Source:http://linkedlifedata.com/resource/pubmed/id/16353147
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
10
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pubmed:dateCreated |
2006-3-6
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pubmed:abstractText |
Multiple myeloma (MM) is a fatal disease that affects plasma cells. Patients with MM have 1 or more osteolytic lesions in their bone tissues, where insulin-like growth factors (IGFs; IGF-I and IGF-II) are mainly stored. The role of bone-derived IGFs in the development of MM has not been extensively studied because reliable animal models are lacking. We established an animal model using a human MM cell line, RPMI8226, in nonobese diabetic/severe-combined immunodeficient (NOD/SCID) mice implanted with human adult bone (HAB) fragments. Treatment with an anti-human IGF-neutralizing monoclonal antibody, KM1468, inhibited the IGF-I-stimulated phosphorylation of type-I IGF receptors (IGF-IR) in RPMI8226 cells and the activation of the downstream PI3-K/Akt signaling pathway in vitro. KM1468 inhibited IGF-I-mediated RPMI8226 cell growth in a dose-dependent manner. In the NOD/SCID-HAB model, treatment with KM1468 significantly inhibited the growth of RPMI8226 cells (p<0.02). These results indicated that the growth of MM cells was predominantly stimulated not by serum-derived IGFs, but by bone-derived IGFs. Furthermore, the targeting of bone-derived IGFs, using a neutralizing antibody, may offer a new therapeutic strategy for MM.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical | |
pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0020-7136
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pubmed:author |
pubmed-author:AkiyamaTadakazuT,
pubmed-author:ArakiKazuhiroK,
pubmed-author:HasebeTakahiroT,
pubmed-author:IshiiGenichiroG,
pubmed-author:KusakaHideakiH,
pubmed-author:MaedaHiroyukiH,
pubmed-author:MinamiHironobuH,
pubmed-author:MiyamotoShin'ichiS,
pubmed-author:NagaiKanjiK,
pubmed-author:NakamuraMichioM,
pubmed-author:OchiaiAtsushiA,
pubmed-author:SangaiTakafumiT,
pubmed-author:TokudaYoshimiY,
pubmed-author:ZhangShi-ChuanSC
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pubmed:copyrightInfo |
Copyright (c) 2005 Wiley-Liss, Inc.
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pubmed:issnType |
Print
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pubmed:day |
15
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pubmed:volume |
118
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
2602-8
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pubmed:dateRevised |
2007-7-24
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pubmed:meshHeading |
pubmed-meshheading:16353147-Animals,
pubmed-meshheading:16353147-Antibodies, Monoclonal,
pubmed-meshheading:16353147-Bone and Bones,
pubmed-meshheading:16353147-Cell Proliferation,
pubmed-meshheading:16353147-Disease Models, Animal,
pubmed-meshheading:16353147-Humans,
pubmed-meshheading:16353147-Ligands,
pubmed-meshheading:16353147-Male,
pubmed-meshheading:16353147-Mice,
pubmed-meshheading:16353147-Mice, Inbred NOD,
pubmed-meshheading:16353147-Mice, SCID,
pubmed-meshheading:16353147-Multiple Myeloma,
pubmed-meshheading:16353147-Phosphorylation,
pubmed-meshheading:16353147-Signal Transduction,
pubmed-meshheading:16353147-Somatomedins,
pubmed-meshheading:16353147-Transplantation, Heterologous
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pubmed:year |
2006
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pubmed:articleTitle |
Inhibition of bone-derived insulin-like growth factors by a ligand-specific antibody suppresses the growth of human multiple myeloma in the human adult bone explanted in NOD/SCID mouse.
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pubmed:affiliation |
Pathology Division, National Cancer Center Research Institute East, Chiba, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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