2,266 results on '"Giaccone, G"'
Search Results
2. Protein network analysis reveals selectively vulnerable regions and biological processes in FTD
- Author
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Bonham, Luke W, Steele, Natasha ZR, Karch, Celeste M, Manzoni, Claudia, Geier, Ethan G, Wen, Natalie, Ofori-Kuragu, Aaron, Momeni, Parastoo, Hardy, John, Miller, Zachary A, Hess, Christopher P, Lewis, Patrick, Miller, Bruce L, Seeley, William W, Baranzini, Sergio E, Desikan, Rahul S, Ferrari, Raffaele, Yokoyama, Jennifer S, Ferrari, R, Hernandez, DG, Nalls, MA, Rohrer, JD, Ramasamy, A, Kwok, JBJ, Dobson-Stone, C, Schofield, PR, Halliday, GM, Hodges, JR, Piguet, O, Bartley, L, Thompson, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, NJ, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Waldö, M Landqvist, Nilsson, K, Nilsson, C, Mackenzie, IRA, Hsiung, G-YR, Mann, D, Grafman, J, Morris, CM, Attems, J, Griffiths, TD, McKeith, IG, Thomas, AJ, Pietrini, P, Huey, ED, Wassermann, EM, Baborie, A, Jaros, E, Tierney, MC, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, JB, Schlachetzki, JCM, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, VM, Grossman, M, Trojanowski, JQ, van der Zee, J, Van Broeckhoven, C, Cappa, SF, Leber, I, Hannequin, D, and Golfier, V
- Subjects
Biological Sciences ,Bioinformatics and Computational Biology ,Genetics ,Aging ,Alzheimer's Disease including Alzheimer's Disease Related Dementias (AD/ADRD) ,Alzheimer's Disease Related Dementias (ADRD) ,Frontotemporal Dementia (FTD) ,Acquired Cognitive Impairment ,Dementia ,Biotechnology ,Neurodegenerative ,Rare Diseases ,Neurosciences ,Brain Disorders ,Human Genome ,Aetiology ,2.1 Biological and endogenous factors ,Neurological ,International FTD-Genomics Consortium ,Clinical sciences - Abstract
ObjectiveThe neuroanatomical profile of behavioral variant frontotemporal dementia (bvFTD) suggests a common biological etiology of disease despite disparate pathologic causes; we investigated the genetic underpinnings of this selective regional vulnerability to identify new risk factors for bvFTD.MethodsWe used recently developed analytical techniques designed to address the limitations of genome-wide association studies to generate a protein interaction network of 63 bvFTD risk genes. We characterized this network using gene expression data from healthy and diseased human brain tissue, evaluating regional network expression patterns across the lifespan as well as the cell types and biological processes most affected in bvFTD.ResultsWe found that bvFTD network genes show enriched expression across the human lifespan in vulnerable neuronal populations, are implicated in cell signaling, cell cycle, immune function, and development, and are differentially expressed in pathologically confirmed frontotemporal lobar degeneration cases. Five of the genes highlighted by our differential expression analyses, BAIAP2, ERBB3, POU2F2, SMARCA2, and CDC37, appear to be novel bvFTD risk loci.ConclusionsOur findings suggest that the cumulative burden of common genetic variation in an interacting protein network expressed in specific brain regions across the lifespan may influence susceptibility to bvFTD.
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- 2018
3. Sex-based differences in response to anti-PD-1 or PD-L1 treatment in patients with non-small-cell lung cancer expressing high PD-L1 levels. A systematic review and meta-analysis of randomized clinical trials
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Conforti, F., Pala, L., Pagan, E., Corti, C., Bagnardi, V., Queirolo, P., Catania, C., De Pas, T., and Giaccone, G.
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- 2021
- Full Text
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4. Small cell lung cancer: a slightly less orphan disease after immunotherapy
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Remon, J., Aldea, M., Besse, B., Planchard, D., Reck, M., Giaccone, G., and Soria, J.-C.
