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Interferon melanoma

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https://www.readbyqxmd.com/read/28627943/the-efficacy-and-safety-of-adjuvant-interferon-alfa-therapy-in-the-evolving-treatment-landscape-for-resected-high-risk-melanoma
#1
Van Anh Trinh, Chrystia Zobniw, Wen-Jen Hwu
Patients with resected stage II or III melanoma are at high risk of recurrence, with 5-year mortality rate of 40-60%. Adjuvant interferon-alfa has demonstrated a small RFS and OS benefit versus observation in this patient population. However, the adjuvant treatment landscape is evolving rapidly. Areas covered: This review aims to summarize the safety and efficacy profiles of adjuvant IFNα/PEG-IFNα, revisit the controversy surrounding its application, and reappraise its position in the rapidly changing treatment landscape of resected melanoma...
June 19, 2017: Expert Opinion on Drug Safety
https://www.readbyqxmd.com/read/28620382/phase-ii-study-of-adjuvant-immunotherapy-with-the-csf-470-vaccine-plus-bacillus-calmette-guerin-plus-recombinant-human-granulocyte-macrophage-colony-stimulating-factor-vs-medium-dose-interferon-alpha-2b-in-stages-iib-iic-and-iii-cutaneous-melanoma-patients
#2
José Mordoh, María Betina Pampena, Mariana Aris, Paula Alejandra Blanco, Mónica Lombardo, Erika María von Euw, Soledad Mac Keon, Michelle Yépez Crow, Alicia Inés Bravo, Juan Manuel O'Connor, Ana Gabriela Orlando, Franco Ramello, Estrella Mariel Levy, María Marcela Barrio
The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette-Guerin (BCG) and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF) is being tested against medium-dose IFN-α2b in stages IIB-III cutaneous melanoma (CM) patients (pts) after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study (ClinicalTrials.gov: NCT01729663). Thirty-one pts were randomized to the CSF-470 vaccine (n = 20) or to the IFN-α2b arm (n = 11)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28613357/optical-coherence-tomography-angiography-in-the-multimodal-imaging-evaluation-of-interferon-associated-retinopathy-a-case-report
#3
Leonardo Mastropasqua, Enrico Borrelli, Francesco Amodei, Agbeanda Aharrh-Gnama, Lisa Toto, Peter A Mattei, Rodolfo Mastropasqua
The authors present the case of a 59-year-old woman in treatment with interferon alfa-2b for stage IV melanoma and widespread metastases who presented with interferon-associated retinopathy. An ocular examination revealed multiple retinal cotton-wool spots and hard exudates. Interferon treatment was suspended. The patient was followed up for 5 months following the baseline visit by means of en face optical coherence tomography (OCT), spectral-domain OCT, and OCT angiography. Multimodal imaging was useful in the follow-up of this condition, permitting the characterization of all the lesions hallmarking the interferon-retinopathy and showing that this illness was related to a reduction of the retinal vascular perfusion...
June 1, 2017: Ophthalmic Surgery, Lasers & Imaging Retina
https://www.readbyqxmd.com/read/28604143/combinatorial-antitumor-effects-of-indoleamine-2-3-dioxygenase-inhibitor-nlg919-and-paclitaxel-in-a-murine-b16-f10-melanoma-model
#4
Xiangjing Meng, Guangying Du, Liang Ye, Shanyue Sun, Qiaofeng Liu, Hongbo Wang, Wenyan Wang, Zimei Wu, Jingwei Tian
Indoleamine 2,3-dioxygenase (IDO) is involved in tumor immune escape and resistance to chemotherapy, and is clinically correlated with tumor progression. IDO inhibitors show marginal efficacy as single agents; therefore, combinations of these inhibitors with other therapies hold promise for cancer therapy. The aim of this study was to investigate the synergistic antitumor effects of IDO inhibitor NLG919 in combination with different regimens of paclitaxel in a murine B16-F10 melanoma model. NLG919 increased the cytotoxic activity of paclitaxel toward B16-F10 cells in the presence of pretreatment with interferon (IFN)-γ in vitro...
June 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28597059/-malignant-melanoma-of-the-urinary-bladder
#5
REVIEW
T Otto, D Barski, R Bug
Primary malignant melanoma of the genitourinary tract is a rare lesion. We report the case of a 52-year-old man with primary manifestation of metastatic melanoma in the bladder. Multimodal therapy with transurethral tumor resection and systemic interferon/dacarbazine was not successful and the patient died 18 months later. Currently immune checkpoint inhibitors, CTLA-4 (cytotoxic T lymphocyte antigen-4) and PD-L1 are currently being tested in phase III studies and show long-lasting response in the case of classical melanoma manifestations...
