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https://www.readbyqxmd.com/read/28436963/a-sting-activating-nanovaccine-for-cancer-immunotherapy
#1
Min Luo, Hua Wang, Zhaohui Wang, Haocheng Cai, Zhigang Lu, Yang Li, Mingjian Du, Gang Huang, Chensu Wang, Xiang Chen, Matthew R Porembka, Jayanthi Lea, Arthur E Frankel, Yang-Xin Fu, Zhijian J Chen, Jinming Gao
The generation of tumour-specific T cells is critically important for cancer immunotherapy. A major challenge in achieving a robust T-cell response is the spatiotemporal orchestration of antigen cross-presentation in antigen-presenting cells with innate stimulation. Here, we report a minimalist nanovaccine, comprising a simple physical mixture of an antigen and a synthetic polymeric nanoparticle, PC7A NP, which generates a strong cytotoxic T-cell response with low systemic cytokine expression. Mechanistically, the PC7A NP achieves efficient cytosolic delivery of tumour antigens to antigen-presenting cells in draining lymph nodes, leading to increased surface presentation while simultaneously activating type I interferon-stimulated genes...
April 24, 2017: Nature Nanotechnology
https://www.readbyqxmd.com/read/28436934/biopolymers-codelivering-engineered-t-cells-and-sting-agonists-can-eliminate-heterogeneous-tumors
#2
Tyrel T Smith, Howell F Moffett, Sirkka B Stephan, Cary F Opel, Amy G Dumigan, Xiuyun Jiang, Venu G Pillarisetty, Smitha P S Pillai, K Dane Wittrup, Matthias T Stephan
Therapies using T cells that are programmed to express chimeric antigen receptors (CAR T cells) consistently produce positive results in patients with hematologic malignancies. However, CAR T cell treatments are less effective in solid tumors for several reasons. First, lymphocytes do not efficiently target CAR T cells; second, solid tumors create an immunosuppressive microenvironment that inactivates T cell responses; and third, solid cancers are typified by phenotypic diversity and thus include cells that do not express proteins targeted by the engineered receptors, enabling the formation of escape variants that elude CAR T cell targeting...
April 24, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28436853/automatic-skin-lesion-segmentation-using-deep-fully-convolutional-networks-with-jaccard-distance
#3
Yading Yuan, Ming Chao, Yeh-Chi Lo
Automatic skin lesion segmentation in dermoscopic images is a challenging task due to the low contrast between lesion and the surrounding skin, the irregular and fuzzy lesion borders, the existence of various artifacts, and various imaging acquisition conditions. In this article, we present a fully automatic method for skin lesion segmentation by leveraging a 19-layer deep convolutional neural networks (CNNs) that is trained end-to- end and does not rely on prior knowledge of the data. We propose a set of strategies to ensure effective and efficient learning with limited training data...
April 18, 2017: IEEE Transactions on Medical Imaging
https://www.readbyqxmd.com/read/28436601/management-of-skin-adverse-events-associated-with-immune-checkpoint-inhibitors-in-patients-with-melanoma-a-nursing-perspective
#4
Melissa Thebeau, Krista Rubin, Matthias Hofmann, Julia Grimm, Alyona Weinstein, Jennifer N Choi
PURPOSE: Immune checkpoint inhibitors are associated with a unique immune-related side effect profile that requires prompt recognition and management. Skin toxicities are the most common, and often earliest occurring, drug-related adverse events (AEs) of any grade observed upon treatment with these agents. The purpose of this review is to provide practical guidance on the identification and treatment of skin AEs associated with the immune checkpoint inhibitors (ipilimumab, nivolumab, and pembrolizumab) from a nursing perspective, and demonstrate hands-on application of the guidance using relevant patient case studies...
