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Hepatic microenvironment

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https://www.readbyqxmd.com/read/28645290/establishment-of-an-orthotopic-patient-derived-xenograft-mouse-model-using-uveal-melanoma-hepatic-metastasis
#1
Ken Kageyama, Masahiro Ohara, Kengo Saito, Shinji Ozaki, Mizue Terai, Michael J Mastrangelo, Paolo Fortina, Andrew E Aplin, Takami Sato
BACKGROUND: Metastatic uveal melanoma is a highly fatal disease; most patients die from their hepatic metastasis within 1 year. A major drawback in the development of new treatments for metastatic uveal melanoma is the difficulty in obtaining appropriate cell lines and the lack of appropriate animal models. Patient-derived xenograft (PDX) tumor models, bearing ectopically implanted tumors at a subcutaneous site, have been developed. However, these ectopically implanted PDX models have obstacles to translational research, including a low engraftment rate, slow tumor growth, and biological changes after multiple passages due to the different microenvironment...
June 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28627746/hepatic-perivascular-mesenchymal-stem-cells-with-myogenic-properties
#2
Sudheer Shenoy P, Bipasha Bose
Pericytes are multipotent mesenchymal stem cells (MSCs) located on the walls of blood vessels in various organs and are characterized as CD146(+) cells.. In this study, we have first immunohistochemically detected such pericytes in the perivascular regions of liver from two mouse genotypes namely wild-type (WT) and myostatin null (Mstn(-/-) ). We further isolated such pericytes using sorting as CD146(+) CD34(-) CD56(-) CD45(-) cells. The main finding of this study involve the contrasting -fibrogenic versus myogenic behavior of liver pericytes from WTMstn(-/-) ) mouse respectively...
June 19, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28615370/molecular-pathways-targeting-the-microenvironment-of-liver-metastases
#3
Simon Milette, Jason K Sicklick, Andrew M Lowy, Pnina Brodt
Curative treatment for metastatic solid cancers remains elusive. The liver, which is nourished by a rich blood supply from both the arterial and portal venous systems is the most common site of visceral metastases, particularly from cancers arising in the gastrointestinal (GI) tract, with colorectal cancer (CRC) being the predominant primary site in Western countries. A mounting body of evidence suggests that the liver microenvironment (LME) provides autocrine and paracrine signals originating from both parenchymal and non-parenchymal cells, that collectively create both pre-and pro-metastatic niches for the development of hepatic metastases...
June 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28614785/drag-reducing-polymers-decrease-hepatic-injury-and-metastases-after-liver-ischemia-reperfusion
#4
Samer Tohme, Marina V Kameneva, Hamza O Yazdani, Vikas Sud, Julie Goswami, Patricia Loughran, Hai Huang, Richard L Simmons, Allan Tsung
INTRODUCTION: Surgery, a crucial therapeutic modality in the treatment of solid tumors, can induce sterile inflammatory processes which can result in metastatic progression. Liver ischemia and reperfusion (I/R) injury, an inevitable consequence of hepatic resection of metastases, has been shown to foster hepatic capture of circulating cancer cells and accelerate metastatic growth. Efforts to reduce these negative consequences have not been thoroughly investigated. Drag reducing polymers (DRPs) are blood-soluble macromolecules that can, in nanomolar concentrations, increase tissue perfusion, decrease vascular resistance and decrease near-wall microvascular concentration of neutrophils and platelets thereby possibly reducing the inflammatory microenvironment...
May 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28608637/regulatory-t-cell-therapy-in-liver-transplantation
#5
REVIEW
Gavin P Whitehouse, Andrew Hope, Alberto Sanchez-Fueyo
Modern immunosuppression drug regimens have produced excellent short term survival after liver transplantation but it is generally accepted that the side effects of these medications remain a significant contributing factor for less satisfactory long term outcomes. The liver has unique tolerogenic properties as evidenced by the higher rates of operational tolerance seen in liver transplant recipients compared to other solid organ transplants and therefore liver transplantation offers an attractive setting in which to study tolerising therapies...
