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1.
J Proteome Res ; 23(6): 2148-2159, 2024 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-38785273

RESUMO

Diverse proteomics-based strategies have been applied to saliva to quantitatively identify diagnostic and prognostic targets for oral cancer. Considering that these targets may be regulated by events that do not imply variation in protein abundance levels, we hypothesized that changes in protein conformation can be associated with diagnosis and prognosis, revealing biological processes and novel targets of clinical relevance. For this, we employed limited proteolysis-mass spectrometry in saliva samples to explore structural alterations, comparing the proteome of healthy control and oral squamous cell carcinoma (OSCC) patients with and without lymph node metastasis. Thirty-six proteins with potential structural rearrangements were associated with clinical patient features including transketolase and its interacting partners. Moreover, N-glycosylated peptides contribute to structural rearrangements of potential diagnostic and prognostic markers. Altogether, this approach utilizes saliva proteins to search for targets for diagnosing and prognosing oral cancer and can guide the discovery of potential regulated sites beyond protein-level abundance.


Assuntos
Neoplasias Bucais , Proteoma , Saliva , Humanos , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Neoplasias Bucais/diagnóstico , Saliva/química , Saliva/metabolismo , Proteoma/análise , Carcinoma de Células Escamosas/metabolismo , Carcinoma de Células Escamosas/patologia , Carcinoma de Células Escamosas/diagnóstico , Feminino , Biomarcadores Tumorais/metabolismo , Masculino , Metástase Linfática , Conformação Proteica , Pessoa de Meia-Idade , Prognóstico , Proteômica/métodos , Transcetolase/metabolismo , Idoso , Espectrometria de Massas , Proteínas e Peptídeos Salivares/metabolismo , Proteínas e Peptídeos Salivares/análise
2.
Dent J (Basel) ; 11(9)2023 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-37754329

RESUMO

Delivering bad news has been widely studied in cancer, thus, this scoping review aims to identify the available evidence concerning the communication of oral potentially malignant disorders (OPMDs) and their clinical and psychosocial impacts. A search was performed using electronic databases (Medline/PubMed, Scopus, Embase, and Web of Science) and one grey literature database (Google Scholar). Studies focused on communicating the diagnosis of OPMDs and the patients' perceptions were included. Study selection and data extraction were performed by two authors in a two-phase process. Five publications were included in the qualitative analysis. Differences regarding the study design, population, OPMDs assessed, and outcomes of professional-patient communication were found in each study. Protocols for OPMD communication have not yet been reported and there is a need to standardize strategies as communication skills may provide better clinical outcomes for patients diagnosed with potentially malignant disorders. Although future studies are needed, a brief list recommending the aspects that must be communicated is proposed.

3.
J Clin Exp Dent ; 14(1): e27-e34, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35070121

RESUMO

BACKGROUND: Juvenile ossifying fibroma (JOF) is an uncommon benign fibro-osseous lesion of the craniofacial skeleton; compared to conventional ossifying fibroma (OF), JOF is characterized by local aggressiveness and propensity for recurrence. The biologic basis for this different biologic behavior between JOF and OF remains elusive. The aim of this study was to evaluate the immunohistochemical expression of MDM2, CDK4 and p53, molecules associated with bone oncogenesis, in the trabecular variant of JOF. MATERIAL AND METHODS: The study material consisted of five cases of trabecular JOF, affecting three male and two female patients with a mean age of 11.8 years. Three cases arose in the maxilla and two in the mandible. All cases were initially treated by enucleation; two cases recurred necessitating more aggressive treatment. Immunohistochemical study of MDM2, CDK4 and p53 was performed in all cases, as well as in five control cases of conventional OF. RESULTS: CDK4 positivity was noted in all JOF cases; the staining pattern was diffuse and strong in 4 cases and focal and weak in one case. In contrast, 4 out of 5 cases of OF were weakly and focally CDK4 positive, the remaining one being negative. Immunostaining for MDM2 was observed in 3 JOF cases; all OF were MDM2 negative. All cases of OF and JOF were negative for p53, except for one focally positive JOF case. CONCLUSIONS: CDK4 and MDM2 expression in the trabecular variant of JOF is higher compared to conventional OF. In contrast, p53 expression is almost universally negative in JOF and OF. Despite some overlapping features, differential expression patterns of proteins involved in bone oncogenesis can elucidate the pathogenesis and may facilitate accurate diagnosis and prediction of behavior of bone tumors in the craniofacial region. Key words:Juvenile ossifying fibroma, trabecular variant, conventional ossifying fibroma, MDM2, CDK4, p53.

