Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

To address the urgent need for novel therapies for multiple myeloma (MM), long-term research efforts have characterized the mechanisms whereby MM cells home to the bone marrow and adhere to bone marrow stromal cells and extracellular matrix proteins. Research also characterizes the functional sequelae of this binding to identify targets for novel therapies. This article describes the mechanisms by which MM cells home to bone marrow and adhere to bone marrow stromal cells and extracellular matrix proteins, and describes the functional sequelae of this binding. Adhesion molecules that mediate MM cell binding to bone marrow stromal cells are identified, and the growth and survival advantage conferred by this binding is discussed. The biologic significance of cytokines in MM pathogenesis and the signaling cascades mediating their effects are delineated. Apoptotic and targeted therapeutic strategies to overcome drug resistance based on interrupting growth or triggering apoptotic-signaling cascades also are identified, providing the basis for novel biologically based therapies, such as thalidomide/immunomodulatory drugs and proteasome inhibitor PS-341.
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PMID:Moving disease biology from the laboratory to the clinic. 1252 Apr 80

Multiple myeloma remains an incurable disease; however, newer biologically based therapies aimed at various molecular-cellular targets are showing promise. Some of these drugs target critical pathways of the tumor cell and the bone marrow microenvironment. A brief review of the pathogenesis of multiple myeloma is presented. Genetic aberrations are hallmarks of the disease. Chromosome 14 translocations are responsible for cellular processes implicated in tumorigenesis. Adhesion to the extracellular matrix and bone marrow stromal cells augments drug resistance and inhibits apoptosis. Bortezomib, a proteasome inhibitor, acts on bone marrow constituents blocking many signaling cascades mediating multiple myeloma cell growth, survival, and drug resistance. Bortezomib and other cell-cycle targeted therapies offer hope in the fight against multiple myeloma.
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PMID:Characteristics, pathogenesis, and novel treatments for multiple myeloma. 1979 22