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1.
Tumour Biol ; 36(9): 7285-92, 2015 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-25895461

RESUMEN

The aim of the present study was to determine the role of vascular endothelial growth factor receptors (VEGFR1 and VEGFR2) in lip carcinogenesis, to investigate correlations between these markers with microvessel density (MVD) and clinicopathological aspects. Medical records from 27 cases of actinic cheilitis (AC) and 46 cases of lower lip squamous cell carcinoma (LLSCC) were analysed and submitted to immunohistochemistry. VEGFR1- and VEGFR2-immunostained sections were analysed based on percentage of positive epithelial and inflammatory cells, while CD31 was submitted to quantitative analysis to determine MVD. Different patterns of VGFR1 and VEGFR2 expression were observed between AC and LLSCC. VEGFR1 expression in epithelial and inflammatory cells and VEGFR2 expression in epithelial cells were higher in AC compared to LLSCC (p < 0.05). VEGFR1 expression in epithelial cells was higher in LLSCC compared to AC (p < 0.001). Expression of both receptors was not associated to MVD or clinicopathological aspects. A direct correlation was found between epithelial VEGFR1 and VEGFR2 expression (p = 0.02) and between VEGFR2 epithelial and inflammatory expression (p < 0.001). Our findings indicate that activation of VEGFR1 and VEGFR2 in epithelial and inflammatory cells appears to be an early event in lip carcinogenesis.


Asunto(s)
Carcinoma de Células Escamosas/genética , Neoplasias de los Labios/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/biosíntesis , Receptor 2 de Factores de Crecimiento Endotelial Vascular/biosíntesis , Carcinogénesis/genética , Carcinogénesis/patología , Carcinoma de Células Escamosas/patología , Células Epiteliales/metabolismo , Células Epiteliales/patología , Femenino , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias de los Labios/patología , Masculino , Microvasos/fisiopatología , Neovascularización Patológica/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 2 de Factores de Crecimiento Endotelial Vascular/genética
2.
Phytother Res ; 29(7): 1102-5, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25891093

RESUMEN

The effect of topical application of Aloe Vera (Aloe barbadensis Miller) extract was assessed on the healing of rat oral wounds in an in vivo model using 72 male Wistar rats divided into three groups (n = 24): control, placebo and Aloe Vera (0.5% extract hydroalcoholic). Traumatic ulcers were caused in the dorsum of the tongue using a 3-mm punch tool. The Aloe Vera and placebo group received two daily applications. The animals were sacrificed after 1, 5, 10 and 14 days. Clinical analysis (ulcer area and percentage of repair) and histopathological analysis (degree of re-epithelialization and inflammation) were performed. The comparison of the differences between scores based on group and experimental period, both in quantitative and semi-quantitative analyses, was performed using the Kruskal-Wallis test. The significance level was 5%. On day 1, all groups showed predominantly acute inflammatory infiltrate. On day 5, there was partial epithelialization and chronic inflammatory infiltrate. On the days 10 and 14 total repair of ulcers was observed. There was no significant difference between groups in the repair of mouth ulcers. It is concluded that treatment using Aloe Vera as an herbal formulation did not accelerate oral wound healing in rats.


Asunto(s)
Aloe/química , Úlceras Bucales/tratamiento farmacológico , Extractos Vegetales/farmacología , Cicatrización de Heridas/efectos de los fármacos , Animales , Antiinfecciosos Locales , Masculino , Distribución Aleatoria , Ratas , Ratas Wistar
3.
Tumour Biol ; 35(8): 7635-44, 2014 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-24798972

