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hepatocellular carcinoma immunotherapy

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https://www.readbyqxmd.com/read/28218682/immune-mediated-therapies-for-liver-cancer
#1
REVIEW
Rajagopal N Aravalli, Clifford J Steer
In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion have enhanced our understanding on the immunology of liver cancer...
February 17, 2017: Genes
https://www.readbyqxmd.com/read/28214839/t-cell-associated-immunotherapy-for-hepatocellular-carcinoma
#2
Weijie Ma, Long Wu, Fuling Zhou, Zhenfei Hong, Yufeng Yuan, Zhisu Liu
Hepatocellular carcinoma (HCC) is one of the most common malignant diseases worldwide with limited therapeutic options. Accumulating evidences suggest that immunotherapy could be a promising option for treating HCC. T cell-associated immunotherapy lights up the hope for the improvement of complementary approach to conventional HCC treatments, which needs further research to consummate the clinical consequences. The present work reviewed several T cells associated cellular immunotherapies for HCC, including immune checkpoint blockade, gene-engineered T cells, bispecific T cell engagers, and so on...
February 3, 2017: Cellular Physiology and Biochemistry
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
#3
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/28184367/novel-immunotherapies-for-autoimmune-hepatitis
#4
REVIEW
Shamir Cassim, Marc Bilodeau, Catherine Vincent, Pascal Lapierre
Autoimmune hepatitis (AIH) is a multifactorial autoimmune disease of unknown pathogenesis, characterized by a loss of immunological tolerance against liver autoantigens resulting in the progressive destruction of the hepatic parenchyma. Current treatments are based on non-specific immunosuppressive drugs. Although tremendous progress has been made using specific biological agents in other inflammatory diseases, progress has been slow to come for AIH patients. While current treatments are successful in the majority of patients, treatment discontinuation is difficult to achieve, and relapses are frequent...
2017: Frontiers in Pediatrics
https://www.readbyqxmd.com/read/28128200/the-immunoreceptor-nkg2d-promotes-tumour-growth-in-a-model-of-hepatocellular-carcinoma
#5
Sam Sheppard, Joana Guedes, Anna Mroz, Anastasia-Maria Zavitsanou, Hiromi Kudo, Stephen M Rothery, Panagiotis Angelopoulos, Robert Goldin, Nadia Guerra
Inflammation is recognized as one of the drivers of cancer. Yet, the individual immune components that possess pro- and anti-tumorigenic functions in individual cancers remain largely unknown. NKG2D is a potent activating immunoreceptor that has emerged as an important player in inflammatory disorders besides its well-established function as tumour suppressor. Here, we provide genetic evidence of an unexpected tumour-promoting effect of NKG2D in a model of inflammation-driven liver cancer. Compared to NKG2D-deficient mice, NKG2D-sufficient mice display accelerated tumour growth associated with, an increased recruitment of memory CD8(+)T cells to the liver and exacerbated pro-inflammatory milieu...
January 27, 2017: Nature Communications
https://www.readbyqxmd.com/read/28116284/strengthening-the-case-that-elevated-levels-of-programmed-death-ligand-1-predict-poor-prognosis-in-hepatocellular-carcinoma-patients
#6
Jian-Hong Zhong, Cheng-Piao Luo, Chun-Yan Zhang, Le-Qun Li
Immunotherapy targeting programmed death receptor 1 and programmed death ligand 1 (PD-L1) has shown impressive antitumor efficacy in several solid cancers, including advanced hepatocellular carcinoma (HCC). Since response rates of various cancers to such immunotherapy appear to correlate with PD-L1 expression levels, several studies have examined whether PD-L1 expression correlates with HCC pathology and patient prognosis. In this paper, we analyzed the strength and limitations of a recent meta-analysis of associations of PD-L1 with HCC characteristics and patient prognosis...
