| Killing tumor cells through their surface beta(2)-microglobulin or major histocompatibility complex class I molecules. | |
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MedLine Citation:
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PMID: 20143445 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Targeted antibody-based therapy has been used successfully to treat cancers. Recent studies have demonstrated that tumor cells treated with antibodies specific for beta(2)-microglobulin (beta(2)M) or major histocompatibility complex (MHC) class I molecules undergo apoptosis in vitro and in vivo (mouse models). Antibodies against beta(2)M or MHC class I induce tumor cell apoptosis by 1) recruiting MHC class I molecules to lipid rafts and activating LYN kinase and the signal-transducing enzyme phospholipase C-gamma2-dependent c-Jun N-terminal kinase signaling pathway and 2) expelling interleukin 6 and insulin-like growth factor 1 receptors out of lipid rafts and inhibiting the growth and survival factor-induced activation of the phosphatidylinositol 3-kinase/Akt and extracellular signal-related kinase pathways. Consequently, mitochondrial integrity is compromised, and the caspase-9-dependent cascade is activated in treated tumor cells. However, although beta(2)M and MHC class I are expressed on normal hematopoietic cells, which is a potential safety concern, the monoclonal antibodies were selective to tumor cells and did not damage normal cells in vitro or in human-like mouse models. These findings suggest that targeting beta(2)M or MHC class I by using antibodies or other agents offers a potential therapeutic approach for beta(2)M/MHC class I-expressing malignancies. Cancer 2010. (c) 2010 American Cancer Society. |
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Authors:
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Jing Yang; Qing Yi |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Review |
Journal Detail:
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Title: Cancer Volume: 116 ISSN: 0008-543X ISO Abbreviation: Cancer Publication Date: 2010 Apr |
Date Detail:
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Created Date: 2010-03-29 Completed Date: 2010-05-06 Revised Date: 2011-09-26 |
Medline Journal Info:
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Nlm Unique ID: 0374236 Medline TA: Cancer Country: United States |
Other Details:
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Languages: eng Pagination: 1638-45 Citation Subset: AIM; IM |
Affiliation:
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Department of Lymphoma and Myeloma, Division of Cancer Medicine, Center for Cancer Immunology Research, The University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Antibodies, Monoclonal / therapeutic use Apoptosis Cell Line, Tumor Drug Delivery Systems Hematologic Neoplasms / drug therapy Histocompatibility Antigens Class I Membrane Microdomains / metabolism Mice Neoplasms / drug therapy* Signal Transduction beta 2-Microglobulin |
| Grant Support | |
ID/Acronym/Agency:
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K99 CA137158-01A1/CA/NCI NIH HHS; K99/R00 CA137158/CA/NCI NIH HHS; R01 CA103978/CA/NCI NIH HHS; R01 CA138402/CA/NCI NIH HHS; R01 CA96569/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Antibodies, Monoclonal; 0/Histocompatibility Antigens Class I; 0/beta 2-Microglobulin |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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