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Introduction: Bone metastasis is one of the causes that mainly decrease survival in patients with advanced breast cancer. Therefore, it is essential to find prognostic markers for the occurrence of this type of metastasis during the early stage of the disease. Currently, cancer-associated fibroblasts, which represent 80% of the fibroblasts present in the tumor microenvironment, are an interesting target for studying new biomarkers and developing alternative therapies. This study evaluated the prognostic significance of the CD105 expression in cancer-associated fibroblasts in early breast cancer patients. Methods: Immunohistochemistry was used to assess CD105 expression in invasive ductal breast carcinomas (n = 342), analyzing its association with clinical and pathological characteristics. Results: High CD105 expression in cancer-associated fibroblasts was associated with an increased risk of metastatic occurrence (p = 0.0003), particularly bone metastasis (p = 0.0005). Furthermore, high CD105 expression was associated with shorter metastasis-free survival, bone metastasis-free survival, and overall survival (p = 0.0002, 0.0006, and 0.0002, respectively). CD105 expression also constituted an independent prognostic factor for metastasis-free survival, bone metastasis-free survival, and overall survival (p = 0.0003, 0.0006, and 0.0001, respectively). Discussion: The high CD105 expression in cancer-associated fibroblasts is an independent prognostic marker for bone metastasis in early breast cancer patients. Therefore, the evaluation of CD105(+) CAFs could be crucial to stratify BCPs based on their individual risk profile for the development of BM, enhancing treatment strategies and outcomes.
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Cancer is one of the diseases with the highest morbidity and mortality rates worldwide, and its therapeutic options are inadequate. The endothelial glycoprotein, also known as CD105, is a type I transmembrane glycoprotein located on the surface of the cell membranes and it is one of the transforming growth factor-ß (TGF-ß) receptor complexes. It regulates the responses associated with binding to transforming growth factor ß1 egg (Activin-A), bone morphogenetic protein 2 (BMP-2), and bone morphogenetic protein 7 (BMP-7). Additionally, it is involved in the regulation of angiogenesis. This glycoprotein is indispensable in the treatment of tumor angiogenesis, and it also plays a leading role in tumor angiogenesis therapy. Therefore, CD105 is considered to be a novel therapeutic target. In this study, we explored the significance of CD105 in the diagnosis, treatment and prognosis of various tumors, and provided evidence for the effect and mechanism of CD105 on tumors.
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Neoplasias , Receptores de Superfície Celular , Antígenos CD , Endoglina , Humanos , Neoplasias/diagnóstico , Neoplasias/terapia , Neovascularização Patológica/patologia , Prognóstico , Fator de Crescimento Transformador beta/metabolismoRESUMO
Objective: The present study evaluated the profile of endoglin (CD105) and vascular endothelial growth factor (VEGF) based on staging and histopathological grading of colorectal cancer as well as their relationship with bevacizumab therapy. Methods: A total of 88 cases of colorectal adenocarcinoma were included in the present study. The levels of VEGF and CD105 protein were evaluated with enzymelinked immunosorbent assay (ELISA). Results: There was a significant difference in the level of CD105 (p=0.002) between metastases and non-metastases subjects, showing that CD105 was higher in metastases subjects (4.59 ng/ml). Therewas no significant difference in the level of VEGF based on the presence of metastasis (p=0.625). There was a significant difference in the levels of CD105 (p=0.038) and VEGF (p=0.010) between the subjects who received chemotherapy and those who did not. The CD105 level was higher in the subjects who received chemotherapy (4.43 ng/ml); conversely, the level of VEGF was lower in subjects who received chemotherapy (543.65 pg/ml). There was a statistically significant difference in the levels of CD105 (p=0.003) and VEGF (p=0.002) between subjects who received bevacizumab therapy and subjects who did not. The levels of CD105 were higher in subjects who received bevacizumab therapy (5.11 ng/ml); in contrast, the level of VEGF was higher in subjects who did not receive bevacizumab therapy (645.92 pg/ml). There was a significant positive correlation between CD105 and VEGF in subjects who did not receive bevacizumab (p<0.01). Conclusion: The results of this study support a hypothesis of "escape mechanism" in the failure of anti-angiogenesis therapy (anti-VEGF). (AU)
