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https://www.readbyqxmd.com/read/28723646/collagen-type-1-promotes-survival-of-human-breast-cancer-cells-by-overexpressing-kv10-1-potassium-and-orai1-calcium-channels-through-ddr1-dependent-pathway
#1
Mehdi Badaoui, Cloé Mimsy-Julienne, Charles Saby, Laurence Van Gulick, Marta Peretti, Pierre Jeannesson, Hamid Morjani, Halima Ouadid-Ahidouch
Collagen type 1 is among the tumor microenvironment (TM) factors, that regulates proliferation, survival, migration and invasion. Ion channels are key players in interactions between tumor cells and TM. Kv10.1 has been shown to play an essential role in breast cancer cell proliferation and migration by permitting Ca2+ influx notably via Orai1. Here, we show that human breast cancer (BC) cells growing, in culture media completely devoid of the serum and seeded on collagen 1 coating, exhibited less apoptotic rate and a decrease in Bax expression when compared to those grown on plastic...
July 7, 2017: Oncotarget
https://www.readbyqxmd.com/read/28723562/integrative-genomics-identifies-the-molecular-basis-of-resistance-to-azacitidine-therapy-in-myelodysplastic-syndromes
#2
Ashwin Unnikrishnan, Elli Papaemmanuil, Dominik Beck, Nandan P Deshpande, Arjun Verma, Ashu Kumari, Petter S Woll, Laura A Richards, Kathy Knezevic, Vashe Chandrakanthan, Julie A I Thoms, Melinda L Tursky, Yizhou Huang, Zara Ali, Jake Olivier, Sally Galbraith, Austin G Kulasekararaj, Magnus Tobiasson, Mohsen Karimi, Andrea Pellagatti, Susan R Wilson, Robert Lindeman, Boris Young, Raj Ramakrishna, Christopher Arthur, Richard Stark, Philip Crispin, Jennifer Curnow, Pauline Warburton, Fernando Roncolato, Jacqueline Boultwood, Kevin Lynch, Sten Eirik W Jacobsen, Ghulam J Mufti, Eva Hellstrom-Lindberg, Marc R Wilkins, Karen L MacKenzie, Jason W H Wong, Peter J Campbell, John E Pimanda
Myelodysplastic syndromes and chronic myelomonocytic leukemia are blood disorders characterized by ineffective hematopoiesis and progressive marrow failure that can transform into acute leukemia. The DNA methyltransferase inhibitor 5-azacytidine (AZA) is the most effective pharmacological option, but only ∼50% of patients respond. A response only manifests after many months of treatment and is transient. The reasons underlying AZA resistance are unknown, and few alternatives exist for non-responders. Here, we show that AZA responders have more hematopoietic progenitor cells (HPCs) in the cell cycle...
July 18, 2017: Cell Reports
https://www.readbyqxmd.com/read/28721050/the-use-of-natalizumab-for-multiple-sclerosis
#3
REVIEW
Rachel Brandstadter, Ilana Katz Sand
Natalizumab is a monoclonal antibody that acts as an α4 integrin antagonist to prevent leukocyte trafficking into the central nervous system. It is US Food and Drug Administration (FDA) approved for the treatment of relapsing-remitting multiple sclerosis (RRMS). Natalizumab demonstrated high efficacy in Phase III trials by reducing the annualized relapse rate, preventing multiple sclerosis (MS) lesion accumulation on magnetic resonance imaging, and decreasing the probability of sustained progression of disability...
2017: Neuropsychiatric Disease and Treatment
https://www.readbyqxmd.com/read/28720870/monocyte-adhesion-to-atherosclerotic-matrix-proteins-is-enhanced-by-asn-gly-arg-deamidation
#4
Bamaprasad Dutta, Jung Eun Park, Subodh Kumar, Piliang Hao, Xavier Gallart-Palau, Aida Serra, Yan Ren, Vitaly Sorokin, Chuen Neng Lee, Hee Hwa Ho, Dominique de Kleijn, Siu Kwan Sze
Atherosclerosis arises from leukocyte infiltration and thickening of the artery walls and constitutes a major component of vascular disease pathology, but the molecular events underpinning this process are not fully understood. Proteins containing an Asn-Gly-Arg (NGR) motif readily undergo deamidation of asparagine to generate isoDGR structures that bind to integrin αvβ3 on circulating leukocytes. Here we report the identification of isoDGR motifs in human atherosclerotic plaque components including extracellular matrix (ECM) proteins fibronectin and tenascin C, which have been strongly implicated in human atherosclerosis...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28720704/cytosolic-interaction-of-type-iii-human-cd38-with-cib1-modulates-cellular-cyclic-adp-ribose-levels
#5
Jun Liu, Yong Juan Zhao, Wan Hua Li, Yun Nan Hou, Ting Li, Zhi Ying Zhao, Cheng Fang, Song Lu Li, Hon Cheung Lee
CD38 catalyzes the synthesis of the Ca(2+) messenger, cyclic ADP-ribose (cADPR). It is generally considered to be a type II protein with the catalytic domain facing outside. How it can catalyze the synthesis of intracellular cADPR that targets the endoplasmic Ca(2+) stores has not been resolved. We have proposed that CD38 can also exist in an opposite type III orientation with its catalytic domain facing the cytosol. Here, we developed a method using specific nanobodies to immunotarget two different epitopes simultaneously on the catalytic domain of the type III CD38 and firmly established that it is naturally occurring in human multiple myeloma cells...
