Quatro décadas de pesquisas mostraram que muitos mecanismos inflamatórios estão intrinsecamente ligados ao desenvolvimento e manutenção do câncer, e ainda, que as citocinas inflamatórias exercem papel primordial nessa relação. Os anti-inflamatórios não esteroides (AINEs) podem reduzir o desenvolvimento neoplásico por afetar a produção de citocinas inflamatórias pelas células neoplásicas. No entanto, até o momento não foi bem definido se o tratamento com AINEs é capaz de modular a expressão de citocinas inflamatórias por células do carcinoma epidermoide oral (CEO). O objetivo deste trabalho foi avaliar a expressão de citocinas inflamatórias em linhagens celulares de CEO após tratamento com ácido acetilsalicílico (AAS) e celecoxibe (CLX). Foi realizado screening da expressão de 84 citocinas e quimiocinas, através de PCR array, das linhagens SCC4, 9 e 25 tratadas com doses de AAS e CLX próximas às concentrações plasmáticas dos fármacos em humanos. Os resultados mostraram que AAS e CLX modularam a expressão de citocinas e que as linhagens responderam de maneira diferente aos tratamentos. Observou-se aumento de expressão de citocinas pró-inflamatórias como a IL-1?, IL-8 e TNF na SCC9 e 25, assim como diminuição de expressão de ACKR4 e CXCL10 na SCC4 e 9. / Four decades of research have shown that many inflammatory mechanisms are intrinsically linked to the development and maintenance of cancer and that inflammatory cytokines play pivotal role in this association. Non-steroidal anti-inflammatory drugs (NSAIDs) can reduce neoplastic growth on affecting the production of inflammatory cytokines by the neoplastic cells. So far, it is not well established if the treatment with NSAIDs can modulate the expression of inflammatory cytokines by OSCC cells. The objective of this study was to evaluate the expression of inflammatory cytokines by OSCC cell lines after treatment with acetylsalicylic acid (ASA) and celecoxib (CLX). Eighty-four cytokines and chemokines mRNA expression were screened by PCR array on SCC4, 9 and 25 cell lines treated with ASA and CLX at plasma concentrations in humans. The results showed that ASA and CLX modulate the expression of cytokines with all cell lines responding differently to the treatments. Increased expression of proinflammatory cytokines such as IL-1?, IL-8 and TNF in SCC9 and 25, and reduced expression of ACKR4 and CXCL10 in SCC4 and 9, was observed. Thus it follows that the treatments of lines SCC4, SCC9 and SCC25 with ASA and CLX at the next plasma concentrations in humans are able to modulate the gene expression of inflammatory cytokines.

Introdução: A mutilação intra-oral, após tratamento de tumores, ocasiona além de deformidades estéticas, perda de função e impacto na qualidade de vida do paciente. Proposição: Avaliar a experiência individual do paciente tratado por lesões benignas e malignas que resultaram em mutilação intra-oral e necessidade de reabilitação complexa maxilo mandibular Material e Método: Através de entrevistas semi estruturadas, à luz da metodologia de análise de conteúdo, proposta por Bardin em 1977, utilizando a pergunta norteadora O que aconteceu na sua vida antes, durante e o que acontecerá depois da lesão/doença que te trouxe aqui, foram entrevistados seis pacientes, como mutilação intra-oral em reabilitação protética maxilo facial. Resultados e Discussão: Após análise, exploração e interpretação dos resultados colhidos em entrevistas semi-estruturadas, que duraram em média 1hora e meia a duas horas cada, foram extraídas duas categorias dos discursos dos sujeitos: Vivendo a mutilação, perdendo os dentes, a comunicação e a socialização e Preservando a esperança de um novo normal, respeitando a doença com a sombra da recidiva. Conclusão: Os dados revelam que o paciente que sofreu mutilação intra-oral após tratamento de tumor, é um sujeito que vive as seqüelas da terapêutica, tem respeito extremo pela doença que o levou àquela condição, tem medo de possíveis recidivas, mas, fundamentalmente, nutre a esperança de retomar sua vida e construir um novo normal. / Introduction: Intra-oral mutilation after treatment of tumors, causes beyond cosmetic deformities, loss of function and impact on quality of life of patients. Proposition: To evaluate the experience of the individual patient treated for benign and malignant lesions that resulted in injury intra-oral and maxillofacial complex rehabilitation needs Methods: Using semi-structured interview, supported of content analysis proposed by Bardin in 1977, using the guiding question \"What happened in your life before, during and what will happen after the injury / illness that brought you here,\" were interviewed six patients, such as mutilation intra-oral maxillo facial prosthetic rehabilitation. Results and Discussion: After analysis, exploration and interpretation of the results collected from semi-structured interviews, which lasted on average 1 hour and a half to two hours each, were extracted from two categories of the speeches: Living mutilation, losing teeth, communication and socialization and preserving the hope of a \"new normal\", respecting the disease in the shadow of recurrence. Conclusion: Our data show that patients who suffered mutilation after intra-oral tumor treatment, is a guy who lives the consequences of therapy, has utmost respect for the disease that led to that condition, afraid of possible relapse, but fundamentally nurtures the hope of resuming their lives and build a \"new normal\".

