Read by QxMD icon Read

Hepatic microenvironment

Deepak Kotiya, Bharti Jaiswal, Sampa Ghose, Rachna Kaul, Kasturi Datta, Rakesh K Tyagi
The role of nuclear receptor PXR in detoxification and clearance of xenobiotics and endobiotics is well-established. However, its projected role in hepatic cancer is rather illusive where its expression is reported altered in different cancers depending on the tissue-type and microenvironment. The expression of PXR, its target genes and their biological or clinical significance have not been examined in hepatic cancer. In the present study, by generating DEN-induced hepatic cancer in mice, we report that the expression of PXR and its target genes CYP3A11 and GSTa2 are down-regulated implying impairment of hepatic detoxification capacity...
2016: PloS One
Maria Celia Fernandez, Roni Rayes, Boram Ham, Ni Wang, France Bourdeau, Simon Milette, Martin Lllemann, Nigel Bird, Ali Majeed, Jun Xu, Tatiana Kisselova, Pnina Brodt
Hepatic stellate cells (HSC) play a major role in initiating the liver fibrogenic (wounding) response of the liver and can also orchestrate a pro-metastatic microenvironment in the liver in response to invading cancer cells. Here we explored the role of the hepatic stellate cells in colon carcinoma liver metastasis with emphasis on the contribution of the insulin-like growth factor (IGF) axis to their activation and function. To this end, we used mice with a Tamoxifen inducible liver IGF-I deficiency. We found that in mice with a sustained IGF-I deficiency, recruitment and activation of HSC into tumor-infiltrated areas of the liver were markedly diminished, resulting in decreased collagen deposition and reduced tumor expansion...
October 12, 2016: Oncotarget
Christine Lin, Salman R Khetani
Drug-induced liver injury (DILI) is a major cause of drug attrition. Testing drugs on human liver models is essential to mitigate the risk of clinical DILI since animal studies do not always suffice due to species-specific differences in liver pathways. While primary human hepatocytes (PHHs) can be cultured on extracellular matrix proteins, a rapid decline in functions leads to low sensitivity (<50%) in DILI prediction. Semiconductor-driven engineering tools now allow precise control over the hepatocyte microenvironment to enhance and stabilize phenotypic functions...
2016: BioMed Research International
Ran-Ran Zhang, Yun-Wen Zheng, Hideki Taniguchi
A novel animal model involving chimeric mice with humanized livers established via human hepatocyte transplantation has been developed. These mice, in which the liver has been repopulated with functional human hepatocytes, could serve as a useful tool for investigating human hepatic cell biology, drug metabolism, and other preclinical applications. One of the key factors required for successful transplantation of human hepatocytes into mice is the elimination of the endogenous hepatocytes to prevent competition with the human cells and provide a suitable space and microenvironment for promoting human donor cell expansion and differentiation...
2016: Journal of Visualized Experiments: JoVE
Ke-Qi Han, Hui Han, Xue-Qun He, Lei Wang, Xiao-Dong Guo, Xue-Ming Zhang, Jie Chen, Quan-Gang Zhu, Hua Nian, Xiao-Feng Zhai, Ma-Wei Jiang
The purpose of this study was to screen for changes in chemokine and chemokine-related genes that are expressed in hepatocellular carcinoma (HCC) as potential markers of HCC progression. Total RNA was extracted from tumor and peritumor tissues from mice with HCC and analyzed using a PCR microarray comprising 98 genes. Changes in gene expression of threefold or more were screened and subsequently confirmed by immunohistochemical analyses and western blotting. Furthermore, whether chemokine knockdown by RNA interference (RNAi) could significantly suppress tumor growth in vivo was also evaluated...
September 28, 2016: Cancer Medicine
Amranul Haque, Pantea Gheibi, Yandong Gao, Elena Foster, Kyung Jin Son, Jungmok You, Gulnaz Stybayeva, Dipali Patel, Alexander Revzin
The approaches for maintaining hepatocytes in vitro are aimed at recapitulating aspects of the native liver microenvironment through the use of co-cultures, surface coatings and 3D spheroids. This study highlights the effects of spatial confinement-a less studied component of the in vivo microenvironment. We demonstrate that hepatocytes cultured in low-volume microfluidic channels (microchambers) retain differentiated hepatic phenotype for 21 days whereas cells cultured in regular culture plates under identical conditions de-differentiate after 7 days...
September 29, 2016: Scientific Reports
Andreas Weltin, Steffen Hammer, Fozia Noor, Yeda Kaminski, Jochen Kieninger, Gerald A Urban
3D hepatic microtissues, unlike 2D cell cultures, retain many of the in-vivo-like functionalities even after long-term cultivation. Such 3D cultures are increasingly applied to investigate liver damage due to drug exposure in toxicology. However, there is a need for thorough metabolic characterization of these microtissues for mechanistic understanding of effects on culture behaviour. We measured metabolic parameters from single human HepaRG hepatocyte spheroids online and continuously with electrochemical microsensors...
