Evidence map›Paper›PMID 18079358›Full record

ArticleNeuro-oncology2008

Flt3L and TK gene therapy eradicate multifocal glioma in a syngeneic glioblastoma model.

Gwendalyn D King, A K M Ghulam Muhammad, James F Curtin, Carlos Barcia, Mariana Puntel, Chunyan Liu, Sarah B Honig, Marianela Candolfi, Sonali Mondkar, Pedro R Lowenstein and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Neuro-oncology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
58citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% 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

58 citing papers in PubMed, 1 synthesis or guideline pooled it, 77 citations in OpenAlex.

  1. Pooled it
  2. Review
  3. Article
  4. Review
  5. Review
  6. Review
  7. Article
  8. Review
  9. Current Immunotherapeutic Approaches for Malignant Gliomas.Brain tumor research and treatment · 2022
    Review
  10. Overcoming delivery barriers in immunotherapy for glioblastoma.Drug delivery and translational research · 2021
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Immunology of Adenoviral Vectors in Cancer Therapy.Molecular therapy. Methods & clinical development · 2019
    Review
  16. Article
  17. Article
  18. Review
  19. Review
  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 2 institutions in 1 country.

Gwendalyn D KingGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Department of Molecular and Medical Pharmacology, University of California Los Angeles 90048, USA.
A K M Ghulam Muhammad
James F Curtin
Carlos Barcia
Mariana Puntel
Chunyan Liu
Sarah B Honig
Marianela Candolfi
Sonali Mondkar
Pedro R Lowenstein
Maria G Castro
University of California, Los Angeles · USCedars-Sinai Medical Center · US

Funding

Trophic gene transfer in MPTP animalsU54NS045309 · NINDS · UNIVERSITY OF ROCHESTER · PI FEDEROFF, HOWARD J. · 2002 to 2006
$9.7M
Gene therapy for chronic neurodegenerative disordersR01NS044556 · NINDS · CEDARS-SINAI MEDICAL CENTER · PI CASTRO, MARIA G · 2002 to 2006
$2.0M
Gene Therapy for Neurological DiseasesR01NS042893 · NINDS · CEDARS-SINAI MEDICAL CENTER · PI LOWENSTEIN, PEDRO R · 2002 to 2006
$1.8M
Targeted Toxin for Brain Cancer Gene TherapyR21NS054143 · NINDS · CEDARS-SINAI MEDICAL CENTER · PI CASTRO, MARIA G · 2007 to 2008
$383k
Gene Therapy for GliomaR21NS047298 · NINDS · CEDARS-SINAI MEDICAL CENTER · PI LOWENSTEIN, PEDRO R · 2003 to 2004
$354k
APOPTOSIS OF ANTERIOR PITUITARY CELLSR03TW006273 · FIC · CEDARS-SINAI MEDICAL CENTER · PI CASTRO, MARIA G · 2004 to 2006
$102k
FIC NIH HHS R03 TW006273FIC NIH HHS R03 TW006273-01NINDS NIH HHS F32 NS0503034-01NINDS NIH HHS R01 NS042893NINDS NIH HHS R01 NS044556NINDS NIH HHS R01 NS42893NINDS NIH HHS R01 NS4456.01NINDS NIH HHS R21 NS047298NINDS NIH HHS R21 NS054143NINDS NIH HHS R21 NS054143-01NINDS NIH HHS R21 NS47298NINDS NIH HHS U54 4 NS04-5309NINDS NIH HHS U54 NS045309
6 · The paper itself

Abstract

The disseminated characteristics of human glioblastoma multiforme (GBM) make it a particularly difficult tumor to treat with long-term efficacy. Most preclinical models of GBM involve treatment of a single tumor mass. For therapeutic outcomes to translate from the preclinical to the clinical setting, induction of an antitumor response capable of eliminating multifocal disease is essential. We tested the hypothesis that expression of Flt3L (human soluble FMS-like tyrosine kinase 3 ligand) and TK (herpes simplex virus type 1-thymidine kinase) within brain gliomas would mediate regression of the primary, treated tumor mass and a secondary, untreated tumor growing at a distant site from the primary tumor and the site of therapeutic vector injection. In both the single-GBM and multifocal-GBM models used, all saline-treated control animals succumbed to tumors by day 22. Around 70% of the animals bearing a single GBM mass treated with an adenovirus expressing Flt3L (AdFlt3L) and an adenovirus expressing TK (AdTK + GCV) survived long term. Approximately 50% of animals bearing a large primary GBM that were implanted with a second GBM in the contralateral hemisphere at the same time the primary tumors were being treated with AdFlt3L and AdTK also survived long term. A second multifocal GBM model, in which bilateral GBMs were implanted simultaneously and only the right tumor mass was treated with AdFlt3L and AdTK, also demonstrated long-term survival. While no significant difference in survival was found between unifocal and multifocal GBM-bearing animals treated with AdFlt3L and AdTK, both treatments were statistically different from the saline-treated control group (p < 0.05). Our results demonstrate that combination therapy with AdFlt3L and AdTK can eradicate multifocal brain tumor disease in a syngeneic, intracranial GBM model.

Indexed as

AdenoviridaeAnimalsBrain NeoplasmsDisease Models, AnimalEnzyme-Linked Immunosorbent AssayGenetic TherapyGenetic VectorsGlioblastomaHumansMaleMembrane ProteinsMicroscopy, ConfocalRatsRats, Inbred LewThymidine KinaseTransplantation, Isogeneicflt3 ligand proteinMembrane ProteinsThymidine Kinase

Identifiers

PMID18079358
PMCPMC2600834
OpenAlexW2144434005

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.