RESUMEN

Epithelial changes observed in actinic cheilitis (AC) and lower lip squamous cell carcinoma (LLSCC) have been studied using different markers in order to observe diagnostic and prognostic factors for both lesions. The aim of the present study was to analyze Ki-67, TGF-ß1, and elastin content in AC and LLSCC to determine the possible role of these proteins in lip carcinogenesis. Medical records of 29 cases of AC and 53 cases of LLSCC were analyzed. Lesions were classified according histological pattern and submitted to immunostaining for Ki-67, TGF-ß1, and elastin. Different percentages of Ki-67-positive cells were found in AC depending on the degree of epithelial dysplasia (p < 0.01). An association was also found between the percentage of Ki-67-positive cells and tumor grade in LLSCC (p < 0.01). An inverse correlation was found between Ki-67 and TGF-ß1 in AC and LLSCC (p < 0.01). Elastosis was thinner and more discontinuous in LLSCC in comparison to AC, and this difference in the elastin immunolabeling pattern was statistically significant between groups (p < 0.01). The present findings indicate that changes in Ki-67 and TGF-ß1 content contribute to lip carcinogenesis. Furthermore, elastin content reflects changes in the extracellular matrix in both AC and LLSCC.


Asunto(s)
Carcinoma de Células Escamosas/etiología , Elastina/análisis , Antígeno Ki-67/análisis , Neoplasias de los Labios/etiología , Factor de Crecimiento Transformador beta1/análisis , Adulto , Anciano , Carcinogénesis , Carcinoma de Células Escamosas/química , Carcinoma de Células Escamosas/patología , Femenino , Humanos , Inmunohistoquímica , Neoplasias de los Labios/química , Neoplasias de los Labios/patología , Modelos Logísticos , Masculino , Persona de Mediana Edad
4.
Nat Commun ; 15(1): 6024, 2024 Jul 17.
Artículo en Inglés | MEDLINE | ID: mdl-39019886

RESUMEN

Respiratory pathogens, commonly colonizing nasopharynx, are among the leading causes of death due to antimicrobial resistance. Yet, antibiotic resistance determinants within nasopharyngeal microbial communities remain poorly understood. In this prospective cohort study, we investigate the nasopharynx resistome development in preterm infants, assess early antibiotic impact on its trajectory, and explore its association with clinical covariates using shotgun metagenomics. Our findings reveal widespread nasopharyngeal carriage of antibiotic resistance genes (ARGs) with resistomes undergoing transient changes, including increased ARG diversity, abundance, and composition alterations due to early antibiotic exposure. ARGs associated with the critical nosocomial pathogen Serratia marcescens persist up to 8-10 months of age, representing a long-lasting hospitalization signature. The nasopharyngeal resistome strongly correlates with microbiome composition, with inter-individual differences and postnatal age explaining most of the variation. Our report on the collateral effects of antibiotics and prolonged hospitalization underscores the urgency of further studies focused on this relatively unexplored reservoir of pathogens and ARGs.


Asunto(s)
Antibacterianos , Hospitalización , Recien Nacido Prematuro , Nasofaringe , Humanos , Nasofaringe/microbiología , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Recién Nacido , Estudios Prospectivos , Femenino , Masculino , Metagenómica/métodos , Lactante , Serratia marcescens/efectos de los fármacos , Serratia marcescens/genética , Microbiota/efectos de los fármacos , Microbiota/genética , Farmacorresistencia Bacteriana/genética , Farmacorresistencia Microbiana/genética , Farmacorresistencia Microbiana/efectos de los fármacos
5.
Int Dent J ; 2024 Oct 05.
Artículo en Inglés | MEDLINE | ID: mdl-39370344

RESUMEN

BACKGROUND: Dentists, as prominent prescribers, are key stakeholders in addressing the antimicrobial resistance (AMR) crisis. Dental students' perceptions about the topic have been underexplored in the Asia-Pacific region, a key location for the development and spread of AMR. Thus, the aim of this study was to evaluate the awareness and confidence to prescribe antimicrobials amongst dental students studying in the region. METHODS: Students from 15 dental schools in 4 countries were invited to participate in a cross-sectional online survey during 2022-2023. A previously validated and standardised 14-item instrument was utilised. RESULTS: In all, 1413 responses were collected from Australia (n = 165), Sri Lanka (n = 112), Japan (n = 173), and Vietnam (n = 963). Of those, 201 were from final-year students (14.2%). On a scale from 1 to 10, awareness on AMR was placed at a mean (SEM) priority of 8.09 (0.05). With regards to target areas to address for mitigation of the AMR crisis, participants placed general public awareness at the top (mean [SEM] 8.53 [0.05]). Final-year students presented a mean (SEM) level of confidence to prescribe antibiotics of 6.01 (0.14) on a scale from 1 to 10, whilst 59.7% and 56.8% indicated feeling pressured to prescribe by patients or when lacking time, respectively. Final-year students participating in research activities assigned a higher priority to AMR compared to their peers not involved in research (mean [SEM] 8.6 [0.19] vs 7.81 [0.16]; P = .01). CONCLUSIONS: This study highlights a need for increased awareness and confidence to prescribe amongst dental students in the Asia-Pacific region, an understudied population thus far. To mitigate this issue, the implementation (followed by assessment) of local educational and antibiotic stewardship initiatives is warranted.

