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hepatocellular carcinoma immunotherapy

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https://www.readbyqxmd.com/read/29344274/immunotherapy-of-patient-with-hepatocellular-carcinoma-using-cytotoxic-t-lymphocytes-ex-vivo-activated-with-tumor-antigen-pulsed-dendritic-cells
#1
Ying Wang, Xijing Yang, Yi Yu, Zenghui Xu, Yan Sun, Hui Liu, Jingbo Cheng, Min Liu, Bibo Sha, Linfang Li, Na Ding, Zhong Li, Huajun Jin, Qijun Qian
Purpose The aim of this study was to evaluate the clinical response of immunotherapy with dendritic cell-cytotoxic T lymphocytes (DC-CTLs) in patients with hepatocellular carcinoma (HCC). Method Sixty-eight patients with a confirmed diagnosis of HCC and who received follow-up until December 2015 were enrolled. We measured immune phenotypes of DCs and activated T cells using flow cytometry and clinical indexes using an electrochemiluminescence method. Results DCs exhibited up-regulation of the maturation markers CD83, CD80, CD11c, and CD86 on day8...
2018: Journal of Cancer
https://www.readbyqxmd.com/read/29332456/the-combined-antitumor-effects-of-125i-radioactive-particle-implantation-and-cytokine-induced-killer-cell-therapy-on-xenograft-hepatocellular-carcinoma-in-a-mouse-model
#2
Junyong Zhang, Nian Wu, Zhengrong Lian, Huyi Feng, Qing Jiang, Xianfeng Chen, Jianping Gong, Zhengrong Qiao
The combination of radiotherapy and immunotherapy has shown great promise in eradicating tumors. For example, 125I radioactive particle implantation and cytokine-induced killer cell therapies have demonstrated efficacy in treating hepatocellular carcinoma. However, the mechanism of this combination therapy remains unknown. In this study, we utilized cytokine-induced killer cells obtained from human peripheral blood mononuclear cells along with 125I radioactive particle implantation to treat subcutaneous hepatocellular carcinoma xenograft tumors in BALB/c nude mice...
December 2017: Technology in Cancer Research & Treatment
https://www.readbyqxmd.com/read/29331106/kbtbd2-inhibits-the-cytotoxic-activity-of-immortalized-nk-cells-through-down-regulating-mtor-signaling-in-a-mouse-hepatocellular-carcinoma-model
#3
Kai Dai, Yabing Huang, Zubing Chen, Xiaomei Sun, Lihua Yang, Yingan Jiang
Natural killer cell (NK cell)-based immunotherapy is a promising therapeutic strategy for hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the regulation of NK cell function in the tumor sites are not completely elucidated. In this study, we identified the enhanced expression of kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) in intratumoral NK cells in a mouse HCC implantation model as a negative regulator of NK cells. To investigate this interaction,, we used a Tet-on inducible expression system to control Kbtbd2 expression in an immortalized mouse NK cell line KIL C...
January 13, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29328436/role-of-exosomes-and-exosomal-micrornas-in-hepatocellular-carcinoma-potential-in-diagnosis-and-antitumour-treatments-review
#4
Jing-Hua Pan, Hong Zhou, Xiao-Xu Zhao, Hui Ding, Wei Li, Li Qin, Yun-Long Pan
Communication between hepatocellular carcinoma (HCC) cells and their environment is essential for the development and progression of HCC. Exosomes, which are microvesicles secreted by a number of cell types, are carriers of intercellular information and regulate the tumour microenvironment. Studies have demonstrated that exosomes are involved in the communication between HCC cells, endothelial cells and stem cells, and that they serve important roles in the metastasis and invasion, immune evasion and immunotherapy of HCC...
January 11, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29326816/immune-checkpoint-inhibition-prospects-for-prevention-and-therapy-of-hepatocellular-carcinoma
#5
REVIEW
Caryn L Elsegood, Janina Ee Tirnitz-Parker, John K Olynyk, George Ct Yeoh
The global prevalence of liver cancer is rapidly rising, mostly as a result of the amplified incidence rates of viral hepatitis, alcohol abuse and obesity in recent decades. Treatment options for liver cancer are remarkably limited with sorafenib being the gold standard for advanced, unresectable hepatocellular carcinoma but offering extremely limited improvement of survival time. The immune system is now recognised as a key regulator of cancer development through its ability to protect against infection and chronic inflammation, which promote cancer development, and eliminate tumour cells when present...
