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Laboratory Investigation - Table of Contents alert Volume 97 Issue 8

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Laboratory Investigation


Volume 97, Issue 8 (August 2017)

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Research Articles
Technical Report

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Inside the USCAP Journals

2017 97: 888-889; 10.1038/labinvest.2017.68

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Research Articles



Spleen-derived lipocalin-2 in the portal vein regulates Kupffer cells activation and attenuates the development of liver fibrosis in mice

A large number of Gr1-positive cells in the enlarged spleens of patients with liver fibrosis express Lcn2, an antimicrobial protein. This splenic Lcn2 production is induced by gut-derived products that flow into the liver through the portal vein. The splenic Lcn2 suppresses excessive Kupffer cell activation, and inhibits hepatic stellate cell activation. Thus, splenic Lcn2 might have an important role in regulating the immune tolerance of the liver during development of liver fibrosis.

Tomonori Aoyama, Kyoko Kuwahara-Arai, Akira Uchiyama, Kazuyoshi Kon, Hironao Okubo, Shunhei Yamashina, Kenichi Ikejima, Shigehiro Kokubu, Akihisa Miyazaki and Sumio Watanabe

2017 97: 890-902; advance online publication, May 15, 2017; 10.1038/labinvest.2017.44

Abstract | Full Text

Thymidine phosphorylase promotes metastasis and serves as a marker of poor prognosis in hepatocellular carcinoma

This study clarifies the important role of thymidine phosphorylase (TP) in metastasis of hepatocellular carcinoma (HCC). High expression of TP is a predictor of high metastasis potential and poor prognosis in HCC patients. The mechanism relies on increasing expression and activity of MMP2 and MMP9, which is regulated by the MAPK pathway under the influence of TP.

Qiang Zhang, Yang Zhang, Xuejiao Hu, Yuan Qin, Weilong Zhong, Jing Meng, Ting Xiao, Chunhong Zhang, Meng Li, Shuang Chen, Huijuan Liu, Yanrong Liu, Tao Sun and Cheng Yang

2017 97: 903-912; advance online publication, May 22, 2017; 10.1038/labinvest.2017.51

Abstract | Full Text


Correlation between histone acetylation and expression of Notch1 in human lung carcinoma and its possible role in combined small-cell lung carcinoma

The authors investigated the role of histone acetylation in the development of combined small cell lung carcinoma (cSCLC). They show that histone deacetylation leads to Notch1 silencing in cSCLC and that restoration of Notch1 expression can cause the concurrent appearance of some epithelial-like areas, thus providing a possible mechanism for histogenesis of cSCLC.

Wael Abdo Hassan, Shin-ichiro Takebayashi, Mohamed Osama Ali Abdalla, Kosuke Fujino, Shinji Kudoh, Yamoto Motooka, Yonosuke Sato, Yoshiki Naito, Koichi Higaki, Joeji Wakimoto, Seiji Okada, Mituyoshi Nakao, Yuichi Ishikawa and Takaaki Ito

2017 97: 913-921; advance online publication, April 17, 2017; 10.1038/labinvest.2017.36

Abstract | Full Text

Activation of NLRP3 inflammasomes contributes to hyperhomocysteinemia-aggravated inflammation and atherosclerosis in apoE-deficient mice OPEN

In this paper, the authors reveal that the activation of NLRP3 inflammasomes modulates the proinflammatory effect of hyperhomocysteinemia (HHcy), thereby contributing to atherogenesis. Reactive oxygen species (ROS) scavenger prevents HHcy-induced activation of NLRP3 inflammasomes in vitro and in vivo, indicating an important role of ROS in NLRP3 inflammasome activation-induced HHcy.

Renqing Wang, Yiqin Wang, Nana Mu, Xiaoying Lou, Weixuan Li, Yanming Chen, Dong Fan and Hongmei Tan

2017 97: 922-934; advance online publication, April 10, 2017; 10.1038/labinvest.2017.30

Abstract | Full Text

Accelerated atherosclerosis development in C57Bl6 mice by overexpressing AAV-mediated PCSK9 and partial carotid ligation

The authors developed an accelerated mouse model of atherosclerosis using an adeno-associated virus containing mutant PCSK9 followed by partial carotid ligation surgery to induce hyperlipidemia, disturbed blood flow and atherosclerosis. This model enables rapid study of a gene-of-interest using transgenic or knockout mice without backcrossing them to ApoE or LDLR null background.

