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https://www.readbyqxmd.com/read/29342200/inhibiting-tgf-beta-signaling-preserves-the-function-of-highly-activated-in-vitro-expanded-natural-killer-cells-in-aml-and-colon-cancer-models
#1
Folashade Otegbeye, Evelyn Ojo, Stephen Moreton, Nathan Mackowski, Dean A Lee, Marcos de Lima, David N Wald
Natural killer cells harnessed from healthy individuals can be expanded ex vivo using various platforms to produce large doses for adoptive transfer into cancer patients. During such expansion, NK cells are increasingly activated and more efficient at killing cancer cells. Adoptive transfer however introduces these activated cells into a highly immunosuppressive tumor microenvironment mediated in part by excessive transforming growth factor beta (TGF-beta) from both cancer cells and their surrounding stroma...
2018: PloS One
https://www.readbyqxmd.com/read/29341892/premature-aging-in-behavior-and-immune-functions-in-tyrosine-hydroxylase-haploinsufficient-female-mice-a-longitudinal-study
#2
A Garrido, J Cruces, N Ceprián, C Hernández-Sánchez, M De la Fuente
Aging is accompanied by impairment in the nervous, immune, and endocrine systems as well as in neuroimmunoendocrine communication. In this context, there is an age-related alteration of the physiological response to acute stress, which is modulated by catecholamine (CA), final products of the sympathetic-adreno-medullary axis. The involvement of CA in essential functions of the nervous system is consistent with the neuropsychological deficits found in mice with haploinsufficiency (hemizygous; HZ) of tyrosine hydroxylase (TH) enzyme (TH-HZ)...
January 13, 2018: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/29339375/tusc2-immunogene-synergizes-with-anti-pd1-through-enhanced-proliferation-and-infiltration-of-natural-killer-cells-in-syngeneic-kras-mutant-mouse-lung-cancer-models
#3
Ismail M Meraz, Mourad Majidi, Xiaobo Cao, Heather Lin, Lerong Li, Jing Wang, Veerabhadran Baladandayuthapani, David Rice, Boris Sepesi, Lin Ji, Jack A Roth
Expression of the multikinase inhibitor encoded by tumor suppressor gene TUSC2 (also known as FUS1) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras-mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1...
January 16, 2018: Cancer Immunology Research
https://www.readbyqxmd.com/read/29339270/proceedings-from-the-fourth-haploidentical-stem-cell-transplantation-symposium-haplo2016-san-diego-california-december-1-2016
#4
REVIEW
Monzr Al Malki, Richard Jones, Qing Ma, Dean Lee, Yair Reisner, Jeffrey S Miller, Peter Lang, Suradej Hongeng, Parameswaran Hari, Samuel Strober, Jianhua Yu, Richard Maziarz, Domenico Mavilio, Denis-Claude Roy, Chiara Bonini, Richard E Champlin, Ephraim J Fuchs, Stefan O Ciurea
The resurgence of haploidentical stem cell transplantation (HaploSCT) over the last decade is one of the most important advances in the field of hematopoietic stem cell transplantation (HSCT). The modified platforms of T cell depletion either ex vivo (CD34+ selection, 'mega-dose' of purified CD34+ cells, or selective depletion of T-cells) or newer platforms of in vivo depletion of T cells, with either post-transplant high-dose cyclophosphamide (PTCy) or intensified immune suppression, have contributed to better outcomes, with survival that is similar to HLA-match donor transplantation...
January 12, 2018: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/29339014/development-of-gpc3-specific-chimeric-antigen-receptor-engineered-natural-killer-cells-for-the-treatment-of-hepatocellular-carcinoma
#5
Min Yu, Hong Luo, Mingliang Fan, Xiuqi Wu, Bizhi Shi, Shengmeng Di, Ying Liu, Zeyan Pan, Hua Jiang, Zonghai Li
Chimeric antigen receptor (CAR)-modified natural killer (NK) cells represent a promising immunotherapeutic modality for cancer treatment. However, their potential utilities have not been explored in hepatocellular carcinoma (HCC). Glypian-3 (GPC3) is a rational immunotherapeutic target for HCC. In this study, we developed GPC3-specific NK cells and explored their potential in the treatment of HCC. The NK-92/9.28.z cell line was established by engineering NK-92, a highly cytotoxic NK cell line with second-generation GPC3-specific CAR...
