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https://www.readbyqxmd.com/read/29342309/prognostic-power-of-a-tumor-differentiation-gene-signature-for-bladder-urothelial-carcinomas
#1
Qianxing Mo, Fotis Nikolos, Fengju Chen, Zoe Tramel, Yu-Cheng Lee, Kazukuni Hayashi, Jing Xiao, Jianjun Shen, Keith Syson Chan
Background: Muscle-invasive bladder cancers (MIBCs) cause approximately 150 000 deaths per year worldwide. Survival for MIBC patients is heterogeneous, with no clinically validated molecular markers that predict clinical outcome. Non-MIBCs (NMIBCs) generally have favorable outcome; however, a portion progress to MIBC. Hence, development of a prognostic tool that can guide decision-making is crucial for improving clinical management of bladder urothelial carcinomas. Methods: Tumor grade is defined by pathologic evaluation of tumor cell differentiation, and it often associates with clinical outcome...
January 12, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/29342134/chromosomal-instability-drives-metastasis-through-a-cytosolic-dna-response
#2
Samuel F Bakhoum, Bryan Ngo, Ashley M Laughney, Julie-Ann Cavallo, Charles J Murphy, Peter Ly, Pragya Shah, Roshan K Sriram, Thomas B K Watkins, Neil K Taunk, Mercedes Duran, Chantal Pauli, Christine Shaw, Kalyani Chadalavada, Vinagolu K Rajasekhar, Giulio Genovese, Subramanian Venkatesan, Nicolai J Birkbak, Nicholas McGranahan, Mark Lundquist, Quincey LaPlant, John H Healey, Olivier Elemento, Christine H Chung, Nancy Y Lee, Marcin Imielenski, Gouri Nanjangud, Dana Pe'er, Don W Cleveland, Simon N Powell, Jan Lammerding, Charles Swanton, Lewis C Cantley
Chromosomal instability is a hallmark of cancer that results from ongoing errors in chromosome segregation during mitosis. Although chromosomal instability is a major driver of tumour evolution, its role in metastasis has not been established. Here we show that chromosomal instability promotes metastasis by sustaining a tumour cell-autonomous response to cytosolic DNA. Errors in chromosome segregation create a preponderance of micronuclei whose rupture spills genomic DNA into the cytosol. This leads to the activation of the cGAS-STING (cyclic GMP-AMP synthase-stimulator of interferon genes) cytosolic DNA-sensing pathway and downstream noncanonical NF-κB signalling...
January 17, 2018: Nature
https://www.readbyqxmd.com/read/29341292/amniotic-fluid-stem-cell-exosomes-therapeutic-perspective
#3
Francesca Beretti, Manuela Zavatti, Francesca Casciaro, Giuseppina Comitini, Fabrizia Franchi, Veronica Barbieri, Giovanni B La Sala, Tullia Maraldi
It is widely accepted that the therapeutic potential of stem cells can be largely mediated by paracrine factors, also included into exosomes. Thus, stem cell-derived exosomes represent a major therapeutic option in regenerative medicine avoiding, if compared to stem cells graft, abnormal differentiation and tumor formation. Exosomes derived from mesenchymal stem cells (MSC) induce damaged tissue repair, and can also exert immunomodulatory effects on the differentiation, activation and function of different lymphocytes...
January 16, 2018: BioFactors
https://www.readbyqxmd.com/read/29340893/a-prospective-study-of-humoral-and-cellular-immune-responses-to-hepatitis-b-vaccination-in-habitual-marijuana-smokers
#4
Sylvia M Kiertscher, Pallavi R Gangalum, Grace Ibrahim, Donald P Tashkin, Michael D Roth
Exposure to Δ9-tetrahydrocannabinol (THC) in vitro and in animal models can significantly impair the differentiation, activation and function of dendritic cells, T cells and B cells. However, studies directly assessing the impact of marijuana smoking on human immunity are lacking. A prospective study of immune responses to a standard hepatitis B vaccination was therefore carried out in a matched cohort of 9 marijuana smokers (MS) and 9 nonsmokers (NS). In addition to their regular marijuana use, MS smoked four marijuana cigarettes in a monitored setting on the day of each vaccination...
