Evidence map›Paper›PMID 15026351›Full record

ArticleCancer research2004

Molecular imaging of drug-modulated protein-protein interactions in living subjects.

Ramasamy Paulmurugan, Tarik F Massoud, Jing Huang, Sanjiv S Gambhir

Open access · bronzeAbstract read
In one paragraph

Article in Cancer research, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 44 papers.

0numbers the graph read from it
0cells of the map it votes in
44citing papers in PubMed
4.1field-weighted citation impact, top 5% 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

44 citing papers in PubMed, 114 citations in OpenAlex.

  1. Article
  2. Bioluminescent Imaging Systems for Assay Developments.Analytical sciences : the international journal of the Japan Society for Analytical Chemistry · 2021
    Review
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Article
  9. Article
  10. Article
  11. Review
  12. Article
  13. Direct detection of alpha synuclein oligomers in vivo.Acta neuropathologica communications · 2013
    Article
  14. Article
  15. Article
  16. Article
  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

4 authors at 3 institutions in 2 countries.

Ramasamy PaulmuruganDepartment of Radiology and the Bio-X Program, James H. Clark Center, Stanford University School of Medicine, 318 Campus Drive, Stanford, CA 94305-5427, USA.
Tarik F Massoud
Jing Huang
Sanjiv S Gambhir
Stanford University · USUniversity of California, Los Angeles · USUniversity of Cambridge · GB

Funding

Transductionally Redirected /Transcriptionally RestricteP50CA086306 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI HERSCHMAN, HARVEY R. · 2000 to 2014
$29.0M
Stanford Nanocharacterization LaboratoryU54CA119367 · NCI · STANFORD UNIVERSITY · PI AGUS, DAVID B · 2006 to 2010
$19.8M
Small Animal ImagingP50CA114747 · NCI · STANFORD UNIVERSITY · PI RAO, JIANGHONG · 2005 to 2014
$18.2M
Reporter Imaging of Protein-Protein InteractionsR01CA082214 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI GAMBHIR, SANJIV S · 1999 to 2019
$5.9M
UCLA Imaging Resource for Mouse Cancer ModelsR24CA092865 · NCI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI PHELPS, MICHAEL E · 2001 to 2006
$4.3M
NCI NIH HHS P50 CA086306NCI NIH HHS P50 CA114747NCI NIH HHS P50 CA 86306NCI NIH HHS R01 CA082214NCI NIH HHS R01 CA 82214NCI NIH HHS R24 CA092865NCI NIH HHS R24 CA 92865NCI NIH HHS U54 CA119367
6 · The paper itself

Abstract

Networks of protein interactions mediate cellular responses to environmental stimuli and direct the execution of many different cellular functional pathways. Small molecules synthesized within cells or recruited from the external environment mediate many protein interactions. The study of small molecule-mediated interactions of proteins is important to understand abnormal signal transduction pathways in cancer and in drug development and validation. In this study, we used split synthetic renilla luciferase (hRLUC) protein fragment-assisted complementation to evaluate heterodimerization of the human proteins FRB and FKBP12 mediated by the small molecule rapamycin. The concentration of rapamycin required for efficient dimerization and that of its competitive binder ascomycin required for dimerization inhibition were studied in cell lines. The system was dually modulated in cell culture at the transcription level, by controlling nuclear factor kappaB promoter/enhancer elements using tumor necrosis factor alpha, and at the interaction level, by controlling the concentration of the dimerizer rapamycin. The rapamycin-mediated dimerization of FRB and FKBP12 also was studied in living mice by locating, quantifying, and timing the hRLUC complementation-based bioluminescence imaging signal using a cooled charged coupled device camera. This split reporter system can be used to efficiently screen small molecule drugs that modulate protein-protein interactions and also to assess drugs in living animals. Both are essential steps in the preclinical evaluation of candidate pharmaceutical agents targeting protein-protein interactions, including signaling pathways in cancer cells.

Indexed as

Protein Interaction MappingAnimalsBinding, CompetitiveCells, CulturedDiagnostic ImagingDimerizationGene ExpressionGenetic Complementation TestHumansImmunosuppressive AgentsLuciferasesMiceNF-kappa BPromoter Regions, GeneticProtein BindingRatsimmunomycinImmunosuppressive AgentsLuciferasesNF-kappa BSirolimusTacrolimusTacrolimus Binding Protein 1A

Identifiers

PMID15026351
PMCPMC4154786
OpenAlexW2142297263

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.