No description available.

Made available in DSpace on 2014-06-11T19:32:13Z (GMT). No. of bitstreams: 0 Previous issue date: 2010-03-31Bitstream added on 2014-06-13T19:42:39Z : No. of bitstreams: 1 ambrosio_ep_dr_botib.pdf: 788460 bytes, checksum: 18c7bc4e895b27a25ad6c61e3df95d08 (MD5) / Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) / O câncer de laringe ocorre em 25% dos carcinomas de cabeça e pescoço e compreende 2% de todas as doenças malignas. É comum o aparecimento de segundos tumores primários e, aproximadamente, 5% dos pacientes apresentam cânceres sincrônicos. Há várias evidências indicando que a população celular presente no fronte de invasão possui características moleculares diferentes das áreas tumorais superficiais, tornando esta região importante para avaliação prognóstica. Neste estudo foram investigadas por CGH cromossômico de alta resolução (HR-CGH) as alterações genômicas na área superficial e no fronte de invasão de carcinomas de laringe e selecionadas regiões específicas para serem avaliadas por outras metodologias para a confirmação dos resultados. O componente superficial e o fronte de invasão de 33 carcinomas de laringe fixados em formalina e em blocos de parafina foram avaliados por HR-CGH. Foram detectadas alterações comuns aos dois componentes assim como alterações exclusivas a cada um deles. Adicionalmente, foi investigada e confirmada a expressão aumentada da proteína ciclina D1 o gene CCND1 esta mapeada em 11q13) por análise de expressão em plataformas de microarranjos de tecidos contendo as areas do tumor e do fronte de invasão. Foi realizada também a análise de marcadores polimórficos de microssatélites mapeados em 3q e 18q em um grupo independente de 33 amostras (DNA tumoral e do sangue periférico) cujos resultados confirmaram as perdas encontradas nestas regiões cromossômicas. A expressão do gene CTTN (mapeada em 11q13) e de sua proteína foram avaliadas e revelaram que os altos níveis de expressão proteica foram correlacionados com invasão perineural nas células do fronte de invasão, sugerindo que esta área pode ser considerada como ferramenta prognóstica em carcinomas de laringe. Foram investigados os ganhos detectados... / Laryngeal cancer occurs in 25% of head and neck carcinomas and comprises 2% of all malignant diseases. The appearance of secondary tumors is common and approximately 5% of patients present concurrent cancers. Preliminary evidence indicates that the cell population present at the source of the invasion front possesses distinct molecular characteristics to surface tumor areas, making this an important region for prognostic evaluation. In this study, genomic alterations in superficial areas and the invasion front of laryngeal carcinomas were investigated by high resolution chromosomal comparative genomic hybridization (HR-CGH) and specific areas were selected for evaluation by other methodologies to confirm the results. The superficial and invasion front components of 33 laryngeal carcinomas fixed in formalin and embedded in paraffin blocks were analyzed by HR-CGH. Alterations common to both components and those exclusive to each area were detected. Additionally, increased ciclin D1 (gene is mapped at 11q13) protein expression was confirmed through immunohistochemistry analysis of tissue microarray platforms containing superficial tumor and invasion front tissues. Polymorphic microsatellites markers mapped at 3q and 18q was also performed on an independent group of 33 samples (tumor and peripheral blood DNA); the results confirmed the losses verified in these chromosomal regions. Expression of the gene CTTN (mapped at 11q13) and its protein were evaluated revealing that high levels of protein expression were correlated with perineural invasion in invasion front cells, suggesting that this area could be considered a prognostic tool in laryngeal carcinomas. The gains detected at 2q24 by HR-CGH were confirmed by FISH and transcript analysis by qRT-PCR. It was found an association between copy number gains of ACVR1 and its overexpression with increased overall survival in laryngeal... (Complete abstract click electronic access below)

Orientador: Silvia Regina Rogatto / Banca: José Guilherme Vartanian / Banca: José Vassalo / Banca: Enilze Ribeiro / Banca: Paula Rahal / Resumo: O câncer de laringe ocorre em 25% dos carcinomas de cabeça e pescoço e compreende 2% de todas as doenças malignas. É comum o aparecimento de segundos tumores primários e, aproximadamente, 5% dos pacientes apresentam cânceres sincrônicos. Há várias evidências indicando que a população celular presente no fronte de invasão possui características moleculares diferentes das áreas tumorais superficiais, tornando esta região importante para avaliação prognóstica. Neste estudo foram investigadas por CGH cromossômico de alta resolução (HR-CGH) as alterações genômicas na área superficial e no fronte de invasão de carcinomas de laringe e selecionadas regiões específicas para serem avaliadas por outras metodologias para a confirmação