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https://www.readbyqxmd.com/read/29348885/drug-resistance-in-doxorubicin-resistant-fl5-12-hematopoietic-cells-elevated-mdr1-drug-efflux-and-side-population-positive-and-decreased-bcl2-family-member-expression
#1
Linda S Steelman, Steve L Abrams, Peter Ruvolo, Vivian Ruvolo, Lucio Cocco, Stefano Ratti, Alberto M Martelli, Luca M Neri, Saverio Candido, Massimo Libra, James A McCubrey
Chemotherapeutic drug treatment can result in the emergence of drug-resistant cells. By culturing an interleukin-3 (IL-3)-dependent cell line, FL5.12 cells in the presence of the chemotherapeutic drug doxorubicin, we isolated FL/Doxo cells which are multi-drug resistant. Increased levels of drug efflux were detected in FL/Doxo cells which could be inhibited by the MDR1 inhibitor verapamil but not by the MRP1 inhibitor MK571. The effects of TP53 and MEK1 were examined by infection of FL/Doxo cells with retroviruses encoding either a dominant negative TP-53 gene (FL/Doxo+ TP53 (DN) or a constitutively-activated MEK-1 gene (FL/Doxo + MEK1 (CA)...
December 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/29340061/analysis-of-the-mutational-landscape-of-classic-hodgkin-lymphoma-identifies-disease-heterogeneity-and-potential-therapeutic-targets
#2
Elena Mata, Antonio Díaz-López, Ana M Martín-Moreno, Margarita Sánchez-Beato, Ignacio Varela, María J Mestre, Carlos Santonja, Fernando Burgos, Javier Menárguez, Mónica Estévez, Mariano Provencio, Beatriz Sánchez-Espiridión, Eva Díaz, Carlos Montalbán, Miguel A Piris, Juan F García
Defining the mutational landscape of classic Hodgkin lymphoma is still a major research goal. New targeted next-generation sequencing (NGS) techniques may identify pathogenic mechanisms and new therapeutic opportunities related to this disease. We describe the mutational profile of a series of 57 cHL cases, enriched in Hodgkin and Reed-Sternberg (HRS) cells. Overall, the results confirm the presence of strong genomic heterogeneity. However, several variants were consistently detected in genes related to relevant signaling pathways, such as GM-CSF/IL-3, CBP/EP300, JAK/STAT, NF-kappaB, and numerous variants of genes affecting the B-cell receptor (BCR) pathway, such as BTK, CARD11, BCL10, among others...
December 19, 2017: Oncotarget
https://www.readbyqxmd.com/read/29296749/high-cd123-levels-enhance-proliferation-in-response-to-il-3-but-reduce-chemotaxis-by-downregulating-cxcr4-expression
#3
Nicole L Wittwer, Gabriela Brumatti, Ceilidh Marchant, Jarrod J Sandow, Melanie K Pudney, Mara Dottore, Richard J D'Andrea, Angel F Lopez, Paul G Ekert, Hayley S Ramshaw
High expression of the α chain of the interleukin-3 receptor (IL-3Rα; CD123) is a hallmark of acute myeloid leukemia (AML) leukemic stem cells (LSCs). Elevated CD123 expression is part of the diagnostic immunophenotyping of myeloid leukemia, and higher expression is associated with poor prognosis. However, the biological basis of the poorer prognosis is unclear, and may include heightened IL-3 signaling and non-cell autonomous interactions with the bone marrow (BM) microenvironment. We used TF-1 cells expressing different levels of CD123 and found elevated CD123 levels amplified the proliferative response to exogenous IL-3 and maintained viability in reducing IL-3 concentrations...
