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

Thesis (doctoral)--Umeå University, Sweden, 1995. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Thesis (doctoral)--Umeå University, Sweden, 1995. / Added t.p. with thesis statement inserted. Includes bibliographical references.

Orientador: Jacks Jorge Junior / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-09T19:48:28Z (GMT). No. of bitstreams: 1 Campagnoli_EduardoBauml_D.pdf: 15962845 bytes, checksum: 0ed7f5d5b20c8803dc7f1a23bf3b1d5d (MD5) Previous issue date: 2007 / Resumo: O carcinoma espinocelular de boca é um dos cânceres mais comuns do mundo, logo a compreensão das vias moleculares envolvidas no processo de carcinogênese poderá auxiliar no desenvolvimento de drogas para o tratamento e prevenção deste tipo de neoplasia. FAS é uma das enzimas metabólicas que participam da síntese endógena de ácidos graxos, enquanto ErbB-2 é um receptor de membrana celular responsável pelo crescimento e diferenciação de vários tipos celulares. Já a proteína p27 é inibidora do ciclo celular e Skp2 é uma ubiquitina ligase que atua na ubiquitinização e degradação de p27. Estudos têm demonstrado que a inibição da FAS desencadeia o processo de apoptose em diversas linhagens de células neoplásicas. Recentemente relatou-se que o Orlistat apresenta efeito inibitório sobre a FAS. Portanto, o objetivo deste estudo foi comparar a expressão de FAS, ErbB-2, p27 e Skp2 em epitélios com displasia leve, moderada, severa e no carcinoma espinocelular quimicamente induzidos, bem como verificar o efeito do Orlistat no processo de carcinogênese bucal. Para tanto, camundongos foram expostos ao 1-óxido 4-nitroquinolina (4NQO) durante 16 semanas e sacrificados ao completarem 16, 18, 20 e 25 semanas. Um dos grupos também recebeu injeção intraperitonial de Orlistat (240 mg/kg) diária, durante quinze dias. Após o sacrifício dos animais, a língua foi removida, emblocada em parafina e cortes histológicos obtidos. Presença de displasias e neoplasias malignas foram avaliadas em lâminas coradas por hematoxilina e eosina. Reações imunohistoquímicas foram realizadas com os anticorpos: Ki-67 (marcador de proliferação celular), FAS, ErbB-2, p27 e Skp2. O índice de proliferação celular (Ki-67) foi de 26,57%, 22,85%, 26,12% e 23,86% nas áreas de displasia leve, moderada, severa e carcinoma invasivo, respectivamente. O epitélio normal teve índice de proliferação celular de 4,31%. ErbB-2 exibiu aumento na expressão tanto nas áreas displásicas como tumorais, sendo que ambas apresentaram mais de 50% de células imunomarcadas. Aumento na expressão da FAS diferiu de modo estatisticamente significante, em relação ao epitélio normal, somente nas áreas com displasia severa e de carcinoma invasivo, embora aumento gradual na expressão desta proteína tenha sido observado durante todo o processo de carcinogênese. A quantidade protéica de p27 aumentou gradualmente durante a carcinogênese, sendo as maiores taxas encontradas nas áreas de displasia severa (57,50% de células imunomarcadas) e carcinoma invasivo (53,55% de células positivas). Para Skp2 verificou-se imunomarcação exclusivamente citoplasmática (Skp2-B), a qual esteve aumentada tanto nas áreas displásicas como tumorais. Os camundongos tratados com Orlistat tiveram área tumoral 67,25% menor do que os animais não tratados. Além disso, houve diminuição na proliferação celular (2,58% de positividade celular), bem como menor número de células imunomarcadas contra as proteínas p27 e Skp2-B. Com base nesses resultados concluiu-se