Anti-Tumor Activity of a Novel HS-Mimetic-Vascular Endothelial Growth Factor Binding Small Molecule

The angiogenic process is controlled by variety of factors of which the vascular endothelial growth factor (VEGF) pathway plays a major role. A series of heparan sulfate mimetic small molecules targeting VEGF/VEGFR pathway has been synthesized. Among them, compound 8 (2-butyl-5-chloro-3-(4-nitro-benzyl)-3H-imidazole-4-carbaldehyde) was identified as a significant binding molecule for the heparin-binding domain of VEGF, determined by high-throughput-surface plasmon resonance assay. The data predicted strong binding of compound 8 with VEGF which may prevent the binding of VEGF to its receptor. We compared the structure of compound 8 with heparan sulfate (HS), which have in common the functional ionic groups such as sulfate, nitro and carbaldehyde that can be located in similar positions of the disaccharide structure of HS. Molecular docking studies predicted that compound 8 binds at the heparin binding domain of VEGF through strong hydrogen bonding with Lys-30 and Gln-20 amino acid residues, and consistent with the prediction, compound 8 inhibited binding of VEGF to immobilized heparin. In vitro studies showed that compound 8 inhibits the VEGF-induced proliferation migration and tube formation of mouse vascular endothelial cells, and finally the invasion of a murine osteosarcoma cell line (LM8G7) which secrets high levels of VEGF. In vivo, these effects produce significant decrease of tumor burden in an experimental model of liver metastasis. Collectively, these data indicate that compound 8 may prevent tumor growth through a direct effect on tumor cell proliferation and by inhibition of endothelial cell migration and angiogenesis mediated by VEGF. In conclusion, compound 8 may normalize the tumor vasculature and microenvironment in tumors probably by inhibiting the binding of VEGF to its receptor

Estimating Dust Temperature and Far-IR Luminosity of High-Redshift Galaxies using ALMA Single-Band Continuum Observations

We present a method that derives the dust temperatures and infrared (IR) luminosities of high-redshift galaxies assuming radiation equilibrium in a simple dust and stellar distribution geometry. Using public data from the Atacama Large Millimeter/submillimeter Array (ALMA) archive, we studied dust temperatures assuming a clumpy interstellar medium (ISM) model for high-redshift galaxies, then tested the consistency of our results with those obtained using other methods. We find that a dust distribution model assuming a clumpiness of ${\rm log}\,\xi_{\rm clp}=-1.02\pm0.41$ may accurately represent the ISM of high-redshift star-forming galaxies. By assuming a value of $\xi_{\rm{clp}}$, our method enables the derivation of dust temperatures and IR luminosities of high-redshift galaxies from dust continuum fluxes and emission sizes obtained from single-band ALMA observations. to demonstrate the method proposed herein, we determined the dust temperature ($T_{\rm d}=95^{+13}_{-17}\,\rm{K}$) of a $z\sim8.3$ star-forming galaxy, MACS0416-Y1. Because the method only requires a single-band dust observation to derive a dust temperature, it is more easily accessible than multi-band observations or high-redshift emission line searches and can be applied to large samples of galaxies in future studies using high resolution interferometers such as ALMA.Comment: Accepted for publication in MNRAS, 8 pages, 3 figures, For our public python scripts, see https://github.com/yfudamoto/FIS22sed.gi

Towards a global model of accounting education

Purpose - The purpose of this paper is to examine the accounting education systems in three countries - Australia, Japan and Sri Lanka - to inform the development and testing (by application) of a Global Model of Accounting Education

Relativistic Equation of State of Nuclear Matter for Supernova and Neutron Star

We construct the equation of state (EOS) of nuclear matter using the relativistic mean field (RMF) theory in the wide density, temperature range with various proton fractions for the use of supernova simulation and the neutron star calculations. We first construct the EOS of homogeneous nuclear matter. We use then the Thomas-Fermi approximation to describe inhomogeneous matter, where heavy nuclei are formed together with free nucleon gas. We discuss the results on free energy, pressure and entropy in the wide range of astrophysical interest. As an example, we apply the resulting EOS on the neutron star properties by using the Oppenheimer-Volkoff equation.Comment: 15 pages, LaTeX, 14 ps-figures, accepted for publication in Nucl.Phys.

