by Cheung Yuk Lung. / Thesis (M.Phil.)--Chinese University of Hong Kong, 2000. / Includes bibliographical references (leaves 95-111). / Abstracts in English and Chinese; questionnaires in Chinese. / Acknowledgements --- p.i-ii / 摘要 --- p.iii-iv / Abstract --- p.v-vi / Table of Contents --- p.vii-viii / List of Tables --- p.ix / List of Figures --- p.x / Chapter Chapter 1. --- Introduction --- p.1 / Chapter Chapter 2. --- Literature Review / Anxiety --- p.3 / Quality of Life --- p.8 / Quality of Life for Stoma Patients --- p.19 / Progressive Muscle Relaxation in Reducing Anxiety and Promoting Quality of Life --- p.24 / The Rationale of Using PMRT in Reducing Anxiety and Promoting Quality of Life --- p.35 / Summary of Literature Review --- p.38 / Chapter Chapter 3. --- Methods / Research Design --- p.40 / Aim and Objectives --- p.41 / Hypotheses --- p.42 / Operational Definitions --- p.43 / Ethical Consideration --- p.44 / Sample --- p.45 / Intervention --- p.47 / Instruments --- p.49 / Data Collection and Randomization --- p.54 / Pilot Study --- p.56 / Method of Data Analysis --- p.57 / Chapter Chapter 4. --- Results / Internal Consistency of the Instruments --- p.59 / Subjects' Characteristics --- p.60 / "Baseline Assessment of State-Anxiety, Trait-Anxiety, QoL-Colostomy and WHO-QoL Scores " --- p.64 / Effect of PMRT on the State-Anxiety and Quality of Life --- p.65 / The Frequency of Practicing PMRT --- p.71 / Chapter Chapter 5. --- Discussion and Conclusion / Discussion --- p.75 / Limitations --- p.84 / Recommendations and Implications for Future Studies --- p.88 / Conclusion --- p.93 / References --- p.95 / Appendixes / Chapter 1 . --- Letters of Ethical Approval / Chapter 2. --- Letter of Request for Access Aapproval / Chapter 3. --- Informed Consent / Chapter 4. --- Questionnaires / Chapter 5. --- Content Validity Index of Chinese Version of QoL-Colostomy

Diss. (sammanfattning) Linköping : Linköpings universitet, 2008. / Härtill 5 uppsatser.

Diss. (sammanfattning) Stockholm : Karolinska institutet, 2007. / Härtill 4 uppsatser.

Human papillomavirus (HPV) infections play a crucial role in human carcinogenesis. Greater than 96% of all cervical carcinomas are positive for high-risk HPV infections; especially types 16 and 18. High-risk HPV onco-proteins, E6 and E7, are consistently expressed in such cancers and function by inactivating p53 and pRb tumor suppressors, respectively. The presence of high-risk HPVs is also correlated with anogenital cancers. In this study, we examined the effect of high-risk HPV type 16 E6 and E7 oncoproteins in two normal human colorectal epithelial cell lines, NCE1 and NCE5. We report that the expression of E6/E7 proteins, alone, induced cellular transformation of both cell lines; consequently, NCE1-E6/E7 and NCE5-E6/E7 form colonies in soft agar with respect to their wild type cells. This is accompanied by cell cycle deregulation, as is demonstrated by the over-expression of cyclin dependant kinases (cdks) and their respective cyclins. Furthermore, we demonstrate that E6/E7 oncoprotein transduction induces migration of colorectal epithelial cells. More still, well analyzed Id gene expression, a family member of the helix-loop-helix (HLH) transcription factors involved in the regulation of cell invasion and metastasis of human cancer cells. In parallel, using tissue microarray analysis we found that the four members of the Id protein family are correlated with the presence of HPV type 16 and 18 in human colon cancer tissues. Our data suggests that high-risk HPV infections are sufficient to induce cellular transformation of normal human colorectal cells, in vitro. Furthermore, the correlation with the Id family of proteins may present a novel set of markers associated with HPV induced colorectal carcinogenesis. Our results may suggest a new approach to detect and prevent colorectal cancer.

