Economic crisis and regional development in Greece

This paper sets out to examine the determinants of regional develop-ment in Greece before and during the economic crisis. By proposing an econo-metric model with spatial effects for the years 2005-2008 and 2009-2011, which represent the sub-periods of growth and decline of the Greek economy respec-tively, we make it possible to capture the different factors that affect the region-al economic development of the NUTS III regions in the country. Results high-light that the most urbanized and high income level regions are more affected by the economic crisis. However, these regions had been the ones that most benefited during the upturn of the economic activity. The same applies to the regions that are based on agriculture, which had benefited during the period of economic development but cannot sustain the gains of development during the recession. Specialization in manufacturing is an important determinant of re-gional development, either in times of growth or in times of crisis, while tourism generates benefits to the neighbouring regions in times of economic crisis. These results are also tested for geographical subsets of the country such as the North-South divide and regions belonging to the development axis of the coun-try (PATHE) versus the rest regions of the countr

Inhibition of angiogenesis- and inflammation-inducing factors in human colon cancer cells in vitro and in ovo by free and nanoparticle-encapsulated redox dye, DCPIP

<p>Abstract</p> <p>Background</p> <p>The redox dye, DCPIP, has recently shown to exhibit anti-melanoma activity <it>in vitro </it>and <it>in vivo</it>. On the other hand, there is increasing evidence that synthetic nanoparticles can serve as highly efficient carriers of drugs and vaccines for treatment of various diseases. These nanoparticles have shown to serve as potent tools that can increase the bioavailability of the drug/vaccine by facilitating absorption or conferring sustained and improved release. Here, we describe results on the effects of free- and nanoparticle-enclosed DCPIP as anti-angiogenesis and anti-inflammation agents in a human colon cancer HCT116 cell line <it>in vitro</it>, and in induced angiogenesis <it>in ovo</it>.</p> <p>Results</p> <p>The studies described in this report indicate that (a) DCPIP inhibits proliferation of HCT116 cells <it>in vitro</it>; (b) DCPIP can selectively downregulate expression of the pro-angiogenesis growth factor, VEGF; (c) DCPIP inhibits activation of the transcriptional nuclear factor, NF-κB; (d) DCPIP can attenuate or completely inhibit VEGF-induced angiogenesis in the chick chorioallantoic membrane; (e) DCPIP at concentrations higher than 6 μg/ml induces apoptosis in HCT116 cells as confirmed by detection of caspase-3 and PARP degradation; and (f) DCPIP encapsulated in nanoparticles is equally or more effective than free DCPIP in exhibiting the aforementioned properties (a-e) in addition to reducing the expression of COX-2, and pro-inflammatory proteins IL-6 and IL-8.</p> <p>Conclusions</p> <p>We propose that, DCPIP may serve as a potent tool to prevent or disrupt the processes of cell proliferation, tissue angiogenesis and inflammation by directly or indirectly targeting expression of specific cellular factors. We also propose that the activities of DCPIP may be long-lasting and/or enhanced if it is delivered enclosed in specific nanoparticles.</p

Nanoparticle-based delivery of siDCAMKL-1 increases microRNA-144 and inhibits colorectal cancer tumor growth via a Notch-1 dependent mechanism

<p>Abstract</p> <p>Background</p> <p>The development of effective drug delivery systems capable of transporting small interfering RNA (siRNA) has been elusive. We have previously reported that colorectal cancer tumor xenograft growth was arrested following treatment with liposomal preparation of siDCAMKL-1. In this report, we have utilized Nanoparticle (NP) technology to deliver DCAMKL-1 specific siRNA to knockdown potential key cancer regulators. In this study, mRNA/miRNA were analyzed using real-time RT-PCR and protein by western blot/immunohistochemistry. siDCAMKL-1 was encapsulated in Poly(lactide-<it>co</it>-glycolide)-based NPs (NP-siDCAMKL-1); Tumor xenografts were generated in nude mice, treated with NP-siDCAMKL-1 and DAPT (γ-secretase inhibitor) alone and in combination. To measure <it>let-7a </it>and <it>miR-144 </it>expression <it>in vitro</it>, HCT116 cells were transfected with plasmids encoding the firefly luciferase gene with <it>let-7a </it>and <it>miR-144 </it>miRNA binding sites in the 3'UTR.</p> <p>Results</p> <p>Administration of NP-siDCAMKL-1 into HCT116 xenografts resulted in tumor growth arrest, downregulation of proto-oncogene c-Myc and Notch-1 via <it>let-7a </it>and <it>miR-144 </it>miRNA-dependent mechanisms, respectively. A corresponding reduction in <it>let-7a </it>and <it>miR-144 </it>specific luciferase activity was observed <it>in vitro</it>. Moreover, an upregulation of EMT inhibitor <it>miR-200a </it>and downregulation of the EMT-associated transcription factors ZEB1, ZEB2, Snail and Slug were observed <it>in vivo</it>. Lastly, DAPT-mediated inhibition of Notch-1 resulted in HCT116 tumor growth arrest and down regulation of Notch-1 via a <it>miR-144 </it>dependent mechanism.</p> <p>Conclusions</p> <p>These findings demonstrate that nanoparticle-based delivery of siRNAs directed at critical targets such as DCAMKL-1 may provide a novel approach to treat cancer through the regulation of endogenous miRNAs.</p

