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1
Schache, Andrew G. "The molecular and clinical implications of human papillomavirus-16 mediated oropharyngeal squamous cell carcinoma". Thesis, University of Liverpool, 2013. http://livrepository.liverpool.ac.uk/13433/.
Testo completoAbstract (sommario):
The last three decades have seen a fundamental change in the profile of oropharyngeal squamous cell carcinoma (OPSCC) within the developed world. The incidence of OPSCC attributable to tobacco and alcohol exposure has been gradually declining whilst Human papillomavirus (HPV)-related OPSCC has seen a rapid increase. Detection of High Risk HPV has profound prognostic significance as it correlates with both a disease-specific and an overall survival advantage. The stringency of testing, both in terms of diagnostic and prognostic capacity is therefore of increasing importance. This study sought to define the relative abilities of the diagnostic tests presently available in clinical practice and to explore the potential of a novel test in reaching the improved stringency called for by the clinical community. Diagnostic biomarkers with prognostic capacity, such as those utilised in defining HPV status in this research have been well described, however, despite HPV positive OPSCC being biologically distinct from HPV negative malignancy, predictive biomarkers defining the transition from persistent to transforming infection are yet to be forthcoming. A lack of an apparent premalignant state, akin to that seen in HPV-mediated cervical malignancy has restricted biomarker recognition. This research aimed to better define the epigenetic state and clarify the impact of viral integration for the virus and host in HPV positive OPSCC. Although detectable epigenetic alterations, within the genome of the virus and that of the host, were capable of providing an improved description of this burgeoning disease state, they fell short of providing clinically relevant biomarkers. It was however demonstrated that the previously held concept of preferential E2 cleavage during viral integration as a means to disrupt gene expression, is overstated and the model persists to the exclusion of other viral and host genome disruptions. A paradigm shift may be necessary in HPV positive OPSCC to an understanding of obligatory viral integration, the significance of which however, is yet to be fully elucidated.
2
Anand, Sumeet M. 1978. "The correlation between tumour volume and survival in oral cavity and oropharyngeal squamous cell carcinoma /". Thesis, McGill University, 2008. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=111587.
Testo completoAbstract (sommario):
The Tumour-Node-Metastasis (TNM) classification system of tumour stage does not always reflect the actual tumour mass present at diagnosis. Recent reports propose that volumetric analysis may allow improved stratification of disease recurrence and survival in head and neck squamous cell cancer (SCC). This study aims to assess the prognostic value of tumour volume on the outcome of patients with oral cavity and oropharyngeal SCC.A retrospective review of 73 patients was completed. Tumours were outlined semi-automatically in digitized computed tomography scans, and volumes computed based on surface triangulations of three-dimensional reconstructions with novel software developed at McGill.
Results illustrate significant interstage variability within the current TNM model. Moreover, in oral cavity and oropharyngeal SCC, tumour volume as well as T-stage are significant and independent predictors of disease free survival and overall survival.
3
Moran, Michael. "HPV-related oropharyngeal squamous cell carcinoma in Northern Ireland : a molecular and population based study". Thesis, Queen's University Belfast, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.678211.
Testo completoAbstract (sommario):
Oropharyngeal cancers are increasing in incidence worldwide, and many of these tumours are caused by the human papillomavirus. This is a DNA virus that integrates into the host's genetic information, and can cause cancer through suppression of important tumour suppressors such as p53. TP53 is a gene that codes for p53, and in many cancers of the head and neck this is thought to be mutated. In NI, limited emigration provides an excellent context for research that depends on long-term follow up of patients. This study assesses molecular and demographic characteristics of patients and their tumours, in order to build a comprehensive of the emerging disease of oropharyngeal cancer. Methods Retrospective review of head and neck pathology reports was conducted for a twelve-year period, and all primary oropharyngeal squamous cell carcinomas were included. Detailed clinical and pathological information was gathered about patients and their tumours, and tissue microarrays were created for analysis of protein markers. In addition, DNA and RNA were extracted from a cohort of tumours, to study the tumour suppressor p53, and its family member p63. Different HPV testing methods were compared with one another, in order to ascertain the most reliable test for diagnosing presence of active virus in the oropharynx. Outcomes It was determined that testing for HPV is necessary in tumours arising in the oropharynx, and the best testing method for this appears to be detection of HPV DNA using chromatin in situ hybridisation. p53 mutations were found at a rate comparable with other studies in the head and neck, however the mutation profile appeared to be slightly different to that of other anatomical subsites. Studies of TP63 gene expression revealed that high levels of delta-Np63 are associated with disease recurrence and decreased survival, suggesting a role for this in tumour invasion and metastasis.
4
Chiriseri, Edina. "Human papilloma virus and oral cancers : sexual behaviour as a risk factor". Thesis, De Montfort University, 2017. http://hdl.handle.net/2086/16084.
Testo completoAbstract (sommario):
AIM & OBJECTIVES: Human papilloma virus (HPV) has been related to cervical infection, however, its part in Head and Neck Squamous Cell Carcinoma (HNSCC) is still debatable and is easy to refute. Suspicion of HPV causation is heightened when carcinomas arise in patients that are young and have never smoked. The present UK based study undertaken at Northampton NHS Trust endeavoured to determine the extent to which HPV is an entity in HNSCC in the UK. Furthermore, the study investigated whether sexual behaviour (as measured by sexual health clinic (SHC) attendance) is linked the acquisition of HPV associated HNSCC in young age groups. HNSCC incidences and sexual trends in the UK were collected from publicly available databases to identify if there were any changes at a national level in sexual behaviours and their influence on HNSCC in young age groups. MATERIALS & METHODS: PCR was used to evaluate the presence of HPV in biopsy samples from of 99 patients diagnosed with HNSCC at Northampton Hospital from 2006 to 2014. Patient demographics on age, sex, smoking, alcohol use and SHC attendance were also collected. All HPV PCR positive biopsies were further genotyped using an ABI 3130xl genetic analyser. Databases in the UK; including GLOBOCAN, NATSAL and PHE were searched for data on HNSCC prevalence, sexual behaviour trends and vaccine uptake. Multinomial regression explored the relationship between HPV positivity and sex, age, smoking, drinking, race and SHC attendance. RESULTS: PCR showed that 25.2% (25/99) of biopsies tested were positive for HPV and were all obtained from white participants. Most specimens (23, 92%) were high-risk (HR) HPV 16 positive with a mean age of 56 for HPV positivity and 72% of the cases 50-60 years old. Smokers were 11% in total (11/99) with most 88.9% participants (88/99) being non-smokers. HPV positivity was strongly linked with non-smoking history (p < 0.001); no alcohol abuse (p < 0.001); male gender (p < 0.001); young age less than 60 years (p < 0.001) and SHC attendance (p < 0.001). A Kruskal-Wallis post hoc test affirmed the impact of age on HPV positivity (p= < 0.05). GLOBOCAN and Cancer Research demonstrated a rising UK HNSCC pattern of over 200% for both sexes from 1975 to 2011. The three NATSAL surveys undertaken in 1990-1991, 1999-2001 and 2010-2012 demonstrated an overall increase in opposite and same sex partners. The UK average of individuals engaging in oral sex was in the younger age groups of between 16 and 54 with at least 70% of males and 63% females of that age engaging in oral sex. Finally, NASTAL 1, 2 and 3 surveys reported 20 vs 15; 25 vs 55; 55 vs 65 of males and females respectively with more than 10 sexual partners to have attended the SHC. The UK immunization take-up was over 90% countrywide. CONCLUSION: Few research studies have been conducted to date on HPV as a cause of HNSCC in the UK. The present research showed 25.2% of HNSCC to be caused by HPV, with the high risk (HR) genotype 16 (the leading cause of cervical cancer) accounting for 92% (23/25) of the cases. These outcomes affirmed the high prevalence of HR-HPV in HNSCC, with a rate of 25.2% similar to those reported previously. Routine HPV testing in those aged below 60 is therefore warranted. Smoking and drinking showed negative correlation; the young age of below 60 and attendance of the SHC for both sexes showed a positive correlation with HPV positive HNSCC. NATSAL data showed increased sexually risky behaviour coupled with attending the SHC in younger ages for both sexes. Increased sexually risky behaviour as shown in NASTAL surveys may be the reason why young age and SHC attendance is positively correlated with HPV HNSCC. The study highlights a conceivable relationship between HPV positive HNSCC in those under 60 years with no smoking history who attended the SHC. Smoking and drinking are known risks for HNSCC in those past 65 years of age; the negative association with HPV HNSCC in the young in the present research revealed smoking and drinking to have reduced association with HPV HNSCC. The reported HR-HPV positive HNSCC in young age groups inform future vaccination strategies and consequently decrease the quantity of HPV HNSCC's.
