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Hepatic microenvironment

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https://www.readbyqxmd.com/read/28428708/indoleamine-2-3-dioxygenase-as-a-potential-prognostic-marker-and-immunotherapeutic-target-for-hepatocellular-carcinoma
#1
REVIEW
Kashif Asghar, Asim Farooq, Bilal Zulfiqar, Muhammad Usman Rashid
Tumor cells induce an immunosuppressive microenvironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma (HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28415775/adverse-genomic-alterations-and-stemness-features-are-induced-by-field-cancerization-in-the-microenvironment-of-hepatocellular-carcinomas
#2
Darko Castven, Michael Fischer, Diana Becker, Stefan Heinrich, Jesper B Andersen, Dennis Strand, Martin F Sprinzl, Susanne Strand, Carolin Czauderna, Stefanie Heilmann-Heimbach, Stephanie Roessler, Arndt Weinmann, Marcus A Wörns, Snorri S Thorgeirsson, Peter R Galle, Matthias S Matter, Hauke Lang, Jens U Marquardt
Hepatocellular Carcinoma (HCC) commonly develops in chronically damaged liver tissues. The resulting regenerative and inflammatory processes create an adverse milieu that promotes tumor-initiation and progression. A better understanding of the hepatic tumor-microenvironment interaction might infer profound therapeutic implications.Integrative whole genome and transcriptome analyses of different tumor regions, the invasive tumor border and tumor-surrounding liver (SL) were performed to identify associated molecular alterations and integrated with our existing HCC database...
March 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28415598/caloric-restriction-delays-early-phases-of-carcinogenesis-via-effects-on-the-tissue-microenvironment
#3
Erika Cadoni, Fabio Marongiu, Maura Fanti, Monica Serra, Ezio Laconi
Caloric restriction (CR) is an effective and consistent means to delay aging and the incidence of chronic diseases related to old age, including cancer. However, the precise mechanisms responsible for the beneficial effect of CR on carcinogenic process are yet to be identified.In the present studies the hypothesis was tested that the CR might delay carcinogenesis via modulatory effects exerted on the age-associated, neoplastic-prone tissue microenvironment. Using a well characterized, orthotopic cell transplantation (Tx) system in the rat, preneoplastic hepatocytes isolated from liver nodules were injected into either old syngeneic rats fed ad libitum (AL) or animals of the same age given a CR diet (70% of AL feeding)...
March 21, 2017: Oncotarget
https://www.readbyqxmd.com/read/28401002/gpr110-deficiency-decelerates-carcinogen-induced-hepatocarcinogenesis-via-activation-of-the-il-6-stat3-pathway
#4
Benting Ma, Junjie Zhu, Juan Tan, Yulei Mao, Lingyun Tang, Chunling Shen, Hongxing Zhang, Ying Kuang, Jian Fei, Xiao Yang, Zhugang Wang
Hepatocarcinogenesis is a complex process that includes pronounced necroinflammation, unregulated hepatocyte damage, subsequent extensive fibrosis, and carcinogenesis. GPR110 was an adhesion G protein-coupled receptor. Analysis of the expression pattern of Gpr110 in mice displayed that Gpr110 was expressed highly in liver, implicating the tissue compartments where Gpr110 could execute its functions, the role of Gpr110 in the physiological and pathological state of liver remains unclear. Based on a Gpr110 knockout mouse model, we evaluated the role of Gpr110 in hepatocarcinogenesis by using a carbon tetrachloride (CCl4)-induced liver injury and fibrosis model, as well as diethylnitrosamine (DEN) plus CCl4-induced liver cancer model...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28400340/eosin-fluorescence-a-diagnostic-tool-for-quantification-of-liver-injury
#5
Hamid Ali, Safdar Ali, Maryam Mazhar, Amjad Ali, Azra Jahan, Abid Ali
Hepatitis is one of the most common life threatening diseases. The diagnosis is mainly based on biochemical analysis such as liver function test. However, histopathological evaluation of liver serves far better for more accurate final diagnosis. The goal of our study was to evaluate the eosin fluorescence pattern in CCl4-induced liver injury model compared with normal and different treatment groups. For this purpose, liver tissues were stained with H/E and examined under bright field microscope but the fluorescence microscopy of H/E stained slides provided an interesting fluorescence pattern and was quite helpful in identifying different structures...
