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Napimoga M.H.,Sao Leopoldo Mandic Institute and Research Center | Nametala C.,Sao Leopoldo Mandic Institute and Research Center | Da Silva F.L.,Sao Leopoldo Mandic Institute and Research Center | Miranda T.S.,Guarulhos University | And 3 more authors.
Journal of Clinical Periodontology | Year: 2014

Aim The regulation of Wnt-β-catenin signalling, which is crucial for osteoblast differentiation and for bone resorption, is driven by critical inhibitors such as sclerostin (SOST) and dickkopf-related protein 1 (DKK1). As such, the aim of this study was to evaluate the involvement of SOST and DKK1 in human chronic periodontitis. Material and Methods Gingival biopsies and serum were sampled from systemically healthy non-periodontitis (n = 15) and chronic periodontitis subjects (n = 15). The mRNA and protein levels of SOST, DKK1 and TNF-α in periodontal tissues were measured by qPCR and by enzyme-linked immunosorbent assay (ELISA) respectively. Serum levels of SOST, DKK1 and TNF-α were assessed by ELISA. Results The mRNA and protein levels of SOST, DKK1 and TNF-α were significantly increased in the gingival tissues of the chronic periodontitis when compared to the non-periodontitis group (p < 0.05). In addition, circulating levels of SOST and TNF-α, but not DKK1, were higher in the periodontitis group than in the non-periodontitis group (p < 0.05). Conclusion SOST and DKK1 were upregulated in the periodontal tissues of chronic periodontitis subjects, suggesting a possible role of these molecules on periodontal tissues. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.


Martinez E.F.,Sao Leopoldo Mandic Institute and Research Center | Demasi A.P.D.,Sao Leopoldo Mandic Institute and Research Center | Napimoga M.H.,Sao Leopoldo Mandic Institute and Research Center | Arana-Chavez V.E.,University of Sao Paulo | And 3 more authors.
Oral Oncology | Year: 2012

In order to investigate the role of myoepithelial cell and tumor microenvironment in salivary gland neoplasma, we have performed a study towards the effect of different extracellular matrix proteins (basement membrane matrix, type I collagen and fibronectin) on morphology and differentiation of benign myoepithelial cells from pleomorphic adenoma cultured with malignant cell culture medium from squamous cell carcinoma. We have also analyzed the expression of α-smooth muscle actin (α-SMA) and FGF-2 by immunofluorescence and qPCR. Our immunofluorescence results, supported by qPCR analysis, demonstrated that α-SMA and FGF-2 were upregulated in the benign myoepithelial cells from pleomorphic adenoma in all studied conditions on fibronectin substratum. However, the myoepithelial cells on fibronectin substratum did not alter their morphology under malignant conditioned medium stimulation and exhibited a stellate morphology and, occasionally focal adhesions with the substratum. In summary, our data demonstrated that the extracellular matrix exerts an important role in the morphology of the benign myoepithelial cells by the presence of focal adhesions and also inducing increase FGF-2 and α-SMA expression by these cells, especially in the fibronectin substratum. © 2011 Elsevier Ltd. All rights reserved.


Martinez E.F.,Sao Leopoldo Mandic Institute and Research Center | Napimoga M.H.,Sao Leopoldo Mandic Institute and Research Center | Montalli V.A.M.,Sao Leopoldo Mandic Institute and Research Center | De Araujo N.S.,Sao Leopoldo Mandic Institute and Research Center | De Araujo V.C.,Sao Leopoldo Mandic Institute and Research Center
Archives of Oral Biology | Year: 2013

