OBJECTIVE In a phase III clinical trial (PLATelet inhibition and patient Outcomes, PLATO), ticagrelor provided better clinical outcomes than clopidogrel in patients with acute coronary syndromes. In addition to P2Y12-receptor antagonism, ticagrelor prevents cell uptake of adenosine and has proven able to augment adenosine effects. Adenosine protects the heart against ischemia-reperfusion injury...

A high-NaCl diet induces renal medullary cyclooxygenase (COX)2 expression, and selective intramedullary infusion of a COX2 inhibitor increases blood pressure in rats on a high-salt diet. The present study characterized the specific prostanoid contributing to the antihypertensive effect of COX2. C57BL/6J mice placed on a high-NaCl diet exhibited increased medullary COX2 and microsomal prostaglan...

Type-1 immune responses, mediated by IFNg and TNFaproducing CTLs, Th1, and NK cells, are essential for effective anti-tumor immunity. Despite recent advances in the induction and stabilization of these responses by cancer immunotherapies, the clinical success of these approaches remain limited. Here, we report that the activation of type-1 immunity within the human tumor microenvironment (TME) ...

Accumulating data demonstrate overexpression of both inducible NO synthase (NOS2) and cyclooxygenase-2 (COX2) in many epithelial neoplasias. In addition, cyclooxygenase inhibitors have been shown to have antineoplastic and prophylactic efficacy against human colon cancer and in mouse models of this disease. Mesothelioma arises in a context of asbestos exposure and chronic inflammation, which wo...

The nuclear factor of activated T cells (NFAT) family of transcription factors plays important roles in many biologic processes, including the development and function of the immune and vascular systems. Cells usually express more than one NFAT member, raising the question of whether NFATs play overlapping roles or if each member has selective functions. Using mRNA knock-down, we show that NFAT...

A number of tumor-specific characteristics are known to associate with a cancer’s growth, metastatic potential, and response to therapy. Among these are mutational load and gene-expression patterns in the tumor cells and the interaction of the tumor cells with the many cellular and noncellular components that comprise the microenvironment of the tumor. One molecule that has received considerabl...

We have investigated the hypothesis that nitric oxide synthase (NOS2), cyclooxygenase-2 (COX2), and vascular endothelial growth factor (VEGF) protein levels individually demonstrate a direct correlation with microvessel density (MVD) and clinical outcome in human non-small cell lung cancer (NSCLC). Furthermore, we hypothesized that MVD may explain the propensity of certain histological lung can...

OBJECTIVE The description of Barrett's esophagus which is a risk factor for esophageal adenocarcinoma has differences, and the need of goblet cells for diagnosis is controversial. However, the pathophysiology in the metaplasia seen in Barrett's esophagus is not totally understood and new methods are searched for the assessment of progression to dysplasia. We aimed to search the immunohistochemi...

An inherited deficiency of the mitochondrial protein frataxin causes Friedreich's ataxia (FRDA); the mechanism by which this deficiency triggers neuro- and cardio-degeneration is unclear. Microarrays of neural tissue of animal models of the disease showed decreases in antioxidant genes, and increases in inflammatory genes. Cyclooxygenase (COX)-derived oxylipins are important mediators of inflam...