Glycolytic pathway candidate markers in the prognosis of oral squamous cell carcinoma: a systematic review with meta-analysis.

Molecular changes that affect mitochondrial glycolysis have been associated with the maintenance of tumor cells. Some metabolic factors have already been described as predictors of disease severity and outcomes. This systematic review was conducted to answer the question: Is the glycolytic pathway correlated with the prognosis of oral squamous cell carcinoma (OSCC)? A search strategy was developed to retrieve studies in English from PubMed, Scopus, and ISI Web of Science using keywords related to squamous cell carcinoma, survival, and glycolytic pathway, with no restriction of publication date. The search retrieved 1273 publications. After the titles and abstracts were analyzed, 27 studies met inclusion criteria. Studies were divided into groups according to two subtopics, glycolytic pathways and diagnosis, which describe the glycolytic profile of OSCC tumors. Several components of tumor energy metabolism found in this review are important predictors of survival of patients with OSCC.

Glycolytic pathway candidate markers in the prognosis of oral squamous cell carcinoma: a systematic review with meta-analysis

Molecular changes that affect mitochondrial glycolysis have been associated with the maintenance of tumor cells. Some metabolic factors have already been described as predictors of disease severity and outcomes. This systematic review was conducted to answer the question: Is the glycolytic pathway correlated with the prognosis of oral squamous cell carcinoma (OSCC)? A search strategy was developed to retrieve studies in English from PubMed, Scopus, and ISI Web of Science using keywords related to squamous cell carcinoma, survival, and glycolytic pathway, with no restriction of publication date. The search retrieved 1273 publications. After the titles and abstracts were analyzed, 27 studies met inclusion criteria. Studies were divided into groups according to two subtopics, glycolytic pathways and diagnosis, which describe the glycolytic profile of OSCC tumors. Several components of tumor energy metabolism found in this review are important predictors of survival of patients with OSCC.

Development of an in vitro model to study tooth cystogenesis.

AIM: To describe an in vitro experimental model of cystic structure formation to conduct research on radicular cyst development. METHODOLOGY: To form spheroid structures, various numbers (1 × 104 , 5 × 104 or 1 × 105 ) of epithelial cells (HaCaT and Cal27) were seeded in 96-well plates previously coated with 1.5% low-melting agarose. After 24 h, the spheroids were collected, embedded in 3D collagen matrix and transferred to 24-well plates previously coated with polymerized collagen and kept for up to 21 days. Images of spheroids were captured at each time-point (1, 5, 9, 15 and 21 days), and samples underwent histological and confocal microscopy analyses. Spheroid area, perimeter and cell dispersion were measured. One-way Anova was used for statistical analysis. RESULTS: Both epithelial cell lines were able to generate regular and circular spheroids after 24 h of incubation regardless of cell density. Spheroid structures in the collagen matrix were uniform in most samples until day 15, when several spots that appeared to be new cultures were seen. Spheroids from HaCaT were significantly more stable than those from Cal27 (P < 0.05). Starting on the third day, the examination of histological sections revealed a cavity with epithelial lining morphology, similar to a pathological radicular cyst. CONCLUSIONS: This study describes an experimental model of cystogenesis in vitro that may be used to test theories and investigates the effects of different growth factors during cyst development and maintenance.

Non-muscle myosin II as a predictive factor in head and neck squamous cell carcinoma.

BACKGROUND: The present study attempted to provide information regarding non-muscle myosin II (MII) isoforms immunoreactivity in patients with head and neck squamous cell carcinoma (HNSCC) and analysis of the patients' clinical status after 5 years of monitoring. MATERIAL AND METHODS: A semiquantitative analysis of the immunoreactivity of the MII isoforms was performed in 54 surgical specimens and its correlation with clinical and pathological variables and prognosis was verified. Data were analyzed using chi-square, Mann-Whitney and Kruskal-Wallis tests. To evaluate the survival over the total monitoring time and any connection with the proteins studied, the Kaplan-Meier analysis was used. P values ≤0.05 were considered statistically significant. RESULTS: In the advanced stages of pathological tumor-node-metastasis, the expression of MIIB in adjacent non-neoplastic epithelial tissues tended to increase (p = 0.057). In tumoral zones there was an association of high expression among the three isoforms (MIIA/MIIB p=0,001, MIIB/MIIC p=0,006 and MIIA/MIIC p=0,012). Negative clinical evolution in patients was directly correlated to increased MIIC expression in the tumoral zone of invasion in HNSCC (p = 0.017). Based on clinical evolution after the monitoring period, patients with tumors expressing MIIC had poorer prognoses (p = 0.048). CONCLUSIONS: The present study suggests that MIIB expression in non-neoplastic adjacent epithelial tissues may indicate a potential for regional metastasis and that MIIC expression in the tumoral zone of invasion is predictive of negative evolution of the disease.

