Academic literature on the topic 'INS-1 cells'
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Journal articles on the topic "INS-1 cells"
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Janjic, D., and M. Asfari. "Effects of cytokines on rat insulinoma INS-1 cells." Journal of Endocrinology 132, no. 1 (January 1992): 67–76. http://dx.doi.org/10.1677/joe.0.1320067.
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ABSTRACT To investigate further the role of cytokines in the pathogenesis of type I insulin-dependent diabetes mellitus, the effects of interleukin-1β (IL-1), tumour necrosis factor-α (TNF) and γ-interferon (IFN) were tested on rat insulinoma INS-1 cells. Whereas TNF and IFN had, respectively, a minor or no effect on insulin production, IL-1 caused a time- and dose-dependent decrease in insulin release and lowered the insulin content as well as the preproinsulin mRNA content of INS-1 cells. Both IL-1 and TNF exerted a cytostatic effect, estimated by a decrease in [3H]thymidine incorporation, while only IL-1 decreased cell viability as measured by the colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) test. The glutathione content of INS-1 cells was shown to be modulated by the presence of 2-mercaptoethanol in the culture medium, but was not affected by IL-1 or TNF. In conclusion, INS-1 cell culture is considered to be a useful model for studying the effect of cytokines on insulin-producing cells. The differentiated features of these cells will permit several questions to be addressed regarding the mechanism of action of IL-1 and eventually other cytokines, both at the level of gene expression and of intracellular signalling. Journal of Endocrinology (1992) 132, 67–76
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Shi, Xiao-li, Yue-zhong Ren, and Jing Wu. "Intermittent High Glucose Enhances Apoptosis in INS-1 Cells." Experimental Diabetes Research 2011 (2011): 1–7. http://dx.doi.org/10.1155/2011/754673.
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To investigate the effect of intermittent high glucose (IHG) and sustained high glucose (SHG) on inducingβ-cell apoptosis and the potential involved mechanisms, INS-1 beta cells were incubated for 72 h in the medium containing different glucose concentrations: control (5.5 mmol/L), SHG (33.3 mmol/L), and IHG (5.5 mmol/L and 33.3 mmol/L glucose alternating every 12 h). Cell viability, apoptosis rate, and oxidative-stress markers were determined. The results showed that the apoptosis induced by IHG was more obvious than that by SHG. Simultaneously, the intracellular level of oxidative stress was more significantly increased in INS-1 cells exposed to IHG. These findings suggest that intermittent high glucose could be more deleterious toβ-cell than a constant high concentration of glucose, this may be due to the aggravation of oxidative stress triggered by intermittent high glucose.
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Ji, Yong, Gao Lu, Guoqiang Chen, Bin Huang, Xian Zhang, Kai Shen, and Song Wu. "Microcystin-LR Induces Apoptosis via NF-κB /iNOS Pathway in INS-1 Cells." International Journal of Molecular Sciences 12, no. 7 (July 22, 2011): 4722–34. http://dx.doi.org/10.3390/ijms12074722.
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Yaney, G. C., V. Schultz, B. A. Cunningham, G. A. Dunaway, B. E. Corkey, and K. Tornheim. "Phosphofructokinase Isozymes in Pancreatic Islets and Clonal -Cells (INS-1)." Diabetes 44, no. 11 (November 1, 1995): 1285–89. http://dx.doi.org/10.2337/diab.44.11.1285.
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FILIPSSON, KARIN, and BO AHRÉN. "PACAP27 Sensitizes Glucose Induced Insulin Secretion in INS-1 Cells." Annals of the New York Academy of Sciences 921, no. 1 (January 25, 2006): 456–59. http://dx.doi.org/10.1111/j.1749-6632.2000.tb07014.x.
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Li, Fengfei, Bijun Chen, Ling Li, Min Zha, S. Zhou, Tongzhi Wu, M. G. Bachem, and Zilin Sun. "INS-1 cells inhibit the production of extracellular matrix from pancreatic stellate cells." Journal of Molecular Histology 45, no. 3 (November 8, 2013): 321–27. http://dx.doi.org/10.1007/s10735-013-9547-y.
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HUANG, Xinyuan, Yanying ZHAO, Shaohui JIA, Dongjing YAN, and Zhengwang CHEN. "Effects of Daintain/AIF-1 on β Cell Dysfunction in INS-1 Cells." Bioscience, Biotechnology, and Biochemistry 75, no. 9 (September 23, 2011): 1842–44. http://dx.doi.org/10.1271/bbb.110317.
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Wong, N. S., C. J. Barker, A. J. Morris, A. Craxton, C. J. Kirk, and R. H. Michell. "The inositol phosphates in WRK1 rat mammary tumour cells." Biochemical Journal 286, no. 2 (September 1, 1992): 459–68. http://dx.doi.org/10.1042/bj2860459.
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1. A detailed structural survey has been made of the inositol phosphates of unstimulated and vasopressin-stimulated WRK-1 rat mammary tumour cells. Inositol phosphate peaks were separated by h.p.l.c., and structural assignments were made for more than 20 compounds by combinations of: (a) co-chromatography with labelled standards; (b) site-specific enzymic dephosphorylation; (c) complete and partial periodate oxidation, followed by h.p.l.c. of polyols and their stereospecific oxidation by dehydrogenases; and (d) ammoniacal hydrolysis. 2. The ‘inositol monophosphates’ fraction from unstimulated cells included an uncharacterized peak, probably containing some glycerophosphoinositol, and Ins(1:2-cyclic)P. Stimulation provoked accumulation of both Ins1P and Ins3P, of Ins2P, and of Ins5P and/or the enantiomers Ins4P and Ins6P. The proportions of Ins1P and Ins3P were determined by partial periodate oxidation and enantiomeric identification of the resulting glucitols. 3. Three inositol bisphosphate peaks were detected in unstimulated cells: Ins(1,4)P2 [this was distinguished chemically from its enantiomer Ins(3,6)P2], Ins(3,4)P2 and/or Ins(1,6)P2, and Ins(4,5)P2 and/or Ins(5,6)P2. On stimulation, Ins(1,4)P2 and Ins(3,4)P2 [and/or Ins(1,6)P2] levels increased, and Ins(1:2-cyclic,4)P2 and Ins(1,3)P2 were also formed. 4. Three inositol trisphosphate peaks were obtained from unstimulated cells: all increased during stimulation. These were Ins(1,3,4)P3 [with some Ins(1:2-cyclic,4,5)P3], Ins(1,4,5)P3 and Ins(3,4,5)P3 [and/or Ins(1,5,6)P3]. During stimulation, another compound, probably Ins(1,4,6)P3, appeared in the ‘Ins(1,4,5)P3 peak’. The ‘Ins(3,4,5)P3 peak’ contained a second trisphosphate, probably Ins(2,4,5)P3. 5. Three inositol tetrakisphosphates, namely Ins(1,3,4,6)P4, Ins(1,3,4,5)P4, were present in unstimulated cells, and all accumulated during stimulation. 6. Ins(1,3,4,5,6)P5, which is the most abundant inositol polyphosphate in these cells, a less abundant inositol pentakisphosphate and inositol hexakisphosphate were all unresponsive to stimulation.
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Chen, Li, Yuyan Zhao, Delu Zheng, Shujing Ju, Yang Shen, and Lei Guo. "Orexin A Affects INS-1 Rat Insulinoma Cell Proliferation via Orexin Receptor 1 and the AKT Signaling Pathway." International Journal of Endocrinology 2013 (2013): 1–7. http://dx.doi.org/10.1155/2013/854623.
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Our aim is to investigate the role of the AKT/PKB (protein kinase B) signaling pathway acting via orexin receptor 1 (OX1R) and the effects of orexin A (OXA) on cell proliferation in the insulin-secreting beta-cell line (INS-1 cells). Rat INS-1 cells were exposed to different concentrations of OXAin vitroand treated with OX1R antagonist (SB334867), PI3K antagonist (wortmannin), AKT antagonist (PF-04691502), or negative control. INS-1 amount of cell proliferation, viability and apoptosis, insulin secretion, OX1R protein expression, caspase-3 activity, and AKT protein levels were determined. We report that OXA (10-10to10-6 M) stimulates INS-1 cell proliferation and viability, reduces the proapoptotic activity of caspase-3 to protect against apoptotic cell death, and increases insulin secretion. Additionally, AKT phosphorylation was stimulated by OXA (10-10to10-6 M). However, the OX1R antagonist SB334867 (10-6 M), the PI3K antagonist wortmannin (10-8 M), the AKT antagonist PF-04691502 (10-6 M), or the combination of both abolished the effects of OXA to a certain extent. These results suggest that the upregulation of OXA-OX1R mediated by AKT activation may inhibit cell apoptosis and promote cell proliferation in INS-1 cells. This finding provides functional evidence of the biological actions of OXA in rat insulinoma cells.
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He, Caigu, Xuehua Zheng, Xiuhong Lin, Xinying Chen, and Chenyi Shen. "Yunvjian-Medicated Serum Protects INS-1 Cells against Glucolipotoxicity-Induced Apoptosis through Autophagic Flux Modulation." Evidence-Based Complementary and Alternative Medicine 2020 (December 14, 2020): 1–15. http://dx.doi.org/10.1155/2020/8878259.
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Yunvjian (YNJ) is a traditional Chinese medicine formula adopted to prevent and treat diabetes. Our previous results from animal experiments showed that YNJ decreased blood glucose. This study aimed to examine the effect of high glucose and high lipid (HG/HL) conditions on the proliferation and apoptosis of INS-1 cells and the possible protective mechanism of YNJ-medicated serum on INS-1 cells exposed to HG/HL conditions. INS-1 cells were cultured in RPMI 1640 medium after being passaged. Then, INS-1 cells in the logarithmic growth phase were collected and divided into five groups: control, HG/HL, HG/HL+5% YNJ-medicated serum, HG/HL+10% YNJ-medicated serum, and HG/HL+20% YNJ-medicated serum. MTT assay and flow cytometry were used to detect proliferation and apoptosis of INS-1 cells, respectively. Protein profiles of INS-1 cells were analyzed using a tandem mass tag (TMT) label-based quantitative proteomic approach. Western blotting was performed to verify the proteomic results. YNJ-medicated serum significantly promoted INS-1 cell proliferation and inhibited apoptosis. Proteomic results from the INS-1 cells in the control, HG/HL, and HG/HL+10% YNJ-medicated serum groups showed that 7,468 proteins were identified, of which 6,423 proteins were quantified. Compared with the HG/HL group,430 differential proteins were upregulated, and 671 were downregulated in the HG/HL+10% YNJ-medicated serum group. Compared with the control group, 711 differential proteins were upregulated and 455 were downregulated in the HG/HL group, whereas 10 differential proteins were upregulated and 9 were downregulated in the HG/HL+10% YNJ-medicated serum group. Furthermore, several proteins related to autophagy, including ATG3, ATG2B, GABARAP, WIPI2, and p62/SQSTM1, were verified by western blotting, and these results were consistent with the results obtained from the proteomics analysis. These results confirmed that the autophagy pathway is critical to glucolipotoxicity in INS-1 cells. YNJ-medicated serum exhibited a protective effect on INS-1 cells cultured under HG/HL conditions by regulating autophagy genes' expression and restoring the autophagic flux.
