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https://www.readbyqxmd.com/read/29223442/exosomes-derived-from-imatinib-resistant-chronic-myeloid-leukemia-cells-mediate-a-horizontal-transfer-of-drug-resistant-trait-by-delivering-mir-365
#1
Qing-Hua Min, Xiao-Zhong Wang, Jing Zhang, Qing-Gen Chen, Shu-Qi Li, Xiao-Qing Liu, Jing Li, Jing Liu, Wei-Ming Yang, Yu-Huan Jiang, Yan-Mei Xu, Jin Lin, Qiu-Fang Gao, Fan Sun, Lei Zhang, Bo Huang
Chronic myeloid leukemia (CML) is a malignant disorder of hematopoietic stem/progenitor cells. Majority of patients can be effectively treated with tyrosine kinase inhibitors (TKIs) such as imatinib, but a portion of patients will develop drug resistance. Accumulated evidences have identified exosomes in cancer as promoters of tumor progression. Herein, we found that exosomes derived from imatinib resistant CML cells can be internalized into sensitive CML cells and confer drug-resistance traits. We also demonstrated a significant higher level of miR-365 in exosomes derived from drug-resistant CML cells compared with those from sensitive ones using microarray and qRT-PCR...
December 6, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/29130994/enhancement-of-anti-leukemia-immunity-by-leukemia-derived-exosomes-via-downregulation-of-tgf-%C3%AE-1-expression
#2
Fang Huang, Jiangbo Wan, Weiwei Hu, Siguo Hao
BACKGROUND/AIMS: Minimal residual leukemia cells (MRLs) are difficult to eradicate through traditional treatment and therefore remain to be a major threat to the long-term survival of leukemia patients. Tumor-derived exosomes (TEXs), which carry tumor associated antigens (TAA), may be a potential cell-free tumor vaccine for the specific eradication of MRLs. However, TEXs are intended to be less immunogenic due to exosomal TGF-β1. To further optimize the efficacy of TEX-based vaccines, we investigated whether exosomes from TGF-β1 silenced leukemia cells (LEXTGF-β1si) had an increased potential to induce a specific antitumor effect compared with non-modified exosomes...
November 9, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29099772/role-of-lfa-1-and-icam-1-in-cancer
#3
REVIEW
Manuel Reina, Enric Espel
The lymphocyte function-associated antigen-1 (LFA-1) (also known as CD11a/CD18 and αLβ₂), is just one of many integrins in the human body, but its significance is derived from its exclusive presence in leukocytes. In this review, we summarize the studies relating LFA-1 and its major ligand ICAM-1 (or CD54) with cancer, through the function of lymphocytes and myeloid cells on tumor cells. We consider how LFA-1 mediates the interaction of leukocytes with tumors and the role of ICAM-1 in tumor dynamics, which can be independent of its interaction with LFA-1...
November 3, 2017: Cancers
https://www.readbyqxmd.com/read/29089618/circulating-exosomes-carrying-an-immunosuppressive-cargo-interfere-with-cellular-immunotherapy-in-acute-myeloid-leukemia
#4
Chang-Sook Hong, Priyanka Sharma, Saigopalakrishna S Yerneni, Patricia Simms, Edwin K Jackson, Theresa L Whiteside, Michael Boyiadzis
Exosomes, small (30-150 nm) extracellular vesicles (EVs) isolated from plasma of patients with acute myeloid leukemia (AML) carry leukemia-associated antigens and multiple inhibitory molecules. Circulating exosomes can deliver suppressive cargos to immune recipient cells, inhibiting anti-tumor activities. Pre-therapy plasma of refractory/relapsed AML patients contains elevated levels of immunosuppressive exosomes which interfere with anti-leukemia functions of activated immune cells. We show that exosomes isolated from pre-therapy plasma of the AML patients receiving adoptive NK-92 cell therapy block anti-leukemia cytotoxicity of NK-92 cells and other NK-92 cell functions...
October 31, 2017: Scientific Reports
https://www.readbyqxmd.com/read/29080983/autoimmune-responses-to-exosomes-and-candidate-antigens-contribute-to-type-1-diabetes-in-non-obese-diabetic-mice
#5
REVIEW
Yang D Dai, Huiming Sheng, Peter Dias, M Jubayer Rahman, Roman Bashratyan, Danielle Regn, Kristi Marquardt
PURPOSE OF REVIEW: The initial autoimmune trigger of type 1 diabetes (T1D) remains unclear. In non-obese diabetic (NOD) mice, islet inflammation starts early in life, suggesting the presence of an endogenous trigger for the spontaneous autoimmune response in this T1D mouse model. In this review, we argue that abnormal release of exosomes might be the trigger of the early inflammatory and autoimmune responses in the islets. RECENT FINDINGS: Exosomes are nano-sized membrane complexes that are secreted by cells following fusion of late endosomes and/or multivesicular bodies with the plasma membrane...
