199 results on '"Magliano, M"'
Search Results
2. Association between age at disease onset of anti-neutrophil cytoplasmic antibody-associated vasculitis and clinical presentation and short-term outcomes
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Monti, S., Craven, A., Klersy, C., Montecucco, C., Caporali, R., Watts, R., Merkel, P. A., Luqmani, R., Achilleos, K., Adler, M., Alba, M. A., Albert, D. A., Alibaz-Oner, F., Allcoat, P., Amano, K., Amarasuriya, M., Amudala, N. A., Andrews, J., Archer, A. M., Arimura, Y., Atukorala, I., Azevedo, E., Bajad, S., Baldwin, C., Barra, L. J., Baslund, B., Basu, N., Baykal, M., Berger, C., Berglin, E., Besada, E., Bhardwaj, M., Bischof, A., Blockmans, D., Blood, J., Draibe, J. B., Brand, S., Brandao, M., Bruce, I. N., Butler, A., Calabrese, L. H., Ferrer, D. C., Carette, S., Carmona, D., Ceunen, H., Chakravarty, K., Chapman, P. T., Chocova, Z., Chung, S. A., Ci, W., Cid, M. C., Clark, T. M., Clarkson, M. R., De Jesus Contreras-Rodriguez, F., Conway, R., Cooke, K., Viros, X. C., Cordeiro, A., Costa, A., Culfear, K., Daikeler, T., Danda, D., Das, S. K., Dasgupta, B., De Castro, A. M., Dehghan, N., Devassy, R., Dhindsa, N., Diamantopoulos, A. P., Direskeneli, H., Dobashi, H., Juan, D., Durrani, M., Edelsten, C., Eifert, J., Elhayek, S., Elsideeg, S., Endo, T., Erden, A., Erer, B., Eriksson, P., Erturk, Z., Espigol-Frigole, G., Felicetti, M., Ferraro, A., Ferro, J. M., Fifi-Mah, A., Flores-Suarez, L. F., Flossmann, O., Flynn, D., Fonseca, J. E., Foot, J., Foote, M., Forbess, L., Fujimoto, S., Fukuoka, K., Furtado, C., Furuta, S., Gaffo, A. L., Gallagher, P., Gao, N., Gatenby, P., Gendi, N., Geraldes, R., Gerits, A., Gioffredi, A., Gomples, L., Goncalves, M. J., Gondo, P., Graham, A., Grainger, R., Gray, D. T., Grayson, P. C., Griffiths, L., Guo, Y., Gupta, R., Gylling, M., Hajj-Ali, R. A., Hammam, N., Harigai, M., Hartley, L., Haslett, J., Hassan, A., Hatemi, G., Hellmich, B., Henckaerts, L., Henes, J. C., Hepburn, J., Herd, V., Hess, C., Hill, C., Hinojosa-Azaola, A., Hirahashi, J., Hirano, F., Hocevar, A., Holle, J., Hollinger, N., Homma, S., Howard, T., Hoyles, R. K., Hruskova, Z., Hutcheon, G., Ignacak, M., Igney-Oertel, A., Ikeda, K., Ikegaya, N., Jagadeesh, S., Jaquith, J., Jayne, D. R. W., Jewell, T., Jones, C., Joshi, A., Kalyoncu, U., Kamall, S., Kamath, S., Lai, K. S., Kaname, S., Kanchinadham, S., Karadag, O., Karube, M., Kaszuba, M., Kaur, R., Kawakami, T., Kawashima, S., Khalidi, N., Khan, A., Kikuchi, M., Kilic, L., Kimura, M., King, M. J., Klapa, S., Klocke, R., Kobayashi, T., Kobayashi, S., Komagata, Y., Kronbichler, A., Kuczia, P., Kumar, M. S., Kurosawa, M., Lamprecht, P., Langford, C. A., Lanyon, P., Laversuch, C., Lee, S. J., Leoni, S., Li, J., Liang, K., Liang, P., Liao, H., Lee, L. A., Luqmani, R. A., Lyle, A., Macdonald, M., Mackie, S. L., Madden, L., Magliano, M., Makino, H., Makol, A., Malaiya, R., Malaviya, A., Manthri, R., Maritati, F., Da Silva, A. M., Mason, J. C., Matara, C., Matsui, K., Matteson, E. L., Mcbride, D., Mccullough, K., Mcgeoch, L., Mclaren, J., Mcmillian, C., Mendiratta, N., Menon, A., Merinopoulos, D., Merkel, P., Messier, S., Micheletti, R. G., Mills, K., Milman, N., Minoda, M., Minz, R. W., Mock, C., Mohammad, A. J., Moiseev, S., Moitinho, M., Molloy, E., Monach, P. A., Montgomery, M., Moosig, F., Moradizadeh, M., Morgan, M., Morgan, A. W., Morgan, A. -M., Muir, A., Mukhtyar, C., Muller, A., Muratore, F., Muso, E., Nada, R., Nakajima, H., Nakajima, T., Nakano, H., Nandagudi, A., Neumann, T., Y. F., Ng, K. H., Ng, Nogueira, E. L., Nolkha, N., Nordstrom, D., Novikov, P., Nugaliyadde, A., O'Donnell, J. L., O'Donoghue, J., O'Neill, L., O'Riordan, E., Oatley, M., Okubo, K., Oliva, E., Oshikawa, H., Ota, Y., Padoan, R., Pagnoux, C., Pan, L., Panaritis, K., Park, J. K., Patel, S., Patil, P., Pazzola, G., Peall, A., Pearce, F., Pehlevan, S., Pereira, L., Pettersson, T., Pineau, C. A., Pirila, L., Poglodek, B., Ponte, C., Prieto-Gonzalez, S., Priya, S. R., Purewal, B., Purschke, S., Putaala, J., Quickert, S., Quincey, V., Raghuvanshi, S., Rajasekhar, L., Ranganathan, D., Rathi, M., Rees, D., Rees, F., Renken, U., Restuccia, G., Rhee, R. L., Rice, B., Robins, D., Robson, J., Rodrigues, M., Romao, V. C., Rotar, C., Ruediger, C., Rutgers, A., A. C., Sa, Saavedra, M. J., Sada, K. -E., Sahbudin, I., Salvarani, C., Sandhu, N., Santos, E., Sato, Y., Schafer, V. S., Schiavon, F., Schmidt, W. A., Segelmark, M., Shahin, A., Sharma, A., Shotton, J., Silva, C., Singer, O. G., Sivasuthan, G., Smolen, S., Solanich-Moreno, X., Boixader, L. S., Song, Y. W., Springer, J., Sreih, A. G., Srivastava, R., Stamp, L. K., Stevens, R., Strbian, D., Sugino, K., Sunderkotter, C., Suppiah, R., Suzuki, K., Szekanecz, Z., Sznajd, J., Taimen, K., Tak, P. P., Takeuchi, T., Takizawa, N., Tames, L., Tan, B. E., Tanaka, M., Tang, M. W., Tatlisumak, T., Tesar, V., Thomas, A., Tian, X., Tokunaga, K., Tombetti, E., Tomsic, M., Toz, B., Tsukamoto, T., Uchida, S., Unal, A. U., Urban, M. L., Usui, J., Vaglio, A., Venkatachalam, S., Vermaak, E., Viswanath, V., Wada, T., Wagh, S., Wallace, D. J., Walters, G., Walz, B., Wan, J., Wang, T., Wang, G., Warrington, K. J., Watts, R. A., Wawrzycka-Adamczyk, K., Weeratunga, P., Weisman, M. H., Wickramasinghe, S., Williams, M., Wojcik, K., Woodruff, L., Xenitidis, T., Yamada, H., Yamagata, K., Yee, C. -S., Yoon, M., Yoshida, K., Yoshifuji, H., Ytterberg, S. R., Yumura, W., Zayed, H., Zeng, X., Zhao, M. -H., Zugaj, A., Zuk, J., İç Hastalıkları, Clinical Haematology, and Translational Immunology Groningen (TRIGR)
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Male ,Outcome ,Antineutrophil Cytoplasmic ,030232 urology & nephrology ,0302 clinical medicine ,Risk Factors ,80 and over ,Pharmacology (medical) ,Age of Onset ,Young adult ,Aged, 80 and over ,education.field_of_study ,age ,anti-neutrophil cytoplasmic antibody-associated vasculitis ,outcome ,Adolescent ,Adult ,Aged ,Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis ,Antibodies, Antineutrophil Cytoplasmic ,Female ,Humans ,Middle Aged ,Morbidity ,Prognosis ,Retrospective Studies ,Risk Assessment ,Survival Rate ,United Kingdom ,Young Adult ,Vasculitis ,Systemic vasculitis ,medicine.medical_specialty ,Population ,anti-neutrophil cytoplasmic antibody–associated vasculitis ,Antibodies ,03 medical and health sciences ,Rheumatology ,Internal medicine ,medicine ,education ,Anti-neutrophil cytoplasmic antibody–associated vasculitis ,Survival rate ,Anti-neutrophil cytoplasmic antibody ,030203 arthritis & rheumatology ,business.industry ,Retrospective cohort study ,medicine.disease ,Age of onset ,business - Abstract
Objectives ANCA-associated vasculitis (AAV) can affect all age groups. We aimed to show that differences in disease presentation and 6 month outcome between younger- and older-onset patients are still incompletely understood. Methods We included patients enrolled in the Diagnostic and Classification Criteria for Primary Systemic Vasculitis (DCVAS) study between October 2010 and January 2017 with a diagnosis of AAV. We divided the population according to age at diagnosis: Results A total of 1338 patients with AAV were included: 66% had disease onset at Conclusion Within 6 months of diagnosis of AAV, patients >65 years of age display a different pattern of organ involvement and an increased risk of significant damage and mortality compared with younger patients.
