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"Melanoma model"

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https://www.readbyqxmd.com/read/29050620/safe-therapeutics-of-murine-melanoma-model-using-a-novel-antineoplasic-the-partially-methylated-mannogalactan-from-pleurotus-eryngii
#1
S M P Biscaia, E R Carbonero, D L Bellan, B S Borges, C R Costa, G R Rossi, J P Gonçalves, C M Melo, F A R Lívero, A C Ruthes, R Zotz, E V Silva, C C Oliveira, A Acco, H B Nader, R Chammas, M Iacomini, C R C Franco, E S Trindade
A heteropolysaccharide was isolated by cold aqueous extraction from edible mushroom Pleurotus eryngii ("King Oyster") basidiocarps and its biological properties were evaluated. Structural assignments were carried out using mono- and bidimensional NMR spectroscopy, monosaccharide composition, and methylation analyses. A mannogalactan having a main chain of (1→6)-linked α-d-galactopyranosyl and 3-O-methyl-α-d-galactopyranosyl residues, both partially substituted at OH-2 by β-d-Manp (MG-Pe) single-unit was found...
December 15, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/29045061/suppression-of-mapk-signaling-in-braf-activated-pten-deficient-melanoma-by-blocking-%C3%AE-catenin-signaling-in-cancer-associated-fibroblasts
#2
Linli Zhou, Kun Yang, Spencer Dunaway, Zalfa Abdel-Malek, Thomas Andl, Ana Luisa Kadekaro, Yuhang Zhang
Cancer-associated fibroblasts (CAFs) in the tumor microenvironment have been associated with formation of a dynamic and optimized niche for tumor cells to grow and evade cell death induced by therapeutic agents. We recently reported that ablation of β-catenin expression in stromal fibroblasts and CAFs disrupted their biological activities in in vitro studies and in an in vivo B16F10 mouse melanoma model. Here, we show that the development of a BRAF-activated PTEN-deficient mouse melanoma was significantly suppressed in vivo after blocking β-catenin signaling in CAFs...
October 17, 2017: Pigment Cell & Melanoma Research
https://www.readbyqxmd.com/read/29030460/hmg-coa-reductase-inhibition-delays-dna-repair-and-promotes-senescence-after-tumor-irradiation
#3
Elena V Efimova, Natalia Ricco, Edwardine Labay, Helena J Mauceri, Amy C Flor, Aishwarya Ramamurthy, Harold G Sutton, Ralph R Weichselbaum, Stephen J Kron
Despite significant advances in combinations of radiotherapy and chemotherapy, altered fractionation schedules and image-guided radiotherapy, many cancer patients fail to benefit from radiation. A prevailing hypothesis is that targeting repair of DNA double strand breaks (DSBs) can enhance radiation effects in the tumor and overcome therapeutic resistance without incurring off-target toxicities. Unrepaired DSBs can block cancer cell proliferation, promote cancer cell death and induce cellular senescence. Given the slow progress to date translating novel DSB repair inhibitors as radiosensitizers, we have explored drug repurposing, a proven route to improving speed, costs and success rates of drug development...
October 13, 2017: Molecular Cancer Therapeutics
https://www.readbyqxmd.com/read/28991225/super-enhancers-define-a-proliferative-pgc-1%C3%AE-expressing-melanoma-subgroup-sensitive-to-bet-inhibition
#4
K A Gelato, L Schöckel, O Klingbeil, T Rückert, R Lesche, J Toedling, E Kalfon, M Héroult, P Lejeune, U Mönning, A E Fernández-Montalván, S Bäurle, S Siegel, B Haendler
Metabolic changes are linked to epigenetic reprogramming and play important roles in several tumor types. PGC-1α is a transcriptional coactivator controlling mitochondrial biogenesis and is linked to oxidative phosphorylation. We provide evidence that melanoma models with elevated PGC-1α levels are characteristic of the proliferative phenotype and are sensitive to bromodomain and extra-terminal domain (BET) inhibitor treatment. A super-enhancer region highly occupied by the BET family member BRD4 was identified for the PGC-1α gene...