October 28, 2017: Current Diabetes Reports
https://www.readbyqxmd.com/read/28918518/micro-rna-profiling-of-exosomes-from-marrow-derived-mesenchymal-stromal-cells-in-patients-with-acute-myeloid-leukemia-implications-in-leukemogenesis
#6
Juliana Barrera-Ramirez, Jessie R Lavoie, Harinad B Maganti, William L Stanford, Caryn Ito, Mitchell Sabloff, Marjorie Brand, Michael Rosu-Myles, Yevgeniya Le, David S Allan
Gene regulatory networks in AML may be influenced by microRNAs (miRs) contained in exosomes derived from bone marrow mesenchymal stromal cells (MSCs). We sequenced miRs from exosomes isolated from marrow-derived MSCs from patients with AML (n = 3) and from healthy controls (n = 3; not age-matched). Known targets of mIRs that were significantly different in AML-derived MSC exosomes compared to controls were identified. Of the five candidate miRs identified by differential packaging in exosomes, only miR-26a-5p and miR-101-3p were significantly increased in AML-derived samples while miR-23b-5p, miR-339-3p and miR-425-5p were significantly decreased...
September 16, 2017: Stem Cell Reviews
https://www.readbyqxmd.com/read/28816238/acute-myeloid-leukemia-transforms-the-bone-marrow-niche-into-a-leukemia-permissive-microenvironment-through-exosome-secretion
#7
B Kumar, M Garcia, L Weng, X Jung, J L Murakami, X Hu, T McDonald, A Lin, A R Kumar, D L DiGiusto, A S Stein, V A Pullarkat, S K Hui, N Carlesso, Y-H Kuo, R Bhatia, G Marcucci, C-C Chen
Little is known about how leukemia cells alter the bone marrow (BM) niche to facilitate their own growth and evade chemotherapy. Here, we provide evidence that acute myeloid leukemia (AML) blasts remodel the BM niche into a leukemia growth-permissive and normal hematopoiesis-suppressive microenvironment through exosome secretion. Either engrafted AML cells or AML-derived exosomes increased mesenchymal stromal progenitors and blocked osteolineage development and bone formation in vivo. Preconditioning with AML-derived exosomes 'primed' the animals for accelerated AML growth...
August 17, 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28776566/response-commentary-exosomes-vs-microvesicles-in-hematological-malignancies
#8
T L Whiteside, M Boyiadzis
No abstract text is available yet for this article.
October 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28775118/chronic-lymphocytic-leukemia-cells-are-active-participants-in-microenvironmental-cross-talk
#9
REVIEW
Martijn Ha van Attekum, Eric Eldering, Arnon P Kater
The importance of the tumor microenvironment in chronic lymphocytic leukemia is widely accepted. Nevertheless, the understanding of the complex interplay between the various types of bystander cells and chronic lymphocytic leukemia cells is incomplete. Numerous studies have indicated that bystander cells provide chronic lymphocytic leukemia-supportive functions, but it has also become clear that chronic lymphocytic leukemia cells actively engage in the formation of a supportive tumor microenvironment through several cross-talk mechanisms...
September 2017: Haematologica
https://www.readbyqxmd.com/read/28754746/tumor-derived-exosomes-modulate-pd-l1-expression-in-monocytes
#10
Franziska Haderk, Ralph Schulz, Murat Iskar, Laura Llaó Cid, Thomas Worst, Karolin V Willmund, Angela Schulz, Uwe Warnken, Jana Seiler, Axel Benner, Michelle Nessling, Thorsten Zenz, Maria Göbel, Jan Dürig, Sven Diederichs, Jérôme Paggetti, Etienne Moussay, Stephan Stilgenbauer, Marc Zapatka, Peter Lichter, Martina Seiffert
In chronic lymphocytic leukemia (CLL), monocytes and macrophages are skewed toward protumorigenic phenotypes, including the release of tumor-supportive cytokines and the expression of immunosuppressive molecules such as programmed cell death 1 ligand 1 (PD-L1). To understand the mechanism driving protumorigenic skewing in CLL, we evaluated the role of tumor cell-derived exosomes in the cross-talk with monocytes. We carried out RNA sequencing and proteome analyses of CLL-derived exosomes and identified noncoding Y RNA hY4 as a highly abundant RNA species that is enriched in exosomes from plasma of CLL patients compared with healthy donor samples...
