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Hepatic microenvironment

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https://www.readbyqxmd.com/read/28218627/gata4-dependent-organ-specific-endothelial-differentiation-controls-liver-development-and-embryonic-hematopoiesis
#1
Cyrill Géraud, Philipp-Sebastian Koch, Johanna Zierow, Kay Klapproth, Katrin Busch, Victor Olsavszky, Thomas Leibing, Alexandra Demory, Friederike Ulbrich, Miriam Diett, Sandhya Singh, Carsten Sticht, Katja Breitkopf-Heinlein, Karsten Richter, Sanna-Maria Karppinen, Taina Pihlajaniemi, Bernd Arnold, Hans-Reimer Rodewald, Hellmut G Augustin, Kai Schledzewski, Sergij Goerdt
Microvascular endothelial cells (ECs) are increasingly recognized as organ-specific gatekeepers of their microenvironment. Microvascular ECs instruct neighboring cells in their organ-specific vascular niches through angiocrine factors, which include secreted growth factors (angiokines), extracellular matrix molecules, and transmembrane proteins. However, the molecular regulators that drive organ-specific microvascular transcriptional programs and thereby regulate angiodiversity are largely elusive. In contrast to other ECs, which form a continuous cell layer, liver sinusoidal ECs (LSECs) constitute discontinuous, permeable microvessels...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28216578/tumor-microenvironment-a-paradigm-in-hepatocellular-carcinoma-progression-and-therapy
#2
REVIEW
Maryam Tahmasebi Birgani, Vinicio Carloni
Hepatocellular carcinoma (HCC) is among the most lethal and prevalent cancers in the human population. Different etiological factors such as hepatitis B and C virus, alcohol and diabetes cause liver injury followed by inflammation, necrosis and hepatocytes proliferation. Continuous cycles of this destructive-regenerative process culminates in liver cirrhosis which is characterized by regenerating nodules that progress to dysplastic nodules and ultimately HCC. Despite its significance, there is only an elemental understanding of the pathogenetic mechanisms, and there are only limited therapeutic options...
February 14, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28202625/gut-microbiota-promotes-obesity-associated-liver-cancer-through-pge2-mediated-suppression-of-antitumor-immunity
#3
Tze Mun Loo, Fumitaka Kamachi, Yoshihiro Watanabe, Shin Yoshimoto, Hiroaki Kanda, Yuriko Arai, Yaeko Nakajima-Takagi, Atsushi Iwama, Tomoaki Koga, Yukihiko Sugimoto, Takayuki Ozawa, Masaru Nakamura, Miho Kumagai, Koichi Watashi, Makoto M Taketo, Tomohiro Aoki, Shuh Narumiya, Masanobu Oshima, Makoto Arita, Eiji Hara, Naoko Ohtani
Obesity increases the risk of cancers, including hepatocellular carcinomas (HCCs). However, the precise molecular mechanisms through which obesity promotes HCC development are still unclear. Recent studies have shown that gut microbiota may influence liver diseases by transferring its metabolites and components. Here, we show that the hepatic translocation of obesity-induced lipoteichoic acid (LTA), a Gram positive gut microbial component, promotes HCC development by creating a tumor-promoting microenvironment...
February 15, 2017: Cancer Discovery
https://www.readbyqxmd.com/read/28192881/stem-cell-biomaterials-and-growth-factors-therapy-for-hepatocellular-carcinoma
#4
REVIEW
Soleiman Jaferian, Maryam Soleymaninejad, Babak Negahdari, Ali Eatemadi
Hepatocellular carcinoma is an antecedent of liver illnesses, including viral hepatitis, alcohol abuse, or metabolic disease. Transforming growth factor-Beta (TGF-b) plays an important role in creating a favorable microenvironment for tumor cell growth via two major mechanisms: an intrinsic activity as an autocrine growth factor and an extrinsic activity by inducing microenvironment changes. Recently stem cell therapy as also been a promising and potential treatment for liver cancer and in addition signaling pathways like GF/GFR systems, SDF-1α/CXC4 ligand receptor interaction and PI3K/Akt signaling, and cytokines has been identified to regulate cell fate decisions, and can be utilized to positively influence cell therapy outcomes...