Objetivo: Este estudo avaliou o perfil da endoglina (CD105) e do fator de crescimento endotelial vascular (FCEV) com base no estadiamento e graduação histopatológica do câncer colorretal, assim como sua relação com a terapia com bevacizumabe. Métodos: No total, 88 casos de adenocarcinoma colorretal foram incluídos no presente estudo. Os níveis das proteínas FCEV e CD105 foram avaliados com ensaio imunoenzimático (ELISA, na sigla em inglês). Resultados Houve uma diferença significativa no nível de CD105 (p=0,002) entre indivíduos commetástases e semmetástases, que indicou que o nível de CD105 émais alto em indivíduos com metástases (4,59 ng/ml). Não houve diferença significativa no nível de FCEV com base na presença de metástases (p=0,625). Houve diferença significativa nos níveis de CD105 (p=0,038) e de FCEV (p=0,010) entre os indivíduos que receberam quimioterapia e os que não receberam. Encontrou-se um nível de CD105 mais alto nos indivíduos que submetidos a quimioterapia (4,43 ng/ml); Em contrapartida, encontrou-se um nível de FCEV mais baixo em indivíduos que submetidos a quimioterapia (543,65 pg/ml). Houve uma diferença estatisticamente significativa nos níveis de CD105 (p=0,003) e de FCEV (p=0,002) entre os indivíduos submetidos e não submetidos à terapia com bevacizumabe. Os níveis de CD105 foram mais elevados em indivíduos submetidos à terapia combevacizumab (5,11 ng/ml); em contraste, observou-se um nível de FCEV mais alto em indivíduos que não foram submetidos à terapia com bevacizumabe (645,92 pg/ml). Houve uma correlação positiva significativa entre CD105 e FCEV em indivíduos que não receberam bevacizumabe (p<0.01). Conclusão: Os resultados deste estudo corroboram a hipótese de "mecanismo de escape" na falha da terapia anti-angiogênica (anti-FCEV). (AU)
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Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Neoplasias Colorretais/tratamento farmacológico , Adenocarcinoma , Receptores de Fatores de Crescimento do Endotélio Vascular , Bevacizumab/uso terapêutico , Metástase NeoplásicaRESUMO
BACKGROUND: The generation of functional human epidermal melanocytes (HEM) from stem cells provides an unprecedented source for cell-based therapy in vitiligo. Despite the important efforts exerted to obtain melanin-producing cells from stem cells, pre-clinical results still lack the safety and scalability characteristics essential for their translational application. METHODS: Here, we report a rapid and efficient protocol based on defined culture conditions capable of differentiating adult adipose-derived stem cells (ADSC) to scalable amounts of proliferative melanocyte precursors (PreMel) within 30 days. PreMel were characterized in vitro through qPCR, Western blot, flow cytometry, biochemical assays, and in vivo assays in immunocompromised mice (NOD.Cg-Prkdcscid Il2rgtm1Wjl/SzJ, or NSG). RESULTS: After 30 days of differentiation, the stem cell-derived PreMel were defined as CD105neg CD73low according to immunophenotypic changes in comparison with parental stem cell markers. In addition, expression of microphthalmia-associated transcription factor (MITF), active tyrosinase (TYR), and the terminal differentiation-involved premelanosome protein (PMEL) were detected. Furthermore, PreMel had the potential to synthesize melanin and package it into melanosomes both in vitro and in vivo in NSG mice skin. CONCLUSIONS: This study proposes a rapid and scalable protocol for the generation of proliferative melanocyte precursors (PreMel) from ADSC. These PreMel display the essential functional characteristics of bona fide HEM, opening a new path for an autologous cellular therapy for vitiligo patients.
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Tecido Adiposo/citologia , Diferenciação Celular , Melanócitos/metabolismo , 5'-Nucleotidase/metabolismo , Adolescente , Adulto , Animais , Linhagem da Célula , Endoglina/metabolismo , Feminino , Humanos , Melaninas/metabolismo , Melanócitos/citologia , Melanócitos/transplante , Camundongos , Camundongos Endogâmicos NOD , Fator de Transcrição Associado à Microftalmia/metabolismo , Pessoa de Meia-Idade , Monofenol Mono-Oxigenase/metabolismo , Pele/patologia , Células-Tronco/citologia , Células-Tronco/metabolismo , Vitiligo/patologia , Vitiligo/terapia , Adulto Jovem , Antígeno gp100 de Melanoma/metabolismoRESUMO
Introdução: a endoglina (ENG, CD105) é um co-receptor da família transforming growth factor-beta e participa da regulação de processos celulares como proliferação, diferenciação, migração e apoptose. ENG é mais conhecida por sua expressão em células endoteliais, desempenhando papel importante na angiogênese e vasculogênese, porém sua expressão já foi associada a diferentes desfechos patogênicos, inclusive devido a mutações no gene ENG. Objetivos: descrever a frequência de variantes genéticas no gene ENG, comparar com populações ancestrais e analisar as variantes genéticas que possam estar envolvidas em processos patogênicos em outras populações. Metodologia: foi utilizado o banco de dados do programa SCAALA (Social Change Asthma and Allergy in Latin America) para a população do estudo, sendo genotipado 1309 indivíduos usando o chip Illumina 2.5 Human Omni Bead e feitas análises in silico utilizando plataformas on-line. Resultados: as variantes genéticas rs10987746, rs10121110, rs11792480 e rs16930129 apresentaram frequência de menor alelo entre 16 a 48% na população estudada, as quais foram mais reiteradamente próximas do padrão africano que do europeu. Os SNVs foram relacionados aos mecanismos regulatórios genéticos conhecidos, pressupondo que essas variantes não estejam envolvidas diretamente em processos funcionais. Conclusão: são necessárias maiores investigações referentes aos mecanismos funcionais deste gene, visto que a endoglina participa de uma gama de processos celulares importantes e mais esforços devem ser feitos para estudos genéticos na população brasileira, considerando a mistura de populações.