5
Velinov, Nikolay. "Matrix metalloproteinase-19 is a predictive marker for tumour invasiveness in patients with oropharyngeal squamous-cell carcinoma /". Bern : [s.n.], 2007. http://www.ub.unibe.ch/content/bibliotheken_sammlungen/sondersammlungen/dissen_bestellformular/index_ger.html.
Testo completo
6
Qian, Xu [Verfasser]. "ALDH1-positive cancer stem-like cells enrich in nodal metastases of oropharyngeal squamous cell carcinoma independently of HPV-status / Xu Qian". Berlin : Medizinische Fakultät Charité - Universitätsmedizin Berlin, 2013. http://d-nb.info/1043197427/34.
Testo completo
7
Schroeder, Lea [Verfasser], e Michael [Akademischer Betreuer] Pawlita. "Human papillomavirus-driven neck lymph node metastases from oropharyngeal or unknown primary squamous cell carcinoma / Lea Schroeder ; Betreuer: Michael Pawlita". Heidelberg : Universitätsbibliothek Heidelberg, 2017. http://d-nb.info/1180986466/34.
Testo completo
8
Smith, Eric A. B. S. "DEK is a Homologous Recombination DNA Repair Protein and Prognostic Marker for a Subset of Oropharyngeal Carcinomas". University of Cincinnati / OhioLINK, 2017. http://rave.ohiolink.edu/etdc/view?acc_num=ucin150480040523791.
Testo completo
9
Dapaah, Gloria Fremah. "The prevalence of HPV-positive Oropharyngeal squamous cell carcinoma at one of the largest tertiary care centers in Sub-Saharan Africa Tygerberg Hospital". University of the Western Cape, 2004. http://hdl.handle.net/11394/8145.
Testo completoAbstract (sommario):
Magister Chirurgiae Dentium (MChD)CONTEXT Limited data on the prevalence of HPV-positive oropharyngeal squamous cell carcinoma (OPSCC) in Sub-Saharan Africa exist. The aim of the current study was to determine the prevalence of HPV-positive OPSCC at one of the largest tertiary care centers in the region (Tygerberg Hospital, Cape Town, South Africa). METHODS Sequential surgical samples of 266 cases of OPSCC diagnosed over a 10-year period (2007-2017) were selected for evaluation and relevant patient characteristics were documented. p16 immunohistochemistry (IHC) was performed as a screening test. All p16 positive cases were further evaluated for HR-HPV using BD onclarity™ HPV assay (BD Diagnostics, Sparks, USA), a real-time PCR assay that detects type-specific E6 and E7 genomic DNA. RESULTS Of 266 OPSCC cases, 14% (n=36) were positive for p16. Of those p16-positive cases, 23 were negative and 13 (13/266=5%) were positive for HR-HPV when evaluated by PCR. P16 was found to have a positive predictive value (PPV) of only 36.1%. HPV subtypes were HPV-16 (n=10), HPV-18 (n=1), HPV-52 (n=1) and HPV-31 (n=1). One case was positive for HPV-16 and HPV-31. HPV-positive OPSCC occurred in 10 men and 3 women (male: female ratio 3.3:1) with a mean age of 51 years (range: 33 to 72 years). All HPV-positive OPSCC arose from the tonsil (n=10) and base of tongue (n=3). Most HPV-positive OPSCC were non-keratinizing (n=10) or partially keratinizing (n=1). In contrast, HPV-negative OPSCC were predominantly keratinizing (n=218). A positive history of smoking was significantly correlated with a negative HPV status (p=0.08) CONCLUSIONS The presence of HR-HPV in 5% of OPSCC cases, in one of the largest tertiary care centers in Sub-Saharan Africa (Tygerberg Hospital), suggests HR-HPV as a minor etiologic agent in OPSCC in this region. Due to its sub-optimal positive predictive value (36.1%), p16 IHC is a less reliable marker for HR-HPV infection due to high incidence of tobacco and alcohol related diseases in this region. When positive, HPV-specific testing should be performed by one of the available platforms. The identification of the less common HR-HPV types; HPV-52 and HPV-31, in our cohort of HPV-positive OPSCC cases, may have implications for in-situ hybridization (ISH) HPV cocktails and current local vaccination strategies.
10
Dugoni, Meredith L. "Role of the Pediatric Dental Provider in Human Papillomavirus (HPV) Education". VCU Scholars Compass, 2017. http://scholarscompass.vcu.edu/etd/4733.
Testo completoAbstract (sommario):
Purpose: This study investigates knowledge about HPV and examines if pediatric dental providers should include HPV education for guardians of patients 10-18 years.
Methods: Legal guardians of 10-18 year-old patients of the Virginia Commonwealth University Pediatric Dental Clinic were enrolled in this prospective cohort study. Participants completed a baseline survey, were provided HPV education, completed an initial follow-up survey, and then completed a 6-month follow-up survey.
Results: A total of 54 participants completed the baseline and initial follow-up surveys and 17 completed the 6-month follow-up survey. The average number of correct responses was 3.4 of 6 knowledge questions, which significantly improved to 5.4 at follow-up (P<.0001). The greatest increase in the percent responding correctly was regarding HPV and oropharyngeal cancer from 22% baseline to 91% at initial follow-up (P<.0001). Regarding Stage of Change, 14 (23%) of those not initially in the Action group had improved at least 1 stage. At the 6-month follow-up, 3 (43%) guardians reported completing the HPV vaccine series.
Conclusions: These results demonstrate limited knowledge about HPV and highlight the pediatric dental provider’s ability to educate. Since the greatest knowledge gap pertained to HPV and oropharyngeal cancer, it is important for pediatric dental providers to increase their role in HPV education. As oral cancers are the purview of dentists, practitioners should be involved with their patients’ consideration of the HPV vaccine.
11
Hanns, Elodie. "Analyse et caractérisation moléculaire de l'hypoxie intratumorale de carcinomes épidermoïdes de l'oropharynx". Thesis, Strasbourg, 2014. http://www.theses.fr/2014STRAJ063/document.
