Methods of diagnosing and treating PARP-mediated diseases

A disease-mediated technology, applied in the direction of biochemical devices and methods, diseases, metabolic diseases, etc., that can address the incidence of therapy resistance and its prevention Insufficiently studied, unsuccessfully detailed delineation of cancer formation Different known Molecular pathway interactions and other issues

Inactive Publication Date: 2011-03-30
BIPAR SCI INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

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Problems solved by technology

[0014] However, studies to date have not succeeded in delineating in detail the interplay of different known molecular pathways in cancer development
Furthermore, despite substantial resources devoted to monotherapies and other combination therapies against a large number of cancer targets, the incidence of resistance to these therapies and its prevention are understudied

Method used

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  • Methods of diagnosing and treating PARP-mediated diseases
  • Methods of diagnosing and treating PARP-mediated diseases
  • Methods of diagnosing and treating PARP-mediated diseases

Examples

Experimental program
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Embodiment 1

[0535] Gene array testing has been widely used to monitor mRNA expression in many biomedical research fields. The high-density oligonucleotide array technology allows researchers to monitor tens of thousands of genes in a single hybridization experiment, because they are expressed differently in tissues and cells. The expression profile of mRNA molecules of genes is obtained by combining the intensity information from the probes in the probe set, which consists of 11-20 probe pairs of oligonucleotides of 25 bp in length, to inquire about the difference in genes Part of the sequence.

[0536] Affymetrix Human Genome genechips (45,000 gene transcripts covering 28,473 UniGene clusters) were used to evaluate gene expression. Approximately 5 μg of total RNA from the sample was labeled using a high-yield transcription labeling kit, and the labeled RNA was hybridized, washed, and scanned (according to the manufacturer's instructions) (Affymetrix, Inc., Santa Clara, CA). Affymetrix Mic...

Embodiment 2

[0538] Up-regulation of PARP1mRNA in normal and tumor tissues

[0539] Research design and materials and methods

[0540] Tissue samples: Normal and cancer tissue samples were collected in the United States or the United Kingdom. The samples are collected as part of normal surgical procedures and are quickly frozen within 30 minutes of resection. The samples are transported at -80°C and stored at -170 to -196°C in the vapor phase of liquid nitrogen until processing. Perform medical pathological examination and confirmation of samples to be analyzed. Combined with the initial diagnosis report, observe the H&E-stained slides obtained from the adjacent part of the tissue, and classify the samples according to the diagnosis category. During the examination of the slide by the pathologist, the visually estimated percentage of tissue involved in the tumor was recorded, and the fraction of malignant nucleated cells was noted. Auxiliary studies such as ER / PR and Her-2 / neu expression st...

Embodiment 3

[0555] Co-expression of PARP1 Mrna and other targets in normal and cancer tissues

[0556] The PARP1 gene is represented by a single probe set with the identifier "208644_at" on the HG-U133A array. Other genes, such as BRCA1, BRCA2, RAD51, MRE11, p53, PARP2 and Mucin 16 are represented by their respective information probe sets in the HG-U133A / B array set. The probe sets corresponding to the 7 genes in the analysis of ovarian cancer samples are listed in Table XXXIII.

[0557] Table XXXIII: Comparison genes and their corresponding HG-U133A / B probe set ID

[0558] Gene symbol

title

Fragment name

BRCA1

Breast cancer 1, early onset

204531_s_at

BRCA2

Breast cancer 2, early onset

214727_at

MRE11A

MRE11 meiotic recombination 11 homolog A (Saccharomyces cerevisiae)

205395_s_at, 242456

MUC16

Mucin 16, cell surface association

220196_at

PARP2

Poly(ADP ribose) polymerase family, member 7

204752x_at, 214086_s_at, 215773_x_at

RAD51

RAD51 homolog (RecA homolog, Esche...

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Abstract

Disclosed are methods of identifying a disease treatable with modulators of differentially expressed genes in a disease, including at least PARP modulators, by identifying the level of expression of differentially expressed genes, including at least PARP, in a plurality of samples from a population, making a decision regarding identifying the disease treatable by modulators to the differentially expressed genes wherein the decision is made based on the level of expression of the differentially expressed genes. The method can further comprise treating the disease in a subject population with modulators of identified differentially expressed genes. The methods relate to identifying up-regulated expression of identified differentially-expressed genes in a disease and making a decision regarding the treatment of the disease. The level of expression of the differentially expressed genes in a disease can also help in determining the efficacy of the treatment with modulators to the differentially expressed genes.

Description

[0001] Cross references to related applications [0002] This application claims priority for US Provisional Application 61 / 026,077, filed on February 4, 2008, entitled "Methods for Diagnosing and Treating PARP-Mediated Diseases", which is incorporated herein by reference in its entirety. Background of the invention [0003] The etiology of cancer and other diseases involves complex interactions between cytokines, including cellular enzyme receptors and other downstream intracellular factors that conduct signals through intracellular signaling networks. Growth factor receptors are considered to be important factors in cancer physiology, and they play an important role in the progression and maintenance of malignant phenotypes (Jones et al., 2006, Endocrine-Rel. Cancer, 13: S45-S51). For example, it has been shown that the expression of epidermal growth factor receptor (EGFR), a tyrosine kinase receptor, is required for the formation of adenomas and tumors in bowel tumors, and the s...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68C12N15/11C07H21/00A61K48/00
CPCC12Q1/6886C12Q2600/112G01N2800/52C12Q2600/16C12Q2600/136C12Q2600/158C12Q2600/106A61P1/04A61P1/18A61P11/00A61P13/02A61P15/00A61P19/02A61P25/00A61P25/16A61P25/18A61P25/28A61P25/36A61P29/00A61P3/04A61P31/12A61P31/14A61P31/18A61P31/20A61P35/00A61P35/02A61P5/00A61P7/00A61P9/00A61P9/10A61P3/10Y02A90/10G16B99/00A61K48/00
Inventor 瓦莱里亚·S·奥索夫斯卡亚巴里·M·舍曼
Owner BIPAR SCI INC
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