June 27, 2017: Blood Advances
https://www.readbyqxmd.com/read/29290262/gcc2-alk-as-a-targetable-fusion-in-lung-adenocarcinoma-and-its-enduring-clinical-responses-to-alk-inhibitors
#4
Junhong Jiang, Xue Wu, Xiaoling Tong, Wangzhi Wei, Anan Chen, Xiaonan Wang, Yang W Shao, Jianan Huang
OBJECTIVES: ALK, RET and ROS1 fusions have been identified as treatable targets in 5%-15% of non-small-cell lung cancers, and thanks to the advanced sequencing technologies, their new partner genes have been steadily detected. Here we identified a rare fusion of ALK (GCC2-ALK) in a patient with advanced lung adenocarcinoma and monitored the treatment efficacy of ALK inhibitors on this patient. We further performed in vitro functional studies of this fusion protein for evaluating its oncogenic potential...
January 2018: Lung Cancer: Journal of the International Association for the Study of Lung Cancer
https://www.readbyqxmd.com/read/29238040/il-3r-alpha-blockade-inhibits-tumor-endothelial-cell-derived-extracellular-vesicle-ev-mediated-vessel-formation-by-targeting-the-%C3%AE-catenin-pathway
#5
Giusy Lombardo, Maddalena Gili, Cristina Grange, Claudia Cavallari, Patrizia Dentelli, Gabriele Togliatto, Daniela Taverna, Giovanni Camussi, Maria Felice Brizzi
The proangiogenic cytokine Interleukin-3 (IL-3) is released by inflammatory cells in breast and ovarian cancer tissue microenvironments and also acts as an autocrine factor for human breast and kidney tumor-derived endothelial cells (TECs). We have previously shown that IL-3-treated endothelial cells (ECs) release extracellular vesicles (EVs), which serve as a paracrine mechanism for neighboring ECs, by transferring active molecules. The impact of an anti-IL-3R-alpha blocking antibody on the proangiogenic effect of EVs released from TECs (anti-IL-3R-EVs) has therefore been investigated in this study...
December 14, 2017: Oncogene
https://www.readbyqxmd.com/read/29203513/il-3-differentially-regulates-membrane-and-soluble-rankl-in-osteoblasts-through-metalloproteases-and-the-jak2-stat5-pathway-and-improves-the-rankl-opg-ratio-in-adult-mice
#6
Kanupriya Singh, Vikrant Piprode, Suhas T Mhaske, Amruta Barhanpukar-Naik, Mohan R Wani
Bone remodeling comprises balanced activities between osteoclasts and osteoblasts, which is regulated by various factors, including hormones and cytokines. We previously reported that IL-3 inhibits osteoclast differentiation and pathological bone loss. IL-3 also enhances osteoblast differentiation and bone formation from mesenchymal stem cells. However, the role of IL-3 in regulation of osteoblast-osteoclast interactions and underlying mechanisms is not yet delineated. In this study, we investigated the role of IL-3 on the regulation of osteoblast-specific molecules, receptor activator of NF-κB ligand (RANKL), and osteoprotegerin (OPG) that modulate bone homeostasis...
December 4, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/29172005/cytokine-profiling-of-serum-allows-monitoring-of-disease-progression-in-inclusion-body-myositis
#7
Umesh A Badrising, Roula Tsonaka, Monika Hiller, Erik H Niks, Teresinha Evangelista, Hanns Lochmüller, Jan Jgm Verschuuren, Annemieke Aartsma-Rus, Pietro Spitali
BACKGROUND: Inclusion body myositis is a late onset inflammatory myopathy lacking reliable serum biomarkers for diagnosis and for disease progression. OBJECTIVE: To identify diagnostic and predictive biomarkers, cytokine profiling is used to assess the potential of cytokines to discriminate between cases and controls and to assess whether treatment with methotrexate can influence biomarkers associated with disease progression. METHODS: The diagnostic and follow-up potential of 48 cytokines was tested using Bioplex-assay and ELISA in sera of healthy individuals, IBM patients and patients with other neuromuscular disorders...
