Keratocystic odontogenic tumour: An experience in the northeast of Brazil

Introduction. Keratocystic odontogenic tumours raise particular interest, because of their high recurrence rate and association with nevoid basal cell carcinoma syndrome. Objective. To analyze the clinical and histopathological features of all cases diagnosed as keratocystic odontogenic tumour in a Brazilian population. Methods. A total of 64 keratocystic odontogenic tumours, arising in forty-six patients, were evaluated using the following parameters: association with nevoid basal cell carcinoma syndrome, gender, age at first diagnosis, race, anatomical location, symptoms, radiographic features, history of recurrence, association with teeth, and treatment. Results. Keratocystic odontogenic tumours were more frequent among women than men (1:0.84). The mean patient age was 31.5 years (SD: ±16.6). Ten tumours (16.4%) involved the maxilla and 51 (83.6%) the mandible. Swelling (n=12; 46.1%), followed by pain and swelling (n=4; 15.3%), were most common clinical manifestations. A unilocular radiotransparency with well-defined margins was the main radiographic finding (n=29; 87.8%). A significant association was observed between the multilocular radiographic pattern and recurrence (p<0.05, Fisher’s Test). Sixty-one (95.3%) tumours were treated by surgical enucleation followed by bone curettage, and the recurrence rate was 13% (n=6). This study showed that the keratocystic odontogenic tumours relapsed within a mean period of 25-36 months. Conclusion. Despite the results of this study being similar to previous reports found in the literature, it provides an important insight about keratocystic odontogenic tumours in a Brazilian population

Identificação dos transcritos e proteínas glipicans 1, 3 e 5 em carcinoma escamocelular de boca: associação com moléculas Hedgehog e Vegfa

