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Hepatic microenvironment

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https://www.readbyqxmd.com/read/28938688/drag-reducing-polymers-decrease-hepatic-injury-and-metastases-after-liver-ischemia-reperfusion
#1
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...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28917627/molecular-and-functional-characterization-of-cd133-stem-progenitor-cells-infused-in-patients-with-end-stage-liver-disease-reveals-their-interplay-with-stromal-liver-cells
#2
Lucia Catani, Daria Sollazzo, Elisa Bianchi, Marilena Ciciarello, Chiara Antoniani, Licia Foscoli, Paolo Caraceni, Ferdinando Antonino Giannone, Maurizio Baldassarre, Rosaria Giordano, Tiziana Montemurro, Elisa Montelatici, Antonia D'Errico, Pietro Andreone, Valeria Giudice, Antonio Curti, Rossella Manfredini, Roberto Massimo Lemoli
BACKGROUND AIMS: Growing evidence supports the therapeutic potential of bone marrow (BM)-derived stem/progenitor cells for end-stage liver disease (ESLD). We recently demonstrated that CD133(+) stem/progenitor cell (SPC) reinfusion in patients with ESLD is feasible and safe and improve, albeit transiently, liver function. However, the mechanism(s) through which BM-derived SPCs may improve liver function are not fully elucidated. METHODS: Here, we characterized the circulating SPCs compartment of patients with ESLD undergoing CD133(+) cell therapy...
September 13, 2017: Cytotherapy
https://www.readbyqxmd.com/read/28901955/hepg2-and-human-healthy-hepatocyte-in-vitro-culture-and-co-culture-in-pcl-electrospun-platforms
#3
Ines Fasolino, Vincenzo Guarino, Marica Marrese, Valentina Cirillo, Marianna Vallifuoco, Maria Luisa Tamma, Valentina Vassallo, Adele Bracco, Fulvio Calise, Luigi Ambrosio
The discovery of new drugs to treat pathological cells in the case of aggressive liver primary cancer is imposing the identification of high-throughput screening systems to predict the in vivo response of new therapeutic molecules, in order to reduce current use of animals and drug testing costs. Recently, micro/nanostructured scaffolds have been adopted to reproduce the hepatic microenvironment due to their higher similarity to the biological niche with respect to the traditional two-dimensional culture plate, so providing novel in vitro models for reliably understanding molecular mechanisms related to cancer cells activity...
September 13, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28893116/imaging-hepatocellular-carcinoma-with-68-ga-citrate-pet-first-clinical-experience
#4
Carina Mari Aparici, Spencer C Behr, Youngho Seo, R Kate Kelley, Carlos Corvera, Kenneth T Gao, Rahul Aggarwal, Michael J Evans
While cross-sectional imaging with computed tomography (CT) and magnetic resonance imaging is the primary method for diagnosing hepatocellular carcinoma (HCC), they provide little biological insight into this molecularly heterogeneous disease. Nuclear imaging tools that can detect molecular subsets of tumors could greatly improve diagnosis and management of HCC. To this end, we conducted a patient study to determine whether HCC can be resolved using (68)Ga-citrate positron emission tomography (PET). One patient with recurrent HCC was injected with 300 MBq of (68)Ga-citrate and imaged with PET/CT 249 minutes post injection...
January 2017: Molecular Imaging
https://www.readbyqxmd.com/read/28881729/the-type-i-insulin-like-growth-factor-regulates-the-liver-stromal-response-to-metastatic-colon-carcinoma-cells
#5
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...
August 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28869866/synergistic-antitumor-effect-mediated-by-a-paclitaxel-conjugated-polymeric-micelle-coated-oncolytic-adenovirus
#6
Dayananda Kasala, Soo-Hwan Lee, Jin Woo Hong, Joung-Woo Choi, Kihoon Nam, Yoon Ho Chung, Sung Wan Kim, Chae-Ok Yun
Combination treatment consisting of oncolytic adenovirus (Ad) and paclitaxel (PTX) is a promising strategy to achieve synergistic antitumor effect. However, a co-administration approach is subject to inherent limitations due to the poor solubility of PTX and chemoresistance of tumor cells. In order to overcome these limitations, an oncolytic Ad expressing a p53 variant (oAd-vp53) that is resistant to p53 inactivation in the tumor microenvironment was complexed with PEGylated and PTX-conjugated polymeric micelle (APP)...