July 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28718435/agrin-to-yap-in-cancer-and-neuromuscular-junctions
#6
Wen-Cheng Xiong, Lin Mei
Agrin is utilized by motor neurons to stimulate the LRP4-MuSK receptor in muscles for neuromuscular junction (NMJ) formation. Recent studies of cancer have identified novel functions of the low-density lipoprotein receptor-related protein 4-muscle-specific kinase (LRP4-MuSK) pathway. Agrin may act as a mechanotransduction signal in the extracellular matrix (ECM) to coordinate the cross-talk between the LRP4-MuSK pathway and integrin-focal adhesion pathway. Ensuing Yes-associated protein (YAP) activation promotes hepatocellular carcinoma (HCC)...
April 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718402/metabolism-during-ecm-detachment-achilles-heel-of-cancer-cells
#7
REVIEW
Joshua A Mason, Kimberly R Hagel, Mark A Hawk, Zachary T Schafer
Integrin-mediated attachment to the extracellular matrix (ECM) is required to combat the induction of programmed cell death in a variety of distinct cell types. If cells fail to maintain proper ECM attachment, they become subject to elimination via an apoptotic cell death program known as anoikis. However, anoikis inhibition is not sufficient to promote the long-term survival of ECM-detached cells. Several recent studies have unveiled the profound (anoikis-independent) impact of cell metabolism on the viability of ECM-detached cells...
July 2017: Trends in Cancer
https://www.readbyqxmd.com/read/28718185/congenital-pulmonary-lymphangiectasia-a-disorder-not-only-of-fetoneonates
#8
Shi-Min Yuan
Congenital pulmonary lymphangiectasia (CPL) is a rare developmental disorder of the lung, characterized by dilation of pulmonary subpleural, interlobar, perivascular and peribronchial lymphatics. The incidence of CPL among stillborn and neonates was estimated to be <1%. The etiology of CPL is unknown. However, it has been suspected to be of a genetic background. Recent basic studies revealed that it might be caused by the FOXC2, Vegfr-3 and integrin α9β1gene mutations. A clinical diagnosis of CPL can be made much easier in full-term neonates who present with respiratory distress, pleural (especially chylous) effusions with or without generalized edema...
July 2017: Klinische Pädiatrie
https://www.readbyqxmd.com/read/28717419/platelet-extracellular-vesicles-induce-a-pro-inflammatory-smooth-muscle-cell-phenotype
#9
Tanja Vajen, Birke J Benedikter, Alexandra C A Heinzmann, Elena M Vasina, Yvonne Henskens, Martin Parsons, Patricia B Maguire, Frank R Stassen, Johan W M Heemskerk, Leon J Schurgers, Rory R Koenen
Extracellular vesicles (EVs) are mediators of cell communication during health and disease, and abundantly released by platelets upon activation or during ageing. Platelet EVs exert modulatory effects on immune and vascular cells. Platelet EVs may modulate the function of vascular smooth muscle cells (SMC). Platelet EVs were isolated from platelet-rich plasma and incubated with SMC in order to assess binding, proliferation, migration and pro-inflammatory phenotype of the cells. Platelet EVs firmly bound to resting SMC through the platelet integrin αIIbβ3, while binding also occurred in a CX3CL1-CX3CR1-dependent manner after cytokine stimulation...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28717358/clinical-response-to-vedolizumab-in-ulcerative-colitis-patients-is-associated-with-changes-in-integrin-expression-profiles
#10
Friederike Fuchs, Daniela Schillinger, Raja Atreya, Simon Hirschmann, Sarah Fischer, Clemens Neufert, Imke Atreya, Markus F Neurath, Sebastian Zundler
BACKGROUND: Despite large clinical success, deeper insights into the immunological effects of vedolizumab therapy for inflammatory bowel diseases are scarce. In particular, the reasons for differential clinical response in individual patients, the precise impact on the equilibrium of integrin-expressing T cell subsets, and possible associations between these issues are not clear. METHODS: Blood samples from patients receiving clinical vedolizumab therapy were sequentially collected and analyzed for expression of integrins and chemokine receptors on T cells...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28717031/phagocytic-receptors-activate-syk-and-src-signaling-during-borrelia-burgdorferi-phagocytosis
#11
Tess L Killpack, Maria Ballesteros, Stephen C Bunnell, Alice Bedugnis, Lester Kobzik, Linden T Hu, Tanja Petnicki-Ocwieja
Phagocytosis of the Lyme disease causing pathogen Borrelia burgdorferi has been shown to be important in generating an inflammatory response to the pathogen. As a result, understanding the mechanisms of phagocytosis has been an area of great interest in the field of Lyme disease. Several cell surface receptors that participate in B. burgdorferi phagocytosis have been reported, including scavenger receptor MARCO and integrin α3β1. We sought to define the mechanisms by which these receptors mediated phagocytosis and to identify signaling pathways activated downstream of these receptors upon contact with B...
