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Hepatic microenvironment

Nikolina Dioufa, Amanda M Clark, Bo Ma, Colin H Beckwitt, Alan Wells
BACKGROUND: Our understanding of the multiple roles exosomes play during tumor progression is still very poor and the contribution of the normal tissue derived exosomes in distant seeding and tumor outgrowth has also not been widely appreciated. METHODS: Using our all-human liver microphysiological system (MPS) platform as a model to closely recapitulate the early metastatic events, we isolated exosomes from both tumor cells and liver microenvironment. RESULTS: We observed that while priming of the hepatic niche (HepN) with MDA-231 breast cancer derived exosomes facilitated seeding of the cancer cells in the liver, subsequent tumor outgrowth was diminished; this was consistent with increased entry into dormancy...
November 14, 2017: Molecular Cancer
Demetrios Moris, Amir A Rahnemai-Azar, XuFeng Zhang, Ioannis Ntanasis-Stathopoulos, Diamantis I Tsilimigras, Jeffery Chakedis, Chrysoula Argyrou, John J Fung, Timothy M Pawlik
Hepatic malignancies are one of the leading causes of cancer death globally. Considering the limited efficacy of current standard treatments in management of patients with advanced liver cancers, there has been a growing interest in identifying novel therapies. Despite achieving promising results in initial clinical trials, the therapeutic benefit of immunotherapy is limited due to strong immune-tolerogenic characteristics of liver tumors. Therapeutic regimens that impede tumor immunosuppressive mechanisms or elaborate tumor-specific immunity may improve clinical outcomes of patients with liver malignancies...
December 2017: Surgical Oncology
Ghulam Jilany Khan, Mohsin Rizwan, Muhammad Abbas, Muhammad Naveed, Yu Boyang, Muhammad Ahsan Naeem, Sara Khan, Shengtao Yuan, Mirza Muhammad Faran Ashraf Baig, Li Sun
DT-13 is an isolated compound from Dwarf lillytruf tuber and currently among active research drugs by National Natural Science foundation of China for its several potential effects. The drug has been reported for its multiple pharmacological actions however no thorough review studies are available on it. Our present study is highlighting the pros and cons of DT-13 focusing on its potential pharmacological actions, therapeutic utilization and further exploration for novel targets. The drug possesses very low toxicity profile, quick onset and long duration of action with slow elimination that combinely makes it favorable for the clinical studies...
October 28, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Daniela Fenoglio, Chiara Dentone, Alessio Signori, Antonio Di Biagio, Alessia Parodi, Francesca Kalli, Giorgia Nasi, Monica Curto, Giovanni Cenderello, Pasqualina De Leo, Valentina Bartolacci, Giancarlo Orofino, Laura Ambra Nicolini, Lucia Taramasso, Edoardo Fiorillo, Valeria Orrù, Paolo Traverso, Bianca Bruzzone, Federico Ivaldi, Eugenio Mantia, Michele Guerra, Simone Negrini, Mauro Giacomini, Sanjay Bhagani, Gilberto Filaci
BACKGROUND: HIV-associated immunodeficiency is related to loss of CD4(+) T cells. This mechanism does not explain certain manifestations of HIV disease, such as immunodeficiency events in patients with greater than 500 CD4(+) T cells/μL. CD8(+)CD28(-)CD127(lo)CD39(+) T cells are regulatory T (Treg) lymphocytes that are highly concentrated within the tumor microenvironment and never analyzed in the circulation of HIV-infected patients. OBJECTIVES: We sought to analyze the frequency of CD8(+)CD28(-)CD127(lo)CD39(+) Treg cells in the circulation of HIV-infected patients...
