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Hepatic microenvironment

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https://www.readbyqxmd.com/read/29339440/repurposing-tin-mesoporphyrin-as-an-immune-checkpoint-inhibitor-shows-therapeutic-efficacy-in-preclinical-models-of-cancer
#1
Tamara Muliaditan, James W Opzoomer, Jonathan Caron, Mary Okesola, Paris Kosti, Sharanpreet Lall, Mieke Van Hemelrijck, Francesco Dazzi, Andrew Tutt, Anita Grigoriadis, Cheryl Gillett, Stephen F Madden, Joy M Burchell, Shahram Kordasti, Sandra S Diebold, James Spicer, James N Arnold
PURPOSE: Unprecedented clinical outcomes have been achieved in a variety of cancers by targeting immune checkpoint molecules. This preclinical study investigates heme oxygenase-1 (HO-1), an immune suppressive enzyme that is expressed in a wide variety of cancers, as a potential immune checkpoint target in the context of a chemotherapy-elicited anti-tumor immune response. We evaluate repurposing tin mesoporphyrin (SnMP), which has demonstrated safety and efficacy targeting hepatic HO in the clinic for the treatment of hyperbilirubinaemia, as an immune checkpoint blockade therapy for the treatment of cancer...
January 16, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29338160/higher-activities-of-hepatic-versus-splenic-cd8-t-cells-in-responses-to-adoptive-t-cell-therapy-and-vaccination-of-b6-mice-with-mhc-class-1-binding-antigen
#2
Mohamed Labib Salem, Randa E El Naggar, Sabry A El Naggar, Maysa A Mobasher, Mohamed H Mahmoud, Gamal Badr
The liver has unique microenvironment which is known to induce tolerance of cytolytic CD8+ T cells to hepatic and extra hepatic antigens, resulting in persistence of infection of the liver by the hepatitis B and C viruses. However, under some conditions, functional immune responses can be elicited in the liver in particular to show preferential retention of activated CD8+ T cells. It is not clear whether this retention depends on the type of the exogenous immunostimulatory or the endogenous innate immune cells...
December 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/29321049/human-liver-organoids-generated-with-single-donor-derived-multiple-cells-rescue-mice-from-acute-liver-failure
#3
Yun-Zhong Nie, Yun-Wen Zheng, Miyuki Ogawa, Etsuko Miyagi, Hideki Taniguchi
BACKGROUND: Acute liver failure (ALF) is a life-threatening disease with a high mortality rate. However, there are limited treatments or devices available for ALF therapy. Here, we aimed to develop a new strategy for ALF treatment by transplanting functional liver organoids (LOs) generated from single donor-derived human induced pluripotent stem cell (hiPSC) endoderm, endothelial cells (ECs), and mesenchymal cells (MCs). METHODS: First, we isolated ECs and MCs from a single donor umbilical cord (UC) through enzyme digestion and characterized the UC-ECs and UC-MCs by flow cytometry...
January 10, 2018: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/29316949/ezh2-promotes-hepatocellular-carcinoma-progression-through-modulating-mir-22-galectin-9-axis
#4
Shaofei Chen, Jiarui Pu, Jie Bai, Yuping Yin, Ke Wu, Jiliang Wang, Xiaoming Shuai, Jinbo Gao, Kaixiong Tao, Guobin Wang, Hang Li
BACKGROUND: Recent studies have shown that interferon-γ (IFN-γ)-induced galectin-9 expression in Kupffer cells plays an essential role in modulatingthe microenvironment of hepatitis-associated hepatocellular carcinoma (HCC). However, whether or not IFN-γ induces galectin-9 expression in HCC cells, its biological role and regulatory mechanism in HCC development and progression are poorly defined. METHODS: Quantitative PCR and western blotting analysis were used to detect galectin-9 and EZH2 levels in HCC cell lines stimulated with IFN-γ...
January 9, 2018: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/29313221/myeloid-cells-and-chronic-liver-disease-a-comprehensive-review
#5
REVIEW
Min Lian, Carlo Selmi, M Eric Gershwin, Xiong Ma
Myeloid cells play a major role in the sensitization to liver injury, particularly in chronic inflammatory liver diseases with a biliary or hepatocellular origin, and the interplay between myeloid cells and the liver may explain the increased incidence of hepatic osteodystrophy. The myeloid cell-liver axis involves several mature myeloid cells as well as immature or progenitor cells with the complexity of the liver immune microenvironment aggravating the mist of cell differentiation. The unique positioning of the liver at the junction of the peripheral and portal circulation systems underlines the interaction of myeloid cells and hepatic cells and leads to immune tolerance breakdown...
