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https://www.readbyqxmd.com/read/28922848/aggressive-behavior-in-silent-subtype-iii-pituitary-adenomas-may-depend-on-suppression-of-local-immune-response-a-whole-transcriptome-analysis
#1
Timothy E Richardson, Zhong-Jian Shen, Mohammed Kanchwala, Chao Xing, Alexander Filatenkov, Ping Shang, Samuel Barnett, Zahidur Abedin, James S Malter, Jack M Raisanen, Dennis K Burns, Charles L White, Kimmo J Hatanpaa
Silent subtype III pituitary adenomas (SS-3) are clinically nonfunctional adenomas that are more aggressive in terms of invasion and risk of recurrence than their conventional null cell counterparts. We previously showed that these tumors can be distinguished by immunohistochemistry based on the identification of a markedly enlarged and fragmented Golgi apparatus. To understand the molecular correlates of differential aggressiveness, we performed whole transcriptome sequencing (RNAseq) on 4 SS-3 and 4 conventional null cell adenomas...
October 1, 2017: Journal of Neuropathology and Experimental Neurology
https://www.readbyqxmd.com/read/28921818/blinatumomab-activity-in-a-patient-with-down-syndrome-b-precursor-acute-lymphoblastic-leukemia
#2
Aman Wadhwa, Matthew A Kutny, Ana C Xavier
Persistent minimal residual disease (MRD) after consolidation may indicate chemotherapy insensitivity in B-precursor acute lymphoblastic leukemia (BP-ALL). Given the strong association of MRD and outcome in non-Down syndrome (non-DS) BP-ALL, it is likely that MRD levels are also of prognostic significance in DS BP-ALL. We report here the successful use of blinatumomab, a bispecific T-cell engager antibody construct, in a patient with DS BP-ALL and persistent MRD at the end of consolidation. Blinatumomab has been shown to have excellent results in patients with relapsed/refractory BP-ALL...
September 17, 2017: Pediatric Blood & Cancer
https://www.readbyqxmd.com/read/28921702/3d-analysis-of-mitosis-distribution-highlights-the-longitudinal-zonation-and-diarch-symmetry-in-proliferation-activity-of-the-arabidopsis-thaliana-root-meristem
#3
V V Lavrekha, T Pasternak, V B Ivanov, K Palme, V V Mironova
To date CYCB1;1 marker and cortex cell lengths are conventionally used to determine the proliferation activity of the Arabidopsis root meristem. By creating a 3D map of mitosis distribution we showed that these markers overlooked that stele and endodermis save their potency to divide longer than cortex and epidermis. Cessation of cell divisions is not a random process, so that the mitotic activity within the endodermis and stele shows a diarch pattern. Mitotic activity of all root tissues peaked at the same distance from the quiescent center (QC); however, different tissues stopped dividing at different distances, with cells of the protophloem exiting the cell cycle first and the procambial cells being the last...
September 16, 2017: Plant Journal: for Cell and Molecular Biology
https://www.readbyqxmd.com/read/28921473/the-development-and-diversity-of-ilcs-nk-cells-and-their-relevance-in-health-and-diseases
#4
Yuxia Zhang, Bing Huang
Next to T and B cells, natural killer (NK) cells are the third largest lymphocyte population. They are recently re-categorized as innate lymphocytes (ILCs), which also include ILC1, ILC2, ILC3, and the lymphoid tissue inducer (LTi) cells. Both NK cells and ILC1 cells are designated as group 1 ILCs because they secrete interferon-γ (IFN-γ) and tumor necrosis factor (TNF). However, in contrast to ILC1 and all other ILCs, NK cells possess potent cytolytic functions that resemble cytotoxic T lymphocytes (CTL)...
2017: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/28920671/development-of-a-multifunctional-nanobiointerface-based-on-self-assembled-fusion-protein-rsbpa-zz-for-blood-cell-enrichment-and-phenotyping
#5
Mario Rothbauer, Martin Frauenlob, Karoline Gutkas, Michael B Fischer, Eva Kathrin Sinner, Seta Küpcü, Peter Ertl
We present a multifunctional nanobiointerface for blood cell capture and phenotyping applications that features both excellent antifouling properties and high antibody activity. Multifunctionality is accomplished by modifying polymeric materials using self-assembled S-layer fusion-protein rSbpA/ZZ to immobilize high density antibodies at the two protein A binding sites of the rSbpA/ZZ nanolattice structure. Controlled orientation and alignment of the antibodies reduced antibody consumption 100-fold and increased cell capture efficiency 4-fold over standard methodologies...
