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hepatocellular carcinoma immunotherapy

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https://www.readbyqxmd.com/read/27910927/novel-chemoimmunotherapeutic-strategy-for-hepatocellular-carcinoma-based-on-a-genome-wide-association-study
#1
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
#2
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
#3
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
#4
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
#5
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
https://www.readbyqxmd.com/read/27716591/tace-combined-with-dendritic-cells-and-cytokine-induced-killer-cells-in-the-treatment-of-hepatocellular-carcinoma-a-meta-analysis
#6
Guangzhi He, Chenhong Zheng, Huiping Huo, Huiming Zhang, Zhiquan Zhu, Junlai Li, Hongpeng Zhang
Patients with hepatocellular carcinoma (HCC), a fatal cancer, have benefited significantly from TACE (transcatheter arterial chemoembolization) and immunotherapy treatments. Immunotherapy that includes dendritic cells and cytokine-induced killer cells (DC-CIK) in combination with TACE has been extensively applied in cases of HCC. Few decisive conclusions about these combined effects on the outcomes of HCC patients have been reached. Therefore, the present meta-analysis was performed to compare the efficacy of the combined usage of DC-CIK with TACE with a TACE therapy alone on the outcomes of HCC patients...
October 4, 2016: International Immunopharmacology
https://www.readbyqxmd.com/read/27713136/the-role-of-extracellular-vesicles-in-mediating-progression-metastasis-and-potential-treatment-of-hepatocellular-carcinoma
#7
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...
October 4, 2016: 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
#8
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...
October 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27622026/pd-l1-expression-as-a-predictive-biomarker-for-cytokine-induced-killer-cell-immunotherapy-in-patients-with-hepatocellular-carcinoma
#9
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
https://www.readbyqxmd.com/read/27622013/the-proto-oncogene-myc-drives-expression-of-the-nk-cell-activating-nkp30-ligand-b7-h6-in-tumor-cells
#10
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/27605882/specific-cd8-t-cell-response-immunotherapy-for-hepatocellular-carcinoma-and-viral-hepatitis
#11
REVIEW
Elia Moreno-Cubero, Juan-Ramón Larrubia
Hepatocellular carcinoma (HCC), chronic hepatitis B (CHB) and chronic hepatitis C (CHC) are characterized by exhaustion of the specific CD8(+) T cell response. This process involves enhancement of negative co-stimulatory molecules, such as programmed cell death protein-1 (PD-1), cytotoxic T-lymphocyte antigen-4 (CTLA-4), 2B4, Tim-3, CD160 and LAG-3, which is linked to intrahepatic overexpression of some of the cognate ligands, such as PD-L1, on antigen presenting cells and thereby favouring a tolerogenic environment...
July 28, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27593937/hepatic-carcinoma-associated-fibroblasts-enhance-immune-suppression-by-facilitating-the-generation-of-myeloid-derived-suppressor-cells
#12
Y Deng, J Cheng, B Fu, W Liu, G Chen, Q Zhang, Y Yang
A major barrier to effective cancer immunotherapy is immune suppression in favor of tumor progression. Additionally, the accumulation of myeloid-derived suppressor cells (MDSCs) has recently been recognized as a major mechanism of the promotion of immune suppression. However, how MDSCs are induced and the cells from which they arise remains unknown. Although studies have demonstrated that tumor-derived cytokines promote MDSC accumulation and activation, little is known regarding the role of the tumor stroma in MDSC accumulation and activation...
September 5, 2016: Oncogene
https://www.readbyqxmd.com/read/27574562/immunobiology-of-hepatocarcinogenesis-ways-to-go-or-almost-there
#13
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/27574444/pd-l1-expression-in-human-cancers-and-its-association-with-clinical-outcomes
#14
REVIEW
Xin Wang, Feifei Teng, Li Kong, Jinming Yu
PD-L1 is an immunoinhibitory molecule that suppresses the activation of T cells, leading to the progression of tumors. Overexpression of PD-L1 in cancers such as gastric cancer, hepatocellular carcinoma, renal cell carcinoma, esophageal cancer, pancreatic cancer, ovarian cancer, and bladder cancer is associated with poor clinical outcomes. In contrast, PD-L1 expression correlates with better clinical outcomes in breast cancer and merkel cell carcinoma. The prognostic value of PD-L1 expression in lung cancer, colorectal cancer, and melanoma is controversial...
2016: OncoTargets and Therapy
https://www.readbyqxmd.com/read/27547002/progress-in-systemic-therapy-of-advanced-hepatocellular-carcinoma
#15
REVIEW
Xin-Lei Gong, Shu-Kui Qin
Primary liver cancer, mainly consisting of hepatocellular carcinoma (HCC), is one of common malignancies worldwide, and prevalent among the Chinese population. A diagnosis of early stage HCC has proven to be very difficult because of its insidious feature in onset and development. At the time of diagnosis, most HCC cases are locally advanced and/or distant metastatic, which results in difficulty to be treated and poor prognosis. For advanced HCC, systemic therapy is frequently adopted as an important palliative method...
