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1.
Diagn Pathol ; 18(1): 92, 2023 Aug 09.
Article in English | MEDLINE | ID: mdl-37559082

ABSTRACT

BACKGROUND: Ameloblastoma (AME) is a benign odontogenic tumour of epithelial origin characterised by slow but aggressive growth, infiltration, and recurrence; it is capable of reaching large dimensions and invading adjacent structures. Stem cell research has proven to be significant in the sphere of tumour biology through these cells' possible involvement in the aetiopathogenesis of this tumour. METHODS: Immunohistochemistry was performed on AME, dentigerous cyst (DC), and dental follicle (DF) samples, and indirect immunofluorescence was performed on the AME-hTERT cell line to determine the expression of SALL4, LIN28A, and KLF4. RESULTS: Expression of proteins related to cellular pluripotency was higher in AME cells than in DC and DF cells. The analysis revealed that the proteins in question were mainly expressed in the parenchyma of AME tissue samples and were detected in the nuclei of AME-hTERT cells. CONCLUSIONS: Stem cells may be related to the origin and progression of AME.


Subject(s)
Ameloblastoma , Odontogenic Tumors , Humans , Ameloblastoma/metabolism , Ameloblastoma/pathology , Immunohistochemistry , Stem Cells/metabolism , Stem Cells/pathology , Transcription Factors
2.
J Oral Pathol Med ; 51(4): 342-349, 2022 Apr.
Article in English | MEDLINE | ID: mdl-35122318

ABSTRACT

BACKGROUND: A glandular odontogenic cyst (GOC) has an intriguing, aggressive behaviour whose mechanisms have not yet been clarified. OBJECTIVE: To conduct a collaborative cross-sectional study on the clinical, demographic, microscopic and immunohistochemical characteristics of GOCs, emphasizing the histopathological characteristics and expression of proteins related to invasiveness. METHODS: Twenty-two cases of GOC from three oral and maxillofacial pathology services in Brazil were selected from 1988 to 2018. Clinical and demographic data were collected. Histopathological features were evaluated in detail. Sixteen cases of GOC were also submitted to immunohistochemistry to detect MT1-MMP, TKS4, TKS5 and cortactin, the key regulators of invadopodia formation. RESULTS: Glandular odontogenic cysts were primarily seen in men over 40 years of age, in the posterior mandible and the anterior maxilla as a unilocular, radiolucent lesion. All cases presented hobnail cells, clear cells and variable thickness of the lining epithelium, 3 of the 10 key histopathological parameters to be evaluated in GOCs. Immunohistochemistry revealed a greater expression of the studied proteins in the GOCs than in the controls (p < 0.0001). CONCLUSION: Overexpression of proteins that regulate cell invasiveness was identified, and the present study's findings suggest that invadopodia activity is a possible mechanism used by GOCs to promote local invasion, which could partly explain its intriguing biological behaviour.


Subject(s)
Odontogenic Cysts , Adult , Cross-Sectional Studies , Humans , Immunohistochemistry , Male , Mandible/pathology , Maxilla/pathology , Middle Aged , Odontogenic Cysts/pathology
3.
Mol Biol Rep ; 49(5): 3665-3674, 2022 May.
Article in English | MEDLINE | ID: mdl-35107738

ABSTRACT

BACKGROUND: The invasive behaviour of squamous cell carcinoma (SCC), a common malignant tumour of the mouth, is a process mediated by cell proliferation, extracellular matrix proteolysis and other factors. Studies have shown a potential relationship between growth factors, metallothionein 2A (MT2A) and matrix metalloproteinase (MMP) activation in malignant tumours. The aim of this study was to downregulate MT2A in cells (Cal27) derived from human squamous cell carcinoma. METHODS: Cal27 cells with reduced MT2A were subjected to proliferation, migration and invasion assays. Immunofluorescence and western blot confirmed MT2A depletion by siRNA. Growth curve assays assessed cell proliferation. Indirect immunofluorescence analysed the expression of MT2A, MMP-2, MMP-9, epidermal growth factor (EGF), transforming growth factor alpha (TGF-α), tumour necrosis factor alpha (TNF-α) and Ki67. Zymography evaluated the effects of MT2A silencing on MMP-2 and -9 expression. Migration and invasion activities were evaluated using migration and invasion assays. RESULTS: CAL27 cells displayed MT2A, MMP-2, MMP-9, EGF, TGF-α, TNF-α and Ki67. MT2A depletion decreased MMP-9, EGF, TGF-α and Ki67 protein levels, while increasing TNF-α. CONCLUSIONS: MT2A downregulation reduced cell proliferation, migration and invasion activities. Therefore, MT2A has an important role in cell proliferation, migration and invasion in human oral SCC cells.


