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Reames, Sherry. "John Mirk’s Festial Edited from British Library MS Cotton Claudius A.II ed. by Susan Powell (review)". Catholic Historical Review 99, n.º 2 (2013): 347–49. http://dx.doi.org/10.1353/cat.2013.0072.
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Oishi, Yu, Haruma Ishida, Takashi Y. Nakajima, Ryosuke Nakamura y Tsuneo Matsunaga. "Preliminary verification for application of a support vector machine-based cloud detection method to GOSAT-2 CAI-2". Atmospheric Measurement Techniques 11, n.º 5 (17 de mayo de 2018): 2863–78. http://dx.doi.org/10.5194/amt-11-2863-2018.
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Abstract. The Greenhouse Gases Observing Satellite (GOSAT) was launched in 2009 to measure global atmospheric CO2 and CH4 concentrations. GOSAT is equipped with two sensors: the Thermal And Near infrared Sensor for carbon Observations (TANSO)-Fourier transform spectrometer (FTS) and TANSO-Cloud and Aerosol Imager (CAI). The presence of clouds in the instantaneous field of view of the FTS leads to incorrect estimates of the concentrations. Thus, the FTS data suspected to have cloud contamination must be identified by a CAI cloud discrimination algorithm and rejected. Conversely, overestimating clouds reduces the amount of FTS data that can be used to estimate greenhouse gas concentrations. This is a serious problem in tropical rainforest regions, such as the Amazon, where the amount of useable FTS data is small because of cloud cover. Preparations are continuing for the launch of the GOSAT-2 in fiscal year 2018. To improve the accuracy of the estimates of greenhouse gases concentrations, we need to refine the existing CAI cloud discrimination algorithm: Cloud and Aerosol Unbiased Decision Intellectual Algorithm (CLAUDIA1). A new cloud discrimination algorithm using a support vector machine (CLAUDIA3) was developed and presented in another paper. Although the use of visual inspection of clouds as a standard for judging is not practical for screening a full satellite data set, it has the advantage of allowing for locally optimized thresholds, while CLAUDIA1 and -3 use common global thresholds. Thus, the accuracy of visual inspection is better than that of these algorithms in most regions, with the exception of snow- and ice-covered surfaces, where there is not enough spectral contrast to identify cloud. In other words, visual inspection results can be used as truth data for accuracy evaluation of CLAUDIA1 and -3. For this reason visual inspection can be used for the truth metric for the cloud discrimination verification exercise. In this study, we compared CLAUDIA1–CAI and CLAUDIA3–CAI for various land cover types, and evaluated the accuracy of CLAUDIA3–CAI by comparing both CLAUDIA1–CAI and CLAUDIA3–CAI with visual inspection (400 × 400 pixels) of the same CAI images in tropical rainforests. Comparative results between CLAUDIA1–CAI and CLAUDIA3–CAI for various land cover types indicated that CLAUDIA3–CAI had a tendency to identify bright surface and optically thin clouds. However, CLAUDIA3–CAI had a tendency to misjudge the edges of clouds compared with CLAUDIA1–CAI. The accuracy of CLAUDIA3–CAI was approximately 89.5 % in tropical rainforests, which is greater than that of CLAUDIA1–CAI (85.9 %) for the test cases presented here.
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Fujita, Hiroki, Kotaro Sugimoto, Shuichiro Inatomi, Toshihiro Maeda, Makoto Osanai, Yasushi Uchiyama, Yoko Yamamoto et al. "Tight Junction Proteins Claudin-2 and -12 Are Critical for Vitamin D-dependent Ca2+ Absorption between Enterocytes". Molecular Biology of the Cell 19, n.º 5 (mayo de 2008): 1912–21. http://dx.doi.org/10.1091/mbc.e07-09-0973.
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Ca2+ is absorbed across intestinal epithelial monolayers via transcellular and paracellular pathways, and an active form of vitamin D3, 1α,25-dihydroxyvitamin D3 [1α,25(OH)2D3], is known to promote intestinal Ca2+ absorption. However, the molecules driving the paracellular Ca2+ absorption and its vitamin D dependency remain obscure. Because the tight junction proteins claudins are suggested to form paracellular channels for selective ions between neighboring cells, we hypothesized that specific intestinal claudins might facilitate paracellular Ca2+ transport and that expression of these claudins could be induced by 1α,25(OH)2D3. Herein, we show, by using RNA interference and overexpression strategies, that claudin-2 and claudin-12 contribute to Ca2+ absorption in intestinal epithelial cells. We also provide evidence showing that expression of claudins-2 and -12 is up-regulated in enterocytes in vitro and in vivo by 1α,25(OH)2D3 through the vitamin D receptor. These findings strongly suggest that claudin-2- and/or claudin-12-based tight junctions form paracellular Ca2+ channels in intestinal epithelia, and they highlight a novel mechanism behind vitamin D-dependent calcium homeostasis.
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Schulz, Donald E. "Can Castro Survive?" Journal of Interamerican Studies and World Affairs 35, n.º 1 (1993): 89–118. http://dx.doi.org/10.2307/166103.
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There is a moment in “I, Claudius” where Claudius, the king, looks back at all that had happened during his lifetime and before and decides that it is all rotten and has to be destroyed. And he makes a statement. He says: “Let all the poisons that lurk in the mud hatch out.”In a very real sense, Claudius’ curse sums up much of what has happened in Cuba during the last several years. All of the weaknesses and pathologies of the Castro regime, many of which had been hidden beneath its monolithic façade, have come to the surface. The revolution has soured. The situation has grown so bad that most political observers today assume that the regime is in its “final hour.” Cuba is “collapsing,” and the only real questions are when and how Fidel will go and what will replace him.While Castro must leave sooner or later, reports of his impending demise have been much exaggerated. A golpe de estado is possible, but not probable.
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SCHINDLER, Claudia. "Claudians 'Argonautica'". Caeculus 6 (1 de diciembre de 2005): 107–23. http://dx.doi.org/10.2143/cae.6.0.2004670.
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Stinger, Charles L. "Kardinal Jean Jouffroy († 1473): Leben und Werk by Claudia Märtl". Catholic Historical Review 84, n.º 1 (1998): 95–96. http://dx.doi.org/10.1353/cat.1998.0159.
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Kong, Yaoyao, Zhangbin Liao, Xiuhua Ma, Mengqing Liang, Houguo Xu, Kangsen Mai y Yanjiao Zhang. "Response of Intestinal Microbiota of Tiger Puffer (Takifugu rubripes) to the Fish Oil Finishing Strategy". Microorganisms 11, n.º 1 (13 de enero de 2023): 208. http://dx.doi.org/10.3390/microorganisms11010208.
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The fish oil finishing (FOF) strategy, that is, re-feeding fish with fish oil (FO)-based diet after a certain period of feeding with alternative lipid source-based diets. On tiger puffer, the present study investigated the response of intestinal microbiota to FOF. Fish were fed four diets based on FO, soybean oil, palm oil and beef tallow as lipid sources, respectively, firstly for 50 days (growing-out period), and then fed the FO-based diet for 30 more days (FOF period). The results showed that dietary terrestrially sourced oils impaired the intestinal function in the growing-out period. However, the activities of amylase, trypsin and anti-oxidative enzymes (SOD, CAT, T-AOC), as well as gene expression of inflammatory cytokines (IL-1β, TNF-α, TGF-β) and tight junction protein (Claudin4, Claudin7, Claudin18, JAM, ZO-1) in the intestine were significantly recovered by FOF. The 16S rDNA sequencing analysis showed that FOF improved the similarity of bacterial community among the groups. The MetaStat analysis confirmed that FOF regulated the abundance of butyric acid-producing bacteria (Lachnospiraceae, Eubacterium, Butyricicoccus, Clostridium and Roseburia) and bacteria related to digestion and absorption (Sphingomonas, Romboutsia and Brevibacillus). In conclusion, FOF can recover the intestine function. The intestinal microbiota probably participated in and played a key role in the recovery process.
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Liebner, Stefan, Monica Corada, Thorsten Bangsow, Jane Babbage, Andrea Taddei, Cathrin J. Czupalla, Marco Reis et al. "Wnt/β-catenin signaling controls development of the blood–brain barrier". Journal of Cell Biology 183, n.º 3 (27 de octubre de 2008): 409–17. http://dx.doi.org/10.1083/jcb.200806024.
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The blood–brain barrier (BBB) is confined to the endothelium of brain capillaries and is indispensable for fluid homeostasis and neuronal function. In this study, we show that endothelial Wnt/β-catenin (β-cat) signaling regulates induction and maintenance of BBB characteristics during embryonic and postnatal development. Endothelial specific stabilization of β-cat in vivo enhances barrier maturation, whereas inactivation of β-cat causes significant down-regulation of claudin3 (Cldn3), up-regulation of plamalemma vesicle-associated protein, and BBB breakdown. Stabilization of β-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature. Loss of β-cat or inhibition of its signaling abrogates this effect. Furthermore, stabilization of β-cat also increased Cldn3 and barrier properties in nonbrain-derived ECs. These findings may open new therapeutic avenues to modulate endothelial barrier function and to limit the devastating effects of BBB breakdown.
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Smith, Mark I. "Claudia and Love". Callaloo 22, n.º 4 (1999): 871. http://dx.doi.org/10.1353/cal.1999.0194.
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Hrynick, Tobias. "On England’s Green and Pleasant Land: Matthew Paris’s Map of Britain as a Reflection of the Levant". Cartographica: The International Journal for Geographic Information and Geovisualization 58, n.º 2 (1 de junio de 2023): 64–80. http://dx.doi.org/10.3138/cart-2022-0020.