Diss. (sammanfattning) Stockholm : Karol. inst., 2001. / Härtill 7 uppsatser.

Thesis (Ph. D.)--Case Western Reserve University, 2005. / [School of Medicine] Department of Epidemiology and Biostatistics. Includes bibliographical references. Available online via OhioLINK's ETD Center.

A Caderina-E està intimamente relacionada com a transiÃÃo epitelial-mesenquimal e com a progressÃo tumoral em muitos tipos de cÃncer, inclusive no cÃncer colorretal. O objetivo deste trabalho foi avaliar a imunoexpressÃo de Caderina-E no cÃncer colorretal primÃrio e nas respectivas metÃstases linfonodais, na mucosa colÃnica normal, e investigar possÃveis correlaÃÃes desta expressÃo com parÃmetros clÃnicopatolÃgicos. Setenta e sete casos de colectomias por carcinoma colorretal e dez casos de linfonodos metastÃticos, dos arquivos do Departamento de Patologia e Medicina Legal/Universidade Federal do CearÃ, foram utilizados. Realizou-se o Tissue Microarray e imunohistoquÃmica, com anticorpo monoclonal anti-Caderina-E. Foram avaliados os seguintes escores: 0 = ausÃncia de expressÃo; 1 = expressÃo citoplasmÃtica; 2 = expressÃo mista (citoplasmÃtica e membranar); 3 = expressÃo membranar pura. Foi utilizada tanto a classificaÃÃo proposta por Jawhari et al., agrupando os casos em expressÃo anormal (escores 0, 1 e 2) e expressÃo normal (escore 3), como os critÃrios propostos por Almeida et al., agrupando os casos como expressÃo nÃo-membranar (escores 0 e 1) e expressÃo membranar (escores 2 e 3). Os tumores primÃrios tiveram mais casos de expressÃo de Caderina-E anormal em comparaÃÃo com a mucosa normal (p < 0.0001). NÃo houve diferenÃa significante entre expressÃo de Caderina-E no tumor intestinal e em metÃstases linfonodais, embora nestas a expressÃo membranar tenha sido mais freqÃente do que no sÃtio primÃrio. Tumores de cÃlulas agrupadas apresentaram maior expressÃo de Caderina-E membranar do que os de cÃlulas isoladas, tanto utilizando a classificaÃÃo de Jawhari et al. (p = 0.0230), como os critÃrios propostos por Almeida et al. (p = 0.0043). Em conclusÃo, a expressÃo anormal de Caderina-E no tumor primÃrio, com persistÃncia freqÃente da imunomarcaÃÃo membranar associada à marcaÃÃo citoplasmÃtica (marcaÃÃo anormal heterogÃnea ou mista), reforÃa as evidÃncias de que esta alteraÃÃo no cÃncer à mais qualitativa do que propriamente quantitativa. O predomÃnio da expressÃo membranar no sÃtio primÃrio da neoplasia e na metÃstase, com ou sem expressÃo citoplasmÃtica associada, principalmente em tumores de cÃlulas agrupadas, sugere que a presenÃa da Caderina-E à essencial para a invasÃo local e progressÃo tumoral, em oposiÃÃo ao clÃssico paradigma de que a progressÃo tumoral se exacerba com a perda desta molÃcula de adesÃo. / E-cadherin is closely related to epitelial-mesenchymal transition and tumor progression in many cancers, including colorectal cancer. The aim of this study is to evaluate the expression of E-cadherin in primary colorectal cancer as well as in lymph node metastasis, establishing also a comparison with the expression of E-cadherin in normal colonic mucosa. We utilized 77 cases of colectomies for colorectal carcinoma and 10 cases of metastatic lymph nodes from the files of the Department of Pathology and Forensic Medicine/Federal University of Ceara. Tissue microarray and immunohistochemistry were performed with monoclonal anti-E-cadherin, evaluated using the following scores: 0 = no staining; 1 = cytoplasmic staining; 2 = mixed staining (cytoplasmic and membranous); 3 = membranous staining. It was used the classification proposed by Jawahri et al. which includes cases of abnormal expression (0, 1 and 2 scores) and cases of normal expression (3 score), and was also used the classification proposed by Almeida et al. which includes cases of non-membranous expression (0 and 1 scores) and membranous expression (2 and 3 scores). Primary tumors presented more cases of abnormal E-cadherin expression in comparison to normal colonic mucosa (p < 0.0001). There were no differences between E-cadherin expression in the primary tumor in comparison to lymph node metastasis. The grouped cell tumors showed increased expression of E-cadherin in comparison to isolated cell tumors, either using the classification proposed by Jawhari et al. (p = 0.0230) and the classification proposed by Almeida et al. (p = 0.0043). In conclusion, abnormal expression of E-cadherin in the primary tumor, with frequent membranar immunostaining associated with the cytoplasmic marking (abnormal heterogeneous or mixed staining), reinforces the evidence that E-cadherin expression change in cancer is more qualitative than quantitative. The predominance of membranar expression in primary tumor and lymph node metastasis, with or without associated cytoplasmatic expression, particularly in cell-grouped tumors, suggests that E-cadherin presence is essential for local invasion and tumor progression, as opposed to the classical paradigm that tumor progression is exacerbated by the loss of this adhesion molecule.

