| FQPD, a novel immunomodulatory drug, has significant in vitro activity in multiple myeloma. | |
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MedLine Citation:
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PMID: 16487170 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Multiple myeloma (MM) is a plasma cell malignancy that claims thousands of lives each year and has considerable morbidity. The disease remains incurable despite recent advances in the understanding of the disease biology and the introduction of more effective drugs is needed. This study evaluated the anti-MM activity of 3-(7-fluoro-4H-quinazolin-3-yl)-piperidine-2,6-dione, hydrochloride (FQPD), a novel immunomodulatory drug. FQPD inhibited the proliferation of multiple MM cell lines, including those resistant to conventional treatments, such as dexamethasone. It induced apoptosis in MM cell lines, as well as freshly isolated patient MM cells, without cytotoxicity on normal human lymphocytes. Moreover, it induced apoptosis in MM cells adherent to bone marrow (BM) stromal cells or in the presence of cytokines, such as interleukin-6 and vascular endothelial growth factor, confirming its ability to overcome the protective effects of the BM milieu. Apoptosis in the MM cells was mediated via poly-ADP ribose polymerase cleavage as well as cleavage of caspase 8 and caspase 9. Our studies therefore demonstrated in vitro anti-MM activity of FQPD and provide the rationale for its in vivo evaluation in animal models and derived clinical trials. |
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Authors:
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Shaji Kumar; Noopur Raje; Teru Hideshima; Kenji Ishitsuka; Klaus Podar; Steven Le Gouille; Dharminder Chauhan; Paul Richardson; Nikhil C Munshi; Kenneth Anderson |
Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: British journal of haematology Volume: 132 ISSN: 0007-1048 ISO Abbreviation: Br. J. Haematol. Publication Date: 2006 Mar |
Date Detail:
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Created Date: 2006-02-20 Completed Date: 2006-05-10 Revised Date: 2007-11-14 |
Medline Journal Info:
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Nlm Unique ID: 0372544 Medline TA: Br J Haematol Country: England |
Other Details:
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Languages: eng Pagination: 698-704 Citation Subset: IM |
Affiliation:
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Division of Hematology, Mayo Clinic, Rochester, MN, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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6-Ketoprostaglandin F1 alpha
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immunology,
therapeutic use* Apoptosis / drug effects Bone Marrow Cells / immunology Cell Adhesion / drug effects, immunology Cell Cycle / drug effects, immunology Cell Division / drug effects, immunology Cell Line, Tumor DNA, Neoplasm / biosynthesis Humans Immunologic Factors / immunology, therapeutic use* Interleukin-6 / immunology Multiple Myeloma / drug therapy*, immunology Somatomedins / immunology Stromal Cells / immunology Vascular Endothelial Growth Factors / immunology |
| Grant Support | |
ID/Acronym/Agency:
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IP50 CA10070-01/CA/NCI NIH HHS; P0-1 78378//PHS HHS; R0-1 CA 50947/CA/NCI NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/DNA, Neoplasm; 0/Immunologic Factors; 0/Interleukin-6; 0/Somatomedins; 0/Vascular Endothelial Growth Factors; 58962-34-8/6-Ketoprostaglandin F1 alpha |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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