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https://www.readbyqxmd.com/read/28317752/facile-preparation-of-magnetic-carbon-nanotubes-immobilized-lipase-for-highly-efficient-synthesis-of-1-3-dioleoyl-2-palmitoylglycerol-rich-human-milk-fat-substitutes
#1
Mingming Zheng, Shi Wang, Xia Xiang, Jie Shi, Juan Huang, Qianchun Deng, Fenghong Huang, Junyong Xiao
In this study, Candida lipolytica lipase (CLL) was immobilized on magnetic multi-walled carbon nanotubes (mMWCNTs) via hydrophobic and cation-exchange interaction. The resultant immobilized CLL showed much better thermal stability, biocatalyst activity and easier recycling than the free form. A method for efficient enzymatic acidolysis of tripalmitin (PPP) with oleic acid (OA), to produce OPO-rich TAGs, was developed, using the immobilized CLL as the biocatalyst. Under optimized conditions (2% water, 20mg/ml enzyme, 1:6 PPP/OA, 50°C, 2h), the content of OPO in the final product reached 46...
August 1, 2017: Food Chemistry
https://www.readbyqxmd.com/read/28288980/human-neutrophils-mediate-trogocytosis-rather-than-phagocytosis-of-cll-b-cells-opsonized-with-anti-cd20-antibodies
#2
Rut Valgardsdottir, Irene Cattaneo, Christian Klein, Martino Introna, Marina Figliuzzi, Josée Golay
Polymorphonuclear neutrophils (PMN) have previously been reported to mediate phagocytosis of anti-CD20 opsonized B-cells from CLL patients. However recent data have suggested that PMN, like macrophages, can also mediate trogocytosis. We have performed experiments to more precisely investigate this point and discriminate between trogocytosis and phagocytosis. In live cell time-lapse microscopy experiments, we could not detect any significant phagocytosis by purified PMN of anti-CD20-opsonized CLL B-cells, but only the repeated close contact between effectors and targets, suggesting trogocytosis...
March 13, 2017: Blood
https://www.readbyqxmd.com/read/28282218/immunotoxins-in-cancer-therapy-review-and-update
#3
Bahman Akbari, Safar Farajnia, Shiva Ahdi Khosroshahi, Fatemeh Safari, Mohammadreza Yousefi, Hassan Dariushnejad, Leila Rahbarnia
Immunotoxins are a novel class of cancer therapeutics that contains a cytotoxic agent fused to a targeting moiety. Various toxic agents from different sources are used in immunotoxin development, including bacterial, plant and human origin cytotoxic elements. Although bacterial and plant-derived toxins are highly toxic and commonly used in immunotoxins, their immunogenicity for human restricted their application in cancer therapy. Here, we discuss the advantages and limitations of bacterial toxins such as Pseudomonas and Diphtheria toxins, plant toxins such as ricin and gelonin, and some endogenous protein of human origin such as RNases and Granzymes...
March 1, 2017: International Reviews of Immunology
https://www.readbyqxmd.com/read/28249016/hla-specificities-are-associated-with-prognosis-in-ighv-mutated-cll-like-high-count-monoclonal-b-cell-lymphocytosis
#4
María García-Álvarez, Miguel Alcoceba, Miriam López-Parra, Noemí Puig, Alicia Antón, Ana Balanzategui, Isabel Prieto-Conde, Cristina Jiménez, María E Sarasquete, M Carmen Chillón, María Laura Gutiérrez, Rocío Corral, José María Alonso, José Antonio Queizán, Julia Vidán, Emilia Pardal, María Jesús Peñarrubia, José M Bastida, Ramón García-Sanz, Luis Marín, Marcos González
INTRODUCTION: Molecular alterations leading progression of asymptomatic CLL-like high-count monoclonal B lymphocytosis (hiMBL) to chronic lymphocytic leukemia (CLL) remain poorly understood. Recently, genome-wide association studies have found 6p21.3, where the human leukocyte antigen (HLA) system is coded, to be a susceptibility risk region for CLL. Previous studies have produced discrepant results regarding the association between HLA and CLL development and outcome, but no studies have been performed on hiMBL...
