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"Melanoma model"

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https://www.readbyqxmd.com/read/28650437/antigen-capturing-nanoparticles-improve-the-abscopal-effect-and-cancer-immunotherapy
#1
Yuanzeng Min, Kyle C Roche, Shaomin Tian, Michael J Eblan, Karen P McKinnon, Joseph M Caster, Shengjie Chai, Laura E Herring, Longzhen Zhang, Tian Zhang, Joseph M DeSimone, Joel E Tepper, Benjamin G Vincent, Jonathan S Serody, Andrew Z Wang
Immunotherapy holds tremendous promise for improving cancer treatment. To administer radiotherapy with immunotherapy has been shown to improve immune responses and can elicit the 'abscopal effect'. Unfortunately, response rates for this strategy remain low. Herein we report an improved cancer immunotherapy approach that utilizes antigen-capturing nanoparticles (AC-NPs). We engineered several AC-NP formulations and demonstrated that the set of protein antigens captured by each AC-NP formulation is dependent on the NP surface properties...
June 26, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28645138/correction-tumor-growth-suppressive-effect-of-il-4-through-p21-mediated-activation-of-stat6-in-il-4r%C3%AE-overexpressed-melanoma-models
#2
Hye Lim Lee, Mi Hee Park, Ju Kyoung Song, Yu Yeon Jung, Youngsoo Kim, Kyung Bo Kim, Dae Yeon Hwang, Do Young Yoon, Min Jong Song, Sang Bae Han, Jin Tae Hong
No abstract text is available yet for this article.
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28643235/design-and-evaluation-of-rgd-modified-gemini-surfactant-based-lipoplexes-for-targeted-gene-therapy-in-melanoma-model
#3
Waleed Mohammed-Saeid, Jackson Chitanda, Mays Al-Dulaymi, Ronald Verrall, Ildiko Badea
PURPOSE: We have developed and evaluated novel peptide-targeted gemini surfactant-based lipoplexes designed for melanoma gene therapy. METHODS: Integrin receptor targeting peptide, cyclic-arginylglycylaspartic acid (cRGD), was either chemically coupled to a gemini surfactant backbone or physically co-formulated with lipoplexes. Several formulations and transfection techniques were developed. Transfection efficiency and cellular toxicity of the lipoplexes were evaluated in an in vitro human melanoma model...
June 22, 2017: Pharmaceutical Research
https://www.readbyqxmd.com/read/28636992/acetylsalicylic-acid-inhibits-the-growth-of-melanoma-tumors-via-sox2-dependent-paf-r-independent-signaling-pathway
#4
Anita Thyagarajan, Jeremiah Saylae, Ravi P Sahu
Acquired resistance to standard therapies remains a serious challenge, requiring novel therapeutic approaches that incorporate potential factors involved in tumor resistance. As cancers including melanoma express inflammatory cyclooxygenases generating prostaglandins implicated in tumor growth, we investigated mechanism of anti-inflammatory drug, acetylsalicylic acid (ASA) which has been shown to inhibit various tumor types, however, its effects against highly aggressive melanoma model are unclear. Given our reports that an activation of platelet-activating factor-receptor (PAF-R) augments the growth and impede efficacies of therapeutic agents in experimental melanoma, we also sought to determine if PAF-R mediates anti-melanoma activity of ASA...
June 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28611198/phase-i-dose-escalation-and-expansion-study-of-the-braf-inhibitor-encorafenib-lgx818-in-metastatic-braf-mutant-melanoma
#5
Jean-Pierre Delord, Caroline Robert, Marta Nyakas, Grant A McArthur, Ragini Kudchakar, Amit Mahipal, Yasuhide Yamada, Ryan J Sullivan, Ana Arance, Richard F Kefford, Matteo S Carlino, Manuel Hidalgo, Carlos Gomez-Roca, Daniela Michel, Abdelkader Seroutou, Vassilios Aslanis, Giordano Caponigro, Darrin Stuart, Laure Moutouh-de Parseval, Tim Demuth, Reinhard Dummer
Purpose: Encorafenib, a selective BRAF-inhibitor (BRAFi), has a pharmacological profile that is distinct from that of other clinically active BRAFis. We evaluated encorafenib in a phase I study in patients with BRAFi treatment-naive and pretreated BRAF-mutant melanoma. <p>Experimental Design: The pharmacological activity of encorafenib was first characterized preclinically. Encorafenib monotherapy was then tested across a range of once-daily (QD; 50-700mg) or twice-daily (75-150mg) regimens in a phase I, open-label, dose-escalation and -expansion study in adult patients with histologically confirmed advanced/metastatic BRAF-mutant melanoma...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28604162/intratumoral-infection-by-cmv-may-change-the-tumor-environment-by-directly-interacting-with-tumor-associated-macrophages-to-promote-cancer-immunity
#6
Dan A Erkes, Nicole A Wilski, Christopher M Snyder
Cytomegalovirus (CMV) is a herpesvirus that induces an extremely robust and sustained immune response. For this reason, CMV has been proposed as a vaccine vector to promote immunity to both pathogens and cancer. However, exploration of CMV as a vaccine vector is at an early stage and there are many questions. Using a mouse melanoma model, we recently found that a CMV-based vaccine induced large populations of melanoma-specific T cells, but was not effective at slowing tumor growth unless it was injected directly into the tumor...
