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natural killer cell hepatocellular carcinoma

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https://www.readbyqxmd.com/read/28550492/microrna-889-is-downregulated-by-histone-deacetylase-inhibitors-and-confers-resistance-to-natural-killer-cytotoxicity-in-hepatocellular-carcinoma-cells
#1
Haitao Xie, Qiugui Zhang, Hui Zhou, Jun Zhou, Ji Zhang, Yan Jiang, Jinghong Wang, Xianglin Meng, Leping Zeng, Xiaoxin Jiang
Major histocompatibility complex class I chain-related gene B (MICB) is expressed on tumor cells and participates in natural killer (NK) cell-mediated antitumor immune response through engagement with the NKG2D receptor. This study was undertaken to identify novel microRNA (miRNA) regulators of MICB and clarify their functions in NK cell-mediated cytotoxicity to hepatocellular carcinoma (HCC) cells. Bioinformatic analysis and luciferase reporter assay were conducted to search for MICB-targeting miRNAs. Overexpression and knockdown experiments were performed to determine the roles of candidate miRNAs in the susceptibility of HCC cells to NK lysis...
May 26, 2017: Cytotechnology
https://www.readbyqxmd.com/read/28529568/a-different-representation-of-natural-t-cells-and-natural-killer-cells-between-tumor-infiltrating-and-periphery-lymphocytes-in-human-hepatocellular-carcinoma
#2
Xiao-Feng Li, Dong Dai, Xiu-Yu Song, Jian-Jing Liu, Lei Zhu, Xiang Zhu, Wenchao Ma, Wengui Xu
Natural T cells [cluster of differentiation (CD) 3(+)CD56(+)] and natural killer (NK) cells (CD3(-)CD56(+)) are particularly abundant in the human liver and serve an important role in immune responses in the liver. The aim of the present study was to extensively determine the phenotypic and functional characteristics of natural T and NK cells in human hepatocellular carcinoma (HCC). Tumorous and non-tumorous tissue infiltrating lymphocytes (TILs and NILs, respectively) and peripheral blood mononuclear cells (PBMCs) from patients with hepatocellular carcinoma (HCC) were obtained to determine the frequency and phenotype of natural T/NK cells by a multicolor fluorescence activated cell sorting analysis...
May 2017: Oncology Letters
https://www.readbyqxmd.com/read/28507442/aberrant-promoter-methylation-profiles-and-association-with-survival-in-patients-with-hepatocellular-carcinoma
#3
Dani Zhong, Hong Cen
The aim of this study was to investigate the prognostic and diagnostic value of genes with promoter methylation in hepatocellular carcinoma (HCC) patients. On the basis of The Cancer Genome Atlas data, we identified genes with differentially methylated promoters in HCC tissues and adjacent non-tumor tissues, using the linear models for microarray data approach. Cox proportional hazard regression analysis was applied to access the prognostic value of identified differentially methylated genes. The diagnostic value of the genes was evaluated through receiver operating characteristic...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28468916/tumor-derived-%C3%AE-fetoprotein-directly-drives-human-natural-killer-cell-activation-and-subsequent-cell-death
#4
Lazar Vujanovic, Elizabeth C Stahl, Angela D Pardee, David A Geller, Allan Tsung, Simon C Watkins, Gregory A Gibson, Walter J Storkus, Lisa H Butterfield
Hepatocellular carcinoma (HCC) patients with reduced natural killer (NK) cell numbers and function have been shown to have a poor disease outcome. Mechanisms underlying NK cell deficiency and dysfunction in HCC patients remain largely unresolved. a-Fetoprotein (AFP) is an oncofetal antigen produced by HCC. Previous studies demonstrated that tumor-derived AFP (tAFP) can indirectly impair NK cell activity by suppressing dendritic cell function. However, a direct tAFP effect on NK cells remains unexplored. The purpose of this study was to examine the ability of cord blood-derived AFP (nAFP) and that of tAFP to directly modulate human NK cell activity and longevity in vitro Short-term exposure to tAFP and, especially, nAFP proteins induced a unique pro-inflammatory, IL2-hyperresponsive phenotype in NK cells as measured by IL1β, IL6, and TNF secretion, CD69 upregulation, and enhanced tumor cell killing...
