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Laboratory Investigation - Table of Contents alert Volume 97 Issue 7

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Laboratory Investigation


Volume 97, Issue 7 (July 2017)

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Inside the USCAP Journals
Research Articles
Technical Reports

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Inside the USCAP Journals


Malignant melanoma: from cause to cure

2017 97: 762-763; 10.1038/labinvest.2017.58

Full Text

Research Articles



Angiotensin-converting enzyme affects the presentation of MHC class II antigens

The peptidase angiotensin converting enzyme participates in processing MHC class II peptides, which, in turn, activate T helper cells and facilitate antibody production. Manipulation of the activity of this peptidase by, for example, pharmacological inhibition, may prove to be a novel strategy to alter the immune response.

Tuantuan Zhao, Kenneth E Bernstein, Jianmin Fang and Xiao Z Shen

2017 97: 764-771; advance online publication, April 10, 2017; 10.1038/labinvest.2017.32

Abstract | Full Text

Disruption of direct 3D telomere–TRF2 interaction through two molecularly disparate mechanisms is a hallmark of primary Hodgkin and Reed–Sternberg cells

Disruption of direct 3D telomere- telomere repeat binding factor 2 (TRF2) interaction is a hallmark of primary Hodgkin and Reed-Sternberg cells. Two different molecular mechanisms appear to be involved: the first, attrition of telomeres and up-regulation of TRF2 protein that is not associated with teleomeres; and the second, with telomere deprotection due to an impressive loss of TRF2 that is physically linked to telomeres. This second pattern is typical of LMP1+ EBV-associated classical Hodgkin lymphoma but is not restricted to it.

Hans Knecht, Nathalie A Johnson, Tina Haliotis, Daniel Lichtensztejn and Sabine Mai

2017 97: 772-781; advance online publication, April 24, 2017; 10.1038/labinvest.2017.33

Abstract | Full Text


Cytochrome P450 (CYP) epoxygenases as potential targets in the management of impaired diabetic wound healing

This paper shows that reduced expression of cytochrome P450 epoxygenases may play a role in the pathogenesis of impaired diabetic wound healing. Exogenous epoxyeicosatrienoic acid administration significantly improves wound healing in ob/ob mice, possibly through attenuation of inflammatory responses and promotion of angiogenesis.

Huichen Zhao, Jicui Chen, Jiachao Chai, Yuchao Zhang, Cong Yu, Zhe Pan, Peng Gao, Chen Zong, Qingbo Guan, Yuqin Fu and Yuantao Liu

2017 97: 782-791; advance online publication, March 20, 2017; 10.1038/labinvest.2017.21

Abstract | Full Text

Advanced oxidation protein products promote NADPH oxidase-dependent β-cell destruction and dysfunction through the Bcl-2/Bax apoptotic pathway

This study reveals new targets for the prevention and treatment of β-cell destruction seen in diverse disorders such as diabetes, chronic kidney disease, obesity and metabolic syndrome. The authors show that accumulation of advanced oxidation protein products triggers β-cell apoptosis and results in deficiency of insulin secretion through NADPH oxidase-dependent O2 generation via Bcl-2 and Bax.

Min Liang, Aiqing Li, Aiju Lou, Xifang Zhang, Youyuan Chen, Lei Yang, Yumin Li, Shenglin Yang and Fan Fan Hou

2017 97: 792-805; advance online publication, March 6, 2017; 10.1038/labinvest.2017.24

Abstract | Full Text


Endothelial cell-specific activation of transforming growth factor-β signaling in mice induces cutaneous, visceral, and microvascular fibrosis

To examine microvascular alterations in systemic sclerosis (SSc), novel transgenic mice with inducible endothelial cell-specific constitutively active TGF-β receptor I expression were generated. The mice displayed severe cutaneous and visceral fibrosis and marked perivascular and subendothelialfibrosis, mimicking SSc characteristic features. Increased fibrosis and myofibroblast activation gene expression were demonstrated.

Peter J Wermuth, Kellan R Carney, Fabian A Mendoza, Sonsoles Piera-Velazquez and Sergio A Jimenez

2017 97: 806-818; advance online publication, March 27, 2017; 10.1038/labinvest.2017.23

Abstract | Full Text


Hedgehog signaling pathway affects the sensitivity of hepatoma cells to drug therapy through the ABCC1 transporter

This study employed a newly characterized CD133/EpCAM subpopulation (Huh-7-DN) that features high hedgehog signaling activity and epithelial-mesenchymal transition to investigate how hedgehog signaling controls chemosensitivity by an ATP-binding complex molecule, ABCC1. The findings demonstrate that transcription factor Gli-2 governs the target gene ABCC1 that modulates drug resistance in this subpopulation.

