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Methods and compositions for modulating prostasin

a prostasin and modulator technology, applied in the field of molecular biology and growth factor regulation, can solve the problems of prostasin expression being significantly down-regulated in high-grade or hormone-refractory prostate tumors, loss, and pn-1 not forming a stable complex with prostasin, and achieve the effect of effectively treating said tumor

Inactive Publication Date: 2010-05-06
GENENTECH INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0026]In one aspect, the invention provides a method of therapeutically treating a mammal having a cancerous tumor comprising a cell that expresses prostasin and / or HAI-1 / 1B, said method comprising administering to said mammal an effective amount of an antagonist of the invention, thereby effectively treating said mammal.
[0029]In one aspect, the invention provides a method of treating a tumor in a mammal, wherein the growth of said tumor is at least in part dependent upon activity of prostasin and / or HAI-1 / 1B, or both, said method comprising contacting said cell with an effective amount of an antagonist of the invention, thereby effectively treating said tumor.

Problems solved by technology

However, prostasin expression is significantly down-regulated in high-grade or hormone-refractory prostate tumors and is lost in highly invasive human and mouse prostate cancer cell lines (Chen, Hodge et al.
However, PN-1 was not found forming a stable complex with prostasin in the extracts of some prostasin abundant tissues such as prostate, lung and salivary glands (Chen, Skinner et al.

Method used

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  • Methods and compositions for modulating prostasin
  • Methods and compositions for modulating prostasin
  • Methods and compositions for modulating prostasin

Examples

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examples

[0337]Reagents—sHAI-1B and its mutants, sHAI-1B(R260A) and sHAI-1B(K401A), were expressed and purified as previously described (Kirchhofer, Peek et al. 2003). KD1 containing amino acids Thr246-Val303 of HAI-1B precursor was expressed in E. coli and purified as described (Shia, Stamos et al. 2004). Aprotinin-agarose was purchased from Sigma, aprotinin from Roche (Indianapolis, Ind.), chromogenic substrate 52765 from DiaPharma Group, Inc. (West Chester, Ohio), OVCAR3 cell line from ATCC (Manassas, Va.), non-immunized mouse IgG from Jackson ImmunoResearch Laboratories, Inc. (West Grove, Pa.). Alzheimer's amyloid B protein precursor inhibitor (APPI) and KALI-DY (Dennis, Herzka et al. 1995) (Genentech, Inc., South San Francisco, Calif., USA).

Screening for protease inhibitors co-expressed with prostasin—The Genesis Enterprise System™ database (Gene Logic, Inc., Gaithersburg, Md.) containing gene expression signatures from over 8000 clinical samples from various normal and disease conditio...

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Abstract

The invention provides methods and compositions related to modulating prostasin.

Description

RELATED APPLICATIONS[0001]This application is a divisional to U.S. patent application Ser. No. 11 / 359,865, filed Feb. 22, 2006, which claims priority under 35 USC 119(e) to provisional application No. 60 / 654,918, filed Feb. 22, 2005, the contents of which are incorporated herein by reference.TECHNICAL FIELD[0002]The present invention relates generally to the fields of molecular biology and growth factor regulation. More specifically, the invention concerns modulators of prostasin, and uses of said modulators.REFERENCE TO SEQUENCE LISTING SUBMITTED IN ELECTRONIC FORM[0003]This application is accompanied by a computer readable copy of the Sequence Listing provided in an ASCII .txt file, electronically filed herewith, which was created on Jan. 4, 2010, is titled P221R1D1SequenceListing(Rev).txt and contains 4,803 bytes, the contents of which are incorporated herein by reference. The sequence listing includes the sequences identified as SEQ ID NOs: 1-9.BACKGROUND[0004]Prostasin is a gly...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K38/16A61P35/00
CPCC12Q1/37G01N33/573G01N33/57434G01N2333/96433G01N2500/00A61P35/00
Inventor FAN, BINKIRCHHOFER, DANIEL K.
Owner GENENTECH INC
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