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In the mid-thirteenth century, the noted English Benedictine chronicler Matthew Paris produced a substantial corpus of regional maps. Especially famous is Paris’s Map of Britain, particularly the version preserved in British Library Cotton Claudius d. vi, known for its mimetic accuracy, artistic presentation, and striking level of detail. Another of Paris’s maps, however, a map of the eastern Mediterranean preserved on Oxford Corpus Christi MS 2*, though little studied, shares many of the features which made the Map of Britain so remarkable. Internal evidence strongly suggests that the Oxford Map and the Claudius Map of Britain derive from a common project which depicted England and the Holy Land as mirror images – a project which would have had profound meaning in the contemporary political context, serving to express horror at Jerusalem’s fall in 1244, articulate support for a new English-led crusade, and comment critically on King Henry III’s performative piety. The subsequent abandonment of the project is equally informative since it demonstrates that medieval maps, far from being formulaic expressions of set religious doctrine, could express political opinions so intensely topical that they could become outdated before they were even complete.
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Rowell, Charles H. "“Aziza” Claudia Gibson-Hunter". Callaloo 38, n.º 4 (2015): 825–29. http://dx.doi.org/10.1353/cal.2015.0114.
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Milatz, Susanne, Nina Himmerkus, Vera Christine Wulfmeyer, Hoora Drewell, Kerim Mutig, Jianghui Hou, Tilman Breiderhoff et al. "Mosaic expression of claudins in thick ascending limbs of Henle results in spatial separation of paracellular Na+ and Mg2+ transport". Proceedings of the National Academy of Sciences 114, n.º 2 (27 de diciembre de 2016): E219—E227. http://dx.doi.org/10.1073/pnas.1611684114.
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The thick ascending limb (TAL) of Henle’s loop drives paracellular Na+, Ca2+, and Mg2+ reabsorption via the tight junction (TJ). The TJ is composed of claudins that consist of four transmembrane segments, two extracellular segments (ECS1 and -2), and one intracellular loop. Claudins interact within the same (cis) and opposing (trans) plasma membranes. The claudins Cldn10b, -16, and -19 facilitate cation reabsorption in the TAL, and their absence leads to a severe disturbance of renal ion homeostasis. We combined electrophysiological measurements on microperfused mouse TAL segments with subsequent analysis of claudin expression by immunostaining and confocal microscopy. Claudin interaction properties were examined using heterologous expression in the TJ-free cell line HEK 293, live-cell imaging, and Förster/FRET. To reveal determinants of interaction properties, a set of TAL claudin protein chimeras was created and analyzed. Our main findings are that (i) TAL TJs show a mosaic expression pattern of either cldn10b or cldn3/cldn16/cldn19 in a complex; (ii) TJs dominated by cldn10b prefer Na+ over Mg2+, whereas TJs dominated by cldn16 favor Mg2+ over Na+; (iii) cldn10b does not interact with other TAL claudins, whereas cldn3 and cldn16 can interact with cldn19 to form joint strands; and (iv) further claudin segments in addition to ECS2 are crucial for trans interaction. We suggest the existence of at least two spatially distinct types of paracellular channels in TAL: a cldn10b-based channel for monovalent cations such as Na+ and a spatially distinct site for reabsorption of divalent cations such as Ca2+ and Mg2+.
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Beggs, Megan R., Ida Appel, Per Svenningsen, Karsten Skjødt, R. Todd Alexander y Henrik Dimke. "Expression of transcellular and paracellular calcium and magnesium transport proteins in renal and intestinal epithelia during lactation". American Journal of Physiology-Renal Physiology 313, n.º 3 (1 de septiembre de 2017): F629—F640. http://dx.doi.org/10.1152/ajprenal.00680.2016.
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Significant alterations in maternal calcium (Ca2+) and magnesium (Mg2+) balance occur during lactation. Ca2+ is the primary divalent cation mobilized into breast milk by demineralization of the skeleton and alterations in intestinal and renal Ca2+ transport. Mg2+ is also concentrated in breast milk, but the underlying mechanisms are not well understood. To determine the molecular alterations in Ca2+ and Mg2+ transport in the intestine and kidney during lactation, three groups of female mice consisting of either nonpregnant controls, lactating mice, or mice undergoing involution were examined. The fractional excretion of Ca2+, but not Mg2+, rose significantly during lactation. Renal 1-α hydroxylase and 24-OHase mRNA levels increased markedly, as did plasma 1,25 dihydroxyvitamin D levels. This was accompanied by significant increases in intestinal expression of Trpv6 and S100g in lactating mice. However, no alterations in the expression of cation-permeable claudin-2, claudin-12, or claudins-15 were found in the intestine. In the kidney, increased expression of Trpv5 and Calb1 was observed during lactation, while no changes in claudins involved in Ca2+ and Mg2+ transport (claudin-2, claudin-14, claudin-16, or claudin-19) were found. Consistent with the mRNA expression, expression of both calbindin-D28K and transient receptor potential vanilloid 5 (TRPV5) proteins increased. Colonic Trpm6 expression increased during lactation, while renal Trpm6 remained unaltered. In conclusion, proteins involved in transcellular Ca2+ and Mg2+ transport pathways increase during lactation, while expression of paracellular transport proteins remained unchanged. Increased fractional Ca2+ excretion can be explained by vitamin D-dependent intestinal hyperabsorption and bone demineralization, despite enhanced transcellular Ca2+ uptake by the kidney.
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Loud, Graham A. "Wege der Integration: Das Papsttum und die lateinische Kirche Apuliens in normannischer Zeit (1059–1189) by Claudia Alraum". Catholic Historical Review 108, n.º 4 (septiembre de 2022): 798–99. http://dx.doi.org/10.1353/cat.2022.0092.
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MOROZOVA, OLGA, EUGENE POPOV, ALINA ALEXANDROVA, THI HA GIANG PHAM y MACHIEL EVERT NOORDELOOS. "Four new species of Entoloma (Entolomataceae, Agaricomycetes) subgenera Cyanula and Claudopus from Vietnam and their phylogenetic position". Phytotaxa 549, n.º 1 (2 de junio de 2022): 1–21. http://dx.doi.org/10.11646/phytotaxa.549.1.1.
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Three new species of Entoloma subgenus Cyanula (Entoloma argus, E. arion, and E. icarus) from Kon Chu Rang Nature Reserve and one species of subgenus Claudopus (E. daphnis) from Cat Tien National Park were discovered during an investigation of the diversity of the mycobiota of Central and South Vietnam and are described here. Illustrated descriptions of their macro- and microscopic features and discussion of similar taxa are given. Phylogenetic analysis was based on nrITS1-5.8S-ITS2 and nrLSU regions. The results confirm the polyphyletic origin of the pleurotoid basidiocarp form in the genus Entoloma.
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Alexander, R. Todd, Juraj Rievaj y Henrik Dimke. "Paracellular calcium transport across renal and intestinal epithelia". Biochemistry and Cell Biology 92, n.º 6 (diciembre de 2014): 467–80. http://dx.doi.org/10.1139/bcb-2014-0061.
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Calcium (Ca2+) is a key constituent in a myriad of physiological processes from intracellular signalling to the mineralization of bone. As a consequence, Ca2+ is maintained within narrow limits when circulating in plasma. This is accomplished via regulated interplay between intestinal absorption, renal tubular reabsorption, and exchange with bone. Many studies have focused on the highly regulated active transcellular transport pathways for Ca2+ from the duodenum of the intestine and the distal nephron of the kidney. However, comparatively little work has examined the molecular constituents creating the paracellular shunt across intestinal and renal epithelium, the transport pathway responsible for the majority of transepithelial Ca2+ flux. More specifically, passive paracellular Ca2+ absorption occurs across the majority of the intestine in addition to the renal proximal tubule and thick ascending limb of Henle’s loop. Importantly, recent studies demonstrated that Ca2+ transport through the paracellular shunt is significantly regulated. Therefore, we have summarized the evidence for different modes of paracellular Ca2+ flux across renal and intestinal epithelia and highlighted recent molecular insights into both the mechanism of secondarily active paracellular Ca2+ movement and the identity of claudins that permit the passage of Ca2+ through the tight junction of these epithelia.
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Curry, Joshua N., Shinsaku Tokuda, Patrick McAnulty y Alan S. L. Yu. "Combinatorial expression of claudins in the proximal renal tubule and its functional consequences". American Journal of Physiology-Renal Physiology 318, n.º 5 (1 de mayo de 2020): F1138—F1146. http://dx.doi.org/10.1152/ajprenal.00057.2019.
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The proximal renal tubule (PT) is characterized by a highly conductive paracellular pathway, which contributes to a significant amount of solute and water reabsorption by the kidney. Claudins are tight junction proteins that, in part, determine the paracellular permeability of epithelia. In the present study, we determined the expression pattern of the major PT claudins. We found that claudin-2 and claudin-10 are coexpressed throughout the PT, whereas claudin-3 is coexpressed with claudin-2 predominantly in the proximal straight tubule. Additionally, claudin-2 and claudin-3 are expressed separately within mutually exclusive populations of descending thin limbs. We developed a novel double-inducible Madin-Darby canine kidney I cell model to characterize in vitro the functional effect of coexpression of PT claudins. In keeping with previous studies, we found that claudin-2 alone primarily increased cation (Na+ and Ca2+) permeability, whereas claudin-10a alone increased anion (Cl−) permeability. Coexpression of claudin-2 and claudin-10a together led to a weak physical interaction between the isoforms and the formation of a monolayer with high conductance but neutral charge selectivity. Claudin-3 expression had a negligible effect on all measures of cell permeability, whether expressed alone or together with claudin-2. In cells coexpressing a claudin-2 mutant, S68C, together with claudin-10a, inhibition of cation permeability through the claudin-2 pore with a thiol-reactive pore blocker did not block anion permeation through claudin-10a. We conclude that claudin-2 and claudin-10a form independent paracellular cation- and anion-selective channels that function in parallel.
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Mráv, Zsolt. "The Roman Army along the Amber Road between Poetovio and Carnuntum in the 1st Century A.D. - Archaeological evidence. A preliminary research report". Communicationes Archaeologicae Hungariae 2013 (7 de diciembre de 2013): 49–100. http://dx.doi.org/10.54640/cah.2013.49.
