A proposal for an evidence-based model of the screening for the colorectal carcinoma in an Italian setting

Introduction. The aim of this paper is to improve the feasibility perception of policymakers, health care workers and target population about the cost-effectiveness of the implementation of colorectal screening as Public Health strategy. Methods. Retrospective study by application of a three-step model designed for a local setting in Sicily (Palermo and its Province) in order to distribute Fecal Occult Blood Tests (FOBTs), offer colonoscopy and surgery, by district allocation of pharmacies, public digestive endoscopic centres and oncologic and general surgery units. Mean adherence to consolidated colorectal screening programs in Italy was applied in order to evaluate the feasibility of an operative model in our area. Results. Applying the model to the target population (269,368 individuals of both sexes), it can be expected a mean percentage of 79% delivered invitation and a mean participation rate of 46.3% accounting for a total of 213,070 invited individuals and 98,651 participating in the first round of the program. Furthermore, considering the national mean of 6% positive FOBT, 82% of colonscopy adhesion and 7% CRC detection rate, it can be scheduled a burden for health care structures involved in the program accounting for 49,325 FOBTs, 2,338 colonscopies and 141 surgeries for each year. Discussion. This work demonstrates the feasibility of a colorectal screening project in our area, showing a sustainable impact for local health care involved structures. Furthermore, this program may be spread as an applicative model to other areas, adapting the project to the needs of the local setting in which the colorectal screening will be organized

Importance of meteorological variables for aeroplankton dispersal in an urban environment

Passive wind dispersal is one of the major mechanisms through which organisms disperse and colonize new areas. The detailed comprehension of which factors affect this process may help to preserve its efficiency for years to come. This is especially important in the current context of climate change, which may seriously alter weather regimes that drive dispersal, and is crucial in urban contexts, where biodiversity is dramatically threatened by pollution and fragmentation of natural patches. Despite its interest, the analysis of factors affecting aeroplankton dispersal in urban environments is rare in literature. We sampled aeroplankton community uninterruptedly every 4 hours from 17th May to 19th September 2011 in the urban garden of Parco d'Orléans, within the campus of the University of Palermo (Sicily). Sampling was performed using a Johnson-Taylor suction trap with automatized sample storing. Weather variables were recorded at a local meteorological station. Overall, 11,739 insects were caught during the present study, about 60% of these belonged to the order Hymenoptera, with particular presence of families Agaonidae and Formicidae. The suction trap also captured specimens of very small size, and in some cases, species caught were new records for Italy. Composition and abundance of aeroplankton community was influenced by alternation day/night, as well as by daily fluctuations of climatic variables, for example fluctuating temperature . The diversity of samples was also studied and resulted higher when wind blew from the nearby green area. Our findings confirm that passive transport of arthropods strictly depends on weather conditions, and that the presence of natural areas within the urban environment significantly contribute to raise aeroplankton diversity, eventually fuelling overall biodiversity at a local scale. We discuss how climate change may affect future dispersal of these organisms

Oleocanthal Exerts Antitumor Effects on Human Liver and Colon Cancer Cells Through ROS Generation

The beneficial health properties of the Mediterranean diet are well recognized. The principle source of fat in Mediterranean diet is extra-virgin olive oil (EVOO). Oleocanthal (OC) is a naturally occurring minor phenolic compound isolated from EVOO, which has shown a potent anti-inflammatory activity, by means of its ability to inhibit the cyclooxygenase (COX) enzymes COX-1 and COX-2. A large body of evidence indicates that phenols exhibit anticancer activities. The aim of the present study was to evaluate the potential anticancer effects of OC in hepatocellular carcinoma (HCC) and colorectal carcinoma (CRC) models. A panel of human HCC (HepG2, Huh7, Hep3B and PLC/PRF/5) and CRC (HT29, SW480) cell lines was used. Cells were treated with OC, and cell viability and apoptosis were evaluated. Compared with classical commercially available COX inhibitors (ibuprofen, indomethacin, nimesulide), OC was more effective in inducing cell growth inhibition in HCC and CRC cells. Moreover, OC inhibited colony for mation and i nduced ap optosis, as confirmed by PARP cleavage, activation of caspases 3/7 and chromatin condensation. OC treatment in a dose dependent-manner induced expression of \uce\ub3H2AX, a marker of DNA damage, increased intracellular ROS production and caused mitochondrial depolarization. Moreover, the effects of OC were suppressed by the ROS scavenger N-acetyl-L-cysteine. Finally, OC was not toxic in primary normal human hepatocytes. In conclusion, OC treatment was found to exert a potent anticancer activity against HCC and CRC cells. Taken together, our findings provide preclinical support of the chemotherapeutic potential of EVOO against cancer

Novel Combination of Sorafenib and Celecoxib Provides Synergistic Anti-Proliferative and Pro-Apoptotic Effects in Human Liver Cancer Cells

Molecular targeted therapy has shown promise as a treatment for advanced hepatocellular carcinoma (HCC). Sorafenib, a multikinase inhibitor, recently received FDA approval for the treatment of advanced HCC. However, although sorafenib is well tolerated, concern for its safety has been expressed. Celecoxib (Celebrex®) is a selective cyclooxygenase-2 (COX-2) inhibitor which exhibits antitumor effects in human HCC cells. The present study examined the interaction between celecoxib and sorafenib in two human liver tumor cell lines HepG2 and Huh7. Our data showed that each inhibitor alone reduced cell growth and the combination of celecoxib with sorafenib synergistically inhibited cell growth and increased apoptosis. To better understand the molecular mechanisms underlying the synergistic antitumor activity of the combination, we investigated the expression profile of the combination-treated liver cancer cell lines using microarray analysis. Combination treatment significantly altered expression levels of 1,986 and 2,483 transcripts in HepG2 and Huh7 cells, respectively. Genes functionally involved in cell death, signal transduction and regulation of transcription were predominantly up-regulated, while genes implicated in metabolism, cell-cycle control and DNA replication and repair were mainly down-regulated upon treatment. However, combination-treated HCC cell lines displayed specificity in the expression and activity of crucial factors involved in hepatocarcinogenesis. The altered expression of some of these genes was confirmed by semi-quantitative and quantitative RT-PCR and by Western blotting. Many novel genes emerged from our transcriptomic analyses, and further functional analyses may determine whether these genes can serve as potential molecular targets for more effective anti-HCC strategies

