Accession Number : ADA553285


Title :   A New Therapeutic Paradigm for Breast Cancer Exploiting Low Dose Estrogen-Induced Apoptosis


Descriptive Note : Annual rept. 19 Feb 2010-18 May 2011


Corporate Author : GEORGETOWN UNIV WASHINGTON DC


Personal Author(s) : Jordan, Virgil C


Full Text : https://apps.dtic.mil/dtic/tr/fulltext/u2/a553285.pdf


Report Date : Jun 2011


Pagination or Media Count : 480


Abstract : The purpose of the CoE is to discover the molecular mechanisms and the modulation of estrogen-induced apoptosis. The laboratory research project is focused on genomics and proteomics with a current focus on molecular interrogation to decipher mechanisms that may be applied to aid patient treatment. In parallel, but not supported by the CoE, is a pilot clinical study of estrogen-induced apoptosis in patients with metastatic breast cancer, that have had repeated cycles of successful antihormone therapy, but have subsequently failed and relapsed. The clinical study was originally at the Fox Chase Cancer Center (FCCC), but the coordinating center is now in the process of being moved to the Lombardi Comprehensive Cancer Center (LCCC). Patient materials are currently being transferred and our resources are being marshaled to allow us to adapt to the disruption of our time table, due to the requirement of moving the grant from FCCC to LCCC. Despite the challenge of re-establishing the molecular pharmacology laboratory of the Principal Investigator (PI), considerable momentum has now been achieved in all areas originally designated in the grant, e.g. a description of the time dependent changes in estrogen-responsive growth and apoptosis in model cell lines, an evaluation and description of the early proteomic pathways associated with estrogen-induced apoptosis dependent on the estrogen receptor (ER) co-activator AIB1 (SRC-3), the critical importance of the shape of the ER complex, c-Src activity to initiate apoptosis and the genomic spectrum of our endocrine resistant cell lines to define cell sensitivity to estrogen-induced apoptosis.


Descriptors :   *APOPTOSIS , *BREAST CANCER , *ESTROGENS , CELLS(BIOLOGY) , CLINICAL MEDICINE , CYCLES , DOSAGE , ENDOCRINE GLANDS , GROWTH(GENERAL) , INTERROGATION , LABORATORIES , LABORATORY TESTS , METASTASIS , MODELS , MODULATION , MOLECULAR PROPERTIES , MOMENTUM , PATIENTS , REQUIREMENTS , RESOURCES , SENSITIVITY , SHAPE , THERAPY , TIME DEPENDENCE , TRANSFER


Subject Categories : Medicine and Medical Research


Distribution Statement : APPROVED FOR PUBLIC RELEASE