Sandeep Kumar, Dong-Won Kang, Amir Rezvan and Hanjoong Jo

2017 97: 935-945; advance online publication, May 15, 2017; 10.1038/labinvest.2017.47

Abstract | Full Text


The kinesin KIF14 is overexpressed in medulloblastoma and downregulation of KIF14 suppressed tumor proliferation and induced apoptosis

Kinesin family member 14 (KIF14) is a member of kinesin family proteins located on chromosome 1q. This study describes the tight association of upregulation of KIF14 and genomic gain of chromosome 1q in medulloblastoma. The authors show that KIF14 affects medulloblastoma tumorigenesis by enhancing cell viability, colony formation, migration and invasion. These results indicate that KIF14 is a potential therapeutic target for MB.

Kay Ka-Wai Li, Yan Qi, Tian Xia, Aden Ka-Yin Chan, Zhen-Yu Zhang, Abudumijiti Aibaidula, Rong Zhang, Liangfu Zhou, Yu Yao and Ho-Keung Ng

2017 97: 946-961; advance online publication, May 15, 2017; 10.1038/labinvest.2017.48

Abstract | Full Text


Pyrimidine tract-binding protein 1 mediates pyruvate kinase M2-dependent phosphorylation of signal transducer and activator of transcription 3 and oncogenesis in anaplastic large cell lymphoma

This study describes the interaction between pyruvate kinase M2 (a critical regulator of glycolysis) and PTBP1 (polypyrimidine tract-binding protein), and outlines the characteristics of this interaction as well as the role the proteins play in promoting downstream signaling and oncogenesis in NPM-ALK-positive anaplastic large cell lymphoma (ALCL). This evidence suggests that PTBP1 is a potential therapeutic target in ALCL.

Steven R Hwang, Carlos Murga-Zamalloa, Noah Brown, Johnvesly Basappa, Scott RP McDonnell, Veronica Mendoza-Reinoso, Venkatesha Basrur, Ryan Wilcox, Kojo Elenitoba-Johnson and Megan S Lim

2017 97: 962-970; advance online publication, April 17, 2017; 10.1038/labinvest.2017.39

Abstract | Full Text


The role of angiopoietin-2 in nucleus pulposus cells during human intervertebral disc degeneration

This study provides new insights into the role of the angiopoietins in the pathogenesis of intervertebral disc (IVD) degeneration. The authors found that Ang-2 in suppresses cell adhesion and viability and promotes the apoptosis of nucleus pulposus (NP) cells, and inhibits pathways stimulated by Ang-1 and fibronectin. Ang-2 release during IVD degeneration causes higher ratio of Ang-2 to Ang-1, which further inhibits NP cell viability and adhesion, promoting apoptosis by blocking PI3K/Akt signaling.

Kun Wang, Wei Liu, Yu Song, Xinghuo Wu, Yukun Zhang, Shuai Li, Yong Gao, Ji Tu, Yingle Liu and Cao Yang

2017 97: 971-982; advance online publication, April 10, 2017; 10.1038/labinvest.2017.35

Abstract | Full Text

Microfluidics for rapid cytokeratin immunohistochemical staining in frozen sections

The authors describe the optimization of a complete pan-cytokeratin chromogenic immunostaining protocol on frozen sections using a microfluidic tissue processor in a protocol that takes less than 12 minutes. The results show specificity and low levels of background. The dimensions of the microfluidic prototype device are compatible with the space constraints of an intraoperative pathology laboratory.

Saska Brajkovic, Diego G Dupouy, Laurence de Leval and Martin AM Gijs

2017 97: 983-991; advance online publication, May 29, 2017; 10.1038/labinvest.2017.49

Abstract | Full Text

Technical Report



Multiplexed ion beam imaging analysis for quantitation of protein expresssion in cancer tissue sections

Multiplexed ion-beam imaging analysis (MIBI) is a tissue section analysis technology that uses mass spectrometry to detect metal-tagged detection reagents. Quantitation based on MIBI analysis corresponds with pathologistdetermined and immunofluorescence-based automated quantitative analysis scores in a blinded study using the well-established HER2 model. These studies provide initial validation for quantitation of protein expression level by MIBI.

Sandra Rost, Jennifer Giltnane, Jennifer M Bordeaux, Chuck Hitzman, Hartmut Koeppen and Scot D Liu

2017 97: 992-1003; advance online publication, May 29, 2017; 10.1038/labinvest.2017.50

Abstract | Full Text

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