Objectives: The myoepithelial cells exert important effects regulating the transition of an in situ to an invasive carcinoma. This cell has been associated with a tumour suppressor phenotype due to its ability to inhibit tumour growth as well as its immunomodulatory role in cancer behaviour. Design: In order to correlate the cancer cell growth and the role of cytokines in regulating the neoplastic process, we have attempted to simulate an in vitro model of tumorigenesis, which mimics a situation where in situ neoplastic cells of carcinoma are surrounded by benign myoepithelial cells from pleomorphic adenoma. To certify the formation of in situ-like neoplasic areas, the cells were immunostained with vimentin and AE1/AE3, markers for tumoral benign myoepithelial cells and squamous cell carcinoma lineage, respectively. We investigated the correlation of the cancer cell growth with the releasing of IL-4, IL-6 and IL-10 associated with the immune response. The cytokines levels were evaluated using ELISA. Results: In in situ neoplastic areas, IL-6 amounts were higher released when compared with IL-4 and IL-10, in all studied periods. Interestingly, the peak of IL-6 release fits with the predominance of malignant cells in the culture. Conclusions: The present results demonstrated that, in this in vitro condition, the myoepithelial cells were not able to suppress the tumour cell proliferation even with high secretion of IL-4 by benign myoepithelial cells which at the beginning is supposed to act as an anti-tumour agent. In addition, these cells favoured the tumour growth by excessive production of IL-6 and IL-10. © 2012 Elsevier Ltd.


Soares A.B.,Sao Leopoldo Mandic Institute and Research Center | Altemani A.,University of Campinas | de Araujo V.C.,Sao Leopoldo Mandic Institute and Research Center
Journal of Oral Pathology and Medicine | Year: 2011

Background: Recurrent pleomorphic adenoma (RPA) is an uncommon and challenging disease. The aim of this study was to review the clinical information obtained by examining RPA patients, to determine its histomorphological features and to verify the expression of the Mcm-2 markers of cell proliferation and the expression of p-53 in pleomorphic adenoma (PA), RPA, and RPA with malignant transformation (TRPA). Methods: A total of 10 cases of PA and 29 cases of RPA were examined in detail for the presence of nodules and their histomorphological features. Cell proliferation and expression of p-53 were detected by the immunohistochemical technique using the antibodies against Mcm-2 and p-53. Results: Histopathologically, RPA is very similar to PA; the only difference found was that all the cases of RPA were multinodular. When comparing primary and recurrent tumor, no significant difference was found in terms of cell proliferation and the expression of p-53; however, in the RPA with areas of malignant transformation there was an increased expression of these proteins. Conclusion: This study showed that recurrences were multinodular, with nodules varying in numbers and sizes. No significant difference in histological features was found between RPA and PA. Moreover, the immunohistochemical study showed a low expression of p-53 and Mcm-2 in PA and RPA and an increased expression of these proteins in the RPA with areas of malignant transformation. © 2010 John Wiley & Sons A/S.


De Araujo V.C.,Sao Leopoldo Mandic Institute and Research Center | Passador-Santos F.,Sao Leopoldo Mandic Institute and Research Center | Turssi C.,Sao Leopoldo Mandic Institute and Research Center | Soares A.B.,Sao Leopoldo Mandic Institute and Research Center | de Araujo N.S.,Sao Leopoldo Mandic Institute and Research Center
Diagnostic Pathology | Year: 2013

Background: This study is an analysis of the prevalence of polymorphous low grade adenocarcinoma (PLGA) in epidemiological surveys of salivary tumors published in the English language from 1992 to 2012.Methods: These surveys included studies from different researchers, countries and continents. The 57 surveys for which it was possible to calculate the percentage of PLGAs among all malignant minor salivary gland tumors (MMSGT) were included in this review.Results: The statistical analyses show significant differences in the PLGA percentage by time period, country and continent in the studies included in this review. The percentage of PLGAs among MMSGTs varied among the studies, ranging from 0.0% to 46.8%. PLGA rates have varied over the period studied and have most recently increased. The frequency of reported PLGA cases also varied from 0.0% to 24.8% by the country in which the MMSGT studies were performed. The PLGA percentages also varied significantly by continent, with frequencies ranging from 3.9% in Asia to 20.0% in Oceania. Conclusion: Based on these results, we concluded that although the accuracy of PLGA diagnoses has improved, they remain a challenge for pathologists. To facilitate PLGA diagnoses, we have therefore made some suggestions for pathologists regarding tumors composed of single-layer strands of cells that form all of the histological patterns present in the tumor, consistency of the cytological appearance and uniformly positive CK7, vimentin and S100 immunohistochemistry, which indicate a single PLGA phenotype.Virtual slide: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1059098656858324. © 2013 de Araujo et al.; licensee BioMed Central Ltd.