May 3, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28448867/immuno-modulatory-and-cellular-antioxidant-activities-of-%C3%AE%C2%BA-selenocarrageenan-in-combination-with-epirubicin-in-h22-hepatoma-bearing-mice
#5
Na Ling, Xiaojun Zhou, Yubin Ji, Wenlan Li, Chenfeng Ji, Zheng Qi
BACKGROUND: Human hepatocellular carcinoma (HCC) has a high rate of tumor recurrence and metastasis, resulting in shortened survival time. The aim of this study is to evaluate the synergistic anti-tumor effects and underlying mechanism of κ-selenocarrageenan (KSC) in combination with the chemotherapy drug epirubicin (EPI) in H22 tumor-bearing mice. METHODS: Hepatocellular carcinoma H22 cells were implanted into mice. After the transplants were successfully established, the animals were divided into four groups: namely the control group, the KSC group, the EPI group and the KSC+EPI group...
April 24, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28428708/indoleamine-2-3-dioxygenase-as-a-potential-prognostic-marker-and-immunotherapeutic-target-for-hepatocellular-carcinoma
#6
REVIEW
Kashif Asghar, Asim Farooq, Bilal Zulfiqar, Muhammad Usman Rashid
Tumor cells induce an immunosuppressive microenvironment which leads towards tumor immune escape. Understanding the intricacy of immunomodulation by tumor cells is essential for immunotherapy. Indoleamine 2,3-dioxygenase (IDO) is an immunosuppressive enzyme which mediates tumor immune escape in various cancers including hepatocellular carcinoma (HCC). IDO up-regulation in HCC may lead to recruitment of regulatory T-cells into tumor microenvironment and therefore inhibit local immune responses and promote metastasis...
April 7, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28428075/immunotherapy-of-hepatocellular-carcinoma-using-chimeric-antigen-receptors-and-bispecific-antibodies
#7
Sayed Shahabuddin Hoseini, Nai-Kong V Cheung
Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide with an overall survival rate of less than 15% in developed countries. Despite attempts at new therapeutic strategies, the majority of patients succumb to this cancer. Buttressed by the highly successful clinical impact in melanoma, immunotherapy is gaining momentum as the next treatment modality for many human cancers. Chimeric antigen receptors (CAR) contain the antigen binding moieties of a monoclonal antibody and the co-stimulatory and signaling domains associated with effector receptor signaling...
April 17, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28287817/liver-metastasis-from-neuroendocrine-carcinoma-after-the-use-of-the-new-direct-action-antivirals-against-hepatitis-c-virus-in-a-patient-with-past-history-of-hepatocellular-carcinoma
#8
María Caldas Álvarez, Lourdes Del Campo, Alwalid Freih-Fraih, Luisa García-Buey
The use of the new direct-action antivirals against hepatitis C virus provides very high viral eradication rates. However, various recently published articles recommend caution with their use after the appearance of some cases of de novo tumors (originated in hepatic and extra-hepatic locations) and a possible shorter time period of recurrence of hepatocellular carcinomas previously treated with surgery or loco-regional therapies. The sudden drop of the number of natural killer cells secondary to the use of these new medicines has been suggested as one of the possible mechanisms responsible for this process...
March 13, 2017: Revista Española de Enfermedades Digestivas
https://www.readbyqxmd.com/read/28240761/hepatocellular-carcinoma-and-cxcr3-chemokines-a-narrative-review
#9
REVIEW
E Giusy, F Poupak
Hepatocellular carcinoma (HCC) results from several factors like viral hepatitis infection [hepatitis B, or C (25%)] or occupational exposure. T-helper (Th)1 inflammatory cells, characterized by interferon (IFN)-γ and interleukin (IL)-2 secretion, predominate in the liver during chronic HCV infection, and chemokines attracting these cells are particularly important in disease progression. Among C-X-C chemokines, the non-ELR group [as IFN-γ-induced protein 10 (IP-10), monokine induced by IFN-γ (MIG) and IFN-inducible T-cell-alpha chemoattractant (I-TAC)], attracts Th1-cells interacting with chemokine C-X-C receptor (CXCR3)...
