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https://www.readbyqxmd.com/read/28813667/human-gw182-paralogs-are-the-central-organizers-for-rna-mediated-control-of-transcription
#1
Jessica A Hicks, Liande Li, Masayuki Matsui, Yongjun Chu, Oleg Volkov, Krystal C Johnson, David R Corey
In the cytoplasm, small RNAs can control mammalian translation by regulating the stability of mRNA. In the nucleus, small RNAs can also control transcription and splicing. The mechanisms for RNA-mediated nuclear regulation are not understood and remain controversial, hindering the effective application of nuclear RNAi and investigation of its natural regulatory roles. Here, we reveal that the human GW182 paralogs TNRC6A/B/C are central organizing factors critical to RNA-mediated transcriptional activation. Mass spectrometry of purified nuclear lysates followed by experimental validation demonstrates that TNRC6A interacts with proteins involved in protein degradation, RNAi, the CCR4-NOT complex, the mediator complex, and histone-modifying complexes...
August 15, 2017: Cell Reports
https://www.readbyqxmd.com/read/28807771/increase-of-intermediate-monocytes-in-gvhd-correlation-with-mdr1-th17-1-levels-and-the-effect-of-prednisolone-and-1%C3%AE-25-dihydroxyvitamin-d3
#2
Katharina Reinhardt-Heller, Insa Hirschberg, Peter Lang, Thomas Vogl, Rupert Handgretinger, Wolfgang A Bethge, Ursula Holzer
Graft-versus-host disease (GvHD) remains one of the major complications after allogeneic hematopoietic stem cell transplantation which is mainly treated with glucocorticoids such as prednisolone. In this study, the influence of monocyte subpopulations, prednisolone and 1α,25-Dihydroxyvitamin D3 on the induction of a pro-inflammatory subset of Th17 cells (MDR(+)Th17.1) characterized by CCR6(+)CXCR3(hi)CCR4(lo)CCR10(-)CD161(+) and stable expression of the multi-drug resistance protein type 1 (MDR1) was investigated...
August 11, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28801066/identification-of-pyrazolopyrimidine-arylsulfonamides-as-cc-chemokine-receptor-4-ccr4-antagonists
#3
Afjal H Miah, Aurelie C Champigny, Rebecca H Graves, Simon T Hodgson, Jonathan M Percy, Panayiotis A Procopiou
A novel 4-aminoindazole sulfonamide hit (13) was identified as a human CCR4 antagonists from testing a focussed library of compounds in the primary GTPγS assay. Replacing the indazole core with a pyrazolopyrimidine, and introduction of a methoxy group adjacent to the sulfonamide substituent, resulted in the identification of pyrazolopyrimidine 37a, which exhibited good binding affinity in the GTPγS assay (pIC50=7.2), low lipophilicity (clogP=2.2, chromlogD7.4=2.4), high LE (0.41), high solubility (CLND solubility ≥581µM), and an excellent PK profile in both the rat (F=62%) and the dog (F=100%)...
July 29, 2017: Bioorganic & Medicinal Chemistry
https://www.readbyqxmd.com/read/28794233/characterization-of-mycobacterium-tuberculosis-specific-cells-using-mhc-class-ii-tetramers-reveals-phenotypic-differences-related-to-hiv-infection-and-tuberculosis-disease
#4
Natalie Strickland, Tracey L Müller, Natacha Berkowitz, Rene Goliath, Mary N Carrington, Robert J Wilkinson, Wendy A Burgers, Catherine Riou
A major challenge for the development of an effective vaccine against tuberculosis (TB) is that the attributes of protective CD4(+) T cell responses are still elusive for human TB. Infection with HIV type 1 is a major risk factor for TB, and a better understanding of HIV-induced alterations of Mycobacterium tuberculosis-specific CD4(+) T cells that leads to failed host resistance may provide insight into protective T cell immunity to TB. A total of 86 participants from a TB-endemic setting, either HIV-infected or uninfected and with latent or active TB (aTB), were screened using M...
August 9, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28793956/hypersensitivity-reaction-to-%C3%AE-lactam-antibiotics-in-patients-with-adult-t-cell-leukemia-lymphoma-treated-with-mogamulizumab%C3%A2
#5
Takeo Yasu, Yoichi Imai, Nobuhiro Ohno, Kaoru Uchimaru, Yosuke Kurokawa, Arinobu Tojo
Mogamulizumab (MOG) is a humanized anti-CCR4 monoclonal antibody that is highly cytotoxic for adult T-cell leukemia/lymphoma (ATL) cells. Most non-hematological adverse events are cutaneous adverse reactions in ATL patients. We reviewed the medical records of 24 patients with CCR4-positive aggressive ATL who had received MOG treatment. The incidence of MOG-induced cutaneous adverse reactions (MCARs) was 25% (6 patients). Four patients with MCAR had an interesting clinical course, compared with MCARs reported in previous reports...
