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https://www.readbyqxmd.com/read/29166609/gpr56-adgrg1-inhibits-mesenchymal-differentiation-and-radioresistance-in-glioblastoma
#1
Marta Moreno, Leire Pedrosa, Laia Paré, Estela Pineda, Leire Bejarano, Josefina Martínez, Veerakumar Balasubramaniyan, Ravesanker Ezhilarasan, Naveen Kallarackal, Sung-Hak Kim, Jia Wang, Alessandra Audia, Siobhan Conroy, Mercedes Marin, Teresa Ribalta, Teresa Pujol, Antoni Herreros, Avelina Tortosa, Helena Mira, Marta M Alonso, Candelaria Gómez-Manzano, Francesc Graus, Erik P Sulman, Xianhua Piao, Ichiro Nakano, Aleix Prat, Krishna P Bhat, Núria de la Iglesia
A mesenchymal transition occurs both during the natural evolution of glioblastoma (GBM) and in response to therapy. Here, we report that the adhesion G-protein-coupled receptor, GPR56/ADGRG1, inhibits GBM mesenchymal differentiation and radioresistance. GPR56 is enriched in proneural and classical GBMs and is lost during their transition toward a mesenchymal subtype. GPR56 loss of function promotes mesenchymal differentiation and radioresistance of glioma initiating cells both in vitro and in vivo. Accordingly, a low GPR56-associated signature is prognostic of a poor outcome in GBM patients even within non-G-CIMP GBMs...
November 21, 2017: Cell Reports
https://www.readbyqxmd.com/read/29166288/spirulina-platensis-affects-factors-involved-in-spermatogenesis-and-increases-ghrelin-receptors-in-testis-tissue-of-rats-fed-a-high-fat-diet
#2
O B B Esener, E Gurel-Gurevin, B Isbilen-Basok, F Yigit, T Bilal, A Altiner, N Yilmazer, E I Armutak
Ghrelin is a peptide hormone which plays important role in maintaining growth hormone release and energy homeostasis in vertebrates. Spirulina platensis (SP) has antioxidant and hypolipidemic effects due to its ingredients. In this study we aimed to investigate the effects of SP on the testicular structure and relation between ghrelin and testosterone in the testis of rats fed a high fat diet (HFD). Sixty four young adult male rats were used and divided to 8 equal groups. Experimental groups received addition of 10% cholesterol (CHL), 43% hydrogenated vegetable oil (HVO) and 3% SP alone or in combination to basal diet while the control group received only basal diet...
September 26, 2017: Polish Journal of Veterinary Sciences
https://www.readbyqxmd.com/read/29166136/the-gamma-aminobutyric-acid-b-receptor-gabab-encephalitis-clinical-manifestations-and-response-to-immunotherapy
#3
Junzhao Cui, Hui Bu, Junying He, Zeyan Zhao, Weixin Han, Ruiping Gao, Xiaoqing Li, Qing Li, Xiaosu Guo, Yueli Zou
PURPOSE: We report 11 patients diagnosed with GABAB receptor (GABABR) antibodies encephalitis in China and aim to analyse the clinical characteristics, laboratory and imaging findings, therapeutic modalities and outcomes. METHODS: Clinical data from patients diagnosed with anti-GABAB receptor encephalitis in the Second Affiliated Hospital of Hebei Medical University from February 2016 to October 2016 January were retrospectively collected and evaluated. RESULTS: Seven of the eleven patients were males, and a mean age at presentation of 63 years (range: 47-79 years)...