October 9, 2017: Oncogene
https://www.readbyqxmd.com/read/28936555/resveratrol-suppresses-melanoma-by-inhibiting-nf-%C3%AE%C2%BAb-mir-221-and-inducing-tfg-expression
#5
Fangfang Wu, Liying Cui
Resveratrol (Res) is a natural compound with anti-cancer effects. The goal of this study is to evaluate the suppression of Res in melanoma and investigate its relationship with miRNAs during this process. The in vitro and in vivo anti-cancer abilities of Res were evaluated using cellular assays and animal model. Two melanoma cell lines (A375 and MV3) were used for both in vitro assay and in vivo experiments. qRT-PCR and Western blot were used to detect the changes in gene expressions and protein levels. Dual-luciferase reporter assay and bioinformatic tools were used to further confirm the protein binding and activation of targeted genes...
September 21, 2017: Archives of Dermatological Research
https://www.readbyqxmd.com/read/28910387/epstein-barr-virus-latent-membrane-protein-1-enhances-dendritic-cell-therapy-lymph-node-migration-activation-and-il-12-secretion
#6
James M Termini, Sachin Gupta, Francesca N Raffa, Elizabeth Guirado, Margaret A Fischl, Liguo Niu, Saravana Kanagavelu, Geoffrey W Stone
Dendritic cells (DC) are a promising cell type for cancer vaccines due to their high immunostimulatory capacity. However, improper maturation of DC prior to treatment may account for the limited efficacy of DC vaccine clinical trials. Latent Membrane Protein-1 (LMP1) of Epstein-Barr virus was examined for its ability to mature and activate DC as a gene-based molecular adjuvant for DC vaccines. DC were transduced with an adenovirus 5 vector (Ad5) expressing LMP1 under the control of a Tet-inducible promoter...
2017: PloS One
https://www.readbyqxmd.com/read/28904226/tumor-lymphangiogenesis-promotes-t-cell-infiltration-and-potentiates-immunotherapy-in-melanoma
#7
Manuel Fankhauser, Maria A S Broggi, Lambert Potin, Natacha Bordry, Laura Jeanbart, Amanda W Lund, Elodie Da Costa, Sylvie Hauert, Marcela Rincon-Restrepo, Christopher Tremblay, Elena Cabello, Krisztian Homicsko, Olivier Michielin, Douglas Hanahan, Daniel E Speiser, Melody A Swartz
In melanoma, vascular endothelial growth factor-C (VEGF-C) expression and consequent lymphangiogenesis correlate with metastasis and poor prognosis. VEGF-C also promotes tumor immunosuppression, suggesting that lymphangiogenesis inhibitors may be clinically useful in combination with immunotherapy. We addressed this concept in mouse melanoma models with VEGF receptor-3 (VEGFR-3)-blocking antibodies and unexpectedly found that VEGF-C signaling enhanced rather than suppressed the response to immunotherapy. We further found that this effect was mediated by VEGF-C-induced CCL21 and tumor infiltration of naïve T cells before immunotherapy because CCR7 blockade reversed the potentiating effects of VEGF-C...
September 13, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28898698/enhancing-cd8-t-cell-fatty-acid-catabolism-within%C3%A2-a-metabolically-challenging-tumor-microenvironment-increases-the-efficacy-of-melanoma-immunotherapy
#8
Ying Zhang, Raj Kurupati, Ling Liu, Xiang Yang Zhou, Gao Zhang, Abeer Hudaihed, Flavia Filisio, Wynetta Giles-Davis, Xiaowei Xu, Giorgos C Karakousis, Lynn M Schuchter, Wei Xu, Ravi Amaravadi, Min Xiao, Norah Sadek, Clemens Krepler, Meenhard Herlyn, Gordon J Freeman, Joshua D Rabinowitz, Hildegund C J Ertl
How tumor-infiltrating T lymphocytes (TILs) adapt to the metabolic constrains within the tumor microenvironment (TME) and to what degree this affects their ability to combat tumor progression remain poorly understood. Using mouse melanoma models, we report that CD8(+) TILs enhance peroxisome proliferator-activated receptor (PPAR)-α signaling and catabolism of fatty acids (FAs) when simultaneously subjected to hypoglycemia and hypoxia. This metabolic switch partially preserves CD8(+) TILs' effector functions, although co-inhibitor expression increases during tumor progression regardless of CD8(+) TILs' antigen specificity...