June 8, 2017: Der Urologe. Ausg. A
https://www.readbyqxmd.com/read/28596641/gene-electrotransfer-of-plasmid-encoding-il-12-recruits-the-m1-macrophages-and-antigen-presenting-cells-inducing-the-eradication-of-aggressive-b16f10-murine-melanoma
#6
Ursa Lampreht Tratar, Luisa Loiacono, Maja Cemazar, Urska Kamensek, Vito Michele Fazio, Gregor Sersa, Emanuela Signori
Cancer immunotherapy is currently one of the leading approaches in cancer treatment. Gene electrotransfer of plasmids encoding interleukin 12 (IL-12) into the cells leads to the production of IL-12, which drives immune cell polarization to an antitumoral response. One of the cell types that shows great promise in targeting tumor cells under the influence of IL-12 cytokine milieu is that of macrophages. Therefore, the aim of this study was to evaluate gene electrotransfer of antibiotic resistance-free plasmid DNA-encoding murine IL-12 (mIL-12) in mice bearing aggressive B16F10 murine melanoma...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28591694/the-nucleocapsid-proteins-of-mouse-hepatitis-virus-and-severe-acute-respiratory-syndrome-coronavirus-share-the-same-ifn-%C3%AE-antagonizing-mechanism-attenuation-of-pact-mediated-rig-i-mda5-activation
#7
Zhen Ding, Liurong Fang, Shuangling Yuan, Ling Zhao, Xunlei Wang, Siwen Long, Mohan Wang, Dang Wang, Mohamed Frahat Foda, Shaobo Xiao
Coronaviruses (CoVs) are a huge threat to both humans and animals and have evolved elaborate mechanisms to antagonize interferons (IFNs). Nucleocapsid (N) protein is the most abundant viral protein in CoV-infected cells, and has been identified as an innate immunity antagonist in several CoVs, including mouse hepatitis virus (MHV) and severe acute respiratory syndrome (SARS)-CoV. However, the underlying molecular mechanism(s) remain unclear. In this study, we found that MHV N protein inhibited Sendai virus and poly(I:C)-induced IFN-β production by targeting a molecule upstream of retinoic acid-induced gene I (RIG-I) and melanoma differentiation gene 5 (MDA5)...
May 17, 2017: Oncotarget
https://www.readbyqxmd.com/read/28589910/pd-l1-pd-1-expression-and-tumor-infiltrating-lymphocytes-in-conjunctival-melanoma
#8
Jinfeng Cao, Niels J Brouwer, Kate E Richards, Marina Marinkovic, Sjoerd van Duinen, Daan Hurkmans, Els M E Verdegaal, Ekaterina S Jordanova, Martine J Jager
Conjunctival melanoma (CM) is an infrequent but potentially lethal malignancy, with limited therapeutic options for metastases. Recent inhibitors of the interaction of programmed cell death protein 1 (PD-1) and its ligand PD-L1 are associated with good clinical responses in many malignancies. To investigate the therapeutic potential of targeting the PD-1/PD-L1 axis in CM, we analyzed the expression of PD-1 and PD-L1 and the density of various types of tumor-infiltrating lymphocytes (TILs) in primary CM (n = 27), using immunofluorescence staining...
May 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28575659/catch-and-release-of-cytokines-mediated-by-tumor-phosphatidylserine-converts-transient-exposure-into-long-lived-inflammation
#9
Jennifer Oyler-Yaniv, Alon Oyler-Yaniv, Mojdeh Shakiba, Nina K Min, Ying-Han Chen, Sheue-Yann Cheng, Oleg Krichevsky, Nihal Altan-Bonnet, Grégoire Altan-Bonnet
Immune cells constantly survey the host for pathogens or tumors and secrete cytokines to alert surrounding cells of these threats. In vivo, activated immune cells secrete cytokines for several hours, yet an acute immune reaction occurs over days. Given these divergent timescales, we addressed how cytokine-responsive cells translate brief cytokine exposure into phenotypic changes that persist over long timescales. We studied melanoma cell responses to transient exposure to the cytokine interferon γ (IFNγ) by combining a systems-scale analysis of gene expression dynamics with computational modeling and experiments...
June 1, 2017: Molecular Cell
https://www.readbyqxmd.com/read/28573185/hcv-t-cell-receptor-chain-modifications-to-enhance-expression-pairing-and-antigen-recognition-in-t-cells-for-adoptive-transfer
#10
Kendra C Foley, Timothy T Spear, David C Murray, Kaoru Nagato, Elizabeth Garrett-Mayer, Michael I Nishimura
T cell receptor (TCR)-gene-modified T cells for adoptive cell transfer can mediate objective clinical responses in melanoma and other malignancies. When introducing a second TCR, mispairing between the endogenous and introduced α and β TCR chains limits expression of the introduced TCR, which can result in impaired efficacy or off-target reactivity and autoimmunity. One approach to promote proper TCR chain pairing involves modifications of the introduced TCR genes: introducing a disulfide bridge, substituting murine for human constant regions, codon optimization, TCR chain leucine zipper fusions, and a single-chain TCR...