Differentiation of Human Malignant Melanoma Cells that Escape Apoptosis After Treatment with 9-Nitrocamptothecin In Vitro

After in-vitro exposure to 0.05 µmol/L 9-nitrocamptothecin (9NC) for periods of time longer than 5 days, 65% to 80% of the human malignant melanoma SB1B cells die by apoptosis, whereas the remaining cells are arrested at the G(2)-phase of the cell cycle. Upon discontinuation of exposure to 9NC the G(2)-arrested cells resume cell cycling or remain arrested depending on the duration of 9NC exposure. In contrast to cycling malignant cells, the cells irreversibly arrested at G(2) exhibit features of normal-like cells, the melanocytes, as assessed by the appearance of dendrite-like structures; loss of proliferative activity; synthesis of the characteristic pigment, melanin; and, particularly, loss of tumorigenic ability after xenografting in immunodeficient mice. Further, the expression of the cyclin-dependent kinase inhibitor p16 is upregulated in the 9NC-treated, G(2)-arrested, but downregulated in density G(1)-arrested cells, whereas the reverse is observed in the expression of another cyclin-dependent kinase inhibitor, p21. These results suggest that malignant melanoma SB1B cells that escape 9NC-induced death by apoptosis undergo differentiation toward nonmalignant, normal-like cells

Camphene, a plant-derived monoterpene, reduces plasma cholesterol and triglycerides in hyperlipidemic rats independently of HMG-CoA reductase activity.

Central to the pathology of coronary heart disease is the accumulation of lipids, cholesterol and triglycerides, within the intima of arterial blood vessels. The search for drugs to treat dislipidemia, remains a major pharmaceutical focus. In this study, we evaluated the hypolipidemic properties of the essential oil from Chios mastic gum (MGO).The hypolipidemic effect of MGO was investigated in naïve as well as in rats susceptible to detergent-induced hyperlipidemia. Serum cholesterol and triglycerides were determined using commercial kits. HMG-CoA (3-hydroxy-3-methylglutaryl coenzyme A) reductase activity was measured in HepG2 cell extracts using a radioactive assay; cellular cholesterol and cholesterol esters were assessed using gas chromatography. MGO administration into naïve rats resulted in a dose-dependent reduction in the constitutive synthesis of serum cholesterol and triglycerides. In hyperlipidemic rats, MGO treatment had also a strong hypolipidemic effect. By testing various components of MGO, we show for the first time that the hypolipidemic action is associated with camphene. Administration of camphene at a dose of 30 µg/gr of body weight in hyperlipidemic rats resulted in a 54.5% reduction of total cholesterol (p<0.001), 54% of Low Density Lipoprotein (LDL)-cholesterol (p<0.001) and 34.5% of triglycerides (p<0.001). Treatment of HepG2 cells with camphene led to a decrease in cellular cholesterol content to the same extend as mevinolin, a known HMG-CoA reductase inhibitor. The hypolipidemic action of camphene is independent of HMG-CoA reductase activity, suggesting that its hypocholesterolemic and hypotriglyceridemic effects are associated with a mechanism of action different than that of statins.Given the critical role that the control of hyperlipidemia plays in cardiovascular disease, the results of our study provide insights into the use of camphene as an alternative lipid lowering agent and merits further evaluation

Effect of MGO and camphene on whole protein content of HepG2 cells.

<p>On day 7 (see <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0020516#s2" target="_blank">Methods</a>), identical cultures of HepG2 cells were incubated with camphene (37 µM) and mevinolin (37 µM) for 1 h and 18 h, and subsequently whole cell protein was quantified. The measurements shown were obtained from three independent experiments performed in triplicate and expressed as the mean values ± SD. <i>p</i>>0.05 by the Student-Newmann-Keuls test.</p