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Dissertations / Theses on the topic 'Novel therapeutic drugs'

Author: Grafiati

Published: 4 June 2021

Last updated: 12 February 2022

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1

Gerrard, Stephen Edmund. "A novel infant therapeutic delivery system for drugs, nutrients and anti-viral agents." Thesis, University of Cambridge, 2014. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.648462.

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2

Aldughaim, Mohammed. "The use of a novel TIMP3 peptide to specifically target therapeutic drugs to tumours." Thesis, University of Sheffield, 2017. http://etheses.whiterose.ac.uk/19957/.

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3

Miller, Mark Russell. "The mechanism of action and therapeutic potential of S-nitrosothiols as novel nitric oxide donor drugs." Thesis, University of Edinburgh, 2003. http://hdl.handle.net/1842/24981.

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Recently, two novel S-nitrosothiols, N-(S-nitroso-<i>N</i>-acetylpenicillamine)-2-amino-2-deoxy-1,3,4,6,tetra-<i>O</i>-acetyl-β-D-glucopyranose (RIG200) and S-nitroso-<i>N</i>-valerylpenicillamine (SNVP), have been described to have selectivity for endothelium-denuded blood vessels. Therefore, they are particularly appealing in the treatment of conditions where the vascular endothelium is damaged. This thesis describes experiments which further elucidate the mechanism of action and therapeutic of these novel S-nitrosothiols, by comparison to conventional NO donors. The key findings were that

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4

Sunkel, Vanessa Ann. "The investigation of novel marine microorganisms for the production of biologically active metabolites." Thesis, Rhodes University, 2009. http://hdl.handle.net/10962/d1004579.

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New drugs, particularly antibiotics, are urgently required to combat the increasing problem of antibiotic resistant human pathogens. Due to the scarcity of products available today, the pharmaceutical industry is now under pressure to reassess compounds derived from plants, soil and marine organisms. Pharmaceutical companies are showing renewed interest in marine biotechnology as the oceans represent a rich source of both biological and chemical diversity of novel molecular structures with anti-cancer, anti-inflammatory and antibiotic properties. Formerly unexplored locations, such as deep oce

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5

Khan, Tasmiyah. "Development of a novel, quantitative assay for determining the rate of activity of antimalarial drugs." Thesis, Rhodes University, 2013. http://hdl.handle.net/10962/d1001618.

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Malaria, caused by an intracellular Plasmodium parasite, remains a devastating disease, having claimed approximately 655 000 lives worldwide in 2010. The Medicines for Malaria Venture suggests a "single-dose radical cure" as the ideal malaria treatment since rapid clearance of blood-stage parasites and symptom relief improves patient compliance and limits drug resistance. Thus, novel antimalarials should be rapid-acting and assessing their rate of activity is critical to drug discovery. Traditional evaluation of this rate by morphological assessments is flawed by highly subjective, operator-sp

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6

Tanner, Delia Caroline. "Over-expression, purification and biochemical characterization of DOXP reductoisomerase and the rational design of novel anti-malarial drugs." Thesis, Rhodes University, 2004. http://hdl.handle.net/10962/d1003990.

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Malaria poses the greatest threat of all parasites to human life. Current vaccines and efficacious drugs are available however their use is limited due to toxicity, emergence of drug resistance, and cost. The discovery of an alternative pathway of isoprenoid biosynthesis, the non-mevalonate pathway, within the malarial parasite has resulted in development of novel anti-malarial drugs. 1-Deoxy-D-xylulose-5-phosphate (DOXP) reductoisomerase, the second enzyme in this pathway, is responsible for the synthesis of 2-C-methyl-D-erythritol 4-phosphate (MEP) in an intramolecular rearrangement step fol

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7

Wabnitz, Paul Andrew. "Chemistry and medical implications of novel amphibian peptides : a thesis submitted for the degree of Doctor of Philosophy /." Title page, contents and abstract only, 1999. http://web4.library.adelaide.edu.au/theses/09PH/09phw112.pdf.

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8

Hojati, Ashkhan. "Pharmacologic profiling of novel compounds via fluorometric analyses of monoamine transporter responses." VCU Scholars Compass, 2019. https://scholarscompass.vcu.edu/etd/5983.

