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Liver cancer immunotherapy

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https://www.readbyqxmd.com/read/28622514/landscape-of-infiltrating-t-cells-in-liver-cancer-revealed-by-single-cell-sequencing
#1
Chunhong Zheng, Liangtao Zheng, Jae-Kwang Yoo, Huahu Guo, Yuanyuan Zhang, Xinyi Guo, Boxi Kang, Ruozhen Hu, Julie Y Huang, Qiming Zhang, Zhouzerui Liu, Minghui Dong, Xueda Hu, Wenjun Ouyang, Jirun Peng, Zemin Zhang
Systematic interrogation of tumor-infiltrating lymphocytes is key to the development of immunotherapies and the prediction of their clinical responses in cancers. Here, we perform deep single-cell RNA sequencing on 5,063 single T cells isolated from peripheral blood, tumor, and adjacent normal tissues from six hepatocellular carcinoma patients. The transcriptional profiles of these individual cells, coupled with assembled T cell receptor (TCR) sequences, enable us to identify 11 T cell subsets based on their molecular and functional properties and delineate their developmental trajectory...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28621802/glypican-3-a-promising-biomarker-for-hepatocellular-carcinoma-diagnosis-and-treatment
#2
REVIEW
Fubo Zhou, Wenting Shang, Xiaoling Yu, Jie Tian
Liver cancer is the second leading cause of cancer-related deaths, and hepatocellular carcinoma (HCC) is the most common type. Therefore, molecular targets are urgently required for the early detection of HCC and the development of novel therapeutic approaches. Glypican-3 (GPC3), an oncofetal proteoglycan anchored to the cell membrane, is normally detected in the fetal liver but not in the healthy adult liver. However, in HCC patients, GPC3 is overexpressed at both the gene and protein levels, and its expression predicts a poor prognosis...
June 16, 2017: Medicinal Research Reviews
https://www.readbyqxmd.com/read/28593566/cellular-and-molecular-targets-for-the-immunotherapy-of-hepatocellular-carcinoma
#3
REVIEW
Vikrant Rai, Joe Abdo, Abdullah N Alsuwaidan, Swati Agrawal, Poonam Sharma, Devendra K Agrawal
Liver cancer is the sixth most common cancer worldwide and 3rd most common cause of cancer-related death. Hepatocellular carcinoma (HCC) represents more than 90% of primary liver cancer and is a major public health problem. Due to the advanced stages of HCC at the time of diagnosis, utilizing the conventional treatment for solid tumors frequently ends with treatment failure, recurrence, or poor survival. HCC is highly refractory to chemotherapy and other systemic treatments, and locoregional therapies or selective internal radiation therapies are largely palliative...
June 7, 2017: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/28585428/anti-hepatocarcinoma-activity-of-tt-1-an-analog-of-melittin-combined-with-interferon-%C3%AE-via-promoting-the-interaction-of-nkg2d-and-mica
#4
Lan-Lan Wan, Da-Qi Zhang, Jin-Nan Zhang, Li-Qun Ren
Hepatocarcinoma is one of the malignant cancers with significant morbidity and mortality. Immunotherapy has emerged in clinical treatment, owing to the limitation and severe side effects of chemotherapy. In the immune system, natural killer (NK) cells are important effectors required to eliminate malignant tumor cells without the limitation of major histocompatibility complex (MHC) molecule issues. Hence, treatment which could stimulate NK cells is of great interest. Here, we investigated the efficacy of the combined therapy of TT-1 (a mutant of melittin) and interferon-α (IFN-α) on NK cells and human liver cancer HepG-2/Huh7 cells in vitro and in vivo, as well as the mechanism involved...
June 2017: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/28509806/advances-in-management-of-hepatocellular-carcinoma
#5
Manon Allaire, Jean-Charles Nault
PURPOSE OF REVIEW: Hepatocellular carcinoma (HCC) is one of the leading causes of death by cancer worldwide due to a dismal prognosis. The aim of this review is to summarize the main advances in the pathophysiology and management of HCC. RECENT FINDINGS: Genomic analysis has recently delineated the key signaling pathways aberrantly deregulated in HCC (telomere maintenance, cell cycle gene, Wnt/β-catenin, epigenetic modifier, oxidative stress etc.). Major advances in the clinical care of patients with HCC are helping to refine the diagnosis algorithm and tumor staging...
