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Non-invasive enzyme screen for tissue remodelling-associated conditions

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

Inactive Publication Date: 2014-06-26
CHILDRENS MEDICAL CENT CORP
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

This patent describes non-invasive methods for diagnosing tissue remodeling-associated conditions, including prostate cancer, using urine samples. The methods involve detecting certain enzymes associated with tissue remodeling, particularly matrix metalloproteinases, which are normally found in urine samples from patients with these conditions. The detection of these enzymes allows for the diagnosis of subjects for tissue remodeling-related disorders, particularly prostate cancer, which can be confirmed by measuring the presence of certain enzymes in urine samples. These methods are fully non-invasive and can help in the diagnosis and monitoring of prostate cancer, providing an effective tool for the diagnosis and management of the disease.

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

[0064]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.

[0065]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

[0066]In the MC patient group, wine 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-13yesyesnonoSubjects CaP-1 through CaP-13 are prostate cancer patients.

TABLE 3Zymograms of Subjects with Other Cancers,Non-Metastatic (11 subjects)enzyme pattern in urine>1509272otherCodekDakDakDaMMPscancerCaB-1nonononobladderCaB-2nonononobladderCaB-3yesyesnonobladderCaB-4yesyesyesnob...

example 3

Enzyme Activity in Urine of Subjects with Benign Prostatic Hypertrophy

[0067]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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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 incorporated 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 cancer...

Claims

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Application Information

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