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Tumor priming

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https://www.readbyqxmd.com/read/28801234/dendritic-cells-but-not-macrophages-sense-tumor-mitochondrial-dna-for-cross-priming-through-signal-regulatory-protein-%C3%AE-signaling
#1
Meng Michelle Xu, Yang Pu, Dali Han, Yaoyao Shi, Xuezhi Cao, Hua Liang, Xiang Chen, Xiao-Dong Li, Liufu Deng, Zhijian J Chen, Ralph R Weichselbaum, Yang-Xin Fu
Inhibition of cytosolic DNA sensing represents a strategy that tumor cells use for immune evasion, but the underlying mechanisms are unclear. Here we have shown that CD47-signal regulatory protein α (SIRPα) axis dictates the fate of ingested DNA in DCs for immune evasion. Although macrophages were more potent in uptaking tumor DNA, increase of DNA sensing by blocking the interaction of SIRPα with CD47 preferentially occurred in dendritic cells (DCs) but not in macrophages. Mechanistically, CD47 blockade enabled the activation of NADPH oxidase NOX2 in DCs, which in turn inhibited phagosomal acidification and reduced the degradation of tumor mitochondrial DNA (mtDNA) in DCs...
August 2, 2017: Immunity
https://www.readbyqxmd.com/read/28796808/pd-l1-and-gastric-cancer-prognosis-a-systematic-review-and-meta-analysis
#2
Lihu Gu, Manman Chen, Dongyu Guo, Hepan Zhu, Wenchao Zhang, Junhai Pan, Xin Zhong, Xinlong Li, Haoran Qian, Xianfa Wang
The expression of Programmed cell Death Ligand 1 (PD-L1) is observed in many malignant tumors and is associated with poor prognosis including Gastric Cancer (GC). The relationship between PD-L1 expression and prognosis, however, is controversial in GC. This paper purports to use a meta-analysis to investigate the relationship between PD-L1 expression and prognosis in GC. For this study, the following databases were searched for articles published from June 2003 until February 2017: PubMed, EBSCO, Web of Science and Cochrane Library...
2017: PloS One
https://www.readbyqxmd.com/read/28791656/egfr-as-a-target-for-glioblastoma-treatment-an-unfulfilled-promise
#3
Manfred Westphal, Cecile L Maire, Katrin Lamszus
The receptor for epidermal growth factor (EGFR) is a prime target for cancer therapy across a broad variety of tumor types. As it is a tyrosine kinase, small molecule tyrosine kinase inhibitors (TKIs) targeting signal transduction, as well as monoclonal antibodies against the EGFR, have been investigated as anti-tumor agents. However, despite the long-known enigmatic EGFR gene amplification and protein overexpression in glioblastoma, the most aggressive intrinsic human brain tumor, the potential of EGFR as a target for this tumor type has been unfulfilled...
August 8, 2017: CNS Drugs
https://www.readbyqxmd.com/read/28791020/p2x7-receptor-induces-tumor-necrosis-factor-%C3%AE-converting-enzyme-activation-and-release-to-boost-tnf-%C3%AE-production
#4
Maria Barberà-Cremades, Ana I Gómez, Alberto Baroja-Mazo, Laura Martínez-Alarcón, Carlos M Martínez, Carlos de Torre-Minguela, Pablo Pelegrín
Tumor necrosis factor (TNF)-α is a major pro-inflammatory cytokine produced in response to toll-like receptor stimulation. TNF-α release is controlled by the activity of TNF-α converting enzyme (TACE) that cut membrane-bound TNF-α to shed its ectodomain as a soluble cytokine. The purinergic receptor P2X ligand-gated ion channel 7 (P2X7) is activated in response to elevated concentrations of extracellular ATP and induces different pro-inflammatory pathways in macrophages to establish an inflammatory response...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28780376/retinoic-acid-induction-of-cd1d-expression-primes-chronic-lymphocytic-leukemia-b-cells-for-killing-by-cd8-invariant-natural-killer-t-cells
#5
Yasmeen G Ghnewa, Vincent P O'Reilly, Elisabeth Vandenberghe, Paul V Browne, Anthony M McElligott, Derek G Doherty
Invariant natural killer T (iNKT) cells are cytotoxic T cells that respond to glycolipid antigens presented by CD1d. Therapeutic activation of iNKT cells with α-galactosylceramide (α-GalCer) can prevent and reverse tumor growth in mice and clinical trials involving α-GalCer-stimulated iNKT cells are ongoing in humans. B cells express CD1d, however, we show that CD1d expression is reduced on B cells from patients with chronic lymphocytic leukemia (CLL). B cells from CLL patients pulsed with α-GalCer failed to stimulate cytolytic degranulation by iNKT cell lines, but could present the more potent glycolipid analogue, 7DW8-5...
