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Spandidos, Athanasia. "Proteomic methods applied to renal cell carcinomas." Thesis, University of Cambridge, 2002. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.620561.
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Llewelyn, Jenefer Kirstin. "Analysis of gene expression in squamous cell carcinomas." Thesis, King's College London (University of London), 2006. https://kclpure.kcl.ac.uk/portal/en/theses/analysis-of-gene-expression-in-squamous-cell-carcinomas(4ce3ae48-c239-4bc0-918e-e4aa691bd0d2).html.
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Xinarianos, George. "Genetic alterations in non-small cell lung carcinomas." Thesis, University of Liverpool, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.343688.
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Dowlatshahi, Mitra. "Suppressed Activity of Tumor-Specific T Cells in Human Merkel Cell Carcinomas." Thesis, Harvard University, 2017. http://nrs.harvard.edu/urn-3:HUL.InstRepos:32676135.
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Merkel cell carcinomas (MCC) are rare but highly malignant skin cancers associated with a novel polyomavirus. We studied T cells in MCC to determine how these virally mediated tumors evade immune responses. MCC tumors were infiltrated by T cells, including effector, central memory and increased numbers of CD4 and CD8 FOXP3+ regulatory T cells. Infiltrating T cells showed markedly reduced activation as evidenced by reduced expression of CD69 and CD25. Treatment of MCC tumors in vitro with IL-2 and IL-15 led to T cell activation, proliferation, enhanced cytokine production and loss of viable tumor cells from cultures. Expanded tumor-infiltrating lymphocytes showed TCR repertoire skewing and upregulation of CD137. MCC tumors implanted into immunodeficient NOD/SCID/IL2 receptor g chainnull mice failed to grow unless human T cells in the tumor grafts were depleted with denileukin diftitox, suggesting tumor-specific T cells capable of controlling tumor growth were present in MCC. 50% of non-activated T cells in MCC expressed PD-1, a marker of T cell exhaustion, and PD-L1 and PD-L2 were expressed by a subset of tumor dendritic cells and macrophages. In summary, we observed tumor-specific T cells with suppressed activity in MCC tumors. Agents that stimulate T cell activity, block Treg function or inhibit PD-1 signaling may be effective in the treatment of this highly malignant skin cancer.
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Hudon, Valerie. "Investigating tumor suppressor genes involved in renal cell carcinomas." Thesis, McGill University, 2010. http://digitool.Library.McGill.CA:80/R/?func=dbin-jump-full&object_id=86607.
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Kidney cancer is a complex disease comprising several types of renal carcinomas, which are classified in different subtypes based on their histological characteristics. A small number of cases of renal cancers are due to hereditary predispositions and nearly all the knowledge on the molecular pathogenesis of kidney cancers was learned by the investigation of these hereditary forms of renal carcinomas. In this thesis, we studied two hereditary diseases predisposing to the development of kidney cancer, von Hippel Lindau (VHL) and Birt-Hogg-Dubé (BHD) syndromes, and their causative genes, VHL and FLCN respectively. First, we investigated the role of the extracellular matrix (ECM) regulation by VHL during tumorigenesis and angiogenesis, and we demonstrated that inactivation of the VHL-ECM assembly pathway results in highly vascularized tumors with a disrupted ECM. We concluded that loss of the ECM assembly promotes and maintains tumor angiogenesis by providing a way for new blood vessels to invade the tumor tissue. In the second part of this thesis, we developed a novel VHL mouse model to investigate the possible cooperation between VHL and p53 during tumorigenesis. We observed that inactivation of both tumor suppressor genes accelerate the formation of liver hemangiomas and splenic hemangiosarcomas. Furthermore, concomitant deletion of VHL and p53 abolished the development of lymphoma usually associated with loss of p53. Our results indicate that the phenotypes arising following the inactivation of VHL and p53 is organ-dependent. Finally, to study the pathogenesis of the BHD syndrome, we developed a new mouse model using an established embryonic stem cell line. We described the murine Flcn expression pattern and noticed that homozygous disruption of Flcn was embryonically lethal early during development. Furthermore, we observed a continuum of kidney lesions from renal tubules hyperproliferation to rare adenoma. FLCN tumor suppressor role was also substantiated usiLe cancer du rein est une maladie complexe qui comprend différents types de cancers classifiés selon leurs caractéristiques histologiques. Certains cas de cancers rénaux sont attribuables à une prédisposition héréditaire et l'étude de ces formes héréditaires de cancer a largement contribué au développement des connaissances concernant la pathogenèse des cancers rénaux. Le travail décrit dans cette thèse porte sur deux maladies héréditaires prédisposant au développement de tumeurs rénales soit la maladie de Von Hippel-Lindau (VHL) et le syndrome de Birt-Hogg-Dubé (BHD) ainsi que les gènes associés à ces dernières, VHL et FLCN respectivement. Premièrement, nous avons étudié le rôle de la régulation de l'assemblage de la matrice extracellulaire (MEC) par VHL durant la tumorigénèse et nous avons démontré que l'assemblage inadéquat de la MEC corrèle avec une croissance tumorale accrue et induit la formation de tumeurs fort vascularisées. Nous avons conclu que la perte de l'intégrité de la MEC favorise l'angiogénèse tumorale en fournissant une voie permettant aux vaisseaux sanguins d'infiltrer la tumeur. Deuxièmement, nous avons développé un modèle murin pour étudier la coopération potentielle entre VHL et p53 durant le développement tumoral. Nous avons observé que l'inactivation simultanée de VHL et p53 accélère la progression d'hémangiomes du foie et d'hémangiosarcomes de la rate. De plus, la perte concomitante de VHL et p53 inhibe le développement de lymphomes normalement associés à l'inactivation de p53. Nos résultats indiquent que les phénotypes apparaissant suite à l'inactivation de VHL et p53 varient selon l'organe étudié. Finalement, nous avons développé un modèle murin pour étudier de la pathologie associée au syndrome BHD et à avons observé la formation d'un continuum de lésions rénales allant de l'hyperprolifération des tubules rénaux à de rares adénomes. Finalement, nous avons conf
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Sandström, Karl. "Radioimmunodiagnosis of Head and Neck Squamous Cell Carcinomas : Preclinical Studies." Doctoral thesis, Uppsala universitet, Öron-, näs- och halssjukdomar, 2011. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-156523.
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Despite improvements in treatment, the prognosis for patients with advanced head and neck squamous cell carcinomas (HNSCC) has only improved to a minor degree. To raise the success rate and minimize morbidity further developments in diagnostics are highly desired. Radioimmunodiagnosis could offer a more specific and sensitive diagnostic method. Herein, we have evaluated different radioimmunoconjugates directed against CD44v6 and epidermal growth factor receptor (EGFR) for imaging of HNSCC. The studies were performed in a murine HNSCC xenograft model. Initially, the 111In-labeled anti CD44v6 chimeric monoclonal antibody U36 (cMAb U36) was evaluated. The novel radioimmunoconjugate showed high and accumulating tumor uptake. Since small molecules might be advantageous for imaging, due mainly to their shorter circulation half-life in the bloodstream, we then investigated antibody fragments F(ab’)2 and Fab’ derived from cMAb U36. The highest tumor-to-blood ratio was achieved with the dimeric antibody fragment F(ab’)2, compared with both the intact anti-body and monomeric Fab’. Furthermore, the possibility of improving EGFR-targeted imaging was explored by pre-blocking EGFR. The liver uptake of injected labeled human epidermal growth factor (hEGF) was significantly reduced when an excess of unlabeled hEGF was injected 30 minutes in advance. However, as hEGF stimulates cell proliferation it may be inadvisable to treat cancer patients with large amounts. Alternatively, pre-blocking with an anti-EGFR Affibody molecule (ZEGFR:955)2 demonstrated similar decrease in liver uptake as unlabeled hEGF. Finally, (ZEGFR:955)2 was compared with other Affibody molecules with higher affinity to EGFR, ZEGFR:1907 and (ZEGFR:1907)2, as pre-blocking agents. In addition, a novel hEGF radioimmunoconjugate, [67Ga]Ga-NOTA-Bn-NCS-hEGF was used for EGFR targeting. The dimeric (ZEGFR:1907)2 showed greatest reduction in non-tumor uptake, and highest tumor-to-organ ratio in EGFR expressing organs, when injected in advance of the radioimmunoconjugate. To summarize, the results presented here demonstrate how different radioimmunoconjugates as well as pre-blocking EGFR can improve the radioimmunodiagnosis of head and neck squamous cell carcinomas.
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Ekberg, Tomas. "Diagnosis and Radioimmunotherapy of Head and Neck Squamous Cell Carcinomas." Doctoral thesis, Uppsala : Acta Universitatis Upsaliensis : Universitetsbiblioteket [distributör], 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-8395.
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Santos, Harim Tavares dos 1989. "Gotas lipídicas intracitoplasmáticas em carcinomas de glândulas salivares = estudo imunohistoquímico." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/289546.
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Orientadores: Albina Messias de Almeida Milani Altemani, Fernanda Viviane MarianoDissertação (mestrado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Introdução: Gotas lipídicas (GL) são organelas altamente reguladas envolvidas na ativação e metabolismo celular assim como em processos inflamatórios e neoplásicos. O aumento da lipogênese levando a um aumento no número de GL é um fenótipo comum a numerosos carcinomas humanos e tem sido associado com: diferenciação, proliferação e agressividade tumoral. Objetivo: Avaliarem carcinomas salivares: a) a frequência e quantidade das GLs citoplasmáticas, correlacionando-as com a morfologia tumoral, grau de diferenciação e proliferação celular e b) a expressão de proteínas relacionadas ao processo secretório celular (STAT5a e mamoglobina). Material e métodos:em 79 casos de carcinomas de glândulas salivares foram utilizados os anticorpos Ki-67, adipophilin, STAT 5a e mamoglobina. A quantificação da imunoreatividade ao adipophilin, STAT 5a e mamoglobina foi através de uma escala semi-quantitativa. A intensidade de marcação do STAT 5a e mamoglobina foi subjetivamente avaliada como fraca/moderada ou intensa. A positividade ao Ki-67 foi calculada através da relação entre o número de células positivas e o número total de células tumorais em três áreas selecionadas da amostra. Resultados:os subtipos histopatológicos que apresentaram positividade ao adipophilin em 50% ou mais das células, foram os casos: MASC (100%), CCA (85,64%), CM (83%), CDS (75%) e CSeb (50%). Índice de proliferação maior que 10% das células tumorais foi observado no CSeb (Ki-67 = 29%), seguido do CDS (Ki-67 = 23,11%) e do CM (Ki-67 = 12,15%). Nos casos de CAC com transformação para alto grau a área transformadaapresentou maior proliferação e lipogênese quando comparada à área convencional. Somente os casos de MASC apresentaram imunorreatividade acentuada para STAT5a e mamoglobina. Conclusões: Embora exista correlação entre o acúmulo de gotas lipídicas e o índice proliferativo do tumor, em alguns tipos de carcinomas salivares tal depósito está possivelmente relacionado à diferenciação celular (CSeb e MASC) ou alteração metabólica (CCA). O acúmulo de Gl refletindo diferenciação celular se apresenta como gotas maiores em contraste com as microgotas frequentemente detectadas nos carcinomas com alto índice proliferativo. No MASC a forte expressão de STAT5a e mamoglobina sugere que a que o acúmulo de GL possivelmente reflete diferenciação do tipo lactacional.Mais estudos são necessários para entender o papel das gotas lipídicas citoplasmáticas em carcinomas de glândulas salivares. (Apoio FAPESP: 2012/18104-4 e 2012/18086-6)
Abstract: Introduction: Lipid droplets (LD) are highly regulated organelles involved in cell activation and metabolism as well as in inflammatory and neoplastic processes Upregulated lipogenesis leading to an increased number of cytoplasmic LD is a common phenotype to numerous human carcinomas and has been associated with: differentiation, proliferation and aggressiveness of the tumor. Objective: to evaluate in salivary carcinomas: a) the frequency and quantity of cytoplasmics LDs, correlating it with tumoral morphology, differentiation grade e cellular proliferation and b) the expression of proteins associated with cellular secretor process (STAT5a and mammaglobin). Material and Methods:in 79 cases of salivary gland carcinomas, an immunohistochemical study was performed with the antibodies Ki-67, adipophilin, STAT 5a and mammaglobin. The positive neoplastic cells were assessed regarding quantity using a semi-quantitative scale. The intensity of expression for each antibody was subjectively evaluated as weak/ moderate or intense.The positivity for Ki-67 was calculated based on the relation between the number of positive cells and the total number of the tumoral cells in three selected areas. Results: the histopatologic subtypes that presented positivity for adipophilin in 50% or more of cells were: AciCC (85,64%), MASC (100%), MC (83%), SDC (75%), SebC (50%). Proliferation index higher than 10% of tumoral cells was observed in SebC (Ki-67 = 29%), SDC (Ki-67 = 23,11%) and MC (Ki-67 = 12,15%). In ACC with high grade transformation the, the transformed area presented both higher proliferation and lipogenesis when compared to the convencional area. Only the cases of MASC presented accentuated immunoreactivity for STAT5a and mammaglobin. Conclusions: Although in salivary carcinomas there is correlation between the accumulation of lipid droplets and the proliferative index of the tumor, in some types of carcinomas such deposit is possibly related to cellular differentiation (SebC and MASC) or metabolic alteration (AciCC). The accumulation of LD that reflects cellular differentiationpresents features of macro droplets in contrast to micro-droplets frequently detected in carcinomas with high proliferative index. In MASC, the strong expression of STAT5a and mammaglobin suggests that LD accumulation is probably due to lactational-like differentiation. More studies are necessary to understand the role of cytoplasmic lipid droplets in salivary gland carcinomas (Supported by FAPESP: 2012/18104-4and2012/18086-6)
Mestrado
Patologia
Mestre em Estomatopatologia
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Kass, Youssef Khalil. "Identification of cellular origin and molecular mechanism in basal and squamous cell carcinomas." Doctoral thesis, Universite Libre de Bruxelles, 2012. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/209771.
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Skin cancers are very common in humans. The two most frequent epithelial skin cancers are the basal cell carcinoma (BCC) and the squamous cell carcinoma (SCC). For the vast majority of cancers, the cell at the origin of tumour initiation is still unknown and assumptions concerning their origin rely mainly on morphological and immunohistochemical studies. Recently, adult stem cells (SCs) have been suggested to be at the origin of tumour initiation based on their long term self-renewing capacities. According to these, two important questions arise; do epithelial skin cancers arise from mutations in a specific cell lineage of the epidermis? And are the stem cells more competent to initiate tumors than committed cells?BCCs result from aberrant activation of HH signaling and several mouse models carrying mutations in HH signaling genes are capable to form tumors resembling to human BCCs.