December 19, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/29337259/mathematical-modeling-of-tumor-induced-immunosuppression-by-myeloid-derived-suppressor-cells-implications-for-therapeutic-targeting-strategies
#6
Seyed Peyman Shariatpanahi, Seyed Pooya Shariatpanahi, Keivan Madjidzadeh, Moustapha Hassan, Manuchehr Abedi-Valugerdi
Myeloid-derived suppressor cells (MDSCs) belong to immature myeloid cells that are generated and accumulated during the tumor development. MDSCs strongly suppress the anti-tumor immunity and provide conditions for tumor progression and metastasis. In this study, we present a mathematical model based on ordinary differential equations (ODE) to describe tumor-induced immunosuppression caused by MDSCs. The model consists of four equations and incorporates tumor cells, cytotoxic T cells (CTLs), natural killer (NK) cells and MDSCs...
January 11, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29336030/the-aryl-hydrocarbon-receptor-modulates-the-function-of-human-cd56bright-nk-cells
#7
Uriel Y Moreno-Nieves, David C Mundy, June Ho Shin, Kenric Tam, John B Sunwoo
Human natural killer (NK) cells are divided into two subsets: CD56bright and CD56dim NK cells, which differ in maturation, function and distribution. Mechanisms regulating NK cell functions are not completely understood. Aryl hydrocarbon receptor (AhR) is a ligand-activated transcription factor, that binds to a variety of endogenous and exogenous molecules, and that has recently been shown to modulate the function and differentiation of immune cells. Here, we studied the expression of AhR and its involvement in the regulation of NK cell functions...
January 16, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29335477/transcriptomic-signatures-of-cellular-and-humoral-immune-responses-in-older-adults-after-seasonal-influenza-vaccination-identified-by-data-driven-clustering
#8
Emily A Voigt, Diane E Grill, Michael T Zimmermann, Whitney L Simon, Inna G Ovsyannikova, Richard B Kennedy, Gregory A Poland
PBMC transcriptomes after influenza vaccination contain valuable information about factors affecting vaccine responses. However, distilling meaningful knowledge out of these complex datasets is often difficult and requires advanced data mining algorithms. We investigated the use of the data-driven Weighted Gene Correlation Network Analysis (WGCNA) gene clustering method to identify vaccine response-related genes in PBMC transcriptomic datasets collected from 138 healthy older adults (ages 50-74) before and after 2010-2011 seasonal trivalent influenza vaccination...
January 15, 2018: Scientific Reports
https://www.readbyqxmd.com/read/29334801/bu-shen-yi-qi-formula-impairs-cytotoxicity-of-nk-cells-by-up-regulating-ido-expression-in-trophoblasts
#9
Shao-Liang Yang, Tian-Tian Niu, Xue-Lian Li, Da-Jin Li, Ming-Qing Li, Hai-Yan Wang
Recurrent spontaneous abortion (RSA) is a common health problem that affects about 5% of fertile women, when it occurs for unknown reasons, it is called unexplained recurrent spontaneous abortion (URSA). Traditional Chinese medicine, such as Bu-Shen-Yi-Qi formula which consists of Dangshen, Tusizi, Baizhu, Baishuo, Duzhong, Sangjisheng, Sugeng, and Tiaohuangqin, has played an invaluable role in the treatment of RSA since ancient times. However, the mechanism of how it takes effect is still not clear. To identify Bu-Shen-Yi-Qi formula could modulate immune condition at maternal-fetal interface via its effect on trophoblasts, HTR-8 of different treatment were co-cultured with peripheral or decidual natural killer (NK) cells, and the receptors such as NKP30 and NKP46 expression on NK cells were measured by flow cytometry (FCM)...
January 15, 2018: Gynecological Endocrinology
https://www.readbyqxmd.com/read/29334771/development-of-anti-human-mesothelin-targeted-chimeric-antigen-receptor-car-messenger-rna-mrna-transfected-peripheral-blood-lymphocytes-carma-hmeso-for-ovarian-cancer-therapy
#10
Chien-Fu Hung, Xuequn Xu, Linhong Li, Ying Ma, Qiu Jin, Angelia Viley, Cornell Allen, Pachai Natarajan, Rama Shivakumar, Madhusudan V Peshwa, Leisha A Emens
CD19-targeted chimeric antigen receptor (CAR) engineered T/natural kill (NK)-cell therapies can result in durable clinical responses in B-cell malignancies. However, CAR-based immunotherapies have been much less successful in solid cancers, in part due to 'on-target off-tumor' toxicity related to expression of target tumor antigens on normal tissue. Based on preliminary observations of safety and clinical activity in proof-of-concept clinical trials, tumor antigen-specific messenger RNA (mRNA) CAR transfection into selected, activated, and expanded T/NK-cells may permit prospective control of 'on-target off-tumor toxicity'...
