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Breast cancer is one of the leading causes of death among women worldwide and can be classified into four major distinct molecular subtypes based on the expression of specific receptors. Despite significant advances, the lack of biomarkers for detailed diagnosis and prognosis remains a major challenge in the field of oncology. This study aimed to identify short single-stranded oligonucleotides known as aptamers to improve breast cancer diagnosis. The Cell-SELEX technique was used to select aptamers specific to the MDA-MB-231 tumor cell line. After selection, five aptamers demonstrated specific recognition for tumor breast cell lines and no binding to non-tumor breast cells. Validation of aptamer specificity revealed recognition of primary and metastatic tumors of all subtypes. In particular, AptaB4 and AptaB5 showed greater recognition of primary tumors and metastatic tissue, respectively. Finally, a computational biology approach was used to identify potential aptamer targets, which indicated that CSKP could interact with AptaB4. These results suggest that aptamers are promising in breast cancer diagnosis and treatment due to their specificity and selectivity.

Background: This study aimed to investigate the differentiation of ameloblastic-like cells and the nature of the secreted eosinophilic materials in adenomatoid odontogenic tumors., Methods: We studied histological and immunohistochemical characteristics of 20 cases using: cytokeratins 14 and 19, amelogenin, collagen I, laminin, vimentin, and CD34., Results: Rosette cells differentiated into ameloblastic-like cells positioned face-to-face, displaying collagen I-positive material between them. Epithelial cells of the rosettes can differentiate into ameloblastic-like cells. This phenomenon probably occurs due to an induction phenomenon between these cells. The secretion of collagen I is probably a brief event. Amelogenin-positive areas were interspersed by epithelial cells in the lace-like areas, outside the rosettes and distant from the ameloblastic-like cells., Conclusions: There are at least two types of eosinophilic material in different areas within the tumor, one in the rosette and solid areas and another in lace-like areas. The secreted eosinophilic material in the rosettes and solid areas is probably a product of well-differentiated ameloblastic-like cells. It is positive for collagen I and negative for amelogenin, whereas some eosinophilic materials in the lace-like areas are positive for amelogenin. We hypothesize that the latter eosinophilic material could be a product of odontogenic cuboidal epithelial or intermediate stratum-like epithelial cells., (© 2023 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

Extrahepatic manifestations are common in people with hepatitis C virus (HCV). Cognitive changes are pointed out, but the mechanisms are still uncertain. The aim of this systematic review was to analyze studies involving spectroscopic magnetic resonance in people infected with HCV, which also included cognitive tests. The research occurred in six databases (Directory of Open Access Journals, Lilacs, Medcaribe, Medline, Scielo and ScienceDirect) and the selection of studies was carried out in two stages: search for titles and abstracts, then reading of the full articles, excluding those that did not meet the eligibility criteria. 12,888 titles and abstracts were selected, but only 6 articles were included in the review. Impairments in attention, concentration, speed of information processing, memory, verbal fluency and executive functions were identified as well as an increase in the Cho/Cr and mI/Cr ratios and a reduction in the NAA/Cr ratio in some included studies. Longitudinal studies, with more homogeneous samples and methods, as well as with better controlled confounding factors, are necessary to adequately identify the effect of HCV on the brain.

Ovarian cancer is among the seven most common types of cancer in women, being the most fatal gynecological tumor, due to the difficulty of detection in early stages. Aptamers are important tools to improve tumor diagnosis through the recognition of specific molecules produced by tumors. Here, aptamers and their potential targets in ovarian cancer cells were analyzed by in silico approaches. Specific aptamers were selected by the Cell-SELEX method using Caov-3 and OvCar-3 cells. The five most frequent aptamers obtained from the last round of selection were computationally modeled. The potential targets for those aptamers in cells were proposed by analyzing proteomic data available for the Caov-3 and OvCar-3 cell lines. Overexpressed proteins for each cell were characterized as to their three-dimensional model, cell location, and electrostatic potential. As a result, four specific aptamers for ovarian tumors were selected: AptaC2, AptaC4, AptaO1, and AptaO2. Potential targets were identified for each aptamer through Molecular Docking, and the best complexes were AptaC2-FXYD3, AptaC4-ALPP, AptaO1-TSPAN15, and AptaO2-TSPAN15. In addition, AptaC2 and AptaO1 could detect different stages and subtypes of ovarian cancer tissue samples. The application of this technology makes it possible to propose new molecular biomarkers for the differential diagnosis of epithelial ovarian cancer.

Objectives: This study aimed to revisit benign odontogenic ghost cell lesions (BOGCL) by hematoxylin and eosin staining and immunohistochemistry., Materials and Methods: Thirty cases of calcifying odontogenic cyst (COC) and 6 cases of dentinogenic ghost cell tumor (DGCT) were selected for histopathological and immunohistochemical analysis. Sections stained for cytokeratin (K) 14, K-19, amelogenin, collagen type 1 (COL-1), and dentin matrix acidic phosphoprotein 1 (DMP-1) were evaluated using qualitative analysis. Sections stained for Ki-67 and minichromosome maintenance protein-2 (MCM-2) were evaluated using semi-quantitative analysis., Results: A morphologic overlap was noticed in all BOGCL. Moreover, no differences were detected in the expression of K-14 and K-19. The expression of proliferative markers Ki-67 and MCM-2 was similar between cystic and tumor lesions (p > .05). The presence of COL-1 and absence of amelogenin in the so-called dysplastic dentin, associated with its histologic pattern, suggest that this is in fact an enameloid-like tissue., Conclusions: The dysplastic dentin should be considered an enameloid-like tissue in these lesions., Clinical Relevance: The similarity in histology, protein expression, and proliferative marker indices between COC and DGCT suggest that they are a sole entity and likely represent types of the same neoplasia.

