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https://www.readbyqxmd.com/read/28928126/chimeric-antigen-receptor-t-cell-therapies-for-multiple-myeloma
#1
Lekha Mikkilineni, James N Kochenderfer
Multiple myeloma (MM) is a nearly always incurable malignancy of plasma cells, so new approaches to treatment are needed. T-cell therapies are a promising approach for treating MM, with a mechanism of action different than those of standard MM treatments. Chimeric antigen receptors (CARs) are fusion proteins incorporating antigen-recognition domains and T-cell signaling domains. T-cells genetically engineered to express CARs can specifically recognize antigens. Success of CAR T-cells against leukemia and lymphoma has encouraged development of CAR T-cell therapies for MM...
September 19, 2017: Blood
https://www.readbyqxmd.com/read/28926641/impact-of-monotherapy-on-hiv-1-reservoir-immune-activation-and-co-infection-with-epstein-barr-virus
#2
Maria Raffaella Petrara, Anna Maria Cattelan, Lolita Sasset, Riccardo Freguja, Francesco Carmona, Silvia Sanavia, Marisa Zanchetta, Paola Del Bianco, Anita De Rossi
OBJECTIVES: Although monotherapy (mART) effectiveness in maintaining viral suppression and CD4 cell count has been extensively examined in HIV-1-infected patients, its impact on HIV-1 reservoir, immune activation, microbial translocation and co-infection with Epstein-Barr Virus (EBV) is unclear. METHODS: This retrospective study involved 32 patients who switched to mART; patients were studied at baseline, 48 and 96 weeks after mART initiation. Thirty-two patients who continued combined antiretroviral therapy (cART) over the same period of time were included in the study...
2017: PloS One
https://www.readbyqxmd.com/read/28920959/targeting-mitochondrial-oxidative-phosphorylation-eradicates-therapy-resistant-chronic-myeloid-leukemia-stem-cells
#3
Elodie M Kuntz, Pablo Baquero, Alison M Michie, Karen Dunn, Saverio Tardito, Tessa L Holyoake, G Vignir Helgason, Eyal Gottlieb
Treatment of chronic myeloid leukemia (CML) with imatinib mesylate and other second- and/or third-generation c-Abl-specific tyrosine kinase inhibitors (TKIs) has substantially extended patient survival. However, TKIs primarily target differentiated cells and do not eliminate leukemic stem cells (LSCs). Therefore, targeting minimal residual disease to prevent acquired resistance and/or disease relapse requires identification of new LSC-selective target(s) that can be exploited therapeutically. Considering that malignant transformation involves cellular metabolic changes, which may in turn render the transformed cells susceptible to specific assaults in a selective manner, we searched for such vulnerabilities in CML LSCs...
September 18, 2017: Nature Medicine
https://www.readbyqxmd.com/read/28915615/expression-of-cd38-in-myeloma-bone-niche-a-rational-basis-for-the-use-of-anti-cd38-immunotherapy-to-inhibit-osteoclast-formation
#4
Federica Costa, Denise Toscani, Antonella Chillemi, Valeria Quarona, Marina Bolzoni, Valentina Marchica, Rosanna Vescovini, Cristina Mancini, Eugenia Martella, Nicoletta Campanini, Chiara Schifano, Sabrina Bonomini, Fabrizio Accardi, Alberto L Horenstein, Franco Aversa, Fabio Malavasi, Nicola Giuliani
It is known that multiple myeloma (MM) cells express CD38 and that a recently developed human anti-CD38 monoclonal antibody Daratumumab mediates myeloma killing. However, the expression of CD38 and other functionally related ectoenzymes within the MM bone niche and the potential effects of Daratumumab on bone cells are still unknown. This study firstly defines by flow cytometry and immunohistochemistry the expression of CD38 by bone marrow cells in a cohort of patients with MM and indolent monoclonal gammopathies...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28905187/altered-b-cell-homeostasis-in-patients-with-major-depressive-disorder-and-normalization-of-cd5-surface-expression-on-regulatory-b-cells-in-treatment-responders
#5
Diana Ahmetspahic, Kathrin Schwarte, Oliver Ambrée, Christian Bürger, Vladislava Falcone, Katharina Seiler, Mehrdad Rahbar Kooybaran, Laura Grosse, Fernand Roos, Julia Scheffer, Silke Jörgens, Katja Koelkebeck, Udo Dannlowski, Volker Arolt, Stefanie Scheu, Judith Alferink
Pro-inflammatory activity and cell-mediated immune responses have been widely observed in patients with major depressive disorder (MDD). Besides their well-known function as antibody-producers, B cells play a key role in inflammatory responses by secreting pro- and anti-inflammatory factors. However, homeostasis of specific B cell subsets has not been comprehensively investigated in MDD. In this study, we characterized circulating B cells of distinct developmental steps including transitional, naïve-mature, antigen-experienced switched, and non-switched memory cells, plasmablasts and regulatory B cells by multi-parameter flow cytometry...
