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Jee K.J.,University of Turku | Jee K.J.,University of Helsinki | Persson M.,Gothenburg University | Heikinheimo K.,University of Turku | And 11 more authors.
Modern Pathology

Mucoepidermoid carcinoma is the most common salivary gland malignancy, and includes a spectrum of lesions ranging from non-aggressive low-grade tumors to aggressive high-grade tumors. To further characterize this heterogeneous group of tumors we have performed a comprehensive analysis of copy number alterations and CRTC1-MAML2 fusion status in a series of 28 mucoepidermoid carcinomas. The CRTC1-MAML2 fusion was detected by RT-PCR or fluorescence in situ hybridization in 18 of 28 mucoepidermoid carcinomas (64%). All 15 low-grade tumors were fusion-positive whereas only 3 of 13 high-grade tumors were fusion-positive. High-resolution array-based comparative genomic hybridization revealed that fusion-positive tumors had significantly fewer copy number alterations/tumor compared with fusion-negative tumors (1.5 vs 9.5; P=0.002). Twelve of 18 fusion-positive tumors had normal genomic profiles whereas only 1 out of 10 fusion-negative tumors lacked copy number alterations. The profiles of fusion-positive and fusion-negative tumors were very similar to those of low-and high-grade tumors. Thus, low-grade mucoepidermoid carcinomas had significantly fewer copy number alterations/tumor compared with high-grade mucoepidermoid carcinomas (0.7 vs 8.6; P<0.0001). The most frequent copy number alterations detected were losses of 18q12.2-qter (including the tumor suppressor genes DCC, SMAD4, and GALR1), 9p21.3 (including the tumor suppressor genes CDKN2A/B), 6q22.1-q23.1, and 8pter-p12.1, and gains of 8q24.3 (including the oncogene MAFA), 11q12.3-q13.2, 3q26.1-q28, 19p13.2-p13.11, and 8q11.1-q12.2 (including the oncogenes LYN, MOS, and PLAG1). On the basis of these results we propose that mucoepidermoid carcinoma may be subdivided in (i) low-grade, fusion-positive mucoepidermoid carcinomas with no or few genomic imbalances and favorable prognosis, (ii) high-grade, fusion-positive mucoepidermoid carcinomas with multiple genomic imbalances and unfavorable prognosis, and (iii) a heterogeneous group of high-grade, fusion-negative adenocarcinomas with multiple genomic imbalances and unfavorable outcome. Taken together, our studies indicate that molecular genetic analysis can be a useful adjunct to histologic scoring of mucoepidermoid carcinoma and may lead to development of new clinical guidelines for management of these patients. © 2013 USCAP, Inc. All rights reserved. Source

Bueno-Silva B.,University of Campinas | Alencar S.M.,University of Sao Paulo | Koo H.,University of Rochester | Ikegaki M.,Federal University of Alfenas | And 3 more authors.
Journal of Agricultural and Food Chemistry

The objective of this study was to evaluate anti-inflammatory and antimicrobial activities of neovestitol and vestitol isolated from Brazilian red propolis (BRP). BRP ethanolic extract (EEP), neovestitol, and vestitol were evaluated by anti-inflammatory properties using a neutrophil migration assay. The antimicrobial activity was evaluated by minimal inhibitory and bactericidal concentrations (MIC and MBC) against Streptococcus mutans, Streptococcus sobrinus, Staphylococcus aureus, and Actinomyces naeslundii. Neovestitol, vestitol, and EEP inhibited neutrophil migration at a dose of 10 mg/kg. Regarding antimicrobial activity, neovestitol showed MICs ranging from <6.25 to 25-50 μg/mL and MBCs ranging from 25-50 to 50-100 μg/mL, while vestitol showed MICs ranging from 25-50 to 50-100 μg/mL and MBCs ranging from 25-50 to 50-100 μg/mL. Both isoflavonoids neovestitol and vestitol are consistent bioactive compounds displaying anti-inflammatory and antimicrobial activities that can strongly act in a low dose and concentration and have a promising potential to be applied in the pharmaceutical and food industries. © 2013 American Chemical Society. Source

Egal E.S.A.,University of Campinas | Mariano F.V.,University of Campinas | Blotta M.H.,University of Campinas | Pina A.R.,University of Campinas | And 3 more authors.

