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1.
Braz Oral Res ; 34: e096, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32813838

RESUMO

Regulatory T (Treg) cells can suppress antitumor immune response, but little is known about possible age-related differences in the number of these cells in the microenvironment of oral tongue squamous cell carcinoma (OTSCC). The aim of this study was to determine the number of FoxP3+ Treg cells in the microenvironment of OTSCC in young (≤ 45 years) and older (≥ 60 years) patients, and to correlate the findings with clinicopathological parameters (sex, tumor size/extent, regional lymph node metastasis, clinical staging, and histopathological grade of malignancy). Forty-eight OTSCCs (24 diagnosed in young patients and 24 diagnosed in older patients) were selected. Lymphocytes exhibiting nuclear immunopositivity for FoxP3 were quantified at the tumor invasive front and the results were analyzed statistically using the non-parametric Mann-Whitney test. FoxP3+ lymphocytes were observed in all cases assessed. The number of FoxP3+ lymphocytes in OTSCC tended to be higher in older patients (p = 0.055). Analysis of OTSCC in males and in early clinical stages revealed a higher number of Treg cells in older patients than in young ones (p < 0.05). In older patients, the number of Treg cells tended to be higher in smaller tumors (p = 0.079). Tumors with intense inflammatory infiltrate exhibited a larger number of Treg cells, both in young (p = 0.099) and older patients (p = 0.005). The results suggest a greater participation of Treg cells in immunoinflammatory responses in the microenvironment of OTSCC in older patients, particularly in males and in early stages.


Assuntos
Carcinoma de Células Escamosas , Linfócitos T Reguladores , Neoplasias da Língua , Fatores de Transcrição Forkhead , Humanos , Masculino , Estadiamento de Neoplasias , Microambiente Tumoral
2.
Toxicol In Vitro ; 66: 104851, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32259559

RESUMO

Considering the successful employment of alternative methods for eye toxicity assessment of products for regulatory purposes, and the recent advances in Brazilian legislative scenario, which adopted the UN GHS classification system for agrochemical formulations toxicity assessment, there is an emerging demand for strategies that allow the evaluation of such products. Based on this, the present study aimed to address the applicability of a mechanistic-based defined approach for eye toxicity assessment of agrochemical formulations. It was investigated the opacity/permeability, depth and location of corneal injury in bovine cornea, and vascular events in chorioallantoic membrane induced for different Brazilian agrochemicals using a Sequential Testing Strategy (STS). Cytotoxicity induced by the agrochemical formulations was evaluated by Short Time exposure (STE) (OECD TG 491) assay (step 1), corneal injury was investigated by standard Bovine Corneal Opacity and Permeability (BCOP) (OECD TG 437) followed by histopathological evaluation (step 2), and Hen Chorionic-allantoic Membrane test (HET-CAM) was used to evaluate vascular injury (step 3). The results demonstrated that the proposed defined approach enabled a classification corresponding UN GHS classification of agrochemical formulations while minimizing the use of live animals. Therefore, this approach may be useful for categorization of agrochemicals in Brazil according to the new regulatory scenario.

3.
Asian Pac J Cancer Prev ; 21(4): 1097-1102, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32334476

RESUMO

BACKGROUND: The objectives of the present study were to evaluate angiogenesis and mast cell density in oral epithelial dysplasia and oral squamous cell carcinoma (OSCC). MATERIALS AND METHODS: This was an observational, retrospective and quantitative study. The samples consisted of 60 tissue specimens from patients with squamous cell carcinoma, epithelial dysplasia and controls (n=20/group). Immunohistochemistry was performed using an anti-tryptase antibody to mast cells and anti-CD31 and anti-CD34 for blood vessels and we count the number of mast cells and determine the percentage of CD31 and CD34 antibody staining (vascular density). RESULTS: The mast cells had lower density in OSCC compared to control and dysplasia (p = 0.009). In angiogenesis, the expression of CD31 showed a higher percentage of blood vessels in OSCC (p < 0.001), however, CD34 showed no difference between groups (p=0.092). The CD31 antibody presented as a high immunostaining in oral mucosa than CD34. CONCLUSIONS: The increased vascularity in squamous cell carcinoma suggests that angiogenesis begins when malignant transformation starts that seems to be inversely associated with the number of mast cells.