June 16, 2017: Molecular Therapy Oncolytics
https://www.readbyqxmd.com/read/28561661/operable-melanoma-screening-prognostication-and-adjuvant-and-neoadjuvant-therapy
#11
Ahmad A Tarhini, Paul Lorigan, Sancy Leachman
The importance of reducing the numbers of patients with late-stage melanoma, identifying which patients are most likely to progress, and treating these patients at the earliest possible stage cannot be overemphasized. Improved screening of patients prior to diagnosis has the advantage of identifying early-stage disease that is for the most part treatable by surgical methods. The process of melanoma screening is rapidly evolving through population-based programs, mobile health technologies, and advanced imaging tools...
2017: American Society of Clinical Oncology Educational Book
https://www.readbyqxmd.com/read/28560754/oncostatin-m-induces-rig-i-and-mda5-expression-and-enhances-the-double-stranded-rna-response-in-fibroblasts
#12
Sabine Hergovits, Christine Mais, Claude Haan, Ana P Costa-Pereira, Heike M Hermanns
Interleukin (IL)-6-type cytokines have no direct antiviral activity; nevertheless, they display immune-modulatory functions. Oncostatin M (OSM), a member of the IL-6 family, has recently been shown to induce a distinct number of classical interferon stimulated genes (ISG). Most of them are involved in antigen processing and presentation. However, induction of retinoic acid-inducible gene (RIG)-I-like receptors (RLR) has not been investigated. Here we report that OSM has the capability to induce the expression of the DExD/H-Box RNA helicases RIG-I and melanoma differentiation antigen 5 (MDA5) as well as of the transcription factors interferon regulatory factor (IRF)1, IRF7 and IRF9 in primary fibroblasts...
May 30, 2017: Journal of Cellular and Molecular Medicine
https://www.readbyqxmd.com/read/28552348/interferon-%C3%AE-drives-treg-fragility-to-promote-anti-tumor-immunity
#13
Abigail E Overacre-Delgoffe, Maria Chikina, Rebekah E Dadey, Hiroshi Yano, Erin A Brunazzi, Gulidanna Shayan, William Horne, Jessica M Moskovitz, Jay K Kolls, Cindy Sander, Yongli Shuai, Daniel P Normolle, John M Kirkwood, Robert L Ferris, Greg M Delgoffe, Tullia C Bruno, Creg J Workman, Dario A A Vignali
Regulatory T cells (Tregs) are a barrier to anti-tumor immunity. Neuropilin-1 (Nrp1) is required to maintain intratumoral Treg stability and function but is dispensable for peripheral immune tolerance. Treg-restricted Nrp1 deletion results in profound tumor resistance due to Treg functional fragility. Thus, identifying the basis for Nrp1 dependency and the key drivers of Treg fragility could help to improve immunotherapy for human cancer. We show that a high percentage of intratumoral NRP1(+) Tregs correlates with poor prognosis in melanoma and head and neck squamous cell carcinoma...
June 1, 2017: Cell
https://www.readbyqxmd.com/read/28538413/a-long-term-survivor-with-esophageal-melanoma-and-pulmonary-metastasis-after-single-stage-esophagectomy-and-lobectomy-case-report-and-literature-review
#14
Tian Zhao, Feng-Wei Kong, Heng Wang, Dong Liu, Chun-Ying Wang, Jin-Hua Luo, Miao Zhang, Wen-Bin Wu
RATIONALE: The optimal therapeutic regimen for primary malignant melanoma of the esophagus (PMME) need to be further elucidated. Besides, the efficacy of surgery for PMME with remote metastasis is uncertain for its rarity. PATIENT CONCERNS: Herein a previously healthy patient was admitted for dysphagia and fatigue, without significant weight loss. DIAGNOSES: The pathological and molecular tests revealed his diagnosis of BRAF-mutant, advanced PMME with localized pulmonary metastasis...
May 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28530548/critical-role-of-rig-i-and-mda5-in-early-and-late-stages-of-tulane-virus-infection
#15
Preeti Chhabra, Priya Ranjan, Theresa Cromeans, Suryaprakash Sambhara, Jan Vinjé
Human noroviruses are a major cause of acute gastroenteritis worldwide, but the lack of a robust cell culture system or small animal model have hampered a better understanding of innate immunity against these viruses. Tulane virus (TV) is the prototype virus of a tentative new genus, Recovirus, in the family Caliciviridae. Its epidemiology and biological properties most closely resemble human norovirus. The host innate immune response to RNA virus infection primarily involves pathogen-sensing toll-like receptors (TLRs) TLR3 and TLR7 and retinoic acid-inducible gene I-like receptor RIG-I and melanoma differentiation associated gene 5 (MDA5)...