January 2017: La Clinica Terapeutica
https://www.readbyqxmd.com/read/28197391/high-nkg2a-expression-contributes-to-nk-cell-exhaustion-and-predicts-a-poor-prognosis-of-patients-with-liver-cancer
#10
Cheng Sun, Jing Xu, Qiang Huang, Mei Huang, Hao Wen, Chuanshan Zhang, Jinyu Wang, Jiaxi Song, Meijuan Zheng, Haoyu Sun, Haiming Wei, Weihua Xiao, Rui Sun, Zhigang Tian
Background and Aims: As the predominant lymphocyte subset in the liver, natural killer (NK) cells have been shown to be highly associated with the outcomes of patients with chronic hepatitis B virus infection (CHB) and hepatocellular carcinoma (HCC). Previously, we reported that NKG2A, a checkpoint candidate, mediates human and murine NK cell dysfunction in CHB. However, NK cell exhaustion and, particularly, the level of NKG2A expression within liver tumors have not been reported. Methods: In this study, we analyzed NKG2A expression and the related dysfunction of NK cells located in intra- or peritumor regions of liver tissue samples from 207 HCC patients, in addition to analyzing disease outcomes...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28184969/augmented-anti-tumor-activity-of-nk-92-cells-expressing-chimeric-receptors-of-tgf-%C3%AE-r-ii-and-nkg2d
#11
Zhongjuan Wang, Linghua Guo, Yuan Song, Yinsheng Zhang, Dandan Lin, Bo Hu, Yu Mei, Dedy Sandikin, Haiyan Liu
The capacity of natural killer (NK) cells to kill tumor cells without specific antigen recognition provides an advantage over T cells and makes them potential effectors for tumor immunotherapy. However, the efficacy of NK cell adoptive therapy can be limited by the immunosuppressive tumor microenvironment. Transforming growth factor-β (TGF-β) is a potent immunosuppressive cytokine that can suppress NK cell function. To convert the suppressive signal induced by TGF-β to an activating signal, we genetically modified NK-92 cells to express a chimeric receptor with TGF-β type II receptor extracellular and transmembrane domains and the intracellular domain of NK cell-activating receptor NKG2D (TN chimeric receptor)...
February 9, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28055304/synergistic-effect-of-cytokine-induced-killer-cell-with-valproate-inhibits-growth-of-hepatocellular-carcinoma-cell-in-a-mouse-model
#12
Dong Hyeon Lee, Joon Yeul Nam, Young Chang, Hyeki Cho, Seong Hee Kang, Young Youn Cho, EunJu Cho, Jeong-Hoon Lee, Su Jong Yu, Yoon Jun Kim, Jung-Hwan Yoon
OBJECTIVE: Long-term prognosis of hepatocellular carcinoma (HCC) remains poor owing to the lack of treatment options for advanced HCC. Cytokine-induced killer (CIK) cells are ex vivo expanded T lymphocytes expressing both NK- and T-cell markers. CIK cell therapy alone is insufficient for treating advanced HCC. Thus, this study aimed to determine whether treatment with CIK cells combined with valproic acid (VPA) could provide a synergistic effect to inhibit tumor growth in a mouse model of HCC...
January 2, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/27941432/immune-reconstitution-after-hcv-clearance-with-direct-antiviral-agents-potential-consequences-for-patients-with-hcc
#13
Jens M Werner, Akinbami Adenugba, Ulrike Protzer
Recent introduction of all-oral direct-acting antiviral (DAA) treatment has revolutionized care of patients with chronic hepatitis C virus infection. Because patients with different liver disease stages have been treated with great success including those awaiting liver transplantation, therapy has been extended to patients with hepatocellular carcinoma as well. From observational studies among compensated cirrhotic hepatitis C patients treated with interferon-containing regimens, it would have been expected that the rate of hepatocellular carcinoma occurrence is markedly decreased after a sustained virological response...
May 2017: Transplantation
https://www.readbyqxmd.com/read/27910927/novel-chemoimmunotherapeutic-strategy-for-hepatocellular-carcinoma-based-on-a-genome-wide-association-study
#14
Kaku Goto, Dorcas A Annan, Tomoko Morita, Wenwen Li, Ryosuke Muroyama, Yasuo Matsubara, Sayaka Ito, Ryo Nakagawa, Yasushi Tanoue, Masahisa Jinushi, Naoya Kato
Pharmacotherapeutic options are limited for hepatocellular carcinoma (HCC). Recently, we identified the anti-tumor ligand MHC class I polypeptide-related sequence A (MICA) gene as a susceptibility gene for hepatitis C virus-induced HCC in a genome-wide association study (GWAS). To prove the concept of HCC immunotherapy based on the results of a GWAS, in the present study, we searched for drugs that could restore MICA expression. A screen of the FDA-approved drug library identified the anti-cancer agent vorinostat as the strongest hit, suggesting histone deacetylase inhibitors (HDACis) as potent candidates...
December 2, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27770537/immunogenetic-factors-influencing-clinical-course-of-hcv-infection-review
#15
REVIEW
G Kamkamidze, M Butsashvili, K Gendzekhadze
Hepatitis C virus (HCV) infection remains one of the most important blood-borne diseases worldwide with about 130-170 million people chronically infected with hepatitis C virus, and more than 350 000 people die from hepatitis C-related liver diseases each year. Infection with HCV becomes chronic in approximately 80% of cases, while in up to 20% of cases hepatitis C virus is cleared from the human organism. Chronic infections of hepatitis C often leads to the end-stage liver diseases such as cirrhosis and hepatocellular carcinoma...