Testo completoAbstract (sommario):
Les carcinomes épidermoïdes des voies aéro-digestives supérieures (VADS) se situent au sixième rang des cancers les plus fréquents dans le monde. Ces tumeurs sont liés à deux facteurs de risque : l’intoxication éthylo-tabagique (80% des cas) et l’infection de l’épithélium des VADS par les papillomavirus humain (HPV) à haut risque oncogène (20% des cas). Ces derniers définissent une sous-population de patients de meilleur pronostic. Une des hypothèses actuellement étudiées, afin d’expliquer la survie améliorée des patients HPV positifs, serait une hypoxie moindre dans ces tumeurs. En effet, les tumeurs des VADS sont fréquemment hypoxiques, et l’hypoxie intratumorale est un facteur de mauvais pronostic. Dans une première partie de cette thèse, nous avons entrepris une caractérisation moléculaire de l’hypoxie intratumorale dans les tumeurs humaines oropharyngées en fonction du statut HPV. Il apparaît que les tumeurs HPV positives présentent un statut hypoxique moindre comparées aux tumeurs HPV négatives. Ces tumeurs se caractérisent également par une abondante vascularisation intratumorale, qui pourrait être à l’origine de ce statut hypoxique moindre. Dans une deuxième partie, nous avons étudié l’adaptation à l’hypoxie de la lignée cellulaire HPV négative SQ20B et la lignée cellulaire HPV positive SCC90. De plus, des modèles de xénogreffes ont été établis à partir de ces mêmes lignées cellulaires et ont été analysés du point de vue de l’hypoxie intratumorale. De façon comparable aux tumeurs HPV positives, les xénogreffes obtenus à partir de la lignée SCC90 montre un statut hypoxique réduit comparés aux xénogreffes SQ20B. Les deux lignées cellulaires s’adaptent également différemment en hypoxie in vitro. La réponse à l’hypoxie dans la lignée SCC90 semble plus dynamique. En effet, la lignée SCC90 tente de s’adapter et de répondre à cet environnement hypoxique en induisant de fort niveau d’expression de gènes comparée à la lignée SQ20BHead and neck squamous cell carcinoma (HNSCC) represents the sixth most common malignancy worldwide. The major risk factors for HNSCC identified are tobacco use and alcohol consumption (80% of all HNSCC), which seem to have a synergistic effect. A subgroup of HNSCCs (20% of cases), particularly those of the oropharynx, is caused by infection with high-risk types of human papillomavirus (HPV). Human papillomavirus HPV-related oropharyngeal squamous cell carcinoma defines a distinct clinical subgroup of head and neck cancer patients with improved prognosis. Currently, one of the several hypothesis studied to account for their improved survival outcomes could be a distinct hypoxia status compared to their HPV-negative counterpart. Indeed, tumour hypoxia is common in solid tumours including head and neck tumours, and hypoxia is a well-known poor prognosis factor. In first part of this thesis, we have performed a molecular characterisation of tumor hypoxia on cohort of oropharyngeal tumours according to HPV status of the patients. The results support the hypothesis that HPV-related tumours display a lesser hypoxia status compared to HPV-negative oropharyngeal tumours. These HPV-related tumours also characterize by an abundant tumour vascularisation, which could be responsible for a lesser hypoxia status. In a second part, we have studied the ability of the adaptation to hypoxia of the HPV-positive SCC90 cell line and HPV-negative SQ20B cell line. Furthermore, HPV-positive and HPV-negative HNSCC xenograft models have been established and have been analysed about tumor hypoxia. Similar to HPV-related HNSCC, tumours-derived HPV positive cell lines display a reduced hypoxic status compared to tumours-derived HPV negative cell lines. The two cell lines adapt also differently to in vitro hypoxia. In the HPV-positive cell line, the hypoxia response pathways could be more dynamics. Indeed, SCC90 cell lines attempt to adapt and to reply to hypoxic environment inducing highly expression of all of the hypoxia related genes compared to SQ20B cell lines
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Santos, Edilmar de Moura. "Valor progn?stico de c?lulas TCD8+ E natural killer em carcinoma epiderm?ide oral e orofaringeano tratado com radioterapia e quimioterapia". Universidade Federal do Rio Grande do Norte, 2012. http://repositorio.ufrn.br:8080/jspui/handle/123456789/17124.
Testo completoAbstract (sommario):
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Previous issue date: 2012-02-09Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior
The most common malignant neoplasm of the oral cavity and oropharynx are squamous cell carcinoma. Injuries to the same stage and subjected to the same treatment protocol have sometimes different evolutionary courses. The scope of this study was to investigate, through a retrospective cohort, associations between the number of CD8 + T cells and natural killer, identified immunohistochemically in the inflammatory infiltrate in a series of cases of oral squamous cell carcinoma and orofaringeano, and the level of tumor response to radiotherapy and chemotherapy, overall survival and relapse-free survival of patients. We identified 54 patients with unresectable disease were treated exclusively with radiotherapy and chemotherapy. The median follow-up was 22 months. The sample was characterized by the predominance of male subjects, median age 60 years, all were smokers. The most frequent site was the tongue and 81.5% were in stage IV. Patients with disease in the oral cavity had a worse response to treatment (p = 0.006), worse relapse-free survival (p = 0.007), worse overall survival (p = 0.007). The advanced T stage was shown a negative prognostic factor (p= 0.006) for the clinical treatment response made. Immunohistochemistry was performed to select CD8 + cells (anti-CD8) and NK cells (anti-CD57). Lymphocytes positive and negative markings were counted using the program ImageJ ?. Two groups were created for each marking evaluated: Group I patients with more than 50% cells positive, Group II: less than 50% of labeled cells. For CD8 + cells detected in 38 (70.3%) of Group I were CD8 + and 16 (29.7%) Group II CD8 +. For NK cells, 26 (48.15%) Group I NK and 28 (51.85%) Group II NK. Regarding the clinical response to treatment, we observed that 39% of patients achieved a complete response and 25.9% remained without recurrence at the end of follow-up. These results were better in Group I CD8 + (p = 0.2). Identified that 72.2% of patients progressed to death, this finding had no association with the immunohistochemical data. There was no statistically significant differences between the number of CD8 + and NK cells and the ability of tumor response to radiotherapy and chemotherapy, or with overall survival and relapse-free survival of patients. However, especially in relation to a learned response, we found that this group of patients with advanced disease have a low count of CD8 + T cells active. Believing in the role that the immune response plays in the local fight against neoplastic cells, however, our results do not support the use of quantitative analysis of CD8 + T cells and NK cells as a prognostic factors for oral squamous cell carcinoma and oropharynx
A neoplasia maligna mais frequente da cavidade oral e da orofaringe ? o carcinoma epiderm?ide. Les?es com o mesmo estadiamento e submetidas ao mesmo protocolo terap?utico apresentam, por vezes, cursos evolutivos diferentes. O escopo do presente trabalho foi investigar, atrav?s de um coorte retrospectivo, associa??es entre a quantidade de c?lulas TCD8+ e natural killer, identificadas imuno-histoquimicamente no infiltrado inflamat?rio de uma s?rie de casos de carcinoma epiderm?ide oral e orofaringeano, e o n?vel de resposta tumoral ao tratamento radioter?pico e quimioter?pico, a sobrevida global e sobrevida livre de recidiva dos pacientes. Foram identificados 54 pacientes com doen?a irressec?vel, tratados exclusivamente com radioterapia e quimioterapia. A mediana de seguimento foi de 22 meses. A amostra se caracterizou pelo predom?nio de indiv?duos masculinos, com idade mediana de 60 anos; todos eram tabagistas. O s?tio mais frequente foi a l?ngua oral e 81,5% encontravam-se no est?dio IV. Os pacientes com doen?a na cavidade oral tiveram uma pior resposta ao tratamento (p=0,006), pior sobrevida livre de recidiva (p=0,007), pior sobrevida global (p=0,007). O est?dio T avan?ado se demonstrou um fator progn?stico negativo (p=0,006) para a resposta ao tratamento cl?nico efetuado. Foi realizada imuno-histoqu?mica para marcar c?lulas CD8+ (anti-CD8) e c?lulas NK (anti-CD57). Os linf?citos positivos e negativos para as marca??es foram contados atrav?s do programa ImageJ?. Dois grupos foram criados para cada marca??o avaliada: Grupo I: pacientes com mais de 50% das c?lulas positivas; Grupo II: menos de 50% das c?lulas marcadas. Para as c?lulas CD8+ detectamos que 38 (70,3%) eram do Grupo I CD8+ e 16 (29,7%) do Grupo II CD8+. Para as c?lulas NK, 26 (48,15%) Grupo I NK e 28 (51,85%) Grupo II NK. Em rela??o ? resposta cl?nica ao tratamento, observamos que 39% dos pacientes obtiveram resposta completa e 25,9% permaneceram sem recidiva ao final do seguimento. Esses resultados foram melhores no Grupo I CD8+ (p=0,2). Identificamos que 72,2% dos pacientes evolu?ram para o ?bito, esse achado n?o teve associa??o com os dados imuno-histoqu?micos. N?o se observou diferen?as estatisticamente significantes entre a quantidade de c?lulas CD8+ e NK e a capacidade de resposta tumoral ao tratamento radioter?pico e quimioter?pico, nem com a sobrevida global e sobrevida livre de recidiva dos pacientes. Contudo, principalmente em rela??o a resposta adquirida, detectamos que este grupo de pacientes com doen?a avan?ada tem uma baixa contagem de c?lulas TCD8+ ativas. Acreditando no papel fundamental que a resposta imune exerce no combate local ?s c?lulas neopl?sicas; no entanto, nossos resultados n?o suportam a utiliza??o da an?lise quantitativa das c?lulas TCD8+ e NK como um dos fatores progn?sticos para o carcinoma epiderm?ide oral e de orofaringe
13
Alliegro, Fernando Canola 1981. "Análise histopatológica convencional versus cortes seriados em esvaziamentos cervicais de pacientes com Carcinoma Espinocelular (CEC) de cavidade oral e orofaringe cN0 = mudança de status cervical e correlação com sobrevida = Increasing neck staging with step-serial sectioning of neck dissection specimens for oral end oropharyngeal SCC patients". [s.n.], 2015. http://repositorio.unicamp.br/jspui/handle/REPOSIP/312536.