July 2017: Current Opinion in Oncology
https://www.readbyqxmd.com/read/28493307/hepatitis-b-virus-screening-and-reactivation-and-management-of-patients-with-nasopharyngeal-carcinoma-a-large-scale-big-data-intelligence-platform-based-analysis-from-an-endemic-area
#6
Jia-Wei Lv, Yu-Pei Chen, Xiao-Dan Huang, Guan-Qun Zhou, Lei Chen, Wen-Fei Li, Ling-Long Tang, Yan-Ping Mao, Ying Guo, Rui-Hua Xu, Jun Ma, Ying Sun
BACKGROUND: Chemotherapy, target therapy, and immunotherapy are increasingly being used in the systematic treatment of nasopharyngeal carcinoma (NPC), during which the occurrence of hepatitis B virus (HBV) reactivation might increase. However, data regarding HBV screening and reactivation and the clinical management of NPC patients with HBV infections are lacking. This study was aimed at clarifying the risk of reactivation for NPC patients on different regimens while providing evidence concerning HBV screening and management in an endemic area...
May 10, 2017: Cancer
https://www.readbyqxmd.com/read/28480062/locoregional-and-systemic-therapy-for-hepatocellular-carcinoma
#7
REVIEW
Olumide B Gbolahan, Michael A Schacht, Eric W Beckley, Thomas P LaRoche, Bert H O'Neil, Maximilian Pyko
The management of hepatocellular carcinoma (HCC) remains challenging due to late presentation and the presence of accompanying liver dysfunction. As such, most patients are not eligible for curative resection and liver transplant. Management in this scenario depends on a number of factors including hepatic function, tumor burden, patency of hepatic vasculature and patients' functional status. Based on these, patients can be offered catheter based intra-arterial therapy for intermediate stage disease and in more advanced disease, sorafenib...
April 2017: Journal of Gastrointestinal Oncology
https://www.readbyqxmd.com/read/28476944/impact-of-age-on-outcomes-with-immunotherapy-for-patients-with-melanoma
#8
Allison S Betof, Ryan D Nipp, Anita Giobbie-Hurder, Romany A N Johnpulle, Krista Rubin, Samuel M Rubinstein, Keith T Flaherty, Donald P Lawrence, Douglas B Johnson, Ryan J Sullivan
BACKGROUND: Monoclonal antibodies (mAb) targeting PD-1/PD-L1 have revolutionized melanoma treatment, yet data regarding effectiveness and tolerability across age groups is limited. We sought to determine the impact of age on overall survival (OS), progression-free survival (PFS), and rates of immune-mediated toxicities in patients treated with anti-PD-1/anti-PD-L1 mAb at two academic medical centers. METHODS: We retrospectively collected data on all patients with metastatic melanoma treated with anti-PD-1/PD-L1 mAb between May 2009 and April 2015...
May 5, 2017: Oncologist
https://www.readbyqxmd.com/read/28454333/a-polysaccharide-component-from-strongylocentrotus-nudus-eggs-inhibited-hepatocellular-carcinoma-in-mice-by-activating-t-lymphocytes
#9
Min Zhang, Yang Liu, Jingwen Li, Mengyun Ke, Jie Yu, Jie Dou, Hui Wang, Changlin Zhou
A component purified from Strongylocentrotus nudus eggs on a diethylaminoethyl cellulose-52 chromatography column and eluted using a NaCl solution gradient (SEP-S), is a homogeneous polysaccharide of α-D-glucan with a reduced molecular weight of 9.33×10(5) Da, compared with that of S. nudus egg polysaccharide (SEP). In an in vivo antitumor assay of histocompatibility-22 hepatocellular carcinoma in tumor-bearing mice, the inhibitory rates at SEP-S doses of 5, 10 and 20 mg/kg/day were 38.8, 50.7 and 70.3%, respectively...
March 2017: Oncology Letters
https://www.readbyqxmd.com/read/28445959/brain-metastases-from-hepatocellular-carcinoma-recent-advances-and-future-avenues
#10
REVIEW
Shanshan Wang, Anqiang Wang, Jianzhen Lin, Yuan Xie, Liangcai Wu, Hanchun Huang, Jin Bian, Xiaobo Yang, Xueshuai Wan, Haitao Zhao, Jiefu Huang
The incidence of brain metastases from hepatocellular carcinoma (BMHCC) is becoming more frequent than that of the past as a result of prolonged survival of patients with HCC. Compared with brain metastases from other types of cancer, BMHCC tends to exhibit a high incidence of intracerebral hemorrhage (ICH) and poor liver function. Unfortunately, the prognosis is extremely poor for patients with BMHCC owing to the limited treatment selection. Currently, optimal treatment requires multidisciplinary approaches including surgery, whole-brain radiation therapy and stereotactic radiosurgery...