September 13, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28904172/fda-approval-summary-daratumumab-for-treatment-of-multiple-myeloma-after-one-prior-therapy
#6
Vishal Bhatnagar, Nicole J Gormley, Lola Luo, Yuan Li Shen, Rajeshwari Sridhara, Sriram Subramaniam, Guoxiang Shen, Lian Ma, Stacy Shord, Kirsten B Goldberg, Ann T Farrell, Amy E McKee, Richard Pazdur
On November 21, 2016, the U.S. Food and Drug Administration granted regular approval to daratumumab in combination with lenalidomide and dexamethasone, or bortezomib and dexamethasone, for the treatment of patients with multiple myeloma who have received at least one prior therapy. Approval was based on two randomized, open-label trials in which daratumumab was added to these backbone therapies. The MMY3003 trial demonstrated substantial improvement in progression-free survival (PFS) when daratumumab was added to lenalidomide and dexamethasone compared with lenalidomide and dexamethasone alone...
September 13, 2017: Oncologist
https://www.readbyqxmd.com/read/28903574/whole-exome-sequencing-of-aberrant-plasma-cells-in-a-patient-with-multiple-myeloma-minimal-residual-disease
#7
M Zatopkova, J Filipová, T Jelínek, P Vojta, T Sevcikova, M Simicek, L Rihova, R Bezdekova, K Growkova, Z Kufová, J Smejkalová, M Hajdúch, L Pour, J Minárik, A Jungová, V Maisnar, F Kryukov, R Hájek
Multiple myeloma is a plasma cell dyscrasia. It is the second most common hematological malignancy which is characterized by proliferation of clonal plasma cells producing harmful monoclonal immunoglobulin. Despite treatment modalities greatly evolved during the last decade, small amount of aberrant residual cells reside in patients after therapy and can cause relapse of the disease. Characterization of the residual, resistant clones can help to reveal important therapeutic targets for application of effective and precious treatment...
2017: Klinická Onkologie: Casopis Ceské a Slovenské Onkologické Spolecnosti
https://www.readbyqxmd.com/read/28903011/inter-individual-responses-to-sprint-interval-training-a-pilot-study-investigating-interactions-with-the-sirtuin-system
#8
Stuart R Gray, Tom P Aird, Andrew J Farquharson, Graham W Horgan, Emily Fisher, John Wilson, Gareth E Hopkins, Bradley Anderson, Syed A Ahmad, Stuart R Davis, Janice E Drew
Sprint intensity interval training (SIT) is reported to improve blood glucose control and may be a useful public health tool. The sirtuins and associated genes are emerging as key players in blood glucose control. This study investigated the interplay between the sirtuin/NAD system and individual variation in insulin sensitivity responses after SIT in young healthy individuals. Before and after 4 weeks of SIT body mass and fat percentage were measured and oral glucose tolerance tests (OGTT) performed in 20 young healthy participants (7 females)...