dos resultados. O componente superficial e o fronte de invasão de 33 carcinomas de laringe fixados em formalina e em blocos de parafina foram avaliados por HR-CGH. Foram detectadas alterações comuns aos dois componentes assim como alterações exclusivas a cada um deles. Adicionalmente, foi investigada e confirmada a expressão aumentada da proteína ciclina D1 o gene CCND1 esta mapeada em 11q13) por análise de expressão em plataformas de microarranjos de tecidos contendo as areas do tumor e do fronte de invasão. Foi realizada também a análise de marcadores polimórficos de microssatélites mapeados em 3q e 18q em um grupo independente de 33 amostras (DNA tumoral e do sangue periférico) cujos resultados confirmaram as perdas encontradas nestas regiões cromossômicas. A expressão do gene CTTN (mapeada em 11q13) e de sua proteína foram avaliadas e revelaram que os altos níveis de expressão proteica foram correlacionados com invasão perineural nas células do fronte de invasão, sugerindo que esta área pode ser considerada como ferramenta prognóstica em carcinomas de laringe. Foram investigados os ganhos detectados... (Resumo completo, clicar acesso eletrônico abaixo) / Abstract: Laryngeal cancer occurs in 25% of head and neck carcinomas and comprises 2% of all malignant diseases. The appearance of secondary tumors is common and approximately 5% of patients present concurrent cancers. Preliminary evidence indicates that the cell population present at the source of the invasion front possesses distinct molecular characteristics to surface tumor areas, making this an important region for prognostic evaluation. In this study, genomic alterations in superficial areas and the invasion front of laryngeal carcinomas were investigated by high resolution chromosomal comparative genomic hybridization (HR-CGH) and specific areas were selected for evaluation by other methodologies to confirm the results. The superficial and invasion front components of 33 laryngeal carcinomas fixed in formalin and embedded in paraffin blocks were analyzed by HR-CGH. Alterations common to both components and those exclusive to each area were detected. Additionally, increased ciclin D1 (gene is mapped at 11q13) protein expression was confirmed through immunohistochemistry analysis of tissue microarray platforms containing superficial tumor and invasion front tissues. Polymorphic microsatellites markers mapped at 3q and 18q was also performed on an independent group of 33 samples (tumor and peripheral blood DNA); the results confirmed the losses verified in these chromosomal regions. Expression of the gene CTTN (mapped at 11q13) and its protein were evaluated revealing that high levels of protein expression were correlated with perineural invasion in invasion front cells, suggesting that this area could be considered a prognostic tool in laryngeal carcinomas. The gains detected at 2q24 by HR-CGH were confirmed by FISH and transcript analysis by qRT-PCR. It was found an association between copy number gains of ACVR1 and its overexpression with increased overall survival in laryngeal... (Complete abstract click electronic access below) / Doutor

Thesis (MSc)--Stellenbosch University, 2004. / ENGLISH ABSTRACT: The work presented in this thesis deals with the association between cancers of the upper gastro-intestinal tract and the tumor suppressor gene, TP53, and can be divided into three parts: (i) the analysis of the mutational spectrum of TP53 with respect to laryngeal cancer, (ii) the analysis of the mutational spectrum of TP53 with respect to esophageal cancer and (iii) the analysis of TP53 transcriptional levels in esophageal cancer. Laryngeal cancer (LC) is the 6th most common cancer in the world and the 2nd most common respiratory cancer, with approximately 500 000 new cases per annum detected worldwide. Over the last few years, LC has become increasingly prevalent within the Coloured Community of the Western Cape. The mechanisms of tumorigenesis in LC remain unknown, although smoking and alcohol consumption are considered to be major risk factors. Mutations within the gene TP53 have been strongly implicated as playing a role in cancer development, as they are frequently found in several cancer types. We therefore screened exons 5 - 8 of TP53 for mutations in DNA from tumor biopsies (n=44) and blood samples (n=42) from Coloured LC patients, using polymerase chain reaction - single strand conformation polymorphism (PCR-SSCP) analysis and direct sequencing. Blood samples from a healthy, matched control group (n=40) were included in the study as controls. Significant correlations were found between the occurrence of LC and age and smoking, whereas daily meat consumption was a possible protective factor. In tumor-derived samples, mutations were found in 3 of the exons under investigation, representing 25% of the samples. The mutations were unique to the tumor biopsies, indicating a somatic origin for mutations. The data confirms that the region between codons 175 and 273 of TP53 is a mutational