4.
Appl Immunohistochem Mol Morphol ; 29(10): 781-790, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34320560

RESUMO

A proper antibody panel selection is one of the most important factors to reach an adequate diagnosis in challenging cases. This retrospective study was designed to determine the contribution of immunohistochemistry (IHC) in the primary diagnosis of oral diseases in one of the main services of oral pathology in the State of São Paulo, Brazil, and to identify the most common antibodies used, and recommend diagnostic algorithms based on our experience with challenging lesions. A total of 1698 IHC stains were performed in 401 cases from a total of 28,804 cases received from public dental clinics and private dental practitioners within a period of 13 years, representing a frequency of 1.4% of IHC solicitations. Among these, 112 (28%) were mandatory to reach a final diagnosis and 255 (63.6%) were confirmative. In 34 (8.4%) cases, it was not possible to reach a conclusive/final diagnosis, even with IHC. Regarding the nature of the lesions, 210 (52.3%) were benign, 163 (40.6%) were malignant tumors, 13 (3.2%) were reactive, 10 (2.5%) were premalignant, and 5 (1.2%) were lesions of uncertain malignancy. Small amount of tissue of some incisional biopsies, overlapping features of spindle cell lesions (epithelial, neural, melanocytic, smooth muscle, endothelial, and fibroblastic/myofibroblastic cell differentiation), and overlapping features of salivary gland lesions were the most frequent challenges in which IHC stains were requested. Spindle cell lesions were the most frequent (22%) among all cases that required IHC to reach a final diagnosis. The implementation of IHC for routine practice requires a wide range of markers, proper antibody selection, and knowledge to interpret the subjectivity of staining. The inherent limitation of incisional biopsies was pointed as a reason to inconclusive diagnosis, despite a wide range of antibodies that our laboratory displays.


Assuntos
Imuno-Histoquímica , Neoplasias Bucais , Patologia Bucal , Lesões Pré-Cancerosas , Brasil , Feminino , Humanos , Masculino , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Lesões Pré-Cancerosas/diagnóstico , Lesões Pré-Cancerosas/metabolismo , Lesões Pré-Cancerosas/patologia , Estudos Retrospectivos
5.
Biochim Biophys Acta Proteins Proteom ; 1869(8): 140659, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-33839314

RESUMO

Saliva is a biofluid that maintains the health of oral tissues and the homeostasis of oral microbiota. Studies have demonstrated that Oral squamous cell carcinoma (OSCC) patients have different salivary microbiota than healthy individuals. However, the relationship between these microbial differences and clinicopathological outcomes is still far from conclusive. Herein, we investigate the capability of using metagenomic and metaproteomic saliva profiles to distinguish between Control (C), OSCC without active lesion (L0), and OSCC with active lesion (L1) patients. The results show that there are significantly distinct taxonomies and functional changes in L1 patients compared to C and L0 patients, suggesting compositional modulation of the oral microbiome, as the relative abundances of Centipeda, Veillonella, and Gemella suggested by metagenomics are correlated with tumor size, clinical stage, and active lesion. Metagenomics results also demonstrated that poor overall patient survival is associated with a higher relative abundance of Stenophotromonas, Staphylococcus, Centipeda, Selenomonas, Alloscordovia, and Acitenobacter. Finally, compositional and functional differences in the saliva content by metaproteomics analysis can distinguish healthy individuals from OSCC patients. In summary, our study suggests that oral microbiota and their protein abundance have potential diagnosis and prognosis value for oral cancer patients. Further studies are necessary to understand the role of uniquely detected metaproteins in the microbiota of healthy and OSCC patients as well as the crosstalk between saliva host proteins and the oral microbiome present in OSCC.


