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Interferon melanoma

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https://www.readbyqxmd.com/read/29136453/randomized-phase-iii-trial-of-adjuvant-therapy-with-locoregional-interferon-beta-versus-surgery-alone-in-stage-ii-iii-cutaneous-melanoma-japan-clinical-oncology-group-study-jcog1309-j-feron
#1
Kenjiro Namikawa, Arata Tsutsumida, Tomonori Mizutani, Taro Shibata, Tatsuya Takenouchi, Shusuke Yoshikawa, Yoshio Kiyohara, Hiroshi Uchi, Masutaka Furue, Dai Ogata, Tetsuya Tsuchida, Naoya Yamazaki
The Dermatologic Oncology Group of Japan Clinical Oncology Group has started a randomized phase III trial to confirm the superiority of adjuvant therapy with locoregional interferon beta in overall survival over surgery alone for patients with pathological stage II/III cutaneous melanoma (JCOG1309). Patients in the interferon beta arm receive intra- or subcutaneous injections of interferon beta directly into the surgical site at a flat dose of 3 million units once per day. Treatment is repeated for 10 consecutive days every 8 weeks for a total of 3 courses during the induction phase, then 1-day injection every 4 weeks for 2...
July 1, 2017: Japanese Journal of Clinical Oncology
https://www.readbyqxmd.com/read/29132350/avian-infectious-bronchitis-virus-disrupts-the-melanoma-differentiation-associated-gene-5-mda5-signaling-pathway-by-cleavage-of-the-adaptor-protein-mavs
#2
Liping Yu, Xiaorong Zhang, Tianqi Wu, Jin Su, Yuyang Wang, Yuexin Wang, Baoyang Ruan, Xiaosai Niu, Yantao Wu
BACKGROUND: Melanoma differentiation associated gene 5 (MDA5) and retinoic acid-inducible gene-I (RIG-I) selectively sense cytoplasmic viral RNA to induce an antiviral immune response. Infectious bronchitis virus (IBV) is one of the most important infectious agents in chickens, and in chicken cells, it can be recognized by MDA5 to activate interferon production. RIG-I is considered to be absent in chickens. However, the absence of RIG-I in chickens raises the question of whether this protein influences the antiviral immune response against IBV infection...
November 13, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/29127039/biodegradable-sting-agonist-nanoparticles-for-enhanced-cancer-immunotherapy
#3
David R Wilson, Rupashree Sen, Joel C Sunshine, Drew M Pardoll, Jordan J Green, Young J Kim
Therapeutic cancer vaccines require adjuvants leading to robust type I interferon and proinflammatory cytokine responses in the tumor microenvironment to induce an anti-tumor response. Cyclic dinucleotides (CDNs), a potent Stimulator of Interferon Receptor (STING) agonist, are currently in phase I trials. However, their efficacy may be limited to micromolar concentrations due to the cytosolic residence of STING in the ER membrane. Here we utilized biodegradable, poly(beta-amino ester) (PBAE) nanoparticles to deliver CDNs to the cytosol leading to robust immune response at >100-fold lower extracellular CDN concentrations in vitro...
November 7, 2017: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/29116432/seom-clinical-guideline-for-the-management-of-malignant-melanoma-2017
#4
A Berrocal, A Arance, V E Castellon, L de la Cruz, E Espinosa, M G Cao, J L G Larriba, I Márquez-Rodas, A Soria, S M Algarra
All melanoma suspected patients must be confirmed histologically and resected. Sentinel node biopsy must be done when tumor is over 1 mm or if less with high-risk factors. Adjuvant therapy with interferon could be offered for patients with high-risk melanoma and in selected cases radiotherapy can be added. Metastatic melanoma treatment is guided by mutational BRAF status. BRAF wild type patients must receive anti-PD1 containing therapy and BRAF mutated patients BRAF/MEK inhibitors or anti-PD1 containing therapy...
November 7, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/29114547/predictive-factors-of-response-to-immunotherapy-a-review-from-the-spanish-melanoma-group-gem
#5
REVIEW
Enrique Espinosa, Ivan Márquez-Rodas, Ainara Soria, Alfonso Berrocal, Jose Luis Manzano, Maria Gonzalez-Cao, Salvador Martin-Algarra
Immunotherapy has become a key element in the treatment of several tumors, such as lung carcinoma and melanoma. Immunotherapy, unlike classical chemotherapy and targeted drugs, may yield long-term survival, even in patients who stop treatment due to toxicity. This fact has generated considerable excitement and a real shift in the paradigm of cancer treatment. However, only a small subset of patients benefit from immunotherapy. Survival curves show that most patients have progression of the disease in the first months after starting immunotherapy, followed by a slower decrease over the first 3 years, until curves reach a plateau...