September 18, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28919995/mammary-tumor-derived-ccl2-enhances-pro-metastatic-systemic-inflammation-through-upregulation-of-il1%C3%AE-in-tumor-associated-macrophages
#6
Kelly Kersten, Seth B Coffelt, Marlous Hoogstraat, Niels J M Verstegen, Kim Vrijland, Metamia Ciampricotti, Chris W Doornebal, Cheei-Sing Hau, Max D Wellenstein, Camilla Salvagno, Parul Doshi, Esther H Lips, Lodewyk F A Wessels, Karin E de Visser
Patients with primary solid malignancies frequently exhibit signs of systemic inflammation. Notably, elevated levels of neutrophils and their associated soluble mediators are regularly observed in cancer patients, and correlate with reduced survival and increased metastasis formation. Recently, we demonstrated a mechanistic link between mammary tumor-induced IL17-producing γδ T cells, systemic expansion of immunosuppressive neutrophils and metastasis formation in a genetically engineered mouse model for invasive breast cancer...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28919897/altered-immune-activation-and-il-23-signaling-in-response-to-candida-albicans-in-autoimmune-polyendocrine-syndrome-type-1
#7
Øyvind Bruserud, Eirik Bratland, Alexander Hellesen, Nicolas Delaleu, Håkon Reikvam, Bergithe E Oftedal, Anette S B Wolff
OBJECTIVE: Autoimmune polyendocrine syndrome type 1 (APS-1) is a rare, childhood onset disease caused by mutations in the autoimmune regulator (AIRE) gene. Chronic mucocutaneous candidiasis (CMC) is one of the three major disease components and is, to date, mainly explained by the presence of neutralizing auto-antibodies against cytokines [interleukin (IL)-17A, IL-17F, and IL-22] from T helper 17 cells, which are critical for the protection against fungal infections. However, patients without current auto-antibodies also present CMC and we, therefore, hypothesized that other immune mechanisms contribute to CMC in APS-1...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28919776/safety-pharmacokinetics-and-pharmacodynamics-of-oral-omaveloxolone-rta-408-a-synthetic-triterpenoid-in-a-first-in-human-trial-of-patients-with-advanced-solid-tumors
#8
Ben C Creelan, Dmitry I Gabrilovich, Jhanelle E Gray, Charles C Williams, Tawee Tanvetyanon, Eric B Haura, Jeffrey S Weber, Geoffrey T Gibney, Joseph Markowitz, Joel W Proksch, Scott A Reisman, Mark D McKee, Melanie P Chin, Colin J Meyer, Scott J Antonia
BACKGROUND: Omaveloxolone is a semisynthetic oleanane triterpenoid that potently activates Nrf2 with subsequent antioxidant function. We conducted a first-in-human Phase I clinical trial (NCT02029729) with the primary objectives to determine the appropriate dose for Phase II studies, characterize pharmacokinetic and pharmacodynamic parameters, and assess antitumor activity. METHODS: Omaveloxolone was administered orally once daily continuously in a 28-day cycle for patients with stage 4 relapsed/refractory melanoma or non-small cell lung cancer...
2017: OncoTargets and Therapy
https://www.readbyqxmd.com/read/28919076/mitochondrial-priming-by-cd28
#9
Ramon I Klein Geltink, David O'Sullivan, Mauro Corrado, Anna Bremser, Michael D Buck, Joerg M Buescher, Elke Firat, Xuekai Zhu, Gabriele Niedermann, George Caputa, Beth Kelly, Ursula Warthorst, Anne Rensing-Ehl, Ryan L Kyle, Lana Vandersarren, Jonathan D Curtis, Annette E Patterson, Simon Lawless, Katarzyna Grzes, Jing Qiu, David E Sanin, Oliver Kretz, Tobias B Huber, Sophie Janssens, Bart N Lambrecht, Angelika S Rambold, Edward J Pearce, Erika L Pearce
T cell receptor (TCR) signaling without CD28 can elicit primary effector T cells, but memory T cells generated during this process are anergic, failing to respond to secondary antigen exposure. We show that, upon T cell activation, CD28 transiently promotes expression of carnitine palmitoyltransferase 1a (Cpt1a), an enzyme that facilitates mitochondrial fatty acid oxidation (FAO), before the first cell division, coinciding with mitochondrial elongation and enhanced spare respiratory capacity (SRC). microRNA-33 (miR33), a target of thioredoxin-interacting protein (TXNIP), attenuates Cpt1a expression in the absence of CD28, resulting in cells that thereafter are metabolically compromised during reactivation or periods of increased bioenergetic demand...