July 17, 2017: Infection and Immunity
https://www.readbyqxmd.com/read/28715655/macrophage-exosomes-as-natural-nanocarriers-for-protein-delivery-to-inflamed-brain
#12
Dongfen Yuan, Yuling Zhao, William A Banks, Kristin M Bullock, Matthew Haney, Elena Batrakova, Alexander V Kabanov
Recent work has stimulated interest in the use of exosomes as nanocarriers for delivery of small drugs, RNAs, and proteins to the central nervous system (CNS). To overcome the blood-brain barrier (BBB), exosomes were modified with brain homing peptides that target brain endothelium but likely to increase immune response. Here for the first time we demonstrate that there is no need for such modification to penetrate the BBB in mammals. The naïve macrophage (Mϕ) exosomes can utilize, 1) on the one hand, the integrin lymphocyte function-associated antigen 1 (LFA-1) and intercellular adhesion molecule 1 (ICAM-1), and, 2) on the other hand, the carbohydrate-binding C-type lectin receptors, to interact with brain microvessel endothelial cells comprising the BBB...
July 10, 2017: Biomaterials
https://www.readbyqxmd.com/read/28714276/human-platelet-lysate-supports-the-formation-of-robust-human-periodontal-ligament-cell-sheets
#13
Bei-Min Tian, Rui-Xin Wu, Chun-Sheng Bi, Xiao-Tao He, Yuan Yin, Fa-Ming Chen
The use of stem cell-derived sheets has become increasingly common in a wide variety of biomedical applications. Although substantial evidence has demonstrated that human platelet lysate (PL) can be used for therapeutic cell expansion, either as a substitute for or as a supplement to xenogeneic fetal bovine serum (FBS), its impact on cell sheet production remains largely unexplored. In this study, we manufactured periodontal ligament stem cell (PDLSC) sheets in vitro by incubating PDLSCs in sheet-induction media supplemented with various ratios of PL and FBS, i...
July 17, 2017: Journal of Tissue Engineering and Regenerative Medicine
https://www.readbyqxmd.com/read/28714035/immunocytochemical-stem-cell-markers-can-predict-clinical-stage-of-breast-cancer
#14
Pedro J Gutiérrez Diez, Yanrong Su, Jose Russo
We present a computational-statistical algorithm that, from data on the staining degree of immunocytochemical markers: i) evaluates the ability of the considered immuno-panel in predicting the breast cancer stage; ii) makes the accurate identification of breast cancer stage possible; iii) provides the best stage prognosis compatible with the considered sample; and iv) does so through the use of the minimum number of markers minimizing time and resource costs. After running the algorithm on two data sets [triple-negative breast cancer, (TNBC), and estrogen receptor-negative breast cancer, (ERNBC)], we conclude that EpCAM and β1 integrin are enough to accurately predict TNBC stage, being ALDH1, CD24, CD61, and CK5 the necessary markers to exactly predict ERNBC stage...