June 12, 2017: Human Vaccines & Immunotherapeutics
https://www.readbyqxmd.com/read/28604143/combinatorial-antitumor-effects-of-indoleamine-2-3-dioxygenase-inhibitor-nlg919-and-paclitaxel-in-a-murine-b16-f10-melanoma-model
#7
Xiangjing Meng, Guangying Du, Liang Ye, Shanyue Sun, Qiaofeng Liu, Hongbo Wang, Wenyan Wang, Zimei Wu, Jingwei Tian
Indoleamine 2,3-dioxygenase (IDO) is involved in tumor immune escape and resistance to chemotherapy, and is clinically correlated with tumor progression. IDO inhibitors show marginal efficacy as single agents; therefore, combinations of these inhibitors with other therapies hold promise for cancer therapy. The aim of this study was to investigate the synergistic antitumor effects of IDO inhibitor NLG919 in combination with different regimens of paclitaxel in a murine B16-F10 melanoma model. NLG919 increased the cytotoxic activity of paclitaxel toward B16-F10 cells in the presence of pretreatment with interferon (IFN)-γ in vitro...
June 1, 2017: International Journal of Immunopathology and Pharmacology
https://www.readbyqxmd.com/read/28595565/gold-nanoparticles-by-laser-ablation-for-x-ray-imaging-and-protontherapy-improvements
#8
Torrisi Lorenzo, Nancy Restuccia, Irene Paterniti
Gold nanoparticles, 5-20 nm in diameter, were generated with a pulsed Nd:YAG laser at 1010 W/cm2 at solution concentrations ranging between 1-100 mg/ml. Nanoparticles were characterized using optical absorbance, X-ray fluorescence, SEM, and TEM. Biocompatible nanoparticle solutions were injected by intravenously into the tail veins of mice followed by X-ray imaging using 20-45 keV photons to evaluate the uptake and the clearance by different organs of the nanoparticles. The incremental X-ray contrast imaging using gold nanoparticles was investigated and measured...
June 8, 2017: Recent Patents on Nanotechnology
https://www.readbyqxmd.com/read/28587956/activated-natural-killer-cells-mediate-the-suppressive-effect-of-interleukin-4-on-tumor-development-via-stat6-activation-in-an-atopic-condition-melanoma-model
#9
Dong Ju Son, Yu Yeon Jung, Mi Hee Park, Hye Lim Lee, Min Ji Song, Hwan-Soo Yoo, Dae Youn Hwang, Sang Bae Han, Jin Tae Hong
A protective effect of allergy for cancer has been suggested, but the results are somewhat conflicting, and the mechanism remains elusive. Interleukin-4 (IL-4) signaling has been identified as a potentially important pathway in the development of allergies and the suppression of cancer development. To evaluate the allergy responses in IL-4-mediated tumor development, we compared the growth of B16F10 melanoma cells in 4% phthalic anhydride (PA)-treated IL-4/Luc/CNS-1 transgenic mice (IL-4 mice) and acetone-olive oil (AOO)-treated IL-4 mice as a control for 3 weeks...
June 3, 2017: Neoplasia: An International Journal for Oncology Research
https://www.readbyqxmd.com/read/28571672/targeting-cd147-for-t-to-nk-lineage-reprogramming-and-tumor-therapy
#10
Jie-Jie Geng, Juan Tang, Xiang-Min Yang, Ruo Chen, Yang Zhang, Kui Zhang, Jin-Lin Miao, Zhi-Nan Chen, Ping Zhu
CD147 is highly expressed on the surface of numerous tumor cells to promote invasion and metastasis. Targeting these cells with CD147-specific antibodies has been validated as an effective approach for lung and liver cancer therapy. In the immune system, CD147 is recognized as a co-stimulatory receptor and impacts the outcome of thymic selection. Using T cell-specific deletion, we showed here that in thymus CD147 is indispensable for the stable αβ T cell lineage commitment: loss of CD147 biases both multipotent DN (double negative) and fully committed DP (double positive) cells into innate NK-like lineages...
