Quantification of matrix metalloproteinase activity in plasma of patients enrolled in a BAY 12-9566 phase I study.
The expression of matrix metalloproteinases (MMPs) is often associated with invasiveness or grade of tumours. Increased blood levels of MMP proteins, including MMP-1, MMP-2, MMP-3 and MMP-9 have been detected in various types of cancers. With the exception of one study, MMPs in serum and plasma have been determined using ELISA. In the present study we measured the activity of the MMPs found in human plasma samples using gelatin enzymography and fluorimetric degradation assays. We used plasma samples from healthy control subjects and cancer patients enrolled in a dose-finding study for the MMP inhibitor, BAY 12-9566, to assess the activity of MMPs found in plasma and screen for efficacy of the MMP inhibitor. BAY 12-9566 has inhibitory activity toward MMP-2, MMP-3 and MMP-9. Patients with advanced solid tumours were enrolled in our study and plasma was collected on day 1 before dosing and at steady-state of the drug on day 15. Our results show that BAY 12-9566 was effective in lowering the plasma gelatinolytic activity in the group of 29 patients when considering the data obtained from a fluorimetric gelatinase assay. The data obtained from gelatin enzymography, however, did not reach significance. The fluorimetric degradation assay could be a useful tool to screen plasma from cancer patients in other clinical trials assessing MMP inhibitors.
Duivenvoorden
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WC
Hamilton Regional Cancer Centre, McMaster University, 699 Concession Street, Hamilton, Ontario, Canada L8V 5C2.
Hirte
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HW
Singh
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D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D008297:Male; D061965:Matrix Metalloproteinase Inhibitors; D020782:Matrix Metalloproteinases / Q000097:blood*; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood / Q000188:drug therapy*; D009930:Organic Chemicals; D010654:Phenylbutyrates
D000970:Antineoplastic Agents; D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D061965:Matrix Metalloproteinase Inhibitors; D009930:Organic Chemicals; D010654:Phenylbutyrates; C113281:Bay 12-9566; D020782:Matrix Metalloproteinases