July 28, 2016: Biosensors & Bioelectronics
Anne Tr Noll, Thorsten Cramer, Steven Wm Olde Damink, Frank G Schaap
Cholangiocarcinoma (CCA) is a relatively rare malignancy of the intra- or extra-hepatic bile ducts that is classified according to its anatomical localization as intrahepatic, perihilar or distal. Overall, CCA has a dismal prognosis due to typical presentation at an advanced irresectable stage, lack of effective non-surgical treatments, and a high rate of disease recurrence. CCA frequently arises on a background of chronic liver inflammation and cholestasis. Chronic inflammation is accompanied by enhanced cell turnover with generation of additional inflammatory stimuli, and a microenvironment rich in pro-inflammatory mediators and proliferative factors that enable accumulation of mutations, transformation and expansion of mutated cells...
September 18, 2016: World Journal of Hepatology
Sha Fu, Rong-Rong Zhou, Ning Li, Yan Huang, Xue-Gong Fan
Encoded by the hepatitis B virus, hepatitis B virus X protein (HBx) is a multifunctional, potentially oncogenic protein that acts primarily during the progression from chronic hepatitis B to cirrhosis and hepatocellular carcinoma (HCC). In recent decades, it has been established that chronic inflammation generates a tumor-supporting microenvironment. HCC is a typical chronic inflammation-related cancer, and inflammation is the main risk factor for HCC progression. The viral transactivator HBx plays a pivotal role in the initiation and maintenance of hepatic inflammatory processes through interactions with components of the tumor microenvironment including tumor cells and the surrounding peritumoral stroma...
September 23, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Misako Sato-Matsubara, Norifumi Kawada
Nielsen SR, Quaranta V, Linford A, et al.(1) (Macrophage-secreted granulin supports pancreatic cancer metastasis by inducing liver fibrosis. Nat Cell Biol. 2016;18:549-60) recently described a new mechanism for the tumor-stromal interaction in the metastatic progression of pancreatic ductal adenocarcinoma (PDAC) in the liver via granulin that is secreted by metastasis-associated macrophages (MAMs).(1) MAM-derived granulin transactivates hepatic stellate cells (hStCs), which leads to the production of periostin and extracellular matrix (ECM) at the metastatic site...
September 19, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Amalia Azzariti, Serena Mancarella, Letizia Porcelli, Anna Elisa Quatrale, Alessandra Caligiuri, Luigi Lupo, Francesco Dituri, Gianluigi Giannelli
BACKGROUND AND AIMS: In patients with HCC receiving sorafenib, drug resistance is common. HCC develops in a microenvironment enriched with extracellular matrix proteins (ECM) including Laminin (Ln)-332, produced by hepatic stellate cells (HSCs). Ln-332 is the ligand of α3β1 and α6β4 integrins, differently expressed on HCC cell surface, that deliver intracellular pathways. Aim of this study is to investigate the effect of Ln-332 on sorafenib's effectiveness. METHODS: HCC cells were challenged with Sorafenib in the presence of Ln-332 and of HSCs conditioned medium (CM)...
September 17, 2016: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
Xin Zhao, Xiaolei Shi, Zhiheng Zhang, Hucheng Ma, Xianwen Yuan, Yitao Ding
BACKGROUND: The imbalance of immunity is an important pathogenesis of acute liver failure (ALF). Neutrophils are the hallmark of acute inflammation, which have an essential role in immune regulation. Mesenchymal stem cell (MSC) transplantation is a promising therapy in ALF treatment. Recent studies indicated a considerable connection between MSCs and neutrophils in immune regulation. AIM: To investigate changes in neutrophils in ALF rats after MSC transplantation, and to explore the therapeutic effect and mechanism of the combined treatment with MSC transplantation and neutrophil depletion in ALF...
September 13, 2016: Clinics and Research in Hepatology and Gastroenterology
Sitelbanat Yassin, Jialiang Hu, Hanmei Xu, Ce Li, Sarra Setrerrahmane
Anti-angiogenesis is an important therapy for cancer treatment. Peptide HM-3 is an integrin antagonist with anti-angiogenic and antitumor activity. Previous research found that HM-3 at an effective dose inhibited tumor growth whereas at higher doses, the inhibitory effect gradually decreased. In the present study, three human tumor cell lines, human colorectal cancer cell (HCT-116) and human hepatic cancer cell (Hep G-2 and SMMC-7721), were selected and their interactions with HM-3 were compared with western blot and flow cytometric assays...
September 9, 2016: Oncology Reports
Yoshikuni Inokawa, Fuminori Sonohara, Mitsuro Kanda, Masamichi Hayashi, Yoko Nishikawa, Hiroyuki Sugimoto, Yasuhiro Kodera, Shuji Nomoto
BACKGROUND/AIM: Post-resection recurrence of hepatocellular carcinoma (HCC) tends to derive from multicentric origins, which indicates that the background liver microenvironment affects carcinogenesis. MATERIALS AND METHODS: We obtained control liver samples [super normal (SN)] from 11 patients with secondary metastatic liver malignancies and used expression and methylation arrays to compare them with non-cancerous liver tissue from a patient with typical HCC with chronic hepatitis C (corresponding normal (CN)]...
