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Hepatic microenvironment

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https://www.readbyqxmd.com/read/28097530/virus-induced-hepatocellular-carcinoma-with-special-emphasis-on-hbv
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/28035785/the-hepatic-matrisome-responds-dynamically-to-injury-characterization-of-transitional-changes-to-the-extracellular-matrix-in-mice
#6
Veronica L Massey, Christine E Dolin, Lauren G Poole, Shanice V Hudson, Deanna L Siow, Guy N Brock, Michael L Merchant, Daniel W Wilkey, Gavin E Arteel
: The extracellular matrix (ECM) consists of diverse components that work bidirectionally with surrounding cells to create a responsive microenvironment. In some contexts (e.g., hepatic fibrosis), changes to the ECM are well recognized and understood. However, it is becoming increasingly accepted that the hepatic ECM proteome (i.e., matrisome) responds dynamically to stress well before fibrosis. The term "transitional tissue remodeling" describes qualitative and quantitative ECM changes in response to injury that do not alter the overall architecture of the organ; these changes in ECM may contribute to early disease initiation and/or progression...
November 5, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28027584/il6-dependent-genomic-instability-heralds-accelerated-carcinogenesis-following-liver-regeneration-on-a-background-of-chronic-hepatitis
#7
Tali Lanton, Anat Shriki, Yael Nechemia-Arbely, Rinat Abramovitch, Orr Levkovitch, Revital Adar, Nofar Rosenberg, Mor Paldor, Daniel Goldenberg, Amir Sonnenblick, Amnon Peled, Stefan Rose-John, Eithan Galun, Jonathan H Axelrod
: Liver cancer, which typically develops on a background of chronic liver inflammation, is now the second leading cause of cancer mortality worldwide. For these patients surgical resection is a principal treatment modality that offers a chance of prolonged survival. However, tumor recurrence after resection, the mechanisms of which remain obscure, markedly limits the long-term survival of these patients. We have previously shown that partial hepatectomy (PH) in Mdr2 knockout (Mdr2(-/-) ) mice, a model of chronic inflammation-associated liver cancer, significantly accelerates hepatocarcinogenesis...
December 27, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28002505/pointing-at-ito-cell-from-structure-to-function-%C3%A2-or-cinderella-story-in-liver-histology
#8
Adriana Grigoraş, Simona Eliza Giuşcă, Elena Roxana Avădănei, Cornelia Amălinei, Irina Draga Căruntu
For more than 130 years, the hepatic stellate cells (also known as Ito cells) have been the object of numerous studies that aimed at their characterization both in normal and postlesional status, where they play a key role in fibrosis progression specific for chronic hepatic pathology. Converged studies on their histophysiology have revealed other functions, namely the involvement in liver embryological development and regeneration, metabolisms regulation, modulation of local inflammatory and immune reactions...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/27991882/tuning-a-cellular-lipid-kinase-activity-adapts-hepatitis-c-virus-to-replication-in-cell-culture
#9
Christian Harak, Max Meyrath, Inés Romero-Brey, Christian Schenk, Claire Gondeau, Philipp Schult, Katharina Esser-Nobis, Mohsan Saeed, Petra Neddermann, Paul Schnitzler, Daniel Gotthardt, Sofia Perez-Del-Pulgar, Christoph Neumann-Haefelin, Robert Thimme, Philip Meuleman, Florian W R Vondran, Raffaele De Francesco, Charles M Rice, Ralf Bartenschlager, Volker Lohmann
With a single exception, all isolates of hepatitis C virus (HCV) require adaptive mutations to replicate efficiently in cell culture. Here, we show that a major class of adaptive mutations regulates the activity of a cellular lipid kinase, phosphatidylinositol 4-kinase IIIα (PI4KA). HCV needs to stimulate PI4KA to create a permissive phosphatidylinositol 4-phosphate-enriched membrane microenvironment in the liver and in primary human hepatocytes (PHHs). In contrast, in Huh7 hepatoma cells, the virus must acquire loss-of-function mutations that prevent PI4KA overactivation...