September 1, 2017: Cell
https://www.readbyqxmd.com/read/28918429/synergy-of-dendritic-cell-vaccines-and-avasimibe-in-treatment-of-head-and-neck-cancer-in-mice
#10
Xin Chen, Qibin Song, Leiming Xia, Ximing Xu
BACKGROUND The main purpose of this study was to explore the antitumor effect and mechanisms of ACAT1 inhibitor combined with CSCs-DC vaccine. MATERIAL AND METHODS We isolated HNSCC CSCs and gained CSCs antigens, then used CSCs antigens to load dendritic cells (DC) and generated a CSCs-DC vaccine. We treated mice after surgical excision of established SCC7 tumors with CSCs-DC vaccine and/or ACAT1 inhibitor, and recorded local tumor relapse and host survival. T cells and B cells were harvested from mice treated with CSCs-DC vaccine and/or ACAT1 inhibitor...
September 17, 2017: Medical Science Monitor: International Medical Journal of Experimental and Clinical Research
https://www.readbyqxmd.com/read/28917721/low-levels-of-the-immunoregulator-semaphorin-4d-cd100-in-sera-of-hiv-patients
#11
Z Vadas, D Elbirt, S Radian, S Bezalel-Rosenberg, K Mahlab-Guri, E Toubi, I Asher, Z Sthoeger
INTRODUCTION: Semaphorin-4D (CD100), generated by CD4/CD8 cells, plays an important role in T cells activation. It also regulates B cell differentiation via its receptor the CD72. Both have soluble forms - sCD100/sCD72. METHODS: sCD100 and sCD72 levels were determined by ELISA (MyBioSource, USA). RESULTS: 28 chronic HIV patients and 50 matched healthy volunteers participated in our study. Before treatment, CD4 cell counts were 267±216cells/mcl and viral load (VL) was 586,675±1,897,431copies/ml...
September 13, 2017: Clinical Immunology: the Official Journal of the Clinical Immunology Society
https://www.readbyqxmd.com/read/28917204/murine-il-4%C3%AE-2-splice-variant-down-regulates-il-4-activities-independently-of-il-4r%C3%AE-binding-and-stat-6-phosphorylation
#12
Gil R Diogo, Adam Sparrow, Matthew J Paul, Alastair Copland, Peter J Hart, Szymon Stelter, Craig van Dolleweerd, Pascal M W Drake, Derek C Macallan, Rajko Reljic
IL-4 is a pleiotropic cytokine that is highly Th2 polarizing. The ratio of IL-4 and its splice variant IL-4Δ2 observed in human health and disease suggests a role for both isoforms. In the present study, the biological function of murine IL-4Δ2 and the potential mechanism of action were studied. We report for the first time the generation of a functional, recombinant murine IL-4Δ2 form which is suggestive of its possible biological role in this species. Recombinant murine IL-4Δ2 inhibited IL-4 mediated cellular processes in macrophages and lymphocytes...
September 13, 2017: Cytokine
https://www.readbyqxmd.com/read/28917086/kostchyienones-a-and-b-new-antiplasmodial-and-cytotoxicity-of-limonoids-from-the-roots-of-pseudocedrela-kotschyi-schweinf-harms
#13
Lazare S Sidjui, Yves O D Nganso, Rufin M K Toghueo, Brussine N K Wakeu, Joel T Dameue, Pierre Mkounga, Achyut Adhikari, Mehreen Lateef, Gabriel N Folefoc, Muhammad S Ali
Two new limonoids, kostchyienones A (1) and B (2), along with 12 known compounds 3-14 were isolated from the roots of Pseudocedrela kostchyi. Compound (7) was isolated for the first time from a natural source. Their structures were elucidated on the basis of spectroscopic evidence. Compounds 1-6 and 13-14 gave IC50 values ranging from 0.75 to 5.62 μg/mL for antiplasmodial activity against chloroquine-sensitive (Pf3D7) and chloroquine-resistant (PfINDO) strains of Plasmodium falciparum. Compound 5 showed moderate potential cytotoxicity against the HEK239T cell line with an IC50 value of 22...