August 3, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28776423/immunomodulatory-effects-of-current-cancer-treatment-and-the-consequences-for-follow-up-immunotherapeutics
#6
Meghan J Mooradian, Ryan J Sullivan
Recent advances in the use of immunotherapy have led to historic advancements in the field of oncology. Checkpoint inhibitors have demonstrated significant effectiveness against a broadening range of cancers. However, despite the success of antibodies against the immune regulators, CTLA4 and PD-L1/PD-1, only a subset of patients will have a durable response to these therapies, which implies that a broader view of cancer immunity is required. It is becoming increasingly apparent that combination therapy to target multiple events in the cancer-immunity cycle is needed and could potentially extend the benefit of immunotherapy to a larger population...
August 4, 2017: Future Oncology
https://www.readbyqxmd.com/read/28772211/autophagy-as-a-potential-therapeutic-target-during-epithelial-to-mesenchymal-transition-in-renal-cell-carcinoma-an-in-vitro-study
#7
Mamta Singla, Shalmoli Bhattacharyya
Cancer progression toward invasive and metastatic disease is aided by reactivation of epithelial-mesenchymal transition (EMT), involving transdifferentiation of epithelial cells into mesenchymal phenotype. This leads to increased migratory and stem cell-like features in the cells. These EMT cells are more resistant to chemotherapy and it is hypothesized that the phenomenon of autophagy induces resistance, providing a survival strategy for cells. In the present study, we induced EMT-like phenotype in renal carcinoma cells and identified corresponding higher autophagy flux in these cells...
July 31, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28763347/ex-vivo-induction-of-multiple-myeloma-specific-immune-responses-by-monocyte-derived-dendritic-cells-following-stimulation-by-whole-tumor-antigen-of-autologous-myeloma-cells
#8
Spyridoula Vasileiou, Ioannis Baltadakis, Sosanna Delimpasi, Maria-Helena Karatza, Konstantinos Liapis, Maria Garofalaki, Eirini Tziotziou, Zoe Poulopoulou, Dimitri Karakasis, Nicholas Harhalakis
The introduction of novel agents has significantly expanded treatment options for multiple myeloma (MM), albeit long-term disease control cannot be achieved in the majority of patients. Vaccination with MM antigen-loaded dendritic cells (DCs) represents an alternative strategy that is currently being explored. The aim of this study was to assess the immunogenic potential of ex vivo-generated monocyte-derived DCs (moDCs), following stimulation with the whole-antigen array of autologous myeloma cells (AMC). MoDCs were loaded with antigens of myeloma cells by 2 different methods: phagocytosis of apoptotic bodies from γ-irradiated AMC, or transfection with AMC total RNA by square-wave electroporation...
July 31, 2017: Journal of Immunotherapy
https://www.readbyqxmd.com/read/28755541/vaccines-targeting-helper-t-cells-for-cancer-immunotherapy
#9
REVIEW
Marit Melssen, Craig L Slingluff
There are compelling arguments for designing cancer vaccines specifically to induce CD4(+) helper T cell responses. Recent studies highlight the crucial role of proliferating, activated effector memory Th1 CD4(+) T cells in effective antitumor immunity and reveal that CD4(+) T cells induce more durable immune-mediated tumor control than CD8(+) T cells. CD4(+) T cells promote antitumor immunity by numerous mechanisms including enhancing antigen presentation, co-stimulation, T cell homing, T cell activation, and effector function...
July 26, 2017: Current Opinion in Immunology
https://www.readbyqxmd.com/read/28752860/enhancing-the-cytotoxicity-of-chemoradiation-with-radiation-guided-delivery-of-anti-mgmt-morpholino-oligonucleotides-in-non-methylated-solid-tumors
#10
P Ambady, Y J Wu, J M Walker, C Kersch, M A Pagel, R L Woltjer, R Fu, L L Muldoon, E A Neuwelt
The DNA repair enzyme O(6)-methylguanine DNA methyltransferase (MGMT) is epigenetically silenced in some tumors by MGMT gene promoter methylation. MGMT-hypermethylated solid tumors have enhanced susceptibility to the cytotoxic effects of alkylating chemotherapy such as temozolomide, compared with non-methylated tumors. In glioblastoma, subjects with MGMT hypermethylation have significantly longer survival rates after chemoradiotherapy. We report the first successful use of a non-ablative dose of ionizing radiation to prime human cancer cells to enhance the uptake of unmodified anti-MGMT morpholino oligonucleotide (AMON) sequences...