O carcinoma epidermóide é uma neoplasia que pode ter origem do revestimento mucoso de vários sítios das vias aerodigestivas superiores, sendo a língua o sítio primário com maior incidência. Entre os fatores de risco para a doença estão a idade, as mutações genômicas, o hábito tabagista e principalmente o consumo de etanol. O etanol é considerado um agente cocarcinogênico no processo de desenvolvimento do câncer de boca. Por outro lado, o acetaldeído, subproduto da oxidação do etanol, é tóxico e participa diretamente na carcinogênese. Assim, polimorfismos genéticos que alteram a oxidação de etanol para acetaldeído promovendo seu acúmulo podem alterar o risco de câncer oral. Os resultados sugerem que pacientes portadores do polimorfismo do gene ADH1C Ile350Val possuem maior risco de tornarem-se etilistas crônicos (OR=2,0199), mas o risco de desenvolverem câncer não é alterado quando comparado aos não portadores. Já os portadores dos polimorfismos nos genes ADH1B Arg47His (OR=0,3445), CY2E1 (ins) (OR=0,3261) e ALDH2 (GA) (OR=0,4811) apresentaram menores riscos de desenvolverem câncer oral, mas estes polimorfismos não estavam associados ao risco de tornarem-se etilistas crônicos. Observou-se também uma possível interação entre a baixa atividade da enzima ALDH2 e a expressão do gene CYP2E1 como um fator protetor no desenvolvimento do câncer de boca. Entretanto, há necessidade de mais estudos para comprovar esses achados / Squamous cell carcinoma is a neoplasm that may originate from the mucosal tissue from various sites of the upper aerodigestive tract, the tongue being the primary site with the highest incidence. Among the risk factors for the disease are age, genomic mutations, smoking habit, and especially the consumption of ethanol. Ethanol is considered a co-carcinogenic agent in the development of oral cancer. Moreover, acetaldehyde, ethanol oxidation product, is toxic and is directly involved in carcinogenesis. Thus, genetic polymorphisms that alter the oxidation of ethanol to acetaldehyde by promoting its accumulation can alter the risk of oral cancer. The results suggest that patients with the ADH1C Ile350Val polymorphism have increased risk of becoming chronic drinkers (OR = 2.0199), but the risk of developing cancer is not changed when compared to non carriers. Since the carriers of polymorphisms in genes ADH1B Arg47His (OR = 0.3445), CY2E1 (ins) (OR =0.3261) and ALDH2 (GA) (OR = 0.4811) lower risk of developing oral cancer, but these polymorphisms were not associated with risk of becoming chronic drinkers .There was also a possible interaction between the low activity of the enzymeALDH2 and CYP2E1 gene expression as a protective factor in the development of oral cancer. However, we need more studies to confirm these findings

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.