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-03-26T19:18:11Z No. of bitstreams: 1 Caroline Brandi_S Sales Identificação....pdf: 2182912 bytes, checksum: 259ec8612d135428b26583b6a9303dcc (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-03-26T19:18:22Z (GMT) No. of bitstreams: 1 Caroline Brandi_S Sales Identificação....pdf: 2182912 bytes, checksum: 259ec8612d135428b26583b6a9303dcc (MD5)Made available in DSpace on 2015-03-26T19:18:22Z (GMT). No. of bitstreams: 1 Caroline Brandi_S Sales Identificação....pdf: 2182912 bytes, checksum: 259ec8612d135428b26583b6a9303dcc (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilINTRODUÇÃO: A Via Hedgehog (HH) está ativada em algumas neoplasias humanas, incluindo o Carcinoma Escamocelular de Boca (CEB), o qual corresponde a mais de 95% dos casos diagnosticados na cavidade bucal. Os glipicans (GPC) participam como reguladores desta cascata, atenuando (GPC1 e GPC3) ou regulando positivamente (GPC5) a via HH. OBJETIVO: O objetivo deste trabalho foi avaliar o perfil de expressão dos genes GPC1, 3 e 5, associando-os com genes da via HH (SHH, PTCH1 e SMO) e VEGFA, bem como caracterizar a imunoexpressão das proteínas GPC, em CEB. MATERIAL E MÉTODOS: Trinta e um casos de CEB foram submetidas a reações de qPCR para os genes SHH, PTCH1, SMO, VEGFA, GPC1, 3 e 5. O RNA total foi extraído utilizando uma coluna composta por membrana de silica (Rneasy Mini Kit). O DNA complementar foi obtido com auxílio da enzima Superscript Vilo™. As reações de qPCR foram conduzidas no aparelho ViiA™ 7 Real-Time PCR System utilizando o sistema Taqman, sendo a quantificação relativa avaliada pelo método comparativo de Cq (ΔΔCQ). Vinte e seis CEBs, 9 casos de margens tumorais (MAT) e 4 casos de mucosa bucal não neoplásica (MNN) foram submetidos à reação imuno-histoquímica para as proteínas GPC1, GPC3, GPC5, CD105 e MCM3 utilizando o sistema polimérico AdvanceTM ou LSABTM. As análises das proteínas GPC1, 3 e 5 foram realizadas de acordo com os parâmetros semi-quantitativos descritos por Gurgel et al. (2008). O número de células MCM3 positivas e de vasos/mm² (microdensidade vascular- MDV) foram avaliados em 5 campos, sendo a mediana de e intervalo de confiança utilizados para agrupar os CEBs em alto e baixo perfil proliferativo (AP e BP) e alta e baixa MDV, respectivamente. A análise estatística foi realizada utilizando GraphPad Prism versão 6.03. RESULTADOS: Transcritos do gene GPC1 (26; 83,87%); GPC3 (n=22; 70,97%) e GPC5 (n=15; 48,38%) foram observados em CEBs. SHH RNAm foi detectado em 5 CEBs (16,13%). A maioria dos CEBS apresentou expressão gênica de PTCH1 (n=25; 80.6%), SMO (n=26; 83,87%) e VEGFA (n=28; 90,32%). Correlação positiva forte e estatisticamente significante foi demonstrada para GPC5 e PTCH1 (rs=0,60; p=0,02) e entre PTCH1 e VEGFA (rs=0,69; p=0,0003). Imunomarcação citoplasmática e membranar de GPC1 foi observada principalmente em epitélio de MNN (n=4;100%) e MAT (n=9; 100%), enquanto que uma perda de imunomarcação desta proteína foi detectada no parênquima do CEB. A imunoexpressão da proteína GPC3 estava ausente em MNN (n= 4; 100%) e MAT (n=9; 100%). O GPC3 ocorreu na membrana e citoplasma de células do parênquima, observadas principalmente na periferia das ilhas tumorais, predominando o escore 3+ (n=5; 19.23%) entre os CEBs positivos (n=23; 88,46%). Ausência de imunomarcação de GPC5 foi observada em MNN (n=4; 0%) e apenas 2 espécimes de MAT (n=2; 22,22%) apresentaram baixa imunoexpressão, escore 1+. GPC5 citoplasmático em células tumorais positivas predominou o escore 1+ (n=5; 38.46%). Ao mesmo tempo, GPC5 foi detectado em estroma de 13 (50%) CEBs, especialmente em células endoteliais e semelhantes a fibroblastos. A expressão dos genes avaliados foi similar em tumores com AP e BP, assim como foi independente da MDV. CONCLUSÕES: A correlação entre os transcritos GPC5 e PTCH1, bem como a superexpressão