To identify the cell lineage at the origin of BCC and to investigate the role of stem cells in tumor initiation, we followed a genetic approach where we conditionally expressed SmoM2 oncogene (a constitutively active Smoothened mutant) in distinct skin epidermal compartments including SCs. Targeting basal epidermis cells, showed that only SmoM2-clones in the inter follicular epidermis (IFE) and the infundibulum can progress into BCC, whereas SmoM2 expression in Bulge SCs or in matrix transit amplifying progenitor cells never leads to BCC formation. Progressively after SmoM2 expression, tumor-initiating cells lose their normal differentiation to adopt a hair placode-like shape and markers, demonstrating that biochemical and morphological tumour features can be misleading in extrapolating their cellular origin.
The molecular changes occurring in tumor initiating cells and the mechanisms regulating the early steps of cancer development are poorly characterized for the majority of tumors. To address these questions in BCC, we took advantage of our ability to isolate SmoM2 expressing cells at different stages of tumor initiation and progression. Transcriptional profiling of SmoM2-basal IFE cells isolated one week (normal histology) and 4 weeks (dysplastic lesion), suggests that adult IFE cells undergo a reprogramming into embryonic hair follicle (EHFP) like fate. In addition, we showed that Wnt/β-catenin signaling is essential for BCC initiating cell reprogramming into EHFP like fate and for tumor initiation in a cell autonomous manner. Finally, we show that EHFP reprogramming occurs also in human BCCs in addition to the presence of a similar canonical Wnt activation signature to the one revealed in the SmoM2-BCC mouse model.
SCC is the second most frequent skin cancers after BCC and mutations in p53 and Ras genes has been suggested to be potentially the primary events in this tumour. SCCs present signs of squamous differentiation, suggesting that SCCs may originate from the inter follicular epidermis (IFE). To identify the cell lineage at the origin of SCC and the role of the hair follicle SCs in tumor initiation, we use a genetic tools driving oncogenic KRas (KRasG12D) expression at physiological levels in different epidermal compartments.
Targeting KRasG12D expression in bulge SCs and their progeny or in IFE results in benign tumor development with no sign of malignant transformation. In contrast, KRasG12D expression in HF Transit amplifying (TA) matrix cells do not promotes any macroscopic tumors or microscopic defects in the epidermis. Interestingly, papillomas arising from the IFE express follicular markers such as CD34 and K17, indicating that the expression of HF markers by tumor cells does not necessarily reflect their cellular origin. Using a combination of deletion of both p53 alleles together with KRasG12D expression, we showed that bulge SCs and/or their progeny but not HF matrix TA cells, promote SCC formation, suggesting that additional genetic hits such as p53 are required to promote full-blown invasive skin SCC.
In summary, our work demonstrated the non-follicular origin of BCC resulting from Smo mutation, as well as the implication of the IFE progenitors in tumor initiation. We also revealed the progressive reprogramming of BCC initiating cells towards an EHFP-like fate and the key role of Wnt/β-catenin pathway in this process. In contrast, we showed the competence of several epidermal lineages to initiate benign tumors upon expression of KRasG12D oncogene at physiological levels. We also demonstrated that lineage -specific markers expression within tumor cells does not necessarily reflect their cellular origin. Finally, we demonstrated the requirement of additional hits, such as P53 loss, to promote malignant progression in the context of oncogenic Ras.
Doctorat en Sciences biomédicales et pharmaceutiques
info:eu-repo/semantics/nonPublished
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Blat, Irene Catherine. "Functional miRNA regulation of metastatic genes promotes tumor cell dissemination in non-small cell and small cell lung carcinomas." Thesis, Massachusetts Institute of Technology, 2013. http://hdl.handle.net/1721.1/80982.
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Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2013.Cataloged from PDF version of thesis. Vita.
Includes bibliographical references.
Tumor progression, from initiation to advanced metastatic disease, requires the orchestration of a diverse group of cell-intrinsic and extrinsic factors. This multifactorial disease is promoted by an accumulation of genetic and epigenetic changes that confer selective advantage to cells and enable unrestrained proliferation, survival, motility, and self-renewal. While much emphasis over the last 35 years has been dedicated to understanding the regulators of tumor initiation, the number of cancer-related deaths worldwide continues to rise, of which the majority are attributed to metastasis. The lengthy progression to metastasis requires invasion out of the primary tumor site and into the bloodstream, survival in and exit from circulation, and colonization and expansion in a foreign environment. Developmental pathways such as the Transforming Growth Factor [beta] (TGF[beta]) signaling network are frequently dysregulated during metastatic progression due to the similarities between early embryogenesis and tumor progression. Furthermore, the TGF[beta] pathway highlights how cell-intrinsic and extrinsic signals help coordinate the complex interactions required between tumor cells, as well as those of the tumor microenvironment to achieve metastasis. Facilitating alterations to pathways such as TGF[beta] and many others are modulators of gene expression that can target multiple nodes of the signaling cascade instead of requiring genetic alterations to single genes. Moreover, in the last decade, emphasis on the role of noncoding RNAs in post-transcriptional modifications has revealed their important contribution in the regulation of developmental programs across metazoan species. More recently, the role of alterations in expression of small noncoding RNAs, microRNAs (miRNAs) has emerged as a significant contributor to disease states, including each stage of tumor progression from initiation to metastatic colonization. miRNAs hold great promise not only as biomarkers but also as potential therapeutics. For these reasons, we have characterized the role of two important examples of miRNA families - the miRNA-200 family and the miRNA-1 7~92 cluster - that regulate early stages of tumor initiation in addition to later steps of cell migration, invasion, survival, and colonization. Examination of their contribution to tumor progression in relevant in vitro and in vivo cellular contexts using genetic tools reveals they are functional contributors to tumor cell dissemination. Furthermore, modulation of their expression in the appropriate tumor microenvironments elucidates a network of targets underlying the molecular mechanisms of metastasis.
by Irene Catherine Blat.
Ph.D.
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Angus, Rachel. "The expression of major histocompatibility complex antigens by renal cell carcinomas." Thesis, University of Bristol, 1993. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.385398.
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Runge, Janine. "Evaluation of single-cell biomechanics as potential marker for oral squamous cell carcinomas: a pilot study." Doctoral thesis, Universitätsbibliothek Leipzig, 2014. http://nbn-resolving.de/urn:nbn:de:bsz:15-qucosa-155174.
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Orale Plattenepithelkarzinome stellen seit Jahrzehnten eine globale Herausforderung
im Gesundheitswesen dar. In dieser Studie wird mit dem Optical Stretcher ein
neuer diagnostischer Ansatz in der Krebserkennung der Mundhöhle untersucht und im
Rahmen einer klinischen Pilotstudie evaluiert. Dabei steht die Beurteilung der viskoelastischen
Eigenschaften von oralen Epithelzellen im Vordergrund. Eine entscheidende
Rolle spielt hierbei vor allem das Zytoskelett einer Zelle, welches aus unterschiedlichen
Faserstrukturen ein komplexes, dynamisches Gerüst bildet und für die Strukturgebung
sowie für die mechanischen Eigenschaften der unterschiedlichen Zelltypen verantwortlich
ist. In dieser Arbeit wurden diesbezüglich einzelne Zellen im Optical Stretcher ohne
direkten mechanischen Kontakt durch zwei gegenüberliegende Laserstrahlen verformt.
Dabei wurde die relative Deformation als Längenänderung entlang der Laserachse von
gedehnter zu ungedehnter Zelle definiert. Die relative Deformation dient als Vergleichsparameter
und unterliegt verschiedenen Einflussfaktoren. Schließlich erlauben das Maß
und die Art der Deformation, welche individuell für jede Zelle sind, Rückschlüsse auf
ihr biologisches Verhalten. In Kombination mit statistischen Auswertungsalgorithmen
war es möglich, signifikante Unterschiede hinsichtlich der relativen Dehnung zwischen
benignen und malignen oralen Zellen darzustellen. Die Ergebnisse zeigen, dass der
Optical Stretcher in der Lage ist, bereits minimale Veränderungen zwischen den verschiedenen
zytoskelettalen Zuständen einer Zelle zu detektieren und somit wird sich
die Dehnungsfähigkeit einer Zelle zukünftig als sensibler Zellmarker zur Dignitätsbestimmung
etablieren.
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Ribeiro, Ana Carolina Prado [UNESP]. "Estudo clínico, morfológico e imunoistoquímico de carcinomas espinocelulares em boca: análise comparativa entre pacientes jovens e idosos." Universidade Estadual Paulista (UNESP), 2008. http://hdl.handle.net/11449/91422.
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A incidência mundial de câncer em jovens tem aumentado e estudos recentes mostram que o câncer de boca também segue esta tendência. O objetivo deste trabalho foi avaliar e comparar as características clínicas, histopatológicas e imunoistoquímicas entre pacientes jovens, com idade igual ou inferior a 40 anos, e pacientes idosos, com idade igual ou superior a 65 anos, diagnosticados com carcinoma espinocelular em língua. Foram selecionados 19 casos de pacientes jovens e 19 casos de pacientes idosos e coletados dados clínicos dos prontuários. A gradação histológica foi realizada utilizando os critérios de classificação de Bryne et al (1992), na região do fronte tumoral. Também foi analisada a expressão imunoistoquímica das proteínas Bcl-2, Cerb-b2 e Ki-67. Neste estudo foi observado maior número de carcinomas espinocelulares moderadamente e pobremente diferenciados no grupo de pacientes jovens enquanto que no grupo de idosos houve maior prevalência de carcinomas bem diferenciados. Houve também no grupo de pacientes jovens um aumento do infiltrado linfoplasmocitário. A expressão imunoistoquímica das proteínas Bcl-2, Cerb-b2 e Ki-67 não mostrou diferenças significantes no fronte tumoral entre pacientes jovens e idosos. Na amostra estudada, foram detectadas diferenças morfológicas entre o grupo de pacientes jovens e idosos, no entanto, estas diferenças não foram expressas de forma significativa na análise imunoistoquímica.
The worldwide incidence of cancer in young is increasing and recent studies show that the oral cancer also follows this trend. The objective of this study was to evaluate and to compare the clinical, histopathological and immunohistochemical features between young patients, with 40 years old or less, and elderly patients, with 65 years old or a superior age, diagnosed with tongue squamous cell carcinoma. Nineteen cases of young patients and 19 cases of elderly patients were selected and clinical data were collected from medical records. The histological grading was carried out using the criteria of classification of Bryne et al (1992) in the tumoral front region. The immunohistochemical expression of the proteins Bcl-2, Cerb-b2 and Ki-67 was also analyzed. In the present study, the group of young patients presented a higher number of moderately and poor differentiated squamous cell carcinomas whereas the elderly group had a greater prevalence of well differentiated carcinomas. The group of young patients also showed an increase in the lympho-plasmacytic infiltration. The immunohistochemical expression of the proteins Bcl-2, Cerb-b2 and Ki-67 did not show significant differences in the tumoral front region between young and elderly patients. In the studied sample, morphological differences between the group of young and elderly patients were detected, however, these differences were not expressed in in the immunohistochemical analysis.
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Bitu, Carolina Cavalcante. "Análise da participação dos genes homeobox HOXA1 e HOXB7 em carcinomas espinocelulares orais." [s.n.], 2011. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288720.
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Orientador: Ricardo Della ColettaTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: Os membros da família HOX de genes homeobox são classicamente conhecidos por regular a proliferação e a diferenciação celular durante o desenvolvimento embrionário. Contudo, inúmeros estudos demonstraram uma expressão alterada de alguns membros desta família em neoplasias, incluindo melanomas, leucemias e cânceres de cólon, pulmão, rim e próstata. Estudos em nosso laboratório caracterizaram o perfil de expressão dos 39 genes da família HOX em amostras orais de tecido normal e carcinoma espinocelular (CEC), identificando alguns genes diferencialmente expressos. Dentre estes genes estavam HOXA1 e HOXB7. Interessantemente, as expressões aberrantes de HOXA1 e/ou HOXB7 em neoplasias malignas foram relacionadas a um controle da proliferação, desdiferenciação, invasão e efetividade no reparo do DNA. Os objetivos deste estudo foram compreender os efeitos da superexpressão e da neutralização dos genes HOXA1 e HOXB7 na modulação dos principais eventos biológicos associados aos fenótipos tumorais e determinar o valor prognóstico da expressão destes genes para pacientes afetados por CEC oral. Para alcançar estes objetivos, construímos clones da linhagem celular de queratinócitos normais HaCAT superexpressando os genes HOXA1 (HaCAT-HOXA1) ou HOXB7 (HaCAT-HOXB7), inibimos a expressão endógena destes genes na linhagem de CEC oral SCC-9 por meio da técnica de RNA de interferência e realizamos análise imunohistoquímica em 132 amostras de CEC oral para correlacionar às positividades de HOXA1 e HOXB7 com as características clínico-patológicas dos tumores. Nossos resultados revelaram que as superexpressões de HOXA1 e HOXB7 significantemente promoveram a proliferação das células HaCAT, enquanto que a inibição destes genes nas células SCC-9 resultou em uma dramática inibição da proliferação. As superexpressões de HOXA1 e HOXB7 não foram capazes de modular as taxas de apoptose, adesão e invasão, a expressão de marcadores da transição epitéliomesênquima (TEM) e não promoveu crescimento independente de ancoragem (softagar). Tumores classificados com expressão elevada de HOXA1 demonstraram estádio clínico T e N mais avançados, menor diferenciação das células neoplásicas e elevado potencial proliferativo. Pacientes apresentando tumores com elevada positividade para HOXA1 demonstraram uma sobrevida de 5 anos significantemente menor que pacientes com tumores demonstrando baixa positividade para HOXA1 (p=0,026). A expressão imuno-histoquímica de HOXB7 correlacionou significantemente com consumo de bebidas alcoólicas, estádio clínico N, infiltração vascular e potencial proliferativo dos tumores. Expressão elevada de HOXB7 foi também significantemente correlacionada com menor sobrevida global (p=0,009) e uma tendência para menor sobrevida livre de doença foi observada para pacientes com tumores classificados com forte expressão de HOXB7 (p=0,083). Uma positiva correlação entre as expressões de HOXA1 e HOXB7 foi evidenciada (rs=0,25 e p=0,008). Em conclusão, nossos resultados sugerem que as superexpressões dos genes HOXA1 e HOXB7 podem contribuir para a progressão tumoral por promoverem a proliferação das células tumorais e indicam que HOXA1 e HOXB7 podem ser determinantes importantes do prognóstico de pacientes com CEC oral
Abstract: HOX genes are master regulators of cellular proliferation and differentiation during embryogenesis. However, some members of the HOX family have been shown to be dysregulated in malignancies, including melanomas, leukemias and cancers of colon, lung, kidney and prostate. In previous studies we have described the expression profile of all 39 HOX genes in oral samples from normal mucosa and squamous cell carcinoma (SCC), identifying some differentially expressed. Among those were HOXA1 and HOXB7. The aberrant expression of both genes has been related with the rgulation of proliferation, differentiation and invasion, and with the control of the DNA repair effectiveness. The goals of this study were to verify the role of HOXA1 and HOXB7 on modulation of tumor-associated phenotypes and to determine whether their expressions are associated with clinicopathological features of the tumors. To achieve our goals, we generated clones from HaCAT human epithelial cell line overexpressing HOXA1 (HaCAT-HOXA1) or HOXB7 (HaCAT-HOXB7), inhibited the endogenous levels of these genes in the SCC-9 human oral carcinoma cell line by interference RNA (iRNA), and performed immunohistochemical analysis in 132 oral SCC samples. Our results demonstrated that both HOXA1 and HOXB7 overexpression in HaCAT cells promote proliferation, whereas downregulation of HOXA1 and HOXB7 endogenous levels in SCC-9 cells decreases it. HOXA1 and HOXB7 overexpression did not influence apoptosis, cellular adhesion and invasion, expression of epithelial-mesenchymal transition (EMT) markers and also did not promote anchorage-independent growth (softagar). High number of HOXA1-positive cells significantly correlated with T and N stage, tumor cellular differentiation and proliferative potential of the tumors. Patients whose tumors contained high number of HOXA1-positive cells had shorter overall survival in 5 years than patients with low positivity of this protein (p=0.026). The immunohistochemical expression of HOXB7 was significantly correlated to alcohol consumption, clinical N stage, vascular infiltration and tumor proliferative potential. High expression of HOXB7 was also significantly correlated to shorter overall survival (p=0.009), and a tendency towards shorter disease-free survival was observed in patients with tumors containing elevate HOXB7 expression (p=0.083). A positive correlation between HOXA1 and HOXB7 immunohistochemical expression was observed (rs=0.25, p<0.008). In conclusion, our results suggest that overexpression of HOXA1 and HOXB7 can contribute to tumor progression by increasing tumor cell proliferation and indicate that both HOXA1 and HOXB7 may be important determinants of OSCC patient's prognosis
Doutorado
Patologia
Doutor em Estomatopatologia
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Brachova, Pavla. "Oncomorphic Tp53 mutations in advanced serous ovarian carcinomas." Diss., University of Iowa, 2014. https://ir.uiowa.edu/etd/4581.