Differential diagnosis among fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias is difficult, since there is considerable overlap of histologic features, but also extremely important, since they differ greatly in etiology, clinical behaviour, prognosis and terapeuthic approach. There is no data about the use of immunohistochemistry, a viable and accessible technique, for this purpose. The objective of this study was to investigate, comparatively, the immunohistochemical expression of major non-collagenous proteins (osteonectin [ON], osteopontin [OP], bone sialoprotein [BSP] and osteocalcin [OC]) of mineralized tissue extracellular matrix in 22 cases of fibrous dysplasias, 16 of cemento-ossifying fibromas and 16 of cemento-osseous dysplasias. ON maintained the same expression profile in all cases; the staining for OP was negative in fusiform cells producing cementoid globules and weak, as well as heterogeneous, in high mineralized matrixes; there was negativity for BSP in cementoid globules and in the fusiform cells that produce them, differently from the strong positive expression found in the majority of bone trabeculae and their peripheral cuboidal osteoblasts; and finally, the immuno-reactivity for OC was weak, except in cuboidal osteoblasts and osteocytes. We can conclude that the nature of mineralized structure and the cellular phenotype are much more responsible for variability in immunohistochemical profile than the type of lesion (fibrous dysplasias, cemento-ossifying fibromas and cemento-osseous dysplasias) which makes difficult, at least for a while, the use of these proteins with diagnosis purpose., (Copyright © 2019. Published by Elsevier GmbH.)

The present study aimed to compare the expression of p63/p40 with smooth muscle actin (SMA) and vimentin (VIM) by myoepithelial cells in minor salivary gland tumors. Fifty-two formalin-fixed paraffin-embedded samples of minor salivary gland tumors derived from intercalated duct (pleomorphic adenoma [PA], adenoid cystic carcinoma [ACC], epithelial-myoepithelial carcinoma [EMC], polymorphous adenocarcinoma [PAC], and secretory carcinoma [SC]) and 3 samples of minor salivary gland tumors derived from excretory duct (mucoepidermoid carcinoma [MEC]) were evaluated by means of immunohistochemistry. The data were analyzed qualitatively. The results indicated that p63 and p40 expression were detected in myoepithelial cells present in PA, ACC, and EMC. However, both proteins were also observed in squamous areas of PA and all cases of MEC. SMA were noticed in some myoepithelial cells of PA, ACC, and EMC. Expression of SMA was negative in the other salivary gland tumors evaluated. VIM was constantly expressed by myoepithelial cells in PA, ACC, and EMC. VIM was also observed in cells of PAC and SC, but not in squamous areas of PA and MEC. In conclusion, p63 expression is almost comparable with VIM in detecting myoepithelial cells, an immunolabeling pattern not followed by p40, and consequently, caution has to be taken during the interpretation of salivary gland tumor exhibiting an p63/p40 phenotype in order to avoid a misdiagnosis.

Background: Adenoid cystic carcinoma (ACC) is a salivary gland malignancy with poor long-term survival, which warrants studies aimed at clarifying the pathogenesis of this disease in order to widen the scope of therapeutic options currently available. Alterations in regulatory mechanisms relating to vascular support, cell death and autophagy are important pathways for tumor growth in cancer. Thus, the present study aimed to access vascular supply, apoptosis, autophagy and cell senescence in ACC of minor salivary glands., Methods: We analyzed 25 cases of minor salivary gland ACC by immunohistochemistry using anti-CD34, anti-CD105, anti-D2-40, anti-Bax, anti-Bcl-2, anti-Beclin-1, anti-LC3B, anti-p21 and anti-p16., Results: Microvessel density was low and based on anti-CD34, anti-CD105 and anti-D2-40 immunostaining. There was positivity for anti-CD34, anti-Bcl-2, anti-Beclin, anti-LC3B and anti-p21 and a positive correlation between Bcl-2 and Beclin (p = 0.014)., Conclusions: Our results showed that ACC does not depend on neo-angiogenesis and is probably associated to anti-apoptotic, autophagic and anti-senescence events.

Considered as an aggressive counterpart of central ossifying fibroma (OF), juvenile ossifying fibroma (JOF) is a benign fibro-osseous neoplasm characterized by an unpredictable destructive behavior, elevated morbidity, mutilating treatment and high potential for local recurrences. The aim of this study is to compare the analysis for cell proliferation and vascular markers between JOF and OF. Cell proliferation index was measured by Ki-67 and Mcm-2 expression and microvessel density (MVD) was obtained by the immunoexpression of CD34/CD105. We observed a reduced expression of vascular markers, where MVD for CD34 was significantly higher in JOF than in OF (p = 0.009), but no statistical difference was found for CD105. JOF and OF showed low expression for Ki-67 and Mcm-2 and no difference was noted between both, suggesting that other mechanisms such as anti-apoptotic and/or pro-autophagic pathways or even increased expression of matrix metalloproteinases may be responsible for the aggressiveness of JOF., (Copyright © 2018 Elsevier Inc. All rights reserved.)

The aim of the present study was to analyze the in vitro effect of various doses of epidermal growth factor (EGF; 5 and 10 ng/ml) on matrix metalloproteinase-2 (MMP-2) secretion and E-cadherin/β-catenin expression by co-cultured cells that mimic an in situ carcinoma ex-pleomorphic adenoma, where benign myoepithelial cells from a pleomorphic adenoma surround malignant epithelial cells. EGF was supplemented in various doses and the effects were evaluated following four days of cell culture. ELISA was performed to determine MMP-2 secretion levels. Gene expression for E-cadherin and β-catenin was analyzed using quantitative polymerase chain reaction. The results revealed that E-cadherin expression decreased when the cells were supplemented with 5 ng/ml EGF. ELISA results indicated that MMP-2 secretion increased when EGF was supplemented at concentrations of 5 and 10 ng/ml. The present findings demonstrated that EGF may be involved in the epithelial-mesenchymal transition process via altering the E-cadherin/β-catenin complex and increasing MMP-2 secretion, which may then favor the dissolution of the basement membrane to the benefit of malignant cell clusters, contributing to the development of an invasive phenotype in this in vitro model of tumorigenesis.