May 18, 2017: EBioMedicine
https://www.readbyqxmd.com/read/28553955/deletion-of-adam-9-in-hgf-cdk4-mice-impairs-melanoma-development-and-metastasis
#11
N Giebeler, A Schönefuß, J Landsberg, T Tüting, C Mauch, P Zigrino
ADAM-9 is a metalloproteinase expressed in peritumoral areas by invading melanoma cells and by adjacent peritumoral stromal cells; however, its function in stromal and melanoma cells is not fully understood. To address this question in vivo in a spontaneous melanoma model, we deleted ADAM-9 in mice carrying the hepatocyte growth factor (Hgf) transgene and knock-in mutation Cdk4(R24C/R24C), demonstrated to spontaneously develop melanoma. Spontaneous melanoma arose less frequently in ADAM-9-deleted mice than in controls...
May 29, 2017: Oncogene
https://www.readbyqxmd.com/read/28546884/in-vivo-and-in-situ-programming-of-tumor-immunity-by-combining-oncolytics-and-pd-1-immune-checkpoint-blockade
#12
Eric Bartee, Zihai Li
Blockade of the programmed cell death protein 1 (PD1) pathway is clinically effective against human cancers. Although multiple types of malignancies have been shown to respond to PD1 agents, only a small percentage of patients typically benefit from this treatment. In addition, PD1 therapy often causes serious immune-related adverse events. A recent study demonstrated that local, intra-tumoral, administration of modified oncolytic myxoma virus which expresses a truncated version of the PD1 protein resulted in both increased efficacy and reduced toxicity in a clinically relevant melanoma model...
2017: Experimental Hematology & Oncology
https://www.readbyqxmd.com/read/28546431/disruption-of-mitochondrial-electron-transport-chain-function-potentiates-the-pro-apoptotic-effects-of-mapk-inhibition
#13
Andrew P Trotta, Jesse D Gelles, Madhavika N Serasinghe, Patrick Loi, Jack L Arbiser, Jerry E Chipuk
The mitochondrial network is a major site of ATP production through the coupled integration of the electron transport chain (ETC) with oxidative phosphorylation. In melanoma, arising from the Val600Glu mutation in the kinase v-RAF murine sarcoma viral oncogene homolog B (BRAFV600E), oncogenic signaling enhances glucose-dependent metabolism, while reducing mitochondrial ATP production. Likewise, when BRAFV600E is pharmacologically inhibited by targeted therapies (e.g. PLX-4032/Vemurafenib), glucose metabolism is reduced and cells increase mitochondrial ATP production to sustain survival...
May 25, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28537894/intratumoral-depletion-of-regulatory-t-cells-using-cd25-targeted-photodynamic-therapy-in-a-mouse-melanoma-model-induces-antitumoral-immune-responses
#14
Dong Sun Oh, Heegon Kim, Ji Eun Oh, Hi Eun Jung, Yun Soo Lee, Ji-Ho Park, Heung Kyu Lee
Tumor immunotherapy aims to overcome the immunosuppressive microenvironment within tumors, and various approaches have been developed. Tumor-associated T regulatory cells (Tregs) suppress the activation and expansion of tumor antigen-specific effector T cells, thus, providing a permissive environment for tumor growth. Therefore, optimal strategies need to be established to deplete tumor-infiltrated Tregs because systemic depletion of Tregs can result in reduced anti-tumor effector cells and autoimmunity. Here, to selectively deplete Tregs in tumors, we intratumorally injected anti-CD25 antibodies conjugated to Chlorin e6 (Ce6), a photosensitizer that absorbs light to generate reactive oxygen species...
May 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28535001/standardization-of-a375-human-melanoma-models-on-chicken-embryo-chorioallantoic-membrane-and-balb-c-nude-mice
#15
Stefana Avram, Dorina-Elena Coricovac, Ioana Zinuca Pavel, Iulia Pinzaru, Roxana Ghiulai, Flavia Baderca, Codruta Soica, Danina Muntean, Daciana E Branisteanu, Demetrios A Spandidos, Aristides M Tsatsakis, Cristina Adriana Dehelean
Cutaneous melanoma is a metastatic disease characterized by high resistance to treatment, the incidence of which has alarmingly increased worldwide over the past years. A thorough characterization of tumor onset, progression and metastasis is compulsory to overcome the gaps existent in melanoma biology. The present study suggests a well‑established protocol and a detailed histological description of human melanoma models in ovo and in vivo obtained by the inoculation of A375 cells to chick embryo chorioallantoic membrane (CAM) and Balb/c nude mice...
