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 21 for “"PARP inhibition"”.
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Tracking Treatment Response and Resistance to Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer.
<p>polyADP ribose polymerase (PARP) inhibitors are a class of drugs that block the PARP enzymes, involved in the repair of singe-stranded DNA breaks through the base excision repair pathway. PARP inhibition leads to replication-associated double stranded DNA breaks, which are repaired by homologous …
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MODELING COHESIN-DEPENDENT ONCOGENESIS IN VITRO AND IN VIVO: POSSIBLE AMELIORATIVE EFFECTS OF PARP INHIBITION
… I also showed that Poly (ADP-ribose) polymerase (PARP) depletion or inhibition which is used to treat forms of cancer with defects in DNA repair ameliorated phenotypes of SA-deficient animals. Finally, I studied the effect of STAG2 downregulation in human in vitro models using shRNA technology in …
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PARP inhibition in combination with radiation therapy for the treatment of feline oral squamous cell carcinoma
… are needed. Poly (ADP-ribose) polymerase (PARP) is a key molecule involved in single stranded DNA break repair. PARP inhibitors (PARPi) are predicted to amplify RT-induced lethal DNA damage, and combinatorial strategies with PARPi and RT are being investigated for treating human solid …
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Nicotinamide Riboside Delivery Generates NAD+ Reserves to Protect Vascular Cells Against Oxidative Damage
… NAD+, which drives poly (ADP-ribose) polymerase (PARP) and sirtuin (SIRT) reactions, can be compromised and strategies for overcoming this limitation in the vasculature do not exist. This study determines if nicotinamide riboside (NR) delivery can augment NAD+ stores and fuel resistance to …
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Poly (Adp) Ribose Polymerase Inhibitors For The Treatment of Malignant Peripheral Nerve Sheath Tumor
… MPNST patients. Poly (ADP) ribose polymerase (PARP) inhibitors were first reported over a decade ago to have substantial anti-tumorigenic effects in malignancies with defective DNA repair, specifically those with <em>BRCA1/2</em> (breast cancer, early onset 1/2)<em> </em>mutations. Further …
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The effect of distinct BRCA1 splice forms on drug sensitivity in breast- and ovarian cancer cell lines
… development, particularly in breast and ovaries. PARP inhibitors are a promising treatment option for carriers of BRCA1/2 mutations diagnosed with these tumor types. Pathogenic spliceogenic variants have been found in BRCA1 that change the expression of BRCA1 transcripts, in which the expression …
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Role of C-Met and Egfr In Acquired Resistance to Parp Inhibitors In Triple-Negative Breast Cancer
… are limited. The Poly (ADP-ribose) polymerase (PARP) inhibitors, olaparib and talazoparib, were recently approved for metastatic breast cancer (including triple-negative breast cancer) in patients with a germline <em>BRCA1/2</em> mutation. Despite impressive response rates of ~60%, the …
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Folate Deficiency and Its Effect On Dna Repair
… another BER enzyme, Poly-ADP-ribose polymerase (PARP1). Moreover, the study also found an increase in sensitivity to PARP inhibition under folate deficient conditions. Taken together, the results demonstrate that BER status influences the sensitivity of cancer cells to folic acid deficiency, and …
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Enzymatic synthesis of defined-length poly(ADP-ribose) and the investigation of cell-permeable poly(ADP-ribose) glycohydrolase inhibitors
… this end, various Poly(ADP-ribose) Polymerase (PARP) inhibitors have been developed to induce sensitivity to genotoxic stress in BRCA-mutated cancer cells, and Poly(ADP-ribose) Glycohydrolase (PARG) inhibition is investigated as an alternate pathway to PARP inhibition in genotoxic chemotherapy. …
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Parp Inhibitor Upregulates Pd-L1 Expression and Enhances Cancer-Associated Immunosuppression
… Inhibitors of poly (ADP-ribose) polymerase (PARP) have shown substantial cytotoxic effects against tumors with defects in DNA damage responses. However, whether a crosstalk between PARP inhibition and immune checkpoints exists remains unclear. Here, it has been shown that PARP inhibitors …