October 28, 2017: Journal of Allergy and Clinical Immunology
Zongqiang Hu, Ding Luo, Dongdong Wang, Linjie Ma, Yingpeng Zhao, Li Li
BACKGROUND/AIMS: We performed this study to determine the role of IL-17 in the immune microenvironment of hepatitis B virus- (HBV-) related hepatocellular carcinoma (HCC). METHODS: HepG2 cells were treated with IL-17, STAT3 inhibitor S31-201 or IL-6 neutralizing monoclonal antibody (IL-6 mAb). Cell proliferation and migration were compared using the Cell Counting kit-8 (CCK-8) and Transwell assays, respectively. Real-time quantitative PCR (RT-qPCR), Western Blot, ELISA, immunofluorescence and histological staining were used for determining the expression levels of IL-17, IL-6, MCP-1, CCL5, VEGF, STAT3 and p-STAT3...
October 27, 2017: Cellular Physiology and Biochemistry
Z Jin, J You, H T Wang
Naïve CD4+T cell differentiates into either Th17 or Treg in the microenvironment of various cytokines, among that, Th17 is induced by TGF-β and IL-6, while differentiates into Treg when there is only TGF-β. As the mainly transcription factors of Th17 and Treg respectively, RORγt and Foxp3 have important role in maintaining balance of Th17/Treg. Th17 and Treg are function antagonistically, so the balance of Th17/Treg means a lot for human body. Liver-a metabolic organof the body, it is susceptible to factors in vivo and in vitro...
August 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Y Bao
Non-alcoholic fatty liver diseases (NAFLD) are liver diseases which are strongly associated with obesity. The incidence of NAFLD has been gradually increased in recent years. According to different pathology of the liver, NAFLD include three disease states: simple fatty liver, hepatitis (nonalcoholic steatohepatitis, NASH) and fatty liver cirrhosis. The accumulations of fat around the internal organs, which secrete a wide range of adipokines, such as interleukin-6, contribute the development and progress of NAFLD in obesity...
July 20, 2017: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
Kenichiro Nishii, Erik Brodin, Taylor Renshaw, Rachael Weesner, Emma Moran, Shay Soker, Jessica L Sparks
The role of fluid stresses in activating the hepatic stem/progenitor cell regenerative response is not well understood. This study hypothesized that immediate early genes (IEGs) with known links to liver regeneration will be upregulated in liver progenitor cells (LPCs) exposed to in vitro shear stresses on the order of those produced from elevated interstitial flow after partial hepatectomy. The objectives were: (1) to develop a shear flow chamber for application of fluid stress to LPCs in 3D culture; and (2) to determine the effects of fluid stress on IEG expression in LPCs...
October 20, 2017: Journal of Cellular Physiology
Daniela Alejandra Rios, Pamela Valva, Paola Cecilia Casciato, Silvia Frias, María Soledad Caldirola, María Isabel Gaillard, Liliana Bezrodnik, Juan Bandi, Omar Galdame, Beatriz Ameigeiras, Diana Krasniansky, Carlos Brodersen, Eduardo Mullen, Elena Noemí De Matteo, María Victoria Preciado
The role of the different lymphocyte populations in liver microenvironment of chronic hepatitis C (CHC) patients is still matter of debate. Since Th17 and Treg have opposite functions, their balance could affect disease progression. The aim was to explore liver microenvironment and its peripheral blood counterpart in adult CHC patients. CD4(+) lymphocytes were predominant in the liver, with high Foxp3(+) but low IL-17A(+) frequency. IL-17A(+) lymphocytes and IL-17A(+)/Foxp3(+) ratio displayed association with advanced fibrosis (p = 0...
October 16, 2017: Scientific Reports
Xiao Yang, Wenli Feng, Rong Wang, Feifei Yang, Lina Wang, Shayan Chen, Chong Chen, Qian Ren, Guoguang Zheng
Tumor-associated macrophages (TAMs) are well accepted and the pathological role of macrophages in hematopoietic malignancies have been proposed. Hepatomegaly is frequently observed in T cell acute lymphoblastic leukemia (T-ALL) patients with poor prognosis. However, the role of leukemia-associated macrophages (LAMs) in hepatic microenvironment remains unclear. Here, the characteristics of hepatic LAMs (H-LAMs) were studied in Notch1 induced T-ALL model. Increase in proportion and absolute counts of H-LAMs was detected with infiltration of inflammatory cells...