Testo completoAbstract (sommario):
Orientadores: Carlos Takahiro Chone, Agricio Nubiato CrespoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Ciências Médicas
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Resumo: Objetivo. Avaliar a mudança no estadiamento cervical de pacientes com carcinoma espino celular (CEC) de cavidade oral e orofaringe, após alteração na padronização da análise anátomo-patológica dos linfonodos de espécimes cirúrgicos de esvaziamentos cervicais, clinicamente livres de metástases (cN0), com cortes seriados de todos os linfonodos. Materiais e Métodos. Estudo retrospectivo com 21 pacientes previamente classificados como cN0 submetidos a cirurgia para exérese do tumor primário e esvaziamento cervical eletivo. Realizou-se inicialmente a revisão das laminas originais e, posteriormente, cortes seriados com 5 µm de espessura e nova análise das lâminas. Para avaliar o impacto da mudança na sobrevida foi realizada análise de Kaplan-Meier (IC 95%). Resultados. Após a avaliação convencional, 14 pacientes foram classificados como pN0, isto é, patologicamente livres de metástases cervicais, e sete (33%) como pN+, ou seja, patologicamente acometidos. A análise com cortes seriados detectou outros três pacientes com acometimento linfonodal, previamente classificados como pN0 e 1 previamente estadiado como N1 mudou para N2b com 10 pacintes pN+ (48%). Houve aumento de 43% (3/7) no número de pacientes com acometimento linfonodal e 19% de aumento no estadiamento linfonodal após a nova padronização anátomo-patológica, porém sem impacto na sobrevida (p=0,554). Conclusão. Análise com cortes seriados de linfonodos de esvaziamento cervicais permitiu um aumento de 14% no número de pescoços com metastases ocultas e de 19% no estadiamento cervical inicial frente à técnica convencional
Abstract: Objective. Asses the change in neck staging in patients with squamous cell carcinoma (SCC) of oral cavity and oropharynx after new methodology for histopathological analysis of lymph nodes of surgical specimens from neck dissections, with step serial sections of all harvested lymph nodes, in clinically neck negative patients (cN0). It was also studied the impact of this changes on survival. Materials and methods. Retrospective study with 21 patients previously classified as cN0 undergoing surgery for excision of the primary tumor and elective neck dissection. Initially was held to revise the original pathology slides and, subsequently, step-serial sectioning with 5 µm thick and re-examination of the slides. In order to assess the impact of change in disease-free survival was held Kaplan-Meier analysis (IC 95%). Results. After conventional evaluation, 14 patients were found to be without lymphatic metastases (pN0) and seven (33%) were affected (pN+). The analysis with step serial section has detected three other patients with lymphatic metastases, previously classified as pN0, and one patient previously as N1 increased to N2b with 10 pN(+) cases (48%). There was an increase of 43% in patients with lymph node metastases and 19% of increase in neck staging after the new histopathological standardization, but without impact on survival (p = 0.554). Conclusion. Analysis of lymph nodes in surgical specimens of neck dissections with step-serial sectioning allowed an increase of 43% of necks with occult metastases and increase of neck staging in 19% when compared to conventional technique
Mestrado
Otorrinolaringologia
Mestre em Ciências Médicas
14
Murphy, Justin Thomas. "Radioresistance in oral squamous cell carcinoma". Thesis, University of Hull, 2008. http://hydra.hull.ac.uk/resources/hull:770.
Testo completoAbstract (sommario):
Head and Neck Squamous Cell Carcinoma (HNSCC) is the sixth most common cancer accounting for approximately 6% of all cancers worldwide. However the distribution across the globe varies considerably. The majority of small tumours of the oral cavity and upper aerodigestive tract, in the absence of metastatic disease, can be successfully treated with surgery or radiotherapy. Despite this most small tumours of the oral cavity are now treated with surgery as the primary treatment modality with radiotherapy being reserved for adjuvant therapy, palliation or in patients unfit for surgery. Radiotherapy is also used in cases where there is doubt about the completeness of resection and where adverse histological characteristics are present. Unfortunately, on average about 10% of tumours treated in this way are resistant to radiotherapy, developing tumour recurrence within the original radiotherapy field during the ensuing 12 months. Patients with radioresistant tumours are not only receiving a therapy that is unnecessary but are also being put at risk of potentially serious complications, e.g. osteoradionecrosis of the cervical spine. The primary aim of this thesis was to investigate the mechanism of radioresistance and create an in vitro model of a radioresistant oral squamous cell carcinoma. The methods of cell culture, microarray analysis and immunohistochemistry were employed to this end. Two novel radioresistant cell lines, PE-CAPJ41RR and PE-CAPJ49RR, were created and a number of targets identified using microarray analysis. Immunohistochemistry was used to investigate the relationship EGFR, Bcl-2, BAX and COX-2 had with radiotherapy response.
15
Hui, King-cheung, e 許景祥. "Biomarkers for esophageal squamous cell carcinoma". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B41634020.
Testo completo
16
Hui, King-cheung. "Biomarkers for esophageal squamous cell carcinoma". Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B41634020.
Testo completo
17
Law, Bic-fai Fian. "Molecular genetics of esophageal squamous cell carcinoma". Click to view the E-thesis via HKUTO, 2006. http://sunzi.lib.hku.hk/hkuto/record/B3660446X.
Testo completo
18
Ash, Cecil Samuel. "Mandibular invasion in oral squamous cell carcinoma". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 1997. http://www.collectionscanada.ca/obj/s4/f2/dsk2/ftp04/mq23202.pdf.
Testo completo
19
Sun, Li. "Molecular cytogenetics of oral squamous cell carcinoma". Click to view the E-thesis via HKUTO, 2002. http://sunzi.lib.hku.hk/HKUTO/record/B38627887.
Testo completo
20
Lim, Kue Peng. "Fibroblasts in human oral squamous cell carcinoma". Thesis, University of Bristol, 2009. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.503859.
Testo completoAbstract (sommario):
The tumour microenvironment is known to play an important role in tumour development and progression. The diversity and role of stromal fibroblasts in human oral cancer, however, is unknown. In this study, fibroblasts were oral cancer, however, is unknown. In this study, fibroblasts were isolated from cultures of normal oral mucosa, oral epithelial dysplasia and mortal and immortal oral carcinomas, the latter malignancy being genetically unstable. Using global gene expression profiling, we demonstrated that fibroblasts clustered according to their tissue of origin.
21
Hu, Yingchuan, e 胡穎川. "Molecular pathogenesis of oesophageal squamous cell carcinoma". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2000. http://hub.hku.hk/bib/B31241797.
