D'Angelo Dott.ssa Luciana
Pubblicazioni su PubMed
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Fusion-negative rhabdomyosarcoma 3D organoids to predict effective drug combinations: A proof-of-concept on cell death inducers.
Cell Rep Med2023 Dec;4(12):101339. doi: 101339.
Savary Clara, Luciana Léa, Huchedé Paul, Tourbez Arthur, Coquet Claire, Broustal Maëlle, Lopez Gonzalez Alejandro, Deligne Clémence, Diot Thomas, Naret Olivier, Costa Mariana, Meynard Nina, Barbet Virginie, Müller Kevin, Tonon Laurie, Gadot Nicolas, Degletagne Cyril, Attignon Valéry, Léon Sophie, Vanbelle Christophe, Bomane Alexandra, Rochet Isabelle, Mournetas Virginie, Oliveira Luciana, Rinaudo Paul, Bergeron Christophe, Dutour Aurélie, Cordier-Bussat Martine, Roch Aline, Brandenberg Nathalie, El Zein Sophie, Watson Sarah, Orbach Daniel, Delattre Olivier, Dijoud Frédérique, Corradini Nadège, Picard Cécile, Maucort-Boulch Delphine, Le Grand Marion, Pasquier Eddy, Blay Jean-Yves, Castets Marie, Broutier Laura
Abstract
Rhabdomyosarcoma (RMS) is the main form of pediatric soft-tissue sarcoma. Its cure rate has not notably improved in the last 20 years following relapse, and the lack of reliable preclinical models has hampered the design of new therapies. This is particularly true for highly heterogeneous fusion-negative RMS (FNRMS). Although methods have been proposed to establish FNRMS organoids, their efficiency remains limited to date, both in terms of derivation rate and ability to accurately mimic the original tumor. Here, we present the development of a next-generation 3D organoid model derived from relapsed adult and pediatric FNRMS. This model preserves the molecular features of the patients' tumors and is expandable for several months in 3D, reinforcing its interest to drug combination screening with longitudinal efficacy monitoring. As a proof-of-concept, we demonstrate its preclinical relevance by reevaluating the therapeutic opportunities of targeting apoptosis in FNRMS from a streamlined approach based on transcriptomic data exploitation.
Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.
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Engineered human hepatocyte organoids enable CRISPR-based target discovery and drug screening for steatosis.
Nat Biotechnol2023 Nov;41(11):1567-1581. doi: 10.1038/s41587-023-01680-4.
Hendriks Delilah, Brouwers Jos F, Hamer Karien, Geurts Maarten H, Luciana Léa, Massalini Simone, López-Iglesias Carmen, Peters Peter J, Rodríguez-Colman Maria J, Chuva de Sousa Lopes Susana, Artegiani Benedetta, Clevers Hans
Abstract
The lack of registered drugs for nonalcoholic fatty liver disease (NAFLD) is partly due to the paucity of human-relevant models for target discovery and compound screening. Here we use human fetal hepatocyte organoids to model the first stage of NAFLD, steatosis, representing three different triggers: free fatty acid loading, interindividual genetic variability (PNPLA3 I148M) and monogenic lipid disorders (APOB and MTTP mutations). Screening of drug candidates revealed compounds effective at resolving steatosis. Mechanistic evaluation of effective drugs uncovered repression of de novo lipogenesis as the convergent molecular pathway. We present FatTracer, a CRISPR screening platform to identify steatosis modulators and putative targets using APOB and MTTP organoids. From a screen targeting 35?genes implicated in lipid metabolism and/or NAFLD risk, FADS2 (fatty acid desaturase?2) emerged as an important determinant of hepatic steatosis. Enhancement of FADS2 expression increases polyunsaturated fatty acid abundancy which, in turn, reduces de novo lipogenesis. These organoid models facilitate study of steatosis etiology and drug targets.
© 2023. The Author(s).
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Age-related changes and longitudinal stability of individual differences in ABCD Neurocognition measures.
Dev Cogn Neurosci2022 Apr;54():101078. doi: 101078.
Anokhin Andrey P, Luciana Monica, Banich Marie, Barch Deanna, Bjork James M, Gonzalez Marybel R, Gonzalez Raul, Haist Frank, Jacobus Joanna, Lisdahl Krista, McGlade Erin, McCandliss Bruce, Nagel Bonnie, Nixon Sara Jo, Tapert Susan, Kennedy James T, Thompson Wesley
Abstract
Temporal stability of individual differences is an important prerequisite for accurate tracking of prospective relationships between neurocognition and real-world behavioral outcomes such as substance abuse and psychopathology. Here we report age-related changes and longitudinal test-retest stability (TRS) for the Neurocognition battery of the Adolescent Brain and Cognitive Development (ABCD) study, which included the NIH Toolbox (TB) Cognitive Domain and additional memory and visuospatial processing tests administered at baseline (ages 9-11) and two-year follow-up. As expected, performance improved significantly with age, but the effect size varied broadly, with Pattern Comparison and the Crystallized Cognition Composite showing the largest age-related gain (Cohen's d:.99 and.97, respectively). TRS ranged from fair (Flanker test: r = 0.44) to excellent (Crystallized Cognition Composite: r = 0.82). A comparison of longitudinal changes and cross-sectional age-related differences within baseline and follow-up assessments suggested that, for some measures, longitudinal changes may be confounded by practice effects and differences in task stimuli or procedure between baseline and follow-up. In conclusion, a subset of measures showed good stability of individual differences despite significant age-related changes, warranting their use as prospective predictors. However, caution is needed in the interpretation of observed longitudinal changes as indicators of neurocognitive development.