6.
Gut Microbes ; 15(1): 2157200, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36576106

RESUMEN

The collateral impact of antibiotics on the microbiome has attained increasing attention. However, the ecological consequences of long-term antibiotic exposure on the gut microbiome, including antibiotic resistance, are still limited. Here, we investigated long-term exposure effects to amoxicillin on the human gut microbiome and resistome. Fecal samples were collected from 20 patients receiving 3-months of amoxicillin or placebo treatment as part of a Norwegian multicenter clinical trial on chronic low back pain (AIM study). Samples were collected at baseline, last day of treatment, and 9 months after antibiotic cessation. The abundance and diversity of microbial and resistome composition were characterized using whole shotgun and functional metagenomic sequencing data. While the microbiome profiles of placebo subjects were stable over time, discernible changes in diversity and overall microbiome composition were observed after amoxicillin treatment. In particular, health-associated short-chain fatty acid producing species significantly decreased in proportion. However, these changes were short-lived as the microbiome showed overall recovery 9 months post-treatment. On the other hand, exposure to long-term amoxicillin was associated with an increase in total antimicrobial resistance gene load and diversity of antimicrobial resistance genes, with persistent changes even at 9 months post-treatment. Additionally, beta-lactam resistance was the most affected antibiotic class, suggesting a targeted response to amoxicillin, although changes at the gene level varied across individuals. Overall, our results suggest that the impact of prolonged amoxicillin exposure was more explicit and long-lasting in the fecal resistome than in microbiome composition. Such information is relevant for designing rational administration guidelines for antibiotic therapies.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Humanos , Amoxicilina/farmacología , Amoxicilina/uso terapéutico , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Heces
7.
Antimicrob Resist Infect Control ; 11(1): 158, 2022 Dec 11.
Artículo en Inglés | MEDLINE | ID: mdl-36503570

RESUMEN

BACKGROUND: The antimicrobial resistance (AMR) crisis is a major global threat and one of its biggest drivers is the overuse of antibiotics in humans. Dentists are responsible for 5-10% antibiotic prescriptions worldwide and recent data suggest that knowledge and prescribing practices need improvement. METHODS: A cross-sectional web-survey was sent to dental students from six universities in Norway, Canada, and Brazil. Topics addressed covered awareness, confidence to prescribe antibiotics, and education needs. Data were presented descriptively and statistical testing was employed to compare group means when applicable. RESULTS: In total, 562 responses were collected across the three countries with a response rate of 28.6%. 'Antibiotic resistance' was among the highest priorities (scale 1-10) with an average of 8.86 (SEM ± 0.05), together with 'Gender inequality' (8.68 ± 0.07) and 'Climate change' (8.68 ± 0.07). Only 28.8% thought that Dentistry was engaged in national/international campaigns promoting awareness on the topic and 8.9% stated to have heard about the 'One Health' concept. Final year dental students showed an average confidence to prescribe antibiotics of 7.59 (± 0.14). Most students demonstrated interest in receiving additional education on all topics listed, with the three most pressing being 'antibiotic prescription for treatment of infections' (82.9%), 'drug interactions' (80.9%), and 'spread of antibiotic resistance' (79.6%). A trend was observed between higher awareness regarding the topic and higher confidence to prescribe. CONCLUSIONS: There is a need to revisit dental education on antibiotic resistance with a global perspective and to create more stewardship initiatives that promote awareness on the topic.