Testo completo
22
Sun, Li, e 孫莉. "Molecular cytogenetics of oral squamous cell carcinoma". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2002. http://hub.hku.hk/bib/B36544267.
Testo completo
23
Law, Bic-fai Fian, e 羅璧輝. "Molecular genetics of esophageal squamous cell carcinoma". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2006. http://hub.hku.hk/bib/B3660446X.
Testo completo
24
Yap, Lee Fah. "Molecular characterization of oral squamous cell carcinoma". Thesis, University of Bristol, 2006. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.435716.
Testo completo
25
Lambert, Sally Ruth. "Molecular profiling of cutaneous squamous cell carcinoma". Thesis, Queen Mary, University of London, 2010. http://qmro.qmul.ac.uk/xmlui/handle/123456789/564.
Testo completoAbstract (sommario):
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of non-melanoma skin cancer and accounts for the majority of deaths from this disease. Its incidence is increasing rapidly, contributing significant morbidity to patients and a burden on healthcare resources. The molecular events underlying cSCC development remain largely uncharacterised, despite the well established role of ultraviolet radiation as a principal carcinogen. Genomewide analyses of the genetic changes underlying cSCC development have shown they are subject to large chromosomal aberrations, which often involve whole chromosome arms. Many of these events occur in a high proportion of tumours, yet the genes they target are unknown. In this study, genomewide expression microarray data has been obtained from a series of cSCC and integrated with single nucleotide polymorphism (SNP) microarray data, to provide a comprehensive analysis of the events associated with tumour development. In total, 222 genes were identified as differentially expressed in cSCC, of which, 21% were concordant with copy number changes. Previous genomewide SNP data of cSCC had identified microdeletions within the PTPRD gene in a subset of tumours (Purdie et al., 2009). This was investigated in further detail and revealed microdeletions in this gene were significantly associated with metastatic cSCC. Sequencing analysis showed 37% of cSCC had a mutation at this locus, which suggests PTPRD is aberrant in a significant proportion of tumours. Decreased expression levels of PTPRD were correspondingly found in moderately and poorly differentiated tumours. The role of PTPRD in skin biology is not known and further functional work is required to elucidate its role in skin cancer. Taken together, these data provide a valuable insight into the genetic background against which cSCC develop. Furthermore, the association of PTPRD disruption with aggressive tumours may potentially be of future benefit as a prognostic biomarker and therapeutic target.
26
Mallipeddi, Rajeev. "Understanding squamous cell carcinoma in epidermolysis bullosa". Thesis, King's College London (University of London), 2005. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.416097.
Testo completo
27
Baldursson, Baldur. "Development of squamous cell carcinoma in venous ulcers /". Stockholm, 2000. http://diss.kib.ki.se/2000/91-628-4079-7/.
Testo completo
28
Bennett, Kristi Lynn. "Methylation in head and neck squamous cell carcinoma". Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1194544327.
Testo completo
29
Liu, Xiaobing. "Dysregulation of microRNAs in tongue squamous cell carcinoma". Click to view the E-thesis via HKUTO, 2008. http://sunzi.lib.hku.hk/hkuto/record/b40203499.
Testo completo
30
Carter, S. A. "Novel cytogenetic abnormalities in cervical squamous cell carcinoma". Thesis, University of Cambridge, 2010. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.597332.
Testo completoAbstract (sommario):
SCC cell lines were karyotyped to identify recurrent aberrations and those providing a selective advantage in individual cases. Karyotypic heterogeneity provided evidence for ongoing chromosomal instability (CIN) in all cell lines but revealed discordance between the levels of numerical CIN (N-CIN) and structural CIN (S-CIN), supporting the notion that different mechanisms underlie these processes. This molecular cytogenetic analysis identified a novel reciprocal translocation t(8:12)(p21.3;p13.31) present in all cells of the SCC cell line MS751, indicative of a selective advantage. The rearrangement resulted in two novel fusion genes, PEX5-LPL on der(8) and LPL-PEX5 on der(12). LPL-PEX5 encodes a truncated transcript but PEX5-LPL encodes a full length chimeric protein, comprising the first exon of PEX5 followed by the majority of LPL coding region, and is the most likely candidate for having driven selection of the translocation. Reverse transcription PCR was used to show that LPL is generally expressed at negligible levels in the cervix whereas PEX5 is expressed constitutively. In concordance, PEX5-LPL was expressed at substantially higher levels than LPL-PEX5. The function of PEX5-LPL might be to drive aberrant expression of the 3’ partner or the chimeric protein might have a modified or novel function. Overexpression of LPL relative to normal cervix was found in over one third of cervical SCC cell lines and primary tumour samples, suggesting it is common in cervical SCC. Findings suggest that PEX5-LPL and LPL overexpression have similar roles in cervical carcinogenesis; functional studies of overexpression elucidated a role for both proteins in increased cellular invasion. The functionally important domain might be shared between these proteins and is most likely to be in the C terminal region of LPL. This C terminal domain may be considered as a novel candidate for targeted therapy of cervical SCC.
31
Liu, Xiaobing, e 劉小兵. "Dysregulation of microRNAs in tongue squamous cell carcinoma". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2008. http://hub.hku.hk/bib/B40203499.
Testo completo
32
Chung, Man-fai Yvonne, e 鍾文暉. "Investigation of biomarkers in esophageal squamous cell carcinoma". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2009. http://hub.hku.hk/bib/B43704025.
Testo completo
33
Yu, Zhuoyou, e 余卓由. "Role of DNAJB6 in esophageal squamous cell carcinoma". Thesis, The University of Hong Kong (Pokfulam, Hong Kong), 2013. http://hdl.handle.net/10722/196454.
Testo completoAbstract (sommario):
Esophageal cancer (EC), which is geographically diverse, has only a 10.7% five-year survival rate. One of the histologic forms, esophageal squamous cell carcinoma (ESCC), in Hong Kong accounts for 81.5% of the total EC cases and its five-year survival rate is only ~14%, due to its high frequency of metastasis.
In our previous studies, functional complementation study of chromosome 9 defects led to the discovery of a novel tumor suppressor gene, Deleted in Esophageal Cancer 1 (DEC1), mapping to 9q32. DEC1 was shown to reduce tumorigenicity in a mouse model and its expression was shown to be associated with lymph node metastasis, early onset of ESCC, and familial ESCC development in a tissue microarray (TMA) study. Moreover, DNAJ (Hsp40) homologue subfamily B member 6 (DNAJB6), a molecular co-chaperone protein and the focus of the current study, was identified as a DEC1-interacting protein through a yeast two-hybrid screening. The interaction was further confirmed by the GST pull-down assay and co-localization studies. Using a TMA constructed with ESCC tissues from Hong Kong, the clinical relevance of DNAJB6 expression was demonstrated.
In the present study, the role of DNAJB6 in ESCC was investigated using cell line-based in vivo and in vitro studies. DNAJB6 was shown to be down-regulated in ESCC cell lines. The two isoforms of DNAJB6 have distinct subcellular localizations, with DNAJB6a mainly localized to the nucleus and DNAJB6b diffused throughout the cell. Existence of a functional nuclear localization signal peptide and a functional nuclear export signal peptide was verified in DNAJB6a and DNAJB6b, respectively. In vitro evidence of possible DNAJB6a truncation was found.
In vivo subcutaneous nude mice tumorigenicity assays showed that over-expression of DNAJB6a, but not DNAJB6b, suppresses tumor growth at the primary site, while DNAJB6a silencing enhances tumor growth. The suppressive effect of DNAJB6a depends on nuclear localization of the protein and the HPD tripeptide motif in the N-terminal J domain. In vitro function studies show that DNAJB6a over-expression impairs cell proliferation by suppressing G1/S transition.
AKT1 phosphorylation is down-regulated in DNAJB6a over-expressed cells, leading to up-regulation of p27KIP1 protein expression and down-regulation of cyclin E1 protein expression, the G1/S transition promoter, in an AKT1-dependent manner. DNAJB6a silencing results in the opposite effect.