Assuntos
Saliva/microbiologia , Carcinoma de Células Escamosas de Cabeça e Pescoço/microbiologia , Adulto , Idoso , Estudos de Coortes , Feminino , Humanos , Masculino , Metagenômica/métodos , Microbiota/genética , Pessoa de Meia-Idade , Neoplasias Bucais/metabolismo , Neoplasias Bucais/microbiologia , Prognóstico , Proteômica/métodos , Carcinoma de Células Escamosas de Cabeça e Pescoço/metabolismo
6.
Head Neck ; 42(9): 2660-2668, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32343457

RESUMO

BACKGROUND: The aim of this study was to integrate the available data published on radiation-induced sarcoma of the oral cavity into an analysis of its clinical features, treatment modalities and prognostic factors. METHODS: An electronic search was undertaken in September 2019. The eligibility criteria included publications that had enough clinical and histological information to confirm the diagnosis. RESULTS: Forty-two publications with 122 radiation-induced sarcoma of the oral cavities (RISOCs) were included. The mean latency period was 114 months and mean radiation total dose was 62.5 Gy. The tumors were more prevalent in males between 50 and 60 years old and the mandible was the most affected site. Osteosarcoma was the most prevalent histological type and patients were mostly treated with radical surgery. CONCLUSIONS: RISOC showed a poor survival rate of 15.1% in 5-year follow-up. Gender and histological type were independently associated with survival.


Assuntos
Neoplasias Ósseas , Neoplasias Induzidas por Radiação , Osteossarcoma , Sarcoma , Neoplasias de Tecidos Moles , Humanos , Masculino , Mandíbula , Pessoa de Meia-Idade , Neoplasias Induzidas por Radiação/epidemiologia , Neoplasias Induzidas por Radiação/etiologia , Sarcoma/epidemiologia , Sarcoma/etiologia , Sarcoma/terapia
7.
J Oral Pathol Med ; 48(6): 441-450, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31062892

RESUMO

The purpose of this study was to perform a systematic review of the literature concerning all documented cases of malignant transformation of craniomaxillofacial fibro-osseous lesions (FOLs). Three electronic databases were searched. Data were evaluated descriptively. Kaplan-Meier survival curves were constructed and compared using the log-rank test. A critical appraisal of included articles was performed through the Joanna Briggs Institute tool. A total of 19 studies including 27 patients were selected for data extraction. Twenty-six cases were initially diagnosed as fibrous dysplasia and one as ossifying fibroma. The mean age at the time of malignant transformation was 38.11 years, and the average time from initial diagnosis to malignant transformation was 18.2 years. The male:female ratio was 1:1.2, and the maxilla:mandible ratio was 1.5:1. The histological type of the malignant tumor was predominantly osteosarcoma. Follow-up was available for 21 patients. The 3-year overall survival rate was 51%. Mandible tumors and diagnoses other than osteosarcoma tended to have poor survival rates, but no significant difference was identified. We concluded that between all FOLs, only fibrous dysplasia seems to have a considerable increased risk of malignant transformation. Thus, a regular and long follow-up period is advised.


Assuntos
Fibroma Ossificante/patologia , Displasia Fibrosa Óssea/patologia , Neoplasias Mandibulares/diagnóstico , Osteossarcoma/diagnóstico , Humanos , Taxa de Sobrevida
8.
Cell Oncol (Dordr) ; 42(2): 143-155, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30539410

