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Liver cancer immunotherapy

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https://www.readbyqxmd.com/read/28423736/laminarin-promotes-anti-cancer-immunity-by-the-maturation-of-dendritic-cells
#1
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...
March 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421272/-the-pathology-of-adverse-events-with-immune-checkpoint-inhibitors
#2
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
#3
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...
February 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
#4
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
#5
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 13, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28396056/connecting-the-metabolic-and-immune-responses-to-cancer
#6
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
#7
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)...
April 3, 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
#8
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
https://www.readbyqxmd.com/read/28353401/effect-of-nk-cell-immunotherapy-on-immune-function-in-patients-with-hepatic-carcinoma-a-preliminary-clinical-study
#9
Zilin Qin, Jibing Chen, Jianying Zeng, Lizhi Niu, Silun Xie, Xiaohua Wang, Yingqing Liang, Zhenyi Wu, Mingjie Zhang
We investigated the effectiveness of adoptive transfer of KIR ligand-mismatched highly activated nature killer (HANK) cells in patients with hepatic carcinoma. Peripheral blood mononuclear cells were obtained and cultured in vitro to induce expansion and activation of HANK cells. After 12 days of culture, the cells were divided into three parts and infused intravenously on days 13 to 15. The patients (n = 16) were given one to six courses of immunotherapy. No side effects were observed. The lymphocyte subsets and cytokine, thymidine kinase 1 (TK1) and circulating tumor cell (CTC) levels were measured 1 day before treatment and 1 month after the final infusion: the absolute number of total T cells and NK cells and the IL-2 and TNF-β levels were significantly higher, and the TK1 and CTC levels were significantly lower at 1 month after treatment...
March 29, 2017: Cancer Biology & Therapy
https://www.readbyqxmd.com/read/28351299/recognizing-and-managing-on-toxicities-in-cancer-immunotherapy
#10
REVIEW
Liu Yang, Huifang Yu, Shuang Dong, Yi Zhong, Sheng Hu
Over the past 4 years, cancer immunotherapy has significantly prolonged survival time of patients with prostate cancer, melanoma, lung cancer, and liver cancer, but its side effects are also impressive. Different types of the immune therapeutic agents have different on-target or off-target toxicity due to high affinity or weak specificity, respectively. Treatment toxicity spectrums vary greatly even in patients with the same type of cancer. Common toxicities are fevers, chills, diarrhea colitis, maculopapular rash, hepatitis, and hormone gland disorder; therefore, routine monitoring of thyroid function, liver function, renal function, and complete blood count are absolutely necessary once treatment begins...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28351116/management-of-people-with-early-or-very-early-stage-hepatocellular-carcinoma-an-attempted-network-meta-analysis
#11
REVIEW
Avik Majumdar, Davide Roccarina, Douglas Thorburn, Brian R Davidson, Emmanuel Tsochatzis, Kurinchi Selvan Gurusamy
BACKGROUND: Hepatocellular carcinoma (primary liver cancer) is classified in many ways. The Barcelona Clinic Liver Cancer (BCLC) group staging classifies the cancer based on patient's life expectancy. People with very early- or early-stage hepatocellular carcinoma have single tumour or three tumours of maximum diameter of 3 cm or less, Child-Pugh status A to B, and performance status 0 (fully functional). Management of hepatocellular carcinoma is uncertain. OBJECTIVES: To assess the comparative benefits and harms of different interventions used in the treatment of early or very early hepatocellular carcinoma through a network meta-analysis and to generate rankings of the available interventions according to their safety and efficacy...
March 28, 2017: Cochrane Database of Systematic Reviews
https://www.readbyqxmd.com/read/28347250/chimeric-antigen-receptor-engineered-t-cells-for-liver-cancers-progress-and-obstacles
#12
REVIEW
Keyu Li, Yaliang Lan, Jiabei Wang, Lianxin Liu
Chimeric antigen receptor-engineered T cells therapy has become the hottest topic of immunotherapy, as its great successes achieved in treating refractory hematological malignancies. These successes also paved the road to novel strategies of treating various solid tumors including liver cancer. Many specific proteins can be expressed aberrantly in liver cancers; therefore, a series of experimental and clinical researches exploring chimeric antigen receptor-engineered T cells and liver cancer are in progress, acquiring obvious antitumor effect and revealing its feasibility in treating liver cancer...
March 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28301139/designing-hydrogels-for-on-demand-therapy
#13
Nuria Oliva, João Conde, Kui Wang, Natalie Artzi
Systemic administration of therapeutic agents has been the preferred approach to treat most pathological conditions, in particular for cancer therapy. This treatment modality is associated with side effects, off-target accumulation, toxicity, and rapid renal and hepatic clearance. Multiple efforts have focused on incorporating targeting moieties into systemic therapeutic vehicles to enhance retention and minimize clearance and side effects. However, only a small percentage of the nanoparticles administered systemically accumulate at the tumor site, leading to poor therapeutic efficacy...