January 15, 2018: Human Gene Therapy
https://www.readbyqxmd.com/read/29332332/a-study-on-cellular-immune-function-of-patients-treated-with-radical-resection-of-pulmonary-carcinoma-with-two-different-methods-of-anesthesia-and-analgesia
#11
Jie Chen, Feng Luo, Min Lei, Zhoumiao Chen
PURPOSE: To compare the influence on the immune system of two different methods of anesthesia and analgesia in patients treated with radical resection of pulmonary carcinoma. METHODS: Thirty-four patients treated with radical resection of pulmonary carcinoma were randomly divided into two groups (group A and group B, 17 cases in each group). Patients in group A were administered total intravenous anesthesia (TIVA) without inhaled hypnotics and intravenous analgesia while patients in group B were administered TIVA combined with epidural anesthesia and epidural analgesia...
November 2017: Journal of B.U.ON.: Official Journal of the Balkan Union of Oncology
https://www.readbyqxmd.com/read/29331138/role-of-non-equilibrium-conformations-on-driven-polymer-translocation
#12
H H Katkar, M Muthukumar
One of the major theoretical methods in understanding polymer translocation through a nanopore is the Fokker-Planck formalism based on the assumption of quasi-equilibrium of polymer conformations. The criterion for applicability of the quasi-equilibrium approximation for polymer translocation is that the average translocation time per Kuhn segment, ⟨τ⟩/NK, is longer than the relaxation time τ0 of the polymer. Toward an understanding of conditions that would satisfy this criterion, we have performed coarse-grained three dimensional Langevin dynamics and multi-particle collision dynamics simulations...
January 14, 2018: Journal of Chemical Physics
https://www.readbyqxmd.com/read/29331106/kbtbd2-inhibits-the-cytotoxic-activity-of-immortalized-nk-cells-through-down-regulating-mtor-signaling-in-a-mouse-hepatocellular-carcinoma-model
#13
Kai Dai, Yabing Huang, Zubing Chen, Xiaomei Sun, Lihua Yang, Yingan Jiang
Natural killer cell (NK cell)-based immunotherapy is a promising therapeutic strategy for hepatocellular carcinoma (HCC). However, the molecular mechanisms underlying the regulation of NK cell function in the tumor sites are not completely elucidated. In this study, we identified the enhanced expression of kelch repeat and BTB (POZ) domain containing 2 (Kbtbd2) in intratumoral NK cells in a mouse HCC implantation model as a negative regulator of NK cells. To investigate this interaction,, we used a Tet-on inducible expression system to control Kbtbd2 expression in an immortalized mouse NK cell line KIL C...
January 13, 2018: European Journal of Immunology
https://www.readbyqxmd.com/read/29330929/adipocytes-affect-castration-resistant-prostate-cancer-cells-to-develop-the-resistance-to-cytotoxic-action-of-nk-cells-with-alterations-of-pd-l1-nkg2d-ligand-levels-in-tumor-cells
#14
Lijun Xu, Mingjing Shen, Xiaodong Chen, Rongying Zhu, Dong-Rong Yang, Ying Tsai, Peter C Keng, Yuhchyau Chen, Soo Ok Lee
BACKGROUND: Obesity affects prostate cancer (PCa) progression, and the periprostatic adipose tissue adjacent to the prostate is considered a driving force of disease progression. Adipocytes are the main cell population in adipose tissues and their paracrine role contributes to PCa progression, however its implication in modulating immune reactions remains largely unknown. We investigated the adipocyte role in controlling the susceptibility of castration-resistant PCa (CRPC) cells to the cytotoxic action of natural killer (NK) cells...
January 12, 2018: Prostate
https://www.readbyqxmd.com/read/29330305/restricted-processing-of-cd16a-fc-%C3%AE-receptor-iiia-n-glycans-from%C3%A2-primary-human-nk-cells-impacts-structure-and-function
#15
Kashyap R Patel, Jacob T Roberts, Ganesh P Subedi, Adam W Barb
CD16a/Fc γ receptor IIIa is the most abundant antibody Fc receptor expressed on human natural killer(NK) cells and activates a protective cytotoxic response following engagement with antibody clustered on the surface of a pathogen or diseased tissue. Therapeutic monoclonal antibodies(mAbs) with greater Fc-mediated affinity for CD16a show superior therapeutic outcome, however, one significant factor that promotes antibody-CD16a interactions, the asparagine-linked carbohydrates(N-glycans), remains undefined...
January 12, 2018: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29330211/olanzapine-based-triple-regimens-versus-neurokinin-1-receptor-antagonist-based-triple-regimens-in-preventing-chemotherapy-induced-nausea-and-vomiting-associated-with-highly-emetogenic-chemotherapy-a-network-meta-analysis
#16
Zhonghan Zhang, Yaxiong Zhang, Gang Chen, Shaodong Hong, Yunpeng Yang, Wenfeng Fang, Fan Luo, Xi Chen, Yuxiang Ma, Yuanyuan Zhao, Jianhua Zhan, Cong Xue, Xue Hou, Ting Zhou, Shuxiang Ma, Fangfang Gao, Yan Huang, Likun Chen, Ningning Zhou, Hongyun Zhao, Li Zhang
BACKGROUND: The current antiemetic prophylaxis for patients treated with highly emetogenic chemotherapy (HEC) included the olanzapine-based triplet and neurokinin-1 receptor antagonists (NK-1RAs)-based triplet. However, which one shows better antiemetic effect remained unclear. MATERIALS AND METHODS: We systematically reviewed 43 trials, involving 16,609 patients with HEC, which compared the following antiemetics at therapeutic dose range for the treatment of chemotherapy-induced nausea and vomiting: olanzapine, aprepitant, casopitant, fosaprepitant, netupitant, and rolapitant...