May 22, 2017: Journal of General Virology
https://www.readbyqxmd.com/read/28519900/type-i-interferon-pathway-in-cns-homeostasis-and-neurological-disorders
#16
REVIEW
Thomas Blank, Marco Prinz
Type I interferons (IFNs), IFN-α and IFN-β, represent the major effector cytokines of the host immune response against viruses and other intracellular pathogens. These cytokines are produced via activation of numerous pattern recognition receptors, including the Toll-like receptor signaling network, retinoic acid-inducible gene-1 (RIG-1), melanoma differentiation-associated protein-5 (MDA-5) and interferon gamma-inducible protein-16 (IFI-16). Whilst the contribution of type I IFNs to peripheral immunity is well documented, they can also be produced by almost every cell in the central nervous system (CNS)...
May 18, 2017: Glia
https://www.readbyqxmd.com/read/28508938/immunotherapy-for-the-treatment-of-uveal-melanoma-current-status-and-emerging-therapies
#17
REVIEW
Kimberly M Komatsubara, Richard D Carvajal
PURPOSE OF REVIEW: Uveal melanoma is a distinct subset of melanoma with a biology and treatment approach that is unique from that of cutaneous melanoma. Here we will review the current data evaluating immunotherapies in both the adjuvant and metastatic settings in uveal melanoma. RECENT FINDINGS: In the adjuvant setting, interferon demonstrated no survival benefit in uveal melanoma, and studies evaluating immune-based strategies such as vaccine therapy are ongoing...
July 2017: Current Oncology Reports
https://www.readbyqxmd.com/read/28508460/treatment-patterns-and-outcomes-of-stage-iiib-iiic-melanoma-in-france-germany-and-the-uk-a-retrospective-and-prospective-observational-study-melabis
#18
Mark Harries, Peter Mohr, Florent Grange, Rainer Ehness, Laure Benjamin, Obukohwo Siakpere, Janina Barth, Ceilidh Stapelkamp, Sylvie Pfersch, Lori McLeod, Sorrel Wolowacz, James A Kaye, Ilias Kontoudis
AIM: Real-world data on treatment patterns/outcomes in patients with advanced melanoma, while scarce, are useful for health technology assessments that govern patient access in many countries. We collected retrospective data on treatment patterns among patients in France, Germany and the UK with Stage IIIB/IIIC melanoma with macroscopic lymph node involvement, whose primary melanoma and regional lymph node metastases had been completely resected. METHODS: Patients ≥18 years were diagnosed between 1 January 2009 and 31 December 2011...
May 2017: International Journal of Clinical Practice
https://www.readbyqxmd.com/read/28507808/pro-necrotic-molecules-impact-local-immunosurveillance-in-human-breast-cancer
#19
Gautier Stoll, Yuting Ma, Heng Yang, Oliver Kepp, Laurence Zitvogel, Guido Kroemer
Necrosis culminates in spilling cellular content through the permeabilized plasma membrane, thereby releasing potentially immunostimulatory molecules in the pericellular space of dead cells. Accordingly, molecules involved in necroptotic signaling, such as receptor-interacting serine/threonine-protein kinase 3 (RIPK3) and mixed lineage kinase-like (MLKL) have been found to stimulate anticancer immune responses in mouse models of chemotherapy. mRNAs encoding prominent pro-necrotic gene products (RIPK1, RIPK3, MLKL, PGAM5 and DFNA5) were correlated with immune-related metagenes in several cancer types (breast, colorectal, lung, ovary, melanoma), revealing the strongest associations in breast cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28494868/interferon-receptor-signaling-pathways-regulating-pd-l1-and-pd-l2-expression
#20
Angel Garcia-Diaz, Daniel Sanghoon Shin, Blanca Homet Moreno, Justin Saco, Helena Escuin-Ordinas, Gabriel Abril Rodriguez, Jesse M Zaretsky, Lu Sun, Willy Hugo, Xiaoyan Wang, Giulia Parisi, Cristina Puig Saus, Davis Y Torrejon, Thomas G Graeber, Begonya Comin-Anduix, Siwen Hu-Lieskovan, Robert Damoiseaux, Roger S Lo, Antoni Ribas
PD-L1 and PD-L2 are ligands for the PD-1 immune inhibiting checkpoint that can be induced in tumors by interferon exposure, leading to immune evasion. This process is important for immunotherapy based on PD-1 blockade. We examined the specific molecules involved in interferon-induced signaling that regulates PD-L1 and PD-L2 expression in melanoma cells. These studies revealed that the interferon-gamma-JAK1/JAK2-STAT1/STAT2/STAT3-IRF1 axis primarily regulates PD-L1 expression, with IRF1 binding to its promoter...
May 9, 2017: Cell Reports
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