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The purpose o f my study is to shed light on the 1st Century Roman occupation o f NW-Pannonia by discussing the military sites along the 270 km long section of the Amber Road between two legionary fortresses, the Augustan Poetovio and the late Tiberio-Claudian Carnuntum. I will also examine the Roman occupation system of its two main branch roads, the Savaria-Brigetio and Scarbantia- Vindobona roads. Besides literary sources, my analysis is based on the archaeologically investigated and proved military buildings and fortifications of the period, the early import goods and inscriptions and, above all, the military equipment and horse gear finds which have long been regarded as characteristics of sites of military nature. The early history o f the Amber Road region is much more nuanced than scholars have hitherto realized, since the recently accumulated and tallied sources, primarily militaria finds, throw new light on the characteristic features of the Roman occupation system of this region.
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Romano, Robert. "Prepare for impact of NCAA settlement". College Athletics and the Law 21, n.º 4 (julio de 2024): 7–8. http://dx.doi.org/10.1002/catl.31342.
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With previous setbacks in both O’Bannon v. NCAA and NCAA v. Alston, the NCAA and the Power Five conferences made a decision to shy away from their traditional aggressive stance when it came to litigating the latest legal challenge attacking their business model in House v. NCAA (No. 4:20‐cv‐03919, (N.D. Ca. 06/15/2020)). And so in May, the leaders in the Power Five (American Athletic Conference, Big 12, Big Ten, Pac‐12, and Southeastern Conference) ended up agreeing to settle the case. The multibillion‐dollar settlement, if approved by Senior District Judge Claudia Wilken — the same federal judge associated with both the Alston and O’Bannon cases — obliges the NCAA to pay out approximately $2.8 billion to former student‐athletes who had been prohibited from monetizing their name, image, and likeness prior to July 1, 2021.
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Peng, Ji-Bin y David G. Warnock. "WNK4-mediated regulation of renal ion transport proteins". American Journal of Physiology-Renal Physiology 293, n.º 4 (octubre de 2007): F961—F973. http://dx.doi.org/10.1152/ajprenal.00192.2007.
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Point mutations in WNK4 [for With No K (lysine)], a serine-threonine kinase that is expressed in the distal nephron of the kidney, are linked to familial hyperkalemic hypertension (FHH). The imbalanced electrolyte homeostasis in FHH has led to studies toward an understanding of WNK4-mediated regulation of ion transport proteins in the kidney. A growing number of ion transport proteins for Na+, K+, Ca2+, and Cl−, including ion channels and transporters in the transcellular pathway and claudins in the paracellular pathway, are shown to be regulated by WNK4 from studies using models ranging from Xenopus laevis oocytes to transgenic and knockin mice. WNK4 regulates these transport proteins in different directions and by different cellular mechanisms. The common theme of WNK4-mediated regulation is to alter the abundance of ion transport proteins at the plasma membrane, with the exception of claudins, which are phosphorylated in the presence of WNK4. The regulation of WNK4 can be blocked by the full-length WNK1, whose action is in turn antagonized by a kidney-specific WNK1 variant lacking the kinase domain. In addition, WNK4 also activates stress-related serine-threonine kinases to regulate members of the SLC12 family members of cation-chloride cotransporters. In many cases, the FHH-causing mutants of WNK4 exhibit differences from wild-type WNK4 in regulating ion transport proteins. These regulations well explain the clinical features of FHH and provide insights into the multilayered regulation of ion transport processes in the distal nephron.
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Wheeler, Ann. "You can hear the smiles in Claudia Covert’s voice". College & Research Libraries News 67, n.º 9 (1 de octubre de 2006): 572–73. http://dx.doi.org/10.5860/crln.67.9.7689.
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Calvo, Thomas. "Claudia Espejel Carbajal, La justicia y el fuego. Dos claves para leer la Relación de Michoacán". Cahiers des Amériques latines 2011/1, n.º 66 (1 de abril de 2011): 203–6. http://dx.doi.org/10.4000/cal.529.
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Redon, Marie. "Claudia Carolina Zamorano-Villarreal, Naviguer dans le désert. Itinéraires résidentiels à la frontière Mexique-États-Unis". Cahiers des Amériques latines, n.º 42 (31 de enero de 2003): 167–69. http://dx.doi.org/10.4000/cal.7222.
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Bertrand, Sarah. "Can the subaltern (in)securitize? A rejoinder to Claudia Aradau". European Journal of International Security 3, n.º 03 (12 de septiembre de 2018): 306–9. http://dx.doi.org/10.1017/eis.2018.15.
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McClane, Bruce y Archana Shrestha. "Using More Than 1 (Path)Way to Kill a Host Cell: Lessons From Clostridium perfringens Enterotoxin". Microbiology Insights 13 (enero de 2020): 117863612093151. http://dx.doi.org/10.1177/1178636120931518.
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Clostridium perfringens enterotoxin (CPE) is responsible for the symptoms of common intestinal infections due to C. perfringens type F isolates. CPE is a pore-forming toxin that uses certain claudins as a receptor. Previous studies showed that, in enterocyte-like Caco-2 cells, low CPE concentrations cause caspase 3-mediated apoptosis but high CPE concentrations cause necrosis. The recent work published in mBio by Shrestha, Mehdizadeh Gohari, and McClane determined that RIP1 and RIP3 are involved in both CPE-mediated apoptosis and necrosis in Caco-2 cells. Furthermore, mixed lineage kinase-domain (MLKL) oligomerization was shown to be important for necrosis caused by CPE, identifying this necrosis as programmed necroptosis. In addition, calpain activation due to Ca2+ influx through the CPE pore was identified as a critical intermediate step for MLKL oligomerization and, thus, CPE-induced necroptosis. These findings may have applicability to understand the action of some other pore-forming toxins that induce necroptosis and may also be important for understanding CPE action in vivo.
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Van Itallie, C. M., O. R. Colegio y J. M. Anderson. "The Cytoplasmic Tails of Claudins Can Influence Tight Junction Barrier Properties through Effects on Protein Stability". Journal of Membrane Biology 199, n.º 1 (mayo de 2004): 29–38. http://dx.doi.org/10.1007/s00232-004-0673-z.
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Bhat, Ajaz A., Shahabuddin Usmani, Hana Q. Sadida, Sheema Hashem, Tariq Masoodi, Ikhlak Ahmed, Rakesh Kumar et al. "Abstract 7643: Prognostic significance and immune infiltration patterns related to Claudin heterogeneity in pancreatic ductal adenocarcinoma patients". Cancer Research 84, n.º 6_Supplement (22 de marzo de 2024): 7643. http://dx.doi.org/10.1158/1538-7445.am2024-7643.
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Abstract Background: Pancreatic ductal adenocarcinoma (PDAC) stands out for its aggressive nature, often manifesting through invasion, metastasis, and recurrence. These characteristics are partly attributable to the Epithelial-mesenchymal transition (EMT), a critical phenomenon that follows the disintegration of epithelial barriers, including tight junctions (TJs), where Claudin (CLDN) proteins are integral components. Objective: This study focused on elucidating the differential expression of claudins in PDAC and exploring their correlations with disease progression, invasiveness, and immune infiltration. Methodology: Utilizing UCSC TOIL RNA-seq, TCGA-PAAD genomic, and clinical data, we investigated the genomic alterations and differential expression of claudins in PDAC. Conducted survival analysis using log-rank tests. Assessed immune infiltration patterns using the EPIC deconvolution algorithm. Results: Of 177 PDAC samples examined, 23 (13%) exhibited at least one form of claudin gene alteration, including mutations, amplifications, or deep deletions. Remarkably, 10 claudins (CLDN1, 2, 4, 5, 7, 11, 12, 15, 18, and 23) were found to be significantly overexpressed in PDAC samples, meeting a log2FC threshold of ≥1 (p < 0.05). Further, we identified a direct correlation between mRNA expression and copy numbers, alongside an inverse relationship with methylation levels, particularly in CLDN1, CLDN12, CLDN15, CLDN23, and CLDN4. Intriguingly, claudin expression escalated from grades G1 to G3 but diminished in G4, with CLDN1, CLDN4, and CLDN7 showing significant variability (Kruskal-Wallis rank test p-values of 1.2E-5, 0.00064, and 0.023, respectively). Survival analysis indicated that high expression levels of CLDN1 and CLDN4 were linked to poorer patient outcomes, while higher levels of CLDN5 and CLDN15 correlated with improved survival (log-rank p-values of 0.007, 0.016, 0.0035, and 0.0012, respectively), findings consistent across both univariate and multivariate analyses. Furthermore, immune infiltration patterns, assessed via the EPIC deconvolution algorithm, varied significantly between high and low CLDN expression groups. Specifically, low CLDN1 expression was associated with increased presence of B-cells, CAF, and CD8+ T-cells but fewer endothelial cells, a pattern reversed in high CLDN1 expression cases. A similar trend was observed for CLDN4. Conclusion: Our study underscores the significant prognostic value of claudin proteins in PDAC, highlighting their potential as indicators of disease progression and survival and their influence on the tumor's immune environment. Citation Format: Ajaz A. Bhat, Shahabuddin Usmani, Hana Q. Sadida, Sheema Hashem, Tariq Masoodi, Ikhlak Ahmed, Rakesh Kumar, Mayank Singh, Punita Dhawan, Shahab Uddin, Muzafar A. Macha, Ammira S. Al-Shabeeb Akil. Prognostic significance and immune infiltration patterns related to Claudin heterogeneity in pancreatic ductal adenocarcinoma patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 7643.
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De Carvalho, Isaías Francisco y Sonia Maria Chacaliaza Cruz. "REPRESENTAÇÕES DE ESTUPRO E TORTURA CONTRA MULHERES EM LA SANGRE DE LA AURORA". Scripta Uniandrade 19, n.º 3 (11 de diciembre de 2021): 208–28. http://dx.doi.org/10.55391/2674-6085.2021.2419.
