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https://www.readbyqxmd.com/read/28737711/the-effects-of-artemisinin-on-the-cytolytic-activity-of-natural-killer-nk-cells
#1
Youn Kyung Houh, Kyung Eun Kim, Sunyoung Park, Dae Young Hur, Seonghan Kim, Daejin Kim, Sa Ik Bang, Yoolhee Yang, Hyun Jeong Park, Daeho Cho
Artemisinin, a chemical compound used for the treatment of malaria, has been known to show anti-cancer activity. However, the effect of this chemical on natural killer (NK) cells, which are involved in tumor killing, remains unknown. Here, we demonstrate that artemisinin exerts a potent anti-cancer effect by activating NK cells. NK-92MI cells pre-treated with artemisinin were subjected to a cytotoxicity assay using K562 cells. The results showed that artemisinin significantly enhances the cytolytic activity of NK cells in a dose-dependent manner...
July 24, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28734803/distribution-of-kir-genes-and-kir2ds4-gene-variants-in-two-mexican-mestizo-populations
#2
Machado-Sulbaran Andrea Carolina, Muñoz-Valle José Francisco, Ramírez-Dueñas María Guadalupe, Baños-Hernández Christian Johana, Machuca-Graciano Omar, Velarde-De la Cruz Erandi Enif, Parra-Rojas Isela, Sánchez-Hernández Pedro Ernesto
Killer immunoglobulin-like receptors (KIR) are transmembrane proteins that regulate NK and T cell subsets by recognizing HLA-I molecules as ligands. The KIR gene family consists of 16 genes, located at chromosome 19q13.4. KIR gene frequencies vary among populations. In Mexico, HLA and genetic ancestry studies show that Mestizo populations have different genetic backgrounds based on admixture with European, African, and Asian ancestry. This study aimed to evaluate the frequencies of KIR genes and genotypes in Guerrero and Jalisco, two Mexican Mestizo populations located in the south and the west of the country, respectively, and to compare these frequencies with those of other populations...
July 19, 2017: Human Immunology
https://www.readbyqxmd.com/read/28733665/human-intrahepatic-cd69%C3%A2-%C3%A2-cd8-t-cells-have-a-tissue-resident-memory-t-cell-phenotype-with-reduced-cytolytic-capacity
#3
Femke Stelma, Annikki de Niet, Marjan J Sinnige, Karel A van Dort, Klaas P J M van Gisbergen, Joanne Verheij, Ester M M van Leeuwen, Neeltje A Kootstra, Hendrik W Reesink
Tissue resident memory T cells (TRM) have been identified in various tissues, however human liver TRM to date remain unidentified. TRM can be recognized by CD69 and/or CD103 expression and may play a role in the pathology of chronic hepatitis B (CHB) and hepatitis C virus infection (CHC). Liver and paired blood mononuclear cells from 17 patients (including 4 CHB and 6 CHC patients) were isolated and CD8+ T cells were comprehensively analysed by flowcytometry, immunohistochemistry and qPCR. The majority of intrahepatic CD8+ T cells expressed CD69, a marker used to identify TRM, of which a subset co-expressed CD103...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733594/cd56-is-a-pathogen-recognition-receptor-on-human-natural-killer-cells
#4
Sabrina Ziegler, Esther Weiss, Anna-Lena Schmitt, Jan Schlegel, Anne Burgert, Ulrich Terpitz, Markus Sauer, Lorenzo Moretta, Simona Sivori, Ines Leonhardt, Oliver Kurzai, Hermann Einsele, Juergen Loeffler
Aspergillus (A.) fumigatus is an opportunistic fungal mold inducing invasive aspergillosis (IA) in immunocompromised patients. Although antifungal activity of human natural killer (NK) cells was shown in previous studies, the underlying cellular mechanisms and pathogen recognition receptors (PRRs) are still unknown. Using flow cytometry we were able to show that the fluorescence positivity of the surface receptor CD56 significantly decreased upon fungal contact. To visualize the interaction site of NK cells and A...
