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MECHANISMS OF AKT-DEPENDENT SENSITIVITY TO RAPAMYCIN

Award Number: R01CA109312
ORGANIZATION: NATIONAL CANCER INSTITUTE
OPDIV: NIH
AWARD CLASS: DISCRETIONARY
AWARD ACTIVITY TYPE: SCIENTIFIC/HEALTH RESEARCH (INCLUDES SURVEYS)
PERIOD OF PERFORMANCE START DATE: 06/01/2004
PERIOD OF PERFORMANCE END DATE: 05/31/2013

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MECHANISMS OF AKT-DEPENDENT SENSITIVITY TO RAPAMYCIN - DESCRIPTION (provided by applicant): The long range goal of the proposal is to investigate the mechanism of cap-independent translation of the c- myc protein with the assumption that its cellular function is a key determinant of tumor cell responses, especially for CNS malignancies. More specifically, the proposal will elucidate how hnRNP A1 (A1) functions as a trans-acting protein that binds to the internal ribosome entry site (IRES) in the 5' UTR of the c-myc transcript, thus facilitating IRES-dependent translation of myc. Furthermore, it will focus on the ability of Akt and MAPK cascades to regulate this A1 translation-promoting activity, testing effects on the IRES-annealing activity of A1, effects on IRES-ribosome binding and effects on A1/IRES subcellular localization. Glioma cell lines, primary tumor cells and xenograft models will be used to exploit the insight gained on A1/myc IRES regulatory controls to understand mechanisms of glioma cell resistance whe treatment with mTOR inhibitors is attempted. PUBLIC HEALTH RELEVANCE: The project details the mechanisms by which glioma tumor cells become resistant to promising new therapeutic agents called mTOR inhibitors. The mechanisms of cell intrinsic resistance to these compounds will be investigated, as well as, the pre-clinical evaluation of combination targeted therapies in glioma in vitro and in vivo models.


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: 2012 ( Subtotal = $198,512 )
2012	2012	SEPULVEDA RESEARCH CORPORATION	16111 PLUMMER STREET	SEPULVEDA	CA	91343	LOS ANGELES	USA	Cancer Treatment Research	000	8	5/30/2012	NON-COMPETING CONTINUATION	$198,512
														Subtotal = $198,512

Issue Date FY: 2011 ( Subtotal = $198,512 )
2011	2011	SEPULVEDA RESEARCH CORPORATION	16111 PLUMMER STREET	SEPULVEDA	CA	91343	LOS ANGELES	USA	Cancer Treatment Research	000	7	5/20/2011	NON-COMPETING CONTINUATION	$198,512
														Subtotal = $198,512

Issue Date FY: 2010 ( Subtotal = $204,651 )
2010	2010	SEPULVEDA RESEARCH CORPORATION	16111 PLUMMER STREET	SEPULVEDA	CA	91343	LOS ANGELES	USA	Cancer Treatment Research	000	6	5/26/2010	NON-COMPETING CONTINUATION	$204,651
														Subtotal = $204,651

Issue Date FY: 2009 ( Subtotal = $204,651 )
2009	2009	SEPULVEDA RESEARCH CORPORATION	16111 PLUMMER STREET	SEPULVEDA	CA	91343	LOS ANGELES	USA	Cancer Treatment Research	000	5	6/18/2009	COMPETING CONTINUATION	$204,651
														Subtotal = $204,651

Issue Date FY: 2008 ( Subtotal = $194,906 )
2008	2008	SEPULVEDA RESEARCH CORPORATION	16111 PLUMMER STREET	SEPULVEDA	CA	91343	LOS ANGELES	USA	Cancer Treatment Research	000	4	4/8/2008	NON-COMPETING CONTINUATION	$194,906
														Subtotal = $194,906

Issue Date FY: 2007 ( Subtotal = $194,906 )
2007	2007	SEPULVEDA RESEARCH CORPORATION	16111 PLUMMER STREET	SEPULVEDA	CA	91343	LOS ANGELES	USA	Cancer Treatment Research	000	3	4/17/2007	NON-COMPETING CONTINUATION	$194,906
														Subtotal = $194,906

Issue Date FY: 2006 ( Subtotal = $200,727 )
2006	2006	SEPULVEDA RESEARCH CORPORATION	16111 PLUMMER STREET	SEPULVEDA	CA	91343	LOS ANGELES	USA	Cancer Treatment Research	000	2	5/3/2006	NON-COMPETING CONTINUATION	$200,727
														Subtotal = $200,727

Issue Date FY: 2005 ( Subtotal = $205,558 )
2005	2005	SEPULVEDA RESEARCH CORPORATION	16111 PLUMMER STREET	SEPULVEDA	CA	91343	LOS ANGELES	USA	Cancer Treatment Research	000	1	7/15/2005	NEW	$205,558
														Subtotal = $205,558

Grand Total All Awards = $1,602,423

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MECHANISMS OF AKT-DEPENDENT SENSITIVITY TO RAPAMYCIN

Award Number: R01CA109312

ORGANIZATION: NATIONAL CANCER INSTITUTE

OPDIV: NIH

AWARD CLASS: DISCRETIONARY

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

PERIOD OF PERFORMANCE START DATE: 06/01/2004

PERIOD OF PERFORMANCE END DATE: 05/31/2013

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