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)

Adhesion of polymorphonuclear granulocytes (PMNs) in microvessels occurs in the presence of shear forces exerted by the blood flow. To model this in vitro, phorbol myristate acetate (PMA)-activated PMN were exposed to shear stress on cultured human umbilical vein endothelial cells (HUVECs) and on plastic dishes coated with bovine serum albumin (BSA). PMN adhesion to HUVECs averaged 36% of the total PMNs added and was reduced to 21% by shear stress of approximately 1.5 dynes.cm-2. On BSA, adhesion was reduced from 59% to 35%. Dextran sulfate (molecular weight 500,000) inhibited PMN adhesion in a dose-dependent manner when shear stress was applied. At a concentration of 1 mg.ml-1, inhibition was 72% on HUVECs and 76% on BSA. Half-maximal inhibition was reached at approximately 1 microgram.mL-1 dextran sulfate, corresponding to 2 nmol/L. Without shear stress, dextran sulfate had no effect on HUVECs and only a moderate effect on BSA. The murine monoclonal antibody (MoAb) 60.3, recognizing an epitope on the leukocyte adhesion glycoprotein CD18, inhibited PMN adhesion equally well with and without shear. A low dose of MoAb 60.3 enhanced the effect of dextran sulfate without shear stress. Flow cytometry (FACS) did not show inhibition of MoAb 60.3 binding to PMNs by dextran sulfate. These results indicate that a dextran sulfate-inhibitable adhesion process is important for PMN adhesion in the presence of shear stress.
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PMID:Shear-dependent inhibition of granulocyte adhesion to cultured endothelium by dextran sulfate. 246 7

Todays, after four decades from the discovery of monoclonal antibodies by Kohler and Milstein in 1975, a dozen of antibodies are used in cancer targeted therapy with different strategies. The success of these antibodies depends on the specificity of antigens expressed on the cancer cells. Epithelial Cell Adhesion Molecule (EpCAM), a homophilic cell-cell adhesion glycoprotein is a well- known tumor antigen, which expresses on epithelial tumors and circulating tumor cells as well as cancer stem cells. The EpCAM signaling pathway is associated with proliferation, differentiation and adhesion of epithelial cancer cells. Here we review EpCAM structure, expression profile and its signaling pathway in cancer cells. In addition, we focused on structure, mechanism of action and success of anti EpCAM antibodies which have been used in different clinical trials. Based on literatures, Edrecolomab showed limited efficacy in the phase III studies. The wholly human monoclonal antibody Adecatumumab is dose- and target-dependent in metastatic breast cancer patients expressing EpCAM. The chimeric antibody, Catumaxomab, has been approved for the treatment of malignant ascites; however, this Mab showed considerable results in intrapleural administration in cancer patients. Anti EpCAM toxin conjugated antibodies like, Oportuzumab Monatox (scFv antibody and Pseudomonas exotoxin A (ETA)), Citatuzumab Bogatox (Fab fragment with bouganin toxin) and immono-conjugate antibody Tucotuzumab (monoclonal antibody with IL2), have shown acceptable results in different clinical trials. Almost, all of the antibodies were well-tolerated; however, still more clinical trials are needed for the approval of antibodies for the treatment of specific tumors.
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PMID:Antibody Based EpCAM Targeted Therapy of Cancer, Review and Update. 2929 96