Thesis (Ph.D.)--Aberdeen University, 2008. / Title from web page (viewed on Dec. 1, 2009). Includes bibliographical references.

Our hypothesis is that the polyamine biosynthetic pathway, a pathway essential in many cellular functions, is modulated by NSAIDs and that this is, at least in part, how NSAID chemoprevention is mediated. An <i>in vitro </i>model of colorectal cancer was used: two cell lines one of which is COX positive and one COX negative to determine the effects of a range of selective and non-selective NSAIDs on various reactions within the polyamine pathway.  NSAIDs are cytotoxic to colorectal cancer cells regardless of their COX expression.  NSAID-mediated inhibition of cell growth is accompanied by inhibition of ODC activity, partial depletion of polyamine concentrations and up-regulation of polyamine catabolism. In order to investigate the importance of polyamine metabolism, a specific polyamine inhibitor α-difluoromethylornithine (DFMO) was used in combination with the NSAIDs.  DFMO <i>per se </i>is not toxic to cells and it does not enhance NSAID mediated toxicity.  DFMO in combination with the NSAIDs did cause increased catabolic activity and more sustained polyamine depletion than either alone, however no additional decrease in ODC activity was observed.  This suggests that NSAID toxicity is not enhanced by DFMO in this <i>in vitro </i>model. Analysis of the mode of death indicated that the NSAIDs caused apoptotic cell death, confirmed through biochemical and morphological studies and that the NSAIDs affected gene expression of key enzymes in the polyamine biosynthetic pathway. Our findings suggest that modulation of the polyamine pathway by NSAIDs is at least part of the mechanism of action involved in cancer chemoprevention. Therefore modulation of the polyamine pathway may be useful for design of new chemopreventative drugs.

Diss. (sammanfattning) Umeå : Umeå universitet, 2005. / Härtill 4 uppsatser.

Thesis (Ph. D.)--West Virginia University, 1999. / Title from document title page. Document formatted into pages; contains xii, 150 p. : ill. Includes abstract. Includes bibliographical references (p. 124-128).

Thesis (M. Sc.)--University of Toronto, 1996. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M. Sc.)--University of Toronto, 1996. / Includes bibliographical references.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2006. / Härtill 4 uppsatser.

Resumo: Os metabólitos do AA exercem um reconhecido papel na patogênese da doença periodontal. O objetivo deste trabalho foi avaliar o efeito do celecoxib, um inibidor seletivo da enzima cicloxigenase-2 (COX-2), sobre o desenvolvimento de doença periodontal induzida por ligadura em ratos. Após a colocação de ligadura de algodão ao redor dos primeiros molares inferiores direitos, 180 ratos Holtzman foram aleatoriamente subdivididos em 3 grupos experimentais com 60 animais cada, os quais receberam diariamente dose oral de celecoxib 10 mg ou 20 mg/ kg de peso corporal (grupos Ce1 e Ce2, respectivamente) ou, dose oral de 10ml/kg de NaCl a 0,9% (grupo Controle). Aos 3, 5, 10, 18 e 30 dias após o início do experimento, 12 animais de cada grupo experimental foram sacrificados. O tratamento com celecoxib, em ambas as concentrações, reduziu significantemente (p<0.05) a perda óssea alveolar radiográfica aos 5 dias e, diminuiu a intensidade da reabsorção óssea, observada histologicamente, aos 30 dias. Ainda, o celecoxib atrasou o início e, diminui a magnitude, do processo inflamatório agudo. Estes resultados demonstram que a inibição seletiva da COX-2 com o celecoxib, pode interferir com a resposta do tecido periodontal frente à presença de ligadura em ratos. / Abstract: Arachidonic acid metabolites have a recognized role in the pathogenesis of periodontal disease. The purpose of this study was to evaluate the effect of a selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, on the progression of periodontal disease in a ligature-induced periodontitis model in rats. After ligature placement in the mandibular right first molars, 180, 6-week-old Holtzman rats were ramdomly assigned to one of the following groups of treatment that consisted in a daily oral dose of 10mg/kg body weight of celecoxib (Ce1), 20mg/kg body weight of celecoxib (Ce2) or 10ml/kg of 0,9%NaCl (Control). At 3, 5, 10, 18 and 30 days later, 12 animals of each group were sacrificed. Treatment with celecoxib significantly (p < 0.05) decreased the radiographic bone loss at 5 days of experiment and, decreased the bone loss activity, histologically observed at 30 days. In addition, celecoxib was shown to delay the onset and to suppress the magnitude of the acute inflammatory process. These results show that selective cyclooxygenase-2 (COX-2) inhibition with celecoxib, can interfer with the periodontal tissue response to ligature placement in rats. / Orientador: Luís Carlos Spolidorio / Coorientador: Elcio Marcantonio Junior / Banca: Joni Augusto Cirelli / Banca: Maria Angela Naval Machado / Mestre

Thesis (M.S.)--West Virginia University, 2002. / Title from document title page. Document formatted into pages; contains viii, 51 p. : ill. Includes abstract. Includes bibliographical references (p. 39-42).

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2010.