das proteínas GPC5 e GPC3 e perda de imunopositividade de GPC1 são consistentes com a participação destas proteoglicanas como reguladoras da via HH em CEB. O perfil de expressão do gene e proteína GPC1 sugere que este glipican pode participa da biologia tumoral como uma proteína supressora tumoral, enquanto GPC3 e GPC5 participariam oncoproteínas. A presença de GPC5 em estroma tumoral (células endoteliais e fibroblastos) pode estar associada a regulação da via HH neste compartimento do microambiente tumoral.INTRODUCTION: The Hedgehog pathway is activated in some human neoplasms, including Oral Squamous Cell Carcinoma (OSCC), which account for more than 95% of all oral cancers diagnosed. Glypicans are involved in the regulation of HH pathway through GPC3 e GPC1 downregulation or/and GPC5 upregulation. AIM: The aim of this study was to evaluate the expression profile of GPC1, 3 and 5 genes, correlating to HH and VEGFA gene, even as to characterize the immunoexpression of these proteins at OSCC. MATERIAL AND METHODS: A total of 31 cases of OSCC were assessed by qPCR for the SHH, PTCH1, SMO, VEGFA, GPC1, GPC3 and GPC5 genes. The total RNA were extracted using silica membrane column (Rneasy Mini Kit). Complementary DNA was obtained using of Superscript ™ Vilo enzyme. The qPCR reactions were performed in VIIA™ 7 Real-Time PCR System using the Taqman enzime, and relative quantification (RQ) was evaluated by the comparative method of Cq (ΔΔCQ). Immunohistochemical reactions for GPC1, GPC3, GPC5, MCM3 and CD105 proteins was performed on twenty-six OSCC, 9 cases of tumor margins (TM) and 4 cases of non-neoplastic oral mucosa (NNM) using AdvanceTM or LSABTM system. The analysis of GPC1, 3 and 5 proteins were conducted according to the semi-quantitative parameters described by Gurgel et al. (2008). The number of MCM3 positive cells and vessels//mm² (microvessel density -MVD) were evaluated in 5-matching areas, and the median and confidence interval being used to group the OSCC in high and low proliferative profile (HP and LP) and high and low MDV, respectively. Statistical analysis were carried out with GraphPad Prism v.6.03. RESULTS: Transcripts of GPC1 (26; 83.87%), GPC3 (n=22; 70.97%) and GPC5 (n=15; 48.38%) genes were observed in OSCC. SHH mRNA was detected in 5 OSCC (16:13%), PTCH1 gene in 25 CEBs (80.6%), SMO in 26 (83.87%) and VEGFA in 28 (90.32%). Strong and statistically significant positive correlation was demonstrated for GPC5 and PTCH1 genes (rs=0.60; p= 0.02) and PTCH1 and VEGFA transcripts (rs = 0.69; p = 0.0003). Cytoplasmic and membrane immunostaining of GPC1 was mainly observed in epithelial MNN (n = 5; 100%) and MAT (n=9; 100%), while a reduction of this protein was detected in parenchymal cells. GPC3 protein were absent in MNN (n = 4; 0%) and MAT (n=9; 0%). The GPC3 occurred in the membrane and cytoplasm of parenchymal cells, mainly observed in the periphery of the tumor islands and the 3+ score was predominat (n=3; 11:56%) in positive OSCC. GPC5 positive tumor cells occurred in the cytoplasm, scored 1+ (n = 5; 38.46%). In addition, GPC5 was detected in the stroma of 13 (50%) OSCC, especially in endothelial and fibroblast cells. The gene expression was similar in tumors with HP and LP, and was independent of MDV. CONCLUSIONS: The correlation between the GPC5 and PTCH1 transcripts, as well the overexpression of GPC5 and GPC3 protein and the loss of GPC1 positive cells are consistent with the participation of these proteoglycans as regulators of HH pathway in OSCC. The gene and protein expression profile of GPC3 indicate that this proteins participates in tumor biology as a tumor suppressor protein, while GPC5 and GPC3 function as oncoproteins. The presence of GPC5 in tumor stroma (endothelial cells and fibroblasts) could be associated with the regulation of the HH pathway in this compartment of the tumor microenvironment