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The tumor suppressor gene TP53 sits at the crux of response to cellular stresses. This is the most frequently inactivated gene in human tumors, being the target of somatic mutations. The protein product of TP53 is p53, and plays a crucial role in anti-proliferative signals through the induction of apoptosis, senescence, and cell-cycle arrest when activated by stresses such as genotoxic chemotherapeutic drugs. Therefore, the status of TP53 mutation in a tumor has profound implications for the tumorigenic potential as well as the response to anti-cancer therapies. Indeed, numerous studies have shown a predictive and prognostic value of TP53 mutations to the response to chemotherapy, but just as many studies show no significant contribution of TP53 mutations to chemotherapy response. This controversy is partly due to the lack of standard methods of TP53 mutation detection, but more importantly, it is due to the categorization of all TP53 mutations into one group. Certain mutations in TP53 can confer a mutant p53 with new, gained activities, not normally present in the WT p53 protein. These have been commonly called "gain of function" (GOF) p53 proteins, and some GOF p53 proteins can even confer oncogenic properties. However, not all gained functions are necessarily implicated in oncogenicity. Using stringent criteria, we have defined a select group of GOF TP53 mutations that do function as oncogenic proteins as oncomorphic TP53 mutations. In this work, we utilize data available from a large patient population through The Cancer Genome Atlas (TCGA) as well as data available from the University of Iowa Gynecologic Oncology Tumor Bank to examine the association of oncomorphic TP53 mutations with patient outcome using advanced serous ovarian cancer as a model. We demonstrate that oncomorphic TP53 mutations are associated with worse progression-free survival, chemoresistance, and higher rates of recurrence than other mutations in TP53 that have no evidence of oncomorphic abilities. We identify molecular alterations in patients with oncomorphic TP53 mutations, particularly the increased expression of β-catenin. We also observe that oncomorphic p53 proteins lose the normal protein:protein interactions with the microRNA microprocessing complex, implicating the role of dysregulated miRNAs in pathways associated with chemoresistance. The cumulative results from our studies provide human evidence for the consideration of different classes of TP53 mutations. Patients with oncomorphic TP53 mutations deserve careful follow-up therapy and may require novel treatment regimens to improve outcomes. We propose that stratification of patients should be considered based upon the individual TP53 mutation identified from their tumors.
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Janes, Samuel McAlpine. "Integrin regulated differentiation and apoptosis in normal keratinocytes and squamous cell carcinomas." Thesis, University College London (University of London), 2003. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.409093.
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Högmo, Anders. "Squamous cell carcinomas and preneoplastic lesions of the oral cavity : biological factors and prognosis /." Stockholm, 1999. http://diss.kib.ki.se/1999/91-628-3370-7/.
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Graflund, Marianne. "Prognostic factors in early stage cervical carcinomas treated with Wertheim-Meigs surgery /." Linköping : Univ, 2002. http://www.bibl.liu.se/liupubl/disp/disp2002/med732s.pdf.
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Lima, Jacqueline Silva Brito. "Expressão de fatores de proliferação e antiapoptóticos em carcinomas basocelulares." Botucatu, 2016. http://hdl.handle.net/11449/148646.
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Orientador: Hélio Amante MiotCoorientador: Mariângela Esther Alencar Marques
Resumo: O carcinoma basocelular (CBC) é a neoplasia maligna mais comum entre os homens e sua incidência está aumentando em nosso meio. Pode se manifestar como lesão nodular, superficial, esclerodermiforme, micronodular e fibroepitelioma de Pinkus. O CBC é um carcinoma de baixa mortalidade, porém com elevada morbidade devido ao potencial destrutivo local e às elevadas taxas de reincidência. As diferenças evolutivas dos diversos tipos de carcinomas basocelulares não são bem definidas. A análise de fatores de proliferação e apoptose pode subsidiar o conhecimento sobre a fisiopatologia e as diferenças evolutivas dessas lesões. A literatura revela a escassez de investigações sobre a expressão diferencial de fatores de proliferação (Ki-67) e relacionados à apoptose (p53, survivina e NF-kB-p105) dos diferentes subtipos de carcinomas basocelulares e ainda tumores recidivados. O objetivo desse estudo é avaliar a expressão de marcadores de proliferação celular e apoptose em carcinomas basocelulares dos tipos nodular, superficial, esclerodermiforme e tumores recidivados. Foram selecionados subtipos histológicos únicos, como forma de tentar compreender o comportamento dos CBCs individualmente. As lâminas desses espécimes foram submetidas ao protocolo de marcação imuno-histoquímica. Foram estudadas 100 amostras, sendo 50 unidades de epiderme normal e as demais distribuídas entre cada subtipo tumoral. O padrão de marcação de cada marcador sobre os diferentes tipos de tecidos foi avaliado a partir ... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Basal cell carcinoma (BCC) is the most common malignant neoplasm among men and its incidence is increasing in our country. It can manifest as nodular, superficial, sclerodermiform, micronodular and Pinkus fibroepithelioma lesions. BCC is a lowmortality carcinoma, but with high morbidity due to local destructive potential and high rates of recurrence. The evolutionary differences of the various types of basal cell carcinomas are not well defined. The analysis of proliferation and apoptosis factors may support knowledge about the pathophysiology and evolutionary differences of these lesions. The literature reveals the scarcity of investigations on the differential expression of proliferation factors (Ki-67) and related apoptosis (p53, survivin and NF-kB-p105) of the different subtypes of basal cell carcinomas and recurrent tumors. The aim of this study is to evaluate the expression of markers of cell proliferation and apoptosis in basal cell carcinomas of the nodular, superficial, sclerodermiform and recurrent tumors. Unique histological subtypes were selected as a way to attempt to understand the behavior of individual BCCs. The slides of these specimens were submitted to the immunohistochemical labeling protocol. A total of 100 samples were studied, being 50 normal epidermal units and the others distributed between each tumor subtype. The marking pattern of each marker on the different tissue types was evaluated from generalized linear models (GLMs) followed by Sidak post-hoc test, when necessary. Statiscally significant differences (p<0,01) in the immunostaining of different tissue types were found for the Ki-67, p53 and survivin markers, but not for the p105 marker (p=0,21). The Ki-67 marker was more expressed in sclerodermiform than in epidermal and nodular cells. Immunoblotting of p53 was less expressed in the epidermis than in superficial subtypes and relapses, and also less expressed in... (Complete abstract click electronic access below)
Doutor
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Ylipalosaari, M. (Merja). "Matrix metalloproteinases (MMPs) in oral carcinomas." Doctoral thesis, University of Oulu, 2005. http://urn.fi/urn:isbn:9514277309.
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Abstract
Matrix metalloproteinases, MMPs, are a family of enzymes capable of modulating connective tissue components. The expression of several MMPs is increased in oral squamous cell carcinomas (OSCCs). They are assumed to have an important role in the development and progression of OSCCs. However, the exact role and mechanism of the regulation of MMPs in malignant transformation are still largely unknown.
In this study, tumour-associated trypsin-2 (TAT-2) was detected in OSCC tissue sections, and its role in MMP-2 and -9 regulation in carcinoma cells was evaluated. The TAT-2 gene was transfected into two different OSCC cell lines and one immortalized oral epithelial cell line. In TAT-2-transfected cells, MMP-9 activation increased OSCC cell invasion in chicken chorionallantoic membrane assay. Increased intravasation was prevented by tumour-associated trypsin inhibitor or specific gelatinase-inhibiting CTT-peptide. TAT-2 also converted MMP-1, -8, -13 and -3 into smaller molecular weight forms in vitro. However, TAT-2-transfected OSCC cells showed no conversion. TAT-2 was demonstrated to degrade powerfully type I collagen into small fragments in vitro. The cell surface receptor αvβ6 integrin is strongly up-regulated in OSCCs. By using β6-transfected OSCC cells, it was demonstrated that αvβ6 integrin down-regulates MMP-13 expression. However, this integrin did not regulate other collagenases or TIMP-1. β6-transfected cells invaded more efficiently through the basement membrane matrix, but their migration through type I collagen remained unchanged. MMP-8 expression was detected for the first time in head and neck squamous cell carcinoma (HNSCC) cell lines and corresponding cultured dermal and tumour fibroblasts. The localization of MMP-8 in HNSCC was determined by immunohistochemical stainings and in situ hybridization. MMP-8 production levels in carcinoma cells were faint and sporadic in HNSCCs sections. Ninety-two primary mobile tongue SCCs were subjected to MMP-8 immunohistochemical staining, and the staining results were compared to survival rates. MMP-8 was associated with improved disease-free survival in females but not in males.
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Napier, Seamus Stephen Mary. "Histopathological predictors of behaviour of potentially malignant lesions of the oral mucosa." Thesis, Queen's University Belfast, 2000. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.326288.
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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.
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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.
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Lima, Jacqueline Silva Brito [UNESP]. "Expressão de fatores de proliferação e antiapoptóticos em carcinomas basocelulares." Universidade Estadual Paulista (UNESP), 2016. http://hdl.handle.net/11449/148646.
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O carcinoma basocelular (CBC) é a neoplasia maligna mais comum entre os homens e sua incidência está aumentando em nosso meio. Pode se manifestar como lesão nodular, superficial, esclerodermiforme, micronodular e fibroepitelioma de Pinkus. O CBC é um carcinoma de baixa mortalidade, porém com elevada morbidade devido ao potencial destrutivo local e às elevadas taxas de reincidência. As diferenças evolutivas dos diversos tipos de carcinomas basocelulares não são bem definidas. A análise de fatores de proliferação e apoptose pode subsidiar o conhecimento sobre a fisiopatologia e as diferenças evolutivas dessas lesões. A literatura revela a escassez de investigações sobre a expressão diferencial de fatores de proliferação (Ki-67) e relacionados à apoptose (p53, survivina e NF-kB-p105) dos diferentes subtipos de carcinomas basocelulares e ainda tumores recidivados. O objetivo desse estudo é avaliar a expressão de marcadores de proliferação celular e apoptose em carcinomas basocelulares dos tipos nodular, superficial, esclerodermiforme e tumores recidivados. Foram selecionados subtipos histológicos únicos, como forma de tentar compreender o comportamento dos CBCs individualmente. As lâminas desses espécimes foram submetidas ao protocolo de marcação imuno-histoquímica. Foram estudadas 100 amostras, sendo 50 unidades de epiderme normal e as demais distribuídas entre cada subtipo tumoral. O padrão de marcação de cada marcador sobre os diferentes tipos de tecidos foi avaliado a partir de modelos lineares generalizados (GLMs) seguidos de teste post-hoc de Sidak, quando necessário. Foram encontradas diferenças estatisticamente significativas (p<0,01) na imunomarcação de diferentes tipos de tecidos para os marcadores Ki-67, p53 e survivina, mas não para o marcador p105 (p=0,21). O marcador Ki-67 foi mais expresso nos esclerodermiformes que em células da epiderme e nos nodulares. A imunomarcação do p53 foi menos expressa na epiderme que nos subtipos superficiais e nas recidivas, e também menos expressa nos esclerodermiformes que em todos os outros subtipos tumorais. A survivina mostrou uma imunomarcação maior na epiderme em relação aos subtipos tumorais estudados. A comparação entre os diferentes marcadores foi avaliada pelo cieficiente de correlação de Spearman, que detectou uma correlação estatisticamente significativa (p<0,01) entre os marcadores, Ki-67 e p53 na imunomarcação dos subtipos estudados e de células da epiderme, e uma correlação entre Ki-67 e survivina quando consideramos apenas as células tumorais. Neste estudo, a expressão simultânea de marcadores permitiu a identificação de padrões de proliferação e apoptose que individualizaram comportamentos em subtipos de CBCs, em consonância com formas recidivadas, e de forma independente na epiderme. Houve diferentes padrões de correlação entre a expressão dos marcadores dos CBCs e da epiderme.