June 13, 2017: Transplant International: Official Journal of the European Society for Organ Transplantation
https://www.readbyqxmd.com/read/28603092/crosstalk-of-liver-immune-cells-and-cell-death-mechanisms-in-different-murine-models-of-liver-injury-and-its-clinical-relevance
#6
Hilal Ahmad Khan, Muhammad Zishan Ahmad, Junaid Ali Khan, Muhammad Imran Arshad
BACKGROUND: Liver inflammation or hepatitis is a result of pluripotent interactions of cell death molecules, cytokines, chemokines and the resident immune cells collectively called as microenvironment. The interplay of these inflammatory mediators and switching of immune responses during hepatotoxic, viral, drug-induced and immune cell-mediated hepatitis decide the fate of liver pathology. The present review aimed to describe the mechanisms of liver injury, its relevance to human liver pathology and insights for the future therapeutic interventions...
June 2017: Hepatobiliary & Pancreatic Diseases International: HBPD INT
https://www.readbyqxmd.com/read/28600137/alternative-splicing-of-hepatitis-b-virus-a-novel-virus-host-interaction-altering-liver-immunity
#7
Marion Duriez, Yassmina Mandouri, Bouchra Lekbaby, Hualin Wang, Aurélie Schnuriger, Francois Redelsperger, Chiara Guerrera, Marine Lefevre, Veronique Fauveau, James Ahodantin, Ivan Quetier, Cerina Chhuon, Samir Gourari, Alexandre Boissonas, Upkar Gill, Patrick Kennedy, Nabil Debzi, Delphine Sitterlin, Mala K Maini, Dina Kremsdorf, Patrick Soussan
BACKGROUND & AIMS: Hepatitis B virus (HBV) RNA can undergo alternative splicing but the relevance of this post-transcriptional regulation remains elusive. Here, the mechanism of HBV alternative splicing regulation and its impact on liver pathogenesis were investigated. METHODS: HBV RNA-interacting proteins were identified by RNA pull-down combined to mass spectrometry analysis. HBV splicing regulation was investigated in chemically and surgically induced liver damage in whole HBV genome transgenic mice and in hepatoma cells...
June 6, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28596109/cytotherapy-with-m1-polarized-macrophages-ameliorates-liver-fibrosis-by-modulating-immune-microenvironment-in-mice
#8
Peng-Fei Ma, Chun-Chen Gao, Jing Yi, Jun-Long Zhao, Shi-Qian Liang, Yang Zhao, Yu-Chen Ye, Jian Bai, Qi-Jun Zheng, Ke-Feng Dou, Hua Han, Hong-Yan Qin
BACKGROUND & AIMS: Macrophages play vital roles in chronic liver injury, and have been tested as a tool for cytotherapy of liver fibrosis. However, macrophages possess ontogenic and functional heterogeneities. Some subsets are pro-fibrotic, whereas others are anti-fibrotic. This study aimed at clarifying which macrophage subset is efficient in cytotherapy of liver fibrosis and the underlying mechanisms. METHODS: Liver fibrosis was induced in mice by carbon tetrachloride (CCl4) injection or bile duct ligation (BDL)...
June 5, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28578016/engineering-in-vitro-models-of-hepatofibrogenesis
#9
Giuseppe Mazza, Walid Al-Akkad, Krista Rombouts
Chronic liver disease is a major cause of morbidity and mortality worldwide marked by chronic inflammation and fibrosis/scarring, resulting in end-stage liver disease and its complications. Hepatic stellate cells (HSCs) are a dominant contributor to liver fibrosis by producing excessive extracellular matrix (ECM), irrespective of the underlying disease aetiologies, and for many decades research has focused on the development of a number of anti-fibrotic strategies targeting this cell. Despite major improvements in two-dimensional systems (2D) by using a variety of cell culture models of different complexity, an efficient anti-fibrogenic therapy has yet to be developed...
May 31, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28572700/peritumoral-epcam-is-an-independent-prognostic-marker-after-curative-resection-of-hbv-related-hepatocellular-carcinoma
#10
Xiao-Meng Dai, Tao Huang, Sheng-Li Yang, Xiu-Mei Zheng, George G Chen, Tao Zhang
Accumulating evidence suggests that the tumor microenvironment has a profound influence on tumor initiation and progression, opening a new avenue for studying tumor biology. Nonetheless, the prognostic values of the peritumoral expression of EpCAM and CD13 remain to be elucidated in hepatocellular carcinoma (HCC) patients. In this study, the expression of EpCAM and CD13 was assessed by immunohistochemistry in peritumoral liver hepatocytes from 106 hepatitis B virus- (HBV-) related HCC patients who had undergone curative hepatectomy...