Subject(s)
Carcinoma, Squamous Cell , Matrix Metalloproteinase 9 , Metallothionein , Carcinoma, Squamous Cell/pathology , Cell Line, Tumor , Cell Movement/genetics , Cell Proliferation/genetics , Down-Regulation/genetics , Epidermal Growth Factor/genetics , Humans , Ki-67 Antigen/metabolism , Matrix Metalloproteinase 2/genetics , Matrix Metalloproteinase 9/genetics , Metallothionein/genetics , Transforming Growth Factor alpha/genetics , Tumor Necrosis Factor-alpha/genetics
4.
Clin Oral Investig ; 26(3): 2807-2815, 2022 Mar.
Article in English | MEDLINE | ID: mdl-34783915

ABSTRACT

OBJECTIVES: This study aimed to investigate the detection of Epstein-Barr virus (EBV) in oral squamous cell carcinoma (OSCC) and to verify the concordance of EBV-DNA frequency in subgingival sites and in the OSCC. METHODS: A cross-sectional study with 30 OSCC patients, aged from 44 to 88 years old, was conducted. Samples were collected in subgingival sites and at the OSCC, then submitted to DNA isolation, qPCR, and genotyping. Descriptive statistic was performed to report the frequency of EBV-DNA in all samples, and McNemar test was applied to verify the concordance among the EBV-DNA frequency in both sites. RESULTS: The individuals presented 62 years old in average, and the majority were male (66.6%). EBV-DNA was detected in 56.7% OSCC lesions. Among the subgroup of 19 dentate individuals, high concordance (73.7%) in both EBV-DNA detection and the absence in subgingival sites and OSCC was observed, and it was statistically significant (p < 0.05). CONCLUSIONS: We report the notable occurrence of EBV-DNA in OSCC; also, the presence of EBV in periodontal sites may contribute to find it in OSCC, although the possible contribution of EBV in the OSCC remains to be investigated. CLINICAL RELEVANCE: The identification of this easily accessible site of EBV latent infection may help to improve the patient's quality of life by maintenance of oral/periodontal health condition and preventing further possible disorders related to the virus, and also encourages new approaches for investigating EBV, periodontitis, and OSCC.


Subject(s)
Carcinoma, Squamous Cell , Epstein-Barr Virus Infections , Head and Neck Neoplasms , Mouth Neoplasms , Adult , Aged , Aged, 80 and over , Carcinoma, Squamous Cell/genetics , Cross-Sectional Studies , Female , Herpesvirus 4, Human/genetics , Humans , Male , Middle Aged , Mouth Neoplasms/genetics , Periodontal Pocket , Quality of Life , Squamous Cell Carcinoma of Head and Neck
6.
Diagn Pathol ; 16(1): 33, 2021 Apr 20.
Article in English | MEDLINE | ID: mdl-33879222

ABSTRACT

BACKGROUND: Oral squamous cell carcinoma (OSCC) is the most relevant malignant neoplasm among all head and neck tumours due to its high prevalence and unfavourable prognosis. Tumour invasion and metastasis that affect prognosis are result of a set of complex events that cells with invasive potential use to spread to other regions. These cells use several mechanisms to invade tissues, including a type of finger-like membrane protrusion called invadopodia. This study aims to investigate the immunoexpression of invaopodia related-proteins TKs5, cortactin, TKs4 and MT1-MMP in OSCC and correlate it to clinicopathological data. METHODS: An immunohistochemical evaluation of fifty cases of OSCCs and 20 cases of oral mucosa (OM) were assessed. The expression of invadopodia proteins were analysed in comparison to normal tissue (OM) and correlated to different clinical-stage and histological grade of OSCC. RESULTS: TKs5, cortactin, TKs4 and MT1-MMP were significantly overexpressed in OSCC when compared to OM (p < 0.0001). Among tumour stages, TKs5 showed a statistical difference in immunolabelling between stage I and III (p = 0.026). Cortactin immunolabelling was statistically higher in grade I than in grade II and III. No differences were seen on TKs4 expression based on tumour staging or grading. MT1-MMP was higher expressed and showed statistical difference between stages I and III and grades I compared to II and III. CONCLUSIONS: The invadopodia related-proteins were found to be overexpressed in OSCC when compared to OM, suggesting invadopodia formation and activity. Besides overexpressed in OSCC, cortactin, TKs4 and TKs5 showed no or ambiguous differences in protein expression when compared among clinical-stages or histological grades groups. Conversely, the expression of MT1-MMP increased in advanced stages and less differentiated tumours, suggesting MT1-MMP expression as a promising prognostic marker in OSCC.


