Laboratory Investigation - Table of Contents alert Volume 92 Issue 7

TABLE OF CONTENTS Volume 92, Issue 7 (July 2012) In this issue Inside LI Research Articles Also new AOP Sign up for e-alerts Recommend to your library Web feed Subscribe Advertisement Recommended by the Editors: Residual dormant cancer stem-cell foci are responsible for tumor relapse after antiangiogenic metronomic therapy in hepatocellular carcinoma xenografts Currently available chemotherapeutic options for hepatocellular carcinoma are ineffective due in part to tumor resistance to conventional therapies. Ines Martin-Padura and colleagues show that low-dose metronomic administration of cyclophosphamide is an effective treatment in terms of tumor delay and increased survival, and that dormant cancer stem cells are a contributor to tumor relapse. Read this full article now.   Inside LI Top Inside Lab Invest 2012 92: 950-951; 10.1038/labinvest.2012.96 Full Text Research Articles Top HEPATIC AND PANCREATIC SYSTEMS Residual dormant cancer stem-cell foci are responsible for tumor relapse after antiangiogenic metronomic therapy in hepatocellular carcinoma xenografts Treatment of hepatocellular carcinoma with cyclophosphamide results in tumor regression, but dormant cancer stem cells are still detectable. Co-treatment with the CD13-targeting drug, bestatin, leads to slower tumor growth and decreased tumor volume. Therefore, targeting cancer stem cells may be necessary to eradicate residual disease and improve the treatment of liver cancer. Ines Martin-Padura, Paola Marighetti, Alice Agliano, Federico Colombo, Leyre Larzabal, Miriam Redrado, Anne-Marie Bleau, Celia Prior, Francesco Bertolini and Alfonso Calvo 2012 92: 952-966; advance online publication, April 30, 2012; 10.1038/labinvest.2012.65 Abstract | Full Text NK cells from HCV-infected patients effectively induce apoptosis of activated primary human hepatic stellate cells in a TRAIL-, FasL- and NKG2D-dependent manner NK cells from hepatitis C(+) patients effectively induce apoptosis of human activated hepatic stellate cells (HSC) in a TRAIL-, NKG2D-, and FasL-dependent manner. Advanced stages of liver fibrosis were associated with reduced anti-HSC activity of NK cells, suggesting that NK cells play an important anti-fibrotic role in hepatitis C. Andreas Glässner, Marianne Eisenhardt, Benjamin Krämer, Christian Körner, Martin Coenen, Tilman Sauerbruch, Ulrich Spengler and Jacob Nattermann 2012 92: 967-977; advance online publication, March 26, 2012; 10.1038/labinvest.2012.54 Abstract | Full Text Expression of platelet-derived growth factor-C and insulin-like growth factor I in hepatic stellate cells is inhibited by miR-29 A novel mechanism for the antifibrogenic effects of miR-29 in the liver is presented. Expression of miR-29 is decreased in hepatic stellate cells (HSC) transdifferentiating into myofibroblasts during liver fibrogenesis. Overexpression of miR-29 inhibits profibrogenic IGF-I and PDGF-C expression in myofibroblastic HSC through posttranscriptional mRNA interaction, in addition to its known effects on collagen biosynthesis. Monika Kwiecinski, Natalia Elfimova, Andrea Noetel, Ulrich Töx, Hans-Michael Steffen, Ulrich Hacker, Roswitha Nischt, Hans Peter Dienes and Margarete Odenthal 2012 92: 978-987; advance online publication, May 7, 2012; 10.1038/labinvest.2012.70 Abstract | Full Text ANGIOGENESIS, CARDIOVASCULAR AND PULMONARY SYSTEMS RAIN-Droplet: a novel 3D in vitro angiogenesis model A novel three-dimensional model for angiogenesis is applied to investigate biological and pharmacological changes in endothelial sprouting due to the anti-angiogenic tyrosine kinase inhibitor, sorafenib. Unexpectedly, a paradoxical, dose-dependent, pro-angiogenic effect is observed that may impact the clinical application and dosing regimen of the drug. Benjamin D Zeitlin, Zhihong Dong and Jacques E Nör 2012 92: 988-998; advance online publication, May 7, 2012; 10.1038/labinvest.2012.77 Abstract | Full Text Kinetic effects of carbon monoxide inhalation on tissue protection in ventilator-induced lung injury In mechanical ventilator-induced lung injury, carbon monoxide (CO) confers protective effects. The critical time-dependency of CO therapy is determined in this study. Pulmonary edema, cytokine release, and neutrophil recruitment are prevented by application of CO during the first hour of ventilation. Delayed treatment can also be somewhat effective, while pre-treatment had no impact. Simone Faller, Michael Foeckler, Karl M Strosing, Sashko Spassov, Stefan W Ryter, Hartmut Buerkle, Torsten Loop, Rene Schmidt and Alexander Hoetzel 2012 92: 999-1012; advance online publication, March 26, 2012; 10.1038/labinvest.2012.55 Abstract | Full Text ORAL AND GASTROINTESTINAL SYSTEMS LARP7 is a potential tumor suppressor gene in gastric cancer LARP7, a negative regulator of positive transcription elongation factor-b (p-TEFb), is mutated and downregulated in primary gastric cancers. LARP7 inhibition lowers levels of 7sk snRNA, a negative regulator of p-TEFb, and promotes cell proliferation and migration in normal gastric epithelial cells. Thus, LARP7 may function as a gastric tumor suppressor gene. Yulan Cheng, Zhe Jin, Rachana Agarwal, Ke Ma, Jian Yang, Soibrahim Ibrahim, Alexandru V