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"Melanoma model"

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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
#1
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
#2
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
#3
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
#4
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
#5
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)...
November 15, 2016: 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
#6
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
#7
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
#8
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
https://www.readbyqxmd.com/read/27791128/targeted-vaccination-against-the-bevacizumab-binding-site-on-vegf-using-3d-structured-peptides-elicits-efficient-antitumor-activity
#9
Madelon Q Wentink, Tilman M Hackeng, Sebastien P Tabruyn, Wouter C Puijk, Klaus Schwamborn, Daniele Altschuh, Rob H Meloen, Teun Schuurman, Arjan W Griffioen, Peter Timmerman
Therapeutic targeting of the VEGF signaling axis by the VEGF-neutralizing monoclonal antibody bevacizumab has clearly demonstrated clinical benefit in cancer patients. To improve this strategy using a polyclonal approach, we developed a vaccine targeting VEGF using 3D-structured peptides that mimic the bevacizumab binding site. An in-depth study on peptide optimization showed that the antigen's 3D structure is essential to achieve neutralizing antibody responses. Peptide 1 adopts a clear secondary, native-like structure, including the typical cysteine-knot fold, as evidenced by CD spectroscopy...
November 1, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27777130/atb-346-a-novel-hydrogen-sulfide-releasing-anti-inflammatory-drug-induces-apoptosis-of-human-melanoma-cells-and-inhibits-melanoma-development-in-vivo
#10
Paola De Cicco, Elisabetta Panza, Giuseppe Ercolano, Chiara Armogida, Giuseppe Sessa, Giuseppe Pirozzi, Giuseppe Cirino, John L Wallace, Angela Ianaro
Inflammation plays a key role in tumor promotion and development. Indeed, cyclooxygenase-2 (COX-2) expression is strongly associated with different types of cancer. An emerging class of compounds with significant anti-inflammatory properties is the hydrogen sulfide-releasing non-steroidal anti-inflammatory drugs (H2S-NSAIDs). They consist of a traditional NSAID to which an H2S-releasing moiety is covalently attached. We have recently demonstrated that H2S donors inhibit melanoma cell proliferation. In the current study, we evaluated the potential beneficial effects of a new H2S-releasing derivative of naproxen, ATB-346 [2-(6-methoxynapthalen-2-yl)-propionic acid 4-thiocarbamoyl phenyl ester] which inhibits COX activity but also releases H2S...
October 21, 2016: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/27694057/melanoma-targeting-with-99m-tc-n-pnp3-labeled-%C3%AE-melanocyte-stimulating-hormone-peptide-analogs-effects-of-cyclization-on-the-radiopharmaceutical-properties
#11
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...
December 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27693672/-18-f-mel050-as-a-melanin-targeted-pet-tracer-fully-automated-radiosynthesis-and-comparison-to-18-f-fdg-for-the-detection-of-pigmented-melanoma-in-mice-primary-subcutaneous-tumors-and-pulmonary-metastases
#12
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...
December 2016: Nuclear Medicine and Biology
https://www.readbyqxmd.com/read/27680682/preclinical-validation-of-a-single-treatment-infusion-modality-that-can-eradicate-extremity-melanomas
#13
Minhyung Kim, Nickolay Neznanov, Chandler D Wilfong, Daria I Fleyshman, Andrei A Purmal, Gary Haderski, Patricia Stanhope-Baker, Catherine A 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 nongenotoxic 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
https://www.readbyqxmd.com/read/27642552/ac-1001-h3-cdr-peptide-induces-apoptosis-and-signs-of-autophagy-in-vitro-and-exhibits-antimetastatic-activity-in-a-syngeneic-melanoma-model
#14
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
https://www.readbyqxmd.com/read/27599066/synergistic-transcutaneous-immunotherapy-enhances-antitumor-immune-responses-through-delivery-of-checkpoint-inhibitors
#15
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
https://www.readbyqxmd.com/read/27567213/impact-of-dose-route-and-composition-on-the-immunogenicity-of-immune-polyelectrolyte-multilayers-delivered-on-gold-templates
#16
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
https://www.readbyqxmd.com/read/27556860/novel-synthetic-cyclic-integrin-%C3%AE-v%C3%AE-3-binding-peptide-alos4-antitumor-activity-in-mouse-melanoma-models
#17
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
https://www.readbyqxmd.com/read/27547269/targeted-programming-of-the-lymph-node-environment-causes-evolution-of-local-and-systemic-immunity
#18
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
https://www.readbyqxmd.com/read/27507060/targeting-antisense-mitochondrial-ncrnas-inhibits-murine-melanoma-tumor-growth-and-metastasis-through-reduction-in-survival-and-invasion-factors
#19
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
https://www.readbyqxmd.com/read/27506450/type-i-interferons-interfere-with-the-capacity-of-mrna-lipoplex-vaccines-to-elicit-cytolytic-t-cell-responses
#20
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, tumor antigen-encoding messenger RNA (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...
September 20, 2016: Molecular Therapy: the Journal of the American Society of Gene Therapy
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