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In humans and other organisms, monoaminergic systems are crucial in neuronal function and behavior. The monoamine transporters (MATs), which can be found on the presynaptic plasma membrane of neurons in the central nervous system (CNS), are crucial in the regulation of neurotransmitter concentration in the synaptic cleft. As the duration and concentration of neurotransmitters in the cleft affect further downstream signaling responses, these proteins are important targets for both understanding neuronal physiology and compounds of interest. Multiple theories exist proponing the contribution of

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9

Cattaneo, Dario. "Therapeutic drug monitoring of novel immunosuppressants." Thesis, Open University, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.424822.

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Therapeutic drug monitoring is primarily undertaken for narrow therapeutic inde:drugs, such as immunosuppressants. These drugs have reduced the incidence of acute rejection and improved allograft survival. However, due to their narrow therapeutic index, small variations in blood levels may result in inadequate levels of immunosuppression or toxic drug concentrations. To overcome these problems individual dose regimen based-on phannacokinetic monitoring has been proposed in the past years. Indeed, several studies have previously documented a significant association between cyclosporine whole bl

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10

Cooper, Remy C. "Novel Therapeutic Delivery via Cell-Nanoparticle Hybridization." VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/5002.

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The immobilization of surface-modified polyamidoamine (PAMAM) dendrimers on the cell surface introduces a novel approach for efficient and specific cellular uptake of therapeutic-carrying nanoparticles. This cell surface-nanoparticle hybridization event takes place via bioorthogonal copper-free click chemistry between a dibenzocyclooctyne (DBCO) group on the dendrimer surface and azide-capped glycans expressed on the cell membrane through metabolic incorporation of azido sugars. This particular cell-nanoparticle hybridization method can be exploited to deliver a variety of therapeutic, genetic

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11

Noordali, Hannah. "Investigating novel drug treatments for heart failure." Thesis, University of Birmingham, 2018. http://etheses.bham.ac.uk//id/eprint/8503/.

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Perhexiline is a metabolic modulator considered to be an alternative pharmacotherapeutic agent in heart failure (HF), a debilitating condition characterised by severe metabolic disturbances (i.e. impaired substrate utilisation and energy production) in which morbidity and mortality are high. However, perhexiline therapy requires regular plasma monitoring, which is clinically unattractive. Moreover, its exact cardioprotective mechanism(s) remains unknown. The work in this thesis aimed to investigate the protective effects and underlying molecular mechanism(s) of perhexiline ex vivo, in Langendo

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12

Rafei, Moutih. "Fusokine design as novel therapeutic strategy for immunosuppression." Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=115882.

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The societal burden of autoimmune diseases and donor organ transplant rejection in developed countries reflects the lack of effective immune suppressive drugs. The main objective of my thesis was to develop novel fusion proteins targeting receptors linked to autoimmunity; strategies that will allow the suppression of autoreactive cells while sparing resting lymphocytes. Interleukin (IL) 15 has been demonstrated to exert its effects mainly on activated T-cells triggered via their T-cell receptor (TCR). Since we found that the fusion of granulocyte-macrophage colony stimulating factor (GMCSF) to

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13

Deosarkar, Sudhir P. "Development of Novel Therapeutic and Diagnostic Approaches for Atherosclerosis." Ohio University / OhioLINK, 2010. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1268371885.

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14

Ignatz-Hoover, James J. "TLR8 and Nuclear GSK3ß are Novel Therapeutic Targets in AML." Case Western Reserve University School of Graduate Studies / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=case1480509044211523.

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15

Luk, Sze Ue. "BIRC6 as novel therapeutic target in advanced prostate cancer : clinical relevance, development of potential therapeutic agents & preclinical drug efficacy." Thesis, University of British Columbia, 2016. http://hdl.handle.net/2429/59547.

