Evidence map›Paper›PMID 17522335›Full record

ArticleNeuro-oncology2007

Optimization of adenoviral vector-mediated transgene expression in the canine brain in vivo, and in canine glioma cells in vitro.

Marianela Candolfi, G Elizabeth Pluhar, Kurt Kroeger, Mariana Puntel, James Curtin, Carlos Barcia, A K M Ghulam Muhammad, Weidong Xiong, Chunyan Liu, Sonali Mondkar and 11 more

Abstract read
In one paragraph

Article in Neuro-oncology, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
–field-weighted citation impact
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

21 citing papers in PubMed.

  1. Adeno-Associated Viral Vectors in the Treatment of Epilepsy.International journal of molecular sciences · 2024
    Review
  2. Cell and gene therapy in neuro-oncology.Handbook of clinical neurology · 2024
    Review
  3. Article
  4. Review
  5. Comparative oncology: what dogs and other species can teach us about humans with cancer.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2015
    Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Article
  11. Article
  12. Article
  13. Gene transfer into rat brain using adenoviral vectors.Current protocols in neuroscience · 2010
    Article
  14. Review
  15. Article
  16. Review
  17. Article
  18. Article
  19. 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

21 authors.

Marianela CandolfiGene Therapeutics Research Institute, Cedars-Sinai Medical Center, Los Angeles, CA 90069, USA.
G Elizabeth Pluhar
Kurt Kroeger
Mariana Puntel
James Curtin
Carlos Barcia
A K M Ghulam Muhammad
Weidong Xiong
Chunyan Liu
Sonali Mondkar
William Kuoy
Terry Kang
Elizabeth A McNeil
Andrew B Freese
John R Ohlfest
Peter Moore
Donna Palmer
Phillip Ng
John D Young
Pedro R Lowenstein
Maria G Castro

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
Gene Therapy and the Brain: Neuroimmune InteractionsR01NS054193 · NINDS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI LOWENSTEIN, PEDRO R. · 2007 to 2011
$1.6M
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
Gutless Adenovirus Mediated Targeted Therapeutics for GliomaF32NS058156 · NINDS · CEDARS-SINAI MEDICAL CENTER · PI CANDOLFI, MARIANELA · 2007 to 2009
$154k
APOPTOSIS OF ANTERIOR PITUITARY CELLSR03TW006273 · FIC · CEDARS-SINAI MEDICAL CENTER · PI CASTRO, MARIA G · 2004 to 2006
$102k
FIC NIH HHS 1R01TW006273-01FIC NIH HHS R03 TW006273NINDS NIH HHS 1F32 NS 058156.01NINDS NIH HHS 1R01 NS054193.01NINDS NIH HHS 1 R01 NS42893NINDS NIH HHS 1R01 NS44556.01NINDS NIH HHS 1R21 NS054143.01NINDS NIH HHS 1U01 NS05246S.01NINDS NIH HHS F32 NS058156NINDS NIH HHS R01 NS042893NINDS NIH HHS R01 NS044556NINDS NIH HHS R01 NS054193NINDS NIH HHS R21 NS047298NINDS NIH HHS R21 NS054143NINDS NIH HHS R21 NS47298NINDS NIH HHS U54 4NS04-5309NINDS NIH HHS U54 NS045309
6 · The paper itself

Abstract

Expression of the immune-stimulatory molecule Fms-like tyrosine kinase 3 ligand (Flt3L) and the conditional cytotoxic enzyme herpes simplex virus type 1 thymidine kinase (HSV1-TK) provides long-term immune-mediated survival of large glioblastoma multiforme (GBM) models in rodents. A limitation for predictive testing of novel antiglioma therapies has been the lack of a glioma model in a large animal. Dogs bearing spontaneous GBM may constitute an attractive large-animal model for GBM, which so far has remained underappreciated. In preparation for a clinical trial in dogs bearing spontaneous GBMs, we tested and optimized adenovirus-mediated transgene expression with negligible toxicity in the dog brain in vivo and in canine J3T glioma cells. Expression of the marker gene beta-galactosidase (beta-Gal) was higher when driven by the murine (m) than the human (h) cytomegalovirus (CMV) promoter in the dog brain in vivo, without enhanced inflammation. In the canine brain, beta-Gal was expressed mostly in astrocytes. beta-Gal activity in J3T cells was also higher with the mCMV than the hCMV promoter driving tetracycline-dependent (TetON) transgene expression within high-capacity adenovirus vectors (HC-Ads). Dog glioma cells were efficiently transduced by HC-Ads expressing mCMV-driven HSV1-TK, which induced 90% reduction in cell viability in the presence of ganciclovir. J3T cells were also effectively transduced with HC-Ads expressing Flt3L under the control of the regulatable TetON promoter system, and as predicted, Flt3L release was stringently inducer dependent. HC-Ads encoding therapeutic transgenes under the control of regulatory sequences driven by the mCMV promoter are excellent vectors for the treatment of spontaneous GBM in dogs, which constitute an ideal preclinical animal model.

Indexed as

Promoter Regions, GeneticAdenoviridaeAnimalsbeta-GalactosidaseBrainBrain NeoplasmsCell Line, TumorCytomegalovirusDogsEnzyme-Linked Immunosorbent AssayGenetic EngineeringGenetic TherapyGenetic VectorsGliomaHerpesvirus 1, HumanHumansbeta-Galactosidaseflt3 ligand proteinMembrane ProteinsProtein-Tyrosine KinasesViral Proteins

Identifiers

PMID17522335
PMCPMC1907414

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.