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Meng Wang, Yu Ping, Zhiqin Li, Jieyao Li, Zhen Zhang, Dongli Yue, Xinfeng Chen, Liping Wang, Lan Huang, Jianmin Huang, Li Yang, Xuan Zhao, Shuangning Yang, Hong Li, Jijing Shi, Jiansheng Li, Yi Zhang
Myeloid-derived suppressor cells (MDSCs) have been described as suppressors of T-cell function in many malignancies. Impaired T-cell responses have been observed in patients with chronic hepatitis C virus infection (CHC), which is reportedly associated with the establishment of persistent HCV infection. Therefore, we hypothesized that MDSCs also play a role in chronic HCV infection. MDSCs in the peripheral blood of 206 patients with CHC and 20 healthy donors were analyzed by flow cytometry. Peripheral blood mononuclear cells (PBMCs) of healthy donors cultured with hepatitis C core protein (HCVc) were stimulated with or without interleukin 10 (IL-10)...
October 19, 2018: Journal of Viral Hepatitis
Nikolaos Gardikas, Myrofora Vikentiou, Evgenia Konsta, Christos K Kontos, Sotirios G Papageorgiou, Aris Spathis, Efthimia Bazani, Anthi Bouchla, Violetta Kapsimali, Katherina Psarra, Periklis Foukas, George Dimitriadis, Vasiliki Pappa
BACKGROUND: Myelodysplastic syndromes (MDS) are clonal hematopoietic stem cell disorders with unknown aetiology. Multiparameter flow cytometry (MFC) is being evaluated for the diagnosis and prognosis of MDS. METHODS: In the present study, five-color MFC was performed on bone marrow aspirates of 50 untreated patients, newly diagnosed with MDS and 27 age matched control samples. Patients were classified according to World Health Organization 2016, International Prognostic Scoring System (IPSS), and Revised IPSS (IPSS-R)...
October 17, 2018: Cytometry. Part B, Clinical Cytometry
Xiaowen Tang, Lin Yang, Zheng Li, Ansel P Nalin, Haiping Dai, Ting Xu, Jia Yin, Fengtao You, Mingqing Zhu, Wenhong Shen, Guanghua Chen, Xiaming Zhu, Depei Wu, Jianhua Yu
[This corrects the article on p. 1083 in vol. 8, PMID: 30034945.].
2018: American Journal of Cancer Research
Kathelijne Cjm Kraal, Ilse Timmerman, Hannah M Kansen, Cor van den Bos, Jozsef Zsiros, Henk van den Berg, Sebastiaan F Somers, Eric Braakman, Annemarie M L Peek, Max van Noesel, C Ellen van der Schoot, Marta Fiocco, Huib N Caron, Carlijn Voermans, Godelieve A M Tytgat
PURPOSE: Targeted radiotherapy with 131 Iodine-meta-iodobenzylguanidine (131 I-MIBG) is effective for neuroblastoma (NBL), although optimal scheduling during high-risk (HR) treatment is being investigated. We aimed to evaluate the feasibility of stem cell apheresis and study hematological reconstitution after autologous stem cell transplantation (ASCT) in HR-NBL patients treated with upfront 131 I-MIBG-therapy. EXPERIMENTAL DESIGN: In two prospective multi-center cohort studies, newly diagnosed HR-NBL patients were treated with two courses of 131 I-MIBG-therapy, followed by a HR-induction protocol...
October 12, 2018: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
Ping Wang, Xian'gui Peng, Xiaojuan Deng, Li Gao, Xi Zhang, Yimei Feng
RATIONALE: The diagnosis of hematological malignancies depends on laboratory analysis and often requires multiple experimental methods to judge, otherwise misdiagnosis is apt to happen. Lymph node biopsy immunohistochemistry (IHC) for T-lymphoblastic lymphoma (T-LBL) requires the establishment of antibody set screening. For identifying T-LBL and early T-cell precursor acute lymphoblastic leukemia (ETP-ALL) by lymph node biopsy and IHC, WHO has not yet proposed a better IHC antibody combination...