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- 2021
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5. Surrogate endpoints for overall survival in randomized clinical trials testing immune checkpoint inhibitors: a systematic review and meta-analysis
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Sala, I, Pagan, E, Pala, L, Oriecuia, C, Musca, M, Specchia, C, De Pas, T, Cortes, J, Giaccone, G, Postow, M, Gelber, R, Bagnardi, V, Conforti, F, Gelber, RD, Sala, I, Pagan, E, Pala, L, Oriecuia, C, Musca, M, Specchia, C, De Pas, T, Cortes, J, Giaccone, G, Postow, M, Gelber, R, Bagnardi, V, Conforti, F, and Gelber, RD
- Abstract
Introduction: There is debate on which are the best surrogate endpoint and metric to capture treatment effect on overall survival (OS) in RCTs testing immune-checkpoint inhibitors (ICIs). Methods: We systematically searched for RCTs testing ICIs in patients with advanced solid tumors. Inclusion criteria were: RCTs i) assessing PD-(L)1 and CTLA-4 inhibitors either as monotherapy or in combination with another ICI, and/or targeted therapy, and/or chemotherapy, in patients with advanced solid tumors; ii) randomizing at least 100 patients. We performed a meta-analysis of RCTs to compare the surrogacy value of PFS and modified-PFS (mPFS) for OS in RCTs testing ICIs, when the treatment effect is measured by the hazard ratio (HR) for OS, and by the HR and the ratio of restricted mean survival time (rRMST) for PFS and mPFS. Results: 61 RCTs (67 treatment comparisons and 36,034 patients) were included in the analysis. In comparisons testing ICI plus chemotherapy, HRPFS and HRmPFS both had a strong surrogacy value (R2 = 0.74 and R2 = 0.81, respectively). In comparisons testing ICI as monotherapy, HRPFS was the best surrogate, although having a moderate correlation (R2 = 0.58). In comparisons testing ICI plus other treatment(s), the associations were very weak for all the surrogate endpoints and treatment effect measures, with R2 ranging from 0.01 to 0.22. Conclusion: In RCTs testing ICIs, the value of potential surrogates for HROS was strongly affected by the type of treatment(s) tested. The evidence available supports HRPFS as the best surrogate, and disproves the use of alternative endpoints, such as the mPFS, or treatment effect measures, such as the RMST.
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- 2024
6. Early and long-term cognitive features in sporadic Creutzfeldt-Jakob disease
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Meattini, M., Giaccone, G., D’Incerti, L., and Giovagnoli, A. R.
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- 2021
- Full Text
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7. Author Correction: Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores (Nature Communications, (2021), 12, 1, (3417), 10.1038/s41467-021-22491-8)
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de Rojas I., de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, I, Pedersen, N, Stringa, N, Zettergren, A, Hernandez, I, Montrreal, L, Antunez, C, Antonell, A, Tankard, R, Bis, J, Sims, R, Bellenguez, C, Quintela, I, Gonzalez-Perez, A, Calero, M, Franco-Macias, E, Macias, J, Blesa, R, Cervera-Carles, L, Menendez-Gonzalez, M, Frank-Garcia, A, Royo, J, Moreno, F, Huerto Vilas, R, Baquero, M, Diez-Fairen, M, Lage, C, Garcia-Madrona, S, Garcia-Gonzalez, P, Alarcon-Martin, E, Valero, S, Sotolongo-Grau, O, Ullgren, A, Naj, A, Lemstra, A, Benaque, A, Perez-Cordon, A, Benussi, A, Rabano, A, Padovani, A, Squassina, A, de Mendonca, A, Arias Pastor, A, Kok, A, Meggy, A, Pastor, A, Espinosa, A, Corma-Gomez, A, Martin Montes, A, Sanabria, A, Destefano, A, Schneider, A, Haapasalo, A, Kinhult