Over-expression of DNAJB6b, but not DNAJB6a, instead suppresses lung colonization in an experimental metastasis assay, and prolongs survival of the mice.
Silencing of DNAJB6a in immortalized normal esophageal epithelial cells initially induces a senescence-like phenotype with greatly reduced proliferation possibly due to oncogenic stress from up-regulation of AKT1 phosphorylation and cyclin E1 protein expression, but promotes EMT-like molecular alterations by up-regulating STAT3 phosphorylation and TWIST1 protein expression and resumes proliferation after prolonged culture.
In summary, these results suggest that DNAJB6 plays a critical role in ESCC initiation, development, and metastasis and provides valuable insight into the understanding of ESCC tumorigenesis and metastasis. This suggests its usefulness as a biomarker candidate for detecting early ESCC tumor initiation.published_or_final_version
Clinical Oncology
Doctoral
Doctor of Philosophy
34
Clark, Richard R. "Lymph node metastasis in auricular squamous cell carcinoma". Thesis, University of Glasgow, 2009. http://theses.gla.ac.uk/547/.
Testo completoAbstract (sommario):
Introduction Squamous cell carcinoma of the auricle has an unusually high rate of lymph node metastases when compared to similar tumours at other sites. The lymph nodes affected are close to the base of the skull and in the neck. Development of metastasis carries a poor prognosis and most patients will subsequently die of failure of loco-regional control. Despite the likelihood of a poor outcome nothing can be done for patients prior to development of metastasis, as the risk of spread is not sufficiently high to warrant intervention in all patients. They are therefore treated with a ‘wait and see policy’ and only offered treatment once clinical evidence of metastatic spread is detected. This thesis sets out to examine what can be done, at the time of initial presentation with an auricular squamous cell carcinoma to identify patients who would benefit from treatment to the regional lymph node basins. Materials and Methods The thesis is divided into four separate studies. A systematic review examines the evidence available to date, an anatomical study examines the lymphatic drainage of the auricle in cadavers, a sentinel lymph node biopsy study examines the use of this technique to identify early tumour spread and a retrospective analysis of cases of auricular squamous cell carcinoma in our unit examines histopathological prognostic indictors of metastatic spread. Results The systematic review found that these tumours have a metastatic rate of about 11%. Patients developing metastasis usually die from failure of loco-regional control. Depth of tumour invasion, tumour size and mode of invasion seem to be potential indicators of metastatic risk. There is a strong argument for prophylactic intervention to the regional lymph nodes but there is no consensus of opinion as to when this should be carried out The anatomical study comprised 5 cadaveric dissections. They showed that the first echelon nodes draining the auricle lie in the superficial parotid gland, post-auricular/ mastoid nodal group and level II of the neck. There are anastamotic pathways around the mastoid and post-auricular nodes that could permit embolic tumour cells to bypass them. Five lymphatic pathways draining the auricle are described and some of these lie on the lateral and anterior surfaces of the mastoid bone and traverse the insertion of sternocleidomastoid. 28 cases of auricular squamous cell carcinoma were enrolled for sentinel lymph node biopsy. None of them were found to have any metastatic spread. One case showed non-viable tumour cells in a lymph node. There was a high incidence of complications (14%) directly related to the sentinel node biopsy procedure. The retrospective analysis identified 229 cases of auricular squamous cell carcinoma treated in our unit from 1992 - 2004. 212 of these cases had the primary pathology available for analysis. 24 (of 212) patients developed metastasis. 17 patients died as a result of their disease usually due to failure of control at the regional lymph node basin. Primary tumours with a depth of invasion greater than 8mm have metastatic rate of 56%. Tumours with a depth of invasion between 2-8mm and evidence of cartilage destruction, lymphovascular invasion or a non-cohesive invasive front have 24% metastatic rate. Tumours outwith these high-risk groups did not metastasise. Conclusions Elective lymph node dissections of the superficial parotid gland, post-auricular/mastoid and level II nodes should be considered in patients with primary auricular squamous cell carcinomas with a depth of invasion >8mm or a depth of invasion between 2 - 8 mm and evidence of cartilage destruction, lymphatic invasion or a non-cohesive invasive front. This should ideally be done as part of an observational study to evaluate the cost / benefit ratio for these patients. The neck dissection must clear the mastoid bone to a sub-periosteal level on its anterior and lateral surfaces. This will require the removal of the upper portion of sternocleidomastoid. Sentinel lymph node biopsy requires further study to evaluate it as a method for early detection of metastatic spread in auricular squamous cell carcinoma. This could be done as part of an observational study of elective neck dissections.
35
Chung, Man-fai Yvonne. "Investigation of biomarkers in esophageal squamous cell carcinoma". Click to view the E-thesis via HKUTO, 2009. http://sunzi.lib.hku.hk/hkuto/record/B43704025.
Testo completo
36
Sáenz, Sardà Xavier. "Progression pathways of squamous cell carcinoma associated with actinic damage: From cancer field to actinic keratosis and invasive squamous cell carcinoma". Doctoral thesis, Universitat Autònoma de Barcelona, 2019. http://hdl.handle.net/10803/667918.
Testo completoAbstract (sommario):
Se pensaba que la progresión de una queratosis actínica (AK) a carcinoma escamoso infiltrante (SCC) de piel ocurría siempre y cuando la neoplasia intra-epidérmica ocupara todo el espesor de la epidermis como ocurre en la vía clásica (CP) descrita en el cáncer de cérvix. Sin embargo, el carcinoma escamoso infiltrante cutáneo puede aparecer directamente desde una displasia que sólo ocupe el tercio inferior de la epidermis (AK I, vía diferenciada o DP). Esta segunda vía de progresión se ha descrito en el SCC de vulva y de cavidad oral , cuyo comportamiento biológico es además más agresivo.
Esta tesis empezó revisando todos los casos correspondientes a biopsias quirúrgicas, obtenidas mediante el BioBanco del Hospital Germans Trias y Pujol, de tres años consecutivos correspondientes al período 2004-2007. Seleccionamos 503 casos de SCC cutáneo, de los que finalmente estudiamos 196. La mayor parte mostraron AK I en superficie (63.8%) o en los bordes (77.9%), concluyendo así que la invasión directa desde AK I (DP) es la forma más frecuente de progresión a SCC cutáneo. Este estudio fue el primero que se propuso investigar la prevalencia de la CP y DP en la transformación de la AK en SCC infiltrante aportando evidencias de su existencia. Estos hallazgos se publicaron en J Eur Acad Dermatol Venereol. 2014 Oct; 29(5):991-7.).
La siguiente etapa del estudio consistió en la realización de una matriz de tejidos (TMA) de las biopsias ya estudiadas y se segregaron los casos con SCC entre los originados por DP y los originados por CP. En total se realizaron ocho TMA que supusieron 756 cores a evaluar. Mediante el uso de técnicas de inmunohistoquímica se evidenció que la transición epitelio-mesénquima participa en la transformación de AK I en SCC (DP) mientras que una capacidad proliferativa mayor facilita la extensión intra-epidérmica en la vía clásica y se hallaron diferencias significativas en cuanto a la expresión de CD31 (angiogénesis) y MMP (metaloproteinasas) hallándose estos marcadores elevados en los tumores que progresan por DP, lo que junto con la transición epitelio-mesenquima podría facilitar la progresión local. Una parte de estos resultados han sido publicados en la revista J Eur Acad Dermatol Venereol. 2018 Apr; 32(4):581-586). Tambien se procedio al uso de técnicas de CISH para el estudio de miRNA hallándose los tumores surgidos por DP expresan mayores niveles de miRNA31 tanto en su intensidad como en su extensión.