October 2018: Medicine (Baltimore)
Yimamu Maimaitili, Aki Inase, Yoshiharu Miyata, Akihito Kitao, Yu Mizutani, Seiji Kakiuchi, Yohei Shimono, Yasuyuki Saito, Takashi Sonoki, Hironobu Minami, Hiroshi Matsuoka
Gemtuzumab ozogamicin (GO), the first antibody-drug conjugate (ADC), has attracted the interest of hematologists because more than 90% of acute myeloid leukemia (AML) blasts express its target, CD33. Although GO and subsequently developed ADCs depend on lysosomes for activation, lysosome number and activity in tumor cells has not been well elucidated. In this study, we investigated whether an mTORC1/2 kinase inhibitor, PP242, which was reported to activate lysosomal function, potentiates the cytotoxicity of GO in AML cells...
October 2, 2018: Leukemia Research
Alejandro Carrillo-Jimenez, Mar Puigdellívol, Anna Vilalta, Jose Luis Venero, Guy Charles Brown, Peter StGeorge-Hyslop, Miguel Angel Burguillos
Microglia, the resident immune cells of the brain, have multiple functions in physiological and pathological conditions, including Alzheimer's disease (AD). The use of primary microglial cell cultures has proved to be a valuable tool to study microglial biology under various conditions. However, more advanced transfection methodologies for primary cultured microglia are still needed, as current methodologies provide low transfection efficiency and induce cell death and/or inflammatory activation of the microglia...
2018: Frontiers in Cellular Neuroscience
Yue-Fang Wang, Ge Zhang, Yong-Mei Jiang, Ju Gao
OBJECTIVE: To determine whether immune differentiation antigen is related with clinical features and minimal residual disease (MRD) in childhood B-cell precursor acute lymphoblastic leukemia (B-ALL), who were treated with CCCG-ALL-2015 protocol. METHODS: A retrospective analysis was conducted in 132 B-ALL children, Multiparametric flow cytometry was used to analyze the immunophenotypes. The children were divided into 2 groups by MRD>0.1% on d 19 and / or d 46 after chemotherapy...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Jiong Ma, Guo-Min He, Hong Liu, Xiao-Yang Gao, Wen-Juan Zhu
OBJECTIVE: To analyze the heterogeneous biological characteristics of acute leukemia (AL) patients with mistranslation expressed lymphoid and myeloid-related antigens, and it's prognosis-related factors. METHODS: Two hundred and fourteen AL patiens with mistranslation expressed lymphoid and myeloid-related antigens were grouped according to immunophenotypes, and the heterogeneous biologic charecteristics and prognosis related factors were analyzed, moreover the survival curves were drawn to analyze the survival of patiens...
October 2018: Zhongguo Shi Yan Xue Ye Xue za Zhi
Olivier Humbert, George S Laszlo, Sophie Sichel, Christina Ironside, Kevin G Haworth, Olivia M Bates, Mary E Beddoe, Ray R Carrillo, Hans-Peter Kiem, Roland B Walter
No abstract text is available yet for this article.
October 5, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Jingjing Duan, Yongwei Xie, Lijuan Qu, Lingxiong Wang, Shunkai Zhou, Yu Wang, Zhongyi Fan, Shengsheng Yang, Shunchang Jiao
BACKGROUND: Immunoscore, as a prognostic tool defined to quantify in situ immune cell infiltrates, appears to be superior to the TNM staging system. In esophageal squamous cell carcinoma (ESCC), no immunoscore has been established; however, in situ tumor immunology is recognized as highly important. Our study aimed to construct a comprehensive immunoprofile for ESCC. METHODS: The infiltration of four immune cell types (CD8+/CD4+/Foxp3+/CD33+ cells), the expression of both inhibitory (PD-1/PD-L1/Tim-3/LAG-3) and stimulatory checkpoints (OX-40/ICOS), and IDO1 were evaluated by IHC staining and multi-color immunofluorescence in two independent cohorts (95 patients in the primary cohort and 55 patients in the validation cohort)...
