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https://www.readbyqxmd.com/read/30551078/prognosis-of-renal-cell-carcinoma-with-bone-metastases-experience-from-a-large-cancer-centre
#1
F Ruatta, L Derosa, B Escudier, E Colomba, A Guida, G Baciarello, Y Loriot, K Fizazi, L Albiges
BACKGROUND: Bone metastases (BMs) are associated with significant morbidity and shorter survival in renal cell carcinoma (RCC). Our purpose was to identify prognostic factors for overall survival (OS) in RCC patients with BMs. METHODS: Data from patients with BMs from RCC treated at Gustave Roussy between April 1992 and March 2016 were retrospectively collected. Age, sex, Eastern Cooperative Oncology Group-Performance Status, Memorial Sloan-Kettering Cancer Center (MSKCC) risk groups, histology, number and site of bone lesions, concomitant metastases (presence and sites), therapy for BMs (radical resection or palliative surgery, radiotherapy and other local and systemic treatments) and time from diagnosis to BMs were analysed...
December 11, 2018: European Journal of Cancer
https://www.readbyqxmd.com/read/30548475/memory-cd4-t-cells-enhance-b-cell-responses-to-drifting-influenza-immunization
#2
Emily Gage, Neal Van Hoeven, Natasha Dubois Cauwelaert, Sasha E Larsen, Jesse Erasmus, Mark T Orr, Rhea N Coler
Influenza A annually infects 5-10% of the world's human population resulting in one million deaths. Influenza causes annual epidemics and re-infects previously exposed individuals because of antigenic drift in the glycoprotein hemagglutinin. Due to antigenic drift, the immune system is simultaneously exposed to novel and conserved parts of the influenza virus via vaccination and/or infection throughout life. Preexisting immunity has long been known to augment subsequent hemagglutination inhibitory antibody (hAb) responses...
December 12, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/30547051/efficient-induction-of-t-cells-against-conserved-hiv-1-regions-by-mosaic-vaccines-delivered-as-self-amplifying-mrna
#3
Nathifa Moyo, Annette B Vogel, Søren Buus, Stephanie Erbar, Edmund G Wee, Ugur Sahin, Tomáš Hanke
Focusing T cell responses on the most vulnerable parts of HIV-1, the functionally conserved regions of HIV-1 proteins, is likely a key prerequisite for vaccine success. For a T cell vaccine to efficiently control HIV-1 replication, the vaccine-elicited individual CD8+ T cells and as a population have to display a number of critical traits. If any one of these traits is suboptimal, the vaccine is likely to fail. Fine-tuning of individual protective characteristics of T cells will require iterative stepwise improvements in clinical trials...
March 15, 2019: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/30546828/decreased-levels-of-regulatory-b-cells-in-patients-with-acute-pancreatitis-association-with-the-severity-of-the-disease
#4
Liannv Qiu, Yonglie Zhou, Qinghua Yu, Junde Yu, Qian Li, Renhua Sun
Early stratification of the severity of acute pancreatitis (AP) is clinically important. Regulatory B cells have been found to be associated with disease activity of autoimmune diseases. However, the role of Regulatory B cells in AP remains unknown. We investigate the dynamic longitudinal changes in circulating IL-10-producing B cells (B10) and memory CD19+ CD24hi CD27hi cells in patients with AP to evaluate their prediction utility for AP severity. B10, CD19+ CD24hi CD27hi cells, inflammatory markers and cytokines were detected in patients with AP immediately after admission to the hospital (day 1), then on the third and seventh days...
