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https://www.readbyqxmd.com/read/28454453/targeting-assay-of-a-fusion-protein-applied-in-enzyme-prodrug-therapy
#1
Hao Wang, Jin-Jian Liu, Xiao-Liang Zhou
Tumor growth and metastasis are dependent on angiogenesis. The overexpression of integrin αvβ3 on angiogenic vessels and on numerous malignant human tumor cells suggests that these labeled ligands of integrin are potentially suitable for molecular imaging and in targeted therapy of tumors. In previous studies, we added a β-lactamase variant with reduced immunogenicity to the cyclic peptide RGD4C, resulting in the fusion protein RGD4CβL, which is suitable for use in targeted enzyme prodrug therapy (TEPT), a promising treatment for tumors...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454435/15-deoxy-%C3%AE-12-14-prostaglandin-j2-inhibits-migration-of-human-thyroid-carcinoma-cells-by-disrupting-focal-adhesion-complex-and-adherens-junction
#2
Ya-Chieh Wu, Yun-Ting Jhao, Yu-Chen Cheng, Ying Chen
Metastasis is frequently observed in human follicular thyroid carcinoma. The present study investigated the peroxisome proliferator-activated receptor γ agonist, 15-deoxy-Δ(12,14)-prostaglandin J(2) (15d-PGJ2), and its effect on the migration of CGTH W-2 human thyroid carcinoma cells. 15d-PGJ2 decreased the survival rate of CGTH W-2 cells in a dose-dependent manner. The Transwell migration assay demonstrated that 15d-PGJ2 reduced the migration rate of CGTH W-2 cells by 35% following treatment with 30 µM 15d-PGJ2 compared with control cells...
April 2017: Oncology Letters
https://www.readbyqxmd.com/read/28454098/the-impact-of-receptor-recycling-on-the-exocytosis-of-%C3%AE-v%C3%AE-3-integrin-targeted-gold-nanoparticles
#3
Yanan Cui, Xiaoning Song, Suxin Li, Bing He, Lan Yuan, Wenbing Dai, Hua Zhang, Xueqing Wang, Bin Yang, Qiang Zhang
Among the diverse factors that may influence the therapeutic outcomes, the exocytosis of targeted drug delivery systems (TDDS) and its relationship with the corresponding receptor receive little attentions. In this study, cRGDfK modified gold nanoparticles (cRGDfK-PEG-AuNPs) were synthesized, and their cellular transportation including endocytosis and exocytosis, as well as the potential relations with αvβ3 integrin were carefully studied. The results showed that the enhanced and fast internalization of cRGDfK-PEG-AuNPs into U87 cells was associated with the high expression level of αvβ3 integrin...
April 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28453955/acoustic-tweezing-cytometry-enhances-osteogenesis-of-human-mesenchymal-stem-cells-through-cytoskeletal-contractility-and-yap-activation
#4
Xufeng Xue, Xiaowei Hong, Zida Li, Cheri X Deng, Jianping Fu
Human mesenchymal stem cells (hMSCs) have great potential for cell-based therapies for treating degenerative bone diseases. It is known that mechanical cues in the cell microenvironment play an important role in regulating osteogenic (bone) differentiation of hMSCs. However, mechanoregulation of lineage commitment of hMSCs in conventional two-dimensional (2D) monocultures or bioengineered three-dimensional (3D) tissue constructs remains suboptimal due to complex biomaterial design criteria for hMSC culture...
April 22, 2017: Biomaterials
https://www.readbyqxmd.com/read/28453768/%C3%AE-e%C3%AE-7-integrin-identifies-subsets-of-pro-inflammatory-colonic-cd4-t-lymphocytes-in-ulcerative-colitis
#5
Christopher A Lamb, John C Mansfield, Gaik W Tew, Deena Gibbons, Anna K Long, Peter Irving, Lauri Diehl, Jeff Eastham-Anderson, Maria B Price, Graeme O'Boyle, David E J Jones, Sharon O'Byrne, Adrian Hayday, Mary E Keir, Jackson G Egen, John A Kirby
Background and Aims: The αEβ7 integrin is crucial for retention of T lymphocytes at mucosal surfaces through its interaction with E-cadherin. Pathogenic or protective functions of these cells during human intestinal inflammation, such as ulcerative colitis [UC], have not previously been defined, with understanding largely derived from animal model data. Defining this phenotype in human samples is important for understanding UC pathogenesis and is of translational importance for therapeutic targeting of αEβ7-E-cadherin interactions...
