Advances, limitations and perspectives in the use of celecoxib-loaded nanocarriers in therapeutics of cancer.

Cancer is highlighted as a major global health challenge in the XXI century. The cyclooxygenase-2 (COX-2) enzyme rises as a widespread tumor progression marker. Celecoxib (CXB) is a selective COX-2 inhibitor used in adjuvant cancer therapy, but high concentrations are required in humans. In this sense, the development of nanocarriers has been proposed once they can improve the biopharmaceutical, pharmacokinetic and pharmacological properties of drugs. In this context, this article reviews the progress in the development of CXB-loaded nanocarriers over the past decade and their prospects. Recent advances in the field of CXB-loaded nanocarriers demonstrate the use of complex formulations and the increasing importance of in vivo studies. The types of CXB-loaded nanocarriers that have been developed are heterogeneous and based on polymers and lipids together or separately. It was found that the work on CXB-loaded nanocarriers is carried out using established techniques and raw materials, such as poly (lactic-co-glicolic acid), cholesterol, phospholipids and poly(ethyleneglycol). The main improvements that have been achieved are the use of cell surface ligands, the simultaneous delivery of different synergistic agents, and the presence of materials that can provide imaging properties and other advanced features. The combination of CXB with other anti-inflammatory drugs and/or apoptosis inducers appears to hold effective pharmacological promise. The greatest advance to date from a clinical perspective is the ability of CXB to enhance the cytotoxic effects of established chemotherapeutic agents.

The hybrid protein BTH2 suppresses allergic airway inflammation in a murine model of HDM-specific immunotherapy.

BACKGROUND: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment approach to change disease-causing allergens. Hypoallergenic derivatives show promise as potential therapeutics, amongst which BTH2 was designed to induce tolerance against Blomia tropicalis allergy. Our aim was to investigate the hypoallergenicity and immunoregulatory activity of BTH2 in vitro and its therapeutic potential in a mouse model of AIT. METHODS: Recombinant Blo t 5 and Blo t 21 allergens and their hybrid derivatives (BTH1 and BTH2) were expressed and purified. IgE binding capacity was tested by ELISA using sera from Brazilian, Colombian, and Ecuadorian subjects. Secretion of cytokines in supernatants from human cell cultures was measured following stimulation with the four recombinants and controls. The capacity of BTH2 to ameliorate allergic airway inflammation induced by B. tropicalis extract was evaluated in a murine model of AIT. RESULTS: rBlo t 5 and rBlo t 21 were identified as major allergens in Latin American patients, and BTH2 had the lowest IgE binding. In vitro stimulation of human cells induced greater levels of IL-10 and IFN-γ and reduced the secretion of Th2 cytokines. BTH2 ameliorated allergic airway inflammation in B. tropicalis-challenged A/J mice, as evidenced by the histopathological and humoral biomarkers: decreased Th2 cytokines and cellular infiltration (especially eosinophils), lower activity of eosinophil peroxidase, an increase in IgG blocking antibodies and strong reduction of mucus production by goblet cells. CONCLUSIONS: Our study shows that BTH2 represents a promising candidate for the treatment of B. tropicalis allergy with hypoallergenic, immune regulatory and therapeutic properties. Further pre-clinical studies are required in murine models of chronic asthma to further address the efficacy and safety of BTH2 as a vaccine against B. tropicalis-induced allergy.

MicroRNAs expression pattern related to mast cell activation and angiogenesis in paraffin-embedded salivary gland tumors.

The aim of this study was evaluate the expression profile of microRNAs related to mast cells activation and angiogenesis in salivary glands tumors. METHOD: We have analyzed the expression of miR-9, miR-16, miR-17, miR-132, miR-195 and miR-221 by real-time RT-PCR, in 11 adenoid cystic carcinomas, 9 mucoepidermoid carcinomas and 11 pleomorphic adenomas. Immunohistochemical investigation was performed to detect mast cells tryptase and CD-34 for microvessels biomarkers. miR-16, miR-17, miR-132, miR-195 and miR-221 showed a decreased expression, whereas miR-9 showed an increased expression in most cases compared to normal tissues. However, in all tumors studied only miR-9 showed a statistical significant negative correlation with microvessel density (p=0.001). It was observed a higher density of mast cells in mucoepidermoid carcinomas (10.55 cells/mm2) when compared to adenoid cystic carcinomas (6.27 cells/mm2) and between mucoepidermoid carcinomas and pleomorphic adenomas (5.97células/mm2). miR-17, miR-132, miR-195 and miR-221 seem to play an important role as tumor suppressor in salivary gland tumors. In addition, the significant correlation between mast cell and microvessel density contributes to the growth and pathogenesis of these tumors and they may become strong therapeutic targets in the future.