July 21, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28733263/consolidation-therapy-for-newly-diagnosed-pediatric-high-risk-neuroblastoma-patients-using-busulfan-melphalan-autologous-hematopoietic-cell-transplant-anti-gd2-antibody-gm-csf-il-2-and-haploidentical-nk-cells
#5
Aimee C Talleur, Brandon M Triplett, Sara Federico, Ewelina Mamcarz, William Janssen, Jianrong Wu, David Shook, Wing Leung, Wayne L Furman
The treatment of pediatric high-risk neuroblastoma is intensive and multimodal. Despite the introduction of immunotherapy for minimal residual disease, survival rates remain suboptimal and new therapies are needed. As part of a phase 2 trial, we are using a consolidation therapy regimen which combines a busulfan/melphalan conditioning schema, autologous hematopoietic cell transplant (AHCT), and experimental immunotherapy with hu14.18K322A (a humanized anti-GD2 monoclonal antibody), GM-CSF, and IL-2, with or without the adoptive transfer of haploidentical natural killer cells (NKs)...
July 18, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28732877/enhanced-antitumor-activity-of-gemcitabine-by-polysaccharide-induced-nk-cell-activation-and-immune-cytotoxicity-reduction-in-vitro-vivo
#6
Xin Xie, Yiran Zhou, Xue Wang, Jian Guo, Jingwen Li, Hongye Fan, Jie Dou, Baiyong Shen, Changlin Zhou
The polysaccharide SEP has been reported to activate NK and T cells via TLR2/4. Here, the combination of gemcitabine (GEM) and SEP against HepG-2 was investigated. SEP apparently enhanced antitumor activity of gemcitabine against liver cancer through stimulating NKG2D and DAP10/Akt pathway to activate NK cells. The NKG2D upregulation could improve the sensitivity of NK-92 cells targeting to its ligand MICA expressed on HepG-2 cells. Meanwhile, GEM up-regulated MICA expression and attenuated soluble MICA secretion through inhibiting ADAM10 expression, which in turn enhanced the cytotoxicity of NK-92 cells against cancer cells...
October 1, 2017: Carbohydrate Polymers
https://www.readbyqxmd.com/read/28732438/investigation-of-killer-immunoglobulin-like-receptor-kir-and-hla-genotypes-to-predict-the-occurrence-of-acute-allograft-rejection-after-kidney-transplantation
#7
Davood Jafari, Mohsen Nafar, Mir Saeed Yekaninejad, Razieh Abdolvahabi, Mahboob Lesan Pezeshki, Efat Razaghi, Ali Akbar Amirzargar
After kidney transplantation, natural killer (NK) cells play a pivotal role in triggering the immune response to the allogeneic grafts primarily by their killer-cell immunoglobulin-like receptors (KIR). This process may be one mechanism that contributes to graft rejection. In this study, we have evaluated whether acute rejection after kidney transplantation was associated with predicted NK cell alloreactivity based on KIR gene and ligand along with KIR/HLA compound genotype analysis. After kidney transplantation, natural killer (NK) cells play a pivotal role in triggering the immune response to the allogeneic grafts primarily by their killer-cell immunoglobulin-like receptors (KIR)...