2017: PloS One
https://www.readbyqxmd.com/read/28202953/fully-human-cd19-specific-chimeric-antigen-receptors-for-t-cell-therapy
#5
D Sommermeyer, T Hill, S M Shamah, A I Salter, Y Chen, K M Mohler, S R Riddell
Impressive results have been achieved by adoptively transferring T-cells expressing CD19-specific CARs with binding domains from murine mAbs to treat B-cell malignancies. T-cell mediated immune responses specific for peptides from the murine scFv antigen-binding domain of the CAR can develop in patients and result in premature elimination of CAR T-cells increasing the risk of tumor relapse. As fully human scFv might reduce immunogenicity, we generated CD19-specific human scFvs with similar binding characteristics as the murine FMC63-derived scFv using human Ab/DNA libraries...
March 21, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28182141/obinutuzumab-in-chronic-lymphocytic-leukemia-design-development-and-place-in-therapy
#6
REVIEW
Othman Al-Sawaf, Kirsten Fischer, Anja Engelke, Natali Pflug, Michael Hallek, Valentin Goede
For decades, treatment of chronic lymphocytic leukemia (CLL) has been based on chemotherapy. This changed when the first CD20 antibody rituximab was introduced. Since 2008, the combination of chemotherapy and CD20 antibodies has become the standard of care for most patients, and a significant fraction of patients had very long-lasting remissions after chemoimmunotherapy. Despite the improvement of response rates and overall survival (OS) by the use of chemoimmunotherapy, most CLL patients will relapse eventually...
2017: Drug Design, Development and Therapy
https://www.readbyqxmd.com/read/28125682/the-number-of-overlapping-aid-hotspots-in-germline-ighv-genes-is-inversely-correlated-with-mutation-frequency-in-chronic-lymphocytic-leukemia
#7
Chaohui Yuan, Charles C Chu, Xiao-Jie Yan, Davide Bagnara, Nicholas Chiorazzi, Thomas MacCarthy
The targeting of mutations by Activation-Induced Deaminase (AID) is a key step in generating antibody diversity at the Immunoglobulin (Ig) loci but is also implicated in B-cell malignancies such as chronic lymphocytic leukemia (CLL). AID has previously been shown to preferentially deaminate WRC (W = A/T, R = A/G) hotspots. WGCW sites, which contain an overlapping WRC hotspot on both DNA strands, mutate at much higher frequency than single hotspots. Human Ig heavy chain (IGHV) genes differ in terms of WGCW numbers, ranging from 4 for IGHV3-48*03 to as many as 12 in IGHV1-69*01...
2017: PloS One
https://www.readbyqxmd.com/read/28097289/binding-of-cll-subset-4-b-cell-receptor-immunoglobulins-to-viable-human-memory-b-lymphocytes-requires-a-distinctive-igkv-somatic-mutation
#8
Rosa Catera, Yun Liu, Chao Gao, Xiao-Jie Yan, Amanda Magli, Steven L Allen, Jonathan E Kolitz, Kanti R Rai, Charles C Chu, Ten Feizi, Kostas Stamatopoulos, Nicholas Chiorazzi
Amino acid replacement mutations in certain CLL stereotyped B-cell receptor (BCR) immunoglobulins (IGs) at defined positions within antigen-binding sites strongly imply antigen selection. Prime examples of this are CLL subset 4 BCR IGs using IGHV4-34/IGHD5-18/IGHJ6 and IGKV2-30/IGKJ2 rearrangements. Conspicuously and unlike most CLL IGs, subset 4 IGs do not bind apoptotic cells. By testing the (auto)antigenic reactivities of subset 4 IGs toward viable lymphoid-lineage cells and specific autoantigens typically bound by IGHV4-34(+) IGs, we found IGs from both subset 4 and non-subset 4 IGHV4-34-expressing CLL cases bind naïve B cells...