September 11, 2017: Cancer Cell
https://www.readbyqxmd.com/read/28874561/localized-cd47-blockade-enhances-immunotherapy-for-murine-melanoma
#9
Jessica R Ingram, Olga S Blomberg, Jonathan T Sockolosky, Lestat Ali, Florian I Schmidt, Novalia Pishesha, Camilo Espinosa, Stephanie K Dougan, K Christopher Garcia, Hidde L Ploegh, Michael Dougan
CD47 is an antiphagocytic ligand broadly expressed on normal and malignant tissues that delivers an inhibitory signal through the receptor signal regulatory protein alpha (SIRPα). Inhibitors of the CD47-SIRPα interaction improve antitumor antibody responses by enhancing antibody-dependent cellular phagocytosis (ADCP) in xenograft models. Endogenous expression of CD47 on a variety of cell types, including erythrocytes, creates a formidable antigen sink that may limit the efficacy of CD47-targeting therapies...
September 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28865485/combination-therapy-of-pkc%C3%AE-and-cox-2-inhibitors-synergistically-suppress-melanoma-metastasis
#10
Ping Zhou, Jiaqi Qin, Yuan Li, Guoxia Li, Yinsong Wang, Ning Zhang, Peng Chen, Chunyu Li
BACKGROUND: Metastatic malignant melanoma is one of the most aggressive malignancies and its treatment remains challenging. Recent studies demonstrate that the melanoma metastasis has correlations with the heightened activations of protein kinase C ζ (PKCζ) and cyclooxygenase-2 (COX-2) signaling pathways. Targeted inhibitions for PKCζ and COX-2 have been considered as the promising strategies for the treatment of melanoma metastasis. Thus, the PKCζ inhibitor J-4 and COX-2 inhibitor Celecoxib were combined to treat melanoma metastasis in this study...
September 2, 2017: Journal of Experimental & Clinical Cancer Research: CR
https://www.readbyqxmd.com/read/28861951/encapsulation-of-hydrophilic-and-hydrophobic-peptides-into-hollow-mesoporous-silica-nanoparticles-for-enhancement-of-antitumor-immune-response
#11
Jun Xie, Chaohua Yang, Qianqian Liu, Jun Li, Ruijing Liang, Chen Shen, Yi Zhang, Ke Wang, Liping Liu, Khurram Shezad, Martin Sullivan, Yong Xu, Guanxin Shen, Juan Tao, Jintao Zhu, Zhiping Zhang
Codelivery of combinational antigenic peptides and adjuvant to antigen presenting cells is expected to amplify tumor specific T lymphocytes immune responses while minimizing the possibility of tumor escaping and reducing immune tolerance to single antigenic peptide. However, the varied hydrophobicities of these multivariant derived short antigenic peptides limit their codelivery efficiency in conventional delivery systems. Here, a facile yet effective route is presented to generate monodisperse and stable hollow mesoporous silica nanoparticles (HMSNs) for codelivering of HGP10025-33 and TRP2180-188 , two melanoma-derived peptides with varied hydrophobicities...
September 1, 2017: Small
https://www.readbyqxmd.com/read/28861325/the-efficacy-of-combination-therapy-with-oncolytic-herpes-simplex-virus-hf10-and-dacarbazine-in-a-mouse-melanoma-model
#12
Rui Tanaka, Fumi Goshima, Shinichi Esaki, Yoshitaka Sato, Takayuki Murata, Yukihiro Nishiyama, Daisuke Watanabe, Hiroshi Kimura
Advanced melanoma has long been treated with chemotherapy using cytotoxic agents like dacarbazine (DTIC), but overall survival rates with these drugs have been generally low. Recently, immunoregulatory monoclonal antibodies and molecularly targeted therapy with a BRAF inhibitor and/or a MEK inhibitor, have been used to treat malignant melanoma and have improved the survival rate of patients with advanced melanoma. However, high prices of these drugs are problematic. In this study, we evaluated the oncolytic efficacy of HF10, an attenuated, replication-competent HSV, with DTIC in immunocompetent mice model of malignant melanoma...
