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Leung E.L.-H.,University of Hong Kong | Fiscus R.R.,Nevada Cancer Institute | Fiscus R.R.,University of Southern Nevada | Tung J.W.,Nevada Cancer Institute | And 7 more authors.
PLoS ONE | Year: 2010

Background: The cancer stem cell theory hypothesizes that cancers are perpetuated by cancer stem cells (CSC) or tumor initiating cells (TIC) possessing self-renewal and other stem cell-like properties while differentiated non-stem/initiating cells have a finite life span. To investigate whether the hypothesis is applicable to lung cancer, identification of lung CSC and demonstration of these capacities is essential. Methodology/Principal Finding: The expression profiles of five stem cell markers (CD34, CD44, CD133, BMI1 and OCT4) were screened by flow cytometry in 10 lung cancer cell lines. CD44 was further investigated by testing for in vitro and in vivo tumorigenecity. Formation of spheroid bodies and in vivo tumor initiation ability were demonstrated in CD44+ cells of 4 cell lines. Serial in vivo tumor transplantability in nude mice was demonstrated using H1299 cell line. The primary xenografts initiated from CD44+ cells consisted of mixed CD44+ and CD44- cells in similar ratio as the parental H1299 cell line, supporting in vivo differentiation. Semi-quantitative Real-Time PCR (RT-PCR) showed that both freshly sorted CD44+ and CD44+ cells derived from CD44+-initiated tumors expressed the pluripotency genes OCT4/POU5F1, NANOG, SOX2. These stemness markers were not expressed by CD44- cells. Furthermore, freshly sorted CD44+ cells were more resistant to cisplatin treatment with lower apoptosis levels than CD44- cells. Immunohistochemical analysis of 141 resected non-small cell lung cancers showed tumor cell expression of CD44 in 50.4% of tumors while no CD34, and CD133 expression was observed in tumor cells. CD44 expression was associated with squamous cell carcinoma but unexpectedly, a longer survival was observed in CD44-expressing adenocarcinomas. Conclusion/Significance: Overall, our results demonstrated that stem cell-like properties are enriched in CD44-expressing subpopulations of some lung cancer cell lines. Further investigation is required to clarify the role of CD44 in tumor cell renewal and cancer propagation in the in vivo environment.© 2010 Leung et al.

Nadimi H.,Boston University | Wesamaa H.,University of Helsinki | Janket S.-J.,Boston University | Bollu P.,University of Southern Nevada | Meurman J.H.,University of Helsinki
British Dental Journal | Year: 2011

Background Various sugar substitutes have been introduced and are widely used in confections and beverages to avoid tooth decay from sugar and other fermentable carbohydrates. One group of sugar substitutes are sugar alcohols or polyols. They have been specifically used in foods for diabetic patients because polyols are not readily absorbed in the intestine and blood stream, preventing post-prandial elevation of glucose level. Additionally they may lower caloric intake. Methods We searched PubMed, Cochrane Controlled Trials Registry, Cochrane Oral Health Review, Centre for Reviews and Dissemination in the UK, National Library for Public Health and a Centre for Evidence Based Dentistry website up to the end of October 2010, using the search terms 'sugar alcohol' or 'sugar-free' or 'polyols' and combined with a search with terms 'dental caries' or 'dental erosion'. Results Xylitol, a polyol, has been approved by the US Food and Drug Administration for its non-cariogenic properties that actually reduce the risk of dental decay and recently, the European Union also officially approved a health claim about xylitol as a 'tooth friendly' component in chewing gums. Although the presence of acidic flavourings and preservatives in sugar-free products has received less attention, these additives may have adverse dental health effects, such as dental erosion. Furthermore, the term sugar-free may generate false security because people may automatically believe that sugar-free products are safe on teeth.Conclusion We concluded that polyol-based sugar-free products may decrease dental caries incidence but they may bring another dental health risk, dental erosion, if they contain acidic flavouring. There is a need for properly conducted clinical studies in this area. © 2011 Macmillan Publishers Limited. All rights reserved.

