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"Melanoma model"

Davide Carta, Nicola Salvarese, Nicolò Morellato, Feng Gao, Wiebke Sihver, Hans Jurgen Pietzsch, Barbara Biondi, Paolo Ruzza, Fiorenzo Refosco, Debora Carpanese, Antonio Rosato, Cristina Bolzati
The purpose of this study was to evaluate the effect of cyclization on the biological profile of a [(99m)Tc(N)(PNP3)]-labeled α-melanocyte stimulating hormone peptide analog. A lactam bridge-cyclized H-Cys-Ahx-βAla(3)-c[Lys(4)-Glu-His-D-Phe-Arg-Trp-Glu(10)]-Arg(11)-Pro-Val-NH2 (NAP-NS2) and the corresponding linear H-Cys-Ahx-βAla-Nle-Asp-His-D-Phe-Arg-Trp-Gly-NH2 (NAP-NS1) peptide were synthetized, characterized by ESI-MS spectroscopy and their melanocortin-1 receptor (MC1R) binding affinity was determined in B16/F10 melanoma cells...
August 31, 2016: Nuclear Medicine and Biology
Nathalie Rizzo-Padoin, Michael Chaussard, Nicolas Vignal, Ewa Kotula, Vadim Tsoupko-Sitnikov, Sofia Vaz, Fortune Hontonnou, Wang-Qing Liu, Jean-Luc Poyet, Michel Vidal, Pascal Merlet, Benoit Hosten, Laure Sarda-Mantel
INTRODUCTION: Melanoma is a highly malignant cutaneous tumor of melanin-producing cells. MEL050 is a synthetic benzamide-derived molecule that specifically binds to melanin with high affinity. Our aim was to implement a fully automated radiosynthesis of [(18)F]MEL050, using for the first time, the AllInOne™ synthesis module (Trasis), and to evaluate the potential of [(18)F]MEL050 for the detection of pigmented melanoma in mice primary subcutaneous tumors and pulmonary metastases, and to compare it with that of [(18)F]FDG...
August 24, 2016: Nuclear Medicine and Biology
Minhyung Kim, Nickolay Neznanov, Chandler D Wilfong, Daria I Fleyshman, Andrei A Purmal, Gary Haderski, Patricia Stanhope-Baker, Catherine Burkhart, Katerina V Gurova, Andrei V Gudkov, Joseph J Skitzki
Isolated limb perfusion (ILP) with the chemotherapeutic agent melphalan is an effective treatment option for extremity in-transit melanoma, but is toxic and technically challenging to deliver locoregionally. CBL0137 is an experimental clinical drug with broad anticancer activity in animal models, owing to its ability to bind DNA in a non-genotoxic manner and inactivate the FACT chromatin modulator essential for tumor cell viability. Here we report that CBL0137 delivered by ILP in a murine melanoma model is as efficacious as melphalan, displaying antitumor activity at doses corresponding to only a fraction of the systemic MTD of CBL0137...
September 28, 2016: Cancer Research
Aline N Rabaça, Denise C Arruda, Carlos R Figueiredo, Mariana H Massaoka, Camyla F Farias, Dayane B Tada, Vera C Maia, Pedro I Silva Junior, Natalia Girola, Fernando Real, Renato A Mortara, Luciano Polonelli, Luiz R Travassos
Antibody-derived peptides modulate functions of the immune system and are a source of anti-infective and antitumor substances. Recent studies have shown that they comprise amino acid sequences of immunoglobulin complementarity-determining regions, but also fragments of constant regions. VH CDR3 of murine mAb AC-1001 displays antimetastatic activities using B16F10-Nex2 murine melanoma cells in a syngeneic model. The peptide was cytotoxic in vitro in murine and human melanoma cells inducing reactive oxygen species (ROS) and apoptosis by the intrinsic pathway...