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- 2021
3. 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis With Polyangiitis
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Grayson, P. C., Ponte, C., Suppiah, R., Robson, J. C., Craven, A., Judge, A., Khalid, S., Hutchings, A., Luqmani, R. A., Watts, R. A., Merkel, P. A., Gatenby, P., Hill, C., Ranganathan, D., Kronbichler, A., Blockmans, D., Barra, L., Carette, S., Pagnoux, C., Dhindsa, N., Fifi-Mah, A., Khalidi, N., Liang, P., Milman, N., Pineau, C., Tian, X., Wang, G., Wang, T., Zhao, M. -H., Tesar, V., Baslund, B., Hammam, N., Shahin, A., Pirila, L., Putaala, J., Hellmich, B., Henes, J., Lamprecht, P., Neumann, T., Schmidt, W., Sunderkoetter, C., Szekanecz, Z., Danda, D., Das, S., Gupta, R., Rajasekhar, L., Sharma, A., Wagh, S., Clarkson, M., Molloy, E., Salvarani, C., Schiavon, F., Tombetti, E., Vaglio, A., Amano, K., Arimura, Y., Dobashi, H., Fujimoto, S., Harigai, M., Hirano, F., Hirahashi, J., Honma, S., Kawakami, T., Kobayashi, S., Kono, H., Makino, H., Matsui, K., Muso, E., Suzuki, K., Ikeda, K., Takeuchi, T., Tsukamoto, T., Uchida, S., Wada, T., Yamada, H., Yamagata, K., Yumura, W., Lai, K. S., Flores-Suarez, L. F., Hinojosa, A., Rutgers, B., Tak, P. -P., Grainger, R., Quincey, V., Stamp, L., Besada, E., Diamantopoulos, A., Sznajd, J., Azevedo, E., Geraldes, R., Rodrigues, M., Santos, E., Song, Y. -W., Moiseev, S., Hocevar, A., Cid, M. C., Moreno, X. S., Atukorala, I., Berglin, E., Mohammed, A., Segelmark, M., Daikeler, T., Direskeneli, H., Hatemi, G., Kamali, S., Karadag, O., Pehlevan, S., Adler, M., Basu, N., Bruce, I., Chakravarty, K., Dasgupta, B., Flossmann, O., Gendi, N., Hassan, A., Hoyles, R., Jayne, D., Jones, C., Klocke, R., Lanyon, P., Laversuch, C., Luqmani, R., Robson, J., Magliano, M., Mason, J., Maw, W. W., Mcinnes, I., Mclaren, J., Morgan, M., Morgan, A., Mukhtyar, C., O'Riordan, E., Patel, S., Peall, A., Venkatachalam, S., Vermaak, E., Menon, A., Watts, R., Yee, C. -S., Albert, D., Calabrese, L., Chung, S., Forbess, L., Gaffo, A., Gewurz-Singer, O., Grayson, P., Liang, K., Matteson, E., Springer, J., Sreih, A., and Translational Immunology Groningen (TRIGR)
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Adult ,Male ,Vasculitis ,Myeloblastin ,Immunology ,Churg-Strauss Syndrome ,Sensitivity and Specificity ,General Biochemistry, Genetics and Molecular Biology ,Antibodies, Antineutrophil Cytoplasmic ,Diagnosis, Differential ,Rheumatology ,Risk Factors ,Humans ,Immunology and Allergy ,anti-neutrophil cytoplasm antibody ,Prospective Studies ,Aged ,Granulomatosis with Polyangiitis ,Reproducibility of Results ,Middle Aged ,United States ,Female ,eosinophilic granulomatosis with polyangiitis ,Eosinophilic Granuloma ,Europe ,classification ,Societies - Abstract
ObjectiveTo develop and validate revised classification criteria for eosinophilic granulomatosis with polyangiitis (EGPA).MethodsPatients with vasculitis or comparator diseases were recruited into an international cohort. The study proceeded in five phases: (1) identification of candidate criteria items using consensus methodology, (2) prospective collection of candidate items present at the time of diagnosis, (3) data-driven reduction of the number of candidate items, (4) expert panel review of cases to define the reference diagnosis and (5) derivation of a points-based risk score for disease classification in a development set using least absolute shrinkage and selection operator logistic regression, with subsequent validation of performance characteristics in an independent set of cases and comparators.ResultsThe development set for EGPA consisted of 107 cases of EGPA and 450 comparators. The validation set consisted of an additional 119 cases of EGPA and 437 comparators. From 91 candidate items, regression analysis identified 11 items for EPGA, 7 of which were retained. The final criteria and their weights were as follows: maximum eosinophil count ≥1×109/L (+5), obstructive airway disease (+3), nasal polyps (+3), cytoplasmic antineutrophil cytoplasmic antibody (ANCA) or anti-proteinase 3–ANCA positivity (−3), extravascular eosinophilic predominant inflammation (+2), mononeuritis multiplex/motor neuropathy not due to radiculopathy (+1) and haematuria (−1). After excluding mimics of vasculitis, a patient with a diagnosis of small- or medium-vessel vasculitis could be classified as having EGPA if the cumulative score was ≥6 points. When these criteria were tested in the validation data set, the sensitivity was 85% (95% CI 77% to 91%) and the specificity was 99% (95% CI 98% to 100%).ConclusionThe 2022 American College of Rheumatology/European Alliance of Associations for Rheumatology Classification Criteria for Eosinophilic Granulomatosis with Polyangiitis demonstrate strong performance characteristics and are validated for use in research.
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- 2022
4. Tobacco rattle virus mediates gene silencing in a plant parasitic root-knot nematode
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Dubreuil, G., Magliano, M., Dubrana, M. P., Lozano, J., Lecomte, P., Favery, B., Abad, P., and Rosso, M. N.
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- 2009
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5. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
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Lyons, P. A., Peters, J. E., Alberici, F., Liley, J., Coulson, R. M. R., Astle, W., Baldini, C., Bonatti, F., Cid, María Cinta, Elding, H., Emmi, G., Epplen, J., Guillevin, L., Jayne, D. R. W., Jiang, T., Gunnarsson, I., Lamprecht, P., Leslie, S., Little, M. A., Martorana, D., Moosig, F., Neumann, T., Ohlsson, S., Quickert, S., Ramirez, G. A., Rewerska, B., Schett, George, Sinico, R. A., Szczeklik, W., Tesar, Vladimir, Vukcevic, D., Akil, M., Barratt, J., Basu, N., Butterworth, A. S., Bruce, I., Clarkson, M., Conlon, N., DasGupta, B., Doulton, T. W. R., Espígol-Frigolé, Georgina, Flossmann, O., Gabrielli, A., Gasior, J., Gregorini, G., Guida, G., Hernández Rodríguez, José, Hruskova, Z., Hudson, A., Knight, A., Lanyon, P., Luqmani, R., Magliano, M., Manfredi, A. A., Marguerie, C., Maritati, F., Marvisi, C., McHugh, N. J., Molloy, E., Motyer, A., Mukhtyar, C., Padyukov, Leonid, Pesci, Alberto, Prieto-Gonzalez, S., Ramentol-Sintas, Marc, Reis, P., Roccatello, D., Rovere-Querini, P., Salvarani, C., Santarsia, F., Solans, Roser, Soranzo, N., Taylor, J., Wessels, J., Zwerina, J., Terrier, B., Watts, R. A., Vaglio, A., Holle, J. U., Wallace, C., Smith, K. G. C., Universitat Autònoma de Barcelona, Lyons, P. A., Peters, J. E., Alberici, F., Liley, J., Coulson, R. M. R., Astle, W., Baldini, C., Bonatti, F., Cid, M. C., Elding, H., Emmi, G., Epplen, J., Guillevin, L., Jayne, D. R. W., Jiang, T., Gunnarsson, I., Lamprecht, P., Leslie, S., Little, M. A., Martorana, D., Moosig, F., Neumann, T., Ohlsson, S., Quickert, S., Ramirez, G. A., Rewerska, B., Schett, G., Sinico, R. A., Szczeklik, W., Tesar, V., Vukcevic, D., Akil, M., Barratt, J., Basu, N., Butterworth, A. S., Bruce, I., Clarkson, M., Conlon, N., Dasgupta, B., Doulton, T. W. R., Espigol-Frigole, G., Flossmann, O., Gabrielli, A., Gasior, J., Gregorini, G., Guida, G., Hernandez-Rodriguez, J., Hruskova, Z., Hudson, A., Knight, A., Lanyon, P., Luqmani, R., Magliano, M., Manfredi, A. A., Marguerie, C., Maritati, F., Marvisi, C., Mchugh, N. J., Molloy, E., Motyer, A., Mukhtyar, C., Padyukov, L., Pesci, A., Prieto-Gonzalez, S., Ramentol-Sintas, M., Reis, P., Roccatello, D., Rovere-Querini, P., Salvarani, C., Santarsia, F., Solans-Laque, R., Soranzo, N., Taylor, J., Wessels, J., Zwerina, J., Terrier, B., Watts, R. A., Vaglio, A., Holle, J. U., Wallace, C., Smith, K. G. C., Lyons, P, Peters, J, Alberici, F, Liley, J, Coulson, R, Astle, W, Baldini, C, Bonatti, F, Cid, M, Elding, H, Emmi, G, Epplen, J, Guillevin, L, Jayne, D, Jiang, T, Gunnarsson, I, Lamprecht, P, Leslie, S, Little, M, Martorana, D, Moosig, F, Neumann, T, Ohlsson, S, Quickert, S, Ramierez, G, Rewerska, B, Schett, G, Sinico, R, Szczeklik, W, Tesar, V, Vukcevic, D, Akil, M, Barratt, J, Basu, N, Butterworth, A, Bruce, I, Clarkson, M, Conlon, N, Dasgupta, B, Doulton, T, Espigol-Frigole, G, Flossmann, O, Gabrielli, A, Gasior, J, Gregorini, G, Guida, G, Hernandez-Rodriguez, J, Hruskova, Z, Hudson, A, Knight, A, Lanyon, P, Luqmani, R, Magliano, M, Manfredi, A, Marguerie, C, Maritati, F, Marvisi, C, Mchugh, N, Molloy, E, Motyer, A, Mukhtyar, C, Padyukov, L, Pesci, A, Prieto-Gonzalez, S, Ramentol-Sintas, M, Reis, P, Roccatello, D, Rovere-Querini, P, Salvarani, C, Santarsia, F, Solans-Laque, R, Soranzo, N, Taylor, J, Wessels, J, Zwerina, J, Terrier, B, Watts, R, Vaglio, A, Holle, J, Wallace, C, Smith, K, and United Kingdom Research and Innovation
