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https://www.readbyqxmd.com/read/28732312/drug-eluting-scaffold-inhibited-in-vivo-pancreatic-tumorigenesis-by-engaging-murine-ccr4-cd8-t-cells
#1
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
#2
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
#3
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
#4
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
#5
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
#6
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
#7
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
#8
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...
July 3, 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
#9
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
#10
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
#11
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
https://www.readbyqxmd.com/read/28640357/rna-sequencing-of-esophageal-adenocarcinomas-identifies-novel-fusion-transcripts-including-npc1-melk-arising-from-a-complex-chromosomal-rearrangement
#12
Zhixiong Wang, Yulan Cheng, John M Abraham, Rong Yan, Xi Liu, Wei Chen, Sariat Ibrahim, Gary P Schroth, Xiquan Ke, Yulong He, Stephen J Meltzer
BACKGROUND: Studies of chromosomal rearrangements and fusion transcripts have elucidated mechanisms of tumorigenesis and led to targeted cancer therapies. This study was aimed at identifying novel fusion transcripts in esophageal adenocarcinoma (EAC). METHODS: To identify new fusion transcripts associated with EAC, targeted RNA sequencing and polymerase chain reaction (PCR) verification were performed in 40 EACs and matched nonmalignant specimens from the same patients...
June 22, 2017: Cancer
https://www.readbyqxmd.com/read/28638728/gene-expression-analysis-in-cutaneous-t-cell-lymphomas-ctcl-highlights-disease-heterogeneity-and-potential-diagnostic-and-prognostic-indicators
#13
Ivan V Litvinov, Michael T Tetzlaff, Philippe Thibault, Pamela Gangar, Linda Moreau, Andrew K Watters, Elena Netchiporouk, Kevin Pehr, Victor G Prieto, Elham Rahme, Nathalie Provost, Martin Gilbert, Denis Sasseville, Madeleine Duvic
Cutaneous T-Cell Lymphomas (CTCL) are rare, but potentially devastating malignancies, whose pathogenesis remains poorly elucidated. Unfortunately, currently it is not possible to predict based on the available criteria in which patients the cancer will progress and which patients will experience an indolent disease course. Furthermore, at early stages this malignancy often masquerades as psoriasis, chronic eczema or other benign inflammatory dermatoses. As a result, it takes on average 6 y to diagnose this lymphoma since its initial presentation...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28628559/the-mir-1206-microrna-variant-is-associated-with-methotrexate-induced-oral-mucositis-in-pediatric-acute-lymphoblastic-leukemia
#14
Angela Gutierrez-Camino, Natanja Oosterom, Marissa A H den Hoed, Elixabet Lopez-Lopez, Idoia Martin-Guerrero, Saskia M F Pluijm, Rob Pieters, Robert de Jonge, Wim J E Tissing, Sandra G Heil, Africa García-Orad, Marry M van den Heuvel-Eibrink
Five-year survival rates of pediatric acute lymphoblastic leukemia (ALL) have reached 90% in the developed countries. However, toxicity because of methotrexate (MTX) occurs frequently. Variety in the occurrence of toxicity is partly determined by single nucleotide polymorphisms (SNPs) in coding regions. Recently, five SNPs in non-coding pre-microRNAs and microRNA processing (miRNA) genes were identified in association with MTX-induced oral mucositis. This study aimed to replicate the association of these miRNA variants in relation to MTX-induced oral mucositis in a prospective childhood ALL cohort...
June 16, 2017: Pharmacogenetics and Genomics
https://www.readbyqxmd.com/read/28627735/genetic-alterations-in-adult-t-cell-leukemia-lymphoma
#15
REVIEW
Yasunori Kogure, Keisuke Kataoka
Adult T-cell leukemia/lymphoma (ATL) is a peripheral T-cell neoplasm with a dismal prognosis, caused by human T-cell leukemia virus type-1 (HTLV-1) retrovirus. A long latency period from HTLV-1 infection to ATL onset suggests that not only HTLV-1 proteins, such as Tax and HBZ, but also additional genetic and/or epigenetic events are required for ATL development. Although many studies have demonstrated the biological functions of viral genes, alterations of cellular genes associated with ATL have not been fully investigated...