September 2016: FEBS Open Bio
Yanqi Ye, Jinqiang Wang, Quanyin Hu, Gabrielle M Hochu, Hongliang Xin, Chao Wang, Zhen Gu
Despite the promising efficacy of immunoregulation in cancer therapy, the clinical benefit has been restricted by inefficient infiltration of lymphocytes in the evolution of immune evasion. Also, immune-related adverse events have often occurred due to the off-target binding of therapeutics to normal tissues after systematic treatment. In light of this, we have developed a synergistic immunotherapy strategy that locally targets the immunoinhibitory receptor programmed cell death protein 1 (PD1) and immunosuppressive enzyme indoleamine 2,3-dioxygenase (IDO) for the treatment of melanoma through a microneedle-based transcutaneous delivery approach...
September 27, 2016: ACS Nano
Peipei Zhang, James I Andorko, Christopher M Jewell
Biomaterial vaccines offer new capabilities that can be exploited for both infectious disease and cancer. We recently developed a novel vaccine platform based on self-assembly of immune signals into immune polyelectrolyte multilayers (iPEMs). These iPEM vaccines are electrostatically assembled from peptide antigens and nucleic acid-based toll-like receptor agonists (TLRas) that serve as molecular adjuvants. Gold nanoparticles (AuNPs) coated with iPEMs stimulate effector cytokine secretion in vitro and expand antigen-specific T cells in mice...
August 27, 2016: Biotechnology and Bioengineering
Shiri Yacobovich, Lena Tuchinsky, Michael Kirby, Tetiana Kardash, Oryan Agranyoni, Elimelech Nesher, Boris Redko, Gary Gellerman, Dror Tobi, Katerina Gurova, Igor Koman, Osnat Ashur Fabian, Albert Pinhasov
ALOS4, a unique synthetic cyclic peptide without resemblance to known integrin ligand sequences, was discovered through repeated biopanning with pIII phage expressing a disulfide-constrained nonapeptide library. Binding assays using a FITC-labeled analogue demonstrated selective binding to immobilized αvβ3 and a lack of significant binding to other common proteins, such as bovine serum albumin and collagen. In B16F10 cell cultures, ALOS4 treatment at 72 h inhibited cell migration (30%) and adhesion (up to 67%)...
August 18, 2016: Oncotarget
James I Andorko, Joshua M Gammon, Lisa H Tostanoski, Qin Zeng, Christopher M Jewell
Biomaterial vaccines offer cargo protection, targeting, and co-delivery of signals to immune organs such as lymph nodes (LNs), tissues that coordinate adaptive immunity. Understanding how individual vaccine components impact immune response has been difficult owing to the systemic nature of delivery. Direct intra-lymph node (i.LN.) injection offers a unique opportunity to dissect how the doses, kinetics, and combinations of signals reaching LNs influence the LN environment. Here, i.LN. injection was used as a tool to study the local and systemic responses to vaccines comprised of soluble antigen and degradable polymer particles encapsulating toll-like receptor agonists as adjuvants...
2016: Cellular and Molecular Bioengineering
Lorena Lobos-González, Verónica Silva, Mariela Araya, Franko Restovic, Javiera Echenique, Luciana Oliveira-Cruz, Christopher Fitzpatrick, Macarena Briones, Jaime Villegas, Claudio Villota, Soledad Vidaurre, Vincenzo Borgna, Miguel Socias, Sebastián Valenzuela, Constanza Lopez, Teresa Socias, Manuel Varas, Jorge Díaz, Luis O Burzio, Verónica A Burzio
We reported that knockdown of the antisense noncoding mitochondrial RNAs (ASncmtRNAs) induces apoptotic death of several human tumor cell lines, but not normal cells, suggesting this approach for selective therapy against different types of cancer. In order to translate these results to a preclinical scenario, we characterized the murine noncoding mitochondrial RNAs (ncmtRNAs) and performed in vivo knockdown in syngeneic murine melanoma models. Mouse ncmtRNAs display structures similar to the human counterparts, including long double-stranded regions arising from the presence of inverted repeats...