May 1, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28449309/tumor-targeting-with-an-isodgr-drug-conjugate
#6
Simone Zanella, Simona Angerani, Pina Arianna, Paula López Rivas, Clelia Giannini, Silvia Panzeri, Daniela Arosio, Michele Caruso, Fabio Gasparri, Ivan Fraietta, Clara Albanese, Aurelio Marsiglio, Luca Pignataro, Laura Belvisi, Umberto Piarulli, Cesare Gennari
Here we report the first example of an isoDGR-drug conjugate (2), designed to release paclitaxel selectively within cancer cells expressing integrin αVβ3. Conjugate 2 was synthesized by connecting the isoDGR peptidomimetic 5 with paclitaxel via the lysosomally cleavable Val-Ala dipeptide linker. Conjugate 2 displayed a low nanomolar affinity for the purified integrin αVβ3 receptor (IC50 = 11.0 nM). The tumor targeting ability of conjugate 2 was assessed in vitro in anti-proliferative assays on two isogenic cancer cell lines characterized by different integrin αVβ3 expression: human glioblastoma U87 (αVβ3 +) and U87 β3-KO (αVβ3 -)...
April 27, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/28449273/systematic-review-the-safety-of-vedolizumab-for-the-treatment-of-inflammatory-bowel-disease
#7
REVIEW
W A Bye, V Jairath, S P L Travis
BACKGROUND: Vedolizumab specifically recognises the α4β7 integrin and selectively blocks gut lymphocyte trafficking: potentially, it offers gut-specific immunosuppression. AIM: To review the safety of vedolizumab and summarise post-marketing data to assess if any safety concerns that differ from registration trials have emerged. METHOD: A systematic bibliographic search identified six registration trials and nine cohort studies. RESULTS: Integrated data from registration trials included 2830 vedolizumab-exposed patients (4811 person-years exposure [PYs]) and 513 placebo patients...
April 27, 2017: Alimentary Pharmacology & Therapeutics
https://www.readbyqxmd.com/read/28448919/mechanochemical-mechanism-of-integrin-clustering-modulated-by-nanoscale-ligand-spacing-and-rigidity-of-extracellular-substrates
#8
Jing Yu, Jianyong Huang, John A Jansen, Chunyang Xiong, X Frank Walboomers
Experimental findings indicate that cell function and behavior such as cell growth, division, migration and differentiation, are subtly regulated via integrin-dependent cell adhesion. Cell adhesion is influenced by nanoscale ligand spacing and rigidity of extracellular substrates, as cell adhesion drops greatly when the ligand spacing is larger than ~60nm, and cell adhesion is stronger on stiff than soft substrates. However, how nanoscale ligand spacing and substrate stiffness jointly affect integrin clustering and hence nascent cell adhesion remains to be elucidated...
April 14, 2017: Journal of the Mechanical Behavior of Biomedical Materials
https://www.readbyqxmd.com/read/28448789/development-of-pre-implantation-porcine-blastocysts-cultured-within-alginate-hydrogel-systems-either-supplemented-with-secreted-phosphoprotein-1-or-conjugated-with-arg-gly-asp-peptide
#9
Taylor D Laughlin, Jeremy R Miles, Elane C Wright-Johnson, Lea A Rempel, Clay A Lents, Angela K Pannier
Although deficiencies in porcine blastocyst elongation play a significant role in early embryonic mortality and establishment of within-litter developmental variation, the exact mechanisms of elongation are poorly understood. Secreted phosphoprotein 1 (SPP1) is increased within the uterine milieu during early porcine pregnancy and contains an Arg-Gly-Asp (RGD) peptide sequence that binds to cell surface integrins on the uterine endometrium and trophectoderm, promoting cell adhesion and migration. The aim of the present study was to evaluate the development of preimplantation porcine blastocysts encapsulated and cultured within alginate hydrogels either supplemented with SPP1 or conjugated with RGD...
April 28, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28448494/integrin-%C3%AE-1-activation-induces-an-anti-melanoma-host-response
#10
Laila Ritsma, Ipsita Dey-Guha, Nilesh Talele, Xavier Sole, Salony, Joeeta Chowdhury, Kenneth N Ross, Sridhar Ramaswamy
TGF-β is a cytokine thought to function as a tumor promoter in advanced malignancies. In this setting, TGF-β increases cancer cell proliferation, survival, and migration, and orchestrates complex, pro-tumorigenic changes in the tumor microenvironment. Here, we find that in melanoma, integrin β1-mediated TGF-β activation may also produce tumor suppression via an altered host response. In the A375 human melanoma cell nu/nu xenograft model, we demonstrate that cell surface integrin β1-activation increases TGF-β activity, resulting in stromal activation, neo-angiogenesis and, unexpectedly for this nude mouse model, increase in the number of intra-tumoral CD8+ T lymphocytes within the tumor microenvironment...