November 16, 2018: Oncotarget
https://www.readbyqxmd.com/read/30545924/prevention-of-the-anti-factor-viii-memory-b-cell-response-by-inhibition-of-the-bruton-s-tyrosine-kinase-in-experimental-hemophilia-a
#5
Sandrine Delignat, Jules Russick, Bagirath Gangadharan, Julie Rayes, Mathieu Ing, Jan Voorberg, Srinivas V Kaveri, Sébastien Lacroix-Desmazes
Hemophilia A is a rare hemorrhagic disorder due to the lack of functional pro-coagulant factor VIII. Factor VIII replacement therapy in patients with severe hemophilia A results in the development of inhibitory anti-factor VIII IgG in up to 30% of the cases. To date, immune tolerance induction upon daily injection of large amounts of factor VIII is the only strategy to eradicate factor VIII inhibitors. It is however efficient in only 60-80% of the patients. Here, we investigated whether blocking B-cell receptor signaling upon inhibition of the Bruton's tyrosine kinase prevents anti-factor VIII immune responses in a mouse model of severe hemophilia A...
December 13, 2018: Haematologica
https://www.readbyqxmd.com/read/30545002/the-stress-inducible-protein-drr1-exerts-distinct-effects-on-actin-dynamics
#6
Anja Kretzschmar, Jan-Philip Schülke, Mercè Masana, Katharina Dürre, Marianne B Müller, Andreas R Bausch, Theo Rein
Cytoskeletal dynamics are pivotal to memory, learning, and stress physiology, and thus psychiatric diseases. Downregulated in renal cell carcinoma 1 (DRR1) protein was characterized as the link between stress, actin dynamics, neuronal function, and cognition. To elucidate the underlying molecular mechanisms, we undertook a domain analysis of DRR1 and probed the effects on actin binding, polymerization, and bundling, as well as on actin-dependent cellular processes. METHODS: DRR1 domains were cloned and expressed as recombinant proteins to perform in vitro analysis of actin dynamics (binding, bundling, polymerization, and nucleation)...
December 11, 2018: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/30541848/contrasting-roles-of-the-pd-1-signaling-pathway-in-dendritic-cell-mediated-induction-and-regulation-of-hiv-1-specific-effector-t-cell-functions
#7
Tatiana M Garcia-Bates, Mariana L Palma, Chengli Shen, Andrea Gambotto, Bernard J C Macatangay, Robert L Ferris, Charles R Rinaldo, Robbie B Mailliard
Eliciting highly functional CD8+ cytotoxic T lymphocyte (CTL) responses against a broad range of epitopes will likely be required for immunotherapeutic control of HIV-1 infection. However, the combination of CTL exhaustion and the ability of HIV-1 to rapidly establish CTL escape variants represent major hurdles towards this goal. Our previous work highlighted the use of monocyte derived, mature, high IL-12-producing type-1 polarized dendritic cells (MDC1) to selectively induce more potent effector CTLs derived from naïve, rather than memory, CD8+ T cell precursors isolated from HIV-1 positive participants in the Multicenter AIDS Cohort Study...
December 12, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30541829/novel-mva-vector-expressing-anti-apoptotic-gene-b13r-delays-apoptosis-and-enhances-humoral-responses
#8
Lynette S Chea, Linda S Wyatt, Sailaja Gangadhara, Bernard Moss, Rama R Amara
Modified vaccinia Ankara (MVA), an attenuated poxvirus, has been developed as a potential vaccine vector for use against cancer and multiple infectious diseases including HIV. MVA is highly immunogenic and elicits strong cellular and humoral responses in pre-clinical models and humans. However, there is potential to further enhance the immunogenicity of MVA as MVA-infected cells undergo rapid apoptosis leading to faster clearance of recombinant antigens and potentially blunting a greater response. Here, we generated MVA-B13R by replacing the fragmented 181R/182R genes of MVA with a functional anti-apoptotic gene B13R and confirmed its anti-apoptotic function against chemically induced apoptosis in vitro In addition, MVA-B13R showed a significant delay in induction of apoptosis in muscle cells derived from mice and humans as well as pDCs and CD141+ DCs from rhesus macaques compared to MVA infected cells...