que durante o processo de carcinogênese bucal induzida por 4NQO houve aumento na proliferação celular (Ki-67) e na expressão das proteínas FAS, ErbB-2, p27 e Skp2-B (citoplasmática), sendo que ErbB-2 e Skp2-B tiveram aumento significativo já nos estágios iniciais da carcinogênese. Além disso, o Orlistat apresentou efeito antitumoral e antiproliferativo em carcinomas espinocelulares de língua quimicamente induzidos / Abstract: Squamous cell carcinoma of the oral cavity is one of the most common malignant epithelial neoplasms, and a better understanding of its molecular pathways could help the development of new treatment or preventive agents. Several proteins such as Fatty Acid Synthase (FAS), ErbB-2, p27 and Skp2 are involved in the tumorigenesis process. FAS has an enzyme with multiple functions, including the endogenous synthesis of saturated fatty acids. ErbB-2 is a transmembrane receptor that may have a role in cellular growth and differentiation. p27 is a cyclin-dependent kinase inhibitor and plays an important role on the negative regulation of the cell cycle. On the other hand, Skp2 is an ubiquitin ligase that targets p27 for ubiquitination and degradation. Studies have demonstrated that FAS inhibition induces apoptosis in various neoplastic cells and can suppress tumor cell proliferation. It has been demonstrated that Orlistat has anti-proliferative and anti-tumor properties through blocked FAS activity. Therefore, the aim of the present study was to investigate FAS, ErbB-2, p27 and Skp2 expression in the epithelium with chemically-induced dysplasia and squamous cell carcinoma, and to verify the effect of Orlistat on the carcinogenic process. Lesions were induced by 4NQO in the drinking water to C57BL/6 mice during 16 weeks. The animals were sacrificed after 16, 18, 20 and 25 weeks of treatment. One group also received intraperitonial injection of Orlistat, 240 mg/kg/day, during fifteen days. The tongues were removed and paraffin embedded tissues were cut and stained with hematoxylin and eosin. Dysplastic lesions and squamous cell carcinomas were analyzed in slides stained with hematoxylin and eosin. Immunohistochemistry assays were performed for Ki-67, FAS, ErbB-2, p27 and Skp2. The percentage of cells that reacted with the Ki-67 antibody was 26.57%, 22.85%, 26.12% and 23.86% in areas with mild, moderate, severe dysplasia and invasive carcinoma, respectively. The normal epithelium had low index of cellular proliferation, 4.31%. ErbB-2 showed increase in the expression in dysplastic and tumor areas, for both presented more 50% of positive cells. High expression of FAS was observed in areas with severe dysplasia and squamous cell carcinoma, although gradual increased was observed during all the carcinogenic process. Expression of p27 protein increased gradually during carcinogenesis and the biggest levels were detected in areas with severe dysplasia (57.50% of immunostaining cells) and invasive carcinoma (53.55% of positive cells). Skp2 immunoexpression was strictly cytoplasmic (Skp2-B), and it was increased in tumoral and dysplastic areas. Lesions of mice treated with Orlistat showed a 67.25% reduction when compared with non-treated animals. Moreover, cellular proliferation was reduced (2.58% of cellular immunostaining), and there were less cells immunostained for p27 and Skp2-B. Therefore dysplastic areas showed increased expression of Ki-67 and high expression of FAS, ErbB-2, p27 and Skp2-B, when compared with normal epithelium. ErbB-2 and Skp2-B had increased expression in the early stages of carcinogenesis. Moreover, Orlistat showed anti-tumoral and anti-proliferative effect in chemically-induced quamous cell carcinomas of the tongue / Doutorado / Estomatologia / Doutor em Estomatopatologia

