Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2004-12-21
pubmed:abstractText
In this study, we investigated the in vitro and in vivo efficacy of patupilone (epothilone B, EPO906), a novel nontaxane microtubule stabilizing agent, in treatment of multiple myeloma (MM). Patupilone directly inhibited growth and survival of MM cells, including those resistant to conventional chemotherapies, such as the taxane paclitaxel. Patupilone induced G2M arrest of MM cells, with subsequent apoptosis. Interleukin-6 (IL-6) and insulin-like growth factor-1 (IGF-1), 2 known growth and survival factors for MM, did not protect MM.1S cells against patupilone-induced cell death. Proliferation of MM cells induced by adherence to bone marrow stromal cells (BMSCs) was also inhibited by patupilone and was paralleled by down-regulation of vascular endothelial growth factor (VEGF) secretion. Importantly, stimulation of cells from patients with MM, either with IL-6 or by adherence to BMSCs, enhanced the anti-proliferative and proapoptotic effects of patupilone. Moreover, patupilone was effective against MM cell lines that overexpress the MDR1/P-glycoprotein multidrug efflux pump. In addition, patupilone was effective in slowing tumor growth and prolonging median survival of mice that received orthotopical transplants with MM tumor cells. Taken together, these preclinical findings suggest that patupilone may be a safe and effective drug in the treatment of MM, providing the framework for clinical studies to improve patient outcome in MM.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-4971
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
105
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
350-7
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15367426-Animals, pubmed-meshheading:15367426-Apoptosis, pubmed-meshheading:15367426-Bone Marrow Cells, pubmed-meshheading:15367426-Cell Cycle, pubmed-meshheading:15367426-Cell Proliferation, pubmed-meshheading:15367426-Cell Survival, pubmed-meshheading:15367426-Cells, Cultured, pubmed-meshheading:15367426-Coculture Techniques, pubmed-meshheading:15367426-Dexamethasone, pubmed-meshheading:15367426-Disease Models, Animal, pubmed-meshheading:15367426-Drug Resistance, Multiple, pubmed-meshheading:15367426-Epothilones, pubmed-meshheading:15367426-Humans, pubmed-meshheading:15367426-Insulin-Like Growth Factor I, pubmed-meshheading:15367426-Interleukin-6, pubmed-meshheading:15367426-Leukocytes, Mononuclear, pubmed-meshheading:15367426-Mice, pubmed-meshheading:15367426-Multiple Myeloma, pubmed-meshheading:15367426-Neoplasm Transplantation, pubmed-meshheading:15367426-Plasmacytoma, pubmed-meshheading:15367426-Time Factors, pubmed-meshheading:15367426-Xenograft Model Antitumor Assays
pubmed:year
2005
pubmed:articleTitle
Patupilone (epothilone B) inhibits growth and survival of multiple myeloma cells in vitro and in vivo.
pubmed:affiliation
Jerome Lipper Multiple Myeloma Center, Department of Adult Oncology, Dana-Farber Cancer Institute, Boston, MA 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't