February 8, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28182873/biomechanically-primed-liver-microtumor-array-as-a-high-throughput-mechanopharmacological-screening-platform-for-stroma-reprogrammed-combinatorial-therapy
#5
Lu Zhu, Xingliang Fan, Bingjie Wang, Longwei Liu, Xiaojun Yan, Lyu Zhou, Yang Zeng, Mark C Poznansky, Lili Wang, Huabiao Chen, Yanan Du
Recent breakthrough in stroma-reprogrammed combinatorial therapy (SRCT) for pancreatic tumor opens a new route for improving conventional chemotherapeutic efficacy, which utilizes VDR ligand to reprogram activated stromal cells in stiffened microenvironment, leading to reduced 'barrier effects' and increased tissue-infiltration of the chemotherapy drug. As a novel therapeutic strategy and mechanism of action, the progress of SRCT relies on tailored in vitro drug assessment platforms to further optimize its efficacy and extend to applications in other tumor types...
January 27, 2017: Biomaterials
https://www.readbyqxmd.com/read/28178856/chemotherapeutic-delivery-using-ph-responsive-affinity-based-release
#6
Erika L Cyphert, Andrew S Fu, Horst A von Recum
Doxorubicin is a chemotherapeutic drug typically administered systemically which frequently leads to cardiac and hepatic toxicities. Local delivery to a tumor has a chance to mitigate some of these toxicities and can further be mitigated by including a means of tumor-specific drug release. Our laboratory has explored the use of molecular interactions to control the rate of drug release beyond that capable of diffusion alone. To this system, we added an additional affinity group (adamantane) to doxorubicin through a pH-sensitive hydrazone bond...
January 1, 2017: Experimental Biology and Medicine
https://www.readbyqxmd.com/read/28176332/low-dose-interleukin-2-promotes-stat5-phosphorylation-treg-survival-and-ctla-4-dependent-function-in-autoimmune-liver-diseases
#7
Hannah C Jeffery, Louisa E Jeffery, Philipp Lutz, Margaret Corrigan, Gwilym J Webb, Gideon M Hirschfield, David H Adams, Ye Htun Oo
CD4(+) CD25(high) CD127(low) FOXP3(+) regulatory T cells (Treg) are essential for the maintenance of peripheral tolerance. Impaired Treg function and an imbalance between effector and regulatory T cells contribute to the pathogenesis of autoimmune diseases. We recently reported that the hepatic microenvironment is deficient in IL-2, a cytokine essential for Treg survival and function. Consequently, few liver-infiltrating Treg demonstrate STAT5 phosphorylation. To establish the potential of IL-2 to enhance Treg therapy, we investigated the effects of very low dose Proleukin (VLDP) on the phosphorylation of STAT5 and the subsequent survival and function of Treg and T effector cells from the blood and livers of patients with autoimmune liver diseases...
February 8, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28167218/tumor-regulation-of-the-tissue-environment-in-the-liver
#8
REVIEW
Tobias Eggert, Tim F Greten
The tumor microenvironment (TME) in the liver plays an important role in primary and metastatic liver tumor formation and tumor growth promotion. Cellular and non-cellular components of the TME significantly influence tumor development, growth, metastatic spread, anti-tumor immunity and response to tumor therapy. The cellular components of the TME in the liver not only consist of infiltrating immune cells, but also of liver-resident cells such as liver sinusoidal endothelial cells (LSEC) and hepatic stellate cells (HSC), which promote tumor growth by negatively regulating tumor-associated immune responses...
February 3, 2017: Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28159899/cross-presentation-of-soluble-and-cell-associated-antigen-by-murine-hepatocytes-is-enhanced-by-collectrin-expression
#9
Joseph S Dolina, Sylvia Cechova, Christine K Rudy, Sun-Sang J Sung, William W Tang, Joey Lee, Young S Hahn, Thu H Le
Cross-presentation is a modular series of intracellular events dictating the internalization and subsequent MHC class I (MHC I) display of extracellular Ags. This process has been defined in dendritic cells and plays a fundamental role in the induction of CD8(+) T cell immunity during viral, intracellular bacterial, and antitumor responses. Herein, acute viral infection of murine liver with adenovirus, a model for intrahepatic cross-presentation, confirms hepatocytes directly contribute to cross-presentation of Ags and priming the pool of naive CD8(+) T cells within the liver microenvironment...
February 3, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28135758/the-diversity-and-plasticity-of-adult-hepatic-progenitor-cells-and-their-niche
#10
REVIEW
Jiamei Chen, Long Chen, Mark A Zern, Neil D Theise, Ann Mae Diehl, Ping Liu, Yuyou Duan
The liver is a unique organ for homoeostasis with regenerative capacities. Hepatocytes possess a remarkable capacity to proliferate upon injury; however, in more severe scenarios liver regeneration is believed to arise from at least one, if not several facultative hepatic progenitor cell compartments. Newly identified pericentral stem/progenitor cells residing around the central vein is responsible for maintaining hepatocyte homoeostasis in the uninjured liver. In addition, hepatic progenitor cells have been reported to contribute to liver fibrosis and cancers...
