Global ETD Search
Search theses and dissertations gathered from participating repositories worldwide. Every result links back to the library that holds it. No account is needed.
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Showing 1 to 20 of 42 for “"HDAC inhibitor"”.
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An improved synthesis of the HDAC inhibitor trichostatin A
<p>Histone deacetylase inhibitors (HDIs) have found a wide variety of medicinal uses and are most noted for their specific apoptotic action towards cancer cells. Several hydroxamate HDIs have since been moved on to phase 1 and 2 clinical drug trials, with one having already been approved for …
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Genomic Analysis of Chemo-Resistance to HDAC inhibitor in Gastric Cancer cells
Histone deacetylase inhibitors (HDACis) are a promising class of anticancer epigenetic drugs, however, molecular factors influencing the responses of individual tumors to HDACi therapies remain obscure. Here, we sought to identify genes associated with HDACi resistance in gastric cancer. Treating a …
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Part 1 Synthesis of a potent histone deacetylase inhibitor; Part 2 Studies towards a stabilized helix-turn-helix peptide
… the synthesis of a new histone deacetylase (HDAC) inhibitor (HDI). HDAC enzymes modify core histones, influence nucleosome structure and change gene transcription by removing the acetyl groups from lysine residues on proteins. HDIs are showing exciting potential as a new class of drugs for …
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Identification of substrate-selective histone deacetylases and their inhibitors that mediate HER2 transcript stability
… include the utilization of histone deacetylase (HDAC) inhibitors. It has been observed that HDAC inhibitors can induce the rapid decay of oncogenic transcripts such as the HER2 mRNA, though the mechanism underlying this process remains undefined. Earlier observations in our lab led to speculation …
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Small Proline Rich Protein-2 Expression and Regulation in the Caco-2 model of Intestinal Epithelial Differentiation along the Crypt-Villus Axis
… involved in this induction using MAP kinase inhibitors. SPRR2 expression was also compared between HIEC crypt cells and 16 to 20 week primary fetal villus cells as well as in different segments in mouse small intestine and colon. We determined if SPRR2 is increased by gram negative bacteria …
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Investigation of the Role of Histone Acetylation in Hippocampus-Dependent Memory Formation
… pharmacologically blocking histone deacetylases (HDAC) enhances long-term memory formation. Memory enhancement by HDAC inhibitors requires the interaction between the transcription factor CREB and CBP, suggesting that these two processes converge at functionally relevant target genes. As reviewed …
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Role of epigenetics in hematopoietic stem cell development
… C646 (histone acetyltransferase, or HAT, inhibitor) and OICR9249 (WDR5 inhibitor), and the two eraser molecules, Ex-527 (Sirt1 inhibitor) and JIB-04 (bromodomain inhibitor), showed varying degrees of increasing HSC formation. Of these molecules, C646 created the most significant increase …
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Valproic Acid Disrupts Hematopoiesis in Xenopus Laevis Through the Inhibition of Histone Deacetylase 3.
