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https://www.readbyqxmd.com/read/28096272/anti-leukemia-efficacy-and-mechanisms-of-action-of-sl-101-a-novel-anti-cd123-antibody-conjugate-in-acute-myeloid-leukemia
#1
Lina Han, Jeffrey L Jorgensen, Christopher Brooks, Ce Shi, Qi Zhang, Graciela M Nogueras González, Antonio Cavazos, Rongqing Pan, Hong Mu, Sa Wang, Jin Zhou, Gheath Alatrash, Stefan O Ciurea, Michael Rettig, John F DiPersio, Jorge E Cortes, Xuelin Huang, Hagop Kantarjian, Michael Andreeff, Farhad Ravandi-Kashani, Marina Konopleva
PURPOSE: The persistence of leukemia stem cells (LSC)-containing cells after induction therapy may contribute to minimal residual disease (MRD) and relapse in acute myeloid leukemia (AML). We investigated the clinical relevance of CD34+CD123+ LSC-containing cells and anti-leukemia potency of a novel antibody-conjugate SL-101 in targeting CD123+ LSCs. Experimental Methods and Results: In a retrospective study on 86 newly diagnosed AML patients, we demonstrated that a higher proportion of CD34+CD123+ LSC-containing cells in remission was associated with persistent MRD, and predicted shorter relapse-free survival in patients with poor-risk cytogenetics...
January 17, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28090317/all-trans-retinoic-acid-enhances-cytotoxic-effect-of-t-cells-with-an-anti-cd38-chimeric-antigen-receptor-in-acute-myeloid-leukemia
#2
Tetsumi Yoshida, Keichiro Mihara, Yoshifumi Takei, Kazuyoshi Yanagihara, Takanori Kubo, Joyeeta Bhattacharyya, Chihaya Imai, Tatsuji Mino, Yoshihiro Takihara, Tatsuo Ichinohe
We reported that T cells with anti-CD38-chimeric antigen receptors (CAR) eliminated B-cell lymphoma cells expressing CD38. To employ anti-CD38-CAR against acute myeloid leukemia (AML) blasts not expressing CD38, it is necessary to induce or increase the intensity of CD38 expression. A lactate dehydrogenase (LDH)-releasing assay and flow cytometry showed that anti-CD38-CAR T cells were cytotoxic against AML lines (THP-1 and CMK) expressing high CD38 levels (>99%), in time- and number of effector-dependent manners...
December 2016: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28077069/a-pilot-study-of-brisk-walking-in-sedentary-combination-antiretroviral-treatement-cart-treated-patients-benefit-on-soluble-and-cell-inflammatory-markers
#3
Matteo Bonato, Laura Galli, Laura Passeri, Valeria Longo, Gaspare Pavei, Simona Bossolasco, Cecilia Bertocchi, Massimo Cernuschi, Giuseppe Balconi, Giampiero Merati, Adriano Lazzarin, Antonio La Torre, Paola Cinque
BACKGROUND: Chronic HIV infection is associated with low-level inflammation and increased risk of chronic diseases and mortality. The objective was to assess the effects of moderate intensity exercise on metabolic and inflammatory markers in HIV-infected treated persons. METHODS: This was a pilot study enrolling cART-treated, sedentary persons with metabolic complications in a 12-week protocol, consisting of three sessions per week of 60 min brisk walking with (strength-walk group) or without (walk group) 30 min circuit-training...
January 11, 2017: BMC Infectious Diseases
https://www.readbyqxmd.com/read/28076376/increased-natural-killer-cell-activation-in-hiv-infected-immunologic-non-responders-correlates-with-cd4-t-cell-recovery-after-antiretroviral-therapy-and-viral-suppression
#4
Zhenwu Luo, Zhen Li, Lisa Martin, Zhiliang Hu, Hao Wu, Zhuang Wan, Michael Kilby, Sonya L Heath, Lei Huang, Wei Jiang
The role of natural killer (NK) cell function in HIV disease especially in the setting of long-term antiretroviral therapy (ART) and viral suppression is not fully understood. In the current study, we have investigated NK cell activation in healthy controls and aviremic ART-treated HIV+ subjects with different degrees of immune restoration. We performed a cross sectional study in 12 healthy controls and 24 aviremic ART-treated HIV-infected subjects including 13 HIV+ subjects with CD4+ T cells above 500 cells/μL defined as "immunologic responders" and 11 HIV+ subjects with CD4+ T cells below 350 cells/μL defined as "immunologic non-responders"...