Density of mast cells and microvessels in minor salivary gland tumors.

The aim of this study was to investigate the density of mast cells and microvessels in minor salivary gland tumors. Forty-one cases of minor salivary gland tumors (pleomorphic adenoma, n = 10; adenoid cystic carcinoma, n = 11; mucoepidermoid carcinoma, n = 10; and polymorphous low-grade adenocarcinoma) were investigated using immunohistochemistry for mast cell tryptase and von-Willebrand factor. Density of mast cells was higher in mucoepidermoid carcinoma; however, no differences in the number of these cells were observed between the different types of tumors (p > 0.05). The number of mast cells was higher in periparenchymal areas in all tumors, but the difference was not significant (p > 0.05). Mucoepidermoid carcinoma showed the largest number of periparenchymal mast cells, whereas pleomorphic adenomas showed the smallest number of intraparenchymal mast cells (p > 0.05). The highest microvessel density was observed in mucoepidermoid carcinomas, being this difference statistically significant when mucoepidermoid carcinoma was compared to pleomorphic adenoma (p = 0.0034) and polymorphous low-grade adenocarcinoma (p = 0.004). Microvessel density was significantly higher in adenoid cystic carcinoma when compared to pleomorphic adenoma (p = 0.0406) and polymorphous low-grade adenocarcinoma (p = 0.0123). Comparison of mast cells and microvessel densities showed no significant difference between tumors. A quantitative difference in mast cells and microvessels was observed, particularly in mucoepidermoid carcinoma, a finding supporting the aggressive behavior of malignant salivary gland tumors without myoepithelial differentiation. Further studies are needed to determine the role of mast cells in angiogenesis, as well as in the development and biological behavior of these tumors.

Histopathological study of radicular cysts diagnosed in a Brazilian population.

The aim of this study was to investigate the histopathological features of radicular cysts (RCs) diagnosed in a Brazilian population. Seventy-three cases of RCs, from a total of 1480 biopsies diagnosed between 2001 and 2008 at the Laboratory of Oral Surgical Pathology of the Dental School of the Federal University of Bahia were investigated regarding their histopathological features. Morphological results showed that exocytosis (n = 50), spongiosis (n = 40), acanthosis (n = 28), atrophic epithelium (n = 27) and apoptotic bodies (n = 21) were the most common findings. Other morphological findings included: foamy macrophages (n = 10), Russell's bodies (n = 7), cholesterol crystals (n = 7) and glandular-like odontogenic epithelial rests (n = 1). Evidence of exogenous material was seen in 16 samples. It was concluded that the clinical and histopathological findings observed in Brazilian patients were comparable with those described for other populations.

Histopathological study of radicular cysts diagnosed in a Brazilian population

The aim of this study was to investigate the histopathological features of radicular cysts (RCs) diagnosed in a Brazilian population. Seventy-three cases of RCs, from a total of 1480 biopsies diagnosed between 2001 and 2008 at the Laboratory of Oral Surgical Pathology of the Dental School of the Federal University of Bahia were investigated regarding their histopathological features. Morphological results showed that exocytosis (n=50), spongiosis (n=40), acanthosis (n=28), atrophic epithelium (n=27) and apoptotic bodies (n=21) were the most common findings. Other morphological findings included: foamy macrophages (n=10), Russell’s bodies (n=7), cholesterol crystals (n=7) and glandular-like odontogenic epithelial rests (n=1). Evidence of exogenous material was seen in 16 samples. It was concluded that the clinical and histopathological findings observed in Brazilian patients were comparable with those described for other populations.

O propósito desse estudo foi investigar os aspectos histopatológicos de cistos radiculares diagnosticados em uma população brasileira. Setenta e três casos de cistos radiculares entre 1480 biópsias diagnosticadas na Faculdade de Odontologia da Universidade Federal da Bahia, entre 2001 e 2008, foram investigados, considerando os seus aspectos histopatológicos. Os resultados morfológicos mostraram que os achados mais comuns foram a exocitose (n=50), espongiose (n=40), acantose (n=28), epitélio atrófico (n=27) e células apoptóticas (n=21). Outros achados encontrados incluíram macrófagos espumosos (n=10), corpúsculos de Russell (n=7), imagens negativas de colesterol (n=7) e restos epiteliais odontogênicos semelhantes à tecido glandular (n=1). Material exógeno foi observado em 16 casos. Concluiu-se que os aspectos histopatológicos e clínicos observados foram comparáveis a outros descritos em outras populações.