There is mounting evidence on the importance of some biological processes in tumor growth, such as vascular supply, apoptosis, autophagy, and senescence. We have investigated these processes in polymorphous low-grade adenocarcinoma (PLGA), in an attempt to identify those that are relevant for this particular lesion. We analyzed 31 cases of PLGA using immunohistochemistry to antibodies against CD34 and CD105 to detect blood vessels; against D2-40 to detect lymphatic vessels; against Bax, Bcl-2, and survivin to explore cell apoptosis; and against Beclin and LCB3 to investigate autophagy and against p21 and p16 to assess senescence. Our results showed that PLGA growth does not depend on newly formed vessels but only on preexisting vasculature. Furthermore, PLGA is promoted by autophagy, sustained by both anti-apoptotic and anti-senescence signals, and stimulated by Bcl-2 and survivin.

Background: Polymorphous low-grade adenocarcinoma (PLGA) remains a diagnostic challenge for most pathologists due to its large spectrum of histological patterns. In this study, the expression of two new markers recently described for salivary gland tumors was studied in PLGA., Methods: The morphology of 33 cases of PLGA was carefully evaluated using hematoxylin-and-eosin-stained sections and confirmed by immunohistochemistry for cytokeratin 7, vimentin, and S-100. Periodic acid-Schiff with diastase digestion was also used. The expression of mammaglobin and DOG-1 was carried out using the EnVision System. Mammaglobin was assessed according to the percentage of positively stained tumor cells, while DOG-1 was evaluated according to its presence and site. For MCM-2 and Ki-67, markers of proliferation, the labeling index of cell nuclei positivity was evaluated using total cell number. The ETV6-NTRK3 fusion was examined by fluorescence in situ hybridization analysis., Results: The histological patterns of the tumor were classified as lobular or non-lobular. For the non-lobular pattern, tubular, cribriform, glomeruliform, trabecular, and papillary patterns were observed. Mammaglobin was present in all PLGA cases, and its expression was stronger (P = 0.01) in the lobular than in the non-lobular pattern. The expression of DOG-1 was present in the apical portion and cytoplasm of the cells. Proliferation markers were low for all cases independent of histological pattern., Conclusions: Polymorphous low-grade adenocarcinoma has been confirmed to originate from the intercalated duct and to feature high expression of mammaglobin in its lobular pattern resembling that of mammary secretory analogue carcinoma, except for the ETV6 gene rearrangement., (© 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.)

In this brief commentary, we have shown how the benign myoepithelial cells from in situ areas of carcinoma ex-pleomorphic adenoma from salivary gland can favor tumor progression, not only dying by autophagy/senescence phenomena, disrupting the physical barrier, but also providing fuel for tumor progression.

Objective: Osteonecrosis of the jaw is a potential side effect when using bisphosphonates. Most studies on the effects of bisphosphonates on teeth have been conducted in vitro or in animal models of tooth development. Therefore, the aim of this study was to describe alterations found in human teeth extracted from areas of bisphosphonate-induced osteonecrosis., Materials and Methods: Using a retrospective study design, 16 teeth from 13 patients were extracted from areas of bisphosphonate-induced osteonecrosis during surgical debridement. The specimens were decalcified and embedded in paraffin. A series of 5-μm sections were prepared, stained with hematoxylin and eosin (H&E) and observed under a light microscope., Results: The majority of the patients were female (53.85 %), with a mean age of 60.23 ± 13.18 years. Zoledronate (IV) was the most common bisphosphonate used (92.3 %), over a mean period of 2 years. The commonest alteration observed was hypercementosis (87.5 %), followed by pulpar necrosis (81.25 %), pulp stones attached to the dentine and loose pulp stones in the pulp chamber and root canals in addition to linear calcifications (68.75 %), dentinoid/osteoid material formation (18.75 %), and dental ankylosis (6.25 %)., Conclusions: Patients undergoing bisphosphonate therapy present diverse tooth alterations, which should be closely monitored by clinicians to prevent complications., Clinical Relevance: It is paramount that the teeth involved in oral lesions are always examined. Attention should be drawn to the need to establish preventive measures, in terms of dental treatment, for patients prior to starting bisphosphonate therapy.

Objective: The aim of this study was to review the use of orthodontic records (OTR's) by Brazilian orthodontists and propose a behavioral approach from a legal point of view, drawing on their interpersonal relationship with their patients., Methods: A statistical cross-analysis was performed to compare five groups. A sixth group was created comprising the intersection of the responses provided by the five aforementioned groups., Results: The results demonstrate that 42.2% of orthodontists require initial and final records and keep orthodontic records throughout their professional career; 13.9% duplicate the initial records and consider patients as the lawful owners of these documents; 19.5% make use of a medical history questionnaire, to be duly signed by all patients; 5.4% acknowledge that the decision to undergo treatment is ultimately the patient's, and, therefore, the alternative response "not perform the treatment" should be included in the questionnaire; 24% recognize the importance of the Consumer Protection Code (CPC), regard the provision of orthodontic services as an obligation of means; and explain to the patient the risks involved in orthodontic treatment. Among the 1,469 orthodontists researched, 0% simultaneously took into account all aspects of this study., Conclusions: It was concluded that Brazilian orthodontists adopt a mistaken legal, professional and behavioral attitude, neglecting to build patient's orthodontic record with due care and in accordance with the law, which makes them vulnerable to patient disputes, contentious or otherwise.