Basal cell carcinoma (BCC) is the most common malignant neoplasm among men and its incidence is increasing in our country. It can manifest as nodular, superficial, sclerodermiform, micronodular and Pinkus fibroepithelioma lesions. BCC is a low-mortality carcinoma, but with high morbidity due to local destructive potential and high rates of recurrence. The evolutionary differences of the various types of basal cell carcinomas are not well defined. The analysis of proliferation and apoptosis factors may support knowledge about the pathophysiology and evolutionary differences of these lesions. The literature reveals the scarcity of investigations on the differential expression of proliferation factors (Ki-67) and related apoptosis (p53, survivin and NF-kB-p105) of the different subtypes of basal cell carcinomas and recurrent tumors. The aim of this study is to evaluate the expression of markers of cell proliferation and apoptosis in basal cell carcinomas of the nodular, superficial, sclerodermiform and recurrent tumors. Unique histological subtypes were selected as a way to attempt to understand the behavior of individual BCCs. The slides of these specimens were submitted to the immunohistochemical labeling protocol. A total of 100 samples were studied, being 50 normal epidermal units and the others distributed between each tumor subtype. The marking pattern of each marker on the different tissue types was evaluated from generalized linear models (GLMs) followed by Sidak post-hoc test, when necessary. Statiscally significant differences (p<0,01) in the immunostaining of different tissue types were found for the Ki-67, p53 and survivin markers, but not for the p105 marker (p=0,21). The Ki-67 marker was more expressed in sclerodermiform than in epidermal and nodular cells. Immunoblotting of p53 was less expressed in the epidermis than in superficial subtypes and relapses, and also less expressed in sclerodermiform than in all other tumor subtypes. Survivin showed a greater immunostaining in the epidermis with respect to the tumor subtypes studied. The comparison between the diferent markers was evaluated by the Spearman correlation coefficient, which detected a statistically significant correlation (p<0,01) between the markers, Ki-67 and p53 in the immunoblotting of the studied subtypes and epidermal cells, and one correlation between Ki-67 and survivin when we considered only tumor cells. In this study, the simultaneous expression of markers allowed the identification of patterns of proliferation and apoptosis that individualized behaviors in subtypes of BCCs, in consonance with relapsed forms, and independently in the epidermis. There were different patterns of correlation between the expression of BCC and epidermal markers.
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Santos, Mariana Rates Gonzaga. "Células T regulatórias e sua associação com a angiogênese em carcinomas espinocelulares de boca." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/25/25150/tde-14082013-101313/.
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As células T regulatórias (Tregs) suprimem a população de células T efetoras e podem capacitar células tumorais a evadir a resposta imune do hospedeiro. Além disso, estas células têm sido correlacionadas com angiogênese em alguns tipos de câncer. O objetivo deste estudo foi avaliar a frequência de células Tregs e sua correlação com angiogênese em carcinomas espinocelulares (CEC) de boca. Amostras de um total de 61 pacientes com CEC de boca, localizados no lábio e na língua e assoalho bucal obtidos dos Departamentos de Patologia dos Hospitais de Base e Estadual da cidade de Bauru, São Paulo, Brasil, no período de 2005 a 2012 foram analisados quanto às características clínicas e demográficas. Avaliou-se também, o índice histopatológico de malignidade e a expressão imunoistoquímica de células Tregs (FOXP-3), densidade microvascular intratumoral (MVD) e VEGF-A. A associação da marcação do anticorpo anti-FOXP-3 e as variáveis clínicas e microscópicas foram avaliadas através do teste qui quadrado. A análise estatística da expressão dos marcadores entre CECs de lábio e CECs de Língua e assoalho bucal foi realizada através do teste t. As correlações entre a frequência de células Treg e MVD, células Tregs e VEGF-A, foram obtidas através do coeficiente de correlação de Pearson, bem como a correlação entre MVD e VEGF-A. Não houve associação da expressão de FOXP-3 com as características clínicas, demográficas e índice de malignidade tumoral. Foram observados valores similares da frequência de células Tregs, índices de MVD e expressão de VEGF-A em CECs de lábio e CECs de língua e assoalho bucal. Uma correlação positiva entre a frequência de células Tregs e a MVD foi observada, embora não estatisticamente significativa (P-valor=0,682). Além disso, uma correlação positiva estatisticamente significativa foi detectada entre a frequência de células Tregs e a expressão de VEGF-A (P-valor=0,029). Não foi observada correlação entre a MVD e a expressão de VEGF-A. Estes resultados sugerem que embora exista uma associação entre a frequência de células Tregs e a angiogênese em CECs de boca, a expressão de FOXP-3 parece não estar associada ao desenvolvimento tumoral.Regulatory T (Treg) cells suppress effector T-cell populations and can enable tumor cells to evade the host immune response. Moreover, Tregs cells have been correlated with angiogenesis in certain types of cancers. The aim of this study was to evaluate the frequency of Treg cells and its correlation with angiogenesis in oral squamous cell carcinomas (OSCC), as well as its implication on growth and tumor aggressiveness. Samples from a total of 61 patients with OSCC, located on the lip and tongue and floor of the mouth were analyzed for clinical and demographic characteristics. The histopathological malignancy index and immunoexpression of Treg cells (FOXP-3), IMD (CD105) and VEGF-A were also evaluated. The association of FOXP-3 expression and the clinical and microscopic changes were evaluated using the chi square test. Statistical analysis of the expression of markers between SCCs lip and SCCs of the tongue and floor of the mouth was performed using the t test. Pearsons rank correlation was performed to evaluate the correlation between the frequencies of both, Tregs cells and VEGF-A expression and Tregs cells and IMD determinations, as well as between VEGF-A expression and IMD values. There was no association of FOXP-3 expression with clinical and demographic characteristics, and tumor malignancy index. Similar values were observed for the frequency of Treg cells, IMD values and VEGF-A expression in OSCCs of the lip and tongue and floor of mouth. A positive correlation between FOXP-3 expression with IMD values was also detected, however, statistically that was non-significant (P-value=0.682). Furthermore, a significant positive correlation was observed between the frequency of tumor-infiltrating Tregs with VEGF-A expression (P-value=0.029). No correlation was observed between IMD values and with VEGF-A expression. These results suggest that although there is an association between the frequency of Treg cells and angiogenesis in OSCC, FOXP-3 expression was not associated with increased tumor aggressiveness.
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Sawazaki-Calone, Iris 1984. "O valor prognóstico dos sistemas de gradação histopatológica em carcinomas espinocelulares orais = The prognostic value of histopathological grading systems in oral squamous cell carcinomas." [s.n.], 2014. http://repositorio.unicamp.br/jspui/handle/REPOSIP/288735.
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Orientadores: Ricardo Della Coletta, Ana Lucia Carrinho Ayroza RangelTese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba
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Resumo: O carcinoma espinocelular (CEC) representa cerca de 95% de todas as neoplasias malignas que acometem a cavidade oral. Rotineiramente o tratamento e prognóstico desta doença são baseados na localização do tumor e no sistema TNM de classificação dos tumores malignos, no entanto há uma grande variação no comportamento biológico entre tumores no mesmo sítio e dentro do mesmo estadio clínico. Diante deste problema, vários sistemas de gradação histopatológica foram propostos para determinar o prognóstico e o plano do tratamento de pacientes com carcinoma espinocelular (CEC) oral. Este estudo avaliou quatro sistemas de gradação histopatológica ¿ (1) sistema OMS (Organização Mundial de Saúde), (2) sistema MG (gradação de malignidade de margens invasivas profundas), (3) modelo HR (modelo de risco histológico) e (4) escore de risco BD (ninho de células tumorais e profundidade de invasão) ¿ e comparou com dados clínico-patológicos e sobrevida em uma amostra de 113 pacientes com CEC oral primário, excluindo lábios. Os critérios de inclusão foram: pacientes diagnosticados e tratados entre 1998 e 2008, dados clínicos e demográficos completos, tratamento baseado em cirurgia radical com ou sem radioterapia e/ou quimioterapia pós-operatória e disponibilidade de todos os blocos de parafina. Associações significativas com sobrevida na análise univariada foram observadas com todos os sistemas de gradação histopatológica, excetuando o sistema MG. No entanto, aplicando a análise multivariada de COX, apenas o escore de risco BD foi significativamente associado com sobrevida livre de doença como um marcador prognóstico independente. A idade (>56 anos), o tamanho do tumor (estágio T3/T4) e a presença de metástase regional (estágio N+) foram também apontados como marcadores independentes da sobrevida dos pacientes. Nenhuma correlação clara entre os quatro sistemas de gradação foi observada aplicando o teste de correlação de Spearman. Os resultados do presente estudo revelaram uma associação significativa entre o escore de risco BD e a evolução clínica dos pacientes com CEC oral, reforçando a importância deste novo sistema de gradação histopatológica como possível ferramenta prognóstica no pós-operatório
Abstract: Squamous cell carcinoma (SCC) represents almost 95% of all malignant tumors that affect the oral cavity. Routinely the treatment and prognosis of this disease are based on its location and in the TNM classification of malignant tumors, however there is a great variation in the biological behavior among tumors at same location and clinical stage. In the view of those difficulties, several histopathological grading systems were proposed in order to determine the prognostic and the treatment plan of patients with oral squamous cell carcinoma (OSCC). This study evaluated four histopathological grading systems ¿ (1) WHO (World Health Organization) system, (2) MG (malignancy grading of the deep invasive margins) system, (3) HR (histological risk ) model and (4) BD (tumor budding and depth of tumor invasion) risk score ¿ and compared with clinicopathological data and survival in a sample of 113 patients with primary OSCC, excluding lips. The inclusion criteria included who were diagnosed and treated from 1998 to 2008, complete demographic and clinical data, treatment based on radical surgery with or without postoperative radiotherapy and/or chemotherapy, and availability of all paraffin-embedded blocks. Significant associations with survival were observed for all histopathological grading systems, with exception of the MG system. However, when multivariate regression analysis was applied, only BD risk score was significantly associated with disease-free survival as an independent prognostic marker. Age (>56 years), tumor size (T3/T4 stage) and presence of regional metastasis (N+ stage) were also independent markers of reduced survival. No clear correlation between the four grading systems was observed applying the Spearman¿s rank test. The results of the present study revealed a significant association between BD risk score and outcome of OSCC patients, reinforcing the importance of this new histopathological grading system as a possible postoperative prognostic tool
Doutorado
Patologia
Doutora em Estomatopatologia
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Shankar, Athiva. "Epidemiological and molecular insights into Human Papillomavirus-related head and neck squamous cell carcinomas." Thesis, University of Dundee, 2016. https://discovery.dundee.ac.uk/en/studentTheses/dfd76e62-d92e-4e51-90b3-dacd1f6e34b0.
Full textAbstract:
Over the last decade, Scotland has witnessed a rising incidence in squamous cell carcinomas of the head and neck (HNSCC), a phenomenon thought to be linked to infection with high-risk Human Papillomavirus (HPV). HPV-associated HNSCC are a distinct disease presenting unique epidemiological, biological and clinical challenges. However, establishing HPV-related disease is impaired by non-standardised testing protocols and lack of a consensus on the efficacy of existing biomarkers such as p16. This is further complicated by the absence of additional biological markers and a dearth in our understanding of the molecular mechanisms underlying HPV-driven tumourigenesis. While HPV positivity is more commonly detected in the oropharynx, its prevalence and clinical impact in other head and neck subsites remains largely unexplored. The research presented in this thesis was undertaken to determine the prevalence of high-risk HPV in a heterogeneous cohort of 293 HNSCC patients from Tayside and to evaluate the validity of EBP50, a scaffolding protein involved in cell polarity which is targeted by high-risk HPV, as a potential marker for HPV-driven HNSCC. The p16 status of the patients in the cohort was already known and tissue specimens were genotyped for HPV using PCR. HPV infection, defined as p16 positivity and a positive HPV DNA status, was identified in 14% of the cohort. The majority (83%) of the HPV-positive tumours involved the oropharynx while the oral cavity, pharynx and the nasal cavity (17%) were involved to a much smaller extent. High-risk HPV type 16 was the most prevalent HPV type. Patients with HPV-positive tumours had significantly improved overall survival (OS) (2 year OS, 77% vs 57%) and recurrence free survival rates (RFS) (2 year RFS, 92% vs 77%) compared to patients with HPV-negative tumours. A positive tumour HPV status was found to be an independent prognostic indicator (HR 0.216; 95% CI 0.06 – 0.771) and so, given the high morbidity and debilitating physical and psychological problems associated with prevailing aggressive treatment regimens, it is imperative that this knowledge is harnessed to develop and improve treatment strategies. EBP50 expression was evaluated, by immunohistochemical analysis, first in normal oral mucosa and followed up in a smaller subset of 156 HNSCC patients from the main cohort. In the normal tissue EBP50 expression was predominantly membranous. In the tumour samples four distinct EBP50 expression patterns were observed and, of these, weak/ negligible cytoplasmic EBP50 expression showed a strong correlation, only marginally lower than p16 overexpression, with HPV DNA status and was observed largely in patients with tumours of the oropharynx and no history of smoking. Absence of EBP50 expression in the plasma membranes of tumour cells was a recurring pattern in a majority of the tumour samples. The scale of this study, comprising a Tayside cohort of unprecedented size, will undoubtedly contribute to the existing knowledge of HPV incidence in head and neck cancer in Scotland. Furthermore, this study presents compelling preliminary evidence for further researching weak/negligible cytoplasmic EBP50 expression as being a potential indicator of HPV-positivity in HNSCC.
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Bhattacharya, P. "Oral squamous cell carcinomas and their genetic variants in association with extra capsular spread." Thesis, University of Liverpool, 2018. http://livrepository.liverpool.ac.uk/3016284/.
