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Silver Spring, MD, United States

Tesfamariam B.,CDER
Pharmacology and Therapeutics | Year: 2016

Extensive experimental evidence indicates that platelets contribute to tumor cell proliferation and metastasis through direct interactions and secreted bioactive proteins. Activated platelets release secretory factors that promote growth factors, chemokines, proangiogenic regulatory proteins, proteolytic enzymes and microparticles within the microenvironment to promote tumor cell growth and invasion. Furthermore, the formation of platelet-tumor cell heteroaggregates by integrin αIIbβ3 (glycoprotein IIb/IIIa) bridging plays an important role in tumor survival by forming a physical shield around tumor cells, and thereby protecting circulating tumor cells from immune-mediated lysis by natural killer (NK) cells. Tumor cells directly activate platelets by enhancing expression of surface integrins, selectins and secretion of granules, which amplify platelet aggregation. In addition to the physical coating of tumor cells, platelets release transforming growth factor-β1 (TGF-β1) that induces phenotypic changes of epithelial to mesenchymal-like transition of tumor cells, thereby facilitating their extravasation and dissemination to distant sites during metastasis. Thus, there is a complex interplay between platelet-induced tumor growth and tumor cell-induced platelet activation, with the involvement of multiple components within the tumor microenvironment that enhance metastasis. This review describes the intimate reciprocal cross-talk between platelets and tumor cells, and the various signaling pathways involved in tumor amplification, which may be potential therapeutic targets to disrupt the platelet-tumor loop to reduce metastatic processes. Published by Elsevier Inc. Source


Desai D.,Bristol Myers Squibb | Wang J.,Bristol Myers Squibb | Wen H.,Pentian Pharmaceuticals Company | Li X.,CDER | Timmins P.,Bristol Myers Squibb
Pharmaceutical Development and Technology | Year: 2013

Fixed dose combination (FDC) products are common in the treatment of hypertension, diabetes, human immunodeficiency virus, and tuberculosis. They make it possible to combine two or more drug molecules with different modes of pharmacological actions in a single dosing unit and optimize the treatment. From a patient perspective, they offer convenience, reduced dosing unit burden, and cost savings. From a clinical perspective, aging population in developed countries will need multiple medications to treat age related diseases and co-morbidities. FDC products simplify dosing regimen and enhance patient compliance. As outlined in the article, the number of FDC products has grown over the years and the trend is likely to continue. This review article gives an overview to pharmaceutical scientists about recent trends in the formulation development of the FDC products and provides decision trees to select most optimum formulation development strategy. While some formulation technologies such as multi-layer tablets, multiparticulate systems, active film coating, and hot-melt granulation are discussed in more detail, a few specialized technologies are also introduced briefly to the readers. © 2013 Informa Healthcare USA, Inc. Source


Boudries R.,CDER | Dizene R.,University of Science and Technology Houari Boumediene
Renewable Energy | Year: 2011

The region of Adrar, is one of the most remote and the most deprived regions in Algeria. The development of this region requires the exploitation of its natural resources more particularly of its solar and wind energy resources. However, the exploitation in an effective and viable way of these huge natural resources requires the conversion of these sources of energy into an energy vector that is versatile in its use, storable, transportable and ecologically acceptable. Solar hydrogen seems to be the best candidate today.In the present work, the meteorological and radiometric data of the region are examined. A system of PV-electrolyzer system of solar hydrogen production is proposed. An estimate of the solar hydrogen potential and its production cost are carried out. Finally, the results are discussed. © 2011 Elsevier Ltd. Source


Singal K.,CDER | Sharma S.,Maharshi Dayanand University
Indian Journal of Forensic Medicine and Toxicology | Year: 2016

Aim and Objectives: The aim and objectives of present study was to record the vertical measurements of mental foramen and to correlate them to assess the sensitivity of these parameters in gender determination. Methodology: Panoramic radiographs of a 100 individuals including 50 males and 50 females were assessed by using three linear vertical measurements and after that data was statistically analyzed. Results: Statistically significant differences were observed in all of the linear measurements between genders where males almost have higher measurements than females. Conclusion: This study concludes that the distances from the superior border of alveolar ridge to the superior margin of mental foramen of the mandible exhibit sexual dimorphism in the Haryana population. © 2015, Indian Journal of Forensic Medicine and Toxicology. All rights reserved. Source


Alosh M.,CDER
Pharmaceutical Statistics | Year: 2010

This paper explores the utility of different approaches for modeling longitudinal count data with dropouts arising from a clinical study for the treatment of actinic keratosis lesions on the face and balding scalp. A feature of these data is that as the disease for subjects on the active arm improves their data show larger dispersion compared with those on the vehicle, exhibiting an over-dispersion relative to the Poisson distribution. After fitting the marginal (or population averaged) model using the generalized estimating equation (GEE), we note that inferences from such a model might be biased as dropouts are treatment related. Then, we consider using a weighted GEE (WGEE) where each subject's contribution to the analysis is weighted inversely by the subject's probability of dropout. Based on the model findings, we argue that the WGEE might not address the concerns about the impact of dropouts on the efficacy findings when dropouts are treatment related. As an alternative, we consider likelihood-based inference where random effects are added to the model to allow for heterogeneity across subjects. Finally, we consider a transition model where, unlike the previous approaches that model the log-link function of the mean response, we model the subject's actual lesion counts. This model is an extension of the Poisson autoregressive model of order 1, where the autoregressive parameter is taken to be a function of treatment as well as other covariates to induce different dispersions and correlations for the two treatment arms. We conclude with a discussion about model selection. Source

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