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JAB1 as a prognostic marker and a therapeutic target for human cancer

Inactive Publication Date: 2005-03-31
BOARD OF RGT THE UNIV OF TEXAS SYST
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

"The patent text describes a protein called JAB1 that is involved in the degradation of another protein called p27. JAB1 is found to be overexpressed in cancer cells and is associated with aggressive cancer behavior. The ratio of JAB1 to p27 is a novel indicator of cancer progression and can be used for diagnosis and therapy. The patent also describes methods for detecting and altering JAB1 expression in cells. Overall, the patent provides a novel approach for cancer diagnosis and treatment."

Problems solved by technology

However, overexpression of HER-2 protein via gene amplification of the HER-2 gene has been found to date in only approximately 25% of breast cancer patients.

Method used

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  • JAB1 as a prognostic marker and a therapeutic target for human cancer
  • JAB1 as a prognostic marker and a therapeutic target for human cancer
  • JAB1 as a prognostic marker and a therapeutic target for human cancer

Examples

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Effect test

example 1

JAB1 and p27 Expression Profiles in Breast Tumors

[0236] Breast tumor samples were obtained from a study group of 53 women with invasive breast carcinoma. The women were 35 to 90 years old and had a mean age of 63.2±13.3 years and a median age of 65. None of the women had a family history of breast cancer. The patients had not undergone any chemotherapy or radiotherapy before surgery. Patient selection was based on the availability of archived paraffin blocks for immunohistochemical studies, which are described below. Six cases (11%) were stage I, 28 (53%) were stage II, 13 (25%) were stage III, and 6 (11%) were stage IV. Five tumors (9%) were grade 1, 29 (55%) were grade 2, and 19 (36%) were grade 3. The tumors were surgically staged according to the American Joint Committee on Cancer's tumor-nodes-metastasis system and graded according to the Nottingham modification of the Bloom-Richardson system. All of tumors excepted for one had a maximum diameter larger than 1 cm. 47 of the br...

example 2

Survival Rates

[0244] The available clinical data on the survival rate of the female patients with breast carcinomas discussed above was examined and is summarized in FIGS. 1A and 1B. FIG. 1B shows that a significant difference in overall survival rates was found between women with breast tumors that had a detected level of JAB1 protein and women with breast tumors that did not have a detected level of JAB1 protein. As defined herein, the “5-year overall survival rate” is the percentage of surviving patients five years after the patients' treatment or cancer diagnosis. The 5-year survival rate includes patients that have experienced relapses or cancer progression. After an average of 70 months, there was a 69% 5-year overall survival rate among the women with breast tumors that had a detected level of JAB1 protein, while there was a 100% 5-year overall survival rate among the women with breast tumors that did not have a detected level of JAB1 protein. In addition, there was also a d...

example 3

High JAB1 Expression is Directly Proportional to HER-2 Expression

[0246] JAB1 protein levels were examined in eight pairs of non-cancerous and cancerous breast tissue samples from eight of the patients of Example 1. The samples were obtained in a biopsy. The samples were washed twice in cold 1×PBS that was diluted from 10×PBS, (Catalog #M6505, available from Fisher) and lysed at 4° C. in lysis buffer (25 mM Hepes, pH 7.7, 400 mM NaCl, 0.5% Triton X-100, 1.5 mM MgCl2, 2 mM EDTA, 2 mM DTT, 0.1 mM PMSF, protease inhibitors [including the following protease inhibitors at the following final concentrations: leupeptin 10 μg / ml, peptstatin 2 μg / ml, antipain 50 μg / ml, aprotinin 2 μg / ml, chymostatin 20 μg / ml, and benzamidine 2 μg / ml] and phosphatase inhibitors [including the following phosphatase inhibitors at the following final concentrations: 50 mM NaF, 0.1 mM Na3VO4, and 20 mM P-glycerophosphate]). Aliquots of cell lysates containing about 70 mg of total protein were run on 10-12% SDS-PA...

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Abstract

Methods of diagnosing and prognosticating the development of human cancers, such as breast cancer, colon cancer, and pancreatic cancer, are provided. The diagnostic and prognostic methods include the detection and / or quantifying of the amount of expression of JAB1 in human cells, particularly in relation to the amount of p27 or c-Jun. In addition, methods for reducing the expression of JAB1 protein in cells and inhibiting its interaction with p27 or c-Jun, for example, are provided.

Description

CROSS-REFERENCE TO RELATED APPLICATIONS [0001] This application claims priority to U.S. Provisional Patent Application 60 / 474,048 filed May 29, 2003, which is incorporated by reference herein in its entirety.STATEMENT REGARDING FEDERALLY SPONSORED RESEARCH OR DEVELOPMENT [0002] This invention was made with U.S. Government support from the National Cancer Institute / National Institutes of Health Grant number 1RO1CA90853-01A1. The U.S. Government may have certain rights in this invention.FIELD OF THE INVENTION [0003] The present invention relates generally to methods of diagnosing, prognosticating and treating human cancers, as well as assaying for therapeutic agents for treating human cancers. More specifically, the invention regards JUN activation binding protein 1 (JAB1)-associated embodiments for cancer diagnosis and therapy, such as breast cancer. BACKGROUND OF THE INVENTION [0004] Cancer can be caused by a wide variety of genetic abnormalities, such as hereditary or non-hereditar...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): C07K14/705C12Q1/68G01N33/574
CPCC07K14/47G01N2500/02C12Q2600/106C12Q2600/112C12Q2600/118C12Q2600/136G01N33/57415G01N33/57419G01N33/57423G01N33/57426G01N33/57434G01N33/57438G01N33/57449G01N33/57496G01N2333/4704C12Q1/6886
Inventor CLARET, FRANCOIS
Owner BOARD OF RGT THE UNIV OF TEXAS SYST
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