Das Plattenepithelkarzinom stellt mit über 90% die häufigste maligne Neubildung innerhalb der Mundhöhle mit gravierenden funktionellen Einschränkungen für die betroffenen Patienten und hoher Mortalität dar. In den meisten Fällen bestehen bereits vor der malignen Transformation visuell erkennbare Veränderungen mit höherem Entartungspotential, sogenannte potenziell maligne Veränderungen. Die vorliegende Arbeit beschäftigt sich mit einem experimentellen Verfahren zur oralen Tumorfrüherkennung und Dignitätsabklärung von potenziell malignen Veränderungen der Mundschleimhaut. Grundlage bildet das Verfahren des „intact cell peptidome profiling“ (ICPP) mittels MALDI-TOF MS anhand von Präparaten oraler Bürstenbiopsien. Untersucht wurden 16 Proben oraler Plattenepithelkarzinome, 69 Fälle von oralem Lichen planus, 26 orale Leukoplakien, 21 andere orale Veränderungen sowie 56 Mundschleimhautläsionen an Fanconi-Anämie erkrankter Patienten. Die Methode eignet sich zur Unterscheidung zwischen gesunder Mundschleimhaut und maligne verändertem Gewebe, wie mit einer Sensitivität von 86 % und einer Spezifität von 100 % belegt wurde. Eine Differenzierung zwischen den einzelnen Mundschleimhautveränderungen und gesundem Gewebe konnte nicht erreicht werden. Die Untersuchungsreihe ist als vielversprechend einzuschätzen, um ein weiterführendes diagnostisches Verfahren zu entwickeln, dass den Untersucher durch eine objektive Messmethode unterstützen und Sensitivität und Spezifität der Bürstenbiopsie steigern könnte.

Das orale Plattenepithelkarzinom ist der weltweit häufigste Tumor der Mundhöhle und des Rachens. Das Ziel dieser retrospektiven Studie war die Evaluation der Treffsicherheit der flüssigkeitsbasierten oralen Bürstenbiopsie als Screening-Methode für das orale Plattenepithelkarzinom. Bei der Bürstenbiopsie handelt es sich um ein Verfahren, das ursprünglich aus der Gynäkologie kommt und dort schon seit Jahrzehnten erfolgreich als Abstrich-Methode eingesetzt wird. Die orale Bürstenbiopsie dient der Gewinnung von Zellen aus klinisch suspekten Läsionen der Mundhöhle, in dieser Studie unter Verwendung des Zellkollektors 'Orcellex'. Die Bürste wird mit Druck etwa zehn Mal auf der zu untersuchenden Läsion rotiert, um eine ausreichende Menge an Zellen zu gewinnen. Bei der Verwendung des flüssigkeitsbasierten Verfahrens wird der Bürstenkopf anschließend in ein Gefäß mit alkoholbasierter Flüssigkeit transferiert und die Probe in ein Labor versandt. Nach der Verarbeitung der Probe wird sie von einem erfahrenen Zythopathologen untersucht und in Wertungsgruppen eingeteilt. Lautet die Diagnose 'Positiv', so können Tumorzellen in der Probe nachgewiesen werden, 'Mit dringendem Verdacht' bedeutet, dass das Vorliegen von bösartigen Zellen sehr wahrscheinlich ist, 'Zweifelhaft', dass das Vorliegen von bösartigen Zellen nicht sicher ausgeschlossen werden kann und 'Negativ' bedeutet, dass keine Tumorzellen vorliegen. Anhand der Einteilung kann dann über das weitere Vorgehen entschieden werden. Die Ergebnisse der Studie zeigen das Vorliegen einer hohen Sensitivität und Spezifität der flüssigkeitsbasierten oralen Bürstenbiopsie. Sie ist nicht-invasiv und schnell und einfach durchzuführen und eignet sich daher optimal als Screening-Methode für das orale Plattenepithelkarzinom.:1. Einführung 1.1 Tumorentstehung 1.2 Risikofaktoren 1.3 Orale Bürstenbiopsie 1.4 Adjuvante Untersuchungsmethoden 1.4.1 DNA-Zytometrie 1.4.2 Intraorale Skalpellbiopsie mit histopathologischer Untersuchung 1.5 TNM-System 1.6 Zielsetzung und Fragestellung 2. Publikationsmanuskript 3. Zusammenfassung der Arbeit 4. Literatur 5. Darstellung des eigenen Beitrags 6. Erklärung über die eigenständige Abfassung der Arbeit 7. Lebenslauf 8. Danksagung