November 22, 2017: International Journal of Neuroscience
https://www.readbyqxmd.com/read/29165691/estradiol-protects-proopiomelanocortin-neurons-against-insulin-resistance
#4
Jian Qiu, Martha A Bosch, Cecilia Meza, Uyen-Vy Navarro, Casey C Nestor, Edward J Wagner, Oline K Rønnekleiv, Martin J Kelly
Insulin resistance is at the core of the metabolic syndrome, and men exhibit a higher incidence of metabolic syndrome than women in early adult life, but this sex advantage diminishes sharply when women reach the postmenopausal state. Since 17β-estradiol (E2) augments the excitability of the anorexigenic POMC neurons, we investigated the neuroprotective effects of E2 against insulin resistance in POMC neurons from diet-induced obese (DIO) female and male mice. The efficacy of insulin to activate canonical transient receptor potential 5 (TRPC5) channels and depolarize POMC neurons was significantly reduced in DIO male but not in DIO female mice...
November 20, 2017: Endocrinology
https://www.readbyqxmd.com/read/29165303/immunoreactivity-to-cyp24a1-but-not-vitamin-d-receptor-is-increased-in-mast-cells-of-keratinocyte-skin-cancers
#5
Antti Kaukinen, Hanna Siiskonen, Jukka Pelkonen, Ilkka T Harvima
In mouse skin models, mast cells have been shown to express vitamin D receptor (VDR) that can mediate the immunosuppressive effects of ultraviolet B radiation and vitamin D3. However, VDR activation leads to the expression of CYP24A1, a hydroxylase that can inactivate vitamin D3 metabolites. To examine immunoreactivity to VDR and CYP24A1 in mast cells from normal human skin, keratinocyte skin cancers, and disorders of chronic inflammation. Frozen biopsies were collected from the non-lesional and lesional skin of patients with actinic keratosis (AK), Bowen's disease/squamous cell carcinoma (SCC), basal cell carcinoma (BCC), and psoriasis...
November 22, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/29165030/in-mammalian-skeletal-muscle-phosphorylation-of-tomm22-by-protein-kinase-csnk2-ck2-controls-mitophagy
#6
Bojana Kravic, Angelika B Harbauer, Vanina Romanello, Luca Simeone, F-Nora Vögtle, Tobias Kaiser, Marion Straubinger, Danyil Huraskin, Martin Böttcher, Cristina Cerqua, Eva Denise Martin, Daniel Poveda-Huertes, Andreas Buttgereit, Adam J Rabalski, Dieter Heuss, Rüdiger Rudolf, Oliver Friedrich, David Litchfield, Michael Marber, Leonardo Salviati, Dimitrios Mougiakakos, Winfried Neuhuber, Marco Sandri, Chris Meisinger, Said Hashemolhosseini
In yeast, Tom22 the central component of the TOMM (translocase of outer mitochondrial membrane) receptor complex is responsible for the recognition and translocation of synthesized mitochondrial precursor proteins, and its protein kinase CK2-dependent phosphorylation is mandatory for TOMM complex biogenesis and proper mitochondrial protein import. In mammals, the biological function of protein kinase CSNK2/CK2 remains vastly elusive and it is unknown whether CSNK2-dependent phosphorylation of TOMM protein subunits has a similar role as that in yeast...
November 22, 2017: Autophagy
https://www.readbyqxmd.com/read/29165008/building-upon-the-success-of-cart19-chimeric-antigen-receptor-t-cells-for-hematologic-malignancies
#7
Antonia Rotolo, Anastasios Karadimitris, Marco Ruella
Chimeric antigen receptor T cell (CART) therapy has dramatically changed the therapeutic prospects for B cell malignancies. Over the last decade CD19-redirected CART have demonstrated the ability to induce deep, long-lasting remissions and possibly cure patients with relapsing B cell neoplasms. Such impressive results with CART19 fostered efforts to expand this technology to other incurable malignancies that naturally do not express CD19, such as acute myeloid leukemia (AML), Hodgkin lymphoma (HL) and multiple myeloma (MM)...
November 22, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/29164585/expression-and-clinical-significance-of-mir-181a-and-mir-203-in-systemic-lupus-erythematosus-patients
#8
H-S Li, Y Ning, S-B Li, P-Y Shao, S-J Chen, Q Ye, X Heng
OBJECTIVE: MiR-181a plays a critical role in modulating T cell and B cell differentiation, as well as immune response. Its abnormal expression probably participates in the pathogenesis of systemic lupus erythematosus (SLE). MiR-203 is involved in regulating Toll-like receptor and inducing immune tolerance. Abnormal expression or function of miR-203 is related to multiple auto-immune diseases but its role in SLE remains unclear. This study, thus, investigated the serum level of miR-181a and miR-203, to analyze their roles in diagnosing and evaluating SLE...
