Laboratory Investigation - Table of Contents alert Volume 93 Issue 8

TABLE OF CONTENTS Volume 93, Issue 8 (August 2013) In this issue Inside LI Pathobiology in Focus Research Articles Also new AOP Sign up for e-alerts Recommend to your library Web feed Subscribe Advertisement   Recommended by the Editors of LI: Melanoma genotypes and phenotypes get personal    Inside LI Top Inside Lab Invest 2013 93: 856-857; 10.1038/labinvest.2013.88 Full Text Pathobiology in Focus Top Melanoma genotypes and phenotypes get personal Melanoma, a chemoresistant tumor with diverse clinical presentations and genomic abnormalities, is often lethal. This review highlights progress in melanoma biology, diagnostics and therapeutics and outlines the challenges that still face the field. Pathologists are making a transitional journey from morphological to molecular-based diagnostics, facilitating the individualization of drug selection for melanoma patients. Jose M Pimiento, Eileen M Larkin, Keiran SM Smalley, Ginger L Wiersma, Noel R Monks, Inna V Fedorenko, Chelsea A Peterson and Brian J Nickoloff 2013 93: 858-867; advance online publication, July 1, 2013; 10.1038/labinvest.2013.84 Abstract | Full Text Research Articles Top ANGIOGENESIS, CARDIOVASCULAR AND PULMONARY SYSTEMS Heme oxygenase-1 expression protects the heart from acute injury caused by inducible Cre recombinase Heme oxygenase-1 (HO-1) plays protective a role in cardiovascular disease, but the temporal requirements for HO-1 induction relative to injury need to be elucidated. This study describes a new transgenic animal model that offers stable HO-1 expression, an improvement over the chemical inducers of HO-1 that are frequently used in animal models to achieve transient upregulation. Travis D Hull, Subhashini Bolisetty, Angela C DeAlmeida, Silvio H Litovsky, Sumanth D Prabhu, Anupam Agarwal and James F George 2013 93: 868-879; advance online publication, June 3, 2013; 10.1038/labinvest.2013.74 Abstract | Full Text Inhibition of reactive oxygen species generation attenuates TLR4-mediated proinflammatory and proliferative phenotype of vascular smooth muscle cells Reactive oxygen species (ROS) are associated with vasculature dysfunction. This study identifies ROS as a key component in toll-like receptor 4 (TLR4)-mediated vascular inflammation and intimal hyperplasia. Inhibiting the primary source of ROS may attenuate the TLR4-mediated proliferative and proinflammatory phenotype of vascular smooth muscle cells, and reduce detrimental arterial remodeling and inflammation found in the early stages of atherosclerosis. Yan Pi, Li-li Zhang, Bing-hu Li, Lu Guo, Xiao-jie Cao, Chang-yue Gao and Jing-cheng Li 2013 93: 880-887; advance online publication, June 17, 2013; 10.1038/labinvest.2013.79 Abstract | Full Text BLOOD, LYMPHATICS, IMMUNE SYSTEM AND STEM CELLS PepT1 expressed in immune cells has an important role in promoting the immune response during experimentally induced colitis The dipeptide co-transporter PepT1 is expressed in immune cells near the lamina propria of the small and large intestines. In PepT1-deficient mice with chemically induced colitis, symptoms are less severe, colonic architecture is less disrupted, and immune cell infiltration is reduced, compared to control animals. PepT1 regulates the secretion of pro-inflammatory cytokines triggered by bacteria and thus plays an important role in the induction of colitis. Saravanan Ayyadurai, Moiz A Charania, Bo Xiao, Emilie Viennois and Didier Merlin 2013 93: 888-899; advance online publication, June 24, 2013; 10.1038/labinvest.2013.77 Abstract | Full Text Dynamics of connective-tissue localization during chronic Borrelia burgdorferi infection Borrelia burgdorferi (Bb), the causative agent of Lyme disease, can persist as a low-level chronic infection. A mouse model of Bb infection reveals that Bb-specific antibodies drive Bb into connective tissue, but re-infection of organs previously cleared by the immune system subsequently occur. A host proteoglycan in connective