January 8, 2018: Clinical Reviews in Allergy & Immunology
https://www.readbyqxmd.com/read/29288236/cd47-blockade-as-an-adjuvant-immunotherapy-for-resectable-pancreatic-cancer
#6
Alex D Michaels, Timothy E Newhook, Sara J Adair, Sho Morioka, Bernadette J Goudreau, Sarbajeet Nagdas, Matthew G Mullen, Jesse B Persily, Timothy Bullock, Craig L Slingluff, Kodi S Ravichandran, J Thomas Parsons, Todd W Bauer
PURPOSE: Patients with pancreatic ductal adenocarcinoma (PDAC) who undergo surgical resection and adjuvant chemotherapy have an expected survival of only two years due to disease recurrence, frequently in the liver. We investigated the role of liver macrophages in progression of PDAC micrometastases to identify adjuvant treatment strategies that could prolong survival. EXPERIMENTAL DESIGN: A murine splenic injection model of hepatic micrometastatic PDAC was used with five patient-derived PDAC tumors...
December 29, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/29286082/ccn1-cyr61-enhances-the-function-of-hepatic-stellate-cells-in-promoting-the-progression-of-hepatocellular-carcinoma
#7
Zhi-Qiang Li, Wei-Ru Wu, Chen Zhao, Chen Zhao, Xiao-Li Zhang, Zhong Yang, Jing Pan, Wei-Ke Si
Hepatic stellate cells (HSCs) are the main extracellular matrix (ECM)‑producing cells in liver fibrosis. Activated HSCs stimulate the proliferation and migration of hepatocellular carcinoma (HCC) cells. Cysteine‑rich 61 (CCN1/Cyr61) is an ECM protein. Our previous studies demonstrated that the expression of CCN1 was significantly higher in benign hepatic cirrhosis tissue and cancer‑adjacent hepatic cirrhosis tissues. CCN1 is a target gene of β‑catenin in HCC and promotes the proliferation of HCC cells...
December 29, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29278438/role-of-hsf1-expression-in-the-microenvironment-of-intrahepatic-cholangiocarcinomas
#8
Yoichiro Kawashita, Yuji Morine, Yu Saito, Chie Takasu, Tetsuya Ikemoto, Shuichi Iwahashi, Hiroki Teraoku, Masato Yoshikawa, Satoru Imura, Toshiyuki Yagi, Mitsuo Shimada
BACKGROUND: Heat shock factor 1 (HSF1), a master regulator of heat shock response, has been shown to play a multifaceted role in cancer progression. However, the clinical significance and biological effect of HSF1 expression in intrahepatic cholangiocarcinoma (IHCC) remain unknown. METHODS: Forty-nine patients with IHCC who underwent hepatic resection were enrolled in this study. HSF1 expression in tumor tissue was determined by immunohistochemistry, and patients were divided into two groups, those with high (n=20) and low (n=29) HSF1 expression...
December 26, 2017: Journal of Gastroenterology and Hepatology
https://www.readbyqxmd.com/read/29258450/serum-cytokine-profiles-predict-survival-benefits-in-patients-with-advanced-hepatocellular-carcinoma-treated-with-sorafenib-a-retrospective-cohort-study
#9
Tomoyuki Hayashi, Taro Yamashita, Takeshi Terashima, Tsuyoshi Suda, Hikari Okada, Yoshiro Asahina, Takehiro Hayashi, Yasumasa Hara, Kouki Nio, Hajime Sunagozaka, Hajime Takatori, Kuniaki Arai, Yoshio Sakai, Tatsuya Yamashita, Eishiro Mizukoshi, Masao Honda, Shuichi Kaneko
BACKGROUND: Sorafenib is a multiple receptor tyrosine kinase inhibitor known to prolong overall survival in patients with advanced hepatocellular carcinoma (HCC). Predicting this drug's survival benefits is challenging because clinical responses are rarely measurable during treatment. In this study, we hypothesized that serum cytokines levels could predict the survival of advanced HCC patients, as sorafenib targets signaling pathways activated in the tumor stromal microenvironment and potentially affects serum cytokine profiles...