Stahlbom, A, Tybjaerg-Hansen, A, Hartmann, A, Spottke, A, Corbaton-Anchuelo, A, Rongve, A, Borroni, B, Arosio, B, Nacmias, B, Nordestgaard, B, Kunkle, B, Charbonnier, C, Abdelnour, C, Masullo, C, Martinez Rodriguez, C, Munoz-Fernandez, C, Dufouil, C, Graff, C, Ferreira, C, Chillotti, C, Reynolds, C, Fenoglio, C, Van Broeckhoven, C, Clark, C, Pisanu, C, Satizabal, C, Holmes, C, Buiza-Rueda, D, Aarsland, D, Rujescu, D, Alcolea, D, Galimberti, D, Wallon, D, Seripa, D, Grunblatt, E, Dardiotis, E, Duzel, E, Scarpini, E, Conti, E, Rubino, E, Gelpi, E, Rodriguez-Rodriguez, E, Duron, E, Boerwinkle, E, Ferri, E, Tagliavini, F, Kucukali, F, Pasquier, F, Sanchez-Garcia, F, Mangialasche, F, Jessen, F, Nicolas, G, Selbaek, G, Ortega, G, Chene, G, Hadjigeorgiou, G, Rossi, G, Spalletta, G, Giaccone, G, Grande, G, Binetti, G, Papenberg, G, Hampel, H, Bailly, H, Zetterberg, H, Soininen, H, Karlsson, I, Alvarez, I, Appollonio, I, Giegling, I, Skoog, I, Saltvedt, I, Rainero, I, Rosas Allende, I, Hort, J, Diehl-Schmid, J, Van Dongen, J, Vidal, J, Lehtisalo, J, Wiltfang, J, Thomassen, J, Kornhuber, J, Haines, J, Vogelgsang, J, Pineda, J, Fortea, J, Popp, J, Deckert, J, Buerger, K, Morgan, K, Fliessbach, K, Sleegers, K, Molina-Porcel, L, Kilander, L, Weinhold, L, Farrer, L, Wang, L, Kleineidam, L, Farotti, L, Parnetti, L, Tremolizzo, L, Hausner, L, Benussi, L, Froelich, L, Ikram, M, Deniz-Naranjo, M, Tsolaki, M, Rosende-Roca, M, Lowenmark, M, Hulsman, M, Spallazzi, M, Pericak-Vance, M, Esiri, M, Bernal Sanchez-Arjona, M, Dalmasso, M, Martinez-Larrad, M, Arcaro, M, Nothen, M, Fernandez-Fuertes, M, Dichgans, M, Ingelsson, M, Herrmann, M, Scherer, M, Vyhnalek, M, Kosmidis, M, Yannakoulia, M, Schmid, M, Ewers, M, Heneka, M, Wagner, M, Scamosci, M, Kivipelto, M, Hiltunen, M, Zulaica, M, Alegret, M, Fornage, M, Roberto, N, van Schoor, N, Seidu, N, Banaj, N, Armstrong, N, Scarmeas, N, Scherbaum, N, Goldhardt, O, Hanon, O, Peters, O, Skrobot, O, Quenez, O, Lerch, O, Bossu, P, Caffarra, P, Dionigi Rossi, P, Sakka, P, Mecocci, P, Hoffmann, P, Holmans, P, Fischer, P, Riederer, P, Yang, Q, Marshall, R, Kalaria, R, Mayeux, R, Vandenberghe, R, Cecchetti, R, Ghidoni, R, Frikke-Schmidt, R, Sorbi, S, Hagg, S, Engelborghs, S, Helisalmi, S, Botne Sando, S, Kern, S, Archetti, S, Boschi, S, Fostinelli, S, Gil, S, Mendoza, S, Mead, S, Ciccone, S, Djurovic, S, Heilmann-Heimbach, S, Riedel-Heller, S, Kuulasmaa, T, del Ser, T, Lebouvier, T, Polak, T, Ngandu, T, Grimmer, T, Bessi, V, Escott-Price, V, Giedraitis, V, Deramecourt, V, Maier, W, Jian, X, Pijnenburg, Y, Smith, A, Saenz, A, Bizzarro, A, Lauria, A, Vacca, A, Solomon, A, Anastasiou, A, Richardson, A, Boland, A, Koivisto, A, Daniele, A, Greco, A, Marianthi, A, Mcguinness, B, Fin, B, Ferrari, C, Custodero, C, Ferrarese, C, Ingino, C, Mangone, C, Reyes Toso, C, Martinez, C, Cuesta, C, Muchnik, C, Joachim, C, Ortiz, C, Besse, C, Johansson, C, Zoia, C, Laske, C, Anastasiou, C, Palacio, D, Politis, D, Janowitz, D, Craig, D, Mann, D, Neary, D, Jurgen, D, Daian, D, Belezhanska, D, Kohler, E, Castano, E, Koutsouraki, E, Chipi, E, De Roeck, E, Costantini, E, Vardy, E, Piras, F, Roveta, F, Prestia, F, Assogna, F, Salani, F, Sala, G, Lacidogna, G, Novack, G, Wilcock, G, Thonberg, H, Kolsch, H, Weber, H, Boecker, H, Etchepareborda, I, Piaceri, I, Tuomilehto, J, Lindstrom, J, Laczo, J, Johnston, J, Deleuze, J, Harris, J, Schott, J, Priller, J, Bacha, J, Snowden, J, Lisso, J, Mihova, K, Traykov, L, Morelli, L, Brusco, L, Rainer, M, Takalo, M, Bjerke, M, Del Zompo, M, Serpente, M, Sanchez