4.
Oral Dis ; 2020 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-32259363

RESUMO

OBJECTIVE: To investigate the expression of programmed death-ligands 1 and 2 (PD-L1, PD-L2), programmed death-1 (PD-1), CD8 and granzyme B (GrB), as well as its correlation with the severity of oral lichen planus (OLP). MATERIALS AND METHODS: In a collaborative study, 33 cases of OLP were evaluated according to the latest criteria proposed by the American Academy of Oral and Maxillofacial Pathology (AAOMP/2016) and were submitted to immunohistochemistry. Positivity was measured semiquantitatively (PD-L1, PD-L2) and quantitatively (PD-1, CD8, GrB). The severity of OLP was assessed according to clinical subtype, symptomatology and response to corticosteroid therapy. RESULTS: Most OLPs were considered to be negative for PD-L1 (66.6%), but high expression of PD-L2 (96.9%) by keratinocytes and immunoinflammatory cells was observed. PD-1+ cell density/mm2 was reduced compared to CD8+ cells. A low cytotoxic immune response (CD8:GrB ratio) was also demonstrated. Interestingly, there were fewer GrB+ cells in the intraepithelial region in reticular OLP compared to erosive/bullous OLP. CONCLUSIONS: PD-L1/PD-1 pathways appear to be compromised in OLP due to low PD-L1 expression in most samples. In contrast, PD-L2 overexpression associated with a possible regulation of the cytotoxic immune response suggests an immune tolerance that may contribute to the chronic profile of OLP.

5.
Med. oral patol. oral cir. bucal (Internet) ; 25(2): e283-e290, mar. 2020. tab, ilus
Artigo em Inglês | IBECS-Express | IBECS | ID: ibc-ET6-1003

RESUMO

BACKGROUND: The purpose of this experimental study was to compare the immunohistochemical expression of SOX2 and BCL-2 in Odontogenic Keratocyst (OKC) and Ameloblastoma (AB) specimens, and to identify a possible correlation in their expression.MATERIAL AND METHODS: Immunohistochemical analysis was performed to evaluate SOX2 and BCL-2 expression in OKC (n = 20) and AB (n = 20). The immunoexpression was analyzed by a quantitative and qualitative scoring system. The comparison between the immunoexpression of SOX 2 and BCL-2 was assessed by the Mann-Whitney U-test. Spearman's correlation coefficient evaluated the correlation between SOX2 and BCL-2 expressions.RESULTS: SOX2 and BCL-2 expression was observed in all specimens of OKC in the full thickness of the epithelium lining. SOX2 immunostaining was higher in OKC, in comparison with AB samples (P<0.05). BCL-2 immunostaining between OKC and AB was not statistically significant. There was no significant correlation between SOX2 and BCL-2 in OKC and AB specimens.CONCLUSIONS: SOX2 and BCL-2 expressions in OKC may suggest their relationship with the biological behavior of this lesion, and the higher expression of SOX2 might be an upstream influence on the Hh signaling pathway


No disponible

6.
Int J Surg Pathol ; 28(5): 526-535, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31986944

RESUMO

A clear cell variant of calcifying epithelial odontogenic tumor is a rare benign odontogenic neoplasm, accounting for 33 cases described in the literature. In this article, we report a challenging example of clear cell variant of calcifying epithelial odontogenic tumor of the posterior maxilla in a 45-year-old female patient showing locally aggressive growth and recurrence. Microscopically, islands of polyhedral cells containing abundant cytoplasm, well-developed intercellular bridges blended with clear cells were observed. The nuclei were frequently pleomorphic and permeated by hyaline calcified material. Immunohistochemistry revealed positivity for pan-cytokeratin (AE1/AE3), cytokeratins (CK-14 and CK-19), Bcl-2, p53, and p63. The Ki-67 proliferative index was ~10%. As odontogenic tumors are rare, when a significant clear cell component is observed, the differential diagnosis with other lesions of the jaws with similar morphology, including other odontogenic tumors with prominent clear cell component, clear cell odontogenic carcinomas, and metastatic tumors, is difficult.

7.
Oral Dis ; 26(1): 43-52, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31605560

RESUMO

OBJECTIVES: The aim of this study was to investigate the prevalence of oral sarcomas from geographic regions of Brazil. MATERIALS AND METHODS: A cross-sectional study was conducted on biopsies obtained from January 2007 to December 2016 at twelve Brazilian oral and maxillofacial pathology centres. Gender, age, evolution time, clinical aspects, tumour location, tumour size at diagnosis, radiographic aspects and histopathological diagnosis were evaluated. Data were analysed using descriptive statistical methods. RESULTS: From 176,537, a total of 200 (0.11%) oral sarcomas were reported, and the most prevalent were osteosarcomas (74 cases; 37%) and Kaposi's sarcomas (52 cases; 26%). Males were more affected than females at a mean age of 32.2 years old (range of 3-87 years). The most common symptoms were swelling¸ localised pain and bleeding at a mean evolution time of 5.14 months (range <1-156 months). The lesions were mostly observed in the mandible (90 cases; 45%), with a mean tumour size of 3.4 cm (range of 0.3-15 cm). Radiographically, the lesions presented a radiolucent aspect showing cortical bone destruction and ill-defined limits. CONCLUSIONS: Oral sarcomas are rare lesions with more than 50 described subtypes. Osteosarcomas and Kaposi's sarcomas were the main sarcomas of the oral cavity in Brazil.