November 2017: European Review for Medical and Pharmacological Sciences
https://www.readbyqxmd.com/read/29164418/inhibition-of-epidermal-growth-factor-receptor-by-ferulic-acid-and-4-vinylguaiacol-in-human-breast-cancer-cells
#9
S Sudhagar, S Sathya, R Anuradha, G Gokulapriya, Y Geetharani, B S Lakshmi
OBJECTIVES: To examine the potential of ferulic acid and 4-vinylguaiacol for inhibiting epidermal growth factor receptor (EGFR) in human breast cancer cells in vitro. RESULTS: Ferulic acid and 4-vinylguaiacol limit the EGF (epidermal growth factor)-induced breast cancer proliferation and new DNA synthesis. Western blot analysis revealed both ferulic acid and 4-vinylguaiacol exhibit sustained inhibition of EGFR activation through down-regulation of Tyr 1068 autophosphorylation...
November 21, 2017: Biotechnology Letters
https://www.readbyqxmd.com/read/29164305/nuclear-transport-of-the-human-aryl-hydrocarbon-receptor-and-subsequent-gene-induction-relies-on-its-residue-histidine-291
#10
A Tkachenko, M Bermudez, S Irmer-Stooff, D Genkinger, F Henkler-Stephani, G Wolber, A Luch
The aryl hydrocarbon receptor (AHR) is a ligand-dependent transcription factor involved in the metabolism of physiological substances and xenobiotics, representing an interesting target in both toxicology and pharmacology. In this study, we investigated the ligand-dependent conjunction of nuclear import of the human AHR in living cells and target gene induction. Our findings strengthen the theory that the AHR triggers a precisely defined and rapid reaction upon binding to endogenous ligands, while the xenobiotic β-naphthoflavone only induces rather unspecific and slow effects...
November 21, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/29164053/synergistic-protective-activity-of-tumor-specific-epitopes-engineered-in-bacterial-outer-membrane-vesicles
#11
Alberto Grandi, Michele Tomasi, Ilaria Zanella, Luisa Ganfini, Elena Caproni, Laura Fantappiè, Carmela Irene, Luca Frattini, Samine J Isaac, Enrico König, Francesca Zerbini, Simona Tavarini, Chiara Sammicheli, Fabiola Giusti, Ilaria Ferlenghi, Matteo Parri, Guido Grandi
Introduction: Bacterial outer membrane vesicles (OMVs) are naturally produced by all Gram-negative bacteria and, thanks to their plasticity and unique adjuvanticity, are emerging as an attractive vaccine platform. To test the applicability of OMVs in cancer immunotherapy, we decorated them with either one or two protective epitopes present in the B16F10EGFRvIII cell line and tested the protective activity of OMV immunization in C57BL/6 mice challenged with B16F10EGFRvIII. Materials and methods: The 14 amino acid B cell epitope of human epidermal growth factor receptor variant III (EGFRvIII) and the mutation-derived CD4+ T cell neo-epitope of kif18b gene (B16-M30) were used to decorate OMVs either alone or in combination...