Abalos, M, Rios, M, Peltonen, M, Herrman, M, Kohler, M, Rojo, M, Jones, M, Orsini, M, Medel, N, Olivar, N, Fox, N, Salvadori, N, Hooper, N, Galeano, P, Solis, P, Bastiani, P, Passmore, P, Heun, R, Antikainen, R, Olaso, R, Perneczky, R, Germani, S, Lopez-Garcia, S, Love, S, Mehrabian, S, Bagnoli, S, Kochen, S, Andreoni, S, Teipel, S, Todd, S, Pickering-Brown, S, Natunen, T, Tegos, T, Laatikainen, T, Strandberg, T, Polvikoski, T, Matoska, V, Ciullo, V, Cores, V, Solfrizzi, V, Lisetti, V, Sevillano, Z, Aguilera, N, Alarcon, E, Boada, M, Buendia, M, Canabate, P, Carracedo, A, Diego, S, Gailhajenet, A, Guitart, M, Ibarria, M, Lafuente, A, Maronas, O, Martin, E, Martinez, M, Marquie, M, Mauleon, A, Moreno, M, Orellana, A, Pancho, A, Peleja, E, Preckler, S, Real, L, Ruiz, A, Saez, M, Serrano-Rios, M, Tarraga, L, Vargas, L, Adarmes-Gomez, A, Alonso, M, Alvarez, V, Amer-Ferrer, G, Antequera, M, Bernal, M, Bullido, M, Burguera, J, Carrillo, F, Carrion-Claro, M, Casajeros, M, Clarimon, J, Cruz-Gamero, J, de Pancorbo, M, Escuela, R, Garrote-Espina, L, Garcia-Alberca, J, Garcia Madrona, S, Garcia-Ribas, G, Gomez-Garre, P, Hevilla, S, Jesus, S, Labrador Espinosa, M, Legaz, A, Lleo, A, Lopez de Munain, A, Macias-Garcia, D, Manzanares, S, Marin, M, Marin-Munoz, J, Marin, T, Martinez, B, Martinez, V, Martinez-Lage Alvarez, P, Medina, M, Mendioroz Iriarte, M, Mir, P, Molinuevo, J, Pastor, P, Perez Tur, J, Perinan-Tocino, T, Pineda-Sanchez, R, Pinol-Ripoll, G, Real de Asua, D, Rodrigo, S, Sanchez del Valle Diaz, R, Sanchez-Juan, P, Sastre, I, Vicente, M, Vigo-Ortega, R, Vivancos, L, Macleod, C, Mccracken, C, Brayne, C, Bresner, C, Grozeva, D, Bellou, E, Sommerville, E, Matthews, F, Leonenko, G, Menzies, G, Windle, G, Harwood, J, Phillips, J, Bennett, K, Luckuck, L, Clare, L, Woods, R, Saad, S, Burholt, V, Kehoe, P, Scheltens, P, Holstege, H, Amouyel, P, Schellenberg, G, Williams, J, Seshadri, S, van Duijn, C, Mather, K, Sanchez-Valle, R, Blennow, K, Huisman, M, Andreassen, O, Posthuma, D, van der Flier, W, Ramirez, A, Lambert, J, van der Lee, S, de Rojas I., Moreno-Grau S., Tesi N., Grenier-Boley B., Andrade V., Jansen I. E., Pedersen N. L., Stringa N., Zettergren A., Hernandez I., Montrreal L., Antunez C., Antonell A., Tankard R. M., Bis J. C., Sims R., Bellenguez C., Quintela I., Gonzalez-Perez A., Calero M., Franco-Macias E., Macias J., Blesa R., Cervera-Carles L., Menendez-Gonzalez M., Frank-Garcia A., Royo J. L., Moreno F., Huerto Vilas R., Baquero M., Diez-Fairen M., Lage C., Garcia-Madrona S., Garcia-Gonzalez P., Alarcon-Martin E., Valero S., Sotolongo-Grau O., Ullgren A., Naj A. C., Lemstra A. W., Benaque A., Perez-Cordon A., Benussi A., Rabano A., Padovani A., Squassina A., de Mendonca A., Arias Pastor A., Kok A. A. L., Meggy A., Pastor A. B., Espinosa A., Corma-Gomez A., Martin Montes A., Sanabria A., DeStefano A. L., Schneider A., Haapasalo A., Kinhult Stahlbom A., Tybjaerg-Hansen A., Hartmann A. M., Spottke A., Corbaton-Anchuelo A., Rongve A., Borroni B., Arosio B., Nacmias B., Nordestgaard B. G., Kunkle B. W., Charbonnier C., Abdelnour C., Masullo C., Martinez Rodriguez C., Munoz-Fernandez C., Dufouil C., Graff C., Ferreira C. B., Chillotti C., Reynolds C. A., Fenoglio C., Van Broeckhoven C., Clark C., Pisanu C., Satizabal C. L., Holmes C., Buiza-Rueda D., Aarsland D., Rujescu D., Alcolea D., Galimberti D., Wallon D., Seripa D., Grunblatt E., Dardiotis E., Duzel E., Scarpini E., Conti E., Rubino E., Gelpi E., Rodriguez-Rodriguez E., Duron E., Boerwinkle E., Ferri E., Tagliavini F., Kucukali F., Pasquier F., Sanchez-Garcia F., Mangialasche F., Jessen F., Nicolas G., Selbaek G., Ortega G., Chene G., Hadjigeorgiou G., Rossi G., Spalletta G., Giaccone G., Grande G., Binetti G., Papenberg G., Hampel H., Bailly H., Zetterberg H., Soininen H., Karlsson