Non-invasive enzyme screen for cancer

Abstract

Methods and kits for diagnosing the presence of and prognosing the appearance of tissue remodelling-associated conditions, involving the presence of enzymes in a biological sample, are disclosed. In particular, the method pertains to diagnosing the presence of or prognosing appearance of cancer, metastatic cancer, and obstructive and degenerative conditions.

1 . A non-invasive method for facilitating the diagnosis of a subject for a tissue remodelling-associated condition, comprising: 
 obtaining a urine sample from a subject; and    detecting an enzyme in the urine sample, thereby facilitating the diagnosis of the subject for the tissue remodelling-associated condition.    
     
     
         2 . The method of  claim 1 , wherein the tissue remodelling-associated condition is cancer.  
     
     
         3 . The method of  claim 1 , wherein the tissue remodelling-associated condition is an arthritic condition, an obstructive condition, or a degenerative condition.  
     
     
         4 . The method of  claim 2 , wherein the cancer is organ-confined prostate cancer.  
     
     
         5 . The method of  claim 2 , wherein the cancer is metastatic prostate cancer.  
     
     
         6 . The method of  claim 2 , wherein the cancer is in cells of epithelial origin.  
     
     
         7 . The method of  claim 6 , wherein the cancer is selected from the group consisting of cancers of the nervous system, breast, retina, lung, skin, kidney, liver, pancreas, genito-urinary tract, and gastrointestinal tract.  
     
     
         8 . The method of  claim 2 , wherein the cancer appears in cells of mesodermal origin.  
     
     
         9 . The method of  claim 2 , wherein the cancer appears in cells of endodermal origin.  
     
     
         10 . The method of  claim 2 , wherein the cancer affects cells of bone or of hematopoietic origin.  
     
     
         11 . The method of  claim 1 , wherein the enzyme is involved in a pathway of tissue remodelling or reshaping.  
     
     
         12 . The method of  claim 1 , wherein the enzyme is a matrix-digesting enzyme.  
     
     
         13 . The method of  claim 1 , wherein the enzyme is a protease.  
     
     
         14 . The method of  claim 13 , wherein the protease is a serine protease.  
     
     
         15 . The method of  claim 13 , wherein the protease is a matrix metalloproteinase.  
     
     
         16 . The method of  claim 1 , wherein the enzyme is a proenzyme.  
     
     
         17 . The method of  claim 1 , further comprising removal of low molecular weight contaminants from the urine prior to the detection step.  
     
     
         18 . The method of  claim 17 , wherein the urine is dialyzed.  
     
     
         19 . A non-invasive method for facilitating the diagnosis of a subject for a disorder of the prostate, comprising: 
 obtaining a urine sample from a subject; and    detecting a prostate disorder-associated enzyme in the urine sample, thereby facilitating the diagnosis of the subject for the prostate disorder.    
     
     
         20 . The method of  claim 19 , wherein the prostate-disorder associated enzyme is a matrix-digesting enzyme.  
     
     
         21 . The method of  claim 19 , wherein the matrix-digesting enzyme is a protease.  
     
     
         22 . The method of  claim 21 , wherein the enzyme is a metalloproteinase.  
     
     
         23 . The method of  claim 19 , wherein the disorder of the prostate is benign prostatic hyperplasia.  
     
     
         24 . The method of  claim 19 , wherein the disorder of the prostate is organ-confined prostate cancer.  
     
     
         25 . The method of  claim 19 , wherein the subject has previously been treated surgically or hormonally.  
     
     
         26 . The method of  claim 25 , wherein the subject has been treated to block testosterone.  
     
     
         27 . The method of  claim 19 , wherein the disorder is metastatic cancer.  
     
     
         28 . A method for facilitating the diagnosis of a subject for prostate cancer, comprising: 
 obtaining a urine sample from a subject suspected of having prostate cancer; and    detecting a prostate cancer-associated enzyme in the urine sample, thereby facilitating the diagnosis of the subject for prostate cancer.    
     
     
         29 . The method of  claim 28 , wherein the prostate cancer-associated enzyme is a protease.  
     
     
         30 . The method of  claim 29 , wherein the protease is a matrix metalloproteinase.  
     
     
         31 . The method of  claim 30 , wherein the matrix metalloproteinase is gelatinase A or gelatinase B.  
     
     
         32 . The method of  claim 28 , wherein the subject has benign prostatic hyperplasia.  
     