September 2016: Anticancer Research
Chang-Long Chen, Qiu-Zhong Pan, Jing-Jing Zhao, Ying Wang, Yong-Qiang Li, Qi-Jing Wang, Ke Pan, De-Sheng Weng, Shan-Shan Jiang, Yan Tang, Xiao-Fei Zhang, Hong-Xia Zhang, Zi-Qi Zhou, Yi-Xin Zeng, Jian-Chuan Xia
Cytokine-induced killer (CIK) cell immunotherapy represents an effective treatment strategy for treating hepatocellular carcinoma (HCC). However, the therapeutic benefits of CIK cell treatment can be influenced by differences in complex immune microenvironment between patients. Herein, we investigated the relationship between PD-L1 expression and survival benefits of CIK cell immunotherapy in HCC patients. This retrospective study included 448 HCC patients: 217 cases underwent hepatectomy alone; 231 cases received hepatectomy and post-operative CIK cell transfusion...
July 2016: Oncoimmunology
Yuan Liu, Xiaodong Guo, Liyuan Wu, Mei Yang, Zhiwei Li, Yinjie Gao, Shuhong Liu, Guangde Zhou, Jingmin Zhao
: Hepatocellular carcinoma (HCC) occurs predominantly in patients with underlying chronic liver disease and cirrhosis. Toll-like receptors (TLRs) play an important role in innate immune responses and TLR signaling has been associated with various chronic liver diseases. Lipid rafts provide the necessary microenvironment for certain specialized signaling events to take place, such as the innate immune recognition. The purpose of this study was to determine the pattern of TLR7 expression in HCC, how to recruit TLR7 into lipid rafts responded to ligands and whether targeting TLR7 might have beneficial effects...
August 30, 2016: Oncotarget
Norio Kubo, Kenichiro Araki, Hiroyuki Kuwano, Ken Shirabe
The hepatic stellate cells in the liver are stimulated sustainably by chronic injury of the hepatocytes, activating myofibroblasts, which produce abundant collagen. Myofibroblasts are the major source of extracellular proteins during fibrogenesis, and may directly, or secreted products, contribute to carcinogenesis and tumor progression. Cancer-associated fibroblasts (CAFs) are one of the components of the tumor microenvironment that promote the proliferation and invasion of cancer cells by secreting various growth factors and cytokines...
August 14, 2016: World Journal of Gastroenterology: WJG
Charlotte R Grant, Rodrigo Liberal
There are several examples of liver tolerance: the relative ease by which liver allografts are accepted and the exploitation of the hepatic microenvironment by the malarial parasite and hepatotrophic viruses are notable examples. The vasculature of the liver supports a unique population of antigen presenting cells specialised to maintain immunological tolerance despite continuous exposure to gut-derived antigens. Liver sinusoidal endothelial cells and Kupffer cells appear to be key to the maintenance of immune tolerance, by promoting T cell anergy or deletion and the generation of regulatory cell subsets...
August 12, 2016: Clinics and Research in Hepatology and Gastroenterology
Wei Dong, Aiguo Lu, Jingkun Zhao, Shuai Yin, Baochi Ou, Hao Feng
Co-cultivation of non-parenchymal cells (NPCs) and tumor cells from the same donor is important for metastatic cancer research. This study aimed to optimize a protocol for liver NPC isolation. Two novel 3D organotypic co‑culture models for hepatocyte, endothelial cell (EC) and Kupffer cell (KC) isolation were used. Long‑term cell co‑culture, density gradient centrifugation and magnetic‑activated cell sorting (MACS) were established. ECs were isolated from the co‑culture system; the purity of the ECs was 92±1...
October 2016: Oncology Reports
Yu You, Jia-Xin Tan, Hai-Su Dai, Hao-Wei Chen, Xue-Jun Xu, Ai-Gang Yang, Yu-Jun Zhang, Lian-Hua Bai, Ping Bie
Hepatic stellate cells (HSCs) induce immune privilege and promote hepatocellular carcinoma (HCC) by suppressing the immune system. On the other hand, galectin-1 and miRNA-22 (miR-22) are dysregulated in HCC and serve as prognostic indicators for patients. In this study, therefore, we measured galectin-1 and miR-22 expression in HSCs isolated from HCC tissues (Ca-HSCs), and in normal liver tissues (N-HSCs) as a control. We also investigated the apoptosis rate among T cells and the production of cytokines (IFN-γ and IL-10) in HSCs co-cultured with T cells...
August 1, 2016: Oncotarget
Fetch more papers »
Fetching more papers... Fetching...
Read by QxMD. Sign in or create an account to discover new knowledge that matter to you.
Remove bar
Read by QxMD icon Read

Search Tips

Use Boolean operators: AND/OR

diabetic AND foot
diabetes OR diabetic

Exclude a word using the 'minus' sign

Virchow -triad

Use Parentheses

water AND (cup OR glass)

Add an asterisk (*) at end of a word to include word stems

Neuro* will search for Neurology, Neuroscientist, Neurological, and so on

Use quotes to search for an exact phrase

"primary prevention of cancer"
(heart or cardiac or cardio*) AND arrest -"American Heart Association"