hotspot for cancers in general. This study reports 6 novel mutations within this same region. Esophageal cancer (EC) has a very high incidence in South Africa, relative to the rest of the world, and is particularly common amongst the Black Transkei population. The goal of this study was to determine whether there are differences in the TP53 mutational pattern observed in the Coloured Western Cape community as compared to that observed in the Black Transkei community. This required the analysis of the molecular structure of TP53, specifically exons 5 - 8, in a group of Coloured EC patients (n=44) treated at Tygerberg Hospital, Cape Town, South Africa. DNA obtained from tumor biopsies and blood (from patients) as well as from apparently healthy surrounding tissue was screened via PCR-SSCP and direct sequencing analysis. Only 4 nucleotide changes were observed from a total of 124 sequences obtained, of which two were novel to esophageal squamous cell carcinoma. These 4 nucleotide alterations were found only within the tumor biopsy sample set, representing 9% of the tumors investigated. This study revealed that the mutational spectrum of TP53 within the Coloured population of the Western Cape greatly differs from that of the Black community of the Transkei. This suggests that a different set of etiological factors are involved in the tumorigenic process for each of these distinct geographical communities, which is the subject of an epidemiological study undertaken by the MRC. The final part of this thesis deals with the quantification and comparison of TP53 transcription levels in esophageal cancer tumor tissue to the TP53 levels in healthy esophageal tissue obtained from patients from a unique geographical and ethnic background. The cohort used in this study consisted of Coloured patients (n=2) treated at Tygerberg Hospital. The LightCycler system was implemented in order to try to accurately quantify TP53 mRNA levels. Unfortunately, the desired results were unattainable due to unforeseen difficulties encountered during the study. These difficulties included the insufficient preservation of samples for RNA based studies. Several recommendations were made concerning future similar studies, including an improved planning strategy as well as the employment of an RNA stabilizing agent. Additionally, a few important contributions were made through this study, including the design and optimization of TP53 primers specifically intended for future RNA studies. These primers would enable the identification of the presence of TP53 RNA species as well as the absence of DNA contamination in a single PCR amplification step. Other contributions include the development of a well-optimized RNA extraction method for the extraction of RNA from tough tissues (such as the human esophageal tissue used in this study). This method makes the extraction of large quantities of RNA from small amounts of tough tissue types possible. In conclusion, this study has made a significant contribution to the field of cancer research, by shedding light on the TP53 mutational spectrum with regards to laryngeal as well as esophageal cancer in a population unique to the Western Cape. The first part of this thesis has been published in Cancer Genetics and Cytogenetics (Barnard, D., K. Lehmann, E.G. Haal, P.O. van Heiden, and l.C. Victor. 2003. The spectrum of mutations in TP53 in laryngeal cancer patients from a high-incidence population shows similarities to many of the known mutational hotspots. Cancer Genetics and Cytogenetics 145:126-132), of which a copy can be found in Appendix I. This work has also been presented (by D. Barnard) at an international conference entitled "Cancer of the Esophagus and Gastric Cardia: From Gene to Cure", held in Amsterdam, the Netherlands during the period 13 - 15 December 2002. / AFRIKAANSE OPSOMMING: Die werk wat in hierdie tesis voorgelê word handel oor die assosiasie tussen kankers van die boonste gastrointestinale weg en die tumor suppressor geen, TP53, en kan in 3 dele gedeel word, (i) die analise van die mutasiespektrum van TP53 in laringiale kanker (LK), (ii) die analise van die mutasiespektrum van TP53 in slukderm kanker (SK) en (iii) die analise van die transkripsievlakke van TP53 in SK. Laringeal kanker (LK) is die 6de algemeenste kanker in die wêreld en die 2de algemeenste respiratoriese kanker, met "n benaderde 500 000 nuwe gevalle jaarliks wêreldwyd. Oor die afgelope paar jare het LK "n toenemende probleem geraak, veral in die Kleurling gemeenskap van die Wes Kaap. Die meganismes van die tumorvorming in LK is onbekend, alhoewel rook-en alkoholgebruik vername risiko faktore is. Die voorkoms van mutasies in TP53 is verskeie kere aangetoon in verskillende kanker tipes en daar word vermoed dat dit "n rol speel in tumorvorming. In hierdie studie is dus na mutasies in eksons 5 - 8 van TP53 gesoek in tumor biopsie weefsel (n=44) en bloed isolate (n=42) van Kleurling LK pasiënte d.m.v. polimerase ketting reaksie - enkelstring konformasie polimorfisme (PKR-ESKP) analisering en direkte volgorde bepaling. Bloed monsters van "n vergelykbare groep (n=40) is ook in die studie ingesluit as "n kontrole. Betekenisvolle positiewe korrelasies is gevind tussen die voorkoms van LK en ouderdom sowel as rook. Daarmee saam is daaglikse vleisinname as potensiële beskermende faktor gevind. In tumor biopsies is mutasies in 3 van die ondersoekte eksons gevind, wat 25% van die biopsie monsters verteenwoordig. Hierdie mutasies is uniek aan die tumor biopsie weefsels en dui op "n somatiese oorsprong van mutasies. Hierdie bevindinge bevestig dat die gedeelte tussen kodons 173 - 273 van TP53 "n hipermuteerbare gebied geassosieer met kankers is. Hierdie studie bevestig 6 nuwe mutasies. Daar is 'n hoë insidensie van slukderm kanker (SK) in Suid Afrika relatief tot die res van die wêreld. Hierdie soort kanker word veral gevind by die Swart populasie van die Transkei. Die doel van hierdie studie was om verskille tussen die TP53 mutasie patroon van die Kleurling gemeenskap van die Wes Kaap en die Swart gemeenskap van die Transkei te vergelyk. Hiervoor is die molekulêre struktuur van TP53, veral eksons 5 - 8, in 'n groep Kleurling SK pasiënte (n=42) wat behandel is by Tygerberg Hospitaal, Kaapstad, Suid Afrika, geanaliseer. Analisering is gedoen deur DNS van tumor, bloed en ook oënskynlike gesonde aangrensende weefsel van dieselfde pasiënte te onderwerp aan PKR-ESKP analise en direkte volgorde bepaling. Slegs 4 nukleotied veranderings is gevind in 124 volgorde bepalings, waarvan 2 nuwe veranderings is in SK. Hierdie 4 nukleotied veranderinge verteenwoordig 9% van al die tumors wat ondersoek is in die studie. Hierdie studie bewys dat die mutasiespektrum van TP53 in die Kleurling gemeenskap van die Wes Kaap grootliks verskil van die Swart gemeenskap van die Transkei. Dit impliseer dat verskillende etiologiese faktore moontlik 'n rol mag speel op die tumorvormingsproses in die 2 afsonderlike geografiese gemeenskappe. Hierdie is die onderwerp van 'n epidemiologiese studie wat deur die MNR onderneem word. Die laaste deel van hierdie tesis handel oor die kwantifisering en vergelyking van TP53 transkripsievlakke in SK tumor weefsel teenoor TP53 vlakke in gesonde slukderm weefsel van pasiënte in 'n unieke geografiese en etniese agtergrond. Die studie populasie in hierdie projek het bestaan uit Kleurling pasiënte (n=2) wat by Tygerberg hospitaal behandel is. Die "LightCycler" sisteem is gebruik vir die akkurate kwantifisering van TP53 boodskapper RNS vlakke. Ongelukkig is die verlangde resultate nie gekry nie as gevolg van onvoorsiene probleme wat ondervind is tydens die studie. Hierdie probleme sluit in die onvoldoende preserv RNS studies. Hierdie inleiers maak dit nou moontlik om die teenwoordigheid van TP53 RNS spesies sowel as die afwesigheid van DNS kontaminasie in een PKR amplifikasie stap te kan identifiseer. 'n Ander belangrike bydrae is die ontwikkeling van 'n goed geoptimaliseerde RNS ekstraksie metode vir moeilike starre weelfsel tipes (soos menslike slukderm weefsel in hierdie studie) en maak die ekstraksie van groot hoeveelhede RNS uit klein hoeveelhede van moeilik hanteerbare weefsel tipes moontlik. Om saam te vat, hierdie studie het betekenisvolle bydraes gemaak tot die veld van kankernavorsing deur die ontrafeling van die TP53 mutasiespektrum in beide laringeale sowel as slukderm kanker, in 'n populasie uniek aan die Wes Kaap. Die eerste deel van hierdie tesis is gepubliseer in Cancer Geneties and Cytogenetics (Barnard, D., K. Lehmann, E. G. Hoal, P. D. van Heiden, and T. C. Victor. 2003. The spectrum of mutations in TP53 in laryngeal cancer patients from a high-incidence population shows similarites to many of the known mutational hotspots. Cancer Genetics and Cytogenetics 145: 126-132) en 'n afskrif van die artikel is ingesluit in Appendix I. Hierdie werk is ook voorgedra (deur D. Barnard) by 'n internasionale kongres getiteld "Cancer of the Esophagus and Gastric Cardia: From Gene to Cure", wat in Amsterdam, Nederland gehou is gedurende 13 - 15 Desember 2002

Kurtinaitienė I. Pacientų, sergančių gerklų vėžiu, gyvenimo kokybės vertinimas prieš ir po spindulinės terapijos, magistranto baigiamasis darbas / mokslinė vadovė dr. L. Spirgienė; Lietuvos sveikatos mokslų universitetas, Slaugos fakultetas, Slaugos ir rūpybos katedra. Kaunas, 2013:97 p. Spindulinė terapija paliečia daugelį pacientų gyvybinių veiklų, todėl svarbu laiku numatyti fizinius, psichologinius ir socialinius aspektus ir įvertinti pacientų gyvenimo kokybę. Darbo tikslas – įvertinti pacientų, sergančių gerklų vėžiu, gyvenimo kokybę prieš ir po spindulinės ir chemospindulinės terapijos. Uždaviniai: 1) įvertinti pacientų gyvenimo kokybės skirtumus po spindulinės ir po chemospindulinės terapijos; 2) įvertinti pacientų slaugos poreikių skirtumus po spindulinės ir po chemospindulinės terapijos; 3) palyginti pacientų gyvenimo kokybę ir slaugos poreikių priklausomybę prieš ir po šešių savaičių spindulinės ir chemospindulinės terapijos. Tyrimo objektas – pacientų, sergančių gerklų vėžiu, gyvenimo kokybė. Metodika. Apklausa atlikta 2012 m. lapkričio – 2013 m. kovo mėn. LSMUL VšĮ Kauno klinikų filialo Onkologijos ligoninėje. Anoniminio anketavimo metodu apklausta 130 pacientų (atsako dažnis – 96,9 proc.). Sudarytos dvi tiriamųjų grupės 100,0 proc. (n=126): pirmoji grupė (n=66) – pacientams taikyta spindulinė terapija; antroji grupė (n=60) – pacientams taikyta chemospindulinė terapija. Tiriamųjų gyvenimo kokybė buvo vertinta Europos vėžio tyrimų ir gydymo organizacijos centro... [toliau žr. visą tekstą] / Kurtinaitienė I. Evaluation of quality of life in patients with laryngeal cancer befor and after radiotherapy, master’s thesis / supervisor L. Spirgienė RN, PhD; Lithuanian University of Health Sciences; Faculty of Nursing, Department of Nursing and Care. Kaunas, 2013:97 pages. Radiotherapy affects many vital activities of patients, it is important in time to provide physical, social and psychological aspects and to assessment of quality of life in patients. Aim: to assess the quality of life in patients with laryngeal cancer before and after radiotherapy and chemoradiotherapy. Goals: 1) to evaluate the differences in the quality of life in patients after radiatiotherapy and after chemoradiotherapy; 2) to assess differences in care needs of patients following radiotherapy and after chemoradiotherapy; 3) to compare the quality of life and care needs of dependent patients before and after six weeks of radiotherapy and chemoradiotherapy. Object of research: the quality of life in patients with laryngeal cancer. Methodology: the survey was conducted from November 2012 till March 2013 in Oncology hospital of Kaunas Clinics of Lithuanian University of Health Sciences. Anonymous questionnaire method surveyed 130 patients (response rate – 96.9%). Involved two groups of subjects 100,0% (n=126): the first group (n=66) – patients with radiatiotherapy, the second group (n=60) – patients received chemoradiotherapy. Related the European Organisation for Research and Treatment of Cancer... [to full text]

Submitted by Renata Lopes (renatasil82@gmail.com) on 2017-03-29T11:26:06Z No. of bitstreams: 1 cristinatostesvieiramaciel.pdf: 4843448 bytes, checksum: 7a1ffce0f381832d62e4362d7b91f5cb (MD5) / Approved for entry into archive by Adriana Oliveira (adriana.oliveira@ufjf.edu.br) on 2017-03-30T11:17:09Z (GMT) No. of bitstreams: 1 cristinatostesvieiramaciel.pdf: 4843448 bytes, checksum: 7a1ffce0f381832d62e4362d7b91f5cb (MD5) / Made available in DSpace on 2017-03-30T11:17:09Z (GMT). No. of bitstreams: 1 cristinatostesvieiramaciel.pdf: 4843448 bytes, checksum: 7a1ffce0f381832d62e4362d7b91f5cb (MD5) Previous issue date: 2009-07-27 / Os tumores de laringe representam 25% dos tumores de cabeça e pescoço e cerca de 2% de todos os cânceres no Brasil. No entanto, é pouco conhecida a evolução dos pacientes portadores deste câncer, após ser determinado o fim das possibilidades de sua cura. Os estudos sobre a qualidade de vida destes pacientes visam sugerir como desenvolver o tratamento para que haja uma menor repercussão dos sintomas do câncer e/ou tratamento no desempenho diário do paciente. Diversos instrumentos específicos foram criados com o objetivo de quantificar a qualidade de vida de pacientes portadores do câncer de cabeça e pescoço, dentre eles o Functional Assessment Cancer Therapy FACT Head and Neck (HN). Este questionário aborda a qualidade de vida durante ou após a terapêutica e reflete a perspectiva do paciente frente ao tratamento discutindo e expondo as possíveis fragilidades do tratamento. Objetivos: Estimar a qualidade de vida de indivíduos submetidos ao tratamento de câncer de laringe no Município de Juiz de Fora, MG, identificando as variáveis que a influenciaram. Metodologia: estudo transversal envolvendo 60 pacientes com tumor primário de laringe com, no mínimo, 1 ano de sobrevida, submetido a tratamento em 02 centros de referência para a assistência oncológica de Juiz de Fora no período compreendido entre 2001 a 2007. Foram aplicados dois instrumentos: um contendo dados exploratórios e o FACT-HN, adaptado para a língua portuguesa. A análise bivariada preliminar selecionou as variáveis com valores de p≤0,20. Em seguida, foi realizada a regressão linear múltipla, utilizando-se a técnica enter. No modelo multivariado final permaneceram as variáveis cujos valores de p foram ≤0,10. Resultados: Na análise bivariada (p≤ 0,20) apresentaram maior significância as variáveis sociodemográficas “sexo”, “anos de escolaridade” e clínico-funcionais “análise do tratamento recebido”, “tratamento fonoaudiológico e nutricional”. Após a análise multivariada, ainda mostraram uma associação significativa a variável sociodemográfica “anos de escolaridade” e as variáveis clínico-funcionais “análise do tratamento recebido”, “tratamento fonoaudiológico e nutricional”. Conclusões: Tanto os fatores sociodemográficos; socioeconômicos e clínico-funcionais, ainda que de forma diferente, interferem na qualidade de vida do paciente. Nos três domínios