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Method for diagnosing, prognosing and treating glioma

A technology for glioma and therapy, applied in biochemical equipment and methods, anti-tumor drugs, pharmaceutical formulations, etc., to solve problems such as inability to reproduce findings

Inactive Publication Date: 2008-12-31
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Findings seen with DLL3 could not be reproduced when DLL3 was replaced with BMP2 in a two-gene model

Method used

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  • Method for diagnosing, prognosing and treating glioma
  • Method for diagnosing, prognosing and treating glioma
  • Method for diagnosing, prognosing and treating glioma

Examples

Experimental program
Comparison scheme
Effect test

preparation example Construction

[1153] Preparation of H.GDM polypeptide

[1154] The following description mainly relates to the production of GDM polypeptides by culturing cells transformed or transfected with vectors comprising nucleic acids encoding the antibodies, polypeptides and oligopeptides. It is of course contemplated that alternative methods known in the art may be employed to prepare the antibodies, polypeptides and oligopeptides. For example, solid-phase techniques can be used to generate suitable amino acid sequences, or portions thereof, by direct peptide synthesis (see, e.g., Stewart et al., Solid-Phase Peptide Synthesis, W.H. Freeman Co., San Francisco, CA (1969); Merrifield, J.Am. Chem. Soc., 85:2149-2154 (1963)). In vitro protein synthesis can be performed using manual techniques or automation. For example, automated synthesis can be accomplished using an Applied Biosystems Peptide Synthesizer (Foster City, CA) according to the manufacturer's instructions. Portions of the antibody, po...

Embodiment 1

[1250] Experimental protocol

[1251] Tumor samples and patient characteristics

[1252] Figure 8A A summary of all tumor cases studied is included in . For survival analysis, 3 expression profiling datasets were analyzed. We obtained frozen tissue samples from 76 cases of MDA, RNA from 39 cases of UCSF (Nigro et al., Cancer Res. 65:1678-1686 (2005), and data from a previously published study at UCLA (Freije et al., supra) Cases analyzed in the first two datasets met the following criteria: Fresh-frozen samples were obtained from patients (age >21 years) who had not previously received radiotherapy or chemotherapy at the time of initial surgical resection. At least 2 years after surgery or Clinical follow-up information was available until death. These retrospective laboratory studies in UCSF and MDA were approved by the Institutional Review Board / Human Subjects. Cases were graded as AA or GBM according to WHO criteria , and all tissue sections were examined by a neuropat...

Embodiment 2

[1300] Example 2: Microarray Analysis to Detect Upregulation of GDM Polypeptides in Cancerous Glioma Tumors

[1301] Nucleic acid microarrays, often containing thousands of gene sequences, can be used to identify genes that are differentially expressed in diseased tissues relative to their normal counterparts. Using nucleic acid microarrays, test and control mRNA samples from test and control tissue samples are reverse transcribed and labeled to generate cDNA probes. Then, the cDNA probes are hybridized to the nucleic acid array immobilized on the solid support. An array is set up such that the sequence and position of each member of the array is known. For example, genes known to be expressed in certain disease states can be selected and arrayed on a solid support. Hybridization of a labeled probe to a particular array member indicates that the sample from which the probe was derived expresses the gene. One or more genes overexpressed in disease tissue are identified if th...

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PUM

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Abstract

The invention provides generally a method of monitoring, diagnosing, prognosing and treating glioma. Specifically, the invention provides for three (3) prognostic subclasses of glioma, which are differentially associated with activation of the akt and notch signaling pathways. Tumor displaying neural or proneural PN lineage markers (including notch pathway elements) show longer median patient survival, while the two remaining tumor markers Prolif and Mes are associated with shortened survival. Tumors classified in this manner may also be treated with the appropriate PN- Prolif- or Mes- therapeutic corresponding to the subclassification in combination with anti-mitotic agents, anti-angiogenic agents, Akt antagonists, and neural differentiation agents. Alternatively, the invention also provides for method of prognosing and diagnosing glioma with a two- gene model based on the expression levels of PTEN and DLL3.

Description

[0001] related application [0002] This application claims priority under 35 U.S.C. §119(e) to USSN 60 / 750,944, filed December 16, 2005. field of invention [0003] The present invention is directed to methods of diagnosis, prognosis and treatment of cancer, in particular glioma. Background of the invention [0004] Malignancy (cancer) is the second leading cause of death in the United States after heart disease (Boring et al., CA Cancel J. Clin. 43:7 (1993)). Cancer is characterized by an increased number of abnormal or neoplastic cells derived from normal tissue that proliferate to form a tumor mass, invade adjacent tissues, and give rise to malignant cells that eventually spread locally via the blood or lymphatic system Lymph nodes and spread to distant places through a process called metastasis. In the cancerous state, cells proliferate under conditions where normal cells would not grow. Cancer manifests itself in many forms, characterized by varying degrees of invas...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68
CPCA61K45/06C12Q1/6886C12Q2600/106C12Q2600/112C12Q2600/118C12Q2600/136C12Q2600/158G01N33/57407G01N2500/00A61P35/00A61P43/00A61K45/00
Inventor 威廉·F·福里斯特萨米尔·卡班达海迪·菲利普斯托马斯·吴
Owner GENENTECH INC
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