Dissertations / Theses on the topic "INS-1 cells"
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Young, Ada. "IL-1β Amplification of Nitric Oxide Production and Its Inhibitory Effects on Glucose Induced Early Growth Response-1 Expression in INS-1 Cells." Digital Commons @ East Tennessee State University, 2012. https://dc.etsu.edu/etd/1463.
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The pathophysiology of cytokines released by infiltrating white blood cells upon pancreatic beta cells is not fully understood. Early growth response gene-1 (Egr-1) expression is specifically and transiently up regulated in pancreatic beta cells in response to glucose. We hypothesized that interleukin-1 beta (IL-1▀) induction of nitric oxide alters glucose induced Egr-1 transcription levels. Egr-1 levels were assessed via western blot, nitric oxide was measured with a Griess Reagent kit and insulin levels via ELISA. Glucose induced both insulin and Egr-1 production in INS-1 cells. IL-1▀ dose dependently increased nitric oxide production over time and significantly attenuated glucose induced Egr-1 expression. Sodium nitroprusside dose dependently reduced glucose induced Egr-1 production. The data suggest a strong relationship between IL-1▀ induced nitric oxide production and the reduction of glucose stimulated Egr-1 production. The pathways altered by this cytokine could provide a better understanding of the pathophysiology leading to pancreatic beta cell death.
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Pouillon, Valérie. "Etude des effets de l'inactivation des isoformes B et C de l'enzyme INS(1,4,5)Pp3s 3-kinase chez la souris ;Rôle de l'INS(1,4,5)Pp3s3-kinase B dans le développement des lymphocytes T." Doctoral thesis, Universite Libre de Bruxelles, 2004. http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/211197.
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L’Ins(1,4,5)P3 joue un rôle évident dans la signalisation cellulaire :il permet la libération du Ca 2+ des stocks intracellulaires par son action au niveau de récepteurs spécifiques. Pour mettre fin à son action, l’Ins(1,4,5)P3 peut être dégradé par une Ins(1,4,5)P3 5-phosphatase en Ins(1,4)P2, un métabolite inactif. L’Ins(1,4,5)P3 peut aussi être transformé en Ins(1,3,4,5)P4 par une Ins(1,4,5)P3 3-kinase. L’Ins(1,3,4,5)P4 semble posséder des capacités de signalisation propres ou au contraire liées à celles de l’Ins(1,4,5)P3.L’Ins(1,3,4,5)P4 est aussi le point de départ de toute une série d’inositol hautement phosphorylés, dont les rôles ne sont pas clairs. Trois isoformes de l’Ins(1,4,5)P3 3-kinase existent (A, B et C). Ces isoformes possèdent un domaine catalytique carboxy-terminal bien conservé. Par contre, les domaines amino-terminaux sont spécifiques et leur permettraient d’établir des interactions ou de subir des régulations propres. Pour tenter d’élucider le rôle fonctionnel de l’Ins(1,3,4,5)P4, nous avons généré et analysé des souris déficientes pour les isoformes B et C de cette enzyme.
Les souris déficientes pour l’Ins(1,4,5)P3 3-kinase C ne présentent pas de phénotype évident, ce qui suggère que son rôle n’est pas crucial ou que son absence peut être compensée par une autre enzyme.
Les souris déficientes pour l’Ins(1,4,5)P3 3-kinase B, par contre, présentent une immunodéficience caractérisée par une absence spécifique des lymphocytes T αβ périphériques. Cette absence fait suite à un blocage dans la différenciation du précurseur du lymphocyte, le thymocyte. Les caractéristiques de la signalisation induite par le récepteur de surface (TCR) permettent la sélection des thymocytes, de manière à constituer un pool de lymphocytes T restreints pour le MHC et tolérants pour le soi. Nous avons montré que ces phénomènes de sélection étaient défectueux dans les thymocytes mutants, du fait de leur hyporéactivité à la stimulation par le TCR. Le mécanisme responsable de cette hyporéactivité n’est pas encore élucidé. A première vue, la mobilisation de Ca 2+ ne semble pas altérée dans ces thymocytes mutants en réponse à des stimulations classiques. Cependant, d’autres types de stimulation, se rapprochant plus de celles réellement rencontrées par le thymocyte in vivo, doivent encore être investigués. L’intégrité d’autres voies de signalisation cruciales du lymphocyte T doit aussi être vérifiée.
En conclusion, l’isoforme B de l’Ins(1,4,5)P3 3-kinase et l’Ins(1,3,4,5)P4 qu’il produit jouent un rôle crucial dans la différenciation du thymocyte, par un mécanisme qui reste encore à déterminer.
Doctorat en sciences biomédicales
info:eu-repo/semantics/nonPublished
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Schubert, Sandra. "The Role of [beta]2-Syntrophin Phosphorylation in Secretory Granule Exocytosis." Doctoral thesis, Saechsische Landesbibliothek- Staats- und Universitaetsbibliothek Dresden, 2006. http://nbn-resolving.de/urn:nbn:de:swb:14-1146851994562-42414.
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The trafficking of insulin secretory granules(SGs) of pancreatic b-cells is a tightly controlled complex network. Increasing evidence indicates that the cortical actin cytoskeleton modulates the mobility and exocytosis of SGs,yet the mechanisms anchoring SGs to the cytoskeleton is not completely understood.It has been shown by Ort et al.(2000,2001) that the cytoplasmic tail of an intrinsic membrane protein of the SGs named ICA512/IA-2 binds the PDZ domain of b2-syntrophin,which in turn binds to the F-actin-binding protein utrophin. These data also indicate that stimulation of SG exocytosis affects the phosphorylation of b2-syntrophin,hence altering its binding to ICA512.Therefore a model was proposed whereby SGs are anchored to the actin cytoskeleton through the ICA512/b2-syntrophin complex, whose dynamics are regulated by phosphorylation.To test this model GFP-b2-syntrophin stable INS-1 cell clones were generated.GFP-b2-syntrophin expression and localization pattern were similar to those of the endogenous protein. Electron microscopy showed that in GFP-b2-syntrophin INS-1 cells the number of SGs with a pear-like shape was increased relative to control cells. Insulin content and stimulated secretion were increased in three GFP-â2-syntrophin INS-1 cell clones,compared to non-transfected INS-1 cells and INS-1 cells expressing GFP. These increments correlated with the different expression levels of GFP-b2-syntrophin in the three GFP-b2-syntrophin INS-1 cell clones. These findings support the hypothesis that b2-syntrophin regulates the trafficking and exocytosis of SGs by modulating their tethering to the actin cytoskeleton.In order to confirm the proposed model, the phosphorylation of b2-syntrophin was investigated in more detail. Similar to endogenous b2-syntrophin,GFP-b2-syntrophin underwent Ca2+-dependent and okadaic acid-sensitive dephosphorylation upon stimulation of insulin secretion. Stimulation-dependent dephosphorylation was confirmed by immunoprecipitation of 32P-labeled GFP-b2-syntrophin.Mass spectrometry of immunoprecipitated GFP-b2-syntrophin allowed the identification of four serine-phosphorylation sites (S75,S90,S213,S373) that could affect the binding to ICA512.Mutants,in which all four phosphoserines, were replaced by either asp or ala to mimic(S/D) or prevent(S/A) phosphorylation were expressed in INS-1 cells. All S/D mutants retained a cortical localization,but by immunoblotting the pattern of the S75D allele differed from wild type and all other S/D alleles.Conversely, all S/A alleles were diffused cytosolically, except S213A,which was still restricted to the cortex. Finally, pull down assays showed increased binding of ICA512 to the S75A and S90D alleles compared to wild type b2-syntrophin,while the opposite was observed with the S75D and S90A mutants.Additionally,both the S75 and the S213 allele conform a consensus for phosphorylation by Cdk5,which is known to modulate insulin secretion. The phosphorylation of GFP-b2-syntrophin and particularly the S75 allele by Cdk5 was exhibited with pharmacological inhibitors,by in vitro phosphorylation and by RNAi. Taken together, these findings are consistent with the model by which phosphorylation of b2-syntrophin modulates the tethering of SGs to the cytoskeleton, and thereby their mobility and exocytosis. Specifically, the data of this thesis suggest that Cdk5-dependent phosphorylation of the S75 site of GFP-b2-syntrophin facilitates insulin secretion by reducing the interaction of b2-syntrophin with ICA512,thereby decreasing the actin cytoskeleton constrain on SG mobility. This process could occur in combination with the phosphatase-dependent dephosphorylation of b2-syntrophin at phosphosites other than S75Der Transport Insulin-gefüllter sekretorische Granula(SG) ist ein streng kontrollierter komplexer Prozess.Es gibt vermehrt Beweise,dass das kortikale Actinzytoskelett die Ausschüttung der SGs beeinflusst.Bisher ist der Mechanismus der Verankerung von SGs am Zytoskelett noch nicht vollständig aufgeklärt.Ort et al.