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https://www.readbyqxmd.com/read/28734795/monoclonal-antibodies-in-multiple-myeloma-a-new-wave-of-the-future
#1
REVIEW
Daniel W Sherbenou, Tomer M Mark, Peter Forsberg
In 2015, 2 monoclonal antibodies were approved for the treatment of relapsed or refractory multiple myeloma (RRMM), elotuzumab and daratumumab. Elotuzumab is a monoclonal IgG-κ antibody directed against SLAMF7 (signaling lymphocytic activation molecule F7), a cell surface receptor involved in natural killer cell activation. Daratumumab is a monoclonal IgG-κ antibody that binds to CD38, a transmembrane protein found on the surface of myeloma cells and responsible for cellular adhesion and ectoenzymatic activity...
June 27, 2017: Clinical Lymphoma, Myeloma & Leukemia
https://www.readbyqxmd.com/read/28727807/digoxin-reveals-a-functional-connection-between-hiv-1-integration-preference-and-t-cell-activation
#2
Alexander Zhyvoloup, Anat Melamed, Ian Anderson, Delphine Planas, Chen-Hsuin Lee, Janos Kriston-Vizi, Robin Ketteler, Andy Merritt, Jean-Pierre Routy, Petronela Ancuta, Charles R M Bangham, Ariberto Fassati
HIV-1 integrates more frequently into transcribed genes, however the biological significance of HIV-1 integration targeting has remained elusive. Using a selective high-throughput chemical screen, we discovered that the cardiac glycoside digoxin inhibits wild-type HIV-1 infection more potently than HIV-1 bearing a single point mutation (N74D) in the capsid protein. We confirmed that digoxin repressed viral gene expression by targeting the cellular Na+/K+ ATPase, but this did not explain its selectivity. Parallel RNAseq and integration mapping in infected cells demonstrated that digoxin inhibited expression of genes involved in T-cell activation and cell metabolism...
July 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28726646/the-prognostic-significance-of-combaind-expression-of-zap-70-and-cd38-in-chronic-lymphocytic-leukemia
#3
T Kirtava, T Vatsadze, E Azrmaiparashili, D Ghirdaladze
Our aim was to assess the inter links of the markers CD38 and ZAP-70 based on our materials, the attitude according to the disease stage, and to document which of them had leading meaning for prognosis and treatmend of the disease. In our study we have used flow cytometry for detection CD38 and ZAP-70+ markers expression. (58 patients to assessments their prognostic value in сhronic lymphocytic leukemia (CLL), Correlation to Rai stages and relationships between this markers and outcome of therapy). We divided all patients in two groups based on level of ZAP-70+ cell and CD38+cells,(I group-patients) ZAP-70+ cells <20% CD38+<30% and ZAP-70+ cells >20% and CD38>30%,(II group) becaus our in investigation shows, that ZAP -70+ is very importance independent prognoctic marker as why in ZAP-70+ cases when its number was <20%, patients had favorable prognosis - the big part of them (13(40...
June 2017: Georgian Medical News
https://www.readbyqxmd.com/read/28722319/immunophenotypic-aberrancies-in-acute-lymphoblastic-leukemia-from-282-iraqi-patients
#4
S D Jalal, N A S Al-Allawi, A A S Al Doski
INTRODUCTION: The identification of aberrancies in leukemia-associated immunophenotype (LAIP) of acute lymphoblastic leukemia (ALL) is quite important in the assessment of minimal residual disease (MRD). This study, the first from Iraq, aimed to assess the frequency and patterns of LAIP among Iraqi patients with ALL, to establish future strategies for evaluating MRD. METHODS: A total of 282 newly diagnosed Iraqi ALL cases were analyzed with six-parameter flow cytometry using a panel of 29 monoclonal antibodies...