O cÃncer coloretal (CRC) à a 3 neoplasia mais prevalente no mundo. O irinotecano (IRI), fÃrmaco de primeira linha para os tratamentos do CRC e sua metÃstase hepÃtica, tem aumentado a sobrevivÃncia dos pacientes. Contudo, seus efeitos colaterais, incluindo a esteato-hepatite nÃo alcoÃlica (NASH), podem limitar o curso do tratamento. Os protocolos baseados em irinotecano foram associados com um aumento no risco de NASH de 3,4 vezes. A silimarina (SIL) tem mostrado ser capaz de prevenir doenÃas do fÃgado gorduroso no contexto clÃnico e em modelos de danos hepÃticos induzidos quimicamente. Assim, nosso objetivo foi estudar o efeito da SIL na NASH induzida pelo IRI, assim como o mecanismo envolvido. MÃtodos e Resultados: Camundongos Swiss fÃmeas (n=8-10), foram divididos em 6 grupos e injetados com salina (SAL 5ml/kg i.p.), IRI (50 mg/kg i.p.), SIL (150 mg/kg v.o.) ou IRI (50 mg/kg i.p.) + SIL (SIL 1,5, 15, 150 mg/kg v.o.) 3x/semana/7 semanas. Amostras de sangue foram coletadas na sÃtima semana para determinar a concentraÃÃo sÃrica das enzimas hepÃticas ALT e AST (U/L). Animais foram mortos para a coleta do fÃgado para avaliar do dano tecidual (escores de Kleiner), dosagem de lipÃdeos totais (mg/g de tecido), MDA (nmol/g tecido), NPSH (mg de NPSH/g tecido), IL-6 (pg/mg de tecido), IL-10 (pg/mg de proteÃna) e IL-1&#946; (pg/mg de tecido), imunomarcaÃÃo de Ãxido nÃtrico sintase induzida (iNOS), 3-Nitrotirosina (Ntyr), e Receptor Toll Like tipo 4 (TLR4), quantificaÃÃo do fator nuclear kappa B (NF&#954;B) e da &#945;-actina de mÃsculo liso (&#945;-SMA) e expressÃo do gene RSS. ANOVA/Teste de Newman-Keuls ou Kruskal Wallis/ Teste de Dunn foram utilizados para anÃlise estatÃstica. Foram consideradas diferentes amostras onde o nÃvel descritivo era inferior a 5%. O trabalho foi aprovado pelo comità de Ãtica em pesquisa animal sob o nÃmero de protocolo: 21/12. O IRI aumentou de forma significante as transaminases hepÃticas, o infiltrado neutrofÃlico, o acÃmo de lipÃdeos, o acÃmulo de MDA, a expressÃo de NTyr, a expressÃo de &#945;-SMA, a expressÃo de NF&#954;B, a expressÃo de IL-1&#946;, a expressÃo de IL-6, a expressÃo de TLR4 e quantificaÃÃo de DNA bacteriano, quando comparados ao grupo SAL. SIL (1,5 mg/kg) melhorou esses parÃmetros, exceto a infiltraÃÃo neutrofÃlica e a quantificaÃÃo do DNA bacteriano quando comparados ao o grupo IRI (P<0,05). Por outro lado, a dose media de SIL (15 mg/kg) foi efetiva apenas no Infiltrado NeutrofÃlico, na expressÃo de NTyr, na expressÃo de NF&#954;B e na expressÃo de IL-6. Adicionalmente, essa dose aumentou a expressÃo hepÃtica de IL-10, a quantificaÃÃo de DNA bacteriano e a expressÃo da &#945;-SMA quando comparados com o grupo IRI (p<0,05). Contudo, a expressÃo de iNOS nÃo foi afetada pelo prÃ-tratamento com SIL (P<0,05) e a maior dose foi ainda mais deletÃria. ConclusÃes: O prÃ-tratamento com SIL previne o dano hepÃtico causado pelo IRI provavelmente atravÃs da mudanÃa da resposta inflamatÃria mediada por receptores TLR4 e citocinas IL-1, IL-6, IL-10 e NF&#954;B. O dano observado no grupo de animais tratados com as maiores doses de SIL parece ser dependente da translocaÃÃo bacteriana do intestido que à associada a ativaÃÃo do TLR4. Adicionalmente, a silimarina contribui para hepatoproteÃÃo por inibir o estresse oxidativo e a nitrosilaÃÃo proteica, prevenindo a ativaÃÃo de mecanismos de fibrose hepÃtica

