Induction of Endothelial Cell Apoptosis by Solid Tumor Cells

The mechanisms by which tumor cells extravasate to form metastasis remain controversial. Previous studies performed in vivo and in vitro demonstrate that the contact between tumor cells and the vascular wall impairs endothelium integrity. Here, we investigated the effect of breast adenocarcinoma MCF-7 cells on the apoptosis of human umbilical vein endothelial cells (HUVEC). TUNEL labeling, nuclear morphology, and DNA electrophoresis indicated that MCF-7 cells induced a two- to fourfold increase in HUVEC apoptosis. Caspase-3 activity was significantly enhanced. Neither normal cells tested (mammary epithelial cells, fibroblasts, leukocytes) nor transformed hematopoietic cells tested (HL60, Jurkat) induced HUVEC apoptosis. On the contrary, cells derived from solid tumors (breast adenocarcinoma, MDA-MB-231 and T47D; fibrosarcoma, HT 1080) had an effect similar to that of MCF-7 cells. The induction of apoptosis requires cell-to-cell contact, since it could not be reproduced by media conditioned by MCF-7 cells cultured alone or cocultured with HUVEC. Our results suggest that cells derived from solid tumors may alter the endothelium integrity by inducing endothelial cell apoptosis. On the contrary, normal or malignant leukocytes appear to extravasate by distinct mechanisms and do not damage the endothelium. Our data may lead to a better understanding of the steps involved in tumor cell extravasation

Ethoxyfagaronine, a synthetic analogue of fagaronine that inhibits vascular endothelial growth factor-1, as a new anti-angiogeneic agent

Angiogenesis plays a pivotal role in tumorigenesis and also contributes to the pathogenesis of hematologic malignancies. A number of plant compounds have shown efficacy in preclinical and clinical studies and some of them possess an anti-angiogenic activity. Our present findings report anti-angiogenic activities of ethoxyfagaronine (etxfag), a synthetic derivative of fagaronine. Once determined the non-cytotoxic concentration of etxfag, we showed that the drug inhibits VEGF-induced angiogenesis in a Matrigel™ plug assay and suppresses ex vivo sprouting from VEGF-treated aortic rings. Each feature leading to neovascularization was then investigated and results demonstrate that etxfag prevents VEGF-induced migration and tube formation in human umbilical vein endothelial cells (HUVEC). Moreover, etxfag also suppresses VEGF-induced VEGFR-2 phosphorylation and inhibits FAK phosphorylation at Y-861 as well as focal adhesion complex turnover. Beside these effects, etxfag modifies MT1-MMP localization at the endothelial cell membrane. Finally, immunoprecipitation assay revealed that etxfag decreases VEGF binding to VEGFR-2. As we previously reported that etxfag is able to prevent leukemic cell invasiveness and adhesion to fibronectin, all together our data collectively support the anti-angiogenic activities of etxfag which could represent an additional approach to current anti-cancer therapies

NADPH oxidase, NOX1, mediates vascular injury in ischemic retinopathy

<b>Aims:</b> Ischemic retinal diseases such as retinopathy of prematurity are major causes of blindness due to damage to the retinal microvasculature. Despite this clinical situation, retinopathy of prematurity is mechanistically poorly understood. Therefore, effective preventative therapies are not available. However, hypoxic-induced increases in reactive oxygen species (ROS) have been suggested to be involved with NADPH oxidases (NOX), the only known dedicated enzymatic source of ROS. Our major aim was to determine the contribution of NOX isoforms (1, 2, and 4) to a rodent model of retinopathy of prematurity. <b>Results:</b> Using a genetic approach, we determined that only mice with a deletion of NOX1, but not NOX2 or NOX4, were protected from retinal neovascularization and vaso-obliteration, adhesion of leukocytes, microglial accumulation, and the increased generation of proangiogenic and proinflammatory factors and ROS. We complemented these studies by showing that the specific NOX inhibitor, GKT137831, reduced vasculopathy and ROS levels in retina. The source of NOX isoforms was evaluated in retinal vascular cells and neuro-glial elements. Microglia, the immune cells of the retina, expressed NOX1, 2, and 4 and responded to hypoxia with increased ROS formation, which was reduced by GKT137831. <b>Innovation:</b> Our studies are the first to identify the NOX1 isoform as having an important role in the pathogenesis of retinopathy of prematurity. <b>Conclusions:</b> Our findings suggest that strategies targeting NOX1 have the potential to be effective treatments for a range of ischemic retinopathie