January 16, 2018: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/29340698/simultaneous-detection-of-chicken-cytokines-in-plasma-samples-using-the-bio-plex-assay
#5
Jitka Mucksová, Karel Chalupský, Jirí Plachý, Jirí Kalina, Pavla Rachacová, Ondrej Stanek, Pavel Trefil
A chicken multiplex cytokine assay (Bio-Plex) to detect four different cytokines (IL-2, IL-12, IL-10, and interferon gamma) simultaneously in plasma samples was designed. Most standard curves range between 1 to 5 pg/mL and 5,000 pg/mL, except for IFNγ with the range of 50 to 25,000 pg/mL. Such a chicken multiplex assay proved to be fast and reliable, and comparable in sensitivity, accuracy, and reproducibility to conventional enzyme-linked immunosorbent assays. Comparison of the multiplex assay with the ELISA technique using the same clones of detection and capture antibodies resulted in correlation coefficients for all cytokines ranging from 0...
January 11, 2018: Poultry Science
https://www.readbyqxmd.com/read/29339750/a-single-dose-of-modified-vaccinia-ankara-expressing-ebola-virus-like-particles-protects-nonhuman-primates-from-lethal-ebola-virus-challenge
#6
Arban Domi, Friederike Feldmann, Rahul Basu, Nathanael McCurley, Kyle Shifflett, Jackson Emanuel, Michael S Hellerstein, Farshad Guirakhoo, Chiara Orlandi, Robin Flinko, George K Lewis, Patrick W Hanley, Heinz Feldmann, Harriet L Robinson, Andrea Marzi
Ebola virus (EBOV), isolate Makona, was the causative agent of the West African epidemic devastating predominantly Guinea, Liberia and Sierra Leone from 2013-2016. While several experimental vaccine and treatment approaches have been accelerated through human clinical trials, there is still no approved countermeasure available against this disease. Here, we report the construction and preclinical efficacy testing of a novel recombinant modified vaccinia Ankara (MVA)-based vaccine expressing the EBOV-Makona glycoprotein GP and matrix protein VP40 (MVA-EBOV)...
January 16, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29339461/cooperative-immune-suppression-by-escherichia-coli-and-shigella-effector-proteins
#7
Maarten F de Jong, Neal M Alto
The enteric attaching and effacing (A/E) pathogens EHEC and EPEC and invasive pathogens EIEC and Shigella encode Type III secretion systems (T3SS) used to inject effector proteins into human host cells during infection. Among these are a group of effectors required for NF-κB mediated host immune evasion. Recent studies have identified several effector proteins from A/E pathogens and EIEC/Shigella that are involved in suppression of NF-κB and uncovered their cellular and molecular functions. A novel mechanism among these effectors from both groups of pathogens is to coordinate effector function during infection...
January 16, 2018: Infection and Immunity
https://www.readbyqxmd.com/read/29339435/corrected-and-republished-from-the-cop9-signalosome-interacts-with-and-regulates-interferon-regulatory-factor-5-protein-stability
#8
Justyna Korczeniewska, Betsy J Barnes
The transcription factor interferon regulatory factor 5 (IRF5) exerts crucial functions in the regulation of host immunity against extracellular pathogens, DNA damage-induced apoptosis, death receptor signaling, and macrophage polarization. Tight regulation of IRF5 is thus warranted for an efficient response to extracellular stressors and for limiting autoimmune and inflammatory responses. Here we report that the COP9 signalosome (CSN), a general modulator of diverse cellular and developmental processes, associates constitutively with IRF5 and promotes its protein stability...
February 1, 2018: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/29339427/pandemic-paradox-early-life-h2n2-pandemic-influenza-infection-enhanced-susceptibility-to-death-during-the-2009-h1n1-pandemic
#9
Alain Gagnon, Enrique Acosta, Stacey Hallman, Robert Bourbeau, Lisa Y Dillon, Nadine Ouellette, David J D Earn, D Ann Herring, Kris Inwood, Joaquin Madrenas, Matthew S Miller
Recent outbreaks of H5, H7, and H9 influenza A viruses in humans have served as a vivid reminder of the potentially devastating effects that a novel pandemic could exert on the modern world. Those who have survived infections with influenza viruses in the past have been protected from subsequent antigenically similar pandemics through adaptive immunity. For example, during the 2009 H1N1 "swine flu" pandemic, those exposed to H1N1 viruses that circulated between 1918 and the 1940s were at a decreased risk for mortality as a result of their previous immunity...
