Décio dos Santos Pinto

Management of solid ameloblastoma of the jaws with liquid nitrogen spray cryosurgery

OBJECTIVE This study evaluated the results of the use of curettage followed by liquid nitrogen spray cryosurgery in a number of solid or multicystic ameloblastomas of the jaws and the postoperative complications related to this treatment modality. STUDY DESIGN Thirty-six patients with solid ameloblastoma of the jaws were treated with curettage followed by cryosurgery. The cryotherapy consisted of hand instrumented curettage of the bone lesion followed by three freezing cycles, of 1 minute each, of the remaining bone cavity with liquid nitrogen spray. Postoperative complications were evaluated clinically and radiographically. RESULTS Local recurrence occurred in 11 (30.6%) patients. Excepting local recurrence, postoperative complications were frequent but not severe: wound dehiscence (5.5%), paraesthesia (5.5%), infection (5.5%), and pathologic fracture (11.1%). CONCLUSION Management of solid or multicystic ameloblastomas of the jaws with curettage followed by cryosurgery may decrease the local recurrence rate and also to reduce the initial indication of resection with continuity defect.

Salivary duct carcinoma: immunohistochemical profile of an aggressive salivary gland tumour

Background: Salivary duct carcinoma (SDC) is considered to be a distinct malignancy of the major salivary glands, because of its highly aggressive behaviour, and the high rate of recurrence, metastasis, and disease related death. Aims: To investigate expression of the proteins involved in the retinoblastoma (pRb) and p53 pathways, which control cell cycle progression at the G1/S checkpoint, and also expression of the c-erbB-2 oncoprotein in SDCs. Methods: Using a streptavidin–biotin method, five cases of SDC were evaluated immunohistochemically for the presence of cyclin D1, CDK4 (cyclin dependent kinase 4), p16 (CDK2A), pRb (retinoblastoma protein), E2F-1, p53, mdm2 (murine double minute 2), bcl-2, and the c-erbB-2 oncoprotein to determine whether there was a correlation between the expression of these proteins and patient outcome. Results: All of the cases showed deregulation of the pRb and p53 pathways. Of the five patients analysed, only the patient with longterm survival (10 years) was not positive for c-erbB-2 expression. Conclusions: c-erbB-2 overexpression was associated with a poor prognosis. Aggressive behaviour, recurrence, and metastatic potential do not appear to be related to cell cycle deregulation, but seem to be associated with the c-erbB-2 oncoprotein, which is involved in matrix degradation and proteolitic activity, in addition to increases in vessel permeability, endothelial cell growth, proliferation, migration, and differentiation. There was a correlation between c-erbB-2 oncoprotein expression and aggressive behaviour in SDCs.

Inhibition of Histone Deacetylase Impacts Cancer Stem Cells and Induces Epithelial-Mesenchyme Transition of Head and Neck Cancer

The genome is organized and packed into the nucleus through interactions with core histone proteins. Emerging evidence suggests that tumors are highly responsive to epigenetic alterations that induce chromatin-based events and dynamically influence tumor behavior. We examined chromatin organization in head and neck squamous cell carcinoma (HNSCC) using acetylation levels of histone 3 as a marker of chromatin compaction. Compared to control oral keratinocytes, we found that HNSCC cells are hypoacetylated and that microenvironmental cues (e.g., microvasculature endothelial cells) induce tumor acetylation. Furthermore, we found that chemical inhibition of histone deacetylases (HDAC) reduces the number of cancer stem cells (CSC) and inhibits clonogenic sphere formation. Paradoxically, inhibition of HDAC also induced epithelial-mesenchymal transition (EMT) in HNSCC cells, accumulation of BMI-1, an oncogene associated with tumor aggressiveness, and expression of the vimentin mesenchymal marker. Importantly, we observed co-expression of vimentin and acetylated histone 3 at the invasion front of human HNSCC tumor tissues. Collectively, these findings suggest that environmental cues, such as endothelial cell-secreted factors, modulate tumor plasticity by limiting the population of CSC and inducing EMT. Therefore, inhibition of HDAC may constitute a novel strategy to disrupt the population of CSC in head and neck tumors to create a homogeneous population of cancer cells with biologically defined signatures and predictable behavior.

Low-level laser therapy can produce increased aggressiveness of dysplastic and oral cancer cell lines by modulation of Akt/mTOR signaling pathway

Low-level laser therapy (LLLT) is a non-thermal phototherapy used in several medical applications, including wound healing, reduction of pain and amelioration of oral mucositis. Nevertheless, the effects of LLLT upon cancer or dysplastic cells have been so far poorly studied. Head and neck cancer patients receiving LLLT for oral mucositis, for example, might have remaining tumor cells that could be stimulated by LLLT. This study demonstrated that LLLT (GaAlAs--660 nm or 780 nm, 40 mW, 2.05, 3.07 or 6.15 J/cm²) can modify oral dysplastic cells (DOK) and oral cancer cells (SCC9 and SCC25) growth by modulating the Akt/mTOR/CyclinD1 signaling pathway; LLLT significantly modified the expression of proteins related to progression and invasion in all the cell lines, and could aggravate oral cancer cellular behavior, increasing the expression of pAkt, pS6 and Cyclin D1 proteins and producing an aggressive Hsp90 isoform. Apoptosis was detected for SCC25 and was related to pAkt levels.

