Reagents and methods useful for detecting diseases of the urinary tract

Abstract

A set of contiguous and partially overlapping cDNA sequences and polypeptides encoded thereby, designated as BL172 and transcribed from urinary tract tissue, is described. These sequences are useful for the detecting, diagnosing, staging, monitoring, prognosticating, in vivo imaging, preventing or treating, or determining the predisposition of an individual to diseases and conditions of the urinary tract, such as urinary tract cancer. Also provided are antibodies which specifically bind to BL172-encoded polypeptide or protein, and agonists or inhibitors which prevent action of the tissue-specific BL172 polypeptide, which molecules are useful for the therapeutic treatment of urinary tract diseases, tumors or metastases.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application is a continuation-in-part of U.S. application Ser. No. 08 / 869,579, filed Jun. 5, 1997, from which priority is claimed pursuant to 35 U.S.C. § 120 and which is incorporated herein by reference in its entirety.BACKGROUND OF THE INVENTION [0002] The invention relates generally to detecting diseases of the urinary tract, and more particularly, relates to reagents such as polynucleotide sequences and the polypeptide sequences encoded thereby, as well as methods which utilize these sequences, which reagents are useful for detecting, diagnosing, staging, monitoring, prognosticating, in vivo imaging, preventing or treating, or determining predisposition to diseases or conditions of the urinary tract such as urinary tract cancers. [0003] The organs of the urinary tract include the bladder, kidneys, and ureter. The incidence of urinary tract cancers in the United States is projected to be 86,300 cases diagnosed and 24,700 related...

AI Technical Summary

Benefits of technology

[0012] The present invention further provides a method of detecting a target BL172 polynucleotide in a test sample suspected of containing target BL172 polynucleotides, which comprises (a) contacting the test sample with at least one BL172 oligonucleotide as a sense primer and at least one BL172 oligonucleotide as an anti-sense primer, and amplifying same to obtain a first stage reaction product; (b) contacting the first stage reaction product with at least one other BL172 oligonucleotide to obtain a second stage reaction product, with the proviso that the other BL172 oligonucleotide is located 3′ to the BL172 oligonucleotides utilized in step (a) and is complementary to the first stage reaction product; and (c) detecting the second stage reaction product as an indication of the presence of a target BL172 polynucleotide in the test sample. The BL172 oligonucleotides selected as reagents in the method have at least 50% identity with a sequence selected from the group consisting of SEQUENCE ID NO 1, SEQUENCE ID NO 2, SEQUENCE ID NO 3, SEQUENCE ID NO 4, SEQUENCE ID NO 5, and fragments or complements thereof. Amplification may be performed by the polymerase chain reaction. The test sample can be reacted either directly or indirectly with a solid phase prior to performing the method, or prior to amplification, or prior to detection. The detection step also comprises utilizing a detectable label capable of generating a measurable signal; further, the detectable label can be attached to a solid phase. Test kits useful for detecting target BL172 polynucleotides in a test sample are also provided which comprise a container containing at least one BL172-specific polynucleotide selected from the group consisting of SEQUENCE ID NO 1, SEQUENCE ID NO 2, SEQUENCE ID NO 3, SEQUENCE ID NO 4, SEQUENCE ID NO 5, and fragments or complements thereof. These test kits further comprise containers with tools useful for collecting test samples (such as, for example, blood, urine, saliva and stool). Such tools include lancets and absorbent paper or cloth for collecting and stabilizing blood; swabs for collecting and stabilizing saliva; and cups for collecting and stabilizing urine or stool samples. Collection materials, such as papers, cloths, swabs, cups, and the like, may optionally be treated to avoid denaturation or irreversible adsorption of the sample. The collection materials also may be treated with or contain preservatives, stabilizers or antimicrobial agents to help maintain the integrity of the specimens.

Problems solved by technology

Currently, the best initial indication of early bladder cancer is the presence of microscopic hematuria which, if detected, may lead to the invasive and costly procedures of cystoscopy and cytology, procedures that are necessary for a definitive diagnosis.

Thus, use of hematuria as a marker for bladder cancer results in many unnecessary cystoscopic and cytological procedures. C. McNeil; J.

In addition, cytology, another mainstay of bladder cancer monitoring, is unreliable in detecting superficial, grade 1 tumors.

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