2017: Disease Markers
https://www.readbyqxmd.com/read/28570270/molecular-imaging-of-oxidized-collagen-quantifies-pulmonary-and-hepatic-fibrogenesis
#11
Howard H Chen, Philip A Waghorn, Lan Wei, Luis F Tapias, Daniel T Schu Hle, Nicholas J Rotile, Chloe M Jones, Richard J Looby, Gaofeng Zhao, Justin M Elliott, Clemens K Probst, Mari Mino-Kenudson, Gregory Y Lauwers, Andrew M Tager, Kenneth K Tanabe, Michael Lanuti, Bryan C Fuchs, Peter Caravan
Fibrosis results from the dysregulation of tissue repair mechanisms affecting major organ systems, leading to chronic extracellular matrix buildup, and progressive, often fatal, organ failure. Current diagnosis relies on invasive biopsies. Noninvasive methods today cannot distinguish actively progressive fibrogenesis from stable scar, and thus are insensitive for monitoring disease activity or therapeutic responses. Collagen oxidation is a universal signature of active fibrogenesis that precedes collagen crosslinking...
June 2, 2017: JCI Insight
https://www.readbyqxmd.com/read/28562206/lipopolysaccharide-induces-the-differentiation-of-hepatic-progenitor-cells-into-myofibroblasts-via-activation-of-the-hedgehog-signalling-pathway
#12
Xiao-Rong Pan, Ying-Ying Jing, Wen-Ting Liu, Zhi-Peng Han, Rong Li, Yang Yang, Jing-Ni Zhu, Xiao-Yong Li, Pei-Pei Li, Li-Xin Wei
Normally, hepatic progenitor cells (HPCs) are activated and differentiate into hepatocytes or bile ductular cells to repair liver damage during liver injury. However, it remains controversial whether the abnormal differentiation of HPCs occurs under abnormal conditions. Lipopolysaccharide (LPS), a component of the microenvironment, promotes liver fibrosis. In the present study, HPCs promoted liver fibrosis in rats following carbon tetrachloride (CCl4) treatment. Meanwhile, the LPS level in the portal vein was elevated and played a primary role in the fate of HPCs...
May 31, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28543403/decellularized-human-liver-is-too-heterogeneous-for-designing-a-generic-extracellular-matrix-mimic-hepatic-scaffold
#13
Giorgio Mattei, Chiara Magliaro, Andrea Pirone, Arti Ahluwalia
Decellularized human livers are considered the perfect extracellular matrix (ECM) surrogate because both three-dimensional architecture and biological features of the hepatic microenvironment are thought to be preserved. However, donor human livers are in chronically short supply, both for transplantation or as decellularized scaffolds, and will become even scarcer as life expectancy increases. It is hence of interest to determine the structural and biochemical properties of human hepatic ECM to derive design criteria for engineering biomimetic scaffolds...
May 23, 2017: Artificial Organs
https://www.readbyqxmd.com/read/28538690/dysregulation-of-mirna-expression-in-cancer-associated-fibroblasts-cafs-and-its-consequences-on-the-tumor-microenvironment
#14
REVIEW
Maren Schoepp, Anda Jana Ströse, Jörg Haier
The tumor microenvironment, including cancer-associated fibroblasts (CAF), has developed as an important target for understanding tumor progression, clinical prognosis and treatment responses of cancer. Cancer cells appear to transform normal fibroblasts (NF) into CAFs involving direct cell-cell communication and epigenetic regulations. This review summarizes the current understanding on miR involvement in cancer cell-tumor environment/stroma communication, transformation of NFs into CAFs, their involved targets and signaling pathways in these interactions; and clinical relevance of CAF-related miR expression profiles...
May 24, 2017: Cancers
https://www.readbyqxmd.com/read/28535799/the-spleen-in-liver-cirrhosis-revisiting-an-old-enemy-with-novel-targets
#15
REVIEW
Liang Li, Mubing Duan, Weisan Chen, An Jiang, Xiaoming Li, Jun Yang, Zongfang Li
The spleen is a secondary lymphoid organ which can influence the progression of multiple diseases, notably liver cirrhosis. In chronic liver diseases, splenomegaly and hypersplenism can manifest following the development of portal hypertension. These splenic abnormalities correlate with and have been postulated to facilitate the progression of liver fibrosis to cirrhosis, although precise mechanisms remain poorly understood. In this review, we summarize the literature to highlight the mechanistic contributions of splenomegaly and hypersplenism to the development of liver cirrhosis, focusing on three key aspects: hepatic fibrogenesis, hepatic immune microenvironment dysregulation and liver regeneration...