October 2017: Annals of Translational Medicine
https://www.readbyqxmd.com/read/29102119/rig-1-and-mda-5-signaling-pathways-contribute-to-ifn-%C3%AE-production-and-viral-replication-in-porcine-circovirus-virus-type-2-infected-pk-15-cells-in-vitro
#6
Bei Huang, Jiansheng Li, Xinchen Zhang, Qiling Zhao, Mingqing Lu, Yingjun Lv
Type I Interferons (IFNs) is known for its antiviral activity; however, it is surprising that in vitro treatment of IFN-α and IFN-γ enhanced the replication of porcine circovirus type 2 (PCV2), indicating a complex relationship between interferon and PCV2. To date, it remains poorly understood how the interferon is produced during PCV2 infection and whether the interferon induced by PCV2 itself can promote viral replication. In this study, PCV2 induced the up-regulation of IFN-β in PK-15 cells, while treatment of PCV2-infected cells with the interferon regulatory factor-3 (IRF3) inhibitor, BX795, decreased the expression of IFN-β, whereas treatment with the nuclear factor kappa-light-chain-enhancer of activated B cells (NF-κB) inhibitor, BAY11-7082, did not...
November 2017: Veterinary Microbiology
https://www.readbyqxmd.com/read/29101107/cytokines-in-cancer-immunotherapy
#7
Thomas A Waldmann
Cytokines that control the immune response were shown to have efficacy in preclinical murine cancer models. Interferon (IFN)-α is approved for treatment of hairy cell leukemia, and interleukin (IL)-2 for the treatment of advanced melanoma and metastatic renal cancer. In addition, IL-12, IL-15, IL-21, and granulocyte macrophage colony-stimulating factor (GM-CSF) have been evaluated in clinical trials. However, the cytokines as monotherapy have not fulfilled their early promise because cytokines administered parenterally do not achieve sufficient concentrations in the tumor, are often associated with severe toxicities, and induce humoral or cellular checkpoints...
November 3, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/29081658/understanding-the-positive-benefit-risk-profile-of-alemtuzumab-in-relapsing-multiple-sclerosis-perspectives-from-the-alemtuzumab-clinical-development-program
#8
REVIEW
Eva Havrdova, Jeffrey A Cohen, Dana Horakova, Ivana Kovarova, Eva Meluzinova
The introduction of high-efficacy therapies for relapsing-remitting multiple sclerosis has driven re-evaluation of treatment goals and benefit:risk considerations in treatment choice. In the alemtuzumab Phase II and III clinical trials, patients treated with alemtuzumab 12 mg versus subcutaneous interferon beta-1a demonstrated significantly reduced annualized relapse rates and improved magnetic resonance imaging outcomes, and were significantly more likely to achieve no evidence of disease activity and reduction in brain volume loss...
2017: Therapeutics and Clinical Risk Management
https://www.readbyqxmd.com/read/29076925/circulating-epithelial-tumor-cells-as-a-prognostic-tool-for-malignant-melanoma
#9
Katharina Pachmann, Regina Willecke-Hochmuth, Katrin Schneider, Martin Kaatz
Although immune therapies with checkpoint inhibitors have gained increasing attention in advanced and metastatic melanoma, interferon-α remains a standard therapy for nonmetastatic malignant melanoma with risk factors. Interferons can successfully prevent relapse; however, the response rate is still not as high as would be desired. Prognostic tools to predict the response are required, which could lead to more individualized treatment regimens. In numerous studies over the past decade, circulating epithelial tumor cells (CETCs) have been shown to be a promising biomarker for estimating the risk of metastatic relapse, and we sought to determine whether they can also be used for this purpose in malignant melanoma...
October 25, 2017: Melanoma Research
https://www.readbyqxmd.com/read/29069650/dnajb1-hsp40-suppresses-melanoma-differentiation-associated-gene-5-mitochondrial-antiviral-signaling-protein-function-in-conjunction-with-hsp70
#10
Ken Takashima, Hiroyuki Oshiumi, Misako Matsumoto, Tsukasa Seya
Melanoma differentiation-associated gene 5 (MDA5) is a pattern recognition receptor that recognizes cytoplasmic viral double-stranded RNA (dsRNA) and initiates rapid innate antiviral responses. MDA5 forms a filament-like multimer along the dsRNA leading to oligomerization, which in turn activates the adaptor protein mitochondrial antiviral signaling protein (MAVS) to provide a signal platform for the induction of type I interferon (IFN) and proinflammatory cytokines. The conformational switch of MDA5 causes antiviral defense, but excessive activation of the MDA5-MAVS pathway may result in autoimmune diseases...
