| Galectin inhibitory disaccharides promote tumour immunity in a breast cancer model. | |
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MedLine Citation:
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PMID: 20826047 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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High level galectin-1 expression results in cancer cell evasion of the immune response, increased tumour survival and aggressive metastases. Using a galectin-1 polyclonal antibody, high levels of galectin-1 protein were shown to be expressed by breast cancer cells established from FVB/N MMTV-c-neu mice as well as by the B16F10 melanoma cell line. In mixed lymphocyte cultures using tumour cells as antigenic stimulators, addition of recombinant galectin-1 dose-dependently inhibited lymphocyte production. Disaccharides were identified that inhibited galectin-1 function and increased growth and activation of CD8(+) CTL's killing cancer cells. X-ray crystallographic structures of human galectin-1 in complex with inhibitory disaccharides revealed their mode of binding. Combining galectin-blocking carbohydrates as adjuvants with vaccine immunotherapy in vivo to promote immune responses significantly decreased tumour progression and improved the outcomes for tumour challenged mice. This is the first report showing that suitably selected galectin-1 blocking disaccharides will act as adjuvants promoting vaccine stimulated immune responses against tumours in vivo. |
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Authors:
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Kimberley A Stannard; Patrick M Collins; Koichi Ito; Emily M Sullivan; Stacy A Scott; Elwyn Gabutero; I Darren Grice; Pauline Low; Ulf J Nilsson; Hakon Leffler; Helen Blanchard; Stephen J Ralph |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2010-09-09 |
Journal Detail:
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Title: Cancer letters Volume: 299 ISSN: 1872-7980 ISO Abbreviation: Cancer Lett. Publication Date: 2010 Dec |
Date Detail:
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Created Date: 2010-11-01 Completed Date: 2010-11-24 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 7600053 Medline TA: Cancer Lett Country: Ireland |
Other Details:
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Languages: eng Pagination: 95-110 Citation Subset: IM |
Copyright Information:
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Crown Copyright © 2010. Published by Elsevier Ireland Ltd. All rights reserved. |
Affiliation:
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School of Medical Science, Griffith University, Southport, QLD 4222, Australia. k.stannard@griffith.edu.au |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blotting, Western CD8-Positive T-Lymphocytes / immunology Cancer Vaccines / administration & dosage, immunology Cell Line, Tumor Cell Proliferation / drug effects Crystallography, X-Ray Cytotoxicity, Immunologic / drug effects Disaccharides / chemistry, metabolism, pharmacology* Female Galectin 1 / chemistry, genetics, metabolism Galectin 3 / chemistry, genetics, metabolism Galectins / chemistry, genetics, metabolism* Humans Immunity / drug effects* Immunotherapy / methods Mammary Neoplasms, Experimental / immunology*, pathology, therapy Mice Mice, Inbred Strains Models, Molecular Protein Binding Thiogalactosides / chemistry, metabolism, pharmacology Tumor Burden / drug effects |
| Chemical | |
Reg. No./Substance:
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0/Cancer Vaccines; 0/Disaccharides; 0/Galectin 1; 0/Galectin 3; 0/Galectins; 0/Thiogalactosides; 96-82-2/lactobionic acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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