July 18, 2017: International Journal of Laboratory Hematology
https://www.readbyqxmd.com/read/28720704/cytosolic-interaction-of-type-iii-human-cd38-with-cib1-modulates-cellular-cyclic-adp-ribose-levels
#5
Jun Liu, Yong Juan Zhao, Wan Hua Li, Yun Nan Hou, Ting Li, Zhi Ying Zhao, Cheng Fang, Song Lu Li, Hon Cheung Lee
CD38 catalyzes the synthesis of the Ca(2+) messenger, cyclic ADP-ribose (cADPR). It is generally considered to be a type II protein with the catalytic domain facing outside. How it can catalyze the synthesis of intracellular cADPR that targets the endoplasmic Ca(2+) stores has not been resolved. We have proposed that CD38 can also exist in an opposite type III orientation with its catalytic domain facing the cytosol. Here, we developed a method using specific nanobodies to immunotarget two different epitopes simultaneously on the catalytic domain of the type III CD38 and firmly established that it is naturally occurring in human multiple myeloma cells...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28720126/a-small-molecule-cytokine-combination-enhances-hematopoietic-stem-cell-proliferation-via-inhibition-of-cell-differentiation
#6
Lan Wang, Xin Guan, Huihui Wang, Bin Shen, Yu Zhang, Zhihua Ren, Yupo Ma, Xinxin Ding, Yongping Jiang
BACKGROUND: Accumulated evidence supports the potent stimulating effects of multiple small molecules on the expansion of hematopoietic stem cells (HSCs) which are important for the therapy of various hematological disorders. Here, we report a novel, optimized formula, named the SC cocktail, which contains a combination of three such small molecules and four cytokines. METHODS: Small-molecule candidates were individually screened and then combined at their optimal concentration with the presence of cytokines to achieve maximum capacity for stimulating the human CD34(+) cell expansion ex vivo...
July 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28718379/expression-of-embryonic-stem-cell-markers-in-acute-myeloid-leukemia
#7
Tiphanie Picot, Carmen Mariana Aanei, Amandine Fayard, Pascale Flandrin-Gresta, Sylvie Tondeur, Marina Gouttenoire, Emmanuelle Tavernier-Tardy, Eric Wattel, Denis Guyotat, Lydia Campos
Acute myeloid leukemia is driven by leukemic stem cells which can be identified by cross lineage expression or arrest of differentiation compared to normal hematopoietic stem cells. Self-renewal and lack of differentiation are also features of stem cells and have been associated with the expression of embryonic genes. The aim of our study was to evaluate the expression of embryonic antigens (OCT4, NANOG, SOX2, SSEA1, SSEA3) in hematopoietic stem cell subsets (CD34(+)CD38(-) and CD34(+)CD38(+)) from normal bone marrows and in samples from acute myeloid leukemia patients...
July 2017: Tumour Biology: the Journal of the International Society for Oncodevelopmental Biology and Medicine
https://www.readbyqxmd.com/read/28713370/persistence-of-activated-and-adaptive-like-nk-cells-in-hiv-individuals-despite-2-years-of-suppressive-combination-antiretroviral-therapy
#8
Anna C Hearps, Paul A Agius, Jingling Zhou, Samantha Brunt, Mkunde Chachage, Thomas A Angelovich, Paul U Cameron, Michelle Giles, Patricia Price, Julian Elliott, Anthony Jaworowski
Innate immune dysfunction persists in HIV(+) individuals despite effective combination antiretroviral therapy (cART). We recently demonstrated that an adaptive-like CD56(dim) NK cell population lacking the signal transducing protein FcRγ is expanded in HIV(+) individuals. Here, we analyzed a cohort of HIV(+) men who have sex with men (MSM, n = 20) at baseline and following 6, 12, and 24 months of cART and compared them with uninfected MSM (n = 15) to investigate the impact of cART on NK cell dysfunction...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28711932/the-pan-bcl-2-blocker-obatoclax-gx15-070-and-the-pi3-kinase-mtor-inhibitor-bez235-produce-cooperative-growth-inhibitory-effects-in-all-cells