November 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/29302641/cancer-immunotherapy-in-patients-with-new-or-recurrent-malignancies-after-liver-transplantation
#6
REVIEW
Mengqi Liu, Wenzhi Guo, Shuijun Zhang
Cancer immunotherapy, as a new treatment modality, has been shown to be effective, especially in metastatic melanoma and lung cancer. Organ transplantation can be a life-saving procedure for patients with end-stage diseases of lung, heart, kidney and liver. While ironically, as improvements in organ transplantation have extended patients' lives, new or recurrent postsurgical malignancies have become an increasing threat to their long-term survival, especially in patients after liver transplantation due to hepatocellular carcinoma...
December 2017: International Journal of Surgery. Oncology
https://www.readbyqxmd.com/read/29279355/gadd45%C3%AE-loss-ablates-innate-immunosuppression-in-cancer
#7
Daniela Verzella, Jason Bennett, Mariafausta Fischietti, Anil Kumar Thotakura, Camilla Recordati, Fabio Pasqualini, Daria Capece, Davide Vecchiotti, Daniel D'Andrea, Barbara Di Francesco, Marcella De Maglie, Federica Begalli, Laura Tornatore, Salvatore Papa, Toby Lawrence, Stuart Forbes, Antonio Sica, Edoardo Alesse, Francesca Zazzeroni, Guido Franzoso
T cell exclusion from the tumour microenvironment (TME) is a major barrier to overcoming immune escape. Here we identify a myeloid-intrinsic mechanism governed by the NF-κB effector molecule GADD45β that restricts tumour-associated inflammation and T cell trafficking into tumors. In various models of solid cancers refractory to immunotherapies, including hepatocellular carcinoma (HCC) and ovarian adenocarcinoma, Gadd45b inhibition in myeloid cells restored activation of pro-inflammatory tumour-associated macrophages (TAM) and intratumoural immune infiltration, thereby diminishing oncogenesis...
December 26, 2017: Cancer Research
https://www.readbyqxmd.com/read/29211363/hierarchical-potential-differentiation-of-liver-cancer-stem-cells
#8
REVIEW
Wenfeng Zhang, Di Mu, Kai Feng
Hepatocellular carcinoma (HCC) is one of the most malignant tumors in Chinese people and offers poor prognosis. Tumor tissue, like normal tissue, is hierarchically differentiated. Thus, minor tumor cell populations able to differentiate, such as stem cells, sustain tumor self-renewal and proliferation. The fact that liver cancer stem cells (CSCs) with different surface markers appear heterogeneous with respect to oncogenesis and drug resistance indicates that subpopulations of surface markers preserve the hierarchical potential of differentiation during proliferation, deterioration and relapse...
October 2017: Advances in Clinical and Experimental Medicine: Official Organ Wroclaw Medical University
https://www.readbyqxmd.com/read/29210217/i131-reinforces-antitumor-activity-of-metuximab-by-reversing-epithelial-mesenchymal-transition-via-vegfr-2-signaling-in-hepatocellular-carcinoma
#9
Lu Wu, Bin Sun, Xuejing Lin, Chunying Liu, Haihua Qian, Lei Chen, Yefa Yang, Feng Shen, Changqing Su
CD147 is highly expressed in hepatocellular carcinoma (HCC) and associated with the invasion and metastasis of HCC. The efficacy of I131 -metuximab (I131 -mab), a newly developed agent that targets CD147, as a radio-immunotherapy for local HCC, has been validated in clinical practice. However, the synergistic anticancer activity and molecular mechanism of different conjugated components within I131 -mab remain unclear. In this study, the cytological experiments proved that I131 -mab inhibited the proliferation and invasion of HCC cells...
December 6, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29184856/optimal-therapy-for-patients-with-hepatocellular-carcinoma-and-resistance-or-intolerance-to-sorafenib-challenges-and-solutions
#10
REVIEW
Emily M Ray, Hanna K Sanoff
The only US Food and Drug Administration (FDA)-approved first-line systemic therapy for hepatocellular carcinoma (HCC) is sorafenib; however, resistance or intolerance to sorafenib is unfortunately common. In this review, we briefly describe systemic therapies that can be considered for patients with HCC who show resistance or intolerance to sorafenib. For all patients with HCC who need systemic therapy, we strongly advocate for participation in clinical trials. Cytotoxic chemotherapy plays a minor role in the treatment of advanced HCC, with some data supporting the use of FOLFOX (infusional fluorouracil, leucovorin, and oxaliplatin) and GEMOX (gemcitabine-oxaliplatin)...