Subject(s)
Biomarkers, Tumor/analysis , Matrix Metalloproteinase 14/analysis , Mouth Neoplasms/enzymology , Podosomes/enzymology , Squamous Cell Carcinoma of Head and Neck/enzymology , Adaptor Proteins, Signal Transducing/analysis , Adaptor Proteins, Vesicular Transport/analysis , Cortactin/analysis , Cross-Sectional Studies , Female , Humans , Immunohistochemistry , Male , Middle Aged , Mouth Neoplasms/pathology , Neoplasm Grading , Neoplasm Staging , Podosomes/pathology , Squamous Cell Carcinoma of Head and Neck/pathology
7.
BMC Oral Health ; 21(1): 102, 2021 03 06.
Article in English | MEDLINE | ID: mdl-33676487

ABSTRACT

BACKGROUND: ADAMTS expression can be associated with several inflammatory processes, and has been correlated with tumorigenesis of some neoplasms, but its participation in the development of periapical lesions has not been investigated. Therefore, our objective was to verify the expression of ADAMTS-1, versican and pEGFR in Periapical Granuloma (PG) and in the Radicular Cyst (RC) since they are the most common lesions of the periapex. METHODS: 25 samples of RC and 10 of PG were used. As a control, 10 samples of inflammatory fibrous hyperplasia (IFH) and 10 of dental follicle (DF) were used. The expression of these proteins was investigated using immunohistochemistry. RESULTS: In the epithelium of RC, IFH and DF, the expression of ADAMTS-1 was greater in DF than in RC (p < .001). Versicano showed greater expression in IFH than in RC, DF than in RC (p < .001). pEGFR showed greater expression in IFH and RC than in DF (p < .01 and p < .05, respectively). In connective tissue, ADAMTS-1 expression was greater in PG and RC than in IFH and DF (p < .001). Versicano showed greater expression in PG, RC and IFH compared to DF (p < .001). In pEGFR there was a higher expression in PG when compared to RC, IFH and DF (p < .001). Greater immunostaining occurred in the RC than in the DF (p < .001). CONCLUSIONS: Our results suggest that the studied proteins may participate in the pathogenesis of PG and RC, through the interaction of these proteins, in the remodeling of the ECM (versican) by ADAMTS-1, producing bioactive fragments, which could activate EGFR, contributing to the formation, growth and maintenance of injuries.


Subject(s)
Periapical Granuloma , Radicular Cyst , ErbB Receptors , Humans , Immunohistochemistry , Versicans
8.
Sci Rep ; 10(1): 17567, 2020 10 16.
Article in English | MEDLINE | ID: mdl-33067558

ABSTRACT

Ameloblastomas are epithelial odontogenic tumours that, although benign, are locally invasive and may exhibit aggressive behaviour. In the tumour microenvironment, the concentration of oxygen is reduced, which leads to intratumoral hypoxia. Under hypoxia, the crosstalk between the HIF-1α, MMP-2, VEGF, and VEGFR-2 proteins has been associated with hypoxia-induced angiogenesis, leading to tumour progression and increased invasiveness. This work showcases 24 ameloblastoma cases, 10 calcifying odontogenic cysts, and 9 dental follicles, used to investigate the expression of these proteins by immunohistochemistry. The anti-HIF-1α, anti-MMP-2, anti-VEGF, and anti-VEGFR-2 primary antibodies are used in this work. The results have been expressed by the mean grey value after immunostaining in images acquired with an objective of 40×. The ameloblastoma samples showed higher immunoexpression of HIF-1α, MMP-2, VEGF, and VEGFR-2 when compared to the dental follicles and calcifying odontogenic cysts. Ameloblastomas show a higher degree of expression of proteins associated with intratumoral hypoxia and proangiogenic proteins, which indicates the possible role of these proteins in the biological behaviour of this tumour.