#9
Gabriele Stefanzl, Daniela Berger, Sabine Cerny-Reiterer, Katharina Blatt, Gregor Eisenwort, Wolfgang R Sperr, Gregor Hoermann, Karin Lind, Alexander W Hauswirth, Peter Bettelheim, Heinz Sill, Junia V Melo, Ulrich Jäger, Peter Valent
Acute lymphoblastic leukemia (ALL) is characterized by leukemic expansion of lymphoid blasts in hematopoietic tissues. Despite improved therapy only a subset of patients can be cured. Therefore, current research is focusing on new drug-targets. Members of the BCL-2 family and components of the PI3-kinase/mTOR pathway are critically involved in the regulation of growth and survival of ALL cells. We examined the effects of the pan-BCL-2 blocker obatoclax and the PI3-kinase/mTOR-inhibitor BEZ235 on growth and survival of ALL cells...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28710745/the-pan-bcl2-inhibitor-at101-activates-the-intrinsic-apoptotic-pathway-and-causes-dna-damage-in-acute-myeloid-leukemia-stem-like-cells
#10
Leisi Zhang, Yong Zhou, Kai Chen, Pengcheng Shi, Yin Li, Manman Deng, Zhiwu Jiang, Xiangmeng Wang, Peng Li, Bing Xu
BACKGROUND: Leukemia stem cells (LSCs) are considered to be the cause of treatment failure and relapse in acute myeloid leukemia (AML). Overexpression of the Bcl-2 family of anti-apoptotic proteins such as Bcl-2, Bcl-xl, and Mcl-1 accounts for survival and self-renewal of LSCs. AT101 binds to the BH3 motif of all Bcl-2 family anti-apoptotic proteins and demonstrates anti-tumor activity in multiple types of tumor. Thus, we hypothesized that this agent might have the potential to deplete LSCs...
July 14, 2017: Targeted Oncology
https://www.readbyqxmd.com/read/28700738/age-dependent-differences-in-the-kinetics-of-%C3%AE-%C3%AE-t-cells-after-influenza-vaccination
#11
Ulrik Stervbo, Dominika Pohlmann, Udo Baron, Cecilia Bozzetti, Karsten Jürchott, Julia Nora Mälzer, Mikalai Nienen, Sven Olek, Toralf Roch, Axel Ronald Schulz, Sarah Warth, Avidan Neumann, Andreas Thiel, Andreas Grützkau, Nina Babel
Immunosenescence is a hallmark of the aging immune system and is considered the main cause of a reduced vaccine efficacy in the elderly. Although γδ T cells can become activated by recombinant influenza hemagglutinin, their age-related immunocompetence during a virus-induced immune response has so far not been investigated. In this study we evaluate the kinetics of γδ T cells after vaccination with the trivalent 2011/2012 northern hemisphere seasonal influenza vaccine. We applied multi-parametric flow cytometry to a cohort of 21 young (19-30 years) and 23 elderly (53-67 years) healthy individuals...
2017: PloS One
https://www.readbyqxmd.com/read/28683133/increased-frequency-of-circulating-cd19-cd24hicd38hi-b-cells-with-regulatory-capacity-in-patients-with-ankylosing-spondylitis-as-na%C3%A3-ve-for-biological-agents
#12
María-Belén Bautista-Caro, Eugenio de Miguel, Diana Peiteado, Chamaida Plasencia-Rodríguez, Alejandro Villalba, Irene Monjo-Henry, Amaya Puig-Kröger, Paloma Sánchez-Mateos, Emilio Martín-Mola, María-Eugenia Miranda-Carús
Our objective was to study the frequency of circulating CD19+CD24hiCD38hi B cells (Breg) in AS patients. To this end, peripheral blood was drawn from AS patients naïve for TNF blockers (AS/nb) (n = 42) and healthy controls (HC) (n = 42). Six patients donated blood for a second time, 6 months after initiating treatment with anti-TNFα drugs. After isolation by Ficoll-Hypaque, PBMCs were stained with antibodies to CD3, CD4, CD19, CD24, and CD38, and examined by cytometry. For functional studies, total CD19+ B cells were isolated from PBMCs of 3 HC by magnetical sorting...