En la siguiente etapa se estudió la extensión de la atipia queratinocitaria por el epitelio de los anejos estando esta presente en el 25.9% de los casos y, de ellos, la infiltración del carcinoma escamoso directamente adyacente a la basal folicular estaba presente en el 58% de los casos. En consecuencia, seria altamente recomendable indicar la profundidad de la extensión folicular en el diagnóstico histológico de biopsias incisionales, dado el riesgo de recurrencia e infiltración que ello implica, así como las derivadas terapéuticas que conlleva. Los hallazgos han sido publicados en la revista J Eur Acad Dermatol Venereol. 2018 Oct; 32(10):1657-1661).
Consideramos que la serie de estudios que conforman esta tesis proporcionan conocimiento nuevo sobre las vías de progresión del SCC cutáneo y de sus lesiones precursoras. Se ha establecido que existen al menos dos vías de progresión de SCC a AK, se ha introducido el concepto de DP en la carcinogénesis cutánea, se han hallado bases moleculares que explican la progresión a través de ambas vías y se ha constatado el riesgo de la extensión folicular en la AK. Todos estos estudios han supuesto en algunos ámbitos un cambio de paradigma y tienen relevancia tanto en el diagnóstico como en el tratamiento de las AK.It was thought that the progression of an actinic keratosis (AK) to invasive squamous cell carcinoma (SCC) occurred as long as the intra-epidermal neoplasm occupied the entire thickness of the epidermis as in the classical pathway (PC) described in cervix cancer. However, cutaneous infiltrative squamous carcinoma can appear directly from a dysplasia that only occupies the lower third of the epidermis (AK I, differentiated pathweay or DP). This second pathway of progression has been described in SCC of the vulva and oral cavity, whose biological behavior is more aggressive. This thesis began by reviewing all cases corresponding to surgical biopsies, obtained through the BioBanco of the Germans Trias and Pujol Hospital, for three consecutive years corresponding to the period 2004-2007. We selected 503 cases of cutaneous SCC, of which we finally studied 196. Most showed AK I on the surface (63.8%) or on the edges (77.9%), thus concluding that the direct invasion from AK I (DP) is the most frequent form of progression to cutaneous SCC. This study was the first one that was proposed to investigate the prevalence of CP and DP in the transformation of AK into infiltrating SCC, providing evidence of its existence. These findings were published in J Eur Acad Dermatol Venereol. 2014 Oct; 29 (5): 991-7.). The next stage of the study consisted in the realization of a tissue microarrays (TMA) of the biopsies already studied and the cases with SCC were segregated between those originated by DP and those originated by CP. In total, eight TMAs were performed, which involved 756 cores to be evaluated. Through the use of immunohistochemical techniques it was demonstrated that the epithelial-mesenchymal transition participates in the transformation of AK I into SCC (DP) while a greater proliferative capacity facilitates the intra-epidermal extension in the classical pathway and significant differences were found in to the expression of CD31 (angiogenesis) and MMP (metalloproteinases), these markers being elevated in tumors that progress through DP, which together with the epithelium-mesenchymal transition could facilitate local progression. A part of these results have been published in the journal J Eur Acad Dermatol Venereol. 2018 Apr; 32 (4): 581-586). We also proceeded to the use of CISH techniques for the study of miRNA, finding that tumors arising from DP express higher levels of miRNA31 both in their intensity and in their extension. In the next stage the extension of the keratinocyte atypia among adnexal structures was studied, being present in 25.9% of the cases and, of them, the infiltration of the squamous carcinoma directly adjacent to the follicular basal was present in 58% of the cases. Consequently, it would be highly advisable to indicate the depth of follicular extension in the histological diagnosis of incisional biopsies, given the risk of recurrence and infiltration that this implies, as well as the therapeutic derivatives that it entails. The findings have been published in the journal J Eur Acad Dermatol Venereol. 2018 Oct; 32 (10): 1657-1661). We consider that the series of studies that make up this thesis provide new knowledge about the pathways of cutaneous SCC progression and its precursor lesions. It has been established that there are at least two pathways of progression from SCC to AK, the concept of PD has been introduced in cutaneous carcinogenesis, molecular bases have been found that explain the progression through both pathways and the risk of follicular extension in the AK. All these studies have led to a paradigm shift in some areas and are relevant both in the diagnosis and treatment of AKs.
37
Wassberg, Cecilia. "Ultraviolet Radiation and Squamous Cell Carcinoma in Human Skin". Doctoral thesis, Uppsala University, Department of Medical Sciences, 2001. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-1479.
Testo completoAbstract (sommario):
Ultraviolet radiation (UVR) is a major risk factor for development of skin cancer. UVR-induced DNA damage and a dysfunctional p53 protein are important steps in the development of squamous cell carcinoman in human skin (SCC). The aim of the present investigation was to analyze incidence trends of SCC in Sweden, quantify the risk of second primary cancer after SCC and further analyze the effects of UVR and p53 protein in human skin in vivo and in vitro. The effect of photoprotection by sunscreens was also evaluated.
We found that the age-standardized incidence rate of SCC in Sweden increased substantially in both men and women during the period 1961-1995, especially in men and at chronically sun-exposed skin sites. Patients with SCC are also at increased risk of developing new primary cancers, especially in the skin, squamous cell epithelium, hematopoietic tissues and respiratory organs. In experimental studies in vivo and in vitro in human skin we observed that repair of UV-induced DNA damage appears to be more efficient in chronically sun-exposed skin despite a less uniform p53 response. Non-sun- exposed skin is more homogeneous with respect to the epidermal p53 response. Keratinocytes in skin exposed frequently to the sun may be prone to react more easily to cytotoxic stress. Two different modalities of photoprotection significantly reduced the amount of DNA damage and the number of p53-positive cells. In addition, we demonstrated that a well-defined system for in vitro culture of explanted skin provides an excellent alternative to in vivo experiments.
In conclusion, this study has increased our knowledge of SCC epidemiology in Sweden and of the effects of artificial and solar UVR and sunscreens on chronically sun-exposed and non-sun-exposed sites, respectively, of human skin.
38
Kim, Hyung Jun. "Surgical management of oral squamous cell carcinoma infiltrating mandible". Diss., lmu, 2008. http://nbn-resolving.de/urn:nbn:de:bvb:19-98143.
Testo completo
39
Sawair, F. A. "Prognostic indicators of outcome for oral squamous cell carcinoma". Thesis, Queen's University Belfast, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.390863.
Testo completo
40
Tang, Cheuk-on. "Cytogenetic and molecular study of oesophageal squamous cell carcinoma /". Hong Kong : University of Hong Kong, 2001. http://sunzi.lib.hku.hk:8888/cgi-bin/hkuto%5Ftoc%5Fpdf?B23339834.
Testo completo
41
Gemenetzidis, Emilios. "The role of FOXM1 in oral squamous cell carcinoma". Thesis, Queen Mary, University of London, 2010. http://qmro.qmul.ac.uk/xmlui/handle/123456789/492.
