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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2007-3-5
pubmed:abstractText
In orthopedic surgery, sterilization of bone used for reconstruction of osteoarticular defects caused by malignant tumors is carried out in various ways. At present, to devitalize tumor-bearing osteochondral segments, extracorporeal irradiation or autoclaving is mainly used, although both methods have substantial disadvantages, leading to a significant loss of biomechanical and biological integrity of the bone. As an alternative approach, a new technology to achieve bone sterilization, the high hydrostatic pressure (HHP) treatment of bone, has been suggested, which is currently being preclinically tested. This novel technique leads to the inactivation of tumor cells without impairing biomechanical properties of the bone, cartilage, or tendons. HHP may not only exert an effect on tumor and normal cells present in the bone but also on tumor-associated proteases released by these cells, which are conductive to tumor bone turnover. In order to investigate this, proteolytic key enzymes, e.g. MMP-9, uPA, t-PA, plasmin, trypsin, and thrombin were subjected to HHP <or=600 MPa. Thereafter, compared to the non-pressurized enzymes, the proteolytic activity of the pressurized enzymes was determined. The proteases studied showed varying degrees of susceptibility to HHP, depending on the pressure level applied. The latent activity of the inactive zymogens prothrombin, plasminogen, and pro-uPA, in addition to the proteolytically active forms of plasmin, thrombin, HMW-uPA, and trypsin were minimally affected by HHP (10 min, 20 degrees C, 600 MPa) with a reduction of activity up to 13% only, whereas t-PA was significantly impaired by a reduction of activity of 30%. In contrast, for pressurized pro-MMP-9 (10 min, 5 degrees C, 400 MPa) a 3-fold increase in enzymatic activity was observed after activation compared to non-pressurized pro-MMP-9. No activation of pro-MMP-9 due to HHP was observed. These data encourage further exploration of the potential of HHP to sterilize tumor-affected bone segments prior to reimplantation. During this treatment tumor cells are irreversibly impaired, while HHP treatment of proteases may not exert any significant autolytic effect on bone tissue.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1107-3756
pubmed:author
pubmed:issnType
Print
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
667-73
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Quantitative analysis of the impact of short-time high hydrostatic pressure on bone tumor-associated proteases.
pubmed:affiliation
Department of Orthopedic Surgery, University of Rostock, Rostock, Germany. p.diehl@lrz.tum.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't