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The lack of effective therapy for advanced prostate cancer (PCa) remains a major unmet clinical need. Recently approved therapeutics, such as enzalutamide (ENZ), have only delayed the inevitable progression of castration-resistant PCa (CRPC), as resistance will typically emerge following treatment. Although increased apoptosis-resisting ability of cancer cells represents a fundamental mechanism for the onset of treatment resistance, no relevant agents have yet been developed. Preliminary work in our laboratory has revealed an association between elevated expression of BIRC6, an Inhibitor of Ap

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Alyamani, Nayef A. "The impact of cancer physicians' and patients' attitudes on personalised prescription of novel targeted anticancer drugs using predictive biomarkers." Thesis, University of Aberdeen, 2014. http://digitool.abdn.ac.uk:80/webclient/DeliveryManager?pid=211204.

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Background: The use of novel targeted anticancer drugs in clinical practice is rapidly increasing. As the use of these drugs increases, so does the need to develop biomarkers to optimise the drugs' clinical and cost effectiveness. The attitudes and views of all stakeholders regarding the optimal use of predictive biomarkers in guiding personalised medicine are crucial for identifying acceptable criteria of predictive biomarker tests to guide future biomarker development. To gain insight into these views, we aimed to develop and validate a survey tool that would aid in assessing attitudes of ca

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17

Kaur, Harneet. "Synthesis And Evaluation Of Novel Tropane Compounds As Potential Therapeutics For Drug Abuse." ScholarWorks@UNO, 2007. http://scholarworks.uno.edu/td/586.

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In an effort to search for potential therapeutic agents for cocaine addiction, a novel class of compounds was synthesized and evaluated for in vitro dopamine and serotonin transporter affinities. These unique 3ƒÀ-aryl-3ƒ¿-arylmethoxytropane analogues incorporated the structure of dopamine selective 2-substituted-3-phenyltropanes and the design of serotonin selective meperidine derivatives. In general, the 3ƒÀ-aryl-3ƒ¿-arylmethoxytropane analogues exhibited greater potency for the serotonin transporter than the dopamine transporter. The most potent compounds of this series were 3ƒÀ-phenyl-3ƒ¿.(

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18

Ahmed, Tasrif. "Discovery of a Novel CCR5 Antagonist as an Effective Therapeutic Agent for Prostate Cancer." VCU Scholars Compass, 2010. http://scholarscompass.vcu.edu/etd/2215.

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Previously, the CCR5 receptor was found to be a good target for treating prostate cancer (PCa). Dr. Yan Zhang’s laboratory designed several CCR5 antagonists, which were screened for their inhibitory effect on the growth and invasion of the M12, DU145 and PC-3 PCa cell lines. Primary in vitro screening showed one compound (Drug 17) significantly inhibited the proliferation of PCa cells at 1μM concentration, with a half-maximal inhibitory concentration of 237.68 nM. Further in vitro assays including a proliferation, cytotoxicity and invasion assay confirmed the inhibitory effect of drug 17. The

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19

Heslop, James. "Investigating novel methods of enhancing in vitro models of drug induced liver injury." Thesis, University of Liverpool, 2015. http://livrepository.liverpool.ac.uk/2053229/.

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Drug induced liver injury (DILI) is a major cause of patient morbidity and mortality inferring considerable burdens onto healthcare and pharmaceutical sectors. As a consequence, substantial resources are directed towards triaging potentially dangerous new compounds at all stages of drug development. However, despite these efforts, hepatotoxic compounds remain the greatest cause of post-marketing drug withdrawal. One of the major factors preventing efficacious screening of new compounds is the lack of a truly representative in vitro model of hepatotoxicity. This thesis describes our efforts to

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20

Hatton, Christopher Martin. "Exploring marine sponges as a source of novel chemical entities for drug development." Thesis, Cardiff University, 2015. http://orca.cf.ac.uk/74792/.

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Antibacterial resistant infections are one of the most challenging problems affecting healthcare and have developed through the overuse of antibiotics and a shortage of new treatments progressing to market. Natural products are the initial source of most antibiotics currently available and marine sponges are a known resource of novel antibacterial compounds; although well-‐studied marine sponges found in UK waters have been scarcely explored. An examination of the chemical research on sponges identified previously unstudied species for collection in both Greece and Wales. Sequential solvent g

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21

Shah, Syeda Amena Batool. "Method development and application of novel analytical techniques for determining illicit and therapeutic drug use." Thesis, Kingston University, 2014. http://eprints.kingston.ac.uk/32207/.