July 28, 2017: Cancer Gene Therapy
https://www.readbyqxmd.com/read/28751442/towards-precision-radiotherapy-for-use-with-immune-checkpoint-blockers
#11
Claire Vanpouille-Box, Silvia C Formenti, Sandra Demaria
The first evidence that radiation therapy (RT) enhances the efficacy of immune checkpoint blockers (ICBs) was obtained a dozen years ago in a mouse model of metastatic carcinoma refractory to anti-CTLA-4 treatment. At the time, ICBs had just entered clinical testing, an endeavor that culminated in 2011 with the approval of the first anti-CTLA-4 antibody for use in metastatic melanoma patients (ipilimumab). Thereafter, some patients progressing on ipilimumab showed systemic responses only upon receiving radiation to one lesion, confirming clinically the pro-immunogenic effects of radiation...
July 27, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28746882/a-landscape-of-therapeutic-cooperativity-in-kras-mutant-cancers-reveals-principles-for-controlling-tumor-evolution
#12
Grace R Anderson, Peter S Winter, Kevin H Lin, Daniel P Nussbaum, Merve Cakir, Elizabeth M Stein, Ryan S Soderquist, Lorin Crawford, Jim C Leeds, Rachel Newcomb, Priya Stepp, Catherine Yip, Suzanne E Wardell, Jennifer P Tingley, Moiez Ali, Mengmeng Xu, Meagan Ryan, Shannon J McCall, Autumn J McRee, Christopher M Counter, Channing J Der, Kris C Wood
Combinatorial inhibition of effector and feedback pathways is a promising treatment strategy for KRAS mutant cancers. However, the particular pathways that should be targeted to optimize therapeutic responses are unclear. Using CRISPR/Cas9, we systematically mapped the pathways whose inhibition cooperates with drugs targeting the KRAS effectors MEK, ERK, and PI3K. By performing 70 screens in models of KRAS mutant colorectal, lung, ovarian, and pancreas cancers, we uncovered universal and tissue-specific sensitizing combinations involving inhibitors of cell cycle, metabolism, growth signaling, chromatin regulation, and transcription...
July 25, 2017: Cell Reports
https://www.readbyqxmd.com/read/28744322/visualization-of-tumor-immune-interaction-target-specific-imaging-of-s100a8-a9-reveals-pre-metastatic-niche-establishment
#13
Michel Eisenblaetter, Fabian Flores-Borja, Jae Jin Lee, Christina Wefers, Hannah Smith, Rebekka Hueting, Margaret S Cooper, Philip J Blower, Dominic Patel, Manuel Rodriguez-Justo, Hanna Milewicz, Thomas Vogl, Johannes Roth, Andrew Tutt, Tobias Schaeffter, Tony Ng
Background Systemic cancer spread is preceded by the establishment of a permissive microenvironment in the target tissue of metastasis - the premetastatic niche. As crucial players in establishment of the pre-metastatic niche, myeloid derived suppressor cells (MDSC) release S100A8/A9, an exosomal protein that contributes to metastasis, angiogenesis, and immune suppression. We report the application of antibody-based single-photon emission computed tomography (SPECT) for detection of S100A8/A9 in vivo as an imaging marker for pre-metastatic tissue priming...
2017: Theranostics
https://www.readbyqxmd.com/read/28743531/metabolic-regulation-of-glioma-stem-like-cells-in-the-tumor-micro-environment
#14
Tom M Thomas, John S Yu
Cancer metabolism has emerged as one of the most interesting old ideas being revisited from a new perspective. In the early 20th century Otto Warburg declared metabolism the prime cause in a disease of many secondary causes, and this statement seems more prescient in view of modern expositions into the true nature of tumor evolution. As the complexity of tumor heterogeneity becomes more clear from a genetic perspective, it is important to consider the inevitably heterogeneous metabolic components of the tumor and the tumor microenvironment...
July 22, 2017: Cancer Letters
https://www.readbyqxmd.com/read/28741502/immune-priming-of-the-tumor-microenvironment-by-radiation
#15
REVIEW
Wen Jiang, Charles K Chan, Irving L Weissman, Betty Y S Kim, Stephen M Hahn
Ionizing irradiation can induce a multitude of alterations within the tumor microenvironment. Unlike targeted therapies, radiation delivered to the tumor bed can prompt phenotypic changes in both normal stromal and cancer cells, leading to molecular and physiological alterations within the tumor microenvironment. These environmental modulations directly influence the degree of immunogenicity of the tumor microenvironment and may ultimately affect tumor responsiveness to cancer immunotherapies. Here we review the preclinical evidence for tumor microenvironment-mediated immune suppression and how radiation can modulate immune properties within a tumor...