October 4, 2017: Immunobiology
Xue Wang, Waseem Hassan, Qaiser Jabeen, Ghulam Jilany Khan, Furqan Iqbal
The novelty of an effective therapeutic targeting for hepatocellular carcinoma (HCC) is based on improved understanding of each component of tumor microenvironment (TME) and its correspondent interactions at biological and molecular levels. In this context, new expansions for the treatment against TME and its communication with HCC are under exploration. Despite of the fact that blockage of growth factor receptors has become a treatment of choice in late phases of HCC in clinical practice, still a precise targeted treatment should address all the components of TME...
October 10, 2017: Cytokine
Shimin Wang, Zhi'an Li, Guoming Hu
IL-17A is an important proinflammatory cytokine which is frequently elevated in tumor microenvironment. However, the role of intratumoral IL-17A in solid tumors remains controversial. Herein, we conducted a meta-analysis to assess the prognostic impact of intratumoral IL-17A in patients with solid tumor. PubMed and EBSCO were searched to identify the studies evaluating the associations between intratumoral IL-17A measured by immunohistochemistry (IHC) and overall survival (OS) and disease-free survival (DFS) in solid tumors...
September 12, 2017: Oncotarget
Paula Constanza Arriola Benitez, Ayelén Ivana Pesce Viglietti, Claudia Karina Herrmann, Vida A Dennis, Diego José Comerci, Guillermo Hernán Giambartolomei, María Victoria Delpino
The liver is frequently affected in patients with active brucellosis. The present study demonstrates that B. abortus infection induces the activation of the autophagic pathway in hepatic stellate cells to create a microenvironment that promote a profibrogenic phenotype through the induction of transforming growth factor-β1 (TGF-β1), collagen deposition and inhibition of matrix metalloproteinase-9 (MMP-9) secretion. Autophagy was revealed by up-regulation of the LC3II/LC3I ratio and beclin-1 expression as well as inhibition of p62 expression in infected cells...
October 9, 2017: Infection and Immunity
Naoto Fujiwara, Scott L Friedman, Nicolas Goossens, Yujin Hoshida
Chronic fibrotic liver disease caused by viral or metabolic etiologies is a high-risk condition for developing hepatocellular carcinoma (HCC). Even after complete HCC tumor resection or ablation, the carcinogenic tissue microenvironment in the remnant liver can give rise to recurrent de novo HCC tumors, which progress into incurable, advanced-stage disease in the majority of patients. Thus, early detection and prevention of HCC development is, in principle, the most impactful strategy to improve patient prognosis...
October 5, 2017: Journal of Hepatology
Sizhe Yu, Yu Wang, Li Jing, F X Claret, Qing Li, Tao Tian, Xuan Liang, Zhiping Ruan, Lili Jiang, Yu Yao, Kejun Nan, Yi Lv, Hui Guo
Autophagy plays a dual role in many types of cancer, such as hepatocellular carcinoma (HCC). Autophagy seems to be inhibited and functions as a tumor-suppression mechanism in the "inflammation-carcinogenesis" pathway of the liver, including hepatitis B virus and hepatitis C virus, alcoholic steatohepatitis and non-alcoholic steatohepatitis related HCC. However, in established tumors, autophagy plays a tumor-promoting role. Because of the varied function of autophagy in HCC, we hypothesized p62 as a marker to evaluate the autophagic level...