April 24, 2017: Journal of the American Association of Nurse Practitioners
https://www.readbyqxmd.com/read/28436451/empirical-modeling-of-physiochemical-immune-response-of-multilayer-zinc-oxide-nanomaterials-under-uv-exposure-to-melanoma-and-foreskin-fibroblasts
#5
Muhammad Fakhar-E-Alam, M Waseem Akram, Seemab Iqbal, K S Alimgeer, M Atif, K Sultana, M Willander, Zhiming M Wang
Carcinogenesis is a complex molecular process starting with genetic and epigenetic alterations, mutation stimulation, and DNA modification, which leads to proteomic adaptation ending with an uncontrolled proliferation mechanism. The current research focused on the empirical modelling of the physiological response of human melanoma cells (FM55P) and human foreskin fibroblasts cells (AG01518) to the multilayer zinc oxide (ZnO) nanomaterials under UV-A exposure. To validate this experimental scheme, multilayer ZnO nanomaterials were grown on a femtotip silver capillary and conjugated with protoporphyrin IX (PpIX)...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436422/rational-design-of-non-resistant-targeted-cancer-therapies
#6
Francisco Martínez-Jiménez, John P Overington, Bissan Al-Lazikani, Marc A Marti-Renom
Drug resistance is one of the major problems in targeted cancer therapy. A major cause of resistance is changes in the amino acids that form the drug-target binding site. Despite of the numerous efforts made to individually understand and overcome these mutations, there is a lack of comprehensive analysis of the mutational landscape that can prospectively estimate drug-resistance mutations. Here we describe and computationally validate a framework that combines the cancer-specific likelihood with the resistance impact to enable the detection of single point mutations with the highest chance to be responsible of resistance to a particular targeted cancer therapy...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28436290/topography-of-protein-kinase-c-%C3%AE-ii-in-benign-and-malignant-melanocytic-lesions
#7
Konstanin Krasagakis, Eleftheria Tsentelierou, Gregory Chlouverakis, Efstathios N Stathopoulos
BACKGROUND: Protein kinase C βII promotes melanogenesis and affects proliferation of melanocytic cells but is frequently absent or decreased in melanoma cells in vitro. OBJECTIVE: To investigate PKC-βII expression and spatial distribution within a lesion in various benign and malignant melanocytic proliferations. METHODS: Expression of PKC-βII was semiquantitatively assessed in the various existing compartments (intraepidermal [not nested], junctional [nested], and dermal) of benign (n = 43) and malignant (n = 28) melanocytic lesions by immunohistochemistry...
April 1, 2017: International Journal of Surgical Pathology
https://www.readbyqxmd.com/read/28436025/melanoma-in%C3%A2-situ-of-lentigo-maligna-type-in-a-young-woman
#8
Matthew F Helm, Michael J Bax, David J Augenblick, Catherine G Chung
No abstract text is available yet for this article.
April 23, 2017: International Journal of Dermatology
https://www.readbyqxmd.com/read/28435677/control-of-immune-cell-entry-through-the-tumour-vasculature-a-missing-link-in-optimising-melanoma-immunotherapy
#9
REVIEW
Lih Yin Tan, Carmela Martini, Zvi G Fridlender, Claudine S Bonder, Michael P Brown, Lisa M Ebert
Metastatic melanoma remains a fatal disease to many worldwide, even after the breakthrough introduction of targeted therapies such as BRAF inhibitors and immune checkpoint blockade therapies such as CTLA-4 and PD-1 inhibitors. With advances in our understanding of this disease, as well as the increasing data gathered from patient studies, the significance of the host immune response to cancer progression and response to treatment is becoming clear. More specifically, the presence of intratumoral CD8(+) cytotoxic T-cells correlates with better prognosis whereas the accumulation of monocytes/macrophages and neutrophils in the tumour is often associated with worse prognosis...
March 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28435664/age-specific-acceleration-in-malignant-melanoma
#10
Brian L Diffey, Steven A Frank
Background: The overall incidence of melanoma has increased steadily for several years. The relative change in incidence at different ages has not been fully described.  Objective: To describe how incidence at different ages has changed over time and to consider what aspects of tumour biology may explain the observed pattern of change in incidence.  Methods: The slope of incidence vs age measures the acceleration of cancer incidence with age. We described the pattern of change over time in the overall incidence of melanoma, as well as in acceleration...
2017: F1000Research
https://www.readbyqxmd.com/read/28435463/design-and-development-of-fluorescent-vemurafenib-analogs-for-in-vivo-imaging
#11
Hannes Mikula, Shawn Stapleton, Rainer H Kohler, Claudio Vinegoni, Ralph Weissleder
Herein we describe fluorescent derivatives of vemurafenib to probe therapeutic BRAF inhibition in live cells and in vivo. The compounds were evaluated and compared by determining target binding, inhibition of mutant BRAF melanoma cell lines and live cell imaging. We show that vemurafenib-BODIPY is a superior imaging drug to visualize the targets of vemurafenib in live cells and in vivo in non-resistant and resistant melanoma tumors.
