US 2011/0300232 A1Published application

EFFECTS OF NITRIC OXIDE (NO) AND iNOS ON EXPRESSION AND SIGNAL TRANSDUCTION IN CANCER AND ITS USE IN DRUG DISCOVERY AND CANCER THERAPY DESIGN

OwnerPooncharas Tipgunlakantinventor

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Abstract

Nitric Oxide (NO) acts as double-edged sword, which induces and prevents cell death, depending on various factors. The mechanism for the NO regulation of cells is not fully understood. The present invention provides experiment design methods and therapy design methods leveraging viable hypothesis supported by current research findings. This invention determines the effects of NO by controlling the majority parameters such as the steady-state concentration of NO, duration of NO exposure and the local level of oxygen. The experiment designs are structured to improve understanding of NO regulation of cells, and further can be directly adapted for therapy design. The invention directs these experiment design and therapy design methods to the study and treatment of cancer. In an application, the effects of exogenous NO on inducible Nitric Oxide Synthase (iNOS) expression and signal transduction in ovarian cancer is applied to drug discovery and therapy design for ovarian and other cancers.

Claims19

Dependent claims

A method for designing experiments for the study of Nitric Oxide (NO) in the control of cell death for use in cancer therapies, the method comprising:

establishing that long term exposure of cells to low concentration of exogenous nitric oxide causes a negative feedback mechanism to induce down-regulation of inducible Nitric Oxide Synthase (iNOS) by choosing a first NO donor that can produce a relatively low level of NO concentration over a relatively long NO-production half-life, applying that NO donor to a cell culture media at selected time points, measuring the levels of iNOS concentration and NO concentration to produce first measurements, and recording first data corresponding to the first measurements;
establishing that high concentration of exogenous NO does not affect to the expression of iNOS but instead will cause apoptosis of cells by choosing a second NO donor that can produce a relatively high level of NO concentration over a relatively short NO-production half-life, applying that NO donor to a cell culture media at selected time points, measuring the levels of iNOS and NO concentration to produce second measurements, and recording second data corresponding to the second measurements;
and
establishing that for a given level of NO concentration, the expression of iNOS down-regulates more in hypoxic conditions than in normal oxygen conditions by choosing a third NO donor that generates a relatively low concentration of NO, applying that NO donor to a cell culture media at selected time points, measuring the levels of iNOS and NO concentration to produce third measurements, recording third data corresponding to the third measurements, and comparing the iNOS response between normal and hypoxic environments,
wherein at least one of the first data, second data, and third data are used to create a cancer therapy that manipulates exogenous NO in a hypoxic area of cancer cells.

2 more elements

Dependencies are inferred from the claim text.

Facts

Application: 13/155,370Filed 7 Jun 2011
Priority: 8 Jun 2010
Published: 8 Dec 2011
Term ends: Not estimatedThe source records don’t support an estimate.

Classification11 codes

A61K 31/04
Medicinal preparations containing organic active ingredients: nitro compounds
A61K 31/15
Amines: oximes ; Hydrazines ; Hydrazones ; Imines
A61K 31/19
Acids; Anhydrides, halides or salts thereof, e.g. sulfur acids, imidic, hydrazonic or hydroximic acids: carboxylic acids, e.g. valproic acid
A61K 31/196
Having an amino group: the amino group being directly attached to a ring, e.g. anthranilic acid, mefenamic acid, diclofenac, chlorambucil