June 2017: Iranian Journal of Allergy, Asthma, and Immunology
https://www.readbyqxmd.com/read/28732386/a-phase-i-trial-of-nk-92-cells-for-refractory-hematological-malignancies-relapsing-after-autologous-hematopoietic-cell-transplantation-shows-safety-and-evidence-of-efficacy
#8
Brent A Williams, Arjun Datt Law, Bertrand Routy, Neal denHollander, Vikas Gupta, Xing-Hua Wang, Amélie Chaboureau, Sowmya Viswanathan, Armand Keating
BACKGROUND: Autologous NK cell therapy can treat a variety of malignancies, but is limited by patient-specific variations in potency and cell number expansion. In contrast, allogeneic NK cell lines can overcome many of these limitations. Cells from the permanent NK-92 line are constitutively activated, lack inhibitory receptors and appear to be safe based on two prior phase I trials. MATERIALS AND METHODS: We conducted a single-center, non-randomized, non-blinded, open-label, Phase I dose-escalation trial of irradiated NK-92 cells in adults with refractory hematological malignancies who relapsed after autologous hematopoietic cell transplantation (AHCT)...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28732383/radiation-alters-pd-l1-nkg2d-ligand-levels-in-lung-cancer-cells-and-leads-to-immune-escape-from-nk-cell-cytotoxicity-via-il-6-mek-erk-signaling-pathway
#9
Ming Jing Shen, Li Jun Xu, Li Yang, Ying Tsai, Peter C Keng, Yongbing Chen, Soo Ok Lee, Yuhchyau Chen
We investigated whether radiation influences the susceptibility of non-small cell lung cancer (NSCLC) cells to NK cell mediated cytotoxicity. We found radiation treatment increased expression of programmed cell death ligand 1 (PD-L1), but decreased NK group 2, member D (NKG2D) ligand expressions in A549 and H157 NSCLC cells. Both types of changes would have protected tumor cells from the cytotoxic action of NK cells. Consistently, we detected similar alteration in these molecules in radioresistant A549R26-1 and H157R24-1 subline cells...
July 12, 2017: Oncotarget
https://www.readbyqxmd.com/read/28729334/cd70-turns-on-nk-cells-to-attack-lymphoma
#10
Todd A Fehniger
No abstract text is available yet for this article.
July 20, 2017: Blood
https://www.readbyqxmd.com/read/28726600/age-and-sex-associated-differences-in-phenotypic-and-functional-characteristics-of-peripheral-blood-lymphocytes-in-chimpanzees-pan-troglodytes
#11
Pramod Nehete, Elizabeth Magden, Bharti Nehete, Lawrence Williams, Christian Abee, K Sastry
Chimpanzees are the closest phylogenetic relatives to humans, sharing more than 98% genetic sequence identity. Thesegenetic similarities prompted the belief that chimpanzees can serve as an ideal model for human disease conditions andvaccine development. However, in light of the recent NIH decision to phase out biomedical research in chimpanzees and retire NIH-supported chimpanzees, data from the present study will continue to provide value for the care of aged and sick chimpanzees located in zoos, sanctuaries, and primate centers...
July 19, 2017: Journal of the American Association for Laboratory Animal Science: JAALAS
https://www.readbyqxmd.com/read/28726100/microrna-in-hormonal-mechanisms-of-regulation-of-nk-cell-function
#12
S V Shirshev, I V Nekrasova, O L Gorbunova, E G Orlova, I L Maslennikova
We investigated the effect of human chorionic gonadotropin, estriol, leptin, ghrelin, and kisspeptin on the microRNA expression in separated NK cells. All of these hormones are able to effectively modulate the expression of microRNAs both stimulating and suppressing the cytotoxic potential of NK cells and thereby indirectly regulate the functions of these lymphocytes.
May 2017: Doklady. Biochemistry and Biophysics
https://www.readbyqxmd.com/read/28725044/cord-blood-nk-cells-engineered-to-express-il-15-and-a-cd19-targeted-car-show-long-term-persistence-and-potent-anti-tumor-activity
#13
E Liu, Y Tong, G Dotti, H Shaim, B Savoldo, M Mukherjee, J Orange, X Wan, X Lu, A Reynolds, M Gagea, P Banerjee, R Cai, M H Bdaiwi, R Basar, M Muftuoglu, L Li, D Marin, W Wierda, M Keating, R Champlin, E Shpall, K Rezvani
Chimeric antigen receptors (CARs) have been used to redirect the specificity of autologous T-cells against leukemia and lymphoma with promising clinical results.(1-3) Extending this approach to allogeneic T-cells is problematic as they carry a significant risk of graft-versus-host disease (GVHD). Natural killer (NK) cells are highly cytotoxic effectors, killing their targets in a non-antigen specific manner without causing GVHD. Cord blood (CB) offers an attractive, allogeneic, off-the-self source of NK cells for immunotherapy...