2017: Journal of Neuromuscular Diseases
https://www.readbyqxmd.com/read/29156883/low-molecular-weight-supramolecular-ionogel-based-on-host-guest-interaction
#8
Aoli Wu, Fei Lu, Panpan Sun, Xuanxuan Qiao, Xinpei Gao, Li-Qiang Zheng
Supramolecular ionogels were prepared by self-assemble of small molecules through host-guest interaction between β-cyclodextrin (β-CD) and a room-temperature ionic liquid (IL) 3-(1-methyl-3-imidazolio)propanesulfonate - lithium bis(trifluoromethanesulfonyl)imide (MIPS-LiTFSI) which contains zwitterion MIPS. 19F NMR and 2D ROESY 1H NMR have been used to prove that only TFSI- is involved in the complexation. 1H NMR, FT-IR and comparative tests indicated that the electrostatic interaction between imidazole cation and TFSI- anion and intermolecular hydrogen bonding between three compounds also contribute to the formation of supramolecular ionogel...
November 20, 2017: Langmuir: the ACS Journal of Surfaces and Colloids
https://www.readbyqxmd.com/read/29126429/rna-sequencing-analysis-of-lung-primary-fibroblast-response-to-eosinophil-degranulation-products-predicts-downstream-effects-on-inflammation-tissue-remodeling-and-lipid-metabolism
#9
Stephane Esnault, Ksenija Bernau, Elizabeth E Torr, Yury A Bochkov, Nizar N Jarjour, Nathan Sandbo
BACKGROUND: The association of eosinophils with inflammation and tissue remodeling is at least partially due to their release of toxic granule proteins and other mediators, including cytokines. Tissue remodeling and consequent functional defects are affected by activity of connective tissue fibroblasts. Exaggerated fibroblast activation, accumulation and change of phenotype may lead to fibrosis and loss of tissue function. So far, little information has been reported on how eosinophils affect inflammation and tissue remodeling via the activation of fibroblasts...
November 10, 2017: Respiratory Research
https://www.readbyqxmd.com/read/29106601/flexible-fate-commitment-of-e2-2high-common-dc-progenitors-implies-tuning-in-tissue-microenvironments
#10
Nobuyuki Onai, Jumpei Asano, Rumiko Kurosaki-Nakamura, Shoko Kuroda, Toshiaki Ohteki
The basic helix-loop-helix transcription factor E2-2 is essential for the development of plasmacytoid dendritic cells (pDCs) but not conventional DCs (cDCs). Here, we generated E2-2 reporter mice and demonstrated that an E2-2high fraction among common DC progenitors (CDPs), which are a major source of pDCs and cDCs in the steady state, strictly gave rise to pDCs in the presence of Flt3 ligand ex vivo or in the secondary lymphoid organs when transferred in vivo. However, in the small intestine, some of these E2-2high progenitors differentiated into cDCs that produced retinoic acid...
November 2, 2017: International Immunology
https://www.readbyqxmd.com/read/29100331/targeting-signaling-and-apoptotic-pathways-involved-in-chemotherapeutic-drug-resistance-of-hematopoietic-cells
#11
Stephen L Abrams, Peter P Ruvolo, Vivian R Ruvolo, Giovanni Ligresti, Alberto M Martelli, Lucio Cocco, Stefano Ratti, Agostino Tafuri, Linda S Steelman, Saverio Candido, Massimo Libra, James A McCubrey
A critical problem in leukemia as well as other cancer therapies is the development of chemotherapeutic drug-resistance. We have developed models of hematopoietic drug resistance that are based on expression of dominant-negative TP53 [TP53 (DN)] or constitutively-active MEK1 [MEK1(CA)] oncogenes in the presence of chemotherapeutic drugs. In human cancer, functional TP53 activity is often lost in human cancers. Also, activation of the Raf/MEK/ERK pathway frequently occurs due to mutations/amplification of upstream components of this and other interacting pathways...
September 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/29068539/eosinophil-persistence-in-vivo-and-sustained-viability-ex-vivo-in-response-to-respiratory-challenge-with-fungal-allergens
#12
Wendy E Geslewitz, Caroline M Percopo, Helene F Rosenberg
BACKGROUND: Eosinophils are immunomodulatory leukocytes that contribute to the pathogenesis of Th2 driven asthma and allergic lung diseases. OBJECTIVE: Our goal was to identify unique properties of eosinophils recruited to the lungs and airways of mice in response to challenge with asthma-associated fungal allergens. METHODS: Mice were challenged intranasally on days 0, 3 and 6 with a filtrate of Alternaria alternata. Recruited eosinophils were enumerated in bronchoalveolar lavage fluid...