2017: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/28114424/cellular-immune-responses-for-squamous-cell-carcinoma-antigen-recognized-by-t-cells-3-in-patients-with-hepatocellular-carcinoma
#7
Kiichiro Kaji, Eishiro Mizukoshi, Tatsuya Yamashita, Kuniaki Arai, Hajime Sunagozaka, Kazumi Fushimi, Hidetoshi Nakagawa, Kazutoshi Yamada, Takeshi Terashima, Masaaki Kitahara, Shuichi Kaneko
BACKGROUND & AIMS: Squamous cell carcinoma antigen recognized by T cells 3 (SART3), a tumor-associated antigen expressed in many cancers, functions in tumor rejection. In this study, we investigated its usefulness as an immunotherapeutic target in hepatocellular carcinoma (HCC). METHODS: The expression of SART3 in hepatoma cell lines and HCC tissues was investigated by immunofluorescence and immunohistochemical analyses. Two peptides derived from SART3 (SART3109 and SART3315) were used for immunological analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28098909/biology-and-function-of-glypican-3-as-a-candidate-for-early-cancerous-transformation-of-hepatocytes-in-hepatocellular-carcinoma-review
#8
Mauro Montalbano, Jeremias Georgiadis, Ashlyn L Masterson, Joshua T McGuire, Janika Prajapati, Ali Shirafkan, Cristiana Rastellini, Luca Cicalese
Glypican-3 (GPC-3), a transmembrane heparan sulfate proteoglycan (HSPG), has recently been investigated as a player in tissue-dependent cellular signaling, specifically as a regulator of growth. Noteworthy, the regulatory protein has been implicated in both stimulatory and inhibitory pathways involving cell growth. Initially, GPC-3 was thought to act as a cell cycle regulator, as a loss-of-function mutation in the gene caused a hyper-proliferative state known as Simpson-Golabi-Behmel (SGB) overgrowth syndrome...
January 18, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28061472/harms-and-benefits-of-adoptive-immunotherapy-for-postoperative-hepatocellular-carcinoma-an-updated-review
#9
Bao-Hong Yuan, Ru-Hong Li, Wei-Ping Yuan, Tian Yang, Tie-Jun Tong, Ning-Fu Peng, Le-Qun Li, Jian-Hong Zhong
The harms and benefits of adoptive immunotherapy (AIT) for patients with postoperative hepatocellular carcinoma (HCC) are controversial among studies. This study aims to update the current evidence on efficacy and safety of AIT for patients with HCC who have received curative therapy. Electronic databases were systematically searched to identify randomized controlled trials (RCTs) and cohort studies evaluating adjuvant AIT for patients with HCC after curative therapies. Recurrence and mortality were compared between patients with or without adjuvant AIT...
January 4, 2017: Oncotarget
https://www.readbyqxmd.com/read/28042519/potential-of-radiofrequency-ablation-in-combination-with-immunotherapy-in-the-treatment-of-hepatocellular-carcinoma
#10
Guangfu Li, Kevin F Staveley-O'Carroll, Eric T Kimchi
Radiofrequency ablation (RFA) is an important treatment option for patients with early hepatocellular carcinoma (HCC). RFA offers a reliable, reproducible modality to effectively treat hepatic lesions with minimal collateral damage to the surrounding hepatic parenchyma. In addition to traditional open operative techniques, RFA can be performed percutaneously or laparoscopically to minimize the physiologic insult to the patient. Due to the concomitant hepatic damage and dysfunction that often is present in patients with HCC these factors make RFA a frequently utilized therapeutic option...