Introduction: the endoglin (ENG, CD105) is a coreceptor of the family transforming growth factor-beta and participates in the regulation of cellular processes such as proliferation, differentiation, migration and apoptosis. ENG She is best known for your expression in endothelial cells, playing an important role in angiogenesis and vasculogenesis, but its expression has already been associated with different pathogenic outcomes, including due to mutations in the ENG gene. Objectives: describe the frequency of genetic variants in the ENG gene in the population of northeastern Brazil, compare with ancestral populations and analyze genetic variants that may be involved in pathogenic processes in other populations. Methodology: we used the SCAALA program database (Social Change Asthma and Allergy in Latin America) for the population of the study, and the DNA of 1309 individuals were genotyped using the Illumina chip 2.5 Human Omni Bead and made in silico analysis. Results: the SNVs rs10987746, rs10121110, rs11792480 and rs16930129 presented lower allele frequency between 16 to 48% in the population studied, which were more consistently next African European standard. The SNVs were related to known genetic regulatory mechanisms assuming that these variants are not directly involved in functional processes. Conclusion: further investigation regarding the functional mechanisms of this gene are necessary, since the endoglin participates in a range of important cellular processes and more efforts should be made for genetic studies in the Brazilian population, considering the mixture of populations.
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Humanos , Pré-Escolar , Criança , Variação Genética/genética , Polimorfismo de Nucleotídeo Único/genética , Endoglina/genética , Frequência do Gene/genética , Genótipo , BrasilRESUMO
A more accurate understanding of the molecular mechanisms and signaling pathways underpinning human mesenchymal stem cell (MSC) plasticity and differentiation properties is pivotal for accomplishing solid and diligent translation of MSC-based experimental therapeutics and clinical trials to broad clinical practice. In addition, this knowledge enables selection of MSC subpopulations with increased differentiation potential and/or use of exogenous factors to boost this potential. Here, we report that CD105 (ENG) is a predictive biomarker of osteogenic potential in two types of MSCs: stem cells from human exfoliated deciduous teeth (SHED) and human adipose-derived stem cells (hASC). We also validate that CD105 can be used to select and enrich for subpopulations of SHED and hASC with higher in vitro osteogenic potential. In addition, we show that hsa-mir-1287 regulates CD105 expression, and propose that fine-tuning hsa-mir-1287 levels could be used to control osteopotential in SHED. These findings provide better discernment of the molecular bases behind MSC osteogenic plasticity and open up new perspectives to leverage osteogenic potential in MSCs by modulation of a specific miRNA.
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Endoglina/metabolismo , MicroRNAs/metabolismo , Biomarcadores/metabolismo , Diferenciação Celular/efeitos dos fármacos , Diferenciação Celular/genética , Células Cultivadas , Criança , Endoglina/genética , Citometria de Fluxo , Humanos , Imunofenotipagem , Fator de Crescimento Insulin-Like II/farmacologia , MicroRNAs/genética , Osteogênese/genética , Osteogênese/fisiologia , Reação em Cadeia da Polimerase em Tempo Real , Células-Tronco/citologia , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismoRESUMO
OBJECTIVE To investigate immunohistochemical markers of angiogenesis and their association with pathological prognostic features in hepatocellular carcinoma and cirrhotic liver. METHODS Vascular endothelial growth factor, CD105, and cyclooxygenase-2 were immunohistochemically detected in 52 hepatocellular carcinoma tissue samples and 48 cirrhotic liver tissue samples. Semiquantitative measurements of vascular endothelial growth factor and cyclooxygenase-2 were evaluated considering the degree and intensity of immunostaining based on a 7-point final scoring scale. CD105 microvascular density (MVD-CD105) was measured using automated analysis. Morphological aspects evaluated in the hepatocellular carcinoma samples included size (≤2 and >2 cm), differentiation grade, and microvascular invasion. RESULTS The mean vascular endothelial growth factor immunoreactivity score was slightly higher in the hepatocellular carcinoma samples (4.83±1.35) than the cirrhotic liver (4.38±1.28) samples. There was a significant and direct correlation between these mean scores (rs=0.645, p=0.0001). Cyclooxygenase-2 was expressed in all the cirrhotic liver samples but was only found in 78% of the hepatocellular carcinoma samples. The mean cyclooxygenase-2 score was higher in the cirrhotic liver samples (4.85±1.38) than the hepatocellular carcinoma samples (2.58±1.68), but there was no correlation between the scores (rs=0.177, p=0.23). The mean CD105 percentage in the hepatocellular carcinoma samples (11.2%) was lower than that in the cirrhotic samples (16.9%). There was an inverse relationship in MVD-CD105 expression between the hepatocellular carcinoma and cirrhotic samples (rs=-0.78, p=0.67). There were no significant associations between vascular endothelial growth factor expression and morphological characteristics. Cyclooxygenase-2 and CD105 were associated with hepatocellular carcinoma differentiation grade (p=0.003 and p=0.05, respectively). CONCLUSION Vascular endothelial growth factor, cyclooxygenase-2, and MVD-CD105 were highly expressed in cirrhotic liver compared to hepatocellular carcinoma and might be involved in liver carcinogenesis. Additionally, cyclooxygenase-2 and CD105 might be involved in hepatocellular carcinoma differentiation grade.
