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"Melanoma model"

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https://www.readbyqxmd.com/read/28074906/antiproliferative-effects-of-1%C3%AE-oh-vitd3-in-malignant-melanoma-potential-therapeutic-implications
#1
Lucia Spath, Alessandra Ulivieri, Luca Lavra, Laura Fidanza, Marta Carlesimo, Maria Giubettini, Alessandra Narcisi, Emidio Luciani, Barbara Bucci, Daniela Pisani, Salvatore Sciacchitano, Armando Bartolazzi
Early detection and surgery represent the mainstay of treatment for superficial melanoma, but for high risk lesions (Breslow's thickness >0.75 mm) an effective adjuvant therapy is lacking. Vitamin D insufficiency plays a relevant role in cancer biology. The biological effects of 1α hydroxycholecalciferol on experimental melanoma models were investigated. 105 melanoma patients were checked for 25-hydroxycholecalciferol (circulating vitamin D) serum levels. Human derived melanoma cell lines and in vivo xenografts were used for studying 1α-hydroxycholecalciferol-mediated biological effects on cell proliferation and tumor growth...
January 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28062694/effective-combination-of-innate-and-adaptive-immunotherapeutic-approaches-in-a-mouse-melanoma-model
#2
Alexander L Rakhmilevich, Mildred Felder, Lauren Lever, Jacob Slowinski, Kayla Rasmussen, Anna Hoefges, Tyler J Van De Voort, Hans Loibner, Alan J Korman, Stephen D Gillies, Paul M Sondel
Most cancer immunotherapies include activation of either innate or adaptive immune responses. We hypothesized that the combined activation of both innate and adaptive immunity will result in better antitumor efficacy. We have previously shown the synergy of an agonistic anti-CD40 mAb (anti-CD40) and CpG-oligodeoxynucleotides in activating macrophages to induce tumor cell killing in mice. Separately, we have shown that a direct intratumoral injection of immunocytokine (IC), an anti-GD2 Ab linked to IL-2, can activate T and NK cells resulting in antitumor effects...
January 6, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28055296/eradication-of-melanoma-in-vitro-and-in-vivo-via-targeting-with-a-killer-red-containing-telomerase-dependent-adenovirus
#3
Kiyoto Takehara, Shuya Yano, Hiroshi Tazawa, Hiroyuki Kishimoto, Nobuhiro Narii, Hiroyuki Mizuguchi, Yasuo Urata, Shunsuke Kagawa, Toshiyoshi Fujiwara, Robert M Hoffman
Melanoma is a highly recalcitrant cancer and transformative therapy is necessary for the cure of this disease. We recently developed a telomerase-dependent adenovirus containing the fluorescent protein Killer-Red. In the present report, we first determined the efficacy of Killer-Red adenovirus combined with laser irradiation on human melanoma cell lines in vitro. Cell viability of human melanoma cells was reduced in a dose-dependent and irradiation time-dependent manner. We used an intradermal xenografted melanoma model in nude mice to determine efficacy of the Killer-Red adenovirus...
January 5, 2017: Cell Cycle
https://www.readbyqxmd.com/read/28036266/combining-vasculature-disrupting-agent-and-toll-like-receptor-7-8-agonist-for-cancer-therapy
#4
Anushree Seth, Hyunseung Lee, Mi Young Cho, Cheongsoo Park, Sovannarith Korm, Joo-Yong Lee, Inpyo Choi, Yong Taik Lim, Kwan Soo Hong
This study evaluates the effect of combination of two different treatment regimens for solid tumor therapy: vasculature targeting agent and immune-stimulation. Poly lactide-co-glycolide (PLGA) nanoparticles were synthesized for intracellular delivery of toll-like receptor (TLR) 7/8 agonist-gardiquimod. Spherical and mono-disperse gardiquimod encapsulated PLGA nanoparticles (Gardi-PLGA), approximately 194 nm in size were formulated. Gardi-PLGA induced immune-stimulation, and vasculature disrupting agent (VDA)-5,6-Dimethylxanthenone-4-acetic acid (DMXAA) was used in combination to assessing the influence on bone marrow derived dendritic cells (BMDCs) and B16-F10 melanoma cells...