October 25, 2017: Clinical and Experimental Allergy: Journal of the British Society for Allergy and Clinical Immunology
https://www.readbyqxmd.com/read/29023488/transgenic-expression-of-human-cytokines-in-immunodeficient-mice-does-not-facilitate-myeloid-expansion-of-bcr-abl1-transduced-human-cord-blood-cells
#13
Maria Askmyr, Sofia von Palffy, Nils Hansen, Niklas Landberg, Carl Högberg, Marianne Rissler, Helena Ågerstam, Thoas Fioretos
Several attempts have been made to model chronic myeloid leukemia (CML) in a xenograft setting but expansion of human myeloid cells in immunodeficient mice has proven difficult to achieve. Lack of cross-reacting cytokines in the microenvironment of the mice has been proposed as a potential reason. In this study we have used NOD/SCID IL2-receptor gamma deficient mice expressing human SCF, IL-3 and GM-CSF (NSGS mice), that should be superior in supporting human, and particularly, myeloid cell engraftment, to expand BCR-ABL1 expressing human cells in order to model CML...
2017: PloS One
https://www.readbyqxmd.com/read/29016427/comparison-of-intended-lengthening-of-magnetically-controlled-growing-rods-ultrasound-versus-x-ray
#14
Mutlu Cobanoglu, Suken A Shah, Peter Gabos, Kenneth Rogers, Petya Yorgova, Geraldine Neiss, Leslie Grissom, William G Mackenzie
BACKGROUND: In the treatment of early onset scoliosis (EOS), there has been a trend to use magnetically controlled growing rods (MCGR) in order to reduce the number of surgeries. To confirm the amount of lengthening, spine radiographs were required. Recently, ultrasound (US) has been added to monitor lengthening of MCGR to avoid radiation exposure. Our aim was to determine whether US is as accurate as plain radiography (x-ray) in determining the amount of length achieved at individual MCGR lengthening episodes...
October 9, 2017: Journal of Pediatric Orthopedics
https://www.readbyqxmd.com/read/28987803/long-acting-%C3%AE-2-adrenoreceptor-agonists-suppress-type-1-interferon-expression-in-human-plasmacytoid-dendritic-cells-via-epigenetic-regulation
#15
Chang-Hung Kuo, San-Nan Yang, Yi-Giien Tsai, Chong-Chao Hsieh, Wei-Ting Liao, Li-Chen Chen, Min-Sheng Lee, Hsuan-Fu Kuo, Ching-Hsiung Lin, Chih-Hsing Hung
The combination of inhaled long-acting β2-adrenoreceptor (LABA) and inhaled glucocorticoid (ICS) is a major therapy for asthma. However, the increased risk of infection is still a concern. Plasmacytoid dendritic cells (pDCs) are the predominant cells producing type 1 interferon (IFN) against infection. The effect of LABA/ICS on type 1 IFN expression in human pDCs is unknown. Circulating pDCs were isolated from healthy human subjects and were pretreated with glucocorticoid (GCS), LABA or a cAMP analog, and were stimulated with Toll-like receptor (TLR) agonist CpG (TLR9) or imiquimod (TLR7) in the presence of IL-3...
October 4, 2017: Pulmonary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28971096/protein-translation-and-signaling-in-human-eosinophils
#16
REVIEW
Stephane Esnault, Zhong-Jian Shen, James S Malter
We have recently reported that, unlike IL-5 and GM-CSF, IL-3 induces increased translation of a subset of mRNAs. In addition, we have demonstrated that Pin1 controls the activity of mRNA binding proteins, leading to enhanced mRNA stability, GM-CSF protein production and prolonged eosinophil (EOS) survival. In this review, discussion will include an overview of cap-dependent protein translation and its regulation by intracellular signaling pathways. We will address the more general process of mRNA post-transcriptional regulation, especially regarding mRNA binding proteins, which are critical effectors of protein translation...