August 6, 2016: Oncotarget
Ans De Beuckelaer, Charlotte Pollard, Sandra Van Lint, Kenny Roose, Lien Van Hoecke, Thomas Naessens, Vimal Kumar Udhayakumar, Muriel Smet, Niek Sanders, Stefan Lienenklaus, Xavier Saelens, Siegfried Weiss, Guido Vanham, Johan Grooten, Stefaan De Koker
Given their high potential to evoke cytolytic T cell responses, tumour antigen-encoding mRNA vaccines are now being intensively explored as therapeutic cancer vaccines. mRNA vaccines clearly benefit from wrapping the mRNA into nano-sized carriers such as lipoplexes that protect the mRNA from degradation and increase its uptake by dendritic cells in vivo. Nevertheless, the early innate host factors that regulate the induction of cytolytic T cells to mRNA lipoplex vaccines have remained unresolved. Here, we demonstrate that mRNA lipoplexes induce a potent type I IFN response upon subcutaneous, intradermal and intranodal injection...
August 10, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
Eva Waldmannová, Veronika Caisová, Julie Fáberová, Petra Sváčková, Markéta Kovářová, Denisa Sváčková, Zuzana Kumžáková, Adéla Jačková, Nikol Vácová, Pavla Nedbalová, Marie Horká, Jan Kopecký, Jan Ženka
The idea of using killed microorganisms or their parts for a stimulation of immunity in the cancer immunotherapy is very old, but the question of interactions and binding of these preparations to tumor cells has not been addressed so far. The attachment of Zymosan A and both Gram-positive and Gram-negative bacteria to tumor cells was tested in in vivo experiments. This binding was accomplished by charge interactions, anchoring based on hydrophobic chains and covalent bonds and proved to be crucial for a strong immunotherapeutic effect...
October 2016: International Immunopharmacology
Malene Bertelsen, Martin Stahlhut, Gunnar Grue-Sørensen, Xifu Liang, Gitte Bach Christensen, Kresten Skak, Karen Margrethe Engell, Thomas Högberg
INTRODUCTION: Ingenol mebutate gel (Picato(®), LEO Pharma A/S) is approved for the field treatment of actinic keratosis and is characterized by high sustained clearance of actinic lesions. The inherent propensity of ingenol mebutate towards chemical rearrangement necessitates refrigeration of the final product. We sought to identify novel ingenol derivatives with enhanced chemical stability and similar or improved in vitro potency and in vivo efficacy. METHODS: A number of ingenol esters were synthesized with full regiocontrol from ingenol...
August 8, 2016: Dermatology and Therapy
Christopher Alderman, Ayoub Sehlaoui, Zhaoyang Xiao, Yixin Yang
MicroRNAs can affect behaviors of tumor cells by modulating the expression of the target genes that involve tumor growth, invasiveness, and death. The goal of this research is to examine the effects of miR-15a on the proliferation and invasiveness of malignant melanoma cells in vitro, as well as the therapeutic effect of miR-15a in a mouse melanoma model. miR-15a displayed inhibitory effects on proliferation and invasiveness of several malignant melanoma cell lines. miR-15a also caused cell cycle arrest at G1/G0 phase...
August 4, 2016: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
Adi Sharbi-Yunger, Mareike Grees, Esther Tzehoval, Jochen Utikal, Viktor Umansky, Lea Eisenbach
Malignant melanoma is characterized by a rapid progression, metastasis to distant organs and resistance to chemo and radiotherapy. Although melanoma is capable of eliciting an immune response, the disease progresses and the overall results of immunotherapeutic clinical studies are not satisfactory. Recently, we have developed a novel genetic platform for improving an induction of peptide-specific CD8(+) T cells by dendritic cell (DC) based on membrane-anchored β2-microglobulin (β2m) linked to a selected antigenic peptide at the N-terminus and to the cytosolic domain of TLR4 at the C-terminus...
June 2016: Oncoimmunology
Dàlia Raïch-Regué, Kellsye P Fabian, Alicia R Watson, Ronald J Fecek, Walter J Storkus, Angus W Thomson
Dendritic cells (DC) play a pivotal role in the induction and regulation of immune responses. In cancer, DC-based vaccines have proven to be safe and to elicit protective and therapeutic immunological responses. Recently, we showed that specific mTORC2 (mechanistic target of rapamycin complex 2) deficiency in DC enhances their ability to promote Th1 and Th17 responses after LPS stimulation. In the present study, bone marrow-derived mTORC2-deficient (Rictor(-/-)) DC were evaluated as a therapeutic modality in the murine B16 melanoma model...