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28443252/open-label-phase-ii-clinical-trial-in-75-patients-with-advanced-hepatocellular-carcinoma-receiving-daily-dose-of-tableted-liver-cancer-vaccine-hepcortespenlisimut-l
#11
Marina G Tarakanovskaya, Jigjidsuren Chinburen, Purev Batchuluun, Chogsom Munkhzaya, Genden Purevsuren, Dorjiin Dandii, Tsogkhuu Hulan, Dandii Oyungerel, Galyna A Kutsyna, Alan A Reid, Vika Borisova, Allen I Bain, Vichai Jirathitikal, Aldar S Bourinbaiar
BACKGROUND: An increasing number of studies is now devoted to immunotherapy of cancer. We evaluated the clinical benefit of hepcortespenlisimut-L (Hepko-V5 [formerly known as V5])-an oral therapeutic vaccine designated by the United States Food and Drug Administration (FDA) as an orphan drug for treatment of hepatocellular carcinoma (HCC). V5 was initially developed by us in 2002 to treat hepatitis B or C viral infections and liver cirrhosis. METHODS: The outcome of open-label Phase II trial of daily dose of V5 pill was analyzed retrospectively...
2017: Journal of Hepatocellular Carcinoma
https://www.readbyqxmd.com/read/28440434/preclinical-studies-for-the-combination-of-paclitaxel-and-curcumin-in-cancer-therapy-review
#12
Yumeng Wei, Xinlin Pu, Ling Zhao
Cancer is one of the most common causes of death and remains the first in China and the second in the US. The common treatments for cancer include surgery, radiation, chemotherapy, targeted therapy and immunotherapy, while chemotherapy remains one of the most important treatments. However, the efficacy of chemotherapy is limited due to drug induced-toxicities and resistance, particularly multiple drug resistance (MDR). Therefore, discovery and development of novel therapeutic drugs and/or combination therapy are urgently needed to reduce toxicity and improve efficacy...
April 20, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28423736/laminarin-promotes-anti-cancer-immunity-by-the-maturation-of-dendritic-cells
#13
Kyeongeun Song, Li Xu, Wei Zhang, Yun Cai, Bian Jang, Junghwan Oh, Jun-O Jin
This research evaluates the effects of laminarin on the maturation of dendritic cells and on the in vivo activation of anti-cancer immunity. In vivo treatment of C56BL/6 mice with laminarin increased the expression levels of co-stimulatory molecules and the production of pro-inflammatory cytokines in spleen dendritic cells. Laminarin enhanced ovalbumin antigen presentation in spleen dendritic cells and promoted the proliferation of OT-I and OT-II T cells. Laminarin also induced the maturation of dendritic cells in tumor-draining lymph nodes and protected interferon-γ and tumor necrosis factor-α and proliferation of OT-I and OT-II T cells in tumors...
June 13, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421272/-the-pathology-of-adverse-events-with-immune-checkpoint-inhibitors
#14
V H Koelzer, K Glatz, L Bubendorf, A Weber, A Gaspert, G Cathomas, A Lugli, A Zippelius, W Kempf, K D Mertz
BACKGROUND: Immunotherapy has gained importance with the development of new effective cancer treatments. Immune checkpoint inhibitors (ICI) are monoclonal antibodies that promote T‑cell mediated tumor immune rejection. Checkpoint blockade also carries the risk of inducing autoimmune reactions ("immune related adverse events", irAEs). The diagnosis and classification of irAEs constitute a new and important field in pathology. AIM: Practice-oriented review of the diagnosis and classification of irAEs...
April 18, 2017: Der Pathologe
https://www.readbyqxmd.com/read/28420805/immunotherapeutic-approaches-for-hepatocellular-carcinoma
#15
REVIEW
Vito Longo, Antonio Gnoni, Andrea Casadei Gardini, Salvatore Pisconti, Antonella Licchetta, Mario Scartozzi, Riccardo Memeo, Vincenzo Ostilio Palmieri, Giuseppe Aprile, Daniele Santini, Patrizia Nardulli, Nicola Silvestris, Oronzo Brunetti
Hepatocellular carcinoma (HCC) is a cancer with a high mortality rate due to the fact that the diagnosis usually occurs at anadvanced stage. Even in case of curative surgical treatment, recurrence is common. Sorafenib and regorafenib are the only therapeutic agents that have been demonstrated to be effective in advanced HCC, thus novel curative approaches are urgently needed. Recent studies focus on the role of immune system in HCC. In fact, the unique immune response in the liver favors tolerance, which can represent a real challenge for conventional immunotherapy in these patients...