January 16, 2018: MBio
https://www.readbyqxmd.com/read/29339377/robust-antitumor-responses-result-from-local-chemotherapy-and-ctla-4-blockade
#10
Charlotte E Ariyan, Mary Sue Brady, Robert H Siegelbaum, Jian Hu, Danielle M Bello, Jamie Green, Charles Fisher, Robert A Lefkowitz, Katherine S Panageas, Melissa Pulitzer, Marissa Vignali, Ryan Emerson, Christopher Tipton, Harlan Robins, Taha Merghoub, Jianda Yuan, Achim Jungbluth, Jorge Blando, Padmanee Sharma, Alexander Y Rudensky, Jedd D Wolchok, James P Allison
Clinical responses to immunotherapy have been associated with augmentation of preexisting immune responses, manifested by heightened inflammation in the tumor microenvironment. However, many tumors have a non-inflamed microenvironment, and response rates to immunotherapy in melanoma have been <50%. We approached this problem by utilizing immunotherapy (CTLA-4 blockade) combined with chemotherapy to induce local inflammation. In murine models of melanoma and prostate cancer, the combination of chemotherapy and CTLA-4 blockade induced a shift in the cellular composition of the tumor microenvironment, with infiltrating CD8+ and CD4+ T cells increasing the CD8/Foxp3 T-cell ratio...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29339270/proceedings-from-the-fourth-haploidentical-stem-cell-transplantation-symposium-haplo2016-san-diego-california-december-1-2016
#11
REVIEW
Monzr Al Malki, Richard Jones, Qing Ma, Dean Lee, Yair Reisner, Jeffrey S Miller, Peter Lang, Suradej Hongeng, Parameswaran Hari, Samuel Strober, Jianhua Yu, Richard Maziarz, Domenico Mavilio, Denis-Claude Roy, Chiara Bonini, Richard E Champlin, Ephraim J Fuchs, Stefan O Ciurea
The resurgence of haploidentical stem cell transplantation (HaploSCT) over the last decade is one of the most important advances in the field of hematopoietic stem cell transplantation (HSCT). The modified platforms of T cell depletion either ex vivo (CD34+ selection, 'mega-dose' of purified CD34+ cells, or selective depletion of T-cells) or newer platforms of in vivo depletion of T cells, with either post-transplant high-dose cyclophosphamide (PTCy) or intensified immune suppression, have contributed to better outcomes, with survival that is similar to HLA-match donor transplantation...
January 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29339210/the-nlrp3-inflammasome-role-in-metabolic-disorders-and-regulation-by-metabolic-pathways
#12
Danlu Jiang, Sheng Chen, Ruyu Sun, Xue Zhang, Di Wang
Inflammasomes are large multimolecular complexes present in the cytosol of stimulated immune cells; they mediate the activation of caspase-1, leading to cellular pyroptosis. So far, a variety of studies on inflammasomes have emerged, and the best-studied is the NLRP3 inflammasome that is involved in many inflammatory responses. Furthermore, its relationship with metabolism is gaining increasing attention in this field. In this review, we discuss the importance of the NLRP3 inflammasome in metabolic disorders and its close association with metabolic pathways...
January 12, 2018: Cancer Letters
https://www.readbyqxmd.com/read/29339144/addressing-barriers-to-effective-cancer-immunotherapy-with-nanotechnology-achievements-challenges-and-roadmap-to-the-next-generation-of-nanoimmunotherapeutics
#13
Enping Hong, Marina A Dobrovolskaia
Cancer is a complex systemic disorder that affects many organs and tissues and arises from the altered function of multiple cellular and molecular mechanisms. One of the systems malfunctioning in cancer is the immune system. Restoring and improving the ability of the immune system to effectively recognize and eradicate cancer is the main focus of immunotherapy, a topic which has garnered recent and significant interest. The initial excitement about immunotherapy, however, has been challenged by its limited efficacy in certain patient populations and the development of adverse effects such as therapeutic resistance and autoimmunity...
January 12, 2018: Advanced Drug Delivery Reviews
https://www.readbyqxmd.com/read/29338732/transcriptional-profile-and-epstein-barr-virus-infection-status-of-laser-cut-immune-infiltrates-from-the-brain-of-patients-with-progressive-multiple-sclerosis
#14
Caterina Veroni, Barbara Serafini, Barbara Rosicarelli, Corrado Fagnani, Francesca Aloisi
BACKGROUND: It is debated whether multiple sclerosis (MS) might result from an immunopathological response toward an active Epstein-Barr virus (EBV) infection brought into the central nervous system (CNS) by immigrating B cells. Based on this model, a relationship should exist between the local immune milieu and EBV infection status in the MS brain. To test this hypothesis, we analyzed expression of viral and cellular genes in brain-infiltrating immune cells. METHODS: Twenty-three postmortem snap-frozen brain tissue blocks from 11 patients with progressive MS were selected based on good RNA quality and prominent immune cell infiltration...
