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 165 for “"Chemotherapeutics"”.
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Insights into the Development of Chemotherapeutics Targeting PFKFB Enzymes
The PFKFB enzymes control the primary checkpoint in the glycolytic pathway and are implicated in a multitude of diseases: from cancer, to schizophrenia, to diabetes, and heart disease. The inducible isoform, PFKFB3, is known to be associated with the upregulation of glycolysis in many cancers. The …
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Transient Metabolic Alterations Induced by Chemotherapeutics in Cancer Persisters
… our data indicate they may be induced by cancer chemotherapeutics. Furthermore, with the use of untargeted metabolomics and phenotype microarrays, we demonstrated a transient upregulation in Krebs cycle metabolism in persister cells. We verified that targeting mitochondrial activity can …
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Synthesis and evaluation of novel azaindolocarbazole derivatives as cancer chemotherapeutics
This thesis details the design and implementation of novel chemical routes towards a series of highly propitious 7-azaindolyl derivatives of the indolocarbazole (ICZ) and bisindolylmaleimide (BIM) families, with subsequent evaluation for use as cancer chemotherapeutic agents. A robust synthetic …
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Peptide-mediated delivery of antisense oligonucleotides and chemotherapeutics across biological barriers
… of antisense oligonucleotides (ASOs) and chemotherapeutics. First, we address the issue that the optimal peptide sequence for the delivery of a macromolecular cargo is often context-dependent and specific to that cargo. With one class of ASO, we develop a paradigm that combines systematic …
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Functional genetics reveals surprises about the mechanisms of action of chemotherapeutics
… anti-cancer agents. First, the platinum-based chemotherapeutics, cisplatin and its analogues, carboplatin and oxaliplatin, were evaluated. Previously all platinum anti-cancer agents were assumed to kill cells via DNA cross-linking. However, using an RNAi-based drug mechanism of action …
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Tumour chemo sensitivity assays: an investigation into the susceptibility of cells to chemotherapeutics
To evaluate and identify new candidate cancer drug targets, there is an ongoing need for a reliable, sensitive and quantitative assay that enables the analysis of larger numbers of compounds in preclinical research. This thesis has developed, and optimized a sensitive enzyme-release assay for …
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Vitellogenin induction in male Japanese medaka exposed to the chemotherapeutics: oxytetracycline, Romet-30, and copper sulfate
… Vitellogenin induction from exposure to the chemotherapeutics: oxytetracycline, Romet-30®, and copper sulfate was evaluate using Japanese medaka (Oryzias latipes). Medaka were exposed to E2 (0.0552 ìg/L) in aquaria water as a positive control. Medaka were fed oxytetracycline medicated feed …
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p53 Functional Interactions: the Study of a New Crosstalk with Estradiol Pathway in Transcriptional Responses to Chemotherapeutics
BACKGROUND: Objective of this thesis has been the analysis of the sequence specific transcription factor p53, a critical tumor suppressor protein, specifically, the crosstalk (or functional interactions) with other transcription factors, namely, the estrogen receptors, and the modeling in …
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Development Of Novel Breast Cancer Chemotherapeutics Directed Towards The Attenuation Of Metastatic And Chemo-Resistant Breast Cancer
… they target the DNA itself. New generations of chemotherapeutics looked to overcome problems that the first had left: improved selectivity, reduced side effects, increased potency, and the ability to target cancer cells more precisely. As such, the first phase in this project aimed to attenuate …
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IGPR-1 promotes colorectal cancer tumor cell survival and modifies the response of cancer cells to chemotherapeutics
… of IGPR-1 in the development of resistance to chemotherapeutics. In addition, non-adherent cell culture conditions promoted activation of the key pro-apoptotic kinase, p38 MAPK in CRC tumor cells. Ectopic expression of IGPR-1 reversed this activation. This data suggests that IGPR-1, by …
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FOLATE RECEPTOR TARGETED LIPOSOMES AS THE ENABLING TECHNOLOGY FOR THE DELIVERY OF CHEMOTHERAPEUTICS IN THE TREATMENT OF OVARIAN CANCER