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O romance peruano La sangre de la aurora, de Claudia Salazar Jiménez (2018), centra-se nas histórias de Melanie, Marcela e Modesta durante o Conflito Armado Interno (CAI). Visamos analisar os métodos usados para reprimir as protagonistas, por parte de senderistas e militares peruanos. Para isso, fundamentamo-nos nas noções de repressão, tortura e estupro definidas por Jelin (2002) e Segato (2003, 2013). Dessa forma, pretende-se mostrar os métodos violentos utilizados contra as mulheres, a modo de uma reescrita da história da guerra desde uma perspectiva feminina que, para além da denúncia, contempla potenciais perspectivas para a emancipação e inclusão de vozes antes silenciadas e ainda no entremeio do poder dizer e da inviabilidade de narrar a violência extremada.
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Kubota, Koji, Mikio Furuse, Hiroyuki Sasaki, Noriyuki Sonoda, Kohji Fujita, Akira Nagafuchi y Shoichiro Tsukita. "Ca2+-independent cell-adhesion activity of claudins, a family of integral membrane proteins localized at tight junctions". Current Biology 9, n.º 18 (septiembre de 1999): 1035—S1. http://dx.doi.org/10.1016/s0960-9822(99)80452-7.
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Sarnella, Annachiara, Ylenia Ferrara, Luigi Auletta, Sandra Albanese, Vincenzo Alterio, Jean-Yves Winum, Claudiu T. Supuran, Laura Cerchia, Giuseppina De Simone y Antonella Zannetti. "Abstract 1040: Blocking hypoxia-induced carbonic anhydrases 9 enhances sensibility to cisplatin of head and neck squamous carcinoma". Cancer Research 82, n.º 12_Supplement (15 de junio de 2022): 1040. http://dx.doi.org/10.1158/1538-7445.am2022-1040.
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Abstract The head and neck squamous carcinomas (HNSSCs) are the sixth most common cancer worldwide. Given the heterogeneous nature of HNSCC, this carcinoma results in higher resistance to chemoradiotherapy. Recent evidence highlight the importance of the hypoxic microenvironment in contributing to cisplatin resistance. Therefore, the aim of this study was to investigate the role played by hypoxia-induced protein carbonic anhydrase 9 (CA9) in supporting HNSCC cisplatin resistance. Furthermore, we purpose to investigate the ability of CA9 inhibitor, SLC-0111, a small molecule already used in Phase I clinical trial, to sensitize HNSSC cells to chemotherapy in vitro and in vivo. We analyzed the expression of CA9 in a public data set of 103 HNSCC samples and 22 oral cavity normal tissues and in two HNSSC cell lines (FaDu; SCC-011). HNSCC cells grown in 2D and 3D models under hypoxic conditions (1% O2) showed increased levels of CA9 and greater resistance to cisplatin than cells grown under normoxic conditions. The addition of CA9 inhibitor SLC-0111 to cisplatin sensitized cells to the chemotherapeutic agent and caused a reduction of colony number, spheroid formation, tumor cell, and spheroid migration and invasiveness. Furthermore, the combination therapy hampered activation of STAT3, AKT, ERK, and EMT program whereas it induced apoptosis. Notably, the combined treatment caused inhibition of tumor growth and induction of apoptosis in HNSCC subcutaneous xenografts, as assessed by high-frequency ultrasonography and fluorescent molecular tomography (FMT) with NIR-Annexin V, respectively, at a higher extent than single agents. In addition, FMT with NIR-Prosense revealed a stronger reduction of lymph nodes metastases when mice bearing orthotopic xenografts were treated with cisplatin plus SLC-0111 with respect to a single treatment. Our findings taken together demonstrate the crucial role played by CA9 in promoting cisplatin resistance in HNSCC and the efficacy of SLC-0111 to sensitize tumor cells and xenografts to chemotherapy. Citation Format: Annachiara Sarnella, Ylenia Ferrara, Luigi Auletta, Sandra Albanese, Vincenzo Alterio, Jean-Yves Winum, Claudiu T Supuran, Laura Cerchia, Giuseppina De Simone, Antonella Zannetti. Blocking hypoxia-induced carbonic anhydrases 9 enhances sensibility to cisplatin of head and neck squamous carcinoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 1040.
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Lair, Eric. "Relatos de la violencia ? Impactos del desplazamiento forzado en la niñez y la juventud, Martha Nubia Bello Albarracín, Leonardo Mantilla Castellanos, Claudia Mosquera Rosero, Edna Ingrid Camelo Fisco". Cahiers des Amériques latines, n.º 35 (31 de diciembre de 2000): 192. http://dx.doi.org/10.4000/cal.6567.
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Angelow, Susanne, Randa El-Husseini, Sanae A. Kanzawa y Alan S. L. Yu. "Renal localization and function of the tight junction protein, claudin-19". American Journal of Physiology-Renal Physiology 293, n.º 1 (julio de 2007): F166—F177. http://dx.doi.org/10.1152/ajprenal.00087.2007.
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Claudins form a family of transmembrane tight junction proteins that play a key role in control and selectivity of paracellular transport. Mutations in claudin-19, which is expressed in kidney, retina, and myelinated peripheral neurons, were identified in familial hypomagnesemia with hypercalciuria and nephrocalcinosis, a hereditary disease causing renal Mg2+ and Ca2+ wasting. Here, we studied the distribution and possible functional role of claudin-19 in the renal tubule. By immunofluorescence staining of mouse kidney, claudin-19 was found to be expressed at the tight junction of the thick ascending limb of Henle, the major site of paracellular Mg2+ reabsorption, where it colocalized with claudin-16, as well as in the thin ascending limb. The role of claudin-19 in paracellular transport was tested by stable transfection into Madin Darby canine kidney II TetOff cells to generate inducible cell lines. Claudin-19 increased the transepithelial electrical resistance and decreased permeability to monovalent and divalent cations, while anion and urea permeability were not affected. Our data suggest that claudin-19 acts as a selective cation barrier at the tight junction. This would be consistent with its physiological role to electrically seal myelinated peripheral neurons. The normal role of claudin-19 in renal tubule function remains to be determined.
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Mendoza, Christopher, Sai Harsha Nagidi y Dario Mizrachi. "Molecular Characterization of the Extracellular Domain of Human Junctional Adhesion Proteins". International Journal of Molecular Sciences 22, n.º 7 (27 de marzo de 2021): 3482. http://dx.doi.org/10.3390/ijms22073482.
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The junction adhesion molecule (JAM) family of proteins play central roles in the tight junction (TJ) structure and function. In contrast to claudins (CLDN) and occludin (OCLN), the other membrane proteins of the TJ, whose structure is that of a 4α-helix bundle, JAMs are members of the immunoglobulin superfamily. The JAM family is composed of four members: A, B, C and 4. The crystal structure of the extracellular domain of JAM-A continues to be used as a template to model the secondary and tertiary structure of the other members of the family. In this article, we have expressed the extracellular domains of JAMs fused with maltose-binding protein (MBP). This strategy enabled the work presented here, since JAM-B, JAM-C and JAM4 are more difficult targets due to their more hydrophobic nature. Our results indicate that each member of the JAM family has a unique tertiary structure in spite of having similar secondary structures. Surface plasmon resonance (SPR) revealed that heterotypic interactions among JAM family members can be greatly favored compared to homotypic interactions. We employ the well characterized epithelial cadherin (E-CAD) as a means to evaluate the adhesive properties of JAMs. We present strong evidence that suggests that homotypic or heterotypic interactions among JAMs are stronger than that of E-CADs.
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Patel, Parul, Susan L. Ford, Mark Baker, Claudia Meyer, Louise Garside, Ronald D’Amico, Rodica Van Solingen-Ristea et al. "885. Pregnancy Outcomes and Pharmacokinetics in Pregnant Women Living with HIV Exposed to Long-Acting Cabotegravir and Rilpivirine in Clinical Trials". Open Forum Infectious Diseases 8, Supplement_1 (1 de noviembre de 2021): S534. http://dx.doi.org/10.1093/ofid/ofab466.1080.
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Abstract Background Limited data exist among women living with HIV who become pregnant while exposed to long-acting (LA) cabotegravir (CAB) and rilpivirine (RPV). We report outcomes in pregnant participants and LA pharmacokinetic (PK) tail data in pregnant women exposed to CAB+RPV with live births. Methods Women of reproductive potential exposed to ≥ 1 dose of CAB+RPV (oral/LA) from ViiV-sponsored Phase 2/3/3b clinical treatment studies and the compassionate use program were included in this analysis and pregnancies identified. Per protocol, upon identification of pregnancy, CAB+RPV was discontinued and an alternative regimen initiated, with continued quarterly PK sampling for 52 weeks post last injection during long-term safety follow-up (LTFU). Descriptive characteristics of pregnant women and birth outcomes and available CAB and RPV PK during pregnancy for those with live births are summarized. Results As of March 31, 2021, 26/325 women of reproductive potential (age 18–49 years) became pregnant while exposed to CAB+RPV (5 oral, 21 LA [including 3 following LA discontinuation]). There were 11 live births (1 oral, 10 LA), of which 10 had no reported congenital abnormalities and 1 had reported congenital ptosis, in a pre-term infant with intrauterine growth restriction. There were 9 elective terminations and 6 miscarriages (5 in first 9 weeks of gestation). Ten women exposed to intramuscular CAB+RPV LA became pregnant with subsequent live birth outcomes, including 3 infants conceived during the PK tail in LTFU. All women were virologically suppressed at time of pregnancy identification. In women becoming pregnant on LA dosing, plasma CAB and RPV concentrations during pregnancy were within the range of expected concentrations in non-pregnant women. Two of 10 women with live births exposed to CAB+RPV LA continued LA therapy during pregnancy (compassionate use program participants). Conclusion Pregnancy outcomes in women exposed to CAB+RPV at conception are consistent with earlier findings. There was 1 reported congenital anomaly among 11 live births. CAB and RPV PK tail in pregnancy was within the expected range for non-pregnant women. Ongoing monitoring of birth defects within the antiretroviral pregnancy registry and pregnancy surveillance within the treatment program continues. Disclosures Parul Patel, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Susan L. Ford, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Mark Baker, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Claudia Meyer, MBChB, MRCP, MSc, FRCPath, DTM&H, GlaxoSmithKline (Employee, Shareholder) Louise Garside, PhD, GlaxoSmithKline (Employee) Ronald D’Amico, DO, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Rodica Van Solingen-Ristea, MD, Janssen Research and Development (Employee)ViiV Healthcare (Employee) Herta Crauwels, PhD, Janssen (Employee) Joseph Polli, PhD, FAAPS, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Ciara Seal, BS, GlaxoSmithKline (Employee, Shareholder) Shanker Thiagarajah, MB ChB, GlaxoSmithKline (Employee, Shareholder) Eileen Birmingham, MD, MPH, Janssen Research and Development (Employee, Shareholder) William Spreen, PharmD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Bryan Baugh, MD, Janssen, Johnson & Johnson (Employee, Shareholder) Matthew Bosse, DO, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Vani Vannappagari, MBBS, MPH, PhD, ViiV Healthcare Limited (Employee)
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Liang, Jiahua, Ying Zhou, Xinyi Cheng, Jiaqi Chen, Huabin Cao, Xiaoquan Guo, Caiying Zhang, Yu Zhuang y Guoliang Hu. "Baicalin Attenuates H2O2-Induced Oxidative Stress by Regulating the AMPK/Nrf2 Signaling Pathway in IPEC-J2 Cells". International Journal of Molecular Sciences 24, n.º 11 (29 de mayo de 2023): 9435. http://dx.doi.org/10.3390/ijms24119435.