The following is a study to determine if sufficient demand exists to start a Bachelor of Science and Master of Science degree program in dental hygiene through a joint agreement for completion degrees between Valencia Community College and the University of Central Florida. To accomplish this objective two survey instruments were administered to randomly selected licensed dentists and dental hygienists in the state of Florida. Dental hygienists represented the potential student base for the proposed programs, and dentists represented the potential and prospective employers of graduated students of the proposed programs. To determine demand and demand characteristics, one survey instrument was mailed to 1,000 dental hygienists who were randomly selected using SAS software from a population of N=12,066 dental hygienists actively licensed to practice in the state of Florida. This sample of hygienists was approximately 8.3% of the total population. Of the 1,000 samples, 134 (or 13.4%) were returned. Of the 134 surveys returned, 123 (n=123) were included in this study. Eleven surveys were not included because of a majority of missing data or because the respondent indicated he or she already possessed a Bachelor or Master degree. A Likert-scale questionnaire was sent to each group of actively licensed dentists and actively licensed dental hygienists from the state of Florida. Responses from dental hygienists were overwhelmingly positive towards the addition of the Bachelor of Science degree program with an online distance-learning component. Those in favor of the Bachelor of Science degree program also provided a favorable response towards adding a Master of Science degree program in dental hygiene. The dentists, as potential future employers, also showed strong support in their responses for the additional degree programs with an additional management track component and believed it would elevate the professional standards of the dental hygiene field.

Inledning:Oral cancer är ett allvarligt tillstånd med hög dödlighet, särskilt vid sen diagnostisering. Brasilien är ett av de länder i världen som har högst prevalens och dödlighet i oral cancer och det är den femte vanligaste cancerformen I landet. Ett hjälpmedel för tidig diagnostisering är önskvärd.Syfte:Att utvärdera skillnaden i diagnostisk tillförlitlighet mellan konventionell oral undersökning och användning av multispektralt ljus (Identafi®) som en metod för tidig upptäckt av potentiellt maligna och maligna lesioner i munslemhinnan i en brasiliansk befolkning.Material och metod:Screening av en befolkning med förhöjd risk för att utveckla oral cancer i Goiânia, Goiás, Brasilien, för att upptäcka potentiellt maligna (PML) eller maligna lesioner (ML). Patienter med misstänkta PML eller ML upptäckta under screeningen undersöktes med multispektralt ljus (Identafi®). Tre oberoende observatörer genomförde bedömning med Identafi® och slutgiltig beslut avseende PML/ML togs i konsensus. Biopsier användes som diagnostisk referensstandard. Interobservatörs överensstämmelse beräknades som procentuell överensstämmelse och kappa-värde (κ).Resultat:Undersökning med Identafi® genererade tolv biopsier. Resultaten blev tre sant positiva, fem falskt positiva, två sant negativa och noll falskt negativa. Sensitiviteten beräknades till 0,29. Specificiteten var inte möjlig att beräkna, då det inte fanns några falska negativa resultat. Interobservatörs överensstämmelse för par av observatörer varierade mellan 78-86% och κ-värden mellan 0,46-0,60.Slutsats:Slutsatsen är att multispektralt ljus, Identafi® inte har inga fördelar jämfört med konventionell klinisk undersökning i fråga om diagnostisk träffsäkerhet för PML eller ML. Dock kan det vara till hjälp för en tandläkare eller oral kirurg som stöd i sitt beslutsfattande. Det kan också hjälpa kirurgen att ta en biopsi från det mest misstänkta delen av lesionen. Det finns inte tillräckligt publicerade studier som tyder på att Identafi® kan skilja mellan normal slemhinna och PML eller ML och denna studie bekräftar detta. Användning av Identafi® som ett hjälpmedel vid screening och undersökning för PML eller ML behöver utredas ytterligare, men baserat på denna studie kan Identafi® inte rekommenderas. / Introduction: Oral cancer is a severe condition with high mortality rate, in particular if diagnosed late. Brazil is one of the countries in the world with high prevalence and mortality from oral cancer and it is the fifth most common cancer there. An aid in early detection of oral cancer as an adjunct to health promotion is desirable.Purpose:The aim of this study was to evaluate the diagnostic accuracy of conventional oral examination and the use of multi spectral light (Identafi®) as an approach for early detection of potentially malignant or malignant lesions in the oral