January 30, 2017: Liver International: Official Journal of the International Association for the Study of the Liver
https://www.readbyqxmd.com/read/28133764/neutrophils-promote-hepatic-metastasis-growth-through-fibroblast-growth-factor-fgf-2-dependent-angiogenesis
#11
Alex N Gordon-Weeks, Su Y Lim, Arseniy E Yuzhalin, Keaton Jones, Bostjan Markelc, Jon N Buzelli, Emmanouil Fokas, Yunhong Cao, Sean Smart, Ruth Muschel
: Hepatic metastases are amenable to ablation, however many patients are not suitable candidates for such therapy and recurrence is common. The tumor microenvironment is known to be essential for metastatic growth, yet identification of plausible targets for cancer therapy in the microenvironment has proven elusive. We found that human colorectal cancer liver metastases and murine gastrointestinal experimental liver metastases are infiltrated by neutrophils. Plasticity in neutrophils has recently been shown to lead to both pro- and anti- tumor effects...
January 30, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28125949/preparation-and-characterization-of-a-chitosan-galactosylated-hyaluronic-acid-heparin-scaffold-for-hepatic-tissue-engineering
#12
Jinyong Fan, Jun Yang
Cell culture microenvironment and hepatocyte-specific three-dimensional tissue-engineering scaffold play important roles for bioartificial liver devices. In the present study, highly porous sponge scaffolds composed of chitosan (CS) and galactosylated hyaluronic acid (GHA, galactose moieties were covalently coupled with hyaluronic acid through ethylenediamine), were prepared by freezing-drying technique. Because the growth factors specifically bind to heparin with a high affinity and biological stability of the growth factors are modulated by heparin...
April 2017: Journal of Biomaterials Science. Polymer Edition
https://www.readbyqxmd.com/read/28123604/association-between-expression-of-carboxypeptidase-4-and-stem-cell-markers-and-their-clinical-significance-in-liver-cancer-development
#13
Lichao Sun, Chunguang Guo, Joseph Burnett, Jian Pan, Zhihua Yang, Yuliang Ran, Duxin Sun
The development of liver cancer would undergo a sequential progression from chronic inflammatory liver disease, cirrhosis to neoplasia. During these pathophysiological changes, abnormal liver microenvironment might induce the hepatocytes to die, abnormally proliferate and initiate cancer stem cells. Metallocarboxypeptidases (MCPs) involved in multiple biological functions including inflammation, fibrosis and stem cell niche formation. This study aimed to evaluate the expression of carboxypeptidase 4 (CPA4) in hepatitis, liver cirrhosis and liver cancer tissues, and revealed its clinical significance in liver cancer progression...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28122964/circulating-and-exosome-packaged-hepatitis-c-single-stranded-rna-induce-monocyte-differentiation-via-tlr7-8-to-polarized-macrophages-and-fibrocytes
#14
Banishree Saha, Karen Kodys, Adeyinka Adejumo, Gyongyi Szabo
Monocytes and macrophages (MΦs) play a central role in the pathogenesis of chronic hepatitis C virus (HCV) infection. The tissue microenvironment triggers monocyte differentiation into MΦs, with polarization ranging within the spectrum of M1 (classical) to M2 (alternative) activation. Recently, we demonstrated that HCV infection leads to monocyte differentiation into polarized MΦs that mediate stellate cell activation via TGF-β. In this study, we aimed to identify the viral factor(s) that mediate monocyte-to-MΦ differentiation...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28112323/mimicking-liver-sinusoidal-structures-and-functions-using-a-3d-configured-microfluidic-chip
#15
Yu Du, Ning Li, Hao Yang, Chunhua Luo, Yixin Gong, Chunfang Tong, Yuxin Gao, Shouqin Lü, Mian Long
Physiologically, four major types of hepatic cells - the liver sinusoidal endothelial cells, Kupffer cells, hepatic stellate cells, and hepatocytes - reside inside liver sinusoids and interact with flowing peripheral cells under blood flow. It is hard to mimic an in vivo liver sinusoid due to its complex multiple cell-cell interactions, spatiotemporal construction, and mechanical microenvironment. Here we developed an in vitro liver sinusoid chip by integrating the four types of primary murine hepatic cells into two adjacent fluid channels separated by a porous permeable membrane, replicating liver's key structures and configurations...