May 16, 2017: Oncotarget
https://www.readbyqxmd.com/read/28419193/a-randomized-phase-ii-iii-study-of-cabazitaxel-versus-vinflunine-in-metastatic-or-locally-advanced-transitional-cell-carcinoma-of-the-urothelium-secavin
#16
J Bellmunt, J M Kerst, F Vázquez, R Morales-Barrera, E Grande, A Medina, Mªb González Graguera, G Rubio, U Anido, O Fernández Calvo, E González-Billalabeitia, Ajm Van den Eertwegh, E Pujol, J L Perez-Gracia, J L González Larriba, R Collado, M Los, S Maciá, R De Wit
BACKGROUND: Despite the advent of immunotherapy in urothelial cancer, there is still a need to find effective cytotoxic agents beyond first and second line. Vinflunine is the only treatment approved in this setting by the European Medicines Agency (EMA) and taxanes are also widely used in second line. Cabazitaxel is a taxane with activity in docetaxel-refractory cancers. A randomized study was conducted to compare its efficacy vs vinflunine. PATIENTS AND METHODS: This is a multicenter, randomized, open-label, phase II/III study, following a Simon's optimal method with stopping rules based on an interim futility analysis and a formal efficacy analysis at the end of the phase II...
April 13, 2017: Annals of Oncology: Official Journal of the European Society for Medical Oncology
https://www.readbyqxmd.com/read/28406012/immunomodulatory-magnetic-microspheres-for-augmenting-tumor-specific-infiltration-of-natural-killer-nk-cells
#17
Wooram Park, Andrew C Gordon, Soojeong Cho, Xiaoke Huang, Kathleen R Harris, Andrew C Larson, Dong-Hyun Kim
The purpose of this research is to develop magnetic resonance imaging (MRI) visible immunomodulatory microspheres (IMM-MS) for efficient image guided cancer immunotherapy. IMM-MS composed of recombinant interferon gamma (IFN-γ), iron oxide nanocubes (IONC), and biodegradable poly(lactide-co-glycolide) (PLGA) were successfully prepared via a double-emulsion method. The prepared IMM-MS exhibited a sustained IFN-γ release and highly sensitive MR T2 contrast effects. Finally, in an orthotopic liver tumor VX2 rabbit model, successful hepatic intra-arterial (IA) transcatheter delivery of IMM-MS to liver tumors was confirmed with MR images...
April 26, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28396056/connecting-the-metabolic-and-immune-responses-to-cancer
#18
REVIEW
Thomas R Flint, Douglas T Fearon, Tobias Janowitz
Separate research fields have advanced our understanding of, on the one hand, cancer immunology and, on the other hand, cachexia, the fatal tumor-induced wasting syndrome. A link between the host's immune and metabolic responses to cancer remained unexplored. Emerging work in preclinical models of colorectal and pancreatic cancer has unveiled tumor-induced reprogramming of liver metabolism in cachexia that leads to suppression of antitumor immunity and failure of immunotherapy. As research efforts in metabolism and immunology in cancer are rapidly expanding, it is timely to discuss the metabolic and immunological determinants of the cancer-host interaction...
April 7, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28385609/investigation-of-phosphorylated-adjuvants-co-encapsulated-with-a-model-cancer-peptide-antigen-for-the-treatment-of-colorectal-cancer-and-liver-metastasis
#19
Tyler J Goodwin, Leaf Huang
The lipid calcium phosphate nanoparticle is a versatile platform capable of encapsulating a wide range of phosphorylated molecules from single nucleotides to pDNA. The use of this platform has shown great success as an immunotherapeutic vaccine carrier, capable of delivering co-encapsulated phosphorylated adjuvants and peptides. Three potent vaccine formulations were investigated for anti-cancer efficacy. The phosphorylated adjuvants, CpG, 2'3'cGAMP, and 5'pppdsRNA were co-encapsulated with a model phosphorylated tumor specific peptide antigen (p-AH1-A5)...
May 2, 2017: Vaccine
https://www.readbyqxmd.com/read/28381173/mesothelin-targeting-chimeric-antigen-receptor-modified-t-cells-by-piggybac-transposon-system-suppress-the-growth-of-bile-duct-carcinoma
#20
Jie-Ying Xu, Zhen-Long Ye, Du-Qing Jiang, Jiang-Chuan He, Yong-Mei Ding, Lin-Fang Li, Sai-Qun Lv, Ying Wang, Hua-Jun Jin, Qi-Jun Qian
Chimeric antigen receptor modified T cell-based immunotherapy is revolutionizing the field of cancer treatment. However, its potential in treating bile duct carcinoma has not been fully explored. Herein, we developed the second-generation mesothelin-targeting chimeric antigen receptor-modified T cells with the 4-1BB co-stimulatory module by the piggyBac transposon system. Mesothelin-targeting chimeric antigen receptor was expressed by 66.0% of mesothelin-targeting chimeric antigen receptor-modified T cells post electrophoretic transfection and stimulation with K562-meso cells; the expressions of activation markers were tested by flow cytometry assay and showed greater activation of mesothelin-targeting chimeric antigen receptor-modified T cells than control T cells (CD107α: 71...
April 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
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