January 16, 2018: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/29338698/enteral-immunonutrition-versus-enteral-nutrition-for-gastric-cancer-patients-undergoing-a-total-gastrectomy-a-systematic-review-and-meta-analysis
#15
Ying Cheng, Junfeng Zhang, Liwei Zhang, Juan Wu, Zhen Zhan
BACKGROUND: Nutrition support is a common means for patients with gastric cancer, especially for those undergoing elective surgery. Recently, enteral immunonutrition (EIN) was increasingly found to be more effective than enteral nutrition (EN) in enhancing the host immunity and eventually improving the prognosis of gastric cancer patients undergoing gastrectomy. However, the results reported were not consistent. This meta-analysis aimed to assess the impact of EIN for patients with GC on biochemical, immune indices and clinical outcomes...
January 16, 2018: BMC Gastroenterology
https://www.readbyqxmd.com/read/29338603/emerging-roles-of-inositol-pyrophosphates-as-key-modulators-of-fungal-pathogenicity
#16
Hyun Ah Kang
Inositol pyrophosphates (PP-IPs) are energy-rich small molecules that are omnipresent in eukaryotic cells, from yeast to mammals, playing central roles in overall cellular homeostasis as a diverse and multifaceted class of intracellular messengers. Recent studies of the metabolic pathways and physiological roles of PP-IPs in the human pathogenic fungus Cryptococcus neoformans have revealed that the PP-IP5 (IP7) is a key metabolite essential for fungal metabolic adaptation to the host environment, immune recognition, and pathogenicity...
January 17, 2018: Virulence
https://www.readbyqxmd.com/read/29337691/the-neutral-sphingomyelinase-2-in-t-cell-receptor-signaling-and-polarity
#17
Lena Collenburg, Sibylle Schneider-Schaulies, Elita Avota
Hydrolyzing its substrate sphingomyelin at the cytosolic leaflet of cellular membranes, the neutral sphingomyelinase 2 (NSM2) generates microdomains which serve as docking sites for signaling proteins and thereby, functions to regulate signal relay. This has been particularly studied in cellular stress responses while the regulatory role of this enzyme in the immune cell compartment has only recently emerged. In T cells, phenotypic polarization by co-ordinated cytoskeletal remodeling is central to motility and interaction with endothelial or antigenpresenting cells during tissue recruitment or immune synapse formation, respectively...
June 27, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/29337673/evaluation-of-immunomodulatory-effects-of-lamotrigine-in-balb-c-mice
#18
Eman Y Abu-Rish, Shada Y Elhayek, Yehia S Mohamed, Islam Hamad, Yasser Bustanji
Modulation of the immune system has recently been shown to be involved in the pharmacological effects of old antiepileptic drugs and in the pathogenesis of epilepsy. Therefore, the most recent guidelines for immunotoxicological evaluation of drugs were consulted to investigate the immunomodulatory effects of lamotrigine, a newer antiepileptic drug, in BALB/c mice. These included the in vivo effects of lamotrigine on delayed-type hypersensitivity (DTH) response to sheep red blood cell (SRBC) antigens, hemagglutination titer assays and hematological changes...
December 20, 2017: Acta Pharmaceutica
https://www.readbyqxmd.com/read/29337247/effects-of-dietary-administration-of-fenugreek-seeds-on-metabolic-parameters-and-immune-status-of-gilthead-seabream-sparus-aurata-l
#19
F A Guardiola, A Bahi, M A Esteban
Medical plants could be used as a prophylactic method in aquaculture because they are considered safe and so very promising alternatives to the use of chemicals. The aim of the present work was to examine the effects of dietary fenugreek (Trigonella foenum graecum) seeds administered for 8 weeks on the metabolic and immune status of gilthead seabream (Sparus aurata L.). Four experimental groups were designated: one receiving a basal diet (control) and three fed powdered fenugreek seeds incorporated in the fish feed at 1%, 5% and 10%...
January 11, 2018: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/29337161/cellular-redox-cancer-and-human-papillomavirus
#20
REVIEW
Alfredo Cruz-Gregorio, Joaquín Manzo-Merino, Marcela Lizano
High-risk Human Papillomavirus (HR-HPV) is the causative agent of different human cancers. A persistent HR-HPV infection alters several cellular processes involved in cell proliferation, apoptosis, immune evasion, genomic instability and transformation. Cumulative evidence from past studies indicates that HR-HPV proteins are associated with oxidative stress (OS) and has been proposed as a risk factor for cancer development. Reactive oxygen and nitrogen species (RONS) regulate a plethora of processes inducing cellular proliferation, differentiation and death...
January 11, 2018: Virus Research
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