December 27, 2016: Oncotarget
https://www.readbyqxmd.com/read/28028438/hvtra-a-novel-trail-receptor-agonist-induces-apoptosis-and-sustained-growth-retardation-in-melanoma
#5
Karianne G Fleten, Vivi Ann Flørenes, Lina Prasmickaite, Oliver Hill, Jaromir Sykora, Gunhild M Mælandsmo, Birgit Engesæter
In recent years, new treatment options for malignant melanoma patients have enhanced the overall survival for selected patients. Despite new hope, most melanoma patients still relapse with drug-resistant tumors or experience intrinsic resistance to the therapy. Therefore, novel treatment modalities beneficial for subgroups of patients are needed. TRAIL receptor agonists have been suggested as promising candidates for use in cancer treatment as they preferentially induce apoptosis in cancer cells. Unfortunately, the first generation of TRAIL receptor agonists showed poor clinical efficacy...
2016: Cell Death Discovery
https://www.readbyqxmd.com/read/28018602/fusion-of-the-dendritic-cell-targeting-chemokine-mip3%C3%AE-to-melanoma-antigen-gp100-in-a-therapeutic-dna-vaccine-significantly-enhances-immunogenicity-and-survival-in-a-mouse-melanoma-model
#6
James T Gordy, Kun Luo, Hong Zhang, Arya Biragyn, Richard B Markham
BACKGROUND: Although therapeutic cancer vaccines have been mostly disappointing in the clinic, the advent of novel immunotherapies and the future promise of neoantigen-based therapies have created the need for new vaccine modalities that can easily adapt to current and future developments in cancer immunotherapy. One such novel platform is a DNA vaccine fusing the chemokine Macrophage Inflammatory Protein-3α (MIP-3α) to an antigen, here melanoma antigen gp100. Previous published work has indicated that MIP-3α targets nascent peptides to immature dendritic cells, leading to processing by class I and II MHC pathways...
2016: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28003746/evaluation-of-%C3%AE-cyclodextrin-modified-gemini-surfactant-based-delivery-systems-in-melanoma-models
#7
Deborah Michel, Waleed Mohammed-Saeid, Heather Getson, Caitlin Roy, Masoomeh Poorghorban, Jackson M Chitanda, Ronald Verrall, Ildiko Badea
Novel drug delivery systems are developed to improve the biological behavior of poorly soluble drugs and to improve therapeutic outcomes. In melanoma therapy, the goal is efficient drug delivery and mitigation of drug resistance. Melphalan (Mel), a currently used therapeutic agent for melanoma, requires solvent system for solubilization, leading to poor chemical stability. Moreover, drug resistance often renders the drug inefficient in clinical setting. A novel β-cyclodextrin-modified gemini surfactant (CDgemini) delivery system was developed to incorporate Mel in order to improve its physicochemical and biological behavior...
2016: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/27999416/dermal-delivery-of-constructs-encoding-cre-recombinase-to-induce-skin-tumors-in-pten-loxp-loxp-braf-ca-mice
#8
Marcel A Deken, Ji-Ying Song, Jules Gadiot, Adriaan D Bins, Paula Kroon, Inge Verbrugge, Christian U Blank
Current genetically-engineered mouse melanoma models are often based on Tyr::CreER(T2)-controlled MAPK pathway activation by the BRAF(V600E) mutation and PI3K pathway activation by loss of PTEN. The major drawback of these models is the occurrence of spontaneous tumors caused by leakiness of the Tyr::CreER(T2) system, hampering long-term experiments. To address this problem, we investigated several approaches to optimally provide local delivery of Cre recombinase, including injection of lentiviral particles, DNA tattoo administration and particle-mediated gene transfer, to induce melanomas in Pten(LoxP/LoxP);Braf(CA/+) mice lacking the Tyr::CreER(T2) allele...
