Evidence map›Paper›PMID 11526490›Full record

ArticleOncogene2001

STI571 inactivation of the gastrointestinal stromal tumor c-KIT oncoprotein: biological and clinical implications.

D A Tuveson, N A Willis, T Jacks, J D Griffin, S Singer, C D Fletcher, J A Fletcher, G D Demetri

Registry-linked trialAbstract read
PubMed Publisher
In one paragraph

Article in Oncogene, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00290485 (A Phase II Study on Preoperative Administration of Gleevec in Patients With Initially Non-Resectable Gastrointestinal Stromal Tumor), which is not on this map. Cited by 215 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
215citing papers in PubMed, 1 pooled it
39.7field-weighted citation impact, top 1% 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.

NCT00290485 phase2unknown statusnot on this mapstarted 2005, after this paper: background citation

A Phase II Study on Preoperative Administration of Gleevec in Patients With Initially Non-Resectable Gastrointestinal Stromal Tumor

TypeinterventionalSponsorMaisonneuve-Rosemont HospitalRan2005Enrolled50ConditionsGastrointestinal Stromal TumorsArmsImatinib mesylate
3 · Its place in the literature

Who cites it

215 citing papers in PubMed, 1 synthesis or guideline pooled it, 697 citations in OpenAlex.

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155 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

8 authors at 4 institutions in 1 country.

D A TuvesonMIT Cancer Center and Department of Biology, Cambridge, MA 02139, USA. dtuveson@mit.edu
N A Willis
T Jacks
J D Griffin
S Singer
C D Fletcher
J A Fletcher
G D Demetri
Harvard University · USBrigham and Women's Hospital · USIIT@MIT · USHoward Hughes Medical Institute · US

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Mutations in the c-KIT receptor occur somatically in many sporadic Gastrointestinal Stromal Tumors (GIST), and similar mutations have been identified at the germline level in kindreds with multiple GISTs. These mutations activate the tyrosine kinase activity of c-KIT and induce constitutive signaling. To investigate the function of activated c-KIT in GIST, we established a human GIST cell line, GIST882, which expresses an activating KIT mutation (K642E) in the first part of the cytoplasmic split tyrosine kinase domain. Notably, the K642E substitution is encoded by a homozygous exon 13 missense mutation, and, therefore, GIST882 cells do not express native KIT. GIST882 c-KIT protein is constitutively tyrosine phosphorylated, but tyrosine phosphorylation was rapidly and completely abolished after incubating the cells with the selective tyrosine kinase inhibitor STI571. Furthermore, GIST882 cells evidenced decreased proliferation and the onset of apoptotic cell death after prolonged incubation with STI571. Similar results were obtained after administering STI571 to a primary GIST cell culture that expressed a c-KIT exon 11 juxtamembrane mutation (K558NP). These cell-culture-based studies support an important role for c-KIT signaling in GIST and suggest therapeutic potential for STI571 in patients afflicted by this chemoresistant tumor.

Indexed as

Stromal CellsApoptosisBenzamidesCell DivisionEnzyme InhibitorsGastrointestinal NeoplasmsHumansImatinib MesylateMutationOncogene ProteinsPiperazinesProtein-Tyrosine KinasesProto-Oncogene Proteins c-kitPyrimidinesTumor Cells, CulturedBenzamidesEnzyme InhibitorsImatinib MesylateOncogene ProteinsPiperazinesProtein-Tyrosine KinasesProto-Oncogene Proteins c-kitPyrimidines

Identifiers

PMID11526490
OpenAlexW2079420659

What OpenQuestion holds

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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.