2017: Theranostics
https://www.readbyqxmd.com/read/28435391/programmed-cell-death-1-checkpoint-inhibitors-in-the-treatment-of-patients-with-advanced-melanoma
#12
REVIEW
Jacek Mackiewicz, Andrzej Mackiewicz
The treatment landscape of advanced melanoma has changed significantly following the discovery and marketing authorisation of immune checkpoints inhibitors. Ipilimumab (anti-CTLA-4) was the first one to be approved, and it. demonstrated long-term survival in about 20% of patients. Subsequently, anti-programmed cell death-1 (a-PD-1) antibodies (pembrolizuamb, nivolumab), inhibitors of PD-1/programmed cell death-1 ligand (PD1-L) synapse, showed higher clinical efficacy with lower toxicity comparing to ipilimumab...
2017: Contemporary Oncology Współczesna Onkologia
https://www.readbyqxmd.com/read/28435246/cuprous-oxide-nanoparticle-inhibited-melanoma-progress-by-targeting-melanoma-stem-cells
#13
Bin Yu, Ye Wang, Xinlu Yu, Hongxia Zhang, Ji Zhu, Chen Wang, Fei Chen, Changcheng Liu, Jingqiang Wang, Haiying Zhu
Recent studies have shown that metal and metal oxide have a potential function in antitumor therapy. Our previous studies demonstrated that cuprous oxide nanoparticles (CONPs) not only selectively induce apoptosis of tumor cells in vitro but also inhibit the growth and metastasis of melanoma by targeting mitochondria with little hepatic and renal toxicities in mice. As a further study, our current research revealed that CONPs induced apoptosis of human melanoma stem cells (CD271(+/high) cells) in A375 and WM266-4 melanoma cell lines and could significantly suppress the expression of MITF, SOX10 and CD271 involved in the stemness maintenance and tumorigenesis of melanoma stem cells...
2017: International Journal of Nanomedicine
https://www.readbyqxmd.com/read/28435024/lkb1-deletion-in-murine-b-lymphocytes-promotes-cell-death-and-cancer
#14
George P Souroullas, Yuri Fedoriw, Louis M Staudt, Norman E Sharpless
LKB1 (aka STK11) is a potent tumor suppressor in solid tumors such as melanoma and lung adenocarcinoma, but inactivation in hematopoietic cells causes cell death, without signs of tumorigenesis. We noted somatic LKB1 deletion or mutation at low frequency in human B cell lymphoma. In order to determine if LKB1 inactivation is a passenger or driver event in lymphoid cancers, we examined the effects of conditional inactivation of Lkb1 in murine lymphocytes. Consistent with prior reports, Lkb1 deletion in either T or B cells resulted in massive, lineage-specific apoptosis...
April 20, 2017: Experimental Hematology
https://www.readbyqxmd.com/read/28434400/role-of-modern-immunotherapy-in-gastrointestinal-malignancies-a-review-of-current-clinical-progress
#15
REVIEW
Zin W Myint, Gaurav Goel
Gastrointestinal (GI) cancers are a group of highly aggressive malignancies with a huge disease burden worldwide. There is clearly a significant unmet need for new drugs and therapies to further improve the treatment outcomes of GI malignancies. Immunotherapy is a novel treatment strategy that is emerging as an effective and promising treatment option against several types of cancers. CTLA-4 and PD-1 are critical immune checkpoint molecules that negatively regulate T cell activation via distinct mechanisms...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434398/the-use-of-immunotherapy-in-the-treatment-of-melanoma
#16
REVIEW
Tala Achkar, Ahmad A Tarhini
Patients with advanced melanoma have a compromised anti-tumor immune response leading to tumor immune tolerance and a tumor microenvironment conducive to disease progression. Immunotherapy that successfully overcomes this tumor-mediated immune suppression has made the greatest impact in the management of this disease over the past few years. This progress through immunotherapy builds upon earlier successes that interferon-α had in the treatment of melanoma in the adjuvant setting, as well as that of high-dose interleukin-2 in advanced melanoma...