December 19, 2017: BMC Cancer
https://www.readbyqxmd.com/read/29248714/foxq1-ndrg1-axis-exacerbates-hepatocellular-carcinoma-initiation-via-enhancing-crosstalk-between-fibroblasts-and-tumor-cells
#10
Qin Luo, Chao-Qun Wang, Lu-Yu Yang, Xiao-Mei Gao, Hao-Ting Sun, Yu Zhang, Kai-Li Zhang, Ying Zhu, Yan Zheng, Yuan-Yuan Sheng, Lu Lu, Hu-Liang Jia, Wen-Qiang Yu, Jie Liu, Qiong-Zhu Dong, Lun-Xiu Qin
Cancer associated fibroblast (CAF) is a well-known microenvironment contributor for the development of hepatocellular carcinoma (HCC), while forkhead box (FOX) proteins are also critical to exacerbate HCC malignancy. However, whether FOX proteins are involved in the crosstalk between CAFs and HCC cells remains unclear. In the present study, we reveal that CAFs induce forkhead box Q1 (FOXQ1) expression, and N-myc downstream-regulated gene 1 (NDRG1) is therefore trans-activated to enhance HCC initiation. Intriguingly, pSTAT6/C-C motif chemokine ligand 26 (CCL26) signaling is induced by FOXQ1/NDRG1 axis, thus recruiting hepatic stellate cells (HSCs), the main cellular source of CAFs, to the tumor microenvironment...
December 15, 2017: Cancer Letters
https://www.readbyqxmd.com/read/29246201/multiparametric-functional-magnetic-resonance-imaging-for-evaluation-of-hepatic-warm-ischemia-reperfusion-injury-in-a-rabbit-model
#11
Qian Ji, Zhi Qiang Chu, Tao Ren, Shi Chao Xu, Long Jiang Zhang, Wen Shen, Guang Ming Lu
BACKGROUND: To assess the feasibility of noninvasive and quantitative evaluation of hepatic pathophysiological changes in rabbit hepatic warm ischemia-reperfusion injury (WIRI) models by using intravoxel incoherent motion (IVIM), diffusion tensor imaging (DTI) and blood oxygen level dependent (BOLD) MRI. METHODS: Twenty rabbits were randomly divided into hepatic WIRI model group and sham-operation group (n = 10 for each group). Hepatic WIRI was induced in rabbit by occluding hepatic inflow for 30 min and reperfusion for 6 h...
December 15, 2017: BMC Gastroenterology
https://www.readbyqxmd.com/read/29222839/decellularized-human-liver-extracellular-matrix-hdlm-mediated-hepatic-differentiation-of-human-induced-pluripotent-stem-cells-hipsc
#12
Maria Jaramillo, Heidi Yeh, Martin L Yarmush, Basak E Uygun
Liver tissue engineering has emerged as a promising approach in organ transplantation, but has been hampered by the lack of a reliable and readily available cell source. Induced pluripotent cells (hiPSC) have been highlighted a desirable source, due to their differentiation potential, ability to self-renew and the possibility of making patient specific cells. We developed a decellularization protocol that efficiently removes cellular material, while retaining extracellular matrix components. Subsequently, hiPSC were differentiated on the decellularized human liver matrix (hDLM) scaffolds using an established hepatic differentiation protocol...
December 8, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/29197664/emerging-metabolic-risk-factors-in-hepatocellular-carcinoma-and-their-influence-on-the-liver-microenvironment
#13
REVIEW
Pasquale Agosti, Carlo Sabbà, Antonio Mazzocca
Despite the reducing incidence of chronic hepatitis infections, an unexpected increasing incidence of hepatocellular carcinoma (HCC) has being occurred. This may be explained by the increasing number of HCCs developing on steatosis (NAFLD) and steatohepatitis (NASH), related to metabolic risk factors (i.e. diabetes mellitus type II, obesity, metabolic syndrome), which are becoming emerging risk factors for HCC. This led to a growing scientific interest on the oncogenic mechanisms underlying the transition from NAFLD to HCC...
November 29, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/29196957/phase-1-and-pharmacokinetic-study-of-ly3007113-a-p38-mapk-inhibitor-in-patients-with-advanced-cancer
#14
Jonathan W Goldman, Lee S Rosen, Anthony W Tolcher, Kyriakos Papadopoulos, Muralidhar Beeram, Peipei Shi, Celine Pitou, Robert Bell, Palaniappan Kulanthaivel, Xuekui Zhang, Aaron Fink, Edward M Chan, Ashwin Shahir, Daphne Farrington, Amita Patnaik
Background The signaling protein p38 mitogen-activated protein kinase (MAPK) regulates the tumor cell microenvironment, modulating cell survival, migration, and invasion. This phase 1 study evaluated the safety of p38 MAPK inhibitor LY3007113 in patients with advanced cancer to establish a recommended phase 2 dose. Methods In part A (dose escalation), LY3007113 was administered orally every 12 h (Q12H) at doses ranging from 20 mg to 200 mg daily on a 28-day cycle until the maximum tolerated dose (MTD) was reached...