Jia Ding, Xiao-Tian Zhou, Hao-Yu Zou and Jian Wu

2017 97: 819-832; advance online publication, April 17, 2017; 10.1038/labinvest.2017.34

Abstract | Full Text

Establishment of a mouse model of enalapril-induced liver injury and investigation of the pathogenesis

A mouse model of enalapril-induced liver injury was established by co-treatment with dexamethasone and L-buthionine-(S,R)-sulfoximine, which cause hepatic steatosis and glutathione depletion, respectively. The authors found that oxidative stress and neutrophil infiltration are involved in the pathogenesis of enalapril-induced liver injury.

Yuji Shirai, Shingo Oda, Sayaka Makino, Koichi Tsuneyama and Tsuyoshi Yokoi

2017 97: 833-842; advance online publication, March 6, 2017; 10.1038/labinvest.2017.22

Abstract | Full Text

The Hippo signaling functions through the Notch signaling to regulate intrahepatic bile duct development in mammals

Using conditional knockout mice, the authors found that the excessive bile duct development induced by deficiency of the Hippo signaling pathway tumor suppressor Nf2 is significantly suppressed by heterozygous and homozygous deletion of Notch2 in a dose-dependent manner. These results suggest that the Notch signaling pathway is a downstream effector of the Hippo signaling pathway in regulating intrahepatic bile duct development.

Nan Wu, Quy Nguyen, Ying Wan, Tiaohao Zhou, Julie Venter, Gabriel A Frampton, Sharon DeMorrow, Duojia Pan, Fanyin Meng, Shannon Glaser, Gianfranco Alpini and Haibo Bai

2017 97: 843-853; advance online publication, June 5, 2017; 10.1038/labinvest.2017.29

Abstract | Full Text

Technical Reports



Increased vasohibin-1 expression is associated with metastasis and poor prognosis of renal cell carcinoma patients

Vasohibin-1 (VASH-1), a regulator of angiogenesis, is predominantly expressed in endothelial cells within clear cell renal cell carcinoma (ccRCC) tissue, whereas it is not expressed in non-neoplastic renal tissues. Elevated VASH-1 density is associated with tumor progression and sunitinib treatment. These data suggest that VASH1 may be a prognostic biomarker of ccRCC.

Shuji Mikami, Mototsugu Oya, Takeo Kosaka, Ryuichi Mizuno, Yasumasa Miyazaki, Yasufumi Sato and Yasunori Okada

2017 97: 854-862; advance online publication, March 13, 2017; 10.1038/labinvest.2017.26

Abstract | Full Text

Optimized expression-based microdissection of formalin-fixed lung cancer tissue

This study provides a workflow for expression-based microdissection adapted for lung adenocarcinoma. The authors improved microdissection by optimizing immunostaining intensity, processing of the stained samples and by providing instructions for laser handling. Using this procedure, the authors could enrich mutated EGFR-DNA from lung adenocarcinoma tissue samples. Selectivity and efficiency of microdissection was further demonstrated by pre-post whole-slide image analysis.

Markus Grafen, Thurid R Hofmann, Andreas H Scheel, Julia Beck, Alexander Emmert, Stefan Küffer, Bernhard C Danner, Ekkehard Schütz, Reinhardt Büttner, Andreas Ostendorf, Philipp Ströbel and Hanibal Bohnenberger

2017 97: 863-872; advance online publication, April 24, 2017; 10.1038/labinvest.2017.31

Abstract | Full Text

Fully automated 5-plex fluorescent immunohistochemistry with tyramide signal amplification and same species antibodies

The authors developed a primary antibody/secondary antibody complex heat-deactivation method which enables fully automated fluorescent multiplex immunohistochemistry using unmodified primary antibodies from same species on formalin-fixed, paraffin embedded tissue. This approach allows evaluation of spatial relationships and the functional states of multiple biomarkers on a single slide, and offers great flexibility for research and possibility for in vitro diagnostic product development.

Wenjun Zhang, Antony Hubbard, Tobin Jones, Adriana Racolta, Srabani Bhaumik, Nick Cummins, Liping Zhang, Karl Garsha, Frank Ventura, Mark R Lefever, Zhenqiang Lu, John K Hurley, William A Day, Lidija Pestic-Dragovich, Larry E Morrison and Lei Tang

2017 97: 873-885; advance online publication, May 15, 2017; 10.1038/labinvest.2017.37

Abstract | Full Text

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