October 26, 2017: Journal of Innate Immunity
https://www.readbyqxmd.com/read/29050360/immunomodulatory-and-antitumor-effects-of-type-i-interferons-and-their-application-in-cancer-therapy
#11
REVIEW
Ruan F V Medrano, Aline Hunger, Samir Andrade Mendonça, José Alexandre M Barbuto, Bryan E Strauss
During the last decades, the pleiotropic antitumor functions exerted by type I interferons (IFNs) have become universally acknowledged, especially their role in mediating interactions between the tumor and the immune system. Indeed, type I IFNs are now appreciated as a critical component of dendritic cell (DC) driven T cell responses to cancer. Here we focus on IFN-α and IFN-β, and their antitumor effects, impact on immune responses and their use as therapeutic agents. IFN-α/β share many properties, including activation of the JAK-STAT signaling pathway and induction of a variety of cellular phenotypes...
September 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29034314/targeting-an-oncolytic-influenza-a-virus-to-tumor-tissue-by-elastase
#12
Irina Kuznetsova, Tobias Arnold, Thomas Aschacher, Cornelia Schwager, Balazs Hegedus, Tamas Garay, Marina Stukova, Maria Pisareva, Stephan Pleschka, Michael Bergmann, Andrej Egorov
Oncolytic viruses are currently established as a novel type of immunotherapy. The challenge is to safely target oncolytic viruses to tumors. Previously, we have generated influenza A viruses (IAVs) containing deletions in the viral interferon antagonist. Those deletions have attenuated the virus in normal tissue but allowed replication in tumor cells. IAV entry is mediated by hemagglutinin (HA), which needs to be activated by a serine protease, for example, through trypsin. To further target the IAV to tumors, we have changed the trypsin cleavage site to an elastase cleavage site...
December 15, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/29033131/oxysterol-restraint-of-cholesterol-synthesis-prevents-aim2-inflammasome-activation
#13
Eric V Dang, Jeffrey G McDonald, David W Russell, Jason G Cyster
Type I interferon restrains interleukin-1β (IL-1β)-driven inflammation in macrophages by upregulating cholesterol-25-hydroxylase (Ch25h) and repressing SREBP transcription factors. However, the molecular links between lipid metabolism and IL-1β production remain obscure. Here, we demonstrate that production of 25-hydroxycholesterol (25-HC) by macrophages is required to prevent inflammasome activation by the DNA sensor protein absent in melanoma 2 (AIM2). We find that in response to bacterial infection or lipopolysaccharide (LPS) stimulation, macrophages upregulate Ch25h to maintain repression of SREBP2 activation and cholesterol synthesis...
October 7, 2017: Cell
https://www.readbyqxmd.com/read/29032405/agaricus-blazei-murill-polysaccharides-protect-against-cadmium-induced-oxidative-stress-and-inflammatory-damage-in-chicken-spleens
#14
Wanqiu Xie, Ai Lv, Ruyue Li, Zequn Tang, Dexing Ma, Xiaodan Huang, Ruili Zhang, Ming Ge
Agaricus blazei Murill polysaccharide (ABP) has exhibited antioxidant and immunoregulatory activity. The aim of this study was to investigate the effect of ABP on cadmium (Cd)-induced antioxidant functions and inflammatory damage in chicken spleens. In this study, groups of 7-day-old chickens were fed with normal saline (0.2 mL single/day), CdCl2 (140 mg/kg/day), ABP (30 mg/mL, 0.2 mL single/day), and Cd + ABP (140 mg/kg/day + 0.2 mL ABP). Spleens were separated on the 20th, 40th, and 60th day for each group...
October 14, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/29032202/pact-is-required-for-mda5-mediated-immunoresponses-triggered-by-cardiovirus-infection-via-interaction-with-lgp2
#15
Masahiko Miyamoto, Akihiko Komuro
Laboratory of genetics and physiology 2 (LGP2) and melanoma differentiation-associated gene 5 (MDA5) cooperatively detect viral RNA in the cytoplasm of Cardiovirus-infected cells and activate innate immune responses. Here, we evaluated whether the double-stranded RNA-binding protein PACT plays a role in this anti-viral response to further elucidate the mechanism. Immunoprecipitation experiments demonstrated that PACT interacts with LGP2 and that this interaction is enhanced by encephalomyocarditis virus (EMCV) infection...
