Patients’ beliefs about their illness are known to influence their experiences of illness, its psychological impact, their health behaviours, and overall health outcomes. Research into illness beliefs has typically involved written or oral methods, yet recent studies have suggested that patients’ beliefs about their illness may be embodied in visual form, in their mental images of the disease. Beliefs embedded in mental images may not be captured via traditional modes of assessment, and thus far the possible significance of this kind of ‘visual knowledge’, has been largely overlooked. Studies using visual methods to explore patients’ mental images suggest this is a viable and useful approach which may provide additional insights into their illness beliefs. Research of this kind is in its infancy however, and there are several fundamental questions concerning the existence and nature of mental images, how best to access such images, and their relationship to illness beliefs, which are as yet unanswered. This thesis employed qualitative methods to address these issues and explore the significance of mental images within the context of head and neck cancer. It consists of three empirical phases – a methodological pilot study, a qualitative meta-synthesis, and a longitudinal study. The findings indicate that many patients do generate a mental image of their cancer, and this is significant in terms of their understanding of both the disease and its treatments. Images appear to enhance patients’ comprehension of what is going on inside their bodies, and may both reflect and influence illness beliefs. In this thesis these findings are considered with reference to the methodological issues intrinsic to researching mental images, and the implications for future research and clinical practice.

A radioterapia (RT), quando aplicada na região de cabeça e pescoço, pode ocasionar alterações estruturais no esmalte e na dentina que poderiam influenciar o comportamento dos sistemas adesivos. O presente estudo teve como objetivo avaliar a influência da RT na adesão dos sistemas adesivos (Clearfil SE Bond e Adper&trade; Single Bond 2) ao esmalte (E) e à dentina (D) de dentes decíduos, em diferentes tempos (antes e após a RT). Foram utilizados 60 molares decíduos seccionados obtendo um total de 120 fragmentos de esmalte e 120 de dentina que, após o preparo da superfície, foram divididos aleatoriamente em 4 grupos (n=30/grupo): G1 (controle) - esmalte/dentina sem irradiação + procedimento restaurador; G2 - procedimento restaurador realizado antes da RT, G3 - procedimento restaurador realizado após a RT; e G4 - procedimento restaurador realizado 6 meses após a RT. Cada um dos grupos foi dividido em 2 subgrupos, sendo no subgrupo A empregado o sistema adesivo etch-rinse Adper&trade; Single Bond 2; e no subgrupo B o adesivo self-etch Clearfil SE Bond. Os espécimes foram irradiados com fração de dose de 2 Gy, por 5 dias consecutivos, até atingir a dose total de 60 Gy, com um total de 30 frações, durante 6 semanas. O procedimento restaurador foi realizado com resina Z350, e para padronização da restauração foi utilizada uma matriz, de forma que os espécimes apresentasse 4 mm de altura e 2 mm de diâmetro. Os corpos de prova foram submetidos ao teste de resistência ao cisalhamento (célula de carga 50 kgf e velocidade 0,5 mm/minuto) obtendo-se o resultado em N, o qual foi transformado em MPa. A análise do padrão de fratura foi realizada em microscopia confocal (MC). Foram selecionados 5 espécimes de esmalte e 5 espécimes de dentina, para realização da análise morfológica da superfície dental por meio de microscopia confocal, sendo estes avaliados a cada 10 Gy. Para a análise da interface adesiva foram selecionados 3 espécimes de cada grupo e estes foram preparados para análise em microscopia eletrônica de varredura (MEV). O esmalte e a dentina foram analisados separadamente, sendo os dados analisados por ANOVA a 2 critérios e pós- teste de tukey (p<0,05). O nível de significância adotado foi 