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., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

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., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to evaluate accuracy of linear measurements assessed from axial tomograms and the influence of the use of different protocols in two cone beam CT (CBCT) units., Methods: A cylinder object consisting of Nylon® (Day Brazil, Sao Paulo, Brazil) with radiopaque markers was radiographically examined applying different protocols from NewTom 3G(TM) (Quantitative Radiology s.r.l, Verona, Veneto, Italy) and i-CAT(TM) (Imaging Sciences International, Hatfield, PA) units. Horizontal (A-B) and vertical (C-D) distances were assessed from axial tomograms and measured using a digital calliper that provided the gold standard for actual values., Results: There were differences when considering acquisition protocols to each CBCT unit. Concerning all analysed protocols from i-CAT(TM) and Newtom 3G(TM), both A-B and C-D distances presented underestimated values. Measurements of the axial images obtained from NewTom 3G(TM) (6 inch 0.16 mm and 9 inch 0.25 mm) were similar to the ones obtained from i-CAT(TM) (13 cm 20 s 0.3 mm, 13 cm 20 s 0.4 mm and 13 cm 40 s 0.25 mm)., Conclusion: The use of different protocols from CBCT machines influences linear measurements assessed from axial images. Linear distances were underestimated in both equipments. Our findings suggest that the best protocol for the i-CAT(TM) is 13 cm 20 s 0.3 mm and for the NewTom 3G(TM), the use of 6 inch or 9 inch is recommended.

Juvenile ossifying fibroma is an uncommon, benign, bone-forming neoplasm that is distinguished from other fibro-osseous lesions primarily by its age of onset, clinical presentation, and potential behavior. It mainly occurs in juveniles and has a slight male predilection and more aggressive behavior than a common ossifying fibroma. There are 2 distinct histopathological variants of this lesion: (1) psammomatoid pattern and (2) trabecular pattern. An aneurysmal bone cyst may occur in association with other bone lesions, such as fibrous dysplasia, ossifying fibroma, and giant cell lesion. The clinical management and prognosis of juvenile ossifying fibroma is somewhat uncertain, and this tumor has high rates of recurrence. Such behavior may be related to younger patient age and the concurrent development of aneurysmal bone cyst. The purpose of this paper was to report a case of trabecular juvenile ossifying fibroma in a 9-year-old girl associated with an aneurysmal bone cyst, presenting an aggressive behavior, and causing significant facial asymmetry.

Altered expression of extracellular matrix (ECM) components has been reported in several pathologies; however, few ECM proteins have been evaluated in adenomatoid odontogenic tumor (AOT). The aim of this study was to analyze the expression and distribution of the ECM proteoglycans: biglycan and decorin; and glycoproteins: osteonectin, osteopontin, bone sialoprotein and osteocalcin in the AOT. Three-micrometer sections from paraffin-embedded specimens were evaluated employing a streptavidin-biotin immunohistochemical method with the antibodies against the proteins previously cited. Only the osteonectin was expressed in the epithelial cells. The eosinophilic amorphous material and the connective tissue showed expression of all components studied. The calcification foci expressed only osteopontin. In conclusion, the low expression of the components studied in neoplastic epithelial cells suggests that the epithelial cells act probably as stimulators of the expression by the stroma, which in turn can act as agonist or antagonist of the tumor growth. These results suggest that the components studied probably have a key role in the biological behavior of the AOT.

Unlabelled: 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 beta-1 (TGFbeta-1), platelet-derived growth factor-A (PDGF-A) and their respective receptors (FGFR-1, FGFR-2, TGFbetaR-II and PDGFR-alpha) 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-alpha had moderate expression by immunohistochemistry and presented punctated deposits throughout cytoplasm of myoepithelial cells. FGFR-2, TGFbeta-1 and TGFbetaR-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.

Objectives: To analyze the expression of tenascin, fibronectin, collagens I and III, osteonectin, and bone morphogenetic protein 4 (BMP4) in the extracellular matrix of pulp tissue in primary teeth during physiologic root resorption., Method and Materials: Eighteen teeth were decalcified and equally distributed into 3 groups (group I, teeth with two-thirds root length; group II, teeth with one-third root length; and group III, teeth lacking the root)., Results: Immunohistochemical analysis showed that all the proteins were expressed. Tenascin, collagen I, and osteonectin showed strong and broad reactivity in group I, with weaker and rare reactivity in groups II and III. The expression of fibronectin, collagen III, and BMP4 did not vary with root resorption phase., Conclusion: The expression of tenascin, collagen I, and osteonectin was reduced in the extracellular matrix and odontoblasts during root resorption. This fact may be related to the decreasing pulp response to damage and treatment during the progression of root resorption.

An immunoperoxidase technique was used to compare the number of CD1a+ and factor XIIIa+ dendritic cells (DCs), and CD68+ Macrophages (M) in 30 gingival samples from subjects with clinically healthy periodontitium (HP) and 10 samples from subjects with drug-induced gingival enlargement (DIGE). Fewer CD1a+ and factor XIIIa+ DCs were found in areas with inflammatory infiltration (II) of the lamina propria (LP) in the group with immunosuppressed DIGE (IDIGE) compared to the group with HP. In the sulcular and junctional/pocket epithelia, the number of CD1a+ DCs was decreased in the group with IDIGE (p<0.05). There was a tendency toward a reduced number of CD1a+ DCs and CD68+ M in areas without inflammatory infiltrate of the LP in the group with IDIGE. The alterations in the number of antigen-presenting cells (APCs) may be the reason for the decreased periodontal inflammation and breakdown clinically observed in subjects who are immunosuppressed.