January 23, 2017: Lab on a Chip
https://www.readbyqxmd.com/read/28097530/virus-induced-hepatocellular-carcinoma-with-special-emphasis-on-hbv
#16
REVIEW
Ming Wang, Dong Xi, Qin Ning
Hepatocellular carcinoma (HCC) is a common malignant tumor with high lethality, and the hepatitis B virus (HBV) is a chief cause. HBV can accelerate HCC via multiple mechanisms. First, HBV induces immune reactions that lead to repeated hepatic inflammation, fibrosis and a deficient immune microenvironment. Subsequently, HBV can modify host genes near the insertion point through DNA integration to cause host cell genome instability and to generate carcinogenic fusion proteins. Additionally, HBV expresses diverse active proteins, especially HBx and HBs, which have a range of transactivation functions such as regulation of apoptosis, interference with intracellular signaling pathways, and alteration of epigenetics...
January 17, 2017: Hepatology International
https://www.readbyqxmd.com/read/28090562/hepatitis-c-virus-induced-monocyte-differentiation-into-polarized-m2-macrophages-promotes-stellate-cell-activation-via%C3%A2-tgf-%C3%AE
#17
Banishree Saha, Karen Kodys, Gyongyi Szabo
BACKGROUND & AIMS: Monocyte and macrophage (MΦ) activation contributes to the pathogenesis of chronic hepatitis C virus (HCV) infection. Disease pathogenesis is regulated by both liver-resident MΦs and monocytes recruited as precursors of MΦs into the damaged liver. Monocytes differentiate into M1 (classic/proinflammatory) or M2 (alternative/anti-inflammatory) polarized MΦs in response to tissue microenvironment. We hypothesized that HCV-infected hepatoma cells (infected with Japanese fulminant hepatitis-1 [Huh7...
May 2016: Cellular and Molecular Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/28073408/-establishment-of-a-cell-co-culture-system-in-accordance-with-the-immunological-characteristics-of-chronic-hbv-infection
#18
H J Li, X Y Yang, F B Kang, F X Liu, D X Sun
Objective: To investigate whether the co-culture of Huh7.93 cells and peripheral blood mononucleated cells from chronic hepatitis B patients (cPBMCs) can simulate the replication features of hepatitis B virus (HBV) and immune function in chronic hepatitis B (CHB) patients, and to provide an in vitro cell co-culture system for the research on immune clearance in chronic HBV infection. Methods: Huh7.93 cells were cultured alone or co-cultured with peripheral blood mononucleated cells from healthy people who underwent physical examination (nPBMCs) or cPBMCs for 7 days...
December 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/28058014/anti-viral-role-of-toll-like-receptor-4-in-hepatitis-b-virus-infection-an-in-vitro-study
#19
Dipanwita Das, Neelakshi Sarkar, Isha Sengupta, Ananya Pal, Debraj Saha, Manikankana Bandopadhyay, Chandrima Das, Jimmy Narayan, Shivram Prasad Singh, Runu Chakravarty
AIM: Toll like receptors plays a significant anti-viral role in different infections. The aim of this study was to look into the role of toll like receptor 4 (TLR4) in hepatitis B virus (HBV) infection. METHODS: Real time PCR was used to analyze the transcription of TLR4 signaling molecules, cell cycle regulators and HBV DNA viral load after triggering the HepG2.2.15 cells with TLR4 specific ligand. Nuclear factor (NF)-κB translocation on TLR4 activation was analyzed using microscopic techniques...
December 21, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28040885/gold-nanoparticle-uptake-by-human-derived-macrophages-and-primary-liver-phagocytic-cells-is-dependent-on-phenotype
#20
Sonya A MacParland, Kim M Tsoi, Ben Ouyang, Xue-Zhong Ma, Justin Manuel, Ali Fawaz, Mario A Ostrowski, Benjamin A Alman, Anton Zilman, Warren C W Chan, Ian D McGilvray
A significant challenge to delivering therapeutic doses of nanoparticles to targeted disease sites is the fact that most nanoparticles become trapped in the liver. Liver resident macrophages, or Kupffer cells, are key cells in the hepatic sequestration of nanoparticles. However, the precise role macrophage phenotype plays in nanoparticle uptake is unknown. Here, we show that human macrophage phenotype modulates hard nanoparticle uptake. Using gold nanoparticles, we examined uptake by human monocyte-derived macrophages that had been driven to a "regulatory" M2 phenotype or an "inflammatory" M1 phenotype and found that M2-type macrophages preferentially take up nanoparticles, with a clear spectrum among the subtypes (M2c>M2>M2a>M2b>M1)...
December 31, 2016: ACS Nano
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