November 2016: Trends in Cancer
https://www.readbyqxmd.com/read/28740213/functional-and-transcriptomic-characterization-of-peritoneal-immune-modulation-by-addition-of-alanyl-glutamine-to-dialysis-fluid
#16
Rebecca Herzog, Lilian Kuster, Julia Becker, Tobias Gluexam, Dietmar Pils, Andreas Spittler, Manoj K Bhasin, Seth L Alper, Andreas Vychytil, Christoph Aufricht, Klaus Kratochwill
Peritonitis remains a major cause of morbidity and mortality during chronic peritoneal dialysis (PD). Glucose-based PD fluids reduce immunological defenses in the peritoneal cavity. Low concentrations of peritoneal extracellular glutamine during PD may contribute to this immune deficit. For these reasons we have developed a clinical assay to measure the function of the immune-competent cells in PD effluent from PD patients. We then applied this assay to test the impact on peritoneal immune-competence of PD fluid supplementation with alanyl-glutamine (AlaGln) in 6 patients in an open-label, randomized, crossover pilot trial (EudraCT 2012-004004-36), and related the functional results to transcriptome changes in PD effluent cells...
July 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28736250/change-in-prostate-cancer-presentation-coinciding-with-uspstf-screening-recommendations-at-a-community-based-urology-practice
#17
Franklin D Gaylis, Jae E Choi, Zachary Hamilton, Paul Dato, Edward Cohen, Renee Calabrese, Hilary Prime, Aaron Rosenbaum, Andrew Karim Kader
OBJECTIVE: The benefits of prostate-specific antigen (PSA)-based prostate cancer screening are controversial. We sought to determine the change in prostate cancer presentation coinciding with the release of the United States Preventative Services Task Force recommendations against screening in a high-volume community-based urology practice. METHODS: Characteristics of men presenting for an elevated PSA at a community urology practice from August 2011 to August 2015 were queried from a prospectively collected database...
July 20, 2017: Urologic Oncology
https://www.readbyqxmd.com/read/28735000/application-of-pharmacometrics-and-quantitative-systems-pharmacology-to-cancer-therapy-the-example-of-luminal-a-breast-cancer
#18
REVIEW
Brett Fleisher, Ashley N Brown, Sihem Ait-Oudhia
Breast cancer (BC) is the most common cancer in women, and the second most frequent cause of cancer-related deaths in women worldwide. It is a heterogeneous disease composed of multiple subtypes with distinct morphologies and clinical implications. Quantitative systems pharmacology (QSP) is an emerging discipline bridging systems biology with pharmacokinetics (PK) and pharmacodynamics (PD) leveraging the systematic understanding of drugs' efficacy and toxicity. Despite numerous challenges in applying computational methodologies for QSP and mechanism-based PK/PD models to biological, physiological, and pharmacological data, bridging these disciplines has the potential to enhance our understanding of complex disease systems such as BC...
July 19, 2017: Pharmacological Research: the Official Journal of the Italian Pharmacological Society
https://www.readbyqxmd.com/read/28732046/qualitative-differences-in-cellular-immunogenicity-elicited-by-hepatitis-c-virus-t-cell-vaccines-employing-prime-boost-regimens
#19
Wendy G Tan, Iryna Zubkova, Alla Kachko, Frances Wells, Heiko Adler, Gerd Sutter, Marian E Major
T-cell based vaccines have been considered as attractive candidates for prevention of hepatitis C virus (HCV) infections. In this study we compared the magnitude and phenotypic characteristics of CD8+ T-cells induced by three commonly used viral vectors, Adenovirus-5 (Ad5), Vaccinia virus (VV) and Modified Vaccinia Ankara (MVA) expressing the HCV NS3/4A protein. C57/BL6 mice were primed with DNA expressing NS3/4A and boosted with each of the viral vectors in individual groups of mice. We then tracked the vaccine-induced CD8+ T-cell responses using pentamer binding and cytokine production analysis...
2017: PloS One
https://www.readbyqxmd.com/read/28731945/the-changing-paradigm-of-radiotherapy-in-the-elderly-population
#20
Myer Raphael Pfeffer, Philip Blumenfeld
There is increasing awareness of the special needs for care of the elderly cancer patient. Newer precise conformal radiotherapy techniques allow the safe delivery of higher doses of radiotherapy to the target tumor while reducing the dose to surrounding critical organs. This has led to a shortening of radiotherapy protocols for both curative and palliative indications. We review these novel techniques and protocols and the published clinical studies that include elderly patients treated with these techniques...
July 2017: Cancer Journal
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