September 13, 2017: Applied Physiology, Nutrition, and Metabolism, Physiologie Appliquée, Nutrition et Métabolisme
https://www.readbyqxmd.com/read/28902679/brief-report-peripheral-monocyte-macrophage-phenotypes-associated-with-the-evolution-of-cognitive-performance-in-hiv-infected-patients
#9
Massimiliano Fabbiani, Antonio Muscatello, Paolo Perseghin, Marco Bani, Arianna Incontri, Nicola Squillace, Giuseppe Lapadula, Andrea Gori, Alessandra Bandera
BACKGROUND: The contribution of monocyte activation in the development of HIV-associated neurocognitive disorders is not completely understood. This study aimed to explore the predictive value of peripheral monocyte/macrophage (M/M) phenotypes on the evolution of cognitive performance in a population of virologically suppressed HIV-infected patients. SETTING: Prospective, observational, longitudinal study. METHODS: HIV-1-infected patients with HIV-RNA <50copies/mL for >12 months underwent neuropsychological examination at baseline and after 1 year...
October 1, 2017: Journal of Acquired Immune Deficiency Syndromes: JAIDS
https://www.readbyqxmd.com/read/28899396/transcriptomic-meta-analysis-identifies-gene-expression-characteristics-in-various-samples-of-hiv-infected-patients-with-nonprogressive-disease
#10
Le-Le Zhang, Zi-Ning Zhang, Xian Wu, Yong-Jun Jiang, Ya-Jing Fu, Hong Shang
BACKGROUND: A small proportion of HIV-infected patients remain clinically and/or immunologically stable for years, including elite controllers (ECs) who have undetectable viremia (<50 copies/ml) and long-term nonprogressors (LTNPs) who maintain normal CD4(+) T cell counts for prolonged periods (>10 years). However, the mechanism of nonprogression needs to be further resolved. In this study, a transcriptome meta-analysis was performed on nonprogressor and progressor microarray data to identify differential transcriptome pathways and potential biomarkers...
September 12, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28894451/inflammatory-conditions-dictate-the-effect-of-mesenchymal-stem-or-stromal-cells-on-b-cell-function
#11
Franka Luk, Laura Carreras-Planella, Sander S Korevaar, Samantha F H de Witte, Francesc E Borràs, Michiel G H Betjes, Carla C Baan, Martin J Hoogduijn, Marcella Franquesa
The immunomodulatory capacity of mesenchymal stem or stromal cells (MSC) makes them a promising tool for treatment of immune disease and organ transplantation. The effects of MSC on B cells are characterized by an abrogation of plasmablast formation and induction of regulatory B cells (Bregs). It is, however, unknown how MSC interact with B cells under inflammatory conditions. In this study, adipose tissue-derived MSC were pretreated with 50 ng/ml IFN-γ for 96 h (MSC-IFN-γ) to simulate inflammatory conditions...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28892514/l-thyroxine-modifies-nephrotoxicity-by-regulating-the-apoptotic-pathway-the-possible-role-of-cd38-adp-ribosyl-cyclase-mediated-calcium-mobilization
#12
Tarek El-Hamoly, Dina M El-Sharawy, Marwa S El Refaye, Sahar S Abd El-Rahman
Thyroid hormones are well-established as a key regulator of many cellular metabolic pathways developed in various pathogeneses. Here, we dedicated the current work to investigate the role of thyroid hormone analogue (L-thyroxine, L-TH) in regulating the renal cytotoxicity using in vivo and in vitro models. Swiss mice were exposed to gamma radiation (IRR, 6Gy) or treated with cisplatin (CIS, 15 mg/kg, i.p.) for induction of nephrotoxicity. Remarkably, pretreatment with L-TH (1μg/kg) ameliorated the elevated kidney function biomarkers, oxidative stress and protected the renal tissue from the subsequent cellular damage...
