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  • About
  • The Global ETD Search service is a free service for researchers to find electronic theses and dissertations. This service is provided by the Networked Digital Library of Theses and Dissertations.
    Our metadata is collected from universities around the world. If you manage a university/consortium/country archive and want to be added, details can be found on the NDLTD website.
1

Exploring Novel Drug Treatments for Chemotherapy Resistance In Human Epithelial Ovarian Cancer (EOC)

Moraya, Amani, Ali, Jennifer, Arthur, Gilbert, Schweizer, Frank, Werbowetski-Ogilvie, Tamra, Nachtigal, Mark, Morrison, Ludivine, Liang, Lisa 01 September 2016 (has links)
Chemotherapy resistance in human epithelial ovarian cancer (EOC) is a significant reason for the high rate of death among patients. We hypothesized that chemotherapy- resistant EOC cells will be killed by novel drug treatments in non-adherent culture conditions. The objective of this study was to test the efficacy of novel drugs to affect platinum resistant EOC cell viability. To achieve this, the cell killing efficacy of several drugs were tested on drug-resistant EOCs growing in non-adherent cultures. Both EOC cell lines and primary EOC cells isolated from patient ascites were used for these studies. Two different classes of drugs were tested including multikinase inhibitors (dorsomorphin and LDN-193189), and an understudied class of novel chemotherapeutic agents called glycosylated antitumor ether lipids (GAELs). EOC cells were treated with the drugs at different doses alone or in combination with cisplatin. Because GAELs exhibited promising results in resistant EOC cells, the mechanism of GAEL-induced cell-death was evaluated. / October 2016
2

Novel Therapy against Malaria Resistance using Meta-analysis

Oguntuyi, Adesola January 2022 (has links)
Malaria causes severe illness and death in some cases if not treated on time. The most vulnerable people are children and pregnant women in areas where it is rampant. The causative agent of the most severe malaria is Plasmodium falciparum this parasite is transmitted by the female anopheles mosquito when infected with Plasmodium parasites. Southeast Asia and sub Saharan Africa have the highest malaria death rate. Meta-analysis is one of the statistical tools used for estimating the mean and variance of underlying effects of a population under study from a collection of data from empirical studies addressing same research question. Meta-analysis has become an increasing valuable tool in research. This study describes the meta-analysis of novel antimalarial drugs. It involved selection of eligible articles based on certain inclusion criteria, calculating effect sizes, conducting the actual analysis using a popular software such as IBM SPSS and thus, estimating the effects of publication bias. This study identified three novel therapies used to treat Artemisinin Combination Therapy (ACT) resistant malaria. The resistance against ACT is developed in malaria due to mutation in K13 gene. It is evident that these different novel therapies in combination with ACT treatment can be used to treat resistant malaria and reduce the mortality rate.
3

Anti-Inflammatory PARP Inhibitor Demonstrates Antidepressant Activity in Animal Model of Treatment Resistant Depression

Ordway, Gregory A., Gill, W. D., Coleman, J. B., Wang-Heaton, Hui, Brown, Russell W. 01 May 2019 (has links)
Background: Major depressive disorder is associated with elevated levels of DNA oxidation, DNA damage, and gene expression of DNA repair enzymes including poly (ADP-ribose) polymerase-1 (PARP1). Elevated PARP1 activity is directly linked to neuroinflammation and PARP inhibitors are anti-inflammatory and neuroprotective. We previously showed that PARP inhibitors produce antidepressant-like effects equivalent to fluoxetine in rodent models. Here, we examined whether the PARP inhibitor 3-aminobenzamide (3AB) is effective in a rat model of treatment-resistant depression. Methods: Treatment-resistant depression was modeled with injections of lipopolysaccharide (LPS; 0.1 ug/kg/day) and daily chronic unpredictable stress (CUS) for 28 days. Anhedonia and helplessness were indexed with sucrose preference and forced swim tests, respectively, in 5 groups of rats (n¼6-8 rats/group) including unstressed, CUS, and CUS+LPS rats treated with saline, and CUS+LPS rats treated with either 3AB or fluoxetine. Results: Anhedonia induced by CUS+LPS was significantly attenuated by 3AB (p¼0.01), while fluoxetine failed to do so. Likewise, 3AB was superior to fluoxetine in reducing helplessness, where latency to immobility times were significantly lower in CUS+LPS rats treated with fluoxetine (p¼0.001) compared to unstressed rats, but not significantly different for 3AB-treated CUS+LPS rats. Conclusions: The PARP inhibitor 3AB demonstrated robust and unique antidepressant activity superior to fluoxetine in the TRD rat model. PARP is linked to neuroinflammation through release of microglia-activating factors including poly (ADP-ribose) and HMGB1, and through NF-kB activation, pathways under investigation by our lab. PARP inhibitors are currently used clinically to facilitate cytotoxicity of DNA-damaging anti-cancer treatments. Further research could implicate re-purposing non-cytotoxic PARP inhibitors for treatment-resistant depression.

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