August 23, 2017: Biomaterials
https://www.readbyqxmd.com/read/28869588/activation-of-pluripotent-genes-in-hepatic-progenitor-cells-in-the-transition-of-nonalcoholic-steatohepatitis-to-pre-malignant-lesions
#7
Gang Xu, Juan Ye, Xue-Jing Liu, Ning-Ping Zhang, Yi-Ming Zhao, Jia Fan, Xiu-Ping Liu, Jian Wu
Nonalcoholic steatohepatitis is considered as a precancerous condition. However, hepatic carcinogenesis from NASH is poorly understood. This study aims to investigate the activation of pluripotent genes (c-Myc, Oct-4, KLF-4, and Nanog) and morphogenic gene (Gli-1) in hepatic progenitor cells from patient specimens and in an animal model to determine the possibility of normal stem/progenitor cells becoming the origin of NASH-HCC. In this study, expression of pluripotent and morphogenic genes in human NASH-HCC tissues was significantly upregulated compared to adjacent non-tumor liver tissues...
September 4, 2017: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/28866620/hepatic-hippo-signaling-inhibits-protumoural-microenvironment-to-suppress-hepatocellular-carcinoma
#8
Wantae Kim, Sanjoy Kumar Khan, Yuchen Liu, Ruoshi Xu, Ogyi Park, Yong He, Boksik Cha, Bin Gao, Yingzi Yang
OBJECTIVE: Hippo signalling is a recently identified major oncosuppressive pathway that plays critical roles in inhibiting hepatocyte proliferation, survival and hepatocellular carcinoma (HCC) formation. Hippo kinase (Mst1 and Mst2) inhibits HCC proliferation by suppressing Yap/Taz transcription activities. As human HCC is mainly driven by chronic liver inflammation, it is not clear whether Hippo signalling inhibits HCC by shaping its inflammatory microenvironment. DESIGN: We have established a genetic HCC model by deleting Mst1 and Mst2 in hepatocytes...
September 2, 2017: Gut
https://www.readbyqxmd.com/read/28852648/hepatic-immune-microenvironment-in-alcoholic-and-nonalcoholic-liver-disease
#9
REVIEW
Jin-Seok Byun, Hyon-Seung Yi
Many types of innate (natural killer cells, natural killer T cells, and Kupffer cells/macrophages) and adaptive (T cells and B cells) immune cells are enriched within the liver and function in liver physiology and pathology. Liver pathology is generally induced by two types of immunologic insults: failure to eliminate antigens derived from the gastrointestinal tract which are important for host defense and an impaired tissue protective tolerance mechanism that helps reduce the negative outcomes of immunopathology...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28829572/immunomodulatory-therapy-of-inflammatory-liver-disease-using-selectin-binding-glycopolymers
#10
Matthias Bartneck, Christopher Thorsten Schlößer, Matthias Barz, Rudolf Zentel, Christian Trautwein, Twan Lammers, Frank Tacke
Immunotherapies have the potential to significantly advance treatment of inflammatory disease and cancer, which are in large parts driven by immune cells. Selectins control the first step in immune cell adhesion and extravasation, thereby guiding leukocyte trafficking to tissue lesions. We analyzed four different highly specific selectin-binding glycopolymers, based on linear poly(2-hydroxypropyl)-methacrylamide (PHPMA) polymers. These glycopolymers contain either the tetrasaccharide sialyl-Lewis(X) (SLe(X)), or the individual carbohydrates fucose, galactose, and sialic acids mimicking the complex SLe(X) binding motive...
August 22, 2017: ACS Nano
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
#11
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
#12
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
#13
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
#14
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...
October 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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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