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Cancer and immune

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https://www.readbyqxmd.com/read/28431250/nuclear-proximity-of-mtr4-to-rna-exosome-restricts-dna-mutational-asymmetry
#1
Junghyun Lim, Pankaj Kumar Giri, David Kazadi, Brice Laffleur, Wanwei Zhang, Veronika Grinstein, Evangelos Pefanis, Lewis M Brown, Erik Ladewig, Ophélie Martin, Yuling Chen, Raul Rabadan, François Boyer, Gerson Rothschild, Michel Cogné, Eric Pinaud, Haiteng Deng, Uttiya Basu
The distribution of sense and antisense strand DNA mutations on transcribed duplex DNA contributes to the development of immune and neural systems along with the progression of cancer. Because developmentally matured B cells undergo biologically programmed strand-specific DNA mutagenesis at focal DNA/RNA hybrid structures, they make a convenient system to investigate strand-specific mutagenesis mechanisms. We demonstrate that the sense and antisense strand DNA mutagenesis at the immunoglobulin heavy chain locus and some other regions of the B cell genome depends upon localized RNA processing protein complex formation in the nucleus...
April 20, 2017: Cell
https://www.readbyqxmd.com/read/28430973/biological-functions-of-fucose-in-mammals
#2
Michael Schneider, Esam Al-Shareffi, Robert S Haltiwanger
Fucose is a 6-deoxy hexose in the L-configuration found in a large variety of different organisms. In mammals, fucose is incorporated into N-glycans, O-glycans and glycolipids by thirteen fucosyltransferases, all of which utilize the nucleotide charged form, GDP-fucose, to modify targets. Three of the fucosyltransferases, FUT8, FUT12/POFUT1, and FUT13/POFUT2, are essential for proper development in mice. Fucose modifications have also been implicated in many other biological functions including immunity and cancer...
April 18, 2017: Glycobiology
https://www.readbyqxmd.com/read/28430970/helicobacter-pylori-outer-membrane-vesicles-inhibit-human-t-cell-responses-via-induction-of-monocyte-cox-2-expression
#3
Barry D Hock, Judith L McKenzie, Jacqueline I Keenan
The modulation of T cell responses by Helicobacter pylori is thought to potentiate both H. pylori persistence and development of gastric pathologies including cancer. Release of outer membrane vesicles (OMV) by H. pylori provides a potential vehicle for modulation of the immune system. Although OMV are thought to have T cell suppressive activity this has not yet been demonstrated. Their suppressive activity was investigated in this study using the responses of peripheral blood mononuclear cells (PBMC) to T cell stimuli as a readout...
April 18, 2017: Pathogens and Disease
https://www.readbyqxmd.com/read/28430654/alpha-ketoglutarate-suppresses-the-nf-%C3%AE%C2%BAb-mediated-inflammatory-pathway-and-enhances-the-pxr-regulated-detoxification-pathway
#4
Liuqin He, Huan Li, Niu Huang, Xihong Zhou, Junquan Tian, Tiejun Li, Jing Wu, Yanan Tian, Yulong Yin, Kang Yao
Alpha-ketoglutarate (AKG) is a critical nutritional factor in the maintenance of intestinal homeostasis. However, the relative mechanism of AKG has not been well understood. It was recently shown that the interaction between nuclear factor kappa B (NF-κB)-mediated inflammatory pathway and pregnane X receptor (PXR)-regulated detoxification pathway is a check and balance mechanism for keeping the homeostatic state of the intestine, preventing the onset of intestinal inflammation which may lead to cancer. In the current study we used lipopolysaccharide (LPS)-challenged piglet and intestinal porcine epithelial cells-J2 models to investigate the effects of dietary AKG supplementation on the intestinal immune system and PXR regulated target expression...
April 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430646/immunotherapeutic-target-expression-on-breast-tumors-can-be-amplified-by-hormone-receptor-antagonism-a-novel-strategy-for-enhancing-efficacy-of-targeted-immunotherapy
#5
Ritika Jaini, Matthew G Loya, Charis Eng
Immunotherapy has historically been successful in highly antigenic tumors but has shown limited therapeutic efficacy in non-antigenic tumors such as breast cancers. Our previous studies in autoimmunity have demonstrated that increased antigen load within a tissue enhances immune reactivity against it. We therefore hypothesized that enhancing expression of target proteins on breast tumors can increase efficacy of targeted immunotherapy. We hypothesized that antagonism of the estrogen receptor (ER) can increase expression of targets that are hormonally regulated and facilitate enhanced tumor recognition by targeted immunotherapy...