2017: Frontiers in Oncology
https://www.readbyqxmd.com/read/29163850/chimeric-antigen-receptor-t-car-t-cell-therapy-for-solid-tumors-challenges-and-opportunities
#12
REVIEW
An-Liang Xia, Xiao-Chen Wang, Yi-Jun Lu, Xiao-Jie Lu, Beicheng Sun
Chimeric antigen receptor (CAR)-engineered T cells (CAR-T cells) have been shown to have unprecedented efficacy in B cell malignancies, most notably in B cell acute lymphoblastic leukemia (B-ALL) with up to a 90% complete remission rate using anti-CD19 CAR-T cells. However, CAR T-cell therapy for solid tumors currently is faced with numerous challenges such as physical barriers, the immunosuppressive tumor microenvironment and the specificity and safety. The clinical results in solid tumors have been much less encouraging, with multiple cases of toxicity and a lack of therapeutic response...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163816/sestrin2-and-sestrin3-suppress-nk-92-cell-mediated-cytotoxic-activity-on-ovarian-cancer-cells-through-ampk-and-mtorc1-signaling
#13
Xuejin Wang, Weifeng Liu, Deyi Zhuang, Shaoxian Hong, Jingfang Chen
Ovarian cancer is one of the major cancer types. NK-92 cell line, which has consistently and reproducibly high anti-tumor cytotoxicity, may be used for immunotherapy against ovarian cancer. Understanding the mechanisms that regulate the anti-tumor activity of NK-92 cells is important for developing novel therapeutic strategies. In the current study, using an ovarian cancer xenograft mouse model, we identified the up-regulation of sestrin2 (SESN2) and sestrin3 (SESN3) in intratumoral NK-92 cells. Lentivirus-transduced NK-92 cells, which overexpressed SESN2 or SESN3 after doxycycline treatment, exhibited less expression of activating receptors, perforin and granzyme B...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163807/macitentan-a-double-antagonist-of-endothelin-receptors-efficiently-impairs-migration-and-microenvironmental-survival-signals-in-chronic-lymphocytic-leukemia
#14
Rossana Maffei, Stefania Fiorcari, Tiziana Vaisitti, Silvia Martinelli, Stefania Benatti, Giulia Debbia, Davide Rossi, Patrizia Zucchini, Leonardo Potenza, Mario Luppi, Gianluca Gaidano, Silvia Deaglio, Roberto Marasca
The crosstalk between chronic lymphocytic leukemia (CLL) cells and tumor microenvironment is essential for leukemic clone maintenance, supporting CLL cells survival, proliferation and protection from drug-induced apoptosis. Over the past years, the role of several soluble factors involved in these processes has been studied. CLL cells express higher levels of endothelin 1 (ET-1) and ETA receptor as compared to normal B cells. Upon ET-1 stimulation, CLL cells improve their survival and proliferation and reduce their sensitivity to the phosphoinositide-3-kinase δ inhibitor idelalisib and to fludarabine...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163802/evaluation-of-somatostatin-cxcr4-chemokine-and-endothelin-a-receptor-expression-in-a-large-set-of-paragangliomas
#15
Daniel Kaemmerer, Jörg Sänger, Ruza Arsenic, Jan G D'Haese, Jens Neumann, Annette Schmitt-Graeff, Ralph Markus Wirtz, Stefan Schulz, Amelie Lupp
Paragangliomas are predominantly benign tumors, but in some cases invasive growth and also metastasis are observed. Given the limited number of nonsurgical treatment options, novel target structures for diagnostics and therapy of this tumor entity are urgently needed. In the present study, expression of all five somatostatin receptor (SST) subtypes, chemokine receptor CXCR4 and endothelin receptor type A (ETA) was assessed by means of immunohistochemistry in a total of 66 paraffin-embedded paraganglioma samples from 55 patients...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163799/jak2-aberrations-in-childhood-b-cell-precursor-acute-lymphoblastic-leukemia
#16
Elisabeth M P Steeghs, Isabel S Jerchel, Willemieke de Goffau-Nobel, Alex Q Hoogkamer, Judith M Boer, Aurélie Boeree, Cesca van de Ven, Marco J Koudijs, Nicolle J M Besselink, Hester A de Groot-Kruseman, Christian Michel Zwaan, Martin A Horstmann, Rob Pieters, Monique L den Boer
JAK2 abnormalities may serve as target for precision medicines in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In the current study we performed a screening for JAK2 mutations and translocations, analyzed the clinical outcome and studied the efficacy of two JAK inhibitors in primary BCP-ALL cells. Importantly, we identify a number of limitations of JAK inhibitor therapy. JAK2 mutations mainly occurred in the poor prognostic subtypes BCR-ABL1-like and non- BCR-ABL1-like B-other (negative for sentinel cytogenetic lesions)...
