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Tumor priming

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https://www.readbyqxmd.com/read/28208020/graphene-oxide-induced-perturbation-to-plasma-membrane-and-cytoskeletal-meshwork-sensitize-cancer-cells-to-chemotherapeutic-agents
#1
Jianqiang Zhu, Ming Xu, Ming Gao, Zhihong Zhang, Yong Xu, Tian Xia, Sijin Liu
The outstanding physicochemical properties endow graphene materials (e.g. graphene oxide, GO) with beneficial potentials in diverse biomedical fields such as bioimaging, drug delivery and biomolecular detection. GO recently emerges to act as chemosensitizer; however, the detailed molecular bases underlying GO-conducted sensitization and according biological effects are still elusive. Based on our recent findings that GO treatment at sublethal concentrations could impair the general cellular priming state including disorders of plasma membrane and cytoskeleton construction, we here aimed to explore the mechanism of GO as a sensitizer to make cancer cells more susceptible to chemotherapeutic agents...
February 16, 2017: ACS Nano
https://www.readbyqxmd.com/read/28202532/cd40-signaling-drives-potent-cellular-immune-responses-in-heterologous-cancer-vaccinations
#2
Supot Nimanong, Dmitrij Ostroumov, Jessica Wingerath, Sarah Knocke, Norman Woller, Engin Guerlevik, Christine Falk, Michael P Manns, Florian Kuehnel, Thomas C Wirth
Antagonistic antibodies targeting co-inhibitory receptors have revolutionized the treatment of cancer by inducing durable immune responses and clinical remissions in patients. In contrast, success of agonistic costimulatory antibodies has thus far been limited due to insufficient induction of adaptive immune responses. Here we describe a novel vaccination method consisting of a primary dendritic cell immunization followed by a composite vaccination including an agonistic CD40 antibody, soluble antigen and a TLR3 agonist, referred to as CoAT...
February 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28197387/ciita-driven-mhc-class-ii-expressing-tumor-cells-can-efficiently-prime-naive-cd4-th-cells-in-vivo-and-vaccinate-the-host-against-parental-mhc-ii-negative-tumor-cells
#3
Farah Bou Nasser Eddine, Greta Forlani, Letizia Lombardo, Alessandra Tedeschi, Giovanna Tosi, Roberto S Accolla
Our previous studies showed that non-immunogenic H-2(d) tumor cells of distinct epithelial histotypes can become highly immunogenic, induce a protective CD4(+) T cell response and vaccinate the animals against parental MHC-II-negative cells if they are rendered MHC class II-positive by stable transfection with the Air-1-encoded MHC-II transcriptional activator CIITA. These studies did not establish, however, whether tumor immunity was the consequence of a direct priming of naive CD4(+) T lymphocytes by CIITA-driven MHC-II-expressing tumor cells or by MHC-II-tumor antigen complexes engulfed by dendritic cells (DC) and exposed on the surface of these professional antigen presenting cells (APC)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28197368/immunosuppressive-cd14-hla-dr-lo-neg-monocytes-are-elevated-in-pancreatic-cancer-and-primed-by-tumor-derived-exosomes
#4
Naureen Javeed, Michael P Gustafson, Shamit K Dutta, Yi Lin, William R Bamlet, Ann L Oberg, Gloria M Petersen, Suresh T Chari, Allan B Dietz, Debabrata Mukhopadhyay
Immunological strategies to treat pancreatic cancer offer new therapeutic approaches to improve patient outcomes. Understanding alterations in the immune systems of pancreatic cancer patients will likely lead to advances in immunotherapy for the disease. We profiled peripheral blood leukocytes from pancreatic cancer patients (n = 22) and age-matched controls (n = 20) using flow cytometry. Immune profiling of pancreatic cancer patients identified phenotypic changes in various immune cell populations, including a population of immunosuppressive monocytes (CD14(+)HLA-DR(lo/neg)), which were shown to be increased in these patients...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28187434/interface-between-breast-cancer-cells-and-the-tumor-microenvironment-using-platelet-rich-plasma-to-promote-tumor-angiogenesis-influence-of-platelets-and-fibrin-bundles-on-the-behavior-of-breast-tumor-cells
#5
Sheila Siqueira Andrade, Joana Tomomi Sumikawa, Eloísa Dognani Castro, Fabricio Pereira Batista, Edgar Paredes-Gamero, Lilian Carolina Oliveira, Izabel Monastério Guerra, Giovani Bravin Peres, Renan Pelluzzi Cavalheiro, Luiz Juliano, Afonso Pinto Nazário, Gil Facina, Siu Mui Tsai, Maria Luiza Vilela Oliva, Manoel João Batista Castello Girão
Cancer progression is associated with an evolving tissue interface of direct epithelial-tumor microenvironment interactions. In biopsies of human breast tumors, extensive alterations in molecular pathways are correlated with cancer staging on both sides of the tumor-stroma interface. These interactions provide a pivotal paracrine signaling to induce malignant phenotype transition, the epithelial-mesenchymal transition (EMT). We explored how the direct contact between platelets-fibrin bundles primes metastasis using platelet-rich plasma (PRP) as a source of growth factors and mimics the provisional fibrin matrix between actively growing breast cancer cells and the tumor stroma...
