Evidence map›Paper›PMID 20197468›Full record

ArticleCancer research2010

Preclinical evaluation of radiation and perifosine in a genetically and histologically accurate model of brainstem glioma.

Oren J Becher, Dolores Hambardzumyan, Talia R Walker, Karim Helmy, Javad Nazarian, Steffen Albrecht, Rebecca L Hiner, Sarah Gall, Jason T Huse, Nada Jabado and 2 more

Registry-linked trialAbstract read
In one paragraph

Article in Cancer research, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01106794 (Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma), which is not on this map. Cited by 109 papers.

0numbers the graph read from it
0cells of the map it votes in
109citing papers in PubMed
5.8field-weighted citation impact, top 3% 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.

NCT01106794 recruitingnot on this map

Molecular Analysis of Samples From Patients With Diffuse Intrinsic Pontine Glioma and Brainstem Glioma

TypeobservationalSponsorChildren's National Research InstituteRan2010 to 2030Enrolled100ConditionsDiffuse Intrinsic Pontine Glioma, Brainstem Glioma
3 · Its place in the literature

Who cites it

109 citing papers in PubMed, 168 citations in OpenAlex.

  1. Article
  2. Review
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Immune Response following FLASH and Conventional Radiation in Diffuse Midline Glioma.International journal of radiation oncology, biology, physics · 2024
    Article
  10. Review
  11. Article
  12. Article
  13. Article
  14. Article
  15. Article
  16. Article
  17. Rat and Mouse Brain Tumor Models for Experimental Neuro-Oncology Research.Journal of neuropathology and experimental neurology · 2022
    Review
  18. Article
  19. Review
  20. Article

49 more citing papers are in PubMed but not listed here.

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

12 authors at 4 institutions in 2 countries.

Oren J BecherDepartments of Cancer Biology and Genetics, Brain Tumor Center, Memorial Sloan-Kettering Cancer Center, New York, New York 10021, USA.
Dolores Hambardzumyan
Talia R Walker
Karim Helmy
Javad Nazarian
Steffen Albrecht
Rebecca L Hiner
Sarah Gall
Jason T Huse
Nada Jabado
Tobey J MacDonald
Eric C Holland
Montreal Children's Hospital · CACarolinas Medical Center · USChildren's National · USMemorial Sloan Kettering Cancer Center · US

Funding

Tumor Microenvironment Interactions in Brain TumorsU54CA126518 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI MASSAGUE, JOAN · 2006 to 2010
$6.1M
P3IK Signaling and Biology of Therapeutic Response in Brain and Prostate TumorsU01CA141502 · NCI · SLOAN-KETTERING INST CAN RESEARCH · PI HOLLAND, ERIC C. · 2009 to 2013
$4.2M
The Role of Signaling Pathways in Brain Tumors in MiceR01CA100688 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI HOLLAND, ERIC C. · 2003 to 2013
$3.8M
NCI NIH HHS R01 CA100688NCI NIH HHS U01 CA141502NCI NIH HHS U54 CA126518
6 · The paper itself

Abstract

Brainstem gliomas (BSG) are a rare group of central nervous system tumors that arise mostly in children and usually portend a particularly poor prognosis. We report the development of a genetically engineered mouse model of BSG using the RCAS/tv-a system and its implementation in preclinical trials. Using immunohistochemistry, we found that platelet-derived growth factor (PDGF) receptor alpha is overexpressed in 67% of pediatric BSGs. Based on this observation, we induced low-grade BSGs by overexpressing PDGF-B in the posterior fossa of neonatal nestin tv-a mice. To generate high-grade BSGs, we overexpressed PDGF-B in combination with Ink4a-ARF loss, given that this locus is commonly lost in high-grade pediatric BSGs. We show that the likely cells of origin for these mouse BSGs exist on the floor of the fourth ventricle and cerebral aqueduct. Irradiation of these high-grade BSGs shows that although single doses of 2, 6, and 10 Gy significantly increased the percent of terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL)-positive nuclei, only 6 and 10 Gy significantly induce cell cycle arrest. Perifosine, an inhibitor of AKT signaling, significantly induced TUNEL-positive nuclei in this high-grade BSG model, but in combination with 10 Gy, it did not significantly increase the percent of TUNEL-positive nuclei relative to 10 Gy alone at 6, 24, and 72 hours. Survival analysis showed that a single dose of 10 Gy significantly prolonged survival by 27% (P = 0.0002) but perifosine did not (P = 0.92). Perifosine + 10 Gy did not result in a significantly increased survival relative to 10 Gy alone (P = 0.23). This PDGF-induced BSG model can serve as a preclinical tool for the testing of novel agents.

Indexed as

Disease Models, AnimalAnimalsBrain Stem NeoplasmsCombined Modality TherapyGenetic EngineeringGliomaInbreedingMiceMice, Inbred BALB CPhosphorylcholineReceptor, Platelet-Derived Growth Factor alphaperifosinePhosphorylcholineReceptor, Platelet-Derived Growth Factor alpha

Identifiers

PMID20197468
PMCPMC3831613
OpenAlexW2130552536

What OpenQuestion holds

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LicenceTDM
Read underepoch 390

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.