September 16, 2017: Zeitschrift Für Naturforschung. C, A Journal of Biosciences
https://www.readbyqxmd.com/read/28916716/deregulation-of-microrna-expression-in-purified-t-and-b-lymphocytes-from-patients-with-primary-sj%C3%A3-gren-s-syndrome
#14
Shu-Fang Wang-Renault, Saida Boudaoud, Gaétane Nocturne, Elodie Roche, Nelly Sigrist, Christian Daviaud, Andreas Bugge Tinggaard, Victor Renault, Jean-François Deleuze, Xavier Mariette, Jörg Tost
OBJECTIVE: MicroRNAs (miRNAs) play an important role in the pathogenesis of autoimmune diseases such as primary Sjögren's syndrome (pSS). This study is the first to investigate miRNA expression patterns in purified T and B lymphocytes from patients with pSS using a high-throughput quantitative PCR (qPCR) approach. METHODS: Two independent cohorts of both patients with pSS and controls, one for discovery and one for replication, were included in this study. CD4+ T cells and CD19+ B cells were isolated from peripheral blood mononuclear cells by magnetic microbeads and expression of miRNAs was profiled using the Exiqon Human miRNome panel I analysing 372 miRNAs...
September 15, 2017: Annals of the Rheumatic Diseases
https://www.readbyqxmd.com/read/28916652/lsd1-mediated-epigenetic-reprogramming-drives-cenpe-expression-and-prostate-cancer-progression
#15
Yi Liang, Musaddeque Ahmed, Haiyang Guo, Fraser Soares, Junjie T Hua, Shuai Gao, Catherine Lu, Christine Poon, Wanting Han, Jens Langstein, Muhammad B Ekram, Brian Li, Elai Davicioni, Mandeep Takhar, Nicholas Erho, R Jeffrey Karnes, Dianne Chadwick, Theodorus van der Kwast, Paul C Boutros, Cheryl H Arrowsmith, Felix Y Feng, Anthony Michael Joshua, Amina Zoubeidi, Changmeng Cai, Housheng H He
Androgen receptor (AR) signaling is a key driver of prostate cancer (PCa), and androgen-deprivation therapy (ADT) is a standard treatment for patients with advanced and metastatic disease. However, patients receiving ADT eventually develop incurable castration-resistant PCa (CRPC). Here we report that the chromatin modifier LSD1, an important regulator of AR transcriptional activity, undergoes epigenetic reprogramming in CRPC. LSD1 reprogramming in this setting activated a subset of cell cycle genes including CENPE, a centromere binding protein and mitotic kinesin...
September 15, 2017: Cancer Research
https://www.readbyqxmd.com/read/28916524/new-methods-to-analyze-b-cell-immune-responses-to-thymus-dependent-antigen-sheep-red-blood-cells
#16
Ellen J McAllister, John R Apgar, Charlotte R Leung, Robert C Rickert, Julia Jellusova
B cells contribute critically to an effective immune response by producing Ag-specific Abs. During the immune response to so-called "thymus-dependent Ags," activated B cells seek T cell help and form germinal centers. In contrast, thymus-independent Ags generally do not induce germinal center formation. In the germinal center, B cells undergo somatic hypermutation, affinity-based clonal expansion, and differentiation to produce plasma cells and memory B cells. Valuable insight into these processes has been gained by using model hapten-carrier complexes or SRBCs...