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Oral squamous cell carcinoma (OSCC) is the sixth most common cancer worldwide with an incidence of ~600,000 cases per year and younger age groups, particularly between 40-69 years, are increasingly becoming affected. OSCC has an overall five-year survival of only ~30% when metastatic disease is present. The most adverse prognostic clinical predictor for OSCC is extracapsular spread (ECS) from lymph node metastasis. The molecular determinants of ECS are undetermined and their characterization could significantly assist patient management, identifying those having increased risk and suggesting new possibilities for therapy. The aim of this study was to identify genetic variants associated with ECS. Previous work using aCGH had found an unexpectedly low frequency of TP53 alteration in OSCCs from a local cohort enriched for cases with ECS. SNP genotyping was therefore used to further investigate allelic imbalance of TP53 and for comparison CCND1 in primary tumour samples from the series (n=46; 19 node negative [N-], 7 [N+ECS-], 20 [N+ECS-]). CCND1 gain and TP53 loss were found to be associated with nodal status but not ECS. Five OSCC primary tumour cell lines (2 N- & 3 N+ECS+) were then screened by whole genome sequencing for genetic variants that may be associated with ECS. Variants were found in a broad range of genes but poor coverage (< 5 fold mean coverage) from some regions of the genome, in particular NOTCH1, suggested that there may have been technical limitations. However, pathway analysis implicated the NOTCH pathway may have had significance, consistent with literature reports. Additional next generation sequencing assays targeting NOTCH1 were therefore developed and used to analyze the gene in these cell lines. High coverage (150-200 fold mean coverage) of NOTCH1 sequences were achieved and in one of the ECS+ve cell lines (Liv7K), a rare, potentially deleterious nonsynonymous polymorphism (rs61751543) was found. Further screening for NOTCH1 and TP53 genetic variants associated with ECS was therefore performed for primary tumour samples (n=50; 21[N-], 11 [N+ECS-], 18 [N+ECS-]). Sanger resequencing was used for independent confirmation of candidate variants identified. Poorly covered samples (n=10) were excluded. 7/40 (17.5%) samples showed NOTCH1 variants, with 6/14 (43%) ECS+ samples confirmed to have NOTCH1 variants, compared to 1/26 (3.8%) ECS-, Fisher’s exact test p =0.0044. None of these samples displayed variants in TP53. Using this approach, comparing the frequency of the variants to node status, we produced evidence for a unique subset of ECS positive OSCC cases characterized by having disruption of NOTCH1 and absence of TP53 alteration. The NOTCH1 variants were clustered within the region for the extracellular domain (ECD), suggesting that intercellular communication and response could be disrupted. Further functional studies using an ECS +ve primary OSCC cell line as well as invasive and noninvasive controls, showed invasive cell lines demonstrated decreased cell growth and migration in response to Notch inhibition by DAPT (25 μM) treatment, with western blotting revealing absence of Notch1 and 3 after week three and Notch4 by week four only in Liv7K. These findings suggested the importance of further functional studies to assess the effect of Notch inhibition on markers of aggressive phenotype. Taken together our observations overall pave the way to future studies exploring the downstream effects of NOTCH1 ECD mutations and their potential role in OSCC.
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Acay, Renata Rodrigues. "\"Detecção do HPV em leucoplasias e carcinomas epidermóides orais\"." Universidade de São Paulo, 2007. http://www.teses.usp.br/teses/disponiveis/23/23141/tde-13032007-094038/.
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É ainda bastante controverso na literatura se o HPV pode ou não ser considerado fator etiológico ou de risco para o desenvolvimento de lesões malignas/malignizantes em boca. Já há um consenso de que existe evidência ao menos numérica da relação entre HPV e carcinogênese oral, pois em geral os estudos encontram uma relação de proporção entre grau de malignidade e infecção por HPV ? os índices de HPV encontrados em carcinoma epidermóide oral são maiores do que os encontrados em lesões potencialmente malignas, que por sua vez são maiores do que os encontrados em mucosa normal. Sabe-se, porém, que as lesões potencialmente malignas podem apresentar variados graus de displasia epitelial, o que não permite analisá-las como um grupo. Assim, nesse contexto, o objetivo desse estudo foi analisar mais refinadamente a relação entre grau de malignidade e infecção por HPV através da detecção de DNA do vírus em leucoplasias e carcinomas epidermóides orais, desmembrando-se o grupo das lesões potencialmente malignas de acordo com o grau de displasia epitelial. Foram selecionados 50 casos diagnosticados como leucoplasia e carcinoma epidermóide orais, os quais foram divididos em 5 grupos: leucoplasia sem displasia, leucoplasia com displasia discreta, leucoplasia com displasia moderada, leucoplasia com displasia intensa e carcinoma epidermóide. Dados clínicos como idade e sexo do paciente e sítio da lesão foram observados e a presença de DNA de HPV foi pesquisada através do método CSA-ISH com sonda de amplo espectro. Nos casos positivos para a sonda de amplo espectro foi realizada a genotipagem com sondas específicas para HPV dos tipos 6/11, 16/18 e 31/33. A prevalência de infecção por HPV foi de 24%, notadamente maior que a reportada em mucosa normal, que é de 1 a 2%. Os resultados mostraram uma discreta relação de proporção entre grau de malignidade e os índices encontrados em leucoplasia sem displasia, leucoplasia com displasia e carcinoma epidermóide, porém sem significância estatística. Desmembrando-se o grupo das leucoplasias com displasia, essa proporcionalidade não foi observada entre os grupos. Na genotipagem, a maior positividade foi para a sonda dos tipos 16/18, de alto potencial oncogênico, e a positividade para a sonda 6/11 só foi encontrada nos grupos de menor grau de malignidade. Apenas um caso mostrou positividade para duas sondas (16/18 e 31/33). Não houve correlação significante entre nenhuma característica clínica e infecção por HPV. Os resultados sugerem portanto que a detecção do HPV não está relacionada com o grau de malignidade das lesões, haja visto a ausência de proporcionalidade entre os índices de detecção do vírus nos grupos analisados. Entretanto, o fato de que a prevalência em nossa casuística, constituída por lesões malignas/malignizantes, foi maior do que àquela encontrada em mucosa normal e que os tipos de alto risco foram os mais prevalentes dentre os casos positivos não nos permite descartar o HPV como fator de risco para a carcinogênese oral.It is still highly controversial whether HPV can be considered an aetiological or risk factor for the development of malignant/premalignant lesions of the oral cavity. There is an agreement that there is at least quantitative evidence to relate HPV and oral carcinogenesis, since in general the studies find a proportional relation between degree of malignancy and HPV infection ? the prevalence of HPV in squamous cell carcinoma is higher than in premalignant lesions which is higher than in normal mucosa. It is known, however, that premalignant lesions can present several degrees of epithelial dysplasia, which does not allow analyzing them as a group. Hence, in this context, the aim of this study was to analyze more refinedly the relation between degree of malignancy and infection by HPV by means of viral DNA detection in oral leucoplakias and oral squamous cell carcinomas, dividing the group of premalignant lesions according to the degree of epithelial dysplasia within the lesion. Fifty cases diagnosed as oral leucoplakia and oral squamous cell carcinoma were selected and divided into 5 groups: leucoplakia with no dysplasia, leucoplakia with mild dysplasia, leucoplakia with moderate dysplasia, leucoplakia with severe dysplasia and squamous cell carcinoma. Clinical data regarding patients? age and gender and anatomic site of the lesion were observed and the presence of HPV DNA was assessed using CSA-ISH method with a wide spectrum probe. In positive cases to the wide spectrum probe, genotyping with specific probes to HPV types 6/11, 16/18 and 31/33 was performed. The overall prevalence of HPV infection was 24%, which is higher than the reported for oral normal mucosa, which stands around 1 and 2%. Results show a discrete proportional relation between degree of malignancy and HPV infection indexes found in leucoplakia with no dysplasia, leucoplakia with dysplasia and squamous cell carcinoma, but with no statistical significance. Dividing the group of leucoplakia with dysplasia, this relation of proportion was not observed. In genotyping, most cases were positive to the probe for types 16/18, of high oncogenic potential, and cases positive to the probe for types 6/11, of low oncogenic potential, were only found within groups of lower degrees of malignancy. Only one case was positive for two specific probes (16/18 and 31/33). There was no correlation between clinical features and HPV infection. These results suggest that HPV detection is not related to the degree of malignancy in these lesions. Nevertheless, the fact that the prevalence in these cases, which were all malignant/premalignant lesions, was higher than the one found in oral normal mucosa, and that the high-risk types of HPV were the most frequently found within the positive cases does not allow excluding HPV as a risk factor in oral carcinogenesis.
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Salo, S. (Sirpa). "Laminin-5:function of the γ2 chain in epithelial cell adhesion and migration, and expression in epithelial cells and carcinomas." Doctoral thesis, University of Oulu, 1999. http://urn.fi/urn:isbn:9514253426.
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Abstract
Laminins are basement membrane glycoproteins consisting of
three polypeptide chains α, β and γ.
Until now 12 members of the protein family have been characterized
and all isoforms have an αβγ chain composition,
but they assemble in varying combinations of chain variants. The
functional properties of laminins include cell adhesion, proliferation,
differentiation, growth and migration. Laminin-5 has a chain composition
of α3β3γ2 with the distribution mainly
restricted to epithelial basement membranes, where its biological
functions involve anchorage and locomotion of cells. The importance
of this protein for the attachment of basal keratinocytes is clearly
demonstrated by the fact that all genes encoding its chains have
been shown to be mutated in the severe skin blistering disease
Epidermolysis bullosa junctionalis.
The present study focused on investigations of the role of
the laminin-5 isoform and particularly its γ2 chain in
cell adhesion and migration. The role of the short arm of the laminin γ2
chain in the process of epithelial cell attachment is to serve
as a kind of a bridging molecule to the extracellular environment,
because it does not have any cell binding activity by itself. It
was also shown that the newly synthesized γ2 chain participates
in the complex process of cell migration, probably as one of the
first attachment components for moving cells. Thus, as a migration
and differentiation-associated molecule, laminin-5 was considered
a potential marker for detection of malignant processes where cell
movement plays a role. Subsequently it was shown that the γ2
chain is expressed not only in a restricted manner in human epithelial
tissues, but also in a number of human epithelium-derived cancers.
In some carcinomas, expression of the γ2 chain appeared
to be a characteristic of cancer cells with invasive properties.
Examination of over 50 dysplasias and cervical tumors revealed
that γ2 chain antibodies were able to distinguish between
lesions with or without invasive capacity. This is the first systematic
study of epithelial cancers where γ2 chain antibodies
have been shown to be a useful marker in the histopathological
diagnostics. In addition, this study showed in a mouse tumor model
that the γ2 chain of laminin-5 has a potential for being
of use for in vivo tumor imaging.
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Iannacone, Michelle R. "Case-Control Study of Sunlight Exposure and Cutaneous Human Papillomavirus Seroreactivity in Basal Cell and Squamous Cell Carcinomas of the Skin." Scholar Commons, 2011. http://scholarcommons.usf.edu/etd/3164.
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Non-melanoma skin cancer (NMSC), comprised of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC), is the most common cancer in Caucasians. Ultraviolet radiation (UVR) exposure is the most important environmental risk factor for both BCC and SCC development. However, the precise relationship between UVR and the risk of NMSC is complex, and the relationship may differ by skin cancer type. It has been hypothesized that intermittent patterns and childhood sunlight exposure are important for BCC while continuous (chronic) and lifelong (i.e. childhood and adulthood) sunlight exposure is important for SCC. Epidemiologic studies have demonstrated that cutaneous human papillomavirus (HPV) infection may also be a risk factor for developing NMSC. However, the pathway by which cutaneous HPV is associated with NMSC remains unclear. It is hypothesized that UVR exposure may interact synergistically with cutaneous HPV in NMSC development.
The goal of the research study was to evaluate the relationship between levels of sunlight exposure and BCC and SCC and to investigate differences in sunlight-associated BCC and SCC risk by genus-specific cutaneous HPV serostatus. To address these goals, we conducted a clinic based case-control study of histologically confirmed BCC and SCC cases recruited from a university dermatology clinic and controls with no history of cancer and screened negative for current skin cancer. Logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI) for the associations between measures of sunlight exposure and BCC and SCC. Multiplicative interactions were tested by placing an interaction term for the product of genus-specific HPV seroreactivity and sunlight related factors in the logistic regression models.
Measures of both intermittent and continuous patterns of sunlight exposure were associated with both types of skin cancer (i.e. BCC and SCC). Specifically, history of blistering sunburn (a marker of intermittent sunlight exposure) and occupational sunlight exposure (i.e. having a job in the sun for at least 3 months for >10 years) were both associated with BCC and SCC. The major differences in patterns of sunlight exposure between BCC and SCC were observed for sunlight exposure in one's thirties. Additionally, sunlight exposure in one's twenties was associated with SCC, regardless of pattern of exposure; similar associations were not observed for BCC. Measures of timing of sunlight exposure consistently demonstrated that childhood/adolescent sunlight exposure was more important for SCC than BCC. These included number of moles on the forearms and entire body (measure of increased childhood sunlight exposure), and younger age at first and tanning bed use. Younger age at first blistering sunburn was statistically significantly associated with both BCC and SCC.
NMSC cases were more likely to be seropositive for cutaneous HPV antibodies compared to controls. Compared to tanning, having a propensity to sun burn (p=0.006), or poor tanning ability (p=0.003) were significantly associated with a higher seroprevalence to genus beta HPV types within SCC cases. Statistically significant interactions were observed between poor tanning ability and genus-specific seropositivity with NMSC. Specifically, the associations between poor tanning ability and BCC (p interaction=0.02) and SCC (p interaction=0.01) were significantly stronger among individuals that were seropositive for antibodies to genus alpha HPV types. Similarly, the association between poor tanning ability and SCC was stronger among those seropositive for genus beta HPV types (p interaction=0.001). No additional significant interactions were observed for BCC or SCC between cutaneous sensitivity, history of blistering sunburn, or cumulative sunlight exposure and genus-specific seroreactivity.
In conclusion, associations with patterns of sunlight exposure appeared to be similar between BCC and SCC cases. With the exception of age at first blistering sunburn, factors measuring timing of sunlight exposure demonstrated stronger and statistically significant relationships with SCC. Additionally, of the sunlight related factors measured, only the associations between poor tanning ability and BCC and SCC were significantly modified by HPV seropositivity to types in genera alpha or beta.
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Eklund, Lena K. "Molecular alterations in squamous cell carcinomas of the skin : emphasis on genes on chromosome 9q /." Linköping : Univ, 2004. http://www.bibl.liu.se/liupubl/disp/disp2004/med850s.pdf.
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Agwae, M. E. "The role of iRhom2 in the pathogenesis of head and neck squamous cell carcinomas (HNSCC)." Thesis, University of Liverpool, 2018. http://livrepository.liverpool.ac.uk/3022143/.
