Looking for breakthrough ideas for innovation challenges? Try Patsnap Eureka!

Treatment of Cancer WIth Dopamine Receptor Antagonists

a technology of dopamine receptor and dopamine receptor, which is applied in the direction of drug compositions, instruments, library screening, etc., can solve the problems that dopamine receptor antagonists at toxic concentrations to cancer cells have a relatively limited effect on normal stem cells, and achieve the effect of less expression

Inactive Publication Date: 2013-12-12
MCMASTER UNIV
View PDF0 Cites 10 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Benefits of technology

[0016]Also provided are methods for screening compounds for anti-cancer activity comprising identifying compounds that are dopamine receptor antagonists. In one embodiment, the anti-cancer activity is reduced proliferation of AML cells or monocytic cells. Optionally, the methods include identifying compounds that preferentially induce the differentiation of cancer stem cells relative to hematopoietic or normal stem cells.

Problems solved by technology

Furthermore, dopamine receptors antagonists at concentrations toxic to cancer cells have been found to have a relatively limited effect on normal stem cells such as hematopoietic stem cells.

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Treatment of Cancer WIth Dopamine Receptor Antagonists
  • Treatment of Cancer WIth Dopamine Receptor Antagonists
  • Treatment of Cancer WIth Dopamine Receptor Antagonists

Examples

Experimental program
Comparison scheme
Effect test

example 1

Thioridazine is Cytotoxic to Leukemic Cell Lines

[0078]The effect of Thioridazine on normalized cell number was evaluated in 3 leukemic cells lines: HL-60, MV4-11 and OCI-AML3. All three lines are leukemic cell lines. HL-60 was derived from promyelocytic AML whereas MV 4-11 and OCI-AML3 are representative of AML. Each compound was incubated with the cells for 72 h. The control was DMSO (ie the vehicle used for the compound) for 72 h. Each condition had three replicates.

[0079]As shown in FIG. 1, doses of 0.1 μM and 1 μM thioridazine had little effect on normalized cell number, while at 10 μM the normalized cell number was reduced to almost zero.

example 2

Differential Activity of Thioridazine on AML Blast-Forming Potential and Colony Forming Potential of Normal Stem Cells

[0080]The effects of thioridazine on blast formation in an AML cell line was compared to the effect of thioridazine on colony formation in normal human stem cells.

[0081]Normal HSCs and progenitors were sourced from either mobilized peripheral blood or umbilical cord blood of health patients. Primary AML cells were taken from patients diagnosed with AML. Both normal HSCs and primary AML cells were cultured under standard in vitro methocellulose assay conditions (see http: / / www.stemcell.com / en / Products / All-Products / MethoCult-H4434-Classic.aspx as well as Clinton Campbell et al. The human stem cell hierarchy is defined by a functional dependence on Mcl-1 for self-renewal capacity. Blood 116 (9) 1433-1442 (Jun. 4, 2010), hereby incorporated by reference) for at least 14 days before the number of colonies were recorded. As shown in FIG. 2, 10 μM thioridazine has a differe...

example 3

Chlorpromazine is Toxic to AML Cell Lines

[0083]The dopamine receptor antagonist and phenothiazine-related compound chlorpromazine was also investigated for effects on the AML cell lines HL-60, MV4-11 and OCI-AML3. Testing was performed as set out in Example 1. As shown in FIG. 4, 10 μM Chlorpromazine is toxic to AML cell lines.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

PropertyMeasurementUnit
timeaaaaaaaaaa
fluorescence activated cell sortingaaaaaaaaaa
resistanceaaaaaaaaaa
Login to View More

Abstract

Described are methods of treating a cancer comprising administering to a subject in need thereof an effective amount of a dopamine receptor (DR) antagonist. The DR antagonist may be a phenothiazine derivative, such as thioridazine or chlorpromazine. Optionally, the cancer is acute myeloid leukemia. Also described are methods for identifying subjects with cancer, methods for providing a prognosis for a subjects with cancer and / or subjects likely to be responsive to therapy with DR receptor antagonists. Methods for identifying cancer stem cells and chemotherapeutic compounds that are DR receptor antagonists as also provided.

Description

RELATED APPLICATIONS[0001]This application is a 35 USC 371 National Stage Entry of PCT / CA2012 / 000175 filed on Feb. 28, 2012, which claims the benefit of U.S. Provisional Application No. 61 / 447,362, filed on Feb. 28, 2011 each of which is incorporated herein by reference in its entirety.FIELD OF THE DISCLOSURE[0002]The disclosure relates to methods for the prognosis or treatment of cancer and particularly to methods for the prognosis or treatment of acute myeloid leukemia (AML) that target dopamine receptors.BACKGROUND OF THE DISCLOSURE[0003]Increasing evidence suggests that cancer / tumor development is due to a rare population of cells, termed cancer stem cells (CSCs) (Dick, 2009; Jordan, 2009; Reya et al., 2001) that are uniquely able to initiate and sustain disease. In addition, experimental evidence indicates that conventional chemotherapeutics, characterized by their ability to inhibit cell proliferation of cancer cell lines (Shoemaker, 2006) or reduce tumor burden in murine mode...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/5415C12Q1/68G01N33/50G01N33/574
CPCA61K31/5415G01N33/57492C12Q1/6886G01N33/5011A61P15/00A61P35/00A61P35/02G01N33/57426G01N33/9413G01N2500/10G01N2800/52G01N2800/56G01N33/574G01N33/57496
Inventor BHATIA, MICKIESACHLOS, ELEFTHERIOSRISUENO, RUTH MUNOZ
Owner MCMASTER UNIV
Who we serve
  • R&D Engineer
  • R&D Manager
  • IP Professional
Why Patsnap Eureka
  • Industry Leading Data Capabilities
  • Powerful AI technology
  • Patent DNA Extraction
Social media
Patsnap Eureka Blog
Learn More
PatSnap group products

Browse by: Latest US Patents, China's latest patents, Technical Efficacy Thesaurus, Application Domain, Technology Topic, Popular Technical Reports.

© 2024 PatSnap. All rights reserved.Legal|Privacy policy|Modern Slavery Act Transparency Statement|Sitemap|About US| Contact US: help@patsnap.com