March 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430642/immunocompetent-mouse-allograft-models-for-development-of-therapies-to-target-breast-cancer-metastasis
#6
Yuan Yang, Howard H Yang, Ying Hu, Peter H Watson, Huaitian Liu, Thomas R Geiger, Miriam R Anver, Diana C Haines, Philip Martin, Jeffrey E Green, Maxwell P Lee, Kent W Hunter, Lalage M Wakefield
Effective drug development to combat metastatic disease in breast cancer would be aided by the availability of well-characterized preclinical animal models that (a) metastasize with high efficiency, (b) metastasize in a reasonable time-frame, (c) have an intact immune system, and (d) capture some of the heterogeneity of the human disease. To address these issues, we have assembled a panel of twelve mouse mammary cancer cell lines that can metastasize efficiently on implantation into syngeneic immunocompetent hosts...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430641/the-regulation-of-%C3%AE-catenin-activity-and-function-in-cancer-therapeutic-opportunities
#7
REVIEW
Shuang Shang, Fang Hua, Zhuo-Wei Hu
Wnt/β-catenin signaling is an evolutionarily conserved and versatile pathway that is known to be involved in embryonic development, tissue homeostasis and a wide variety of human diseases. Aberrant activation of this pathway gives rise to the accumulation of β-catenin in the nucleus and promotes the transcription of many oncogenes such as c-Myc and CyclinD-1. As a result, it contributes to carcinogenesis and tumor progression of several cancers, including colon cancer, hepatocellular carcinoma, pancreatic cancer, lung cancer and ovarian cancer...
February 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28430349/prognostic-significance-of-infiltrating-immune-cell-subtypes-in-invasive-ductal-carcinoma-of-the-breast
#8
Yangmei Xu, Suzhen Lan, Qiuhong Zheng
PURPOSE: To explore the correlation between tumor-infiltrating immune cell subsets and breast cancer prognosis. MATERIALS AND METHODS: Specimens of 102 patients with invasive ductal carcinoma of the breast were analyzed for immune-related markers (CD8, CD20, FOXP3 and CD68). The number of positive cells in the 3 most highly stained intratumoral stroma areas of the primary tumor was counted. The mean number was calculated and used to divide patients into 2 groups for each marker (CD8-high/CD8-low, CD20-high/CD20-low, FOXP3-high/FOXP3-low, and CD68-high/CD68-low)...
April 20, 2017: Tumori
https://www.readbyqxmd.com/read/28430160/subverting-host-cell-p21-activated-kinase-a-case-of-convergent-evolution-across-pathogens
#9
REVIEW
Simona John Von Freyend, Terry Kwok-Schuelein, Hans Netter, Gholamreza Haqshenas, Jean-Philippe Semblat, Christian Doerig
Intracellular pathogens have evolved a wide range of strategies to not only escape from the immune systems of their hosts, but also to directly exploit a variety of host factors to facilitate the infection process. One such strategy is to subvert host cell signalling pathways to the advantage of the pathogen. Recent research has highlighted that the human serine/threonine kinase PAK, or p21-activated kinase, is a central component of host-pathogen interactions in many infection systems involving viruses, bacteria, and eukaryotic pathogens...
April 21, 2017: Pathogens
https://www.readbyqxmd.com/read/28430133/nuclear-molecular-imaging-strategies-in-immune-checkpoint-inhibitor-therapy
#10
REVIEW
Kasper F Guldbrandsen, Helle W Hendel, Seppo W Langer, Barbara M Fischer
Immune checkpoint inhibitor therapy (ICT) is a new treatment strategy developed for the treatment of cancer. ICT inhibits pathways known to downregulate the innate immune response to cancer cells. These drugs have been shown to be effective in the treatment of a variety of cancers, including metastatic melanoma and lung cancer. Challenges in response evaluation of patients in ICT have risen as immune related side effects and immune cell infiltration may be confused with progressive disease. Furthermore, the timing of the evaluation scan may be challenged by relatively slow responses...