(2000,2001) haben gezeigt,daß der zytosoplasmatische Teil des trans-membranen SG-Proteins ICA512 mit der PDZ-Domäne von b2-Syntrophin interagiert.Dieses Protein bindet das F-Actin-Bindeprotein Utrophin.Die Ergebnisse zeigen außerdem,daß durch Stimulation der SG-Exozytose der Phosphorilierungsstatus von b2-Syntrophin beeinflusst wird,woraus ein verändertes Bindungsvermögen zu ICA512 resultiert.Es wurde ein Funktionsmodel vorgestellt,in dem sich SGs durch die Interaktion des ICA512/b2-Syntrophin Komplexes an das Actinzytoskelett binden.Dabei wird die Bindedynamik durch Phosphorilierung reguliert.Um dieses Model zu etablieren,wurden stabile GFP-b2-Syntrophin produzierende INS-1-Zellklone erzeugt.Die zelluläre Lokalisation und das Expressionsmuster von GFP-b2-Syntrophin stimmen mit dem des endogenen Proteins überein.Elektronenmikroskopie zeigte eine größe Anzahl oval-verformter SGs in GFP-b2-Syntrophin INS-1-Zellen im Vergleich zu Kontrollzellen.Verglichen mit nicht-transfizierten INS-1 Zellen waren in drei GFP-b2-Syntrophin INS-1-Zellklonen der Insulingehalt der Zellen und die stimulierte Insulinsekretion erhöht.Die Werte korrelierten mit den unterschiedlichen GFP-b2-Syntrophin Expressionsmengen der Klone.Diese Ergebnisse untermauern die Hypothese,daß b2-Syntrophin den Transport und die Sekretion der SGs durch Modulation ihres Bindevermögens an Actin reguliert.Um das postulierte Model genauer zu prüfen,wurde die Phosphorilierung von b2-Syntrophin detaillierter untersucht.Das GFP-Protein wurde,ähnlich dem endogenen b2-Syntrophin,durch Stimulation der Insulinausschüttung dephosphoriliert.Diese Dephosphorilierung ist Ca2+-abhängig und Okadeinsäuresensitiv.Die stimulationsabhängige Dephosphorilierung wurde durch Immunoprezipitation von 32P-markiertem GFP-b2-Syntrophin bestätigt.Massenspektrometrie des präzipitierten Proteins ermöglichte die Identifikation von vier Serin-Phosphorilierungsstellen(S75,S90,S213,S373),welche die Bindung zu ICA512 beeinflussen könnten.Mutanten,in denen die vier Phosphoserine durch Asp beziehungsweise Ala ersetzt wurden,um entweder eine Phosphorilierung(S/D) oder Dephosphorilierung(S/A) nachzuahmen,wurden in INS-1-Zellen exprimiert.Alle S/D Mutanten blieben kortikal lokalisiert.Das Expressionsmuster des S75D Allels unterschied sich jedoch von denen des Wild-Typs(wt).Im Gegensatz dazu waren alle S/A Allele zytosolisch verteilt.Eine Ausnahme bildete S213A,das an der Zellkortex lokalisiert blieb.Im Vergleich zu wt b2-Syntrophin zeigten PullDown-Assays eine erhöhte Bindung von ICA512 zu den S75A und S90D Allelen.Das Gegenteil konnte für die S75D und S90A Mutanten nachgewiesen werden.S75,S90 und S213 sind in einer Konsensussequenz für Cdk5-Phosphorilierung enthalten.Diese Kinase kann die Insulinsekretion regulieren.Die Phosphorilierung von b2-Syntrophin,insbesondere des S75 Allels durch Cdk5 wurde durch pharmakologische Inhibitoren,in vitro-Phosphorilierung und RNAi demonstriert.Zusammenfassend stimmen diese Erkenntnisse mit dem Model überein,daß die Phosphorilierung von b2-Syntrophin die Vernetzung von SGs mit Actin und dadurch deren Mobilität und Exozytose moduliert.Im Speziellen postulieren die Ergebnisse dieser Arbeit eine Cdk5-abhängige Phosphorilierung der S75 Stelle des b2-Syntrophins.Durch eine verminderte Interaktion von b2-Syntrophin und ICA512 erleichtert diese Mutante vermutlich die Insulinsekretion,da der Einfluss des Actinzytoskeletts auf die Granulamobilität vermindert ist.Dieser Prozess ereignet sich möglicherweise in Kombination mit einer Dephosphorilierung des b2-Syntrophins.in Kombination mit einer Dephosphorilierung des b2-Syntrophins
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Schubert, Sandra. "The Role of [beta]2-Syntrophin Phosphorylation in Secretory Granule Exocytosis." Doctoral thesis, Technische Universität Dresden, 2005. https://tud.qucosa.de/id/qucosa%3A23710.
Full textAbstract:
The trafficking of insulin secretory granules(SGs) of pancreatic b-cells is a tightly controlled complex network. Increasing evidence indicates that the cortical actin cytoskeleton modulates the mobility and exocytosis of SGs,yet the mechanisms anchoring SGs to the cytoskeleton is not completely understood.It has been shown by Ort et al.(2000,2001) that the cytoplasmic tail of an intrinsic membrane protein of the SGs named ICA512/IA-2 binds the PDZ domain of b2-syntrophin,which in turn binds to the F-actin-binding protein utrophin. These data also indicate that stimulation of SG exocytosis affects the phosphorylation of b2-syntrophin,hence altering its binding to ICA512.Therefore a model was proposed whereby SGs are anchored to the actin cytoskeleton through the ICA512/b2-syntrophin complex, whose dynamics are regulated by phosphorylation.To test this model GFP-b2-syntrophin stable INS-1 cell clones were generated.GFP-b2-syntrophin expression and localization pattern were similar to those of the endogenous protein. Electron microscopy showed that in GFP-b2-syntrophin INS-1 cells the number of SGs with a pear-like shape was increased relative to control cells. Insulin content and stimulated secretion were increased in three GFP-â2-syntrophin INS-1 cell clones,compared to non-transfected INS-1 cells and INS-1 cells expressing GFP. These increments correlated with the different expression levels of GFP-b2-syntrophin in the three GFP-b2-syntrophin INS-1 cell clones. These findings support the hypothesis that b2-syntrophin regulates the trafficking and exocytosis of SGs by modulating their tethering to the actin cytoskeleton.In order to confirm the proposed model, the phosphorylation of b2-syntrophin was investigated in more detail. Similar to endogenous b2-syntrophin,GFP-b2-syntrophin underwent Ca2+-dependent and okadaic acid-sensitive dephosphorylation upon stimulation of insulin secretion. Stimulation-dependent dephosphorylation was confirmed by immunoprecipitation of 32P-labeled GFP-b2-syntrophin.Mass spectrometry of immunoprecipitated GFP-b2-syntrophin allowed the identification of four serine-phosphorylation sites (S75,S90,S213,S373) that could affect the binding to ICA512.Mutants,in which all four phosphoserines, were replaced by either asp or ala to mimic(S/D) or prevent(S/A) phosphorylation were expressed in INS-1 cells. All S/D mutants retained a cortical localization,but by immunoblotting the pattern of the S75D allele differed from wild type and all other S/D alleles.Conversely, all S/A alleles were diffused cytosolically, except S213A,which was still restricted to the cortex. Finally, pull down assays showed increased binding of ICA512 to the S75A and S90D alleles compared to wild type b2-syntrophin,while the opposite was observed with the S75D and S90A mutants.Additionally,both the S75 and the S213 allele conform a consensus for phosphorylation by Cdk5,which is known to modulate insulin secretion. The phosphorylation of GFP-b2-syntrophin and particularly the S75 allele by Cdk5 was exhibited with pharmacological inhibitors,by in vitro phosphorylation and by RNAi. Taken together, these findings are consistent with the model by which phosphorylation of b2-syntrophin modulates the tethering of SGs to the cytoskeleton, and thereby their mobility and exocytosis. Specifically, the data of this thesis suggest that Cdk5-dependent phosphorylation of the S75 site of GFP-b2-syntrophin facilitates insulin secretion by reducing the interaction of b2-syntrophin with ICA512,thereby decreasing the actin cytoskeleton constrain on SG mobility. This process could occur in combination with the phosphatase-dependent dephosphorylation of b2-syntrophin at phosphosites other than S75.Der Transport Insulin-gefüllter sekretorische Granula(SG) ist ein streng kontrollierter komplexer Prozess.Es gibt vermehrt Beweise,dass das kortikale Actinzytoskelett die Ausschüttung der SGs beeinflusst.Bisher ist der Mechanismus der Verankerung von SGs am Zytoskelett noch nicht vollständig aufgeklärt.Ort et al.(2000,2001) haben gezeigt,daß der zytosoplasmatische Teil des trans-membranen SG-Proteins ICA512 mit der PDZ-Domäne von b2-Syntrophin interagiert.Dieses Protein bindet das F-Actin-Bindeprotein Utrophin.Die Ergebnisse zeigen außerdem,daß durch Stimulation der SG-Exozytose der Phosphorilierungsstatus von b2-Syntrophin beeinflusst wird,woraus ein verändertes Bindungsvermögen zu ICA512 resultiert.Es wurde ein Funktionsmodel vorgestellt,in dem sich SGs durch die Interaktion des ICA512/b2-Syntrophin Komplexes an das Actinzytoskelett binden.Dabei wird die Bindedynamik durch Phosphorilierung reguliert.Um dieses Model zu etablieren,wurden stabile GFP-b2-Syntrophin produzierende INS-1-Zellklone erzeugt.Die zelluläre Lokalisation und das Expressionsmuster von GFP-b2-Syntrophin stimmen mit dem des endogenen Proteins überein.Elektronenmikroskopie zeigte eine größe Anzahl oval-verformter SGs in GFP-b2-Syntrophin INS-1-Zellen im Vergleich zu Kontrollzellen.Verglichen mit nicht-transfizierten INS-1 Zellen waren in drei GFP-b2-Syntrophin INS-1-Zellklonen der Insulingehalt der Zellen und die stimulierte Insulinsekretion erhöht.Die Werte korrelierten mit den unterschiedlichen GFP-b2-Syntrophin Expressionsmengen der Klone.Diese Ergebnisse untermauern die Hypothese,daß b2-Syntrophin den Transport und die Sekretion der SGs durch Modulation ihres Bindevermögens an Actin reguliert.Um das postulierte Model genauer zu prüfen,wurde die Phosphorilierung von b2-Syntrophin detaillierter untersucht.Das GFP-Protein wurde,ähnlich dem endogenen b2-Syntrophin,durch Stimulation der Insulinausschüttung dephosphoriliert.Diese Dephosphorilierung ist Ca2+-abhängig und Okadeinsäuresensitiv.Die stimulationsabhängige Dephosphorilierung wurde durch Immunoprezipitation von 32P-markiertem GFP-b2-Syntrophin bestätigt.Massenspektrometrie des präzipitierten Proteins ermöglichte die Identifikation von vier Serin-Phosphorilierungsstellen(S75,S90,S213,S373),welche die Bindung zu ICA512 beeinflussen könnten.Mutanten,in denen die vier Phosphoserine durch Asp beziehungsweise Ala ersetzt wurden,um entweder eine Phosphorilierung(S/D) oder Dephosphorilierung(S/A) nachzuahmen,wurden in INS-1-Zellen exprimiert.Alle S/D Mutanten blieben kortikal lokalisiert.Das Expressionsmuster des S75D Allels unterschied sich jedoch von denen des Wild-Typs(wt).Im Gegensatz dazu waren alle S/A Allele zytosolisch verteilt.Eine Ausnahme bildete S213A,das an der Zellkortex lokalisiert blieb.Im Vergleich zu wt b2-Syntrophin zeigten PullDown-Assays eine erhöhte Bindung von ICA512 zu den S75A und S90D Allelen.Das Gegenteil konnte für die S75D und S90A Mutanten nachgewiesen werden.S75,S90 und S213 sind in einer Konsensussequenz für Cdk5-Phosphorilierung enthalten.Diese Kinase kann die Insulinsekretion regulieren.Die Phosphorilierung von b2-Syntrophin,insbesondere des S75 Allels durch Cdk5 wurde durch pharmakologische Inhibitoren,in vitro-Phosphorilierung und RNAi demonstriert.Zusammenfassend stimmen diese Erkenntnisse mit dem Model überein,daß die Phosphorilierung von b2-Syntrophin die Vernetzung von SGs mit Actin und dadurch deren Mobilität und Exozytose moduliert.Im Speziellen postulieren die Ergebnisse dieser Arbeit eine Cdk5-abhängige Phosphorilierung der S75 Stelle des b2-Syntrophins.Durch eine verminderte Interaktion von b2-Syntrophin und ICA512 erleichtert diese Mutante vermutlich die Insulinsekretion,da der Einfluss des Actinzytoskeletts auf die Granulamobilität vermindert ist.Dieser Prozess ereignet sich möglicherweise in Kombination mit einer Dephosphorilierung des b2-Syntrophins.in Kombination mit einer Dephosphorilierung des b2-Syntrophins.