Expressão de componentes da via de sinalização sonic hedgehog ( HHI, PTCH1 e SHH) e VEGF-A em carcinoma escamocelular: associação com imunomarcação de VEGF-A e microdensidade vascular.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2012-06-05T21:22:13Z No. of bitstreams: 1 Caroline Brandi Schlaaepfer Sales Expressao de componentes da via de sinalizacao....pdf: 1798926 bytes, checksum: d4bb00f0a9c879a36a9a0c59bc3a1be8 (MD5)Made available in DSpace on 2012-06-05T21:22:13Z (GMT). No. of bitstreams: 1 Caroline Brandi Schlaaepfer Sales Expressao de componentes da via de sinalizacao....pdf: 1798926 bytes, checksum: d4bb00f0a9c879a36a9a0c59bc3a1be8 (MD5) Previous issue date: 2012Universidade Federal da Bahia. Centro de Pesquisas Gonçalo Moniz. Salvador, Bahia, BrasilOs mecanismos moleculares envolvidos no desenvolvimento do carcinoma escamocelular oral (CECO) ainda são pouco conhecidos. Vias de sinalização que participam do desenvolvimento embrionário, como a via Sonic Hedgehog (SHH), podem estar associadas ao desenvolvimento de tumores e ainda participar da progressão tumoral através do estímulo a angiogênese. Este trabalho teve como objetivo avaliar o perfil de expressão gênica de componentes da via de sinalização SHH, Sonic Hedegehog (SHH), Patched 1 (PTCH1) e Hedgehog interacting protein (HHIP), que possam estar relacionados a angiogênese em CECO, bem como os níveis de expressão do vascular endothelial growth factor (VEGF-A) e a microdensidade vascular (MDV) nestes tumores. Após aprovação do CEP (Parecer 229/10), a casuística foi composta por 66 casos de CECO no total. Para as reações de PCR quantitativo (qPCR) foram utilizadas amostras criopreservadas de 50 casos de CECOs, 8 casos de Mucosa Adjacente ao Tumor (MAT) e 2 casos de Mucosa Não Neoplásica de paciente saudável (MNN). Após extração de RNA, o DNA complementar foi obtido com o auxílio de High-Capacity cDNA Reverse-Transcription. As reações de qPCR foram conduzidas no aparelho ABI Prism 7900 utilizando o sistema Taqman, sendo a quantificação relativa avaliada pelo método comparativo de Cq (ΔΔCQ). Foram utilizados 56 blocos parafinizados para a confecção do tissue microarray (TMA) e análise da expressão de proteínas VEGF-A e CD34 (MDV), utilizando sistema EnVision AdvancedTM . Foi detectada expressão de HHIP e PTCH1 em CECO e MAT indicando ativação da via SHH nestas lesões. Dezessete (34%) casos de CECO não apresentaram expressão de SHH, os outros 33 (66%) tumores expressaram tal gene, indicando que a ativação desta via de sinalização pode ser através ou não do ligante. Correlação positiva foi observada entre a expressão de SHH e HHIP (rs=0.29; p=0.044, Teste de Spearman) e SHH e PTCH1 (rs=0.49; p=0.0003, Teste de Spearman) em CECO. A correlação positiva entre SHH e VEGF-A (rs=0.37; p=0.0086; Teste de Spearman) sugere uma participação da via SHH na angiogênese em CECOs, ao mesmo tempo maiores níveis de expressão de VEGFA, parecem favorecer um aumento da densidade de vasos sanguíneos (rs=0.55;p=0.0050; Teste de Sperman). Maiores níveis de transcritos e da proteína VEGF-A estavam relacionados a CECOs com invasão perineural e moderadamente diferenciados. Por último, maior expressão de VEGF-A foi detectada em MAT (p=0.034, Teste de Mann Whitney). Assim, a correlação positiva entre a expressão gênica de SHH e VEGF-A indica esta via pode participar da angiogênese tumoral. Além disso, isoladamente, a expressão do gene VEGF-A foi o fator que mais contribui para uma maior MDV e uma maior expressão deste, em nível de transcrito e de proteína, esteve relacionado a CECO de comportamentos mais agressivos. A expressão de HHIP, PTCH1 e VEGF-A em MAT indica que via SHH pode estar ativada nas margens tumorais e, corrobora para a existência de um campo de cancerização que envolve tecidos fenotipicamente normais. Além disso, maior expressão de VEGF-A nesta localização, sugere que a margem tumoral pode participar na secreção de fatores de crescimento para o tumor.Sonic Hedgehog (SHH) signaling has been implicated in tumor development and progression by stimulating angiogenesis, and its molecular mechanisms involving these events are little known in oral squamous cell carcinomas (OSCC). The aim of this study was to characterize the transcripts expression involved in the SHH pathway (SHH, PTCH1, HHIP, VEGF-A) and microvessel density in these neoplasms. In this study, a total of 50 CECOs, eight non-tumor epithelium adjacent to oral cancer (NTEA), and two oral mucosa obtained from healthy individuals were included. After RNA extraction, complementary DNA was obtained using the High-Capacity cDNA Reverse-Transcriptio. qPCR reactions were conducted in the ABI Prism 7900 using Taqman Gene Expression System. Cq (ΔΔCQ) relative quantification method was perfomed for gene expression analysis. Fifty six paraffin-embedded specimens of OSCC were used for tissue microarray (TMA) and by immunohistochemistry, VEGF and CD34 using EnVision System Advanced TM were used. HHIP and PTCH1 transcripts were detected in OSCC and NTEA indicating their SHH pathway activation. Seventeen (34%) OSCC cases were negative for SHH gene expression. This results indicate that activation of SHH pathway may be either through SHH ligand or not. Our results showed a positive correlation between SHH and HHIP (rs=0.29; p=0.044, Spearman test) and SHH and PTCH1 (rs=0.49; p=0.0003, Spearman test) gene expression in OSCC. The positive correlation between the expression of SHH and VEGF-A (rs=0.37; p=0.0086; Spearman test) suggests an involvement of the SHH pathway on angiogenesis of OSCC, whereas higher levels of VEGF-A expression seems to increase the microvessel density of OSCC (rs=0.55;p=0.0050; Sperman test). Higher levels of transcripts and VEGF-A protein were related to OSCC with perineural invasion and those moderately differentiated. Finally, increased expression of VEGF-A was detected in NTEA (p = 0.034, Mann Whitney test). Thus, the positive correlation between the gene expression of SHH and VEGF-A indicates that pathway could participate in tumor angiogenesis. Moreover, VEGF-A gene expression was the only factor that contributed to a greater MVD in our series. In addition, increased expression of this gene and protein was related to more aggressive behavior of OSCC. The expression of HHIP, PTCH1 and VEGF-A in NTEA also indicates that SHH pathway can be activated in the tumor margins and might suggest existence of a field cancerization involving phenotypically normal cells. At the same time, increased gene expression of VEGF-A in this location suggests that adjacent cells to oral cancer could actively participate in the secretion of important growth factors to the tumor developing