April 2016: Journal of Clinical Trials
https://www.readbyqxmd.com/read/28035433/development-of-t-cells-carrying-two-complementary-chimeric-antigen-receptors-against-glypican-3-and-asialoglycoprotein-receptor-1-for-the-treatment-of-hepatocellular-carcinoma
#11
Cheng Chen, Kesang Li, Hua Jiang, Fei Song, Huiping Gao, Xiaorong Pan, Bizhi Shi, Yanyu Bi, Huamao Wang, Hongyang Wang, Zonghai Li
Adoptive immunotherapy leveraging chimeric antigen receptor-modified T (CAR-T) cells holds great promise for the treatment of cancer. However, tumor-associated antigens often have low expression levels in normal tissues, which can cause on-target, off-tumor toxicity. Recently, we reported that GPC3-targeted CAR-T cells could eradicate hepatocellular carcinoma (HCC) xenografts in mice. However, it remains unknown whether on-target, off-tumor toxicity can occur. Therefore, we proposed that dual-targeted CAR-T cells co-expressing glypican-3 (GPC3) and asialoglycoprotein receptor 1 (ASGR1) (a liver tissue-specific protein)-targeted CARs featuring CD3ζ and 28BB (containing both CD28 and 4-1BB signaling domains), respectively, may have reduced on-target, off-tumor toxicity...
December 29, 2016: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28011330/current-progress-in-immunotherapy-of-hepatocellular-carcinoma
#12
EDITORIAL
Martin F Sprinzl, Peter R Galle
No abstract text is available yet for this article.
December 20, 2016: Journal of Hepatology
https://www.readbyqxmd.com/read/28006010/is-adjuvant-cellular-immunotherapy-essential-after-tace-predominant-minimally-invasive-treatment-for-hepatocellular-carcinoma-a-systematic-meta-analysis-of-studies-including-1774-patients
#13
Min Ding, Ying Wang, Jiachang Chi, Tao Wang, Xiaoyin Tang, Dan Cui, Qijun Qian, Bo Zhai
PURPOSE: Cellular immunotherapy has appeared to be a promising modality for the treatment of malignant tumor. The objective of this study was to evaluate the efficacy of cellular immunotherapy combined with minimally invasive therapy. METHODS: We searched PubMed, Web of Science and The Cochrane Library through March 2016 for relevant studies. Short-term efficacy (the disease control rate, the control rate of quality life and the AFP descent rate) and long-term efficacy (overall survival (OS) and progression-free survival (PFS) rate) were compared as the major outcome measures...
2016: PloS One
https://www.readbyqxmd.com/read/27980102/blocking-the-ccl2-ccr2-axis-using-ccl2-neutralizing-antibody-is-an-effective-therapy-for-hepatocellular-cancer-in-a-mouse-model
#14
Kun-Yu Teng, Jianfeng Han, Xiaoli Zhang, Shu-Hao Hsu, Shun He, Nissar A Wani, Juan M Barajas, Linda A Snyder, Wendy L Frankel, Michael A Caligiuri, Samson T Jacob, Jianhua Yu, Kalpana Ghoshal
Hepatocellular carcinoma, a deadly disease, commonly arises in the setting of chronic inflammation. C-C motif chemokine ligand 2 (CCL2/MCP1), a chemokine that recruits CCR2-positive immune cells to promote inflammation, is highly upregulated in hepatocellular carcinoma patients. Here, we examined the therapeutic efficacy of CCL2-CCR2 axis inhibitors against hepatitis and hepatocellular carcinoma in the miR-122 knockout (a.k.a. KO) mouse model. This mouse model displays upregulation of hepatic CCL2 expression, which correlates with hepatitis that progress to hepatocellular carcinoma with age...
February 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/27936483/perspectives-of-immunotherapy-in-hepatocellular-carcinoma-hcc
#15
N Büttner, N Schmidt, R Thimme
Immunotherapy is considered a new treatment option for many tumor entities, as decades of research into cancer immunotherapy have recently yielded promising results. Indeed, impressive clinical results of checkpoint blockade inhibitors in malignant melanoma and non-small cell lung cancer indicate the therapeutic potential of tumor-specific immune restoration. Over the years, different immunotherapeutic approaches have been evaluated for the treatment of hepatocellular carcinoma (HCC) with some respectable results...