Subject(s)
Ameloblastoma/metabolism , Ameloblastoma/pathology , Hypoxia , Neovascularization, Pathologic , Odontogenic Tumors/metabolism , Odontogenic Tumors/pathology , Biomarkers/metabolism , Dental Sac/metabolism , Disease Progression , Humans , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Immunohistochemistry , Matrix Metalloproteinase 2/metabolism , Neoplasm Invasiveness , Prognosis , Tumor Microenvironment , Vascular Endothelial Growth Factor A/metabolism , Vascular Endothelial Growth Factor Receptor-2/metabolism
9.
Int J Surg Case Rep ; 70: 243-248, 2020.
Article in English | MEDLINE | ID: mdl-32422587

ABSTRACT

INTRODUCTION: Carcinosarcomas are rare malignant neoplasms formed by embryonic tissues (ectoderm and mesoderm) and present remarkably aggressive character with unfavourable prognosis. These lesions are rarely diagnosed in the sinonasal cavity and only a few cases are reported in the literature. This manuscript aimed to report a rare case of a large and aggressive sinonasal carcinosarcoma that involved the facial middle third and to discuss the proposed treatment. PRESENTATION OF CASE: A 54-year-old female patient sought treatment for a large swelling on the left side of the face. A CT-scan revealed an expansive hypodense image in the facial middle third. An incisional biopsy was performed under local anaesthesia and the material was sent for histopathological analysis. DISCUSSION: Due to the extremely aggressive character of carcinosarcomas, the optimal management of carcinosarcomas remains uncertain and a challenge for clinicians. In this case report, the prognosis of such a large tumour became unfavourable since the patient sought late for treatment. Therefore, suspicion and early detection are crucial for improving the prognosis and quality of life of the patients with such neoplasia. CONCLUSION: Besides being rare and extremely aggressive, sinonasal carcinosarcomas present worse patient survival when compared to other carcinosarcomas in the head and neck region. Thus, this report may contribute to a better understanding of this tumour behaviour.

10.
Diagn Pathol ; 15(1): 47, 2020 May 09.
Article in English | MEDLINE | ID: mdl-32386517

ABSTRACT

BACKGROUND: Among cancers affecting the oral cavity, adenoid cystic carcinoma (ACC) is a relatively common malignant neoplasm. It has high rates of metastasis and recurrence and is associated with significant morbidity. During the progression of ACC, the oxygen concentration is reduced in specific areas of the tumour microenvironment, leading to intratumoural hypoxia. The expression of NOTCH1, a disintegrin and metalloproteinase 12 (ADAM-12), hypoxia-inducible factor 1 alpha (HIF-1α), and heparin-binding epidermal growth factor (HB-EGF) under hypoxic conditions has been implicated in invadopodia formation, tumour invasiveness, and metastasis. The aim of this study was to analyse the expression of these proteins to elucidate the mechanisms underlying ACC invasiveness. METHODS: Fifteen ACC samples and 10 normal-looking salivary gland (SG) samples were used to investigate the expression of these proteins by immunohistochemistry. Primary antibodies against NOTCH1, ADAM-12, HIF-1α, and HB-EGF were used. RESULTS: The immunoexpression of all proteins was higher in ACC samples than in SG samples (p < 0.05). CONCLUSIONS: There was increased expression of proteins associated with hypoxia and tumour invasiveness in ACC samples, which indicates a possible role of these proteins in the biological behaviour of this tumour.


Subject(s)
Carcinoma, Adenoid Cystic/pathology , Cell Hypoxia/physiology , Salivary Gland Neoplasms/pathology , Tumor Microenvironment/physiology , Adult , Aged , Carcinoma, Adenoid Cystic/metabolism , Female , Humans , Male , Middle Aged , Salivary Gland Neoplasms/metabolism
11.
Head Neck Pathol ; 14(2): 497-502, 2020 Jun.
Article in English | MEDLINE | ID: mdl-31297738

ABSTRACT

Central giant cell granuloma (CGCG) is a benign intraosseous lesion of the head and neck with potential for aggressive and locally destructive behaviour. Lesions of the maxilla tend to expand more than those of the mandible due to the thinner cortices and spongy tissue of this location. Surgical removal is the most common treatment; however, it may be disfiguring in aggressive cases, especially for lesions located in the maxilla. Alternative treatments, such as intralesional corticosteroid injections, have been performed with satisfactory results. We report a case of a 12-year-old female patient with a CGCG of the left maxilla that was treated with 40 doses of intralesional triamcinolone acetonide infiltrations combined with alendronate sodium and calcium carbonate. Clinical and imaging follow-up over 12 years demonstrates improvement in the patient's condition.