August 10, 2017: International Journal of Clinical Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28783702/natural-killer-cell-mediated-inflammation-resolution-is-disabled-in-severe-asthma
#6
Melody G Duvall, Cindy Barnig, Manuela Cernadas, Isabell Ricklefs, Nandini Krishnamoorthy, Nicole L Grossman, Nirav R Bhakta, John V Fahy, Eugene R Bleecker, Mario Castro, Serpil C Erzurum, Benjamin M Gaston, Nizar N Jarjour, David T Mauger, Sally E Wenzel, Suzy A Comhair, Andrea M Coverstone, Merritt L Fajt, Annette T Hastie, Mats W Johansson, Michael C Peters, Brenda R Phillips, Elliot Israel, Bruce D Levy
Severe asthma is typically characterized by chronic airway inflammation that is refractory to corticosteroids and associated with excess morbidity. Patients were recruited into the National Heart, Lung, and Blood Institute-sponsored Severe Asthma Research Program and comprehensively phenotyped by bronchoscopy. Bronchoalveolar lavage (BAL) cells were analyzed by flow cytometry. Compared with healthy individuals (n = 21), patients with asthma (n = 53) had fewer BAL natural killer (NK) cells. Patients with severe asthma (n = 29) had a marked increase in the ratios of CD4(+) T cells to NK cells and neutrophils to NK cells...
March 10, 2017: Science Immunology
https://www.readbyqxmd.com/read/28776876/mogamulizumab-for-relapsed-adult-t-cell-leukemia-lymphoma-updated-follow-up-analysis-of-phase-i-and-ii-studies
#7
Takashi Ishida, Atae Utsunomiya, Tatsuro Jo, Kazuhito Yamamoto, Koji Kato, Shinichiro Yoshida, Shigeki Takemoto, Hitoshi Suzushima, Yukio Kobayashi, Yoshitaka Imaizumi, Kenichi Yoshimura, Kouichi Kawamura, Takeshi Takahashi, Kensei Tobinai, Ryuzo Ueda
The present study sought to elucidate the prognosis of adult T-cell leukemia-lymphoma (ATL) patients receiving mogamulizumab, a defucosylated anti-CCR4 monoclonal antibody. Progression-free survival (PFS) and overall survival (OS) of ATL patients enrolled in two studies are updated here, namely NCT00355472 (phase I study of mogamulizumab in relapsed patients with ATL and peripheral T-cell lymphoma) and NCT00920790 (phase II study for relapsed ATL). Of 13 patients with relapsed aggressive ATL in the phase I study, four (31%) survived > 3 years...
August 4, 2017: Cancer Science
https://www.readbyqxmd.com/read/28756726/mogamulizumab-for-the-treatment-of-relapsed-or-refractory-adult-t-cell-leukemia-lymphoma
#8
Frank Winsett, Madeleine Duvic
Adult T-cell leukemia-lymphoma (ATL) is an aggressive variant of peripheral T-cell lymphoma of CD4+ T malignant cells caused by human T-lymphotropic virus type-1. Despite aggressive treatment with multidrug combination chemotherapies, ATL confers a poor prognosis and commonly develops resistance to conventional treatments. Areas covered: Mogamulizumab is a humanized, defucosylated monoclonal antibody that acts by targeting the CC chemokine receptor 4 (CCR4) on malignant cells of ATL. In phase I and II clinical trials, it has achieved overall response rates of 31-50% in CCR4+ malignancies...
July 31, 2017: Expert Review of Hematology
https://www.readbyqxmd.com/read/28736230/pro-inflammatory-chemokines-and-cytokines-dominate-the-blister-fluid-molecular-signature-in-epidermolysis-bullosa-patients-and-affect-leukocyte-and-stem-cell-migration
#9
Vitali Alexeev, Julio Cesar Salas-Alanis, Francis Palisson, Lila Mukhtarzada, Giulio Fortuna, Jouni Uitto, Andy South, Olga Igoucheva
Hereditary epidermolysis bullosa (EB) is associated with skin blistering and the development of chronic non-healing wounds. Although clinical studies have shown that cell-based therapies improve wound healing, recruitment of therapeutic cells to blistering skin and to more advanced skin lesions remains a challenge. Here, we analyzed cytokines and chemokines in blister fluids (BF) of patients affected by dystrophic, junctional and simplex EB. Our analysis revealed high levels of CXCR1, CXCR2, CCR2 and CCR4 ligands, particularly dominant in dystrophic and junctional EB...