July 28, 2017: Science Immunology
https://www.readbyqxmd.com/read/28656959/do-we-need-to-distinguish-exosomes-from-microvesicles-in-hematological-malignancies
#11
A Caivano, L Del Vecchio, P Musto
No abstract text is available yet for this article.
September 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28601924/tgf-%C3%AE-1-silenced-leukemia-cell-derived-exosomes-target-dendritic-cells-to-induce-potent-anti-leukemic-immunity-in-a-mouse-model
#12
Fang Huang, Jiangbo Wan, Siguo Hao, Xiaohui Deng, Linjun Chen, Liyuan Ma
Tumor-derived exosomes (TEX) can induce a specific antitumor immune response and have been developed as a promising tumor vaccine. Despite promising preclinical data, TEX exhibit relatively low efficacy and limited clinical benefit in clinical trials. In the present study, we investigated whether exosomes from the TGF-β1 silenced L1210 cells (LEXTGF-β1si) can enhance the efficacy of DC-based vaccines. We silenced TGF-β1 in L1210 cells with a lentiviral shRNA vector and prepared the LEXTGF-β1si. It was shown that LEXTGF-β1si can significantly decrease TGF-β1 expression of dendritic cells (DC) and effectively promote their maturation and immune function...
June 10, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28596424/s100-a9-protein-in-exosomes-from-chronic-lymphocytic-leukemia-cells-promotes-nf-%C3%AE%C2%BAb-activity-during-disease-progression
#13
Daniel Prieto, Natalia Sotelo, Noé Seija, Sandra Sernbo, Cecilia Abreu, Rosario Durán, Magdalena Gil, Estefanía Sicco, Victoria Irigoin, Carolina Oliver, Ana Inés Landoni, Raúl Gabus, Guillermo Dighiero, Pablo Oppezzo
Chronic lymphocytic leukemia (CLL) is an incurable disease characterized by accumulation of clonal B lymphocytes, resulting from a complex balance between cell proliferation and apoptotic death. Continuous crosstalk between cancer cells and local/distant host environment is required for effective tumor growth. Among the main actors of this dynamic interplay between tumoral cells and their microenvironment are the nano-sized vesicles called exosomes. Emerging evidence indicates that secretion, composition, and functional capacity of exosomes are altered as tumors progress to an aggressive phenotype...
August 10, 2017: Blood
https://www.readbyqxmd.com/read/28596280/extracellular-vesicles-of-bone-marrow-stromal-cells-rescue-chronic-lymphocytic-leukemia-b-cells-from-apoptosis-enhance-their-migration-and-induce-gene-expression-modifications
#14
Emerence Crompot, Michael Van Damme, Karlien Pieters, Marjorie Vermeersch, David Perez-Morga, Philippe Mineur, Marie Maerevoet, Nathalie Meuleman, Dominique Bron, Laurence Lagneaux, Basile Stamatopoulos
Interactions between chronic lymphocytic leukemia (CLL) B cells and the bone marrow (BM) microenvironment play a major function in the physiopathology of CLL. Extracellular vesicles (EVs), which are composed of exosomes and microparticles, play an important role in cell communication. However, little is known about their role in CLL / microenvironment interactions. In the present study, EVs purified by ultracentrifugation from BM mesenchymal stromal cell (BM-MSC) cultures were added to CLL B cells. After their integration into CLL B cells, we observed a decrease of leukemic cell spontaneous apoptosis and an increase in their chemoresistance to several drugs, including fludarabine, ibrutinib, idelalisib and venetoclax after 24 hours...
September 2017: Haematologica
https://www.readbyqxmd.com/read/28545761/ultrastructural-analysis-of-human-leukemia-u-937-cells-after-apoptosis-induction-localization-of-proteasomes-and-perichromatin-fibers
#15
Ekaterina S Snigirevskaya, Yan Yu Komissarchik
We studied the ultrastructure of human histiocytic lymphoma U-937cells after apoptosis induction with two external agents, hypertonic shock and etoposide. Appearance of aggregates of particles of nuclear origin within the nuclei and cytoplasm of the induced cells was the first and the most prominent morphological sign of apoptosis. These aggregates were not coated by a membrane, had variable shape, density and size. Two types of particles dominated in the aggregates: perichromatin fibers (PFs) and proteasomes (PRs)...