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Oxidative stress can adversely affect the health status of the body, more specifically by causing intestinal damage by disrupting the permeability of the intestinal barrier. This is closely related to intestinal epithelial cell apoptosis caused by the mass production of reactive oxygen species (ROS). Baicalin (Bai) is a major active ingredient in Chinese traditional herbal medicine that has antioxidant, anti-inflammatory, and anti-cancer properties. The purpose of this study was to explore the underlying mechanisms by which Bai protects against hydrogen peroxide (H2O2)-induced intestinal injury in vitro. Our results indicated that H2O2 treatment caused injury to IPEC-J2 cells, resulting in their apoptosis. However, Bai treatment attenuated H2O2-induced IPEC-J2 cell damage by up-regulating the mRNA and protein expression of ZO-1, Occludin, and Claudin1. Besides, Bai treatment prevented H2O2-induced ROS and MDA production and increased the activities of antioxidant enzymes (SOD, CAT, and GSH-PX). Moreover, Bai treatment also attenuated H2O2-induced apoptosis in IPEC-J2 cells by down-regulating the mRNA expression of Caspase-3 and Caspase-9 and up-regulating the mRNA expression of FAS and Bax, which are involved in the inhibition of mitochondrial pathways. The expression of Nrf2 increased after treatment with H2O2, and Bai can alleviate this phenomenon. Meanwhile, Bai down-regulated the ratio of phosphorylated AMPK to unphosphorylated AMPK, which is indicative of the mRNA abundance of antioxidant-related genes. In addition, knockdown of AMPK by short-hairpin RNA (shRNA) significantly reduced the protein levels of AMPK and Nrf2, increased the percentage of apoptotic cells, and abrogated Bai-mediated protection against oxidative stress. Collectively, our results indicated that Bai attenuated H2O2-induced cell injury and apoptosis in IPEC-J2 cells through improving the antioxidant capacity through the inhibition of the oxidative stress-mediated AMPK/Nrf2 signaling pathway.
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Almenara, Erika. "Trauma y memoria en La sangre de la aurora de Claudia Salazar y Magallanes de Salvador del Solar". Letras Femeninas 43, n.º 2 (1 de noviembre de 2017): 55–67. http://dx.doi.org/10.14321/letrfeme.43.2.0055.
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Resumen A dieciséis años del fin del conflicto armado interno entre el Estado peruano y el PCP-Sendero Luminoso (1980-2000), continúan emergiendo nuevas voces en el extenso mapa de la producción cultural que siguen inquiriendo, desde novedosas técnicas, acerca de las razones, lógicas y consecuencias de dicho conflicto. El sistemático maltrato sexual y físico perpetrado por parte de los representantes del Estado, específicamente hacia mujeres indígenas quechua-hablantes, durante este conflicto ha sido una constante dentro de la producción cultural peruana de los últimos años. Este artículo reflexionará acerca de cómo la novela La sangre de la aurora (2013) de Claudia Salazar y la película Magallanes (2015) de Salvador del Solar, desestabilizan las relaciones de poder entre víctima y victimario, articulando una memoria histórica-política-cultural distinta a la trabajada por publicaciones anteriores con respecto a la victimización de la mujer indígena peruana durante el conflicto armado interno. Estos dos objetos culturales, pues, presentan a la misma desde una posición empoderada que no cae en el retrato simple de la mujer violada sin agencia y rompe con la representación de la mujer sin recursos ante la lógica patriarcal abusiva.
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Raiko, Laura, Elina Siljamäki, Mỹ G. Mahoney, Heli Putaala, Erkki Suominen, Juha Peltonen y Sirkku Peltonen. "Hailey-Hailey disease and tight junctions: Claudins 1 and 4 are regulated by ATP2C1 gene encoding Ca2+/Mn2+ATPase SPCA1 in cultured keratinocytes". Experimental Dermatology 21, n.º 8 (29 de mayo de 2012): 586–91. http://dx.doi.org/10.1111/j.1600-0625.2012.01520.x.
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Potenza, Alessia, Chiara Balestrieri, Luca Albarello, Federica Pedica, Lorena Stasi, Francesco Manfredi, Martina Spiga et al. "Abstract 567: CRISPR/Cas9-mediated CD39 disruption can be combined with TCR editing in T cells to improve the adoptive T cell therapy of colorectal cancer". Cancer Research 82, n.º 12_Supplement (15 de junio de 2022): 567. http://dx.doi.org/10.1158/1538-7445.am2022-567.
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Abstract Colorectal cancer (CRC) is the 2nd cause of cancer-related death. Despite standard therapies, more than 50% of patients experience relapse, eventually with metastatic disease. The CRC microenvironment is densely infiltrated by T-cells, which presence correlates with improved overall survival, thus sustaining the rational for immunotherapy. Here, we paired high-dimensional flow cytometry, bulk RNA sequencing and immunohistochemistry to describe the phenotype and the exhaustion status of T-cells infiltrating primary and metastatic CRC. Analysis of the healthy, peritumoral and neoplastic tissues of treatment-naïve primary CRCs and of the peritumoral and tumoral tissues of CRC patients undergoing surgery for liver metastasis, revealed extensive transcriptional and spatial remodeling across tumors. Unsupervised analysis of flow cytometry data performed by an advanced pipeline of data handling by dimensionality reduction and clustering algorithms allowed the definition of a peculiar inhibitory receptors signature on TILs enriched both in primary CRCs and liver metastases. Of note, CD39 was upregulated in both the signatures retrieved from primary and metastatic CRC, thus suggesting its relevance as molecular target for T-cells engineering. By CRISPR/Cas9 we disrupted the CD39 gene in T cells with >80% efficiency. We combined CD39 knock-out with the genetic disruption of alpha and beta chains of the endogenous TCR, observing >90% efficiency for both genes, thus generating triple-knockout T-cells. By repetitively stimulating healthy donors’ peripheral blood mononuclear cells with autologous antigen-presenting cells loaded with a pool of peptides selected to be immunogenic and expressed by CRC, we obtained a library of anti-tumor TCRs to redirected the specificity of triple knock-out lymphocytes. Our preliminary experiments showed a functional advantage for TCR-redirected, CD39 disrupted T-cells in recognizing and killing CRC target cells. Citation Format: Alessia Potenza, Chiara Balestrieri, Luca Albarello, Federica Pedica, Lorena Stasi, Francesco Manfredi, Martina Spiga, Elena Tassi, Beatrice Claudia Cianciotti, Danilo Abbati, Ugo Elmore, Andrea Biondi, Luca Aldrighetti, Claudia De Lalla, Giulia Di Lullo, Paolo Dellabona, Eliana Ruggiero, Riccardo Rosati, Chiara Bonini. CRISPR/Cas9-mediated CD39 disruption can be combined with TCR editing in T cells to improve the adoptive T cell therapy of colorectal cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 567.
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Ibrahim, Doaa, Hassainen I. El-sayed, Elsabbagh R. Mahmoud, Ghada I. Abd El-Rahman, Shefaa M. Bazeed, Abdelwahab A. Abdelwarith, Aya Elgamal et al. "Impacts of Solid-State Fermented Barley with Fibrolytic Exogenous Enzymes on Feed Utilization, and Antioxidant Status of Broiler Chickens". Veterinary Sciences 10, n.º 10 (27 de septiembre de 2023): 594. http://dx.doi.org/10.3390/vetsci10100594.
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The present and future high demand of common cereals as corn and wheat encourage the development of feed processing technology that allows for the dietary inclusion of other cereals of low nutritional value in poultry feeding. Barley grains contain anti-nutritional factors that limit their dietary inclusion in the poultry industry. The treatment of barley with solid-state fermentation and exogenous enzymes (FBEs) provides a good alternative to common cereals. In this study, barley grains were subjected to solid-state microbial fermentation using Lactobacillus plantarum, Bacillus subtilis and exogenous fibrolytic enzymes. This study aimed to assess the impact of FBEs on growth, feed utilization efficiency, immune modulation, antioxidant status and the expression of intestinal barrier and nutrient transporter-related genes. One-day-old broiler chicks (Ross 308, n = 400) comprised four representative groups with ten replicates (10 chicks/replicate) and were fed corn-soybean meal basal diets with inclusions of FBEs at 0, 5, 10 and 15% for 38 days. Solid-state fermentation of barley grains with fibrolytic enzymes increased protein content, lowered crude fiber and reduced sugars compared to non-fermented barley gains. In consequence, the group fed FBEs10% had the superior feed utilization efficiency and body weight gain (increased by 4.7%) with higher levels of nutrient metabolizability, pancreatic digestive enzyme activities and low digesta viscosity. Notably, the group fed FBEs10% showed an increased villi height and a decreased crypt depth with a remarkable hyperactivity of duodenal glands. In addition, higher inclusion levels of FBEs boosted serum immune-related parameters and intestinal and breast muscle antioxidants status. Intestinal nutrient transporters encoding genes (GLUT-1, CAAT-1, LAT1 and PepT-1) and intestinal barriers encoding genes (MUC-2, JAM-2, occludin, claudins-1 and β-defensin 1) were upregulated with higher dietary FBEs levels. In conclusion, feeding on FBEs10% positively enhanced broiler chickens’ performance, feed efficiency and antioxidant status, and boosted intestinal barrier nutrient transporters encoding genes.