[Genotoxic effect of ethanol on oral mucosa cells]. / Efeito genotóxico do etanol em células da mucosa bucal.

Ethanol is one of the chemicals related to the development of oral malignant neoplasms. Micronuclei are chromatin fragments which, after aberrant mitoses, do not become included in the main nucleus. They have been used as indicators of genotoxic damage in cells exposed to carcinogens. The aim of this study was to assess the frequency of micronuclei in exfoliated cells from the tongue and buccal mucosa of alcoholic individuals. Samples were taken from the tongue and buccal mucosa of 40 alcoholic individuals who did not smoke, and from 20 alcohol and tobacco abstainers. Cells were stained with the Feulgen reaction and counterstained with Fast Green. A significant increase in the frequency of micronuclei in tongue cells was found in the group of subjects exposed to alcohol, when compared to the control group (p < 0.01). The frequency of micronuclei in buccal mucosa cells was higher in the group of alcoholic individuals, when compared to the control group, although there was no significant difference (p > 0.05). Our results indicate that excessive alcohol consumption may induce effective alterations on oral mucosa cells, even without exposure to tobacco. These alterations are more expressive in the tongue, which is a site more exposed to the action of carcinogens, when compared to the buccal mucosa.

Efeito genotóxico do etanol em células da mucosa bucal / Genotoxic effect of ethanol on oral mucosa cells

O etanol é um dos agentes químicos relacionados ao desenvolvimento de neoplasias malignas bucais. Os micronúcleos säo porçöes de cromatina que permanecem próximas ao núcleo, resultantes de mitoses aberrantes após a açäo de agentes genotóxicos. Dessa forma, sua ocorrência reflete o grau de exposiçäo celular a carcinógenos. O objetivo deste trabalho foi avaliar a freqüência de micronúcleos em células esfoliadas da língua e da mucosa jugal de indivíduos dependentes químicos de etanol. A amostra constou de células esfoliadas da língua e da mucosa jugal de 40 indivíduos alcoólatras näo fumantes e de 20 abstêmios de álcool e fumo. As células obtidas foram coradas pelo método de Feulgen e contra-coradas pelo Fast Green. Observou-se um aumento estatisticamente significativo da freqüência de micronúcleos em células esfoliadas da língua no grupo de indivíduos expostos ao etanol em relaçäo ao grupo controle (p<0,01). A freqüência de micronúcleos em células esfoliadas da mucosa jugal apresentou-se maior no grupo de indivíduos alcoólatras quando comparado ao grupo controle, porém näo houve diferença estatisticamente significante (p>0,05). Conclui-se, portanto, que o consumo excessivo de etanol promove alteraçöes efetivas em células da mucosa bucal, mesmo na ausência de exposiçäo ao fumo. Tais alteraçöes apresentam-se mais expressivas no bordo lateral de língua, um sítio mais exposto à açäo de carcinógenos quando comparado à mucosa jugal

Estudo macroscópico da sutura palatina mediana / Midpalatal suture: a macroscopy study

A sutura palatina mediana é importante no desenvolvimento da face, pela sua localização e pelo ossos com os quais se articula, sendo também relevante na correção de determinadas maloclusões. O sucesso de certos procedimentos ortodônticos está intimamente relacionado com o processo de maturação da sutura palatina mediana. Esse processo, por sua vez, tem relação direta com a idade dos indivíduos. Os autores avaliaram num estudo miscrocópico seccional, a sutura palatina mediana de crânios humanos secos em diferentes faixas etárias. Foram selecionados crânios com as seguintes idades cronológicas: 1 ano, 3 anos, 4 anos, 5 anos, 6 anos, 10 anos, 20 anos, 62 anos, 76 anos e 86 anos. Esses crânios foram lavados em solução de hipoclorito de sódio e, para uma melhor avaliação, fotografados numa vista inferior. Observou-se que o processo de maturação da sutura palatina mediana apresenta grau de aproximação relacionado de forma especifica com a idade cronológica, mostrando-se mais ampla na criança e altamente fusionada no idoso