Histone deacetylases (HDACs) are important regulators of developmental processes and cellular functions. However, their role in hematopoiesis has not been determined, and in Xenopus laevis, a specific function for HDACs has yet to be identified. In the present work, we employed the class I …
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Nuclear receptor co-repressor functions in prostate cancer; in vitro, in vivo and in silico approaches
… 1 (NCOR1) complexes with Histone Deacetylases (HDACs) to repress the action of unliganded NRs, hence, inhibiting their transcriptional and phenotypical effects. NCOR1 was found to be over-expressed in PC-3 cells when compared to non-malignant RWPE-1 cells. Chemical inhibition of NCOR1, via the …
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EFFECTS OF HISTONE DEACETYLASE INHIBITORS ON ENERGY METABOLISM
… such as members of the histone deacetylase (HDAC) family, in particular those belonging to class I and class II, which modulate post-translational modifications on target proteins. The current knowledge on HDACs is that they function in general as transcriptional repressors, however their …
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MECHANISM OF TRANSCRIPTIONAL REPRESSION OF MMP-9 BY INTERFERON-β
… deletion constructs we show that IFN-beta's inhibitory effects require a region of the promoter between -154 and -72, which contains an AP-1 binding site. Chromatin immunoprecipitation (ChIP) studies indicate that IFN-beta increases histone deacetylase (HDAC)-1 recruitment to the MMP-9 …
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MUSCLE-SPECIFIC MECP2 MISEXPRESSION INDUCES SKELETAL AND VISCERAL MUSCLE DEFECTS RESCUED BY BUTYRATE SUPPLEMENTATION IN DROSOPHILA
… Indeed, supplementation with sodium butyrate, an HDAC inhibitor with energetic role, specifically restored muscle structure and gut motility. Valproic acid, a pan-HDAC inhibitor without metabolic properties, produced similar improvements, suggesting an epigenetic mechanism of action. Finally, we …
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The Elucidation of the Mechanisms of CD8+ T Cell-Mediated Suppression of Human Immunodeficiency Virus Type 1 Replication
… subset of human genes, histone deacetylases (HDACs) are epigenetic regulators that condense chromatin to repress transcription. We examined the role of epigenetics in modulating the HIV-1 suppressive factors expressed by primary CD8<super>+</super> T cells from subjects naturally controlling …
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Leveraging Single Cell Technologies For The Characterization and Treatment of Refractory Pancreatic Cancer
… of epigenetically-modifying therapeutic agents (HDAC inhibitors). I describe a novel HDACi resistance mechanism of AP1 activation, which can be intercepted by using an AP1 inhibitor in combination with an HDAC inhibitor to achieve tumor cell death. Finally, in an effort to explore and …
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Roles of H2A.z in Fission Yeast Chromatin
… to be sensitive to TSA, a histone deacetylase (HDAC) inhibitor suggesting that H2A.z cooperates with HDACs. TSA treatment of wild type cells cause an increase in H4 K16 Ac and a decrease in H4 K20 Me3. Gene expression profiles of h2A.z, swr1 and msc1 are significantly similar and upregulated …
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Mechanisms of mTOR Signal Transduction Regulating Cell Growth and Differentiation
… the reported miR-1 target in skeletal muscle-HDAC4, and separately, a myogenic factor that is reportedly inhibited by HDACs-follistatin. Anti-miR-1 LNA dampens follistatin mRNA level, which is rescued by HDAC inhibitor trichostatin A (TSA). Concurrently, anti-miR-1 LNA also inhibits myotube …
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G2/M checkpoint associated repression of polo-like kinase-1 mediated by the tumour suppressor, p53
… role. Down-regulation of PLK1 is relieved by the HDAC inhibitor TSA and supports the transcriptional repression mechanism described in this thesis. Silencing of PLK1 expression by siRNA interferes with cell cycle progression consistent with a role in the p53-mediated checkpoint. This thesis …
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Histone Deacetylase 1: Mutagenesis And Small Molecule Studies
<p>Histone deacetylase 1 (HDAC1) has been linked to cell growth and cell cycle regulation, which makes it a widely recognized target for anticancer drugs. The 14 Å channel of Class 1 HDAC isotypes has long being hypothesized to be the exit cavity for acetate following deacetylation. The amino acids …
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Development of orthogonal nanotherapeutics for colorectal cancer treatment
… This led to the discovery of the small molecule inhibitors, MDM2 antagonists which prevent the p53-MDM2 interaction and leads to rapid stabilisation of p53 protein. However, treatment with MDM2 antagonists often leads to the induction of cell cycle arrest but not cell death. <br/><br/>During the …
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Human Organotypic Retinal Cultures as a model of human retinal ganglion cell degeneration in glaucoma. Effects of epigenetic regulation and mesenchymal stem cell derived growth factors.
… survival in long-term HORCs, whereas leukaemia inhibitory factor (LIF) failed to exert this effect. The loss of RGC-derived gene markers expression was selectively altered by the histone deacetylase inhibitor (HDACI) trichostatin A (TSA). Conclusions: The timing for long-term HORCs use ex vivo …
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