Dentin matrix protein 1 (DMP1) is an acidic phosphoprotein that plays an important role in mineralized tissue formation by initiation of nucleation and modulation of mineral phase morphology. The purpose of the present study was to examine the immunoexpression of DMP1 in tooth germs of 7 human fetuses at different gestational ages (14, 16, 19, 20, 21, 23 and 24 weeks) comparing with completed tooth formation erupted teeth. The results showed the presence of DMP1 in the dental lamina, as well as in the cells of the external epithelium, stellate reticulum and stratum intermedium of the enamel organ. However, in the internal dental epithelium, cervical loop region and dental papilla some cells have not labeled for DMP1. In the crown stage, DMP1 was expressed in the ameloblast and odontoblast layer, as well as in the dentinal tubules of coronal dentin near the odontoblast area. Erupted teeth with complete tooth formation exhibited immunolabeling for DMP1 only in the dentinal tubules mainly close to the dental pulp. No staining was observed in the enamel, predentin or dental pulp matrix. DMP1 is present in all developing dental structures (dental lamina, enamel organ, dental papilla) presenting few immunoexpression variations, with no staining in mineralized enamel and dentin.

Background and Objective: Substance P may play a role in the pathogenesis of periodontal disease; however, its mechanisms of modulation are not clear. This study evaluated the effect of two concentrations of Substance P on the expression of matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) in cultured human gingival fibroblasts., Material and Methods: Fibroblasts were stimulated for 48 h with 10(-4) or 10(-9) m Substance P; untreated fibroblasts served as controls. The expression of MMP-1, -2, -3, -7 and -11 and of TIMP-1 and -2 was evaluated using real-time polymerase chain reaction and western blotting., Results: There was a significant, concentration-dependent stimulatory effect of Substance P on MMP-1, -2, -3 and -7 and TIMP-2 gene expression (p < 0.05), and a probable effect on MMP-11 (p = 0.06). At the higher concentration (10(-4) m Substance P), MMP-1, -2, -3, -7 and -11 and TIMP-2 showed the greatest up-regulation; at the lower concentration (10(-9) m Substance P), MMP-1, -3 and -7 and TIMP-2 exhibited diminished up-regulation, with MMP-2 and -11 showing down-regulation (p < 0.05). Expression of TIMP-1 was not affected by Substance P (p > 0.05). Western blotting confirmed that Substance P up-regulated MMP-1, -2, -3 and -11 and TIMP-2. MMP-1, -3 and -11 and TIMP-2 showed greater up-regulation at the higher Substance P concentration and diminished up-regulation at the lower concentration. MMP-2 was up-regulated to a similar degree at both Substance P concentrations., Conclusion: In gingival fibroblast cells, Substance P at the higher concentration (10(-4) m) induced greater up-regulation of MMP-1, -3 and -11 and TIMP-2 expression, but at the lower concentration (10(-9) m) induced diminished up-regulation, which may represent a mechanism for modulating periodontal breakdown.

The aim of the present study was to evaluate the signal transducer and activator of transcription (STAT3) expression, which is constitutively active in different types of malignant tumours, in salivary gland tumours. Fifty biopsies of salivary gland tumours (9 pleomorphic adenomas, 12 adenoid cystic carcinomas, 7 epithelial-myoepithelial carcinomas, 10 polymorphous low-grade adenocarcinomas and 12 mucoepidermoid carcinomas) and 10 normal salivary glands were immunohistochemically labeled for STAT3 and Phospho-STAT3 (STAT3P). The labeled sections were qualitatively and quantitatively evaluated. The results showed that, in normal salivary gland, STAT3 was expressed in cytoplasm and STAT3P in nuclei of all tissue cells, except in large mucous acinar cells for which both antibodies were negative. In pleomorphic adenoma, the expression was the same as in normal glands. In malignant tumours, there were variations in the expression of these antibodies. The most important one was the presence of STAT3 in the nuclei of the malignant tumour cells, most evident in the cribriform-type of adenoid cystic carcinoma. Both loss and variation of STAT3P expression were also observed. The presence of STAT3 in the nuclei of malignant salivary gland tumours may represent an important event in oncogenesis probably contributing to tumour cell proliferation while blocking apoptosis. However, further investigation will be necessary to support this hypothesis.

This study was conducted to analyze the participation of tenascin and fibronectin, components of the extracellular matrix, in different types of carcinoma ex pleomorphic adenoma (CXPA). Seventeen cases of CXPA, classified according to the presence of epithelial and myoepithelial cells and the degree of invasion-intracapsular, minimally, and frankly invasive carcinoma-were immunohistochemically labeled for tenascin and fibronectin. Normal salivary gland included in the specimens showed tenascin only around the excretory duct, and fibronectin slightly expressed all over the stroma of the gland. In reminiscent pleomorphic adenoma, tenascin and fibronectin were observed around tubular structures and in the stroma. Both tenascin and fibronectin were expressed in all the CXPA studied. In areas of in situ carcinoma of the intracapsular type, the expression of these extracellular matrix proteins was enhanced compared with areas of residual pleomorphic adenoma. In intracapsular and minimally invasive types of CXPA, some areas of the tumor border presented tenascin and no fibronectin, pattern that may represent the real invasive front. In frankly invasive CXPA type with only epithelial component, fibronectin was strongly observed in a fibrillar network pattern, and tenascin was only focal. In frankly invasive type with myoepithelial component, tenascin staining was very strong and diffuse. This study showed different patterns of expression of tenascin and fibronectin along the process of tumorigenesis and tumor progression in CXPA, a fact that might play a role in invasion properties of these tumors.

