Methods and compositions useful for diagnosis, staging, and treatment of cancers and tumors

• US 7,078,180 B2
• Filed: 08/30/2002
• Issued: 07/18/2006
• Est. Priority Date: 09/05/2001
• Status: Active Grant

• Current Assignee: Children's Hospital of Philadelphia (Children's Hospital of Philadelphia Foundation)
• Original Assignee: Children's Hospital of Philadelphia (Children's Hospital of Philadelphia Foundation)
• Inventors: Genetta, Thomas
• Primary Examiner(s): HUFF, SHEELA JITENDRA
• Application Number:
  US10/232,561
• Publication Number:
  US 20030119772A1
• Time in Patent Office: 1,418 Days
• Field of Search: 435/975, 435/7.2, 435/7.23, 530/350, 536/23.1
• US Class Current: 435/7.23
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: C12Q 1/6886 for cancer immunoassay for cancer G01N33/574
• CPC Class Codes: C12Q 2600/158 Expression markers
• CPC Class Codes: G01N 2333/4704 Inhibitors; Supressors
• CPC Class Codes: G01N 33/57407 Specifically defined cancers
• CPC Class Codes: G01N 33/57484 involving compounds serving as markers for tumor, cancer, neoplasia, e.g. cellular determinants, receptors, heat shock/stress proteins, A-protein, oligosaccharides, metabolites
• CPC Class Codes: Y10S 435/975 Kit

Abstract

Methods, compositions and kits which employ one or more ZEB specific detection reagents for detection and localization of ZEB associated molecules in tumor cells are disclosed. Also provided are methods for determining stage and progression of cancer in a mammal based on alterations in ZEB expression levels and subcellular localization. Also provided are methods for treating a cancer in a mammal by modulating ZEB expression levels and activity.

Claims

1. A method of diagnosing a cancer or a tumor in a mammal, said method comprising

a) obtaining a biological sample from said mammal;

b) contacting said sample with a composition comprising one or more ZEB specific detection reagent in an amount effective to permit detection and quantitation of a ZEB polypeptide, if present, in said sample, wherein said ZEB polypeptide is selected from the group consisting of SEQ ID NO;

10, the amino acid sequence encoded by nucleotides 2537 to 3473 of SEQ ID NO;

9, and the amino acid sequence encoded by nucleotides 481 to 1132 of SEQ ID NO;

9;

c) determining from b) one or more of the amount and the sub-cellular location of said ZEB polypeptide; and

d) determining from c) altered expression levels and/or localization of said ZEB polypeptide relative to normal control samples, thereby diagnosing a cancer or a tumor in said mammal.

2. A method as claimed in claim 1, wherein said cancer is of epithelial origin.

3. A method as claimed in claim 1, wherein said cancer is selected from the group consisting of melanoma, stomach, prostate, ovary, colon or breast cancer.

4. A kit for diagnosing and/or staging a tumor in a mammal, said kit comprising:

a) a container for storing a biological sample obtained from said mammal, said sample comprising cells or tissues;

b) a normal control biological sample for comparison to the sample obtained said mammal;

c) a composition comprising one or more ZEB-specific detection reagents in an amount effective to permit detection of a ZEB polypeptide if present, in said sample, wherein said ZEB polypeptide is selected from the group consisting of SEQ ID NO;

10, the amino acid sequence encoded by nucleotides 2537 to 3473 of SEQ ID NO;

9, and the amino acid sequence encoded by nucleotides 481 to 1132 of SEQ ID NO;

9; and

d) an instructional material setting forth a protocol suitable for use in detection and quantifying said ZEB polypeptide.

5. A kit as claimed in claim 4, wherein said ZEB-specific detection reagent is selected from the group consisting of antibodies or fragments thereof which have specific binding for said ZEB polypeptide.