December 2016: Zeitschrift Für Gastroenterologie
https://www.readbyqxmd.com/read/27910927/novel-chemoimmunotherapeutic-strategy-for-hepatocellular-carcinoma-based-on-a-genome-wide-association-study
#16
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/27848888/immunotherapy-in-liver-diseases-a-balance-between-immunity-and-tolerance
#17
Alaknanda Mishra, Pramod K Upadhyay, Perumal Nagarajan
In today's context when liver diseases have spread across countries and people of all ages, it is of high importance to consider novel methods of non-toxic and long lived therapeutics. Among various therapies, immunotherapy for acute and chronic liver diseases is rapidly moving to the forefront among treatment options in hepatology medicine. Liver has a unique immuno- biological advantage which is utilized to maintain a balance between immunity and tolerance. This intricate balance of hepatic immune cells can be modulated to effect treatments in various liver diseases...
November 16, 2016: Current Drug Metabolism
https://www.readbyqxmd.com/read/27749555/overexpression-of-cd39-in-hepatocellular-carcinoma-is-an-independent-indicator-of-poor-outcome-after-radical-resection
#18
Xiao-Yan Cai, Xiao-Chun Ni, Yong Yi, Hong-Wei He, Jia-Xing Wang, Yi-Peng Fu, Jian Sun, Jian Zhou, Yun-Feng Cheng, Jian-Jun Jin, Jia Fan, Shuang-Jian Qiu
Nucleoside triphosphate diphosphohydrolase-1 (ENTPD1/CD39) is the rate-limiting enzyme in a cascade leading to the generation of immunosuppressive adenosine and plays an important role in tumor progression. This study aimed to evaluate the expression of CD39 and CD39Foxp3 regulatory T cells (Tregs) and to determine their prognostic role in patients with hepatocellular carcinoma (HCC) after radical resection.Immunohistochemistry (IHC) and double IHC were used to analyze CD39 expression or the expression of CD39 and Foxp3 in a cohort of 324 HCC patients who underwent curative resection...
October 2016: Medicine (Baltimore)
https://www.readbyqxmd.com/read/27746013/cytokine-induced-killer-cell-infusion-combined-with-conventional-treatments-produced-better-prognosis-for-hepatocellular-carcinoma-patients-with-barcelona-clinic-liver-cancer-b-or-earlier-stage-a-systematic-review-and-meta-analysis
#19
Yun-Chen Li, Lin Zhao, Jiang-Ping Wu, Chen-Xu Qu, Qing-Kun Song, Rui-Bin Wang
BACKGROUND AIMS: To investigate the clinical benefits of cytokine-induced killer (CIK) cell infusions on hepatocellular carcinoma (HCC) patients, combined with other conventional treatments. METHODS: This was a systematic review and meta-analysis conducted among phase II and III randomized control trials worldwide. Review manager 5.2 version was used to pool the effect size across studies. Sensitivity analyses and risk of bias were estimated among included studies...
October 13, 2016: Cytotherapy
https://www.readbyqxmd.com/read/27733149/rna-binding-protein-nova1-promotes-tumor-growth-in-vivo-and-its-potential-mechanism-as-an-oncogene-may-due-to-its-interaction-with-gabaa-receptor-%C3%AE-2
#20
Yi-An Zhang, Hai-Ning Liu, Ji-Min Zhu, Dan-Ying Zhang, Xi-Zhong Shen, Tao-Tao Liu
BACKGROUND: The mechanism of Nova1's role in hepatocellular carcinoma has not been delineated. Also its interaction with GABAA receptor γ2 in HCC is unveiled. This study is aimed to make it clear the distribution, prognostic value of GABAARγ2 in human hepatocellular carcinoma. And its role in HCC tumorigenesis under the regulation of its alternative splicing factor Nova1. METHODS: Immunohistochemistry staining was used to investigate the distribution and clinical significance of GABAARγ2 protein expression in hepatocellular carcinoma...
October 12, 2016: Journal of Biomedical Science
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