I. K., Alvarez I., Appollonio I., Giegling I., Skoog I., Saltvedt I., Rainero I., Rosas Allende I., Hort J., Diehl-Schmid J., Van Dongen J., Vidal J. -S., Lehtisalo J., Wiltfang J., Thomassen J. Q., Kornhuber J., Haines J. L., Vogelgsang J., Pineda J. A., Fortea J., Popp J., Deckert J., Buerger K., Morgan K., Fliessbach K., Sleegers K., Molina-Porcel L., Kilander L., Weinhold L., Farrer L. A., Wang L. -S., Kleineidam L., Farotti L., Parnetti L., Tremolizzo L., Hausner L., Benussi L., Froelich L., Ikram M. A., Deniz-Naranjo M. C., Tsolaki M., Rosende-Roca M., Lowenmark M., Hulsman M., Spallazzi M., Pericak-Vance M. A., Esiri M., Bernal Sanchez-Arjona M., Dalmasso M. C., Martinez-Larrad M. T., Arcaro M., Nothen M. M., Fernandez-Fuertes M., Dichgans M., Ingelsson M., Herrmann M. J., Scherer M., Vyhnalek M., Kosmidis M. H., Yannakoulia M., Schmid M., Ewers M., Heneka M. T., Wagner M., Scamosci M., Kivipelto M., Hiltunen M., Zulaica M., Alegret M., Fornage M., Roberto N., van Schoor N. M., Seidu N. M., Banaj N., Armstrong N. J., Scarmeas N., Scherbaum N., Goldhardt O., Hanon O., Peters O., Skrobot O. A., Quenez O., Lerch O., Bossu P., Caffarra P., Dionigi Rossi P., Sakka P., Mecocci P., Hoffmann P., Holmans P. A., Fischer P., Riederer P., Yang Q., Marshall R., Kalaria R. N., Mayeux R., Vandenberghe R., Cecchetti R., Ghidoni R., Frikke-Schmidt R., Sorbi S., Hagg S., Engelborghs S., Helisalmi S., Botne Sando S., Kern S., Archetti S., Boschi S., Fostinelli S., Gil S., Mendoza S., Mead S., Ciccone S., Djurovic S., Heilmann-Heimbach S., Riedel-Heller S., Kuulasmaa T., del Ser T., Lebouvier T., Polak T., Ngandu T., Grimmer T., Bessi V., Escott-Price V., Giedraitis V., Deramecourt V., Maier W., Jian X., Pijnenburg Y. A. L., Smith A. D., Saenz A., Bizzarro A., Lauria A., Vacca A., Solomon A., Anastasiou A., Richardson A., Boland A., Koivisto A., Daniele A., Greco A., Marianthi A., McGuinness B., Fin B., Ferrari C., Custodero C., Ferrarese C., Ingino C., Mangone C., Reyes Toso C., Martinez C., Cuesta C., Muchnik C., Joachim C., Ortiz C., Besse C., Johansson C., Zoia C. P., Laske C., Anastasiou C., Palacio D. L., Politis D. G., Janowitz D., Craig D., Mann D. M., Neary D., Jurgen D., Daian D., Belezhanska D., Kohler E., Castano E. M., Koutsouraki E., Chipi E., De Roeck E., Costantini E., Vardy E. R. L. C., Piras F., Roveta F., Prestia F. A., Assogna F., Salani F., Sala G., Lacidogna G., Novack G., Wilcock G., Thonberg H., Kolsch H., Weber H., Boecker H., Etchepareborda I., Piaceri I., Tuomilehto J., Lindstrom J., Laczo J., Johnston J., Deleuze J. -F., Harris J., Schott J. M., Priller J., Bacha J. I., Snowden J., Lisso J., Mihova K. Y., Traykov L., Morelli L., Brusco L. I., Rainer M., Takalo M., Bjerke M., Del Zompo M., Serpente M., Sanchez Abalos M., Rios M., Peltonen M., Herrman M. J., Kohler M., Rojo M., Jones M., Orsini M., Medel N., Olivar N., Fox N. C., Salvadori N., Hooper N. M., Galeano P., Solis P., Bastiani P., Passmore P., Heun R., Antikainen R., Olaso R., Perneczky R., Germani S., Lopez-Garcia S., Love S., Mehrabian S., Bagnoli S., Kochen S., Andreoni S., Teipel S., Todd S., Pickering-Brown S., Natunen T., Tegos T., Laatikainen T., Strandberg T., Polvikoski T. M., Matoska V., Ciullo V., Cores V., Solfrizzi V., Lisetti V., Sevillano Z., Aguilera N., Alarcon E., Boada M., Buendia M., Canabate P., Carracedo A., Diego S., Gailhajenet A., Guitart M., Ibarria M., Lafuente A., Maronas O., Martin E., Martinez M. T., Marquie M., Mauleon A., Moreno M., Orellana A., Pancho A., Peleja E., Preckler S., Real L. M., Ruiz A., Saez M. E., Serrano-Rios M., Tarraga L., Vargas L., Adarmes-Gomez A. D., Alonso M. D., Alvarez V., Amer-Ferrer G., Antequera