Assuntos
Neoplasias Bucais/epidemiologia , Sarcoma/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biópsia , Brasil/epidemiologia , Criança , Pré-Escolar , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Osteossarcoma/epidemiologia , Estudos Retrospectivos , Sarcoma de Kaposi/epidemiologia , Adulto Jovem
8.
J Oral Pathol Med ; 49(3): 219-226, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31782199

RESUMO

BACKGROUND: Analyze the clinical, demographic, histopathological, and immunohistochemical features of oral lymphoepithelial cyst (OLEC). METHODS: Samples were retrospectively retrieved from five oral pathology services. Clinical and demographic data were collected from patient charts. Histopathological and immunohistochemical (CD3 and CD20) features were evaluated. Data analysis involved descriptive statistics and bivariate analyses (P ≤ .05). RESULTS: Seventy-seven cases were found among a total of 146 150 specimens (0.05%). OLEC was predominantly diagnosed in females (70.1%). Mean patient age was 46.51 years. The lesions arose mainly on the lateral border of the tongue (40.3%), measured up to 1 cm (61.0%), and were asymptomatic (64.9%). Twenty-four lesions (31.2%) were white. Forty-one cases (53.2%) presented lymphocytic inflammatory infiltrate with no specific arrangement. The cystic lining was composed of a non-keratinized stratified epithelium (59.7%) presenting hyperplasia (39.0%). Connection with the surface, epithelium was found in 23 cases (29.9%) and 31 (40.3%) cases had two or more cystic cavities. The lumen content was predominantly desquamated cells (48.1%). Subgemmal neurogenous plaque was found in 11/42 (26.2%) cases involving the tongue. CD20+ cells predominated in 36/63 cases (57.2%), and lymphocytic inflammatory infiltrate was not always continuous around the cystic cavity (52.4%). CONCLUSION: Lymphoepithelial cyst is an uncommon lesion of the oral cavity. The present study offers the largest sample of OLEC for which clinical, demographic, histopathological, and immunohistochemical features were evaluated. The clinical and demographic findings were similar to those described in previous reports, but the microscopic analyses revealed interesting aspects of the cystic epithelium and the lymphocytic inflammatory infiltrate in OLEC.


Assuntos
Cistos/patologia , Epitélio/patologia , Doenças da Boca/patologia , Língua/patologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Adulto Jovem
9.
J Clin Exp Dent ; 11(12): e1109-e1119, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31824590

RESUMO

Background: The aim of the present series was to analyze the sociodemographic characteristics, clinicopathologic features, and oral health-related quality of life of 41 individuals with oral lichen planus (OLP). Material and Methods: In a retrospective analysis (1998-2018), individuals with a clinical diagnosis of OLP from a referral service of Oral Medicine of Brazil were invited for follow-up. The individuals were assessed using the Oral Health Impact Profile-14 (OHIP-14) form. Histopathological data were reviewed according to the latest criteria proposed by the American Academy of Oral and Maxillofacial Pathology (AAOMP/2016). Results: This series mainly consisted of females (70.7%) in their forties (31.7%). The buccal mucosa (68.2%) was the most commonly affected site. Reticular (56.1%) and erosive (34.3%) appearances were the most frequent. According to OHIP-14, individuals with OLP at multiple sites in the oral cavity showed worse values in the handicap domain and those who did not respond to corticosteroids showed a higher score on the psychological discomfort domain. Conclusions: The findings of the present study, using the AAOMP/2016 criteria, agree with case series and retrospective studies reported in the literature. Besides, OLP in its more severe clinical forms had an influence on patient quality of life. Key words:Diagnosis, epidemiology, oral lichen planus, oral mucosa, quality of life.

10.
Braz Oral Res ; 33: e103, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31778473

RESUMO

The immunoexpression of p16, p53, and Bax in oral tongue squamous cell carcinoma (OTSCC) in young and elderly patients is assessed based on clinical and morphological parameters. The sample consists of 60 OTSCC cases: 30 in young (age ≤ 45 years) and 30 in elderly (age ≥ 60 years) patients. Clinical (tumor size, regional node metastasis, distant metastasis, and clinical stage) and morphological (histological grade of malignancy) parameters were evaluated. Immunohistochemical quantitative analysis was performed using anti-p16, anti-p53, and anti-Bax antibodies. None of the evaluated proteins exhibited statistically significant differences between young and elderly patients (p>0.05). There was a significant association of p16 immunoexpression with clinical parameters in elderly patients. There were no associations of p53 and Bax with any of the clinico-morphological parameters. Correlations between p16 and Bax and between p53 and Bax immunoexpression were observed in young patients (r = 0.363; p = 0.048) and in elderly patients (r = 0.433; p = 0.017), respectively. In conclusion, the assessed proteins could not be used to determine differences in the biological behavior of OTSCC between young and elderly patients. Therefore, all proteins activated the pro-apoptotic pathway of OTSCC in both groups.


