Official websites use .gov

A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS

A lock ( 🔒 ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

Need Help

PRECLINICAL TESTING OF GALECTIN-3C FOR MULTIPLE MYELOMA

Award Number: R43CA135862
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 09/15/2008
PERIOD OF PERFORMANCE END DATE: 08/31/2011

Group Awards By:

View Award Description

PRECLINICAL TESTING OF GALECTIN-3C FOR MULTIPLE MYELOMA - DESCRIPTION (provided by applicant): The overall goal is development of a novel human protein, Galectin-3C, as a treatment for multiple myeloma (MM) that can be given with other agents to increase the percentage of patients who are responsive to therapy, and the survival rate. MM is rarely curable despite the introduction of new therapeutic regimens and more efficacious treatments are sorely needed. The 10-year survival rate has recently increased, but is still just 17.4%. Current therapeutic agents for MM including dexamethasone, thalidomide, and bortezomib are thought to act partially through induction of apoptosis. Galectin-3C contains the carbohydrate recognition domain of Galectin-3 but lacks its N-terminal domain that functions in multimerization. Galectin-3C acts as a dominant negative inhibitor of Galectin-3 by binding to the same carbohydrate ligands but not multimerizing. Previously, we showed that Galectin-3C reduced the growth and metastasis of tumors in a mouse model of human breast cancer. Our preliminary data indicate that Galectin-3C can induce or facilitate apoptosis mediated by anticancer agents such as dexamethasone in multiple myeloma and other types of cancer cells. The Specific Aims of the Phase I research are as follows: Aim #1. To determine the ability of Galectin-3C to inhibit growth of MM cells from patients and human cell lines and to provide evidence of the mechanism of action and potential biomarkers. The effect of GAL3C on proliferation and apoptosis of MM cell lines, and patient cells will be assessed. The CD138negative MM cells that are postulated to possess the tumor-initiating and maintaining characteristics of cancer stem cells will be isolated and tested with Galectin-3C. Efficacy will be tested on MM cells adherent to immortalized human stromal cells in conditions that give rise to "extracellular matrix drug resistance" that protects MM cells from apoptosis. We will determine the expression of Galectin-3 and Bcl-2 family members, Mcl-1, Bax, Bad, and Bcl-2. Aim #2. To assess the ability of Galectin-3C to facilitate response to dexamethasone, thalidomide, and bortezomib in MM cells from patients and human cell lines. Proliferation of cell lines with Galectin- 3C and each agent will be determined, and the best combination will be tested with patient cells. Aim #3. To determine the effect of Galectin-3C alone and in combination therapy of NOD/SCID mouse models of disseminated and subcutaneous human MM. One agent will be selected based on results in Aim #2 and tested with Galectin-3C in disseminated and subcutaneous NOD/SCID mouse models of MM. Galectin-3C will be administered by intramuscular injection and continuous intravenous delivery by mini-pump in the disseminated model. The methodology producing the best response will be used for administration in the subcutaneous model. Phase II would focus on completing preclinical development towards initiation of a Phase 1 human clinical trial. PUBLIC HEALTH RELEVANCE: Multiple myeloma is rarely curable despite the introduction of new therapeutic regimens and more efficacious treatments are needed. More than 19,900 new cases and 10,700 deaths from multiple myeloma are expected in the U.S. in 2007. Although the 10-year survival rate has recently increased it is only 17.4%. The overall goal of this research is the development of a novel human protein, Galectin-3C, as a treatment for multiple myeloma that can be given with other agents to facilitate the induction of apoptosis, to increase the percentage of patients who are responsive to therapy, and the survival rate.


Issue Date FY	Funding FY	Legal Entity Name	Legal Entity Address	Legal Entity City	Legal Entity State	Legal Entity Zip Code	Legal Entity COUNTY	Legal Entity COUNTRY	Assistance Listing	Award Code	Budget Year	Action Date	Action Type	Action Amount

Issue Date FY: 2011 ( Subtotal = $0 )
2011	2008	MANDALMED, INC	2645 OCEAN AVENUE SUITE 302	SAN FRANCISCO	CA	94132	SAN FRANCISCO	USA	Cancer Treatment Research	000	1	11/30/2010	NEW	$0
														Subtotal = $0

Issue Date FY: 2009 ( Subtotal = $0 )
2009	2008	MANDALMED, INC	2645 OCEAN AVENUE SUITE 302	SAN FRANCISCO	CA	94132	SAN FRANCISCO	USA	Cancer Treatment Research	000	1	5/4/2009	NEW	$0
														Subtotal = $0

Issue Date FY: 2008 ( Subtotal = $363,936 )
2008	2008	MANDALMED, INC	2645 OCEAN AVENUE SUITE 302	SAN FRANCISCO	CA	94132	SAN FRANCISCO	USA	Cancer Treatment Research	000	1	9/15/2008	NEW	$363,936
														Subtotal = $363,936

Grand Total All Awards = $363,936

Top

All Categories

About

Search

Reports

Data Submission

Award Information

PRECLINICAL TESTING OF GALECTIN-3C FOR MULTIPLE MYELOMA

Award Number: R43CA135862

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)

PERIOD OF PERFORMANCE START DATE: 09/15/2008

PERIOD OF PERFORMANCE END DATE: 08/31/2011

Federal Websites

Department of Health & Human Services

HHS Operating Divisions

HHS Staff Divisions

Download A Document Viewer