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0301 basic medicine ,Candidate gene ,Antineutrophil Cytoplasmic ,General Physics and Astronomy ,Genome-wide association study ,Autoimmunity ,Genome-wide association studies ,0302 clinical medicine ,Rheumatic diseases ,immune system diseases ,Eosinophilic ,Eosinophilia ,lcsh:Science ,education.field_of_study ,Multidisciplinary ,Genome-wide association, eosinophilic granulomatosis with polyangiitis, ANCA status ,3. Good health ,medicine.symptom ,Vasculitis ,Granulomatosis with polyangiitis ,Antibodies, Antineutrophil Cytoplasmic ,Eosinophils ,Genetic Association Studies ,Granulomatosis with Polyangiitis ,Humans ,Mendelian Randomization Analysis ,Genetic Loci ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,European Vasculitis Genetics Consortium ,Science ,Population ,General Biochemistry, Genetics and Molecular Biology ,Article ,Antibodies ,03 medical and health sciences ,medicine ,Immunogenetics ,education ,Rheumatology and Autoimmunity ,Anti-neutrophil cytoplasmic antibody ,030203 arthritis & rheumatology ,Reumatologi och inflammation ,business.industry ,General Chemistry ,medicine.disease ,respiratory tract diseases ,030104 developmental biology ,Immunology ,EGPA, HLA, ANCA, genetics ,lcsh:Q ,business - Abstract
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA., Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disorder characterised by asthma, eosinophilia and vasculitis. Here, the authors describe a genome-wide association study of EGPA that reveals clinical and genetic differences between subgroups stratified by autoantibody status (ANCA).
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- 2019
6. Extra-cranial giant cell arteritis: a diagnostic challenge
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Tucker, L.J., Mankia, K.S., and Magliano, M.
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- 2015
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7. Multi-dimensional analyses identify genes of high priority for pancreatic cancer research
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Rosa E. Menjivar, Hu B, Costas A. Lyssiotis, Charlestin, Shuze Wang, Pasca di Magliano M, Samantha Kemp, Zeribe C. Nwosu, Jun Hu, Nassif M, Nina Steele, Giza H, and David D. Kim
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Downregulation and upregulation ,Pancreatic cancer ,Gene expression ,Multi dimensional ,medicine ,Computational biology ,DNA microarray ,Cell cycle ,Biology ,Biomarker discovery ,medicine.disease ,Gene - Abstract
Genomic profiling has unveiled the molecular subtypes and mutational landscape of pancreatic ductal adenocarcinoma (PDAC). However, there is a knowledge gap on the consistency of gene expression across PDAC tumors profiled in independent studies and this limits follow up research. To facilitate novel drug target prioritization and biomarker discovery, we investigated the most consistently expressed genes in human PDAC. We identified ~4,000 genes highly or lowly expressed in at least 4 of 5 microarrays (adjusted PHighlightsIdentifies ~4,000 consistent genes across PDAC microarrays, >50% of which have not been studiedGlycolysis and cell cycle are the most consistent processes in PDACHeterogeneous pathways underlie or correlate with clinicopathological variablesIdentifies 205 genes with similar expression pattern in PDAC tissues and peripheral bloodHighlights 185 upregulated genes that are high priority therapeutic targets in PDAC
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- 2021
8. 1662P Targeting stress granule formation as a synthetic lethality strategy for kras-induced pancreatic cancer initiation
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Santofimia, P., Fraunhoffer, N., Liu, X., Fernandez-Bessone, I., Pasca di Magliano, M., Audebert, S., Camoin, L., Modesti, M., Lomberk, G., Urrutia, R., Soubeyran, P., Neira, J.L., and Iovanna, J.L.
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- 2023
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9. Origin of flooding water through hydrogeochemical identification, the Buenos Aires plain, Argentina
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Alconada-Magliano, M. M., Fagundo-Castillo, J. R., Carrillo-Rivera, J. J., and Hernández, P. G.
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- 2011
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10. PRIMER REPORTE DE Spodoptera eridania (Stoll) (Lepidoptera: Noctuidae) EN EL CENTRO DE LA PROVINCIA DE SANTA FE
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LUTZ, A., primary, BERTOLACCINI, I., primary, SCOTTA, R. R., primary, MANTICA, F., primary, MAGLIANO, M. F., primary, SANCHEZ, P. D., primary, and CURIS, M. C., primary
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- 2019
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11. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
- Author
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Lyons, P.A., Peters, J.E., Alberici, F., Liley, J., Coulson, R.M.R., Astle, W., Baldini, C., Bonatti, F., Cid, M.C., Elding, H., Emmi, G., Epplen, J., Guillevin, L., Jayne, D.R.W., Jiang, T., Gunnarsson, I., Lamprecht, P., Leslie, S., Little, M.A., Martorana, D., Moosig, F., Neumann, T., Ohlsson, S., Quickert, S., Ramirez, G.A., Rewerska, B., Schett, G., Sinico, R.A., Szczeklik, W., Tesar, V., Vukcevic, D., Akil, M., Barratt, J., Basu, N., Butterworth, A.S., Bruce, I., Clarkson, M., Conlon, N., DasGupta, B., Doulton, T.W.R., Espígol-Frigolé, Georgina, Flossmann, O., Gabrielli, A., Gasior, J., Gregorini, G., Guida, G., Hernández Rodríguez, José, Hruskova, Z., Hudson, A., Knight, A., Lanyon, P., Luqmani, R., Magliano, M., Manfredi, A.A., Marguerie, C., Maritati, F., Marvisi, C., McHugh, N.J., Molloy, E., Motyer, A., Mukhtyar, C., Padyukov, L., Pesci, A., Prieto-Gonzalez, S., Ramentol-Sintas, Marc, Reis, P., Roccatello, D., Rovere-Querini, P., Salvarani, C., Santarsia, F., Solans-Laque, R., Soranzo, N., Taylor, J., Wessels, J., Zwerina, J., Terrier, B., Watts, R.A., Vaglio, A., Holle, J.U., Wallace, C., Smith, K.G.C., and Universitat Autònoma de Barcelona
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Eosinophils ,Genetic Loci ,Granulomatosis with Polyangiitis ,Humans ,Genetic Predisposition to Disease ,Mendelian Randomization Analysis ,Genetic Association Studies ,Antibodies, Antineutrophil Cytoplasmic ,Genome-Wide Association Study - Abstract
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
- Published
- 2019
12. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
- Author
-
Lyons, P, Peters, J, Alberici, F, Liley, J, Coulson, R, Astle, W, Baldini, C, Bonatti, F, Cid, M, Elding, H, Emmi, G, Epplen, J, Guillevin, L, Jayne, D, Jiang, T, Gunnarsson, I, Lamprecht, P, Leslie, S, Little, M, Martorana, D, Moosig, F, Neumann, T, Ohlsson, S, Quickert, S, Ramierez, G, Rewerska, B, Schett, G, Sinico, R, Szczeklik, W, Tesar, V, Vukcevic, D, Akil, M, Barratt, J, Basu, N, Butterworth, A, Bruce, I, Clarkson, M, Conlon, N, Dasgupta, B, Doulton, T, Espigol-Frigole, G, Flossmann, O, Gabrielli, A, Gasior, J, Gregorini, G, Guida, G, Hernandez-Rodriguez, J, Hruskova, Z, Hudson, A, Knight, A, Lanyon, P, Luqmani, R, Magliano, M, Manfredi, A, Marguerie, C, Maritati, F, Marvisi, C, Mchugh, N, Molloy, E, Motyer, A, Mukhtyar, C, Padyukov, L, Pesci, A, Prieto-Gonzalez, S, Ramentol-Sintas, M, Reis, P, Roccatello, D, Rovere-Querini, P, Salvarani, C, Santarsia, F, Solans-Laque, R, Soranzo, N, Taylor, J, Wessels, J, Zwerina, J, Terrier, B, Watts, R, Vaglio, A, Holle, J, Wallace, C, Smith, K, Lyons, PA, Peters, JE, Cid, MC, Little, MA, Ramierez, GA, Butterworth, AS, DasGupta, B, Doulton, TWR, Manfredi, AA, McHugh, NJ, Watts, RA, Holle, JU, Smith, KGC, Lyons, P, Peters, J, Alberici, F, Liley, J, Coulson, R, Astle, W, Baldini, C, Bonatti, F, Cid, M, Elding, H, Emmi, G, Epplen, J, Guillevin, L, Jayne, D, Jiang, T, Gunnarsson, I, Lamprecht, P, Leslie, S, Little, M, Martorana, D, Moosig, F, Neumann, T, Ohlsson, S, Quickert, S, Ramierez, G, Rewerska, B, Schett, G, Sinico, R, Szczeklik, W, Tesar, V, Vukcevic, D, Akil, M, Barratt, J, Basu, N, Butterworth, A, Bruce, I, Clarkson, M, Conlon, N, Dasgupta, B, Doulton, T, Espigol-Frigole, G, Flossmann, O, Gabrielli, A, Gasior, J, Gregorini, G, Guida, G, Hernandez-Rodriguez, J, Hruskova, Z, Hudson, A, Knight, A, Lanyon, P, Luqmani, R, Magliano, M, Manfredi, A, Marguerie, C, Maritati, F, Marvisi, C, Mchugh, N, Molloy, E, Motyer, A, Mukhtyar, C, Padyukov, L, Pesci, A, Prieto-Gonzalez, S, Ramentol-Sintas, M, Reis, P, Roccatello, D, Rovere-Querini, P, Salvarani, C, Santarsia, F, Solans-Laque, R, Soranzo, N, Taylor, J, Wessels, J, Zwerina, J, Terrier, B, Watts, R, Vaglio, A, Holle, J, Wallace, C, Smith, K, Lyons, PA, Peters, JE, Cid, MC, Little, MA, Ramierez, GA, Butterworth, AS, DasGupta, B, Doulton, TWR, Manfredi, AA, McHugh, NJ, Watts, RA, Holle, JU, and Smith, KGC