2017: PloS One
https://www.readbyqxmd.com/read/28072402/prostate-cancer-on-the-down-low-low-luminal-cell-cd38-expression-is-prognostic
#5
Louise Stone
No abstract text is available yet for this article.
January 10, 2017: Nature Reviews. Urology
https://www.readbyqxmd.com/read/28069005/prognostic-efficacy-of-the-human-b-cell-lymphoma-prognostic-genes-in-predicting-disease-free-survival-dfs-in-the-canine-counterpart
#6
Mohamad Zamani-Ahmadmahmudi, Sina Aghasharif, Keyhan Ilbeigi
BACKGROUND: Canine B-cell lymphoma is deemed an ideal model of human non-Hodgkin's lymphoma where the lymphomas of both species share similar clinical features and biological behaviors. However there are some differences between tumor features in both species. In the current study, we sought to evaluate the prognostic efficacy of human B-cell lymphoma prognostic gene signatures in canine B-cell lymphoma. METHODS: The corresponding probe sets of 36 human B-cell lymphoma prognostic genes were retrieved from 2 canine B-cell lymphoma microarray datasets (GSE43664 and GSE39365) (76 samples), and prognostic probe sets were thereafter detected using the univariate and multivariate Cox proportional-hazard model and the Kaplan-Meier analysis...
January 9, 2017: BMC Veterinary Research
https://www.readbyqxmd.com/read/28063722/concordance-of-two-approaches-in-monitoring-of-minimal-residual-disease-in-b-precursor-acute-lymphoblastic-leukemia-fusion-transcripts-and-leukemia-associated-immunophenotypes
#7
Ying-Jung Huang, Elaine Coustan-Smith, Hsiao-Wen Kao, Hsi-Che Liu, Shih-Hsiang Chen, Chih-Cheng Hsiao, Chao-Ping Yang, Tang-Her Jaing, Ting-Chi Yeh, Ming-Chung Kuo, Chang-Liang Lai, Chia-Hui Chang, Dario Campana, Der-Cherng Liang, Lee-Yung Shih
BACKGROUND: Real-time quantitative polymerase chain reaction (RQ-PCR) for fusion transcripts and flow cytometry for leukemia-specific markers are widely used for minimal residual disease (MRD) detection in acute lymphoblastic leukemia, but the relation between the results of either method is unclear. METHODS: Mononucleated cells from 108 bone marrow samples collected from 55 B-precursor acute lymphoblastic leukemia patients (30 with t(12;21)/ETV6-RUNX1, 16 with t(9;22)/BCR-ABL1 and nine with t(1;19)/TCF3-PBX1) were examined in tandem by RQ-PCR and six-color flow cytometry...
January 4, 2017: Journal of the Formosan Medical Association, Taiwan Yi Zhi
https://www.readbyqxmd.com/read/28046052/integrative-analysis-of-immunological-data-to-explore-chronic-immune-t-cell-activation-in-successfully-treated-hiv-patients
#8
Marie-Quitterie Picat, Isabelle Pellegrin, Juliette Bitard, Linda Wittkop, Cécile Proust-Lima, Benoît Liquet, Jean-François Moreau, Fabrice Bonnet, Patrick Blanco, Rodolphe Thiébaut
OBJECTIVES: To unravel the complex relationships between cytomegalovirus-induced-, autoimmune-induced responses, microbial translocation and chronic immune activation (CIA) in successfully treated HIV-infected patients and to explore the mediating role of alpha-interferon in these processes. DESIGN: Cross-sectional study nested in the ANRS CO3 Aquitaine Cohort, a prospective hospital-based cohort of HIV-1-infected patients in South-Western France. METHODS: Patients initiated antiretroviral therapy between 2005 and 2008 and were treated with sustained virological suppression for at least two years...
