E-Cadherin gene expression in oral cancer: Clinical and prospective data.

BACKGROUND: Low protein expression of E-cadherin in oral squamous cell carcinoma (OSCC) has been associated with clinical and histopathological traits such as metastases, recurrence, low survival and poor tumor differentiation, and it is considered a high-risk marker of malignancy. However, it is still unknown whether low expression of E-cadherin is also present at the mRNA level in OSCC cases. OBJECTIVE: The aim of this study was to compare E-cadherin mRNA expression in OSCC patients and controls and to correlate the expression with clinical and prospective characteristics. MATERIAL AND METHODS: Forty patients and 40 controls were enrolled. E-cadherin mRNA expression was evaluated by quantitative real-time polymerase chain reaction using TaqMan probes. RESULTS: E-cadherin mRNA expression was significantly decreased in OSCC patients compared to that of controls (p<0.001). Whereas no significant association between clinical parameters and E-cadherin expression levels was observed, we noted lower E-cadherin expression levels in patients with positive lymph node metastasis. CONCLUSIONS: E-cadherin mRNA expression was markedly diminished in OSCC, in agreement with previous results that examined E-cadherin expression at the protein level. E-cadherin is downregulated in the early clinical stages of OSCC, and its mRNA levels do not change significantly in the advanced stages, suggesting that there is limited usefulness of this parameter for predicting disease progression.

Current model systems for the study of preeclampsia.

Preeclampsia (PE) is a pregnancy complex disease, distinguished by high blood pressure and proteinuria, diagnosed after the 20th gestation week. Depending on the values of blood pressure, urine protein concentrations, symptomatology, and onset of disease there is a wide range of phenotypes, from mild forms developing predominantly at the end of pregnancy to severe forms developing in the early stage of pregnancy. In the worst cases severe forms of PE could lead to systemic endothelial dysfunction, eclampsia, and maternal and/or fetal death. Worldwide the fetal morbidity and mortality related to PE is calculated to be around 8% of the total pregnancies. PE still being an enigma regarding its etiology and pathophysiology, in general a deficient trophoblast invasion during placentation at first stage of pregnancy, in combination with maternal conditions are accepted as a cause of endothelial dysfunction, inflammatory alterations and appearance of symptoms. Depending on the PE multifactorial origin, several in vitro, in vivo, and in silico models have been used to evaluate the PE pathophysiology as well as to identify or test biomarkers predicting, diagnosing or prognosing the syndrome. This review focuses on the most common models used for the study of PE, including those related to placental development, abnormal trophoblast invasion, uteroplacental ischemia, angiogenesis, oxygen deregulation, and immune response to maternal-fetal interactions. The advances in mathematical and computational modeling of metabolic network behavior, gene prioritization, the protein-protein interaction network, the genetics of PE, and the PE prediction/classification are discussed. Finally, the potential of these models to enable understanding of PE pathogenesis and to evaluate new preventative and therapeutic approaches in the management of PE are also highlighted. Impact statement This review is important to the field of preeclampsia (PE), because it provides a description of the principal in vitro, in vivo, and in silico models developed for the study of its principal aspects, and to test emerging therapies or biomarkers predicting the syndrome before their evaluation in clinical trials. Despite the current advance, the field still lacking of new methods and original modeling approaches that leads to new knowledge about pathophysiology. The part of in silico models described in this review has not been considered in the previous reports.

Anti-Inflammatory Effects of Modified Adenoviral Vectors for Gene Therapy: A View through Animal Models Tested.

The central dogma of gene therapy relies on the application of novel therapeutic genes to treat or prevent diseases. The main types of vectors used for gene transfer are adenovirus, retrovirus, lentivirus, liposome, and adeno-associated virus vectors. Gene therapy has emerged as a promising alternative for the treatment of inflammatory diseases. The main targets are cytokines, co-stimulatory molecules, and different types of cells from hematological and mesenchymal sources. In this review, we focus on molecules with anti-inflammatory effects used for in vivo gene therapy mediated by adenoviral gene transfer in the treatment of immune-mediated inflammatory diseases, with particular emphasis on autoinflammatory and autoimmune diseases.

Expression levels of seven candidate genes in human peripheral blood mononuclear cells and their association with preeclampsia.

OBJECTIVE: To evaluate the peripheral blood mononuclear cell (PBMC) expression levels of hemeoxygenase 1 (HMOX-1), superoxide dismutase 1 (SOD-1), vascular endothelial growth factor A (VEGF-A), transforming growth factor beta 1 (TGF-ß1), interleukin (IL)-6, IL-15 and AdipoQ genes to study their association with preeclampsia (PE). METHODS: A total of 177 pregnant women were recruited: 108 cases and 69 controls. Quantification of gene expression was measured by quantitative real-time polymerase chain reaction (PCR) using TaqMan probes. RESULTS: Underexpression of VEGF-A and TGF-ß1 was a constant in most of the cases (80.91% and 76.36%, respectively) and their expression was associated with onset and/or severity of disease (p values < 0.05). IL-6, IL-15 and AdipoQ, showed low or no expression in PBMC samples evaluated. CONCLUSION: PBMC underexpression of VEGF-A and TGF-ß1 is a hallmark of PE in the study population.

Positive association between vascular endothelial growth factor (VEGF) -2578 C/A variant and prostate cancer.

BACKGROUND: Vascular endothelial growth factor (VEGF) gene is an important angiogenesis regulator related to cancer development and progression. We evaluated the association between -2578 C/A (rs699947) VEGF polymorphism and PCa in Mexican subjects, to contribute to knowledge of VEGF role in genetic epidemiology of prostate cancer (PCa). OBJECTIVE: The aim of this study was to evaluate the association between -2578 C/A VEGF variant and PCa in Mexican population. METHODS: A total of 249 men (77 PCa cases and 172 controls) from the Northwestern region of Mexico were screened for the -2578 C/A VEGF variant. The polymorphism was determined by polymerase chain reaction-based restriction analysis. RESULTS: Genotype frequencies for C/C, C/A, and A/A, were 0.48, 0.49, 0.03 for cases and 0.41, 0.45, 0.14 for controls respectively. Genotype A/A of -2578 VEGF variant reduces the risk of PCa in an 84% among studied population (Odds Ratio 0.16; 95% CI: 0.04-0.71, P=0.007). C/C carriers showed an increased PCa risk of 6.1 times among the study population. CONCLUSIONS: Inheritance of -2578 A/A genotype of VEGF gene may modify PCa susceptibility risk in Mexican population.