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Targeting transcription-regulating cyclin dependent kinase 12 for the treatment of breast cancer
… Pol II) at serine 2. Previous work showed that inhibition of CDK12 leads to decreased expression of DNA damage response (DDR) genes and sensitizes cancer cells to DNA damage-inducing agents. However, the exact mechanism by which this is achieved remains unclear. This study aimed to investigate …
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Two Redundant Ubiquitin-dependent Pathways of BRCA1 Localization to DNA Damage Sites
… RAP80-BRCA1 interaction are hypersensitive to PARP inhibition and are unable to form RAD51 foci. Our results suggest that in the absence of RAP80, the BRCA1 E3 ligase activity is necessary for recognition of histone H2A Lys13/Lys15 ubiquitylation by BARD1 although I cannot rule out the …
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Biomolecular effects and bioclinical applications of PARPs inhibitors
Abstract Section I Inhibitors of PARP-1(Poly(ADP-ribose) polymerase-1) act by competing with NAD+, the enzyme physiological substrate, which play a protective role in many pathological conditions characterized by PARP-1 overactivation. It has been shown that PARP-1 also promotes tumor growth and …
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Developing 1,2,3,4-tetrahydro-5H-aryl[1,4]diazepin-5-ones and Related Scaffolds as Poly-(ADP-ribosyl) Polymerase (PARP) Inhibitors and Exploring Their Targeted Polypharmacology with Kinases
Poly-(ADP-ribsoyl) Polymerases (PARPs) are a superfamily of enzymes comprised of 17 known isoforms. PARP inhibitors (PARPi) have shown success in clinical trials for the treatment of homologous recombination-deficient cancers. Though proven effective initially, tumors treated with PARPi eventually …
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Unleashing the potential of liquid biopsy: allele-informed evaluation of plasma samples for cancer patients management
… plasma samples from three patients receiving PARP inhibition harboring DNA repair gene aberrations, PCF_SELECT demonstrated high sensitivity in detecting BRCA2 allelic imbalance with decreasing tumor fractions resultant from treatment and identified complex ATM genomic states that may be …
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Study of the Gain-of-Function Mutant p53 and PARP1 in Triple-Negative Breast Cancer
… replication factors including PCNA, MCM2-7, and PARP1 (termed the mtp53-PARP-MCM axis). In this thesis, we explore the contribution of mutant p53 and PARP1 in castration-resistant prostate cancer (mutant p53 P223L and V274F) and triple-negative breast cancer (mutant p53 R273H). In the …
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Characterization and therapeutic evaluation of a traumatic brain injury model in compliance with common data elements
… (Lynparza®) is a Poly(ADP-polymerase) 1 (PARP1) inhibitor approved by the FDA for the treatment of breast and ovarian cancer. Several studies reported the activation of PARP1 after injury in the central nervous system. This activation has been correlated with increased inflammation, …
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FANCD2 in relation to BRCA2 mutated breast cancer
… error prone DNA repair pathways controlled by PARP-1 and FANCD2, take over (Kais et al., 2016). Tissue staining for the active unit of telomerase (hTERT) and FANCD2 was performed on 470 BC samples on tissue microarrays (TMAs). It was evaluated whether overexpression of these proteins in the …
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Combination Chemotherapy and In vivo Modeling of BRCA-deficient, High-grade Serous Ovarian Cancer
… platinum sensitivity. Novel therapeutics such as PARP inhibitors have also been developed by exploiting the synthetic lethal phenotype of BRCA inactivation and PARP inhibition. However over 80% of patients still relapse with resistant disease. Therefore, strategies for more effective treatment are …
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The impact of chronic loss of STAG2 on DNA damage repair and the epigenome in acute myeloid leukaemia
… in ΔSTAG2 cells and excitingly, this conferred PARP inhibitor sensitivity. To further investigate the potential for therapeutic targeting of ΔSTAG2 the isogenic cells were screened against Selleckchem’s DNA Damaging Compounds Library identifying 32 compounds to which mutant cells were …
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