Assuntos
Carcinoma de Células Escamosas/patologia , Inibidor p16 de Quinase Dependente de Ciclina/análise , Neoplasias da Língua/patologia , Proteína Supressora de Tumor p53/análise , Proteína X Associada a bcl-2/análise , Adulto , Fatores Etários , Idoso , Apoptose , Biomarcadores Tumorais/análise , Ciclo Celular , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Estatísticas não Paramétricas , Carga Tumoral
11.
Braz Dent J ; 30(4): 404-409, 2019 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-31340232

RESUMO

Crossover studies continue to be published in spite of warnings about their inherent risks in relation to behavioral outcomes. This study took the opportunity of access to secondary data analysis in order to demonstrate the impact of a crossover design on the outcomes of randomized clinical trials aimed at the behavior of children during dental treatment. We evaluated the effect of the sequence of sedative administration, the sedative and the participant's age on the behavior of children undergoing two sequential dental visits. Eighteen uncooperative healthy young children were equally randomly assigned to: (G1) 1.0 mg/kg oral midazolam (first session) and oral placebo (second session); (G2) oral placebo (first) and 1.0 mg/kg oral midazolam (second). One trained observer assessed children's behavior. Data were analyzed by three-way mixed ANOVA. Both midazolam [mean(SD); 71.7%(16.5)] and placebo [48.6%(33.1)] produced more struggling behavior when they were administered in the first session compared to the second one (p=0.001). For the placebo, children aged 2-3 years exhibited more struggling behavior [G1 54.9%(36.2); G2 80.5%(8.3)] than those aged 4-5 years (p=0.04). Also, the reduction of percentage of struggling behavior was higher in G1 for older children (76.2%) and in G2 for younger children (32.9%). There were significant interactions between drug and sequence of administration, and between drug and age. The results of our study confirm the conventional wisdom that crossover study design is inappropriate to evaluate children's behavior/anxiety related-dental treatment under sedation and the results of crossover studies of dental sedation should be treated with extreme caution.


Assuntos
Anestesia Dentária , Sedação Consciente , Criança , Comportamento Infantil , Pré-Escolar , Estudos Cross-Over , Humanos , Hipnóticos e Sedativos , Midazolam
12.
Braz. dent. j ; 30(4): 404-409, July-Aug. 2019. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1011571

RESUMO

Abstract Crossover studies continue to be published in spite of warnings about their inherent risks in relation to behavioral outcomes. This study took the opportunity of access to secondary data analysis in order to demonstrate the impact of a crossover design on the outcomes of randomized clinical trials aimed at the behavior of children during dental treatment. We evaluated the effect of the sequence of sedative administration, the sedative and the participant's age on the behavior of children undergoing two sequential dental visits. Eighteen uncooperative healthy young children were equally randomly assigned to: (G1) 1.0 mg/kg oral midazolam (first session) and oral placebo (second session); (G2) oral placebo (first) and 1.0 mg/kg oral midazolam (second). One trained observer assessed children's behavior. Data were analyzed by three-way mixed ANOVA. Both midazolam [mean(SD); 71.7%(16.5)] and placebo [48.6%(33.1)] produced more struggling behavior when they were administered in the first session compared to the second one (p=0.001). For the placebo, children aged 2-3 years exhibited more struggling behavior [G1 54.9%(36.2); G2 80.5%(8.3)] than those aged 4-5 years (p=0.04). Also, the reduction of percentage of struggling behavior was higher in G1 for older children (76.2%) and in G2 for younger children (32.9%). There were significant interactions between drug and sequence of administration, and between drug and age. The results of our study confirm the conventional wisdom that crossover study design is inappropriate to evaluate children's behavior/anxiety related-dental treatment under sedation and the results of crossover studies of dental sedation should be treated with extreme caution.