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Dargan, Sheila Louise. "Patch-clamp studies of single type-1 Ins(1,4,5)P3 receptor channels." Thesis, University of East Anglia, 2001. http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.393131.
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Nishi, Yuichi. "Role of mitochondrial phosphate carrier in metabolism-secretion coupling in rat insulinoma cell line INS-1." Kyoto University, 2011. http://hdl.handle.net/2433/151914.
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MOORE, ZACHARY W. Q. "APOLIPOPROTEIN E MODULATION OF VASCULAR SMOOTH MUSCLE CELL RESPONSE TO INJURY." University of Cincinnati / OhioLINK, 2005. http://rave.ohiolink.edu/etdc/view?acc_num=ucin1127219075.
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Zamani, Marzieh. "The role of the JNK/AP-1 pathway in the induction of iNOS and CATs in vascular cells." Thesis, University of Hertfordshire, 2013. http://hdl.handle.net/2299/10626.
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Nitric oxide (NO) is an important biological molecule within the body, which over production of this molecule in response to different stimulations can cause various inflammatory diseases. Over production of this molecule is caused by the induction of the inducible nitric oxide synthase (iNOS) enzyme. This enzyme uses L-arginine as a substrate and therefore the presence and transport of this amino acid into the cells can be a key factor in regulating NO over production. Different signalling mechanisms have been implicated in the regulation of this pathway and one of which involves the Mitogen Activated Protein Kinases (MAPK). This family of proteins respond to inflammatory conditions and may mediate effects induced by inflammatory mediators. Of the MAPKs, the role of the c-Jun-N-terminal kinase (JNK) pathway in the induction of iNOS is still controversial. JNK and its downstream target, the transcription factor Activator Protein-1 (AP-1), have shown contradictory effects on iNOS induction leading to controversies over their role in regulating iNOS expression in different cell systems or with various stimuli. The studies described in this thesis have determined the role of JNK/AP-1 on iNOS expression, NO production, L-arginine uptake and also on the transporters responsible for L-arginine transport into the cells. The studies were carried out in two different cell types: rat aortic smooth muscle cells (RASMCs) and J774 macrophages which are both critically associated with the over production of NO in vascular inflammatory disease states. The first approach was to block the expression of the inducible L-arginine-NO pathway using SP600125 and JNK Inhibitor VIII which are both pharmacological inhibitors of JNK. The results from these studies showed that the pharmacological intervention was without effect in RASMCs, but inhibited iNOS, NO and L-arginine transport in J774 macrophages. In contrast, the molecular approach employed using two dominant negative constructs of AP-1 (TAM-67 and a-Fos) revealed a different profile of effects in RASMCs, where a-Fos caused an induction in iNOS and NO while TAM-67 had an inhibitory effect on iNOS, NO, L-arginine transport and CAT-2B mRNA expression. The latter was unaffected in RASMCs but suppressed in J774 macrophages by SP600125. Examination of JNK isoforms expression showed the presence of JNK1 and 2 in both cell systems. Moreover, stimulation with LPS/IFN- or LPS alone resulted in JNK phosphorylation which did not reveal any difference between smooth muscle cells and macrophages. In contrast, expression and activation of AP-1 subunits revealed differences between the two cell systems. Activation of cells with LPS and IFN- (RASMCs) or LPS alone (J774 macrophages) resulted in changes in the activated status of the different AP-1 subunit which was different for the two cell systems. In both cell types c-Jun, JunD and Fra-1 were increased and in macrophages, FosB activity was also enhanced. Inhibition of JNK with SP600125 caused down-regulation in c-Jun in both cell types. Interestingly this down-regulation was in parallel with increases in the subunits JunB, JunD, c-Fos and Fra-1 in RASMCs or JunB and Fra-1 in J774 macrophages. Since, SP600125 was able to exert inhibitory effects in the latter cell type but not in RASMCs, it is possible that the compensatory up-regulation of certain AP-1 subunits in the smooth muscle cells may compensate for c-Jun inhibition thereby preventing suppression of iNOS expression. This notion clearly needs to be confirmed but it is potentially likely that hetero-dimers formed between JunB, JunD, c-Fos and Fra-1 could sustain gene transcription in the absence of c-Jun. The precise dimer required has not been addressed but unlikely to exclusively involve JunB and Fra-1 as these are up-regulated in macrophages but did not sustain iNOS, NO or induced L-arginine transport in the presence of SP600125. To further support the argument above, the dominant negatives caused varied effects on the activation of the different subunits. a-Fos down-regulated c-Jun, c-Fos, FosB, Fra-1 whereas TAM-67 reduced c-Jun and c-Fos but marginally induced Fra-1 activity. Associated with these changes was an up-regulation of iNOS-NO by a-Fos and inhibition by TAM-67. Taken together, the data proposes a complex mechanism(s) that regulate the expression of the inducible L-arginine-NO pathway in different cell systems and the complexity may reflect diverse intracellular changes that may be different in each cell type and not always be apparent using one experimental approach especially where this is pharmacological. Moreover, these findings strongly suggest exercising caution when interpreting pure pharmacological findings in cell-based systems particularly where these are inconsistent or contradictory.
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Hatfield, Meghan. "PROSTASIN IS EXPRESSED IN BENIGN PROSTATIC HYPERPLASIA AND REGULATES CELL PROLIFERATION AND INVASION VIA INOS, ICAM-1, AND CYCLI." Master's thesis, University of Central Florida, 2008. http://digital.library.ucf.edu/cdm/ref/collection/ETD/id/4260.
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ABSTRACT Prostasin is expressed in normal prostate epithelial cells but down-regulated in prostate cancers, while prostasin re-expression in invasive prostate cancer cells reduced invasion. We examined prostasin expression and function in benign prostatic hyperplasia (BPH). We evaluated prostasin expression in 12 BPH specimens by immunohistochemistry, and evaluated the impact of prostasin silencing by siRNA on the expression of the inducible nitric oxide synthase (iNOS), intercellular adhesion molecule-1 (ICAM-1), and cyclin D1, as well as on cell proliferation and invasion, using the BPH-1 human prostate epithelial cell line model. Prostasin expression was localized in the glands of BPH tissues by immunohistochemistry, in either the tall columnar-shaped or the flattened epithelial cells. We silenced prostasin expression by >50% at both the mRNA and protein levels using siRNA in the BPH-1 human prostate epithelial cell line, and this silencing of prostasin expression was associated with an induction of iNOS and ICAM-1 expression and a down-regulation of cyclin D1 expression. The protein expression of EGFR, a putative prostasin substrate, was not affected by prostasin silencing in this cell line. The prostasin-silenced cells displayed a reduced cell proliferation rate and reduced invasiveness, cell behaviors regulated by cyclin D1, iNOS, and ICAM-1 in the BPH-1 cells. We believe that this down-regulation of cyclin D1 is due to prostasin's augmentative effect on iNOS. We also believe that the decrease in cell motility is due to an increase in iNOS and ICAM-1 as well as a decrease in cyclin D1, since all of these molecules can play a role in cell motility. In conclusion, Prostasin is somehow involved in the regulation of inflammatory gene expression (iNOS and ICAM-1) in prostate epithelial cells, as well as cyclin D1 expression, cell proliferation and invasion, involving molecular mechanisms different than those in the prostate cancer cells. These studies suggest that prostasin is a player in the glandular components of benign prostatic hyperplasia.M.S.
Department of Molecular Biology and Microbiology
Burnett College of Biomedical Sciences
Molecular and Microbiology MS
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Garr, Edmund Dzigbordi. "JAK/STAT signalling in the induction of the L-arginine-nitric oxide pathway in macrophages and vascular smooth muscle cells." Thesis, University of Hertfordshire, 2014. http://hdl.handle.net/2299/13825.
