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 58 for “"Drug combination"”.
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Accurate estimation of drug combination synergies with uncertainty quantification
… frameworks to estimate the synergistic effect of drug combinations. However, the varying assumptions and the absence of a universal gold standard across these frameworks make it difficult to quantitatively prioritise which drug combinations from large screening experiments should advance for …
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IDENTIFICATION OF AN EFFECTIVE RIBONUCLEOSIDE ANALOGUE AND IMMUNOMODULATORY IMIDE DRUG COMBINATION FOR MULTIPLE MYELOMA
… the current standard treatments mainly involve combination therapies targeting multiple pathways. Despite rapid advance in therapeutics, MM remains incurable and most patients eventually relapse. To identify effective novel drug combinations against MM, we applied our quadratic phenotypic …
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Discovery of Dihydroartemisinin and Dasatinib Drug Combination to Cure Pooroutcome BCR-ABL+ Acute Lymphoblastic Leukemia
… and chronic myelogenous leukemia (CML). Food and Drug Administration (FDA)- approved BCR-ABL-specific kinase inhibitors (BCR-ABL–KIs) imatinib, dasatinib and nilotinib induce prolonged remissions in CML but poor leukemia-reduction and relapse-control in Ph+ ALL. The relative primary …
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Sample size determination for Emax model, equivalence / non-inferiority test and drug combination in fixed dose trials.
… used models defining the relationship of drug efficacy with respect to its dosing levels in pharmacokinetic /pharmacodynamic studies. In frequentist approach, sample sizes are determined by desired accuracy for the parameter of interest ED₅₀. Non-linear mixed effects model is applied to …
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The characterization of pharmacokinetic properties and evaluation of in vitro drug combination efficacies of novel antimalarial compounds
… of the Chinese peroxidic antimalarial drug artemisinin primarily used in first-line combination therapy for treatment of P. falciparum malaria have proved to be highly effective. However, their use also is now compromised by the development of resistance by the parasite to the …
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Overcoming Acquired Resistance to BRAF Inhibitors by Novel Synergistic Drug Combination and Discovery of Novel Smac Mimetics as Selective Survivin Inhibitors
… 1 and 2) of this dissertation presents a novel combination study of melanoma therapy. Acquired clinical resistance to vemurafenib, a selective BRAFV600E inhibitor, arises frequently after short term chemotherapy. Since the inhibitions of targets in the RAFMEK-ERK pathway result in G0/G1 cell …
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Repurposing Alzheimer’s disease medications in a drug combination for the study of the crosstalk between cell apoptosis and autophagy in the modulation of cell death in chronic myeloid leukaemia
… number of studies have reported certain AD drugs to possess anti-cancer properties. This raises the possibility of repurposing these AD drugs for the treatment of cancers such as chronic myeloid leukaemia (CML). This requires the understanding of the possible interconnection between CML and …
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Inferring effective cancer combination therapies using network-based multi-omics data integration
… resistance to monotherapy-based interventions. Drug combination therapies hold the promise of higher efficacy by simultaneously targeting compensatory mechanisms in tumours and reducing toxicity through the use of lower drug doses. However, identifying effective combination therapies and the …
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Investigating the Anti-Melanoma Activity of Combinatorial Paclitaxel and MEK Inhibitor
… Traditional and newly-developed anti-melanoma drugs do not produce a satisfactory therapeutic response for the treatment of late stage melanoma. Nanomedicine is a potent tool for clinicians to circumvent many of the existing shortcomings in cancer therapy. Combination of more than one drug may …
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Combinatorial therapy for triple negative breast cancer and the effect of nanoscale surfaces
… to explore combinatorial therapy regime. A combination of STAT-3 specific inhibitor, reported to act synergistically with metformin in reducing cell growth and inducing apoptosis in TNBCs and agents targeting DNA repair, can produce a new approach to TNBC therapy. Towards this aim, we have …
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Targeting the intestinal stem cell niche through energy and metabolism signaling, for colorectal cancer chemoprevention using aspirin and metformin
… protective role in obese individuals. Both drugs reduce stemness in CRC cell lines independently, however, the potential of the combination of aspirin and metformin for the chemoprevention of obesity- driven CRC remains to be explored. Hence, this thesis aims to understand whether aspirin …
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Enhancing the use of opioids in pain management: antinociceptive potentiation with opioid agonist/antagonist combinations.
… are the most effective and widely used class of drug for the management of moderate to severe pain, their use may be limited by adverse effects that are unpleasant and potentially dangerous. Research is increasingly directed towards strategies to improve the use of opioids in pain management, …
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Induction of death in myeloid leukaemia cells by doxorubicin and betulinic acid, singly and in combination was associated with the regulation of apoptosis, autophagy and the PI3K/Akt pathways
… agents could modulate these signalling pathways. Drugs such as doxorubicin (Dox) are effective but displayed some clinical drawbacks, while compounds such as betulinic acid (BetA) have shown some interesting activity against cancerous cells. These drugs may complement each other in sensitising and …
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MANIPULATING CELL STATES FOR LEUKAEMIA DIFFERENTIATION THERAPY USING NETWORK PHARMACOLOGY
… utility of the MOGRIFY® algorithm in identifying combinations of transcription factors (TFs) and drugs which induce granulocytic differentiation of the NB4 acute promyelocytic leukaemia (APL) cell line. Connectivity Map (CMAP) analysis of these TFs and their target networks identified dimaprit and …
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Evaluating the Effect of Chronic Alcohol, Cocaine, and Co-Administration on Endogenous Adult Neural Stem Cell Survival, Differentiation, and Proliferation
… co-abused substances, and the third most fatal drug combination. Efforts in drug addiction research primarily focus on preventing or stopping abuse; however little work is being done to reverse brain damage incurred by chronic drug abuse. Neural stem cells (NSCs) are a promising target to …
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Tracking Treatment Response and Resistance to Parp Inhibition (Talazoparib) In Hereditary Pancreatic Cancer.
… 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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Combinatorial Modulation of Multiple Signaling Pathways to Gain Therapeutic Response in Breast and Prostate Cell Carcinomas
… and radiation. In our studies, we utilized novel drug combinations with and without radiation to enhance breast & prostate tumor cell death both in vitro and in vivo. Previous studies from our group have shown that UCN-01 and MEK1/2 inhibitors interact to cause tumor cell death in transformed cell …
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Bayesian Adaptive Clinical Trial Design
<p>The landscape of drug development in oncology has changed from conventional chemotherapies to molecular targeted therapies and immunotherapies, which provide innovative therapeutic modalities for treating cancers. These novel therapeutic agents work through mechanisms that fundamentally differ …
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Rational drug combinations to selectively target 9p21-deleted bladder cancer
… tumors. Here, we performed a multi-parametric drug screening using 9p21 isogenic BLCA cells to uncover drugs with a 9p21-selective activity on cell morphology and viability. Two drugs resulted significantly more effective in cells with 9p21 loss, cytarabine and methotrexate, however with …
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