que constituem o FACT-HN (TOI, FACTG e FACTHN), houve aparente influência de fatores sociodemográficos e clínico-funcionais na qualidade de vida dos pacientes. / Although laryngeal cancer accounts for 25% of head and neck malignancies, and 2% of all malignancies in Brazil, the outcome of patients with no possibility of cure is not well known. Studies on the quality of life of such patients focus on measures to limit the impact of clinical symptoms and treatment untoward effects on daily performance. Several specific tools were developed to quantify the quality of life of head and neck cancer patients, the Functional Assessment Cancer Therapy - Head and Neck (FACT-HN) among them. Focusing on the quality of life during or after therapy, this questionnaire reflects the patient`s perspective concerning therapy and reveals possible treatment weaknesses. Objectives: Assess the quality of life of subjects undergoing treatment for laryngeal cancer in the municipality of Juiz de Fora, MG, Brazil, and identify significant variables. Method: Cross-sectional study of 60 patients with primary laryngeal cancer, with at least 1-year-survival, and treated at 2 oncology reference centers in Juiz de Fora, in the year 2001/2007. An investigative tool consisting of exploratory data and the Portuguese-adapted FACTHN were used. Preliminary bivariate analysis selected variables with p values ≤0.20. Subsequent multiple linear regression analysis was performed with the enter technique. On the final multivariate model, variables with p values ≤0.10 remained. Results: On bivariate analysis (p≤ 0.20) greater significance was found for the sociodemographic variables (gender and years of schooling) and for the clinicalfunctional variables (treatment appraisal with hindsight and speech and nutritional therapies). Treatment appraisal with hindsight and speech and nutritional therapies still showed a significant association after multivariate analysis. Conclusions: Sociodemographic, socioeconomic and clinical-functional factors interfere with the quality of life of such patients, albeit in a different way. In the three domains that make up the FACT-HN (TOI, FACTG e FACTHN), sociodemographic and clinicalfunctional factors seemingly influenced the quality of life of these patients.

Deterioration in voice quality following radiation therapy for the treatment of laryngeal cancers (LC) is well documented in literature. The majority of studies show that these voice problems are long term and in some cases permanent. Deterioration in voice quality, especially over a period of time could lead to significant communication difficulties in daily life or in some cases could even result in loss of profession. Despite the negative effects of radiation therapy on voice quality being well documented, few studies have focused on the efficacy of voice therapy in the irradiated LC population. The purpose of this study was to investigate the efficacy of a well researched, evidence based voice therapy approach, known as Vocal Function Exercises (VFEs) in improving vocal function in patients who have been irradiated for LCs. The present study conducted in three systematic stages with distinct and related study aims. The first involved characterizing the head and neck cancer treatment seeking population at the University of Kentucky (UK). Stage 2 involved characterizing vocal function following irradiation for LC using a multidimensional assessment approach. Stage 3 was a phase 2 clinical trial aimed at treating these deficits in vocal function identified through stage 2 using a systematic evidence based voice therapy approach, Vocal Function Exercises. For the phase 2 clinical trial, the comparison group received vocal hygiene (VH) counseling. Observations from stage 1 showed that majority of patients from the treatment seeking population at UK between a 3 year time period from 2008 to 2010 were diagnosed with laryngeal cancers and were treated with chemoradiation therapy. Stage 2 demonstrated a multidimensional deterioration in vocal function following radiation therapy for laryngeal cancers. Stage 3 demonstrated a significant improvement in vocal function across the primary outcome measure (Voice Handicap Index) as a result of VFE+VH. Improvements were also seen in select parameters across the five domains of voice assessment in the VFE group. No significant improvements were observed in the vocal hygiene group in any parameters in each domain of voice assessment. Our study demonstrated adults irradiated for laryngeal cancers demonstrated a multi-dimensional deterioration of vocal function. These changes were long term since study participants were 2- 7 years post radiation therapy. Implementation of VFE+VH demonstrated a significant improvement in voice related quality of life and select parameters across the five domains of voice assessment. The present study demonstrated promising preliminary evidence for the use of VFE+VH to improve vocal function in patients irradiated for laryngeal cancers.