tissue, decorin, protects Bb from clearance by the immune system by binding to an immunogenic epitope. Denise M Imai, Sunlian Feng, Emir Hodzic and Stephen W Barthold 2013 93: 900-910; advance online publication, June 24, 2013; 10.1038/labinvest.2013.81 Abstract | Full Text DEVELOPMENT, MATRIX BIOLOGY AND AGING Fibroblasts endocytose and degrade transthyretin aggregates in transthyretin-related amyloidosis Transthyretin (TTR)-related amyloidosis is a fatal disorder characterized by systemic extracellular deposition of TTR amyloid fibrils. This paper reveals that fibroblasts have the capacity to endocytose and degrade transthyretin aggregates extracellularly by secreting matrix metalloproteinases. TTR clearance by fibroblasts may have important implications for the development, progression, and regression of this disease. Yohei Misumi, Yukio Ando, Nádia P Gonçalves and Maria J Saraiva 2013 93: 911-920; advance online publication, July 1, 2013; 10.1038/labinvest.2013.83 Abstract | Full Text Podoplanin-mediated cell adhesion through extracellular matrix in oral squamous cell carcinoma Podoplanin (PDPN), a glycoprotein specific to lymphatic endothelial cells, is a biomarker for oral cancer. This study elucidates the molecular role of PDPN in oral squamous carcinoma cells. PDPN, in collaboration with CD44, tethers the cells to extracellular matrices to inhibit their scattering but does not directly affect their proliferation and migration. Masayuki Tsuneki, Manabu Yamazaki, Satoshi Maruyama, Jun Cheng and Takashi Saku 2013 93: 921-932; advance online publication, July 1, 2013; 10.1038/labinvest.2013.86 Abstract | Full Text GENITOURINARY AND REPRODUCTIVE SYSTEMS Chronic administration of EP4-selective agonist exacerbates albuminuria and fibrosis of the kidney in streptozotocin-induced diabetic mice through IL-6 This study investigates the role of prostaglandin E2 (PGE2) and its receptor, prostaglandin E receptor 4 (EP4), in diabetic nephropathy. Because hyperglycemia increases COX-2-mediated production of PGE2, the authors employed an EP4 agonist in a mouse model of diabetes. They found that EP4 activation exacerbates inflammation and fibrosis of the kidney by increasing production of interleukin 6 (IL-6), which is a novel function for this cytokine. Riyaz Mohamed, Calpurnia Jayakumar and Ganesan Ramesh 2013 93: 933-945; advance online publication, July 1, 2013; 10.1038/labinvest.2013.85 Abstract | Full Text MODELS AND TECHNIQUES Ex vivo evaluation of antifibrotic compounds in skin scarring: EGCG and silencing of PAI-1 independently inhibit growth and induce keloid shrinkage Keloid disease is a disfiguring fibroproliferative disorder without effective treatments. A newly developed human keloid organ culture model was used to test two candidate anti-fibrotic therapies that target plasminogen activator 1, (-) - epigallcatechin-3-gallate and an interfering RNA. This study shows that both compounds effectively inhibit growth and induce shrinkage of human keloid tissue. Farhatullah Syed, Rania A Bagabir, Ralf Paus and Ardeshir Bayat 2013 93: 946-960; advance online publication, July 8, 2013; 10.1038/labinvest.2013.82 Abstract | Full Text Integrated RNA extraction and RT-PCR for semi-quantitative gene expression studies on a microfluidic device Cytochrome P450 enzymes are involved in the metabolism of xenobiotics, including many commonly prescribed drugs. This paper describes the development of a rapid throughput microfluidic methodology for investigating expression levels of cytochrome P450 genes, which may be useful for development of pharmaceutical drug screens and diagnostic tests to guide personalized drug regimens. Kirsty J Shaw, Elizabeth M Hughes, Charlotte E Dyer, John Greenman and Stephen J Haswell 2013 93: 961-966; advance online publication, May 27, 2013; 10.1038/labinvest.2013.76 Abstract | Full Text Please note that you need to be a subscriber or site-licence holder to enjoy full-text access to Laboratory Investigation. 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