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Non-invasive enzyme screen for tissue remodeling associated conditions

a tissue remodeling and enzyme technology, applied in the field of non-invasive enzyme screening for tissue remodeling associated conditions, can solve the problems of psa testing being somewhat invasive, unable to detect tissue remodeling, so as to facilitate the diagnosis of a subj

Inactive Publication Date: 2007-01-18
CHILDRENS MEDICAL CENT CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0006] The present invention features non-invasive methods for facilitating diagnosis of a subject for a tissue remodelling-associated condition. The method involves obtaining a biological sample from that subject and detecting an enzyme in that sample, facilitating the diagnosis. The non-invasive method was based at least in part, on the observation of full length, active intact enzymes that are normally associated with the process of tissue remodelling, in urine samples from patients with certain conditions. For example, gelatin-degrading matrix metalloproteinases and other proteases have been found in the urine of cancer patients. Further, high statistical associations between presence of prostate cancer and appearance of certain enzymes in urine, and between metastatic cancer and certain enzymes in urine, have been found.
[0010] Another aspect of the methods features a fully non-invasive means for facilitating the diagnosis of a subject for a disorder of the prostate. A urine sample is obtained from the subject, and a prostate disorder-associated enzyme is detected in the urine sample, facilitating the diagnosis of that subject for the prostate disorder. More preferably, the prostate disorder-associated enzyme is a matrix-digesting enzyme, most preferably, a proteinase which is a metalloproteinase. The disorders of the prostate include benign prostatic hyperplasia, “problematic” prostatic hyperplasia, organ-defined prostate cancer, this cancer which may previously have been treated surgically or chemically, and particularly, situations in which metastatic cancer is suspected. The method encompasses diagnosis of subjects who are being treated hormonally with agents that block testosterone.

Problems solved by technology

The PSA test is somewhat non-specific for distinguishing CaP and BPH, and produces a degree of false negative results (Garnick, M., (1993), Am. Inst. Med, 118:804-818).
Further, the PSA test is somewhat invasive, requiring the subject to give a blood sample, a procedure that requires trained personnel, in the setting of a doctor's office or clinic.
The PSA test, a major advance over previous procedures, thus leaves much to be desired.
CaP metastasis to other sites is inevitably fatal.

Method used

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Examples

Experimental program
Comparison scheme
Effect test

example 1

Enzyme Activity in Urine of Prostate Cancer Patients and Other Cancer Patients

[0063] Analysis of urine of CaP patients showed gelatinase in 12 of the 13 samples (Table 2) Thus 92% of urine from CaP patients contained a band of 92 kDa or higher molecular weight, and 48% of the 52 possible zymogram activity categories are positive for the CaP group. These frequencies are over 3-fold higher than comparable findings for the urines from the normal controls.

[0064] Urine samples from 5 out of 11 of patients with other types of cancer showed metalloproteinase activity (Table 3). Enzymes were found in urine from 3 out of 5 bladder cancer patients, and in urine from one out of 2 patients with renal cancer, and one out of 2 patients with lymphoma

example 2

Enzyme Activity in Urine of Metastatic Cancer Patients

[0065] In the MC patient group, urine samples of all 8 patients displayed metalloproteinase activity (Table 4). Of the 32 possible enzyme band categories recorded, 66% were positive for patients with metastatic cancer. Further, the urine of all MC patients contained either enzyme of 92 kDa size, enzyme of molecular weight greater than 150 kDa, or both.

TABLE 2Zymograms of Subjects with Prostate Cancer (13 subjects)enzyme pattern in urineCode>150 kDa92 kDa72 kDaother MMPsCaP-1yesyesyesnoCaP-2yesyesyesnoCaP-3yesyesyesnoCaP-4yesyesyesnoCaP-5noyesnonoCaP-6noyesnonoCaP-7yesyesnonoCaP-8noyesnonoCaP-9nonononoCaP-10noyesnonoCaP-11yesyesnonoCaP-12yesyesyesnoCaP-13yesyesnono

Subjects CaP-1 through CaP-13 are prostate cancer patients.

[0066]

TABLE 3Zymograms of Subjects with Other Cancers,Non-Metastatic (11 subjects)enzyme pattern in urine>1509272otherCodekDakDakDaMMPscancerCaB-1nonononobladderCaB-2nonononobladderCaB-3yesyesnonobladderCaB-...

example 3

Enzyme Activity in Urine of Subjects with Benign Prostatic Hypertrophy

[0069] Eight subjects with BPH were assayed for metalloproteinase content of urine (Table 5). Of the 32 possible enzyme pattern observations, 10 were positive (31%), and 6 of these 8 patients (75%) had urine containing one or more bands of activity, a frequency higher than that of the normal subjects and those with no evidence of disease. None of the BPH subjects' urines (0%) showed 72 kDa metalloproteinase band. The MMP pattern of the BPH subjects as a function of time can be used to facilitate prognosis of patients likely to develop problematic BPH or other conditions.

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PUM

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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.

Description

RELATED APPLICATIONS [0001] This application is a continuation-in-part application of Ser. No. 08 / 639,373 filed on Apr. 26, 1996, now pending. The contents of the aforementioned application is expressly incorprated herein by reference.BACKGROUND OF THE INVENTION [0002] A class of disorders may be characterized as tissue remodelling-associated conditions, and includes cancers, arthritic conditions, obstructive disorders, degenerative disorders, and problematic wound-healing and ulcerative disorders. Paradigmatic among these is prostate cancer (CaP), the leading source of new cases of cancer in men in this country, and the second leading cancer cause of cancer death after lung cancer. Over 40,000 Americans are estimated to have died of CaP in 1995, and about 244,000 new cases of prostate cancer were detected (Cancer Facts and Figures-1995, American Cancer Society, Inc., 1995) and these numbers have increased annually at an alarming rate. Further, the rate of appearance of prostate can...

Claims

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Application Information

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IPC IPC(8): G01N33/53G01N33/564G01N33/573G01N33/574
CPCG01N33/564G01N33/573G01N33/574G01N2333/96486G01N33/57434G01N33/57488G01N33/57415
Inventor MOSES, MARSHA A.FREEMAN, MICHAEL R.WIEDERSCHAIN, DMITRI
Owner CHILDRENS MEDICAL CENT CORP