5%. Pode-se observar que, para ambos os substratos, o Clearfil SE Bond (E: 20,19 MPa; D: 17,61 MPa) apresentou adesão estatisticamente superior ao Single Bond (E: 17,21 MPa; D: 15,45 MPa) (p<0,05). Quanto ao momento da realização da restauração, tanto no esmalte quanto na dentina, o grupo 2 apresentou os menores valores. Na comparação fator irradiação observou-se que a irradiação afetou negativamente a adesão do esmalte e da dentina (p<0,05), no entanto no grupo 4 não observou-se alteração (p>0,05). O tipo de fratura predominante foi adesiva, que aumentou a predominância com a irradiação. Na análise em MC houve alterações morfológicas em esmalte e dentina após a dose cumulativa de 40 Gy. Em MEV observou-se a alterações na formação de tags e de camada híbrida. Pôde-se concluir que a radioterapia alterou a morfologia da superfície do esmalte e da dentina, e afetou a adesão dos sistemas adesivos, sendo necessário esperar pelo menos 6 meses para a realização dos procedimentos restauradores, tendo o sistema Clearfil SE Bond menos influenciado. / When radiotherapy (RT) is performed in the head and neck region, it could lead to structural alteration in enamel and dentin that could influence the behavior of the bonding agents. The present study aimed to evaluate whether the RT interferes in the bonding o two adhesive systems (Clearfil SE Bond e AdperTM Single Bond 2) to enamel (E) and dentin (D) of primary teeth, in different times (before and after RT). Sixty primary molars were cut in a total of 120 fragments of enamel and 120 of dentin, which after the surface polishing were randomly divided into 4 groups (n=30/group): G1 (control) - enamel and dentin without RT + restorative procedures; G2 - restorative procedures performed before RT; G3 - restorative procedures performed after RT; and G4 - restorative procedures performed 6 months after RT. Each one of the groups was then divided into 2 subgroups: subgroup A using the etch-rinse Adper&trade; Single Bond 2; and subgroup B using the self-etch Clearfil SE Bond. The specimens were irradiated in dose fractions of 2 Gy, for 5 consecutive days, until reaching the final dose of 60Gy, in a total of 30 fractions, during 6 weeks. The restorative procedures were done using the Z350 composite, and for standardization of the restorations a matrix was used, so the specimens all presented 4 mm height and 2 mm of diameter. The specimens were submitted to the shear bond strength test (load of 50 kgf and speed of 0.5 mm/minute), the result was obtained in N and then transformed to Mpa. The fracture pattern was analyzed in a confocal microscopy (MC). Five specimens of enamel and 5 of dentin were chosen to the morphological analyzes also by MC, those specimens were evaluated every 10 Gy. As for the bonding interface 3 specimens of each group were chosen, and prepared for scanning electron microscopy (SEM). Enamel and dentin were evaluated separately, data was analyzed by the ANOVA and Post Test Tukey (p<0.05). Significance level was 5%. It could be observed that for both substrates the Clearfil SE Bond (E: 20.19 MPa; D: 17.61 MPa) was statically superior than Single Bond (E: 17.21 MPa; D: 15.45 MPa) (p<0.05). As for the time of restoration, group 2 had the worst results, in both enamel and dentin. It was observed that that radiation affected negatively the bonding in enamel and dentin (p<0.05), however, in the group 4 no alterations were observed (p<0.05). The predominant fracture pattern was the adhesive, which had raised its prevalence according to the radiation. In the MC analyses there were morphological alteration in enamel and dentin after the cumulative doses of 40 Gy. It was observed, by SEM, tags formations and alterations on the hybrid layer. It could be concluded that RT had affected the morphological surface of enamel and dentin, and that it affected the adhesion of the bonding systems, indicating that it should be waited at least 6 months after RT to perform restorative procedures, in which the Clearfil SE Bond was less affected.