De Melo Neto J.P.,University of Novafapi | Melo M.S.A.E.,University of Novafapi | Dos Santos-Pereira S.A.,Sao Leopoldo Mandic Institute and Research Center | Martinez E.F.,Sao Leopoldo Mandic Institute and Research Center | And 2 more authors.
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2013

The aim of this study was to evaluate if the presence of periodontal infections (PI) is associated with community-acquired pneumonia (CAP) in a group of patients admitted to a hospital. A total of 140 patients were enrolled in this case-control study, with 70 patients having CAP (case group) and the other 70 patients diagnosed with other systemic diseases (control group). A periodontal examination was carried out to assess pocket probing depth (PPD), clinical attachment loss (CAL), bleeding on probing (BOP), and presence of bacterial plaque (BP). CAL and BOP showed higher scores in the case group over the control group. They were, respectively, 3.16 ± 2.43 mm and 0.33 ± 0.24 % for the case group, and 1.99 ± 2.23 mm and 0.25 ± 0.24 % for the control group (p < 0.05). High scores for BP were observed in both groups (case: 97.1 %; control: 98.6 %, p = 1.0000). Chronic periodontitis (CP) was more frequent in patients with CAP (case: 61.4 %; control: 41.4 %). The presence of moderate or severe CP increased the risk for CAP [odds ratio (OR) = 4.4, 95 % confidence interval (CI) = 1.4-13.8], even when adjusted for age, ethnicity, gender, and smoking. Moderate and severe chronic periodontitis were associated with CAP in this study. © 2012 Springer-Verlag.


Rosa M.B.,Sao Leopoldo Mandic Institute and Research Center
The International journal of oral & maxillofacial implants | Year: 2013

The mental foramen is an important landmark during surgical procedures such as osseous grafting or the placement of dental implants. To avoid injuring the mental nerve, it is important both to carefully assess the location of the mental foramen and to determine whether an anterior loop of the mental nerve or the incisive canal lies mesial to it. The objective of this study was to quantify the ability of cone beam computed tomography (CBCT) to measure the length of the mental nerve loop, the length and diameter of the incisive nerve canals, and the incisive canal path. The study included 352 CBCT scans that had originally been used for preoperative planning of implant placement in the interforaminal region of the anterior mandible. For each scan, the length of the mental nerve loop and the length, diameter, and path of the incisive canal were determined. Mean values were compared between groups based on sex, right versus left side, and whether the patient was edentulous. The inferior alveolar nerve loop and incisive canal had a mean length of 2.40 ± 0.93 mm and 9.11 ± 3.00 mm, respectively. The mean incisive canal diameter was 1.48 ± 0.66 mm and showed a downward path in 51.3% of CBCT images and a linear or upward path in 38.29% and 10.41% of scans, respectively. CBCT provides an accurate means to identify critical anatomical features in the anterior mandible during preoperative surgical planning.


Soares A.B.,Sao Leopoldo Mandic Institute and Research Center | Demasi A.P.D.,Sao Leopoldo Mandic Institute and Research Center | Altemani A.,University of Campinas | De Araujo V.C.,Sao Leopoldo Mandic Institute and Research Center
Histopathology | Year: 2011

Aims: Pleomorphic adenoma (PA) is the most common salivary gland tumour with a tendency to recur (RPA) and a risk of malignant transformation. Mucin 1 (MUC-1) plays a role in the progression of many tumours and may be a marker to predict RPA. The aim of this study was to evaluate MUC-1 expression in different phases of the adenoma to carcinoma sequence. Methods and results: Twenty-one cases of PA, 18 cases of RPA, three cases of RPA with focal transformation (TRPA) and 11 cases of carcinoma ex-pleomorphic adenoma (CXPA) were analysed immunohistochemically for MUC1 expression using an antibody to MUC1/DF3. MUC1 reactivity in RPA was stronger than that observed in PA and, in all the different carcinoma groups, MUC-1 expression was significantly higher in carcinoma than in RPA and PA. Conclusion: This study has confirmed that MUC-1 is related to the recurrence of PA and that this molecule is associated with malignant transformation of PA with carcinoma cells overexpressing MUC-1. © 2011 Blackwell Publishing Limited.