2017: PloS One
https://www.readbyqxmd.com/read/28042457/an-update-on-the-role-of-daratumumab-in-the-treatment-of-multiple-myeloma
#9
REVIEW
Caitlin Costello
Monoclonal antibodies (mAbs) have emerged as a promising new drug class for the treatment of multiple myeloma (MM). Daratumumab (DARA), a CD38 mAb, has demonstrated safety, tolerability and activity in a range of clinical trials, both as monotherapy and in combination strategies for MM. The favorable efficacy results in heavily pretreated patients with advanced MM have provided the rationale for the investigation of DARA in a number of ongoing and future phase II and III trials. The general tolerability of mAbs has allowed for widespread investigation and use of DARA among a variety of MM patients, however their use requires special consideration...
January 2017: Therapeutic Advances in Hematology
https://www.readbyqxmd.com/read/28039305/effect-of-antiretroviral-therapy-on-the-memory-and-activation-profiles-of-b-cells-in-hiv-infected-african-women
#10
Ramla F Tanko, Andreia P Soares, Tracey L Müller, Nigel J Garrett, Natasha Samsunder, Quarraisha Abdool Karim, Salim S Abdool Karim, Catherine Riou, Wendy A Burgers
Human immunodeficiency virus infection induces a wide range of effects in B cells, including skewed memory cell differentiation, compromised B cell function, and hypergammaglobulinemia. However, data on the extent to which these B cell abnormalities can be reversed by antiretroviral therapy (ART) are limited. To investigate the effect of ART on B cells, the activation (CD86) and differentiation (IgD, CD27, and CD38) profiles of B cells were measured longitudinally in 19 HIV-infected individuals before (median, 2 mo) and after ART initiation (median, 12 mo) and compared with 19 age-matched HIV-uninfected individuals using flow cytometry...
December 30, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28038356/mrna-overexpression-of-the-hypoxia-inducible-factor-1-alpha-subunit-gene-hif1a-an-independent-predictor-of-poor-overall-survival-in-chronic-lymphocytic-leukemia
#11
Christos K Kontos, Sotirios G Papageorgiou, Marios A Diamantopoulos, Andreas Scorilas, Efthimia Bazani, Diamantina Vasilatou, Konstantinos Gkontopoulos, Eirini Glezou, Georgia Stavroulaki, George Dimitriadis, Vasiliki Pappa
The hypoxia inducible factor 1 (HIF1) is a heterodimeric transcription factor that ultimately regulates cellular responses to changes in oxygen tension. In this study, we examined the potential diagnostic and prognostic potential of the mRNA expression of HIF1 regulatory α-subunit (HIF1A) in chronic lymphocytic leukemia (CLL). For this purpose, total RNA was isolated from peripheral blood mononuclear cells collected from 88 CLL patients and 33 non-leukemic blood donors, and poly(A)-RNA was reversely transcribed...
November 29, 2016: Leukemia Research
https://www.readbyqxmd.com/read/28035914/antibody-mimicry-receptors-and-clinical-applications
#12
Alberto L Horenstein, Antonella Chillemi, Valeria Quarona, Andrea Zito, Valentina Mariani, Angelo C Faini, Fabio Morandi, Ilaria Schiavoni, Clara Maria Ausiello, Fabio Malavasi
This review focuses on the concept of antibodies acting as receptor agonists and antagonists, and on the potential relevance of this notion in applied medicine. Antibodies are composed of three functional units: two antigen-binding fragments (Fabs) that confer antigen specificity and one constant fragment (Fc) linking antibodies to immune effector functions. The proof-of-concept that large amounts of highly specific and homogeneous antibodies could be produced was provided in 1975 by César Milstein and Georges Köhler...