Hemophilic pseudotumor of the jaws : report of two cases

Hemophilic pseudotumor of bone is a rare condition that occurs in patients with hemophilia. To date only 10 cases have been reported in the mandible, and none has been reported in the maxilla. The clinical, radiographic, and histologic features and treatment approaches of two cases of hemophilic pseudotumor occurring in the jaws are presented. One of them is probably the first one reported in the maxilla. Both patients had a history of trauma to the area.

MDM2, P53, P21WAF1 and pAKT protein levels in genesis and behaviour of adenoid cystic carcinoma ☆

BACKGROUND MDM2, P53, P21(WAF1) and pAKT are proteins associated with the balance between cell death and survival. There are many hypotheses regarding the role of these proteins in salivary gland tumours. However, many molecular events that activate or inactivate regulatory genes remain unknown. The aim of this study was to evaluate and to correlate MDM2, P53, P21(WAF1) and pAKT protein expressions in adenoid cystic carcinomas (ACC). METHODS Twenty-two cases of ACC were evaluated by immunohistochemistry and one cell line derived from ACC was analyzed by Western Blotting and immunofluorescence techniques. RESULTS Strong MDM2 and pAKT, variable P53 and null P21 expressions were found in the cases analyzed, but no statistical correlation was established when comparing MDM2 and pAKT expressions in the 3 different ACC subtypes. The ACC cell line showed intense nuclear and cytoplasmatic MDM2 and pAKT expressions and null P53 and P21 expressions. CONCLUSIONS Results indicate that MDM2 and pAKT are related to the tumorigenesis of ACC, but they might not be directly connected to tumour progression. We also demonstrate that the pAKT pathway is active in ACC and it seems to be activating the MDM2 shuttle from the cytoplasm to the nucleus, where it phosphorylates P53 and carries it to the cytoplasm for degradation.

Report of four cases of Ameloblastic fibro-odontoma in mandible and discussion of the literature about the treatment

The ameloblastic fibro-odontoma is defined as a tumour with the general features of the ameloblastic fibroma but that also contains enamel and dentine. AFO normally presents as a painless swelling in the posterior portion of the maxilla or mandible. Radiographs show a well-defined radiolucent area containing various amounts of radiopaque material of irregular size and form. The most appropriate treatment for a large AFO has not been completely determined. This paper reports four large AFO cases and reviews the relevant literature regarding the clinical and surgical features of this lesion.

Comparison of two cellular harvesting methods for primary human oral culture of keratinocytes

The possibility of obtaining transplantable oral epithelia opens new perspectives for oral treatments. Most of them are surgical, resulting in mucosal failures. As reconstructive material this in vitro epithelia would be also useful for other parts of the human body. Many researchers still use controversial methods; therefore it was evaluated and compared the efficiency of the enzymatic and direct explant methods to obtain oral keratinocytes. To this project oral epithelia fragments were used. This work compared: time needed for cell obtainment, best cell amount, life-span and epithelia forming cell capacity. The results showed the possibility to obtain keratinocytes from a small oral fragment and we could verify the advantages and peculiar restrictions. We concluded that under our conditions the enzymatic method showed the best results: in the cells obtaining time needed, cell amount and life-span. Both methods showed the same capacity to form in vitro epithelia.

Nuclear factor κB and cyclooxygenase-2 immunoexpression in oral dysplasia and oral squamous cell carcinoma

Oral leukoplakia is the main potentially malignant oral lesion, and oral squamous cell carcinoma accounts for more than 95% of all malignant neoplasms in the oral cavity. Therefore, the aim of this study was to verify the immunoexpression of nuclear factor κB (NF-κB) and cyclooxygenase-2 (COX-2) proteins in dysplastic oral lesions and oral squamous cell carcinoma. Immunohistochemical reactions were performed on 6 inflammatory fibrous hyperplasia, 28 oral leukoplakia, and 15 oral squamous cell carcinoma paraffin-embedded samples. Immunoperoxidase reaction for NF-κB and COX-2 was applied on the specimens, and the positivity of the reactions was calculated for 1000 epithelial cells. Using the analysis of variance and the Tukey post hoc statistical analyses, a significantly increased immunoexpression for NF-κB was observed when oral squamous cell carcinoma samples were compared with the other groups studied. However, using the Kruskal-Wallis and the Dunn post hoc tests, a statistically significant result for COX-2 expression was obtained only when the moderate dysplasia group was compared with the inflammatory fibrous hyperplasia group. Nuclear factor κB may participate in the malignant phenotype acquisition process of the oral squamous cell carcinoma in its late stages, whereas COX-2 may be involved in the early stages of oral carcinogenesis process.

Mdm2, p53, p21 and pAKT protein pathways in benign neoplasms of the salivary gland

The p53 protein can be altered virtually in all human cancers. In the absence of p53 mutations, p53 inactivation is possible via complex formation with other proteins, such as Mdm2. Previous studies have shown an overexpression of Mdm2 and lack of p53 expression in pleomorphic adenomas. The pAkt protein is closely related to Mdm2, and has not been previously reported in salivary gland tumors. The aim of this study was to analyze the expression of Mdm2, p53, p21 and pAkt proteins in pleomorphic adenomas and myoepitheliomas by immunohistochemistry, Western blotting and immunofluorescence techniques. Overexpression of Mdm2 and pAkt was present in all the cell lines and tumors studied, whereas the expression of p53 and p21 proteins was considered absent. In conclusion, the signaling pathway in benign salivary gland neoplasm showed an important participation of Mdm2 overexpression protein in tumor formation, progression through inactivation of p53 action, or both, and of pAkt overexpression through increased translocation of Mdm2 protein to cellular nuclei.