Sérgio de Melo Alves Júnior

EGFR signaling downstream of EGF regulates migration, invasion, and MMP secretion of immortalized cells derived from human ameloblastoma.

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.

Traumatic pseudoaneurysm of the facial artery: late complication and effects on local blood flow

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.

Expression of metallothionein in ameloblastoma. A regulatory molecule

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.

Clinical and imagiological findings of central giant cell lesion and cherubism

Cone beam computed tomography (CBCT) is the best examination for bone lesions of the maxilla, allowing the dentist to evaluate precisely the behavior and components of the lesion and their relationship to the surrounding structures. Central giant cell lesion and cherubism are histologically very similar lesions. Therefore clinical and radiological examinations are fundamentally important for the diagnosis. The aim of this paper is to report two cases diagnosed as central giant cell lesions and cherubism using CBCT. This imaging modality was very important for the diagnosis of the lesions presented in the current study. It also allowed observing precisely the limits of the lesions, the components, the behavior and the exact relationship to adjacent structures.

Invadopodia proteins, cortactin and membrane type I matrix metalloproteinase (MT1‐MMP) are expressed in ameloblastoma

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Expression of molecules related to AKT pathway as putative regulators of ameloblastoma local invasiveness

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), β-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. Spearmans 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 β-catenin. β-catenin correlated with Cyclin-D1 and COX-2 in neoplastic cells. AKT (phospho-AKT) correlated with β-catenin; β-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.

Abnormal activation of the Akt signaling pathway in adenoid cystic carcinoma

PurposeAdenoid 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.MethodsThe expression of the Akt, p-Akt, NFκB, β-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).Resultsp-Akt was overexpressed in ACC when compared to NSG. NFκB, β-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, β-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.ConclusionsOur 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, β-catenin and COX-2, which can potentially influence cell survival in ACC.

The importance of early diagnosis and an accurate tumoral evaluation in the treatment of mandibular osteossarcoma

OBJETIVO: O osteossarcoma e uma neoplasia maligna do osso que possui um comportamento clinico agressivo, geralmente diagnosticado em estados tardios da doenca, quando o tumor primario atinge dimensoes significativas. Em muitos casos, tratamento cirurgico agressivo com grandes resseccoes osseas e a necessidade de associacao a radio ou quimioterapia se fazem necessarios para melhor controle de recidivas locais e metastases em tais lesoes. DESCRICAO DO CASO: No presente trabalho os autores relataram um caso de osteossarcoma na regiao de corpo e ramo mandibular esquerdo diagnosticado precocemente e avaliado de forma precisa pela tomografia computadorizada tipo cone beam. CONCLUSAO: O diagnostico precoce do osteossarcoma e uma condicao pouco comum que afeta de forma favoravel tanto o tratamento quanto o prognostico deste tumor. A associacao deste diagnostico precoce com uma avaliacao precisa do envolvimento tumoral foram determinantes na execucao de um tratamento cirurgico conservador e ainda assim com finalidade curativa, com um minimo de sequelas. O espaco pericementario deve ser especialmente observado, pois seu espessamento e muito mais comum em osteossarcomas. Estudos que possibilitem identificar esta lesao de forma mais precoce e precisa devem realizados, a fim de possibilitar uma sobrevida maior com melhor qualidade de vida.