July 20, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28725030/a-practical-model-evaluating-antiviral-cytokines-by-natural-killer-cells-in-treatment-na%C3%A3-ve-patients-with-chronic-hepatitis-b-virus-infection
#14
Xiaoyan Li, Yurong Gu, Xiaobo Guo, Lin Gu, Liang Zhou, Xiaojuan Wu, Xueqin Wang, Zania Stamataki, Yuehua Huang
Natural killer (NK) cells play a major role in anti-viral immunity as first line defense during hepatitis B infection, particularly in untreated patients whose T cells functions are profoundly impaired. Cytokine interferon (IFN)-γ and tumor necrosis factor (TNF)-α produced by NK cells are important anti-viral factors. However, there is lack of a quantifiable model to evaluate cytokine responses by NK cells. In this study, almost half of the patients (47.9%) beyond treatment criteria had high cytokine activity, although it was lower than those recommended for antiviral therapy (78...
July 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28724773/nkp46-recognizes-the-sigma1-protein-of-reovirus-implications-for-reovirus-based-cancer-therapy
#15
Yotam Bar-On, Yoav Charpak-Amikam, Ariella Glasner, Batya Isaacson, Alexandra Duev-Cohen, Pinchas Tsukerman, Alexander Varvak, Michal Mandelboim, Ofer Mandelboim
The recent approval of onclolytic virus for therapy of melanoma patients has increased the need for precise evaluation of the mechanisms by which oncolytic viruses affect tumor growth. Here we show that the human NK activating receptor, NKp46, and its mouse orthologous protein, NCR1, recognize the reovirus sigma1 protein in a sialic-acid-dependent manner. We identify NKp46/NCR1 binding sites to sigma1 and show that sigma1 binding by NKp46/NCR1 leads to NK cell activation in vitro Finally, we demonstrate that NCR1 activation is essential for reovirus-based therapy in vivo Collectively, we identified sigma1 as a novel ligand for NKp46/NCR1 and demonstrated that NKp46/NCR1 is needed for both clearance of reovirus infections and reovirus-based tumor therapy...
July 19, 2017: Journal of Virology
https://www.readbyqxmd.com/read/28724658/a-daily-dose-of-5-mg-folic-acid-for-90-days-is-associated-with-increased-serum-unmetabolized-folic-acid-and-reduced-natural-killer-cell-cytotoxicity-in-healthy-brazilian-adults
#16
Clovis Paniz, Juliano Felix Bertinato, Maylla Rodrigues Lucena, Eduardo De Carli, Patrícia Mendonça da Silva Amorim, Guilherme Wataru Gomes, Cecília Zanin Palchetti, Maria Stella Figueiredo, Christine M Pfeiffer, Zia Fazili, Ralph Green, Elvira Maria Guerra-Shinohara
Background: The effects of high-dose folic acid (FA) supplementation in healthy individuals on blood folate concentrations and immune response are unknown.Objective: The aim of the study was to evaluate the effects of daily consumption of a tablet containing 5 mg FA on serum folate; number and cytotoxicity of natural killer (NK) cells; mRNA expression of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR), interferon γ (IFNG), tumor necrosis factor α (TNFA), and interleukin 8 (IL8) genes; and concentrations of serum inflammatory markers...