Full textAbstract:
It has been proposed that the Notch signalling pathway plays a key role in the pathogenesis of head and neck squamous cell carcinomas (HNSCC). It has also been shown that the sheddase, ADAM17, whose intracellular trafficking and subsequent maturation is dependent on iRhom2, is key in the activation of the Notch pathway at the cell membrane, leading to the release of an intracellular domain for downstream activities. This thesis investigates the levels and distribution of iRhom2 and ADAM17 in HNSCC, and functional changes resulting from up-regulation of iRhom2 in HNSCC cell lines. Immunoblotting, using protein samples extracted from fresh, snap-frozen tissues (68 HNSCC and 27 paired normal tissues), and probing for iRhom2 identified relatively high expression levels of this protein in 43/68 tumour samples compared to 5/27 normal samples (p < 0.05). Similar observations were obtained for ADAM17 expression, with high expression in 27/68 tumour samples compared to 4/27 normal samples (P < 0.05). A positive correlation was observed between levels of expressions of iRhom2 and ADAM17 in these tissues (though not statistically significant), but only iRhom2 expression correlated with patient survival (p < 0.05). Non-correlation of iRhom2 expression with other clinicopathological features was perhaps due to the relatively small number of samples investigated. Using a different cohort of HNSCC tissues, we also assessed levels of iRhom2 and ADAM17 and their intracellular distribution using tissue microarray (TMA) approach. Western blot results could not be corroborated with this methodology, given that most of the tissues stained negative for iRhom2, and 76/88 stained “highly positive” for ADAM17, with no observable specificity with ADAM17 staining pattern. Up-regulation of iRhom2 was achieved in the HNSCC cell lines, PE/CA-PJ15 and LIV37K; and in NOK (normal oral keratinocyte) cells and was, followed by shRNA knock-down of RHBDF2 (which codes for iRhom2). No observable differences were observed in the rate of cell replication when comparing wild-type, over-expressing and knock-down clones across each of the cell lines. However, a higher rate of cell migration was demonstrated in association with iRhom2 up-regulation, more in the HNSCC cell lines than the NOK. This higher rate of migration was shown to be reversed by the shRNA knock-down of RHBDF2, demonstrating that it is increased iRhom2 that is causative. Furthermore, a significant increase in the level of expression of mature ADAM17 was observed, following upregulation of iRhom2. iRhom2 and ADAM17 are both up-regulated in HNSCC, with up-regulation of iRhom2 associated with increased cell migration and decreased patient survival. Further experiments should aim to address whether it is the increased ADAM17 expression / activity and / or Notch activity that is the downstream effector of the observed effects. If will be important to expand the cohort of samples and cell lines used for this study to further validate the present findings, while also optimising some of the aspects that have not achieved significant results.
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Nardi, Carlos Eduardo Molinari. "O papel da via proteica Wnt em carcinomas de laringe." Universidade de São Paulo, 2018. http://www.teses.usp.br/teses/disponiveis/5/5160/tde-23042018-121343/.
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Introdução: O câncer de laringe é a segunda neoplasia maligna mais comum no segmento cervicofacial. As caderinas epiteliais (E-caderinas) em conjunto com cateninas formam o complexo E-caderina-catenina que atuam na adesão célula-célula. A perda dessa molécula pode levar à redução ou até mesmo ausência de expressão de E-caderina na membrana celular, acúmulo citoplasmático de beta-catenina e sua translocação para o núcleo, contribuindo para eventos carcinogênicos. Objetivo: Avaliar a expressão de E-caderina e beta-catenina em pacientes com tumor laríngeo precoce ou avançado e na presença ou ausência de metástase cervical. Métodos: Realizou-se estudo retrospectivo de 52 pacientes portadores de carcinoma epidermoide glótico ou supraglótico, tratados entre 1998 a 2011 e avaliados de acordo com o sítio de localização tumoral, grau de diferenciação histológica, estádio TNM, dados de sobrevida e confrontados com a expressão imunoistoquímica de E-caderina e beta-catenina. Resultados: Observou-se associação com significância estatística entre a queda da expressão de E-caderina com a localização supraglótica da lesão, a presença de metástase cervical, em tumores pouco diferenciados e em tumores localmente avançados quando em topografia glótica. Com relação à expressão de beta-catenina, também foi encontrada significância estatística ao relacionar a presença de metástase cervical e tumor de baixa diferenciação com a diminuição de expressão deste marcador. Quanto à análise de sobrevida, a baixa expressão de beta-catenina está relacionada a pior sobrevida global e a redução da expressão de ambos os marcadores a pior sobrevida livre de doença. Conclusão: A expressão anômala dos marcadores estudados levam a impacto prognóstico por poder propiciar tumores com maior agressividade local e presença de metástase cervicalIntroduction: Larynx cancer is the second most common malignant neoplasm in the cervicofacial segment. Epithelial cadherins (E-cadherins) together with catenins form the E-cadherin-catenin complex that acts on cell-to-cell adhesion. The loss of this molecule may lead to the reduction or even absence of E-cadherin expression in the cell membrane, cytoplasmic accumulation of beta-catenin and its translocation to the nucleus, contributing to carcinogenic events. Objective: To evaluate the expression of E-cadherin and beta-catenin in patients with laryngeal tumor in different locoregional situations. Methods: A study retrospective of 52 patients with glottic or supraglottic squamous cell carcinoma treated between 1998 and 2011 was conducted, evaluated according to the tumor localization site, the degree of histological differentiation, TNM stage and survival analysis. These data were confronted with the immunohistochemical expression of E-cadherin and ?-catenin. Results: We observed statistically significant association between the fall of E-cadherin expression and the supraglottic localization of the lesion, the presence of cervical metastasis, poorly differentiated tumors and locally advanced tumors when in glottic topography. Related to the expression of beta-catenin, statistical significance was also found for the presence of cervical metastasis and tumor of low differentiation with the decreased expression of this marker. Regarding survival analysis, the low expression of beta-catenin is related to worse overall survival and the reduction of expression of both markers to worse disease-free survival. Conclusion: The anomalous expression of the markers studied leads to a prognostic impact in order to provide tumors with greater local aggressiveness and presence of cervical metastasis
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SPÍNDULA, FILHO José Vieira de. "Detecção de HPV e avaliação do índice de proliferação celular entre carcinomas espinocelulares e carcinomas verrucosos de boca." Universidade Federal de Goiás, 2006. http://repositorio.bc.ufg.br/tede/handle/tde/1364.
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Previous issue date: 2006-11-27Squamous cell carcinoma (SCC) is the most common malignant neoplasm of the bucal cavity, and one of its variants is verrucous carcinoma (VC), of low degree malignancy. The diagnosis of VC is difficult from the clinical as well as from the histopathological point of view, and an effective diagnosis is vital when deciding on the treatment and prognosis of this tumor. The aim of this research was to evaluate cell proliferation and investigate the presence of HPV in spindle cell carcinoma of the mouth so as to check for possible differences in the aetiopathogenesis and biological behavior of these lesions. Forty-seven samples were selected and divided as follows: 39 SCCs, 8 VCs and 9 control (CT). Cell proliferation was qualitatively evaluated according to the location of the expression of the immunomarker in the cell and epithelium layers and by quantitatively considering the percentage of positive cells expressed. The analysis of HPV+ carcinomas was undertaken by means of the polymerase chain reaction (PCR), having GP5+/6+ as primers for identification of the virus. The qualitative analysis showed that the immunomarking in the VC as well as in the control group was concentrated mainly in the basal and parabasal layers and the counting of the positive cells at the base of the epithelium showed a significant statistical difference in the expressions of all three markers (p<0,05). The quantitative analysis of the cell proliferation markers was calculated by means of the Mann-Whitney and Kruskal Wallis tests and through the Pearson and Spermans correlation. They pointed to differences between the SCC and VC groups for the PCNA and cyclin B1 markers (p<0,05). On considering the three groups, it was proved that there was a positive correlation between Ki67 and the cyclin B1 (r=0,56) but not between the PCNA and the Ki67. The PCNA immunomarking was greater in the control group (average=100%), and the Ki67 showed itself to be effective as a proliferation cell marker although it showed no significant difference between the carcinoma variants. Whereas the cyclin B1 showed a significant difference in the comparison between the SCC and the VC groups (p<0,05), and a positive correlation to the extent that the histological grading of the malignancy (WHO model) of the carcinomas increased (r=0,44). All tumor samples were negative for HPV. Although the lesions showed different biological behaviors, the cell proliferation index in both types of mouth carcinoma was higher than in the control group, as shown by the analysis of the Ki67 and cyclin B1 markers. On considering the total sample of carcinomas, independently of the tumor variety, cyclin B1 showed a positive correlation with the histological degree of malignancy according to WHO. There is a need for further study to be carried out in the field of cell proliferation and detection of HPV especially with regard to VC, because it is a rare variant of SCC.
O carcinoma espinocelular (CEC) é a neoplasia maligna mais comum na cavidade bucal, e uma de suas variantes é o carcinoma verrucoso (CV), considerado de baixo grau de malignidade. O diagnóstico do CV é difícil, tanto do ponto de vista clínico quanto histopatológico e um efetivo diagnóstico é fundamental para estabelecer o tratamento e o prognóstico desse tumor. Neste estudo foi avaliada a proliferação celular e investigada a presença de HPV em carcinomas espinocelulares de boca com intuito de verificar possíveis diferenças na etiopatogênese e comportamento biológico destas lesões. Foram selecionadas 47 amostras de CEC assim distribuídas: 39 CECs, 8 CVs e 9 controles (CT). A proliferação celular foi avaliada qualitativamente de acordo com a localização da expressão do imunomarcador na célula e nas camadas do epitélio e quantitativamente considerando o percentual de células positivas expressas. A análise de carcinomas HPV+ foi realizada por meio da reação em cadeia da polimerase (PCR), tendo como primers GP5+/6+ na identificação do vírus. A análise qualitativa revelou que a imunomarcação tanto no CV como no controle concentrava se principalmente nas camadas basal e parabasal e a contagem das células positivas na base do epitélio mostraram diferença estatisticamente significativa na expressão dos três marcadores (p<0,05). A análise quantitativa dos marcadores de proliferação celular foi calculada pelos testes estatísticos Mann-Whitney, Kruskal Wallis, correlação de Pearson e Spermans, que revelaram diferenças entre o grupo CEC e CV para os marcadores PCNA e ciclina B1 (p<0,05). Considerando os três grupos, verificou-se correlação positiva entre Ki67 e a ciclina B1 (r=0,56) e inexistência de correlação entre o PCNA e Ki67. A imunomarcação do PCNA foi maior no grupo controle (média=100%), e o Ki67, mostrou-se efetivo como marcador de proliferação celular, entretanto, não mostrou diferença significativa entre as variantes de carcinomas. Já a ciclina B1 apresentou diferença significativa na comparação entre o grupo CEC e o grupo CV (p<0,05) e correlação positiva na medida em que a gradação histológica de malignidade (padrão OMS) dos carcinomas aumentava (r=0,44). Todas as amostras de tumores foram negativas para o HPV. Embora as lesões apresentem comportamento biológico diferente, o índice de proliferação celular nos dois tipos de carcinomas de boca mostrou ser superior ao do grupo controle, por meio da análise dos marcadores Ki67 e ciclina B1. Quando considerada a amostra total de carcinomas, independente da variante tumoral, a ciclina B1 mostrou correlação positiva com o grau histológico de malignidade segundo a OMS. Há necessidade que mais estudos possam ser empreendidos na área de proliferação celular e detecção de HPV em especial com relação ao CV, por se tratar de uma variante rara do CEC.
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Hahn-Strömberg, Victoria. "Cell adhesion proteins in different invasive patterns of colon carcinomas : a morphometric and molecular genetic study." Doctoral thesis, Örebro universitet, Hälsoakademin, 2008. http://urn.kb.se/resolve?urn=urn:nbn:se:oru:diva-2603.
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Colorectal carcinoma is the second most common type of cancer in both men and women in Sweden. Cancer of the colon and rectum are often considered together and their ten year survival rate is approximately 50 – 60 % depending on sex and location. Different histopathological characteristics of such cancers, including the complexity of growth, are of importance for prognosis. This thesis has compared different morphometric methods in order to achieve a quantitative and objective measurement of the invasive front of colon carcinoma. Since the growth pattern is dependent on the cell adhesiveness of different proteins we studied the distribution and localization of E-cadherin, Beta-catenin, Claudin 1,2,7 and Occludin as well as screened the genes for mutations. We found a perturbed protein expression of E-cadherin, Beta-catenin, Claudin 1,2,7 and Occludin in tumor sections compared to normal mucosa, but no relation to tumor volume or growth pattern could be seen. The tumor volume was found to be correlated to the growth pattern but not responsible to the perturbed protein expression. In the mutation screening we found a SNP in exon 13 the E-cadherin gene in the tumor, as well as in exon 2 of Claudin 1 and exon 4 of Claudin 7 in both tumor and normal mucosa. No correlation between mutations and growth pattern or tumor volume was found. In conclusion, this thesis shows that the computer image analysis with estimation of fractal dimension and number of free tumor cell clusters is superior to the semi quantitative visual grading of tumor invasive complexity. The aberrant expression of cell adhesion proteins in the tumor compared to normal mucosa as well as polymorphisms in the cell adhesion genes CLDN1 and CLDN7 in both tumor and normal mucosa can suggest that these aberrations are important in the tumorigenesis of colon carcinoma.
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Alkamal, Imad [Verfasser]. "Pharmacological unmasking of epigenetically regulated genes in renal cell carcinomas under clinical chemistry aspects / Imad Alkamal." Berlin : Freie Universität Berlin, 2014. http://d-nb.info/1060367823/34.
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Kuo, Michael Jeo-Ming. "Aberrations of chromosome arms 5q and 8p in squamous cell carcinomas of the head and neck." Thesis, University of Birmingham, 1998. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.340558.
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Hawkins, William Tressel II. "Combinatorial Modulation of Multiple Signaling Pathways to Gain Therapeutic Response in Breast and Prostate Cell Carcinomas." VCU Scholars Compass, 2006. http://scholarscompass.vcu.edu/etd/1043.
