Document Detail


The effects of chemotherapeutic agents on the regulation of thrombin on cell surfaces.
MedLine Citation:
PMID:  12542493     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Thromboembolic disorders are common in cancer patients. Two major contributing factors are central venous catheters for drug delivery and the use of l-aparaginase, which decreases the plasma antithrombin level, but the causes of the hypercoagulable state in these patients are not fully understood. In this study, the T24/83 cell line was used as a model to investigate the effects of chemotherapeutic agents on cell surface thrombin regulation. Plasma thrombin generation and prothrombin consumption was increased in most of the treated cells, particularly vincristine- and adriamycin-treated cells (P < 0.05), compared with controls. However, no free thrombin generation or prothrombin consumption was observed in factor VII (FVII)-depleted plasma. No significant differences in the levels of thrombin-alpha2-macroglobulin (IIa-alpha2M) and thrombin-anti-thrombin (TAT) were observed between controls and any of the treatments, except for vincristine- and adriamycin-treated cells, which showed a significant difference in TAT production (P < 0.05). Also, there was an upregulation in tissue factor (TF) mRNA expression in etoposide-, methotrexate- and vincristine-treated monolayers compared with controls, as well as an upregulation in TF protein production in vincristine-treated cells. The data suggests that thrombin generation occurs via the extrinsic (TF-dependent) coagulation pathway on cell surfaces and that some chemotherapeutic agents are able to upregulate TF mRNA and protein expression in T24/83 cells.
Authors:
Nethnapha Paredes; Ling Xu; Leslie R Berry; Anthony K C Chan
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  British journal of haematology     Volume:  120     ISSN:  0007-1048     ISO Abbreviation:  Br. J. Haematol.     Publication Date:  2003 Jan 
Date Detail:
Created Date:  2003-01-24     Completed Date:  2003-03-21     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0372544     Medline TA:  Br J Haematol     Country:  England    
Other Details:
Languages:  eng     Pagination:  315-24     Citation Subset:  IM    
Affiliation:
Henderson Research Centre, Hamilton, Ontario, Canada.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / adverse effects*
Antithrombins / metabolism
Cell Membrane / metabolism*
Doxorubicin / adverse effects
Etoposide / adverse effects
Humans
Methotrexate / adverse effects
Prothrombin / metabolism
Thrombin / metabolism*
Thromboplastin / analysis,  metabolism*
Thrombosis / chemically induced*
Tumor Cells, Cultured
Urinary Bladder Neoplasms
Vincristine / adverse effects
alpha-Macroglobulins / metabolism
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Antithrombins; 0/alpha-Macroglobulins; 23214-92-8/Doxorubicin; 33419-42-0/Etoposide; 57-22-7/Vincristine; 59-05-2/Methotrexate; 9001-26-7/Prothrombin; 9035-58-9/Thromboplastin; EC 3.4.21.5/Thrombin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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