May 23, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28531915/bone-marrow-stem-cells-anti-liver-fibrosis-potency-inhibition-of-hepatic-stellate-cells-activity-and-extracellular-matrix-deposition
#16
Ervina Julien Sitanggang, Radiana Dhewayani Antarianto, Sri Widia A Jusman, Jeanne Adiwinata Pawitan, Ahmad Aulia Jusuf
Transplantation of bone marrow derived stem cells (BMSCs) has been reported inhibits liver fibrosis. Several in vitro studies by co-culturing BMSCs and hepatic stellate cells (HSCs) indirectly or directly in 2D models showed inhibition of HSC as the key player in liver fibrosis. In this study, we investigated direct effect of BMSCs on HSCs by co-culturing BMSCs and HSCs in 3D model as it represents the liver microenvironment with intricate cell-cell and cell-matrix interactions. Primary isolated rat HSCs and BMSCs were directly co-cultured at 1:1 ratio with hanging drop method...
May 30, 2017: International Journal of Stem Cells
https://www.readbyqxmd.com/read/28506744/hepatic-stellate-cells-as-key-target-in-liver-fibrosis
#17
Takaaki Higashi, Scott L Friedman, Yujin Hoshida
Progressive liver fibrosis, induced by chronic viral and metabolic disorders, leads to more than one million deaths annually via development of cirrhosis, although no antifibrotic therapy has been approved to date. Transdifferentiation (or "activation") of hepatic stellate cells is the major cellular source of matrix protein-secreting myofibroblasts, the major driver of liver fibrogenesis. Paracrine signals from injured epithelial cells, fibrotic tissue microenvironment, immune and systemic metabolic dysregulation, enteric dysbiosis, and hepatitis viral products can directly or indirectly induce stellate cell activation...
May 12, 2017: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/28506372/hepatic-progenitor-cells-an-update
#18
REVIEW
Matthias Van Haele, Tania Roskams
Liver regeneration is a fascinating and complex process with many medical implications. An important component of this regenerative process is the hepatic progenitor cell (HPC). These appealing cells are able to participate in the renewal of hepatocytes and cholangiocytes when the normal homeostatic regeneration is exhausted. Moreover, the HPC niche is of vital importance toward the activation, differentiation, and proliferation of the HPC. This niche provides a rich microenvironment for the regulation of the HPC, thanks to the intercellular secretion of molecules...
June 2017: Gastroenterology Clinics of North America
https://www.readbyqxmd.com/read/28474506/expression-of-the-inhibitory-receptor-nkg2a-correlates-with-increased-liver-and-splenic-nk-cell-response-to-activating-receptor-engagement
#19
Claire E Meyer, Phillip N Key, Toby Zhu, Mark Shabsovich, Ann Ni, Sandeep K Tripathy
INTRODUCTION: Natural killer (NK) cells play a critical role in the innate immune response to viruses and tumors, and comprise a large proportion of the hepatic lymphocyte population. They must remain tolerant to non-pathogenic antigens while protecting the host from harmful agents. Herein, we investigate how the NK cell response to activation receptor engagement is altered in the liver. METHODS: In this study, we assess IFN-γ production and degranulation of splenic NK cells and selected subsets of liver NK cells...
June 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28467181/pre-clinical-and-clinical-investigations-of-metabolic-zonation-in-liver-diseases-the-potential-of-microphysiology-systems
#20
Alejandro Soto-Gutierrez, Albert Gough, Lawrence A Vernetti, D L Taylor, Satdarshan P Monga
The establishment of metabolic zonation within a hepatic lobule ascribes specific functions to hepatocytes based on unique, location-dependent gene expression patterns. Recently, there have been significant developments in the field of metabolic liver zonation. A little over a decade ago, the role of β-catenin signaling was identified as a key regulator of gene expression and function in pericentral hepatocytes. Since then, additional molecules have been identified that regulate the pattern of Wnt/β-catenin signaling within a lobule and determine gene expression and function in other hepatic zones...
January 1, 2017: Experimental Biology and Medicine
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