Η αναδιοργάνωση του κυτταροσκελετού ακτίνης έχει κρίσιμο ρόλο στη διήθηση και τη μετάσταση των καρκινικών κυττάρων. Οι πρωτεΐνες κοφιλίνη και N-WASP συνδέονται με την ακτίνη και ρυθμίζουν τη δυναμική του κυτταροσκελετού, ενώ η πρωτεΐνη β-παρβίνη εντοπίζεται στις εστιακές συνδέσεις και διαμεσολαβεί τη σηματοδότηση διαμέσου των ιντεγκρινών με επίσης σημαντική επίδραση στον κυτταροσκελετό ακτίνης. Μεταβολή της έκφρασης των παραπάνω πρωτεϊνών έχει παρατηρηθεί σε διάφορα νεοπλάσματα στον άνθρωπο. Η παρούσα μελέτη επιχειρεί να προσδιορίσει το ρόλο τους στον καρκίνο του λάρυγγα. Για αυτό το λόγο μελετήθηκε με ανοσοϊστοχημεία η έκφραση των πρωτεϊνών κοφιλίνη, N-WASP β-παρβίνη σε 72 ιστικά δείγματα ασθενών με πλακώδες καρκίνωμα του λάρυγγα και αξιολογήθηκε η συσχέτιση της έκφρασης τους με κλινικές και παθολογοανατομικές παραμέτρους καθώς και με την επιβίωση. Θετική ανοσοϊστοχημικη έκφραση των πρωτεϊνών κοφιλίνη, N-WASP β-παρβίνη παρατηρήθηκε στο 86,1%, 93,1% και 94,4% των περιπτώσεων καρκινώματος του λάρυγγα αντίστοιχα, σε αντίθεση με τον παρακείμενο φυσιολογικό ιστό όπου η έκφραση ήταν ασθενής ή απούσα. Η κυταροπλασματική έκφραση της κοφιλίνης έδειξε τάση συσχέτισης με τα προχωρημένα στάδια της νόσου (p=0,063), ενώ η πυρηνική της έκφραση συσχετίστηκε σε στατιστικά σημαντικό βαθμό (p=0,031) με την προχωρημένη ηλικία (>65 ετών) των ασθενών. Η κυτταροπλασματική έκφραση του N-WASP ήταν μεγαλύτερη στα γλωττιδικά καρκινώματα (p=0,068) και συσχετίστηκε σε στατιστικά σημαντικό βαθμό με τα καλά διαφοροποιημένα καρκινώματα (p=0,031). Η κυτταροπλασματική έκφραση της β-παρβίνης συσχετίστηκε σε στατιστικά σημαντικό βαθμό (p=0,038) με τα προχωρημένα στάδια της νόσου. Παρόλο που οι ασθενείς με υψηλότερη έκφραση του N-WASP εμφάνιζαν καλύτερες επιβιώσεις, δεν επιβεβαιώθηκαν στατιστικά σημαντικές συσχετίσεις της έκφρασης των 3 υπό μελέτη πρωτεϊνών με την επιβίωση. Η αυξημένη έκφραση των πρωτεϊνών κοφιλίνη, N-WASP και β-παρβίνη στον καρκίνο του λάρυγγα μπορεί να υποδεικνύει την πιθανή συμμετοχή τους στην παθογένεση της νόσου. Ενώ η υψηλή έκφραση της κοφιλίνης και της β-παρβίνης φάνηκε να ευνοεί την προαγωγή/εξέλιξη του καρκίνου, τα αυξημένα επίπεδα της πρωτεΐνης N-WASP συσχετιστήκαν με ευνοϊκούς προγνωστικούς παράγοντες. / Actin cytoskeleton dynamics are critically implicated in cancer invasion and metastasis. Actin binding proteins cofilin and N-WASP regulate actin filament turnover and the focal adhesion protein β-parvin mediates integrin signaling to actin cytoskeleton. Altered expression of these proteins has been implicated in human malignancies. This study addresses their role in human laryngeal cancer. Protein expression of cofilin, N-WASP and β-parvin were investigated by immunohistochemistry in 72 FFPE samples of human laryngeal squamous cell carcinoma. Correlations with clinicopathological data and survival were evaluated. Positive immunostaining of cofilin, N-WASP and β-parvin were observed in 86.1%, 93,1% and 94,4% cases respectively, in contrast to the weak or absent staining at the non neoplastic adjacent mucosa. Cytoplasmic cofilin immunoreactivity tended to correlate with advanced disease stage (p=0.063), while its nuclear immunoreactivity correlated significantly with advanced (>65 years) patient age (p=0,031). N-WASP immunoreactivity was higher in glottic laryngeal carcinomas (p=0.068) and significantly correlated with low grade tumors (p=0.031). Expression of β-parvin also correlated significantly with advanced disease stage (p= 0.038). Although patients with high N-WASP expression showed higher survival rates no statistical significant correlation between cofilin, N-WASP or β-parvin immunoreactivity and survival was found. Overexpression of cofilin, N-WASP and β-parvin may be implicated in human laryngeal carcinogenesis. While high expression of cofilin and β-parvin seems to favor tumor progression increased levels of N-WASP associated with favorable prognostic factors.