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The production of Nitric Oxide (NO) under physiological conditions has beneficial roles in acting as a key signaling component of many biological processes as well as having an anti-microbial effect. However its effects following excess production by the inducible NO pathway is potentially detrimental in the pathogenesis of chronic inflammation including sepsis and several other inflammatory diseases. Understanding the mechanisms that regulate the expression of the inducible nitric oxide synthase (iNOS) responsible for producing the excessive amounts of NO in disease states is therefore critical. In this regards, experiments were carried out to identify the signaling pathways that may mediate this process, focusing specifically on the JAK/STAT cascade. The reason for selecting the latter is because our research group, amongst others, has carried out extensive work investigating other signaling pathways, including the mitogen activated kinases (MAPK). Moreover, studies have also been carried out in an attempt to identify the critical role of JAK/STAT signaling for iNOS induction. These studies however failed to conclusively demonstrate whether, as with the MAPKs, the JAK/STATs may also play an essential role. Furthermore there is indeed controversy in the literature with researchers unable to agree whether expression of iNOS does require JAK/STAT activation. Thus, the aim of the project described in this thesis was to establish unequivocally whether activation of the JAK/STATs preceeds induction of iNOS. The studies were extended to L-arginine transport as well because the latter is widely reported to be induced in parallel with iNOS and substrate supply to iNOS may be critical for sustained NO production. Changes in transporter activity as well as their expression profiles were assessed. All experiments were carried out in either rat aortic smooth muscle cells (RASMCs) or in the J774 macrophage cell line. These cell types were selected because RASMCs are one of the prime targets for induced NO production in vascular inflammation and the macrophages are involved in host defence, acting in part through NO production. To establish the role of JAK/STATs, pharmacological and molecular approaches were used. Pharmacologically, two inhibitors were used and these were AG490 and JAK inhibitor I. The former is reported to be a selective JAK2 inhibitor and the other blocks all known JAK proteins. The potential of the GTPases to regulate the induction of iNOS was also examined using selective inhibitor known to regulate these proteins. In addition to these drugs, siRNA targeting JAK2 was also exploited and western blotting was extensively used to detect expression of various proteins including iNOS, native and phosphorylated JAK2 and TYK2. Changes in iNOS activity was monitored by determining nitrite production using the Griess assay and L-arginine transport was monitored using tritiated arginine (L-[3H]arginine). RASMCs were treated with a combination of LPS (100 µg/ml) and IFN- (100 U/ml) and the macrophages with LPS (1 µg/ml) to induce iNOS and transporter activity. Consistent with previous reports, the above treatment of both cell types resulted in the expression of iNOS, production of NO and enhanced transport of L-arginine. These effects were not affected by AG490 but blocked by JAK inhibitor I. Furthermore, although both cell types expressed the key JAKs (JAK2 and TYK2), neither of these proteins were phosphorylated under conditions of induced NO production. Moreover, siRNA experiments showed that JAK2 expression could be abolished without any significant change in NO production, confirming that at least JAK2 may not be required for this process. Whether TYK2 is involved still remains to be resolved as the phosphor-protein could not be detected. However the conclusive siRNA knockdown studies could not be carried out due to time and cost constraints. Apart from iNOS and NO production, changes in induced L-arginine transport were also not significantly affected under the experimental conditions described above suggesting that like with iNOS, induction of L-arginine transport is independent of at least JAK2. Interestingly however, STAT-1 was phosphorylated and this was blocked by JAK inhibitor I but not AG490. Thus, STAT-1 activation may be essential but its activation may be independent of the JAKs. One possible alternate upstream activator of STAT-1 may be the GTPases. Indeed these proteins have been indicated to phosphorylate STAT-1 independent of the JAKs. However, in this project, inhibition of the GTPase pathway enhanced NO production and L-arginine transport suggesting that the GTPases downregulate these processes. In conclusion, the studies carried out in this thesis have shown that induction of iNOS, NO production and L-arginine transport in both RASMCs and J774 macrophages are independent of JAK2 but require STAT-1 activation which may be phosphorylated independently of the JAKs. The role of other JAKs such as TYK2 although unlikely, will need to be resolved using a more specific approach such as siRNA.
Books on the topic "INS-1 cells"
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Moerdler, Scott, and Xingxing Zang. PD-1/PDL-1 Inhibitors as Immunotherapy for Ovarian Cancer. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190248208.003.0010.
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Programmed death 1 (PD-1), a member of the B7-CD28 immunoglobulin superfamily, and its ligands PD-L1/PD-L2 inhibit T-cell activation. They also play a key role in the tumor microenvironment, allowing for cancer immune escape. PD-1 is induced on a variety of immune cells, including tumor-infiltrating lymphocytes (TILs), while PD-L1 is found on many types of solid tumors including ovarian cancer and some TILs. The use of immunocheckpoint inhibitors like anti-PD-1 and anti-PD-L1 therapies has been shown to reactivate the immune system to attack tumor cells. Ovarian cancers have been shown to be responsive to anti-PD-1 and anti-PD-L1 therapies, though immunocheckpoint inhibitors are not enough. Current research is evaluating combination therapies to improve response rates.
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Ng, Ann, and Erin S. Williams. Sickle Cell Disease. Edited by Erin S. Williams, Olutoyin A. Olutoye, Catherine P. Seipel, and Titilopemi A. O. Aina. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190678333.003.0033.
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Sickle cell anemia (sickle cell disease) is a common hemoglobinopathy with anywhere from 90,000 to 100,000 Americans affected. This chronic condition has a predominance in populations of African descent, occurring in approximately 1 out of 365 African American births, compared to 1 out of 16,300 Hispanic births. The sickle cell trait can be detected in 1 of 13 African American births. One of the most common complications associated with sickle cell anemia, vaso-occlusive crises by sickled cells, results in severe pain. Other issues associated with this condition include acute chest syndrome, lung infections, end organ damage, and stroke. With improvements in the management and prevention of pain crises, infection, and other systemic involvement, these patients are living longer, thus increasing the potential for surgical needs. Whether it is for routine surgeries or surgeries that are due to the natural history of the disease; the pediatric anesthesiologist must be knowledgeable of the management of these patients in order to prevent morbidity and mortality.
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Kamdar, Pravin P. Numerical simulation of Al [subscript x] Ga [subscript 1-x] As/GaAs and (Al [subscript x] Ga [subscript 1-x]) [subscript 0.47] In [subscript 0.53] As/InP bandgap engineered solar cells. 1990.
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Badimon, Lina, and Gemma Vilahur. Atherosclerosis and thrombosis. Oxford University Press, 2015. http://dx.doi.org/10.1093/med/9780199687039.003.0040.
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Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the extracellular matrix and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated monocytes differentiate into macrophages which acquire a specialized phenotypic polarization (protective or harmful), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoprotein via low-density lipoprotein receptor-related protein-1 receptors. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Both lipid-laden vascular smooth muscle cells and macrophages release the procoagulant tissue factor, contributing to thrombus propagation. Platelets also participate in progenitor cell recruitment and drive the inflammatory response mediating the atherosclerosis progression. Recent data attribute to microparticles a potential modulatory effect in the overall atherothrombotic process. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be modulated.
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Moriuchi, Hiroyuki. Human T-cell Lymphotropic Virus. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780190604813.003.0010.
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Human T-cell lymphotropic virus type 1 (HTLV-1), a human retrovirus that infects an estimated 10–20 million people worldwide, has endemic foci in Japan, West and Central Africa, the Caribbean, Central and South America, and Melanesia. Also, it is the etiological agent of a lymphoproliferative malignancy, adult T-cell leukemia/lymphoma (ATLL), as well as chronic inflammatory diseases such as HTLV-1-associated myelopathy/tropical spastic paraparesis (HAM/TSP). HTLV-1 can be transmitted vertically, sexually, or by blood-borne transmission. ATLL occurs in approximately 5% of carriers who are infected during early childhood, and primary prevention is the only strategy likely to reduce this fatal disease. Children born to carrier mothers acquire the virus predominantly from breastfeeding. In endemic areas, mother-to-child transmission (MTCT) can be significantly reduced by screening pregnant women for the HTLV-1 antibody, followed by replacing breastfeeding with exclusive formula feeding. Indications for serological screening and recommendations for prevention of perinatal transmission are reviewed in this chapter.
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Hartigan-O’Connor, Dennis J., and Christian Brander. Immunology. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780190493097.003.0005.
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The key factor in HIV pathogenesis is the decline in CD4+ T cells with resultant immunodeficiency and chronic inflammation. Depletion of CD4+ T cells from the gastrointestinal mucosa followed by microbial translocation and subsequent immune activation are components of disease progression in untreated patients. Symptomatic and occult opportunistic infections including cytomegalovirus contribute to chronic inflammation in persons infected with HIV. Antiretroviral therapy (ART) results in immune reconstitution, with increases in peripheral CD4+ T cell lymphocytes in most persons infected with HIV, although immune recovery is quite variable. A subset of patients with AIDS will develop immune reconstitution inflammatory syndromes after initiation of ART. Approximately 1% of persons with HIV are able to control infection without the need for ART (“elite” controllers). A variety of immune-based therapies, including hydroxyurea, growth hormone, and statins, are being studied in clinical trials and may ultimately play a role in treating persons with HIV infection.
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Badimon, Lina, and Gemma Vilahur. Atherosclerosis and thrombosis. Oxford University Press, 2017. http://dx.doi.org/10.1093/med/9780199687039.003.0040_update_001.
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Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the intimal layer and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles attached to the extracellular matrix suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated pro-atherogenic monocytes (mainly Mon2) differentiate into macrophages which acquire a specialized phenotypic polarization (protective/M1 or harmful/M2), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoproteins via low-density lipoprotein receptor-related protein-1 receptors becoming foam cells. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels and calcium deposits increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces rich in tissue factor that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Platelets also participate in leucocyte and progenitor cell recruitment are likely to mediate atherosclerosis progression. Recent data attribute to microparticles a modulatory effect in the overall atherothrombotic process and evidence their potential use as systemic biomarkers of thrombus growth. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be prevented and modulated.
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Badimon, Lina, and Gemma Vilahur. Atherosclerosis and thrombosis. Oxford University Press, 2018. http://dx.doi.org/10.1093/med/9780199687039.003.0040_update_002.
Full textAbstract:
Atherosclerosis is the main underlying cause of heart disease. The continuous exposure to cardiovascular risk factors induces endothelial activation/dysfunction which enhances the permeability of the endothelial layer and the expression of cytokines/chemokines and adhesion molecules. This results in the accumulation of lipids (low-density lipoprotein particles) in the intimal layer and the triggering of an inflammatory response. Accumulated low-density lipoprotein particles attached to the extracellular matrix suffer modifications and become pro-atherogenic, enhancing leucocyte recruitment and further transmigration across the endothelium into the intima. Infiltrated pro-atherogenic monocytes (mainly Mon2) differentiate into macrophages which acquire a specialized phenotypic polarization (protective/M1 or harmful/M2), depending on the stage of the atherosclerosis progression. Once differentiated, macrophages upregulate pattern recognition receptors capable of engulfing modified low-density lipoprotein, leading to foam cell formation. Foam cells release growth factors and cytokines that promote vascular smooth muscle cell migration into the intima, which then internalize low-density lipoproteins via low-density lipoprotein receptor-related protein-1 receptors becoming foam cells. As the plaque evolves, the number of vascular smooth muscle cells decline, whereas the presence of fragile/haemorrhagic neovessels and calcium deposits increases, promoting plaque destabilization. Disruption of this atherosclerotic lesion exposes thrombogenic surfaces rich in tissue factor that initiate platelet adhesion, activation, and aggregation, as well as thrombin generation. Platelets also participate in leucocyte and progenitor cell recruitment are likely to mediate atherosclerosis progression. Recent data attribute to microparticles a modulatory effect in the overall atherothrombotic process and evidence their potential use as systemic biomarkers of thrombus growth. This chapter reviews our current understanding of the pathophysiological mechanisms involved in atherogenesis, highlights platelet contribution to thrombosis and atherosclerosis progression, and provides new insights into how atherothrombosis may be prevented and modulated.