2017: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/29182438/high-numbers-of-myeloid-derived-suppressor-cells-in-peripheral-blood-and-ascitic-fluid-of-cirrhotic-and-hcc-patients
#11
Nadia Elwan, Mohamed Labib Salem, Abdelrahman Kobtan, Ferial El-Kalla, Loai Mansour, Mohamed Yousef, Ashraf Al-Sabbagh, Abdel-Aziz A Zidan, Sherief Abd-Elsalam
BACKGROUND: Hepatocellular carcinoma (HCC) is the 3rd most common cause of cancer-related death worldwide. It has evolved different immune escape mechanisms, which might include emergence of lymphoid and myeloid regulatory cells. Aim of this work: To determine the numbers of Myeloid-derived suppressor cells (MDSCs) in peripheral blood and ascitic fluid in cirrhosis and HCC and their relation to IFN-γ and α-fetoprotein (α-FP). PATIENTS AND METHODS: Sixty individuals were enrolled in this study; forty cirrhotic patients with ascites; twenty without HCC (Group I), and twenty with HCC (group II) as well as twenty healthy individuals as a control group (group III)...
November 28, 2017: Immunological Investigations
https://www.readbyqxmd.com/read/29166754/advances-in-oncological-treatment-limitations-of-recist-1-1-criteria
#12
Serena Grimaldi, Marie Terroir, Caroline Caramella
INTRODUCTION: RECIST 1.1 criteria are the standard for the response assessment of most solid tumors on computed tomography (CT). Nevertheless, the emergence of new classes of treatment in the lasts decades has brought new challenges in the response evaluation. EVIDENCE ACQUISITION: A PubMed online database literature search was performed in order to identify papers in English with full text available published up to September 2017. EVIDENCE SYNTHESIS: Some oncologic treatments, such as anti-angiogenic agents, immunotherapy and local treatments, have proven to be effective despite atypical patterns of responses...
November 22, 2017: Quarterly Journal of Nuclear Medicine and Molecular Imaging
https://www.readbyqxmd.com/read/29163709/the-anti-hepatocellular-carcinoma-activity-of-mel-p15-is-mediated-by-natural-killer-cells
#13
Tao Xu, Tongxing Cui, Lipan Peng, Shuai Kong, Jianqiang Zou, Xingsong Tian
Mel-P15 is a peptide derived from melittin, the main toxic component in the venom of the European honeybee Apis mellifera. In the present study, the antitumor effects of Mel-P15 and the underlying molecular mechanisms of these effects in vivo were investigated. Mel-P15 directly stimulated natural killer (NK) cell cytotoxicity in vitro, which was increased to 55.45% at a 4 µg/ml dose of Mel-P15. In the mouse liver cancer (H22) xenograft mice model, Mel-P15 suppressed tumor growth in vivo; the tumor inhibitory rate was 61...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29157287/safety-in-treatment-of-hepatocellular-carcinoma-with-immune-checkpoint-inhibitors-as-compared-to-melanoma-and-non-small-cell-lung-cancer
#14
Zachary J Brown, Bernd Heinrich, Seth M Steinberg, Su Jong Yu, Tim F Greten
BACKGROUND: Hepatocellular carcinoma (HCC) is a major health problem worldwide with increasing incidence rates. As HCC traditionally occurs in chronically inflamed livers, this inflammation aids to drive oncogenesis and often renders these lesions to be immunogenic and therefore potential targets for immunotherapy. As patients with HCC generally have underlying liver dysfunction, we sought to determine if immune checkpoint inhibitors were safe to use in patients with HCC as compared to melanoma and non-small cell lung cancer (NSCLC) in terms of the gastrointestinal side effects of elevation of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and diarrhea as well as patients who drop out of the study due to drug toxicity and death secondary to drug toxicity...