RESUMO

PURPOSE: Emerging evidence indicates that bromodomains comprise a conserved class of epigenome readers involved in cancer development and inflammation. Bromodomains are associated with epigenetic modifications of gene transcription through interactions with lysine residues of histone tails. Particularly, the bromodomain and extra-terminal domain (BET) family member BRD4 has been found to be involved in the control over oncogenes, including c-MYC, and in the maintenance of downstream inflammatory processes. The objective of this study was to evaluate the effect of pharmacologically displacing BRD4 in mucoepidermoid carcinoma (MEC) cells. METHODS: We assessed the presence of BRD4 levels in a panel of human MEC tissue samples in conjunction with histological grading and clinical information. In vitro studies were carried out using human MEC-derived cell lines. The BET inhibitor iBET762 was administered to MEC cells to assess the impact of disrupted BRD4 signaling on colony forming capacities and cell cycle status. The activation of cellular senescence induced by iBET762 was determined by immunohistochemical staining for p16ink4. Flow cytometry was used to identify populations of cancer stem cells in MEC-derived cell lines. RESULTS: We found that primary human MECs and MEC-derived cell lines are endowed with high BRD4 expression levels compared to those in normal salivary glands. We also found that, by displacing BRD4 from chromatin using the BET inhibitor iBET762, MEC cells lose their colony forming capacities and undergo G1 cell cycle arrest and senescence. Finally, we found that targeted displacement of BRD4 from chromatin results in depletion of cancer stem cells from the overall MEC cell populations. CONCLUSIONS: Our findings indicate that bromodomain-mediated gene regulation constitutes an epigenetic mechanism that is deregulated in MEC cells and that the use of BET inhibitors may serve as a feasible therapeutic strategy to manage MECs.


Assuntos
Carcinoma Mucoepidermoide/tratamento farmacológico , Carcinoma Mucoepidermoide/genética , Epigênese Genética , Terapia de Alvo Molecular , Adolescente , Adulto , Idoso , Benzodiazepinas/farmacologia , Carcinoma Mucoepidermoide/patologia , Proteínas de Ciclo Celular , Linhagem Celular Tumoral , Senescência Celular/efeitos dos fármacos , Epigênese Genética/efeitos dos fármacos , Feminino , Histonas/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Biológicos , Células-Tronco Neoplásicas/efeitos dos fármacos , Células-Tronco Neoplásicas/metabolismo , Células-Tronco Neoplásicas/patologia , Proteínas Nucleares/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Transcrição/metabolismo , Ensaio Tumoral de Célula-Tronco , Adulto Jovem
9.
J Oral Pathol Med ; 47(1): 32-39, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28626969

RESUMO

OBJECTIVES: Oral squamous cell carcinoma (OSCC) predominantly affects males in the fifth decade of life; nevertheless, an increased incidence in young patients has been reported worldwide, and the clinical and behavioral characteristics of tumors in this group are controversial, and the literature shows divergent results. PURPOSE: To investigate the clinicopathological features and prognostic significance of the immunoexpression of cell cycle and local invasion proteins in OSCC affecting young patients (≤40 years old). METHODS: A tissue microarray was performed with 132 OSCC samples (61 cases of young patients vs 71 cases of elderly patients) and submitted to immunohistochemical reactions with Ki67, p53, p16, Bcl-2, Cyclin D1, C-ErbB2, p21, Myc, EGFR, MMP-9, SMA, Cathepsin K and FGF-2 antibodies. RESULTS: Clinicopathological features and survival rates were similar in both groups. Although overexpression of EGFR (P=.042) and MMP-9 (P=.001) was more frequent in young patients, only C-ErbB-2 (P=.048) and SMA (P=.048) expression correlated with lower disease-free survival (DFS) in this group of patients. CONCLUSION: Clinicopathological features and survival rates are similar between younger and older patients with OSCC. The different patterns of C-ErbB2, EGFR, MMP-9, and SMA expression between the groups merits further investigation to understand their role in the early tumor onset in young patients.