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Humanos , Masculino , Feminino , Adolescente , Adulto , Pessoa de Meia-Idade , Idoso , Adulto Jovem , Carcinoma Hepatocelular/patologia , Ciclo-Oxigenase 2/metabolismo , Endoglina/metabolismo , Cirrose Hepática/metabolismo , Neoplasias Hepáticas/patologia , Fatores de Crescimento do Endotélio Vascular/metabolismo , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/irrigação sanguínea , Carcinoma Hepatocelular/metabolismo , Endotélio Vascular/metabolismo , Imuno-Histoquímica , Neoplasias Hepáticas/irrigação sanguínea , Neoplasias Hepáticas/metabolismo , Gradação de Tumores , Estatísticas não ParamétricasRESUMO
UNLABELLED: Angiogenesis is a key process for metastatic progression. While it has been established that the evaluation of breast tumoral microvessel density by CD105 marker is a potential prognostic parameter, its evaluation by CD146 marker has been poorly studied. AIM: The purpose of this study was to compare the prognostic value of intra-tumoral microvessel density assayed by CD105 and CD146 in early breast cancer patients. METHODS: 42 women with breast infiltrative ductal carcinoma (I and II-stages) were retrospectively reviewed. Intra-tumoral microvessel density was immunohistochemically examined using antibodies anti-CD105 and CD146 in paraffin-embedded tissues, and their association with classical prognostic-markers, metastatic recurrence, metastasis-free survival and overall survival was analyzed. RESULTS: High microvessel density assessed by CD146 was significantly associated with a higher risk of developing metastasis (p=0.0310) and a shorter metastasis-free survival (p=0.0197). In contrast, when we used the CD105-antibody, we did not find any significant association. Finally, CD146 showed to be an independent predictive indicator for metastasis-free survival (p=0.0055). CONCLUSION: Our data suggest that the intra-tumoral microvessel density evaluated by CD146 may be a more suitable predictor of metastatic development than that evaluated by CD105 in early breast cancer.
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Biomarcadores Tumorais/análise , Neoplasias da Mama/irrigação sanguínea , Carcinoma Ductal de Mama/irrigação sanguínea , Endoglina/análise , Adulto , Neoplasias da Mama/mortalidade , Neoplasias da Mama/patologia , Antígeno CD146/análise , Carcinoma Ductal de Mama/mortalidade , Carcinoma Ductal de Mama/patologia , Feminino , Humanos , Imuno-Histoquímica , Estimativa de Kaplan-Meier , Pessoa de Meia-Idade , Neovascularização Patológica/patologia , Projetos Piloto , Prognóstico , Modelos de Riscos Proporcionais , Estudos RetrospectivosRESUMO
A angiogênese é um mecanismo fundamental para o desenvolvimento tumoral, sendo utilizada para fins de diagnóstico diferencial e determinação de prognóstico em várias neoplasias de cabeça e pescoço. Este trabalho se propôs avaliar a atividade angiogênica através da expressão imuno-histoquímica dos anticorpos anti-CD105 e anti-CD34 em 20 casos de hemangiomas e 20 casos de granulomas piogênicos orais, além de averiguar a utilidade destes marcadores como um dos recursos de diagnóstico diferencial para estas duas lesões orais. Os resultados deste experimento demonstraram que não houve diferença estatisticamente significativa entre as médias de contagem microvascular (MVC) determinadas pelos os anticorpos anti-CD105 (p=0,803) e anti-CD34 (p=0,279). O número médio dos vasos obtidos pela MVC nos espécimes de hemangiomas orais imunomarcados pelo anti-CD105 e anti-CD34 foram respectivamente 18,75 e 59,72, enquanto nos granulomas piogênicos orais, o número médio dos vasos obtidos pela MVC pelo anti-CD105 e anti-CD34 foram respectivamente 20,22 e 48,09. Foi verificado, também, que o CD34 foi mais efetivo na identificação de vasos sangüíneos quando comparado com o CD105. Entretanto, faz-se necessário destacar, que o anticorpo anti-CD105 parece estar mais relacionado com a neoformação vascular. Em linhas gerais, este ensaio reforça a participação dos fatores angiogênicos na etiopatogênese dos hemangiomas e granulomas piogênicos orais, porém os resultados mostraram que a quantificação da angiogênese não pode ser utilizada como parâmetro de diagnóstico diferencial entre as duas lesões analisadas. (AU)
Angiogenesis, a fundamental mechanism in tumor development, is used for differential diagnosis and prognosis purposes in various neoplasias of the head and neck. This study proposes to assess angiogenic activity using immunohistochemical expression by anti-CD105 and anti-CD34 antibodies in 20 cases of hemangiomas and 20 cases of oral pyogenic granulomas, in addition to determining the usefulness of these markers as one of the differential diagnosis resources for these two oral lesions. The results showed no statistically significant difference between microvascular count (MVC) means determined by anti-CD105 (p = 0.803) and anti-CD34 (p = 0.279) antibodies. The mean number of vessels obtained by MVC in the oral hemangiomas immunostained by anti-CD105 and anti-CD34 was 18.75 and 59.72, respectively, whereas in the oral pyogenic granulomas, the mean number was 20.22 and 48.09 respectively. It was also shown that CD34 was more effective than CD105 in identifying blood vessels. However, it must be pointed out that the anti-CD105 antibody seems to be more related to vascular neoformation. Overall, this assay reinforces the role of angiogenic factors in the etiopathogenesis of hemangiomas and oral pyogenic granulomas, but the results showed that angiogenesis quantification cannot be used as a differential diagnosis parameter between the two lesions analyzed. (AU)