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Pitzalis, Costantino, Frances Humby, and Michael P. Seed. Synovial pathology. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199642489.003.0052.
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Synovial pathology is seen in a variety of disease states, including rheumatoid arthritis (RA), osteoarthritis (OA), psoriatic arthritis, and systemic lupus erythmatosus (SLE). This chapter highlights recent advances that characterize the cellular composition of these tissues according to surface markers and chemokine and cytokine expression, and describes synovial functional status and response to therapeutics. In RA, after initiation, pannus migrates over and under cartilage, and into subchondral bone, in a destructive process. Cartilage-pannus junction (CPJ) is characterized as invasive or 'quiescent' or 'indistinct'. Invasive CPJ can comprise macrophages, fibroblast-like synoviocytes (FLS), mast cells, and/or neutrophils. CPJ activity is related to the state of activation of the overlying subintima. Subintimal inflammation can be graded to a variety of degrees (I–IV) according to established criteria and is illustrated. In some RA synovia, cellular aggregates organize into ectopic lymphoid structures (ELS) through the expression of lymphorganogenic signals, to exhibit T- or B-cell zones accompanied by dendritic cells and lymphangiogenesis. ELS synthesize rheumatoid factor (RF) and anti-citrullinated peptide antibodies (ACAP), considered to be indicative of aggressive disease. The selective cellular expression of macrophage and dendritic cell chemokines and cytokines such as TNF, GMCSF, TGFβ, IL-1, IL-6, IL-23, and chemokines can be seen in synovia, to form a regulated and cooperative environment that sustains the cellular organization and pathological function. Important to this process are FLS and CD68+ macrophages. CD68 expression correlates with disease severity and can be useful as a surrogate marker of disease modifying activity of therapeutics, such as anti-TNF and anti-B-cell biologics.
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Kriemler, Susi. Exercise, physical activity, and cystic fibrosis. Oxford University Press, 2013. http://dx.doi.org/10.1093/med/9780199232482.003.0033.
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Cystic fibrosis (CF) is the most common genetic autosomal recessive disease of the Caucasian race, generally leading to death in early adulthood.1 The frequency of the gene carrier (heterozygote) is 1:20–25 in Caucasian populations, 1:2000 in African-Americans, and practically non-existent in Asian populations. The disease occurs in about 1 in every 2500 life births of the white population. Mean survival has risen from 8.4 years in 1969 to 32 years in 2000 due to improvements in treatment. The genetic defect causes a pathological electrolyte transport through the cell membranes by a defective chloride channel membrane transport protein [cystic fibrosis transmembrane conductance regulator (CFTR)]. With respect to the function, this affects mainly the exocrine glands of secretory cells, sinuses, lungs, pancreas, liver, and the reproductive tract of the human body leading to a highly viscous, water-depleted secretion. The secretion cannot leave the glands and in consequence causes local inflammation and destruction of various organs. The main symptoms include chronic inflammatory pulmonary disease with a progressive loss of lung function, exocrine and sometimes endocrine pancreas insufficiency, and an excessive salt loss through the sweat glands.1 A summary of the signs and symptoms of CF will be given with a special emphasis on the effect of exercise performance and capacity.
Book chapters on the topic "INS-1 cells"
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Sazeides, Christos, and Anne Le. "Metabolic Relationship Between Cancer-Associated Fibroblasts and Cancer Cells." In The Heterogeneity of Cancer Metabolism, 189–204. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-65768-0_14.
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AbstractCancer-associated fibroblasts (CAFs), a major component of the tumor microenvironment (TME), play an important role in cancer initiation, progression, and metastasis. Recent findings have demonstrated that the TME not only provides physical support for cancer cells but also directs cell-to-cell interactions (in this case, the interaction between cancer cells and CAFs). As cancer progresses, the CAFs also coevolve, transitioning from an inactivated state to an activated state. The elucidation and understanding of the interaction between cancer cells and CAFs will pave the way for new cancer therapies [1–3].
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Jung, Jin G., and Anne Le. "Targeting Metabolic Cross Talk Between Cancer Cells and Cancer-Associated Fibroblasts." In The Heterogeneity of Cancer Metabolism, 205–14. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-65768-0_15.
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AbstractAlthough cancer has classically been regarded as a genetic disease of uncontrolled cell growth, the importance of the tumor microenvironment (TME) [1, 2] is continuously emphasized by the accumulating evidence that cancer growth is not simply dependent on the cancer cells themselves [3, 4] but also dependent on angiogenesis [5–8], inflammation [9, 10], and the supporting roles of cancer-associated fibroblasts (CAFs) [11–13]. After the discovery that CAFs are able to remodel the tumor matrix within the TME and provide the nutrients and chemicals to promote cancer cell growth [14], many studies have aimed to uncover the cross talk between cancer cells and CAFs. Moreover, a new paradigm in cancer metabolism shows how cancer cells act like “metabolic parasites” to take up the high-energy metabolites, such as lactate, ketone bodies, free fatty acids, and glutamine from supporting cells, including CAFs and cancer-associated adipocytes (CAAs) [15, 16]. This chapter provides an overview of the metabolic coupling between CAFs and cancer cells to further define the therapeutic options to disrupt the CAF-cancer cell interactions.
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Jung, Jin G., and Anne Le. "Metabolism of Immune Cells in the Tumor Microenvironment." In The Heterogeneity of Cancer Metabolism, 173–85. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-65768-0_13.
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AbstractThe tumor microenvironment (TME) is a complex biological structure surrounding tumor cells and includes blood vessels, immune cells, fibroblasts, adipocytes, and extracellular matrix (ECM) [1, 2]. These heterogeneous surrounding structures provide nutrients, metabolites, and signaling molecules to provide a cancer-friendly environment. The metabolic interplay between immune cells and cancer cells in the TME is a key feature not only for understanding tumor biology but also for discovering cancer cells’ vulnerability. As cancer immunotherapy to treat cancer patients and the use of metabolomics technologies become more and more common [3], the importance of the interplay between cancer cells and immune cells in the TME is emerging with respect to not only cell-to-cell interactions but also metabolic pathways. This interaction between immune cells and cancer cells is a complex and dynamic process in which immune cells act as a determinant factor of cancer cells’ fate and vice versa. In this chapter, we provide an overview of the metabolic interplay between immune cells and cancer cells and discuss the therapeutic opportunities as a result of this interplay in order to define targets for cancer treatment. It is important to understand and identify therapeutic targets that interrupt this cancerpromoting relationship between cancer cells and the surrounding immune cells, allowing for maximum efficacy of immune checkpoint inhibitors as well as other genetic and cellular therapies.
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Brownbill, Robert, and Adam Roberts. "Development of a Low-Cost, High Accuracy, Flexible Panel Indexing Cell with Modular, Elastic Architecture." In IFIP Advances in Information and Communication Technology, 168–83. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-72632-4_12.
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AbstractThe global aerospace industry is driving a demand for flexible manufacturing systems to accommodate multiple programs with variable capacities within a modular, economical production cell [1]. Traditional manufacturing cells often involve bespoke, monolithic hardware limited to single program use. This inherent restraint results in significant incurred costs and program disruption when reacting to design and capacity changes. This paper describes the development of a reconfigurable panel-indexing cell with a dynamic cost architecture as an alternative approach to established, monolithic tooling structures.
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Park, Joshua K., Nathan J. Coffey, Aaron Limoges, and Anne Le. "The Heterogeneity of Lipid Metabolism in Cancer." In The Heterogeneity of Cancer Metabolism, 39–56. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-65768-0_3.
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AbstractThe study of cancer cell metabolism has traditionally focused on glycolysis and glutaminolysis. However, lipidomic technologies have matured considerably over the last decade and broadened our understanding of how lipid metabolism is relevant to cancer biology [1–3]. Studies now suggest that the reprogramming of cellular lipid metabolism contributes directly to malignant transformation and progression [4, 5]. For example, de novo lipid synthesis can supply proliferating tumor cells with phospholipid components that comprise the plasma and organelle membranes of new daughter cells [6, 7]. Moreover, the upregulation of mitochondrial β-oxidation can support tumor cell energetics and redox homeostasis [8], while lipid-derived messengers can regulate major signaling pathways or coordinate immunosuppressive mechanisms [9–11]. Lipid metabolism has, therefore, become implicated in a variety of oncogenic processes, including metastatic colonization, drug resistance, and cell differentiation [10, 12–16]. However, whether we can safely and effectively modulate the underlying mechanisms of lipid metabolism for cancer therapy is still an open question.
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Li, Ting, Christopher Copeland, and Anne Le. "Glutamine Metabolism in Cancer." In The Heterogeneity of Cancer Metabolism, 17–38. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-65768-0_2.
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AbstractMetabolism is a fundamental process for all cellular functions. For decades, there has been growing evidence of a relationship between metabolism and malignant cell proliferation. Unlike normal differentiated cells, cancer cells have reprogrammed metabolism in order to fulfill their energy requirements. These cells display crucial modifications in many metabolic pathways, such as glycolysis and glutaminolysis, which include the tricarboxylic acid (TCA) cycle, the electron transport chain (ETC), and the pentose phosphate pathway (PPP) [1]. Since the discovery of the Warburg effect, it has been shown that the metabolism of cancer cells plays a critical role in cancer survival and growth. More recent research suggests that the involvement of glutamine in cancer metabolism is more significant than previously thought. Glutamine, a nonessential amino acid with both amine and amide functional groups, is the most abundant amino acid circulating in the bloodstream [2]. This chapter discusses the characteristic features of glutamine metabolism in cancers and the therapeutic options to target glutamine metabolism for cancer treatment.