July 20, 2017: Journal of Investigative Dermatology
https://www.readbyqxmd.com/read/28732312/drug-eluting-scaffold-inhibited-in-vivo-pancreatic-tumorigenesis-by-engaging-murine-ccr4-cd8-t-cells
#10
Qian Zhan, Baiyong Shen, Yuan Fang, Xiaxing Deng, Hao Chen, Jiabin Jin, Chenghong Peng, Hongwei Li
CCL17 is well known for its ability to engage CCR4(+)CD8(+) T cells, which have been shown to play a critical role in preventing tumorigenesis. In this study, we attempted to inhibit in vivo pancreatic tumorigenesis by engaging murine CCR4(+)CD8(+) T cells through a drug-eluting scaffold with a payload of CCL17. The drug-eluting scaffold was fabricated by electrospinning polyglyconate and porcine gelatin. The electrospun scaffold featured randomly distributed non-woven fibers with diameters ranging from 1μm to 4μm...
July 10, 2017: Colloids and Surfaces. B, Biointerfaces
https://www.readbyqxmd.com/read/28721932/ccr4-and-ccr5-expression-in-a-case-of-subcutaneous-panniculitis-like-t-cell-lymphoma
#11
Naomi Kitayama, Atsushi Otsuka, Yuki Honda, Yumi Matsumura, Tetsuya Honda, Kenji Kabashima
No abstract text is available yet for this article.
July 19, 2017: European Journal of Dermatology: EJD
https://www.readbyqxmd.com/read/28706220/opportunities-for-therapeutic-antibodies-directed-at-g-protein-coupled-receptors
#12
REVIEW
Catherine J Hutchings, Markus Koglin, William C Olson, Fiona H Marshall
G-protein-coupled receptors (GPCRs) are activated by a diverse range of ligands, from large proteins and proteases to small peptides, metabolites, neurotransmitters and ions. They are expressed on all cells in the body and have key roles in physiology and homeostasis. As such, GPCRs are one of the most important target classes for therapeutic drug discovery. The development of drugs targeting GPCRs has therapeutic value across a wide range of diseases, including cancer, immune and inflammatory disorders as well as neurological and metabolic diseases...
July 14, 2017: Nature Reviews. Drug Discovery
https://www.readbyqxmd.com/read/28680001/progress-in-the-management-of-atl
#13
Kenji Ishitsuka
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell malignancy caused by human T-lymphotropic virus type I (HTLV-1), and its prognosis remains poor. Three to five percent of HTLV-1 carriers, infected mainly by breast feeding, develop ATL after a latency period as long as 70 years. The standard of care for aggressive ATL and indolent ATL comprises intensive chemotherapy followed by allogeneic hematopoietic stem cell transplantation, if applicable, and watchful waiting, respectively. Outside Japan, a combination of interferon-α and zidovudine has also been used as a therapeutic option for acute, chronic, and smoldering-type ATLs...
2017: [Rinshō Ketsueki] the Japanese Journal of Clinical Hematology
https://www.readbyqxmd.com/read/28677152/significant-augmentation-of-regulatory-t-cell-numbers-occurs-during-the-early-neonatal-period
#14
Seiichi Hayakawa, Norioki Ohno, Satoshi Okada, Masao Kobayashi
Regulatory T cells (Tregs) control immune responses by suppressing various inflammatory cells. Tregs in newborn babies may play an important role in preventing excessive immune responses during their environmental change. We examined the number and phenotype of Tregs during the neonatal period in 49 newborn babies. Tregs were characterized by flow cytometry using cord blood (CB) and peripheral blood (PB) from the early (7-8 days after birth) and late (2-4 weeks after birth) neonatal periods. CD4(+) Foxp3(+) T cells were classified into resting Tregs (CD45RA(+) Foxp3(low) ), activated Tregs (CD45RA(-) Foxp3(high) ), and newly activated T cells (CD45RA(-) Foxp3(low) )...
July 5, 2017: Clinical and Experimental Immunology
https://www.readbyqxmd.com/read/28672408/ginger-extract-modulates-the-expression-of-chemokines-ccl20-and-ccl22-and-their-receptors-ccr6-and-ccr4-in-the-central-nervous-system-of-mice-with-experimental-autoimmune-encephalomyelitis
#15
Abdollah Jafarzadeh, Zahra Arabi, Rayhaneh Ahangar-Parvin, Marziyeh Mohammadi-Kordkhayli, Maryam Nemati
Background Chemokines facilitate the leukocytes infiltration into the central nervous system (CNS) which is an essential step in the pathogenesis of multiple sclerosis. Ginger has also a broad anti-inflammatory properties. The aim was to evaluate the effects of ginger extract on the expression of CCL20 and CCL22 and their receptors (CCR6 and CCR4, respectively) in experimental autoimmune encephalomyelitis (EAE). Material and Methods Female C57BL/6 mice used for EAE induction by immunization with myelin oligodendroglial glycoprotein...