Resumo Pouco se sabe sobre o impacto de um delineamento cruzado nos desfechos de ensaios clínicos randomizados voltados ao comportamento de crianças durante tratamento odontológico. Este estudo objetivou avaliar o efeito da sequência de administração do sedativo, da droga em si e da idade dos participantes no comportamento de crianças que receberam duas consultas odontológicas consecutivas. Dezoito crianças saudáveis não colaboradoras, 2-5 anos de idade, foram randomizadas em dois grupos: G1 - 1,0 mg/kg midazolam oral (primeira sessão) e placebo oral (segunda sessão); G2 - placebo (primeira) e 1,0 mg/kg midazolam oral (segunda). Um observador treinado avaliou o comportamento infantil. Os dados foram analisados por ANOVA de três fatores (alfa=0,05). Midazolam [média(DP); 71,7%(16,5)] e placebo [48,6%(33,1)] resultaram em mais comportamento não cooperativo quando administrados na primeira sessão comparado com a segunda (p=0,001). Com o uso do placebo, crianças de 2-3 anos de idade exibiram mais comportamento não cooperativo [G1 54,9%(36,2); G2 80,5%(8,3)] que as de 4-5 anos de idade (p=0,04). Além disso, a porcentagem de redução do comportamento não cooperativo foi maior em crianças mais velhas em G1 (76,2%) e em crianças mais novas em G2 (32,9%). Considerando a avaliação do comportamento infantil sob sedação, a primeira sessão odontológica influenciou a segunda visita. Os resultados deste estudo confirmam a especulação de que o delineamento cruzado é inadequado para avaliar o comportamento odontológico relacionado à ansiedade/comportamento infantil; os resultados dos ensaios cruzados de sedação odontológica devem ser tratados com extrema cautela.

13.
J Endod ; 45(6): 716-723, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-31060815

RESUMO

INTRODUCTION: There is evidence that acute periapical lesions present a greater potential for cyst formation. Recently, it was found that these lesions have cells with characteristics of pluripotent stem cells, which may influence cyst development. However, a more complete phenotype investigation of stem cells in a specific sample of periapical abscesses is required. The aim of this study was to analyze the immunohistochemical expression of mesenchymal stem cell (MSC) markers in periapical abscesses and to evaluate differences in their expression in relation to acute and chronic periapical lesions. METHODS: Immunohistochemistry was used to access MSC marker expression (CD44, CD73, and CD105) in samples of periapical abscesses (n = 10), granulomas (n = 10), cysts (n = 10), and apical papillae (n = 10). Immunohistochemical expression was evaluated by a quantitative scoring system. The chi-square test was used to assess the association between MSC marker expression and the histopathological diagnosis at a 5% significance level. RESULTS: CD44 and CD73 immunostaining was observed in mesenchymal cells located in the outer portion of the abscess and periapical cyst specimens. CD105 immunoexpression was found predominantly in mesenchymal and vascular endothelial cells of the lesions studied. MSC marker expression was higher in the periapical abscesses, with a significant association between MSCs and the histopathological diagnosis of an abscess (P < .05). CONCLUSIONS: The periapical region is a rich source of MSCs. The greater presence of MSCs in periapical abscesses found in this study could hold an important clue into understanding the pathological pathway of periapical cyst formation.


Assuntos
Biomarcadores , Células-Tronco Mesenquimais , Abscesso Periapical , Granuloma Periapical , Cisto Radicular , Biomarcadores/metabolismo , Células Endoteliais , Humanos , Imuno-Histoquímica , Células-Tronco Mesenquimais/metabolismo , Abscesso Periapical/metabolismo , Células-Tronco
14.
Oral Oncol ; 93: 52-58, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-31109696

RESUMO

The presence of lymphovascular invasion is considered a prognostic determinant for different human neoplasms and is frequently taken into account by surgeons and oncologists to determine patients' treatment. However, the exact frequency of this microscopic event and its prognostic impact for patients affected by adenoid cystic carcinoma (AdCC) remains unclear. Therefore, the aim of this study was to carry out a systematic review and meta-analysis to address the prevalence and the prognostic potential of lymphovascular invasion in head and neck AdCC. A literature search on PubMed, Scopus, ClinicalTrials.gov, Web of Science and ProQuest databases was undertaken in January 2019. The primary outcomes of interest were overall survival (OS) and disease-free survival (DFS). The relative frequency of lymphovascular invasion and its possible association with other clinicopathological parameters were addressed. A total of 22 studies and 2117 patients were included in this study. The frequency of lymphovascular invasion ranged from 5.2% to 72.5%. Lymphovascular invasion was associated with an increased likelihood of lymph node metastasis (OR = 2.58; 95% CI 1.61-4.12; p = 0.0001) and death (OR = 3.09; 95% CI 1.82-5.26; p = 0.0001), solid/higher-grade AdCC were more likely to present lymphovascular invasion (OR = 5.51; 95% CI 1.87-16-21; p = 0.002) and patients with this microscopic finding had a significantly lower OS (HR = 8.30; 95% CI 1.68-40.91; p = 0.009) and DFS (HR = 3.76; 95% CI 1.13-12.53; p = 0.03). In conclusion, lymphovascular invasion seems to be a significant predictor of poor prognosis for head and neck AdCC patients.