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Ayodele, Olubukola, and Lillian L. Siu. "New Drugs for Recurrent or Metastatic Nasopharyngeal Cancer." In Critical Issues in Head and Neck Oncology, 337–52. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-63234-2_23.
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AbstractChemotherapy has been the backbone for the treatment of recurrent or metastatic nasopharyngeal carcinoma (RMNPC), which remains an incurable disease. Currently the most active area of therapeutic investigations in RMNPC is in immunotherapy, especially after the results of five anti-programmed death-1 (anti-PD-1) antibodies, i.e. pembrolizumab, nivolumab, camrelizumab, toripalimab and tislelizumab, have demonstrated monotherapy objective response rates of 21%–43%. Combinations using anti-PD1/L1 antibodies as backbone to evaluate their additivity or synergy with cytotoxic chemotherapy, molecularly targeted agents, or other immuno-oncology compounds are actively being developed. Besides immune checkpoint blockade, additional ways to modulate the host immune system, such as Epstein-Barr virus (EBV)-directed vaccination against viral antigens (such as EBNA1, LMP1, LMP2) with dendritic cells or peptides, adoptive cell transfer of autologous or HLA-matched allogeneic EBV-specific cytotoxic T lymphocytes, CAR or TCR T-cell therapy, personalized cancer vaccines and oncolytic viruses are being explored. Finally, novel molecularly targeted agents that have entered human testing in RMNPC include apatinib and anlotinib (antiangiogenic agents), MAK683 (an embryonic ectoderm development or EED protein inhibitor), among others. This review provides an update of ongoing clinical trials evaluating these new compounds in RMNPC.
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Rischin, Danny. "Biomarkers for Immune Modulatory Treatment in Head and Neck Squamous Cell Carcinoma (HNSCC)." In Critical Issues in Head and Neck Oncology, 83–91. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-63234-2_6.
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AbstractImmune checkpoint inhibitors have changed the standard of care for recurrent/metastatic head and neck squamous cell carcinoma (R/M HNSCC). However, only a minority of patients respond, hence the search for predictive biomarkers. Potential predictive biomarkers for immune checkpoint inhibitors discussed in this chapter include (1) Immune checkpoint ligand expression e.g., PD-L1, (2) biomarkers of a T-cell inflamed tumour microenvironment (TME) such as gene expression profiles of activated T cells, (3) biomarkers of tumour neoepitope burden such as tumour mutation burden (TMB) and (4) multidimensional quantitative techniques. At present only PD-L1 expression has been shown to have clinical utility in head and neck cancer. It enriches for populations more likely to respond, but the false positive predictive value remains high. In the pivotal Keynote−048 trial that established a role for pembrolizumab (anti-PD1) monotherapy and pembrolizumab + chemotherapy as treatment options in first-line R/M HNSCC, primary endpoints included overall survival in defined subgroups based on PD-L1 expression. In this trial the combined positive score (CPS) was used which takes into account PD-L1 expression in tumour and immune cells. Based on this trial regulatory approvals for first-line pembrolizumab in R/M HNSCC require assessment of PD-L1 expression using the CPS. Finally we discuss emerging evidence that locoregionally advanced HPV-associated oropharyngeal cancers that have high expression of CD103 positive CD8 T cells have an excellent prognosis and features that suggest increased probability of responding to anti-PD1/PD-L1, raising the possibility of incorporating these immune therapies as part of a de-escalation trial strategy.
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Alvina, Fidelia B., Arvin M. Gouw, and Anne Le. "Cancer Stem Cell Metabolism." In The Heterogeneity of Cancer Metabolism, 161–72. Cham: Springer International Publishing, 2021. http://dx.doi.org/10.1007/978-3-030-65768-0_12.
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AbstractCancer stem cells (CSCs), also known as tumorinitiating cells (TICs), are a group of cells found within cancer cells. Like normal stem cells, CSCs can proliferate, engage in self-renewal, and are often implicated in the recurrence of tumors after therapy [1, 2]. The existence of CSCs in various types of cancer has been proven, such as in acute myeloid leukemia (AML) [3], breast [4], pancreatic [5], and lung cancers [6], to name a few. There are two theories regarding the origin of CSCs. First, CSCs may have arisen from normal stem/progenitor cells that experienced changes in their environment or genetic mutations. On the other hand, CSCs may also have originated from differentiated cells that underwent genetic and/or heterotypic modifications [7]. Either way, CSCs reprogram their metabolism in order to support tumorigenesis.
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Janoudi, Nahid, and Ammar AlDabbagh. "The Blood in Rheumatology." In Skills in Rheumatology, 291–308. Singapore: Springer Singapore, 2021. http://dx.doi.org/10.1007/978-981-15-8323-0_13.
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AbstractHematologic disorders including anemia, white blood cells abnormalities, platelet abnormalities, coagulopathy, and hematologic malignancies can be manifested in many autoimmune rheumatic diseases [1].
Conference papers on the topic "INS-1 cells"
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Kongsuphol, Patthara, Fang Kok Boon, and Tushar Bansal. "Recording I–V signals from INS-1 Cells using silicon based patch clamp device." In 2012 7th IEEE Conference on Industrial Electronics and Applications (ICIEA). IEEE, 2012. http://dx.doi.org/10.1109/iciea.2012.6361010.
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Juhan-Vague, I., P. Vague, M. C. Alessi, C. Atlan, J. Valadier, and C. Badier. "PARALLEL VARIATIONS OF PLASMA INSULIN, TRIGLYCERIDE AND PLASMINOGEN ACTIVATOR INHIBITOR 1 (PAI 1) LEVELS IN OBESE NON DIABETIC SUBJECTS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1644456.
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We had shown in non diabetic healthy subjects with Body Mass Index (BMI) varying largely, a significant correlation (r) between PAI activity levels and BMI : (r=0.66) and insulinemia (r=0.52).PAI levels were then studied in non diabetic Obese women (0)(n=50) and in age matched healthy women with normal BMI (N) (m ± SEM) = 0 versus N : BMI : 33.4± 0.8/ 20.2± 0.8 ; plasma insulin (Ins -uu/ml) : 22.7±1.5/12±1; Triglyceride(TG-mmol/1):1.240.09/0.8±0.1.The low value of euglobulin fibrinolytic activity (EFA) in Obese was due to high levels of PAI 1 : 0 versus N : EFA (mm) : 5.2 ±0.3/ 9 ±0.3 ; PAI activity (PAIact.- Verheijen's method-u/ml) :14 ± 2.1/5.04 ±0.6 -(p 0.01). In 10 0 and 10 N PAIact and PAI 1 antigen (PAI 1 Ag- Kruithof's method-ng/ml) were determined in parallel : 0 versus N : PAIact.: 29.4±3.8/ 5.8±0.9 ; PAI 1 Ag : 100±14.2/19.7 ±1.7, (p0.01). In Obesegroup correlations between, PAIact. and BMI (r=0.51), and insulin (r=0.69) and Triglyceride (r=0.48) were significant (p 0.01).When in Obese subjects, insulinemia was decreased by 24 hours Fast (n=10) or by 15 days Metformin treatment (1.7g/day) (n=9), PAI activity (measured on fibrin plates)decreased significantly in a parallel way : compared to initial values -after 24 hours Fast =Ins : 75 %, PAIact. 73% -after Metformin treatment=Ins :75%, PAIact. :57%, TG :73%.From these results, a direct action of insulin on the synthesis cells of PAI 1 could be evoked. An effect of Triglyceride levels cannot be excluded, the variation of Triglyceride, insulin, PAI levels being parallel.As hyperinsulinemia, hypertriglyceridemia are risk factors for atherothrombosis, as there is a link between insulin, triglyceride, PA Inhibitor 1 levels, the pathogenic role of hyperinsulinemia and hypertriglyceridemia in the development of atherothrombosis could be in part mediated by plasma hypofibrinolysis due to high level of PAI 1.
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Demolle, D., E. J. Cragoe, and J. M. Boeynaems. "MECHANISMS INVOLVED IN 5-HT STIMULATION OF PROSTACYCLIN PRODUCTION BY BOVINE AORTIC SMOOTH MUSCLE CELLS." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1642841.
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Serotonin (5-HT) stimulates prostacyclin (PGI2) production by bovine aortic smooth muscle cells in culture via 5-HT2 receptors (1). These cells express a synthetic phenotype (2), whereas the majority of the smooth muscle cells in the media from adult arteries are in a contractile state. We have now shown that 5-HT (1-10 μM) also stimulates PGI2 production by a preparation of contractile smooth muscle cells : explants from bovine aortic media cultured for short periods. This effect is independent from 5-HT2 receptors : it is only partially inhibited (±30%) by ketan-serin (a selective and potent 5-HT2 antagonist) and is perfectly mimicked by a 5-HT1 agonist, 5-carboxamidotryptamine. 5-HT2 receptors seem to be linked to a phospholipase C (3), with subsequent accumulation of inositol tr isphosphate , Ins(1,4,5)P3, and diacylglycerol, an activator of protein kinase C. We have observed a stimulatory effect of phorbol 12-myristate, 13-acetate (a selective activator of kinase C) on PGI2 production by the bovine aortic smooth muscle cells (synthetic state), whereas it was totally ineffective on media explants preparation (contractile state). Furthermore, in the smooth muscle cells in culture, the 5-HT effect can be inhibited by (ethyl-isopropyl)amiloride, a potent and selective inhibitor of the Na+/H+ antiporter. In conclusion it appears that the regulation mechanisms of PGI2 production in arterial smooth muscle cells are strongly dependent an the phenotypic state of these cells. The control of PGI2 release via 5-HT2 receptors seems to involve a cytoplasmic alkalinization, via the activation of protein kinase C. The mechanism of 5-HT action in the media explants remains to be elucidated.(1) Coughlin, S.R. et al.: Proc . Natl. Acad. Sci. USA 78(11), 7134-7138, 1981.(2) Chamley-Campbell, J.H. and Campbell, G.K.: Atherosclerosis 40, 347-357, 1981.(3) Roth, B.L. et al.: J. Pharm. Exp. Ther. 238(2), 480-485, 1986.
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Aguilar, L., F. Newman, I. Serdiukova, C. Monier, M. F. Vilela, A. Freundlich, A. Delaney, and S. Street. "Improvement and optimization of InAs[sub x]P[sub 1−x]/InP multi quantum well solar cells." In Space technology and applications international forum - 1998. AIP, 1998. http://dx.doi.org/10.1063/1.54940.
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Sheets, Kevin, and Amrinder Nain. "Cell Shape Control and Related Focal Adheshion Dynamics on Aligned Fiber Networks." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80917.