Subject(s)
Adrenal Cortex Hormones/administration & dosage , Diphosphonates/administration & dosage , Granuloma, Giant Cell/drug therapy , Granuloma, Giant Cell/pathology , Maxillary Diseases/drug therapy , Maxillary Diseases/pathology , Alendronate/administration & dosage , Anti-Inflammatory Agents/administration & dosage , Bone Density Conservation Agents/administration & dosage , Calcium Carbonate/administration & dosage , Child , Female , Follow-Up Studies , Humans , Injections, Intralesional , Time , Triamcinolone Acetonide/administration & dosage
12.
Eur Arch Otorhinolaryngol ; 275(12): 3039-3047, 2018 Dec.
Article in English | MEDLINE | ID: mdl-30367261

ABSTRACT

PURPOSE: Adenoid cystic carcinoma (ACC) is an intriguing lesion because it shows a slow growth in the beginning, but a late poor prognosis due to perineural invasion, metastasis and recurrence. This study aimed to investigate whether Akt signaling would be deregulated in adenoid cystic carcinoma and its consequence in the expression of associated proteins. METHODS: The expression of the Akt, p-Akt, NFκB, ß-catenin, cyclin D1 and COX-2 was assessed by immunohistochemistry in 10 cases of ACC, 17 cases of pleomorphic adenoma (PA), and 7 cases of normal salivary gland (NSG). RESULTS: p-Akt was overexpressed in ACC when compared to NSG. NFκB, ß-catenin, and COX-2 were overexpressed in ACC and PA when compared to NSG. Most proteins were slightly higher expressed in ACC than in PA, but they never reached significance. p-Akt expression positively correlated with NFκB, ß-catenin, cyclin D1 and COX-2 in ACC and PA, while this correlation trended to be negative in for these proteins (except for NFκB) in NSG using Person's correlation analysis, but without reaching significance. CONCLUSIONS: Our results indicate an abnormal activation of Akt signaling pathway, which can be an important regulator of tumor biology in ACC. Activated Akt correlated with the expression of NFκB, ß-catenin and COX-2, which can potentially influence cell survival in ACC.


Subject(s)
Adenoma, Pleomorphic/metabolism , Carcinoma, Adenoid Cystic/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Salivary Gland Neoplasms/metabolism , Adenoma, Pleomorphic/pathology , Carcinoma, Adenoid Cystic/pathology , Cyclin D1/metabolism , Cyclooxygenase 2/metabolism , Humans , Immunohistochemistry , NF-kappa B p50 Subunit/metabolism , Salivary Gland Neoplasms/pathology , Salivary Glands/pathology , Signal Transduction , beta Catenin/metabolism
13.
J Oral Maxillofac Surg ; 74(12): 2480.e1-2480.e12, 2016 Dec.
Article in English | MEDLINE | ID: mdl-27643631

ABSTRACT

PURPOSE: Facial fractures are an important health problem worldwide that can cause temporary or permanent disability and an economic burden. Identifying the risk factors associated with facial fractures is a valuable tool to create preventive public health strategies. This study evaluated the epidemiologic profile of facial fractures in northern Brazil. PATIENTS AND METHODS: Medical records of 1,969 patients who sustained facial fractures were analyzed for characteristics of the population, types of facial fractures, and treatment performed. RESULTS: The zygomatic complex was the most prevalent fracture site (28.8%). Road traffic accident (RTA) was the most common etiology (52%), followed by interpersonal violence (IPV; 34%). Among IPV cases, gunshot wounds were responsible for 14% of cases and 3% resulted from stab wounds. The third decade of life was the most prevalent age group, with a remarkable change in prevalence and etiology pattern at 15 years of age. Open reduction and internal fixation was the most used treatment, especially when the mandible was involved and at least 2 facial bones were fractured. There were 37 deaths (1.9%), with a higher risk observed for stab wounds (3.1-fold higher) and when at least 3 bones were fractured (4.1-fold higher). CONCLUSIONS: This epidemiologic survey identified RTA and IPV as important risk factors for facial fractures and a high prevalence of fractures caused by gunshot wounds. A unique preponderance of facial fractures caused by stab wounds was found, which was responsible for the highest risk of mortality.