April 21, 2017: Diagnostics
https://www.readbyqxmd.com/read/28429788/the-hsp90-chaperone-machinery
#11
REVIEW
Florian H Schopf, Maximilian M Biebl, Johannes Buchner
The heat shock protein 90 (HSP90) chaperone machinery is a key regulator of proteostasis under both physiological and stress conditions in eukaryotic cells. As HSP90 has several hundred protein substrates (or 'clients'), it is involved in many cellular processes beyond protein folding, which include DNA repair, development, the immune response and neurodegenerative disease. A large number of co-chaperones interact with HSP90 and regulate the ATPase-associated conformational changes of the HSP90 dimer that occur during the processing of clients...
April 21, 2017: Nature Reviews. Molecular Cell Biology
https://www.readbyqxmd.com/read/28429765/repolarizing-macrophages-improves-breast-cancer-therapy
#12
Luca Cassetta, Jeffrey W Pollard
Tumor-associated macrophages (TAMs) contribute to breast cancer progression and dissemination; TAM-targeting strategies aimed at their reprogramming show promising preclinical results. In a new report Guerriero and colleagues demonstrate that a novel HDAC Class IIa inhibitor, TMP195, can reprogram monocytes and macrophages in the tumor into cells able to sustain a robust CD8 T cell-mediated anti-tumoral immune response.
April 21, 2017: Cell Research
https://www.readbyqxmd.com/read/28429331/the-correlation-of-cd19%C3%A2-%C3%A2-cd24%C3%A2-%C3%A2-cd38%C3%A2-%C3%A2-b-cells-and-other-clinicopathological-variables-with-the-proportion-of-circulating-tregs-in-breast-cancer-patients
#13
Mohammad Kazzem Gheybi, Shokrollah Farrokhi, Mohammad Reza Ravanbod, Afshin Ostovar, Valiollah Mehrzad, Pardis Nematollahi
BACKGROUND: T regulatory cells (Tregs) are known to negatively control immune response. The frequency of these cells was inversely correlated with clinical outcomes of breast cancer. CD19(+)CD24(hi)CD38(hi) cells also play a critical role in inflammation and autoimmune disease. However, their function in tumor immune response is less studied. In this study we aimed to determine the role of CD19(+)CD24(hi)CD38(hi) cells and some other clinicopathological variables in increasing the proportion of Tregs in breast cancer patients...
April 20, 2017: Breast Cancer: the Journal of the Japanese Breast Cancer Society
https://www.readbyqxmd.com/read/28429196/expression-of-programmed-cell-death-protein-1-by-tumor-infiltrating-lymphocytes-and-tumor-cells-is-associated-with-advanced-tumor-stage-in-patients-with-esophageal-adenocarcinoma
#14
Dagmar Kollmann, Desislava Ignatova, Julia Jedamzik, Yun-Tsan Chang, Gerd Jomrich, Matthias Paireder, Ivan Kristo, Dmitry Kazakov, Michal Michal, Antonio Cozzio, Wolfram Hoetzenecker, Tobias Schatton, Reza Asari, Matthias Preusser, Emmanuella Guenova, Sebastian F Schoppmann
BACKGROUND: Despite recent advances in the therapy for adenocarcinoma of the esophagogastric junction (AEG), overall prognosis remains poor. Programmed cell death protein 1 (PD1) is a co-inhibitory receptor primarily expressed by T-cells. Tumor cells can escape anticancer immune responses by triggering the PD1 pathway. Moreover, PD1 receptor engagement on cancer cells may trigger tumor-intrinsic growth signals. This study aimed to evaluate the potential clinical relevance of PD1 expression by tumor-infiltrating lymphocytes (TILs) and cancer cells in the AEG...
April 20, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28429012/correction-identifying-the-optimal-anticancer-targets-from-the-landscape-of-a-cancer-immunity-interaction-network
#15
Chunhe Li
Correction for 'Identifying the optimal anticancer targets from the landscape of a cancer-immunity interaction network' by Chunhe Li et al., Phys. Chem. Chem. Phys., 2017, 19, 7642-7651.
April 21, 2017: Physical Chemistry Chemical Physics: PCCP
https://www.readbyqxmd.com/read/28428965/natural-killer-cells-in-the-orchestration-of-chronic-inflammatory-diseases
#16
REVIEW
Luca Parisi, Barbara Bassani, Marco Tremolati, Elisabetta Gini, Giampietro Farronato, Antonino Bruno
Inflammation, altered immune cell phenotype, and functions are key features shared by diverse chronic diseases, including cardiovascular, neurodegenerative diseases, diabetes, metabolic syndrome, and cancer. Natural killer cells are innate lymphoid cells primarily involved in the immune system response to non-self-components but their plasticity is largely influenced by the pathological microenvironment. Altered NK phenotype and function have been reported in several pathological conditions, basically related to impaired or enhanced toxicity...