September 15, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28916185/alveolar-eosinophilia-in-current-smokers-with-chronic-obstructive-pulmonary-disease-in-the-spiromics-cohort
#17
Carlos H Martinez, Sara X Li, Andrew J Hirzel, Valerie R Stolberg, Neil E Alexis, R Graham Barr, Eugene R Bleecker, Elizabeth E Carretta, Stephanie A Christenson, Christopher B Cooper, David J Couper, Claire M Doerschuk, MeiLan K Han, Nadia N Hansel, Annette T Hastie, Eric A Hoffman, Robert J Kaner, Fernando J Martinez, Deborah A Meyers, Wanda K O'Neal, Robert Paine, Nirupama Putcha, Stephen I Rennard, Prescott G Woodruff, Michelle Zeidler, Jeffrey L Curtis, Christine M Freeman
Active smoking in stable COPD subjects significantly increased eosinophil accumulation in the distal airspaces, but not in sputum or peripheral blood. Our findings support the need to investigate this cell-type as a potential driver of COPD symptomatology and progression.
September 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28916184/role-of-the-il-12-il-35-balance-in-sj%C3%A3-gren-s-syndrome
#18
Olivier Fogel, Elodie Rivière, Raphaèle Seror, Gaetane Nocturne, Saida Boudaoud, Bineta Ly, Jacques-Eric Gottenberg, Véronique Le Guern, Jean-Jacques Dubost, Joanne Nititham, Kimberly E Taylor, Philippe Chanson, Philippe Dieudé, Lindsey A Criswell, Bernd Jagla, Alice Thai, Michael Mingueneau, Xavier Mariette, Corinne Miceli-Richard
BACKGROUND: An interferon (IFN) signature is involved in the pathogenesis of primary Sjögren's syndrome (pSS), but whether the signature is type 1 or 2 remains controversial. Mouse models and genetic studies suggested the involvement of T helper 1 and type 2 IFN pathways. Likewise, polymorphisms of interleukin 12A gene (IL-12A), which encodes for IL-12p35, have been associated with pSS. IL-12p35 subunit is shared by 2 heterodimers, IL-12 and IL-35. OBJECTIVE: To confirm the genetic association of IL-12A polymorphism and pSS and elucidate the involvement of the IL-12/IL-35 balance in pSS by functional studies...
September 12, 2017: Journal of Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/28915659/data-driven-analysis-of-immune-infiltrate-in-a-large-cohort-of-breast-cancer-and-its-association-with-disease-progression-er-activity-and-genomic-complexity
#19
Ruth Dannenfelser, Marianne Nome, Andliena Tahiri, Josie Ursini-Siegel, Hans Kristian Moen Vollan, Vilde D Haakensen, Åslaug Helland, Bjørn Naume, Carlos Caldas, Anne-Lise Børresen-Dale, Vessela N Kristensen, Olga G Troyanskaya
The tumor microenvironment is now widely recognized for its role in tumor progression, treatment response, and clinical outcome. The intratumoral immunological landscape, in particular, has been shown to exert both pro-tumorigenic and anti-tumorigenic effects. Identifying immunologically active or silent tumors may be an important indication for administration of therapy, and detecting early infiltration patterns may uncover factors that contribute to early risk. Thus far, direct detailed studies of the cell composition of tumor infiltration have been limited; with some studies giving approximate quantifications using immunohistochemistry and other small studies obtaining detailed measurements by isolating cells from excised tumors and sorting them using flow cytometry...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28915576/hepatic-b-cell-leukemia-3-suppresses-chemically-induced-hepatocarcinogenesis-in-mice-through-altered-mapk-and-nf-%C3%AE%C2%BAb-activation
#20
Nadine Gehrke, Marcus A Wörns, Amrit Mann, Yvonne Huber, Nadine Hoevelmeyer, Thomas Longerich, Ari Waisman, Peter R Galle, Jörn M Schattenberg
The transcriptional nuclear factor kappa B (NF-κB)-coactivator B cell leukemia-3 (Bcl-3) is a molecular regulator of cell death and proliferation. Bcl-3 has been shown to be widely expressed in different cancer types including hepatocellular carcinoma (HCC). Its influence on hepatocarcinogenesis is still undetermined. To examine the role of Bcl-3 in hepatocarcinogenesis mice with hepatocyte-specific overexpression of Bcl-3 (Bcl-3(Hep)) were exposed to diethylnitrosamine (DEN) and phenobarbital (PB). Hepatic Bcl-3 overexpression attenuated DEN/PB-induced hepatocarcinogenesis...
August 22, 2017: Oncotarget
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