15.
Arch Toxicol ; 93(7): 1955-1964, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31020376

RESUMO

Acetaminophen (APAP) is one of the most widely consumed drugs in the world. Studies have shown renal and hepatic damage as the direct result of high oxidative stress induced by APAP. Since the cardiovascular system is sensitive to oxidative stress and literature describes increased cardiovascular dysfunction in APAP consumers, this work aimed to evaluate harmful effects of APAP on the vascular system. Rats were exposed to APAP (400 mg/kg/day in drinking water) for 14 days. Plasma and aortas were collected and stored in - 80 °C and a selection of arteries was prepared for isometric tension recordings, morphological, immunohistochemical and protein expression analysis. The APAP-treated group presented increased transaminases (ALT/AST) and malondialdehyde levels in the plasma compared to controls. Lipid peroxidation, glutathione reductase and superoxide dismutase levels were increased in the plasma and arteries of the APAP group. Nevertheless, glutathione level was reduced as compared to control group. The vasodilation response to acetylcholine and sodium nitroprusside (0.1 nM to 10 µM) was also impaired after APAP treatment; however, the vascular relaxation was restored after treatment with vitamin C (100 µM). Arteries from the APAP group presented reduced wall thickness, collagen deposition, elastic fibers and increased immunoreactivity to nitrotyrosine. eNOS and sGC protein expression remained unchanged and were at similar levels as controls. These findings showed higher oxidative stress and impaired vasodilation in rats exposed to APAP. Furthermore, arteries presented reduced cell layers, collagen, elastin deposition and significantly increased immunoreactivity to nitrotyrosine after APAP treatment.

16.
Trials ; 20(1): 97, 2019 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-30709370

RESUMO

BACKGROUND: Oral mucositis (OM) is the most frequent and debilitating acute side effect associated with head and neck cancer (HNC) treatment. When present, severe OM negatively impacts the quality of life of patients undergoing HNC treatment. Photobiomodulation is a well-consolidated and effective therapy for the treatment and prevention of severe OM, and is associated with a cost reduction of the cancer treatment. Although an increase in the quality of life and a reduction in the severity of OM are well described, there is no study on cost-effectiveness for this approach considering the quality of life as a primary outcome. In addition, little is known about the photobiomodulation effects on salivary inflammatory mediators. Thus, this study aimed to assess the cost-effectiveness of the photobiomodulation therapy for the prevention and control of severe OM and its influence on the salivary inflammatory mediators. METHODS/DESIGN: This randomized, double-blind clinical trial will include 50 HNC patients undergoing radiotherapy or chemoradiotherapy. The participants will be randomized into two groups: intervention group (photobiomodulation) and control group (preventive oral care protocol). OM (clinical assessment), saliva (assessment of collected samples) and quality of life (Oral Health Impact Profile-14 and Patient-Reported Oral Mucositis Symptoms questionnaires) will be assessed at the 1st, 7th, 14th, 21st and 30th radiotherapy sessions. Oxidative stress and inflammatory cytokine levels will be measured in the saliva samples of all participants. The costs are identified, measured and evaluated considering the radiotherapy time interval. The incremental cost-effectiveness ratio will be estimated. The study will be conducted according to the Brazilian public health system perspective. DISCUSSION: Photobiomodulation is an effective therapy that reduces the cost associated with OM treatment. However, little is known about its cost-effectiveness, mainly when quality of life is the effectiveness measure. Additionally, this therapy is not supported by the Brazilian public health system. Therefore, this study widens the knowledge about the safety of and strengthens evidence for the use of photobiomodulation therapy, providing information for public policy-makers and also for dental care professionals. This study is strongly encouraged due to its clinical relevance and the possibility of incorporating new technology into public health systems. TRIAL REGISTRATION: Brazilian Registry of Clinical Trials-ReBEC, RBR-5h4y4n . Registered on 13 June 2017.


Assuntos
Quimiorradioterapia/efeitos adversos , Irradiação Craniana/efeitos adversos , Neoplasias de Cabeça e Pescoço/radioterapia , Terapia com Luz de Baixa Intensidade/métodos , Lesões por Radiação/prevenção & controle , Glândulas Salivares/efeitos da radiação , Estomatite/prevenção & controle , Biomarcadores/metabolismo , Brasil , Quimiorradioterapia/economia , Análise Custo-Benefício , Irradiação Craniana/economia , Citocinas/metabolismo , Método Duplo-Cego , Neoplasias de Cabeça e Pescoço/economia , Custos de Cuidados de Saúde , Humanos , Mediadores da Inflamação/metabolismo , Terapia com Luz de Baixa Intensidade/efeitos adversos , Terapia com Luz de Baixa Intensidade/economia , Estresse Oxidativo , Lesões por Radiação/economia , Lesões por Radiação/etiologia , Lesões por Radiação/metabolismo , Ensaios Clínicos Controlados Aleatórios como Assunto , Fatores de Risco , Saliva/metabolismo , Glândulas Salivares/metabolismo , Índice de Gravidade de Doença , Estomatite/economia , Estomatite/etiologia , Estomatite/metabolismo , Fatores de Tempo , Resultado do Tratamento
17.
Phytother Res ; 33(4): 881-890, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30672024

