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Molecular Actions Of The Novel Histone Deacetylase Inhibitor Cg-1521 In Models Of Inflammatory Breast Cancer, Namita Chatterjee
Molecular Actions Of The Novel Histone Deacetylase Inhibitor Cg-1521 In Models Of Inflammatory Breast Cancer, Namita Chatterjee
Legacy Theses & Dissertations (2009 - 2024)
Inflammatory breast cancer (IBC) is a rare and particularly lethal form of breast cancer. Despite aggressive therapeutic approaches, the 5-year survival rate is only 34%. As this disease is severely understudied, we have investigated the therapeutic potential of the novel hydroxamic acid-derived histone deacetylase inhibitor (HDACi), CG-1521 in comparison to a structurally similar compound, Trichostatin A (TSA) in two IBC cell lines: SUM149PT and SUM190PT. In these cells, CG-1521 and TSA induce dose- and time-dependent induction of cell cycle arrest and apoptosis regardless of the presence of 17β-estradiol (E2). Interestingly, the cell lines have considerably different sensitivities to these treatments …
A Functional Genomics Approach To Investigate The Mechanism Of Action Of The Histone Deacetylase Inhibitor Cg-1521, Ann-Christin Gaupel
A Functional Genomics Approach To Investigate The Mechanism Of Action Of The Histone Deacetylase Inhibitor Cg-1521, Ann-Christin Gaupel
Legacy Theses & Dissertations (2009 - 2024)
Epigenetic alterations are common in human cancers. Loss of histone acetylation occurs early in tumorigenesis, correlates with advanced stage and poor clinical outcome, and histone acetyltransferases (HATs) and histone deacetylases (HDACs) are aberrantly expressed or recruited to promoters in a variety of cancers. Histone deacetylase inhibitors (HDACis) are attractive anti-cancer therapeutics because of their selectivity for transformed cells and their ability to induce growth arrest, cell death, senescence and differentiation, enhance tumor immunogenicity and inhibit angiogenesis and invasion. However, many questions remain regarding their mechanism(s) of action. While monotherapy with HDACis for solid tumors is not effective, combination therapies show …
Mechanisms Of Age-Related Inflammation And Cancer : The Synergistic Effect Of Oxidants And Calcium, Donald A. Mccarthy
Mechanisms Of Age-Related Inflammation And Cancer : The Synergistic Effect Of Oxidants And Calcium, Donald A. Mccarthy
Legacy Theses & Dissertations (2009 - 2024)
The accumulation of senescent cells during the process of aging has been implicated as causal in numerous age-related pathologies. Senescent cells adopt a secretory phenotype consisting of many factors including matrix remodeling enzymes, growth factors, cytokines, and chemokines. Their secretory nature is the primary reason that they are associated with disease, but it remains unclear why they become so inflammatory. Using primary human fibroblasts cultured to senescence, we mechanistically determined why senescent cells are such potent inducers of inflammation. Our findings indicate that the early production of the cytokine Interleukin 1-α (IL-1α) is central to this transition. We found that …