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Diss. (sammanfattning) Stockholm : Karolinska institutet, 2002. / Härtill 5 uppsatser.

Thesis (Ph. D.)--Memorial University of Newfoundland, Faculty of Medicne, 2001. / Typescript. Includes bibliographical references (leaves 156-172).

Orientador: Nelson Adami Andreollo / Dissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciencias Medicas / Made available in DSpace on 2018-08-13T09:17:24Z (GMT). No. of bitstreams: 1 Modena_SergioFerreira_M.pdf: 1827923 bytes, checksum: 65534a0b51b23922df11c4977531952b (MD5) Previous issue date: 2009 / Resumo: Os compostos de nitrito e nitrato são sais há muito empregados como conservantes de alimentos, que neste atual contexto de aumento acentuado da população mundial e escassez de alimentos, será cada vez mais empregado. Por outro lado, o perfil da sociedade é, cada vez mais, se utilizar de alimentos industrializados prontos para consumo, nos quais estão embutidos vários conservantes na sua elaboração. Estes sais, por sua vez, têm ação danosa ao organismo em situações específicas, como demonstram vários experimentos. A Doença do Refluxo Gastro-Esofágico tem crescido em incidência por todo mundo e em especial em países desenvolvidos como os Estados Unidos e Europa, onde são relatados índices alarmantes do crescimento da freqüência dos carcinomas da junção esôfago-gástrica. O objetivo desta pesquisa foi analisar o modelo experimental de refluxo duodeno-esôfago-gástrico e a ingestão de solução de nitrito de sódio na gênese do adenocarcinoma associado ao esôfago de Barrett. Sessenta ratos machos Wistar foram divididos em quatro grupos, com vinte animais controles não operados (10 animais ingeriram somente água e 10 animais ingeriram água mais solução de nitrito de sódio) e quarenta animais submetidos a anastomose duodeno-esôfago-gástrico látero-lateral (20 animais ingeriram somente água e 20 animais ingeriram água mais solução de nitrito de sódio). A classificação de Viena para displasia e adenocarcinoma foi empregada na análise dos resultados. Após 42 semanas de observação, nos animais operados sem ingestão de nitritos o esôfago de Barrett foi registrado em 26,3% (5/19) dos animais, enquanto no grupo operado associado à ingestão de nitritos, foi encontrado em 72,3% (13/18) dos animais, sendo que neste grupo também foi encontrado seis adenocarcinomas (33,3%). Nenhum animal não operado apresentou o esôfago de Barrett. As categorias 2, 3 e 5 da classificação de Viena somente foram encontradas nos animais operados que ingeriram nitrito de sódio (66,7%). Concluem que a ingestão de nitrito de sódio associado ao refluxo duodeno-esôfago-gástrico têm importante participação na gênese do adenocarcinoma associado ao esôfago de Barrett. / Abstract: The nitrates and nitrites are salts has been using a lot as conservants and chemical additives of foods, that in this current context of accentuated increase of the world population and shortage of foods, they will be used more. On the other hand, the profile of the society is more and more to use industrialized foods ready for consumption, which they utilize several conservants in its elaboration. These salts have harmful action to the organism in specific situations, as demonstrated in many experiments. The gastroesophageal reflux disease has been growing in incidence all over the world mainly in the United States and Europe and related to the alarming indexes of growth of the frequency of carcinomas of the esophagogastric junction. The objective of this research was to analyze the experimental model of duodenum-gastro- esophagic reflux and the ingestion of a solution of sodium nitrite in the genesis of the adenocarcinoma associated to the Barrett's esophagus. Sixty Wistar male rats were divided in four groups: twenty animals controls not operated (10 animals ingested only water and 10 animals ingested water plus sodium nitrite) and forty animals submitted to the side-to-side duodenum-gastro-esophagic anastomosis (20 animals ingested only water and 20 animals ingested water plus solution of sodium nitrite). The Vienna Classification for dysplasia and adenocarcinoma was used in the analysis of the results. After 42 weeks of observation, in the group operated without nitrite ingestion the Barrett's esophagus was found in 26,3% (5/19) of the animals, while in the group operated associate to the nitrite ingestion, it was found in 72,3% (13/18) of the animals, and in this last group it was also found six adenocarcinomas (33,3%). Any animal no operated presented Barrett's esophagus. The categories 2, 3 and 5 of the Vienna Classification were only found in the animals operated that they ingested sodium nitrite (66,7%). The final conclusion is that the ingestion of sodium nitrite associated to duodenum-gastro-esophagic reflux has important participation in the genesis of the adenocarcinoma associated to the Barrett's esophagus. / Mestrado / Cirurgia / Mestre em Cirurgia