October 3, 2018: Journal for Immunotherapy of Cancer
Daniel G Guy, Geoffrey L Uy
PURPOSE OF REVIEW: Bispecific antibodies combine antigen recognition sites from two or more antibodies into a single construct allowing simultaneous binding to multiple targets. Bispecific antibodies exist which can redirect immune effector cells against acute myeloid leukemia (AML) targets. This review will highlight the progress to date and the challenges in developing bispecific antibodies for the treatment of AML. RECENT FINDINGS: Currently, a number of bispecific antibody formats including bispecific T cell engagers, dual affinity retargeting proteins, and tandem diabodies are in clinical development for AML...
October 2, 2018: Current Hematologic Malignancy Reports
Monika Herrmann, Christina Krupka, Katrin Deiser, Bettina Brauchle, Anetta Marcinek, Ana Ogrinc Wagner, Felicitas Rataj, Ralph Mocikat, Klaus H Metzeler, Karsten Spiekermann, Sebastian Kobold, Nadja C Fenn, Karl-Peter Hopfner, Marion Subklewe
The CD33-targeting bispecific T-cell engager (BiTE®) AMG 330 proved to be highly efficient in mediating cytolysis of acute myeloid leukemia (AML) cells in vitro and in mouse models. Yet, T-cell activation is correlated with upregulation of PD-L1 and other inhibitory checkpoints on AML cells that confer adaptive immune resistance. PD 1 and PD-L1 blocking agents may counteract T-cell dysfunction, however, at the expense of broadly distributed immune-related adverse events (irAEs). We developed a bifunctional checkpoint inhibitory T-cell-engaging (CiTE) antibody that combines T-cell redirection to CD33 on AML cells with locally restricted immune checkpoint blockade...
October 1, 2018: Blood
Alice Tzeng, C Marcela Diaz-Montero, Patricia A Rayman, Jin S Kim, Paul G Pavicic, James H Finke, Pedro C Barata, Marcelo Lamenza, Sarah Devonshire, Kim Schach, Hamid Emamekhoo, Marc S Ernstoff, Christopher J Hoimes, Brian I Rini, Jorge A Garcia, Timothy D Gilligan, Moshe C Ornstein, Petros Grivas
BACKGROUND: The identification of prognostic and/or predictive biomarkers for response to immune checkpoint inhibitors (ICI) could help guide treatment decisions. OBJECTIVE: We assessed changes in programmed cell death-1 (PD1)/PD1 ligand (PDL1) expression in key immunomodulatory cell subsets (myeloid-derived suppressor cells [MDSC]; cytotoxic T lymphocytes [CTL]) following ICI therapy and investigated whether these changes correlated with outcomes in patients with metastatic urothelial carcinoma (mUC)...
October 2018: Targeted Oncology
Todd A Braciak, Claudia C Roskopf, Sarah Wildenhain, Nadja C Fenn, Christian B Schiller, Ingo A Schubert, Uwe Jacob, Annemarie Honegger, Christina Krupka, Marion Subklewe, Karsten Spiekermann, Karl-Peter Hopfner, Georg H Fey, Michael Aigner, Stefan Krause, Andreas Mackensen, Fuat S Oduncu
A number of agents designed for immunotherapy of Acute Myeloid Leukemia (AML) are in preclinical and early clinical development. Most of them target a single antigen on the surface of AML cells. Here we describe the development and key biological properties of a tri-specific agent, the dual-targeting triplebody SPM-2, with binding sites for target antigens CD33 and CD123, and for CD16 to engage NK cells as cytolytic effectors. Primary blasts of nearly all AML patients carry at least one of these target antigens and the pair is particularly promising for the elimination of blasts and leukemia stem cells (LSCs) from a majority of AML patients by dual-targeting agents...
2018: Oncoimmunology
S J A M Santegoets, A F de Groot, E M Dijkgraaf, A M Carnaz Simões, V E van der Noord, J J van Ham, M J P Welters, J R Kroep, S H van der Burg
Epithelial ovarian cancer (EOC) may cause abnormal blood levels of leukocytes. This paraneoplastic manifestation is associated with a worse response to therapy and shorter survival. To understand the complexity and nature of these leukocytes, we dissected the different populations of myeloid cells and analyzed their relation to clinical outcome. Therefore, baseline blood samples of 36 EOC patients treated either with carboplatin/doxorubucin or with gemcitabine were analyzed for different subsets of monocytes/macrophages, myeloid derived suppressor cells (MDSC) and dendritic cells (DC) using multiparameter flow cytometry as well as functional assays for myeloid cell mediated suppression of antigen-specific T cell reactivity...