2017: Frontiers in Medicine
https://www.readbyqxmd.com/read/28965767/jak1-integrates-cytokine-sensing-to-regulate-hematopoietic-stem-cell-function-and-stress-hematopoiesis
#17
Maria Kleppe, Matthew H Spitzer, Sheng Li, Corinne E Hill, Lauren Dong, Efthymia Papalexi, Sofie De Groote, Robert L Bowman, Matthew Keller, Priya Koppikar, Franck T Rapaport, Julie Teruya-Feldstein, Jorge Gandara, Christopher E Mason, Garry P Nolan, Ross L Levine
JAK1 is a critical effector of pro-inflammatory cytokine signaling and plays important roles in immune function, while abnormal JAK1 activity has been linked to immunological and neoplastic diseases. Specific functions of JAK1 in the context of hematopoiesis, and specifically within hematopoietic stem cells (HSCs), have not clearly been delineated. Here, we show that conditional Jak1 loss in HSCs reduces their self-renewal and markedly alters lymphoid/myeloid differentiation in vivo. Jak1-deficient HSCs exhibit decreased competitiveness in vivo and are unable to rescue hematopoiesis in the setting of myelosuppression...
October 5, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28947270/a-novel-in-vivo-model-for-predicting-myelotoxicity-of-chemotherapeutic-agents-using-il-3-gm-csf-transgenic-humanized-mice
#18
R Ito, D Nagai, N Igo, Y Okuda, K Sekine, E Ichimura, I Katano, T Mizushima, M Goto, Y Ohnishi, M Ito, K Okamoto
Evaluating myelotoxicity is essential for ensuring the safety of novel drugs before they are approved for clinical applications. Although in vivo prediction of the maximum tolerated doses (MTDs) of anticancer drugs is usually performed in rodents, the results are not always applicable to clinical treatment because drugs may have different effects in human and rodent cells. Previously, we generated a human IL-3 and GM-CSF transgenic humanized mouse (hu-IL-3/GM Tg), in which human granulocytes effectively differentiated after hematopoietic stem cell transplantation...
November 5, 2017: Toxicology Letters
https://www.readbyqxmd.com/read/28944512/comprehensive-evaluation-of-decellularized-porcine-corneal-after-clinical-transplantation
#19
Yan Shi, Timur Bikkuzin, Zhen Song, Xin Jin, Hao Jin, Xinlei Li, Hong Zhang
Corneal disease is the second most common blinding disease in the world. The shortage of cornea donors has become the greatest challenge in curing corneal disease. Decellularized porcine corneas have the potential to be clinically applied as a substitute for human cornea in lamellar keratoplasty. Porcine corneas will help relieve the cornea donor shortage. To comprehensively evaluate the characteristics of the grafts and the effect of the decellularized porcine cornea on the host cornea after clinical transplantation, we assessed the microstructure of the transplanted decellularized porcine corneal tissues...
September 24, 2017: Xenotransplantation
https://www.readbyqxmd.com/read/28934227/hemorrhage-enhances-cytokine-complement-component-3-and-caspase-3-and-regulates-micrornas-associated-with-intestinal-damage-after-whole-body-gamma-irradiation-in-combined-injury
#20
Juliann G Kiang, Joan T Smith, Marsha N Anderson, Thomas B Elliott, Paridhi Gupta, Nagaraja S Balakathiresan, Radha K Maheshwari, Barbara Knollmann-Ritschel
Hemorrhage following whole-body γ-irradiation in a combined injury (CI) model increases mortality compared to whole-body γ-irradiation alone (RI). The decreased survival in CI is accompanied by increased bone marrow injury, decreased hematocrit, and alterations of miRNA in the kidney. In this study, our aim was to examine cytokine homeostasis, susceptibility to systemic bacterial infection, and intestinal injury. More specifically, we evaluated the interleukin-6 (IL-6)-induced stress proteins including C-reactive protein (CRP), complement 3 (C3), Flt-3 ligand, and corticosterone...
2017: PloS One
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