A radioterapia (RT), quando aplicada na região de cabeça e pescoço, pode ocasionar alterações estruturais no esmalte e na dentina que poderiam influenciar o comportamento dos sistemas adesivos. O presente estudo teve como objetivo avaliar a influência da RT na adesão dos sistemas adesivos (Clearfil SE Bond e Adper&trade; Single Bond 2) ao esmalte (E) e à dentina (D) de dentes decíduos, em diferentes tempos (antes e após a RT). Foram utilizados 60 molares decíduos seccionados obtendo um total de 120 fragmentos de esmalte e 120 de dentina que, após o preparo da superfície, foram divididos aleatoriamente em 4 grupos (n=30/grupo): G1 (controle) - esmalte/dentina sem irradiação + procedimento restaurador; G2 - procedimento restaurador realizado antes da RT, G3 - procedimento restaurador realizado após a RT; e G4 - procedimento restaurador realizado 6 meses após a RT. Cada um dos grupos foi dividido em 2 subgrupos, sendo no subgrupo A empregado o sistema adesivo etch-rinse Adper&trade; Single Bond 2; e no subgrupo B o adesivo self-etch Clearfil SE Bond. Os espécimes foram irradiados com fração de dose de 2 Gy, por 5 dias consecutivos, até atingir a dose total de 60 Gy, com um total de 30 frações, durante 6 semanas. O procedimento restaurador foi realizado com resina Z350, e para padronização da restauração foi utilizada uma matriz, de forma que os espécimes apresentasse 4 mm de altura e 2 mm de diâmetro. Os corpos de prova foram submetidos ao teste de resistência ao cisalhamento (célula de carga 50 kgf e velocidade 0,5 mm/minuto) obtendo-se o resultado em N, o qual foi transformado em MPa. A análise do padrão de fratura foi realizada em microscopia confocal (MC). Foram selecionados 5 espécimes de esmalte e 5 espécimes de dentina, para realização da análise morfológica da superfície dental por meio de microscopia confocal, sendo estes avaliados a cada 10 Gy. Para a análise da interface adesiva foram selecionados 3 espécimes de cada grupo e estes foram preparados para análise em microscopia eletrônica de varredura (MEV). O esmalte e a dentina foram analisados separadamente, sendo os dados analisados por ANOVA a 2 critérios e pós- teste de tukey (p<0,05). O nível de significância adotado foi 5%. Pode-se observar que, para ambos os substratos, o Clearfil SE Bond (E: 20,19 MPa; D: 17,61 MPa) apresentou adesão estatisticamente superior ao Single Bond (E: 17,21 MPa; D: 15,45 MPa) (p<0,05). Quanto ao momento da realização da restauração, tanto no esmalte quanto na dentina, o grupo 2 apresentou os menores valores. Na comparação fator irradiação observou-se que a irradiação afetou negativamente a adesão do esmalte e da dentina (p<0,05), no entanto no grupo 4 não observou-se alteração (p>0,05). O tipo de fratura predominante foi adesiva, que aumentou a predominância com a irradiação. Na análise em MC houve alterações morfológicas em esmalte e dentina após a dose cumulativa de 40 Gy. Em MEV observou-se a alterações na formação de tags e de camada híbrida. Pôde-se concluir que a radioterapia alterou a morfologia da superfície do esmalte e da dentina, e afetou a adesão dos sistemas adesivos, sendo necessário esperar pelo menos 6 meses para a realização dos procedimentos restauradores, tendo o sistema Clearfil SE Bond menos influenciado. / When radiotherapy (RT) is performed in the head and neck region, it could lead to structural alteration in enamel and dentin that could influence the behavior of the bonding agents. The present study aimed to evaluate whether the RT interferes in the bonding o two adhesive systems (Clearfil SE Bond e AdperTM Single Bond 2) to enamel (E) and dentin (D) of primary teeth, in different times (before and after RT). Sixty primary molars were cut in a total of 120 fragments of enamel and 120 of dentin, which after the surface polishing were randomly divided into 4 groups (n=30/group): G1 (control) - enamel and dentin without RT + restorative procedures; G2 - restorative procedures performed before RT; G3 - restorative procedures performed after RT; and G4 - restorative procedures performed 6 months after RT. Each one of the groups was then divided into 2 subgroups: subgroup A using the etch-rinse Adper&trade; Single Bond 2; and subgroup B using the self-etch Clearfil SE Bond. The specimens were irradiated in dose fractions of 2 Gy, for 5 consecutive days, until reaching the final dose of 60Gy, in a total