M., Bernal M., Bullido M. J., Burguera J. A., Carrillo F., Carrion-Claro M., Casajeros M. J., Clarimon J., Cruz-Gamero J. M., de Pancorbo M. M., Escuela R., Garrote-Espina L., Garcia-Alberca J. M., Garcia Madrona S., Garcia-Ribas G., Gomez-Garre P., Hevilla S., Jesus S., Labrador Espinosa M. A., Legaz A., Lleo A., Lopez de Munain A., Macias-Garcia D., Manzanares S., Marin M., Marin-Munoz J., Marin T., Martinez B., Martinez V., Martinez-Lage Alvarez P., Medina M., Mendioroz Iriarte M., Mir P., Molinuevo J. L., Pastor P., Perez Tur J., Perinan-Tocino T., Pineda-Sanchez R., Pinol-Ripoll G., Real de Asua D., Rodrigo S., Sanchez del Valle Diaz R., Sanchez-Juan P., Sastre I., Vicente M. P., Vigo-Ortega R., Vivancos L., Macleod C., McCracken C., Brayne C., Bresner C., Grozeva D., Bellou E., Sommerville E. W., Matthews F., Leonenko G., Menzies G., Windle G., Harwood J., Phillips J., Bennett K., Luckuck L., Clare L., Woods R., Saad S., Burholt V., Kehoe P. G., Scheltens P., Holstege H., Amouyel P., Schellenberg G. D., Williams J., Seshadri S., van Duijn C. M., Mather K. A., Sanchez-Valle R., Blennow K., Huisman M., Andreassen O. A., Posthuma D., van der Flier W. M., Ramirez A., Lambert J. -C., van der Lee S. J., de Rojas I., de Rojas, I, Moreno-Grau, S, Tesi, N, Grenier-Boley, B, Andrade, V, Jansen, I, Pedersen, N, Stringa, N, Zettergren, A, Hernandez, I, Montrreal, L, Antunez, C, Antonell, A, Tankard, R, Bis, J, Sims, R, Bellenguez, C, Quintela, I, Gonzalez-Perez, A, Calero, M, Franco-Macias, E, Macias, J, Blesa, R, Cervera-Carles, L, Menendez-Gonzalez, M, Frank-Garcia, A, Royo, J, Moreno, F, Huerto Vilas, R, Baquero, M, Diez-Fairen, M, Lage, C, Garcia-Madrona, S, Garcia-Gonzalez, P, Alarcon-Martin, E, Valero, S, Sotolongo-Grau, O, Ullgren, A, Naj, A, Lemstra, A, Benaque, A, Perez-Cordon, A, Benussi, A, Rabano, A, Padovani, A, Squassina, A, de Mendonca, A, Arias Pastor, A, Kok, A, Meggy, A, Pastor, A, Espinosa, A, Corma-Gomez, A, Martin Montes, A, Sanabria, A, Destefano, A, Schneider, A, Haapasalo, A, Kinhult Stahlbom, A, Tybjaerg-Hansen, A, Hartmann, A, Spottke, A, Corbaton-Anchuelo, A, Rongve, A, Borroni, B, Arosio, B, Nacmias, B, Nordestgaard, B, Kunkle, B, Charbonnier, C, Abdelnour, C, Masullo, C, Martinez Rodriguez, C, Munoz-Fernandez, C, Dufouil, C, Graff, C, Ferreira, C, Chillotti, C, Reynolds, C, Fenoglio, C, Van Broeckhoven, C, Clark, C, Pisanu, C, Satizabal, C, Holmes, C, Buiza-Rueda, D, Aarsland, D, Rujescu, D, Alcolea, D, Galimberti, D, Wallon, D, Seripa, D, Grunblatt, E, Dardiotis, E, Duzel, E, Scarpini, E, Conti, E, Rubino, E, Gelpi, E, Rodriguez-Rodriguez, E, Duron, E, Boerwinkle, E, Ferri, E, Tagliavini, F, Kucukali, F, Pasquier, F, Sanchez-Garcia, F, Mangialasche, F, Jessen, F, Nicolas, G, Selbaek, G, Ortega, G, Chene, G, Hadjigeorgiou, G, Rossi, G, Spalletta, G, Giaccone, G, Grande, G, Binetti, G, Papenberg, G, Hampel, H, Bailly, H, Zetterberg, H, Soininen, H, Karlsson, I, Alvarez, I, Appollonio, I, Giegling, I, Skoog, I, Saltvedt, I, Rainero, I, Rosas Allende, I, Hort, J, Diehl-Schmid, J, Van Dongen, J, Vidal, J, Lehtisalo, J, Wiltfang, J, Thomassen, J, Kornhuber, J, Haines, J, Vogelgsang, J, Pineda, J, Fortea, J, Popp, J, Deckert, J, Buerger, K, Morgan, K, Fliessbach, K, Sleegers, K, Molina-Porcel, L, Kilander, L, Weinhold, L, Farrer, L, Wang, L, Kleineidam, L, Farotti, L, Parnetti, L, Tremolizzo, L, Hausner, L, Benussi, L, Froelich, L, Ikram, M, Deniz-Naranjo, M, Tsolaki, M, Rosende-Roca, M, Lowenmark, M, Hulsman, M, Spallazzi, M, Pericak-Vance, M, Esiri, M, Bernal