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 27 for “"olaparib"”.
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PARP inhibition in combination with radiation therapy for the treatment of feline oral squamous cell carcinoma
… human solid tumors. We hypothesized that Olaparib, an orally bioavailable PARPi, combined with RT will improve therapeutic outcomes in FOSCC. Three feline squamous cell carcinoma (SCC) cell lines (SCCF1, SCCF2 and SCCF3), and a human SCC cell line (HN31) were used to characterize the …
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Investigating the role of protein ubiquitylation in the maintenance of genome stability
… the poly-ADP ribose polymerase (PARP) inhibitor olaparib, as a means of screening for new HR factors. In this manner, I identify the E2 ubiquitin conjugating enzyme UBE2S as a novel factor required for olaparib resistance, and confirm its direct involvement in DNA repair by showing that it …
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Targeting DNA Repair in Prostate Cancer: Therapeutic Combinations & Disease Models
… (Enza) when combined with either PARP inhibitor Olaparib or ATM inhibition (ATMi). Olaparib and Enzalutamide combination treatment were determined to transcriptionally downregulate cell cycle progression signatures. Cell cycle analysis demonstrated G2/M accumulation, providing indications of …
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Combination Chemotherapy and In vivo Modeling of BRCA-deficient, High-grade Serous Ovarian Cancer
… entities. The combination of carboplatin and olaparib resulted in profound synergism in BRCA-deficient high-grade serous ovarian cancer cell lines when carboplatin was administered at a higher molar ratio relative to olaparib. The combination achieved effective cytotoxicity by inducing greater …
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The effect of distinct BRCA1 splice forms on drug sensitivity in breast- and ovarian cancer cell lines
… the drug sensitivity to the PARP inhibitor olaparib. Drug sensitivity was studied by clonogenic assay, and treatment with olaparib demonstrated that cells with loss of BRCA1 expression are more sensitive to PARP inhibitors than cells expressing wildtype (WT) BRCA1. The clonogenic assay also …
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DNA repair proteins Metnase and PARP1 regulate DNA integration
… the effects of two PARP1 inhibitors PJ34 and Olaparib on DNA integration. Surprisingly, the two inhibitors showed opposite effects on DNA integration. PJ34 suppressed DNA integration, while Olaparib promoted DNA integration. We then confirmed PARP1 promoted DNA integration in a stable PARP1 …
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Characterization and therapeutic evaluation of a traumatic brain injury model in compliance with common data elements
… therapeutic drug to treat neurotrauma. Olaparib (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 …
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FANCD2 in relation to BRCA2 mutated breast cancer
… was to look for improved therapy options against olaparib PARP inhibition treatment tolerance with alisertib Aurora-A inhibition that could work against FANCD2 activation in cells lacking BRCA2 expression. Statistical significance was found for high FANCD2 nuclear expression and low age at …
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Clinical Significance of Homologous Recombination Deficiency Score Testing In Endometrial Cancer
… lines and their in vivo growth and response to olaparib and chemotherapy were assessed. Tumor growth and patterns of metastatic spread were assessed in orthotopic mouse models of endometrial cancer.</p> <p><strong>Results: </strong>Median age at diagnosis was 62 years. The majority of patients …
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The Development of Peroxide-Responsive Arylboronic Acids for Antibody-Drug Conjugates and Small-Molecule Prodrugs
… prodrugs. Non-targeted drugs, such as olaparib and navitoclax, often suffer from poor tolerability and toxicity because they exert their function on healthy cells as well as target cancer cells. Thus, to improve their efficacy and safety profile, inactive prodrugs of olaparib and …
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Tracking Treatment Response and Resistance to Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer.
… instability and cell death.</p> <p>In 2014, Olaparib became the first FDA-approved PARP inhibitor for the treatment of <em>BRCA</em>-mutant ovarian cancer. In the phase III POLO (Pancreas cancer OLaparib Ongoing) trial presented at the American Society for Clinical Oncology (ASCO) conference …
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Identifying and Targeting Adaptive Changes to Bet Inhibition In Ovarian Cancer
… poly (ADP-ribose) polymerase (PARP) inhibitor olaparib, as well as the mechanistic target of rapamycin (mTOR) inhibitors rapamycin and INK-128 were also used. Statistical analyses of <em>in vitro </em>and <em>in vivo</em> experiments were performed using either Student <em>t </em>test or …
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An innate immune response to DNA damage in prostate cancer
… and increased sensitivity to cisplatin and olaparib. Ten patients (19.23%) were DDRD positive and 42 (80.76%) were DDRD negative; 80% of DDRD positive and 47% of DDRD negative patients failed to benefit from docetaxel. DDRD positive tumour samples demonstrated an association with poorer …
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Characterisation of Pharmacological Mechanisms and Potential Therapeutic uses of FK866
… effects of FK866 and the oral PARP inhibitor, Olaparib, were investigated using 3D cell culture (spheroids) and compared with 2D monolayer cultures. The effects of FK866 showed little difference in spheroid or monolayer culture. However, when treating with Olaparib there was higher level of …
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Targeting the DNA damage response protein ATR kinase in pancreatic cancer
… poly(ADP-ribose) polymerase (PARP) inhibitor, olaparib. While AZD6738 and olaparib synergistically inhibited the growth of PDAC cells proficient in homologous recombination (HR) in vitro, I identified no anti-tumour effect in HR-proficient in vivo models. This could indicate that a DDR …
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Tumor suppressive effect of PARP1-FOXO3 pathway
… 설명되어지지 않고 있다. 따라서, 위암 세포를 이용하여 PARP1 저해제인 올라파립 (Olaparib) 뿐만 아니라 PARP1 siRNA를 가지고 PARP1의 저해가 암세포의 성장을 어떻게 조절하는지를 보여주었으며 PARP1저해에 의한 FOXO3의 발현 증가를 통해 종양을 억제하는 효과를 가져온다. 뿐만 아니라, 166개의 tumor stage-matched 위암 환자 샘플을 사용하여 PARP1과 FOXO3 발현을 조직 마이크로 어레이로 평가하였다. 다변량 분석을 통해 PARP1 및 FOXO3 의 발현 차이에 따른 생존 곡선을 …
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Nuclear translocation of Gasdermin D (GSDMD) sensitizes chemotherapy through inhibiting PARP-1 in colorectal cancer
… to act similarly like the PARP inhibitor Olaparib. My findings confirmed that GSDMD related apoptosis is nuclear translocation dependent. My final objective was to dissect the potential clinical value of GSDMD nuclear translocation for chemosensitization by manipulating GSDMD expression …
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Role of C-Met and Egfr In Acquired Resistance to Parp Inhibitors In Triple-Negative Breast Cancer
… 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 prolongation in median …
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Pharmaceuticals in the Environment: Assessing Potential Risks to Fish
… clozapine (antipsychotic) and olaparib (antineoplastic). Inter-relationships between API exposure and drug clearance processes in trout hepatocytes were also investigated by quantifying selected gene transcripts and the activity of cytochrome P4501A – an important phase I …
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Targeting transcription-regulating cyclin dependent kinase 12 for the treatment of breast cancer
… of DNA repair including inhibitors of PARP (olaparib) and CHK1 (AZD7762) using a colony formation assay. The preliminary results indicate that combining CDK12 and CHK1 inhibition will likely have greater therapeutic potential than the combination of CDK12 and PARP inhibition. Future studies …
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