- Abstract
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
- Published
- 2019
13. Genome-wide association study of eosinophilic granulomatosis with polyangiitis reveals genomic loci stratified by ANCA status
- Author
-
Lyons, PA, Peters, JE, Alberici, F, Liley, J, Coulson, RMR, Astle, W, Baldini, C, Bonatti, F, Cid, MC, Elding, H, Emmi, G, Epplen, J, Guillevin, L, Jayne, DRW, Jiang, T, Gunnarsson, I, Lamprecht, P, Leslie, S, Little, MA, Martorana, D, Moosig, F, Neumann, T, Ohlsson, S, Quickert, S, Ramirez, GA, Rewerska, B, Schett, G, Sinico, RA, Szczeklik, W, Tesar, V, Vukcevic, D, Akil, M, Barratt, J, Basu, N, Butterworth, AS, Bruce, I, Clarkson, M, Conlon, N, DasGupta, B, Doulton, TWR, Espigol-Frigole, G, Flossmann, O, Gabrielli, A, Gasior, J, Gregorini, G, Guida, G, Hernandez-Rodriguez, J, Hruskova, Z, Hudson, A, Knight, A, Lanyon, P, Luqmani, R, Magliano, M, Manfredi, AA, Marguerie, C, Maritati, F, Marvisi, C, McHugh, NJ, Molloy, E, Motyer, A, Mukhtyar, C, Padyukov, L, Pesci, A, Prieto-Gonzalez, S, Ramentol-Sintas, M, Reis, P, Roccatello, D, Rovere-Querini, P, Salvarani, C, Santarsia, F, Solans-Laque, R, Soranzo, N, Taylor, J, Wessels, J, Zwerina, J, Terrier, B, Watts, RA, Vaglio, A, Holle, JU, Wallace, C, Smith, KGC, Lyons, PA, Peters, JE, Alberici, F, Liley, J, Coulson, RMR, Astle, W, Baldini, C, Bonatti, F, Cid, MC, Elding, H, Emmi, G, Epplen, J, Guillevin, L, Jayne, DRW, Jiang, T, Gunnarsson, I, Lamprecht, P, Leslie, S, Little, MA, Martorana, D, Moosig, F, Neumann, T, Ohlsson, S, Quickert, S, Ramirez, GA, Rewerska, B, Schett, G, Sinico, RA, Szczeklik, W, Tesar, V, Vukcevic, D, Akil, M, Barratt, J, Basu, N, Butterworth, AS, Bruce, I, Clarkson, M, Conlon, N, DasGupta, B, Doulton, TWR, Espigol-Frigole, G, Flossmann, O, Gabrielli, A, Gasior, J, Gregorini, G, Guida, G, Hernandez-Rodriguez, J, Hruskova, Z, Hudson, A, Knight, A, Lanyon, P, Luqmani, R, Magliano, M, Manfredi, AA, Marguerie, C, Maritati, F, Marvisi, C, McHugh, NJ, Molloy, E, Motyer, A, Mukhtyar, C, Padyukov, L, Pesci, A, Prieto-Gonzalez, S, Ramentol-Sintas, M, Reis, P, Roccatello, D, Rovere-Querini, P, Salvarani, C, Santarsia, F, Solans-Laque, R, Soranzo, N, Taylor, J, Wessels, J, Zwerina, J, Terrier, B, Watts, RA, Vaglio, A, Holle, JU, Wallace, C, and Smith, KGC
- Abstract
Eosinophilic granulomatosis with polyangiitis (EGPA) is a rare inflammatory disease of unknown cause. 30% of patients have anti-neutrophil cytoplasmic antibodies (ANCA) specific for myeloperoxidase (MPO). Here, we describe a genome-wide association study in 676 EGPA cases and 6809 controls, that identifies 4 EGPA-associated loci through conventional case-control analysis, and 4 additional associations through a conditional false discovery rate approach. Many variants are also associated with asthma and six are associated with eosinophil count in the general population. Through Mendelian randomisation, we show that a primary tendency to eosinophilia contributes to EGPA susceptibility. Stratification by ANCA reveals that EGPA comprises two genetically and clinically distinct syndromes. MPO+ ANCA EGPA is an eosinophilic autoimmune disease sharing certain clinical features and an HLA-DQ association with MPO+ ANCA-associated vasculitis, while ANCA-negative EGPA may instead have a mucosal/barrier dysfunction origin. Four candidate genes are targets of therapies in development, supporting their exploration in EGPA.
- Published
- 2019
14. Suicide attempts in patients with systemic lupus erythematosus
- Author
-
Karassa, F B, Magliano, M, and Isenberg, D A
- Published
- 2003
15. Pulmonary Hypertension in Autoimmune Rheumatic Diseases: Where Are We Now?
- Author
-
Magliano, M, Isenberg, D A., and Hillson, J
- Published
- 2002
16. EFICACIA DE HALOXIFOP-R-METIL CON DISTINTOS COADYUVANTES
- Author
-
SANCHEZ, P., primary, LUTZ, A. L., primary, MAGLIANO, M. F., primary, MENAPACE, P., primary, and SCOTTA,, R. R., primary
- Published
- 2019
- Full Text
- View/download PDF
17. Electron Heat Transport in JET from Ion to Electron scales: Experimental Investigation and Gyro-kinetic Simulations
- Author
-
BONANOMI, NICOLA, SOZZI, CARLO, Mantica, P, Citrin, J, Goerler, T, Hawkes, N, Lerche, E, Magliano, M, Peeters, AG, Szepesi, G, Tsalas, M, Van Eester, D., Bonanomi, N, Mantica, P, Citrin, J, Goerler, T, Hawkes, N, Lerche, E, Magliano, M, Peeters, A, Sozzi, C, Szepesi, G, Tsalas, M, and Van Eester, D
- Subjects
Tokamak JET ,Turbulent transport ,Plasma physic ,Gyro-kinetic simulations - Abstract
The TEM driven electron heat transport has been investigated experimentally in JET C-wall L-mode plasmas with dominant ICRH electron heating, by flux scans at constant total electron power and power modulation using ICRH in (3He)-D mode conversion scheme. The dependence of the TEM threshold on s and q has been studied by implementing ad hoc time waveforms of the plasma current in order to extend the range of s explored and to decouple it from q. Linear simulations have been made using the gyro-kinetic code GKW. A strong dependence on s has been identified in the experiments and no dependence on q, in agreement with linear GKW results. The experimental estimate of the electron stiffness in these plasmas is however significantly higher than predicted by non-linear TEM gyro-kinetic simulations. This discrepancy is even worse in plasmas with comparable electron and ion heating (ICRH+NBI), in which the electron stiffness increases and a macroscopic drop of R/L_Te is observed with respect to pure ICRH plasmas. Non-linear simulations using GENE show that in both cases it is not possible to account for the experimental electron flux by just considering the ITG-TEM turbulence. Therefore, the idea that electron scale ETG turbulence could account for the missing flux has been explored, supported by the fact that the ETG threshold is predicted to decrease with the increasing T_i/T_e due to NBI heating. A first study of the ETG contribution to the heat flux, using linear and non-linear local GENE simulations, was based on separate simulations of ion and electron scales. For the ETG saturation, either an ad hoc external flow shear or electron scale zonal flows were used. In both ICRH and ICRH+NBI cases it was found that a non-neglibile electron heat flux can be carried by the ETG modes, explaining the observations. However, a high sensitivity of the results on multiple parameters was found. In addition, recent studies show that multi-scale simulations with real electron to ion mass ratio are needed for a proper ETG study. Computationally heavy multi-scale simulations have then been started using GENE for these JET shots. The results will help to clarify if and when the electron scale instabilities can carry significant electron heat flux in JET plasmas, also in view of extrapolations to ITER scenarios, where the electron channel will be key for fusion performance
- Published
- 2016
18. Erratum to: Origin of flooding water through hydrogeochemical identification, the Buenos Aires plain, Argentina
- Author
-
Alconada-Magliano, M. M., Fagundo-Castillo, J. R., Carrillo-Rivera, J. J., and Hernández, P. G.
