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Methods for Diagnosis and Treatment of Endometrial Cancer

a technology for endometrial cancer and diagnosis, applied in the field of endometrial cancer detection and treatment, can solve the problems of heterogeneity in this population, low predictive power, and risk of recurrence and death, and achieve the effect of reducing the surface expression of integrins and/or fibronectin

Inactive Publication Date: 2010-08-05
MEMORIAL SLOAN KETTERING CANCER CENT +1
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0020]In one embodiment, a method of treating endometrial cancer in a subject in need thereof is disclosed including administering a therapeutically effect amount of a pharmaceutical composition comprising a candidate compound identified by determining the level of endothelial membrane protein 2 (EMP2) expression in the cultured tissue or cells at a first time point, contacting the cultured tissue or cells with a candidate compound, determining the level of EMP2 expression into the cultured tissue or cells subsequent to compound contact, and comparing the levels of EMP2 before and after compound contact, where a change in the amount of binding after compound contact correlates with an agent induced alteration in the level of EMP2, and where the compound inhibits EMP2 expression, thereby modulating the regulation of GPI-lipid rafts and / or caveolae. In a related aspect, the modulation decreases surface expression of integrins and / or fibronectin.

Problems solved by technology

Premalignancy (atypical hyperplasia) is poorly understood, and risk of recurrence and death is currently only stratafiable by grade and stage parameters.
However, such findings are not highly predictive, indicating heterogeneity in this population with regard to malignant potential (e.g., a Pap test is helpful but undependable, since 30-40% of smears yield false-negative results).

Method used

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  • Methods for Diagnosis and Treatment of Endometrial Cancer
  • Methods for Diagnosis and Treatment of Endometrial Cancer
  • Methods for Diagnosis and Treatment of Endometrial Cancer

Examples

Experimental program
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example 1

[0155]EMP2 is spatially and temporally regulated during the window of implantation in the endometrium.

[0156]EMP2, which is highly expressed in the uterus, translocates from an intracellular location to the apical surface of the endometrial epithelium during implantation in mice (FIG. 1).

[0157]EMP2 expression is regulated in part by steroid sex hormones.

[0158]Normal endometrium is a dynamic organ, with a phenotype that alters with the menstrual cycle. Simply, this can be described as an interplay between estrogen during the proliferative phase and progesterone during the secretory phase (Mutter et al., Gynecol Oncol (2001) 83:177-185). First, FIG. 1 shows that EMP2 is temporally regulated in mice. Similarly in humans, EMP2 expression is upregulated in secretory endometrium compared to the proliferative phase (FIG. 2). This data suggests that EMP2 is in part regulated by progesterone. To support this conclusion, human and mouse promoters were analyzed using the Genomatrix MatInspector...

example 2

Phage Display Generated Antibodies

[0179]Phage display, first established by Smith et al in 1985, has provided an in vitro immune system which can be used to create high affinity antibodies to virtually any antigens with a bare minimal recognition region (Bradbury, A. R. & Marks, J. D., Immunol Methods (2004) 290:29-49; Marks, J. D. & Bradbury, A., Methods Mol Biol (2004) 248:161-76; Pavlik, P. et al., Hum Antibodies (2003) 12:99-112; Persic, L. et al., FEBS Lett (1999) 443:112-6; Smith, G. P., Science (1985) 228:1315-7). Selection of antibody using phage antibody libraries with filamentous phase and phagemids mimics humoral immune system that lack cell-mediated responses. Thus, generation of purified antibodies with affinities comparable to ones made by conventional hybridoma technology can be achieved without complications such as self-tolerance, T cell help and antigen presentation (Bradbury, A. R. & Marks, J. D., J Immunol Methods (2004) 290:29-49; Pavlik, P. et al., Hum Antibodi...

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Abstract

The present invention discloses methods of using endothelial membrane protein 2 (EMP2) as a biomarker for stratification of endometrial premalignancy, diagnosing, staging and imaging of endometrial neoplasia. Further, methods for identifying pharmaceutical / therapeutic modalities are described, including compositions which modulate glycolipid-enriched lipid raft microdomains (GEMs).

Description

RELATED APPLICATION[0001]This application claims priority under 35 U.S.C. §119(e) to U.S. Provisional Application Ser. No. 60 / 657,607 filed Feb. 28, 2005, herein incorporated by reference in its entirety.STATEMENT OF GOVERNMENT SUPPORT[0002]This invention was made in part with government support under Grant No. HD048540-01 awarded by the National Institutes of Health. The government has certain rights in this invention.FIELD OF THE INVENTION[0003]This invention relates in general to detecting and treating cancers and more specifically to detecting and treating endometrial cancer (EC).BACKGROUND INFORMATION[0004]Endometrial carcinoma (EC), the most common of the gynecological malignancies, has 39,000 new cases and 6,500 deaths yearly. Premalignancy (atypical hyperplasia) is poorly understood, and risk of recurrence and death is currently only stratafiable by grade and stage parameters.[0005]Preliminary treatment for EC is surgical excision. However, recurrence is significant, and che...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K33/24C12Q1/68G01N33/53A61K31/4355A61K31/56A61K31/7088A61P35/00
CPCC12Q1/6886C12Q2600/118C12Q2600/136G01N33/57442G01N33/57407G01N2500/02G01N2500/10C12Q2600/158A61P35/00
Inventor BRAUN, JONATHANWADEHRA, MADHURINATARAJAN, SATHIMASOSLOW, ROBERT
Owner MEMORIAL SLOAN KETTERING CANCER CENT
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