Linked Life Data

11870521

Source:http://linkedlifedata.com/resource/pubmed/id/11870521

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2002-2-28
pubmed:abstractText
Cytotoxins directed to interleukin-4 receptors have shown to mediate relatively selective cytotoxicity against a variety of human cancer cells in vitro and in vivo. In an ongoing Phase I clinical trial, a recombinant protein comprised of circularly permuted IL-4 fused to a mutated form of Pseudomonas exotoxin (the fusion protein termed IL-4(38-37)-PE38KDEL or cpIL4-PE) has shown antitumour activity against malignant glioma. Human medulloblastomas are neuroectodermal tumours that occur in children and have a poor prognosis. The goal of this study was to determine whether human medulloblastoma derived cell lines express interleukin-4 receptor and whether interleukin-4 receptor expression is accompanied by sensitivity to cpIL4-PE. Medulloblastoma cell lines express interleukin-4 receptor at the protein and mRNA levels as determined by binding, indirect immunofluorescence and RT--PCR studies. These cells expressed IL-4Ralpha (also known as IL-4Rbeta) and IL-13Ralpha1 (also known as IL-13Ralpha') chains, however common gamma(c), a component of the interleukin-4 receptor system in immune cells was not detected. Consistent with the expression of IL-4R, cpIL4-PE was found to be highly and specifically cytotoxic to four of five medulloblastoma cell lines. Susceptibility of medulloblastoma cell lines to cpIL4-PE seemed to correlate closely to the functional IL-4 binding sites in general as demonstrated by 125I-IL-4 binding, but did not seem to correlate with mRNA or cell surface immunoreactive receptor protein expression. The sensitivity of medulloblastoma cells to cpIL4-PE could be eliminated by concurrent incubation with IL-4 or IL-13, but not with IL-2. None of these cell lines showed any change in proliferation upon treatment with exogenous IL-4. These studies establish the interleukin-4 receptor as a medulloblastoma-associated target for possible tumour-directed cancer therapy. Further studies are warranted to investigate interleukin-4 receptor expression in primary medulloblastoma tumours and sensitivity to cpIL-4PE in vitro and in vivo.
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-10395328, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-10728667, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-10799519, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-10850446, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-10873064, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-10965493, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-11052816, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-11719427, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-1728401, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-1742231, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-1901239, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-2032239, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-7614471, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-8056454, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-8423237, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-8530527, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-8534928, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-8589260, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-8660841, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-8866661, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-8971168, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-8992992, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-9009165, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-9299458, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-9573026, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-9721874, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-9816099, http://linkedlifedata.com/resource/pubmed/commentcorrection/11870521-9852261
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0007-0920
pubmed:author
pubmed:copyrightInfo
Copyright 2002 The Cancer Research Campaign
pubmed:issnType
Print
pubmed:day
21
pubmed:volume
86
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
285-91
pubmed:dateRevised
2009-11-18
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
IL-4 receptors on human medulloblastoma tumours serve as a sensitive target for a circular permuted IL-4-Pseudomonas exotoxin fusion protein.
pubmed:affiliation
Laboratory of Molecular Tumour Biology, Division of Cellular and Gene Therapies, Center for Biologics, Evaluation and Research, Food and Drug Administration, NIH Building 29B, Room 2NN10, 29 Lincoln Dr., Bethesda, Maryland, MD 20892, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't