Treatment decision-making in head and neck oncology is gaining complexity by the increasing evidence pointing towards more individualized and selective treatment options. Therefore, decision making in multidisciplinary teams is becoming the key point in the clinical pathways. Clinical decision-support systems based on Bayesian networks can support complex decision-making processes by providing mathematically correct and transparent advises. In the last three decades, different clinical applications of Bayesian networks have been proposed. Because appropriate data for model learning and testing is often unobtainable, expert modeling is required. To decrease the modeling and validation effort, networks usually represent small or highly simplified decision structures. However, especially systems for supporting multidisciplinary treatment decisions may only gain a user’s confidence if the systems’ results are comprehensive and comprehensible. Challenges in developing such systems relate to knowledge engineering, model validation, system interaction, clinical implementation and standardization. These challenges are well-known, however, they are not or only partially addressed by the developers. The thesis presented a methodology for the development of Bayesian network-based clinical treatment decision support systems. For this purpose, a concept introduced interactions between actors and systems. The proposed concept emphasizes model development with an exemplary use case of model interaction. A graph model design was presented that allows integrating all relevant variables of multidisciplinary treatment decisions. At the current stage, we developed TreLynCa: A graph model representing the treatment decisions of laryngeal cancer. From TreLynCa, a subnetwork that represents the TNM staging is completed by the required probabilistic parameters, and finally validated. The model validation required the development of a validation cycle in combination with existing data- and expert-based validation methods. Furthermore, modeling methods were developed that enable domain experts to model autonomously without Bayesian network expertise. Specifically, a novel graph modeling method was developed, and an existing method for modeling probabilistic parameters was extended. Both methods transform Bayesian network modeling tasks into a natural language form and provide a regulated modeling environment. A method for graph modeling is based on the presented graph model design with a regulated and restricted modeling procedure. This modeling procedure is supposed to enable collaborative modeling of compatible models. The method is currently under development. A method for probabilistic modeling is extended to reduce the modeling effort to a linear time. The method has been implemented as a web tool and was tested and evaluated in two studies. Finally, for clinical application of the TNM model, requirements were collected and constructed in a visual framework. In collaboration with visual scientists, the framework has been implemented and evaluated.

Larynxcancer är den tredje vanligaste formen av huvud- och halscancer och drabbar cirka 175 personer årligen i Sverige. En vanlig behandlingsmetod vid larynxcancer är strålbehandling. Detta är en retrospektiv journalstudie med syfte att undersöka hur svälj- och röstfunktion samt nutritionsstatus påverkas av strålbehandling för larynxcancer. Studiens syfte är även att undersöka om det finns något samband mellan tumörgrad och sväljförmåga efter avslutad behandling samt om och när svälj- och röstfunktion återhämtas. Studien har även undersökt andelen patienter som erbjudits logopedkontakt. I studien har 52 patienter med larynxcancer (C.32) inom region Gävleborg inkluderats. Resultaten indikerar att strålbehandling påverkar svälj- och röstfunktion samt nutritionsstatus. Vid strålavslut hade 24 av 48 patienter tecken på sväljsvårigheter och 33 av 52 patienter hade en påverkan på röstfunktionen. Under behandlingen noterades ett ökat behov av näringsdryck och 24 av 37 deltagare gick ner i vikt under eller efter behandling vilket indikerar nutritionssvårigheter. Andelen patienter som var i behov av enteral nutrition vid strålavslut var 7 av 52 patienter. Sammanlagt erbjöds 33 av 52 patienter logopedkontakt. Återhämtning av sväljfunktionen rapporterades hos 22 av 39 patienter inom ett år efter avslutad strålbehandling. Återhämtning av röstfunktionen noterades hos 8 av 40 patienter inom fem år efter avslutad strålbehandling. Studiens resultat ger värdefull information om strålbehandlingens påverkan på livsviktiga funktioner och hoppas kunna bidra med underlag till prospektiva studier inom huvud- och halscancer. / Laryngeal cancer is the third most common form of head- and neck cancer and each year approximately 175 people receive the diagnosis in Sweden. Radiotherapy is a common treatment against laryngeal cancer. This is a retrospective cohort study, and it has investigated how swallowing, voice function and nutritional status can be affected by radiotherapy. The aim of the study was to explore whether there is a correlation between the grade of tumor and swallowing after treatment and when swallowing and voice function recover. The aim was also to research how many patients received contact with a speech- and language pathologist before or during treatment. The following study included 52 patients with laryngeal cancer (C.32) within the region of Gävleborg, Sweden. The results indicate that radiotherapy affects swallowing, voice function, and nutritional status. By the end of treatment, 24 of 48 patients had signs of dysphagia and voice function was affected in 33 of 52 patients. An increase in the need for nutritional drinks was noted throughout radiotherapy and 24 of 37 patients lost weight during or after treatment, which indicates nutritional difficulties. At the end of the treatment, 7 of 52 patients needed enteral nutrition. In total, 33 of 52 patients were offered contact with a speech- and language pathologist. Recovery of the swallowing function was reported in 22 of 39 patients at some point during the first year after radiotherapy. Recovery of voice function was reported in 8 of 40 patients at some point during five years after radiotherapy. The results of the study indicates possible implications that radiotherapy might have on vital functions, and it can suffice as a basis for further prospective studies within the area of head- and neck cancer.