February 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28187046/effect-of-hydroxyethyl-starch-priming-on-the-systemic-inflammatory-response-and-lung-edema-following-cardiopulmonary-bypass-in-a-rat-model
#6
Yutaka Fujii, Takayuki Tanabe, Tsubasa Yamashiro, Mikiyasu Shirai, Yoshiaki Takewa, Eisuke Tatsumi
Cardiopulmonary bypass (CPB) preserves patients' lives during open heart surgery by providing sufficient oxygen delivery and blood supply to vital organs. However, previous studies have suggested that the interaction of hemodilution and vascular hyperpermeability induces tissue edema and an inflammatory response during CPB. In this study, we hypothesized that suppression of the systemic inflammatory response and tissue edema during CPB by a plasma substitute (hydroxyethyl starch: HES).Rats (450-500 g) were divided into a SHAM group (n=5), a Ringer's acetate CPB group (n=7), and an HES CPB group (n=7)...
February 7, 2017: ASAIO Journal: a Peer-reviewed Journal of the American Society for Artificial Internal Organs
https://www.readbyqxmd.com/read/28182873/biomechanically-primed-liver-microtumor-array-as-a-high-throughput-mechanopharmacological-screening-platform-for-stroma-reprogrammed-combinatorial-therapy
#7
Lu Zhu, Xingliang Fan, Bingjie Wang, Longwei Liu, Xiaojun Yan, Lyu Zhou, Yang Zeng, Mark C Poznansky, Lili Wang, Huabiao Chen, Yanan Du
Recent breakthrough in stroma-reprogrammed combinatorial therapy (SRCT) for pancreatic tumor opens a new route for improving conventional chemotherapeutic efficacy, which utilizes VDR ligand to reprogram activated stromal cells in stiffened microenvironment, leading to reduced 'barrier effects' and increased tissue-infiltration of the chemotherapy drug. As a novel therapeutic strategy and mechanism of action, the progress of SRCT relies on tailored in vitro drug assessment platforms to further optimize its efficacy and extend to applications in other tumor types...
January 27, 2017: Biomaterials
https://www.readbyqxmd.com/read/28182330/heat-shock-protein-27-hsp27-hspb1-is-synthetic-lethal-to-cells-with-oncogenic-activation-of-met-egfr-and-braf
#8
John David Konda, Martina Olivero, Daniele Musiani, Simona Lamba, Maria Flavia Di Renzo
The small Heat Shock Protein of 27 KDa (HSP27) is highly expressed in many cancers and is associated with aggressive tumor behaviour, metastasis, poor prognosis and resistance to chemotherapy. We aimed at assessing the role of HSP27 in modulating responses to target therapies. We selected several oncogene-addicted cancer cell lines, which undergo either cell cycle blockade or cell death in response to agents that target the specific oncogene. Surprisingly, HSP27 suppression alone resulted in the apoptotic death of MET-addicted EBC-1 lung cancer cells, EGFR-addicted colorectal carcinoma DiFi cells and BRAF-addicted colorectal carcinoma COLO205 and OXCO-1 and melanoma COLO741 cells, all of which also undergo death when treated with the specific targeted agent...
February 9, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28178658/prime-boost-immunization-by-both-dna-vaccine-and-oncolytic-adenovirus-expressing-gm-csf-and-shrna-of-tgf-%C3%AE-2-induces-anti-tumor-immune-activation
#9
So Young Kim, Dongxu Kang, Hye Jin Choi, Yeonsoo Joo, Joo-Hang Kim, Jae J Song
A successful DNA vaccine for the treatment of tumors should break established immune tolerance to tumor antigen. However, due to the relatively low immunogenicity of DNA vaccines, compared to other kinds of vaccines using live virus or protein, a recombinant viral vector was used to enhance humoral and cellular immunity. In the current study, we sought to develop a novel anti-cancer agent as a complex of DNA and oncolytic adenovirus for the treatment of malignant melanoma in the C57BL/6 mouse model. MART1, a human melanoma-specific tumor antigen, was used to induce an increased immune reaction, since a MART1-protective response is required to overcome immune tolerance to the melanoma antigen MelanA...