Assuntos
Carcinoma de Células Escamosas/metabolismo , Pontos de Checagem do Ciclo Celular/fisiologia , Regulação Neoplásica da Expressão Gênica/fisiologia , Neoplasias Bucais/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Brasil , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Catepsina K/metabolismo , Pontos de Checagem do Ciclo Celular/genética , Ciclina D1/metabolismo , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Inibidor de Quinase Dependente de Ciclina p21/metabolismo , Intervalo Livre de Doença , Células Epiteliais/patologia , Receptores ErbB/metabolismo , Feminino , Fator 2 de Crescimento de Fibroblastos/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Masculino , Metaloproteinase 9 da Matriz/metabolismo , Pessoa de Meia-Idade , Neoplasias Bucais/genética , Neoplasias Bucais/mortalidade , Neoplasias Bucais/patologia , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , Prognóstico , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Proteínas Proto-Oncogênicas c-myc/metabolismo , Receptor ErbB-2/metabolismo , Taxa de Sobrevida , Proteína Supressora de Tumor p53/metabolismo
10.
Caries Res ; 51(2): 119-128, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28122368

RESUMO

OBJECTIVE: To analyze macroscopic, microscopic, and ultrastructural aspects of enamel from head-and-neck cancer patients submitted to radiotherapy. MATERIALS AND METHODS: Twenty sound extracted permanent molars were used and divided into 2 groups. The experimental group consisted of 10 molars from head-and-neck cancer patients submitted to radiotherapy with total doses that ranged from 50 to 70 Gy. Ten molars from patients who did not receive radiotherapy were matched with experimental-group samples by anatomic tooth group and comprised the control group. To perform a macroscopic analysis, standardized photos of different enamel faces were taken with a camera. Teeth were subjected to longitudinal cuts and hand polished to a final thickness of 0.1 mm. Enamel was analyzed under polarized light microscopy, and optical retardation values of birefringence were calculated in cervical, cusp, and occlusal pit areas. Subsequently, the same enamel areas were analyzed by scanning electron microscopy. Data from optical retardation values were statistically analyzed by 2-way ANOVA and Fisher's test (α < 0.05). RESULTS: No macroscopic differences were observed between the irradiated and control groups. Polarized light microscopy analysis revealed that cervical enamel exhibited darker areas characterized by discrete birefringence patterns compared to the control enamel. Optical retardation values were only significantly different in the cervical enamel of the irradiated and control groups (p < 0.0001). Scanning electron microscopy analysis revealed more evident interprismatic spaces in the cervical and outer cusp enamel of irradiated samples. CONCLUSIONS: Head-and-neck radiotherapy reduced optical retardation values of birefringence in cervical enamel, and the interprismatic spaces became more evident.


Assuntos
Esmalte Dentário/anatomia & histologia , Esmalte Dentário/efeitos da radiação , Neoplasias de Cabeça e Pescoço/radioterapia , Idoso , Humanos , Masculino , Pessoa de Meia-Idade , Dosagem Radioterapêutica
11.
Clin Sci (Lond) ; 130(10): 785-99, 2016 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-26823560

RESUMO

EEF1D (eukaryotic translation elongation factor 1δ) is a subunit of the elongation factor 1 complex of proteins that mediates the elongation process during protein synthesis via enzymatic delivery of aminoacyl-tRNAs to the ribosome. Although the functions of EEF1D in the translation process are recognized, EEF1D expression was found to be unbalanced in tumours. In the present study, we demonstrate the overexpression of EEF1D in OSCC (oral squamous cell carcinoma), and revealed that EEF1D and protein interaction partners promote the activation of cyclin D1 and vimentin proteins. EEF1D knockdown in OSCC reduced cell proliferation and induced EMT (epithelial-mesenchymal transition) phenotypes, including cell invasion. Taken together, these results define EEF1D as a critical inducer of OSCC proliferation and EMT.