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Granuloma Piogênico/patologia , Hemangioma/etnologia , Hemangioma/patologia , Imuno-Histoquímica/métodos , Distribuição de Qui-QuadradoRESUMO
AIM: To evaluate the correlation between the immunoexpression of angiogenic markers [CD31, CD105 and vascular endothelial growth factor (VEGF)], proliferative index (Ki67), and prognosis of patients with gastrointestinal stromal tumors (GIST). METHODS: This is a retrospective study of 54 GIST cases. Medical records were searched to obtain the GIST patients' demographic and clinical data, and paraffin-embedded blocks of tumor samples were retrieved from the hospital archives to conduct a new immunohistochemical evaluation. The tumor samples of GIST patients were subject to immunohistochemical evaluation for endoglin (CD105), CD31, VEGF, and Ki67 expression. The CD105 and CD31 intratumoral microvascular density (IMVD) was measured using automated analysis. We determined the correlation between the immunoexpression of CD105, CD31, VEGF, Ki67 and prognosis. In addition, we conducted a cutoff analysis using the receiver-operating characteristic curve. VEGF positivity was classified as either null/weak or strong. Ki67 was evaluated using a cutoff of 5% positive cells. The prognosis was classified as good (patient alive without recurrence) or poor (patient with recurrence/death). RESULTS: The distribution of tumor sites among the 54 analyzed samples was as follows: 27 (50%) in the stomach, 20 (37.1%) in the small intestine, 6 (11.1%) in the colon, and 1 (1.8%) in the esophagus. The size of the tumors ranged from 2 to 33 cm (median: 8 cm); in 12 cases (22.2%), the tumor was below 5 cm at the largest diameter, but in 42 cases (77.7%), the tumor was larger than 5 cm. The means of CD105 and CD31 were significantly higher in the group with poor prognosis (P < 0.001). The cut-off values of CD105 (> 1.2%) and CD31 (> 2.5%) in the receiver-operating characteristic curve were related to a poorer prognosis. Cases with a better prognosis showed significantly null/weak staining for VEGF (P < 0.001). Ki-67 expression of ≥ 5% was strongly correlated with a worse prognosis (P < 0.001). In the multivariate analysis, CD105 was the variable that most strongly correlated with prognosis. CONCLUSION: The IMVD cutoff values for the angiogenic markers CD105 and CD31, may be prognostic factors for GIST, in addition to VEGF and Ki67.
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Antígenos CD/análise , Proliferação de Células , Neoplasias Gastrointestinais/química , Tumores do Estroma Gastrointestinal/química , Antígeno Ki-67/análise , Neovascularização Patológica , Molécula-1 de Adesão Celular Endotelial a Plaquetas/análise , Receptores de Superfície Celular/análise , Fator A de Crescimento do Endotélio Vascular/análise , Adulto , Idoso , Idoso de 80 Anos ou mais , Área Sob a Curva , Distribuição de Qui-Quadrado , Intervalo Livre de Doença , Endoglina , Feminino , Neoplasias Gastrointestinais/irrigação sanguínea , Neoplasias Gastrointestinais/mortalidade , Neoplasias Gastrointestinais/patologia , Neoplasias Gastrointestinais/terapia , Tumores do Estroma Gastrointestinal/irrigação sanguínea , Tumores do Estroma Gastrointestinal/mortalidade , Tumores do Estroma Gastrointestinal/patologia , Tumores do Estroma Gastrointestinal/terapia , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Recidiva Local de Neoplasia , Valor Preditivo dos Testes , Curva ROC , Estudos Retrospectivos , Fatores de Risco , Análise de Sobrevida , Fatores de Tempo , Adulto JovemRESUMO
La ingeniería tisular basada en las células troncales de pulpa dental se considera como un enfoque prometedor para la odontología regenerativa, con el objetivo final de reemplazar morfológica y funcionalmente los tejidos periodontales y/o los dientes perdidos a través de la síntesis in vitro de sustitutos análogos tisulares o, incluso, de un diente humano denominado biodiente. Las células troncales de la pulpa dental representan una colonia de células adultas que tienen la capacidad de autorrenovación y diferenciación en diferentes linajes. El origen exacto de las células troncales de la pulpa dental no ha sido completamente determinado y estas células troncales parecen ser la fuente de los odontoblastos que contribuyen a la formación del complejo dentinopulpar. Recientemente, los logros obtenidos a partir de la investigación de las células troncales nos han permitido contemplar las posibles aplicaciones terapéuticas de las células troncales de la pulpa dental. Algunos estudios han demostrado que las células troncales de la pulpa dental son capaces de producir tejidos dentales in vivo, incluyendo la dentina, la pulpa dental y las estructuras de la corona. Mientras que otras investigaciones han demostrado que estas células troncales se diferencian in vitro e in vivo, por ejemplo, en osteoblastos, neuroblastos, condrocitos, fibroblastos y endotelio. En teoría, un biodiente sintetizado a partir de las células troncales de la pulpa dental debe ser la mejor opción para recuperar la totalidad de la estructura y función de un diente humano. El objetivo de este artículo de revisión es hacer una breve descripción de la localización, origen, aislamiento y marcadores candidatos de células troncales de pulpa dental, para así plantear las perspectivas de aplicación en la clínica odontológica.