August 7, 2016: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/27530312/redirecting-t-cells-to-glypican-3-with-4-1bb-zeta-chimeric-antigen-receptors-results-in-th1-polarization-and-potent-antitumor-activity
#16
Wenpeng Li, Linjie Guo, Purva Rathi, Ekaterina Marinova, Xiuhua Gao, Meng-Feng Wu, Hao Liu, Gianpietro Dotti, Stephen Gottschalk, Leonid S Metelitsa, Andras Heczey
T cells engineered to express CD19-specific chimeric antigen receptors (CARs) have shown breakthrough clinical successes in patients with B-cell lymphoid malignancies. However, similar therapeutic efficacy of CAR T cells in solid tumors is yet to be achieved. In this study we systematically evaluated a series of CAR constructs targeting glypican-3 (GPC3), which is selectively expressed on several solid tumors. We compared GPC3-specific CARs that encoded CD3ζ (Gz) alone or with costimulatory domains derived from CD28 (G28z), 4-1BB (GBBz), or CD28 and 4-1BB (G28BBz)...
August 16, 2016: Human Gene Therapy
https://www.readbyqxmd.com/read/27486853/oncolytic-virus-therapy-a-new-era-of-cancer-treatment-at-dawn
#17
Hiroshi Fukuhara, Yasushi Ino, Tomoki Todo
Oncolytic virus therapy is perhaps the next major breakthrough in cancer treatment following the success in immunotherapy using immune checkpoint inhibitors. Oncolytic viruses are defined as genetically engineered or naturally occurring viruses that selectively replicate in and kill cancer cells without harming the normal tissues. T-Vec (talimogene laherparepvec), a second-generation oncolytic herpes simplex virus type 1 (HSV-1) armed with GM-CSF, was recently approved as the first oncolytic virus drug in the USA and Europe...
August 3, 2016: Cancer Science
https://www.readbyqxmd.com/read/27481586/adjuvant-immunotherapy-with-autologous-cytokine-induced-killer-cells-for-hepatocellular-carcinoma-patients-after-curative-resection-a-systemic-review-and-meta-analysis
#18
Haiqing Wang, Aixiang Liu, Wentao Bo, Xielin Feng, Yong Hu, Lang Tian, Hui Zhang, Xiaoli Tang
BACKGROUND: Cytokine-induced killer cells have been used as an adjuvant treatment for hepatocellular carcinoma with curative treatment. However, the outcomes remain controversial. AIM: We conducted this meta-analysis to assess the safety and efficacy of cytokine-induced killer cells. METHODS: Randomized controlled trials on cytokine-induced killer cells for hepatocellular carcinoma after curative treatments were identified by electronic searches...
July 18, 2016: Digestive and Liver Disease
https://www.readbyqxmd.com/read/27470884/-prediction-and-preventive-strategies-for-recurrence-after-surgery-for-hepatocellular-carcinoma
#19
H L Jia, L X Qin
Many advances have been achieved in the clinical and basic studies on metastasis and recurrence of hepatocellular carcinoma (HCC) over the past 20 years. The achievements mainly include the following aspects: (1) a group of molecules related to metastasis and recurrence including osteopontin have been identified, and multi-molecular predictive models for metastasis have been established and optimized; (2) it has been found that the imbalance of immune response in tumor microenvironment is important in promoting metastasis and can be used to predict metastasis and recurrence; (3) it has been found and confirmed that interferon can prevent postoperative recurrence, and patients with a lower miR-26a expression level can achieve greater benefits; (4) the breakthroughs in liquid biopsy and immunotherapy bring a promising future for the prediction, prevention, and treatment of HCC metastasis and recurrence...
May 20, 2016: Zhonghua Gan Zang Bing za Zhi, Zhonghua Ganzangbing Zazhi, Chinese Journal of Hepatology
https://www.readbyqxmd.com/read/27463001/exosomes-small-vesicles-with-big-roles-in-hepatocellular-carcinoma
#20
Zhitong Wu, Qinghai Zeng, Ke Cao, Yifan Sun
Despite improvements in the diagnosis and treatment of hepatocellular carcinoma (HCC), the prognosis is still poor. Pioneering work has demonstrated a potential role for tumour cell-derived exosomes (TEXs) in HCC. TEXs can mediate immune responses, antigen presentation and intracellular communication by serving as vehicles for the transfer of proteins, viruses, lipids and RNA between cells. An improved understanding of the roles played by exosomes could lead to a powerful new strategy for preventing and treating HCC...
July 24, 2016: Oncotarget
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