2017: Journal of Immunology Research
https://www.readbyqxmd.com/read/28428947/update-on-programmed-death-1-and-programmed-death-ligand-1-inhibition-in-the-treatment-of-advanced-or-metastatic-non-small-cell-lung-cancer
#17
REVIEW
Marco A J Iafolla, Rosalyn A Juergens
PURPOSE: Non-small-cell lung cancer (NSCLC) has a large worldwide prevalence with a high mortality rate. Chemotherapy has offered modest improvements in survival over the past two decades. Immune checkpoint modulation with programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibition has shown the promise of changing the future landscape of cancer therapy. This update reviews recent advances in the treatment of NSCLC with immune checkpoint modulation. METHODS: Publications and proceedings were identified from searching PubMed and proceedings from the annual meetings of the American Society of Clinical Oncology, European Society for Medical Oncology, and European Lung Cancer Conference...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/28428887/differential-intratumoral-distributions-of-cd8-and-cd163-immune-cells-as-prognostic-biomarkers-in-breast-cancer
#18
Sotirios P Fortis, Michael Sofopoulos, Nectaria N Sotiriadou, Christoforos Haritos, Christoforos K Vaxevanis, Eleftheria A Anastasopoulou, Nicole Janssen, Niki Arnogiannaki, Alexandros Ardavanis, Graham Pawelec, Sonia A Perez, Constantin N Baxevanis
BACKGROUND: Tumor immune cell infiltrates are essential in hindering cancer progression and may complement the TNM classification. CD8+ and CD163+ cells have prognostic impact in breast cancer but their spatial heterogeneity has not been extensively explored in this type of cancer. Here, their potential as prognostic biomarkers was evaluated, depending on their combined densities in the tumor center (TC) and the tumor invasive margin (IM). METHODS: CD8+ and CD163+ cells were quantified by immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) tumor tissue samples from a cohort totaling 162 patients with histologically-confirmed primary invasive non-metastatic ductal breast cancer diagnosed between 2000 and 2015...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428886/vaccination-with-inhibin-%C3%AE-provides-effective-immunotherapy-against-testicular-stromal-cell-tumors
#19
Robert Aguilar, Justin M Johnson, Patrick Barrett, Vincent K Tuohy
BACKGROUND: Testicular cancer is the most common male neoplasm occurring in men between the ages of 20 and 34. Although germ-line testicular tumors respond favorably to current standard of care, testicular stromal cell (TSC) tumors derived from Sertoli cells or Leydig cells often fail to respond to chemotherapy or radiation therapy and have a 5-year overall survival significantly lower than the more common and more treatable germ line testicular tumors. METHODS: To improve outcomes for TSC cancer, we have developed a therapeutic vaccine targeting inhibin-α, a protein produced by normal Sertoli and Leydig cells of the testes and expressed in the majority of TSC tumors...
2017: Journal for Immunotherapy of Cancer
https://www.readbyqxmd.com/read/28428884/phase-i-clinical-trial-of-combination-imatinib-and-ipilimumab-in-patients-with-advanced-malignancies
#20
Matthew J Reilley, Ann Bailey, Vivek Subbiah, Filip Janku, Aung Naing, Gerald Falchook, Daniel Karp, Sarina Piha-Paul, Apostolia Tsimberidou, Siqing Fu, JoAnn Lim, Stacie Bean, Allison Bass, Sandra Montez, Luis Vence, Padmanee Sharma, James Allison, Funda Meric-Bernstam, David S Hong
BACKGROUND: Imatinib mesylate can induce rapid tumor regression, increase tumor antigen presentation, and inhibit tumor immunosuppressive mechanisms. CTLA-4 blockade and imatinib synergize in mouse models to reduce tumor volume via intratumoral accumulation of CD8+ T cells. We hypothesized that imatinib combined with ipilimumab would be tolerable and may synergize in patients with advanced cancer. METHODS: Primary objective of the dose-escalation study (3 + 3 design) was to establish the maximum tolerated dose (MTD) and recommended phase II dose...
2017: Journal for Immunotherapy of Cancer
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