March 16, 2017: Accounts of Chemical Research
https://www.readbyqxmd.com/read/28278221/antitumor-activity-of-orally-administered-maitake-%C3%AE-glucan-by-stimulating-antitumor-immune-response-in-murine-tumor
#14
Yuki Masuda, Yoshiaki Nakayama, Akihiro Tanaka, Kenta Naito, Morichika Konishi
Maitake α-glucan, YM-2A, isolated from Grifola frondosa, has been characterized as a highly α-1,6-branched α-1,4 glucan. YM-2A has been shown to possess an anti-virus effect in mice; however, it does not directly inhibit growth of the virus in vitro, indicating that the anti-virus effect of YM-2A might be associated with modulation of the host immune system. In this study, we found that oral administration of YM-2A could inhibit tumor growth and improve survival rate in two distinct mouse models of colon-26 carcinoma and B16 melanoma...
2017: PloS One
https://www.readbyqxmd.com/read/28271729/egfr-tki-combination-with-immunotherapy-in-non-small-cell-lung-cancer
#15
REVIEW
Myung-Ju Ahn, Jong-Mu Sun, Se-Hoon Lee, Jin Seok Ahn, Keunchil Park
Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) has significantly improved clinical outcomes compared with chemotherapy in non-small cell lung cancer (NSCLC) patients with sensitizing EGFR gene mutation. Areas covered: Almost all patients treated with EGFR TKIs eventually develop acquired resistance. It has been reported that activation of the oncogenic EGFR pathway enhances susceptibility of the lung tumors to PD-1 blockade in mouse model, suggesting combination of PD1 blockade with EGFR TKIs may be a promising therapeutic strategy...
April 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28246107/comprehensive-meta-analysis-of-key-immune-related-adverse-events-from-ctla-4-and-pd-1-pd-l1-inhibitors-in-cancer-patients
#16
Guillermo De Velasco, Youjin Je, Dominick Bossé, Mark M Awad, Patrick A Ott, Raphael B Moreira, Fabio Schutz, Joaquim Bellmunt, Guru P Sonpavde, F Stephen Hodi, Toni K Choueiri
Immune-related adverse events (irAE) have been described with immune checkpoint inhibitors (ICI), but the incidence and relative risk (RR) of irAEs associated with these drugs remains unclear. We selected five key irAEs from treatments with approved cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), programmed cell death 1 (PD-1), and programmed death ligand 1 (PD-L1) inhibitors (ipilimumab, nivolumab, or pembrolizumab, and atezolizumab, respectively) to better characterize their safety profile. We performed a meta-analysis of randomized phase II/III immunotherapy trials, with non-ICI control arms, conducted between 1996 and 2016...
April 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28223846/prospect-of-the-use-of-checkpoint-inhibitors-in-hepatocellular-cancer-treatments
#17
REVIEW
Ali Raufi, Maria Tria Tirona
Hepatocellular cancer (HCC) is a very fatal disease due to limited therapeutic options as well as due to its association with underlying chronic liver disease in the majority of cases. The immune evasion in HCC signifies a major barrier to the delivery of effective immunotherapy. Sorafenib is the only Food and Drug Administration-approved drug available with an overall response rate of 2%-3% and overall survival of 2.8 months. Chemotherapy has not been used routinely because of the relative refractoriness of advanced HCC...
2017: Cancer Management and Research
https://www.readbyqxmd.com/read/28218682/immune-mediated-therapies-for-liver-cancer
#18
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/28197373/systemic-activation-of-antigen-presenting-cells-via-rna-loaded-nanoparticles
#19
Elias J Sayour, Gabriel De Leon, Christina Pham, Adam Grippin, Hanna Kemeny, Joshua Chua, Jianping Huang, John H Sampson, Luis Sanchez-Perez, Catherine Flores, Duane A Mitchell
While RNA-pulsed dendritic cell (DC) vaccines have shown promise, the advancement of cellular therapeutics is fraught with developmental challenges. To circumvent the challenges of cellular immunotherapeutics, we developed clinically translatable nanoliposomes that can be combined with tumor-derived RNA to generate personalized tumor RNA-nanoparticles (NPs) with considerable scale-up capacity. RNA-NPs bypass MHC restriction, are amenable to central distribution, and can provide near immediate immune induction...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28193529/heterogeneity-in-immune-marker-expression-after-acquisition-of-resistance-to-egfr-kinase-inhibitors-analysis-of-a-case-with-small-cell-lung-cancer-transformation
#20
Kenichi Suda, Isao Murakami, Hui Yu, Jihye Kim, Kim Ellison, Christopher J Rivard, Tetsuya Mitsudomi, Fred R Hirsch
INTRODUCTION: Expression of immune-markers is of scientific interest due to their potential roles as predictive biomarkers for immunotherapy. Although the microenvironment of metastatic tumors and/or therapy-inducible histological transformation may affect the expression of these immune-markers, there is little data regarding this context. METHODS: A 76-year-old never-smoking female with epidermal growth factor receptor (EGFR) mutated lung adenocarcinoma (AC) acquired resistance to gefitinib...
February 10, 2017: Journal of Thoracic Oncology
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