Linked Life Data

10887096

Source:http://linkedlifedata.com/resource/pubmed/id/10887096

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2000-8-17
pubmed:abstractText
Bisphosphonates are well-known inhibitors of osteoclastic bone resorption, but recent clinical reports support the possibility of direct or indirect antitumor effects by these compounds. Because bisphosphonates share structural homologies with recently identified gamma delta T-cell ligands, we examined the stimulatory capacity of bisphosphonates to gamma delta T cells and determined whether gamma delta T-cell stimulation by bisphosphonates could be exploited to generate antiplasma cell activity in multiple myeloma (MM). All tested aminobisphosphonates (alendronate, ibandronate, and pamidronate) induced significant expansion of gamma delta T cells (V gamma 9V delta 2++ subset) in peripheral blood mononuclear cell cultures of healthy donors at clinically relevant concentrations (half-maximal activity, 0.9-4 mcmol/L). The proliferative response of gamma delta T cells to aminobisphosphonates was IL-2 dependent, whereas activation of gamma delta T cells (up-regulation of CD25 and CD69) occurred in the absence of exogenous cytokines. Pamidronate-activated gamma delta T cells produced cytokines (ie, interferon [IFN]-gamma) and exhibited specific cytotoxicity against lymphoma (Daudi) and myeloma cell lines (RPMI 8226, U266). Pamidronate-treated bone marrow (BM) cultures of 24 patients with MM showed significantly reduced plasma cell survival compared with untreated cultures, especially in cultures in which activation of BM-gamma delta T cells was evident (14 of 24 patients with MM). gamma delta T-cell depletion from BM cultures completely abrogated the cytoreductive effect on myeloma cells in 2 of 3 tested patients with MM. These results show that aminobisphosphonates stimulating gamma delta T cells have pronounced effects on the immune system, which might contribute to the antitumor effects of these drugs. (Blood. 2000;96:384-392)
pubmed:commentsCorrections
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
15
pubmed:volume
96
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
384-92
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:10887096-Alendronate, pubmed-meshheading:10887096-Antigens, CD, pubmed-meshheading:10887096-Antigens, Differentiation, T-Lymphocyte, pubmed-meshheading:10887096-Bone Marrow Cells, pubmed-meshheading:10887096-Cell Division, pubmed-meshheading:10887096-Cell Survival, pubmed-meshheading:10887096-Cytotoxicity, Immunologic, pubmed-meshheading:10887096-Diphosphonates, pubmed-meshheading:10887096-Humans, pubmed-meshheading:10887096-Interferon-gamma, pubmed-meshheading:10887096-Interleukin-2, pubmed-meshheading:10887096-Kinetics, pubmed-meshheading:10887096-Lectins, C-Type, pubmed-meshheading:10887096-Lymphocyte Activation, pubmed-meshheading:10887096-Multiple Myeloma, pubmed-meshheading:10887096-Plasma Cells, pubmed-meshheading:10887096-Receptors, Interleukin-2, pubmed-meshheading:10887096-T-Lymphocytes, pubmed-meshheading:10887096-Tumor Cells, Cultured
pubmed:year
2000
pubmed:articleTitle
Stimulation of gammadelta T cells by aminobisphosphonates and induction of antiplasma cell activity in multiple myeloma.
pubmed:affiliation
Medizinische Poliklinik Wuerzburg, Julius-Maximilians Universität Wuerzburg, Wuerzburg, Germany.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't