Linked Life Data

12389628

Source:http://linkedlifedata.com/resource/pubmed/id/12389628

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
7
pubmed:dateCreated
2002-10-22
pubmed:abstractText
Here we show that the Janus kinase 3 (JAK3) inhibitor 4-(3'-hydroxyphenyl)-amino-6,7-dimethoxyquinazoline (JANEX-3) exhibits potent anti-GVHD activity and consequently improves the post-BMT survival outcome of C57BL/6 (H-2b) recipient mice transplanted with allogeneic bone marrow/splenocyte (BM/S) grafts from MHC disparate BALB/c mice (H-2d). One hundred percent of the vehicle-treated allograft recipients developed severe GVHD and died with a median survival of 41 days. Treatment of recipient mice with JANEX-3 (30 mg/kg/day, 3 x/day) after the onset of rapidly progressive severe GVHD in the 3rd week after BMT significantly improved the survival of BMT recipients with GVHD and prolonged the median survival time to 78 days (P < 0.0001, log-rank test). The probability of survival at two and three months post-BMT was 6 +/- 6% and 0 +/- 0% for vehicle-treated control mice and 100 +/- 0% and 38 +/- 17% for mice treated with JANEX-3. These results prompted the hypothesis that JAK3 plays a pivotal role in the pathophysiology of GVHD. To test this hypothesis, we examined if mice transplanted with allogeneic BM/S grafts from Jak3 knockout mice Jak3-/- develop GVHD. The allografts from (Jak3-/-) C57BL/6 (H-2b) mice rescued MHC-disparate recipient BALB/c mice (H-2d) of the lethal toxicity of TBI without causing fatal GVHD. Taken together, these observations establish JAK3 as a key mediator of severe GVHD after allogeneic BMT in the context of a major-HLA disparity.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1042-8194
pubmed:author
pubmed:issnType
Print
pubmed:volume
43
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1447-53
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Treatment of post-bone marrow transplant acute graft-versus-host disease with a rationally designed JAK3 inhibitor.
pubmed:affiliation
Experimental BMT Program, Parker Hugher Cancer Center, St. Paul, MN 55113, USA.
pubmed:publicationType
Journal Article