December 23, 2016: Human Antibodies
https://www.readbyqxmd.com/read/28025713/cyclic-adp-ribose-as-an-endogenous-inhibitor-of-the-mtor-pathway-downstream-of-dopamine-receptors-in-the-mouse-striatum
#13
Haruhiro Higashida, Shin-Ya Kamimura, Takeshi Inoue, Osamu Hori, Mohammad Saharul Islam, Olga Lopatina, Chiharu Tsuji
The role of cyclic ADP-ribose (cADPR) as a second messenger and modulator of the mTOR pathway downstream of dopamine (DA) receptors and/or CD38 was re-examined in the mouse. ADP-ribosyl activity was low in the membranes of neonates, but DA stimulated it via both D1- and D2-like receptors. ADP-ribosyl cyclase activity increased significantly during development in association with increased expression of CD38. The cADPR binding proteins, FKBP12 and FKBP12.6, were expressed in the adult mouse striatum. The ratio of phosphorylated to non-phosphorylated S6 kinase (S6K) in whole mouse striatum homogenates decreased after incubation of adult mouse striatum with extracellular cADPR for 5 min...
December 26, 2016: Journal of Neural Transmission
https://www.readbyqxmd.com/read/28018598/cd34-and-cd38-are-prognostic-biomarkers-for-acute-b-lymphoblastic-leukemia
#14
REVIEW
Zhiwu Jiang, Di Wu, Shouheng Lin, Peng Li
CD34 and CD38 proteins are usually used as surface markers to identify HSCs and Leukemic stem cells. However, there have been cases that lacked CD34 or CD38 protein but still had leukemia initiating capacity in B-ALL suggesting the restrictive of these two markers. CD34 and CD38 expression were detected in most B-ALL and can serve as a specific biomarker for the prognosis of this subset of leukemia. Lack of CD34 or high CD38 expression is associated with favorable prognosis.
2016: Biomarker Research
https://www.readbyqxmd.com/read/28018346/low-double-negative-cd3-cd4-cd8-t-cells-are-associated-with-incomplete-restoration-of-cd4-t-cells-and-higher-immune-activation-in-hiv-1-immunological-non-responders
#15
Xiaofan Lu, Bin Su, Huan Xia, Xin Zhang, Zhiying Liu, Yunxia Ji, Zixuan Yang, Lili Dai, Luzia M Mayr, Christiane Moog, Hao Wu, Xiaojie Huang, Tong Zhang
Failure of immune reconstitution increases the risk of AIDS or non-AIDS related morbidity and mortality in HIV-1-infected patients. CD3(+)CD4(-)CD8(-) T cells, which are usually described as double-negative (DN) T cells, display CD4-like helper and immunoregulatory functions. Here, we have measured the percentage of DN T cells in the immune reconstituted vs. non-immune reconstituted HIV-1-infected individuals. We observed that immunological non-responders (INRs) had a low number of DN T cells after long-term antiretroviral therapy (ART), and the number of these cells positively correlated with the CD4(+) T cell count...
2016: Frontiers in Immunology
https://www.readbyqxmd.com/read/28017425/vaccination-of-rhesus-macaques-with-the-live-attenuated-hsv-1-vaccine-vc2-stimulates-the-proliferation-of-mucosal-t-cells-and-germinal-center-responses-resulting-in-sustained-production-of-highly-neutralizing-antibodies
#16
Brent A Stanfield, Bapi Pahar, Vladimir N Chouljenko, Ronald Veazey, Konstantin G Kousoulas
We have shown that the live-attenuated HSV-1 VC2 vaccine strain with mutations in glycoprotein K (gK) and the membrane protein UL20 is unable to establish latency in vaccinated animals and produces a robust immune response capable of completely protecting mice against lethal vaginal HSV-1 or HSV-2 infections. To better understand the immune response generated by vaccination with VC2, we tested its ability to elicit immune responses in rhesus macaques. Vaccinated animals showed no signs of disease and developed increasing HSV-1 and HSV-2 reactive IgG1 after two booster vaccinations, while IgG subtypes IgG2 and IgG3 remained at low to undetectable levels...