April 8, 2017: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/28372286/research-progress-in-liver-tissue-engineering
#6
Lei Zhang, Zheng Guan, Jun-Song Ye, Yan-Feng Yin, Jean-François Stoltz, Natalia de Isla
Liver transplantation is the definitive treatment for patients with end-stage liver diseases (ESLD). However, it is hampered by shortage of liver donor. Liver tissue engineering, aiming at fabricating new livers in vitro, provides a potential resolution for donor shortage. Three elements need to be considered in liver tissue engineering: seeding cell resources, scaffolds and bioreactors. Studies have shown potential cell sources as hepatocytes, hepatic cell line, mesenchymal stem cells and others. They need scaffolds with perfect biocompatiblity, suitable micro-structure and appropriate degradation rate, which are essential charateristics for cell attachment, proliferation and secretion in forming extracellular matrix...
2017: Bio-medical Materials and Engineering
https://www.readbyqxmd.com/read/28358369/mirna199a-3p-suppresses-tumor-growth-migration-invasion-and-angiogenesis-in-hepatocellular-carcinoma-by-targeting-vegfa-vegfr1-vegfr2-hgf-and-mmp2
#7
Alip Ghosh, Debanjali Dasgupta, Amit Ghosh, Shrabasti Roychoudhury, Dhiraj Kumar, Mahadeo Gorain, Ramesh Butti, Simanti Datta, Shaleen Agarwal, Subash Gupta, Gopal Krishna Dhali, Abhijit Chowdhury, Thomas D Schmittgen, Gopal C Kundu, Soma Banerjee
Increasing significance of tumor-stromal interaction in development and progression of cancer implies that signaling molecules in the tumor microenvironment (TME) might be the effective therapeutic targets for hepatocellular carcinoma (HCC). Here, the role of microRNA miR-199a-3p in the regulation of TME and development of HCC has been investigated by several in vitro and in vivo assays. Expression of miR-199a-3p was observed significantly low in HCC tissues and its overexpression remarkably inhibited in vivo tumor growth and metastasis to lung in NOD-SCID mice...
March 30, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28349484/in-vitro-and-ex-vivo-models-to-study-t-cell-migration-through-the-human-liver-parenchyma
#8
Benjamin G Wiggins, Konstantinos Aliazis, Scott P Davies, Gideon Hirschfield, Patricia F Lalor, Gary Reynolds, Zania Stamataki
The liver is the largest internal organ and filters around 3 pints of blood per minute. This continuous flux of blood should not be confused with rapid egress of lymphocytes through the liver; this organ has intricate corridors of specialized sinusoidal spaces, ensuring that immune cells decelerate to shear flow rates, and providing ample opportunities to interact with parenchymal cells. Migration has been intricately linked to T cell function; it is therefore important to study liver T cell biology into context within the liver microenvironment...
2017: Methods in Molecular Biology
https://www.readbyqxmd.com/read/28301139/designing-hydrogels-for-on-demand-therapy
#9
Nuria Oliva, João Conde, Kui Wang, Natalie Artzi
Systemic administration of therapeutic agents has been the preferred approach to treat most pathological conditions, in particular for cancer therapy. This treatment modality is associated with side effects, off-target accumulation, toxicity, and rapid renal and hepatic clearance. Multiple efforts have focused on incorporating targeting moieties into systemic therapeutic vehicles to enhance retention and minimize clearance and side effects. However, only a small percentage of the nanoparticles administered systemically accumulate at the tumor site, leading to poor therapeutic efficacy...
March 16, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28299331/contribution-of-liver-nonparenchymal-cells-to-hepatic-fibrosis-interactions-with-the-local-microenvironment
#10
EDITORIAL
Michel Fausther, Michele T Pritchard, Yury V Popov, Kim Bridle
No abstract text is available yet for this article.
2017: BioMed Research International
https://www.readbyqxmd.com/read/28293730/liver-macrophages-in-healthy-and-diseased-liver
#11
REVIEW
Zeinab Abdullah, Percy A Knolle
Kupffer cells, the largest tissue resident macrophage population, are key for the maintenance of liver integrity and its restoration after injury and infections, as well as the local initiation and resolution of innate and adaptive immunity. These important roles of Kupffer cells were recently identified in healthy and diseased liver revealing diverse functions and phenotypes of hepatic macrophages. High-level phenotypic and genomic analysis revealed that Kupffer cells are not a homogenous population and that the hepatic microenvironment actively shapes both phenotype and function of liver macrophages...