- Published
- 2011
- Full Text
- View/download PDF
19. An audit of an emergency rheumatology clinic have we improved our service?
- Author
-
Wong, E, Magliano, M, Flynn, J, and Luqmani, R
- Published
- 2016
20. ER stress protein AGR2 precedes and is involved in the regulation of pancreatic cancer initiation
- Author
-
Dumartin, L, primary, Alrawashdeh, W, additional, Trabulo, S M, additional, Radon, T P, additional, Steiger, K, additional, Feakins, R M, additional, di Magliano, M P, additional, Heeschen, C, additional, Esposito, I, additional, Lemoine, N R, additional, and Crnogorac-Jurcevic, T, additional
- Published
- 2016
- Full Text
- View/download PDF
21. Electron Heat Transport in JET from Ion to Electron scales: Experimental Investigation and Gyro-kinetic Simulations
- Author
-
Bonanomi, N, Mantica, P, Citrin, J, Goerler, T, Hawkes, N, Lerche, E, Magliano, M, Peeters, A, Sozzi, C, Szepesi, G, Tsalas, M, Van Eester, D, BONANOMI, NICOLA, SOZZI, CARLO, Peeters, AG, Van Eester, D., Bonanomi, N, Mantica, P, Citrin, J, Goerler, T, Hawkes, N, Lerche, E, Magliano, M, Peeters, A, Sozzi, C, Szepesi, G, Tsalas, M, Van Eester, D, BONANOMI, NICOLA, SOZZI, CARLO, Peeters, AG, and Van Eester, D.
- Abstract
The TEM driven electron heat transport has been investigated experimentally in JET C-wall L-mode plasmas with dominant ICRH electron heating, by flux scans at constant total electron power and power modulation using ICRH in (3He)-D mode conversion scheme. The dependence of the TEM threshold on s and q has been studied by implementing ad hoc time waveforms of the plasma current in order to extend the range of s explored and to decouple it from q. Linear simulations have been made using the gyro-kinetic code GKW. A strong dependence on s has been identified in the experiments and no dependence on q, in agreement with linear GKW results. The experimental estimate of the electron stiffness in these plasmas is however significantly higher than predicted by non-linear TEM gyro-kinetic simulations. This discrepancy is even worse in plasmas with comparable electron and ion heating (ICRH+NBI), in which the electron stiffness increases and a macroscopic drop of R/L_Te is observed with respect to pure ICRH plasmas. Non-linear simulations using GENE show that in both cases it is not possible to account for the experimental electron flux by just considering the ITG-TEM turbulence. Therefore, the idea that electron scale ETG turbulence could account for the missing flux has been explored, supported by the fact that the ETG threshold is predicted to decrease with the increasing T_i/T_e due to NBI heating. A first study of the ETG contribution to the heat flux, using linear and non-linear local GENE simulations, was based on separate simulations of ion and electron scales. For the ETG saturation, either an ad hoc external flow shear or electron scale zonal flows were used. In both ICRH and ICRH+NBI cases it was found that a non-neglibile electron heat flux can be carried by the ETG modes, explaining the observations. However, a high sensitivity of the results on multiple parameters was found. In addition, recent studies show that multi-scale simulations with real electron to ion ma
- Published
- 2016
22. 'La valutazione del rischio stress lavoro-correlato in ambiente sanitario: studio preliminare in una struttura ospedaliera della Regione Campania'
- Author
-
LIOTTI F, MAGLIANO M, FEOLA D, RUBERTO M, CAPPELLUCCIO R, SANTALUCIA L, SANNOLO, Nicola, Liotti, F, Magliano, M, Feola, D, Ruberto, M, Cappelluccio, R, Santalucia, L, and Sannolo, Nicola
- Published
- 2009
23. Una 'nota' calcistica: L’utilizzo della musica negli allenamenti di calcio giovanile
- Author
-
Marasso, Danilo, Magliano, M., and Lissiotto, Angelo
- Subjects
Bambini ,sport ,Abilità motorie ,musica - Published
- 2014
24. EFICACIA DE HALOXIFOP-R-METIL CON DISTINTOS COADYUVANTES.
- Author
-
SANCHEZ, P., LUTZ, A. L., MAGLIANO, M. F., MENAPACE, P., and SCOTTA, R. R.
- Abstract
Copyright of Revista FAVE is the property of Universidad Nacional del Litoral and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)
- Published
- 2018
- Full Text
- View/download PDF
25. Pax8 has a key role in thyroid cell differentiation
- Author
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PASCA DI MAGLIANO M., DI LAURO R., ZANNINI, MARIASTELLA, PASCA DI MAGLIANO, M., DI LAURO, R., and Zannini, Mariastella
- Published
- 2000
26. The Thyroid Transcription Factor-2 (TTF-2) is a promoter-specific DNA-binding independent repressor
- Author
-
PERRONE L., PASCA DI MAGLIANO M., DI LAURO R., ZANNINI, MARIASTELLA, Perrone, L., PASCA DI MAGLIANO, M., Zannini, Mariastella, and DI LAURO, R.
- Published
- 2000
27. Sistemas ligantes para concretos refratários mulitizáveis
- Author
-
Magliano, M. V. M and Pandolfelli, V. C
- Subjects
mulita ,binding system ,refractory concrete ,colloidal silica ,sílica coloidal ,sistema ligante ,mullite ,concreto refratário - Abstract
Concretos mulitizados são comumente utilizados na indústria siderúrgica devido as suas excelentes propriedades. Entretanto, a presença de cimento de aluminato de cálcio, juntamente com SiO2, forma eutéticos e fases de baixo ponto de fusão, motivando assim a seleção de ligantes alternativos. Neste trabalho os três principais ligantes para refratários (cimento de aluminato de cálcio, alumina hidratável e sílica coloidal) foram incorporados em concretos com alto potencial de mulitização e suas propriedades a verde e a quente foram comparadas, definindo quais ligantes apresentam melhor desempenho. Os resultados indicam que a sílica coloidal, além de facilitar a etapa de secagem, resulta em excelentes propriedades a quente e em menor teor de líquido residual após queima, quando comparados com uma composição referência de alta alumina. Mullite based castables are usually applied for lining steel industries processing ladles due to their superior working performance. However, the presence of aluminate cement and SiO2 can deteriorate their hot properties by the formation of eutectics and low melting point phases, which motivates the search for alternatives biding systems. In this paper, the three main binders for refractory castables (aluminate cement, hydratable alumina and colloidal silica) were added to different compositions and their green and hot properties were compared, aiming to define which one presents better performance. The results indicated the colloidal silica as a promising substitute to the aluminate cement as it favors the drying process, provides excellent hot properties, higher refractoriness and generates low residual liquid phase after sintering, when compared to a high alumina composition.
- Published
- 2010
28. Suicide attempts in patients with systemic lupus erythematosus
- Author
-
Karassa, F. B., Magliano, M., and Isenberg, D. A.
- Subjects
Adult ,Male ,Risk Factors ,Lupus Erythematosus, Systemic/immunology/*psychology ,Suicide, Attempted/*psychology ,Humans ,Female ,Antibodies, Antinuclear/analysis ,Depression/psychology ,Suicide/psychology ,Follow-Up Studies - Abstract
BACKGROUND: Suicide and suicide attempts, although well recognised in patients with systemic lupus erythematosus (SLE), have been commented on relatively little. OBJECTIVE: To obtain a better understanding of the reasons for suicidal behaviour in patients with SLE. METHODS: The records of 300 patients with SLE were reviewed to identify completed or attempted suicides. RESULTS: Five patients made seven attempts at suicide over a 20 year follow up period; one of them was fatal. All of those attempting suicide had a history of neuropsychiatric SLE (NPSLE) presenting with depression and they made the attempts soon after the onset of NPSLE (median time 12.5 months). Two patients had appreciable disease activity at the time of the suicide attempt. Lymphopenia was present in five suicide attempts. Anti-SSA/Ro antibodies were detected in three patients, none of whom had anti-SSB/La. All patients apart from one responded to treatment for depression; the remaining female patient made two subsequent suicide attempts, with a fatal outcome despite intensive treatment. CONCLUSION: Greater awareness of the risk of suicide in patients with psychiatric manifestations of SLE may help to reduce the incidence of this potentially fatal phenomenon. Ann Rheum Dis
- Published
- 2003
29. Occurrence of extended-spectrum β-lactamases in members of the family Enterobacteriaceae in italy: Implications for resistance to β-lactams and other antimicrobial drugs
- Author
-
Spanu, T., Luzzaro, F., Perilli, Mariagrazia, Amicosante, Gianfranco, Toniolo, A., Fadda, G, Fortina, G., Civile, O., Vaiani, N. R., San Raffaele, O., Magliano, M. E., Niguarda, O., Goglio, M., Riuniti, O., Nicoletti, B. P., Careggi, O., Menichetti, F. F., Monteluce, O., and Miragliottan, P. G.
