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Hepatic microenvironment

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https://www.readbyqxmd.com/read/28798979/mucosa-associated-invariant-t-cells-infiltrate-hepatic-metastases-in-patients-with-colorectal-carcinoma-but-are-rendered-dysfunctional-within-and-adjacent-to-tumor-microenvironment
#1
Christopher R Shaler, Mauro E Tun-Abraham, Anton I Skaro, Khashayarsha Khazaie, Alexandra J Corbett, Tina Mele, Roberto Hernandez-Alejandro, S M Mansour Haeryfar
Mucosa-associated invariant T (MAIT) cells are innate-like T lymphocytes that are unusually abundant in the human liver, a common site of colorectal carcinoma (CRC) metastasis. However, whether they contribute to immune surveillance against colorectal liver metastasis (CRLM) is essentially unexplored. In addition, whether MAIT cell functions can be impacted by chemotherapy is unclear. These are important questions given MAIT cells' potent immunomodulatory and inflammatory properties. Herein, we examined the frequencies and functions of peripheral blood, healthy liver tissue, tumor-margin and tumor-infiltrating MAIT cells in 21 CRLM patients who received no chemotherapy, FOLFOX, or a combination of FOLFOX and Avastin before they underwent liver resection...
August 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28775168/jcad-promotes-progression-of-non-alcoholic-steatohepatitis-to-liver-cancer-by-inhibiting-lats2-kinase-activity
#2
Juan Ye, Tian Sheng Li, Gang Xu, Yi-Ming Zhao, Ning-Ping Zhang, Jia Fan, Jian Wu
Non-alcoholic steatohepatitis-associated hepatocellular carcinoma (NASH-HCC) is a malignancy whose incidents is rapidly increasing. However, the mechanisms that drive development of HCC in a steatotic microenvironment remain unknown. Here we report that the obesity-associated protein JCAD is expressed at significantly higher levels in human NASH-HCC specimens compared to peri-carcinoma specimens. High JCAD expression was verified in multiple hepatoma cell lines. Forced overexpression of JCAD in hepatoma cells promoted tumor growth and proliferation; whereas JCAD silencing yielded opposite effects...
August 3, 2017: Cancer Research
https://www.readbyqxmd.com/read/28755421/smoking-is-a-risk-factor-of-pulmonary-metastasis-in-colorectal-cancer
#3
Masashi Yahagi, Masashi Tsuruta, Hirotoshi Hasegawa, Koji Okabayashi, Naoyuki Toyoda, Nozomi Iwama, Satoru Morita, Yuko Kitagawa
AIM: The hepatic microenvironment, which may include chronic inflammation and fibrosis, is considered to contribute to the pathogenesis of liver metastases of colorectal cancer. A similar mechanism is anticipated in pulmonary metastases, although no reports are available. Smoking causes pulmonary inflammation and fibrosis. Thus, we hypothesized that smokers would be especially affected by pulmonary metastases of colorectal cancer. In this study, we attempted to clarify the impact of smoking on pulmonary metastasis of colorectal cancer...
July 29, 2017: Colorectal Disease: the Official Journal of the Association of Coloproctology of Great Britain and Ireland
https://www.readbyqxmd.com/read/28715713/metastasis-systems-biology-how-are-macro-environmental-signals-transmitted-into-microenvironmental-cues-for-disseminated-tumor-cells
#4
REVIEW
Candice Alexandra Grzelak, Cyrus Michael Ghajar
Disseminated breast tumor cells reside on or near stable microvascular endothelium. Currently, the cues that disrupt DTC dormancy and facilitate outgrowth are largely unknown. This article explores the hypothesis that specific patient lifestyle exposures (e.g., alcohol abuse) may disrupt the microenvironments that maintain disseminated tumor cell (DTC) dormancy in a tissue-specific fashion. We suggest that such exposures are 'transmitted' to the dormant niche in the form of injury. Thus, we discuss the relationship between wound healing and metastasis using liver as an example to illustrate how injury steers the phenotype of liver endothelium and perivascular hepatic stellate cells to a potentially pro-metastatic one...
July 14, 2017: Current Opinion in Cell Biology
https://www.readbyqxmd.com/read/28706144/prognostic-role-of-intratumoral-il-17a-expression-by-immunohistochemistry-in-solid-tumors-a-meta-analysis
#5
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...
June 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28694740/review-of-hepatocellular-carcinoma-epidemiology-etiology-and-carcinogenesis
#6
REVIEW
Yezaz Ahmed Ghouri, Idrees Mian, Julie H Rowe
Since the 1970s, the epidemic of hepatocellular carcinoma (HCC) has spread beyond the Eastern Asian predominance and has been increasing in Northern hemisphere, especially in the United States (US) and Western Europe. It occurs more commonly in males in the fourth and fifth decades of life. Among all cancers, HCC is one of the fastest growing causes of death in the US and poses a significant economic burden on healthcare. Chronic liver disease due to hepatitis B virus or hepatitis C virus and alcohol accounts for the majority of HCC cases...