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Our laboratory is primarily interested in novel pharmacological intervention of cell proliferation and survival pathways expressed in various types of cancer. These cyto-protective pathways can be activated in response to growth factor stimulation, toxic insult and radiation. In our studies, we utilized novel drug combinations with and without radiation to enhance breast & prostate tumor cell death both in vitro and in vivo. Previous studies from our group have shown that UCN-01 and MEK1/2 inhibitors interact to cause tumor cell death in transformed cell lines in vitro. We extended this observation to an in vivo animal model system using the estrogen dependent breast cell carcinoma line MCF-7 and the estrogen independent breast cell carcinoma line MDA-MB-231. This drug combination was shown to profoundly reduce tumor cell proliferation in vivo and also exhibited the ability to significantly reduce ex-vivo tumor cell colony formation 30 days after cessation of the combination drug treatment. In addition, tumor cell death coincided with decreased ERK112 phosphorylation, reduced immunoreactivity of Ki67 and CD31. Overall, these studies demonstrate that UCN-01 and MEK112 inhibitors have the potential to suppress mammary tumor growth in vivo which is independent of p53 status, estrogen dependency, caspase-3 levels or oncogenic K-RAS expression. In our LnCap prostate carcinoma cell studies we demonstrated the impact of hCG and lovastatin in combination with ionizing radiation to radiosensitize and enhance tumor cell lethality. This enhancement was attributed to the hCG-induced activation of ERBB1 via a GPCR, MEK112 and metalloprotease dependent paracrine mechanism which was further enhanced by radiation. This enhanced cell killing effect was shown to involve prolonged activation of PARP1 which could be suppressed by inhibition of ERBB1, MEKl , PI3 kinase or PARP1. Therefore, the combination of hCG, lovastatin and radiation may represent a novel approach to kill prostate cancer cells and potential new therapy.
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Garcia, Alexandre Simões. "Correlação da imunoexpressão de podoplanina e ezrin em carcinomas espinocelulares de lábio." Universidade de São Paulo, 2013. http://www.teses.usp.br/teses/disponiveis/25/25150/tde-14082013-093702/.
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A podoplanina humana consiste em uma proteína associada ao processo de invasão das células epiteliais neoplásicas, sendo sua alta expressão correlacionada com um pior prognóstico para os pacientes com câncer de cabeça e pescoço. A porção citoplasmática da podoplanina pode se ligar a ezrin, uma proteína que vem sendo associada com a ocorrência de metástases e menor sobrevida para os pacientes com neoplasias malignas. O objetivo do presente estudo foi avaliar em 48 carcinomas espinocelulares de lábio inferior a expressão imuno-histoquímica da podoplanina e da ezrin, nas células do front de invasão tumoral, e verificar a correlação entre a expressão das duas proteínas nas células epiteliais neoplásicas. A expressão membranosa e citoplasmática da podoplanina e da ezrin foi avaliada nas células neoplásicas periféricas e centrais das ilhotas tumorais, por meio de um método semi-quantitativo de escores. A associação entre a expressão membranosa e citoplasmática da podoplanina e da ezrin nos tumores foi feita pelo teste de qui-quadrado, com nível de significância de 5% e a correlação entre a expressão das duas proteínas foi realizada pelo teste de correlação de Spearman. Os resultados demonstraram uma forte expressão membranosa e citoplasmática da podoplanina nas células periféricas do front de invasão tumoral com ausência desta expressão na região central das ilhotas tumorais. A imunomarcação da ezrin foi homogênea nos tumores e predominantemente citoplasmática. Uma diferença estatisticamente significativa foi encontrada entre a expressão da podoplanina nas células neoplásicas periféricas e centrais (p<0,001), como também entre a expressão da ezrin membranosa e citoplasmática (p<0,001) nos carcinomas espinocelulares de lábio. Houve uma correlação positiva, porém sem significância estatística, entre a expressão da podoplanina membranosa e da ezrin membranosa ou citoplasmática nas células neoplásicas periféricas. Estes resultados comprovam que a podoplanina e ezrin são fortemente expressas pelas células neoplásicas do front de invasão tumoral e sugerem que ambas proteínas podem estar participando do processo de invasão dos carcinomas espinocelulares de lábio.The human podoplanin consists in a protein associated to the invasion process of the epithelial malignant cells, being your high expression correlated with poor prognosis in patients with head and neck cancer. The cytoplasmic tail of the podoplanin can bind to ezrin, a protein that have been associated with metastasis and lower survival rate in patients with malignant neoplasms. The aim of this study was evaluate in 48 squamous cell carcinomas of the lower lip, the immunohistochemical expression of podoplanin and ezrin, in the invasive front, and verify correlation between the expression of both proteins by epithelial neoplastic cells. The membranous and cytoplasmic expression of podoplanin and ezrin was evaluated in peripheral and central areas of the tumor islets, using a semi-quantitative score method. The association between the membranous and cytoplasmic expression of podoplanin and ezrin in the tumors was performed by chi-square test, using a significance level of 5% and the correlation between the expression of both proteins was performed by Spearman correlation test. The results showed a high membranous and cytoplasmic podoplanin expression in the peripheral cells of the invasive front, with no expression of this protein in the central cells. The ezrin immunostaining was homogeneous and observed mainly in the cytoplasm of malignant cells. A statistically significant difference was found between the expression of podoplanin in peripheral and central tumor cells (p<0,001), as well between the membranous and cytoplasmic expression of ezrin (p<0.001) in squamous cell carcinoma of the lip. There was a positive correlation, but without statistical significance, between the expression of membranous podoplanin and membranous or cytoplasmic ezrin in the peripheral tumor cells. These results prove that podoplanin and ezrin are strongly expressed by malignant cells of the invasive front tumor and suggest that both proteins may be participating in the invasive process of the squamous cell carcinoma of the lip.
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PEREIRA, LARISSA M. "Clonagem, expressao, purificacao e caracterizacao estrutural da proteina ribossomal L10 humana recombinante." reponame:Repositório Institucional do IPEN, 2009. http://repositorio.ipen.br:8080/xmlui/handle/123456789/9478.
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Dissertacao (Mestrado)
IPEN/D
Instituto de Pesquisas Energeticas e Nucleares - IPEN-CNEN/SP
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Oliveira, Maykon Kennedy Schulz. "Expressão de CD10, Vimentina, Ki-67 e Ciclina D1 em carcinomas espinocelulares de cabeça e pescoço : avaliação clínico-patológica /." Araraquara, 2018. http://hdl.handle.net/11449/153290.
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Orientador: Andreia BufalinoResumo: O carcinoma espinocelular (CEC) é a sexta malignidade mais comum do mundo, e na região de cabeça e pescoço representa mais de 90% das malignidades. Mesmo com os recentes avanços nos protocolos de tratamento cirúrgico, radioterápico e quimioterápico, a taxa de sobrevida de 5 anos para pacientes com carcinoma espinocelular de cabeça e pescoço (CECCP) permanece reduzida. Diversos fatores podem contribuir para esse baixo índice de sobrevida e, somado a isso, ainda não existem marcadores biológicos que possam contribuir na orientação da melhor opção terapêutica dos pacientes e na previsão do seu diagnóstico. Estudos desta natureza representam uma valiosa oportunidade para esclarecer os mecanismos moleculares envolvidos na patogênese do CECCP. Dentre estes eventos moleculares, o processo da diferenciação celular é capaz de regular a expressão de genes ligados a importantes funções celulares, incluindo o controle da proliferação celular. Neste contexto, o objetivo deste estudo foi avaliar a relação de marcadores de proliferação e diferenciação celular com parâmetros clínico-patológicos de amostras de CECCP por meio da imuno-histoquimica (IQ). Diante disto, nosso estudo avaliou um total de 46 amostras de CECCP. Quanto a expressão dos marcadores de proliferação celular, avaliamos Ki-67 (n=46) e Ciclina D1 (n=46). Para os marcadores de diferenciação celular, avaliamos CD10 (n=42) e Vimentina (n=41). A expressão aumentada de Ki- 67 foi significantemente associada com pior prognóstico (p... (Resumo completo, clicar acesso eletrônico abaixo)
Abstract: Squamous cell carcinoma (SCC) is the sixth most common malignancy in the world, and in the head and neck region it represents more than 90% of malignancies. Even with recent advances in surgical, radiotherapeutic and chemotherapeutic treatment protocols, the 5-year survival rate for patients with squamous cell carcinoma of the head and neck (HNSCC) remains low. Several factors may contribute to this low survival rate and, in addition, there are still no biological markers that can contribute to the orientation of the best therapeutic option of the patients and the prediction of their diagnosis. Studies of this nature represent a valuable opportunity to clarify the molecular mechanisms involved in the pathogenesis of HNSCC. Among these molecular events, the process of cell differentiation is able to regulate the expression of genes linked to important cellular functions, including the control of cell proliferation. In this context, the objective of this study was to evaluate the relationship of proliferation and cellular differentiation markers with clinical-pathological parameters of HNSCC samples by means of immunohistochemistry (IQ). In view of this, our study evaluated a total of 46 HNSCC samples. Regarding the expression of the cellular proliferation markers, we evaluated Ki-67 (n = 46) and Cyclin D1 (n = 46). For cell differentiation markers, we evaluated CD10 (n = 42) and Vimentin (n = 41). Increased Ki-67 expression was significantly associated with poorer prognosis (p... (Complete abstract click electronic access below)
Mestre
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Lemos, Mayra Borges. "Estudo histopatológico das displasias epiteliais em lesões inflamatórias crônicas da cavidade oral." Universidade Federal de Sergipe, 2017. https://ri.ufs.br/handle/riufs/5908.
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Introduction: Chronic inflammation plays an important role on the transformation
and tumor progression during oral carcinogenesis. There is a great number of
chronic inflammatory lesions (CIL) in the oral cavity which are related to dysplastic
processes of the epithelium, immune response and changes on the collagen
deposition. Objectives: To investigate the presence of dysplasia and to histologically
grade them in the CIL of traumatic cause, as well as toaccessthe density of mast
cells and different types of collagen fibers in cases of epithelial dysplasias and oral
squamous cell carcinomas (OSCC). Material and Method: Initially, 183 CIL cases
were evaluated as to the presence of dysplasia and also classified according to its
degree of epithelial dysplasia. Among those lesions, 45 CIL cases were selected and
divided into two groups: group 1 (15 cases of mild dysplasia), group 2 (15 cases of
moderate/severe dysplasia). The control group was composed by 15 cases of
OSCC.They were stained with toluidine blue in order to quantify the mast cells and
picrosirius red to semi-quantify the collagen type fibers. Results: The mast cells were
detected in all groups presenting a mean of 6,76 cells/mm2, 10.82 cells/mm2 and
19.18 cells/mm2 in the control, group 1and 2 respectively. Regarding the collagen
fibers, type III was more prevalent on groups 2 and control while type I fibers were
more abundant on group 1. Conclusion: Oral chronic inflammatory lesions showed
dysplastic changes in most analyzed cases. The results suggests an active
participation of mast cells in the stage of tumor transformation, since it was detected
a higher density onthe dysplasia cases when compared to the OSCC cases.
Nevertheless, the gradual change of collagen type fibers indicates that collagenproducing
cells become altered during the stages of dysplasia (tumor
transformation).Introdução: A inflamação crônica tem um papel importante na transformação e progressão tumoral durante a carcinogênese oral. Muitas lesões inflamatórias crônicas (LIC) da cavidade oral estão relacionadas a processos displásicos do epitélio, à resposta imune e à mudança na deposição do colágeno. Objetivos: Investigar a presença de displasia e graduá-las histologicamente nas LIC de origem traumática, como também, avaliar a densidade de mastócitos e de diferentes tipos de fibras colágenas nas LIC com displasias epiteliais e comprar aos casos de carcinomas de células escamosas (CCE). Material e Métodos: Inicialmente 183 LIC foram avaliadas quanto à presença de displasia e classificadas em relação ao grau. Em seguida, 45 casos foram divididos em: Grupo controle (CCE), Grupo 1 (displasia leve- DL), Grupo 2 (displasia moderada/severa- DM/S). Foram corados com Azul de Toluidina para quantificar os mastócitos e Picrosirius Red para avaliação dos tipos de fibras colágenas I e III. Resultados: As LIC foram mais frequentes em mulheres (n=107) com idade de 36,6 anos. O sítio mais afetado foi a mucosa do lábio inferior (29,7%), já a lesão mais frequente foi o fibroma traumático (39,2%). A displasia leve esteve presente em 56,3% da amostra. Os mastócitos foram evidenciados nos três grupos: grupo controle (6,76 mastócitos/mm), grupo 1 (10,82 mastócitos/mm2) e grupo 2 (19,18 mastócitos/mm2).Quando analisadas as fibras colágenas, observouse no grupo controle e no grupo 2 que as fibras tipo III foram mais prevalentes, já no grupo 1 prevaleceu-se as fibras tipo I. Conclusão: Lesões inflamatórias crônicas orais apresentaram alterações displásicas na maior parte dos casos. O estudo sugere uma participação dos mastócitos na fase de transformação tumoral. E a alteração gradativa dos colágenos tipo I e III indica alteração das células produtoras de colágeno, durante transformação tumoral.
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Chang, Julia Yu-Fong, and 張玉芳. "Human papillomavirus in oral squamous cell carcinomas." Thesis, 2003. http://ndltd.ncl.edu.tw/handle/40717354793569397156.