     
         33 . The method of  claim 28 , wherein the subject is under treatment to block testosterone.  
     
     
         34 . The method of  claim 28 , further comprising removal of low molecular weight contaminants from the urine prior to the detection step.  
     
     
         35 . A method for facilitating the prognosis of prostate cancer in a subject, comprising: 
 obtaining a biological sample from a subject; and    detecting a prostate cancer-associated enzyme, thereby facilitating the prognosis of prostate cancer in a subject.    
     
     
         36 . The method of  claim 35 , wherein the biological sample is urine.  
     
     
         37 . The method of  claim 35 , wherein the prostate cancer associated-enzyme is a tissue remodelling-associated enzyme.  
     
     
         38 . The method of  claim 37 , wherein the prostate-cancer associated enzyme is a protease.  
     
     
         39 . The method of  claim 38 , wherein the protease is a type IV collagenase.  
     
     
         40 . The method of  claim 39 , wherein the metalloproteinase has a molecular weight of approximately equal to or greater than 82 kDa or 92 kDa.  
     
     
         41 . The method of  claim 39 , wherein the metalloproteinase has a molecular weight of approximately 72 kDa.  
     
     
         42 . The method of  claim 35 , wherein the subject has benign prostatic hyperplasia.  
     
     
         43 . A method for prognosis of problematic prostatic hyperplasia in a subject, comprising: 
 obtaining a biological sample from a subject; and    detecting a problematic prostatic hyperplasia-associated enzyme in the biological sample, thereby facilitating the prognosis of problematic prostatic hyperplasia in a subject.    
     
     
         44 . The method of  claim 43 , wherein the prostatic hyperplasia-associated enzyme is a metalloproteinase.  
     
     
         45 . The method of  claim 44 , wherein the metalloproteinase has a molecular weight of approximately equal to or greater than 92 kDa.  
     
     
         46 . A method for prognosis of metastatic prostate cancer comprising: 
 obtaining a biological sample from a subject; and    detecting a metastatic prostate cancer-associated enzyme in the biological sample, thereby facilitating the prognosis of metastatic prostate cancer in a subject.    
     
     
         47 . The method of  claim 1 , wherein the enzyme has a molecular weight of approximately 72 kDa or approximately 92 kDa.  
     
     
         48 . The method of  claim 1 , wherein the enzyme has a molecular weight equal to or greater than approximately 150 kDa.  
     
     
         49 . The method of  claim 43  or  46 , further comprising removal of low molecular weight contaminants from the urine prior to the detection step.  
     
     
         50 . The method of  claim 1 , wherein the enzyme is detected electrophoretically.  
     
     
         51 . The method of  claim 50 , wherein the electrophoretic pattern is a zymogram.  
     
     
         52 . The method of  claim 51 , wherein the zymogram substrate is gelatin, casein, fibronectin, vitronectin, plasmin, plasminogen, type IV collagen, or a derivative of type IV collagen.  
     
     
         53 . The method of  claim 1 , wherein the enzyme is detected immunochemically.  
     
     
         54 . The method of  claim 53 , wherein the enzyme is detected by a radio-immune assay.  
     
     
         55 . The method of  claim 53 , wherein the enzyme is detected by an enzyme-linked immunosorbant assay.  
     
     
         56 . A kit for facilitating the diagnosis and prognosis of a tissue remodelling-associated condition, comprising: 
 a container having a reagent for detecting an enzyme in a urine sample; and    instructions for using said reagent for detecting the enzyme for facilitating the diagnosis and prognosis of a tissue remodelling-associated condition.    
     
     
         57 . The kit of  claim 56 , wherein the tissue remodelling-associated condition is cancer.  
     
     
         58 . The kit of  claim 56 , wherein the tissue remodelling-associated condition is an arthritic condition, an obstructive condition, or a degenerative condition.  
     
     
         59 . The kit of  claim 57 , wherein the cancer is organ-confined prostate cancer.  
     
     
         60 . The kit of  claim 57 , wherein the cancer is metastatic prostate cancer.  
     
     
         61 . The kit of  claim 56 , wherein the enzyme is a matrix metalloproteinase.  
     
     
         62 . The kit of  claim 61 , wherein the matrix metalloproteinase is a gelatinase.  
     
     
         63 . The kit of  claim 56 , further comprising an apparatus for separating urine into components for removal of low molecular weight contaminants.