2017: American Journal of Cancer Research
https://www.readbyqxmd.com/read/28833504/cytotoxic-anti-melanoma-drugs-suppress-the-activation-of-m2-macrophages
#13
Taku Fujimura, Aya Kakizaki, Yumi Kambayashi, Yota Sato, Kayo Tanita, Chunbing Lyu, Sadanori Furudate, Setsuya Aiba
Together with regulatory T cells (Tregs), tumor-associated macrophages (TAMs) play roles in maintaining the tumor microenvironment. Though cytotoxic anti-melanoma drugs such as dacarbazine (DTIC), nimustine hydrochloride (ACNU), and vincristine (VCR) have been used for the treatment of malignant melanoma as adjuvant therapy in Japan, the detailed mechanisms of their immunomodulatory effects are not fully understood. Since the majority of TAMs are alternatively activated M2 macrophages that favor tumor development, the aim of this study was to elucidate the immunomodulatory effects of these reagents on human monocyte-derived M2 macrophages...
August 20, 2017: Experimental Dermatology
https://www.readbyqxmd.com/read/28806730/a-systems-approach-reveals-distinct-metabolic-strategies-among-the-nci-60-cancer-cell-lines
#14
Maike K Aurich, Ronan M T Fleming, Ines Thiele
The metabolic phenotype of cancer cells is reflected by the metabolites they consume and by the byproducts they release. Here, we use quantitative, extracellular metabolomic data of the NCI-60 panel and a novel computational method to generate 120 condition-specific cancer cell line metabolic models. These condition-specific cancer models used distinct metabolic strategies to generate energy and cofactors. The analysis of the models' capability to deal with environmental perturbations revealed three oxotypes, differing in the range of allowable oxygen uptake rates...
August 2017: PLoS Computational Biology
https://www.readbyqxmd.com/read/28751755/tctp-as-a-therapeutic-target-in-melanoma-treatment
#15
M Boia-Ferreira, A B Basílio, A E Hamasaki, F H Matsubara, M H Appel, C R V Da Costa, R Amson, A Telerman, O M Chaim, S S Veiga, A Senff-Ribeiro
BACKGROUND: Translationally controlled tumour protein (TCTP) is an antiapoptotic protein highly conserved through phylogeny. Translationally controlled tumour protein overexpression was detected in several tumour types. Silencing TCTP was shown to induce tumour reversion. There is a reciprocal repression between TCTP and P53. Sertraline interacts with TCTP and decreases its cellular levels. METHODS: We evaluate the role of TCTP in melanoma using sertraline and siRNA...
August 22, 2017: British Journal of Cancer
https://www.readbyqxmd.com/read/28735040/co-encapsulation-of-paclitaxel-and-c6-ceramide-in-tributyrin-containing-nanocarriers-improve-co-localization-in-the-skin-and-potentiate-cytotoxic-effects-in-2d-and-3d-models
#16
Vanessa F M Carvalho, Amanda Migotto, Daniela V Giacone, Débora P de Lemos, Thalita B Zanoni, Silvya S Maria-Engler, Leticia V Costa-Lotufo, Luciana B Lopes
Considering that tumor development is generally multifactorial, therapy with a combination of agents capable of potentiating cytotoxic effects is promising. In this study, we co-encapsulated C6 ceramide (0.35%) and paclitaxel (0.50%) in micro and nanoemulsions containing tributyrin (a butyric acid pro-drug included for potentiation of cytotoxicity), and compared their ability to co-localize the drugs in viable skin layers. The nanoemulsion delivered 2- and 2.4-fold more paclitaxel into viable skin layers of porcine skin in vitro at 4 and 8h post-application than the microemulsion, and 1...