Yam Hin-Fai. / Thesis (M.Phil.)--Chinese University of Hong Kong, 1990. / Bibliography: leaves 138-157. / ABSTRACT --- p.2 / ACKNOWLEDGEMENT --- p.5 / CONTENT --- p.6 / Chapter I. --- INTRODUCTION --- p.8 / Chapter II. --- LITERATURE REVIEWS / Chapter 1. --- Esophagus and Esophageal Carcinoma --- p.11 / Chapter 2. --- Characterization of Cell Line --- p.23 / Chapter 3. --- Membrane Surface --- p.26 / Chapter 4. --- Differentiation and Cancer --- p.36 / Chapter 5. --- Calcium Ion --- p.42 / Chapter III. --- MATERIALS AND METHODS / Chapter 1. --- Characterizations of EC/CUHK2 Cell Line --- p.48 / Chapter 2. --- SQM1 Localization on EC/CUHK2 Cells --- p.57 / Chapter 3. --- SQM1 Localization on Other Cells and Cell Lines --- p.62 / Chapter 4. --- Characterizations of EC/CUHK2 Cells in Different Extracellular Calcium Ion Concentrations --- p.65 / Chapter 5. --- SQM1 Localization on EC/CUHK2 Cells in Different Extracellular Calcium Ion Concentrations --- p.71 / Chapter 6. --- SQM1 Localization on EC/CUHK2 Cells with Changes of Extracellular Calcium Ion Concentrations --- p.73 / Chapter IV. --- RESULTS / Chapter 1. --- Characterizations of EC/CUHK2 Cell Line --- p.74 / Chapter 2. --- SQM1 Localization on EC/CUHK2 Cells --- p.81 / Chapter 3. --- SQM1 Localization on Other Cells and Cell Lines --- p.83 / Chapter 4. --- Characterization of EC/CUHK2 Cells in Different Extracellular Calcium Ion Concentrations --- p.87 / Chapter 5. --- SQM1 Localization on EC/CUHK2 Cells in Different Extracellular Calcium Ion Concentrations --- p.96 / Chapter 6. --- SQM1 Localization on EC/CUHK2 Cells with Changes of Extracellular Calcium Ion Concentrations --- p.105 / Chapter V. --- DISCUSSIONS / Chapter 1. --- Characterizations of Carcinoma Cell Line --- p.107 / Chapter 2. --- SQM1 Distribution on Esophageal Cancer Cells --- p.118 / Chapter 3. --- SQM1 Distribution on Other Cells --- p.122 / Chapter 4. --- Calcium-Induced Differentiation of Esophageal Carcinoma Cells --- p.125 / Chapter 5. --- SQM1 Distribution on Calcium-Induced Esophageal Carcinoma Cells 6 --- p.132 / Chapter VI. --- CONCLUSION --- p.136 / Chapter VII. --- REFERENCES --- p.138 / Chapter VIII. --- ILLUSTRATIONS --- p.158

Cheung Tsz Man. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2004. / Includes bibliographical references (leaves 187-203). / Abstracts in English and Chinese. / Acknowledgements --- p.is / Abbreviations --- p.II / Abstracts --- p.V / List of Figures --- p.IX / List of Tables --- p.XIII / Contents / Chapter Chapter 1. --- General Introduction / Chapter 1.1 --- Cancer --- p.1 / Chapter 1.2 --- Growth Factor --- p.2 / Chapter 1.3 --- Growth Factor and Growth Factor Receptor --- p.4 / Chapter Chapter 2. --- Alteration of EGF Responses and EGFR Signaling in EGF-conditioned A431 cells / Chapter 2.1 --- Background Information / Chapter 2.1.1 --- Epidermal Growth Factor (EGF) --- p.6 / Chapter 2.1.2 --- Epidermal Growth Factor Receptor (EGFR) --- p.10 / Chapter 2.1.2.1 --- The Structure of EGFR --- p.10 / Chapter 2.1.2.2 --- The EGFR Family --- p.11 / Chapter 2.1.2.3 --- EGFR Activation --- p.13 / Chapter 2.1.3 --- The Intracellular Signal Transduction Pathways in EGFR Signaling --- p.18 / Chapter 2.1.3.1 --- The Ras/Raf/MAPK Pathway (MAPK pathway) --- p.19 / Chapter 2.1.3.2 --- The Jak/Stat