June 2016: Oncoimmunology
Morad-Rémy Muhsin-Sharafaldine, Sarah C Saunderson, Amy C Dunn, James M Faed, Torsten Kleffmann, Alexander D McLellan
Extracellular vesicles (EV) are lipid particles released from eukaryotic cells into the extracellular fluid. Depending on the cell type or mechanism of release, vesicles vary in form and function and exert distinct functions in coagulation and immunity. Tumor cells may constitutively shed vesicles known as exosomes or microvesicles (MV). Alternatively, apoptosis induces the release of apoptotic blebs or vesicles (ApoV) from the plasma membrane. EV have been implicated in thrombotic events (the second highest cause of death in cancer patients) and tumor vesicles contribute to the anti-cancer immune response...
July 22, 2016: Oncotarget
Batool Shannan, Andrea Watters, Quan Chen, Stefan Mollin, Markus Dörr, Eric Meggers, Xiaowei Xu, Phyllis A Gimotty, Michela Perego, Ling Li, Joseph Benci, Clemens Krepler, Patricia Brafford, Jie Zhang, Zhi Wei, Gao Zhang, Qin Liu, Xiangfan Yin, Katherine L Nathanson, Meenhard Herlyn, Adina Vultur
Therapeutic strategies for the treatment of metastatic melanoma show encouraging results in the clinic; however, not all patients respond equally and tumor resistance still poses a challenge. To identify novel therapeutic targets for melanoma, we screened a panel of structurally diverse organometallic inhibitors against human-derived normal and melanoma cells. We observed that a compound that targets PIM kinases (a family of Ser/Thr kinases) preferentially inhibited melanoma cell proliferation, invasion, and viability in adherent and three-dimensional (3D) melanoma models...
July 19, 2016: Oncotarget
Kimberley A Beaumont, Nethia Mohana-Kumaran, Nikolas K Haass
The behavior of melanoma cells has traditionally been studied in vitro in two-dimensional cell culture with cells adhering to plastic dishes. However, in order to mimic the three-dimensional architecture of a melanoma, as well as its interactions with the tumor microenvironment, there has been the need for more physiologically relevant models. This has been achieved by designing 3D in vitro models of melanoma, such as melanoma spheroids embedded in extracellular matrix or organotypic skin reconstructs. In vivo melanoma models have typically relied on the growth of tumor xenografts in immunocompromised mice...
2013: Healthcare (Basel, Switzerland)
Tomoya Takeda, Masanobu Tsubaki, Kotaro Sakamoto, Eri Ichimura, Aya Enomoto, Yuri Suzuki, Tatsuki Itoh, Motohiro Imano, Genzoh Tanabe, Osamu Muraoka, Hideaki Matsuda, Takao Satou, Shozo Nishida
Advanced metastatic melanoma, one of the most aggressive malignancies, is currently without reliable therapy. Therefore, new therapies are urgently needed. Mangiferin is a naturally occurring glucosylxanthone and exerts many beneficial biological activities. However, the effect of mangiferin on metastasis and tumor growth of metastatic melanoma remains unclear. In this study, we evaluated the effect of mangiferin on metastasis and tumor growth in a mouse metastatic melanoma model. We found that mangiferin inhibited spontaneous metastasis and tumor growth...
September 1, 2016: Toxicology and Applied Pharmacology
Ciorsdan A Campion, Declan Soden, Patrick F Forde
BACKGROUND: The ever increasing knowledge in the areas of cell biology, the immune system and the mechanisms of cancer are allowing a new phase of immunotherapy to develop. The aim of cancer vaccination is to activate the host immune system and some success has been observed particularly in the use of the BCG vaccine for bladder cancer as an immunostimulant. Reovirus, an orphan virus, has proven itself as an oncolytic virus in vitro and in vivo. Over 80 % of tumour cell lines have been found to be susceptible to Reovirus infection and it is currently in phase III clinical trials...
2016: BMC Cancer
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