Evidence map›Paper›PMID 32493277›Full record

ArticleBMC cancer2020

Up-regulation of GLI1 in vincristine-resistant rhabdomyosarcoma and Ewing sarcoma.

Joon Won Yoon, Marilyn Lamm, Christopher Chandler, Philip Iannaccone, David Walterhouse

Open access · goldAbstract read
In one paragraph

Article in BMC cancer, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.

0numbers the graph read from it
0cells of the map it votes in
17citing papers in PubMed
1.5field-weighted citation impact, top 18% 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

17 citing papers in PubMed, 31 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Review
  5. Article
  6. Unlocking epigenetics for precision treatment of Ewing's sarcoma.Chinese journal of cancer research = Chung-kuo yen cheng yen chiu · 2024
    Article
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Targeting hedgehog-driven mechanisms of drug-resistant cancers.Frontiers in molecular biosciences · 2023
    Review
  13. Review
  14. Article
  15. Article
  16. Review
  17. 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

5 authors at 1 institution in 1 country.

Joon Won YoonDepartment of Pediatrics, Division of Hematology/Oncology, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine Chicago, Box 30, 225 East Chicago Ave., Chicago, IL, 60611, USA.
Marilyn LammDepartment of Pediatrics, Division of Hematology/Oncology, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine Chicago, Box 30, 225 East Chicago Ave., Chicago, IL, 60611, USA.
Christopher ChandlerDepartment of Pediatrics, Division of Hematology/Oncology, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine Chicago, Box 30, 225 East Chicago Ave., Chicago, IL, 60611, USA.
Philip IannacconeDepartment of Pediatrics, Division of Hematology/Oncology, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine Chicago, Box 30, 225 East Chicago Ave., Chicago, IL, 60611, USA.
David WalterhouseDepartment of Pediatrics, Division of Hematology/Oncology, Ann & Robert H. Lurie Children's Hospital of Chicago, Northwestern University Feinberg School of Medicine Chicago, Box 30, 225 East Chicago Ave., Chicago, IL, 60611, USA. d-walterhouse@northwestern.edu.ORCID http://orcid.org/0000-0002-1067-0900
Northwestern University · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe clinical significance of GLI1 expression either through canonical Hedgehog signal transduction or through non-canonical mechanisms in rhabdomyosarcoma (RMS) or Ewing sarcoma (EWS) is incompletely understood. We tested a role for Hedgehog (HH) signal transduction and GL11 expression in development of vincristine (VCR) resistance in RMS and EWS.

methodsWe characterized baseline expression and activity of HH pathway components in 5 RMS (RD, Rh18, Ruch-2, Rh30, and Rh41) and 5 EWS (CHLA9, CHLA10, TC32, CHLA258, and TC71) cell lines. We then established VCR-resistant RMS and EWS cell lines by exposing cells to serially increasing concentrations of VCR and determining the IC

resultsWe found evidence for HH pathway activity and GLI1 expression in RMS and EWS cell lines at baseline, and evidence that GLI1 contributes to survival and proliferation of these sarcoma cells. We were able to establish 4 VCR-resistant cell lines (Ruch-2VR, Rh30VR, Rh41VR, and TC71VR). GLI1 was significantly up-regulated in the Rh30VR, Rh41VR, and TC71VR cells. The only other gene in the drug resistance panel that was significantly up-regulated in each of these VCR-resistant cell lines compared with their corresponding parental cells was the GLI1 direct target and multidrug resistance gene, ATP-binding cassette sub-family B member 1 (MDR1). We established major vault protein (MVP), which was up-regulated in both vincristine-resistant alveolar RMS cell lines (Rh30VR and Rh41VR), as another direct target of GLI1 during development of drug resistance. Treatment of the VCR-resistant cell lines with the small molecule inhibitor GANT61 or GLI1 siRNA together with VCR significantly decreased cell viability at doses that did not reduce viability individually.

conclusionsThese experiments demonstrate that GLI1 up-regulation contributes to VCR resistance in RMS and EWS cell lines and suggest that targeting GLI1 may benefit patients with RMS or EWS by reducing multidrug resistance.

Indexed as

ATP Binding Cassette Transporter, Subfamily BCell Line, TumorCell SurvivalDrug Resistance, MultipleDrug Resistance, NeoplasmGene Expression Regulation, NeoplasticHedgehog ProteinsHumansInhibitory Concentration 50PyridinesPyrimidinesRhabdomyosarcomaRNA, Small InterferingSarcoma, EwingSignal TransductionUp-RegulationABCB1 protein, humanATP Binding Cassette Transporter, Subfamily BGANT 61GLI1 protein, humanHedgehog ProteinsPyridinesPyrimidinesRNA, Small InterferingVincristineZinc Finger Protein GLI1Drug resistanceEwing sarcomaGLI1Hedgehog pathwayRhabdomyosarcomaVincristine

Identifiers

PMID32493277
PMCPMC7310145
OpenAlexW3032126073

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.