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The research described in this thesis is based on novel analytical approaches to develop new methods for determining psychoactive and therapeutic drugs in biological matrices. All the analytical methods developed were according to Food and Drug Administration (FDA) guidelines. The first project involved development and validation of an analytical method for quantification of psychoactive drug mephedrone and its two metabolites 4- methylephedrine and 4-methylnorephedrine in human hair using liquid chromatography tandem mass spectrometry (LC-MS/MS). Recent abuse of designer drugs such as mephedr

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22

Bailey, Helen Victoria. "Drug design and novel anti-cancer therapeutics : inhibitors of 17β hydroxysteroid dehydrogenase type 3". Thesis, University of Bath, 2007. https://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.512267.

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Herein, we describe the design and synthesis of novel inhibitors of 17β-hydroxysteroid dehydrogenase type 3 which convert androstenedione into testosterone, which is then converted into dihydrotestosterone (DHT). This isozyme has been implicated in the growth of prostate cancer. Using an in silico pharmacophore model initial targets were planned, based around a diphenylether hydrophobic head linked to a 4-substituted piperidine ring. Over 45 compounds were synthesised and many show significant biological activity when evaluated in a 17β-HSD type 3 biological assay. The most potent compound in

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23

Reynolds, James Patrick. "Development of a novel means of drug administration to the female genital tract." Thesis, University of Brighton, 1995. https://research.brighton.ac.uk/en/studentTheses/8abe45cb-6f5f-45f6-8a50-81d11fecc4d1.

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The treatment of menopausal symptoms by combined hormone replacement therapy (HRT) utilises drug formulations whereby a progestii1 is added to the oestrogen component to decrease the risk of endometrial carcinoma prnduced by the oestrogen. However, administration of large doses of progestins can increase low density lipid cholesterol, as well as reduce some of the beneficial effects of oestrogens. Local administration of progestins to the uterus may allow a much smaller dose to be used reducing the antagonism produced by progestins on desired oestrogenic effects. The simplest way to administer

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24

Malalasekera, Aruni Peiris. "Development of novel therapeutic and diagnostic approaches utilizing tools from the physical sciences." Diss., Kansas State University, 2016. http://hdl.handle.net/2097/35779.

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Doctor of Philosophy<br>Department of Chemistry<br>Stefan Bossmann<br>Numerous Proteases are implicated in cancer initiation, survival, and progression. Therefore, it is important to diagnose the levels of protease expression by tumors and surrounding tissues, which are reflected in blood and tissue samples. Nanoplatforms for Cathepsin(CTS) B and L, matrix metalloproteinases(MMP) 1, 2, 3, 7, 9, 13 and urokinase plasminogen activator(uPA) detection have been synthesized. Nanoplatforms feature a central dopamine-coated core/shell Fe/Fe₃O₄ nanoparticle. Cyanine 5.5 is permanently tethered to the

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25

Brynne, Niclas. "Consequences of CYP2D6 polymorphism for the disposition and dynamics of tolterodine : a novel drug in the treatment of urinary bladder overactivity /." Stockholm, 1998. http://diss.kib.ki.se/1998/91-628-3205-0/.

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26

Garcia, Mayea Yoelsis. "Novel therapeutic approaches against Head and Neck Squamous Cell Carcinoma." Doctoral thesis, Universitat de Barcelona, 2020. http://hdl.handle.net/10803/672185.

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Head and neck squamous cell carcinoma (HNSCC) is usually diagnosed in advanced stages. The treatment has not changed much on the last decades, being limited to surgery followed by radiotherapy and/or chemotherapy [mainly cisplatin (CDDP) and 5-fluorouracil (5-FU)]. However, the acquisition of chemotherapy resistance is very common, which usually leads to recurrences and metastases. On the other hand, the role of autophagy in HNSCC is not clearly defined. This is the reason why in this thesis we have proposed: 1) to determine the role of autophagy in HNSCC models and its relationship with chemo

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27

Steen, Kayla M. "In silico and in vitro Toxicity Study of Two Novel Compounds that Exhibit Promising Therapeutic Potential." Ohio University / OhioLINK, 2019. http://rave.ohiolink.edu/etdc/view?acc_num=ohiou1564760758005406.