Asunto(s)
Antibacterianos , Farmacorresistencia Bacteriana , Humanos , Antibacterianos/uso terapéutico , Estudios Transversales , Encuestas y Cuestionarios , Prescripciones
8.
Front Microbiol ; 13: 1038120, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36620054

RESUMEN

Introduction: Low microbial biomass and high human DNA content in nasopharyngeal aspirate samples hinder comprehensive characterization of microbiota and resistome. We obtained samples from premature infants, a group with increased risk of developing respiratory disorders and infections, and consequently frequent exposure to antibiotics. Our aim was to devise an optimal protocol for handling nasopharyngeal aspirate samples from premature infants, focusing on host DNA depletion and microbiome and resistome characterization. Methods: Three depletion and three DNA extraction protocols were compared, using RT-PCR and whole metagenome sequencing to determine the efficiency of human DNA removal, taxonomic profiling and assignment of antibiotic resistance genes. Protocols were tested using mock communities, as well as pooled and individual patient samples. Results: The only extraction protocol to retrieve the expected DNA yield from mock community samples was based on a lytic method to improve Gram positive recovery (MasterPure™). Host DNA content in non-depleted aliquots from pooled patient samples was 99%. Only samples depleted with MolYsis™ showed satisfactory, but varied reduction in host DNA content, in both pooled and individual patient samples, allowing for microbiome and resistome characterisation (host DNA content from 15% to 98%). Other depletion protocols either retrieved too low total DNA yields, preventing further analysis, or failed to reduce host DNA content. By using Mol_MasterPure protocol on aliquots from pooled patient samples, we increased the number of bacterial reads by 7.6 to 1,725.8-fold compared to non-depleted reference samples. PCR results were indicative of achieved microbial enrichment. Individual patient samples processed with Mol_MasterPure protocol varied greatly in total DNA yield, host DNA content (from 40% to 98%), species and antibiotic resistance gene richness. Discussion: Despite high human DNA and low microbial biomass content in nasopharynx aspirates of preterm infants, we were able to reduce host DNA content to levels compatible with downstream shotgun metagenomic analysis, including bacterial species identification and coverage of antibiotic resistance genes. Whole metagenomic sequencing of microbes colonizing the nasopharynx may contribute to explaining the possible role of airway microbiota in respiratory conditions and reveal carriage of antibiotic resistance genes.

9.
Artículo en Inglés | MEDLINE | ID: mdl-31001492

RESUMEN

The mitis group of streptococci comprises species that are common colonizers of the naso-oral-pharyngeal tract of humans. Streptococcus pneumoniae and Streptococcus mitis are close relatives and share ~60-80% of orthologous genes, but still present striking differences in pathogenic potential toward the human host. S. mitis has long been recognized as a reservoir of antibiotic resistance genes for S. pneumoniae, as well as a source for capsule polysaccharide variation, leading to resistance and vaccine escape. Both species share the ability to become naturally competent, and in this context, competence-associated killing mechanisms such as fratricide are thought to play an important role in interspecies gene exchange. Here, we explore the general mechanism of natural genetic transformation in the two species and touch upon the fundamental clinical and evolutionary implications of sharing similar competence, fratricide mechanisms, and a large fraction of their genomic DNA.


Asunto(s)
Competencia de la Transformación por ADN , Transferencia de Gen Horizontal , Streptococcus mitis/genética , Streptococcus pneumoniae/genética , Transformación Bacteriana , Genoma Bacteriano
10.
Front Mol Biosci ; 5: 116, 2018.
Artículo en Inglés | MEDLINE | ID: mdl-30662898