- Subjects
Imipenem ,Cefotaxime ,Klebsiella pneumoniae ,Cefepime ,Ceftazidime ,Microbial Sensitivity Tests ,Aztreonam ,Biology ,beta-Lactams ,beta-Lactam Resistance ,beta-Lactamases ,Microbiology ,chemistry.chemical_compound ,Enterobacteriaceae ,Gene Frequency ,Mechanisms of Resistance ,polycyclic compounds ,medicine ,Humans ,Pharmacology (medical) ,Cefoxitin ,Pharmacology ,biochemical phenomena, metabolism, and nutrition ,bacterial infections and mycoses ,biology.organism_classification ,Anti-Bacterial Agents ,Ciprofloxacin ,Aminoglycosides ,Infectious Diseases ,Italy ,chemistry ,bacteria ,medicine.drug - Abstract
An Italian nationwide survey was carried out to assess the prevalences and the antimicrobial susceptibilities of members of the family Enterobacteriaceae producing extended-spectrum β-lactamases (ESBLs). Over a 6-month period, 8,015 isolates were obtained from hospitalized patients and screened for resistance to extended-spectrum cephalosporins and monobactams. On the basis of a synergistic effect between clavulanate and selected β-lactams (ceftazidime, aztreonam, cefotaxime, cefepime, and ceftriaxone), 509 isolates were found to be ESBL positive (6.3%). Colony blot hybridization with bla TEM and bla SHV DNA probes allowed one to distinguish four different genotypes: TEM-positive, SHV-positive, TEM- and SHV-positive, and non-TEM, non-SHV ESBL types. MICs for each isolate (E-test) were obtained for widely used β-lactams, combinations of β-lactams with β-lactamase inhibitors, aminoglycosides, and fluoroquinolones. Among ESBL-positive strains, Klebsiella pneumoniae , Proteus mirabilis , and Escherichia coli accounted for 73.6% of isolates. Overall, TEM-type ESBLs were more prevalent than SHV-type enzymes (234 versus 173), whereas the prevalence of strains producing both TEM- and SHV-type ESBLs was similar to that of isolates producing non-TEM, non-SHV enzymes (55 and 38, respectively). In vitro, all but one of the ESBL-producing isolates remained susceptible to imipenem. Susceptibility to other drugs varied: piperacillin-tazobactam, 91%; amoxicillin-clavulanic acid, 85%; cefoxitin, 78%; amikacin, 76%; ampicillin-sulbactam, 61%; ciprofloxacin, 58%; and gentamicin, 56%. Associated resistance to aminoglycosides and ciprofloxacin was observed most frequently among TEM-positive strains. Since therapeutic options for multiresistant Enterobacteriaceae are limited, combinations of β-lactams and β-lactamase inhibitors appear to represent an important alternative for treating infections caused by ESBL-producing Enterobacteriaceae .
- Published
- 2002
30. The Root-Knot Nematode Calreticulin Mi-CRT Is a Key Effector in Plant Defense Suppression
- Author
-
Jaouannet, M., primary, Magliano, M., additional, Arguel, M. J., additional, Gourgues, M., additional, Evangelisti, E., additional, Abad, P., additional, and Rosso, M. N., additional
- Published
- 2013
- Full Text
- View/download PDF
31. ER stress protein AGR2 precedes and is involved in the regulation of pancreatic cancer initiation
- Author
-
Dumartin, L, Alrawashdeh, W, Trabulo, S M, Radon, T P, Steiger, K, Feakins, R M, di Magliano, M P, Heeschen, C, Esposito, I, Lemoine, N R, and Crnogorac-Jurcevic, T
- Abstract
The mechanisms of initiation of pancreatic ductal adenocarcinoma (PDAC) are still largely unknown. In the present study, we analysed the role of anterior gradient-2 (AGR2) in the earliest stages of pancreatic neoplasia. Immunohistochemical analysis of chronic pancreatitis (CP) and peritumoral areas in PDAC tissues showed that AGR2 was present in tubular complexes (TC) and early pancreatic intraepithelial neoplasia (PanINs). Moreover, AGR2 was also found in discrete subpopulations of non-transformed cells neighbouring these pre-neoplastic lesions. In primary cells derived from human patient-derived xenograft (PDX) model, flow-cytometry revealed that AGR2 was overexpressed in pancreatic cancer stem cells (CSC) compared with non-stem cancer cells. In LSL-KrasG12D;Pdx1-Cre (KC) mouse model Agr2 induction preceded the formation of pre-neoplastic lesions and their development was largely inhibited by Agr2 deletion in engineered LSL-KrasG12D;Pdx1-Cre; Agr2−/−mice. In vitro, AGR2 expression was stimulated by tunicamycin-induced endoplasmic reticulum (ER) stress in both KRAS wild-type normal pancreas cells, as well as in KRAS mutated pancreatic cancer cells and was essential for ER homoeostasis. The unfolded protein response proteins GRP78, ATF6 and XBP1s were found expressed in CP and PDAC peritumoral tissues, but in contrast to AGR2, their expression was switched off during TC and PanIN formation. Real-time PCR and ELISA analyses showed that ER stress induced a pro-inflammatory phenotype in pancreatic normal, cancer and stellate cells. Moreover, AGR2 expression was inducible by paracrine transfer of ER stress and pro-inflammation between different pancreatic cell types. Our findings demonstrate that AGR2 induced in ER-stressed and inflammatory pre-neoplastic pancreas is a potential marker of cancer progenitor cells with an important functional role in PDAC initiation.
- Published
- 2017
- Full Text
- View/download PDF
32. Carbon monoxide poisoning masquerading as giant cell arteritis
- Author
-
Xue, K, primary, Mota, M, additional, Rahman, K, additional, Magliano, M, additional, and Manuchehri, K, additional
- Published
- 2011
- Full Text
- View/download PDF
33. Mulitização em refratários utilizando diferentes fontes precursoras: revisão
- Author
-
Magliano, M. V. M., primary and Pandolfelli, V. C., additional
- Published
- 2010
- Full Text
- View/download PDF
34. Origin of flooding water through hydrogeochemical identification, the Buenos Aires plain, Argentina
- Author
-
Alconada-Magliano, M. M., primary, Fagundo-Castillo, J. R., additional, Carrillo-Rivera, J. J., additional, and Hernández, P. G., additional
- Published
- 2010
- Full Text
- View/download PDF
35. Sistemas ligantes para concretos refratários mulitizáveis
- Author
-
Magliano, M. V. M, primary and Pandolfelli, V. C, additional
- Published
- 2010
- Full Text
- View/download PDF
36. Características da sílica coloidal e seus efeitos em concretos refratários
- Author
-
Magliano, M. V. M, primary and Pandolfelli, V. C, additional
- Published
- 2010
- Full Text
- View/download PDF
37. Genetics of Ovarian Differentiation: Rspo1, a Major Player
- Author
-
Chassot, A.A., primary, Gregoire, E.P., additional, Magliano, M., additional, Lavery, R., additional, and Chaboissier, M.C., additional
- Published
- 2008
- Full Text
- View/download PDF
38. Transcriptome analysis of root‐knot nematode functions induced in the early stages of parasitism*
- Author
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Dubreuil, G., primary, Magliano, M., additional, Deleury, E., additional, Abad, P., additional, and Rosso, M. N., additional
- Published
- 2007
- Full Text
- View/download PDF
39. Cirrhosis associated with multiple transfusions in thalassaemia.
- Author
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JEAN, G., TERZOLI, S., MAURI, R., BORGHETTI, L., DI PALMA, A., PIGA, A., MAGLIANO, M., MELEVENDI, M., and CATTANEO, M.
- Abstract
The study of surgical liver biopsy specimens obtained during splenectomy in 86 children with thalassaemia indicated that such patients may develop liver disease that evolves into cirrhosis. Histological characteristics suggest that it is post-necrotic cirrhosis. Onset of cirrhosis in some patients may occur as early as 7-8 years old, and at age about 15-16 years most children with thalassaemia show features of cirrhosis. In addition to fibrosis, hepatitis, or even aggressive hepatitis may develop as has also been observed in patients without thalassaemia who have undergone multiple transfusions. This study presents the current probable evolution of liver disease in patients with thalassaemia and may thus serve as a reference from which to evaluate any future progress in the treatment and care of patients with Cooley's disease. [ABSTRACT FROM AUTHOR]
- Published
- 1984
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40. Carbon monoxide poisoning masquerading as giant cell arteritis.
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Xue, K, Mota, M, Rahman, K, Magliano, M, and Manuchehri, K
- Subjects
LETTERS to the editor ,TOXICOLOGY of carbon monoxide ,GIANT cell arteritis ,DRUG side effects ,GLAUCOMA - Abstract
Two letters to the editor related to eye medicine are presented, where one is a case study on carbon monoxide poisoning with symptoms similar to giant cell arteritis (GCA) and on the article "Non-steroidal drug-induced glaucoma," by M. R. Razeghinejad, M. J. Pro, and L. J. Katz, in the 2011 issue.