2017: PloS One
https://www.readbyqxmd.com/read/28680905/high-cellular-monocyte-activation-in-people-living-with-human-immunodeficiency-virus-on-combination-antiretroviral-therapy-and-lifestyle-matched-controls-is-associated-with-greater-inflammation-in-cerebrospinal-fluid
#13
Thijs Booiman, Ferdinand W Wit, Irma Maurer, Davide De Francesco, Caroline A Sabin, Agnes M Harskamp, Maria Prins, Paolo Garagnani, Chiara Pirazzini, Claudio Franceschi, Dietmar Fuchs, Magnus Gisslén, Alan Winston, Peter Reiss, Neeltje A Kootstra
BACKGROUND: Increased monocyte activation and intestinal damage have been shown to be predictive for the increased morbidity and mortality observed in treated people living with human immunodeficiency virus (PLHIV). METHODS: A cross-sectional analysis of cellular and soluble markers of monocyte activation, coagulation, intestinal damage, and inflammation in plasma and cerebrospinal fluid (CSF) of PLHIV with suppressed plasma viremia on combination antiretroviral therapy and age and demographically comparable HIV-negative individuals participating in the Comorbidity in Relation to AIDS (COBRA) cohort and, where appropriate, age-matched blood bank donors (BBD)...
2017: Open Forum Infectious Diseases
https://www.readbyqxmd.com/read/28678809/the-number-of-cd34-cd38-cd117-hla-dr-cd13-cd33-cells-indicates-post-chemotherapy-hematopoietic-recovery-in-patients-with-acute-myeloid-leukemia
#14
Runxia Gu, Hui Wei, Ying Wang, Dong Lin, Bingcheng Liu, Chunlin Zhou, Kaiqi Liu, Benfa Gong, Shuning Wei, Guangji Zhang, Xiaoyuan Gong, Yuntao Liu, Yan Li, Xingli Zhao, Shaowei Qiu, Huijun Wang, Min Wang, Yingchang Mi, Jianxiang Wang
Hematopoietic recovery is considered to be associated with the number of multipotent hematopoietic stem cells in the bone marrow, as observed in functional assays involving stem cell transplantation. However, there is little evidence related to hematopoietic recovery in non-transplantation settings, which is accomplished by endogenous hematopoietic cells. A recent study suggested that progenitors are the main contributors during this steady-state hematopoiesis, which differs from exogenous transplantation. We hypothesized that endogenous progenitor support post-chemotherapy hematopoietic recovery...
2017: PloS One
https://www.readbyqxmd.com/read/28674539/combining-flow-and-mass-cytometry-in-the-search-for-biomarkers-in-chronic-graft-versus-host-disease
#15
Arwen Stikvoort, Yang Chen, Emelie Rådestad, Johan Törlén, Tadepally Lakshmikanth, Andreas Björklund, Jaromir Mikes, Adnane Achour, Jens Gertow, Berit Sundberg, Mats Remberger, Mikael Sundin, Jonas Mattsson, Petter Brodin, Michael Uhlin
Chronic graft-versus-host disease (cGVHD) is a debilitating complication arising in around half of all patients treated with an allogeneic hematopoietic stem cell transplantation. Even though treatment of severe cGVHD has improved during recent years, it remains one of the main causes of morbidity and mortality in affected patients. Biomarkers in blood that could aid in the diagnosis and classification of cGVHD severity are needed for the development of novel treatment strategies that can alleviate symptoms and reduce the need for painful and sometimes complicated tissue biopsies...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28671679/2-deoxyadenosine-5-diphosphoribose-is-an-endogenous-trpm2-superagonist
#16
Ralf Fliegert, Andreas Bauche, Adriana-Michelle Wolf Pérez, Joanna M Watt, Monika D Rozewitz, Riekje Winzer, Mareike Janus, Feng Gu, Annette Rosche, Angelika Harneit, Marianne Flato, Christelle Moreau, Tanja Kirchberger, Valerie Wolters, Barry V L Potter, Andreas H Guse
Transient receptor potential melastatin 2 (TRPM2) is a ligand-gated Ca(2+)-permeable nonselective cation channel. Whereas physiological stimuli, such as chemotactic agents, evoke controlled Ca(2+) signals via TRPM2, pathophysiological stimuli such as reactive oxygen species and genotoxic stress result in prolonged TRPM2-mediated Ca(2+) entry and, consequently, apoptosis. To date, adenosine 5'-diphosphoribose (ADPR) has been assumed to be the main agonist for TRPM2. Here we show that 2'-deoxy-ADPR was a significantly better TRPM2 agonist, inducing 10...