December 12, 2018: Journal of Virology
https://www.readbyqxmd.com/read/30540814/fingerprints-of-cd8-t-cells-on-human-pre-plasma-and-memory-b-cells
#9
Ulrike Strittmatter-Keller, Caroline Walter, Celine Rauld, Nicole Egli, Camille Regairaz, Sabine Rabe, Gerhard Zenke, José Carballido, Tamás Schweighoffer
Differentiation of B cells is a stringently controlled multi-step process, which is still incompletely understood. Here we identify and characterize a rare population of human B cells, which surprisingly carry CD8AB on their surface. Existence of such cells was demonstrated both in tonsils and in human apheresis material. Gene expression profiling and real time PCR detected however no CD8A or CD8B message in these cells. Instead, we found that surface CD8 was hijacked from activated CD8+ T cells by a transfer process that required direct cell-to-cell contact...
2018: PloS One
https://www.readbyqxmd.com/read/30540497/amelioration-of-amyloid-%C3%AE-fc%C3%AE-riib-neurotoxicity-and-tau-pathologies-by-targeting-lyn
#10
Youngdae Gwon, Seo-Hyun Kim, Hyun Tae Kim, Tae-In Kam, Jisu Park, Bitna Lim, Hyunju Cha, Ho-Jin Chang, Yong Rae Hong, Yong-Keun Jung
SRC-family kinases (SFKs) have been implicated in Alzheimer's disease (AD), but their mode of action was scarcely understood. Here, we show that LYN plays an essential role in amyloid β (Aβ)-triggered neurotoxicity and tau hyperphosphorylation by phosphorylating Fcγ receptor IIb2 (FcγRIIb2). We found that enzyme activity of LYN was increased in the brain of AD patients and was promoted in neuronal cells exposed to Aβ 1-42 (Aβ1-42 ). Knockdown of LYN expression inhibited Aβ1-42 -induced neuronal cell death...
December 12, 2018: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/30539801/the-role-of-epstein-barr-virus-in-multiple-sclerosis-from-molecular-pathophysiology-to-in-vivo-imaging
#11
REVIEW
Yi Guan, Dejan Jakimovski, Murali Ramanathan, Bianca Weinstock-Guttman, Robert Zivadinov
Multiple sclerosis (MS) is a disease of the central nervous system characterized by inflammation, demyelination, and neuronal damage. Environmental and genetic factors are associated with the risk of developing MS, but the exact cause still remains unidentified. Epstein-Barr virus (EBV), vitamin D, and smoking are among the most well-established environmental risk factors in MS. Infectious mononucleosis, which is caused by delayed primary EBV infection, increases the risk of developing MS. EBV may also contribute to MS pathogenesis indirectly by activating silent human endogenous retrovirus-W...
March 2019: Neural Regeneration Research
https://www.readbyqxmd.com/read/30539468/an-efficient-method-to-generate-monoclonal-antibodies-from-human-b-cells
#12
Jenna J Guthmiller, Haley L Dugan, Karlynn E Neu, Linda Yu-Ling Lan, Patrick C Wilson
In the age of personalized medicine, an efficient method to generate monoclonal antibodies (mAbs) is essential for biomedical and immunotherapeutic research. Numerous aspects of basic B-cell biology can be studied at the monoclonal level, including B-cell development, antibody responses to infection or vaccination, and autoimmune responses. Single-cell B-cell receptor cloning allows for the rapid generation of antigen-specific mAbs in a matter of several weeks. In this chapter, we provide an efficient method to generate mAbs from peripheral blood plasmablasts and memory B cells induced by infection and vaccination...
2019: Methods in Molecular Biology
https://www.readbyqxmd.com/read/30538968/development-and-applications-of-oncolytic-maraba-virus-vaccines
#13
REVIEW
Jonathan G Pol, Matthew J Atherton, Byram W Bridle, Kyle B Stephenson, Fabrice Le Boeuf, Jeff L Hummel, Chantal G Martin, Julia Pomoransky, Caroline J Breitbach, Jean-Simon Diallo, David F Stojdl, John C Bell, Yonghong Wan, Brian D Lichty
Oncolytic activity of the MG1 strain of the Maraba vesiculovirus has proven efficacy in numerous preclinical cancer models, and relied not only on a direct cytotoxicity but also on the induction of both innate and adaptive antitumor immunity. To further expand tumor-specific T-cell effector and long-lasting memory compartments, we introduced the MG1 virus in a prime-boost cancer vaccine strategy. To this aim, a replication-incompetent adenoviral [Ad] vector together with the oncolytic MG1 have each been armed with a transgene expressing a same tumor antigen...