RESUMEN

Natural transformation is regarded as an important mechanism in bacteria that allows for adaptation to different environmental stressors by ensuring genome plasticity. Since the discovery of this phenomenon in Streptococcus pneumoniae, remarkable progress has been made in the understanding of the molecular mechanisms and pathways coordinating this process. Recently, the advent of high-throughput sequencing allows the posing of questions that address the system at a larger scale but also allow for the creation of high-resolution maps of transcription. Thus, while much is already known about genetic competence in streptococci, recent studies continue to reveal intricate novel regulation pathways and components. In this perspective article, we highlight the use of transcriptional profiling and mapping as a valuable resource in the identification and characterization of "hidden gems" pertinent to the natural transformation system. Such strategies have recently been employed in a variety of different species. In S. mutans, for example, genome editing combined with the power of promoter mapping and RNA-Seq allowed for the identification of a link between the ComCDE and the ComRS systems, a ComR positive feedback loop mediated by SigX, and the XrpA peptide, encoded within sigX, which inhibits competence. In S. pneumoniae, a novel member of the competence regulon termed BriC was found to be directly under control of ComE and to promote biofilm formation and nasopharyngeal colonization but not competence. Together these new technologies enable us to discover new links and to revisit old pathways in the compelling study of natural genetic transformation.

11.
Methods Mol Biol ; 1537: 219-232, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27924597

RESUMEN

The discovery that Streptococcus pneumoniae uses a competence-stimulating peptide (CSP) to induce competence for natural transformation, and that other species of the mitis and the anginosus streptococcal groups use a similar system, has expanded the tools to explore gene function and regulatory pathways in streptococci. Two other classes of pheromones have been discovered since then, comprising the bacteriocin-inducing peptide class found in Streptococcus mutans (also named CSP, although different from the former) and the SigX-inducing peptides (XIP), in the mutans, salivarius, bovis, and pyogenes groups of streptococci. The three classes of peptide pheromones can be ordered from peptide synthesis services at affordable prices, and used in transformation assays to obtain competent cultures consistently at levels usually higher than those achieved during spontaneous competence. In this chapter, we present protocols for natural transformation of oral streptococci that are based on the use of synthetic pheromones, with examples of conditions optimized for transformation of S. mutans and Streptococcus mitis.


Asunto(s)
Boca/microbiología , Feromonas/farmacología , Streptococcus/efectos de los fármacos , Streptococcus/fisiología , Transformación Bacteriana/efectos de los fármacos , Proteínas Bacterianas/metabolismo , Proteínas Bacterianas/farmacología , Humanos , Péptidos/farmacología , Feromonas/síntesis química , Streptococcus mutans/efectos de los fármacos , Streptococcus mutans/fisiología
12.
mSphere ; 2(5)2017.
Artículo en Inglés | MEDLINE | ID: mdl-28932816

RESUMEN

Despite vaccines, Streptococcus pneumoniae kills more than a million people yearly. Thus, understanding how pneumococci transition from commensals to pathogens is particularly relevant. Quorum sensing regulates collective behaviors and thus represents a potential driver of commensal-to-pathogen transitions. Rgg/small hydrophobic peptide (SHP) quorum-sensing systems are widespread in streptococci, yet they remain largely uncharacterized in S. pneumoniae. Using directional transcriptome sequencing, we show that the S. pneumoniae D39 Rgg0939/SHP system induces the transcription of a single gene cluster including shp and capsule gene homologs. Capsule size measurements determined by fluorescein isothiocyanate-dextran exclusion allowed assignment of the system to the regulation of surface polysaccharide expression. We found that the SHP pheromone induced exopolysaccharide expression in R36A, an unencapsulated derivative of D39. In the encapsulated parent strain, overexpression of the Rgg system resulted in a mutant with increased capsule size. In line with previous studies showing that capsule expression is inversely associated with biofilm formation, we found that biofilm formed on lung epithelial cells was decreased in the overexpression strain and increased in an rgg deletion mutant. Although no significant differences were observed between D39 and the rgg deletion mutant in a mouse model of lung infection, in competitive assays, overexpression reduced fitness. This is the first study to reveal a quorum-sensing system in streptococci that regulates exopolysaccharide synthesis from a site distinct from the original capsule locus. IMPORTANCE Quorum sensing regulates bacterial social behaviors by production, secretion, and sensing of pheromones. In this study, we characterized a new quorum-sensing system of the Rgg/SHP class in S. pneumoniae D39. The system was found to directly induce the expression of a single gene cluster comprising the gene for the SHP pheromone and genes with putative functions in capsule synthesis. Capsule size, as measured by dextran exclusion, was increased by SHP exposure in R36A, an unencapsulated derivative of D39. In the encapsulated parent strain, overexpression of the gene cluster increased capsule size, supporting the role of Rgg/SHP in the synthesis of surface polysaccharides. Further, we found that biofilm formation on epithelial cells was reduced by overexpression of the system and increased in a mutant with an rgg deletion. Placing surface polysaccharide expression under quorum-sensing regulation may enable S. pneumoniae to tune interactions with the host and other bacteria in accordance with environmental and cell density conditions.