January 12, 2018: Oncologist
https://www.readbyqxmd.com/read/29330011/mutations-in-pi3k110%C3%AE-cause-impaired-nk-cell-function-partially-rescued-by-rapamycin-treatment
#17
Raquel Ruiz-García, Alexander Vargas-Hernandez, Ivan K Chinn, Laura S Angelo, Tram N Cao, Zeynep Coban-Akdemir, Shalini N Jhangiani, Qingchang Meng, Lisa R Forbes, Donna M Muzny, Luis M Allende, Mohammed S Ehlayel, Richard A Gibbs, James R Lupski, Gulbu Uzel, Jordan S Orange, Emily M Mace
BACKGROUND: Heterozygous gain-of-function mutations in PI3K110 lead to lymphadenopathy, lymphoid hyperplasia, Epstein-Barr virus (EBV) and cytomegalovirus (CMV) viremia, and sinopulmonary infections. OBJECTIVE: The known role of NK cell function in the control of EBV and CMV prompted us to investigate the functional and phenotypic effect of PI3K110δ mutations on NK cell subsets and cytotoxic function. METHODS: Patient mutations were identified by whole exome or targeted sequencing...
January 9, 2018: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29329948/nkp46-receptor-mediated-interferon-%C3%AE-production-by-natural-killer-cells-increases-fibronectin-1-to-alter-tumor-architecture-and-control-metastasis
#18
Ariella Glasner, Assi Levi, Jonatan Enk, Batya Isaacson, Sergey Viukov, Shari Orlanski, Alon Scope, Tzahi Neuman, Claes D Enk, Jacob H Hanna, Veronika Sexl, Stipan Jonjic, Barbara Seliger, Laurence Zitvogel, Ofer Mandelboim
Natural killer (NK) cells are innate lymphoid cells, and their presence within human tumors correlates with better prognosis. However, the mechanisms by which NK cells control tumors in vivo are unclear. Here, we used reflectance confocal microscopy (RCM) imaging in humans and in mice to visualize tumor architecture in vivo. We demonstrated that signaling via the NK cell receptor NKp46 (human) and Ncr1 (mouse) induced interferon-γ (IFN-γ) secretion from intratumoral NK cells. NKp46- and Ncr1-mediated IFN-γ production led to the increased expression of the extracellular matrix protein fibronectin 1 (FN1) in the tumors, which altered primary tumor architecture and resulted in decreased metastases formation...
January 4, 2018: Immunity
https://www.readbyqxmd.com/read/29329284/identification-of-an-elaborate-nk-specific-system-regulating-hla-c-expression
#19
Hongchuan Li, Martin A Ivarsson, Victoria E Walker-Sperling, Jeff Subleski, Jenna K Johnson, Paul W Wright, Mary Carrington, Niklas K Björkström, Daniel W McVicar, Stephen K Anderson
The HLA-C gene appears to have evolved in higher primates to serve as a dominant source of ligands for the KIR2D family of inhibitory MHC class I receptors. The expression of NK cell-intrinsic MHC class I has been shown to regulate the murine Ly49 family of MHC class I receptors due to the interaction of these receptors with NK cell MHC in cis. However, cis interactions have not been demonstrated for the human KIR and HLA proteins. We report the discovery of an elaborate NK cell-specific system regulating HLA-C expression, indicating an important role for HLA-C in the development and function of NK cells...
January 12, 2018: PLoS Genetics
https://www.readbyqxmd.com/read/29328024/endometrial-polyps-in-women-of-reproductive-age-clinical-and-pathogene-tic-variations
#20
N Kosei, N Zakharenko, D Herman
The aim of the study was to study the relationship between the morphofunctional characteristics of the endometrium, hormonal homeostasis and microbiocenosis of the reproductive system in patients with endometrial polyps. The study involved 130 patients aged 18-35 years: 34 patients with endometrial polyps, 30 patients with micropolyps, 36 patients with endometrial polyps and micropolyps, 30 healthy women of the control group. Hysteroscopy was performed for women who had been suspected for endometrial polyps and who had infertility or repeated recurrent miscarriages...
December 2017: Georgian Medical News
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