Stroma desmoplasia was studied by immunohistochemistry for alpha-smooth muscle actin (alpha-SMA) in 17 instances of carcinoma ex-pleomorphic adenoma (CXPA) classified according to the presence of epithelial and myoepithelial cells and the degree of invasion: intracapsular, minimally and frankly invasive carcinoma. In "resident" pleomorphic adenoma, no desmoplasia was detected. In invasive areas of the intracapsular type of CXPA with only an epithelial component, desmoplasia started to be revealed by the presence of myofibroblasts close to the capsule. In the minimally invasive type, myofibroblasts were seen in the septum between islands of malignant cells and in focal peripheral areas of the tumor interpreted as the actual front of invasion. In the frankly invasive type of CXPA showing large blocks of cells, intense desmoplasia was seen, also separating the tumor cells from the neighboring normal tissue. In tumors with cords and/or small nests of cells, desmoplasia was very slight. In the invasive type of CXPA with a myoepithelial component, alpha-SMA expression was seen in the septum between the islands of cells. The expression was less intense and not present in all areas of the stroma. In CXPA with epithelial and myoepithelial cells, myofibroblasts were rarely seen in the septum separating sheets of cells. Thus, we may deduce that the presence of desmoplasia parallels the capacity of invasion of CXPA by epithelial cells, being minimum in the intracapsular and minimally invasive type of CXPA and increasing as the tumor becomes frankly invasive. Furthermore, we may also conclude that in CXPA with a myoepithelial component, desmoplasia is very rare.

Background: This study compared clinical and radiographic findings for the treatment of Class II furcation defects in human mandibular molars using anorganic bovine-derived hydroxyapatite matrix (ABM)/cell-binding peptide (P-15) or open flap debridement (OFD)., Methods: Twelve subjects showing two comparable Class II furcation defects in their mandibular molars were enrolled. The defects in each subject were assigned randomly to the test (ABM/P-15) or the control (OFD) group. Clinical measurements and standardized radiographs were taken at baseline and 6 to 7 months after surgery., Results: There were no statistically significant differences between the test and control groups for any clinical or radiographic parameter (P >0.05). On comparing the baseline and final measurements, the gain in horizontal clinical attachment level and reduction in gingival recession were significant only in the test group (P < or =0.02), whereas the gain in the vertical clinical attachment level was significant in both groups (P < or =0.04). In the test group, four of 12 sites showed complete closure, and five showed partial closure; in the control group, three defects showed complete closure, and four showed partial closure (P = 0.42). Subtraction radiography revealed similar gains in bone height and increases in mean bone density with both treatments (P >0.05)., Conclusions: ABM/P-15 yielded favorable results in the treatment of Class II furcation defects over a 6-month evaluation period; however, there was no difference compared to OFD. Further studies using a larger sample size are needed to confirm the present findings.

Background: The present study evaluates the signal transducer and activator of transcription-3 (STAT-3) expression and activation in actinic cheilitis (AC) and the relationship of this protein with the degree of epithelial dysplasia., Methods: Twenty-five cases of AC were analyzed. Normal lip mucosa was used as a control group. AC lesions were graded as mild, moderate and severe dysplasias. Immunohistochemistry for STAT-3 and phospho-STAT-3 (STAT-3P) was performed using the biotin-streptavidin-peroxidase method, and the sections were evaluated by three blinded examiners., Results: In normal lip mucosa, only cytoplasmic expression of STAT-3 was observed in the basal and parabasal layers. In AC, STAT-3 was expressed in the cell cytoplasm of the epithelial layers, except in the superficial layer. Nuclear expression of STAT-3 in occasional basal and parabasal cells was seen in moderate and severe dysplasias. In normal lip mucosa, nuclear expression of STAT-3P was found throughout the epithelium, except in the superficial layers, and it was more intense in the deeper layers. In AC, STAT-3P was also expressed in all layers, except for the superficial layer. However, in moderate and severe dysplasias, some epithelial cells exhibited loss of STAT-3P expression., Conclusion: In AC, STAT-3 expression depends on the degree of dysplasia, and STAT-3 activation is dysregulated compared with normal tissue.

Objective: Matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs) play a role in the breakdown of the extracellular matrix during normal physiological processes, and in pathological processes, including periodontitis. The aim of this study was to evaluate the effect of epidermal growth factor (EGF) on the expression of MMPs and TIMPs in cultured human gingival fibroblasts., Methods: Fibroblasts were stimulated with 10(-3), 10(-6) or 10(-12)M EGF for 24h; untreated fibroblasts served as controls. Alterations in the expression of MMP-1, 2, 3, 7, 11, TIMP-1 and 2 were evaluated using real-time PCR and Western blotting. beta-Actin expression was used as a reference to normalize gene expression., Results: Increased MMP-1, 3, 7 and 11 expressions were observed at all EGF concentrations (p<0.05). At the lowest EGF concentration, MMP-1, 3 and 7 presented the lowest expression and MMP-11 presented the greatest expression; at higher EGF concentrations, MMP-1, 3 and 7 presented greater up-regulation, and MMP-11 lower up-regulation (p<0.05). Protein expression was similarly regulated by EGF: increased up-regulation of MMP-1, 3 and 7 was observed with increasing EGF concentrations, except for MMP-11 that exhibited greater up-regulation at the lower EGF concentration. The gene expression of MMP-2, TIMP-1 and 2 was not affected by EGF (p<0.05)., Conclusions: We conclude that EGF regulates expression for MMP-1, 3, 7 and 11 in a dose-dependent manner, suggesting that EGF may play a role in periodontal destruction and wound repair.

