Leptin-signaling inhibition results in efficient anti-tumor activity in estrogen receptor positive or negative breast cancer

Introduction: We have shown previously that treatment with pegylated leptin peptide receptor antagonist 2 (PEG-LPrA2) reduced the expression of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor type 2 (VEGFR2) and growth of 4T1-breast cancer (BC) in syngeneic mice. In this investigation, PEG-LPrA2 was used to evaluate whether the inhibition of leptin signaling has differential impact on the expression of pro-angiogenic and pro-proliferative molecules and growth of human estrogen receptor-positive (ER+) and estrogen receptor-negative (ER-) BC xenografts hosted by immunodeficient mice. Methods: To test the contribution of leptin signaling to BC growth and expression of leptin-targeted molecules, PEG-LPrA2 treatment was applied to severe immunodeficient mice hosting established ER+ (MCF-7 cells; ovariectomized/supplemented with estradiol) and ER- (MDA-MB231 cells) BC xenografts. To further assess leptin and PEG-LPrA2 effects on ER+ and ER- BC, the expression of VEGF and VEGFR2 (protein and mRNA) was investigated in cell cultures. Results: PEG-LPrA2 more effectively reduced the growth of ER+ (>40-fold) than ER- BC (twofold) and expression of pro-angiogenic (VEGF/VEGFR2, leptin/leptin receptor OB-R, and IL-1 receptor type I) and pro-proliferative molecules (proliferating cell nuclear antigen and cyclin D1) in ER+ than in ER- BC. Mouse tumor stroma in ER+ BC expressed high levels of VEGF and leptin that was induced by leptin signaling. Leptin upregulated the transcriptional expression of VEGF/VEGFR2 in MCF-7 and MDA-MB231 cells. Conclusions: These results suggest that leptin signaling plays an important role in the growth of both ER+ and ER- BC that is associated with the leptin regulation of pro-angiogenic and pro-proliferative molecules. These data provide support for the potential use of leptin-signaling inhibition as a novel treatment for ER+ and ER- BC

Polymer Composites Containing Gated Mesoporous Materials for On-Command Controlled Release

Polyamidic nanofibrous membranes containing gated silica mesoporous particles, acting as carriers, are described as novel hybrid composite materials for encapsulation and on-command delivery of garlic extracts. The carrier system consists of MCM-41 solids functionalized in the outer surface, with linear polyamines (solid P1) and with hydrolyzed starch (solid P2), both acting as molecular gates. Those particles were adsorbed on electospun nylon-6 nanofibrous membranes yielding to composite materials M1 and M2. FE-SEM analysis confirmed the presence of particles incorporated on the nylon nanofibers. The release of the entrapped molecules (garlic extract) from the P1, P2, M1, and M2 materials was evaluated using cyclic voltammetry measurements. Electrochemical studies showed that at acidic pH P1 and M1 were unable to release their entrapped cargo (closed gate), whereas at neutral pH both materials release their loading (open gate). Dealing with P2 and M2 materials, in the absence of pancreatin a negligible release is observed (closed gate), whereas in the presence of enzyme the load is freely to diffuse to the solution. These newly developed composite nanomaterials, provide a homogeneous easy-to-handle system with controlled delivery and bioactive-protective features, having potential applications on pharmacology, medical and engineering fields.The authors wish to express their gratitude to the Generalitat Valenciana (Grisolia scholarship 2011/012, project PROM-ETEO/2009/016), Spanish Government (MINECO Projects AGL2012-39597-C02-01, AGL2012-39597-C02-02 and MAT2012-38429-C04-01) and the CIBER-BBN for their support. IILA thanks DISTAM and Universita degli di Milano for a specialization scholarship. We would also like to thank the Institut de Ciencia dels Materials (ICMUV) and to the Microscopy Service of the Universitat Politecnica de Valencia for technical support. We thank Roquette for the Glucidex samples.Acosta Romero, C.; Pérez Esteve, E.; Fuenmayor, CA.; Benedetti, S.; Cosio, MS.; Soto Camino, J.; Sancenón Galarza, F.... (2014). Polymer Composites Containing Gated Mesoporous Materials for On-Command Controlled Release. ACS Applied Materials and Interfaces. 6(9):6453-6460. https://doi.org/10.1021/am405939y645364606

A feasibility study on Kitchen Care by Woodworks, Incorporated

This study aims to study the feasibility of venturing into the manufacturing and selling of a kitchen rack. This study also shows the feasibility of venturing into a new rack business taking into consideration several aspects. These include the presentation of the marketing, technical, management and legal, financial, and socio-economic aspects. A demand for the product is shown in the marketing aspect with a Gross Market Acceptability Rate of 83%. The population consists of the homeowners of Kalaw Hill Subdivision, Filinvest Homes 11, and Maywood Village 2. Through the results of the survey questionnaire used, the product specifications such as the product features, price, place of distribution, packaging, and promotional tools to be employed by the proponents are determined. Pricing analysis is done with the use of the product\u27s direct and indirect competitors and the survey results. The survey questionnaire is a method used for gathering the primary data. Secondary data is gathered with the use of reference materials like marketing, legal, management, and financial books. The technical aspect of the study shows that the product can be produced with the availability of its raw materials, which is determined with the use of the canvassing method. The plan for the layout is determined through the careful selection of the most accessible plant site both for the suppliers and the proponents. Also shown are the computation for the project cost amounting to P 14,000.00 and the annual break-even point in units of 69 and break-even point in peso of P16,215.46. A time and motion study is undergone by the proponents showing the suitability of an assembly line with a total task time of 169 minutes compared to the job shop in manufacturing process with task time totaling to 238 minutes. Based on the time and motion study, the group is able to come up with their desired number of output of 8 units per production day. Considering all factors, total production cost is equal to P 175.08 subject to a 37% mark-up which is P 64.78. The selling price is set at P 249.00 In the financial aspect of the study, a set of assumptions is given by the proponents. A projection of the company\u27s financial performance for a period of ten (10) months is shown. Such assumptions generated a net income of P 16,364.77 with total assets of P 339,859.38. The financial budgets assimilated a 0.68 return on investments. And for the socio-economic study, several factors were enumerated contributing to its being socially desirable. Also stated are the benefits that can be obtained by businessmen and other researchers from this study. The proponents recommended that the proposed be implemented since the group is able to cater to the needs and meet the demands of its market and provide numerous benefits to the society well