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Susik, Kristen. "Joseph P. Allen and Claudia W. Allen: Escaping the Endless Adolescence: How We Can Help Our Teenagers Grow up before They Grow Old". Journal of Youth and Adolescence 41, n.º 7 (12 de mayo de 2012): 969–72. http://dx.doi.org/10.1007/s10964-012-9771-x.
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Hwang, I. H. y E. B. Jeung. "146 DIFFERENTIAL EXPRESSION OF TRANSCELLULAR CALCIUM TRANSPORT AND PARACELLULAR TIGHT JUNCTION GENES IN THE PLACENTAE OF CALBINDIN-D9k, -D28k AND -D9k/D28k KNOCKOUT MICE". Reproduction, Fertility and Development 24, n.º 1 (2012): 185. http://dx.doi.org/10.1071/rdv24n1ab146.
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The placenta has many essential roles in the maintenance of pregnancy and homeostasis. Calcium transport and regulation are also controlled by the placenta. In general, calcium transport is divided into an active transcellular pathway and a passive paracellular pathway. Transient receptor potential cation channel subfamily V member 5/6 (TRPV5/6), calbindin-D9k/-28k (CaBP-9k/-28k) and Na+/Ca2+ exchanger (NCX1) are involved in the transcellular pathway. The paracellular pathway is determined by the expression of tight junction genes, such as occludin, claudins and ZO-1. In this study, we analysed the difference in calcium transport in the placentae of CaBP-9k and CaBP-28k knockout (KO) mice compared with that of wild-type (WT) mice. Placentae were collected and used for mRNA and protein evaluation from 9 mice of each type (a total of 36 mice). All mice were killed on gestational Day 19. We confirmed mRNA expression by RT-qPCR and protein expression by Western blot analysis. The data were statistically analysed by one-way ANOVA using Tukey's test. In the transcellular pathway, the expression levels of NCX1 and TPRV6 were shown to be significantly increased in KO mice compared with WT mice. In the paracellular pathway, occluding, which is directly related to permeability, mRNA and protein expression was significantly increased in single KO mice compared with WT, but not in double KO mice. Claudin-4, which is a cation barrier, mRNA and protein expression patterns were significantly decreased in single KO mice compared with WT, but not in double KO mice. These results imply that the disability of calcium buffering due to CaBP-9k or CaBP-28k KO may lead to an accelerated transcellular pathway. In addition, a single KO of calcium-binding proteins may lead to decreased paracellular permeability to weaken the leakage of calcium through the tight junction and may also lead to increased cation selectivity of tight junctions. Taken together, these results might indicate that KO of calcium-binding proteins may induce activation of a compensating transcellular pathway in the placenta of mice and a paracellular pathway may support the maintenance of calcium homeostasis.
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Pellizas, Claudia G., Aldo H. Coleoni, Ana M. Cabanillas, Ana M. Masini-Repiso y María E. Costamagna. "Response of triiodothyronine-dependent enzyme activities to insulin-like growth factor I and growth hormone in cultured rat hepatocytes". European Journal of Endocrinology 134, n.º 2 (febrero de 1996): 215–20. http://dx.doi.org/10.1530/eje.0.1340215.
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Pellizas CG, Coleoni AH, Cabanillas AM, Masini-Repiso AM, Costamagna ME. Response of triiodothyronine-dependent enzyme activities to insulin-like growth factor I and growth hormone in cultured cat hepatocytes. Eur J Endocrinol 1996:134:215–20. ISSN 0804–4643 Triiodothyronine (T3) is involved in the regulation of the growth hormone-insulin-like growth factor I (GH-IGF-I) axis. In this study we investigated the effect of GH and IGF-I on the metabolic response of T3 in target tissues by evaluating the activity of two T3-dependent liver enzymes: mitochondrial α-glycerophosphate dehydrogenase (α-GPD) and cytosolic malic enzyme (ME) in rat hepatocytes in primary culture. Growth hormone (35 nmol/l) as well as IGF-I (0.5 μmol/l) reduced α-GPD and ME activities (p < 0.01) compared to the control group. Timecourse studies indicated that IGF-I 1.5 μmol/l) significantly decreased α-GPD and ME activities (p < 0.01) after 24 h, whereas the effect of GH (35 nmol/l) was recorded only after 36 h (p < 0.01). This delayed effect of GH compared to IGF-I suggested the possibility that the effect of GH could be mediated by IGF-I synthesis. To test this hypothesis, the effect of GH on the two enzyme activities was studied in the presence of anti-IGF-I antibodies. A gradual recovery of α-GPD and ME activities (p < 0.01) was observed in the presence of GH (35 nmol/l) plus increasing concentrations of anti-IGF-I antiserum. The maximal α-GPD and ME activities attained after the incubation of the liver cells with 1 μmol/l T3. a concentration high enough to fully saturate the nuclear T3 receptors for 24 h, were lowered significantly by 1.0 μmol/l IGF-I (p < 0.01). This finding suggests that the IGF-I effect might be independent of the saturation of the nuclear T3 receptors. In conclusion, in cultured rat hepatocytes, GH and IGF-I reduced the metabolic response of T3 evaluated by two liver T3-dependent enzyme activities. The effect of GH was mediated at least in part by IGF-I. Claudia G Pellizas, Dpto Bioquímica Clínica, Facultad de Ciencias Químicas, Universidad Nacional de Códoba, Casilla de Correo 61, Sucursal 16, (5016) Córdoba, Argentina.
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Carrozzo, Francesco, Gennaro Bruno, Claudia Masi, Alessia Boaretto, Claudio Favre y Maura Calvani. "Abstract 4797: β3-AR blockade induces differentiation of malignant leukemia T cells in mature T lymphocytes". Cancer Research 83, n.º 7_Supplement (4 de abril de 2023): 4797. http://dx.doi.org/10.1158/1538-7445.am2023-4797.
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Abstract Acute lymphoblastic leukemia (ALL) is a genetically heterogeneous cancer that arises from diverse genetic alterations during early lymphocyte development. About 10-15% of T-cell acute lymphoblastic leukemia (T-ALL) cases occur in childhood; despite having an event-free survival (EFS) rate of 85%, relapse is the main problem of this type of cancer. Mitochondria metabolic reprogramming plays a crucial role in the development of lymphocytes both in physiological and pathological processes such as differentiation and neoplastic transformation respectively. Mitochondria are the main actors of cellular homeostasis. They use glycolysis products exploiting them in the Krebs cycle and in oxidative phosphorylation to produce energy and plays key roles in reactive oxygen species (ROS) generation, Ca2+ signaling, cell death induction, and cellular differentiation. In particular, the increase of ROS is important to reduce tumor cell viability and at the same time is involved in induction of hematopoiesis. β3-adrenoreceptors (β3-Ars) is a class of receptors associated with pro-tumoral signaling in different tumors. In this study, we first have observed the expression of β3-Ars in leukemia T cells and then we studied how the modulation of this receptors affected tumor-related pathways. The treatment with an antagonist of β3-Ars (SR59230A) induced an increase of ROS leading to lymphoblastic cells differentiation, decrease of proliferation and enhanced induction of apoptosis signaling. Overall, these results suggest that β3-Ars could be a possible target for treatment of T-ALL. Citation Format: Francesco Carrozzo, Gennaro Bruno, Claudia Masi, Alessia Boaretto, Claudio Favre, Maura Calvani. β3-AR blockade induces differentiation of malignant leukemia T cells in mature T lymphocytes. [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 4797.
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Lyu, Chenchen, Bao Yuan, Yu Meng, Shuai Cong, Haoyu Che, Xingyu Ji, Haoqi Wang et al. "Puerarin Alleviates H2O2-Induced Oxidative Stress and Blood–Milk Barrier Impairment in Dairy Cows". International Journal of Molecular Sciences 24, n.º 9 (24 de abril de 2023): 7742. http://dx.doi.org/10.3390/ijms24097742.
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During the perinatal period, the bovine mammary epithelial cells of dairy cows exhibit vigorous metabolism and produce large amounts of reactive oxygen species (ROS). The resulting redox balance disruption leads to oxidative stress, one of the main causes of mastitis. Puerarin (PUE) is a natural flavonoid in the root of PUE that has attracted extensive attention as a potential antioxidant. This study first investigated whether PUE could reduce oxidative damage and mastitis induced by hydrogen peroxide (H2O2) in bovine mammary epithelial cells in vitro and elucidated the molecular mechanism. In vitro, BMECs (Bovine mammary epithelial cells) were divided into four treatment groups: Control group (no treatment), H2O2 group (H2O2 stimulation), PUE + H2O2 group (H2O2 stimulation before PUE rescue) and PUE group (positive control). The growth of BMECs in each group was observed, and oxidative stress-related indices were detected. Fluorescence quantitative PCR (qRT–PCR) was used to detect the expression of tightly linked genes, antioxidant genes, and inflammatory factors. The expression of p65 protein was detected by Western blot. In vivo, twenty cows with an average age of 5 years having given birth three times were divided into the normal dairy cow group, normal dairy cow group fed PUE, mastitis dairy cow group fed PUE, and mastitis dairy cow group fed PUE (n = 5). The contents of TNF-α, IL-6, and IL-1β in milk and serum were detected. In BMECs, the results showed that the PUE treatment increased the activities of glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC); ROS and malondialdehyde (MDA) levels were reduced. Thus, PUE alleviated H2O2-induced oxidative stress in vitro. In addition, the PUE treatment eliminated the inhibition of H2O2 on the expression of oxidation genes and tight junction genes, and the enrichment degree of NRF-2, HO-1, xCT, and tight junctions (claudin4, occludin, ZO-1 and symplekin) increased. The PUE treatment also inhibited the expression of NF-κB-associated inflammatory factors (IL-6 and IL-8) and the chemokine CCL5 in H2O2-induced BMECs. In vivo experiments also confirmed that feeding PUE can reduce the expression of inflammatory factors in the milk and serum of lactating dairy cows. In conclusion, PUE can effectively reduce the oxidative stress of bovine mammary epithelial cells, enhance the tight junctions between cells, and play an anti-inflammatory role. This study provides a theoretical basis for PUE prevention and treatment of mastitis and oxidative stress. The use of PUE should be considered as a feed additive in future dairy farming.