Subject(s)
Facial Bones/injuries , Skull Fractures/epidemiology , Adolescent , Adult , Aged , Aged, 80 and over , Brazil/epidemiology , Child , Child, Preschool , Female , Fracture Fixation , Humans , Infant , Logistic Models , Male , Middle Aged , Prevalence , Retrospective Studies , Risk Factors , Skull Fractures/diagnosis , Skull Fractures/etiology , Young Adult
14.
Article in English | MEDLINE | ID: mdl-27554376

ABSTRACT

OBJECTIVE: Keratocystic odontogenic tumor (KOT) is an odontogenic neoplasm that shows aggressive clinical behavior and local invasiveness. Invadopodia are actin-rich cellular protrusions exhibiting proteolytic pericellular activity, thereby inducing focal invasion in neoplastic cells and increasing neoplasms aggressiveness. Thus, this study aimed to evaluate immunoexpression of invadopodia-related proteins, cortactin, MT1-MMP, Tks4, and Tks5, in KOT. STUDY DESIGN: Immunohistochemistry of 16 cases of KOT, eight cases of calcifying cystic odontogenic tumor (CCOT), and eight samples of the oral mucosa (OM) was carried out to assess the expression of the above described invadopodia-related proteins in the basal and suprabasal layer. RESULTS: KOT samples showed higher and significant immunoexpression of cortactin, MT1-MMP, TKs4, and TKs5 compared with the CCOT and OM samples. Significant expression of all these proteins was observed in the basal layer compared with the suprabasal layer in KOT. CONCLUSIONS: Overexpression of cortactin, MT1-MMP, TKs4, and TKs5 was observed in KOT compared with samples of CCOT and OM. These proteins were also overexpressed in the basal over the suprabasal layer of KOT samples. Taken together, these results suggest the participation of invadopodia-related proteins on the pathogenesis of this lesion.


Subject(s)
Odontogenic Tumors/metabolism , Podosomes/metabolism , Adaptor Proteins, Signal Transducing/metabolism , Adaptor Proteins, Vesicular Transport/metabolism , Cortactin/metabolism , Humans , Immunohistochemistry , Matrix Metalloproteinase 14/metabolism , Neoplasm Invasiveness , Odontogenic Tumors/pathology
15.
Article in English | MEDLINE | ID: mdl-25921710

ABSTRACT

OBJECTIVE: To identify the oral carriage of Candida spp in patients infected by human immunodeficiency virus (HIV) and the possible correlation with clinical characteristics. STUDY DESIGN: Mucosal swab samples collected from 246 patients who were infected by HIV, did not have oral candidiasis, and were being treated with highly active antiretroviral therapy were analyzed. Yeast colonies that developed were identified by using the VITEK 2 automated system. RESULTS: Candida yeasts were present in 41.87% of the samples, and Candida albicans was the most prevalent (32.52%). Other identified Candida species were C tropicalis (4.88%), C parapsilosis (2.85%), C dubliniensis (0.81%), and C famata (0.81%). CONCLUSIONS: There was low rate of oral Candida carriage in patients infected by HIV who were on highly active antiretroviral therapy. A greater prevalence of C albicans than non-albicans Candida species was found at the species level. Prior candidiasis predicted the oral carriage of C albicans; however, it did not influence the carriage of non-albicans species. This is the first report of oral carriage of C famata in patients with HIV infection.


Subject(s)
Antiretroviral Therapy, Highly Active , Candida/isolation & purification , Candidiasis, Oral/microbiology , HIV Infections/drug therapy , Mouth/microbiology , Adolescent , Adult , Aged , Blotting, Western , Brazil/epidemiology , Candidiasis, Oral/epidemiology , Enzyme-Linked Immunosorbent Assay , Female , Humans , Male , Middle Aged , Prevalence
16.
Tumour Biol ; 35(11): 11107-20, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25099616

ABSTRACT

Ameloblastoma is an odontogenic tumor characterized by local invasiveness and frequent recurrence. The surrounding stroma, composed of different cell types and extracellular matrix (ECM), may influence ameloblastoma invasive behavior. Furthermore, tumor and stromal cells secrete matrix metalloproteases (MMPs), which, in turn, can modulate the matrix and promote the release of ECM-bound growth factors. Among these growth factors, epidermal growth factor (EGF) and its receptor, EGFR, have already been shown to stimulate MMP synthesis, suggesting that an interdependent mechanism, involving MMP activity and growth factors release, may contribute to tumor invasiveness. The aim of this study was to evaluate the effects of the EGF/EGFR signaling pathway on migration, invasion, and MMP activity, in a primary cell line derived from human ameloblastoma. We established and characterized a primary cell line (AME-1) from a human ameloblastoma sample. This cell line was transduced with human papillomavirus type 16 (HPV16) E6/E7 oncogenes, generating the AME-HPV continuous cell line. EGF, MMP2, and MMP9 expression in ameloblastoma biopsies and in the AME-HPV cell line was analyzed by immunohistochemistry and immunofluorescence, respectively. Migratory activity of EGF-treated AME-HPV cells was investigated using monolayer wound assays and Transwell chambers. EGF-induced invasion was assessed in Boyden chambers coated with Matrigel. Conditioned medium from EGF-treated cells was subjected to zymography. EGFR expression in AME-HPV cells was silenced by small interfering RNA (siRNA), to verify the relationship between this receptor and MMP secretion. Ameloblastoma samples and AME-HPV cells expressed EGF, EGFR, MMP2, and MMP9. AME-HPV cells treated with EGF showed increased rates of migration and invasion, as well as enhanced MMP2 and MMP9 activity. EGFR knockdown decreased MMP2 and MMP9 levels in AME-HPV cells. EGFR signaling downstream of EGF probably regulates migration, invasion, and MMP secretion of ameloblastoma-derived cells.


