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Cedars Sinai Medical Center in Los Angeles, CA
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January 2010
$25,000 was awarded to Dr. Sandra Orsulic of Cedars Sinai Medical Center in Los Angeles, CA. This is the second installment of a $50,000 grant provided by
LMSarcoma Direct Research Foundation. Dr. Orsulic has also received grants from NIH (R01-CA103924), Ovarian Cancer Research Fund, Liddy Shriver Sarcoma Initiative, and the Sarcoma Foundation of America.
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Priority Report: 'A Role for BRCA1 in Uterine Leiomyosarcoma'
published by the American Association for Cancer Research
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Progress Report provided by Dr. Orsulic.
LMSarcoma Direct Research Foundation
PI: Sandra Orsulic, PhD
A Preclinical Mouse Model for Targeted Therapy in Uterine Leiomyosarcoma
Specific Aim 1. Define the mechanism of BRCA1 downregulation in human ULMS
Specific Aim 2. Determine the efficacy of PARP-1 inhibition in a mouse model of ULMS
We are pleased to report significant progress on our proposed project. This work has already resulted in one publication, in which funding from the LMSarcoma Direct Research Foundation is acknowledged. The publication was featured as a Priority Report in the journal Cancer Research (see below).
Specifically, we have obtained additional evidence that BRCA1 may play a role in human ULMS development. Our immunohistochemistry results from a larger number of patient samples (85 ULMS and 76 benign uterine leiomyoma tissue specimens) showed a significant difference in BRCA1 protein expression between ULMS and benign uterine leiomyoma. BRCA1 protein expression was absent in 29% of ULMS samples and in 4% of benign leiomyoma samples. Consistent with the view that BRCA1 silencing may play a role in the development or progression of ULMS, we demonstrated that the BRCA1 promoter is methylated in samples with negative BRCA1 immunohistochemical staining.
The results summarized above have been published in Xing D, Scangas G, Nita M, He L, Xu X, Ioffe YJM, Aspuria P-J, Hedvat CY, Anderson ML, Oliva E, Karlan BY, Mohapatra G, Orsulic S. A Role for BRCA1 in Uterine Leiomyosarcoma. Cancer Research 2009; 69:8231-8235. Very recently, our reported finding that the loss of BRCA1 function may be an important step in the progression of ULMS in a mouse model was corroborated by two independent research groups who published similar findings in the journal PLoS ONE (Clark-Knowles et al., 2010; Quinn et al., 2010).
In summary, we have completed Specific Aim 1 and are making progress towards Specific Aim 2 in which we propose to use our animal model to investigate therapies that target BRCA1 deficiency in ULMS. Completion of Specific Aim 2 is an important step towards initiating clinical trials to test these therapies in human ULMS patients.
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August 2009
$25,000 was awarded to Dr. Sandra Orsulic of Cedars Sinai Medical Center in Los Angeles, CA. This is the first installment of a $50,000 grant provided by
LMSarcoma Direct Research Foundation. Dr. Orsulic has also received grants from NIH (R01-CA103924), Ovarian Cancer Research Fund, Liddy Shriver Sarcoma Initiative, and the Sarcoma Foundation of America.
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Last Edited -
25 February 2010 13:39 pm
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