RESUMO

We explored the effects of a mucoadhesive formulation containing curcuminoid (MFC) from Curcuma longa L. extract on oral mucositis (OM) induced by 5-fluorouracil (5-FU) in hamsters. Seventy-two golden Syrian hamsters were randomly allocated into four groups: control, placebo, chamomilla, and MFC. Animals received an intraperitoneal injection of 5-FU at Days 0 and 2. On Days 3 and 4, the buccal mucosa was scratched. Therapy was initiated on Day 5. Animals received two applications of the substances per day according to the experimental group. Six animals were euthanized on Days 8, 10, and 14. Clinical analysis were performed using photography and histopathological sections of 3 µm were stained by hematoxylin-eosin for semiquantitative analysis of re-epithelization and inflammation. Immunohistochemistry was used for angiogenesis (CD31) and transforming growth factor beta 1 (TGF-ß1) analysis. On Day 5, all groups exhibited OM. Clinical and histopathological findings revealed that on Day 8, both MFC and chamomilla groups exhibited better wound healing. In addition, the MFC group demonstrated lower angiogenesis and TGF-ß1 levels on Day 8 compared with placebo and control groups. Collectively, these findings suggest that MFC has a therapeutic effect on OM, accelerating wound healing through re-epithelization and anti-inflammatory action as modulation of angiogenesis and TGF-ß1 expression.


Assuntos
Fluoruracila/toxicidade , Extratos Vegetais/uso terapêutico , Estomatite/tratamento farmacológico , Animais , Cricetinae , Curcuma , Composição de Medicamentos , Masculino , Mesocricetus , Estomatite/induzido quimicamente , Cicatrização/efeitos dos fármacos
18.
Mod Pathol ; 32(6): 799-806, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30643167

RESUMO

Adenomatoid odontogenic tumor is a benign encapsulated epithelial odontogenic tumor that shows an indolent clinical behavior. We have reported in a few adenomatoid odontogenic tumors mutations in KRAS, which is a proto-oncogene frequently mutated in cancer such as lung, pancreas, and colorectal adenocarcinomas. We aimed to assess KRAS mutations in the hotspot codons 12, 13, and 61 in a large cohort of adenomatoid odontogenic tumors and to test the association of these mutations with clinical (age, site, tumor size, follicular/extrafollicular subtypes) and histopathological parameters. Thirty eight central cases were studied. KRAS codon 12 mutations were assessed by TaqMan allele-specific qPCR (p.G12V/R) and/or Sanger sequencing, and codon 13 and 61 mutations were screened by Sanger. Histological tumor capsule thickness was evaluated by morphometric analysis. Additionally, the phosphorylated form of the MAPK downstream effector ERK1/2 was investigated. Statistical analysis was carried out to test the association of KRAS mutations with clinicopathological parameters. KRAS c.35 G >T mutation, leading to p.G12V, was detected in 15 cases. A novel mutation in adenomatoid odontogenic tumor, c.34 G >C, leading to p.G12R, was detected in 12 cases and the other 11 were wild-type. Codon 12 mutations were not associated with the clinicopathological parameters tested. RAS mutations are known to activate the MAPK pathway, and we show that adenomatoid odontogenic tumors express phosphorylated ERK1/2. In conclusion, a high proportion of adenomatoid odontogenic tumors (27/38, 71%) have KRAS codon 12 mutations, which occur independently of the clinicopathological features evaluated. Collectively, these findings indicate that KRAS mutations and MAPK pathway activation are the common features of this tumor and some cancer types. Although it is unclear why different codon 12 alleles occur in different disease contexts and the complex interactions between tumor genotype and phenotype need clarification, on the basis of our results the presence of KRAS p.G12V/R favors the adenomatoid odontogenic tumor diagnosis in challenging oral neoplasm cases.