April 24, 2017: Journal of Hematology & Oncology
https://www.readbyqxmd.com/read/28434095/patient-reported-outcomes-in-cancer-survivors-a-population-wide-cross-sectional-study
#17
Michael Jefford, Andrew C Ward, Karolina Lisy, Karen Lacey, Jon D Emery, Adam W Glaser, Hannah Cross, Mei Krishnasamy, Sue-Anne McLachlan, Jim Bishop
PURPOSE: There is a lack of robust population-based data regarding the lived experience of cancer survivors. This study assessed the quality of life (QoL) of survivors of breast, colorectal, or prostate cancer, non-Hodgkin lymphoma or melanoma 1, 3 and 5 years post-diagnosis. Associations between various demographic and disease-related factors and QoL were assessed. METHODS: A cross-sectional postal survey was undertaken. Eligible participants were identified from a population-based cancer registry...
April 22, 2017: Supportive Care in Cancer: Official Journal of the Multinational Association of Supportive Care in Cancer
https://www.readbyqxmd.com/read/28434031/fkbp51s-signature-in-peripheral-blood-mononuclear-cells-of-melanoma-patients-as-a-possible-predictive-factor-for-immunotherapy
#18
Simona Romano, Ester Simeone, Anna D'Angelillo, Paolo D'Arrigo, Michele Russo, Mario Capasso, Vito Alessandro Lasorsa, Nicola Zambrano, Paolo A Ascierto, Maria Fiammetta Romano
The inhibitory immune checkpoint PD-L1/PD1 promotes the alternative splicing of the FKBP5 gene, resulting in increased expression of its variant 4 in the peripheral blood mononuclear cells of melanoma patients. The variant 4 transcript is translated into the truncated FKBP51s protein. Given the importance of co-inhibitory signalling in tumour immune escape, here we tested the potential for using FKBP51s expression to predict immunotherapy outcomes. To do this, we immunophenotyped PBMCs from 118 melanoma patients and 77 age- and sex-matched healthy controls...
April 22, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28433833/in-vitro-antitumor-activity-metal-uptake-and-reactivity-with-ascorbic-acid-and-bsa-of-some-gold-iii-complexes-with-n-n-ethylenediamine-bidentate-ester-ligands
#19
Nebojša Pantelić, Bojana B Zmejkovski, Branka Kolundžija, Marija Đorđić Crnogorac, Jelena M Vujić, Biljana Dojčinović, Srećko R Trifunović, Tatjana P Stanojković, Tibor J Sabo, Goran N Kaluđerović
Four novel gold(III) complexes of general formulae [AuCl2{(S,S)-R2eddl}]PF6 (R2eddl=O,O'-dialkyl-(S,S)-ethylenediamine-N,N'-di-2-(4-methyl)pentanoate, R=n-Pr, n-Bu, n-Pe, i-Bu; 1-4, respectively), were synthesized and characterized by elemental analysis, UV/Vis, IR, and NMR spectroscopy, as well as high resolution mass spectrometry. Density functional theory calculations pointed out that (R,R)-N,N'-configuration diastereoisomers were energetically the most favorable. Duo to high cytotoxic activity complex 3 was chosen for stability study in DMSO, no decomposition occurs within 24h, and for the reaction with ascorbic acid in which was reduced immediately...
April 4, 2017: Journal of Inorganic Biochemistry
https://www.readbyqxmd.com/read/28433799/affinity-proteomics-exploration-of-melanoma-identifies-proteins-in-serum-with-associations-to-t-stage-and-recurrence
#20
Sanna Byström, Claudia Fredolini, Per-Henrik Edqvist, Etienne-Nicholas Nyaiesh, Kimi Drobin, Mathias Uhlén, Michael Bergqvist, Fredrik Pontén, Jochen M Schwenk
BACKGROUND: Blood-based proteomic profiling may aid and expand our understanding of diseases and their different phenotypes. The aim of the presented study was to profile serum samples from patients with malignant melanoma using affinity proteomic assays to describe proteins in the blood stream that are associated to stage or recurrence of melanoma. MATERIAL AND METHODS: Multiplexed protein analysis was conducted using antibody suspension bead arrays. A total of 232 antibodies against 132 proteins were selected from (i) a screening with 4595 antibodies and 32 serum samples from melanoma patients and controls, (ii) antibodies used for immunohistochemistry, (iii) protein targets previously related with melanoma...
April 20, 2017: Translational Oncology
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