December 19, 2016: Nature Microbiology
https://www.readbyqxmd.com/read/27990121/targeting-mechanotransduction-at-the-transcriptional-level-yap-and-brd4-are-novel-therapeutic-targets-for-the-reversal-of-liver-fibrosis
#10
REVIEW
Altynbek Zhubanchaliyev, Aibar Temirbekuly, Kuralay Kongrtay, Leah C Wanshura, Jeannette Kunz
Liver fibrosis is the result of a deregulated wound healing process characterized by the excessive deposition of extracellular matrix. Hepatic stellate cells (HSCs), which are activated in response to liver injury, are the major source of extracellular matrix and drive the wound healing process. However, chronic liver damage leads to perpetual HSC activation, progressive formation of pathological scar tissue and ultimately, cirrhosis and organ failure. HSC activation is triggered largely in response to mechanosignaling from the microenvironment, which induces a profibrotic nuclear transcription program that promotes HSC proliferation and extracellular matrix secretion thereby setting up a positive feedback loop leading to matrix stiffening and self-sustained, pathological, HSC activation...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27974211/dual-shp2-and-pten-deficiencies-promote-non-alcoholic-steatohepatitis-and-genesis-of-liver-tumor-initiating-cells
#11
Xiaolin Luo, Rui Liao, Kaisa L Hanley, Helen He Zhu, Kirsten N Malo, Carolyn Hernandez, Xufu Wei, Nissi M Varki, Nazilla Alderson, Catherine Chu, Shuangwei Li, Jia Fan, Rohit Loomba, Shuang-Jian Qiu, Gen-Sheng Feng
The complexity of liver tumorigenesis is underscored by the recently observed anti-oncogenic effects of oncoproteins, although the mechanisms are unclear. Shp2/Ptpn11 is a proto-oncogene in hematopoietic cells and antagonizes the effect of tumor suppressor Pten in leukemogenesis. In contrast, we show here cooperative functions of Shp2 and Pten in suppressing hepatocarcinogenesis. Ablating both Shp2 and Pten in hepatocytes induced early-onset non-alcoholic steatohepatitis (NASH) and promoted genesis of liver tumor-initiating cells likely due to augmented cJun expression/activation and elevated ROS and inflammation in the hepatic microenvironment...
December 13, 2016: Cell Reports
https://www.readbyqxmd.com/read/27965466/oxidative-stress-a-trigger-of-hepatitis-c-and-b-virus-induced-liver-carcinogenesis
#12
REVIEW
Alexander V Ivanov, Vladimir T Valuev-Elliston, Daria A Tyurina, Olga N Ivanova, Sergey N Kochetkov, Birke Bartosch, Maria G Isaguliants
Virally induced liver cancer usually evolves over long periods of time in the context of a strongly oxidative microenvironment, characterized by chronic liver inflammation and regeneration processes. They ultimately lead to oncogenic mutations in many cellular signaling cascades that drive cell growth and proliferation. Oxidative stress, induced by hepatitis viruses, therefore is one of the factors that drives the neoplastic transformation process in the liver. This review summarizes current knowledge on oxidative stress and oxidative stress responses induced by human hepatitis B and C viruses...
December 11, 2016: Oncotarget
https://www.readbyqxmd.com/read/27959632/the-role-of-cancer-associated-fibroblasts-and-fibrosis-in-liver-cancer
#13
Silvia Affo, Lexing Yu, Robert F Schwabe
Liver cancer is the second leading cause of cancer mortality worldwide, causing more than 700,000 deaths annually. Because of the wide landscape of genomic alterations and limited therapeutic success of targeting tumor cells, a recent focus has been on better understanding and possibly targeting the microenvironment in which liver tumors develop. A unique feature of liver cancer is its close association with liver fibrosis. More than 80% of hepatocellular carcinomas (HCCs) develop in fibrotic or cirrhotic livers, suggesting an important role of liver fibrosis in the premalignant environment (PME) of the liver...
December 5, 2016: Annual Review of Pathology
https://www.readbyqxmd.com/read/27933310/dynamics-of-antigen-presentation-to-transgene-product-specific-cd4-t-cells-and-of-treg-induction-upon-hepatic-aav-gene-transfer
#14
George Q Perrin, Irene Zolotukhin, Alexandra Sherman, Moanaro Biswas, Ype P de Jong, Cox Terhorst, Andrew M Davidoff, Roland W Herzog
The tolerogenic hepatic microenvironment impedes clearance of viral infections but is an advantage in viral vector gene transfer, which often results in immune tolerance induction to transgene products. Although the underlying tolerance mechanism has been extensively studied, our understanding of antigen presentation to transgene product-specific CD4(+) T cells remains limited. To address this, we administered hepatotropic adeno-associated virus (AAV8) vector expressing cytoplasmic ovalbumin (OVA) into wt mice followed by adoptive transfer of transgenic OVA-specific T cells...
2016: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/27930836/hepatitis-c-virus-infection-propagates-through-interactions-between-syndecan-1-and-cd81-and-impacts-the-hepatocyte-glycocalyx
#15
Boyan Grigorov, Emma Reungoat, Alice Gentil Dit Maurin, Mihayl Varbanov, Julie Blaising, Maud Michelet, Rachel Manuel, Romain Parent, Birke Bartosch, Fabien Zoulim, Florence Ruggiero, Eve-Isabelle Pécheur
The hepatitis C virus (HCV) infects hepatocytes after binding to heparan sulfate proteoglycans, in particular Syndecan-1, followed by recognition of the tetraspanin CD81 and other receptors. Heparan sulfate proteoglycans are found in a specific microenvironment coating the hepatocyte surface called the glycocalyx and are receptors for extracellular matrix proteins, cytokines, growth factors, lipoproteins, and infectious agents. We investigated the mutual influence of HCV infection on the glycocalyx and revealed new links between Syndecan-1 and CD81...