Lonomia obliqua bristle extract modulates Rac1 activation, membrane dynamics and cell adhesion properties.

Lonomia obliqua is a caterpillar of potential therapeutic interest whose venom is able to induce severe blood leakage and modulate leukocyte migration. Since both phenotypes are associated with changes in cytoskeleton dynamics and cell adhesion properties, the aim of this study was to analyze the effects of Lonomia obliqua bristle extract (LOBE) in cell adhesion and migration signaling. Proteomic analysis revealed that epithelial cells (CHO-K1) exposed to LOBE (30 µg/mL, 30 min) exhibited changes in levels of actin regulatory proteins, including RhoGTPases. These changes correlated with an increase in the activity of the RhoGTPase family member Rac as measured by Förster resonance energy transfer (FRET). When plated in migration promoting conditions, CHO-K1 cells exposed to LOBE (10 µg/mL) showed an increase in membrane ruffling after short (30 min) period of incubation that was accompanied by changes in the distribution of the adhesion markers paxillin, vinculin and an increase of focal adhesion kinase autophosphorylation levels (Y397), suggesting changes in cell-extracellular matrix (ECM) adhesion properties and signaling. These data suggest that LOBE possesses bioactive molecules that are capable to modulated cell migration signaling, cytoskeletal dynamics and cell-ECM properties of several cell types.

Na+-glucose cotransporter SGLT1 protein in salivary glands: potential involvement in the diabetes-induced decrease in salivary flow.

Oral health complications in diabetes include decreased salivary secretion. The SLC5A1 gene encodes the Na(+)-glucose cotransporter SGLT1 protein, which not only transports glucose, but also acts as a water channel. Since SLC5A1 expression is altered in kidneys of diabetic subjects, we hypothesize that it could also be altered in salivary glands, contributing to diabetic dysfunction. The present study shows a diabetes-induced decrease (p < 0.001) in salivary secretion, which was accompanied by enhanced (p < 0.05) SGLT1 mRNA expression in parotid (50%) and submandibular (30%) glands. Immunohistochemical analysis of parotid gland of diabetic rats revealed that SGLT1 protein expression increased in the luminal membrane of ductal cells, which can stimulate water reabsorption from primary saliva. Furthermore, SGLT1 protein was reduced in myoepithelial cells of the parotid from diabetic animals, and that, by reducing cellular contractile activity, might also be related to reduced salivary flux. Six-day insulin-treated diabetic rats reversed all alterations. In conclusion, diabetes increases SLC5A1 gene expression in salivary glands, increasing the SGLT1 protein content in the luminal membrane of ductal cells, which, by increasing water reabsorption, might explain the diabetes-induced decrease in salivary secretion.

Chronic hyperglycaemia increases TGFbeta2 signaling and the expression of extracellular matrix proteins in the rat parotid gland.

The majority of the oral manifestations of diabetes mellitus are secondary to a reduced salivary flow, whose causes are still poorly understood. In the kidney, diabetes complications involve increased Transforming Growth Factor beta (TGFbeta) production and the thickening of basement membrane in small vessels. By using immunohistochemistry and western blotting, we studied the expression and signaling of TGFbeta and the distribution of extracellular matrix (ECM) proteins: laminin, fibronectin, collagens III, IV and V in the parotid gland of control and diabetic rats, 30 and 60 days after streptozotocin injection (D30 and D60). At D30, there was an important increase of laminin whereas fibronectin and collagen V were moderately augmented. At D60, an additional increase of all ECM proteins was observed. TGFbeta1 expression was not affected at any time. In contrast, TGFbeta2 levels were significantly higher at D30, concomitant with increased TGFbeta receptor II (TbetaRII), phosphorylated Smads 2 and 3 (pSmads 2-3) and Latent TGFbeta Binding Protein 1 (LTBP1). At D60, TGFbeta2 and TbetaRII were still increased, whereas phosphorylation of Smads was markedly decreased, and LTBP1 returned to control levels. In the control groups, TGFbeta2 labeling was localized preferentially in ductal cells, whereas at D30 and D60 the staining was also observed in acinar cells. The same pattern of distribution was observed for pSmads 2-3 at D30, especially in nuclei. At D60, labeling was weak and dispersed throughout the cytoplasm. These data suggest that hyperglycaemia increases the deposition of ECM proteins in the rat parotid gland, possibly through augmentation of TGFbeta2 expression and signaling.