Introduction: ICAM-1 expression on the villous syncytiotrophoblast (ST) is believed to participate in migration of maternal cells into the inflamed villi regardless of villitis etiology. However, its expression on immune cells in chronic villitis (CV) has yet to be analyzed. ICAM-1 induces cellecell adhesion allowing intercellular communication, T cell-mediated defense mechanism, and inflammatory response. Material and methods: 21 cases of CV (all without an identifiable etiologic agent) and 3 control placentas were analyzed using ICAM-1, and for immune cells CD45, CD3 and CD68. These cells were subdivided according to their location in inflamed villi: a) within the inflamed villi and b) outside forming perivillous aggregates. Results: Large amounts of CD45, CD3 and CD68 were found within the inflamed villi and forming perivillous aggregates attached to areas of trophoblastic loss. Inflamed villi usually showed ICAM-1+ ST. The majority of immune cells surrounding areas of trophoblastic rupture presented marked expression of ICAM-1. In contrast, a small number of immune cells within the inflamed villi exhibited ICAM-1 expression. Only some (<5%) inflamed villi without trophoblastic rupture and with ICAM-1+ ST presented adherence of immune cells. Discussion: In inflamed villi of chronic villitis, the level of ICAM-1 expression on immune cells depends on their location: high in number of cells in the perivillous region and low within the villi. The strongest expression of ICAM-1 on immune cells attached to areas of trophoblastic rupture suggests that the loss of trophoblast can lead to an amplification of the inflammatory response. Copyright © 2014 Elsevier Ltd. All rights reserved. Source

Barreto I.,University of Campinas | Costa A.F.,University of Campinas | Martins M.T.,University of Sao Paulo | Furuse C.,Sao Leopoldo Mandic Institute | And 2 more authors.
Virchows Archiv

Tonsillar polyps are nonneoplastic lesions usually composed of variable amounts of lymphoid and vascular and connective tissues. All of them are generally assumed to be hamartomatous proliferations, but the profile of vascular and connective components has yet to be explored. The vascular system of the tonsils is complex and includes highly specialized structures (i.e., high endothelial venules (HEVs)) involved in lymphocyte homing into lymphoid tissues. In 14 tonsillar polyps and 26 control tonsils, an immunohistochemical study was performed using CD34 (blood vessels and HEVs), MECA-79 (HEVs), D2-40 (lymphatic vessels), Ki-67, collagens I and III, fibronectin, and tenascin-C. The polyps showed increased total lymphatic area, whereas the number of blood vessels and lymphatics and the blood vascular area did not differ significantly from those of control tonsils. Rare Ki-67+ endothelial cells were found. In the polyps, we detected, possibly for the first time, HEVs amid lymphoid tissue, and that the amount of the latter correlated positively with HEV density. The polyps also presented lesser amounts of fibronectin and collagens I and III than in normal tonsils, which were distributed in a disorganized fashion. Tenascin-C expression was uncommon in the polyps and control tonsils. Tonsillar polyps are composed of disorganized connective tissue and lymphatic channels which can be considered hamartomatous proliferations. However, the lymphoid component is possibly reactive due to its relationship with the HEVs. The highly differentiated phenotype of the HEVs and their complex biology are not in agreement with what would be expected for a component of hamartomatous nature. © 2011 Springer-Verlag. Source

Lepri T.P.,University of Sao Paulo | Colucci V.,University of Sao Paulo | Turssi C.P.,Sao Leopoldo Mandic Institute | Corona S.A.M.,University of Sao Paulo
Lasers in Medical Science

This study evaluated the combined effect of fluoride compounds and CO 2 laser in controlling the permeability of eroded enamel. Bovine enamel slabs (3 × 2 mm) were cycled twice through an alternating erosion and remineralization regimen. Slabs were immersed in 20 ml of orange juice (pH 3.84) for 5 min under agitation, rinsed with deionized water, and stored in artificial saliva for 4 h to form erosive lesions. Specimens were then divided into four groups (n = 10), which were treated for 1 min with either a control or with one of the following gels: amine fluoride (AmF), titanium tetrafluoride (TiF4), or sodium fluoride (NaF). Half of the specimens were irradiated with a CO2 laser (λ = 10.6 μm; 2.0 W). Specimens were cycled two more times through the aforementioned erosion-remineralization regimen and were subjected to permeability assessment. ANOVA demonstrated a significant interaction between fluoride and laser treatment (p = 0.0152). Tukey's test showed that when fluoride was applied alone, TiF4 resulted in lower enamel permeability than that observed after application of the placebo gel. Intermediate permeability values were noted after NaF and AmF had been used. A significant reduction in enamel permeability was obtained when fluoride was combined with CO2 laser treatment, with no difference between fluoride gels. Permeability of eroded enamel may be reduced by combining the application of fluoride gels with CO2 laser irradiation. © 2012 Springer-Verlag London Ltd. Source

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