2018: Oncolytic Virotherapy
https://www.readbyqxmd.com/read/30538817/type-i-interferon-receptor-blockade-with-anifrolumab-corrects-innate-and-adaptive-immune-perturbations-of-sle
#14
Kerry A Casey, Xiang Guo, Michael A Smith, Shiliang Wang, Dominic Sinibaldi, Miguel A Sanjuan, Liangwei Wang, Gabor G Illei, Wendy I White
Objective: Anifrolumab is a fully human immunoglobulin G1 κ monoclonal antibody specific for subunit 1 of the type I interferon (IFN) α receptor. In a phase IIb study of adults with moderate to severe SLE, anifrolumab treatment demonstrated substantial reductions in multiple clinical endpoints. Here, we evaluated serum proteins and immune cells associated with SLE pathogenesis, type I interferon gene signature (IFNGS) test status and disease activity, and how anifrolumab affected these components...
2018: Lupus Science & Medicine
https://www.readbyqxmd.com/read/30538246/single-human-b-cell-derived-monoclonal-anti-candida-antibodies-enhance-phagocytosis-and-protect-against-disseminated-candidiasis
#15
Fiona M Rudkin, Ingrida Raziunaite, Hillary Workman, Sosthene Essono, Rodrigo Belmonte, Donna M MacCallum, Elizabeth M Johnson, Lisete M Silva, Angelina S Palma, Ten Feizi, Allan Jensen, Lars P Erwig, Neil A R Gow
The high global burden of over one million annual lethal fungal infections reflects a lack of protective vaccines, late diagnosis and inadequate chemotherapy. Here, we have generated a unique set of fully human anti-Candida monoclonal antibodies (mAbs) with diagnostic and therapeutic potential by expressing recombinant antibodies from genes cloned from the B cells of patients suffering from candidiasis. Single class switched memory B cells isolated from donors serum-positive for anti-Candida IgG were differentiated in vitro and screened against recombinant Candida albicans Hyr1 cell wall protein and whole fungal cell wall preparations...
December 11, 2018: Nature Communications
https://www.readbyqxmd.com/read/30529561/a-dual-fluorescent-reverse-targeting-drug-delivery-system-based-on-curcumin-loaded-ovalbumin-nanoparticles-for-allergy-treatment
#16
Jie Liang, Xia Dong, Afeng Yang, Dunwan Zhu, Deling Kong, Feng Lv
A reverse targeting drug delivery based on antigen-modified nanoparticles provided an innovative strategy for effectively alleviating or inhibiting immune response. In this study, a dual fluorescent reverse targeting drug delivery system based on curcumin-loaded ovalbumin nanoparticles is developed for allergy treatment. The self-crosslinked ovalbumin nanoparticles achieved the double function of reverse targeting and sustained delivery carriers to maximize the anti-allergy of curcumin. Using a murine model of ovalbumin-induced allergy, this drug delivery system suppressed antigen-specific IgG1 and IgE production, inhibited CD4+ T activity, and decreased the level of ovalbumin-sensitized memory B cells...