June 26, 2017: Nature Chemical Biology
https://www.readbyqxmd.com/read/28670966/malnutrition-in-hiv-infected-children-is-an-indicator-of-severe-disease-with-an-impaired-response-to-antiretroviral-therapy
#17
Maximilian Muenchhoff, Michael Healy, Ravesh Singh, Julia Roider, Andreas Groll, Chirjeev Kindra, Thobekile Sibaya, Angeline Moonsamy, Callum McGregor, Michelle Q Phan, Alejandro Palma, Henrik Kloverpris, Alasdair Leslie, Raziya Bobat, Philip S LaRussa, Thumbi Ndung'u, Philip Jr Goulder, Magdalena E Sobieszczyk, Mohendran Archary
Objectives This observational study aimed to describe immunopathogenesis and treatment outcomes in children with and without severe acute malnutrition (SAM) and HIV-infection. Design We studied markers of microbial translocation (16sDNA), intestinal damage (iFABP), monocyte activation (sCD14), T-cell activation (CD38, HLA-DR) and immune exhaustion (PD1) in 32 HIV-infected children with and 41 HIV-infected children without SAM prior to initiation of antiretroviral therapy (ART) and cross-sectionally compared these children to 15 HIV-uninfected children with and 19 HIV-uninfected children without SAM...
July 2, 2017: AIDS Research and Human Retroviruses
https://www.readbyqxmd.com/read/28666691/direct-targeting-of-cancer-cells-with-antibodies-what-can-we-learn-from-the-successes-and-failure-of-unconjugated-antibodies-for-lymphoid-neoplasias
#18
REVIEW
Josée Golay
Following approval in 1997 of the anti-CD20 antibody rituximab for the treatment of B-NHL and CLL, many other unconjugated IgG1 MAbs have been tested in pre-clinical and clinical trials for the treatment of lymphoid neoplasms. Relatively few have been approved however and these are directed against a limited number of target antigens (CD20, CD52, CCR4, CD38, CD319). We review here the known biological properties of these antibodies and discuss which factors may have led to their success or may, on the contrary, limit their clinical application...
June 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28663101/improving-gene-therapy-efficiency-through-the-enrichment-of-human-hematopoietic-stem-cells
#19
Katelyn E Masiuk, Devin Brown, Jennifer Laborada, Roger P Hollis, Fabrizia Urbinati, Donald B Kohn
Lentiviral vector (LV)-based hematopoietic stem cell (HSC) gene therapy is becoming a promising clinical strategy for the treatment of genetic blood diseases. However, the current approach of modifying 1 × 10(8) to 1 × 10(9) CD34(+) cells per patient requires large amounts of LV, which is expensive and technically challenging to produce at clinical scale. Modification of bulk CD34(+) cells uses LV inefficiently, because the majority of CD34(+) cells are short-term progenitors with a limited post-transplant lifespan...
June 26, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28658717/bone-marrow-on-a-chip-long-term-culture-of-human-hematopoietic-stem-cells-in-a-3d-microfluidic-environment
#20
Stefan Sieber, Lorenz Wirth, Nino Cavak, Marielle Koenigsmark, Uwe Marx, Roland Lauster, Mark Rosowski
Multipotent hematopoietic stem and progenitor cells (HSPCs) are the source for all blood cell types. The bone marrow stem cell niche in which the HSPCs are maintained is known to be vital for their maintenance. Unfortunately, to this date no in vitro model exists that truthfully mimics the aspects of the bone marrow niche and simultaneously allows the long-term culture of HSPCs. In this study, we present a novel 3D co-culture model, based on a hydroxyapatite coated zirconium oxide scaffold, comprising of human mesenchymal stromal cells (MSCs) and cord blood derived HSPCs, enabling successful HSPC culture for a time span of 28 days within the microfluidic Multi-Organ-Chip (MOC)...
June 28, 2017: Journal of Tissue Engineering and Regenerative Medicine
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