Tissue engineering based on dental pulp stem cells is considered as a promising approach for regenerative dentistry. It purports the final target of morphologically and functionally replacing periodontal tissues and/or lost teeth by means of the in vitro synthesis of tissue-analog substitutes, or even a human tooth (called bio-tooth). Dental pulp stem cells represent a colony of adult cells which have the ability to auto-renovate and differentiate in different lineages. Dental pulp stem cells exact origin has yet to be fully determined; these stem cells seem to be the source of odontoblasts, which contribute to the formation of the dentin-pulp complex. Recently, achievements obtained through research conducted on stem cells, have allowed us to contemplate the possible therapeutic applications of dental pulp stem cells. Some studies have shown that dental pulp stem cells are able to produce in vivo dental tissues, including dental pulp and crown structures. Other research has demonstrated that these stem cells differentiate in vivo and in vitro into osteoblasts, neuroblasts, chondrocytes fibroblasts, and endothelium. In theory, a bio-tooth synthesized from autogenic dental pulp stem cells should be the best option to recover the whole structure and function of a human tooth. The aim of the present review article was to undertake a brief description of the location, origin, isolation and candidate markers of dental pulp stem cells in order to thus present application perspectives to be used in the dental clinic.
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The typical characteristics of mesenchymal stem cells (MSCs) can be affected by inflammatory microenvironment; however, the exact contribution of HTLV-1 to MSC dysfunction remains to be elucidated. In this study, we demonstrated that MSC cell surface molecules VCAM-1 and ICAM-1 are upregulated by contact with HTLV-1, and HLA-DR was most highly expressed in MSCs co-cultured with MT2 cells. The expression levels of VCAM-1 and HLA-DR were increased in MSCs cultured in the presence of PBMCs isolated from HTLV-1-infected symptomatic individuals compared with those cultured with cells from asymptomatic infected individuals or healthy subjects. HTLV-1 does not impair the MSC differentiation process into osteocytes and adipocytes. In addition, MSCs were efficiently infected with HTLV-1 in vitro through direct contact with HTLV-1-infected cells; however, cell-free virus particles were not capable of causing infection. In summary, HTLV-1 can alter MSC function, and this mechanism may contribute to the pathogenesis of this viral infection.
Assuntos
Infecções por HTLV-I/virologia , Vírus Linfotrópico T Tipo 1 Humano/fisiologia , Células-Tronco Mesenquimais/virologia , Diferenciação Celular , Células Cultivadas , Infecções por HTLV-I/genética , Infecções por HTLV-I/imunologia , Infecções por HTLV-I/fisiopatologia , Humanos , Molécula 1 de Adesão Intercelular/genética , Molécula 1 de Adesão Intercelular/imunologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/imunologia , Fenótipo , Molécula 1 de Adesão de Célula Vascular/genética , Molécula 1 de Adesão de Célula Vascular/imunologiaRESUMO
Introdução: O carcinoma de pênis (CaPe) incide predominantemente em regiões menos desenvolvidas do globo. Seus fatores de risco incluem má higiene genital, fimose e infecção por HPV (human papillomavirus). A ativação angiogênica é essencial à sobrevivência das células neoplásicas, porém não há dados desse processo em CaPe. Objetivo: O presente estudo tem como objetivo correlacionar a infecção pelo HPV com o processo angiogênico em CaPe. Métodos: Foram incluídos 60 pacientes com diagnóstico de carcinoma de células escamosas de pênis, provenientes do A.C. Camargo Cancer Center, diagnosticados entre 1954 e 2010, genotipados para HPV (33 negativos ou com HPV de baixo risco e 27 positivos para HPV de alto risco). Foi feita a análise imunoistoquimica da microvasculatura relacionada à neoplasia (marcadores endoteliais CD34, CD31, CD105 e D2-40) e de fatores pró-angiogênicos (VEGF, VEGFR1 e VEGFR2) nas células neoplásicas. Resultados/Conclusão: Apenas a neoangiogênese, marcada pelo CD105, esteve mais pronunciada em casos associados ao HPV de alto risco. Isto aponta para um mecanismo adjuvante da neoangiogênese promovida ou facilitada por esse vírus. Além disto, maior expressão de VEGF e VEGFR1 pelas células neoplásicas associou-se com a presença de infiltração linfonodal, fator de pior prognóstico da doença. Nossos dados não apóiam a utilização da imunorreatividade para a proteína p16 como substituto para a genotipagem para HPV de alto risco em CaPe
Background: Penile carcinoma (PeCa) incides predominantly in regions with unfavorable socioeconomic conditions. Inadequate genital hygienic habits, fimosis, and high risk-HPV (human papillomavirus) infection represent its most important risk factors. Angiogenic activation is fundamental for survival of neoplastic cells, but this process has not yet been addressed in PeCa. Objective: To correlate HPV infection with the angiogenic process in cases of PeCa. Methods: Sixty patients diagnosed with squamous cell carcinoma of the penis, from 1954 to 2010, at the A C Camargo Cancer Center; 27 were positive for high risk HPV and 33 negative (3 of which had low risk HPV). Immunohistochemical analysis of microvasculature using markers for CD31, CD34, CD105 and D2-40, and evaluation of proangiogenic factors (VEGF, VEGFR1 and VEGFR2) in neoplastic cells were performed. Results/Conclusions: Only neoangiogenesis detected by more prominentimmunostaining for CD105 was related to high risk HPV. This may indicate that neoangiogenesis might be promoted or facilitated by viral infection. In addition, stronger expression of VEGF and VEGFR1 in neoplastic cells was associated with lymph node neoplastic infiltration, known factor of unfavorable outcome. Our data do not support using immunoreactivity of p16 protein as indicator of genotyping for high risk HPV in PeCa.