of 30 fractions, during 6 weeks. The restorative procedures were done using the Z350 composite, and for standardization of the restorations a matrix was used, so the specimens all presented 4 mm height and 2 mm of diameter. The specimens were submitted to the shear bond strength test (load of 50 kgf and speed of 0.5 mm/minute), the result was obtained in N and then transformed to Mpa. The fracture pattern was analyzed in a confocal microscopy (MC). Five specimens of enamel and 5 of dentin were chosen to the morphological analyzes also by MC, those specimens were evaluated every 10 Gy. As for the bonding interface 3 specimens of each group were chosen, and prepared for scanning electron microscopy (SEM). Enamel and dentin were evaluated separately, data was analyzed by the ANOVA and Post Test Tukey (p<0.05). Significance level was 5%. It could be observed that for both substrates the Clearfil SE Bond (E: 20.19 MPa; D: 17.61 MPa) was statically superior than Single Bond (E: 17.21 MPa; D: 15.45 MPa) (p<0.05). As for the time of restoration, group 2 had the worst results, in both enamel and dentin. It was observed that that radiation affected negatively the bonding in enamel and dentin (p<0.05), however, in the group 4 no alterations were observed (p<0.05). The predominant fracture pattern was the adhesive, which had raised its prevalence according to the radiation. In the MC analyses there were morphological alteration in enamel and dentin after the cumulative doses of 40 Gy. It was observed, by SEM, tags formations and alterations on the hybrid layer. It could be concluded that RT had affected the morphological surface of enamel and dentin, and that it affected the adhesion of the bonding systems, indicating that it should be waited at least 6 months after RT to perform restorative procedures, in which the Clearfil SE Bond was less affected.

Made available in DSpace on 2014-07-29T15:10:31Z (GMT). No. of bitstreams: 1 antonio marcio.pdf: 1664898 bytes, checksum: a51767c9c1070efdc7346160e72afa12 (MD5) Previous issue date: 2009-10-20 / Head and neck cancer arises in the oral cavity and nearby regions, larynx, pharynx, including oropharynx, nasopharynx, and hipopharynx. Extensive epidemiologic studies have revealed that chronic tobacco smoking and alcohol consumption as the two main risk factors associated with the multifactorial etiology of head and neck cancers. Additionally, nutritional status, HPV infection, and genetic polymorphism were also related with the disease. A frequently studied polymorphism in Squamous Cell Carcinoma (SCC) of head and neck is a G-to-C SNP (Single Nucleotide Polymorphism) at codon 72 in the p53 gene, which codes for an Arg or Pro (Arginine or Proline) in P53 protein. In order to investigate the distribution and potential association of that SNP in SCC, biological samples were obtained from 331 cases of head and neck SCC from Araújo Jorge Hospital and 271 healthy control individuals from Goiânia (Brazil) population. DNA was isolated and subsequently used for PCR amplification to genotype cases and controls with respect to their p5372 SNP. Additionaly, a meta-analysis was carried out using 29 relevant case-control studies that used p5372 SNP genotyping in SCC of the head and neck. Allelic frequencies for cases were 73.3% and 27.7% for Arg and Pro, respectively. On the other hand, control allelic frequencies were 74.2% and 25.8% for Arg and Pro, respectively (p = 0.119). Genotypic frequencies were 56.8% Arg/Arg, 32.9% Arg/Pro, and 10.3% Pro/Pro for all cases. The control genotypic frequencies were 61.3% Arg/Arg, 25.8% Arg/Pro and 12.9% Pro/Pro (p = 0,137). According to the current data and meta-analysis, no association between p5372 SNP and the development of SCC of the head and neck was found. Although, the homozygous genotype Arg/Arg was found as an important oncogenic risk factor associated with the carcinoma of the oropharynx. / O câncer de cabeça e pescoço ocorre nas regiões da cavidade oral, da faringe (orofaringe, nasofaringe e hipofaringe) e da laringe. Aspectos epidemiológicos evidenciam a etiologia multifatorial das neoplasias de cabeça e pescoço, destacando, o tabagismo e o etilismo crônicos como principais fatores de risco, seguidos dos aspectos nutricionais, infecções pelo HPV e polimorfismos genéticos. No contexto dos polimorfismos genéticos tem-se o gene p5372(RP). O objetivo