mucosa in a Brazilian population.Material and method:Screening of high-risk population in Goiania, Goias, Brazil, for oral potentially malignant lesions (PML) or malignant lesions (ML) as a selection phase. Patients collected from the screening were examined with multi spectral light (Identafi®) to evaluate diagnostic accuracy. Three observers independently assessed all lesions with Identafi® and the final decision if a lesion was present was taken in consensus. Inter observer agreement was calculated as overall agreement and as kappa value (κ). Biopsies were used as diagnostic reference standard.Results:Identafi® generated, from twelve biopsies, three true positive, five false positive, two true negative and zero false negative. Sensitivity was calculated to 0.29 and specificity was not possible to calculate since there were no false negative results.Inter observer agreement for the use of Identafi® was calculated as overall agreement and as kappa value (κ). The overall agreement for the three pairs of observers varied between 78-86% and κ-values between 0.46 and 0.60.Conclusion:The conclusion of this study is that Identafi® does not have any benefits over conventional oral examination in diagnostic accuracy for potentially malignant or malignant lesions in the oral mucosa. It might, however, be an aid for a dentists or oral surgeons that are unsure whether to take a biopsy or not. It can also aid the surgeon when taking a biopsy to take the most suspicious part of the lesion. There are not enough published evidence that Identafi® can discriminate between normal mucosa and PML or ML, and this study confirms previous results. The use of Identafi® as an aid in screening and examination for PML or ML needs further investigation.

CDC73, also known as HRPT2, is a tumour suppressor gene whose expression is lost or downregulated in parathyroid, renal, breast, uterine and gastric cancers. However, the reports regarding the role of CDC73 in oral squamous cell carcinoma (OSCC) are lacking. As part of the Paf1 complex, it remains associated with ribonucleic acid (RNA) polymerase II and is involved in transcript site selection, transcriptional elongation, histone H2B ubiquitination, histone H3 methylation, poly(A) length control and, coupling of transcriptional and posttranscriptional events. It has been reported to negatively regulate cellularproliferation by targeting oncogenes CCND1 (cyclin D1) and MYC (c-Myc). Moreover, it has also been indicated to inhibitβ-catenin-mediated transcription. Taken together, these findings strongly suggest that it contributes to the expression of genes whose products have an important role in the suppression of tumor development and cell death. In this study, we have attempted to study the transcriptional and posttranscriptional regulation of CDC73 and its role in OSCC. The main findings of the present study are listed below. 1. To begin with, the expression analysis of CDC73 was performed both at the RNA and the protein levels by qRT-PCR and IHC, respectively. As expected, a majority of the OSCC samples showed downregulation of CDC73 both at the RNA and the protein levels compared to their normal oral tissues. 2. Loss-of-heterozygosity (LOH), mutation and promoter methylation are the hallmarks of a tumor suppressor gene (TSG). Therefore, to characterize CDC73 as a TSG in OSCC and to look into the mechanisms that could be the cause of CDC73 downregulation in OSCC, LOH, mutation and promoter methylation of CDC73 were studied. The results showed that LOH, mutation and promoter methylation are not the major causes of CDC73 downregulation in OSCC. 3. To identify the alternate mechanisms as the cause of CDC73 downregulation in OSCC, a combination of bioinformatics and molecular approaches were used. The results showed that the upregulation of an inhibitory transcription factor WT1 (Wilms tumor protein 1) and an oncogenic microRNA-155 are the major causes of its downregulation in OSCC. 4. The luciferase reporter assay of SCC131 cells co-transfected with a WT1 construct and a CDC73 promoter construct showed that WT1 over expression represses CDC73 expression in a dose-dependent manner. 