Method and kit to profile tumours by biomarker analyses including transcriptional factor assays

A technology of transcription factors and biomarkers, applied in the fields of biochemical equipment and methods, analytical materials, anti-tumor drugs, etc., can solve the problem of not providing tumor profiles and other problems

Inactive Publication Date: 2008-02-06
EPPENDORF ARRAY TECH SA
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0027] However, none of the above methods provide sufficient information to establish a tumor profile of a biological sample obtained from a patient
[0028] In particular, these documents do not provide comprehensive information on the presence and possible modification of the same protein that is a tumor biomarker, and more specifically, for tumor diagnosis and for enabling selection or rejection of available or experimental anti-inflammatory agents. Transcription Factors for Cancer Therapy

Method used

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  • Method and kit to profile tumours by biomarker analyses including transcriptional factor assays
  • Method and kit to profile tumours by biomarker analyses including transcriptional factor assays
  • Method and kit to profile tumours by biomarker analyses including transcriptional factor assays

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

2. Example 1: Method for Classifying Breast Tumor Responsiveness to Different Drugs

[0133] Two microarrays were spotted on glass slides: the first microarray consisted of triplicate spots of double-stranded DNA capture probes containing binding sites specific for ERα. The sequence of the sense strand is as follows: 5'-CAGGTCACAGTGACCTGATCAAAGTT-3'. The second microarray consisted of triplicate spots of protein capture probes corresponding to antibodies specific for Erα, ErbB1, ErbB2 and mTOR, respectively. A hybridization chamber was attached to a glass slide to physically separate the two microarrays.

[0134] The first microarray was contacted with protein extracts of breast tumor samples diluted in binding buffer consisting of Hepes buffer supplemented with salt, EDTA, glycerol, protease and phosphatase inhibitors. A second microarray was exposed to protein extracts of the same breast tumor samples diluted in MOPSO buffer supplemented with salts, detergents and proteas...

Embodiment 2

3. Example 2: Method of Analyzing Tumors for Tailored p53 Therapy

[0141] Each well of the 96-well plate was coated with different capture molecules: the first group of 5 wells was coated with p53 monoclonal antibody; the second group of 5 wells coated with streptavidin was coated with p53-specific Binding sites are coated with biotinylated dsDNA capture probes. The sequence of the sense strand is as follows: 5'-CTTGGACATGCCCGGGCATGTCCCTC-3'; the 5 wells of the third group were coated with the monoclonal antibody of Mdm2; the 5 wells of the fourth group were coated with the p53 as used in the first group Antibody coating.

[0142] Two wells of each set were exposed to binding buffer only ("blank") and the remaining 3 wells of each set were exposed to protein extracts of test samples diluted in binding buffer ("test"). Binding buffer for groups 1, 3 and 4 consisted of MOPSO buffer containing salts, detergents, proteins and protease inhibitors. The binding buffer used for g...

Embodiment 3

4. Example 3: Other tumor profiling

[0150] The inventors have also obtained other tumor profiling based on the method according to the invention, which allows the treatment of specific cancers.

a) Angiogenesis:

[0151] The growth of new vessels from preexisting vessels is considered an important event essential for tumor survival and growth. Anti-angiogenic therapies have thus been developed that target angiogenic tumor biomarkers such as the transcription factor HIF1α. The presence and DNA binding activity of HIF1α (monitored by signals #1 and #2 of the present invention) would indicate the use of anti-angiogenic molecules, such as the specific HIF1α inhibitor astatin. However, binding of p53 to HIF1α results in the inactivation of HIF1α. Thus monitoring the presence or absence of p53 via signal #3 and the p53-HIF1α interaction via signal #5 may not help give any precise information about the anti-angiogen (ie, the molecule used), but will enable the clinician Abando...

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Abstract

The present invention is related to a method and kit (or device) for the detection and / or the quantification of biomarkers related to tumourigenesis. Said method is advantageously used to propose or adapt an anti-tumoural therapeutic protocol to be administered to a subject. Furthermore, said method and kit (or device) are a technical platform for the identification of new compounds, which are preferably used at (a) specific step(s) of an anti-tumoural therapeutic protocol.

Description

field of invention [0001] The present invention relates to methods and kits (or devices) for the detection and / or quantification of biomarkers associated with tumorigenesis. [0002] The method is conveniently used to suggest or modify an antineoplastic treatment regimen to be administered to a subject. [0003] Furthermore, the methods and kits (or devices) are technological platforms for the identification of new compounds, which are preferably used in specific steps of anti-tumor treatment regimens. Background of the invention [0004] Despite continuous and combined anti-cancer efforts by the scientific and medical communities, a large proportion of the population in Western countries will suffer from and die from this disease. [0005] Once a tumor is detected, standard first-line treatment usually relies on a combination of chemotherapy and radiation therapy. Unfortunately, the success of this treatment regimen is largely limited by the onset of resistance, which is ...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68B01L3/00G01N33/574
CPCG01N33/574A61P35/00
Inventor V·曼弗鲁瓦J·勒马克勒
Owner EPPENDORF ARRAY TECH SA
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