Anti-tumor and anti-angiogenic activity of novel hydantoin derivatives: Inhibition of VEGF secretion in liver metastatic osteosarcoma cells

A series of new azaspiro bicyclic hydantoin derivatives has been designed and synthesized. Initially, the anti-proliferative effect of the hydantoin derivatives was evaluated against human ovarian cancer cells (SKOV-3 and OVSAHO) and murine osteosarcoma cells (LM8 and LM8G7). Among the tested compounds, 8-(3-fluorobenzyl)-1′-(4-(methylsulfonyl)benzyl)-8-azaspiro[bicyclo[3.2.1]octane-3,4′-imidazolidine]-2′,5′-dione (7h) and 8-(3,4-difluorobenzyl)-1′-(4-(methylsulfonyl)benzyl)-8-azaspiro[bicyclo[3.2.1]octane-3,4′-imidazolidine]-2′,5′-dione (7i) showed a significant anti-proliferative activity against the OVSAHO and LM8G7 cells. The real-time monitoring of the effect of the compounds 7h and 7i against the proliferation of LM8G7 was revealed that resulting IC50 values were 102 μM and 13 μM, respectively. We reasoned that the presence of fluorine atom at the 3rd position of the phenyl ring of the hydantoin side chain may determine the potency of the molecule. Furthermore, the compound 7i inhibited the tube formation of the mouse endothelial cells. Finally, the treatment of the compound 7i against the proliferation of LM8G7 cells demonstrated the down regulation of the secretion of VEGF, indicate the potential angioinhibitory effects. In conclusion, our findings demonstrate the suppression of the secretion of VEGF by LM8G7 cells by the compound 7i might contribute at least in part to the antitumor action

ARSENIC REMOVAL FROM GROUNDWATER USING INDIGENOUS IRON AND MANGANESE OXDIZING BACTERIA

Joint Research on Environmental Science and Technology for the Eart

A small oxazine compound as an anti-tumor agent: A novel pyranoside mimetic that binds to VEGF, HB-EGF, and TNF-α

A novel pyranoside mimetic compound, DMBO (2-(2,6-difluorophenyl)-5-(4-methoxyphenyl)-1-oxa-3-azaspiro5.5undecane), was designed and synthesized. The sugar mimicking behavior of DMBO was addressed by its ability to bind several growth factors/cytokines such as vascular endothelial growth factor (VEGF), heparin-binding epidermal growth factor-like growth factor (HB-EGF), and tumor necrosis factor (TNF)-α as demonstrated by the recently developed surface plasmon resonance assay. DMBO exhibited strong anti-proliferation activity in vitro against tumor cells including a highly metastatic murine osteosarcoma cell line LM8G7 that secretes VEGF as well as two human ovarian cell lines, OVSAHO and SKOV-3, which secrete TNF-α and HB-EGF respectively. Furthermore, DMBO inhibited the metastatic activity to the mouse liver of LM8G7 cells injected from a lateral tail vein, and affected the heparan-degrading activity of LM8G7 cells. Here, we report that DMBO acts as a human heparanase inhibitor in vitro possibly as a substrate mimetic. DMBO also inhibited the migration and invasion of LM8G7 cells and angiogenic events such as endothelial cell proliferation, migration and capillary tube-like formation in vitro. More prominently, the administration of DMBO with heparin resulted in synergistic anti-tumor effects in mouse model. of. osteosarcoma. These preclinical data shows the potential anti-cancer effects of DMBO. © 2010 Elsevier Ireland Ltd