13.
Front Microbiol ; 7: 1009, 2016.
Artículo en Inglés | MEDLINE | ID: mdl-27458432

RESUMEN

OBJECTIVE: Streptococcus mitis is a predominant oral colonizer, but difficulties in genetic manipulation of this species have hampered our understanding of the mechanisms it uses for colonization of oral surfaces. The aim of this study was to reveal optimal conditions for natural genetic transformation in S. mitis and illustrate its application in direct genome editing. METHODS: Luciferase reporter assays were used to assess gene expression of the alternative sigma factor (σ(X)) in combination with natural transformation experiments to evaluate the efficiency by which S. mitis activates the competence system and incorporates exogenous DNA. Optimal amounts and sources of donor DNA (chromosomal, amplicon, or replicative plasmid), concentrations of synthetic competence-stimulating peptide, and transformation media were assessed. RESULTS: A semi-defined medium showed much improved results for response to the competence stimulating peptide when compared to rich media. The use of a donor amplicon with large homology flanking regions also provided higher transformation rates. Overall, an increase of transformation efficiencies from 0.001% or less to over 30% was achieved with the developed protocol. We further describe the construction of a markerless mutant based on this high efficiency strategy. CONCLUSION: We optimized competence development in S. mitis, by use of semi-defined medium and appropriate concentrations of synthetic competence factor. Combined with the use of a large amplicon of donor DNA, this method allowed easy and direct editing of the S. mitis genome, broadening the spectrum of possible downstream applications of natural transformation in this species.

14.
Braz Oral Res ; 30(1): e135, 2016 Dec 22.
Artículo en Inglés | MEDLINE | ID: mdl-28001243

RESUMEN

The aim of this study was to assess the accuracy of clinical diagnosis for lip lesions based on sensitivity and specificity. The retrospective analysis focused on the detection of lesions caused by potentially malignant disorders (PMDs) and malignant lesions (n = 1195). All cases were classified as benign, PMD, and malignant lesions. Concordance between diagnoses based on clinical examination and those based on histopathological analysis was assessed, and accuracy for the identification of PMD and malignant lesions was calculated. Histopathological analysis revealed 44 lesion types; PMD and malignant lesions comprised 8.3% of all cases. Compared with histopathological analysis, clinical examination showed 97.4% accuracy for the identification of non-malignant and potentially malignant/malignant cases. Degrees of specific sensitivity ranged from 34% to 77% for different lesions, and were highest for autoimmune (77%) and reactive (72%) lesions. Positive and negative predictive values for the identification of PMD and malignant lesions were 81.9% and 98.9%, respectively. Clinical examination showed a high degree of accuracy for the detection of PMD and malignant lip lesions, indicating good reliability.


Asunto(s)
Neoplasias de los Labios/patología , Labio/patología , Adolescente , Adulto , Distribución por Edad , Factores de Edad , Anciano , Anciano de 80 o más Años , Biopsia , Brasil/epidemiología , Niño , Preescolar , Diagnóstico Bucal/métodos , Femenino , Humanos , Lactante , Enfermedades de los Labios/epidemiología , Enfermedades de los Labios/patología , Neoplasias de los Labios/epidemiología , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Distribución por Sexo , Factores Sexuales , Adulto Joven
15.
Medicine (Baltimore) ; 95(22): e3725, 2016 May.
Artículo en Inglés | MEDLINE | ID: mdl-27258499