Copyright © 2022. Published by Elsevier Ltd.
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Staining and High-Resolution Imaging of Three-Dimensional Organoid and Spheroid Models.
J Vis Exp2021 Mar;(169):. doi: 10.3791/62280.
Gonzalez Alejandro Lopez, Luciana Léa, Le Nevé Clémentine, Valantin Julie, Francols Laura, Gadot Nicolas, Vanbelle Christophe, Davignon Laurianne, Broutier Laura
Abstract
In vitro three-dimensional (3D) cell culture models, such as organoids and spheroids, are valuable tools for many applications including development and disease modeling, drug discovery, and regenerative medicine. To fully exploit these models, it is crucial to study them at cellular and subcellular levels. However, characterizing such in vitro 3D cell culture models can be technically challenging and requires specific expertise to perform effective analyses. Here, this paper provides detailed, robust, and complementary protocols to perform staining and subcellular resolution imaging of fixed in vitro 3D cell culture models ranging from 100 µm to several millimeters. These protocols are applicable to a wide variety of organoids and spheroids that differ in their cell-of-origin, morphology, and culture conditions. From 3D structure harvesting to image analysis, these protocols can be completed within 4-5 days. Briefly, 3D structures are collected, fixed, and can then be processed either through paraffin-embedding and histological/immunohistochemical staining, or directly immunolabeled and prepared for optical clearing and 3D reconstruction (200 µm depth) by confocal microscopy.
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Effect of metals on Daphnia magna and cladocerans representatives of the Argentinean fluvial littoral.
J Environ Biol2014 Jul;35(4):689-97.
Luciana Regaldo, Reno Ulises, Gervasio Susana, Horacio Troiani, Gagneten Ana María
Abstract
Chronic toxicity tests were conducted to assess the effect of Cu, Cr and Pb on Moinodaphnia macleayi and Ceriodaphnia dubia -two cladoceran species from the Argentinian Fluvial Littoral Zone (AFLZ)- and Daphnia magna -an holarctic species-. The specimens were exposed to three concentrations of each metal. As endpoints, the number of living and dead organisms, molts, neonates released, and the age of first reproduction were recorded. Chronic assays showed that Cu significantly affected the analyzed life history traits in the three species. The lowest Pb and Cr concentrations did not affect survival, molting or fecundity in D. magna. Conversely, in M. macleayi and C. dubia, survival, molting and fecundity showed highly significant differences in all the concentrations tested compared to control assay. The present study stresses the importance of using biological parameters as bioindicators, as well as the study species from the Southern Hemisphere to assess metal pollution.
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Ameliorative effects of ethanolic leaf extract of Azadirachta indica on renal histologic alterations in streptozotocin-induced diabetic rats.
Am J Chin Med2011 ;39(5):903-16. doi: 10.1142/S0192415X11009299.
Oluwole Busayo Akinola, Laura Zatta, Olufunke Olubusola Dosumu, Oluwafunmike Sharon Akinola, Luciana Dini, Ezekiel Ademola Caxton-Martins
Abstract
We studied the effect of ethanolic leaf extract of Azadirachta indica (AIE) on the microanatomy of the kidney of streptozotocin-induced diabetic rats. Thirty male Wistar rats (161-190 g) were randomly assigned to one of five treatment groups of six animals each: control, diabetic, diabetic + AIE, diabetic + metformin, AIE only. Diabetes was induced with a single intraperitoneal dose of streptozotocin (70 mg/kg body weight). AIE and metformin were administered orally for 50 days (50 d) at 500 mg/kg bw/d and 350 mg/kg bw/d, respectively. Blood glucose was estimated by glucose oxidase method; plasma urea and creatinine were assayed; and paraffin sections of the kidney were stained by periodic acid-Schiff technique. Untreated diabetic rats exhibited marked hyperglycemia. Renal histopathology of these animals showed features of diabetic nephropathy, with nodular glomerulosclerosis and vacuolation of proximal tubule cells (Armanni-Ebstein phenomenon). These feature were absent in the diabetic rats treated with AIE. Besides, plasma urea and creatinine were not significantly different from the control in this group (p > 0.05), in contrast to the untreated diabetic rats, where significant increases in these markers (p
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Perinatal iron deficiency decreases cytochrome c oxidase (CytOx) activity in selected regions of neonatal rat brain.
Pediatr Res2000 Aug;48(2):169-76.
de Deungria M, Rao R, Wobken J D, Luciana M, Nelson C A, Georgieff M K
Abstract
Intrauterine growth retardation and diabetes mellitus during human gestation result in significant losses of fetal and neonatal brain iron. Brain iron deficiency is associated with impaired cognitive processes including memory and attention. The regional distribution of iron staining and cytochrome c oxidase (CytOx) activity have not been mapped in the iron-sufficient or -deficient neonatal rat. CytOx is the iron-containing terminal enzyme in oxidative phosphorylation; its activity reflects neuronal metabolism. We hypothesized that neonatal brain iron deficiency differentially decreases iron and CytOx activity in brain regions, with more pronounced losses in structures involved in recognition memory. Pregnant Sprague Dawley rats were fed either an iron-deficient or -fortified diet from gestational d 1 until postnatal d 10. Iron staining and CytOx activity of 20 brain structures were mapped histochemically in 25 rats from each group. Brain iron staining was reduced from 75% to 100% and CytOx staining was decreased from 0% to 42% in the iron deficient group (p
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