October 5, 2017: Cancer Letters
Ho-Joon Lee, Myung Jin Son, Jiwon Ahn, Soo Jin Oh, Mihee Lee, Ansoon Kim, Yun-Ji Jeung, Han-Gyeul Kim, Misun Won, Jung Hwa Lim, Nam-Soon Kim, Cho-Rock Jung, Kyung-Sook Chung
Current in vitro liver models provide three-dimensional (3-D) microenvironments in combination with tissue engineering technology and can perform more accurate in vivo mimicry than two-dimensional models. However, a human cell-based, functionally mature liver model is still desired, which would provide an alternative to animal experiments and resolve low-prediction issues on species differences. Here, we prepared hybrid hydrogels of varying elasticity and compared them with a normal liver, to develop a more mature liver model that preserves liver properties in vitro...
December 2017: Acta Biomaterialia
Jesse D Riordan, Charlotte R Feddersen, Barbara R Tschida, Pauline Jackson, Vincent W Keng, Michael A Linden, Khalid Amin, Christopher S Stipp, David A Largaespada, Adam J Dupuy
Most hepatocellular carcinomas (HCCs) develop in a chronically injured liver, yet the extent to which this microenvironment promotes neoplastic transformation or influences selective pressures for genetic drivers of HCC remains unclear. We sought to determine the impact of hepatic injury in an established mouse model of HCC induced by Sleeping Beauty transposon mutagenesis. Chemically-induced chronic liver injury dramatically increased tumor penetrance and significantly altered driver mutation profiles, likely reflecting distinct selective pressures...
September 29, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Da-Yong Zhou, Jie Qin, Jian Huang, Feng Wang, Guo-Peng Xu, Yan-Tian Lv, Ji-Bin Zhang, Li-Ming Shen
Hepatic transcatheter arterial chemoembolization (TACE), a minimally invasive procedure to block the blood supply of tumors and release of cytotoxic agents, is preferentially applied to patients with hepatocellular carcinoma (HCC) who are not able to receive radical treatments. However, the long-term effects of TACE are unsatisfactory, as the microenvironment following procedure stimulates tumor angiogenesis, which promotes recurrence and metastasis of residual tumors. Tumor associated macrophages (TAMs) have been revealed to stimulate tumor growth and angiogenesis associated with poor prognosis in HCC...
October 2017: Oncology Letters
M V Novikova, N V Khromova, P B Kopnin
This review summarizes recently published data on the mechanisms of tumor cell interaction with the tumor microenvironment. Tumor stroma influences the processes of hepatocarcinogenesis, epithelial-to-mesenchymal transition, invasion, and metastasis. The tumor microenvironment includes both cellular and noncellular components. Main cellular components of hepatocellular carcinoma (HCC) stroma are tumor-associated fibroblasts, hepatic stellate cells, immune cells, and endothelial cells that produce extracellular components of tumor microenvironment such as extracellular matrix, various proteins, proteolytic enzymes, growth factors, and cytokines...
August 2017: Biochemistry. Biokhimii︠a︡
Jingying Zhou, Man Liu, Hanyong Sun, Yu Feng, Liangliang Xu, Anthony W H Chan, Joanna H Tong, John Wong, Charing Ching Ning Chong, Paul B S Lai, Hector Kwong-Sang Wang, Shun-Wa Tsang, Tyler Goodwin, Rihe Liu, Leaf Huang, Zhiwei Chen, Joseph Jy Sung, King Lau Chow, Ka Fai To, Alfred Sze-Lok Cheng
OBJECTIVE: Myeloid-derived suppressor cells (MDSCs) contribute to tumour immunosuppressive microenvironment and immune-checkpoint blockade resistance. Emerging evidence highlights the pivotal functions of cyclin-dependent kinases (CDKs) in tumour immunity. Here we elucidated the role of tumour-intrinsic CDK20, or cell cycle-related kinase (CCRK) on immunosuppression in hepatocellular carcinoma (HCC). DESIGN: Immunosuppression of MDSCs derived from patients with HCC and relationship with CCRK were determined by flow cytometry, expression analyses and co-culture systems...
September 22, 2017: Gut
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