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28

Huang, Xiaomeng. "Targeted Delivery of MicroRNAs by Nanoparticles: A Novel Therapeutic Strategy in Acute Myeloid Leukemia." The Ohio State University, 2014. http://rave.ohiolink.edu/etdc/view?acc_num=osu1405095496.

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29

Amin, Amit Dipak, Lingxiao Li, Soumya S. Rajan, et al. "TKI sensitivity patterns of novel kinase-domain mutations suggest therapeutic opportunities for patients with resistant ALK+ tumors." IMPACT JOURNALS LLC, 2016. http://hdl.handle.net/10150/617186.

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The anaplastic lymphoma kinase (ALK) protein drives tumorigenesis in subsets of several tumors through chromosomal rearrangements that express and activate its C-terminal kinase domain. In addition, germline predisposition alleles and acquired mutations are found in the full-length protein in the pediatric tumor neuroblastoma. ALK-specific tyrosine kinase inhibitors (TKIs) have become important new drugs for ALK-driven lung cancer, but acquired resistance via multiple mechanisms including kinase-domain mutations eventually develops, limiting median progression-free survival to less than a year

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30

Ullah, Imran. "A novel in vitro bioluminescence rate-of-kill (BRoK) assay to study the pharmacodynamic properties of antimalarial drug action in Plasmodium falciparum." Thesis, Keele University, 2016. http://eprints.keele.ac.uk/2411/.

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Massive screens of chemical libraries for antimalarial activity have identified thousands of compounds that exhibit sub-micromolar potency against the blood stage of the malaria parasite Plasmodium falciparum. Triaging these compounds to establish priorities to take forward for development requires additional information regarding their activity. Key amongst their pharmacodynamics (PD) properties is the rate of kill– with a rapid cytocidal effect specifically identified as a key requirement for a Single Exposure Radical Cure and Prophylaxis (SERCaP) product. Compounds that exert an immediate c

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31

Assadian, Sarah. "Rodent FDG-PET imaging for the pre-clinical assessment of novel glioma therapies." Thesis, McGill University, 2007. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=101836.

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The rapid discovery of novel therapeutic agents, targeting the specific mechanism of cancer progression, invasion and angiogenesis, necessitates the development and validation of efficient techniques to assess the therapeutic efficacy of these drugs in vivo. Recently the development of dedicated PET scanners for the imaging of small animals, such as the microPET system (CTI Concorde R4), has allowed for the high-resolution functional and molecular imaging of murine and rodent models of disease. This study, investigates the ability of microPET imaging, using the 18F labelled 2-fluoro-2-deoxyglu

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32

Perni, Michele. "Establishing C. elegans as a high-throughput system for the identification of novel therapeutic strategies for Parkinson's disease." Thesis, University of Cambridge, 2017. https://www.repository.cam.ac.uk/handle/1810/270233.

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33

Verma, Abha. "Design, Synthesis and Biological Evaluation of Novel Cannabinoid Antagonist." ScholarWorks@UNO, 2012. http://scholarworks.uno.edu/td/1527.

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This study was aimed at the development of novel CB1 cannabinoid receptor antagonists that may have clinical applications for the treatment of cannabinoid and psychostimulant addiction. The rationale for the design for our target was to incorporate a bioisosteric 1,2,3-triazole ring into the vicinal diaryl group revealed in the prototypical antagonist/inverse agonist SR141716 (Rimonabant) that was presumed to interact with a unique region in the CB1 receptors. Based on our preliminary results we identified a novel series of 1,2,3-triazole ester and keto derivatives as lead compounds for bi

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34

Kia, Richard. "Novel approaches using human induced pluripotent stem cells and microRNAs in the development of relevant human hepatocyte models for drug-induced liver injury." Thesis, University of Liverpool, 2014. http://livrepository.liverpool.ac.uk/2010059/.

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Drug-induced liver injury (DILI) remains a prominent cause of patient morbidity and mortality, partly due to the lack of relevant in vitro hepatic models for accurate screening for drug-induced hepatotoxicity at the early stages of drug development, and also the lack of sophisticated in vitro model systems to mechanistically understand the pathways that are perturbed following drug exposure. This thesis describes our endeavour to develop more relevant in vitro human hepatocyte models via novel investigative approaches using insights gained from the rapidly advancing research areas of human ind

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35

Capdevila, Busquets Eva. "Network biology identifies novel apoptosis-related proteins and synergistic drug combinations in breast cancer." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/397786.