July 19, 2017: Journal of Nutrition
https://www.readbyqxmd.com/read/28724544/mica-expressing-monocytes-enhance-natural-killer-cell-fc-receptor-mediated-antitumor-functions
#17
Amanda R Campbell, Megan C Duggan, Lorena P Suarez-Kelly, Neela Bhave, Kallan S Opheim, Elizabeth McMichael, Prashant Trikha, Robin Parihar, Eric Luedke, Adrian Lewis, Bryant Yung, Robert Lee, David Raulet, Susheela Tridandapani, Veronika Groh, Lianbo Yu, Vedat Yildiz, John C Byrd, Michael A Caligiuri, William E Carson
Natural Killer (NK) cells are large granular lymphocytes that promote the antitumor response via communication with other cell types in the tumor microenvironment. Previously, we have shown that NK cells secrete a profile of immune stimulatory factors (e.g., IFNgamma, MIP-1alpha, TNFalpha) in response to dual stimulation with the combination of antibody (Ab)-coated tumor cells and cytokines, such as interleukin (IL) 12. We now demonstrate that this response is enhanced in the presence of autologous monocytes...
July 19, 2017: Cancer Immunology Research
https://www.readbyqxmd.com/read/28723738/phosphatase-and-tensin-homolog-pten-is-down-regulated-in-human-nk-t-cell-lymphoma-and-corrects-with-clinical-outcomes
#18
Xiaorui Fu, Xudong Zhang, Jinli Gao, Xin Li, Lei Zhang, Ling Li, Xinhua Wang, Zhenchang Sun, Zhaoming Li, Yu Chang, Qingjiang Chen, Mingzhi Zhang
Nasal-type natural killer/T-cell (NK/T-cell) lymphoma is a more aggressive sub-group of non-Hodgkin lymphoma, which is more common in Asia. The phosphatase and tensin homolog (PTEN) was originally discovered as a candidate tumor suppressor mutated and lost in various cancers. However, its clinical value and role in NK/T-cell lymphoma remain to be further explored. In the present study, we analyzed PTEN protein expression in 60 cases of human NK/T-cell lymphoma tissues and 40 cases of control nasal mucosa tissues specimens by immunohistochemical analysis...
July 2017: Medicine (Baltimore)
https://www.readbyqxmd.com/read/28723565/the-transcription-factor-tcf1-contributes-to-normal-nk-cell-development-and-function-by-limiting-the-expression-of-granzymes
#19
Beena Jeevan-Raj, Jasmine Gehrig, Mélanie Charmoy, Vijaykumar Chennupati, Camille Grandclément, Paolo Angelino, Mauro Delorenzi, Werner Held
The transcription factor Tcf1 is essential for the development of natural killer (NK) cells. However, its precise role has not been clarified. Our combined analysis of Tcf1-deficient and transgenic mice indicated that Tcf1 guides NK cells through three stages of development. Tcf1 expression directed bone marrow progenitors toward the NK cell lineage and ensured the survival of NK-committed cells, and its downregulation was needed for terminal maturation. Impaired survival of NK-committed cells was due to excessive expression of granzyme B (GzmB) and other granzyme family members, which induced NK cell self-destruction during maturation and following activation with cytokines or target cells...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28723548/the-fc-domain-of-immunoglobulin-is-sufficient-to-bridge-nk-cells-with-virally-infected-cells
#20
Hong-Sheng Dai, Nathaniel Griffin, Chelsea Bolyard, Hsiaoyin Charlene Mao, Jianying Zhang, Timothy P Cripe, Tadahiro Suenaga, Hisashi Arase, Ichiro Nakano, E A Chiocca, Balveen Kaur, Jianhua Yu, Michael A Caligiuri
Clearance of pathogens or tumor cells by antibodies traditionally requires both Fab and Fc domains of IgG. Here, we show the Fc domain of IgG alone mediates recognition and clearance of herpes simplex virus (HSV1)-infected cells. The human natural killer (NK) cell surface is naturally coated with IgG bound by its Fc domain to the Fcγ receptor CD16a. NK cells utilize the Fc domain of bound IgG to recognize gE, an HSV1-encoded glycoprotein that also binds the Fc domain of IgG but at a site distinct from CD16a...
July 18, 2017: Immunity
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