2017: PloS One
https://www.readbyqxmd.com/read/28447099/endogenous-developmental-endothelial-locus-1-limits-ischaemia-related-angiogenesis-by-blocking-inflammation
#11
Anne Klotzsche-von Ameln, Sebastian Cremer, Jedrzej Hoffmann, Peggy Schuster, Sherif Khedr, Irina Korovina, Maria Troullinaki, Ales Neuwirth, David Sprott, Antonios Chatzigeorgiou, Matina Economopoulou, Alessia Orlandi, Andreas Hain, Andreas M Zeiher, Andreas Deussen, George Hajishengallis, Stefanie Dimmeler, Triantafyllos Chavakis, Emmanouil Chavakis
We have recently identified endothelial cell-secreted developmental endothelial locus-1 (Del-1) as an endogenous inhibitor of β2-integrin-dependent leukocyte infiltration. Del-1 was previously also implicated in angiogenesis. Here, we addressed the role of endogenously produced Del-1 in ischaemia-related angiogenesis. Intriguingly, Del-1-deficient mice displayed increased neovascularisation in two independent ischaemic models (retinopathy of prematurity and hind-limb ischaemia), as compared to Del-1-proficient mice...
April 27, 2017: Thrombosis and Haemostasis
https://www.readbyqxmd.com/read/28446746/peripheral-blood-akap7-expression-as-an-early-marker-for-lymphocyte-mediated-post-stroke-blood-brain-barrier-disruption
#12
Grant C O'Connell, Madison B Treadway, Ashley B Petrone, Connie S Tennant, Noelle Lucke-Wold, Paul D Chantler, Taura L Barr
Our group recently identified 16 genes whose peripheral blood expression levels are differentially regulated in acute ischemic stroke. The purpose of this study was to determine whether the early expression levels of any of these 16 genes are predictive for post-stroke blood brain barrier (BBB) disruption. Transcriptional expression levels of candidate genes were measured in peripheral blood sampled from ischemic stroke patients at emergency department admission, and BBB permeability was assessed at 24 hour follow up via perfusion-weighted imaging...
April 26, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28446705/diverse-integrin-adhesion-stoichiometries-caused-by-varied-actomyosin-activity
#13
Natalia A Bulgakova, Jutta Wellmann, Nicholas H Brown
Cells in an organism are subjected to numerous sources of external and internal forces, and are able to sense and respond to these forces. Integrin-mediated adhesion links the extracellular matrix outside cells to the cytoskeleton inside, and participates in sensing, transmitting and responding to forces. While integrin adhesion rapidly adapts to changes in forces in isolated migrating cells, it is not known whether similar or more complex responses occur within intact, developing tissues. Here, we studied changes in integrin adhesion composition upon different contractility conditions in Drosophila embryonic muscles...
April 2017: Open Biology
https://www.readbyqxmd.com/read/28446591/nfat5-sensitive-orai1-expression-and-store-operated-ca-2-entry-in-megakaryocytes
#14
Itishri Sahu, Lisann Pelzl, Basma Sukkar, Hajar Fakhri, Tamer Al-Maghout, Hang Cao, Stefan Hauser, Ravi Gutti, Meinrad Gawaz, Florian Lang
The transcription factor NFAT5 is up-regulated in several clinical disorders including dehydration. NFAT5-sensitive genes include serum and glucocorticoid-inducible kinase (SGK)-1. The kinase is a powerful regulator of Orai1, a Ca(2+)-channel accomplishing store-operated Ca(2+)-entry (SOCE). Orai1 is stimulated after intracellular store depletion by the Ca(2+) sensors stromal interaction molecule (STIM)-1, or STIM2, or both. In the present study, we explored whether nuclear factor of activated T cell (NFAT)-5 influences Ca(2+)-signaling in megakaryocytes...
April 26, 2017: FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology
https://www.readbyqxmd.com/read/28446539/transient-mechanical-strain-promotes-the-maturation-of-invadopodia-and-enhances-cancer-cell-invasion-in-vitro
#15
Alexander N Gasparski, Snehal Ozarkar, Karen A Beningo
Cancer cell invasion is influenced by various biomechanical forces found within the microenvironment. We have previously found that invasion is enhanced in fibrosarcoma cells when transient mechanical stimulation is applied within an in vitro mechano-invasion assay. This enhancement of invasion is dependent on cofilin, a known regulator of invadopodia maturation. Invadopodia are actin-rich structures present in invasive cancer cells that are enzymatically active and degrade the surrounding extracellular matrix to facilitate invasion...