Assuntos
Humanos , Masculino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Neoplasias Penianas , Carcinoma de Células Escamosas , Infecções por Papillomavirus , Papillomaviridae , Imuno-Histoquímica , Moduladores da Angiogênese , Indutores da AngiogêneseRESUMO
OBJECTIVE: To demonstrate the role of angiogenesis in the progression of cutaneous squamous cell carcinoma. INTRODUCTION: Angiogenesis is a pivotal phenomenon in carcinogenesis. Its time course in cutaneous squamous cell carcinoma has not yet been fully established. METHODS: We studied the vascular bed in 29 solar keratoses, 30 superficially invasive squamous cell carcinomas and 30 invasive squamous cell carcinomas. The Chalkley method was used to quantify the microvascular area by comparing panendothelial (CD34) with neoangiogenesis (CD105) immunohistochemical markers. The vascular bed from non-neoplastic adjacent skin was evaluated in 8 solar keratoses, 10 superficially invasive squamous cell carcinomas and 10 invasive squamous cell carcinomas. RESULTS: The microvascular area in CD105-stained specimens significantly increased in parallel with cutaneous squamous cell carcinoma progression. However, no differences between groups were found in CD34 sections. Solar keratosis, superficially invasive squamous cell carcinoma and invasive squamous cell carcinoma samples showed significant increases in microvascular area for both CD34- and CD105-stained specimens compared with the respective adjacent skin. DISCUSSION: The angiogenic switch occurs early in the development of cutaneous squamous cell carcinoma, and the rate of neovascularization is parallel to tumor progression. In contrast to panendothelial markers, CD105 use allows a dynamic evaluation of tumor angiogenesis. CONCLUSION: This study demonstrated the dependence of skin carcinogenesis on angiogenesis.
Assuntos
Humanos , Carcinoma de Células Escamosas/irrigação sanguínea , Neovascularização Patológica/fisiopatologia , Neoplasias Cutâneas/irrigação sanguínea , Antígenos CD/análise , /análise , Contagem de Células , Ceratose Actínica/patologia , Receptores de Superfície Celular/análise , Pele/irrigação sanguíneaRESUMO
Blood and lymphatic vessel proliferation is essential for tumor growth and progression. Most colorectal carcinomas develop from adenomas (adenoma-carcinoma sequence) in a process due to accumulation of molecular genetic alterations. About 5% of adenomatous polyps are expected to become malignant, but data on the differential angiogenic patterns of these lesions in patients with and without concomitant cancer are missing. The aim of the present study is to compare the angiogenic and lymphatic patterns of adenomatous polyps from patients with and without sporadic cancer. Thirty adenomatous polyps (15 from patients with another principal malignant lesion, and 15 from patients without cancer) were submitted to immunohistochemical staining for CD105 (marker for neoangiogenesis) and D2-40 (marker for lymphatic endothelium). Microvessel density and total vascular area were determined by computer image analysis to quantify the immunostained and total areas, and to assess the number of microvessels. Adenomas from patients with carcinoma showed significantly higher values of total vascular area determined by immunostaining for CD105 (cutoff value = 4386 µm²; P = 0.019) and of lymphatic microvessel density determined by immunostaining with D2-40 (cutoff value = 11.5; P = 0.041) when compared with those from patients without cancer. The present data indicate a significant increase in blood microvascular area and in lymphatic microvascular counts in adenomas removed from patients with cancer.
Assuntos
Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Adenomatosos/patologia , Neoplasias Colorretais/patologia , Linfangiogênese/fisiologia , Neovascularização Patológica/patologia , Pólipos Adenomatosos/irrigação sanguínea , Pólipos Adenomatosos/química , Anticorpos Monoclonais/análise , Antígenos CD/análise , Biomarcadores/análise , Neoplasias Colorretais/irrigação sanguínea , Neoplasias Colorretais/química , Imuno-Histoquímica , Vasos Linfáticos/química , Vasos Linfáticos/patologia , Microcirculação , Estudos Retrospectivos , Receptores de Superfície Celular/análiseRESUMO
As BMPs (proteinas morfogenéticas ósseas) são citocinas relacionadas com a proliferação e angiogênese em diversos tipos de câncer humano. Com este trabalho foi analisada a expressão imunohistoquímica das proteínas NMP-2, BMPR-IA, BMPR-II e endoglina (CD105), correlacionando-a com o comportamento biológico e a angiogênese local nos carcinomas epidermóides de língua (CEL). A amostra foi composta de 25 casos de CEL sem metástase (CELSM), 25 CEL com metástase (CELCM) graduados segundo Bryne (1198) e adaptado por Miranda (2002), além de 25 casos de hiperplasia fibrosa inflamatória (HFI), utilizado como grupo controle. Foi utilizado escore 0 para marcação ausente-fraca e 1 para forte; tipo de distribuição focal ou difuso. Adicionalmente, para o CD105 foi realizada a contagem microvascular (MVC). A maior parte dos pacientes com CEL foi do sexo masculino, no grupo CELSM a faixa etária foi maior que 65 anos e o CELCM se encontrou entre 45-65 anos; houve predomínio do estágio II do TNM, assim como de...