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Breast cancer is a very heterogeneous disease with a poor prognostic outcome, largely due to its resistance to current cancer therapies. The balance between cell proliferation and apoptosis plays a critical role in determining the overall growth or regression of the tumor in response to treatments. Hence, identifying treatments involved in apoptosis resistance is essential in order to find new therapeutic approaches. The heterogeneity of cancer is rarely due to abnormalities in single genes, but rather reflects the discontinuation of complex intercellular processes. Therefore, a useful way

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36

Morel, Daphné. "Identifying Synthetic Lethal and Selective Approaches to Target PBRM1-Deficiency in Clear Cell Renal Cell Carcinoma PBRM1 Deficiency in Cancer is Synthetic Lethal with DNA Repair Inhibitors Exploiting Epigenetic Vulnerabilities in Solid Tumors: Novel Therapeutic Opportunities in the Treatment of SWI/SNF-Defective Cancers Combining Epigenetic Drugs with other Therapies for Solid Tumours — Past Lessons and Future Promise Targeting Chromatin Defects in Selected Solid Tumors Based on Oncogene Addiction, Synthetic Lethality and Epigenetic Antagonism." Thesis, université Paris-Saclay, 2020. http://www.theses.fr/2020UPASL017.

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L’inactivation de polybromo-1 (PBRM1) est un évènement fréquent dans de nombreux cancers. En particulier, les carcinomes rénaux à cellules claires présentent une déficience en PBRM1 dans 40 à 50% des cas. A ce jour, il n’existe pas d’approche de médecine précision connue capable de cibler spécifiquement les cellules tumorales déficientes en PBRM1.Pour identifier des cibles de létalité synthétique associées à la perte de PBRM1, nous avons (i) réalisé un criblage pharmacologique à haut débit évaluant la sensibilité à 167 molécules dans un modèle cellulaire isogénique pour PBRM1, et (ii) étudié l

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Vilà, Rico Marta. "Transthyretin familial amyloid polyneuropathy: novel therapeutics derived from drug repurposing and new insights in diagnosis through proteomic analysis of clinical samples." Doctoral thesis, Universitat Ramon Llull, 2015. http://hdl.handle.net/10803/299374.

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La transtirretina (TTR) és una proteïna tetramèrica amiloidogènica (55 kDa) present al plasma humà i responsable del transport de la hormona T4 i del retinol a través de la proteïna d’unió a retinol (RBP). La proteïna TTR està associada amb diverses amiloïdosis, concretament la polineuropatia amiloide familiar (FAP), la cardiomiopatia amiloide familiar (FAC) i l’amiloïdosi senil sistèmica (SSA). La variabilitat associada a la TTR es deu tant a mutacions puntuals al gen codificant per aquesta com a modificacions post-traduccionals (PTMs) al residu Cys-10. Les PTMs més comuns associades a la Cys

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Bazzocco, Sarah. "Identification of novel therapeutic targets and tumor suppressor genes in colon cancer using genome-wide high‐throughput approaches." Doctoral thesis, Universitat de Barcelona, 2016. http://hdl.handle.net/10803/350805.

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Colorectal cancer is a disease caused by genetic and epigenetic changes. Inactivation of tumor suppressor genes and activation of oncogenes are key landmarks in tumor progression. However, the list of tumor suppressor genes and oncogenes is far from complete, even in the case of the tumor types that are best characterized, such as colorectal cancer. Colorectal cancer is the second most frequent cause of cancer-related death in the Western world and is a serious health issue for the European Union. Patients having stage III or IV cancer undergo surgery followed by chemotherapy. However, the cli

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Aitken, Laura. "Investigating protein-protein interactions in order to develop novel therapeutics for the treatment of Alzheimer's disease." Thesis, University of St Andrews, 2013. http://hdl.handle.net/10023/3531.