Srpski Arhiv za Celokupno Lekarstvo

p. 291-297Introduction. Keratocystic odontogenic tumours raise particular interest, because of their high recurrence rate and association with nevoid basal cell carcinoma syndrome. Objective. To analyze the clinical and histopathological features of all cases diagnosed as keratocystic odontogenic tumour in a Brazilian population. Methods. A total of 64 keratocystic odontogenic tumours, arising in forty-six patients, were evaluated using the following parameters: association with nevoid basal cell carcinoma syndrome, gender, age at first diagnosis, race, anatomical location, symptoms, radiographic features, history of recurrence, association with teeth, and treatment. Results. Keratocystic odontogenic tumours were more frequent among women than men (1:0.84). The mean patient age was 31.5 years (SD: ±16.6). Ten tumours (16.4%) involved the maxilla and 51 (83.6%) the mandible. Swelling (n=12; 46.1%), followed by pain and swelling (n=4; 15.3%), were most common clinical manifestations. A unilocular radiotransparency with well-defined margins was the main radiographic finding (n=29; 87.8%). A significant association was observed between the multilocular radiographic pattern and recurrence (p<0.05, Fisher’s Test). Sixty-one (95.3%) tumours were treated by surgical enucleation followed by bone curettage, and the recurrence rate was 13% (n=6). This study showed that the keratocystic odontogenic tumours relapsed within a mean period of 25-36 months. Conclusion. Despite the results of this study being similar to previous reports found in the literature, it provides an important insight about keratocystic odontogenic tumours in a Brazilian population

Journal of Molecular Histology

Trabalho completo: acesso restrito, p.269–275Keratocystic odontogenic tumor (KOT) is a benign cystic tumor that affects the jaw bones and may be associated with the nevoid basal cell carcinoma syndrome (NBCCS). Twenty-five cases diagnosed as KOT, including primary and recurrent tumors and those associated with NBCCS, were submitted to immunohistochemical study for analysis of cytokeratins (CKs) 7, 8, 10, 13, 14, 18 and 19. The results showed CK13 immunostained on the intermediate layers and upper cells. CK14 was expressed in all epithelial layers and in those areas where inflammation and subepithelial splits were present; this protein was preserved within the basal cells. CK 18 was expressed mainly in the basal layer, whereas CK19 was expressed mainly on the intermediate and superficial layers. The remaining CKs tested were not immuoreactive. The status of maturation of cytokeratin seems to be altered on KOTs, and this is not distinct when different tumors are compared

Altered expression of cytokeratins in primary, recurrent and syndrome keratocystic odontogenic tumors.

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2015-06-17T14:21:06Z No. of bitstreams: 1 Santos JN Altered expression....pdf: 332259 bytes, checksum: cabe5a7981bb691f423b52719e8a2f82 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2015-06-17T16:45:18Z (GMT) No. of bitstreams: 1 Santos JN Altered expression....pdf: 332259 bytes, checksum: cabe5a7981bb691f423b52719e8a2f82 (MD5)Made available in DSpace on 2015-06-17T16:45:18Z (GMT). No. of bitstreams: 1 Santos JN Altered expression....pdf: 332259 bytes, checksum: cabe5a7981bb691f423b52719e8a2f82 (MD5) Previous issue date: 2009Federal University of Bahia. School of Dentistry. Laboratory of Oral Surgical Pathology. Department of Oral Pathology. Salvador, BA, BrasilFederal University of Bahia. School of Dentistry. Laboratory of Oral Surgical Pathology. Department of Oral Pathology. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia e Biologia Molecular. Salvador, BA, BrasilFederal University of Bahia. School of Dentistry. Laboratory of Oral Surgical Pathology. Department of Oral Pathology. Salvador, BA, BrasilFederal University of Bahia. School of Dentistry. Laboratory of Oral Surgical Pathology. Department of Oral Pathology. Salvador, BA, BrasilFederal University of Bahia. School of Dentistry. Laser Center. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Laboratório de Patologia e Biologia Molecular. Salvador, BA, BrasilKeratocystic odontogenic tumor (KOT) is a benign cystic tumor that affects the jaw bones and may be associated with the nevoid basal cell carcinoma syndrome (NBCCS). Twenty-five cases diagnosed as KOT, including primary and recurrent tumors and those associated with NBCCS, were submitted to immunohistochemical study for analysis of cytokeratins (CKs) 7, 8, 10, 13, 14, 18 and 19. The results showed CK13 immunostained on the intermediate layers and upper cells. CK14 was expressed in all epithelial layers and in those areas where inflammation and subepithelial splits were present; this protein was preserved within the basal cells. CK 18 was expressed mainly in the basal layer, whereas CK19 was expressed mainly on the intermediate and superficial layers. The remaining CKs tested were not immuoreactive. The status of maturation of cytokeratin seems to be altered on KOTs, and this is not distinct when different tumors are compared