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碩士國立臺灣大學
臨床牙醫學研究所
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Abstract Background: Human papillomaviruses (HPV) infection is a significant risk factor for uterine cervical carcinomas. However, the role of HPV infection in the development of oral squamous cell carcinoma (SCC) is still unclear due to the lack of normal control samples for comparison and the masking effect of other risk factors such as areca quid, tobacco and alcohol on the etiologic role of HPV. Methods: In order to evaluate the etiologic role of HPV in oral carcinogenesis, DNA samples were purified from 103 oral SCC specimens and 30 normal oral mucosal specimens. A nested-polymerase chain reaction (PCR) was used to amplify the consensus L1 region of the HPV genome in DNA samples using two sets of HPV primers (MY09/GP6+ and GP5+/GP6+). This procedure combined with a genechip HPV typing was able to detect a broad spectrum of HPV types in our samples. The HPV prevalence rates in normal oral mocosa (NOM) samples, all SCC samples, oral habits (OH)-associated SCC samples, and non-OH-associated SCC samples were determined and compared between groups. The expression of p53 in oral SCCs was studied by immunohistochemistry and its correlation with clinicopathological parameters was analyzed by chi-square test. Furthermore, we used biotinyl-tyramide-based in situ hybridization (BTBISH) to localize the HPV DNA in the nuclei of SCC cells. This method was able to differentiate whether the HPV DNA was integrated into the host cell genome or only in an episomal form. Results: We found that the overall HPV-positive rate was significantly higher in oral SCC samples (51/103, 49.5%) than in NOM samples (6/30, 20%, P<0.01) and significantly higher in non-OH-associated SCC samples (31/51, 60.8%) than in OH-associated SCC samples (20/52, 38.5%, P<0.05). The positive rate of high-risk HPV types or of HPV type 18 was also significantly greater in all SCC samples (41.7% or 26.2%, respectively) than in NOM samples (16.7%, P<0.05 or 0%, P<0.01, respectively) and significantly greater in non-OH-associated SCC samples (54.9% or 39.2%, respectively) than in OH-associated SCC samples (28.8%, P<0.001 or 13.5%, P<0.05, respectively). High-risk HPV types and all HPV types had an Odds ratio of 3.97 (95% CI, 1.40-11.28, P=0.0097) and of 3.92 (95% CI, 1.48-10.39, P=0.006), respectively. The overexpression rate of p53 protein was significant higher in HPV-positive oral SCCs (33.3%) than in HPV-negative oral SCCs (13.5%, P<0.05). By BTBISH, we found multiple punctate signals in the nuclei of oral SCC cells. This finding suggests that the HPV DNA has been integrated into the genomes of some of oral SCC cells. Conclusion: Our results suggest that HPVs, particularly high-risk HPV types, may play an important role in the development of oral SCCs, especially the non-OH-associated oral SCCs. HPV type 18 seems to play a more important role than HPV type 16 in oral carcinogenesis in Taiwan. However, further studies are needed to elucidate the exact role of HPV type 18 in the development of oral SCC. Non-OH-associated oral SCC is considered to be a specific disease entity with distinct molecular, pathologic, and clinical characteristics. Clinically, this kind of cancer is more common in females than in males, located at the tongue, initiated with tongue ulcers, and not associated with any OH. All poorly-differentiaed SCCs belong to this group. High-degree HPV association and p53 overexpression also implicate the different etiologies and pathogeneses of this group of oral cancers.
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Pop, Mihaela Paula. "Radio-frequency thermal therapy of renal cell carcinomas." 2004. http://link.library.utoronto.ca/eir/EIRdetail.cfm?Resources__ID=80997&T=F.
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Boardman, Mitzi Lynn. "Fas-mediated apoptosis in oral squamous cell carcinomas." 1998. http://catalog.hathitrust.org/api/volumes/oclc/48171980.html.
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Sydney, Clive. "A histopathological and immunohistochemical evaluation of scar basal cell carcinomas." Thesis, 2006. http://hdl.handle.net/10413/2061.
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Infiltrative morphological mimicry at sites of biopsy-proven nodular basal cell carcinoma has been described. The immunoprofile of scar BCCs (scar BCCs,SBCCs) has not been documented. The aim of this study was to assess the histopathological spectrum, stromal (fibronectin, laminin, actin, desmin and vimentin) response and proliferation (bcl-2, MIB1 and p53) status of SBCCs. Twenty nine BCCs occurring in scars, unrelated to previous malignancy (de novo scar BCCS, DN-SBCCs), 27 BCCs that were incompletely excised and regrew at the same site (regrowth scar BCCs, RG-SBCCs) and 25 BCCs that were completely excised with tumour free margins, but recurred at the same site (recurrent scar BCCs, R-SBCCs) were accessed from the files of the Department of Pathology and Plastic and Reconstructive Surgery of the Faculty of Medicine, University of KwaZulu Natal, and formed the basis of this study. The morphological features of DN-SBCCs was pure (3%), predominantly nodular (79%), micronodular (7%) and infiltrative (11 %). RG-SBCCs were predominantly nodular (82%), micronodular (7%) and infiltrative (11%). RSBCCs were predominantly nodular (80%), micronodular (4%) and infiltrative (16%). The majority of DN-SBCCs, RG-SBCCs and R-SBCCs showed intact basement membrane laminin staining, while two (7%) DN-SBCCs showed 1 + and 2+ loss of basement membrane laminin staining. Three (11 %) and two (8%) RG-SBCCs and R-SBCCs,respectively, showed 2+ or 3+ basement membrane laminin discontinuity. The majority of DN-SBCCs (83%), RGSBCCs (75%) and R-SBCCs (88%) were actin negative. No desmin immunopositivity was demonstrated in the epithelial or stromal components of DN-SBCCs, RG-SBCCs and R-SBCCs. All BCC groups showed high 3+ or 4+ vimentin immunopositivity. The majority (>50%) of the SBCCs showed low (2+) bcl-2 immunopositivity. There was no significant difference in p53 immunopositivity in all SBCCs. SBCCs demonstrate phenotypic and immunophenotypic heterogeneity. That DN-SBCCs with the infiltrative and micronodular patterns have not recurred implies that the histomorphology is a pseudo-aggressive pattern. A similar view could pertain to RG-SBCCs, but because the scar did not cicatrise the incompletely excised BCC implies that the histomorphology of RG-BCC may be a potentially more aggressive phenotype. The recurrence of a completely excised basal cell carcinoma may be viewed as a feature of an aggressive tumour, especially when the recurrent BCC contains micronodular and infiltrative components. However, as most R-SBCCs occurred at head and neck sites that are exposed to ultraviolet light, it is also possible that these are simply new BCCs occurring within scars in head and neck sites prone to BCCs. Furthermore, these R-SBCCs were not destructive tumours. CONCLUSION: None of the infiltrative foci of DN-SBCCs demonstrated laminin loss. Three of 5 with intra-epithelial actin immunopositivity also demonstrated low bcl-2 and high p53 staining, immunoprofiling these with an aggressive infiltrative component. Of 11 RG-SBCCs with high p53 staining, 4 had high p53 staining in the infiltrative component, but only one had a low bcl-2 composite score and low bcl-2 score in the infiltrative focus. In addition, these infiltrative foci demonstrated intraepithelial MSA positivity and a "VA" immunophenotype of the stromal cells, indicating one RG-SBCC with an established, aggressive immunophenotype. Those positive with one or more, but not all, aggressive immunostains, are hypothesised to be RG-SBCCs evolving/developing an aggressive immunophenotype. Only one R-SBCC, with a predominantly infiltrative pattern, had a "full-house" of aggressive immunostaining in the infiltrative foci: low bcl-2, high p53, 2+ laminin discontinuity and intra-epithelial and stromal MSA positivity. Of significance is that 7 with a predominant nodular pattern had a high p53 score. Of these, 5 had high bcl-2 scores. Hence, while high p53 may be a feature of aggressive growth, it is important that this staining be complemented with that of bcl-2, laminin and MSA.Thesis (M.Med.Sc.)-University of KwaZulu-Natal, Durban, 2006.
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Huang, Kuo Hao, and 黃國豪. "Promoter methylation profiling in oral squamous cell carcinomas in Taiwan." Thesis, 2009. http://ndltd.ncl.edu.tw/handle/08422435463447834404.
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博士長庚大學
生物醫學研究所
97
Promoter methylation is one of the mechanisms for gene silencing leading to cancer. To investigate the relationship between promoter methylation and tumor clinicopathological paramaters, risk factors and patient’s clinical outcome, the promoter of 12 tumor suppressor / DNA repair genes was evaluated in 482 oral squamous cell carcinomas (OSCCs), using bisulfite PCR- denature high performance liquid chromatography (DHPLC). Overall, OSCCs had at least one gene methylation (74.1%, 357/482). The frequency of promoter methylation detected in the p14ARF (13.3%, 64/482); p15INK4b (3.7%, 18/482); p16INK4a (18.9%, 91/482); MLH1 (10.8%, 52/482); MGMT (12.9%, 62/482); HIN1 (7.3%, 35/482); RASSF1A (22.4%, 108/482); RASSF2A (27.8%, 134/482); CDH1 (8.1%, 39/482); DAPK (1.2%, 6/482); p73 (7.7%, 37/482) and PTEN (1.2%, 6/482), respectively. The major findings were summarized as follows: (1) Promoter methylation in the RASSF1A gene was significantly higher in tongue cancer cases than other cases and in tumor size < 4 cm versus > 4 cm. (2) Promoter methylation in the p73 gene was positively association with age. (3) Promoter methylation of RASSF2A as well as the combination of RASSF1A and RASSF2A promoter methylation was found to be significantly associated with a poor disease-free survival (DFS). Further, combined with Ras mutation and activation of PI3K/Akt through PTEN and HIN1 promoter methylation, a gene dosage effect on DFS was observed in patients who had undergoing radiotherapy after surgery. The patients who were detected having one alteration showed a significantly poor DFS compared with those with no alteration (HR=1.49, 95% CI = 1.05-2.12); and those patients who detected as having at least two alterations showed a further worsening of their DFS (HR=2.25, 95% CI = 1.07-4.72). This phenomenon was prominent in patients with age >49 years; the HR for patients with one alteration and least 2 alterations was 1.65 (95% CI = 1.09-2.50) and 2.97 (95% CI=1.16-7.57), respectively. (4) In patients age < 49 years with promoter methylation of the cell cycle control related genes (p14ARF, p15INK4b, p16INK4a and p73) was associated with good DFS (HR=0.60, 95% CI = 0.38-0.95) and overall survival (OS) (HR=0.62, 95% CI = 0.39-0.99). (5) In patients with age >49 years and lymph node negative patients, promoter methylation of the DNA repair related genes (MLH1 and MGMT) was associated with good OS (HR=0.61 [95% CI = 0.37-0.99] and HR=0.56 [95% CI = 0.33-0.96]), respectively. Taker together, the clinical impact of promoter methylation in different gene was different in Taiwanese OSCCs and these fingings indicate that analysis of DNA methylation in OSCC may provide a rationale for exploring novel treatment strategies.
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Francisco, João Pedro Dinis. "MicroR-21 overexpression in pulmonary adenocarcinomas and squamous cell carcinomas." Master's thesis, 2010. http://hdl.handle.net/10316/19074.
Full textAbstract:
Introduction: MicroRNA’s (miRNA) as class of small cellular RNA’s acting agents of the interference pathway lead to silencing their cognate target genes and are differentially expressed in human cancer. The precise role of microRNA’s in specific stages of malignant progression, including metastasis, is still unknown.
Objectives: Our goal was to analyse the expression profile of miR-21 in lung cancer.
Materials and Methods: For that purpose, a microRNA qRT-PCR was performed.in 7 pulmonary adenocarcinomas and 5 squamous cell carcinomas and respective metastasis in order to try to understand its role in tumorogenesis.
Results and Discussion: We found an increase in miR-21 expression in primary tumour and metastases in pulmonary adenocarcinomas when compared with miR-21 overexpression in squamous cell carcinoma. Despite the small sample studied, further investigation may indicate therapeutic and prognostic relevance of this determination as previous studies suggest that miR-21 functions as an oncogene and has a role in tumorogenesis through regulation of tumour suppressor genes.Introdução: Os microRNA’s (miRNA) são uma classe de pequenos RNA’s celulares que actuam na via de interferência e conduzem ao silenciamento de determinados genes-alvo, exprimindo-se de forma distinta no cancro humano. O papel preciso dos microRNA’s nos estadios da progressão tumoral, incluindo a metastização, é ainda desconhecido. Objectivos: consistiu na pesquisa do perfil de expressão do miR-21 no cancro do pulmão. Materiais e Métodos: para este propósito, fez-se uma qRT-PCR dos microRNA em 7 adenocarcinomas, em 5 carcinomas de células epidermóides e nas respectivas metástases, com o objectivo de tentar compreender o seu papel na tumorogénese. Resultados e Discussão: encontrou-se um aumento da expressão de miR-21 nos tumores primários e metástases nos adenocarcinomas pulmonares, quando comparados com a sobre-expressão nos carcinomas de células epidermóides. Apesar do número reduzido de amostras estudadas, investigações futuras podem mostrar a importância terapêutica e prognóstica desta descoberta, dado que estudos anteriores sugerem que o miR-21 se comporta como um oncogene e tem um papel na tumorogénese, através da regulação de genes supressores tumorais.
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Yang, Fang-Yu, and 楊方瑜. "The Expression of SOX-9 in Oral Squamous Cell Carcinomas." Thesis, 2010. http://ndltd.ncl.edu.tw/handle/18429133943679978016.
Full textAbstract:
碩士臺灣大學
臨床牙醫學研究所
98
Background: SOX-9 plays an important role in many tissue differentiation processes, eg. chondrogenesis, male sex gonad differentiation, respiratory epithelim development, melanocyte differentiation, and the differentiation of the Paneth cells in guts. Also, numerous cancer studies focused on the influences of SOX-9, on colorectal cancer, prostate cancer, and ovarian cancer. Lots of the studies showed that the up-regulation of SOX-9 was correlated to the tumor growth and tumor cell metastasis, and the overexpression of SOX-9 indicated a poor prognosis. However, other studies pointed out that SOX-9 may act as a tumor repressor. So the role of SOX-9 in cancers was still equivocal. Until now, the relationship between SOX-9 and oral squamous cell carcinoma is unclear. Therefore, this study tried to elucidate the expression pattern of SOX-9 in OSCC and to correlate the expression of SOX-9 to the clinicopathological findings and long-term prognosis. Material and Method: In this study, we examined the expression of SOX-9 in 100 specimens of oral squamous cell carcinoma (OSCC), 61 specimens of oral epithelial dysplasia (OED), and 40 specimens of normal oral mucosa (NOM) by immunohistochemistry. The correlation between the expression of SOX-9 in OSCCs and clinicopathological parameters or the survival of OSCC patients was analyzed by ANOVA, Chi-square and Kaplan-Meier survival analysis. Univariate and multivariate analyses (Cox proportional hazard regression model) were used to find the correlation between expression of SOX-9 and clinicopathological parameters or survival, and tried to find out the independent predictors for the patients’ survival. Results: The labeling indices of SOX-9 significantly increased from NOM (4%, the lowest), through mild dysplasia (9%), moderate dysplasia (18%), and severe dysplasia (29%) to OSCC (48%) (p<0.001). The expression of SOX-9 was correlated with tumor size, lymph node status and clinical stage (p<0.05). Univariate analysis showed that tumor size, lymph node status, clinical stage and SOX-9 LI are related to the survival time (p<0.05). Multivariate analysis demonstrated that lymph node metastasis, clinical stage and SOX-9 LI were independent predictors for the patients’ survival (p<0.05). Conclusion: In this study, the expression of SOX-9 was significantly higher in OSCC than that in NOM and OED. In addition, SOX-9 was correlated with several clinical parameters and patients’ survival. SOX-9 may be a prognostic factor for OSCC patients.
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Chiu, Cheng-Hsuan. "Expression of erythropoietin and its receptor in oral squamous cell carcinomas." 2004. http://www.cetd.com.tw/ec/thesisdetail.aspx?etdun=U0001-2807200415104100.
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