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Alzheimer's disease (AD) accounts for around two thirds of all dementia cases and an increase in life expectancy of the population has resulted in a substantial increase in dementia cases and with that a rise in AD. AD is a debilitating and ultimately fatal neurodegenerative disorder of the elderly, and despite being identified over a century ago, the current treatments do not treat the underlying causes behind the disease, instead they help to mask the symptoms of the disease and prolong the brain's remaining function. It is therefore vital that an effective, disease modifying treatment for t

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Recasens, Zorzo Clara. "Preclinical evaluation of the antitumor activity of a new CXCR4 inhibitor: a novel therapeutic approach in diffuse large B-cell lymphoma." Doctoral thesis, Universitat de Barcelona, 2018. http://hdl.handle.net/10803/663897.

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Constitutive activation of the chemokine receptor CXCR4 is associated with tumor progression, invasion and resistance to treatment. Overexpression of CXCR4 in diffuse large B-cell lymphoma (DLBCL) confers a reduced prognosis. However, the biological relevance of this receptor in DLBCL progression remains underexplored. In this thesis, the new CXCR4 inhibitor IQS-01.01 has been preclinicaly evaluated in in vitro and in vivo models of DLBCL. It has been concluded that 1) inhibition of CXCR4 presents antitumor properties in DLBCL, 2) that IQS-01.01RS holds better pharmacological properties than t

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Lopes, da Rosa-Spiegler Jessica. "Targeting the Histone Acetyl-Transferase, RTT109, for Novel Anti-Fungal Drug Development: A Dissertation." eScholarship@UMMS, 2012. https://escholarship.umassmed.edu/gsbs_diss/624.

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Discovery of new antifungal chemo-therapeutics for humans is limited by the large degree of conservation among eukaryotic organisms. In recent years, the histone acetyl-transferase Rtt109 was identified as the sole enzyme responsible for an abundant and important histone modification, histone H3 lysine 56 (H3K56) acetylation. In the absence of Rtt109, the lack of acetylated H3K56 renders yeast cells extremely sensitive to genotoxic agents. Consequently, the ability to sustain genotoxic stress from the host immune system is crucial for pathogens to perpetuate an infection. Because Rtt109 is con

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42

O'Farrell, Alice C. "Development of in vivo tumour models for non-invasive proof-of-principle investigation of novel therapeutic agents. Engineering and characterisation of bioluminescent cell reporter systems for in vivo analysis of anti-cancer therapy pharmacodynamics." Thesis, University of Bradford, 2011. http://hdl.handle.net/10454/5391.

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Despite significant advances in cancer treatment, clinical response remains suboptimal and there is a continued requirement for improved chemotherapeutics. The attrition rate for new therapies is high, due principally to lack of in vivo efficacy and poor pharmacodynamics. Consequently better systems are required to determine in vivo preclinical efficiency and drug-target interactions. Engineering of cancer cells to express fluorescent or bioluminescent proteins, either endogenously or under the control of specific gene promoters, and their detection by noninvasive optical imaging has the poten

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O'Farrell, Alice Claire. "Development of in vivo tumour models for non-invasive proof-of-principle investigation of novel therapeutic agents : engineering and characterisation of bioluminescent cell reporter systems for in vivo analysis of anti-cancer therapy pharmacodynamics." Thesis, University of Bradford, 2011. http://hdl.handle.net/10454/5391.

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Despite significant advances in cancer treatment, clinical response remains suboptimal and there is a continued requirement for improved chemotherapeutics. The attrition rate for new therapies is high, due principally to lack of in vivo efficacy and poor pharmacodynamics. Consequently better systems are required to determine in vivo preclinical efficiency and drug-target interactions. Engineering of cancer cells to express fluorescent or bioluminescent proteins, either endogenously or under the control of specific gene promoters, and their detection by noninvasive optical imaging has the poten

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Reipas, Kristen May. "Inhibiting p90 ribosomal S6 kinase (RSK)/Y-box binding protein-1 (YB-1) signaling is a novel targeted therapeutic strategy with the ability to overcome drug resistance in triple-negative breast cancer." Thesis, University of British Columbia, 2013. http://hdl.handle.net/2429/44616.