December 8, 2016: Cellular Microbiology
https://www.readbyqxmd.com/read/27929382/aging-promotes-neoplastic-disease-through-effects-on-the-tissue-microenvironment
#16
Fabio Marongiu, Maria Paola Serra, Silvia Doratiotto, Marcella Sini, Maura Fanti, Erika Cadoni, Monica Serra, Ezio Laconi
A better understanding of the complex relationship between aging and cancer will provide important tools for the prevention and treatment of neoplasia. In these studies, the hypothesis was tested that aging may fuel carcinogenesis via alterations imposed in the tissue microenvironment. Preneoplastic hepatocytes isolated from liver nodules were orthotopically injected into either young or old syngeneic rats and their fate was followed over time using the dipeptidyl-peptidase type IV (DPPIV) system to track donor-derived-cells...
December 6, 2016: Aging
https://www.readbyqxmd.com/read/27916538/myofibroblasts-derived-from-hepatic-progenitor-cells-create-the-tumor-microenvironment
#17
Sayaka Sekiya, Shizuka Miura, Kanae Matsuda-Ito, Atsushi Suzuki
Hepatic progenitor cells (HPCs) appear in response to several types of chronic injury in the human and rodent liver that often develop into liver fibrosis, cirrhosis, and primary liver cancers. However, the contribution of HPCs to the pathogenesis and progression of such liver diseases remains controversial. HPCs are generally defined as cells that can differentiate into hepatocytes and cholangiocytes. In this study, however, we found that HPCs isolated from the chronically injured liver can also give rise to myofibroblasts as a third type of descendant...
December 13, 2016: Stem Cell Reports
https://www.readbyqxmd.com/read/27913196/nf-kb-regulated-exosomal-mir-155-promotes-the-inflammation-associated-with-arsenite-carcinogenesis
#18
Chao Chen, Fei Luo, Xinlu Liu, Lu Lu, Hui Xu, Qianlei Yang, Junchao Xue, Le Shi, Jun Li, Aihua Zhang, Qizhan Liu
In the cancer microenvironment, extracellular communication allows various types of cells to coordinate and execute biological functions. Emerging evidence indicates that exosomes, as mediators of cell communication, are involved in tumor progression. Little is known, however, about the mechanism by which exosomal miRNAs regulate inflammatory infiltration in arsenite-induced liver cancer. The present research aimed to determine if miRNAs secreted from arsenite-transformed human hepatic epithelial (L-02) cells are transferred into normal L-02 and THLE-3 cells, which are functionally active in the recipient cells...
November 30, 2016: Cancer Letters
https://www.readbyqxmd.com/read/27910780/naringenin-ameliorates-doxorubicin-toxicity-and-hypoxic-condition-in-dalton-s-lymphoma-ascites-tumor-mouse-model-evidence-from-electron-paramagnetic-resonance-imaging
#19
Venkatesan Kathiresan, Swathika Subburaman, Arun Venkatesh Krishna, Mathivanan Natarajan, Gandhidasan Rathinasamy, Kumaresan Ganesan, Murugesan Ramachandran
Doxorubicin (DOX) is a well-known cytotoxic agent used extensively as a chemotherapeutic drug to eradicate a wide variety of human cancers. Reactive oxygen species (ROS)-mediated oxidative stress during DOX treatment can induce cardiac, renal, and hepatic toxicities, which can constrain its use as a potential cytotoxic agent. The present work investigates the antioxidant potential of naringenin (NAR) against DOXinduced toxicities of a Dalton's lymphoma ascites (DLA) tumor-bearing mouse model. Mice were randomized into four groups: a negative control, positive control, DOX (2...
2016: Journal of Environmental Pathology, Toxicology and Oncology
https://www.readbyqxmd.com/read/27908206/the-role-of-mesenchymal-stem-cells-in-oncology-and-regenerative-medicine
#20
Maliha Khan, Syeda Ezze Rukhshan Adil, Amanda L Olson
Mesenchymal stem cells (MSCs) have long been used as therapeutic agents in disease affecting various organ systems. However, MSCs are fast emerging as promising anticancer agents which have the potential to treat a number of different cancer types, including glioblastoma and metastatic breast, ovarian and hepatic carcinoma. The ability of MSC to migrate directly into the tumor microenvironment and to produce IFN-α and -β makes this possible. However, the possibility of MSC undergoing either malignant transformation or transformation into protumorigenic fibroblasts currently limits their role in clinical use...
December 2, 2016: Future Oncology
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