Assuntos
Carcinoma de Células Escamosas/genética , Proliferação de Células/genética , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias de Cabeça e Pescoço/genética , Neoplasias Bucais/genética , Fator 1 de Elongação de Peptídeos/genética , Carcinoma de Células Escamosas/diagnóstico , Linhagem Celular Tumoral , Movimento Celular/genética , Neoplasias de Cabeça e Pescoço/diagnóstico , Humanos , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/metabolismo , Neoplasias Bucais/patologia , Fenótipo , Carcinoma de Células Escamosas de Cabeça e Pescoço
12.
J Oral Pathol Med ; 45(2): 119-26, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26199980

RESUMO

BACKGROUND: Salivary gland tumors (SGT) account for 3-10% of all head and neck neoplasms, and little is known about their angiogenic properties. Despite semaphorins and neuropilins have been demonstrated to be prognostic determinants in many human cancers, they remain to be investigated in SGT. Therefore, the objective of this study was to analyze the clinical significance of the expression of class 3 semaphorins A (Sema3A) and B (Sema3B) and neuropilins-1 (Np-1) and neuropilins-2 (Np-2), in SGT. METHODS: Two hundred and forty-eight SGT were organized in tissue microarray paraffin blocks and expression of CD34, Sema3A, Sema3B, Np-1, and Np-2 was determined through immunohistochemistry. The immunoreactions were quantified using digital algorithms and the results correlated with clinicopathological parameters. RESULTS: Malignant tumors had an increased vascular density than their benign counterparts and their increased vascular area significantly correlated with recurrences (P < 0.05). Patients older than 40 years and the presence of recurrences determined an inferior survival rate (P = 0.0057 and P = 0.0303, respectively). In normal salivary glands, Np-1 and Np-2 expression was restricted to ductal cells, whereas Sema3A and Sema3B were positive in the serous acinar compartment. Tumors were positive for all markers and the co-expression of Np-1/Np-2 significantly correlated with the presence of paresthesia and advanced stages of the tumors (P = 0.01 and P = 0.04, respectively). CONCLUSION: Sema3A, Sema3B, Np-1, and Np-2 may be involved in the pathogenesis of SGT, but their expression did not present a statistically significant prognostic potential in this study.


Assuntos
Neuropilinas/biossíntese , Neoplasias das Glândulas Salivares/metabolismo , Semaforinas/biossíntese , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD34/sangue , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Criança , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Recidiva Local de Neoplasia/genética , Recidiva Local de Neoplasia/metabolismo , Recidiva Local de Neoplasia/patologia , Estadiamento de Neoplasias , Neuropilinas/genética , Prognóstico , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/patologia , Semaforinas/genética , Taxa de Sobrevida , Adulto Jovem
14.
Histopathology ; 62(4): 551-62, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23347057

RESUMO

AIMS: To assess the DNA content of cases of oral proliferative verrucous leukoplakia (PVL) and correlate the DNA ploidy findings with the expression of Mcm2, geminin, and Ki67, and with clinicopathological data. METHODS AND RESULTS: DNA quantification was performed by image cytometry using the ACIS III Automated Cellular Imaging System. Expression of Ki67, Mcm2 and geminin was determined by immunohistochemistry. There were 21 cases of PVL, the female/male ratio was 6:1, and the average age was 65.5 years. Seventeen patients (81.0%) did not report tobacco and alcohol consumption. Nine patients (42.9%) developed verrucous or squamous cell carcinoma. Levels of Mcm2 expression showed a positive correlation with increasingly severe epithelial changes (P = 0.03). Twenty patients had their DNA examined by ACIS III, and 19 (95%) showed aneuploidy. The frequency and severity of aneuploidy (P < 0.0001), the mean values of the DNA heterogeneity index (P < 0.0001) and the 5n-exceeding fractions (P = 0.0007) increased according to epithelial alterations. Abnormal DNA content was observed even in the more indolent lesions. CONCLUSIONS: Mcm2 expression and DNA ploidy analysis could be used to predict areas of malignant transformation. The clinicopathological findings associated with the immunohistochemical and DNA ploidy results support the distinct and aggressive profile of this entity.