Subject(s)
Ameloblastoma/pathology , Cell Movement/drug effects , Cell Transformation, Viral , Epidermal Growth Factor/pharmacology , ErbB Receptors/metabolism , Jaw Neoplasms/pathology , Matrix Metalloproteinases/metabolism , Ameloblastoma/drug therapy , Ameloblastoma/metabolism , Blotting, Western , Cell Proliferation/drug effects , ErbB Receptors/antagonists & inhibitors , ErbB Receptors/genetics , Fluorescent Antibody Technique , Humans , Jaw Neoplasms/drug therapy , Jaw Neoplasms/metabolism , Neoplasm Invasiveness , RNA, Messenger/genetics , RNA, Small Interfering/genetics , Real-Time Polymerase Chain Reaction , Reverse Transcriptase Polymerase Chain Reaction , Signal Transduction/drug effects , Tumor Cells, Cultured , Wound Healing/drug effects
17.
Oral Maxillofac Surg ; 18(4): 431-7, 2014 Dec.
Article in English | MEDLINE | ID: mdl-24263242

ABSTRACT

PURPOSE: Hemangiomas are benign vascular anomalies characterized by benign proliferation of blood vessels. There are no well-defined criteria for the diagnosis and treatment of oral capillary hemangioma (OCH). The objective of this study is to report a safe, effective, and low-cost protocol for diagnosis and treatment of OCH. MATERIALS AND METHODS: Eight patients were diagnosed with OCH, through two physical examination maneuvers-the diascopy and head lowering maneuver with abdominal compression (HLMAC). The treatment performed was sclerotherapy with ethanolamine oleate, weekly, until the disappearance of the lesion. No local anesthetics were administered prior to the sclerosing agent injection. RESULTS: All cases showed a complete remission of the lesions after sclerotherapy. There were no visible scars or compromise esthetics or normal function, and there was no evidence of recurrence. Only one patient had superficial ulceration, which remained asymptomatic and healed without specific treatment. CONCLUSIONS: This protocol was effective in the diagnosis of OCH through two physical examination maneuvers with low-cost and easy implementation, the diascopy and the HLMAC. The low concentration associated with a reduced amount of the sclerosing agent was responsible for the excellent results in the cases treated.


Subject(s)
Hemangioma, Capillary/diagnosis , Mouth Neoplasms/diagnosis , Adult , Clinical Protocols , Head Movements/physiology , Hemangioma, Capillary/therapy , Humans , Mouth Neoplasms/therapy , Oleic Acids/therapeutic use , Physical Examination , Pressure , Remission Induction , Sclerosing Solutions/therapeutic use , Sclerotherapy/methods
18.
J Oral Pathol Med ; 43(2): 143-7, 2014 Feb.
Article in English | MEDLINE | ID: mdl-23837696

ABSTRACT

BACKGROUND: Ameloblastoma is an odontogenic neoplasm with local invasiveness and high recurrence. We previously suggested that growth factors, matrix metalloproteinases (MMPs), and TIMPs influence ameloblastoma invasiveness (Pathol. Res. Pract., 208, 2012, 225; Oral. Surg. Oral. Med. Oral. Pathol. Oral Radiol. Endod., 111, 2011, 474). Signals generated by this molecular network would be transduced by ERK 1/2 pathway (Oral. Surg. Oral. Med. Oral. Pathol. Oral Radiol. Endod., 111, 2011, 474). Others signaling pathways may influence ameloblastoma biology. Here, we studied expression of AKT and related molecules in ameloblastoma. METHODS: Fourteen cases of solid/multicystic ameloblastomas were examined. Immunohistochemistry was carried out to detected AKT (phospho-AKT), NF-қB (phospho-NF-қB), ß-catenin, cyclin-D1, and COX-2 in ameloblastoma samples. These molecules were evaluated in neoplastic cells and stroma. RESULTS: All proteins were detected in ameloblastoma. Expression of these markers was quantified and compared. Spearman's rank test was carried out to address positive correlations between proteins (P < 0.05). Ameloblastoma had a significant positive correlation of AKT (phospho-AKT) with ß-catenin. ß-catenin correlated with Cyclin-D1 and COX-2 in neoplastic cells. AKT (phospho-AKT) correlated with ß-catenin; ß-catenin with Cyclin-D1; AKT (phospho-AKT) with NF-қB (phospho-NF-қB); and NF-қB (phospho-NF-қB) with COX-2 in stromal cells. CONCLUSIONS: Results suggest that proteins studied are present and probably involved in a functional pathway in neoplastic cells and stroma and may therefore influence the local invasiveness of ameloblastoma.