December 22, 2016: Vaccine
https://www.readbyqxmd.com/read/28005028/-causes-of-t-lymphocyte-activation-in-hiv-infected-patients-coinfected-with-hepatitis-c-virus
#17
K V Shmagel', N G Shmagel', L B Korolevskaya, E V Saidakova, V A Chereshnev
AIM: To establish the causes of T lymphocyte activation in human immunodeficiency virus (HIV)-infected patients coinfected with hepatitis C (HCV) who are adherent to their antiretroviral therapy regimen and interferon untreated. SUBJECTS AND METHODS: Examinations were made in 62 people who were HIV+HCV-positive (n=21), HIV+HCV-negative (n=21), and noninfected volunteers (n=20). The activation (CD38+HLA-DR+) and proliferation (Ki-67+) of CD4+ and CD8+ T lymphocytes were estimated...
2016: Terapevticheskiĭ Arkhiv
https://www.readbyqxmd.com/read/27999737/immunotherapies-targeting-cd38-in-multiple-myeloma
#18
REVIEW
Djordje Atanackovic, Mary Steinbach, Sabarinath Venniyil Radhakrishnan, Tim Luetkens
Recently, the monoclonal antibody daratumumab was approved as a single agent for the treatment of patients with relapsed/refractory Multiple Myeloma (MM). Daratumumab is an antibody targeting surface molecule CD38 on myeloma cells and the agent is already widely being used based on its good tolerability and proven efficacy. We believe, however, that the efficacy of this drug and other anti-CD38 monoclonal antibodies can be further improved by combining it with other types of immunotherapies. Furthermore, surface molecule CD38 can be used as a target for immunotherapies other than just naked monoclonal antibodies...
2016: Oncoimmunology
https://www.readbyqxmd.com/read/27997758/comprehensive-mass-cytometry-analysis-of-cell-cycle-activation-and-co-inhibitory-receptors-expression-in-cd4-t-cells-from-healthy-and-hiv-infected-individuals
#19
REVIEW
Aurélien Corneau, Antonio Cosma, Sophie Even, Christine Katlama, Roger Legrand, Véronique Frachet, Catherine Blanc, Brigitte Autran
RATIONALE: Mass cytometry allows large multiplex analysis of cell cycle stages together with differentiation, activation and exhaustion markers, allowing further assessment of the quiescence status of resting CD4 T cells. METHODS: peripheral blood CD4 T lymphocytes from 8 individuals, 4 healthy donors (HD) and 4 HIV-infected on anti-retroviral treatment (T) were stained with the same 26 monoclonal antibodies and dyes targeting surface and intra-cellular markers of differentiation, activation, exhaustion and cell cycle stages...
December 20, 2016: Cytometry. Part B, Clinical Cytometry
https://www.readbyqxmd.com/read/27993172/immune-reconstitution-20%C3%A2-years-after-treatment-with-alemtuzumab-in-a-rheumatoid-arthritis-cohort-implications-for-lymphocyte-depleting-therapies
#20
Faye A H Cooles, Amy E Anderson, Tracey Drayton, Rachel A Harry, Julie Diboll, Lee Munro, Nishanthi Thalayasingham, Andrew J K Östör, John D Isaacs
BACKGROUND: Alemtuzumab, an anti-CD52 monoclonal antibody, was administered to patients with RA between 1991 and 1994. We have followed a cohort of recipients since that time and previously reported significant delays in immune reconstitution. Here we report >20 years of follow-up data from this unique cohort. METHOD: Surviving alemtuzumab recipients were age, sex and disease duration matched with RA controls. Updated mortality and morbidity data were collected for alemtuzumab recipients...
December 20, 2016: Arthritis Research & Therapy
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