July 14, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28713977/analysis-of-gene-expression-profile-microarray-data-in-complex-regional-pain-syndrome
#15
Wulin Tan, Yiyan Song, Chengqiang Mo, Shuangjian Jiang, Zhongxing Wang
The aim of the present study was to predict key genes and proteins associated with complex regional pain syndrome (CRPS) using bioinformatics analysis. The gene expression profiling microarray data, GSE47603, which included peripheral blood samples from 4 patients with CRPS and 5 healthy controls, was obtained from the Gene Expression Omnibus (GEO) database. The differentially expressed genes (DEGs) in CRPS patients compared with healthy controls were identified using the GEO2R online tool. Functional enrichment analysis was then performed using The Database for Annotation Visualization and Integrated Discovery online tool...
July 12, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713908/comparison-of-gene-expression-profiles-between-dental-pulp-and-periodontal-ligament-tissues-in-humans
#16
Ai-Xiu Gong, Jing-Han Zhang, Jing Li, Jun Wu, Lin Wang, Deng-Shun Miao
There are anatomical and functional differences between human dental pulp (DP) and periodontal ligament (PDL). However, the molecular biological differences and function of these tissues are poorly understood. In the present study, we employed a cDNA microarray array to screen for differentially expressed genes (DEGs) between human DP and PDL tissues, and used the online software WebGestalt to perform the functional analysis of the DEGs. In addition, the STRING database and KEGG pathway analysis were applied for interaction network and pathway analysis of the DEGs...
July 12, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28713860/icam-1-targeted-nanocarriers-attenuate-endothelial-release-of-soluble-icam-1-an-inflammatory-regulator
#17
Rachel L Manthe, Silvia Muro
Targeting of drug nanocarriers (NCs) to intercellular adhesion molecule-1 (ICAM-1), an endothelial-surface protein overexpressed in many pathologies, has shown promise for therapeutic delivery into and across this lining. Yet, due to the role of ICAM-1 in inflammation, the effects of targeting this receptor need investigation. Since ICAM-1 binding by natural ligands (leukocyte integrins) results in release of the "soluble ICAM-1" ectodomain (sICAM-1), an inflammatory regulator, we investigated the influence of targeting ICAM-1 with NCs on this process...
March 2017: Bioengineering & Translational Medicine
https://www.readbyqxmd.com/read/28711718/phospholipase-d1-is-a-regulator-of-platelet-mediated-inflammation
#18
Meike Klier, Nina Sarah Gowert, Sven Jäckel, Christoph Reinhardt, Margitta Elvers
Glycoprotein (GP)Ib is not only required for stable thrombus formation but for platelet-mediated inflammatory responses. Phospholipase (PL)D1 is essential for GPIb-dependent aggregate formation under high shear conditions while nothing is known about PLD1-induced regulation of GPIb in platelet-mediated inflammation and the underlying mechanisms. This study aimed to investigate the relevance of PLD1 for platelet-mediated endothelial and leukocyte recruitment and activation in vitro and in vivo. Pld1(-/-) platelets showed strongly reduced adhesion to TNFα stimulated endothelial cells (ECs) under high shear conditions ex vivo...
July 12, 2017: Cellular Signalling
https://www.readbyqxmd.com/read/28708806/understanding-the-cautions-and-contraindications-of-immunomodulator-and-biologic-therapies-for-use-in-inflammatory-bowel-disease
#19
H Matthew Cohn, Maneesh Dave, Edward V Loftus
Ulcerative colitis and Crohn's disease are chronic inflammatory bowel diseases for which there are no cures. These diseases are immunopathogenic, and medical treatment is centered on the temperance of a dysregulated immune response to allow mucosal healing and prevent the sequelae of fistulation and stenosis. Accordingly, the armamentarium of medications, which has expanded immensely in recent history, is not without significant infectious and neoplastic risks. Many of these untoward effects can be mitigated by screening and avoidance of contraindicated medications...
August 2017: Inflammatory Bowel Diseases
https://www.readbyqxmd.com/read/28708243/the-depletion-of-marveld1-leads-to-murine-placenta-accreta-via-integrin-%C3%AE-4-dependent-trophoblast-cell-invasion
#20
Yue Chen, Hui Zhang, Fang Han, Lei Yue, Chunxiao Qiao, Yao Zhang, Peng Dou, Weizhe Liu, Yu Li
The placenta is a remarkable organ, it serves as the interface between the mother and the fetus. Proper invasion of trophoblast cells is required for a successful pregnancy. Previous studies have found that the adhesion molecule integrin β4 plays important roles during trophoblast cell invasion. Here, we found that the overall birth rate of the MARVELD1 knockout mouse is much lower than that of the wild-type mouse (P<0.001). In E18.5 MARVELD1 knockout mice, we observed an over-invasion of trophoblast cells, and indeed, the pregnant mice had a partial placenta accreta phenotype...
July 14, 2017: Journal of Cellular Physiology
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