RESUMEN

The DNA mismatch repair (MMR) system is responsible for the detection and correction of errors created during DNA replication, thereby avoiding the incorporation of mutations in dividing cells. The prognostic value of alterations in MMR system has not previously been analyzed in oral squamous cell carcinoma (OSCC).The study comprised 115 cases of OSCC diagnosed between 1996 and 2010. The specimens collected were constructed into tissue microarray blocks. Immunohistochemical staining for MutSα complex proteins hMSH2 and hMSH6 was performed. The slides were subsequently scanned into high-resolution images, and nuclear staining of hMSH2 and hMSH6 was analyzed using the Nuclear V9 algorithm. Univariable and multivariable Cox proportional hazard regression models were performed to evaluate the prognostic value of hMSH2 and hMSH6 in OSCC.All cases in the present cohort were positive for hMSH2 and hMSH6 and a direct correlation was found between the expression of the proteins (P < 0.05). The mean number of positive cells for hMSH2 and hMSH6 was 64.44 ±â€Š15.21 and 31.46 ±â€Š22.38, respectively. These values were used as cutoff points to determine high protein expression. Cases with high expression of both proteins simultaneously were classified as having high MutSα complex expression. In the multivariable analysis, high expression of the MutSα complex was an independent prognostic factor for poor overall survival (hazard ratio: 2.75, P = 0.02).This study provides a first insight of the prognostic value of alterations in MMR system in OSCC. We found that MutSα complex may constitute a molecular marker for the poor prognosis of OSCC.


Asunto(s)
Carcinoma de Células Escamosas/genética , ADN de Neoplasias/genética , Regulación Neoplásica de la Expresión Génica , Neoplasias de la Boca/genética , Proteína 2 Homóloga a MutS/genética , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Reparación de la Incompatibilidad de ADN , Humanos , Inmunohistoquímica , Neoplasias de la Boca/diagnóstico , Neoplasias de la Boca/metabolismo , Proteína 2 Homóloga a MutS/biosíntesis , Estadificación de Neoplasias , Estudios Retrospectivos
16.
Braz Oral Res ; 302016.
Artículo en Inglés | MEDLINE | ID: mdl-26676198

RESUMEN

Salivary gland tumors (SGT) are rare neoplasms that generate interest due to their histopathological diversity and clinical behavior. The aims of the present study were to investigate clinicopathological aspects of SGTs diagnosed at a tertiary health center and compare the findings with epidemiological data from different geographic locations. Cases of tumor in the head and neck region at a single health center in the period between 1995 and 2010 were reviewed. Patient gender, age and ethnic group as well as anatomic location, histological type and clinical behavior of the tumor were recorded. Availability of complete information about these aspects was considered the inclusion criteria. Descriptive statistical analysis of the data was performed using the frequencies of categorical variables. Among the 2168 cases of tumors in the head and neck region, 243 (11.20%) cases were diagnosed in the salivary glands, 109 of which met the inclusion criteria: 85 (78%) benign tumors and 24 (22%) malignant tumors. Mean patient age was 46.47 years. The female gender accounted for 56 cases (51.4%) and the male gender accounted for 53 (48.3%). The major salivary glands were affected more (75.2%) than the minor glands. The most frequent benign and malignant SGTs were pleomorphic adenoma (81.2%) and adenoid cystic carcinoma (58.3%), respectively. In conclusion, pleomorphic adenoma and adenoid cystic carcinoma are the most frequent benign and malignant lesions, respectively. Comparing the present data with previous studies on SGTs, one may infer that some demographic characteristics and the predominance of malignant tumors vary in different geographic regions.