January 12, 2017: Molecular Medicine
https://www.readbyqxmd.com/read/28070536/establishment-a-cho-cell-line-expressing-human-cd52-molecule
#9
Tati Kadijeh, Yazdanpanah-Samani Mahsa, Ramezani Amin, Mahmoudi Maymand Elham, Ghaderi Abbas
BACKGROUND: CD52 is a small glycoprotein with a GPI anchor at its C-terminus. CD52 is expressed by Normal and malignant T and B lymphocytes and monocytes. There are detectable amounts of soluble CD52 in plasma of patients with CLL and could be used as a tumor marker. Although the biological function of CD52 is unknown but it seems that CD52 may be involved in migration and activation of T-cells .The aim of this study was to clone and express human CD52 gene in CHO cell line and studying its function in more details...
October 2016: Reports of Biochemistry & Molecular Biology
https://www.readbyqxmd.com/read/28024470/-establishment-of-human-chronic-lymphocytic-leukemia-model-in-the-balb-c-nude-mice-by-using-mec-1-and-hg3-cell-lines
#10
Chun-Ling Fu, Yan-Qing Gong, Yan Wan, Kai-Lin Xu
OBJECTIVE: To explore the the optimal condition for establishing immune deficiency mouse(BALB/c) model with CLL via subcutaneous inoculation of human chronic lymphocytic leukemia (CLL) cells at different inoculative locations and different cell concentrations. METHODS: Firstly, Two CLL cell lines (MEC-1-GFP and HG3-GFP)with the green fluorescent protein (GFP) were established by lentivirus system respectively, and then the MEC-1-GFP cells (5×10(7)/ml) were inoculated into forelimb, hindlimb and abdomen to observe the tumorigenesis...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28004361/a-review-of-obinutuzumab-ga101-a-novel-type-ii-anti-cd20-monoclonal-antibody-for-the-treatment-of-patients-with-b-cell-malignancies
#11
REVIEW
Kensei Tobinai, Christian Klein, Naoko Oya, Günter Fingerle-Rowson
Obinutuzumab (GA101) is a novel, type II, glycoengineered, humanized anti-CD20 monoclonal antibody that has been developed to address the need for new therapeutics with improved efficacy in patients with lymphocytic leukemia and lymphoma of B-cell origin. Obinutuzumab has a distinct mode of action relative to type I anti-CD20 antibodies, such as rituximab, working primarily by inducing direct cell death and antibody-dependent cell-mediated cytotoxicity. Obinutuzumab is under investigation in a wide-ranging program of clinical trials in patients with B-cell malignancies...
February 2017: Advances in Therapy
https://www.readbyqxmd.com/read/28003273/ebi2-overexpression-in-mice-leads-to-b1-b-cell-expansion-and-chronic-lymphocytic-leukemia-like-b-cell-malignancies
#12
Kristine Niss Arfelt, Line Barington, Tau Benned-Jensen, Valentina Kubale, Alexander L Kovalchuk, Viktorija Daugvilaite, Jan Pravsgaard Christensen, Allan Randrup Thomsen, Kristoffer L Egerod, Maria R Bassi, Katja Spiess, Thue W Schwartz, Hongsheng Wang, Herbert C Morse, Peter J Holst, Mette M Rosenkilde
Human and mouse chronic lymphocytic leukemia (CLL) develops from CD5(+) B cells that in mice and macaques are known to define the distinct B1a B-cell lineage. B1a cells are characterized by lack of germinal center (GC) development, and the B1a cell population is increased in mice with reduced GC formation. As a major mediator of follicular B-cell migration, the G protein-coupled receptor Epstein-Barr virus-induced gene 2 (EBI2 or GPR183) directs B-cell migration in the lymphoid follicles in response to its endogenous ligands, oxysterols...
February 16, 2017: Blood
https://www.readbyqxmd.com/read/27993930/metabolism-and-disposition-of-a-novel-b-cell-lymphoma-2-inhibitor-venetoclax-in-humans-and-characterization-of-its-unusual-metabolites
#13
Hong Liu, Melissa J Michmerhuizen, Yanbin Lao, Katty Wan, Ahmed Hamed Salem, James Sawicki, Michael Serby, Srirajan Vaidyanathan, Shekman L Wong, Suresh Agarwal, Martin Dunbar, Jens Sydor, Sonia M de Morais, Anthony J Lee
Venetoclax (ABT-199), a B-cell lymphoma-2 (Bcl-2) protein inhibitor, is currently in clinical development for the treatment of hematologic malignancies. We characterized the absorption, metabolism, and excretion of venetoclax in humans. After a single oral dose of [(14)C]venetoclax to healthy volunteers, the recovery of total radioactive dose was 100%, with feces being the major route of elimination of the administered dose, whereas urinary excretion was minimal (<0.1%). The extent of absorption was estimated to be at least 65%...