Assuntos
Ameloblastoma/genética , Ameloblastoma/patologia , Proteínas Proto-Oncogênicas p21(ras)/genética , Adolescente , Adulto , Criança , Feminino , Humanos , Sistema de Sinalização das MAP Quinases/fisiologia , Masculino , Pessoa de Meia-Idade , Mutação , Adulto Jovem
19.
Oral Oncol ; 88: 95-101, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30616805

RESUMO

OBJECTIVES: The objective of the present study was to investigate the expression of immune checkpoints (PD-L1, PD-L2, PD-1 and CTLA-4), immune inhibitory molecule HLA-G, markers of tumor-infiltrating lymphocytes (TIL) and dendritic cells (DC), as well as its association with clinicopathological features of adenoid cystic carcinomas (ACC) of the salivary glands. MATERIALS AND METHODS: Thirty-six samples from patients with ACC were analyzed immunohistochemically for the expression of PD-L1, PD-L2, PD-1, CTLA-4, HLA-G, CD8, GrB, CD1a and CD83. Positivity of HLA-G, PD-L1 and PD-L2 expression was defined by cut-offs values. CD8+ TIL was measured semiquantitatively and also using cut-off values obtained by the ROC curve considering recurrence of the lesion. RESULTS: ACC showed low CD8+, GrB+  TIL, CD1a and CD83 populations, as well as scarce positivity for CTLA-4 and PD-1. In contrast, PD-L2 and HLA-G expression was increased, while no PD-L1 expression was detected. Interestingly, cases with lower CD8+ TIL density presented greater recurrence rates. CONCLUSION: Our findings suggest that the ACC microenvironment exhibits low immunogenicity, represented by low TIL and DC density. Moreover, there seems to be activation of the immune inhibitory proteins/PD-L2 and HLA-G, a scenario that may favor tumor escape from the immune system and partially explain the poor prognosis of ACC.


Assuntos
Carcinoma Adenoide Cístico/imunologia , Neoplasias das Glândulas Salivares/imunologia , Evasão Tumoral/imunologia , Microambiente Tumoral/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno B7-H1/metabolismo , Linfócitos T CD8-Positivos/metabolismo , Antígeno CTLA-4/metabolismo , Carcinoma Adenoide Cístico/patologia , Carcinoma Adenoide Cístico/cirurgia , Estudos Transversais , Células Dendríticas/metabolismo , Feminino , Seguimentos , Antígenos HLA-G/metabolismo , Humanos , Contagem de Linfócitos , Linfócitos do Interstício Tumoral/imunologia , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/imunologia , Prognóstico , Proteína 2 Ligante de Morte Celular Programada 1/metabolismo , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologia , Neoplasias das Glândulas Salivares/cirurgia , Adulto Jovem
20.
Arch Oral Biol ; 98: 99-107, 2019 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30468994

RESUMO

OBJECTIVES: Programmed death ligand-1 (PD-L1) and human leukocyte antigen-G (HLA-G) are considered immune checkpoint molecules that inhibit T-cell effectiveness, contributing to tumor immune escape. This study investigated PD-L1, HLA-G, CD8, and granzyme B (GrB) expression at different stages of lip carcinogenesis. DESIGN AND RESULTS: Forty cases of lip squamous cell carcinoma (LSCC), 55 actinic cheilitis (AC), and 10 healthy lip mucosa (HLM) were submitted to immunohistochemistry. Semiquantitative (PD-L1, HLA-G), and quantitative (CD8, GrB) analysis were performed. PD-L1 and HLA-G expression in neoplastic cells/keratinocytes and stroma/connective tissue was significantly higher in LSCC and AC, compared to HLM (p<0.05). PD-L1 was not associated with clinicopathological features of the lesions. HLA-G expression by malignant cells was significantly higher in LSCCs with distant metastasis (p = 0.041).CD8+ and GrB+ cell numbers progressively increased from HLMs to LSCC, with AC exhibiting intermediate numbers (p<0.01). Most LSCCs showed coexistence of PD-L1+ and CD8+ cells (72.5%). PD-L1 was directly correlated to CD8+ and GrB+ lymphocytic infiltration in LSCCs (p<0.05). Low cytotoxic immune response was associated with lymph node metastasis in LSCC (p<0.05). CONCLUSIONS: PD-L1 and HLA-G-mediated immune evasion mechanisms are likely to occur from early pre-malignant to advanced malignant stages of lip carcinogenesis, which might provide a rationale for therapeutic blockade of these pathways. PD-L1 expression in LSCCs was correlated with the cytotoxic markers, suggesting that PD-L1 may appear as an escape mechanism in response to an active antitumor response.


Assuntos
Carcinogênese/imunologia , Neoplasias Labiais/imunologia , Linfócitos T CD8-Positivos/imunologia , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Queilite/imunologia , Queilite/patologia , Estudos Transversais , Feminino , Granzimas/imunologia , Antígenos HLA-G/imunologia , Humanos , Evasão da Resposta Imune , Imuno-Histoquímica , Queratinócitos/imunologia , Queratinócitos/patologia , Neoplasias Labiais/patologia , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Mucosa Bucal/imunologia , Mucosa Bucal/patologia , Receptor de Morte Celular Programada 1/imunologia , Estudos Retrospectivos , Células Estromais/imunologia , Células Estromais/patologia , Microambiente Tumoral/imunologia
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