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Pantazis P.,ADNA Inc. | Dimas K.,University of Thessaly | Wyche J.H.,Howard University | Anant S.,University of Kansas Medical Center | And 3 more authors.
Methods in Molecular Biology | Year: 2012

Nanoparticles (NPs) formulated using poly (d,l-lactide-co-glycolide) (PLGA), a biodegradable, biocompatible, and clinically approved polymer, have been widely used for targeted drug delivery. Here we provide methods for preparing PLGA NPs that encapsulate small interfering RNA (siRNA). The siRNA NPs are formulated using a double-emulsion solvent evaporation technique with the addition of a small amount of the cationic polymer, polyethyleneimine, which significantly increases siRNA encapsulation. © 2012 Springer Science+Business Media, LLC. Source

Dimas K.S.,University of Thessaly | Pantazis P.,University of Thessaly | Ramanujam R.,ADNA Inc.
In Vivo | Year: 2012

Chios mastic gum (CMG) is a resin produced by the plant Pistacia lentiscus var. chia. CMG is used to extract the mastic gum essential oil (MGO). CMG and MGO consist of nearly 70 constituents and have demonstrated numerous and diverse biomedical and pharmacological properties including (a) eradication of bacteria and fungi that may cause peptic ulcers, tooth plaque formation and malodor of the mouth and saliva; (b) amelioration or dramatic reduction of symptoms of autoimmune diseases by inhibiting production of pro-inflammatory substances by activated macrophages, production of cytokines by peripheral blood mononuclear cells in patients with active Crohn's disease, and suppression of production of inflammatory cytokines and chemokines in an asthma model in mice; (c) protection of the cardiovascular system by effectively lowering the levels of total serum cholesterol, low-density lipoprotein and triglycerides in rats, and protection of low-density lipoprotein from oxidation in humans; (d) induction of apoptosis in human cancer cells in vitro and extensive inhibition of growth of human tumors xenografted in immunodeficient mice; and (e) improvement of symptoms in patients with functional dyspepsia. Collectively taken, these numerous and diverse medical and pharmaceutical properties of CMG and MGO warrant further research in an effort to enhance specific properties and identify specific constituent(s) that might be associated with each property. Source

Bowman C.D.,ADNA Inc. | Johnson R.P.,Muons, Inc.
IPAC 2011 - 2nd International Particle Accelerator Conference | Year: 2011

Reactors built using solid fissile materials sealed in fuel rods have an inherent safety problem in that volatile radioactive materials in the rods are accumulated and can be released in dangerous amounts. Accelerator parameters for subcritical reactors that have been considered in recent studies have primarily been based on using solid nuclear fuel much like that used in all operating critical reactors. An attractive alternative reactor design that used molten salts was experimentally studied at ORNL in the 1960s, where a critical molten salt reactor was successfully operated using enriched U235 or U233 tetrafluoride fuels. These experiments give confidence that accelerator-driven subcritical molten salt reactors will work as well or better than conventional reactors since they will have better efficiency due to their higher operating temperature, the inherent safety of subcritical operation, and constant purging of volatile radioactive elements to eliminate their accumulation and potential accidental release in dangerous amounts. Copyright © 2011 by IPAC'11/EPS-AG. Source

Sureban S.M.,The University of Oklahoma Health Sciences Center | May R.,The University of Oklahoma Health Sciences Center | Lightfoot S.A.,The University of Oklahoma Health Sciences Center | Hoskins A.B.,The University of Oklahoma Health Sciences Center | And 12 more authors.
Cancer Research | Year: 2011

Pancreatic cancer is an exceptionally aggressive disease in great need of more effective therapeutic options. Epithelial-mesenchymal transition (EMT) plays a key role in cancer invasion and metastasis, and there is a gain of stem cell properties during EMT. Here we report increased expression of the putative pancreatic stem cell marker DCAMKL-1 in an established KRAS transgenic mouse model of pancreatic cancer and in human pancreatic adenocarcinoma. Colocalization of DCAMKL-1 with vimentin, a marker of mesenchymal lineage, along with 14-3-3 s was observed within premalignant PanIN lesions that arise in the mouse model. siRNA-mediated knockdown of DCAMKL-1 in human pancreatic cancer cells induced microRNA miR-200a, an EMT inhibitor, along with downregulation of EMT-associated transcription factors ZEB1, ZEB2, Snail, Slug, and Twist. Furthermore, DCAMKL-1 knockdown resulted in downregulation of c-Myc and KRAS through a let-7a microRNA-dependent mechanism, and downregulation of Notch-1 through a miR-144 microRNA-dependent mechanism. These findings illustrate direct regulatory links between DCAMKL-1, microRNAs, and EMT in pancreatic cancer. Moreover, they demonstrate a functional role for DCAMKL-1 in pancreatic cancer. Together, our results rationalize DCAMKL-1 as a therapeutic target for eradicating pancreatic cancers. ©2011 AACR. Source

May R.,The University of Oklahoma Health Sciences Center | Sureban S.M.,The University of Oklahoma Health Sciences Center | Lightfoot S.A.,The University of Oklahoma Health Sciences Center | Hoskins A.B.,The University of Oklahoma Health Sciences Center | And 10 more authors.
American Journal of Physiology - Gastrointestinal and Liver Physiology | Year: 2010

Stem cells are critical in maintaining adult homeostasis and have been proposed to be the origin of many solid tumors, including pancreatic cancer. Here we demonstrate the expression patterns of the putative intestinal stem cell marker DCAMKL-1 in the pancreas of uninjured C57BL/6 mice compared with other pancreatic stem/progenitor cell markers. We then determined the viability of isolated pancreatic stem/progenitor cells in isotransplantation assays following DCAMKL-1 antibody-based cell sorting. Sorted cells were grown in suspension culture and injected into the flanks of athymic nude mice. Here we report that DCAMKL-1 is expressed in the main pancreatic duct epithelia and islets, but not within acinar cells. Coexpression was observed with somatostatin, NGN3, and nestin, but not glucagon or insulin. Isolated DCAMKL-1+ cells formed spheroids in suspension culture and induced nodule formation in isotransplantation assays. Analysis of nodules demonstrated markers of early pancreatic development (PDX-1), glandular epithelium (cytokeratin-14 and Ep-CAM), and isletlike structures (somatostatin and secretin). These data taken together suggest that DCAMKL-1 is a novel putative stem/progenitor marker, can be used to isolate normal pancreatic stem/progenitors, and potentially regenerates pancreatic tissues. This may represent a novel tool for regenerative medicine and a target for anti-stem cell-based therapeutics in pancreatic cancer. Copyright © 2010 the American Physiological Society. Source

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