2018: Oncoimmunology
Marius Ilié, Mélanie Beaulande, Saima Ben Hadj, Emmanuel Chamorey, Renaud Schiappa, Elodie Long-Mira, Sandra Lassalle, Catherine Butori, Charlotte Cohen, Sylvie Leroy, Olivier Guérin, Jérôme Mouroux, Charles-Hugo Marquette, Jean-François Pomerol, Gilles Erb, Véronique Hofman, Paul Hofman
With underrepresentation of elderly patients with lung adenocarcinoma (LADC) in anti-PD-1/PD-L1 clinical trials, better understanding of the interplay of PD-L1 and tumor-associated immune cells (TAICs) could assist clinicians in stratifying these patients for immunotherapy. One hundred and one patients with LADCs, stratified by age, were included for analysis of PD-L1 expression and density of TAICs expressing CD4, CD8, and CD33, by using multiplex chromogenic immunohistochemistry (IHC) assays and automated digital quantification...
September 13, 2018: Cancers
Karsten Spiekermann, Anne-Sophie Shen
There are several changes in the revised WHO classification for acute leukemia. The latest version of the European Leukemia Network (ELN)-risk classification defines AML with mutations in RUNX1, ASXL1 or TP53 to fall in the unfavorable risk group. Consequently, the somatic molecular genetic testing at the time of initial diagnosis should encompass these before mentioned three genes next to the already routine testing of NPM1, CEBPA and FLT3-ITD. Several new innovative substances have been developed and approved for AML therapy...
September 2018: Deutsche Medizinische Wochenschrift
Roberto R Rosato, Daniel Dávila-González, Dong Soon Choi, Wei Qian, Wen Chen, Anthony J Kozielski, Helen Wong, Bhuvanesh Dave, Jenny C Chang
BACKGROUND: Breast cancer has been considered not highly immunogenic, and few patients benefit from current immunotherapies. However, new strategies are aimed at changing this paradigm. In the present study, we examined the in vivo activity of a humanized anti-programmed cell death protein 1 (anti-PD-1) antibody against triple-negative breast cancer (TNBC) patient-derived xenograft (PDX) tumor models. METHODS: To circumvent some of the limitations posed by the lack of appropriate animal models in preclinical studies of immunotherapies, partially human leukocyte antigen-matched TNBC PDX tumor lines from our collection, as well as human melanoma cell lines, were engrafted in humanized nonobese diabetic/severe combined immunodeficiency IL2Rγnull (hNSG) mice obtained by intravenous injection of CD34+ hematopoietic stem cells into nonlethally irradiated 3-4-week-old mice...
September 5, 2018: Breast Cancer Research: BCR
Douglas D Leipold, Isabel Figueroa, Shabkhaiz Masih, Brandon Latifi, Victor Yip, Ben-Quan Shen, Randall C Dere, Montserrat Carrasco-Triguero, M Violet Lee, Ola M Saad, Luna Liu, Jintang He, Dian Su, Keyang Xu, Brian R Vuillemenot, Steven T Laing, Melissa Schutten, Katherine R Kozak, Bing Zheng, Andrew G Polson, Amrita V Kamath
Few treatment options are available for acute myeloid leukemia (AML) patients. DCLL9718A is an antibody-drug conjugate that targets C-type lectin-like molecule-1 (CLL-1). This receptor is prevalent on monocytes, neutrophils, and AML blast cells, and unlike CD33, is not expressed on hematopoietic stem cells, thus providing possible hematopoietic recovery. DCLL9718A comprises an anti-CLL-1 IgG1 antibody (MCLL0517A) linked to a pyrrolobenzodiazepine (PBD) dimer payload, via a cleavable disulfide-labile linker...
September 5, 2018: MAbs
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