do presente estudo foi estabelecer a associação entre o polimorfismo do gene p53, no códon 72 (Arginina/Prolina), e o câncer de cabeça e pescoço. O estudo contou com 602 participantes, divididos em: 331 pacientes com câncer de cabeça e pescoço provenientes do Hospital Araújo Jorge (grupo caso) e 271 indivíduos saudáveis selecionados randomicamente na população da cidade de Goiânia/GO (grupo controle). As amostras foram processadas e o DNA foi isolado para a avaliação molecular, por PCR, do polimorfismo do gene p5372(RP). Realizou-se também uma meta-análise com 29 estudos do tipo caso-controle de avaliação do referido polimorfismo em câncer de cabeça e pescoço. As frequências alélicas, dos 602 participantes para p53Arg e p53Pro, foram, respectivamente, 73,3% e 26,7% no grupo caso e 74,2% e 25,8% no grupo controle (p = 0,119). As frequências genotípicas foram, para o grupo caso, 56,8% Arg/Arg, 32,9% Arg/Pro e 10,3% Pro/Pro; e para o grupo controle, 61,3% Arg/Arg, 25,8% Arg/Pro e 12,9% Pro/Pro (p = 0,137). A meta-análise agrupou 29 estudos sobre o polimorfismo de p5372(RP) em câncer de cabeça e pescoço e não indicou nenhum tipo de correlação entre as variáveis consideradas. Os dados da presente avaliação e da meta-análise sugerem ausência de correlação entre o polimorfismo do gene p5372(RP) e o risco de desenvolver o câncer de cabeça e pescoço. Por outro lado, ao estratificar os dados por sítio anatômico, o genótipo Arg/Arg se revelou como um importante fator de risco oncogênico para o desenvolvimento do câncer da orofaringe quando comparado com os outros genótipos.

Background: This prospective study was conducted to assess changes in quality of life (QoL) of patients who undergo a partial laryngectomy (PLE). Methods: The European Organization for Research and Treatment of Cancer questionnaires QLQ-C30 and QLQ-H&N35 were used pre-procedure (n=218), one week (n=159), three months (n=122) and one year after PLE (n=88). Changes over time were analyzed with the Wilcoxon-signed-rank-test and the Holm-Bonferroni-method, and interpreted regarding clinical relevance. Results: Most subscales worsened one week post-procedure, but many recovered to baseline level after one year. Dyspnea and cognitive functioning deteriorated over time, with worst scores recorded after one year. Financial difficulties and fatigue increased after surgery and maintained that level throughout the follow-up period; sticky saliva remained worse than at baseline, despite some improvements over time. Conclusions: The discovered limitations of QoL should be observed more closely during follow-up treatment, and patients should be informed about these potential eaffects before PLE.:1 Einführung ........................................................................................................... 3 1.1 Das Larynxkarzinom ......................................................................................... 3 1.2 Therapiemöglichkeiten des Larynxkarzinoms ................................................... 4 1.3 Lebensqualität ................................................................................................... 5 1.4 Methodik bei der Evaluierung von Lebensqualität ............................................. 7 1.5 Lebensqualität bei Krebspatienten .................................................................... 8 1.6 Lebensqualität nach Therapie von Kopf-Hals-Tumoren .................................. 10 2 Zielstellung der Studie ....................................................................................... 13 3 Publikation ......................................................................................................... 14 4 Zusammenfassung ............................................................................................ 37 4.1 Einführung....................................................................................................... 38 4.2 Methoden ........................................................................................................ 39 4.3 Ergebnisse ...................................................................................................... 39 4.4 Diskussion....................................................................................................... 41 5 Literaturverzeichnis ............................................................................................ 44 6 Anlagen ............................................................................................................. 49 6.1 Darstellung des eigenen Beitrags ................................................................... 49 6.2 Selbstständigkeitserklärung ............................................................................ 50