December 20, 2016: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/27987437/theranostic-approach-for-metastatic-pigmented-melanoma-using-icf15002-a-multimodal-radiotracer-for-both-pet-imaging-and-targeted-radionuclide-therapy
#9
Latifa Rbah-Vidal, Aurélien Vidal, Emilie M F Billaud, Sophie Besse, Isabelle Ranchon-Cole, Florence Mishellany, Yann Perrot, Lydia Maigne, Nicole Moins, Jean-Luc Guerquin-Kern, Françoise Degoul, Jean-Michel Chezal, Philippe Auzeloux, Elisabeth Miot-Noirault
PURPOSE: This work reports, in melanoma models, the theranostic potential of ICF15002 as a single fluorinated and iodinated melanin-targeting compound. METHODS: Studies were conducted in the murine syngeneic B16BL6 model and in the A375 and SK-MEL-3 human xenografts. ICF15002 was radiolabeled with fluorine-18 for positron emission tomography (PET) imaging and biodistribution, with iodine-125 for metabolism study, and iodine-131 for targeted radionuclide therapy (TRT)...
December 14, 2016: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/27974798/mechanism-of-early-dissemination-and-metastasis-in-her2-mammary-cancer
#10
Kathryn L Harper, Maria Soledad Sosa, David Entenberg, Hedayatollah Hosseini, Julie F Cheung, Rita Nobre, Alvaro Avivar-Valderas, Chandandaneep Nagi, Nomeda Girnius, Roger J Davis, Eduardo F Farias, John Condeelis, Christoph A Klein, Julio A Aguirre-Ghiso
Metastasis is the leading cause of cancer-related deaths; metastatic lesions develop from disseminated cancer cells (DCCs) that can remain dormant. Metastasis-initiating cells are thought to originate from a subpopulation present in progressed, invasive tumours. However, DCCs detected in patients before the manifestation of breast-cancer metastasis contain fewer genetic abnormalities than primary tumours or than DCCs from patients with metastases. These findings, and those in pancreatic cancer and melanoma models, indicate that dissemination might occur during the early stages of tumour evolution...
December 14, 2016: Nature
https://www.readbyqxmd.com/read/27940380/biomimetic-biodegradable-artificial-antigen-presenting-cells-synergize-with-pd-1-blockade-to-treat-melanoma
#11
A K Kosmides, R A Meyer, J W Hickey, K Aje, K N Cheung, J J Green, J P Schneck
Biomimetic materials that target the immune system and generate an anti-tumor responses hold promise in augmenting cancer immunotherapy. These synthetic materials can be engineered and optimized for their biodegradability, physical parameters such as shape and size, and controlled release of immune-modulators. As these new platforms enter the playing field, it is imperative to understand their interaction with existing immunotherapies since single-targeted approaches have limited efficacy. Here, we investigate the synergy between a PLGA-based artificial antigen presenting cell (aAPC) and a checkpoint blockade molecule, anti-PD1 monoclonal antibody (mAb)...
February 2017: Biomaterials
https://www.readbyqxmd.com/read/27927165/innate-immunity-based-cancer-immunotherapy-b16-f10-murine-melanoma-model
#12
Veronika Caisová, Andra Vieru, Zuzana Kumžáková, Simona Glaserová, Hana Husníková, Nikol Vácová, Gabriela Krejčová, Lucie Paďouková, Ivana Jochmanová, Katherine I Wolf, Jindřich Chmelař, Jan Kopecký, Jan Ženka
BACKGROUND: Using killed microorganisms or their parts to stimulate immunity for cancer treatment dates back to the end of 19(th) century. Since then, it undergone considerable development. Our novel approach binds ligands to the tumor cell surface, which stimulates tumor phagocytosis. The therapeutic effect is further amplified by simultaneous application of agonists of Toll-like receptors. We searched for ligands that induce both a strong therapeutic effect and are safe for humans. METHODS: B16-F10 murine melanoma model was used...