April 26, 2017: Journal of Cell Science
https://www.readbyqxmd.com/read/28445994/correction-amphiregulin-enhances-alpha6beta1-integrin-expression-and-cell-motility-in-human-chondrosarcoma-cells-through-ras-raf-mek-erk-ap-1-pathway
#16
Jui-Chieh Chen, Yu-Ju Chen, Chih-Yang Lin, Yi-Chin Fong, Chin-Jung Hsu, Chun-Hao Tsai, Jen-Liang Su, Chih-Hsin Tang
No abstract text is available yet for this article.
April 11, 2017: Oncotarget
https://www.readbyqxmd.com/read/28445705/mutation-characterization-and-heterodimer-analysis-of-patients-with-leukocyte-adhesion-deficiency-including-one-novel-mutation
#17
Shahram Teimourian, Martin De Boer, Dirk Roos, Anna Isaian, Ehsan Moghanloo, Sharhzad Lashkary, Bita Hassani, Hasan Mollanoori, Vahid Babaei, Asaad Azarnezhad
BACKGROUND AND AIM: Leukocyte adhesion deficiency type 1 (LAD-I) is a rare, autosomal recessive disorder of neutrophil migration, characterized by severe, recurrent bacterial infections, inadequate pus formation and impaired wound healing. The ITGB2 gene encodes the β2 integrin subunit (CD18) of the leukocyte adhesion cell molecules, and mutations in this gene cause LAD-I. The aim of the current study was to investigate the mutations in patients diagnosed with LAD-I and functional studies of the impact of two previously reported and a novel mutation on the expression of the CD18/CD11a heterodimer...
April 23, 2017: Immunology Letters
https://www.readbyqxmd.com/read/28445073/plasminogen-activator-inhibitor-1-is-critical-in-alcohol-enhanced-acute-lung-injury-in-mice
#18
Lauren G Poole, Veronica L Massey, Deanna L Siow, Edilson Torres-González, Nikole L Warner, James P Luyendyk, Jeffrey D Ritzenthaler, Jesse Roman, Gavin E Arteel
RATIONALE: Chronic alcohol exposure is a clinically important risk factor for development of acute respiratory distress syndrome, the most severe form of acute lung injury (ALI). However, the mechanisms by which alcohol sensitizes the lung to development of this disease are poorly understood. OBJECTIVES: We determined the role of the anti-fibrinolytic protein plasminogen activator inhibitor-1 (PAI-1) in alcohol enhancement of experimental endotoxin-induced ALI. METHODS: Wild-type (WT), PAI-1(-/-) and Integrin β3(-/-) mice were fed ethanol-containing Lieber-DeCarli liquid or control diet for 6 weeks followed by systemic lipopolysaccharide (LPS) challenge...
April 26, 2017: American Journal of Respiratory Cell and Molecular Biology
https://www.readbyqxmd.com/read/28444343/lysolecithin-as-feed-additive-enhances-collagen-expression-and-villus-length-in-the-jejunum-of-broiler-chickens
#19
D L Brautigan, R Li, E Kubicka, S D Turner, J S Garcia, M L Weintraut, E A Wong
Adding lysolecithin to feed has reportedly improved the performance of broiler chickens. Lysolecithin is generated by phospholipase catalyzed hydrolysis of lecithin. The enzymatic reaction converts various phospholipids into the corresponding lysophospholipids, with lysophosphatidylcholine (LPC) one of the primary products. Here we compared supplementation with a commercial lysolecithin (Lysoforte®) with comparable levels of highly purified LPC for effects on broilers. Despite no differences in weight gain during the starter period, we discovered a significant increase in average villus length with lysolecithin and an increase in villus width with purified LPC...
April 24, 2017: Poultry Science
https://www.readbyqxmd.com/read/28443208/roles-of-rap1-signaling-in-tumor-cell-migration-and-invasion
#20
Yi-Lei Zhang, Ruo-Chen Wang, Ken Cheng, Brian Z Ring, Li Su
Ras-associated protein-1 (Rap1), a small GTPase in the Ras-related protein family, is an important regulator of basic cellular functions (e.g., formation and control of cell adhesions and junctions), cellular migration, and polarization. Through its interaction with other proteins, Rap1 plays many roles during cell invasion and metastasis in different cancers. The basic function of Rap1 is straightforward; it acts as a switch during cellular signaling transduction and regulated by its binding to either guanosine triphosphate (GTP) or guanosine diphosphate (GDP)...
February 2017: Cancer Biology & Medicine
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