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Proteínas Morfogenéticas Ósseas , Carcinoma de Células Escamosas/diagnóstico , Hiperplasia Gengival/epidemiologia , Imuno-Histoquímica , Metástase Neoplásica/fisiopatologia , Neovascularização Patológica/patologia , Estudos de Avaliação como Assunto/métodos , Estudos de Avaliação como Assunto/métodos , Distribuição de Qui-Quadrado , Interpretação Estatística de DadosRESUMO
Nesta pesquisa buscou-se avaliar a expressão imunoistoquímica dos anticorpos CD105 e FvW na angiogênese do Carcinoma Epidermóide Oral (CEO), correlacionando-o com o estadiamento clínico pelo sistema TNM, visando uma melhor compreensão do seu comportamento biológico e utilização como indicador de prognóstico. A amostra foi composta por 30 casos de CE, sendo 10 de assoalho bucal, 10 da região retromolar e 10 de língua, além de 10 casos de granuloma piogênico, integrantes do grupo controle. Os resultados desta pesquisa mostraram que as médias da MVC foram correspondentemente mais elevadas no grupo do granuloma piogênico (CD105 = 57,26 vasos e FvW = 39,64) do que no grupo do CE (CD105 = 10,09 e FvW = 12,20) e as diferenças se revelaram estatisticamente significantes entre os grupos para cada um dos biomarcadores angiogênicos (p=0,002 para o CD105 e p<0,001 para o FvW ). O CD105 se mostrou com melhor positividade no granuloma piogênico (média = 57,26 vasos) e, para o CE, o FvW foi o que apresentou maior marcação (média = 12,20 vasos). Com relação ao CE, a faixa etária mais acometida foi entre 51 e 70 anos (n=14; 46,7%), apresentando uma MVC representativa para ambos os marcadores. Não se comprovou diferença estatisticamente significante entre os sexos para nenhum dos marcadores (p=0,967 para o CD105 e p=0,744 para o FvW). A média do CD105 foi bem mais elevada entre os pacientes com estadiamento T3 e T4 (17,13) e menos elevada entre os pacientes com estadiamento N+ (6,36). Quando se avaliou o FvW, a média foi mais elevada no grupo dos pacientes com T1 e T2 (12,23), sendo mais baixa nos pacientes com T3 e T4 (12,10), porém sem diferença estatisticamente significante. Em relação à localização anatômica, comprovou-se diferença estatisticamente significante entre as localizações assoalho bucal e retromolar (p=0,013) para o marcador FvW. Portanto, este estudo sugere que a marcação do CD105 na angiogênese do CEO, ao contrário de outros tipos de neoplasias malignas, pode não estar correlacionada com o prognóstico e agressividade do tumor, enquanto que o FvW se mostrou um anticorpo mais efetivo na marcação desta lesão (AU).
The purpose of this study was to assess the immunohistochemical expression of CD105 and FvW antibodies in the angiogenesis of oral epidermoid carcinoma (OEC), correlating it with the TNM clinical staging system, seeking a better understanding of its biological behavior and use as an indicator of prognosis.The sample consisted of 30 epidermoid carcinoma (EC) cases, 10 of the floor of the mouth, 10 of the retromolar region and 10 of the tongue, in addition to 10 cases of pyogenic granuloma, which made up the control group. The results showed that mean microvessel counts (MVC) were correspondingly higher in the pyogenic granuloma group (CD105 = 57.26 vessels and FvW = 39.64) than in the EC group (CD105 = 10.09 and FvW = 12.20) and that the differences were statistically significant between the groups for each of the angiogenic biomarkers (p = 0.002 for CD105 and p< 0.001 for FvW). CD105 had better positivity in the pyogenic granuloma group (mean = 57.26 vessels) and for EC, FvW had the highest expression (mean = 12.20 vessels). With respect to EC, the most affected age group was between 51 and 70 years (n = 14; 46.7%), with a representative MVC for both markers. No statistically significant difference was found between the sexes for any of the markers (p = 0.967 for CD105 and p = 0.744 for FvW). Mean CD105 levels were much higher in patients with stage T3 and T4 (17.13) and lower in those with stage N+ (6.36). Mean FvW levels were higher in the patients with stage T1 and T2 (12.23) and lower in patients with T3 and T4 (12.10), but without a statistically significant difference. In regard to anatomic location, a statistically significant difference was observed between FvW sites, with a statistically significant difference between floor of the mouth cases and those located in the retromolar region (p = 0.013). Therefore, this study suggests that CD105 expression in OEC angiogenesis, in contrast to other types of malignant neoplasias, may not be correlated with prognosis and tumor aggressiveness, whereas FvW was a more effective antibody for staining this lesion (AU).