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https://www.readbyqxmd.com/read/28333145/the-cryo-thermal-therapy-eradicated-melanoma-in-mice-by-eliciting-cd4-t-cell-mediated-antitumor-memory-immune-response
#1
Kun He, Ping Liu, Lisa X Xu
Tumor metastasis is a major concern in tumor therapy. In our previous studies, a novel tumor therapeutic modality of the cryo-thermal therapy has been presented, highlighting its effect on the suppression of distal metastasis and leading to long-term survival in 4T1 murine mammary carcinoma model. To demonstrate the therapeutic efficacy in other aggressive tumor models and further investigate the mechanism of long-term survival induced, in this study, spontaneous metastatic murine B16F10 melanoma model was used...
March 23, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28273716/lipid-nanoparticle-assisted-mrna-delivery-for-potent-cancer-immunotherapy
#2
Matthias A Oberli, Andreas M Reichmuth, J Robert Dorkin, Michael J Mitchell, Owen S Fenton, Ana Jaklenec, Daniel G Anderson, Robert Langer, Daniel Blankschtein
The induction of a strong cytotoxic T cell response is an important prerequisite for successful immunotherapy against many viral diseases and tumors. Nucleotide vaccines, including mRNA vaccines with their intracellular antigen synthesis, have been shown to be potent activators of a cytotoxic immune response. The intracellular delivery of mRNA vaccines to the cytosol of antigen presenting immune cells is still not sufficiently well understood. Here, we report on the development of a lipid nanoparticle formulation for the delivery of mRNA vaccines to induce a cytotoxic CD 8 T cell response...
March 8, 2017: Nano Letters
https://www.readbyqxmd.com/read/28238718/towards-therapeutic-advances-in-melanoma-management-an-overview
#3
REVIEW
Swarnendra Singh, Atif Zafar, Saman Khan, Imrana Naseem
Melanoma is one of the most aggressive types of skin cancer with rapidly increasing incidence rate. The disease is largely considered incurable and the patients diagnosed with metastatic melanoma have a survival of not more than five years. Despite of the recent advances in anti-melanoma chemo- and immunotherapies, the available drugs are relatively toxic and responsive to only a limited subset of lesions. Currently, topical pharmacotherapy is demonstrated as an effective approach for the treatment of various skin cancers...
February 23, 2017: Life Sciences
https://www.readbyqxmd.com/read/28197308/novel-small-molecule-probes-for-metastatic-melanoma
#4
Anyanee Kamkaew, Nanyan Fu, Weibo Cai, Kevin Burgess
Actively targeting probe 1b, an unsymmetrical bivalent dipeptide mimic, selectively bound melanoma over healthy skin tissue in histological samples from patients and Sinclair swine. Modifications to 1b gave agents 2-4 that contain a near-IR aza-BODIPY fluor. Contrary to our expectations, symmetrical probe 3 gave the highest melanoma-to-healthy skin selectivity in histochemistry and experiments with live cells; this was surprising because 2, not 3, is unsymmetrical like the original lead 1. Optical imaging of 3 in a mouse melanoma model failed to show tumor accumulation in vivo, but the probe did selectively accumulate in the tumor (some in lung and less in the liver) as proven by analysis of the organs post mortem...
February 9, 2017: ACS Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28194418/antineoplastic-effects-of-honokiol-on-melanoma
#5
Ruth Guillermo-Lagae, Sreevidya Santha, Milton Thomas, Emily Zoelle, Jonathan Stevens, Radhey S Kaushik, Chandradhar Dwivedi
Honokiol, a plant lignan has been shown to have antineoplastic effects against nonmelanoma skin cancer developments in mice. In this study, antineoplastic effects of honokiol were investigated in malignant melanoma models. In vitro effects of honokiol treatment on SKMEL-2 and UACC-62 melanoma cells were evaluated by measuring the cell viability, proliferation, apoptosis, cell cycle analysis, and expressions of various proteins associated with cell cycle progression and apoptosis. For the in vivo study, male nude mice inoculated with SKMEL-2 or UACC-62 cells received injections of sesame oil or honokiol for two to seven weeks...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28135100/zinc-oxide-nanoparticle-poly-i-c-rna-complexes-implication-as-therapeutics-against-experimental-melanoma
#6
Meghana Ramani, Miranda C Mudge, R Tyler Morris, Yuntao Zhang, Stanislaw A Warcholek, Miranda N Hurst, Jim E Riviere, Robert K DeLong
There is current interest in harnessing the combined anticancer and immunological effect of nanoparticles (NPs) and RNA. Here, we evaluate the bioactivity of poly I:C (pIC) RNA, bound to anticancer zinc oxide NP (ZnO-NP) against melanoma. Direct RNA association to unfunctionalized ZnO-NP is shown by observing change in size, zeta potential, and absorption/fluorescence spectra upon complexation. RNA corona was visualized by transmission electron microscopy (TEM) for the first time. Binding constant (Kb = 1.6-2...