Subject(s)
Ameloblastoma/pathology , Proto-Oncogene Proteins c-akt/analysis , Cell Nucleus/pathology , Cyclin D1/analysis , Cyclooxygenase 2/analysis , Cytoplasm/pathology , Humans , Immunohistochemistry , NF-kappa B/analysis , Neoplasm Invasiveness , Signal Transduction/physiology , Stromal Cells/pathology , beta Catenin/analysis
19.
Article in English | MEDLINE | ID: mdl-21669358

ABSTRACT

OBJECTIVE: Pseudoaneurysms are vascular injuries resulting from a rupture of the vessel walls with blood extravasation into perivascular tissues. Proper treatment is required to prevent rupture and intense bleeding. This article reports a case of pseudoaneurysm of the facial artery that evolved to a late complication, presenting dehiscence of suture and exposure of the wound and bleeding after the initial injury and also discusses the effects of vascular response from the involved vessels by comparing them against the contralateral side. CASE REPORT: A healthy 17-year-old male was admitted with an injury of approximately 35 mm in length in the right cheek with an exposed clot inside the injury and local bleeding after a stabbing 11 days before. CT angiography showed rupture of the facial artery and formation of a pseudoaneurysm with an organized clot. The patient was treated by means of surgery under local anesthesia and intravenous sedation. The facial artery was located and attached by suture. The wound was explored and clots were removed. The patient was discharged on the first postoperative day and he had an excellent scarring standard with no unfavorable event. CONCLUSIONS: The authors conclude that this surgical technique is an effective method for treating such injuries, as it is easily performed and can be conducted by the oral and maxillofacial surgeon assistant.


Subject(s)
Aneurysm, False/etiology , Cheek/injuries , Face/blood supply , Wounds, Stab/complications , Adolescent , Aneurysm, False/surgery , Angiography , Arteries/injuries , Hematoma/etiology , Humans , Male , Postoperative Hemorrhage/etiology , Regional Blood Flow/physiology , Reoperation , Rupture , Surgical Wound Dehiscence/etiology , Thrombosis/etiology , Tomography, X-Ray Computed
20.
J Oral Pathol Med ; 40(6): 516-9, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21371124

ABSTRACT

BACKGROUND: Ameloblastoma is a benign odontogenic tumor, exhibiting local invasiveness and high rate of recurrence. Metallothionein is a protein associated with tumorigenesis, serving as prognostic factor in different neoplasms. We are interested in mechanisms underlying ameloblastoma local invasiveness. Thus, we decided to analyze expression of metallothionein in this tumor. MATERIALS AND METHODS: An immunohistochemical evaluation of metallothionein in ameloblastoma was carried out. As control, we assessed expression of the same molecule in calcifying cystic odontogenic tumor (CCOT), a non-invasive odontogenic neoplasm with ameloblastomatous epithelium. RESULTS: We studied 12 cases of solid/multicystic ameloblastomas. Metallothionein was observed in all samples. This molecule was observed in columnar cells in the periphery and in central polyhedral cells. CCOT (four cases) also showed the presence of metallothionein. Morphometry of stained areas showed that expression of metallothionein in ameloblastoma was significantly higher compared to CCOT (P < 0.0001). CONCLUSIONS: This protein may have an impact on ameloblastoma behavior. Metallothionein would act as a zinc reservoir for important proteases related to ameloblastoma biology, such as MMPs. This protein could also display pro-mitotic and anti-apoptotic features in the tumor.


Subject(s)
Ameloblastoma/metabolism , Gene Expression Regulation, Neoplastic , Metallothionein/biosynthesis , Case-Control Studies , Humans , Metallothionein/genetics , Neoplasm Invasiveness , Odontogenic Tumors/metabolism , Skin Neoplasms/metabolism
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