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Tiago, Manoela, Timothy J. Purwin, Mitchell E. Fane, Yash Chhabra, Jessica L. F. Teh, Rama Kadamb, Weijia Cai et al. "Abstract A005: The aged tumor microenvironment influences tolerance to targeted therapy via NR2F1 overexpression in BRAF-mutant melanoma". Cancer Research 83, n.º 2_Supplement_1 (15 de enero de 2023): A005. http://dx.doi.org/10.1158/1538-7445.agca22-a005.
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Abstract Despite the clinical success of targeted inhibitors, tumor responses to these agents are transient, and drug-tolerant residual cells seed resistance. Understanding the role of tumor-intrinsic mechanisms and effects of the tumor microenvironment in mediating drug tolerance will guide and optimize targeted therapies. Given similarities between drug tolerance and cellular dormancy, we studied the role of nuclear receptor subfamily 2 group F member 1 (NR2F1) in response to targeted therapy. We used BRAF-mutant cutaneous melanoma models treated with BRAF and MEK inhibitors (BRAFi + MEKi) since patients treated with this combination typically develop resistance. The aged tumor microenvironment has been shown to increase therapy resistance, and we find that melanoma cells in aged mice express higher levels of NR2F1 than when the same cells are injected into young animals. Transcriptomic analysis of melanoma patient samples treated with BRAFi + MEKi showed increased expression of NR2F1 post-treatment. Similarly, NR2F1 was highly expressed in minimal residual disease collected on BRAFi + MEKi treatment in patient- and xenograft-derived tumors. High expression of NR2F1 promotes tumor survival and invasion in the presence of BRAFi + MEKi in vitro leading to tolerance to BRAFi + MEKi efficacy in vivo. Depletion of NR2F1 in YUMM1.7 allografts grown in aged mice improved response to the combination therapy. Altogether, our findings suggest that NR2F1 promotes drug tolerance leading to minimal residual disease in melanoma and that NR2F1-high cells may be targeted with CDK4/6 inhibitors to improve targeted therapy outcomes in melanoma patients. Citation Format: Manoela Tiago, Timothy J. Purwin, Mitchell E. Fane, Yash Chhabra, Jessica L. F. Teh, Rama Kadamb, Weijia Cai, Inna Chervoneva, Sheera Rosenbaum, Vivian Chua, Nir Hacohen, Michael A. Davies, Jessie Villanieva, Ashani T. Weeraratna, Claudia Capparelli, Julio A. Aguirre-Ghiso, Andrew E. Aplin. The aged tumor microenvironment influences tolerance to targeted therapy via NR2F1 overexpression in BRAF-mutant melanoma [abstract]. In: Proceedings of the AACR Special Conference: Aging and Cancer; 2022 Nov 17-20; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2022;83(2 Suppl_1):Abstract nr A005.
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Cascini, Caterina, Daniele Lecis, Valeria Cancila, Katia Scotlandi, Claudio Tripodo, Mario P. Colombo y Claudia Chiodoni. "Abstract 3349: Identification of new potential vulnerabilities for differentiation-based therapeutic strategies against osteosarcoma". Cancer Research 84, n.º 6_Supplement (22 de marzo de 2024): 3349. http://dx.doi.org/10.1158/1538-7445.am2024-3349.
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Abstract Osteosarcoma (OS), a mesenchymal bone tumor affecting mainly children and adolescents is characterized by a particularly aggressive behavior, with 20% of patients showing lung metastasis already at diagnosis. Current OS treatment strategies rely on multi-drug chemotherapy, and the prognosis for metastatic cases remains grim, underscoring the pressing need for novel therapeutic approaches. OS is considered a differentiation-related disorder, stemming from the inability of mesenchymal stem cells or osteoblastic progenitors to progress towards terminal differentiation. In our study we explored the impact of targeting ZEB1, a transcription factor known to play a pivotal role in maintaining mesenchymal and stemness characteristics in cancer, on OS cells. We employed CRISPR-Cas9 and shRNA interference techniques to inhibit ZEB1 expression in mouse immune competent OS models. In vitro, ZEB1 deficiency significantly diminished the stemness potential of OS cells, as assessed by spheroid formation assays, while promoting osteogenic differentiation. In vivo, ZEB1 deletion in OS cells led to a significant reduction in primary tumor growth. Tumors originating from ZEB1 KO cells exhibited a more differentiated morphology and higher extracellular matrix deposition compared to controls. Intriguingly, the absence of ZEB1 in tumor cells also influenced the immune infiltrate, with ZEB1-deficient tumors showing significantly fewer pro-tumoral CD206+ M2-like macrophages. This observation is in line with the significant down-modulation of CCL2 expression we detected in ZEB1 KO cells. When injected intravenously, ZEB1-deficient cells produced fewer and smaller lung metastases than control cells. Transcriptional changes induced by ZEB1 deletion were investigated by gene expression profile (GEP) and identified 849 down-regulated and 1093 up-regulated genes in ZEB1 knockout (KO) clones versus ZEB1-competent controls. Gene set enrichment analysis showed a down-modulation of pathways related to cellular proliferation and survival, such as MTORC1 signaling, MYC targets, GM2 checkpoint, E2F targets and oxidative phosphorylation in the absence of ZEB1. Single gene analysis identified among the most up-regulated genes in ZEB1-deficient cells Sfrp1, a negative regulator of the WNT/b-CAT pathway, which in turn regulates MYC, whose pathway is indeed repressed in ZEB1 KO cells. We hypothesize that a high expression of SFRP1 could vicariate the effects of ZEB1 inhibition on OS cell stemness, differentiation state, and in vivo aggressiveness, and therefore could act as a tumor suppressor, which could be potentially exploited for therapeutic strategies. Citation Format: Caterina Cascini, Daniele Lecis, Valeria Cancila, Katia Scotlandi, Claudio Tripodo, Mario P. Colombo, Claudia Chiodoni. Identification of new potential vulnerabilities for differentiation-based therapeutic strategies against osteosarcoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3349.
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Zhang, J. Q., J. Luo, Q. Y. Su, J. Qiao, S. X. Zhang, X. Li y C. Wang. "POS0021 CHANGES OF GUT MICROBIOTA IN CONNECTIVE TISSUE DISEASE AND ITS RELATIONSHIP WITH LYMPHOCYTE SUBSETS AND CYTOKINES". Annals of the Rheumatic Diseases 81, Suppl 1 (23 de mayo de 2022): 225.2–225. http://dx.doi.org/10.1136/annrheumdis-2022-eular.3440.
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BackgroundConnective tissue disease (CTD) is a group of autoimmune diseases characterized by the damage of connective tissue components in various parts of the body, which involved multiple organs and systems. Dysbiosis in the gut microbiome is associated with various autoimmune diseases such as CTD.ObjectivesTo explore the characters of gut microbiota and their relationship with peripheral lymphocyte subsets and cytokines in patients with CTD.MethodsStool samples were collected from 63 CTD patients and 63 age- and sex-matched healthy controls(HCs). Microbial genomes were extracted for 16S rRNA gene sequencing. Gut microbiota characters (alpha diversity, beta diversity, and microbial composition) were analysed by R (version 4.0.1). Peripheral lymphocyte subsets were assessed by flow cytometry. Pearson correlation analysis was used to detect the correlation between the relative abundance of genus in the sample and the activity index; correlations with p < 0.05 were considered significant.ResultsShannon and Simpson index revealed a decreased alpha diversity in CTD compared with that of HCs (p < 0.05), though not significantly difference in ACE and Chao1 parameters (p > 0.05, Figure 1A). Bray curtis distance-based beta-diversity analysis indicated significant differences in microbial communities between CTD and HCs (p = 0.0014, ANOSIM, Figure 1B). At the genus level, CTD patients had higher abundances of Terrisporobacter (p<0.01), Paraprevotella (p<0.01), CAG−352 (p<0.01), et al. but lower abundances of Streptococcus (p<0.01), Pseudomonas (p<0.01), Bacteroides(p<0.01), et al (Figure 1D). IgM was positively correlated with Lactococcus (p<0.05), Family_XIII_AD3011_group (p<0.05), Streptococcus (p<0.05). Th17 was positively correlated with Pseudomonas (p<0.01). Th2 was positively correlated with Christensenellaceae_R−7_group (p<0.001), UCG−010 (p<0.001) was positively correlated. Treg and Th2 were positively correlated with Christensenellaceae_R−7_group (p<0.01), UCG−010 (p<0.01). Treg was positively correlated with Lachnoclostridium (p<0.05) (Figure 1E).ConclusionPattients with CTD had disbiosis of gut microbiota charaterized by impared diversity and abnomal composition,which was closely correlated with peripheral lymphocyte subsets.References[1]Laura Ghezzi,Claudia Cantoni,Gabriela V Pinget,et al.Targeting the gut to treat multiple sclerosis.J Clin Invest.2021 Jul 1;131(13):e143774. doi: 10.1172/JCI143774.[2]Yoshihiko Tomofuji,Toshihiro Kishikawa,Yuichi Maeda,et al.Whole gut virome analysis of 476 Japanese revealed a link between phage and autoimmune disease.Ann Rheum Dis. 2022 Feb;81(2):278-288. doi: 10.1136/annrheumdis-2021-221267. Epub 2021 Dec 8.AcknowledgementsThis work was supported by the National Natural Science Foundation of China (No. 82001740).Disclosure of InterestsNone declared
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Kinsella, Zak, Hannah Nyarko, Anna Blümel, Mairi Lucas, Daria Kalinska-Lysiak, Claudia Aura Gonzalez, Arman Rahman et al. "Abstract PS16-10: SPATIAL IMMUNE CELL DISTRIBUTION CAN REFINE PROGNOSIS IN EARLY-STAGE ER+/HER2-/LN- BREAST CANCER". Cancer Research 84, n.º 9_Supplement (2 de mayo de 2024): PS16–10—PS16–10. http://dx.doi.org/10.1158/1538-7445.sabcs23-ps16-10.