November 21, 2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/29156048/unmet-needs-in-clinical-and-basic-hepatitis-b-virus-research
#15
REVIEW
Tung-Hung Su, Jia-Horng Kao
Chronic hepatitis B (CHB) has become a treatable and controllable disease. The current nucleos(t)ide analogue (NUC) and pegylated interferon therapies effectively help slow disease progression and reduce the risk of cirrhosis, hepatocellular carcinoma (HCC), and CHB-associated mortality. Long-term viral suppression is easily achievable by NUC therapy, with limited adverse reactions. However, several unmet requirements still exist, including safety and risk-stratified HCC surveillance among patients who received long-term NUC therapy...
November 16, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29156047/immunopathogenesis-of-hepatitis-b-virus
#16
Tai-Chung Tseng, Li-Rung Huang
Chronic hepatitis B virus (HBV) infection is a global public health issue. There are >250 million people chronically infected with HBV, and these chronic carriers are at high risk of developing end-stage liver diseases and hepatocellular carcinoma. Patients with chronic hepatitis B (CHB) usually acquire the virus perinatally, while most patients infected during adulthood develop acute hepatitis B (AHB), which usually results in viral clearance. HBV infection is noncytopathic, and liver injury is mostly contributed by host immune responses...
November 16, 2017: Journal of Infectious Diseases
https://www.readbyqxmd.com/read/29150490/gut-roundtable-meeting-paper-selected-recent-advances-in-hepatocellular-carcinoma
#17
REVIEW
Alexander Gerbes, Fabien Zoulim, Herbert Tilg, Jean-François Dufour, Jordi Bruix, Valérie Paradis, Riad Salem, Markus Peck-Radosavljevic, Peter R Galle, Tim F Greten, Jean-Charles Nault, Matias A Avila
Hepatocellular carcinoma (HCC) ranks number three among the most frequent causes of death from solid tumors worldwide. With obesity and fatty liver diseases as risk factors on the rise, HCC represents an ever increasing challenge. While there is still no curative treatment for most patients numerous novel drugs have been proposed, but most ultimately failed in phase III trials. This manuscript targets therapeutic advances and most burning issues. Expert key point summaries and urgent research agenda are provided regarding risk factors, including microbiota, need for prognostic and predictive biomarkers and the equivocal role of liver biopsy...
November 17, 2017: Gut
https://www.readbyqxmd.com/read/29150141/hepatocellular-carcinoma-in-the-era-of-immunotherapy
#18
REVIEW
Hao-Wen Sim, Jennifer Knox
Hepatocellular carcinoma is a common malignancy which usually emerges on a background of chronic liver disease. Unfortunately, with contemporary management, patients with advanced hepatocellular carcinoma have few treatment options, and prognosis is poor. The emergence of immunotherapy has afforded new therapeutic opportunities. This article reviews the clinical evidence for immunotherapy in advanced hepatocellular carcinoma and presents ideas for future drug development.
November 14, 2017: Current Problems in Cancer
https://www.readbyqxmd.com/read/29145036/liver-immunotolerance-and-hepatocellular-carcinoma-patho-physiological-mechanisms-and-therapeutic-perspectives
#19
REVIEW
Gaël S Roth, Thomas Decaens
At the moment of the diagnosis of hepatocellular carcinoma (HCC), 70% of patients have only access to palliative treatments, with very few therapeutic options. Liver immunology is very specific, and liver immunotolerance is particularly developed because of the constant and massive influx of antigens. Deregulation of hepatic immunotolerance is implicated in chronic liver diseases development and particularly in liver carcinogenesis. For these reasons, HCC may be an excellent candidate for anticancer immunotherapies such as immune checkpoint inhibitors targeting CTLA-4 and PD-L1/PD-1...
November 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/29138342/immunotherapy-of-hepatocellular-carcinoma-facts-and-hopes
#20
Mercedes Iñarrairaegui, Ignacio Melero, Bruno Sangro
Treatment of patients with hepatocellular carcinoma in the advanced stage remains a great challenge, with very few drugs approved. After decades of failures of immune therapies, immune checkpoint inhibitors have emerged as potentially effective treatments for patients with hepatocellular carcinoma in the advanced stage. Immune checkpoints, including human cancer, cytotoxic T-lymphocyte protein 4 (CTLA-4) and programmed cell death protein 1 (PD-1), are surface proteins expressed in a variety of immune cells, and mostly provide immunosuppressive signals...
November 14, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
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