2017: PloS One
https://www.readbyqxmd.com/read/28888074/early-recovery-of-circulating-immature-b-cells-in-b-lymphoblastic-leukemia-patients-after-cd19-targeted-car-t-cell-therapy-a-pitfall-for-minimal-residual-disease-detection
#13
Wenbin Xiao, Dalia Salem, Catherine McCoy, Daniel Lee, Nirali N Shah, Maryalice Stetler-Stevenson, Constance M Yuan
BACKGROUND: CD19-targeted chimeric-antigen receptor-modified T-cells (CAR-T) are promising in the treatment of refractory B-lymphoblastic leukemia (B-ALL). Minimal residual disease (MRD) detection by multicolor flow cytometry (FCM) is critical to distinguish B-ALL MRD from regenerating, non-neoplastic B-cell populations. METHODS: FCM was performed on samples from 9 patients with B-ALL treated with CAR-T. RESULTS: All 9 patients showed response to CAR-T...
September 9, 2017: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/28886017/b-cell-phenotype-and-igd-cd27-memory-b-cells-are-affected-by-tnf-inhibitors-and-tocilizumab-treatment-in-rheumatoid-arthritis
#14
Rita A Moura, Cláudia Quaresma, Ana R Vieira, Maria J Gonçalves, Joaquim Polido-Pereira, Vasco C Romão, Nádia Martins, Helena Canhão, João E Fonseca
BACKGROUND: The use of TNF-inhibitors and/or the IL-6 receptor antagonist, tocilizumab, in rheumatoid arthritis (RA) have pleiotropic effects that also involve circulating B-cells. The main goal of this study was to assess the effect of TNF-inhibitors and tocilizumab on B-cell phenotype and gene expression in RA. METHODS: Blood samples were collected from untreated early RA (ERA) patients, established RA patients under methotrexate treatment, established RA patients before and after treatment with TNF-inhibitors and tocilizumab, and healthy donors...
2017: PloS One
https://www.readbyqxmd.com/read/28884705/cryptochrome-1-gene-expression-is-a-reliable-prognostic-indicator-in-egyptian-patients-with-chronic-lymphocytic-leukemia-a-cohort-prospective-study
#15
Deena Mohamed Habashy, Deena Samir Eissa, Mona Mahmoud Aboelez
Objectives Traditional prognostic factors have proven insufficient to account for the observed heterogeneity in the clinical behavior of chronic lymphocytic leukemia (CLL). Cryptochrome-1 (CRY-1) is a circadian clock gene essential in maintaining circadian rhythm and regulating cell proliferation. We evaluated CRY-1 gene expression in CLL patients, and assessed its putative role as a prognostic indicator for the clinical course of CLL. Materials and Methods Hundred CLL patients at diagnosis were studied for CRY-1 gene expression by qRT-PCR, and were followed up for assessment of time to first treatment (TFT)...
September 8, 2017: Turkish Journal of Haematology: Official Journal of Turkish Society of Haematology
https://www.readbyqxmd.com/read/28883263/combination-therapy-with-monoclonal-antibodies-for-treatment-of-newly-diagnosed-multiple-myeloma
#16
Noriko Nishimura, Yasuhito Terui, Kiyohiko Hatake
Monoclonal antibodies (mAbs) with new mechanisms of action are emerging as promising agents for patients with multiple myeloma (MM). Of these, anti-CD38 antibodies and anti-signaling lymphocytic activation molecule F7 (SLAMF7) antibody have demonstrated efficacy for relapsed and refractory myeloma (RRMM). Two CD38-targeting antibodies, daratumumab and isatuximab had significant activity as single agents, whereas the SLAMF7-targeting antibody, elotuzumab, did not. Patients with RRMM treated with 16 mg/kg daratumumab achieved at least PR of 36% and 29% in two distinct phase 2 studies...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28877980/nad-metabolism-fuels-human-and-mouse-intestinal-inflammation
#17
Romana R Gerner, Victoria Klepsch, Sophie Macheiner, Kathrin Arnhard, Timon E Adolph, Christoph Grander, Verena Wieser, Alexandra Pfister, Patrizia Moser, Natascha Hermann-Kleiter, Gottfried Baier, Herbert Oberacher, Herbert Tilg, Alexander R Moschen
OBJECTIVE: Nicotinamide phosphoribosyltransferase (NAMPT, also referred to as pre-B cell colony-enhancing factor or visfatin) is critically required for the maintenance of cellular nicotinamide adenine dinucleotide (NAD) supply catalysing the rate-limiting step of the NAD salvage pathway. NAMPT is strongly upregulated in inflammation including IBD and counteracts an increased cellular NAD turnover mediated by NAD-depleting enzymes. These constitute an important mechanistic link between inflammatory, metabolic and transcriptional pathways and NAD metabolism...