December 7, 2016: BMC Cancer
https://www.readbyqxmd.com/read/27918556/effects-of-fatty-acid-synthase-inhibitors-on-lymphatic-vessels-an-in-vitro-and-in-vivo-study-in-a-melanoma-model
#13
Débora C Bastos, Jenny Paupert, Catherine Maillard, Fabiana Seguin, Marco A Carvalho, Michelle Agostini, Ricardo D Coletta, Agnès Noël, Edgard Graner
Fatty acid synthase (FASN) is responsible for the endogenous production of fatty acids from acetyl-CoA and malonyl-CoA. Its overexpression is associated with poor prognosis in human cancers including melanomas. Our group has previously shown that the inhibition of FASN with orlistat reduces spontaneous lymphatic metastasis in experimental B16-F10 melanomas, which is a consequence, at least in part, of the reduction of proliferation and induction of apoptosis. Here, we sought to investigate the effects of pharmacological FASN inhibition on lymphatic vessels by using cell culture and mouse models...
December 5, 2016: Laboratory Investigation; a Journal of Technical Methods and Pathology
https://www.readbyqxmd.com/read/27904768/combined-vegfr-and-ctla-4-blockade-increases-the-antigen-presenting-function-of-intratumoral-dcs-and-reduces-the-suppressive-capacity-of-intratumoral-mdscs
#14
Stephanie Du Four, Sarah K Maenhout, Simone P Niclou, Kris Thielemans, Bart Neyns, Joeri L Aerts
Melanoma brain metastases (MBM) occur in 10% to 50% of melanoma patients. They are often associated with a high morbidity and despite the improvements in the treatment of advanced melanoma, including immunotherapy, patients with MBM still have a poor prognosis. Antiangiogenic treatment was shown to reduce the immunosuppressive tumor microenvironment. Therefore we investigated the effect of the combination of VEGFR- and CTLA-4 blockade on the immune cells within the tumor microenvironment. In this study we investigated the effect of the combination of axitinib, a TKI against VEGFR-1, -2 and -3, with therapeutic inhibition of CTLA-4 in subcutaneous and intracranial mouse melanoma models...
2016: American Journal of Cancer Research
https://www.readbyqxmd.com/read/27903862/improved-cancer-immunotherapy-by-a-cd25-mimobody-conferring-selectivity-to-human-interleukin-2
#15
Natalia Arenas-Ramirez, Chao Zou, Simone Popp, Daniel Zingg, Barbara Brannetti, Emmanuelle Wirth, Thomas Calzascia, Jiri Kovarik, Lukas Sommer, Gerhard Zenke, Janine Woytschak, Catherine H Regnier, Andreas Katopodis, Onur Boyman
Interleukin-2 (IL-2) immunotherapy is an attractive approach in treating advanced cancer. However, by binding to its IL-2 receptor α (CD25) subunit, IL-2 exerts unwanted effects, including stimulation of immunosuppressive regulatory T cells (Tregs) and contribution to vascular leak syndrome. We used a rational approach to develop a monoclonal antibody to human IL-2, termed NARA1, which acts as a high-affinity CD25 mimic, thereby minimizing association of IL-2 with CD25. The structure of the IL-2-NARA1 complex revealed that NARA1 occupies the CD25 epitope of IL-2 and precisely overlaps with CD25...