October 12, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29023759/cord-blood-derived-t-cells-allow-the-generation-of-a-more-na%C3%A3-ve-tumor-reactive-cytotoxic-t-cell-phenotype
#16
Julian Kwoczek, Sebastian B Riese, Sabine Tischer, Szilvia Bak, Julia Lahrberg, Mathias Oelke, Holger Maul, Rainer Blasczyk, Martin Sauer, Britta Eiz-Vesper
BACKGROUND: Transplantation of hematopoietic stem cells (HSCs) from peripheral blood (PB) or cord blood (CB) is well established. HSCs from CB are associated with a lower risk of graft-versus-host disease (GVHD), but antigen-independent expanded CB- and PB-derived T cells can induce GVHD in allo-HSC recipients. CB-derived cells might be more suitable for adoptive immunotherapy as they have unique T-cell characteristics. Here, we describe functional differences between CB and PB T cells stimulated with different cytokine combinations involved in central T-cell activation...
October 11, 2017: Transfusion
https://www.readbyqxmd.com/read/28994212/high-frequency-of-brain-metastases-after-adjuvant-therapy-for-high-risk-melanoma
#17
Wolfram E Samlowski, James Moon, Merle Witter, Michael B Atkins, John M Kirkwood, Megan Othus, Antoni Ribas, Vernon K Sondak, Lawrence E Flaherty
The incidence of CNS progression in patients with high-risk regional melanoma (stages IIIAN2a-IIIC) is not well characterized. Data from the S0008 trial provided an opportunity to examine the role of CNS progression in treatment failure and survival. All patients were surgically staged. Following wide excision and full regional lymphadenectomy, patients were randomized to receive adjuvant biochemotherapy (BCT) or high-dose interferon alfa-2B (HDI). CNS progression was retrospectively identified from data forms...
November 2017: Cancer Medicine
https://www.readbyqxmd.com/read/28985469/programmed-cell-death-protein-ligand-1-silencing-with-polyethylenimine-dermatan-sulfate-complex-for-dual-inhibition-of-melanoma-growth
#18
Gijung Kwak, Dongkyu Kim, Gi-Hoon Nam, Sun Young Wang, In-San Kim, Sun Hwa Kim, Ick-Chan Kwon, Yoon Yeo
Programmed cell death protein-1 (PD-1) is a prominent immune checkpoint receptor interacting with its ligand, programmed cell death protein ligand-1 (PD-L1, B7-H1). The PD-1/PD-L1 interaction induces functional exhaustion of tumor-reactive cytotoxic T cells and, thus, interferes with antitumor T-cell immunity. In addition, PD-1/PD-L1 interaction promotes tumorigenesis via the mTOR signaling pathway in a group of cancers including melanoma. Based on the dual functions of PD-1/PD-L1 interactions in tumor progression, we hypothesize that siRNA targeting PD-L1 (siPD-L1) will suppress melanoma growth, acting on both immune checkpoint and intrinsic tumorigenesis pathways...
October 24, 2017: ACS Nano
https://www.readbyqxmd.com/read/28976130/a-retrospective-analysis-of-tolerance-and-outcomes-of-cutaneous-malignant-melanoma-in-patients-receiving-adjuvant-interferon-alpha-2b-a-community-oncology-perspective
#19
Muhammad Zubair Afzal, Vani Pinnamaneni, K C Birendra, Alan T Davis, Tracy J Koehler, Nehal Lakhani
INTRODUCTION: Interferon alpha 2B (IFN-α) therapy in malignant melanoma has improved relapse free survival and overall survival but is considerably toxic and lowers the overall quality of life (QoL) substantially. A significant number of patients do not complete the full duration (one year) of therapy. OBJECTIVE: The aim of this study was to evaluate patients' ability to tolerate IFN-α therapy and to compare our results to reported data in the literature. METHODS: We conducted a retrospective review of patients diagnosed with cutaneous malignant melanoma who received IFN therapy after surgical resection...
September 2017: Journal of Experimental Therapeutics & Oncology
https://www.readbyqxmd.com/read/28968566/the-2017-complete-overhaul-of-adjuvant-therapies-for-high-risk-melanoma-and-its-consequences-for-staging-and-management-of-melanoma-patients
#20
Alexander M M Eggermont, Reinhard Dummer
The spectacular outcomes of the phase III trials regarding nivolumab versus ipilimumab in fully resected stage IIIB/C-IV and of the combination of dabrafenib (D) plus trametinib (T) in BRAF-mutant stage III patients demonstrate that effective treatments in advanced melanoma are also highly effective in the adjuvant setting. In 2016, an overall survival benefit with adjuvant high-dose ipilimumab was demonstrated, and the European Organisation for Research and Treatment of Cancer trial 1325 comparing pembrolizumab versus placebo will complete the picture in the early 2018...
September 28, 2017: European Journal of Cancer
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