February 2, 2017: Oncotarget
https://www.readbyqxmd.com/read/28175556/362%C3%A2-priming-of-the-brain-tumor-microenvironment-enables-improved-nanomedicine-delivery
#10
Yuanxin Chen, Wen Jiang, Yaqing Qie, Xiujie Liu, Christina von Roemeling, Kevin Shih, Robert E Wharen, Betty Y S Kim
No abstract text is available yet for this article.
August 1, 2016: Neurosurgery
https://www.readbyqxmd.com/read/28169347/attenuation-of-lymphocyte-immune-responses-during-mycobacterium-avium-complex-induced-lung-disease-due-to-increasing-expression-of-programmed-death-1-on-lymphocytes
#11
Chin-Chung Shu, Jann-Yuan Wang, Ming-Fang Wu, Chen-Tu Wu, Hsin-Chih Lai, Li-Na Lee, Bor-Luen Chiang, Chong-Jen Yu
Mycobacterium avium complex-induced lung disease (MAC-LD) becomes important due to its increasing prevalence. Attenuated cellular immunity associated with programmed cell death (PD)-1 may play a pathophysiological role in MAC-LD but lacks of investigation. We enrolled 80 participants in this prospective study, including 50 with MAC-LD and 30 healthy controls. Peripheral blood mononuclear cells (PBMCs), lymphocytes and monocyte-derived macrophages were used for MAC antigen stimulation. Patients with MAC-LD had lower tumor necrosis factor-α and interferon-γ responses compared to the healthy controls in PBMC stimulation assays with MAC bacilli...
February 7, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28159928/a-meta-analysis-of-hla-peptidome-composition-in-different-hematological-entities-entity-specific-dividing-lines-and-pan-leukemia-antigens
#12
Linus Backert, Daniel Johannes Kowalewski, Simon Walz, Heiko Schuster, Claudia Berlin, Marian Christoph Neidert, Mirle Schemionek, Tim H Brümmendorf, Vladan Vucinic, Dietger Niederwieser, Lothar Kanz, Helmut Rainer Salih, Oliver Kohlbacher, Katja Weisel, Hans-Georg Rammensee, Stefan StevanoviÄ, Juliane Sarah Walz
Hematological malignancies (HM) are highly amenable targets for immunotherapeutic intervention and may be effectively treated by antigen-specific T-cell based treatment. Recent studies demonstrate that physiologically occurring anti-cancer T-cell responses in certain HM entities target broadly presented non-mutated epitopes. HLA ligands are thus implied as prime targets for broadly applicable and antigen-specific off-the-shelf compounds. With the aim of assessing the presence of common targets shared among different HM which may enable addressing a larger patient collective we conducted a meta-analysis of 83 mass spectrometry-based HLA peptidome datasets (comprising 40,361 unique peptide identifications) across four major HM (19 AML, 16 CML, 35 CLL, and 13 MM/MCL samples) and investigated similarities and differences within the HLA presented antigenic landscape...
January 31, 2017: Oncotarget
https://www.readbyqxmd.com/read/28157493/soil-primes-the-seed-epigenetic-landscape-drives-tumor-behavior
#13
Ramon J Whitson, Anthony E Oro
Whether invasive tumor phenotypes like EMT arise from oncogenic drivers or from priming of the pre-tumor cell of origin remains unknown. In this issue of Cell Stem Cell, Latil et al. (2017) show that the pre-tumor niche establishes a chromatin state predisposing squamous cell carcinomas to undergo EMT and metastasis, suggesting that the pre-tumor epigenome has prognostic value.
February 2, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28154569/regulation-of-nk-cell-activation-and-effector-functions-by-the-il-12-family-of-cytokines-the-case-of-il-27
#14
REVIEW
Norberto Walter Zwirner, Andrea Ziblat
Natural killer (NK) cells are characterized by their ability to detect and induce apoptosis of susceptible target cells and by secretion of immunoregulatory cytokines such as IFN-γ. Activation of these effector functions is triggered upon recognition of tumor and pathogen (mostly virus)-infected cells and because of a bidirectional cross talk that NK cells establish with other cells of myeloid origin such as dendritic cells (DC) and macrophages. A common characteristic of these myeloid cells is their ability to secrete different members of the IL-12 family of cytokines such as IL-12, IL-23, and IL-27 and cytokines such as IL-15 and IL-18...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28153512/paclitaxel-releasing-mesenchymal-stromal-cells-inhibit-in-vitro-proliferation-of-human-mesothelioma-cells
#15
Francesco Petrella, Valentina Coccè, Carla Masia, Martina Milani, Emanuela Omodeo Salè, Giulio Alessandri, Eugenio Parati, Francesca Sisto, Francesca Pentimalli, Anna T Brini, Augusto Pessina, Lorenzo Spaggiari
INTRODUCTION: Malignant pleural mesothelioma (MPM) is a rare fatal asbestos-related malignancy originating in the mesothelial cells of the pleura. A platinum-based doublet containing a third-generation antifolate is the front-line standard of care whilst there are no approved second-line treatments for MPM which remains a disease setting to test the efficacy of new therapeutic agents. METHODS: Bone marrow mesenchymal stromal cells (BM-MSCs) were loaded with pemetrexed (PMX) and paclitaxel (PTX) according to a standardized procedure...