Olaru, Stefan David, Hassan Ashktorab, Duane T Smoot, Mark D Duncan, David F Hutcheon, John M Abraham, Stephen J Meltzer and Yuriko Mori 2012 92: 1013-1019; advance online publication, April 9, 2012; 10.1038/labinvest.2012.59 Abstract | Full Text Metformin protects against the development of fructose-induced steatosis in mice: role of the intestinal barrier function The antidiabetic drug metformin prevents fructose-induced hepatic steatosis and activation of TLR-4-dependent signalling pathways in the liver. Metformin decreases translocation of bacterial endotoxin from the gut through attenuation of the loss of tight junction proteins and the induction of matrix metalloproteinases. Thus, metformin may be a treatment option for nonalcoholic fatty liver disease. Astrid Spruss, Giridhar Kanuri, Carolin Stahl, Stephan C Bischoff and Ina Bergheim 2012 92: 1020-1032; advance online publication, April 23, 2012; 10.1038/labinvest.2012.75 Abstract | Full Text Gene silencing of EREG mediated by DNA methylation and histone modification in human gastric cancers Epiregulin (EREG), a ligand of epidermal growth factor receptor (EGFR), is downregulated in human gastric cancer cells by aberrent methylation of the EREG gene and histone modification. Upregulation of EREG by the hypomethylating agent 5-aza-2′-deoxycytidine enhances the sensitivity of the EGFR inhibitor cetuximab and reduces tumor viability. Jiyeon Yun, Sang-Hyun Song, Jinah Park, Hwang-Phill Kim, Young-Kwang Yoon, Kyung-Hun Lee, Sae-Won Han, Do-Youn Oh, Seock-Ah Im, Yung-Jue Bang and Tae-You Kim 2012 92: 1033-1044; advance online publication, April 16, 2012; 10.1038/labinvest.2012.61 Abstract | Full Text IFNγ contributes to the development of gastric epithelial cell metaplasia in Huntingtin interacting protein 1 related (Hip1r)-deficient mice Loss of gastric parietal cells leads to the emergence of a preneoplastic metaplasia termed SPEM, which is also associated with infiltration of inflammatory cells. This study demonstrates that the proinflammatory cytokine IFNγ is essential for hypertrophy and hyperplasia of the metaplastic mucous cells that develop in SPEM. Zhiping Liu, Elise S Demitrack, Theresa M Keeley, Kathryn A Eaton, Mohamad El-Zaatari, Juanita L Merchant and Linda C Samuelson 2012 92: 1045-1057; advance online publication, April 23, 2012; 10.1038/labinvest.2012.73 Abstract | Full Text BREAST, SKIN, SOFT TISSUE AND BONE Pathological crosstalk in vitro between T lymphocytes and lesional keratinocytes in psoriasis: necessity of direct cell-to-cell contact Keratinocytes from psoriasis vulgaris are greatly affected by IL-2-activated lymphocytes, which modulate the keratinocytes to produce cytokines and chemokines. The absence of contact between keratinocytes and lymphocytes greatly reduces crosstalk. These results highlight the importance of immune mediators produced by cellular interactions in pathological conditions. Guillaume Martin, Simon Guérard, Marie-Michèle Rosa Fortin, Daniel Rusu, Jacques Soucy, Patrice E Poubelle and Roxane Pouliot 2012 92: 1058-1070; advance online publication, April 23, 2012; 10.1038/labinvest.2012.69 Abstract | Full Text Gene disruption of the calcium channel Orai1 results in inhibition of osteoclast and osteoblast differentiation and impairs skeletal development The role of the calcium release-activated calcium channel Orai1 is shown by examination of skeletal changes in Orai1 knockout mice. Both osteoclasts and osteoblasts are impaired by Orai1 deficiency, which results in a complex skeletal phenotype with abnormalities of both bone formation and resorption. Lisa J Robinson, Salvatore Mancarella, Duangrat Songsawad, Irina L Tourkova, John B Barnett, Donald L Gill, Jonathan Soboloff and Harry C Blair 2012 92: 1071-1083; advance online publication, April 30, 2012; 10.1038/labinvest.2012.72 Abstract | Full Text Loss of microRNA-205 expression is associated with melanoma progression Expression of miR-205 in melanoma cells impairs cell motility and migration and decreases F-actin polymerization with only a modest reduction in cell proliferation. Mechanistically, miR-205 overexpression decreases expression of the zinc finger E-box binding homeobox 2 and increases expression of E-cadherin. This study provides a new opportunity for the design of melanoma therapies. Shujing Liu, Michael T Tetzlaff, Aihua Liu, Bernadette Liegl-Atzwanger, Jun Guo and Xiaowei Xu 2012 92: 1084-1096; advance online publication, April 23, 2012; 10.1038/labinvest.2012.62 Abstract | Full Text Advertisement Laboratory Investigation Web Focus: Renal Pathology Kidney disease affects over 26 million Americans, resulting in a high demand for elucidating the pathways that lead to renal pathologies and identifying potential therapeutic targets. In this web focus presented by Laboratory Investigation, recent research in the field of renal pathology is highlighted, FREE for a limited time. Visit www.nature.com/labinvest/webfocus/index.html to access the full listing of articles in this special web focus FREE for a limited time.   Please note that you need to be a subscriber or site-licence holder to enjoy full-text access to Laboratory Investigation. In order to do so, please purchase a subscription. 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