Sanchez-Arjona, M, Dalmasso, M, Martinez-Larrad, M, Arcaro, M, Nothen, M, Fernandez-Fuertes, M, Dichgans, M, Ingelsson, M, Herrmann, M, Scherer, M, Vyhnalek, M, Kosmidis, M, Yannakoulia, M, Schmid, M, Ewers, M, Heneka, M, Wagner, M, Scamosci, M, Kivipelto, M, Hiltunen, M, Zulaica, M, Alegret, M, Fornage, M, Roberto, N, van Schoor, N, Seidu, N, Banaj, N, Armstrong, N, Scarmeas, N, Scherbaum, N, Goldhardt, O, Hanon, O, Peters, O, Skrobot, O, Quenez, O, Lerch, O, Bossu, P, Caffarra, P, Dionigi Rossi, P, Sakka, P, Mecocci, P, Hoffmann, P, Holmans, P, Fischer, P, Riederer, P, Yang, Q, Marshall, R, Kalaria, R, Mayeux, R, Vandenberghe, R, Cecchetti, R, Ghidoni, R, Frikke-Schmidt, R, Sorbi, S, Hagg, S, Engelborghs, S, Helisalmi, S, Botne Sando, S, Kern, S, Archetti, S, Boschi, S, Fostinelli, S, Gil, S, Mendoza, S, Mead, S, Ciccone, S, Djurovic, S, Heilmann-Heimbach, S, Riedel-Heller, S, Kuulasmaa, T, del Ser, T, Lebouvier, T, Polak, T, Ngandu, T, Grimmer, T, Bessi, V, Escott-Price, V, Giedraitis, V, Deramecourt, V, Maier, W, Jian, X, Pijnenburg, Y, Smith, A, Saenz, A, Bizzarro, A, Lauria, A, Vacca, A, Solomon, A, Anastasiou, A, Richardson, A, Boland, A, Koivisto, A, Daniele, A, Greco, A, Marianthi, A, Mcguinness, B, Fin, B, Ferrari, C, Custodero, C, Ferrarese, C, Ingino, C, Mangone, C, Reyes Toso, C, Martinez, C, Cuesta, C, Muchnik, C, Joachim, C, Ortiz, C, Besse, C, Johansson, C, Zoia, C, Laske, C, Anastasiou, C, Palacio, D, Politis, D, Janowitz, D, Craig, D, Mann, D, Neary, D, Jurgen, D, Daian, D, Belezhanska, D, Kohler, E, Castano, E, Koutsouraki, E, Chipi, E, De Roeck, E, Costantini, E, Vardy, E, Piras, F, Roveta, F, Prestia, F, Assogna, F, Salani, F, Sala, G, Lacidogna, G, Novack, G, Wilcock, G, Thonberg, H, Kolsch, H, Weber, H, Boecker, H, Etchepareborda, I, Piaceri, I, Tuomilehto, J, Lindstrom, J, Laczo, J, Johnston, J, Deleuze, J, Harris, J, Schott, J, Priller, J, Bacha, J, Snowden, J, Lisso, J, Mihova, K, Traykov, L, Morelli, L, Brusco, L, Rainer, M, Takalo, M, Bjerke, M, Del Zompo, M, Serpente, M, Sanchez Abalos, M, Rios, M, Peltonen, M, Herrman, M, Kohler, M, Rojo, M, Jones, M, Orsini, M, Medel, N, Olivar, N, Fox, N, Salvadori, N, Hooper, N, Galeano, P, Solis, P, Bastiani, P, Passmore, P, Heun, R, Antikainen, R, Olaso, R, Perneczky, R, Germani, S, Lopez-Garcia, S, Love, S, Mehrabian, S, Bagnoli, S, Kochen, S, Andreoni, S, Teipel, S, Todd, S, Pickering-Brown, S, Natunen, T, Tegos, T, Laatikainen, T, Strandberg, T, Polvikoski, T, Matoska, V, Ciullo, V, Cores, V, Solfrizzi, V, Lisetti, V, Sevillano, Z, Aguilera, N, Alarcon, E, Boada, M, Buendia, M, Canabate, P, Carracedo, A, Diego, S, Gailhajenet, A, Guitart, M, Ibarria, M, Lafuente, A, Maronas, O, Martin, E, Martinez, M, Marquie, M, Mauleon, A, Moreno, M, Orellana, A, Pancho, A, Peleja, E, Preckler, S, Real, L, Ruiz, A, Saez, M, Serrano-Rios, M, Tarraga, L, Vargas, L, Adarmes-Gomez, A, Alonso, M, Alvarez, V, Amer-Ferrer, G, Antequera, M, Bernal, M, Bullido, M, Burguera, J, Carrillo, F, Carrion-Claro, M, Casajeros, M, Clarimon, J, Cruz-Gamero, J, de Pancorbo, M, Escuela, R, Garrote-Espina, L, Garcia-Alberca, J, Garcia Madrona, S, Garcia-Ribas, G, Gomez-Garre, P, Hevilla, S, Jesus, S, Labrador Espinosa, M, Legaz, A, Lleo, A, Lopez de Munain, A, Macias-Garcia, D, Manzanares, S, Marin, M, Marin-Munoz, J, Marin, T, Martinez, B, Martinez, V, Martinez-Lage Alvarez, P, Medina, M, Mendioroz Iriarte, M, Mir, P, Molinuevo, J, Pastor, P, Perez Tur, J, Perinan-Tocino, T, Pineda-Sanchez, R, Pinol-Ripoll, G, Real de Asua, D, Rodrigo, S, Sanchez del Valle Diaz, R, Sanchez-Juan, P, Sastre, I, Vicente, M, Vigo-Ortega, R, Vivancos, L, Macleod, C, Mccracken, C, Brayne, C, Bresner, C, Grozeva, D, Bellou, E, Sommerville, E, Matthews, F, Leonenko, G, Menzies, G, Windle, G, Harwood, J, Phillips, J, Bennett, K, Luckuck, L, Clare, L, Woods, R, Saad, S, Burholt, V, Kehoe, P, Scheltens, P, Holstege, H, Amouyel, P, Schellenberg, G, Williams, J, Seshadri, S, van