September 6, 2017: Gut
https://www.readbyqxmd.com/read/28875010/anti-apoptotic-effects-of-osteopontin-via-the-up-regulation-of-akt-mtor-%C3%AE-catenin-loop-in-acute-myeloid-leukemia-cells
#18
Mahdi Zahed Panah, Mohsen Nikbakht, Seyed Mehdi Sajjadi, Shahrbano Rostami, Amir Hossein Norooznezhad, Hosein Kamranzadeh Fumani, Ardeshir Ghavamzadeh, Saeed Mohammadi
Background: The conventional chemotherapeutic regimens which applied for treatment of acute myeloid leukemia (AML) mostly target tumor bulk but not leukemic stem cells (LSCs). Aberrant expression or activation of mediators such as osteopontin (OPN) or PI3K/PTEN/Akt/mTOR pathway plays a key role in making prone to develop leukemia. Preventing or treating cancer by curcumin (CUR) has been suggested recently. CUR induces apoptosis and growth inhibition through various mechanisms in leukemic cells. In present study, we tried to measure the toxic response in vitro to CUR for evaluation ofchangesin cell viability, survival and molecular-mediated resistance in primary AML cells...
April 1, 2017: International Journal of Hematology-oncology and Stem Cell Research
https://www.readbyqxmd.com/read/28865941/a-field-study-of-the-association-between-cd38-gene-and-altruistic-behavior-empathic-response-as-a-mediator
#19
Jinting Liu, Pingyuan Gong, Hong Li, Xiaolin Zhou
Inspired by the enhancement effects of oxytocin on empathic responses and altruistic behaviors, we conducted a field study with a real fundraising event and investigated to what extent oxytocin pathway genes (CD38 and OXTR) modulate individual differences in charitable donation. Participants were informed that a teacher in their university was diagnosed with uremia and could not afford the cost of medication. They were given the opportunity to donate any amount of money and report their empathic responses to the misfortune of the teacher...
August 12, 2017: Psychoneuroendocrinology
https://www.readbyqxmd.com/read/28865180/automated-and-simplified-identification-of-normal-and-abnormal-plasma-cells-in-multiple-myeloma-by-flow-cytometry
#20
Elina Alaterre, Sébastien Raimbault, Jean-Michel Garcia, Thierry Rème, Guilhem Requirand, Bernard Klein, Jérôme Moreaux
BACKGROUND: Multiple myeloma (MM) is an incurable disease characterized by clonal plasma cell (PC) proliferation within the bone marrow (BM). Next-generation flow cytometry has become the reference tool to follow minimal residual disease (MRD). We developed a new simpler and cheaper flow cytometry method to analyze bone marrow samples in patients with MM. METHODS: To identify and characterize abnormal PC, we designed a simple panel composed of anti-CD38, anti-kappa and anti-lambda light chain antibodies, combined with two antibody pools with the same fluorophore (anti-CD19 and anti-CD27 for the negative pool, and anti-CD56, anti-CD117 and anti-CD200 antibodies for the positive pool)...
September 2, 2017: Cytometry. Part B, Clinical Cytometry
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