Scott M.A.,University of Southern Nevada | Nguyen V.T.,University of California at Los Angeles | Levi B.,Stanford University | James A.W.,University of California at Los Angeles
Stem Cells and Development | Year: 2011

There has been a recent increase in our understanding in the isolation, culture, and differentiation of mesenchymal stem cells (MSCs). Concomitantly, the availability of MSCs has increased, with cells now commercially available, including human MSCs from adipose tissue and bone marrow. Despite an increased understanding of MSC biology and an increase in their availability, standardization of techniques for adipogenic differentiation of MSCs is lacking. The following review will explore the variability in adipogenic differentiation in vitro, specifically in 3T3-L1 and primary MSCs derived from both adipose tissue and bone marrow. A review of alternative methods of adipogenic induction is also presented, including the use of specific peroxisome proliferator- activated receptor-gamma agonists as well as bone morphogenetic proteins. Finally, we define a standard, commonly used adipogenic differentiation medium in the hopes that this will be adopted for the future standardization of laboratory techniques-however, we also highlight the essentially arbitrary nature of this decision. With the current, rapid pace of electronic publications, it becomes imperative for standardization of such basic techniques so that interlaboratory results may be easily compared and interpreted. © Copyright 2011, Mary Ann Liebert, Inc.

Leung E.L.,University of Nevada, Las Vegas | Leung E.L.,Chinese University of Hong Kong | Wong J.C.,University of Nevada, Las Vegas | Johlfs M.G.,University of Nevada, Las Vegas | And 6 more authors.
Molecular Cancer Research | Year: 2010

Previously, we showed that basal activity of nitric oxide (NO)/cyclic GMP (cGMP)/protein kinase G (PKG) signaling pathway protects against spontaneous apoptosis and confers resistance to cisplatin-induced apoptosis in human ovarian cancer cells. The present study determines whether basal PKG kinase activity regulates Src family kinase (SFK) activity and proliferation in these cells. PKG-Iα was identified as predominant isoform in both OV2008 (cisplatin-sensitive, wild-type p53) and A2780cp (cisplatin-resistant, mutated p53) ovarian cancer cells. In both cell lines, ODQ (inhibitor of endogenous NO-induced cGMP biosynthesis), DT-2 (highly specific inhibitor of PKG-Iα kinase activity), and PKG-Iα knockdown (using small interfering RNA) caused concentration-dependent inhibition of DNA synthesis (assessed by bromodeoxyuridine incorporation), indicating an important role of basal cGMP/PKG-Iα kinase activity in promoting cell proliferation. DNA synthesis in OV2008 cells was dependent on SFK activity, determined using highly selective SFK inhibitor, 4-(4′-phenoxyanilino)-6,7-dimethoxyquinazoline (SKI-1). Studies using DT-2 and PKG-Iα small interfering RNA revealed that SFK activity was dependent on PKG-Iα kinase activity. Furthermore, SFK activity contributed to endogenous tyrosine phosphorylation of PKG-Iα in OV2008 and A2780cp cells. In vitro coincubation of recombinant human c-Src and PKG-Iα resulted in c-Src-mediated tyrosine phosphorylation of PKG-Iα and enhanced c-Src autophosphorylation/activation, suggesting that human c-Src directly tyrosine phosphorylates PKG-Iα and the c-Src/PKG-Iα interaction enhances Src kinase activity. Epidermal growth factor-induced stimulation of SFK activity in OV2008 cells increased PKG-Iα kinase activity (indicated by Ser239 phosphorylation of the PKG substrate vasodilator-stimulated phosphoprotein), which was blocked by both SKI-1 and SU6656. The data suggest an important role of Src/PKG-Iα interaction in promoting DNA synthesis/cell proliferation in human ovarian cancer cells. The NO/cGMP/PKG-Iα signaling pathway may provide a novel therapeutic target for disrupting ovarian cancer cell proliferation. ©2010 AACR.

Hatcher D.C.,University of Southern Nevada
Sleep Medicine Clinics | Year: 2010

Imaging plays a role in the anatomic assessment of the airway and adjacent structures. This article discusses the use of 3-dimensional (3D) imaging (cone beam computed tomography [CBCT]) to evaluate the airway and selected regional anatomic variables that may contribute to obstructive sleep-disordered breathing (OSDB) in patients. CBCT technology uses a cone-shaped x-ray beam with a special image intensifier and a solid-state sensor or an amorphous silicon plate for capturing the image. Incorporation of 3D imaging into daily practice will allow practitioners to readily evaluate and screen patients for phenotypes associated with OSDB. © 2010 Elsevier Inc. All rights reserved.

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