November 30, 2016: Science Translational Medicine
https://www.readbyqxmd.com/read/27903823/in%C3%A2-vitro-skin-models-and-tissue-engineering-protocols-for-skin-graft-applications
#16
REVIEW
Lucas B Naves, Chetna Dhand, Luis Almeida, Lakshminarayanan Rajamani, Seeram Ramakrishna
In this review, we present a brief introduction of the skin structure, a concise compilation of skin-related disorders, and a thorough discussion of different in vitro skin models, artificial skin substitutes, skin grafts, and dermal tissue engineering protocols. The advantages of the development of in vitro skin disorder models, such as UV radiation and the prototype model, melanoma model, wound healing model, psoriasis model, and full-thickness model are also discussed. Different types of skin grafts including allografts, autografts, allogeneic, and xenogeneic are described in detail with their associated applications...
November 30, 2016: Essays in Biochemistry
https://www.readbyqxmd.com/read/27863995/tumor-targeted-delivery-of-sunitinib-base-enhances-vaccine-therapy-for-advanced-melanoma-by-remodeling-the-tumor-microenvironment
#17
Meirong Huo, Yan Zhao, Andrew Benson Satterlee, Yuhua Wang, Ying Xu, Leaf Huang
Development of an effective treatment against advanced tumors remains a major challenge for cancer immunotherapy. We have previously developed a potent mannose-modified lipid calcium phosphate (LCP) nanoparticle (NP)-based Trp2 vaccine for melanoma therapy, but because this vaccine can induce a potent anti-tumor immune response only during the early stages of melanoma, poor tumor growth inhibition has been observed in more advanced melanoma models, likely due to the development of an immune-suppressive tumor microenvironment (TME)...
January 10, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/27846237/integrated-genomics-identifies-mir-32-mcl-1-pathway-as-a-critical-driver-of-melanomagenesis-implications-for-mir-replacement-and-combination-therapy
#18
Prasun J Mishra, Pravin J Mishra, Glenn Merlino
AIMS: Cutaneous malignant melanoma is among the deadliest human cancers, broadly resistant to most clinical therapies. A majority of patients with BRAFV600E melanomas respond well to inhibitors such as vemurafenib, but all ultimately relapse. Moreover, there are no viable treatment options available for other non-BRAF melanoma subtypes in the clinic. A key to improving treatment options lies in a better understanding of mechanisms underlying melanoma progression, which are complex and heterogeneous...
2016: PloS One
https://www.readbyqxmd.com/read/27821803/oncolytic-adenovirus-coexpressing-interleukin-12-and-shvegf-restores-antitumor-immune-function-and-enhances-antitumor-efficacy
#19
Hyo Min Ahn, Jin Woo Hong, Chae-Ok Yun
Tumor microenvironment is extremely immunosuppressive, preventing efficient induction of antitumor immunity. To overcome tumor-mediated immunosuppression and enhance the potency of immunogene therapy, oncolytic adenovirus (Ad) co-expressing interleukin (IL)-12 and vascular endothelial growth factor (VEGF)-specific short hairpin ribonucleic acid (shVEGF; RdB/IL12/shVEGF) was generated. Intratumoral injection of RdB/IL12/shVEGF induced a strong antitumor effect in an immune competent B16-F10 melanoma model. RdB/IL12/shVEGF restored immune surveillance function in tumor tissues and actively recruited immune cells by elevating the expression levels of IL-12 and interferon-γ...
November 4, 2016: Oncotarget
https://www.readbyqxmd.com/read/27798280/inference-of-the-drivers-of-collective-movement-in-two-cell-types-dictyostelium-and-melanoma
#20
Elaine A Ferguson, Jason Matthiopoulos, Robert H Insall, Dirk Husmeier
Collective cell movement is a key component of many important biological processes, including wound healing, the immune response and the spread of cancers. To understand and influence these movements, we need to be able to identify and quantify the contribution of their different underlying mechanisms. Here, we define a set of six candidate models-formulated as advection-diffusion-reaction partial differential equations-that incorporate a range of cell movement drivers. We fitted these models to movement assay data from two different cell types: Dictyostelium discoideum and human melanoma...
October 2016: Journal of the Royal Society, Interface
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