5. Due to the presence of zinc fingers in its C-terminal half, WT1 has been found to be a potent transcriptional regulator of genes. Therefore, to determine if WT1 down regulates CDC73 via binding its promoter, the chromatin immunoprecipitation (ChIP) assay was performed. The results showed the binding of WT1 to the CDC73 promoter in vivo. Binding of WT1 to the CDC73 promoter was further confirmed in vitro by the electrophoretic mobility shift assay (EMSA). 6. The 5-aza-2’-deoxycytidine (AZA) treatment of SCC131 cells led to upregulation of WT1 with a concomitant downregulation of CDC73. The COBRA technique demonstrated that the upregulation of WT1 upon the 5-AZA treatment was due to its promoter methylation. 7. To determine if the WT1-mediated reduction of CDC73 expression has a functional relevance in cell growth and proliferation, we knocked down CDC73 expression by transient over expression of WT1 in SCC131 cells and quantitated cell proliferation by the MTT assay. As expected, the results demonstrated that the reduced CDC73 level was associated with an increased cell proliferation. Cotransfection of CDC73 with WT1 in SCC131 cells attenuated the pro-oncogenic effect of WT1 by apoptosis induction. 8. After validating CDC73 as the target of WT1 by bioinformatics and in vitro assays, we quantitated the expression levels of WT1 and CDC73 by qRT-PCR in OSCC samples and their matched normal oral tissue samples. The results showed an inverse correlation between the expression levels of WT1 and CDC73 in a majority of the samples. To exclude the possibility of alternate mechanisms as the cause of CDC73 downregulation in OSCC, we selected a subset of OSCC samples with downregulated level of CDC73 and analysed them for LOH at the CDC73 locus and promoter methylation. Further, some of these OSCC samples were also analyzed for mutations in CDC73. The results showed that these OSCC samples did not have LOH, promoter methylation or any mutation, again validating the fact that CDC73 is a biological target of oncogenic WT1, and the transcriptional repression of CDC73 by WT1 could be a major mechanism for CDC73 downregulation in OSCC. 9. Recent studies have shown that a growing class of noncoding RNAs called microRNAs (miRNAs) is involved in posttranscriptional regulation of genes. There is a growing body of literature supporting the potential role of miRNAs in tumorigenesis. The importance of CDC73 in orchestration of several cellular functions and its role in tumorigenesis make it an attractive candidate for miRNA-mediated regulation of cell growth and proliferation. Using bioinformatics approaches, we identified an oncogenic microRNA-155 (miR-155) that could posttranscriptionally regulate CDC73 expression. 10. Consistent with its oncogenic role, miR-155 was found dramatically upregulated in OSCC samples and was found to be another mechanism for downregulation of CDC73 in a panel of human cell lines and a subset of OSCC samples in the absence of LOH, mutations and promoter methylation. 11. miRNAs regulate posttranscriptional gene expression generally via binding to their cognate sites in the 3’UTR. Therefore, a luciferase reporter construct was made by cloning the 3’UTR of CDC73 downstream to the luciferase reporter gene and the reporter assay was performed. Our experiments clearly indicated that the mature miR-155 regulates CDC73 expression by interacting with its 3’UTR in a site specific manner. 12 Ectopic expression of miR-155 in HEK293 cells dramatically reduced CDC73 levels, enhanced cell viability and decreased apoptosis. Conversely, the delivery of a miR-155 antagonist (antagomir-155) to KB cells over expression miR-155 resulted in increased CDC73 level, decreased cell viability, increased apoptosis and marked regression of engrafts in nude mice. Cotransfection of miR-155 with CDC73 in HEK293 cells abrogated its pro-oncogenic effect. Reduced cell proliferation and increased apoptosis of KB cells were dependent on the presence or absence of the 3’UTR in CDC73. In nutshell, the knockdown of CDC73 expression due to over expression of WT1 and miR-155 not only adds a novelty to the list of mechanisms responsible for its downregulation in different tumors, but the restoration of CDC73 levels by the use of inhibitors to WT1 and antagomir-155 may also have an important role in therapeutic intervention of cancers, including OSCC.