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Cellular elasticity, a measure of a cell’s resistance to changing its shape in response to external stimuli, has been shown in the recent past to be a potential indicator of cell health [1]. A variety of methods including AFM techniques [1, 2], magnetic/optical tweezers [3, 4], and micropillar arrays [6–8] have been used to quantify cellular elasticity to identify cell disease state, including stages of progression in cancerous cells. Since cellular behavior is heavily dependent on the physical nature of the surrounding extracellular matrix (ECM), understanding mechanical cell-substrate interactions may lead to connections between the elasticity of a cell and the cell’s health state [1]. In this study, the STEP (Spinneret-based Tunable Engineered Parameters) technique is used to create suspended nanofibrous polystyrene substrates with tight control on fiber diameter and spacing in single and multiple layers. As cells interact with these various substrates, they take on repeatable configurations and allow the probing of biophysical traits. Specifically, cytoskeletal arrangements provide information on the behavior of the cell nucleus, f-actin stress fibers, and focal adhesions via paxillin staining, which allow for calculation of cellular elasticity.
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Tanizuka, Noboru. "The power spectrum of 1/f noise in biological cells and discharge cells." In Noise in physical systems and 1/. AIP, 1993. http://dx.doi.org/10.1063/1.44634.
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Wilson, Jim R., and Neil A. Duncan. "Modelling the Ion Channel Behaviour of Articular Chondrocytes." In ASME 2002 International Mechanical Engineering Congress and Exposition. ASMEDC, 2002. http://dx.doi.org/10.1115/imece2002-32661.
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All cells have a membrane potential; this voltage difference arises from the different intracellular and extracellular ion concentrations. In excitable tissue the cell membranes contain ion channels which control the movement of ions and hence control the cell’s membrane potential. Extensive measurements of the electrophysiology of excitable cells has allowed considerable understanding of the ion channels. The Hodgkin-Huxley model [1] was developed from measurements on a squid nerve axon, and it quantifies the changes in membrane conductance due to the opening and closing of specific ion channels. This model has been very successful in describing the electrical behaviour of neurons. Ion channels also exist in non-excitable tissue cells. Patch clamp experiments have demonstrated that ion channels in chondrocytes influence cell’s membrane potential [2]; controls the influx of Ca2+ [3] and may regulate cell proliferation [2]. The objective of this research was to develop a model of ion channel behaviour for connective tissue cells based on the Hodgkin-Huxley model, and to apply this model to reported patch clamp measurements of articular chondrocytes.
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Szatmary, Alex C., Rohan J. Banton, and Charles D. Eggleton. "Deformation of White Blood Cells Firmly Adhered to Endothelium." In ASME 2012 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2012. http://dx.doi.org/10.1115/sbc2012-80894.
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Circulating white blood cells adhere to endothelium near an infection site; this occurs because infection causes ligands to be expressed on activated endothelium. Initially, a white blood cell rolls on the substrate, but eventually forms a firm adhesion, allowing it to crawl through the endothelial layer toward the infected tissue. A computational model of bond kinetics, cell deformability, and fluid dynamics was used to model the forces experienced by a cell during this process. The cell was modeled as a fluid-filled membrane; on its surface were hundreds of deformable microvilli—little fingers, ruffles in the white blood cell’s wrinkly membrane. These microvilli were deformable and their tips were decorated with PSGL-1 chemical receptors which bound to P-selectin ligands on the surface. Softer cells and cells subjected to higher fluid shear stress deformed more, and having more contact area, they formed more bonds and were able to resist more hydrodynamic load.
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Schiele, Nathan R., Douglas B. Chrisey, and David T. Corr. "Novel Method of Laser Direct Writing for Precise Patterning of Human Dermal Fibroblasts." In ASME 2010 Summer Bioengineering Conference. American Society of Mechanical Engineers, 2010. http://dx.doi.org/10.1115/sbc2010-19675.
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The ability to control a cell’s location, pattern geometry, and proximity to neighboring cells, in vitro, is highly desired to gain insight into cell-cell interactions, such as the modes of cellular signaling (direct cell contact, paracrine, or endocrine). A laser-based cell patterning technique, laser direct write, enables the precise spatial placement of living cells, with all the advantages of CAD/CAM control [1]. However, this technique is limited in usefulness due to the dependence on Matrigel® (BD Biosciences, Bedford, MA). The growth factor constituents of Matrigel® may interfere with many cellular processes under investigation and may preclude or greatly limit the utility of laser direct writing for precise cell cultures [2]. Therefore, to address this limitation, the objective of this study was to develop a Matrigel®-free laser direct writing method. Through the use of customized gelatin coatings on both the ribbon and receiving substrate, we effectively adapted the direct write technique to precisely pattern cells without the use of Matrigel®, as demonstrated with human dermal fibroblasts. The gelatin partially encapsulates the trypsinized cells on the ribbon, providing a volitization zone to protect the cells, and on the receiving substrate cushions the impact of transfer while maintaining moisture. Gelatin liquefies at 37°C, which allows it to be removed from the growth surface ensuring cellular proliferation, uninhibited by growth surface treatments. This represents a fundamental change from the original direct write technique in which cells must first form initial attachments to the ribbon via Matrigel® and then are written to a Matrigel® coated receiving substrate for their sustained growth. Additionally, we have developed a method to monitor the location of the patterned cells post-transfer to show that a gelatin coated-receiving substrate is effective as a patterning surface and ensures the registry of the pattern until cell attachment, even after the gelatin has been removed with the first growth medium application. This precise patterning technique can now be used in many biomedical applications, including those that involve cell types highly sensitive to growth factors, such as stem cells and cancer cells.
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de Agostini, A., J. Marcum, and R. Rosenberg. "THE BINDING OF ANTITHROMBIN TO CAPILLARY ENDOTHELIAL CELLS GROWN IN VITRO." In XIth International Congress on Thrombosis and Haemostasis. Schattauer GmbH, 1987. http://dx.doi.org/10.1055/s-0038-1643343.
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Cloned endothelial cells from rat epididymal fat pads synthesize anticoagulantly active heparan sulfate proteoglycans containing the disaccharide, GlcA→ AMN-3,6-O-SO3, which is a marker for the antithrombin-binding domain of heparin. To demonstrate that antithrombin (AT) binds to cell surface heparan sulfate, a binding assay employing 125I-AT and cell monolayers has been developed. Post-confluent endothelial cells (7 days) were incubated with radiolabeled AT for 1 h at 4° and washed with PBS. Bound radioactivity was quantitated after solubilizing whole cells. Under these conditions, ∼1% (2174±50 cpm/5x104 cells) of the 125I-AT bound to the endothelial cell monolayer, whereas none of the radiolabeled protein bound to CHO cells or bovine smooth muscle cells. Utilization of unlabeled AT (1 μM) in experiments conducted as described above resulted in a reduction (73%) of the binding of the labeled species to endothelial cells. To assess whether heparan sulfate was responsible for AT binding, cell monolayers were incubated for 1 h at 37° with purified Flavobacterium heparinase (0.2 units). Over 90% of 125I-AT binding to these cellular elements was suppressed with the bacterial enzyme. Internalization of radiolabeled AT by endothelial cells was examined by incubating the protease inhibitor and cells at 4° and 37 . An initial rapid binding was observed at both temperatures. At 4° AT binding plateaued within 15 min, whereas at 37° binding did not plateau until 60 min and was 30% greater than that observed at 4. These data suggest that surface-associated AT can be internalized by endothelial cells. In addition, AT binding was shown to increase with the length of endothelial cell postconfluence, indicating an accumulation of heparan sulfate by these cells during quiescence. In conclusion, our studies support the hypothesis that the vascular endothelium is coated with heparan sulfate-bound AT, which is responsible for the antithrombotic properties of these natural surfaces.
Reports on the topic "INS-1 cells"
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Ring, S. Environmental, health, and safety issues of fuel cells in transportation. Volume 1: Phosphoric acid fuel-cell buses. Office of Scientific and Technical Information (OSTI), December 1994. http://dx.doi.org/10.2172/10102189.
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Kim, Isaac Y., Joseph Bertino, and Hatem E. Sabaawy. Therapeutic Role of Bmi-1 Inhibitors in Eliminating Prostate Tumor Stem Cells. Fort Belvoir, VA: Defense Technical Information Center, October 2013. http://dx.doi.org/10.21236/ada598365.
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Sabaawy, Hatem E. Therapeutic Roles of Bmi-1 Inhibitors in Eliminating Prostate Tumor Stem Cells. Fort Belvoir, VA: Defense Technical Information Center, October 2013. http://dx.doi.org/10.21236/ada598609.
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Ahmed, Mansoor M. Role of Early Growth Response-1 (Egr-1) Gene in Radiation-Induced Apoptosis of Prostate Cancer Cells. Fort Belvoir, VA: Defense Technical Information Center, May 2001. http://dx.doi.org/10.21236/ada398097.
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Junghans, Richar P. Trial of Anti-PSMA Designer T Cells in Advanced Prostate Cancer. Phase 1. Fort Belvoir, VA: Defense Technical Information Center, July 2006. http://dx.doi.org/10.21236/ada484575.
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Tesfaigzi, J., M. B. Wood, and N. F. Johnson. Expression of cyclin D{sub 1} during endotoxin-induced aleveolar type II cell hyperplasia in rat lung and the detection of apoptotic cells during the remodeling process. Office of Scientific and Technical Information (OSTI), December 1995. http://dx.doi.org/10.2172/381386.
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Lorenz, Ulrike. Role of the Tyrosine Phosphatase SHP-1 and Regulatory T Cells in Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, September 2008. http://dx.doi.org/10.21236/ada501068.
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Lorenz, Ulrike. Role of the Tyrosine Phosphatase SHP-1 and Regulatory T Cells in Breast Cancer. Fort Belvoir, VA: Defense Technical Information Center, September 2007. http://dx.doi.org/10.21236/ada510570.
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Junghans, Richard P. Trials of Anti-PSMA Designer T Cells in Advanced Prostate Cancer (Phase 1). Revision. Fort Belvoir, VA: Defense Technical Information Center, July 2007. http://dx.doi.org/10.21236/ada477450.
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SPIRE CORP BEDFORD MA. Radiation-Hard High-Efficiency InP Space Solar Cell Development. Phase 1. Fort Belvoir, VA: Defense Technical Information Center, July 1996. http://dx.doi.org/10.21236/ada310729.
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