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Despite advances in treating breast cancer, disease recurrence rates remain high and secondary tumors are often refractory to chemotherapy. Currently, the treatment for triple-negative breast cancer (TNBC) relies upon conventional chemotherapeutics as no targeted therapies are available. Although these tumors initially respond well, they paradoxically have the highest relapse rates. Y-box binding protein-1 (YB-1) is an oncogenic transcription/translation factor abundantly expressed in TNBC (~70% of patients) and associated with disease relapse. It is activated predominantly by phosphorylation

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Dalmet, Christophe. "La notion de denrées alimentaires." Phd thesis, Université d'Avignon, 2009. http://tel.archives-ouvertes.fr/tel-00629627.

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Avec l'apparition massive des borderline products, les frontières traditionnelles entre la denrée alimentaire et les autres catégories de produits que l'on ingère ne cessent de se brouiller. Certes des éléments de définition de cette denrée se trouvent dans divers textes juridiques, notamment communautaires à l'image du règlement Food Law, mais toujours est-il que malgré tout demeure en partie le mystère identitaire qui entoure cette notion. Aussi, afin de pouvoir appliquer aux produits litigieux un statut adéquat et déterminer par la même le régime juridique qui doit être le leur, des référen

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Rakkanka, Vipaporn. "A novel self-sealing chewable sustained release tablet of acetaminophen ; Development and evaluation of novel itraconazole oral formulations ; A novel zero order release matrix tablet." Thesis, 2003. http://hdl.handle.net/1957/30894.

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Chen, Hsing-Jung, and 陳星蓉. "Screening Novel Potential Therapeutic Drugs for Spinocerebellar Ataxia Type 3 through Inducible Cell system." Thesis, 2011. http://ndltd.ncl.edu.tw/handle/28586103063289149972.

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碩士<br>國立臺灣師範大學<br>生命科學研究所<br>99<br>Spinocerebellar ataxia type 3 (SCA3), also called Machado–Joseph disease (MJD), is an autosomal dominant neurodegenerative disease results from expanded CAG repeat of MJD1 gene. The CAG repeat expansion encodes polyglutamine (polyQ) stretch in mutant ataxin-3 protein and causes protein cleaved, insoluble, accumulated and aggregated in the neurons. These inclusions further elevate cellular oxidative stress and lead to cell death. We established inducible cell system expressing human full length ataxin-3 containing 27Q or 75Q in PC12 cells. Cells with 75Q ataxi

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Chen, Hsin-Mei. "3' substituted indolones as novel therapeutic candidate drugs for the treatment of neurodegenerative diseases /." 2008. http://proquest.umi.com/pqdweb?did=1654488501&sid=2&Fmt=2&clientId=10361&RQT=309&VName=PQD.

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Omar, Ismail Naadhira. "Functional characterization of a peptide fragment, Os(3-12), derived from the carboxy-terminal region of a defensin from the tick Ornithodoros savignyi." Diss., 2015. http://hdl.handle.net/2263/49614.

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The rapid increase of multi-drug resistant bacteria and associated deaths has stimulated research into the development of novel therapeutic options. Antimicrobial peptides (AMPs) display a high therapeutic potential in solving this problem. Research focuses on new ways to enhance the antibacterial activity of AMPs and this includes the amidation of the C-terminus. Once the structure of an AMP is altered it is altered it is necessary to revaluate the properties of this AMP compared to the unaltered peptide. In this study, a peptide fragment Os(3-12), based on a defensin from the tick Ornithodor

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Caetano, Marta Daniela Passadouro. "MicroRNA modulation in combination with chemotherapeutic drugs as a novel therapeutic strategy for pancreatic cancer." Doctoral thesis, 2014. http://hdl.handle.net/10316/26516.

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Tese de doutoramento em Bioquímica, na especialidade de Tecnologia Bioquímica, apresentada ao Departamento de Ciências da Vida da Faculdade de Ciência e Tecnologia da Universidade de Coimbra<br>O adenocarcinoma ductal do pâncreas (ACP) é uma neoplasia altamente agressiva, com um carácter acentuadamente invasivo e um perfil de expressão de microRNAs anormal, que tem sido fortemente associado à malignidade do ACP. A gemcitabina é o fármaco mais utilizado na terapia deste tipo de cancro, embora sem grande impacto na sobrevivência dos pacientes. A falta de tratamentos eficazes para o ACP levou-no

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