalAdenocarcinomaAntineoplastic AgentsApoptosisBlotting, WesternBromodeoxyuridineCaspasesCell Line, TumorCell ProliferationDrug Resistance, NeoplasmFlow CytometryGene ExpressionGene Knockdown TechniquesHedgehog ProteinsHumansInhibitory Concentration 50Antineoplastic AgentsBromodeoxyuridineCaspasescyclopamineGLI3 protein, humanHedgehog ProteinsKruppel-Like Transcription FactorsNerve Tissue ProteinsRNA, Small InterferingVeratrum AlkaloidsZinc Finger Protein Gli3

Identifiers

PMID20814245
PMCPMC3230294
OpenAlexW2024805529

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.