June 19, 2017: Cancer Science
https://www.readbyqxmd.com/read/28624538/analysis-of-mrna-deadenylation-by-multi-protein-complexes
#16
Michael W Webster, James A W Stowell, Terence T L Tang, Lori A Passmore
Poly(A) tails are found at the 3' end of almost every eukaryotic mRNA and are important for the stability of mRNAs and their translation into proteins. Thus, removal of the poly(A) tail, a process called deadenylation, is critical for regulation of gene expression. Most deadenylation enzymes are components of large multi-protein complexes. Here, we describe an in vitro deadenylation assay developed to study the exonucleolytic activities of the multi-protein Ccr4-Not and Pan2-Pan3 complexes. We discuss how this assay can be used with short synthetic RNAs, as well as longer RNA substrates generated using in vitro transcription...
June 13, 2017: Methods: a Companion to Methods in Enzymology
https://www.readbyqxmd.com/read/28619088/chemokine-signals-are-crucial-for-enhanced-homing-and-differentiation-of-circulating-osteoclast-progenitor-cells
#17
Alan Sucur, Zrinka Jajic, Marinko Artukovic, Marina Ikic Matijasevic, Branimir Anic, Darja Flegar, Antonio Markotic, Tomislav Kelava, Sanja Ivcevic, Natasa Kovacic, Vedran Katavic, Danka Grcevic
BACKGROUND: The peripheral blood (PB) monocyte pool contains osteoclast progenitors (OCPs), which contribute to osteoresorption in inflammatory arthritides and are influenced by the cytokine and chemokine milieu. We aimed to define the importance of chemokine signals for migration and activation of OCPs in rheumatoid arthritis (RA) and psoriatic arthritis (PsA). METHODS: PB and, when applicable, synovial fluid (SF) samples were collected from 129 patients with RA, 53 patients with PsA, and 110 control patients in parallel to clinical parameters of disease activity, autoantibody levels, and applied therapy...
June 15, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28615693/the-ccr4-not-complex-contributes-to-repression-of-major-histocompatibility-complex-class-ii-transcription
#18
Alfonso Rodríguez-Gil, Olesja Ritter, Vera V Saul, Jochen Wilhelm, Chen-Yuan Yang, Rudolf Grosschedl, Yumiko Imai, Keiji Kuba, Michael Kracht, M Lienhard Schmitz
The multi-subunit CCR4 (carbon catabolite repressor 4)-NOT (Negative on TATA) complex serves as a central coordinator of all different steps of eukaryotic gene expression. Here we performed a systematic and comparative analysis of cells where the CCR4-NOT subunits CNOT1, CNOT2 or CNOT3 were individually downregulated using doxycycline-inducible shRNAs. Microarray experiments showed that downregulation of either CNOT subunit resulted in elevated expression of major histocompatibility complex class II (MHC II) genes which are found in a gene cluster on chromosome 6...
June 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28615072/chemokine-receptor-co-expression-reveals-aberrantly-distributed-th-effector-memory-cells-in-gpa-patients
#19
Lucas L Lintermans, Abraham Rutgers, Coen A Stegeman, Peter Heeringa, Wayel H Abdulahad
BACKGROUND: Persistent expansion of circulating CD4(+) effector memory T cells (TEM) in patients with granulomatosis with polyangiitis (GPA) suggests their fundamental role in disease pathogenesis. Recent studies have shown that distinct functional CD4(+) TEM cell subsets can be identified based on expression patterns of chemokine receptors. The current study aimed to determine different CD4(+) TEM cell subsets based on chemokine receptor expression in peripheral blood of GPA patients...
June 14, 2017: Arthritis Research & Therapy
https://www.readbyqxmd.com/read/28597329/safety-and-efficacy-of-mogamulizumab-in-patients-with-adult-t-cell-leukemia-lymphoma-in-japan-interim-results-of-postmarketing-all-case-surveillance
#20
Kenji Ishitsuka, Satoshi Yurimoto, Kouichi Kawamura, Yukie Tsuji, Manabu Iwabuchi, Takeshi Takahashi, Kensei Tobinai
We present the interim results of a postmarketing all-case surveillance study in patients with C-C chemokine receptor 4 (CCR4)-positive, relapsed or refractory adult T-cell leukemia-lymphoma (ATL) treated with the anti-CCR4 monoclonal antibody mogamulizumab since its 2012 launch in Japan. The safety and efficacy analysis populations comprised 484 and 442 patients, respectively. The ATL subtype was acute in 58.9% and lymphoma in 34.2% of patients. All patients were scheduled to receive intravenous infusions of mogamulizumab (1...
June 9, 2017: International Journal of Hematology
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