December 1, 2017: Investigational New Drugs
https://www.readbyqxmd.com/read/29186062/viral-oncology-molecular-biology-and-pathogenesis
#15
REVIEW
Uyen Ngoc Mui, Christopher T Haley, Stephen K Tyring
Oncoviruses are implicated in approximately 12% of all human cancers. A large number of the world's population harbors at least one of these oncoviruses, but only a small proportion of these individuals go on to develop cancer. The interplay between host and viral factors is a complex process that works together to create a microenvironment conducive to oncogenesis. In this review, the molecular biology and oncogenic pathways of established human oncoviruses will be discussed. Currently, there are seven recognized human oncoviruses, which include Epstein-Barr Virus (EBV), Human Papillomavirus (HPV), Hepatitis B and C viruses (HBV and HCV), Human T-cell lymphotropic virus-1 (HTLV-1), Human Herpesvirus-8 (HHV-8), and Merkel Cell Polyomavirus (MCPyV)...
November 29, 2017: Journal of Clinical Medicine
https://www.readbyqxmd.com/read/29175445/adipocyte-biology-in-breast-cancer-from-silent-bystander-to-active-facilitator
#16
REVIEW
Junjeong Choi, Yoon Jin Cha, Ja Seung Koo
Adipocytes account for the largest proportion among the cells that comprise breast tissue; therefore, they are considered to be a critical cell type in the tumor microenvironment of breast cancer. In breast cancer, adipocytes are not only found adjacent to cancer cells, but they also play an active role in the entire process of cancer development, progression, metastasis, and treatment response. Factors including the secretion of adipokines such as leptin and adiponectin, as well as autotaxin, interleukin 6, tumor necrosis factor alpha, and hepatic growth factor, metabolic remodeling that supports the growth of breast cancer by transfer of fatty acids to increase mitochondrial β-oxidation, extracellular matrix remodeling and endotrophin production from type IV collagen, and cancer-associated fibroblast phenotype changes have all been implicated in this comprehensive process...
November 21, 2017: Progress in Lipid Research
https://www.readbyqxmd.com/read/29163520/the-injury-related-activation-of-hedgehog-signaling-pathway-modulates-the-repair-associated-inflammation-in-liver-fibrosis
#17
REVIEW
Xin Shen, Yu Peng, Hanmin Li
Liver fibrosis is a wound healing response initiated by inflammation responding for different iterative parenchymal damages caused by diverse etiologies. Immune cells, which exert their ability of either inducing injury or promoting repair, have been regarded as crucial participants in the fibrogenic response. A characteristic feature of the fibrotic microenvironment associated with chronic liver injury is aberrant activation of hedgehog (Hh) signaling pathway. Growing evidence from a number of different studies in vivo and in vitro has indicated that immune-mediated events involved in liver fibrogenesis are regulated by Hh signaling pathway...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29155718/the-murine-choline-deficient-ethionine-supplemented-cde-diet-model-of-chronic-liver-injury
#18
Jully Gogoi-Tiwari, Julia Köhn-Gaone, Corey Giles, Dirk Schmidt-Arras, Francis D Gratte, Caryn L Elsegood, Geoffrey W McCaughan, Grant A Ramm, John K Olynyk, Janina E E Tirnitz-Parker
Chronic liver diseases, such as viral hepatitis, alcoholic liver disease, or non-alcoholic fatty liver disease, are characterized by continual inflammation, progressive destruction and regeneration of the hepatic parenchyma, liver progenitor cell proliferation, and fibrosis. The end-stage of every chronic liver disease is cirrhosis, a major risk factor for the development of hepatocellular carcinoma. To study processes regulating disease initiation, establishment, and progression, several animal models are used in laboratories...
October 21, 2017: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/29152658/hepatic-differentiation-of-mouse-bone-marrow%C3%A2-derived-mesenchymal-stem-cells-using-a-novel-3d-culture-system
#19
Qiong Wu, Jing Tang, Yi Li, Li Li, Yujia Wang, Ji Bao, Hong Bu
The development of novel culture systems that mimic the in vivo microenvironment may be beneficial for inducing the differentiation of stem cells and promoting liver function. In the present study, spheroid cultures and decellularized liver scaffolds (DLSs) were utilized to obtain differentiated hepatocyte‑like cells. Mouse bone marrow (BM)‑derived mesenchymal stem cells (MSCs) self‑aggregated into spheroids under low‑attachment conditions and implanted into the DLSs via a negative pressure suction device...
October 19, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/29137633/bi-directional-exosome-driven-intercommunication-between-the-hepatic-niche-and-cancer-cells
#20
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
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