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published_or_final_version / abstract / Surgery / Doctoral / Doctor of Philosophy

This thesis demonstrates a pulse-chase assay that describes the turnover of the .r J normal human oesophageal epithelium and Barretr~- metaplasia. to be approximately 11 days. This assay also identified the existence of label-retaining cells after 67 days within the basal layer of the human oesophagus and showed that these cells were epithelial in origin, capable of division yet are not frequently dividing. Furthermore, label-retaining cells were identified within the base of Barrett's glands and were also epithelial and primarily undifferentiated. This thesis suggests that these cells may represent a population of stem cells within the human oesophagus. Using mtDNA mutations as markers of clonal expansion, this thesis demonstrates the presence of a stem cell niche within the normal human oesophagus. Furthermore, clonal patches covering large areas of squamous epithelium were observed. In Barrett's oesophagus, partially-mutated glands were observed indicating that glands are maintained by multiple stem cells. Wholly-mutated Barrett's glands contain all the expected differentiated cell lineages; demonstrating multilineage differentiation from single stem cells. Patches of clonally-related Barrett's glands were also observed; indicating that glands can divide by fission. In one patient the squamous epithelium and the underlying glandular tissue were shown to be derived from a common progenitor cell. TNFa was shown to induce migration of Barrett's cells in vitro suggesting that the inflammatory environment contributes to the expansion of Barrett's lesion. Furthermore, data presented here shows that NSAIDs can act as TNFa inhibitors in the human oesophagus, by decreasing epithelial cell membrane TNFa levels in vivo. This suggests that anti-TNFa therapy may prevent further growth of Barrett's lesions. III

The aim of this study was to investigate COX-2 expression in squamous cell carcinoma of the oesophagus (SCC), and the potential of non-steroidal anti-inflammatory drugs, which inhibit the action of the enzyme, for chemoprevention of this cancer. The epidemiology of SCC and the outcome from surgery for this disease in Hebei Province, China, were reviewed. The rate of postoperative complications and deaths following oesophagectomy fell steadily over the last five decades, but the long-term survival remained disappointing. Improved survival is likely to be dependent on earlier diagnosis and better adjunctive therapies. Tissue was obtained from patients who had an oesophagectomy for SCC over 20 years earlier. The expression of COX-2 was elevated and correlated with TNM stage and lymph node metastases. Survival was longer in those patients whose tumours expressed lower levels of COX-2. The mechanism of action of aspirin, a non-selective COX inhibitor, and NS-398, a selective COX-2 inhibitor, was investigated in vitro. Both drugs inhibited the proliferation of and induced apoptosis in the SCC cell line TE-13. These changes correlated with a reduction in COX-2 mRNA and protein expression, prostaglandin synthesis, inhibition of NF-KappaB nuclear translocation and an increase in cytoplasmic IKappaB. Similar changes were seen in tumour tissue resected from patients given the selective COX-2 inhibitor Mobic daily for 14 days before surgery. These results suggested that aspirin and similar drugs might have value in cancer therapy. A clinical trial was established to determine if treatment with aspirin post-operatively would improve survival of patients who had had an oesophagectomy for SCC. Preliminary results suggested that treatment had no effect on survival in patients operated on for SCC. / http://proxy.library.adelaide.edu.au/login?url= http://library.adelaide.edu.au/cgi-bin/Pwebrecon.cgi?BBID=1289296 / Thesis (Ph.D.) -- University of Adelaide, School of Medicine, 2007

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