Diss. (sammanfattning) Stockholm : Karol. inst., 2005. / Härtill 4 uppsatser.

Thesis (Ph. D.)--West Virginia University, 2005. / Title from document title page. Document formatted into pages; contains xi, 292 p. : ill. (some col.). Vita. Includes abstract. Includes bibliographical references (p. 253-268).

Many studies have reported the anti-cancer effects of n-3 long chain polyunsaturated fatty acids (n-3 LCPUFAs). In this study, the anticancer effects of n-3 LCPUFAs and their derivatives, n-3 n-acyl ethanolamides (n-3 NAEs) were investigated in MCF-7 and MDA-MB-231 breast cancer cell lines. The focus was on their effects on cell proliferation, the role of CB1 and CB2 receptors, the effects of their main metabolising enzyme, FAAH, and which molecular signalling pathways are involved. In addition, the effects on the redox system, particularly in the modulation of redox genes, proteins and enzymes, the role of epigenetic regulation, and the effects on cell invasion and migration were also investigated. The results showed that n-3 NAEs were more potent than their parent LCPUFAs at reducing cell viability while the effects of both n-3 LCPUFAs and n-3 NAEs appear to be CB receptor mediated. In addition, MAPK pathways were also affected to varying extents following treatment, in particular p38 and JNK. Furthermore, global methylation, antioxidant gene expression, migration and invasion were in general all modulated by treatment. However, the effects observed were found to be both treatment- and cell- type dependent. Nevertheless, these results confirm that n-3 LCPUFAs and n-3 NAEs inhibit breast cancer cell growth, and modulate important cancer related pathways albeit by different mechanisms. This suggests that dietary intervention with cheap, safe, readily available fatty acids could be introduced to breast cancer patients to enhance treatment.

published_or_final_version / Medical Sciences / Master / Master of Medical Sciences

No description available.

No description available.

Class of 2012 Abstract / OBJECTIVES: Therapeutic response to chemotherapeutic agents in vitro can be studied using immortalized lymphoblastoid cell lines (LCLs). While LCLs provide a valuable model to study heritable factors and anticancer drug reponse in large populations, the results may be confounded by properties inherent to the model. This study is used to explore possible confounders in Choy et al.’s publicially available dataset (Accession#: GSE11582). METHODS: This study utilized Affymetrics U133A array gene expression and phenotypic data for 162 unrelated LCLs. SPSS was used for two-tailed bivariate Pearson correlation analysis comparing relative 6-mercaptopurine (6-MP), 5-fluorouracil (5-FU), and methotrexate sensitivities, growth rate and ATP levels. GeneSpring was used to compare the top and bottom quartiles of relative ATP levels using the unpaired T-test with a significance threshold of 0.001 and Benjamin-Hochberg FDR (n=82). RESULTS: It was found that relative sensitivities of 5-FU and 6-MP are significantly correlated (r2= 0.627, p<0.0001). Furthermore, it was determined that 5-FU sensitivity and growth rate and ATP levels are also correlated; however, no significant correlation was found between growth rate and ATP levles (r2=0.127, p=0.107). Relative ATP level was found to be a more significant determinant of 5-FU sensitivity than growth rate. GeneSpring analysis showed that 1500 genes are differentially regulated based on ATP levels. The gene ontology related to nucleic acid metabolism was overrepresented (p=1.425E-15). CONCLUSIONS: The results above suggest that growth rate and, to a greater extent, baseline ATP levels influence genetic expression of LCLs and may confound in vitro studies of antineoplastic agents.

by Tim-tak Kwok. / Bibliography: leaves 157-171 / Thesis (M.Phil.)--Chinese University of Hong Kong, 1982

No description available.

Thesis (Ph. D.)--Ohio State University, 2006. / Available online via OhioLINK's ETD Center; full text release delayed at author's request until 2007 Jun 14