Purpose: The present study investigates the association between a specific polymorphism in the tumor necrosis factor (TNF)-alpha gene, consisting of allele 2 of TNF-alpha-308, and peri-implant bone loss following prosthetic reconstruction., Materials and Methods: This case-control study included 36 patients (20 women, 16 men; mean age 46 years) who had used implant-supported prostheses for a minimum of 6 months and a maximum of 31 months. The patients were nonsmoking, white Caucasian Brazilians, in good general health, and were not receiving medication. In the case group, patients exhibited 1 or more implants with a diagnosis of peri-implant bone loss following prosthetic reconstruction; control patients had 1 or more healthy implants., Results: Polymorphism in the TNF-alpha gene, allele 2 of TNF-alpha, was not associated with an increased risk for peri-implant bone loss following prosthetic reconstruction (P=0.19; chi2=1.71; df=1), although 21.1% of the subjects carried allele in the control group 2, and 41.2% carried allele 2 in the case group., Conclusions: Polymorphism in allele 2 of the TNF-alpha-308 gene is not associated with an increased risk for peri-implant bone loss following prosthetic reconstruction. However, further studies based on a greater number of patients are necessary.

The aim of this article is to describe a case of leiomyosarcoma of the mandible with immunohistochemical analysis that was useful in making the final diagnosis. A 40-year-old woman was referred to the Stomatology Clinic of Sao Paulo Tatuape Hospital, for evaluation of a lesion on the left side of the mandible. This lesion presented a fast growth in the last 6 months. Intraoral examination showed a firm, fixed, red colored mass measuring, approximately 60-mm in diameter. No lymph nodes involvement was found. The radiographic examination showed a lytic lesion showed ill-demarcated radiolucent with facial and lingual cortical bone destruction. Microscopic examination of the mandibular lesion showed a neoplasm composed by interlacing fascicles of spindle-shaped cells. Most of the cells presented a blut-ended elongated shape. A marked cellular pleomorphism was observed, represented by cells with irregular shape and abundant eosinophilic cytoplasm. Nuclei were large, hyperchromatic, either vacuoled or cigar-shape. The cytoplasm of the cells stained red with Masson s trichrome stain. Neoplastic cells expressed vimentin, smooth-muscle actin, HHF-35 and desmin. These findings were consistent with the diagnosis of leiomyosarcoma.

The myoepithelial cell (MC) is a component of various secretory glands, including salivary glands. Besides its function, a tumor suppressor and a tumor facilitating functions have been attributed to this cell. We investigated the immunoprofile of benign MC in intraductal areas of carcinoma ex-pleomorphic adenoma (CXPA), comparing them with the MC in duct-like areas of pleomorphic adenoma, origin of the malignant tumor. Antibodies against myoepithelial markers-CK14, alpha-SMA, calponin, P63, CD10, and D2-40-plus laminin and maspin was applied in four selected cases of intracapsular and minimal invasive CXPA with only luminal differentiation presenting areas of intraductal carcinoma. The immunohistochemical reactions of all the antibodies showed stronger staining in benign MC surrounding the malignant epithelial cells than in benign MC in duct-like areas of pleomorphic adenoma, thus revealing that in the malignization process the benign MC become differentiated and produce important proteins related to the tumor suppressor function.

This study evaluated the expression of E-cadherin and beta-catenin in salivary gland tumors. Twelve biopsy specimens from cases diagnosed as pleomorphic adenoma, 17 adenoid cystic carcinomas, 10 epithelial-myoepithelial carcinomas, and 4 polymorphous low-grade adenocarcinomas were immunohistochemically labeled for E-cadherin and beta-catenin antibodies. Healthy salivary glands were used as controls. Membrane-associated E-cadherin and beta-catenin expression was present in all the tumor types studied. E-cadherin and beta-catenin showed a similar distribution; however, beta-catenin labeling was weaker than that for E-cadherin. In the epithelial-myoepithelial carcinomas, myoepithelial cells exhibited diffuse nuclear staining, although occasional cells presented only focal labeling. Epithelial-myoepithelial carcinomas present changes in [.beta]-catenin expression but the other salivary tumors studied do not, which may reflect divergence in tumorigenesis of this extensive subset of salivary gland tumors.

With the evolution of IHC techniques, a broad range of antibodies have become available to diagnostic immunohistology. The authors observed different expressions of vimentin in salivary gland tumors using two clones of this antibody. This study was undertaken to show these differences comparing the immunoexpression of two clones of vimentin (V9 and Vim 3B4, DAKO, Carpenteria, CA) using 10 pleomorphic adenomas, 10 adenoid cystic carcinomas, and 4 epithelial/myoepithelial carcinomas of the salivary glands. The V9 clone of vimentin was much more efficient in demonstrating the myoepithelial cells in the different tumors studied. The Vim 3B4 clone was capable of detecting some myoepithelial cells, the plasmacytoid or modified myoepithelial cells in the pleomorphic adenoma, but was very weak in epithelial/-myoepithelial carcinomas. The difference between the two clones studied is a warning that pathologists need to know the specificity and sensitivity of the reagent they are using.

Background: Osteoma is a benign often asymptomatic neoplasm, consisting of well-differentiated mature bone. This paper reports a case of peripheral osteoma located in the anterior mandibular region and provides a review of the literature about this lesion in the jaws., Patient and Methods: A 43-year-old white woman presented with a swelling in the left mandible of 7 years duration. The English literature was reviewed over the past 76 years and data about location, histopathology and number of the peripheral osteomas, sex, and age of the patients were evaluated., Results: Data analysis showed 69 well-documented cases of peripheral osteoma. Peripheral osteomas are more frequent in the mandible than the maxilla and the cancellous type was most frequent; males and females are equally affected in the mandible; the age range was 9-85 years., Conclusion: The peripheral type of osteoma is most common in the lower jaws, occurs at the surface of the cortical bone and is sessile or pedicled.

