The Autotaxin-Lysophosphatidic Acid Axis Promotes Lung Carcinogenesis.

Pathogenesis and progression of lung cancer are governed by complex interactions between the environment and host genetic susceptibility, which is further modulated by genetic and epigenetic changes. Autotaxin (ATX, ENPP2) is a secreted glycoprotein that catalyzes the extracellular production of lysophosphatidic acid (LPA), a growth-factor-like phospholipid that is further regulated by phospholipid phosphatases (PLPP). LPA's pleiotropic effects in almost all cell types are mediated through at least six G-protein coupled LPA receptors (LPAR) that exhibit overlapping specificities, widespread distribution, and differential expression profiles. Here we use both preclinical models of lung cancer and clinical samples (from patients and healthy controls) to investigate the expression levels, activity, and biological role of the above components of the ATX/LPA axis in lung cancer. ENPP2 was genetically altered in 8% of patients with lung cancer, whereas increased ATX staining and activity were detected in patient biopsies and sera, respectively. Moreover, PLPP3 expression was consistently downregulated in patients with lung cancer. Comparable observations were made in the two most widely used animal models of lung cancer, the carcinogen urethane-induced and the genetically engineered K-rasG12D -driven models, where genetic deletion of Enpp2 or Lpar1 resulted in disease attenuation, thus confirming a procarcinogenic role of LPA signaling in the lung. Expression profiling data analysis suggested that metabolic rewiring may be implicated in the procarcinogenic effects of the ATX/LPA axis in K-ras- G12D -driven lung cancer pathogenesis.Significance: These findings establish the role of ATX/LPA in lung carcinogenesis, thus expanding the mechanistic links between pulmonary fibrosis and cancer. Cancer Res; 78(13); 3634-44. ©2018 AACR.

Attitudes and behaviours of Greeks concerning blood donation: recruitment and retention campaigns should be focused on need rather than altruism.

BACKGROUND: Blood supplies in Greece are insufficient to meet the high transfusion needs arising from car accidents and treatment of thalassaemia. This study was designed to determine Greeks' opinions about blood donation, in order to identify the reasons for the lack of motivation to donate and allow experts to establish better recruitment campaigns for the enrichment of the donor pool, based on our findings. MATERIALS AND METHODS: The opinions of randomly selected Greek citizens (n=800) about volunteer blood donation were assessed by means of a standardised, anonymous questionnaire. The results were analysed using the χ(2) test and Spearman's correlation coefficient. RESULTS: With regards to attitudes towards intention to donate, only 7.1% were indifferent, while 88.0% of the individuals believed that donating blood was an "offer". Reasons for not donating mainly involved safety (36.0%) and fear (24.0%), whereas need (77.9%) was the most fundamental positive motivation. Of the people enrolled in the present study, 10.0% were active donors, 31.3% occasional donors, 15.0% rare donors and 36.6% non-donors. DISCUSSION: The considerable percentages of occasional and rare donors in comparison with the low proportion of active donors in the Greek donor pool indicates that "need" is a more important motivation for blood donation than altruism in Greece. These results could be useful for establishing advertising campaigns on blood donation and for a more direct approach to the population, aiming for a change in mentality in favour of active blood donation.

Milestones in the history of research on cardiac energy metabolism.

The present study summarizes the history of research on cardiac metabolism from antiquity till the 21st century. It describes important landmarks regarding the discovery of oxygen and of the 3 steps of cellular respiration, as well as major research on cardiac energy metabolism. For this purpose, we conducted a thorough search of original manuscripts, books, and contemporary reviews published in PubMed. The first views and concepts about the heart's function appear in Greek philosophic manuscripts of 2500 years ago. According to Aristotle, the heart is responsible for heat production, which is essential for life. The understanding of cardiac metabolism awaited new discoveries. The discovery of oxygen during the 18th century, along with the idea of energy conservation, or what is now known as one of the first versions of the first law of thermodynamics, played an important role in initiating the study of energy metabolism in general and heart metabolism later. The discovery of glycolysis, of the Krebs cycle, and of adenosine triphosphate offered a better understanding of cellular respiration, necessary for later research. Indeed, many researchers dedicated their studies to energy metabolism, but Richard John Bing, the renowned German research cardiologist, is the one who guided the exploration of cardiac metabolism, and he is therefore considered to be the father of cardiac energy metabolism. Since then, encouraging new research has been taking place, offering important clinical applications for heart patients.