Elastin Accumulation in Actinic Cheilitis with Different Degrees of Epithelial Dysplasia / Acumulación de Elastina en Queilitis Actínica con Diferentes Grados de Displasia Epitelial

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2012-12-17T21:18:02Z No. of bitstreams: 1 Araújo, Caliandra Pinto et al. Elastin Accumulation in Actinic....pdf: 418478 bytes, checksum: f41130e5776925b00a557850a7f1b9b9 (MD5)Made available in DSpace on 2012-12-17T21:18:02Z (GMT). No. of bitstreams: 1 Araújo, Caliandra Pinto et al. Elastin Accumulation in Actinic....pdf: 418478 bytes, checksum: f41130e5776925b00a557850a7f1b9b9 (MD5) Previous issue date: 2012Universidade Federal da Bahia. School of Dentistry. Salvador, BA, BrasilUniversidade Federal da Bahia. School of Dentistry. Salvador, BA, BrasilUniversidade Federal da Bahia. School of Dentistry. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversity of Feira de Santana. Feira de Santana, BA, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal da Bahia. School of Dentistry. Salvador, BA, BrasilUniversidade Federal da Bahia. School of Dentistry. Salvador, BA, BrasilLa matriz extracelular (MEC) juega un papel importante en la regulación de los eventos biológicos, tales como, el desarrollo de la migración celular, proliferación y diferenciación. La exposición solar crónica provoca cambios presentes en la MRC de la queilitis actínica (QA), una lesión premaligna del labio inferior que contribuye a entender la carcinogénesis del labio. Este estudio tuvo como objetivo investigar la elastina, el componente principal de la elastosis solar en corriente alterna en un intento de establecer la relación entre esta proteína y la MEC en displasia epitelial. Se incluyeron en parafina cortes de tejido de las lesiones de 35 casos de QC fueron analizadas mediante técnicas de inmunohistoquímica para elastina, y se hizo la asociación con los grados de displasia epitelial y la edad. La más alta puntuación de la elastina (+3) fue predominante en el 45,7% de los casos de QA, especialmente en los casos de displasia severa (n = 3). Al comparar las puntuaciones de elastina entre los diferentes grados de displasia epitelial, no mostró diferencia significativa (P> 0,05, Kruskall-Wallis). Este estudio no fue capaz de demostrar la influencia de la elastina sobre gravedad de la displasia epitelial en QA. Estudios adicionales sobre otras proteínas de la MEC deben llevarse a cabo en un intento por comprender mejor el mecanismo de progresión maligna de la QCThe extracellular matrix (ECM) plays an important role in the regulation of biological events such as the development of cell migration, proliferation and differentiation. Chronic sun exposure causes changes present in the ECM of actinic cheilitis (AC), a premalignant lesion of the lower lip which helps to understand the carcinogenesis of the lip. This study aimed to investigate elastin, the main component of solar elastosis alternating current in an attempt to establish the relationship between this protein and ECM in epithelial dysplasia. Paraffin embedded tissue sections of the lesions of 35 cases of AC were analyzed by immunohistochemistry for elastin, and became the association with the degree of epithelial dysplasia and age. Highest scores of elastin (+3) was predominant in 45.7% of cases of AC, especially in cases of severe dysplasia (n = 3). When comparing the scores of elastin between the different grades of epithelial dysplasia showed no significant difference (P> 0.05, Kruskal-Wallis). This study was not able to demonstrate the influence of elastin on the severity of epithelial dysplasia in AC. Additional studies on other ECM proteins must be conducted in an attempt to better understand the mechanism of malignant progression of the A