April 2017: Pflügers Archiv: European Journal of Physiology
https://www.readbyqxmd.com/read/28293634/secs-sinusoidal-endothelial-cells-liver-microenvironment-and-fibrosis
#12
REVIEW
Vaishaali Natarajan, Edward N Harris, Srivatsan Kidambi
Liver fibrosis is a wound-healing response to chronic liver injury such as alcoholic/nonalcoholic fatty liver disease and viral hepatitis with no FDA-approved treatments. Liver fibrosis results in a continual accumulation of extracellular matrix (ECM) proteins and paves the way for replacement of parenchyma with nonfunctional scar tissue. The fibrotic condition results in drastic changes in the local mechanical, chemical, and biological microenvironment of the tissue. Liver parenchyma is supported by an efficient network of vasculature lined by liver sinusoidal endothelial cells (LSECs)...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28281193/oxidative-stress-indicated-by-elevated-expression-of-nrf2-and-8-ohdg-promotes-hepatocellular-carcinoma-progression
#13
Chakriwong Ma-On, Anapat Sanpavat, Patcharawalai Whongsiri, Surasit Suwannasin, Nattiya Hirankarn, Pisit Tangkijvanich, Chanchai Boonla
Reactive oxygen species (ROS) is excessively generated in tumors creating an oxidative stress in tumor microenvironment. We investigated hepatic expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and 8-hydroxydeoxyguanosine (8-OHdG) in hepatocellular carcinoma (HCC) patients, and asked if ROS epigenetically upregulated Nrf2 and enhanced aggressiveness in HCC cells. Expression of Nrf2 (n = 100) and 8-OHdG (n = 53) was remarkably increased in HCC tissues compared with the noncancerous hepatic tissues...
April 2017: Medical Oncology
https://www.readbyqxmd.com/read/28279493/effect-of-melanoma-cells-on-proliferation-and-migration-of-activated-hepatic-stellate-cells-in-vitro
#14
Theresa Meyer, Andreas Koch, Eva-Vanessa Ebert, Barbara Czech, Martina Mueller, Anja Bosserhoff, Sven Arke Lang, Claus Hellerbrand
Melanoma is a highly aggressive tumor of the skin. The clinical outcome is determined by the presence or absence of metastases, and the liver is a common site of distant metastases. Hepatic metastasis is causing activation of hepatic stellate cells (HSC), which form the stroma of hepatic metastases and are increasingly recognized as a crucial component of the pro- metastatic liver microenvironment. Most studies have focused on the effects of HSC on (metastasizing) tumor cells. Here, we aimed to analyze functional in vitro effects of conditioned medium (CM) of twelve different human melanoma cell lines on LX2 cells and HSC(htert) cells, two well established human activated HSC cell lines...
December 26, 2016: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28267621/targeting-hepatic-macrophages-to-treat-liver-diseases
#15
REVIEW
Frank Tacke
Our view on liver macrophages in the context of health and disease has been reformed by the recognition of a remarkable heterogeneity of phagocytes in the liver. Liver macrophages consist of ontogenically distinct populations termed Kupffer cells and monocyte-derived macrophages. Kupffer cells are self-renewing, resident and principally non-migratory phagocytes, serving as sentinels for liver homeostasis. Liver injury triggers Kupffer cell activation, leading to inflammatory cytokine and chemokine release. This fosters the infiltration of monocytes into liver that give rise to large numbers of inflammatory monocyte-derived macrophages...
March 3, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28260498/treatment-with-proprotein-convertase-subtilisin-kexin-type-9-pcsk9-inhibitors-to-reduce-cardiovascular-inflammation-and-outcomes
#16
Aldo Bonaventura, Federico Carbone, Alessandra Vecchié, Franco Dallegri, Giovanni G Camici, Fabrizio Montecucco, Luca Liberale
Proprotein Convertase Subtilisin/Kexin type 9 (PCSK9) is a serine protease involved in cholesterol homeostasis. After binding to the complex low-density lipoprotein (LDL)-receptor, PCSK9 induces its intracellular degradation, thus reducing serum LDL clearance. PCSK9 is mainly secreted by the liver, but it is also expressed to a lesser extent in other organs. Apart from the well-known activity concerning hepatic LDL receptor-mediated pathway, PCSK9 has been supposed to potentially interfere with vascular inflammation in atherogenesis...
March 3, 2017: Current Medicinal Chemistry
https://www.readbyqxmd.com/read/28218627/gata4-dependent-organ-specific-endothelial-differentiation-controls-liver-development-and-embryonic-hematopoiesis
#17
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...
March 1, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28216578/tumor-microenvironment-a-paradigm-in-hepatocellular-carcinoma-progression-and-therapy
#18
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
#19
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
#20
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...
April 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
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