May 22, 2017: Acta Histochemica
https://www.readbyqxmd.com/read/28435469/interleukin-3-receptor-targeted-exosomes-inhibit-in-vitro-and-in-vivo-chronic-myelogenous-leukemia-cell-growth
#16
Daniele Bellavia, Stefania Raimondo, Giovanna Calabrese, Stefano Forte, Marta Cristaldi, Agostina Patinella, Lorenzo Memeo, Mauro Manno, Samuele Raccosta, Patrizia Diana, Girolamo Cirrincione, Gianluca Giavaresi, Francesca Monteleone, Simona Fontana, Giacomo De Leo, Riccardo Alessandro
Despite Imatinib (IM), a selective inhibitor of Bcr-Abl, having led to improved prognosis in Chronic Myeloid Leukemia (CML) patients, acquired resistance and long-term adverse effects is still being encountered. There is, therefore, urgent need to develop alternative strategies to overcome drug resistance. According to the molecules expressed on their surface, exosomes can target specific cells. Exosomes can also be loaded with a variety of molecules, thereby acting as a vehicle for the delivery of therapeutic agents...
2017: Theranostics
https://www.readbyqxmd.com/read/28321122/the-emerging-roles-of-tumor-derived-exosomes-in-hematological-malignancies
#17
REVIEW
M Boyiadzis, T L Whiteside
Exosomes are small (30-150 nm) membranous vesicles of endocytic origin produced by all cells under physiological and pathological conditions. They have recently emerged as vehicles for intercellular transfer of molecular and genetic contents from parent to recipient cells. Exosome-mediated transfer of proteins or genes (RNA, miRNA, DNA) results in reprogramming of recipient cell functions. Exosomes carry and deliver information that is essential for health, and they participate in pathological events, including malignant transformation...
June 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28245982/comparative-analysis-of-microrna-and-mrna-expression-profiles-in-cells-and-exosomes-under-toluene-exposure
#18
Jung-Hee Lim, Mi-Kyung Song, Yoon Cho, Woong Kim, Sung Ok Han, Jae-Chun Ryu
Recent studies have illustrated the growing importance of exosomes (small extracellular vesicles) and their constituent microRNAs (miRNAs) in the fields of toxicology and pathology. The mechanism of toxicity of toluene, a highly-prevalent and volatile organic compound, is largely unknown. To examine the role of miRNAs in toluene-induced toxicity, we investigated miRNAs and toluene-induced gene expression in HL-60 human promyelocytic leukemia cells and exosomes using microarrays. A total of 54 miRNAs were differentially expressed in HL-60 cell lines exposed to toluene and exosomes from the cells...
February 27, 2017: Toxicology in Vitro: An International Journal Published in Association with BIBRA
https://www.readbyqxmd.com/read/28213497/mitochondrial-damage-elicits-a-tcdd-inducible-poly-adp-ribose-polymerase-mediated-antiviral-response
#19
Tatsuya Kozaki, Jun Komano, Daiki Kanbayashi, Michihiro Takahama, Takuma Misawa, Takashi Satoh, Osamu Takeuchi, Taro Kawai, Shigeomi Shimizu, Yoshiharu Matsuura, Shizuo Akira, Tatsuya Saitoh
The innate immune system senses RNA viruses by pattern recognition receptors (PRRs) and protects the host from virus infection. PRRs mediate the production of immune modulatory factors and direct the elimination of RNA viruses. Here, we show a unique PRR that mediates antiviral response. Tetrachlorodibenzo-p-dioxin (TCDD)-inducible poly(ADP ribose) polymerase (TIPARP), a Cysteine3 Histidine (CCCH)-type zinc finger-containing protein, binds to Sindbis virus (SINV) RNA via its zinc finger domain and recruits an exosome to induce viral RNA degradation...
March 7, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28008175/cll-cell-mediated-mdsc-induction-by-exosomal-mir-155-transfer-is-disrupted-by-vitamin-d
#20
H Bruns, M Böttcher, M Qorraj, M Fabri, S Jitschin, J Dindorf, L Busch, R Jitschin, A Mackensen, D Mougiakakos
No abstract text is available yet for this article.
April 2017: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
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