January 30, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28153097/dendritic-cells-cross-present-immunogenic-lentivector-encoded-antigen-from-transduced-cells-to-prime-functional-t-cell-immunity
#16
Alastair Hotblack, Sara Seshadri, Lei Zhang, Sahar Hamrang-Yousefi, Ronjon Chakraverty, David Escors, Clare L Bennett
Recombinant lentiviral vectors (LVs) are highly effective vaccination vehicles that elicit protective T cell immunity in disease models. Dendritic cells (DCs) acquire antigen at sites of vaccination and migrate to draining lymph nodes, where they prime vaccine-specific T cells. The potency with which LVs activate CD8(+) T cell immunity has been attributed to the transduction of DCs at the immunization site and durable presentation of LV-encoded antigens. However, it is not known how LV-encoded antigens continue to be presented to T cells once directly transduced DCs have turned over...
February 1, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28152014/apigenin-selective-ck2-inhibitor-increases-ikaros-expression-and-improves-t-cell-homeostasis-and-function-in-murine-pancreatic-cancer
#17
Nadine Nelson, Karoly Szekeres, Cristina Iclozan, Ivannie Ortiz Rivera, Andrew McGill, Gbemisola Johnson, Onyekachi Nwogu, Tomar Ghansah
Pancreatic cancer (PC) evades immune destruction by favoring the development of regulatory T cells (Tregs) that inhibit effector T cells. The transcription factor Ikaros is critical for lymphocyte development, especially T cells. We have previously shown that downregulation of Ikaros occurs as a result of its protein degradation by the ubiquitin-proteasome system in our Panc02 tumor-bearing (TB) mouse model. Mechanistically, we observed a deregulation in the balance between Casein Kinase II (CK2) and protein phosphatase 1 (PP1), which suggested that increased CK2 activity is responsible for regulating Ikaros' stability in our model...
2017: PloS One
https://www.readbyqxmd.com/read/28149620/adjuvant-chemotherapy-for-a-t3-additional-tumor-nodule-in-the-same-lobe-ready-for-prime-time
#18
EDITORIAL
M Jawad Latif, David R Jones
No abstract text is available yet for this article.
December 2016: Journal of Thoracic Disease
https://www.readbyqxmd.com/read/28149332/the-immunomodulatory-anticancer-agent-rrx-001-induces-an-interferon-response-through-epigenetic-induction-of-viral-mimicry
#19
Hongjuan Zhao, Shoucheng Ning, Rosalie Nolley, Jan Scicinski, Bryan Oronsky, Susan J Knox, Donna M Peehl
BACKGROUND: RRx-001, a dinitroazetidine derivative, is a novel anticancer agent currently in phase II clinical trials. It mediates immunomodulatory effects either directly through polarization of tumor associated macrophages or indirectly through vascular normalization and increased T-lymphocyte infiltration. With multiple additional mechanisms of action including upregulation of oxidative stress, depletion of GSH and NADPH, anti-angiogenesis and epigenetic modulation, RRx-001 is being studied as a radio- and chemo-sensitizer to resensitize tumors to prior therapy and to prime tumors to respond to radiation, chemotherapy and immunotherapy in combination therapy studies...
2017: Clinical Epigenetics
https://www.readbyqxmd.com/read/28147313/mapk-pathway-inhibition-induces-met-and-gab1-levels-priming-braf-mutant-melanoma-for-rescue-by-hepatocyte-growth-factor
#20
Sean Caenepeel, Keegan Cooke, Sarah Wadsworth, Guo Huang, Lidia Robert, Blanca Homet Moreno, Giulia Parisi, Elaina Cajulis, Richard Kendall, Pedro Beltran, Antoni Ribas, Angela Coxon, Paul E Hughes
Therapeutic resistance is a major obstacle to achieving durable clinical responses with targeted therapies, highlighting a need to elucidate the underlying mechanisms responsible for resistance and identify strategies to overcome this challenge. An emerging body of data implicates the tyrosine kinase MET in mediating resistance to BRAF inhibitors in BRAFV600E mutant melanoma. In this study we observed a dominant role for the HGF/MET axis in mediating resistance to BRAF and MEK inhibitors in models of BRAFV600E and NRAS mutant melanoma...
January 27, 2017: Oncotarget
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