Pathway --- p.23 / Chapter 2.1.3.3 --- The PI3K/Akt Pathway --- p.28 / Chapter 2.1.4 --- EGFR and Cancer --- p.31 / Chapter 2.1.5 --- EGFR-targeted Cancer Therapy --- p.35 / Chapter 2.1.5.1 --- Monoclonal Antibody (MAb) --- p.36 / Chapter 2.1.5.2 --- Immunotoxin Conjugates --- p.37 / Chapter 2.1.5.3 --- Bispecific Antibody --- p.37 / Chapter 2.1.5.4 --- Small-molecule EGFR Tyrosine Kinase Inhibitor (EGFR-TKI) --- p.38 / Chapter 2.1.5.5 --- Antisense Oligonucleotide --- p.39 / Chapter 2.2 --- Objectives --- p.41 / Chapter 2.3 --- Materials and Methods / Chapter 2.3.1 --- Materials --- p.42 / Chapter 2.3.2 --- Methods / Chapter 2.3.2.1 --- Cell Lines --- p.44 / Chapter 2.3.2.1.1 --- Establishment of Epidermal Growth Factor (EGF)-conditioned A431 Cells (EGF-conditioned Cells) ´ؤ AC Cells --- p.44 / Chapter 2.3.2.2 --- Growth Curve between A431 Parent Cells and EGF-conditioned Cells --- p.45 / Chapter 2.3.2.3 --- Epidermal Growth Factor (EGF) Sensitivity Assay --- p.45 / Chapter 2.3.2.4 --- Western Blot Analysis --- p.47 / Chapter 2.3.2.4.1 --- Protein Samples Preparation --- p.47 / Chapter 2.3.2.4.2 --- Protein Assay (by BCA Protein Assay Reagent) --- p.48 / Chapter 2.3.2.4.3 --- Protein Electrophoresis --- p.49 / Chapter 2.3.2.4.4 --- Electroblot (Protein Transfer) --- p.50 / Chapter 2.3.2.4.5 --- Antibody Probing (Immunoblotting) --- p.51 / Chapter 2.4 --- Results / Chapter 2.4.1 --- Growth Curve --- p.53 / Chapter 2.4.2 --- EGF Responses of A431 Parent Cells and EGF-conditioned Cells by MTT Assay --- p.55 / Chapter 2.4.3 --- The EGFR Expression Levels in A431 Parent Cells and EGF-conditioned Cells by Western Blot Analysis --- p.57 / Chapter 2.4.4 --- EGF-induced Protein Tyrosine Phosphorylation Pattern in A431 Parent Cells and EGF-conditioned Cells by Western Blot Analysis --- p.59 / Chapter 2.4.5 --- The Expression Profiles of EGFR Signaling Molecules in A431 Parent Cells and EGF-conditioned Cells by Western Blot Analysis --- p.61 / Chapter 2.4.5.1 --- The Ras/Raf/MAPK Pathway --- p.62 / Chapter 2.4.5.2 --- The Jak/Stat Pathway --- p.63 / Chapter 2.4.5.3 --- The PI3K/Akt Pathway --- p.64 / Chapter 2.4.6 --- The Cellular Responses to the Modifiers that Targeting the EGFR Signaling --- p.68 / Chapter 2.4.6.1 --- The Sensitivity of A431 Parent Cells and EGF-conditioned Cells to Various Signaling Modifiers --- p.69 / Chapter 2.4.6.2 --- The Influence of EGFR Signaling Modifiers on EGF --- p.76 / Chapter 2.5 --- Discussion --- p.85 / Chapter Chapter 3. --- The Inter-relationship between the Differential Anti-cancer Drugs Sensitivity and Alteration of EGFR Signaling in EGF-conditioned A431 Cells / Chapter 3.1 --- Background Information / Chapter 3.1.1 --- Drug Resistance and its Mechanisms in Tumor Cells --- p.90 / Chapter 3.1.2 --- Anti-cancer Drugs ´ؤ Introduction / Chapter 3.1.2.1 --- Camptothecin (CPT) --- p.93 / Chapter 3.1.2.2 --- Methotrexate (MTX) --- p.95 / Chapter 3.1.2.3 --- 5-fluorouracil (5-Fu) --- p.98 / Chapter 3.1.2.4 --- Vincristine (VCR) and Taxol --- p.104 / Chapter 3.1.2.5 --- Cisplatin (cis-DDP) --- p.108 / Chapter 3.2 --- Objectives --- p.110 / Chapter 3.3. --- Materials and Methods / Chapter 3.3.1 --- Materials --- p.112 / Chapter 3.3.2 --- Methods / Chapter 3.3.2.1 --- Cell Lines --- p.115 / Chapter 3.3.2.2 --- Determination of Drug Sensitivity by MTT Assay --- p.115 / Chapter 3.3.2.2.1 --- Determination the Influence of EGFR Signaling Modifiers on the Differential Anticancer Drugs Sensitivity by MTT Assay --- p.115 / Chapter 3.3.2.3 --- Semi-quantitative RT-PCR --- p.116 / Chapter 3.3.2.3.1 --- Preparation of RNA Samples --- p.116 / Chapter 3.3.2.3.2 --- RT-PCR --- p.117 / Chapter 3.3.2.4 --- DNA Fragmentation Assay --- p.118 / Chapter 3.3.2.5 --- Western Blot Analysis --- p.120 / Chapter 3.3.2.6 --- Northern Blot Analysis --- p.120 / Chapter 3.4 --- Results / Chapter 3.4.1 --- The Responses to Various Anti-cancer Drugs / Agents in A431 Parent Cells and EGF-conditioned Cells --- p.122 / Chapter 3.4.2 --- The Expressions of Classical Cellular Drug Resistant Factors in EGF-conditioning-associated Differential Anti-cancer Drugs Sensitivity --- p.126 / Chapter 3.4.2.1 --- Camptothecin Sensitivity --- p.126 / Chapter 3.4.2.2 --- Methotrexate Sensitivity --- p.130 / Chapter 3.4.2.3 --- 5-fluorouracil Sensitivity --- p.135 / Chapter 3.4.2.4 --- Vincristine and Taxol Sensitivity --- p.141 / Chapter 3.4.3 --- EGFR Signaling Modifiers and Differential Anti-cancer Drugs Sensitivity by MTT Assay --- p.143 / Chapter 3.4.3.1 --- Methotrexate --- p.143 / Chapter 3.4.3.2 --- Vincristine --- p.147 / Chapter 3.4.3.3 --- Taxol --- p.149 / Chapter 3.5 --- Discussion --- p.153 / Chapter Chapter 4. --- Identification of Differentially Expressed Genes in A431 Parent Cells and EGF-conditioned Cells by Differential Display (DD) / Chapter 4.1 --- Introduction 一 Differential Display (DD) --- p.156 / Chapter 4.2 --- Objectives --- p.160 / Chapter 4.3 --- Materials and Methods / Chapter 4.3.1 --- Materials --- p.161 / Chapter 4.3.2 --- Methods / Chapter 4.3.2.1 --- Cell Lines --- p.163 / Chapter 4.3.2.2 --- RT-PCR-based mRNA Differential Display --- p.163 / Chapter 4.3.2.2.1 --- Preparation of RNA Samples --- p.163 / Chapter 4.3.2.2.2 --- Identification of Differentially Expressed Genes by RT-PCR --- p.164 / Chapter 4.3.2.2.3 --- Reamplification of cDNA Probes --- p.164 / Chapter 4.3.2.2.4 --- Subcloning of the Differentially Expressed cDNAs --- p.165 / Chapter 4.3.2.2.4.1 --- Preparation of the Ultra-competent E.coli Cells for Transformation --- p.165 / Chapter 4.3.2.2.4.2 --- Preparation of Cloning Vector --- p.166 / Chapter 4.3.2.2.4.3 --- Transformation --- p.166 / Chapter 4.3.2.2.5 --- Verification of cDNA Differentially Expression by Colony-PCR and Northern Blot Analysis --- p.167 / Chapter 4.3.2.2.5.1 --- Colony-PCR --- p.167 / Chapter 4.3.2.2.5.2 --- Preparation of Cloned Plasmid cDNA and Bacterial Glycerol Stocks --- p.167 / Chapter 4.3.2.2.5.3 --- Preparation of cDNA Probes for Northern Blot Analysis --- p.168 / Chapter 4.3.2.2.5.4 --- Northern Blot Analysis --- p.168 / Chapter 4.3.2.2.6 --- Sequencing of the Desired Cloned cDNA Inserts --- p.170 / Chapter 4.3 --- Results --- p.171 / Chapter 4.4 --- Discussion --- p.180 / Chapter Chapter 5. --- General Conclusion and Future Perspectives / Chapter 5.1 --- General Conclusion --- p.182 / Chapter 5.2 --- Future Perspectives --- p.185 / References --- p.187

Diss. (sammanfattning)--Stockholm : Karolinska institutet, 2009.

Diss. (sammanfattning) Stockholm : Karol. inst., 2003. / Härtill 4 uppsatser.

Dissertation (Ph.D.).--University of Texas Graduate School of Biomedical Sciences at San Antonio, 2007. / Vita. Includes bibliographical references.

Thesis (M.S.)--University of Missouri-Columbia, 2007. / "May 2007" The entire dissertation/thesis text is included in the research.pdf file; the official abstract appears in the short.pdf file (which also appears in the research.pdf); a non-technical general description, or public abstract, appears in the public.pdf file. Vita. Includes bibliographical references.