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- 2012
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41. Fotografia soggettiva e vedutismo architettonico
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BELFIORE, Pasquale, F. Cappiello Magliano, M. Ferrara, E. Schiavoni, and Belfiore, Pasquale
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Architettura, Fotografia, Arte - Abstract
Rassegna critica di fotografie d'autore riferite all'arte e all'architettura contemporanee.
- Published
- 2016
42. The thyroid transcription factor 2 (TTF-2) is a promoter-specific DNA-binding independent transcriptional repressor
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Perrone, Pasca di Magliano, Zannini, Di Lauro, Perrone, L., PASCA DI MAGLIANO, M., Zannini, M., and DI LAURO, Roberto
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endocrine system ,Thyroid Nuclear Factor 1 ,Biophysics ,Thyroid Gland ,Repressor ,Biology ,Transfection ,Biochemistry ,Iodide Peroxidase ,Thyroglobulin ,Substrate Specificity ,03 medical and health sciences ,PAX8 Transcription Factor ,0302 clinical medicine ,Sp3 transcription factor ,Genes, Reporter ,Humans ,Paired Box Transcription Factors ,Promoter Regions, Genetic ,Molecular Biology ,030304 developmental biology ,0303 health sciences ,General transcription factor ,YY1 ,Nuclear Proteins ,Promoter ,Forkhead Transcription Factors ,Cell Biology ,TCF4 ,DNA ,respiratory system ,Molecular biology ,Cell biology ,Protein Structure, Tertiary ,DNA-Binding Proteins ,Repressor Proteins ,Enhancer Elements, Genetic ,GATAD2B ,030220 oncology & carcinogenesis ,TAF2 ,Mutation ,Trans-Activators ,HeLa Cells ,Protein Binding ,Transcription Factors - Abstract
The thyroid transcription factor TTF-2 is a forkhead-containing protein involved in thyroid-specific gene expression and necessary for thyroid morphogenesis. In this paper, we demonstrate that TTF-2 is able to inhibit the activity of the thyroid-specific transcription factors TTF-1 and Pax-8 only on certain promoters. We identified the minimal protein domain responsible for repressor activity, which behaves as an independent functional domain, and we show that repression by TTF-2 is DNA-binding independent. We suggest that TTF-2 is able to interfere with a specific cofactor required for TTF-1 and Pax-8 activity. (C) 2000 Academic Press.
- Published
- 2000
43. Pancreatic Cancer-Associated Fibroblasts: Where Do We Go from Here?
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Carpenter ES, Vendramini-Costa DB, Hasselluhn MC, Maitra A, Olive KP, Cukierman E, Pasca di Magliano M, and Sherman MH
- Subjects
- Humans, Animals, Cancer-Associated Fibroblasts pathology, Cancer-Associated Fibroblasts metabolism, Pancreatic Neoplasms pathology, Tumor Microenvironment, Carcinoma, Pancreatic Ductal pathology
- Abstract
Pancreatic ductal adenocarcinoma is a deadly disease and is projected to become the second leading cause of cancer-related death by 2030. A major hallmark is the exuberant host response comprising the tumor microenvironment, of which, cancer-associated fibroblasts (CAF) are a prevalent component. Despite the gains in understanding of their heterogeneity and functionality from CAF studies in recent years, there are many unanswered questions surrounding this diverse population of cells. Here, we summarize the views of several experts in the field, focusing on the current understanding of CAFs and challenges to address., (©2024 American Association for Cancer Research.)
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- 2024
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44. KRAS-mediated upregulation of CIP2A promotes suppression of PP2A-B56α to initiate pancreatic cancer development.
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Tinsley SL, Chianis ERD, Shelley RA, Mall GK, Dhiman A, Baral G, Kothandaraman H, Thoma MC, English IA, Daniel CJ, Acosta LCS, Solorio L, Atallah Lanman N, Pasca di Magliano M, Narla G, Dykhuizen EC, Sears RC, and Allen-Petersen BL
- Abstract
Oncogenic mutations in KRAS are present in ~95% of patients diagnosed with pancreatic ductal adenocarcinoma (PDAC) and are considered the initiating event of pancreatic intraepithelial neoplasia (PanIN) precursor lesions. While it is well established that KRAS mutations drive the activation of oncogenic kinase cascades during pancreatic oncogenesis, the effects of oncogenic KRAS signaling on regulation of phosphatases during this process is not fully appreciated. Protein Phosphatase 2A (PP2A) has been implicated in suppressing KRAS-driven cellular transformation and low PP2A activity is observed in PDAC cells compared to non-transformed cells, suggesting that suppression of PP2A activity is an important step in the overall development of PDAC. In the current study, we demonstrate that KRAS
G12D induces the expression of an endogenous inhibitor of PP2A activity, Cancerous Inhibitor of PP2A (CIP2A), and phosphorylation of the PP2A substrate, c-MYC. Consistent with these findings, KRASG12D sequestered the specific PP2A subunit responsible for c-MYC degradation, B56α, away from the active PP2A holoenzyme in a CIP2A-dependent manner. During PDAC initiation in vivo, knockout of B56α promoted KRASG12D tumorigenesis by accelerating acinar-to-ductal metaplasia (ADM) and the formation of PanIN lesions. The process of ADM was attenuated ex vivo in response to pharmacological re-activation of PP2A utilizing direct small molecule activators of PP2A (SMAPs). Together, our results suggest that suppression of PP2A-B56α through KRAS signaling can promote the MYC-driven initiation of pancreatic tumorigenesis., (© 2024. The Author(s), under exclusive licence to Springer Nature Limited.)- Published
- 2024
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45. Oncogenic KRAS-Dependent Stromal Interleukin-33 Directs the Pancreatic Microenvironment to Promote Tumor Growth.
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Donahue KL, Watkoske HR, Kadiyala P, Du W, Brown K, Scales MK, Elhossiny AM, Espinoza CE, Lasse Opsahl EL, Griffith BD, Wen Y, Sun L, Velez-Delgado A, Renollet NM, Morales J, Nedzesky NM, Baliira RK, Menjivar RE, Medina-Cabrera PI, Rao A, Allen B, Shi J, Frankel TL, Carpenter ES, Bednar F, Zhang Y, and Pasca di Magliano M
- Subjects
- Animals, Mice, Humans, Stromal Cells metabolism, Cancer-Associated Fibroblasts metabolism, Mice, Knockout, Cell Line, Tumor, Tumor Microenvironment, Interleukin-33 metabolism, Interleukin-33 genetics, Pancreatic Neoplasms pathology, Pancreatic Neoplasms genetics, Pancreatic Neoplasms metabolism, Proto-Oncogene Proteins p21(ras) genetics
- Abstract
Pancreatic cancer is characterized by an extensive fibroinflammatory microenvironment. During carcinogenesis, normal stromal cells are converted to cytokine-high cancer-associated fibroblasts (CAF). The mechanisms underlying this conversion, including the regulation and function of fibroblast-derived cytokines, are poorly understood. Thus, efforts to therapeutically target CAFs have so far failed. Herein, we show that signals from epithelial cells expressing oncogenic KRAS-a hallmark pancreatic cancer mutation-activate fibroblast autocrine signaling, which drives the expression of the cytokine IL33. Stromal IL33 expression remains high and dependent on epithelial KRAS throughout carcinogenesis; in turn, environmental stress induces interleukin-33 (IL33) secretion. Using compartment-specific IL33 knockout mice, we observed that lack of stromal IL33 leads to profound reprogramming of multiple components of the pancreatic tumor microenvironment, including CAFs, myeloid cells, and lymphocytes. Notably, loss of stromal IL33 leads to an increase in CD8+ T-cell infiltration and activation and, ultimately, reduced tumor growth. Significance: This study provides new insights into the mechanisms underlying the programming of CAFs and shows that during this process, expression of the cytokine IL33 is induced. CAF-derived IL33 has pleiotropic effects on the tumor microenvironment, supporting its potential as a therapeutic target., (©2024 The Authors; Published by the American Association for Cancer Research.)
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- 2024
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46. From Inception to Malignancy: the Co-evolution of Pancreatic Cancer and Its Immunosuppressive Microenvironment.
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Bednar F, Olsen LY, and Pasca di Magliano M
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- Animals, Humans, Mice, Disease Progression, Immune Tolerance genetics, History, 21st Century, Pancreatic Neoplasms genetics, Pancreatic Neoplasms history, Pancreatic Neoplasms immunology, Pancreatic Neoplasms pathology, Tumor Microenvironment genetics, Tumor Microenvironment immunology
- Abstract
Published in Cancer Research in 2007, Clark and colleagues first introduced the concept that the immune microenvironment evolves in lockstep with the progression of pancreatic cancer. Leveraging genetically engineered mouse models of the disease that were described a few years earlier, Clark and colleagues used a combination of approaches to describe the dynamics of immune evolution in precursor lesions all the way to overt malignancy. They discovered that immunosuppression is established at the earliest stages of carcinogenesis. Here, we discuss their findings, how they led to a wealth of functional work, and how they have been expanded upon since the advent of -omics technologies. See related article by Clark and colleagues, Cancer Res 2007;67:9518-27., (©2024 American Association for Cancer Research.)
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- 2024
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47. Unveiling the Culprit: IL17 Signaling in the Pancreatic Epithelium Drives Tumorigenesis.