March 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/27977057/randomized-phase-2-study-of-otlertuzumab-and-bendamustine-versus-bendamustine-in-patients-with-relapsed-chronic-lymphocytic-leukaemia
#14
Tadeusz Robak, Andrzej Hellmann, Janusz Kloczko, Javier Loscertales, Ewa Lech-Maranda, John M Pagel, Anthony Mato, John C Byrd, Farrukh T Awan, Holger Hebart, Jose A Garcia-Marco, Brian T Hill, Michael Hallek, Amy J Eisenfeld, Scott C Stromatt, Ulrich Jaeger
Otlertuzumab (TRU-016) is a humanized anti-CD37 protein therapeutic that triggers direct caspase-independent apoptosis of malignant B cells and induces antibody-dependent cell-mediated cytotoxicity. Patients with relapsed chronic lymphocytic leukaemia (CLL) received either otlertuzumab (20 mg/kg) weekly by IV infusion for two 28-day cycles then every 14 days for four 28-day cycles and IV bendamustine (70 mg/m(2) ) on Days 1 and 2 of each cycle for up to six 28-day cycles or bendamustine alone. Thirty-two patients were treated with otlertuzumab and bendamustine and 33 with bendamustine alone...
February 2017: British Journal of Haematology
https://www.readbyqxmd.com/read/27933341/intragenic-variations-in-btla-gene-influence-mrna-expression-of-btla-gene-in-chronic-lymphocytic-leukemia-patients-and-confer-susceptibility-to-chronic-lymphocytic-leukemia
#15
Lidia Karabon, Anna Partyka, Monika Jasek, Ewa Lech-Maranda, Olga Grzybowska-Izydorczyk, Agnieszka Bojarska-Junak, Edyta Pawlak-Adamska, Anna Tomkiewicz, Tadeusz Robak, Jacek Rolinski, Irena Frydecka
The aim of this study was to determine the association between polymorphisms in gene encoding B- and T-lymphocyte attenuator (BTLA) and susceptibility to chronic lymphocytic leukemia (CLL) and their influence on mRNA expression of BTLA gene in T and B cells from CLL patients (pts.). The following BTLA single-nucleotide polymorphisms (SNPs): rs2705511, rs1982809, rs9288952, rs76844316, rs16859633, rs9288953, rs2705535, rs1844089, rs2705565, rs2633580 were genotyped with use of TaqMan probes in 321 CLL pts. and in 470 controls...
December 2016: Archivum Immunologiae et Therapiae Experimentalis
https://www.readbyqxmd.com/read/27908880/an-anti-cd3-anti-cll-1-bispecific-antibody-for-the-treatment-of-acute-myeloid-leukemia
#16
Steven R Leong, Siddharth Sukumaran, Maria Hristopoulos, Klara Totpal, Shannon Stainton, Elizabeth Lu, Alfred Wong, Lucinda Tam, Robert Newman, Brian R Vuillemenot, Diego Ellerman, Chen Gu, Mary Mathieu, Mark S Dennis, Allen Nguyen, Bing Zheng, Crystal Zhang, Genee Lee, Yu-Waye Chu, Rodney A Prell, Kedan Lin, Steven T Laing, Andrew G Polson
Acute myeloid leukemia (AML) is a major unmet medical need. Most patients have poor long-term survival, and treatment has not significantly changed in 40 years. Recently, bispecific antibodies that redirect the cytotoxic activity of effector T cells by binding to CD3, the signaling component of the T-cell receptor, and a tumor target have shown clinical activity. Notably, blinatumomab is approved to treat relapsed/refractory acute lymphoid leukemia. Here we describe the design, discovery, pharmacologic activity, pharmacokinetics, and safety of a CD3 T cell-dependent bispecific (TDB) full-length human IgG1 therapeutic antibody targeting CLL-1 that could potentially be used in humans to treat AML...