September 2016: Georgian Medical News
https://www.readbyqxmd.com/read/27713136/the-role-of-extracellular-vesicles-in-mediating-progression-metastasis-and-potential-treatment-of-hepatocellular-carcinoma
#16
REVIEW
Naibin Yang, Shanshan Li, Guoxiang Li, Shengguo Zhang, Xinyue Tang, Shunlan Ni, Xiaomin Jian, Cunlai Xu, Jiayin Zhu, Mingqin Lu
Hepatocellular carcinoma (HCC) is a major cause of cancer-related death worldwide. As vectors for intercellular information exchange, the potential role of extracellular vesicles (EVs) in HCC formation, progression and therapy has been widely investigated. In this review, we explore the current status of the researches in this field. Altogether there is undeniable evidence that EVs play a crucial role in HCC development, metastasis. Moreover, EVs have shown great potential as drug delivery systems (DDSs) for the treatment of HCC...
January 10, 2017: Oncotarget
https://www.readbyqxmd.com/read/27713135/recombinant-heat-shock-protein-70-functional-peptide-and-alpha-fetoprotein-epitope-peptide-vaccine-elicits-specific-anti-tumor-immunity
#17
Xiao-Ping Wang, Qiao-Xia Wang, Huan-Ping Lin, Bing Xu, Qian Zhao, Kun Chen
Alpha-fetoprotein (AFP) is a marker of hepatocellular carcinoma (HCC) and serves as a target for immunotherapy. However, current treatments targeting AFP are not reproducible and do not provide complete protection against cancer. This issue may be solved by developing novel therapeutic vaccines with enhanced immunogenicity that could effectively target AFP-expressing tumors. In this study, we report construction of a therapeutic peptide vaccine by linking heat shock protein 70 (HSP70) functional peptide to the AFP epitope to obtain HSP70-P/AFP-P...
November 1, 2016: Oncotarget
https://www.readbyqxmd.com/read/27622013/the-proto-oncogene-myc-drives-expression-of-the-nk-cell-activating-nkp30-ligand-b7-h6-in-tumor-cells
#18
Sonja Textor, Felicitas Bossler, Kai-Oliver Henrich, Moritz Gartlgruber, Julia Pollmann, Nathalie Fiegler, Annette Arnold, Frank Westermann, Nina Waldburger, Kai Breuhahn, Sven Golfier, Mathias Witzens-Harig, Adelheid Cerwenka
Natural Killer (NK) cells are innate effector cells that are able to recognize and eliminate tumor cells through engagement of their surface receptors. NKp30 is a potent activating NK cell receptor that elicits efficient NK cell-mediated target cell killing. Recently, B7-H6 was identified as tumor cell surface expressed ligand for NKp30. Enhanced B7-H6 mRNA levels are frequently detected in tumor compared to healthy tissues. To gain insight in the regulation of expression of B7-H6 in tumors, we investigated transcriptional mechanisms driving B7-H6 expression by promoter analyses...
July 2016: Oncoimmunology
https://www.readbyqxmd.com/read/27574562/immunobiology-of-hepatocarcinogenesis-ways-to-go-or-almost-there
#19
REVIEW
Pavan Patel, Steven E Schutzer, Nikolaos Pyrsopoulos
Hepatocellular carcinoma is on the rise and occurs in the setting of chronic liver disease and cirrhosis. Though treatment modalities are available, mortality from this cancer remains high. Medical therapy with the utilization of biologic compounds such as the Food and Drug Administration approved sorafenib might be the only option that can increase survival. Immunotherapy, with modern pharmacologic developments, is a new frontier in cancer therapy and therefore the immunobiology of hepatocarcinogenesis is under investigation...
August 15, 2016: World Journal of Gastrointestinal Pathophysiology
https://www.readbyqxmd.com/read/27556180/distinct-role-of-interleukin-6-and-tumor-necrosis-factor-receptor-1-in-oval-cell-mediated-liver-regeneration-and-inflammation-associated-hepatocarcinogenesis
#20
Tong Ji, Gaofeng Li, Jiang Chen, Jie Zhao, Xi Li, Hui Lin, Xiujun Cai, Yong Cang
Interleukin 6 (IL6), tumor necrosis factor α (TNFα) and TNF receptor-1(TNFR1) have been shown to involve in oval cell proliferation and hepatocellular carcinoma (HCC) development. However, their role in these processes is still unclear. In the present study, by using hepatocytes-specific DDB1 deletion mouse models, we explored the role and mechanism of IL6, TNFα and TNFR1 in oval cell proliferation and HCC development in the context of inflammation, which is the common features of HCC pathogenesis in humans...
October 11, 2016: Oncotarget
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