Tumor Biology

Texto completo: acesso restrito. p. 455-461The aim of this study was to investigate the presence of mast cells in a series of odontogenic tumors. Forty-five cases of odontogenic tumors were investigated using immunohistochemistry for mast cell triptase, and differences between groups were statistically evaluated. Mast cells were present in 96% of odontogenic tumors. Mast cells present in solid ameloblastoma were observed in the tumor stroma surrounding more solid and follicular epithelial islands, with or without squamous metaplasia. The odontogenic mixoma showed few mast cells. In odontogenic tumors with a cystic structure, the mast cells were distributed throughout all areas of the lesions, mainly in keratocystic odontogenic tumor. In addition, the total density of mast cells between all odontogenic tumors showed no significant difference (p > 0.05). A greater mast cells distribution was found in keratocystic odontogenic tumor in relation to adenomatoid odontogenic tumor (p < 0.01), and when the unicystic ameloblastoma and keratocistic odontogenic tumor were compared to the odontogenic myxoma (p < 0.05). Syndrome keratocystic odontogenic tumor showed a higher mean of mast cells when compared with the other tumors of the sample. Mast cells values presented by syndrome keratocystic odontogenic tumor were significantly greater than those of the sporadic keratocystic odontogenic tumor that were not associated with the syndrome (p = 0.03). Mast cells are probably one of the major components of the stromal scaffold in odontogenic tumors. We found significant differences of mast cells between syndrome nonsyndrome keratocystic odontogenic tumors, although their distribution did not seem to have any influence on the biologic behavior of benign odontogenic tumors

Ruthenium(II) complexes with 6-methyl-2-thiouracil selectively reduce cell proliferation, cause DNA double-strand break and trigger caspase-mediated apoptosis through JNK/p38 pathways in human acute promyelocytic leukemia cells

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2019-10-08T14:08:30Z No. of bitstreams: 1 Bomfim M, l. Ruthenium (II).pdf: 5950873 bytes, checksum: 69b76d29b685a484dd9c71691535be5e (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2019-10-08T14:32:30Z (GMT) No. of bitstreams: 1 Bomfim M, l. Ruthenium (II).pdf: 5950873 bytes, checksum: 69b76d29b685a484dd9c71691535be5e (MD5)Made available in DSpace on 2019-10-08T14:32:30Z (GMT). No. of bitstreams: 1 Bomfim M, l. Ruthenium (II).pdf: 5950873 bytes, checksum: 69b76d29b685a484dd9c71691535be5e (MD5) Previous issue date: 2019-01-07Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Federal University of Bahia. Institute of Health Sciences. Department of Biomorphology. Salvador, BA, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Federal University of Ouro Preto. Department of Chemistry. Ouro Preto, MG, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Federal University of São Carlos. Department of Chemistry. São Carlos, SP, Brazil.Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil.Ruthenium(II) complexes with 6-methyl-2-thiouracil cis-[Ru(6m2tu)2(PPh3)2] (1) and [Ru(6m2tu)2(dppb)] (2) (where PPh3 = triphenylphosphine; dppb = 1,4-bis(diphenylphosphino)butane; and 6m2tu = 6-methyl-2-thiouracil) are potent cytotoxic agents and able to bind DNA. The aim of this study was to evaluate in vitro cellular underlying mechanism and in vivo effectiveness of these ruthenium(II) complexes in human acute promyelocytic leukemia HL-60 cells. Both complexes displayed potent and selective cytotoxicity in myeloid leukemia cell lines, and were detected into HL-60 cells. Reduction of the cell proliferation and augmented phosphatidylserine externalization, caspase-3, -8 and -9 activation and loss of mitochondrial transmembrane potential were observed in HL-60 cells treated with both complexes. Cotreatment with Z-VAD(OMe)-FMK, a pan-caspase inhibitor, reduced Ru(II) complexes-induced apoptosis. In addition, both metal complexes induced phosphorylation of histone H2AX (S139), JNK2 (T183/Y185) and p38α (T180/Y182), and cotreatment with JNK/SAPK and p38 MAPK inhibitors reduced complexes-induced apoptosis, indicating DNA double-strand break and activation of caspase-mediated apoptosis through JNK/p38 pathways. Complex 1 also reduced HL-60 cell growth in xenograft model. Overall, the outcome indicated the ruthenium(II) complexes with 6-methyl-2-thiouracil as a novel promising antileukemic drug candidates

Asociaci n entre las Caracter sticas Radiogr ficas y la Proliferaci n Celular en el Tumor Odontog nico Queratoqu stico