O carcinoma espinocelular oral (CECO) corresponde a aproximadamente 95% das neoplasias malignas que acometem a cavidade oral. Os fatores de risco clássicos incluem o tabagismo e etilismo; no entanto, as disfunções do sistema imune em decorrência do envelhecimento (imunossenescência) na patogênese do CECO são muito pouco estudados. Análises comparativas vêm sendo feitas para melhor caracterização do perfil de pacientes jovens e idosos acometidos pelo CECO, o qual permanece ainda controverso. Vários estudos têm mostrado que os macrófagos associados ao tumor (MATs) no CECO de pacientes idosos exibem um fenótipo M2 (pró-tumoral), com propriedades moduladoras do estroma vascular, promovendo a angiogênese. No entanto, considerando a imunossenescência, não se sabe o perfil de MATs e seus efeitos na angiogenese no CECO afetando pacientes jovens. Assim, este estudo analisou por meio da técnica imunoistoquímica, a frequência e localização de MATs em correlação com a angiogênese, no CECO, afetando pacientes jovens e idosos. Cinquenta e sete biópsias de CECO divididos em 3 grupos (I: <40 anos [n=17]; II: 40-65 anos [n=20]; III: >65 anos [n=20]) foram selecionados para compor o estudo, sendo classificados morfologicamente seguindo às recomendações da OMS (2017). Os grupos I, II e III foram comparados quanto à imunoexpressão de CD68 e CD163 para análise de MATs e de CD34 (vasos sanguíneos) e D2-40 (vasos linfáticos) para avaliação da densidade microvascular (DMV), área microvascular (AMV) e área vascular total (AVT). A análise imunoistoquímica evidenciou similar expressão de CD68 e CD163 nos três grupos (p>0,05). A avaliação da DMV, AMV e AVT sanguínea e linfática também exibiu padrões similares, com predominância significativa (p<0.05) de vasos sanguíneos, nos três grupos analisados. Não houve correlação significativa quando avaliados marcadores macrofágicos e angiogênicos. Nossos resultados mostram um similar perfil de MATs e angiogênese quando comparados os três grupos estudados, sugerindo participação de mecanismos moleculares do microambiente tumoral na manutenção da predominância de macrófagos M2 e vasos sanguíneos no CECO afetando pacientes jovens e idosos / Oral squamous cell carcinoma (OSCC) corresponds to approximately 95% of all cases of oral cavity malignancies. The classic risk factors include smoking and alcoholism; however, immune system dysfunctions due to aging (immunoscencence) in OSCC pathogenesis are poorly studied. Comparative analyzes have been made to better characterize the profile of young and old patients affected by the OSCC, which remains controversial. Several studies have shown that tumor-associated macrophages (TAMs) in OSCC of elderly patients exhibit a pro-tumoral M2 phenotype, with vascular stroma modulating properties, promoting angiogenesis. However, considering immunoscencence, the profile of TAMs and their effects on angiogenesis in OSCC affecting young patients is unknown. Thus, this study analyzed by immunohistochemical technique, the frequency and location of TAMs in correlation with angiogenesis in OSCC affecting young and elderly patients. Fiftyseven biopsies were divided into three groups (I: <40 years [n=17]; II: 40-65 years [n=20]; III: > 65 years [n=20]) and selected to compose this study, being classified morphologically following WHO (2017) recommendations. Groups I, II and III were compared for immunoexpression of CD68 and CD163 for analysis of TAMs, and CD34 (blood vessels) and D2-40 (lymphatic vessels) for evaluation of microvessel density (MVD), microvascular area (MVA) and total vascular area (TVA). Immunohistochemical analysis showed similar expression of CD68 and CD163 in the three groups (p>0.05). The evaluation of blood and lymphatic MVD, MVA and TVA also showed similar patterns, with a significant predominance (p<0.05) of blood vessels in the three groups analyzed. There was no significant correlation when evaluating macrophage and angiogenic markers. Our results show a similar profile of TAMs and angiogenesis when compared to the three groups studied, suggesting participation of molecular mechanisms of the tumor microenvironment in the maintenance of M2-polarized macrophages and blood vessels in OSCC affecting young and elderly patients