Asunto(s)
Adenolinfoma/patología , Adenoma Pleomórfico/patología , Carcinoma/patología , Neoplasias de las Glándulas Salivales/patología , Adenolinfoma/epidemiología , Adenoma Pleomórfico/epidemiología , Adolescente , Adulto , Distribución por Edad , Anciano , Anciano de 80 o más Años , Brasil/epidemiología , Carcinoma/epidemiología , Niño , Femenino , Geografía Médica , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/epidemiología , Glándulas Salivales/patología , Distribución por Sexo , Adulto Joven
17.
Braz. oral res. (Online) ; 30(1): e135, 2016. tab, graf
Artículo en Inglés | LILACS | ID: biblio-952072

RESUMEN

Abstract: The aim of this study was to assess the accuracy of clinical diagnosis for lip lesions based on sensitivity and specificity. The retrospective analysis focused on the detection of lesions caused by potentially malignant disorders (PMDs) and malignant lesions (n = 1195). All cases were classified as benign, PMD, and malignant lesions. Concordance between diagnoses based on clinical examination and those based on histopathological analysis was assessed, and accuracy for the identification of PMD and malignant lesions was calculated. Histopathological analysis revealed 44 lesion types; PMD and malignant lesions comprised 8.3% of all cases. Compared with histopathological analysis, clinical examination showed 97.4% accuracy for the identification of non-malignant and potentially malignant/malignant cases. Degrees of specific sensitivity ranged from 34% to 77% for different lesions, and were highest for autoimmune (77%) and reactive (72%) lesions. Positive and negative predictive values for the identification of PMD and malignant lesions were 81.9% and 98.9%, respectively. Clinical examination showed a high degree of accuracy for the detection of PMD and malignant lip lesions, indicating good reliability.


Asunto(s)
Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Adulto Joven , Neoplasias de los Labios/patología , Labio/patología , Biopsia , Brasil/epidemiología , Neoplasias de los Labios/epidemiología , Factores Sexuales , Reproducibilidad de los Resultados , Estudios Retrospectivos , Sensibilidad y Especificidad , Factores de Edad , Distribución por Sexo , Distribución por Edad , Diagnóstico Bucal/métodos , Enfermedades de los Labios/patología , Enfermedades de los Labios/epidemiología , Persona de Mediana Edad
18.
Braz. oral res. (Online) ; 30(1): 1-7, 2016. tab, graf
Artículo en Inglés | LILACS | ID: lil-768262

RESUMEN

Abstract Salivary gland tumors (SGT) are rare neoplasms that generate interest due to their histopathological diversity and clinical behavior. The aims of the present study were to investigate clinicopathological aspects of SGTs diagnosed at a tertiary health center and compare the findings with epidemiological data from different geographic locations. Cases of tumor in the head and neck region at a single health center in the period between 1995 and 2010 were reviewed. Patient gender, age and ethnic group as well as anatomic location, histological type and clinical behavior of the tumor were recorded. Availability of complete information about these aspects was considered the inclusion criteria. Descriptive statistical analysis of the data was performed using the frequencies of categorical variables. Among the 2168 cases of tumors in the head and neck region, 243 (11.20%) cases were diagnosed in the salivary glands, 109 of which met the inclusion criteria: 85 (78%) benign tumors and 24 (22%) malignant tumors. Mean patient age was 46.47 years. The female gender accounted for 56 cases (51.4%) and the male gender accounted for 53 (48.3%). The major salivary glands were affected more (75.2%) than the minor glands. The most frequent benign and malignant SGTs were pleomorphic adenoma (81.2%) and adenoid cystic carcinoma (58.3%), respectively. In conclusion, pleomorphic adenoma and adenoid cystic carcinoma are the most frequent benign and malignant lesions, respectively. Comparing the present data with previous studies on SGTs, one may infer that some demographic characteristics and the predominance of malignant tumors vary in different geographic regions.


Asunto(s)
Humanos , Masculino , Femenino , Niño , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Adulto Joven , Adenolinfoma/patología , Adenoma Pleomórfico/patología , Carcinoma/patología , Neoplasias de las Glándulas Salivales/patología , Adenolinfoma/epidemiología , Adenoma Pleomórfico/epidemiología , Distribución por Edad , Brasil/epidemiología , Carcinoma/epidemiología , Geografía Médica , Estudios Retrospectivos , Neoplasias de las Glándulas Salivales/epidemiología , Glándulas Salivales/patología , Distribución por Sexo
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