京都大学 / 0048 / 新制・課程博士 / 博士(医学) / 甲第21014号 / 医博第4360号 / 新制||医||1028(附属図書館) / 京都大学大学院医学研究科医学専攻 / (主査)教授 武藤 学, 教授 木原 正博, 教授 森田 智視 / 学位規則第4条第1項該当 / Doctor of Medical Science / Kyoto University / DFAM

Dietary starch that escapes digestion in the small intestine may be quantitatively more important than dietary fibre as substrate for fermentation. The products of fermentation have important implications in the pathogenesis of colorectal cancer and other diseases of the large bowel which are uncommon in Africans, but have a high prevalence in Western populations. Maize porridge is a staple of most Blacks in South Africa. Stale maize porridge (high resistant starch - HRS) seems to induce greater fermentation in the large bowel than fresh maize porridge (low resistant starch - LRS). In the present study, healthy colostomy subjects fed stale maize porridge had significantly more production of SCFA (short chain fatty acids) (mean SCFA - HRS = 182,6; mean SCFA - LRS = 116,1; p<0,05) in their colostomy effluent together with a significant drop in stool pH (mean pH - HRS = 5,91; mean pH - LRS = 6,70; p<0.G01). The SCFA butyrate tmean - HRS = 35,1; mean - LRS - LRS = 17,6; p<0,05) and acetate (mean - HRS = 93,9; mean - LRS = 65,8; p <0,05) were significantly elevated on the stale maize porridge diet when compared with consumption of fresh maize porridge. SCFA, propionate (mean - HRS = 43,1; mean - LRS = 24,8; p=G,Q5), also increased with stale maize porridge, but was not statistically significant. A high resistant starch diet and its resultant increase in fermentation products may be partly responsible in protecting the Black population against colorectal cancers and other large bowel diseases.