Mendonca J.A.,Sao Leopoldo Mandic Institute and Research Center | Francischone C.E.,Sao Leopoldo Mandic Institute and Research Center | Senna P.M.,Health Science University | De Oliveira A.E.M.,Federal University of Juiz de fora | Sotto-Maior B.S.,Federal University of Juiz de fora
Journal of Periodontology | Year: 2014

The aim of the present study is to evaluate the survival rate and bone loss around short implants (≥10 mm) supporting splinted or non-splinted posterior prostheses during a follow-up period of 3 to 16 years. Methods: A total of 453 implants from 198 patients was divided into splinted or non-splinted groups. Implant survival rate was calculated for each group, and potential risk was represented as odds ratio (OR). The final linear distance from implant platform level to the first bone-to-implant contact was compared to this same reference just after loading by digital periapical radiographs to determine the marginal bone loss (BL). Results: The splinted group comprised 219 implants in 86 patients, whereas the non-splinted group included 234 implants from 112 patients. The mean follow-up period was 9.7 ± 3.7 years. Although different success rates were found for splinted (97.7%) and non-splinted (93.2%) groups, they exhibited similar BL (1.22 ± 0.95 mm and 1.27 ± 1.15 mm, respectively). The success of splinted implants was associated with no other variable, whereas non-splinted implants exhibited higher risk of failure when placed in men (OR = 3.2) and when implants shorter than 10 mm were used (OR = 3.6 and 4.1 for 8.5 mm and 7 mm, respectively). Regardless of group, 71.4% of the unsuccessful implants failed before the end of the first year after loading. Conclusion: Non-splinted posterior short implants had a somewhat lower success rate than splinted short implants, and the failure rate in non-splinted short implants appeared to be greater in males as well as in implants ≥10 mm.


Miguita L.,Sao Leopoldo Mandic Institute and Research Center | Martinez E.F.,Sao Leopoldo Mandic Institute and Research Center | de Araujo N.S.,Sao Leopoldo Mandic Institute and Research Center | de Araujo V.C.,Sao Leopoldo Mandic Institute and Research Center
Journal of Applied Oral Science | Year: 2010

Myoepithelial cells have an important role in salivary gland tumor development, contributing to a low grade of aggressiveness of these tumors. Normal myoepithelial cells are known by their suppressor function presenting increased expression of extracellular matrix genes and protease inhibitors. The importance of stromal cells and growth factors during tumor initiation and progression has been highlighted by recent literature. Many tumors result from the alteration of paracrine growth factors pathways. Growth factors mediate a wide variety of biological processes such as development, tissue repair and tumorigenesis, and also contribute to cellular proliferation and transformation in neoplastic cells. Objectives: This study evaluated the expression of fibroblast growth factor-2 (FGF-2), transforming growth factor β-1 (TGFβ-1), platelet-derived growth factor-A (PDGF-A) and their respective receptors (FGFR-1, FGFR-2, TGFβR-II and PDGFR-α) in myoepithelial cells from pleomorphic adenomas (PA) by in vivo and in vitro experiments. Material and Methods: Serial sections were obtained from paraffin-embedded PA samples obtained from the school's files. Myoepithelial cells were obtained from explants of PA tumors provided by surgery from different donors. Immunohistochemistry, cell culture and immunofluorescence assays were used to evaluate growth factor expression. Results: The present findings demonstrated that myoepithelial cells from PA were mainly positive to FGF-2 and FGFR-1 by immunohistochemistry and immunofluorescence. PDGF-A and PDGFR-α had moderate expression by immunohistochemistry and presented punctated deposits throughout cytoplasm of myoepithelial cells. FGFR-2, TGFβ-1 and TGFβR-II were negative in all samples. Conclusions: These data suggested that FGF-2 compared to the other studied growth factors has an important role in PA benign myoepithelial cells, probably contributing to proliferation of these cells through the FGFR-1.

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