Chemotherapeutic agents encapsulated in FR-targeted liposomes have shown potential for increased therapeutic efficacy and decreased toxicity. Folate receptors are over-expressed in almost 90% of the ovarian cancers. Thus intracellular delivery of carboplatin through FR targeted liposomes could …
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Assessment of the in vitro efficacy of aspirin and aspirin analogues in combination with standard chemotherapeutics in glioma cell lines
Glioblastoma multiforme (GBM) is the most common and most malignant primary brain tumour. The prognosis for patients remains poor with a median survival time falling well short of a year in spite of surgical removal of tumour followed by radiotherapy. GBM is resistant to the current treatment …
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Novel drug interaction for improving intracellular accumulation and efficacy of chemotherapeutics in retinoblastoma and mitochondrial localization of transporters in corneal epithelial cells
Chemoreduction is the key treatment for retinoblastoma management. However, anticancer agents suffer from poor cell permeability and chemoresistance due to major interaction with multidrug resistant (MDR) efflux proteins (MDR1 and MRP2) over-expressed on retinoblastoma tumor. Ocular cells have …
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Drug Design, Biological Activity, and Metabolic Consequences of Cytotoxic Platinum Compounds: Utilizing Fluorescent Tagging to Understand Drug Action and Metabolism
Platinum drugs are among the most commonly used chemotherapeutics for the treatment of testicular, head and neck, ovarian, small cell lung, and colorectal carcinomas. Although the current set of platinum chemotherapeutics has proven somewhat successful, the overall success of platinum based drugs …
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Anticancer Activity of Natural Health Products (Dandelion Root, Lemongrass, and Hibiscus Extracts); A Study of Efficacy, Interaction, and Mechanism of Action
… as well as their interactions with standard chemotherapeutics have not been studied to determine if they will be suitable for adjuvant therapies. If successful, these extracts could potentially be used in conjunction with chemotherapeutics to minimize the risk of drug-related toxicity and …
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CRISPRi screens to identify combination therapies for the improved treatment of ovarian cancer
… resistance in tumor cells treated with platinum chemotherapeutics, I performed genome-wide screens combining cisplatin or oxaliplatin with CRISPRi pooled gene knockdowns. Screens were analyzed at 9-days to mimic patient care, and at 48-hours to isolate the short-term DNA damage response. Genes …
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High Resolution Mass Spectrometry (HRMS) Based Investigation of Small Molecule, Bioactive Secondary Metabolites as Probes in the Examination of Bacterial Resistance and Virulence
<p>The widespread availability of antimicrobial chemotherapeutics over the last half of the twentieth century has offered dramatic increases in life expectancy. Unfortunately, many pathogenic agents are exhibiting ever increasing resistance to many frontline antibiotics. New chemotherapeutic agents …
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Probing the mechanisms of action and resistance of mixed-ligand platinum(II) complexes with dual-stage antiplasmodium activity
… and spread of resistance to most clinical chemotherapeutics. With the reported development of partial resistance to the current front-line artemisinin-based combination therapies, there is an increased risk of malaria morbidity and mortality as limited replacement treatments are currently …
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The Role of the Aryl Hydrocarbon Receptor in Tumor Growth and Chemoresistance
… assays coupled with dosing of commonly used chemotherapeutics, the effects of the AHR on the chemo-resistance of SCC2s was tested. Three commonly used chemotherapeutics were tested at various dose ranges: Cisplatin (0-10uM), doxorubicin (0-1uM), and 5-Fluorouracil (0-10uM). In addition, cells …
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Biologically Inspired Design of Protein-Silica Hybrid Nanoparticles for Drug Delivery Applications
… vexing health problems. Traditionally utilized chemotherapeutics are limited in efficacy due to poor bioavailability as a result of their size and solubility as well as significant deleterious effects to healthy tissue through their inability to preferentially target pathological cells and …
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