February 14, 2017: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/28132934/sustained-epidermal-powder-drug-delivery-via-skin-microchannels
#7
Yan Cao, Prateek Kakar, Md Nazir Hossen, Mei X Wu, Xinyuan Chen
Transdermal delivery of hydrophilic drugs is challenging. This study presents a novel sustained epidermal powder delivery technology (sEPD) for safe, efficient, and sustained delivery of hydrophilic drugs across the skin. sEPD is based on coating powder drugs into high-aspect-ratio, micro-coating channels (MCCs) followed by topical application of powder drug-coated array patches onto ablative fractional laser-generated skin MCs to deliver drugs into the skin. We found sEPD could efficiently deliver chemical drugs without excipients and biologics drugs in the presence of sugar excipients into the skin with a duration of ~12h...
January 27, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28110170/tailoring-polymeric-hybrid-micelles-with-lymph-node-targeting-ability-to-improve-the-potency-of-cancer-vaccines
#8
Qin Zeng, Hanmei Li, Hao Jiang, Jiao Yu, Ying Wang, Huan Ke, Tao Gong, Zhirong Zhang, Xun Sun
It has been widely accepted that lymph nodes (LNs) are critical targets of cancer vaccines and particles sized between 10 and 100 nm with a neutral or negative surface charge are preferred for lymphatic transfer after subcutaneous or intradermal injection. However their limited uptake by antigen presenting cells (APCs) and inadequate retention within LNs undoubtedly restrains their strength on activating T cell immunity. Here, we address this issue by tailoring the physicochemical properties of polymeric hybrid micelles (HMs), which are self-assembled from two amphiphilic diblock copolymers, poly-(ethylene glycol) phosphorethanolamine (PEG-PE) and polyethylenimine-stearic acid conjugate (PSA) via hydrophobic and electrostatic interactions...
January 11, 2017: Biomaterials
https://www.readbyqxmd.com/read/28096290/the-epidermal-polarity-protein-par3-is-a-non-cell-autonomous-suppressor-of-malignant-melanoma
#9
Melina Mescher, Peter Jeong, Sina K Knapp, Matthias Rübsam, Michael Saynisch, Marina Kranen, Jennifer Landsberg, Max Schlaak, Cornelia Mauch, Thomas Tüting, Carien M Niessen, Sandra Iden
Melanoma, an aggressive skin malignancy with increasing lifetime risk, originates from melanocytes (MCs) that are in close contact with surrounding epidermal keratinocytes (KCs). How the epidermal microenvironment controls melanomagenesis remains poorly understood. In this study, we identify an unexpected non-cell autonomous role of epidermal polarity proteins, molecular determinants of cytoarchitecture, in malignant melanoma. Epidermal Par3 inactivation in mice promotes MC dedifferentiation, motility, and hyperplasia and, in an autochthonous melanoma model, results in increased tumor formation and lung metastasis...
February 2017: Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28091396/anti-angiogenic-activity-and-antitumor-efficacy-of-amphiphilic-twin-drug-from-ursolic-acid-and-low-molecular-weight-heparin
#10
Wenming Cheng, Fatima Zohra Dahmani, Juan Zhang, Hui Xiong, Yuanyuan Wu, Lifang Yin, Jianping Zhou, Jing Yao
Heparin, a potential blood anti-coagulant, is also known for its binding ability to several angiogenic factors through electrostatic interactions due to its polyanionic character. However, the clinical application of heparin for cancer treatment is limited by several drawbacks, such as unsatisfactory therapeutic effects and severe anticoagulant activity that could induce hemorrhaging. Herein, low molecular weight heparin (LMWH) was conjugated to ursolic acid (UA), which is also an angiogenesis inhibitor, by binding the amine group of aminoethyl-UA (UA-NH2) with the carboxylic groups of LMWH...
February 17, 2017: Nanotechnology
https://www.readbyqxmd.com/read/28074906/antiproliferative-effects-of-1%C3%AE-oh-vitd3-in-malignant-melanoma-potential-therapeutic-implications
#11
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
#12
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...
February 15, 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
#13
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
#14
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
#15
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
#16
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
#17
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
#18
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
#19
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
#20
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
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