February 2, 2017: Blood
https://www.readbyqxmd.com/read/27903679/the-bruton-s-tyrosine-kinase-btk-inhibitor-acalabrutinib-demonstrates-potent-on-target-effects-and-efficacy-in-two-mouse-models-of-chronic-lymphocytic-leukemia
#17
Sarah E M Herman, Arnau Montraveta, Carsten U Niemann, Helena Mora-Jensen, Michael Gulrajani, Fanny Krantz, Rose Mantel, Lisa L Smith, Fabienne McClanahan, Bonnie Harrington, Dolors Colomer, Todd Covey, John C Byrd, Raquel Izumi, Allard Kaptein, Roger Ulrich, Amy Johnson, Brian J Lannutti, Adrian Wiestner, Jennifer A Woyach
PURPOSE: Acalabrutinib (ACP-196) is a novel, potent, and highly selective BTK inhibitor, which binds covalently to Cys481 in the ATP-binding pocket of BTK. We sought to evaluate the anti-tumor effects of acalabrutinib treatment in two established mouse models of chronic lymphocytic leukemia (CLL). EXPERIMENTAL DESIGN: Two distinct mouse models were used, the TCL1 adoptive transfer model where leukemic cells from Eμ-TCL1 transgenic mice are transplanted into C57BL/6 mice, and the human NSG primary CLL xenograft model...
November 30, 2016: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/27890931/a-tlr7-agonist-enhances-the-antitumor-efficacy-of-obinutuzumab-in-murine-lymphoma-models-via-nk-cells-and-cd4-t-cells
#18
E J Cheadle, G Lipowska-Bhalla, S J Dovedi, E Fagnano, C Klein, J Honeychurch, T M Illidge
Anti-CD20 monoclonal antibodies (mAb) such as rituximab have been proven to be highly effective at improving outcome in B-cell malignancies. However, many patients ultimately relapse and become refractory to treatment. The glycoengineered anti-CD20 mAb obinutuzumab was developed to induce enhanced antibody-dependent cellular cytotoxicity, antibody-dependent phagocytosis and direct cell death and was shown to lead to improved outcomes in a randomized study in B-CLL. We hypothesized that immune stimulation through Toll-like receptor 7 (TLR7) agonism in combination with obinutuzumab would further enhance lymphoma clearance and the generation of long-term antitumor immune responses...
January 3, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/27859015/hla-e-allelic-genotype-correlates-with-hla-e-plasma-levels-and-predicts-early-progression-in-chronic-lymphocytic-leukemia
#19
Bettina Wagner, Fabiola da Silva Nardi, Sabine Schramm, Thomas Kraemer, Alexander A Celik, Jan Dürig, Peter A Horn, Ulrich Dührsen, Holger Nückel, Vera Rebmann
BACKGROUND: Human leukocyte antigen-E (HLA-E) is a nonclassical major histocompatibility complex class I molecule that recently came into sharper focus as a putative marker of advanced tumor stages and disease progression. In solid tumors, increased HLA-E expression as well as elevated soluble HLA-E (sHLA-E) plasma levels are associated with a poor prognosis; however, a role for HLA-E in hematologic malignancies remains to be established. METHODS: The authors analyzed HLA-E alleles and sHLA-E levels in a cohort of 110 individuals with chronic lymphocytic leukemia (CLL)...
November 2, 2016: Cancer
https://www.readbyqxmd.com/read/27843137/pi3k%C3%AE-inhibition-elicits-anti-leukemic-effects-through-bim-dependent-apoptosis
#20
M J Carter, K L Cox, S J Blakemore, A H Turaj, R J Oldham, L N Dahal, S Tannheimer, F Forconi, G Packham, M S Cragg
PI3Kδ plays pivotal roles in the maintenance, proliferation and survival of malignant B-lymphocytes. Although not curative, PI3Kδ inhibitors (PI3Kδi) demonstrate impressive clinical efficacy and, alongside other signaling inhibitors, are revolutionizing the treatment of hematological malignancies. However, only limited in vivo data are available regarding their mechanism of action. With the rising number of novel treatments, the challenge is to identify combinations that deliver curative regimes. A deeper understanding of the molecular mechanism is required to guide these selections...
December 20, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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