Testo completoAbstract (sommario):
FOXM1 transcription factor regulates the expression of a multitude of genes, which are important for cell proliferation, mitosis, and differentiation. Although it is abundantly expressed in majority of human solid tumours, its role in early stages of human neoplasia remains unclear. Oral squamous cell carcinoma (OSCC) is characterized by sequential genomic alterations, which lead to invasive malignancy. In this study, it is shown that FOXM1 is significantly upregulated in early oral pre-malignant and OSCC tissues and cultured keratinocytes. Furthermore, the current study suggests that FOXM1B is the main isoform driving the cell cycle dependent expression of FOXM1, and that it is expressed mainly at the G2 phase of human epithelial keratinocytes. In an attempt to understand why FOXM1 precedes epithelial malignancy, the present study investigated 1) the genomic profile of FOXM1B overexpressing human epithelial keratinocytes, and 2) whether FOXM1B overexpression interferes with the innate program of keratinocyte differentiation, which is frequently reported as being the earliest oncogenic event in epithelial neoplasia. First, by using a high-resolution Affymetrix single nucleotide polymorphism (SNP) mapping technique, this study provides the first evidence that FOXM1B overexpression alone in primay human keratinocytes was sufficient to induce genomic instability, mainly in the form of copy number alterations. FOXM1B overexpression also cooperated with damaging agents relevant to human epidermal (UVB) and oral epithelial cancer (Nicotine), to promote genomic instability in human keratinocytes. Second, by using a 3D-organotypic culture model of oral mucosa, sustained overexpression of FOXM1 was found to induce a hyper-proliferative phenotype with suprabasal proliferation, exhibiting perturbed markers of epithelial differentiation such as cytokeratin 13 and filaggrin, resembling early oral dysplastic epithelium. Based on these observations it is hypothesised that aberrant upregulation of FOXM1B serves as a ‘first hit’ whereby cells acquire genomic instability, and an abnormal differentiation program. The latter event promotes epithelial proliferation at the expense of terminal differentiation, allowing sufficient time for the accumulation of additional genetic aberrations/mutations required for tumour promotion and expansion. The Role of FOXM1 in Oral Squamous Cell Carcinoma
42
Qadir, Fatima. "Cellular and molecular signature of oral squamous cell carcinoma". Thesis, Queen Mary, University of London, 2018. http://qmro.qmul.ac.uk/xmlui/handle/123456789/39763.
Testo completoAbstract (sommario):
Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide. It is a result of numerous aetiological factors such as genetic predisposition, smoking, excessive alcohol consumption and viruses such as the human papilloma virus. Due to late diagnosis it has a high mortality and morbidity rates which has remained unchanged over the last 5 decades. Currently no screening is available for high risk patients for better monitoring. Diagnosing OSCC relies on histopathology of biopsy tissue, reviewed for dysplasia and advancing lesions. Although the technique has been used for decades for successful diagnosis it fails to identify the molecular signature of OSCC which appears much before the visual signs. It also falls short in predicting the malignant transformation of pre-malignant oral lesions. Identifying the molecular and genetic changes leading to OSCC lesion will aid in more specific (quantitative) and early diagnosis of the disease reducing the financial burden of treating late-stage OSCC patients on the healthcare system. This study focuses on developing new adjuncts which can be used alongside histopathology for early diagnosis. There is a need to monitor high risk patients through non-invasive methods causing less patient discomfort. We therefore explored the potentials of exosomes which are extracellular vesicles secreted by normal and tumour cells. They can be isolated from body fluids such as blood and saliva. In cancer biology exosomes offer both diagnostic and therapeutic advantage. Their involvement in cell-cell communication indicates their influence in tumour development, progression, metastasis and therapeutic efficacy. Exosomes released by cancerous cells carry numerous biomarkers, which are passed on to healthy cells via microenvironment, causing stromal and angiogenic activation along with immune escape. In this study exosomes were successfully isolated from body fluids (blood, saliva and plasma) and cell line supernatant through ultracentrifugation and characterised by visual and particle size quantification techniques including Scanning Electron Microscopy (SEM) and Transmission Electron Microscopy (TEM), Zetasizer and Nanosight Tracking Analysis (NTA). Exosomal specific membrane proteins were identified through Western blotting. 5 We report the presence of a potential protein biomarker located exclusively on the outer membrane of cancer exosomes. Since body fluids consist of a heterogeneous population of exosomes derived from multiple cell types, such surface biomarker can potentially be used to isolate OSCC exosomes. Characterisation of exosomal mRNA cargo was done using Agilent Bioanalyzer (for RNA quantity and quality assurance) and reverse transcription-quantitative PCR (RT-qPCR; for gene specific quantitation). Functional significance of exosomes was studied by transfecting normal oral keratinocyte cells with self and cancer-derived exosomes. Through gene-expression microarray and subsequent RT-qPCR verification, we report a panel of differentially expressed genes involved in essential cellular functions being modulated by exosome transfection. A previously developed molecular diagnostic system by our research group called quantitative malignancy index diagnostic system (qMIDS) based on FOXM1 oncogene and its downstream targets was validated on archival formalin fixed paraffin embedded OSCC patient biopsy samples. We report that qMIDS index successfully correlates with the disease stages including dysplasia, tumour and lymph node metastasis. Furthermore, through meta-analysis of 8 OSCC microarray studies we identified a panel of six genes including PLAU, FN1, CDCA5, CRNN, CLEC3B and DUOX1 (q6) which are able to identify two clinically distinct sub-groups of OSCC patient population. Through RT-qPCR the expression of q6 biomarkers was established in 100 OSCC biopsy samples. This information can be of immense importance in developing personalized treatment strategies based on the molecular makeup of the presenting tumour.
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LE, HOANG BA PATRICK. "Interet diagnostic du squamous cell carcinoma en pathologie pleuropulmonaire". Nice, 1988. http://www.theses.fr/1988NICE6550.
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supsavhad, wachiraphan. "Novel Molecular Targets for Feline Oral Squamous Cell Carcinoma". The Ohio State University, 2016. http://rave.ohiolink.edu/etdc/view?acc_num=osu1471628009.
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Ota, Juri. "Local photodynamic therapy for equine squamous cell carcinoma in a murine model". Diss., Columbia, Mo. : University of Missouri-Columbia, 2007. http://hdl.handle.net/10355/4934.
Testo completoAbstract (sommario):
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.
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Emich, Helena. "Clinical implications of cancer stem cell properties in oral squamous cell carcinoma". Thesis, Queen Mary, University of London, 2014. http://qmro.qmul.ac.uk/xmlui/handle/123456789/8479.
Testo completoAbstract (sommario):
CD44 has been described as a marker of cancer stem cells in oral squamous cell carcinoma (OSCC). The main objective of this study was to characterise expression of CD44 in both fresh samples of human OSCC and in cell lines generated from them, and to examine its correlation with selected clinicopathological parameters of the tumours of origin. The epithelial fraction in 20 fresh OSCC samples was identified by the standard method using the negative selection technique with antibodies against non-tumour cells. A novel method of identifying the epithelial fraction, termed positive selection, was also developed and used for analysis of 14 additional OSCC samples. This new method, using epithelial-specific antibodies, led to a considerable improvement in the efficiency and the accuracy of the procedure. The frequency of CD44+ cells in the epithelial fraction of the tumour specimens was assessed by FACS and varied widely (3-97%). High frequency of CD44+ cells in tumour samples was found to be associated with high tumour grade, discohesive invasion front and presence of lymph node metastases (p<0.01, as calculated with Spearman’s ranked test and Fisher’s exact test). It was also observed, that the percentage of CD44+ cells changes when cells isolated from tumour samples are propagated in culture. Nearly all cells in cell lines generated from OSCC samples showed CD44 expression when analysed by FACS. However, a markedly higher level of CD44 expression (as assessed by median fluorescence intensity for cell surface CD44) was found for early passage cell lines generated from metastatic OSCC and lymph node metastases as compared to cell lines generated from nonmetastatic OSCC. These findings show that a high frequency of CD44+ cells in fresh OSCC tissue and a high level of CD44 expression in cultured OSCC cells correlate 11 with more aggressive tumour behaviour. These results might provide important information of prognostic and therapeutic value.
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Akdeniz, Gözde. "Quantitative characterisation of cell fate in human keratinocytes and squamous cell carcinoma". Thesis, University of Cambridge, 2012. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.609952.
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Frede, Julia. "Cellular dynamics in Oesophageal Squamous Carcinogenesis". Thesis, University of Cambridge, 2015. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.708817.
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Torchia, Mark G. "Minimally invasive evaluation of head and neck squamous cell carcinoma". Thesis, National Library of Canada = Bibliothèque nationale du Canada, 2001. http://www.collectionscanada.ca/obj/s4/f2/dsk3/ftp05/NQ57639.pdf.
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Bradburn, Jennifer Elizabeth. "Reactive species promotion of head and neck squamous cell carcinoma". Columbus, Ohio : Ohio State University, 2007. http://rave.ohiolink.edu/etdc/view?acc%5Fnum=osu1166555968.
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