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Abstract Lymphocytic infiltrate is a known prognostic biomarker in estrogen receptor(ER)-negative breast cancers (BCs). Comparatively ER+ disease is putatively cold, however, there exists an infiltrate-rich subset of ER+ tumours with significant spatial heterogeneity and unknown clinical impact. Using serial sections taken from early-stage, ER+/HER2- breast tumours of Irish patients enrolled in the TAILORx trial (n=450), we aimed to investigate the prognostic potential of markers encompassing tumour architecture. Immunohistochemistry for Ki67 and CD45 (leukocyte common-antigen), and staining for haematoxylin and eosin was applied to all sections [1]. Classifiers for stromal fraction (SF), stromal-infiltrate (sTIL), Ki67-LI, and their spatial relationships within the tumour were generated using QuPath [2] and R Studio. Trained marker classifiers were validated against an expert pathologist (R2 of M-Score to: CD45%: 0.968, Ki67-LI: 0.814, sTIL: 0.864) to define observed lymphocytes as tumour or stromal-infiltrating, retain only tumour Ki67+ density, and to investigate SF. Cohort mean SF was 67.69% (range 16.35 – 98.29%), with marginally significant differences in recurrence prediction for cohort high v low SF by mean (c-index = 0.58, p< 0.032), and luminal A disease (p=0.037) only. sTILs did not differ significantly between high/low mean SF (Mann-Whitney p=0.6201), though sTIL was prognostic in the OncotypeDx intermediate Recurrence Score (RS) category overall (p=0.0076). This trend appeared strongest in intermediate RS patients receiving chemo-endocrine therapy (HT+CT) (p < 0.0001) vs endocrine therapy (HT) alone (p=0.86). Investigating the effects of prescribed therapy on sTIL-derived recurrence risk also revealed significant trends in those patients receiving HT+CT only (p < 0.00001) vs HT alone (p=0.26). Spatial analysis of sTILs suggest that tumours become more immune excluded as Oncotype Dx RS increases - particularly from intermediate to high RS (Wilcoxon Intermediate v High: p=0.0077), with significant differences in survival for high/low tumour-immune hotspots observed in Intermediate RS, HT+CT treated patients (p=0.0052). Further spatial analysis suggests that high normalised frequency of infiltrate [method adapted from 3] (within 7um of tumour cells) have negative prognostic impact for premenopausal patients (p=0.017), and inter-sectional analysis identifies niche tumour environments where high Ki67-LI colocalize with immune infiltrates[methods adapted from 4, 5], most notable in Intermediate RS tumours.. Overall these data suggest immune-spatial subsets can be used to refine risk stratification of ER+ breast cancer. References: [1] Lucas, M., Kinsella, Z., Gonzalez, C.A. et al. CD45-positive tumour infiltrating lymphocytes in early-stage hormone-positive, HER2-negative (ER+/HER2-) breast cancer: Correlation with proliferation and prognostic signature scores. Meeting Abstract ASCO Annual Meeting I. 2022. [2] Bankhead, P., Loughrey, M.B., Fernandez, J.A. et al. QuPath: Open source software for digital pathology image analysis. Scientific Reports. 2017;7:16878. [3] Yuan. Y. Modelling the spatial heterogeneity and molecular correlates of lymphocytic infiltration in triple-negative breast cancer. Journal of the Royal Society Interface. 2015;12(103):201411532 [4] Maley, C.C., Koelble, K., Natrajan, R. et al. An ecological measure of immune-cancer colocalization as a prognostic factor for breast cancer. Breast Cancer Research. 2022;17(1):131. [5] Ord, J.K., Getis, A. Local spatial autocorrelation statistics: Distributional issues and an application. Geographical Analysis. 1995;27(4):286-306. Citation Format: Zak Kinsella, Hannah Nyarko, Anna Blümel, Mairi Lucas, Daria Kalinska-Lysiak, Claudia Aura Gonzalez, Arman Rahman, Joanna Fay, Tony O'Grady, Verena Murphy, John Crown, Cathy Kelly, William Gallagher, Darran O'Connor. SPATIAL IMMUNE CELL DISTRIBUTION CAN REFINE PROGNOSIS IN EARLY-STAGE ER+/HER2-/LN- BREAST CANCER [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PS16-10.
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Stein, Robert, Ralph Wirtz, Andrea Marshall, Jane Bayani, Sebastian Eidt, Claudia Schumacher, Hans-Peter Sinn et al. "Abstract PO4-16-02: Can high progesterone receptor (PgR) expression identify tumours with low-risk tumour gene expression scores?" Cancer Research 84, n.º 9_Supplement (2 de mayo de 2024): PO4–16–02—PO4–16–02. http://dx.doi.org/10.1158/1538-7445.sabcs23-po4-16-02.
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Abstract Background Strong PgR expression predicts favorable outcomes for ER+ve HER2-ve breast cancer and has been proposed as a surrogate marker to distinguish between IHC-defined luminal A and luminal B subtypes. It is therefore possible that strong PgR expression may be able to predict tumor gene expression test results and independently identify tumors that are unlikely to be chemotherapy sensitive. PgR expression is traditionally determined by immunohistochemistry (IHC). Several validated RNA-based PGR expression tests have been developed that may outperform IHC. Methods We compared Oncotype DX RS with Oncotype DX reported PGR in 4 independent datasets which included 407 cases from the OPTIMA prelim trial. We further analyzed 251 OPTIMA prelim cases which had additional tumor gene expression data. All gene expression assays were performed by the test vendor, including PGR gene expression determined using the Mammatyper assay. PgR IHC was determined in a single laboratory on triplicate tissue micro-arrays using quantitative image analysis including a 10% manual quality control check. We analyzed PGR expression using cutoffs that correspond to approximately 20% staining; the standard Oncotype DX PGR assay is reported as positive if the score is >5.4, corresponding to approximately 1% staining by IHC. We used Spearman’s rank correlation coefficient to compare PGR data. Results The four Oncotype DX datasets consistently demonstrated that high Oncotype PGR expression was associated with a low RS (table). Combining the 3 validation data sets consisting of 633 cases, 70.9% had high PGR expression of which 92.7% had a an Oncotype RS ≤25. Approximately 50% of cases with low Oncotype PGR expression had an Oncotype RS >25. Mammatyper and Oncotype PGR were highly correlated (Rs = 0.9258, P< 0.001) in the OPTIMA prelim dataset (n=251), with only 8.4% of tumors having discordant high/low Mammatyper and Oncotype PGR scores. 93.2% of 176 Mammatyper high PGR expression cases had an RS ≤25. The Mammatyper PGR and PgR IHC correlation was weaker (Rs=0.763, P< 0.001); 87.2% of 211 cases with >20% staining had RS ≤25. PgR IHC staining had a bimodal distribution and there was little effect on the prediction of low RS score up to a 67% cut-off. Mammatyper and Oncotype PGR scores both appear to have a normal distribution. We took advantage of this to perform an exploratory analysis using a higher Mammatyper PGR cutoff. We were able to show superior prediction of a low RS (96.8%) but with a reduced proportion (50.2%) of high PGR score tumors. High PGR gene expression was weakly associated with low (≤60) Prosigna ROR_PT score and MammaPrint low risk (72.2% and 65.9% respectively) and with Prosigna and MammaPrint luminal A subtype (both 64.8%). Conclusion High progesterone receptor gene expression measured using locally performed RNA-based assays may allow the reliable prediction of Oncotype DX low-risk tumours. This analysis provides additional information for the clinical utility of PGR measurement. Additional data will be presented on the optimal PGR cutoff. OPTIMA prelim is registered as ISRCTN42400492 and funded by the UK NIHR Health Technology Assessment Programme, award number 10/34/01. Views expressed are those of the authors and not those of the HTA Programme, NIHR, NHS or the Department of Health. Table. Oncotype DX RS and PGR in 4 datasets Distribution of RS according to %cases with high or low PGR Citation Format: Robert Stein, Ralph Wirtz, Andrea Marshall, Jane Bayani, Sebastian Eidt, Claudia Schumacher, Hans-Peter Sinn, Andreas Schneeweiss, Andreas Makris, Iain Macpherson, Luke Hughes-Davies, Tammy Piper, Monika Sobol, Georgina Dotchin, Helen Higgins, Sarah Pinder, Abeer Shaaban, Janet Dunn, John MS Bartlett. Can high progesterone receptor (PgR) expression identify tumours with low-risk tumour gene expression scores? [abstract]. In: Proceedings of the 2023 San Antonio Breast Cancer Symposium; 2023 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2024;84(9 Suppl):Abstract nr PO4-16-02.
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Sarnat, Harvey B. "LA SURVEILLANCE NEUROLOGIQUE AU COURS DE LA PREMIÈRE ANNÉE DE LA VIE. Par Claudine Amiel-Tison et Albert Grenier. Publié par Masson Éditeur. Paris, France. (Disponible au Canada chez Somabec Ltée, Case postale295, St-Hyacinthe, Québec J3S5T5.) 175pages. 108figures. Prix 16 $ can." Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques 13, n.º 3 (agosto de 1986): 273–74. http://dx.doi.org/10.1017/s0317167100036453.
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