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-02T19:25:35Z No. of bitstreams: 1 Sales S Association between radiographic....pdf: 468490 bytes, checksum: e1f5f912ce4ca657bdbfab8ed3ccb24a (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-02T19:37:45Z (GMT) No. of bitstreams: 1 Sales S Association between radiographic....pdf: 468490 bytes, checksum: e1f5f912ce4ca657bdbfab8ed3ccb24a (MD5)Made available in DSpace on 2018-04-02T19:37:45Z (GMT). No. of bitstreams: 1 Sales S Association between radiographic....pdf: 468490 bytes, checksum: e1f5f912ce4ca657bdbfab8ed3ccb24a (MD5) Previous issue date: 2015Fundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biologia Molecular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biologia Molecular. Salvador, BA, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biologia Molecular. Salvador, BA, BrasilFederal University of Bahia. School of Dentistry. Laboratory of Oral Surgical Pathology. Salvador, BA, BrazilFederal University of Bahia. School of Dentistry. Laboratory of Oral Surgical Pathology. Salvador, BA, BrazilFederal University of Bahia. School of Dentistry. Laboratory of Oral Surgical Pathology. Salvador, BA, BrazilFederal University of Bahia. School of Dentistry. Department of Oral Radiology. Salvador, BA, BrazilFundação Oswaldo Cruz. Centro de Pesquisa Gonçalo Moniz. Laboratório de Patologia e Biologia Molecular. Salvador, BA, Brasil / Federal University of Bahia. School of Dentistry. Laboratory of Oral Surgical Pathology. Salvador, BA, BrazilLas caracter sticas radiogr ficas de una lesi n intra sea se asocian generalmente con el comportamiento biol gico del tumor. Debido a esto, el crecimiento y comportamiento de los tumores odontog nicos queratoqu sticos se asocian principalmente con la proliferaci n del epitelio qu stico. El objetivo del estudio fue evaluar la relaci n entre los marcadores de proliferaci n celular y las caracter sticas radiol gicas de este tumor. Se escanearon y evaluaron 37 radiograf as de tumores odontog nicos queratoqu sticos obtenidos de 30 pacientes y las secciones de sus biopsias fueron sometidas a evaluaci n inmunohistoqu mica para las prote neas Ki-67, p63 y p53 en un sistema Envisionª. Se observaron 31 tumores odontog nicos queratoqu sticos en el rea posterior de la mand bula, con predominio del aspecto unilocular (n= 26). Diecinueve tumores odontog nicos queratoqu sticos distorsionaron el canal mandibular y se observaron 11 dientes desplazados. Los quistes sat lites se asociaron con el aspecto multilocular (P= 0,016). La distribuci n de c lulas positivas para Ki-67, p63 y p53 fue similar entre tumores odontog nicos queratoqu sticos con aspectos uniformes y multiloculares, y no estaban relacionadod con la distorsi n del canal mandibular (P>0,05) o con el desplazamiento del diente (P>0,05). Los resultados del presente estudio sugieren que la proliferaci n celular en tumores odontog nicos queratoqu sticos contribuye a las caracter sticas radiogr ficas de este tumor.The radiographic features of an intraosseous lesion are usually associated with the biological behavior of the tumor. In view of the fact that the growth and behavior of keratocystic odontogenic tumors (KCOT) is mainly associated with the proliferation of the cystic epithelium, the objective of the present study was to evaluate the relationship between cell proliferation markers and radiographic features of this tumor. Thirty-seven radiographs of KCOT obtained from 30 patients were scanned and evaluated on a monitor. Sections were submitted to immunohistochemistry for Ki-67, p63, and p53 proteins on an EnVisionª system. Thirty-one KCOTs were observed in the posterior of the mandible, and the unilocular aspect was predominant (n= 26). Nineteen KCOTs distorted the mandibular canal and 11 displaced teeth. Satellite cysts were associated with a multilocular aspect (P= 0.016). p53 was in KCOTS with diffuse margins (p=0.049), p63 with NBCCS (p=0.049) KOT and higher KI-67 positive cells was observed in KCOTs presenting distortion of the mandibular canal (p=0.042). The distribution of Ki-67, p63, and p53 positive cells was similar between KCOTs with uni- and multilocular aspects. The results of the present study suggest that cell proliferation in KCOT contributes to the radiographic features of this tumor