2017: Journal of Carcinogenesis
https://www.readbyqxmd.com/read/28677743/yi-guan-jian-decoction-may-enhance-hepatic-differentiation-of-bone-marrow%C3%A2-derived-mesenchymal-stem-cells-via-sdf%C3%A2-1-in%C3%A2-vitro
#7
Lin-Lin Fu, Bing-Yao Pang, Ying Zhu, Ling Wang, Ai-Jing Leng, Hai-Long Chen
A previous study reported that Yi Guan Jian (YGJ) may increase the proliferation and differentiation of hepatic oval cells in a rat liver cirrhosis model. The aim of the present study was to investigate the effect and mechanism of action of YGJ on inducing hepatic differentiation in bone marrow‑derived mesenchymal stem cells (BM‑MSCs) via stromal‑cell derived factor‑1 (SDF‑1). Murine BM‑MSCs were isolated with whole bone marrow adherence, then identified by immunocytochemical staining and flow cytometry...
September 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28668389/inducible-liver-specific-overexpression-of-gankyrin-in-zebrafish-results-in-spontaneous-intrahepatic-cholangiocarcinoma-and-hepatocellular-carcinoma-formation
#8
Shin-Jie Huang, Chih-Lun Cheng, Jim-Ray Chen, Hong-Yi Gong, Wangta Liu, Jen-Leih Wu
Liver cancer is the second leading cause of death worldwide. As such, establishing animal models of the disease is important for both basic and translational studies that move toward developing new therapies. Gankyrin is a critical oncoprotein in the genetic control of liver pathology. In order to evaluate the oncogenic role of gankyrin without cancer cell inoculation and drug treatment, we overexpressed gankyrin under the control of the fabp10a promoter. A Tet-Off system was used to drive expression in hepatocytes...
August 26, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28667437/an-elf2-like-transcription-factor-acts-as-repressor-of-the-mouse-ecto-5-nucleotidase-gene-expression-in-hepatic-myofibroblasts
#9
Michel Fausther, Elise G Lavoie, Jessica R Goree, Jonathan A Dranoff
Hepatic fibrosis represents a pathological wound healing and tissue repair process triggered in response to chronic liver injury. A heterogeneous population of activated non-parenchymal liver cells, known as liver myofibroblasts, functions as the effector cells in hepatic fibrosis. Upon activation, liver myofibroblasts become fibrogenic, acquiring contractile properties and increasing collagen production capacity, while developing enhanced sensitivity to endogenous molecules and factors released in the local microenvironment...
June 30, 2017: Purinergic Signalling
https://www.readbyqxmd.com/read/28665890/the-impact-of-liver-graft-injury-on-cancer-recurrence-posttransplantation
#10
Chang-Xian Li, Kwan Man, Chung-Mau Lo
Liver transplantation is the most effective treatment for selected patients with hepatocellular carcinoma (HCC). However, cancer recurrence, posttransplantation, remains to be the critical issue which affects the long-term outcome of HCC recipients. In addition to tumor biology itself, increasing evidence demonstrates that acute phase liver graft injury is a result of hepatic ischemia reperfusion (I/R) injury (which is an inevitable consequence during liver transplantation) and may promote cancer recurrence at late phase posttransplantation...
June 29, 2017: Transplantation
https://www.readbyqxmd.com/read/28645290/establishment-of-an-orthotopic-patient-derived-xenograft-mouse-model-using-uveal-melanoma-hepatic-metastasis
#11
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
#12
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
#13
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
#14
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
#15
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 tolerizing therapies...
August 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
#16
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
#17
Marion Duriez, Yassmina Mandouri, Bouchra Lekbaby, Hualin Wang, Aurélie Schnuriger, Francois Redelsperger, Chiara Ida Guerrera, Marine Lefevre, Veronique Fauveau, James Ahodantin, Ivan Quetier, Cerina Chhuon, Samir Gourari, Alexandre Boissonnas, 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. 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 with 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 7, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28596109/cytotherapy-with-m1-polarized-macrophages-ameliorates-liver-fibrosis-by-modulating-immune-microenvironment-in-mice
#18
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 in liver fibrosis. However, macrophages possess ontogenic and functional heterogeneities. Some subsets are pro-fibrotic, whereas others are anti-fibrotic. This study aimed to clarify which macrophage subset is efficient for cytotherapy in liver fibrosis and to elucidate the underlying mechanisms. METHODS: Liver fibrosis was induced in mice by carbon tetrachloride injection or bile duct ligation...
July 26, 2017: Journal of Hepatology
https://www.readbyqxmd.com/read/28578016/engineering-in-vitro-models-of-hepatofibrogenesis
#19
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
#20
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
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