December 6, 2018: Nanomedicine: Nanotechnology, Biology, and Medicine
https://www.readbyqxmd.com/read/30528250/different-frequencies-of-memory-b-cells-induced-by-tetanus-botulinum-and-heat-labile-toxin-binding-domains
#17
Ehsan Rezaie, Hekmat Nekoie, Ali Miri, Gholamreza Oulad, Ali Ahmadi, Mojtaba Saadati, Mahmood Bozorgmehr, Marzieh Ebrahimi, Jafar Salimian
Along with robust immunogenicity, an ideal vaccine candidate should be able to produce a long lasting protection. In this regard, the frequency of memory B-cells is possibly an important factor in memory B-cell persistency and duration of immunological memory. On this basis, binding domains of tetanus toxin (HcT), botulinum type A1 toxin (HcA), and heat-labile toxin (LTB) were selected as antigen models that induced long-term, midterm and short-term immune memory, respectively. In the present study, the frequency of total memory B-cells after immunization with HcT, HcA and LTB antigens after 90 and 180 days, and also after one booster, in 190 days, was evaluated...
December 4, 2018: Microbial Pathogenesis
https://www.readbyqxmd.com/read/30524962/role-and-regulation-of-pro-survival-bcl-2-proteins-in-multiple-myeloma
#18
REVIEW
Anne Slomp, Victor Peperzak
Apoptosis plays a key role in protection against genomic instability and maintaining tissue homeostasis, and also shapes humoral immune responses. During generation of an antibody response, multiple rounds of B-cell expansion and selection take place in germinal centers (GC) before high antigen affinity memory B-cells and long-lived plasma cells (PC) are produced. These processes are tightly regulated by the intrinsic apoptosis pathway, and malignant transformation throughout and following the GC reaction is often characterized by apoptosis resistance...
2018: Frontiers in Oncology
https://www.readbyqxmd.com/read/30524448/signatures-of-t-and-b-cell-development-functional-responses-and-pd-1-upregulation-after-hcmv-latent-infections-and-reactivations-in-nod-rag-gamma-mice-humanized-with-cord-blood-cd34-cells
#19
Sebastian J Theobald, Sahamoddin Khailaie, Michael Meyer-Hermann, Valery Volk, Henning Olbrich, Simon Danisch, Laura Gerasch, Andreas Schneider, Christian Sinzger, Dirk Schaudien, Stefan Lienenklaus, Peggy Riese, Carlos A Guzman, Constanca Figueiredo, Constantin von Kaisenberg, Loukia M Spineli, Stephanie Glaesener, Almut Meyer-Bahlburg, Arnold Ganser, Michael Schmitt, Michael Mach, Martin Messerle, Renata Stripecke
Human cytomegalovirus (HCMV) latency is typically harmless but reactivation can be largely detrimental to immune compromised hosts. We modeled latency and reactivation using a traceable HCMV laboratory strain expressing the Gaussia luciferase reporter gene (HCMV/GLuc) in order to interrogate the viral modulatory effects on the human adaptive immunity. Humanized mice with long-term (more than 17 weeks) steady human T and B cell immune reconstitutions were infected with HCMV/GLuc and 7 weeks later were further treated with granulocyte-colony stimulating factor (G-CSF) to induce viral reactivations...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/30524426/microphysiologic-human-tissue-constructs-reproduce-autologous-age-specific-bcg-and-hbv-primary-immunization-in-vitro
#20
Guzman Sanchez-Schmitz, Chad R Stevens, Ian A Bettencourt, Peter J Flynn, Klaus Schmitz-Abe, Gil Metser, David Hamm, Kristoffer J Jensen, Christine Benn, Ofer Levy
Current vaccine development disregards human immune ontogeny, relying on animal models to select vaccine candidates targeting human infants, who are at greatest risk of infection worldwide, and receive the largest number of vaccines. To help accelerate and de-risk development of early-life effective immunization, we engineered a human age-specific microphysiologic vascular-interstitial interphase, suitable for pre-clinical modeling of distinct age-targeted immunity in vitro . Our Tissue Constructs (TCs) enable autonomous extravasation of monocytes that undergo rapid self-directed differentiation into migratory Dendritic Cells (DCs) in response to adjuvants and licensed vaccines such as Bacille Calmette-Guérin (BCG) or Hepatitis B virus Vaccine (HBV)...
2018: Frontiers in Immunology
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