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HIGH-THROUGHPUT EX VIVO TUMOR CELL MOTILITY ASSAY

Award Number: R43CA150763
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 07/01/2010
PERIOD OF PERFORMANCE END DATE: 08/31/2011

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HIGH-THROUGHPUT EX VIVO TUMOR CELL MOTILITY ASSAY - DESCRIPTION (provided by applicant): Gliomas are the most aggressive and least successfully treated brain tumors because of their distinctive ability to infiltrate surrounding brain tissue. Even if the bulk of the tumor is removed, migratory cells left behind are not detected by the immune system and resist current cytotoxic therapies. Tumor recurrence then typically involves a rapid and deadly outcome. Understanding the mechanisms of glioma cell migration and designing novel targeting strategies are major challenges in devising more successful therapies against these tumors. Using a highly collaborative, multidisciplinary approach, we will investigate microenvironmental and topographic cues that direct glioma migration on biocompatible nanofibers designed to mimic the substrate topography within the brain. Our specific aims are: 1) optimize a high-throughput in vitro migration assay using electrospun fiber mimicking nanoscale neural tissue topography to determine the potential of this model as a predictive bioassay of motility in ex vivo clinical glioma samples; 2) utilize the high-throughput assay to explore mechanisms that direct migration of clinical glioma cells and molecular factors regulating motility; and 3) assay anti-migratory strategies against cell dispersion to determine the potential of this model as a predictive bioassay of motility in clinical glioma samples. To pursue these aims we will 1) produce high-throughput multiwell cell culture plates with aligned, electrospun nanofiber on the bottom to mimic the aligned structure of white matter, 2) analyze glioma cell migration and characterize the cellular/molecular changes that occur on nanofibers presenting different topographies, 3) investigate potential molecular targets and anti-migratory chemotherapeutics against glioma migration on these devices, and 4) analyze the migration of ex vivo tumor cells and test anti-migratory strategies on those samples to determine the potential of the nanofiber model as a predictive bioassay with immediate clinical relevance. These aims address the goals and scope of the Small Business Catalyst Awards for Accelerating Innovative Research (R43) and are directly relevant to the health mission of the NIH while showing a large commercial potential. We expect that these studies will provide improved, more accurate models of glioma migration, having better predictive power and higher translational potential to improve public health. At the same time, we believe that our research may identify key factors that regulate glioma cell migration, potentially helping to devise a broad range of effective therapies against these devastating tumors. If this high-throughput motility assay is proven successful in this work, then it will provide an innovative tool to researchers from a large variety of backgrounds beyond gliomas. PUBLIC HEALTH RELEVANCE: Malignant brain tumors are highly invasive leading to infiltration of the surrounding normal brain tissue. This makes them extremely difficult or impossible to 'cure' even after surgical removal of the main tumor. Therapeutic targeting of this migrating cell population is thought to be essential if these diseases are to be managed effectively. In order to identify improved therapeutic approaches, we propose an innovative model using biocompatible nanofibers to mimic local aspects of brain structure that regulate glioma cell migration. We will use this novel model to assay clinical samples and predict strategies to prevent tumor recurrence. If proven successful, we propose that this innovative high-throughput device will have a large commercial value as it will help devise novel approaches that lead to improved patient outcomes.


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: 2010 ( Subtotal = $199,365 )
2010	2010	NANOFIBER SOLUTIONS LLC	1275 KINNEAR ROAD	COLUMBUS	OH	43212	FRANKLIN	USA	Trans-NIH Recovery Act Research Support	000	1	6/29/2010	NEW	$199,365
														Subtotal = $199,365

Grand Total All Awards = $199,365

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HIGH-THROUGHPUT EX VIVO TUMOR CELL MOTILITY ASSAY

Award Number: R43CA150763

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 07/01/2010

PERIOD OF PERFORMANCE END DATE: 08/31/2011

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