Background: Root resorption and ankylosis have been reported rarely as sequelae to guided tissue regeneration (GTR). The authors describe a clinical case of root resorption following GTR that involved the use of a bioabsorbable membrane., Case Description: Two years after GTR was performed on a Class II furcation defect, the clinical examination revealed root resorption reaching the pulp chamber. The furcation defect was filled with epithelium and connective tissue, which contained inflammatory infiltrate and fragments of the membrane. The authors also observed areas of the tooth that exhibited points of ankylosis and root resorption., Clinical Implications: Clinical trials have reported favorable clinical and histologic results with GTR. However, this case report, along with other case reports and studies in animals, suggests a high risk of root resorption and ankylosis after GTR, which could limit the indications for this technique.

Immunoexpression of the extracellular matrix (ECM) proteins laminin, fibronectin, tenascin and types I, III and IV collagen was analyzed in the major and minor salivary glands of seven human fetuses at different gestational ages. The results showed the presence and localization of laminin, collagen IV and fibronectin around glandular structures at all stages of development. Tenascin was only detectable around excretory ducts. In the earliest stages of development, type I and type III collagen were presented as fine fibers delineating the glandular structures and delimiting the extension of the future lobule. As glandular development proceeded, the lobule was gradually filled with collagens and glandular tissue., (Copyright Eur J Oral Sci, 2004.)

Objective: Mucoepidermoid carcinoma (MEC) is the most common malignant salivary tumour, classified as low, intermediate and high grade. Myofibroblasts are the main stromal component and are included as prognostic factor in some tumours. The aim of this study was to evaluate the myofibroblasts in the stroma of MEC with possible relationship to malignancy grading., Methods: Twenty-five cases of MEC (six low grade, 11 intermediate grade, four high grade and four metastasis) were stained for vimentin, desmin and smooth muscle actin (SMA) for the identification of myofibroblasts. Transforming growth factors (TGFbeta1 and TGFbetaRII) were also assessed in our study., Results: Myofibroblasts were present in all cases, in amounts varying according to histological grading. TGFbeta1 was positive in squamous cells of intermediate grade tumours, and in the stroma of only four cases. TGFbetaRII was positive in most squamous and intermediate cells, regardless of malignancy grading., Conclusions: Our study showed that the analysis of neoplastic stroma must be added to the studies of neoplastic cells to draw a better picture leading to tumour diagnosis and prognosis.

The objective was to investigate two cases of solitary fibrous tumor (SFT) of oral mucosa, emphasizing the differential diagnosis with one case of oral hemangiopericytoma (HPC), in terms of their morphological and immunohistochemical features. Solitary fibrous tumors showed cellularity and collagenization varying from area to area, focal perivascular hyalinization, scattered giant nuclei cells and abundant mast cells throughout the tumor. The hemangiopericytoma case exhibited thin-walled and dilated vessels lined with flat endothelial cells, identified by "staghorn appearance". Tumoral cells of solitary fibrous tumor exhibited immunohistochemical positivity for CD34, as well as endothelial cells. The hemangiopericytoma was positive only in endothelial cells. In solitary fibrous tumor, alpha-smooth muscle actin, h-caldesmon and laminin stained the wall vessels. In hemangiopericytoma, on the other hand, the wall vessels were positive only for laminin, which staining was also observed in perivascular tumoral cells. The morphological and immunohistochemical differences observed allowed us to infer these lesions constitute distinct entities., (Copyright 2003 Elsevier Science Ltd.)

Three young, female dogs were operated for compound odontoma. All tumors were considered stage III with treatment consisting of partial mandibulectomy or maxillectomy. Microscopic examination of the resected tissue confirmed the diagnosis. Relatively aggressive, resective surgery resulted in prolonged tumor-free intervals.

A case of peripheral calcifying epithelial odontogenic tumor, clear cell variant, located on the right gingival maxilla of a 48-year-old woman, presenting as a 2.0-cm solitary, firm nodule was studied. Microscopically, it was composed of polyhedral and clear epithelial cells associated with amyloid-like deposition. The clear epithelial cells exhibited granules that were positive for periodic acid-Schiff, and the amyloid-like deposit stained with Congo red showed a green birefringence in the polarized light. Polyhedral and clear epithelial cells were immunopositive for AE1/AE3 and cytokeratin 14. Immunoexpression of fibronectin and types I and III collagen were different between the amyloid-like deposits and the connective tissue stroma. Tenascin surrounded epithelial cells located inside the amyloid-like deposits. Laminin and type IV collagen were immunodetectable around the strands, cords, and nests of epithelial cells. This report represents the seventh case of peripheral calcifying epithelial odontogenic tumor, clear cell variant.

A cross-sectional study was conducted to evaluate prenatal and childbirth care interviewing mothers of infants in the municipality of Embu (Greater Metropolitan São Paulo) in 1996, according to four socioeconomic strata. A door-to-door survey included a probabilistic sample consisting of 483 infants. In all strata more than 90% of the mothers had received prenatal care, but with late access in stratum 4 (residents of favelas, or slums). Breast examination during prenatal care, reported by only 60.8% of the mothers, was the worst single indicator of quality of prenatal care in the municipality. The outcome indicator - first prenatal consultation after the first trimester and total number of consultations less than six - was associated with maternal age (less than 20 years), low per capita family income (less than one minimum wage), and lack of private health plan. As for deliveries, 97.7% occurred in hospital, of which 32.5% by cesarean section, with the latter more frequent in private health care facilities (63.2%). No population segments were identified as being excluded from the health care system, but some indicators suggest greater deficiencies in socioeconomic stratum 4. These results have supported local health system managers in redefining health measures for the municipality.