Deregulation of gene expression caused by genetic or epigenetic changes plays an important role in pathogenesis of cancer. The thesis is a commented collection of ten publications dealing with the molecular biology of tumours. The author has significantly contributed to all of them. All the articles contained in the thesis are linked to the topic of assessment of molecules involved in gene expression regulation (microRNAs) or DNA alterations that affect gene expression (promoter methylation, presence of a fusion gene). MicroRNAs are short single-stranded RNA molecules involved in posttranscriptional regulation of gene expression by triggering mRNA degradation or inhibiting translation. It is a basic mechanism with an impact on all cellular processes including the pathogenesis of various diseases. MicroRNAs can either act as oncogenes by decreasing the expression of tumour-suppressor genes or as tumour-suppressor genes by decreasing the expression of oncogenes. However, the network of microRNA - RNA interactions is much more complex. Our published results that are part of this thesis are focused on colorectal carcinoma (CRC), prostate cancer, head and neck squamous cell carcinoma (HNSCC), gastric cancer and non-small cell lung cancer (NSCLC). In patients with CRC, we demonstrated the prognostic...

Deregulation of gene expression caused by genetic or epigenetic changes plays an important role in pathogenesis of cancer. The thesis is a commented collection of ten publications dealing with the molecular biology of tumours. The author has significantly contributed to all of them. All the articles contained in the thesis are linked to the topic of assessment of molecules involved in gene expression regulation (microRNAs) or DNA alterations that affect gene expression (promoter methylation, presence of a fusion gene). MicroRNAs are short single-stranded RNA molecules involved in posttranscriptional regulation of gene expression by triggering mRNA degradation or inhibiting translation. It is a basic mechanism with an impact on all cellular processes including the pathogenesis of various diseases. MicroRNAs can either act as oncogenes by decreasing the expression of tumour-suppressor genes or as tumour-suppressor genes by decreasing the expression of oncogenes. However, the network of microRNA - RNA interactions is much more complex. Our published results that are part of this thesis are focused on colorectal carcinoma (CRC), prostate cancer, head and neck squamous cell carcinoma (HNSCC), gastric cancer and non-small cell lung cancer (NSCLC). In patients with CRC, we demonstrated the prognostic...

Background: The landmark EXTREME trial established cisplatin, 5-fluorouracil and cetuximab (PFE) as first-line chemotherapy (1L-ChT) for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). We were interested in outcome differences of R/M HNSCC in 1L-ChT and factors influencing outcome in certain subgroups, especially patients receiving PFE, and the value of PFE compared to other 1L-ChT regimens to provide real world evidence (RWE). Methods: For this retrospective monocentric study, 124 R/M HNSCC patients without curative surgical or radiotherapy options receiving at least one cycle of 1L-ChT were eligible. We analyzed their outcome using Kaplan-Meier plot and Cox regression to identify predictors for prolonged survival. Results: Subgroups benefiting significantly from PFE were patients suffering from an index HNSCC outside the oropharynx. The PFE regimen proved to be superior to all other 1L-ChT regimens in clinical routine. Significant outcome differences between PFE treatment within or outside controlled trials were not seen. Conclusion: This retrospective analysis provides RWE for factors linked to improved outcome. Subgroup analyses highlight the lasting value of PFE among the growing spectrum of 1L-ChT. Importantly, fit smokers with high level alcohol consumption benefit from PFE; considering the patient’s lifestyle factors, PFE should not be ignored in decision-making.