Overexpression of prostacyclin synthase (PGIS) decreases lung tumor multiplicity in chemical-and cigarette-smoke-induced murine lung cancer models. Prostacyclin signals through a single G-protein-coupled receptor (IP), which signals through cyclic AMP. To determine the role of this receptor in lung cancer chemoprevention by prostacyclin, PGISoverexpressing mice were crossed to mice that lack the IP receptor [IP(−/−)]. Carcinogeninduced lung tumor incidence was similar in IP(+/+), IP(+/−), and IP(−/−) mice, and overexpression of PGIS gave equal protection in all three groups, indicating that the protective effects of prostacyclin are not mediated through activation of IP. Because prostacyclin can activate members of the peroxisomal proliferator-activated receptor (PPAR) family of nuclear receptors, we examined the role of PPARγ in the protection of prostacyclin against lung tumorigenesis. Iloprost, a stable prostacyclin analogue, activated PPARγ in nontransformed bronchial epithelial cells and in a subset of human non-small-cell lung cancer cell lines. Iloprost-impregnated chow fed to wild-type mice resulted in elevated lung macrophages and decreased lung tumor formation. Transgenic animals with lung-specific PPARγ overexpression also developed fewer lung tumors. This reduction was not enhanced by administration of supplemental iloprost. These studies indicate that PPARγ is a critical target for prostacyclin-mediated lung cancer chemoprevention and may also have therapeutic activity.In the United States, lung cancer continues to be the leading cause of cancer death in both men and women, and worldwide the lung cancer epidemic will result in millions of cases yearly (1). Whereas tobacco abstinence and smoking cessation are the critical first steps in reducing lung cancer rates, the majority of U.S. lung cancers are diagnosed in former smokers. To date, no effective chemopreventive agents have been discovered. The large at-risk population (current and former smokers) and poor 5-year lung cancer survival rates (2) underscore the need for a better understanding of chemopreventive mechanisms and effective agents.Prostaglandins play an important role in lung tumorigenesis, and prostaglandin manipulation has been investigated for lung cancer chemoprevention. Cyclooxygenase (COX) inhibition decreases levels of prostaglandins, and large epidemiologic surveys have shown fewer lung cancers in "frequent aspirin users" (3). Human trials evaluating COX inhibition and lung cancer chemoprevention are currently being conducted, but conflicting data in murine studies evaluating the role of nonspecific COX or selective COX-2 inhibition make interpretation of these results difficult. Studies using nonselective COX inhibitors have shown inhibition of lung tumorigenesis in mice (4, 5). However, mice receiving celecoxib (a selective COX-2 inhibitor) showed reduced pulmonary inflammation, but no differences in tumor multiplicity, and an actual increase in tumor size after exposure to an initiator-promoter model of lung tumorigen...

The growth of bariatric surgery in the USA followed the adoption of gastric bypass (RYGB). The recent introduction of sleeve gastrectomy (SG) has been met with wide adoption. A single state report suggests that the popularity of SG has surpassed that of RYGB. Our study aimed to assess the nationwide changes in trend of bariatric procedures performed, using data from the National Surgical Quality Improvement Program from 2010 to 2013. In this cohort of 74,790 bariatric patients, there was a significant difference in trend between laparoscopic RYGB and SG. By 2013, SG was the most common bariatric procedure performed (49.4 %). This report underlines the exponential adoption of SG and aims to alert patients, physicians, and funding agencies of the need for longitudinal prospective long-term data.

The endothelial-specific expression of plasmalemmal vesicle associated protein-1 (PV-1) is typical of fenestrated endothelium observed in pulmonary capillaries and some endocrine organs. In the central nervous system (CNS) it is expressed during development but disappears concomitant with maturation of the blood-CNS barrier [1]. Consistent with observations made in models of stroke, Alzheimer's disease, and tumorigenesis, we show PV-1 expression in the spinal cord specifically upregulated by pathologically-activated endothelial cells (ECs) in response to traumatic spinal cord injury (SCI). Adult female C57Bl/6 mice received a moderate T9/10 contusive SCI. PV-1 assessed by qRT-PCR and immunohistochemistry 3 hours to 14 days post-injury showed expression as early as 1 day post-SCI, with levels decreasing by 14 days. This expression was associated with microvessels in the injury epicenter and penumbral zone, with the time course and distribution correlated with progressing peripheral inflammatory cell infiltration. PV-1-immunoreactive ECs were angiogenic as demonstrated by intravascular binding of Griffonia simplicifolia isolectin B4 (IB4). ECs expressing high levels of PV-1 were anatomically and physiologically abnormal with altered/absent immunostaining for occludin and zonula occludens-1 (ZO-1), and decreased expression of glial fibrillary acidic protein (GFAP) and aquaporin-4 (AQP4). Glucose transporter type I (Glut-1) expression decreased in affected, PV-1 positive microvessels with little colocalization of PV-1 and Glut-1 apparent by 7 days post-SCI. These data suggest that upregulation of microvascular expression of PV-1 post-SCI may promote major components of secondary injury including extravasation of cellular and acellular mediators of inflammation and may accelerate loss of neuropil and decline in the functional and anatomical integrity of the neurovascular unit (NVU).