Exploiting PI 3 K /m TOR signaling to accelerate epithelial wound healing

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/99096/1/odi12070.pd

Identificação de subcentros de emprego: o caso do Município de São Paulo, Brasil

Theoretical models concerned with multiple centers have been brought to the debate on sprawling urban employment. However, empirical methods that identify these centers are not a specific focus of the specialized literature. The purpose of this paper is to apply a new empirical methodology in the identification and characterization of urban employment subcenters (Small Business Districts, SBD) using the case of the Municipality of São Paulo. To this end, we adopted a two-step approach, developing: 1) Exploratory Spatial Data Analysis and 2) Spatial Hedonic Price Model. As a result, we found seven regions that can be considered SBDs.Modelos teóricos preocupados com centros múltiplos foram trazidos para o debate sobre o espraiamento do emprego urbano. No entanto, os métodos empíricos que identificam esses centros não são um foco específico da literatura especializada. O objetivo deste artigo é aplicar uma nova metodologia empírica na identificação e caracterização de subcentros de emprego urbano (Pequenos Distritos Comercial, SBD) utilizando o caso do Município de São Paulo. Para tanto, adotamos uma abordagem em duas etapas, desenvolvendo: 1) Análise Exploratória de Dados Espaciais e 2) Modelo de Preço Hedônico Espacial. Como resultado, encontramos sete regiões que podem ser consideradas SBDs

Cyclin D 1‐induced proliferation is independent of beta‐catenin in H ead and N eck C ancer

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/106775/1/odi12124.pd

BMI-1 expression increases in oral leukoplakias and correlates with cell proliferation

Oral leukoplakia (OL) is a white lesion of an indeterminate risk not related to any excluded (other) known diseases or disorders that carry no increased risk for cancer. Many biological markers have been used in an attempt to predict malignant transformation; however, no reliable markers have been established so far. Objective: To evaluate cell proliferation and immortalization in OL, comparing non-dysplastic (Non-dys OL) and dysplastic OL (Dys OL). Methodology: This is a cross-sectional observational study. Paraffin-embedded tissue blocks of 28 specimens of Non-dys OL, 33 of Dys OL, 9 of normal oral mucosa (NOM), 17 of inflammatory hyperplasia (IH), and 19 of oral squamous cell carcinomas (OSCC) were stained for Ki-67 and BMI-1 using immunohistochemistry. Results: A gradual increase in BMI-1 and K-i67 expression was found in oral carcinogenesis. The immunolabeling for those markers was higher in OSCC when compared with the other groups (Kruskal-Wallis, p<0.05). Ki-67 expression percentage was higher in OL and in IH when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). Increased expression of BMI-1 was also observed in OL when compared with NOM (Kruskal-Wallis/Dunn, p<0.05). No differences were observed in expression of both markers when non-dysplastic and dysplastic leukoplakias were compared. A significant positive correlation between Ki-67 and BMI-1 was found (Spearman correlation coefficient, R=0.26, p=0.01). High-grade epithelial dysplasia was associated with malignant transformation (Chi-squared, p=0.03). Conclusions: These findings indicate that BMI-1 expression increases in early oral carcinogenesis and is possibly associated with the occurrence of dysplastic changes. Furthermore, our findings indicate that both Ki-67 and BMI-1 are directly correlated and play a role in initiation and progression of OSCC

Characterization of macrophage polarization in periodontal disease

AimTo explore the M1/M2 status of macrophage polarization from healthy, gingivitis, and periodontitis patient samples.Materials and methodsGingival biopsies were collected from 42 individuals (14 gingivitis, 18 periodontitis, and 10 healthy samples) receiving periodontal therapy. Histomorphology analysis was performed with haematoxylin and eosin staining. Immunofluorescence was performed using a combination of CD68 (macrophages), iNOS (M1), and CD206 (M2) in order to acquire changes in macrophage polarization at a singleâ cell resolution. Macrophages were quantified under microscopy using narrow wavelength filters to detect Alexa 488, Alexa 568, Alexa 633 fluorophores, and Hoechst 33342 to identify cellular DNA content.ResultsGingivitis and periodontitis samples showed higher levels of macrophages compared with healthy samples. Unexpectedly, periodontitis samples displayed lower levels of macrophages dispersed in the stromal tissues compared with gingivitis samples; however, it remained higher than healthy tissues. The polarization of macrophages appears to be reduced in periodontitis and showed similar levels to those observed in healthy tissues.ConclusionsOur study found that gingivitis and periodontitis differ from each other by the levels of macrophage infiltrate, but not by changes in macrophage polarization.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/150506/1/jcpe13156_am.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/150506/2/jcpe13156.pd

Entinostat is a novel therapeutic agent to treat oral squamous cell carcinoma

IntroductionAlterations of the epigenome may influence cancer initiation and progression. At the cellular level, histones are key regulators of chromatin accessibility and gene transcription; thus, the inhibition of histone deacetylase enzymes (HDACs) constitutes an attractive target for therapy. In this study, we investigated the effects of the HDAC inhibitor entinostat on oral squamous cell carcinoma (OSCC).Materials and MethodsWe tested the effects of entinostat on OSCC cell lines. Cell viability and growth were analyzed using MTT assay. Cell cycle analysis, cell apoptosis, cancer stem cell (CSC) content, and the concentration of reactive oxygen species (ROS) in OSCC tumor cells were assessed using flow cytometry. The expression of histones and cell cycle regulatory proteins was examined by Western blot.ResultsThe administration of entinostat resulted in reduced proliferation of OSCC cells, followed by cell cycle arrest at the G0/G1 phase, as well as substantial tumor apoptosis. We found an increase in ROS production and significant reductions in CSCs. We also found that entinostat caused increased acetylation histone H3 and histone H4, and changes in the expression of cell cycle‐associated proteins such as p21.ConclusionThis study indicates that entinostat is a potential novel therapeutic agent for OSCC by halting tumor proliferation, inducing cytotoxicity and intracellular ROS, and attacking the CSCs.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/162762/2/jop13039.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/162762/1/jop13039_am.pd

Overcoming adaptive resistance in mucoepidermoid carcinoma through inhibition of the IKK-β/IκBα/NFκB axis

Patients with mucoepidermoid carcinoma (MEC) experience low survival rates and high morbidity following treatment, yet the intrinsic resistance of MEC cells to ionizing radiation (IR) and the mechanisms underlying acquired resistance remain unexplored. Herein, we demonstrated that low doses of IR intrinsically activated NFκB in resistant MEC cell lines. Moreover, resistance was significantly enhanced in IR-sensitive cell lines when NFκB pathway was stimulated. Pharmacological inhibition of the IKK-β/IκBα/ NFκB axis, using a single dose of FDA-approved Emetine, led to a striking sensitization of MEC cells to IR and a reduction in cancer stem cells. We achieved a major step towards better understanding the basic mechanisms involved in IR-adaptive resistance in MEC cell lines and how to efficiently overcome this critical problem