May 22, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28522750/inhibition-of-mitochondrial-matrix-chaperones-and-anti-apoptotic-bcl-2-family-proteins-empower-antitumor-therapeutic-responses
#16
Georg Karpel-Massler, Chiaki Tsuge Ishida, Elena Bianchetti, Chang Shu, Rolando Perez-Lorenzo, Basil Horst, Matei Banu, Kevin A Roth, Jeffrey N Bruce, Peter Canoll, Dario C Altieri, Markus D Siegelin
Rational therapeutic approaches based on synthetic lethality may improve cancer management. Based on a high-throughput drug screen, we provide preclinical proof of concept that targeting the mitochondrial Hsp90 chaperone network (mtHsp90) and inhibition of Bcl-2, Bcl-xL and Mcl-1 is sufficient to elicit synthetic lethality in tumors recalcitrant to therapy. Our analyses focused on BH3 mimetics that are broad acting (ABT263 and Obatoclax) or selective (ABT199, WEHI-539 and A1210477), along with the established mitochondrial matrix chaperone inhibitor Gamitrinib-TPP...
May 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28522738/imaging-of-programmed-death-ligand-1-pd-l1-impact-of-protein-concentration-on-distribution-of-anti-pd-l1-spect-agent-in-an-immunocompetent-melanoma-murine-model
#17
Jessie R Nedrow, Anders Josefsson, Sunju Park, Sagar Ranka, Sanchita Roy, George Sgouros
Programmed cell Death Ligand 1 (PD-L1) is part of an immune checkpoint system that is essential for preventing autoimmunity and cancer. Recent approaches in immunotherapy targeting immune checkpoints have shown great promise in a variety of cancers, including metastatic melanoma. The use of targeted molecular imaging would help identify patients who will best respond to anti-PD-L1 treatment while potentially providing key information to limit immune-related adverse effects (irAEs). Recently, we developed an antibody based PD-L1-targeted imaging agent to identify PD-L1 positive tumors in vivo...
May 18, 2017: Journal of Nuclear Medicine: Official Publication, Society of Nuclear Medicine
https://www.readbyqxmd.com/read/28502199/ceramide-lipid-based-nanosuspension-for-enhanced-delivery-of-docetaxel-with-synergistic-antitumor-efficiency
#18
Tianqi Wang, Lixia Feng, Shaomei Yang, Yongjun Liu, Na Zhang
Ceramide (CE), a bioactive lipid with tumor suppression, has been widely used as a drug carrier and enhancer for cancer therapy. CE-based combination therapy was prone to be attractive in cancer therapy. In our previous study, the combination of CE and docetaxel (DTX) was proved to be an effective strategy for cancer therapy. To further improve the antitumor efficiency of DTX, the CE lipid-based nanosuspensions (LNS) was prepared for the delivery of DTX to exhibit synergistic therapeutic effect. The enhanced delivery and synergistic therapeutic effect of DTX-loaded CE-LNS (CE + DTX-LNS) were evaluated...
November 2017: Drug Delivery
https://www.readbyqxmd.com/read/28501941/paracrine-release-of-il-2-and-anti-ctla-4-enhances-the-ability-of-artificial-polymer-antigen-presenting-cells-to-expand-antigen-specific-t-cells-and-inhibit-tumor-growth-in-a-mouse-model
#19
Lei Zhang, Limin Wang, Khawar Ali Shahzad, Tao Xu, Xin Wan, Weiya Pei, Chuanlai Shen
Accumulating evidence indicates that bead-based artificial antigen-presenting cells (aAPCs) are a powerful tool to induce antigen-specific T cell responses in vitro and in vivo. To date, most conventional aAPCs have been generated by coupling an antigen signal (signal 1) and one or two costimulatory signals, such as anti-CD28 with anti-LFA1 or anti-4-1BB (signal 2), onto the surfaces of cell-sized or nanoscale magnetic beads or polyester latex beads. The development of a biodegradable scaffold and the combined use of multiple costimulatory signals as well as third signals for putative clinical applications is the next step in the development of this technology...
May 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28497782/raf-proteins-exert-both-specific-and-compensatory-functions-during-tumour-progression-of-nras-driven-melanoma
#20
Coralie Dorard, Charlène Estrada, Céline Barbotin, Magalie Larcher, Alexandra Garancher, Jessy Leloup, Friedrich Beermann, Manuela Baccarini, Celio Pouponnot, Lionel Larue, Alain Eychène, Sabine Druillennec
NRAS and its effector BRAF are frequently mutated in melanoma. Paradoxically, CRAF but not BRAF was shown to be critical for various RAS-driven cancers, raising the question of the role of RAF proteins in NRAS-induced melanoma. Here, using conditional ablation of Raf genes in NRAS-induced mouse melanoma models, we investigate their contribution in tumour progression, from the onset of benign tumours to malignant tumour maintenance. We show that BRAF expression is required for ERK activation and nevi development, demonstrating a critical role in the early stages of NRAS-driven melanoma...
May 12, 2017: Nature Communications
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