July 3, 2017: Drug Research
https://www.readbyqxmd.com/read/28666691/direct-targeting-of-cancer-cells-with-antibodies-what-can-we-learn-from-the-successes-and-failure-of-unconjugated-antibodies-for-lymphoid-neoplasias
#16
REVIEW
Josée Golay
Following approval in 1997 of the anti-CD20 antibody rituximab for the treatment of B-NHL and CLL, many other unconjugated IgG1 MAbs have been tested in pre-clinical and clinical trials for the treatment of lymphoid neoplasms. Relatively few have been approved however and these are directed against a limited number of target antigens (CD20, CD52, CCR4, CD38, CD319). We review here the known biological properties of these antibodies and discuss which factors may have led to their success or may, on the contrary, limit their clinical application...
June 27, 2017: Journal of Autoimmunity
https://www.readbyqxmd.com/read/28649848/mogamulizumab-for-the-treatment-of-t-cell-lymphoma
#17
Shinichi Makita, Kensei Tobinai
T-cell lymphoma is a relatively rare hematologic malignancy that accounts for 10-20% of non-Hodgkin lymphomas. Treatment strategies for T-cell lymphomas are different from that for B-cell lymphomas and have poor prognoses. Among various subtypes of T-cell lymphomas, adult T-cell leukemia-lymphoma (ATL) has the worst prognosis. To achieve further improvement in the treatment outcome of T-cell lymphomas, several novel agents such as brentuximab vedotin, lenalidomide, romidepsin, and pralatrexate are actively being studied...
September 2017: Expert Opinion on Biological Therapy
https://www.readbyqxmd.com/read/28645775/altered-populations-of-natural-killer-cells-cytotoxic-t-lymphocytes-and-regulatory-t-cells-in-major-depressive-disorder-association-with-sleep-disturbance
#18
Hideo Suzuki, Jonathan Savitz, T Kent Teague, Siva K Gandhapudi, Chibing Tan, Masaya Misaki, Brett A McKinney, Michael R Irwin, Wayne C Drevets, Jerzy Bodurka
A subset of individuals with major depressive disorder (MDD) have impaired adaptive immunity characterized by a greater vulnerability to viral infection and a deficient response to vaccination along with a decrease in the number and/or activity of T cells and natural killer cells (NKC). Nevertheless, it remains unclear which specific subsets of lymphocytes are altered in MDD, a shortcoming we address here by utilizing an advanced fluorescence-activated cell sorting (FACS) method that allows for the differentiation of important functionally-distinct lymphocyte sub-populations...
June 20, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28645139/correction-ccr4-promotes-metastasis-via-erk-nf-%C3%AE%C2%BAb-mmp13-pathway-and-acts-downstream-of-tnf-%C3%AE-in-colorectal-cancer
#19
Baochi Ou, Jingkun Zhao, Shaopei Guan, Hao Feng, Xiongzhi Wangpu, Congcong Zhu, Yaping Zong, Junjun Ma, Jing Sun, Xiaohui Shen, Minhua Zheng, Aiguo Lu
No abstract text is available yet for this article.
June 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28642092/chemokine-ccl17-is-expressed-by-dendritic-cells-in-the-cns-during-experimental-autoimmune-encephalomyelitis-and-promotes-pathogenesis-of-disease
#20
Christina Ruland, Hannes Renken, Ivan Kuzmanov, Arezoo Fattahi Mehr, Kathrin Schwarte, Manuela Cerina, Alexander Herrmann, David-Marian Otte, Andreas Zimmer, Nicholas Schwab, Sven G Meuth, Volker Arolt, Luisa Klotz, Irmgard Förster, Stefanie Scheu, Judith Alferink
The CC chemokine ligand 17 (CCL17) and its cognate CC chemokine receptor 4 (CCR4) are known to control leukocyte migration, maintenance of TH17 cells, and regulatory T cell (Treg) expansion in vivo. In this study we characterized the expression and functional role of CCL17 in the pathogenesis of experimental autoimmune encephalomyelitis (EAE). Using a CCL17/EGFP reporter mouse model, we could show that CCL17 expression in the CNS can be found in a subset of classical dendritic cells (DCs) that immigrate into the CNS during the effector phase of MOG-induced EAE...
June 19, 2017: Brain, Behavior, and Immunity
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