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Lee KE and Pasca di Magliano M
- Subjects
- Humans, Animals, Carcinogenesis metabolism, Epithelium metabolism, Epithelium immunology, Receptors, Interleukin-17 metabolism, Pancreas metabolism, Pancreas pathology, Pancreas immunology, Mice, Interleukin-17 metabolism, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Pancreatic Neoplasms immunology, Signal Transduction
- Abstract
IL17 signaling promotes pancreatic cancer development, yet the cell compartment responsible for the protumorigenic function of IL17 has not been defined. In this article, Castro-Pando and colleagues demonstrate that IL17/IL17 receptor A signaling in the pancreatic epithelium is critical for pancreatic cancer initiation and for establishing immunosuppression, whereas its signaling in the immune compartment is dispensable. This work provides an important mechanistic insight on the role of IL17 signaling and identifies a potential new immune checkpoint as a target in pancreatic cancer. See related article by Castro-Pando et al., p. 1170., (©2024 American Association for Cancer Research.)
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- 2024
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48. Metabolic landscape of the healthy pancreas and pancreatic tumor microenvironment.
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Bonilla ME, Radyk MD, Perricone MD, Elhossiny AM, Harold AC, Medina-Cabrera PI, Kadiyala P, Shi J, Frankel TL, Carpenter ES, Green MD, Mitrea C, Lyssiotis CA, and Pasca di Magliano M
- Subjects
- Humans, Lipid Metabolism, Pancreas metabolism, Pancreas pathology, Tumor-Associated Macrophages metabolism, Tumor-Associated Macrophages immunology, Cholesterol metabolism, Oxidative Phosphorylation, Mitochondria metabolism, Single-Cell Analysis, Tumor Microenvironment, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms pathology, Pancreatic Neoplasms genetics
- Abstract
Pancreatic cancer, one of the deadliest human malignancies, is characterized by a fibro-inflammatory tumor microenvironment and wide array of metabolic alterations. To comprehensively map metabolism in a cell type-specific manner, we harnessed a unique single-cell RNA-sequencing dataset of normal human pancreata. This was compared with human pancreatic cancer samples using a computational pipeline optimized for this study. In the cancer cells we observed enhanced biosynthetic programs. We identified downregulation of mitochondrial programs in several immune populations, relative to their normal counterparts in healthy pancreas. Although granulocytes, B cells, and CD8+ T cells all downregulated oxidative phosphorylation, the mechanisms by which this occurred were cell type specific. In fact, the expression pattern of the electron transport chain complexes was sufficient to identify immune cell types without the use of lineage markers. We also observed changes in tumor-associated macrophage (TAM) lipid metabolism, with increased expression of enzymes mediating unsaturated fatty acid synthesis and upregulation in cholesterol export. Concurrently, cancer cells exhibited upregulation of lipid/cholesterol receptor import. We thus identified a potential crosstalk whereby TAMs provide cholesterol to cancer cells. We suggest that this may be a new mechanism boosting cancer cell growth and a therapeutic target in the future.
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- 2024
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49. Malic enzyme 1 knockout has no deleterious phenotype and is favored in the male germline under standard laboratory conditions.
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Alektiar JM, Shan M, Radyk MD, Zhang L, Halbrook CJ, Lin L, Espinoza C, Mier IF, Lavoie BL, Salvatore L, Pasca di Magliano M, Cantley LC, Mueller JL, and Lyssiotis CA
- Subjects
- Animals, Male, Mice, Female, Germ Cells metabolism, Mice, Inbred C57BL, Malate Dehydrogenase metabolism, Malate Dehydrogenase genetics, Mice, Knockout, Phenotype
- Abstract
Malic Enzyme 1 (ME1) plays an integral role in fatty acid synthesis and cellular energetics through its production of NADPH and pyruvate. As such, it has been identified as a gene of interest in obesity, type 2 diabetes, and an array of epithelial cancers, with most work being performed in vitro. The current standard model for ME1 loss in vivo is the spontaneous Mod-1 null allele, which produces a canonically inactive form of ME1. Herein, we describe two new genetically engineered mouse models exhibiting ME1 loss at dynamic timepoints. Using murine embryonic stem cells and Flp/FRT and Cre/loxP class switch recombination, we established a germline Me1 knockout model (Me1 KO) and an inducible conditional knockout model (Me1 cKO), activated upon tamoxifen treatment in adulthood. Collectively, neither the Me1 KO nor Me1 cKO models exhibited deleterious phenotype under standard laboratory conditions. Knockout of ME1 was validated by immunohistochemistry and genotype confirmed by PCR. Transmission patterns favor Me1 loss in Me1 KO mice when maternally transmitted to male progeny. Hematological examination of these models through complete blood count and serum chemistry panels revealed no discrepancy with their wild-type counterparts. Orthotopic pancreatic tumors in Me1 cKO mice grow similarly to Me1 expressing mice. Similarly, no behavioral phenotype was observed in Me1 cKO mice when aged for 52 weeks. Histological analysis of several tissues revealed no pathological phenotype. These models provide a more modern approach to ME1 knockout in vivo while opening the door for further study into the role of ME1 loss under more biologically relevant, stressful conditions., Competing Interests: L.C.C. and C.A.L. are inventors on patents pertaining to Kras regulated metabolic pathways, redox control pathways in pancreatic cancer, and targeting GOT1 or ME1 as a therapeutic approach (US Patent No: 2015126580-A1, 05/07/2015; US Patent No: 20190136238, 05/09/2019; International Patent No: WO2013177426-A2, 04/23/2015). L.C.C. owns equity in, receives compensation from, and serves on the Scientific Advisory Boards of Faeth Therapeutics, Agios Pharmaceuticals, Volastra Therapeutics, and Larkspur Biosciences. L.C.C.’s laboratory has previously received financial support from Petra Pharmaceuticals. Agios Pharmaceuticals is identifying metabolic pathways of cancer cells and developing drugs to inhibit such enzymes to disrupt tumor cell growth and survival. In the last 3 years, C.A.L. has received consulting fees from Astellas Pharmaceuticals, Odyssey Therapeutics, Third Rock Ventures, and T-Knife Therapeutics. This does not alter our adherence to PLOS ONE policies on sharing data and materials., (Copyright: © 2024 Alektiar et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.)
- Published
- 2024
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50. KRT17high/CXCL8+ Tumor Cells Display Both Classical and Basal Features and Regulate Myeloid Infiltration in the Pancreatic Cancer Microenvironment.
- Author
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Carpenter ES, Kadiyala P, Elhossiny AM, Kemp SB, Li J, Steele NG, Nicolle R, Nwosu ZC, Freeman J, Dai H, Paglia D, Du W, Donahue K, Morales J, Medina-Cabrera PI, Bonilla ME, Harris L, The S, Gunchick V, Peterson N, Brown K, Mattea M, Espinoza CE, McGue J, Kabala SM, Baliira RK, Renollet NM, Mooney AG, Liu J, Bhalla S, Farida JP, Ko C, Machicado JD, Kwon RS, Wamsteker EJ, Schulman A, Anderson MA, Law R, Prabhu A, Coulombe PA, Rao A, Frankel TL, Bednar F, Shi J, Sahai V, and Pasca Di Magliano M
- Subjects
- Humans, Single-Cell Analysis, Biomarkers, Tumor, Gene Expression Regulation, Neoplastic, Organoids pathology, Female, Tumor Microenvironment immunology, Pancreatic Neoplasms pathology, Pancreatic Neoplasms immunology, Pancreatic Neoplasms metabolism, Pancreatic Neoplasms genetics, Pancreatic Neoplasms drug therapy, Carcinoma, Pancreatic Ductal pathology, Carcinoma, Pancreatic Ductal immunology, Carcinoma, Pancreatic Ductal genetics, Carcinoma, Pancreatic Ductal metabolism, Myeloid Cells metabolism, Myeloid Cells pathology, Myeloid Cells immunology, Interleukin-8 metabolism
- Abstract
Purpose: Pancreatic ductal adenocarcinoma (PDAC) is generally divided in two subtypes, classical and basal. Recently, single-cell RNA sequencing has uncovered the coexistence of basal and classical cancer cells, as well as intermediary cancer cells, in individual tumors. The latter remains poorly understood; here, we sought to characterize them using a multimodal approach., Experimental Design: We performed subtyping on a single-cell RNA sequencing dataset containing 18 human PDAC samples to identify multiple intermediary subtypes. We generated patient-derived PDAC organoids for functional studies. We compared single-cell profiling of matched blood and tumor samples to measure changes in the local and systemic immune microenvironment. We then leveraged longitudinally patient-matched blood to follow individual patients over the course of chemotherapy., Results: We identified a cluster of KRT17-high intermediary cancer cells that uniquely express high levels of CXCL8 and other cytokines. The proportion of KRT17high/CXCL8+ cells in patient tumors correlated with intratumoral myeloid abundance, and, interestingly, high protumor peripheral blood granulocytes, implicating local and systemic roles. Patient-derived organoids maintained KRT17high/CXCL8+ cells and induced myeloid cell migration in a CXCL8-dependent manner. In our longitudinal studies, plasma CXCL8 decreased following chemotherapy in responsive patients, while CXCL8 persistence portended worse prognosis., Conclusions: Through single-cell analysis of PDAC samples, we identified KRT17high/CXCL8+ cancer cells as an intermediary subtype, marked by a unique cytokine profile and capable of influencing myeloid cells in the tumor microenvironment and systemically. The abundance of this cell population should be considered for patient stratification in precision immunotherapy. See related commentary by Faraoni and McAllister, p. 2297., (©2023 The Authors; Published by the American Association for Cancer Research.)
- Published
- 2024
- Full Text
- View/download PDF
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