Inhibition of iNOS as a Novel Effective Targeted Therapy Against Triple-Negative Breast Cancer

INTRODUCTION: Triple-negative breast cancer (TNBC) is an aggressive form of breast cancer with no effective targeted therapy. Inducible nitric oxide synthase (iNOS) is associated with poor survival in patients with breast cancer by increasing tumor aggressiveness. This work aimed to investigate the potential of iNOS inhibitors as a targeted therapy for TNBC. We hypothesized that inhibition of endogenous iNOS would decrease TNBC aggressiveness by reducing tumor initiation and metastasis through modulation of epithelial-mesenchymal transition (EMT)-inducing factors. METHODS: iNOS protein levels were determined in 83 human TNBC tissues and correlated with clinical outcome. Proliferation, mammosphere-forming efficiency, migration, and EMT transcription factors were assessed in vitro after iNOS inhibition. Endogenous iNOS targeting was evaluated as a potential therapy in TNBC mouse models. RESULTS: High endogenous iNOS expression was associated with worse prognosis in patients with TNBC by gene expression as well as immunohistochemical analysis. Selective iNOS (1400 W) and pan-NOS (L-NMMA and L-NAME) inhibitors diminished cell proliferation, cancer stem cell self-renewal, and cell migration in vitro, together with inhibition of EMT transcription factors (Snail, Slug, Twist1, and Zeb1). Impairment of hypoxia-inducible factor 1α, endoplasmic reticulum stress (IRE1α/XBP1), and the crosstalk between activating transcription factor 3/activating transcription factor 4 and transforming growth factor β was observed. iNOS inhibition significantly reduced tumor growth, the number of lung metastases, tumor initiation, and self-renewal. CONCLUSIONS: Considering the effectiveness of L-NMMA in decreasing tumor growth and enhancing survival rate in TNBC, we propose a targeted therapeutic clinical trial by re-purposing the pan-NOS inhibitor L-NMMA, which has been extensively investigated for cardiogenic shock as an anti-cancer therapeutic

Relationships within the Araceae: comparison of morphological patterns with molecular phylogenies.

Premise of the study: The first family-wide molecular phylogeny of the Araceae, a family of about 3800 published species in 120 genera, became available in 1995, followed by a cladistic analysis of morpho-anatomical data in 1997. The most recent and comprehensive family-wide molecular phylogeny was published in 2008 and included species from 102 genera. We reanalyzed the molecular data with a more complete genus sampling and compared the resulting phylogeny with morphological and anatomical data, with a view to contributing to a new formal classification of the Araceae. • Methods: We analyzed 113 aroid genera and 4494 aligned nucleotides that resulted from adding 11 genera to the 2008 molecular matrix. We also analyzed 81 morphological characters in the context of the molecular phylogeny, using an extended version of the 1997 morpho-anatomical data set. • Key results: The resulting maximum-likelihood phylogeny is well resolved and supported, and most of the 44 larger clades also have morphological or anatomical synapomorphies as well as ecological or geographic cohesion. Of the 44 clades, 16 are here newly circumscribed and informally named. However, some relationships remain poorly supported within the Aroideae subfamily. The most problematic placement is Calla within Aroideae, which conflicts with the distribution of morphological, anatomical, and palynological character states. • Conclusions: The comparison of the molecular analysis with morphological and anatomical data presented here represents an important basis for a new formal classification for the Araceae and for the understanding of the evolution of this ancient family, a monocot group known in the fossil record from the early Cretaceous

[OP.5C.05] SERUM URIC ACID IS INCREASED IN NORMOTENSIVE OBESE CHILDREN WITH A PARENTAL HYSTORY OF HYPERTENSION

Objective: Increased uric acid levels are closely associated with new-onset hypertension in children, and pilot studies showed that pharmacological lowering of uric acid may reduce blood pressure (BP) in obese pediatric patients. Nevertheless, controversy remains concerning a direct causative role of serum uric acid (SUA) in the pathogenesis of essential hypertension (EH). Our study was aimed to determine if normotensive obese children and adolescent offspring of adults with EH show SUA levels different than those of pediatric subjects in whom there is non family history of EH. Design and method: Fifty-nine obese normotensive children and adolescents, attending for metabolic assessment the Pediatric Diabetes Unit, Children's Hospital "G. Di Cristina", and for cardiovascular evaluation the ESH Hypertension excellence center of the University of Palermo, were studied. All the subjects, aged between 8 and 17 years, underwent routine blood chemistry and oral glucose tolerance test with glucose and insulin determinations. All subjects had blood pressure determinations below the 90th percentile and had no previous history of elevated blood pressure. Results: There were 14 subjects whose parents were both normotensive (FH-), and the remaining 45 subjects whose one or both parents were hypertensive. FH + did not differ regarding age, sex distribution, blood pressure values, body mass index, waist circumference, serum glucose levels when compared to FH-. Among the metabolic parameters assessed, only SUA was significantly higher in FH+ than in FH - (p = 0.007; figure 1)