October 27, 2017: Oncotarget
https://www.readbyqxmd.com/read/29163684/novel-peptide-screened-from-a-phage-display-library-antagonizes-the-activity-of-cc-chemokine-receptor-9
#17
Yi Hu, Aiping Ma, Shan Lin, Yang Yang, Guolin Hong
CC chemokine receptor 9 (CCR9) serves a role in the drug resistance and metastasis of tumors. In the present study, a peptide specifically bound to CCR9 was obtained and the effect on tumor cells was observed. A Ph.D.-12 phage display peptide library was used to screen for peptides binding specifically to the second extracellular loop of CCR9. The ratios of the input and output of phage clones increased gradually following three rounds of biopanning. A total of 8 positive phage clones were identified from DNA analysis...
December 2017: Oncology Letters
https://www.readbyqxmd.com/read/29163548/emodin-alleviates-sodium-taurocholate-induced-pancreatic-acinar-cell-injury-via-microrna-30a-5p-mediated-inhibition-of-high-temperature-requirement-a-transforming-growth-factor-beta-1-inflammatory-signaling
#18
Hong Xiang, Xufeng Tao, Shilin Xia, Jialin Qu, Huiyi Song, Jianjun Liu, Dong Shang
Pancreatitis is an inflammatory disease that is responsible for substantial morbidity and mortality, and it can induce pancreatic necrosis that starts within pancreatic acinar cells in severe cases. Emodin, a pleiotropic natural product isolated from the Chinese herb Rheum palmatum L., has effective anti-inflammatory activities. In this paper, we investigated the protective effects and molecular mechanism of emodin against sodium taurocholate (STC)-induced pancreatic acinar cells injury in vitro and in vivo; and the results showed that emodin could significantly alleviate STC-induced pancreatic acinar cells injury through decreasing trypsin, amylase and the release of inflammatory factors (tumor necrosis factor alpha, interleukin-1β, and interleukin-6)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163533/chronic-nkg2d-engagement-in-vivo-differentially-impacts-nk-cell-responsiveness-by-activating-nk-receptors
#19
Christine Koch, Younghoon Kim, Tobias Zöller, Christina Born, Alexander Steinle
Immunosuppression is a typical hallmark of cancer and frequently includes perturbations of the NKG2D tumor recognition system as well as impaired signaling by other activating NK cell receptors. Several in vitro studies suggested that sustained engagement of the NKG2D receptor, as it is occurring in the tumor microenvironment, not only impairs expression and function of NKG2D but also impacts signaling by other activating NK receptors. Here, we made use of a transgenic mouse model of ubiquitous NKG2D ligand expression (H2-K(b)-MICA mice) to investigate consequences of chronic NKG2D engagement in vivo for functional responsiveness by other activating NK receptors such as NKp46 and Ly49D...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/29163509/downregulated-il-21-response-and-t-follicular-helper-cell-exhaustion-correlate-with-compromised-cd8-t-cell-immunity-during-chronic-toxoplasmosis
#20
Magali M Moretto, SuJin Hwang, Imtiaz A Khan
CD8 T cells are important for maintaining the chronicity of Toxoplasma gondii infection. In a T. gondii encephalitis susceptible model, we recently demonstrated that CD4 T cells play an essential helper role in the maintenance of the effector response and CD8 T cell dysfunctionality was linked to CD4 T cell exhaustion. However, CD4 T cells are constituted of different subsets with various functions and the population(s) providing help to the CD8 T cells has not yet been determined. In the present study, T follicular helper cells (Tfh), which are known to be essential for B cell maturation and are one of the main sources of IL-21, were significantly increased during chronic toxoplasmosis...
2017: Frontiers in Immunology
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