July 19, 2017: European Journal of Pharmaceutical Sciences
https://www.readbyqxmd.com/read/28725894/quantifying-spontaneous-metastasis-in-a-syngeneic-mouse-melanoma-model-using-real-time-pcr
#17
Wentao Deng, Sarah L McLaughlin, David J Klinke
Modeling metastasis in vivo with animals is a priority for both revealing mechanisms of tumor dissemination and developing therapeutic methods. While conventional intravenous injection of tumor cells provides an efficient and consistent system for studying tumor cell extravasation and colonization, studying spontaneous metastasis derived from orthotopic tumor sites has the advantage of modeling more aspects of the metastatic cascade, but is challenging as it is difficult to detect small numbers of metastatic cells...
August 7, 2017: Analyst
https://www.readbyqxmd.com/read/28724603/effects-of-microrna-136-on-melanoma-cell-proliferation-apoptosis-and-epithelial-mesenchymal-transition-by-targetting-pmel-through-the-wnt-signaling-pathway
#18
Jiu-Jiang Wang, Zhi-Feng Li, Xiao-Jing Li, Zhao Han, Ling Zhang, Zhi-Jun Liu
The study aims to evaluate the effects of miR-136 on the proliferation, apoptosis, and epithelial-mesenchymal transition (EMT) of melanoma cells by targetting premelanosome protein (PMEL) through the Wnt signaling pathway. After establishment of melanoma mouse models, melanoma (model group) and normal tissues (normal group) were collected. Immunohistochemistry was performed to determine PMEL protein concentration. Mouse melanoma cells were assigned into control, blank, negative control (NC), miR-136 mimics, miR-136 inhibitors, siRNA-PMEL, and miR-136 inhibitors + siRNA-PMEL, LiC1 (Wnt signaling pathway activator), and siRNA-PMEL+ LiCl groups...
October 31, 2017: Bioscience Reports
https://www.readbyqxmd.com/read/28668835/immunomodulatory-effect-of-imiquimod-through-ccl22-produced-by-tumor-associated-macrophages-in-b16f10-melanomas
#19
Sadanori Furudate, Taku Fujimura, Yumi Kambayashi, Aya Kakizaki, Takanori Hidaka, Setsuya Aiba
BACKGROUND/AIM: Tumor-associated macrophages (TAMs), together with splenic CD11b(+) cells, help maintain the tumor microenvironment. The immunomodulatory compound imiquimod (IQM) stimulates innate immune cells, including macrophages, to induce antitumor effects. In order to elucidate the effects of IQM on the tumor microenvironment, we investigated the immunomodulatory effect of IQM during melanoma growth by using the B16F10 melanoma model. MATERIALS AND METHODS: To elucidate the immunomodulatory effects of IQM on the tumor microenvironment, we isolated CD11b(+) TAMs and splenic CD11b(+) cells and evaluated the immunomodulatory effects of IQM, using the B16F10 melanoma model...
July 2017: Anticancer Research
https://www.readbyqxmd.com/read/28666979/predicting-the-response-to-ctla-4-blockade-by-longitudinal-noninvasive-monitoring-of-cd8-t-cells
#20
Mohammad Rashidian, Jessica R Ingram, Michael Dougan, Anushka Dongre, Katherine A Whang, Camille LeGall, Juan J Cragnolini, Brian Bierie, Monica Gostissa, James Gorman, Gijsbert M Grotenbreg, Atul Bhan, Robert A Weinberg, Hidde L Ploegh
Immunotherapy using checkpoint-blocking antibodies against targets such as CTLA-4 and PD-1 can cure melanoma and non-small cell lung cancer in a subset of patients. The presence of CD8 T cells in the tumor correlates with improved survival. We show that immuno-positron emission tomography (immuno-PET) can visualize tumors by detecting infiltrating lymphocytes and, through longitudinal observation of individual animals, distinguish responding tumors from those that do not respond to therapy. We used (89)Zr-labeled PEGylated single-domain antibody fragments (VHHs) specific for CD8 to track the presence of intratumoral CD8(+) T cells in the immunotherapy-susceptible B16 melanoma model in response to checkpoint blockade...
August 7, 2017: Journal of Experimental Medicine
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