Implementation of the Indonesian Banking Architecture as a Blueprint of the Direction And Order of the National Banking System: Empirical Study of Indonesian Commercial Banking

This study aims to examine the influence of Capital Adequacy Ratio (CAR), earning assets, and liquidity against Return on Asset (ROA) in the conventional bank which has the biggest asset listed in Indonesian Stock Exchange (IDX) during the period of 2006 to 2010. This research used time series data from Bank Indonesia’s report and financial reports annually published by banking firms listed in IDX. After passing the purposive sampling, there were 27 conventional banks listed in IDX as sample in this study. By using multiple regression analysis (F-test), results showed that CAR, Non Performing Loan (NPL), and Non Performing Loan (NPL) collectively have significant influence on ROA. However, by using individual analysis (t-test), NPL has a negative and significant influence on ROA, while CAR and LDR have no significant influence on ROA

ENHANCEMENT INSTITUTIONAL CAPACITY OF CAMPUS ENTREPRENEURSHIP THROUGH BUSINESS COMMUNITY DEVELOPMENT IN SOME COLLEGES IN INDONESIA

This study aims to determine the factors that affect entrepreneurship capital among students at several universities in Indonesia. The focus of this research is to identify the determinants of entrepreneurial attitudes and intentions. Specifically, this study investigates the views of respondents regarding entrepreneurship in terms of enhancing the institutional capacity of campus entrepreneurship. It further examines the respondents through self-assessment on entrepreneurship quality and their views on entrepreneurs. In addition, the importance of the various benefits and values for starting a business and the role of influencers according to their perceptions of entrepreneurship will also be analyzed. This study was analyzed through descriptive research method with the aim of obtaining profiling in terms of certain demographic attributes. Thus, entrepreneurship attitudes and intentions can build entrepreneurship skills through appropriate learning methods supported by strengthening the institutional capacity of campus entrepreneurship as a business incubator, container assistance, and entrepreneurship training

The System of Proof on Extraordinary Crime in Case Criminal Which Based on the Intelligent Investigation Report (A Case Study)

Terrorism is an extraordinary crime which is transnational activity that is way to combat terrorism not an easy operation, what more difficult and need highly activity and hardly unable to catch the terrorist, due process of it and challenging current criminal system procedure, whiles the burden of proof in terrorism is very complicated. Based on recent experience in Indonesia, due process of law for the act of terrorism does use the ordinary criminal system of procedure law, which does not adopt the intelligence investigation report as evidence based. In other word the law of criminal procedure act does not qualify yet or not clearly amend the intelligence report as clear convincing evidence. This study is tried to explore this gap on what other legal tool can be used to challenge this hole. What common practices is used to render this problem and what adjudge has been follow recently to this matter of law. The methodology in study this issues by collecting (i) all information related facts of intelligence operation analysis in formed part by part information followed by field cross-check examination, (ii) managing the crime of terrorism as extraordinary one and as the transnational of Crime against humanity based on the article 184 Criminal Procedure Act, with add some strong clues about terrorism activity as an preliminary evidence to continuing the depth investigation has been regulated according to article 26 Act No. 15 Year 2003 Regarding to The Prevention of Terrorism.(iii) By using intelligence investigation report as evidence the system of proof will bring some developing method for the law to foster the burden of proof system and may deter the crime of terrorism.  As a conclusion this study may contribute some ways or other method of proof involving the extraordinary crime on terrorism which not been adopted by current law and system. Keywords: burden of proof, evidence and terrorism, intelligence investigation DOI: 10.7176/JLPG/90-15 Publication date:October 31st 201

Mouse Aortic Ring Assay: A New Approach of the Molecular Genetics of Angiogenesis

Angiogenesis, a key step in many physiological and pathological processes, involves proteolysis of the extracellular matrix. To study the role of two enzymatic families, serine-proteases and matrix metalloproteases in angiogenesis, we have adapted to the mouse, the aortic ring assay initially developed in the rat. The use of deficient mice allowed us to demonstrate that PAI-1 is essential for angiogenesis while the absence of an MMP, MMP-11, did not affect vessel sprouting. We report here that this model is attractive to elucidate the cellular and molecular mechanisms of angiogenesis, to identify, characterise or screen "pro- or anti-angiogenic agents that could be used for the treatment of angiogenesis-dependent diseases. Approaches include using recombinant proteins, synthetic molecules and adenovirus-mediated gene transfer