Assuntos
Aneuploidia , Carcinoma Verrucoso/patologia , Proteínas de Ciclo Celular/metabolismo , Leucoplasia Oral/patologia , Neoplasias Bucais/patologia , Proteínas Nucleares/metabolismo , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Verrucoso/genética , Carcinoma Verrucoso/metabolismo , Proliferação de Células , Transformação Celular Neoplásica , DNA de Neoplasias/genética , Feminino , Geminina , Humanos , Citometria por Imagem , Imuno-Histoquímica , Antígeno Ki-67/metabolismo , Leucoplasia Oral/genética , Leucoplasia Oral/metabolismo , Masculino , Pessoa de Meia-Idade , Componente 2 do Complexo de Manutenção de Minicromossomo , Neoplasias Bucais/genética , Neoplasias Bucais/metabolismo , Estudos Retrospectivos
15.
J Clin Exp Dent ; 5(2): e108-11, 2013 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-24455057

RESUMO

Kohlschütter-Tönz Syndrome is a rare disorder clinically characterized by amelogenesis imperfecta, epilepsy and progressive mental deterioration. We present an additional case of this syndrome of a nine year-old boy who was referred by pigmented teeth. The mental deterioration was associated with speech delay, impulsive behavior, attention-deficit/hyperactivity disorder, and learning problems. The physical examination revealed a reduction of lower third, slightly palpebral fissures, low ear and hair implantation, coarse hair and hypertrichosis. The intraoral examination showed alteration in teeth pigmentation diagnosed as amelogenesis imperfecta. Although rare, the present case report illustrates a syndrome that has dental anomalies and systemic alterations. It is important to recognize this syndrome as early as possible and paediatric dentist may contribute to the diagnosis and consequently to better manage the patients. Key words:Kohlschütter-Tönz syndrome, amelogenesis imperfecta, seizures, mental deterioration.

16.
J Oral Pathol Med ; 41(8): 589-97, 2012 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-22487508

RESUMO

BACKGROUND: Mucoepidermoid carcinomas are the most frequent malignant neoplasia of the salivary glands and are histologically classified as low, intermediate, and high grade. At present, histochemical stains such as periodic acid-Schiff or mucicarmine are useful tools in making a diagnosis. Recently, expression of the PLUNC proteins has been described in mucin-producing salivary gland tumors, with the suggestion that they could provide a powerful tool for the diagnosis of difficult cases. METHODS: This study evaluates the expression of PLUNC proteins in 30 cases of salivary gland mucoepidermoid carcinomas. Tumors were reviewed and classified according to histological grade. Periodic acid-Schiff, mucicarmine, and immunohistochemical staining for SPLUNC1, LPLUNC1, SPLUNC2, and LPLUNC2 were carried out. Immunostaining was classified as positive or negative. RESULTS: The majority of the tumors (63%) were classified as low grade, 13% were intermediate grade, and 23% were high grade. SPLUNC1 (90%) and LPLUNC1 (93%) were positive in the majority of cases, mainly in mucous cells, mucin plugs, and intermediate cells. SPLUNC2 and LPLUNC2 did not present significative expression within the tumors; however, LPLUNC2 was found to stain positively in mast cells in 83% of the samples. CONCLUSIONS: SPLUNC1 and LPLUNC1 showed a similar pattern of expression and could prove useful in the diagnosis of high-grade cases because of the differential staining in intermediate and epidermoid cells. The expression of LPLUNC2 in mast cells has not previously been reported, but further studies are necessary to validate this finding and to determine its significance.


Assuntos
Biomarcadores Tumorais/análise , Carcinoma Mucoepidermoide/diagnóstico , Glicoproteínas/análise , Zíper de Leucina , Fosfoproteínas/análise , Neoplasias das Glândulas Salivares/diagnóstico , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Autoantígenos , Carcinoma Mucoepidermoide/patologia , Carmim/análise , Criança , Pré-Escolar , Proteínas de Ligação a Ácido Graxo , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Humanos , Imuno-Histoquímica , Zíper de Leucina/genética , Masculino , Mastócitos/patologia , Pessoa de Meia-Idade , Mucinas/análise , Mucosa/patologia , Gradação de Tumores , Proteínas/análise , Estudos Retrospectivos , Neoplasias das Glândulas Salivares/patologia , Glândulas Salivares Menores/patologia , Proteínas e Peptídeos Salivares/análise , Adulto Jovem
19.
Oral Oncol ; 47(9): 840-6, 2011 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-21727023

RESUMO

Myofibroblasts are essential during wound healing and are often found in the stroma of oral squamous cell carcinomas (OSCC). Although the molecular mechanisms by which myofibroblasts influence OSCC remain largely unknown, previous studies demonstrated that presence of myofibroblast in OSCC stroma is an important risk factor of patient's shortened survival. Here we showed that some growth factors are produced in higher levels by tumor-associated myofibroblasts compared to tumor-associated fibroblasts, including activin A. Myofibroblast-conditioned media containing activin A significantly increased OSCC cell proliferation and tumor volume, whereas down-regulation of activin A in the conditioned media decreased proliferation. In addition, myofibroblasts induced in vitro invasion of OSCC cells, which was accompanied by an increased production of matrix metalloproteinases (MMP). In vivo, a significant correlation between presence of myofibroblasts and activities of MMP-2 and MMP-9 was observed in OSCC samples. However, blockage of activin A synthesis by myofibroblasts did not affect invasion and MMP production by OSCC cells. Together, our data demonstrate that activin A is required for the proliferative effects of myofibroblasts on OSCC cells. We conclude that myofibroblasts in the stroma of OSCC may influence proliferation and invasion, resulting in more aggressive tumor.


Assuntos
Ativinas/metabolismo , Carcinoma de Células Escamosas/metabolismo , Metaloproteinases da Matriz/metabolismo , Mucosa Bucal/patologia , Neoplasias Bucais/metabolismo , Miofibroblastos/metabolismo , Ativinas/fisiologia , Animais , Proliferação de Células , Regulação para Baixo , Ensaio de Imunoadsorção Enzimática/métodos , Fibroblastos/metabolismo , Humanos , Metaloproteinase 2 da Matriz/metabolismo , Metaloproteinase 9 da Matriz/metabolismo , Camundongos , Camundongos Nus , Invasividade Neoplásica , Células Estromais/patologia
20.
Int J Oncol ; 36(1): 141-9, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-19956843

RESUMO

A growing body of evidence has confirmed the involvement of dysregulated expression of HOX genes in cancer. HOX genes are a family of 39 transcription factors, divided in 4 clusters (HOXA to HOXD), that during normal development regulate cell proliferation and specific cell fate. In the present study it was investigated whether genes of the HOXB cluster play a role in oral cancer. We showed that most of the genes in the HOXB network are inactive in oral tissues, with exception of HOXB2, HOXB7 and HOXB13. Expression of HOXB7 was significantly higher in oral squamous cell carcinomas (OSCC) compared to normal oral mucosas. We further demonstrated that HOXB7 overexpression in HaCAT human epithelial cell line promoted proliferation, whereas downregulation of HOXB7 endogenous levels in human oral carcinoma cells (SCC9 cells) decreased proliferation. In OSCCs, expression of HOXB7 and Ki67, a marker of proliferation, correlate strongly with each other (rs=0.79, p<0.006). High immunohistochemical expression of HOXB7 was correlated with T stage (p=0.06), N stage (p=0.07), disease stage (p=0.09) and Ki67 expression (p=0.01), and patients with tumors showing high number of HOXB7-positive cells had shorter overall survival (p=0.08) and shorter disease-free survival after treatment (p=0.10) compared with patients with tumors exhibiting low amount of HOXB7-positive cells. Our data suggest that HOXB7 may contribute to oral carcinogenesis by increasing tumor cell proliferation, and imply that HOXB7 may be an important determinant of OSCC patient prognosis.


Assuntos
Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/metabolismo , Regulação Neoplásica da Expressão Gênica , Proteínas de Homeodomínio/biossíntese , Neoplasias Bucais/diagnóstico , Neoplasias Bucais/metabolismo , Idoso , Apoptose , Proliferação de Células , Intervalo Livre de Doença , Feminino , Perfilação da Expressão Gênica , Humanos , Imuno-Histoquímica/métodos , Antígeno Ki-67/biossíntese , Masculino , Pessoa de Meia-Idade , Prognóstico , Resultado do Tratamento
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