Duijn, C, Mather, K, Sanchez-Valle, R, Blennow, K, Huisman, M, Andreassen, O, Posthuma, D, van der Flier, W, Ramirez, A, Lambert, J, van der Lee, S, de Rojas I., Moreno-Grau S., Tesi N., Grenier-Boley B., Andrade V., Jansen I. E., Pedersen N. L., Stringa N., Zettergren A., Hernandez I., Montrreal L., Antunez C., Antonell A., Tankard R. M., Bis J. C., Sims R., Bellenguez C., Quintela I., Gonzalez-Perez A., Calero M., Franco-Macias E., Macias J., Blesa R., Cervera-Carles L., Menendez-Gonzalez M., Frank-Garcia A., Royo J. L., Moreno F., Huerto Vilas R., Baquero M., Diez-Fairen M., Lage C., Garcia-Madrona S., Garcia-Gonzalez P., Alarcon-Martin E., Valero S., Sotolongo-Grau O., Ullgren A., Naj A. C., Lemstra A. W., Benaque A., Perez-Cordon A., Benussi A., Rabano A., Padovani A., Squassina A., de Mendonca A., Arias Pastor A., Kok A. A. L., Meggy A., Pastor A. B., Espinosa A., Corma-Gomez A., Martin Montes A., Sanabria A., DeStefano A. L., Schneider A., Haapasalo A., Kinhult Stahlbom A., Tybjaerg-Hansen A., Hartmann A. M., Spottke A., Corbaton-Anchuelo A., Rongve A., Borroni B., Arosio B., Nacmias B., Nordestgaard B. G., Kunkle B. W., Charbonnier C., Abdelnour C., Masullo C., Martinez Rodriguez C., Munoz-Fernandez C., Dufouil C., Graff C., Ferreira C. B., Chillotti C., Reynolds C. A., Fenoglio C., Van Broeckhoven C., Clark C., Pisanu C., Satizabal C. L., Holmes C., Buiza-Rueda D., Aarsland D., Rujescu D., Alcolea D., Galimberti D., Wallon D., Seripa D., Grunblatt E., Dardiotis E., Duzel E., Scarpini E., Conti E., Rubino E., Gelpi E., Rodriguez-Rodriguez E., Duron E., Boerwinkle E., Ferri E., Tagliavini F., Kucukali F., Pasquier F., Sanchez-Garcia F., Mangialasche F., Jessen F., Nicolas G., Selbaek G., Ortega G., Chene G., Hadjigeorgiou G., Rossi G., Spalletta G., Giaccone G., Grande G., Binetti G., Papenberg G., Hampel H., Bailly H., Zetterberg H., Soininen H., Karlsson I. K., Alvarez I., Appollonio I., Giegling I., Skoog I., Saltvedt I., Rainero I., Rosas Allende I., Hort J., Diehl-Schmid J., Van Dongen J., Vidal J. -S., Lehtisalo J., Wiltfang J., Thomassen J. Q., Kornhuber J., Haines J. L., Vogelgsang J., Pineda J. A., Fortea J., Popp J., Deckert J., Buerger K., Morgan K., Fliessbach K., Sleegers K., Molina-Porcel L., Kilander L., Weinhold L., Farrer L. A., Wang L. -S., Kleineidam L., Farotti L., Parnetti L., Tremolizzo L., Hausner L., Benussi L., Froelich L., Ikram M. A., Deniz-Naranjo M. C., Tsolaki M., Rosende-Roca M., Lowenmark M., Hulsman M., Spallazzi M., Pericak-Vance M. A., Esiri M., Bernal Sanchez-Arjona M., Dalmasso M. C., Martinez-Larrad M. T., Arcaro M., Nothen M. M., Fernandez-Fuertes M., Dichgans M., Ingelsson M., Herrmann M. J., Scherer M., Vyhnalek M., Kosmidis M. H., Yannakoulia M., Schmid M., Ewers M., Heneka M. T., Wagner M., Scamosci M., Kivipelto M., Hiltunen M., Zulaica M., Alegret M., Fornage M., Roberto N., van Schoor N. M., Seidu N. M., Banaj N., Armstrong N. J., Scarmeas N., Scherbaum N., Goldhardt O., Hanon O., Peters O., Skrobot O. A., Quenez O., Lerch O., Bossu P., Caffarra P., Dionigi Rossi P., Sakka P., Mecocci P., Hoffmann P., Holmans P. A., Fischer P., Riederer P., Yang Q., Marshall R., Kalaria R. N., Mayeux R., Vandenberghe R., Cecchetti R., Ghidoni R., Frikke-Schmidt R., Sorbi S., Hagg S., Engelborghs S., Helisalmi S., Botne Sando S., Kern S., Archetti S., Boschi S., Fostinelli S., Gil S., Mendoza S., Mead S., Ciccone S., Djurovic S., Heilmann-Heimbach S., Riedel-Heller S., Kuulasmaa T., del Ser T., Lebouvier T., Polak T., Ngandu T., Grimmer T., Bessi V., Escott-Price V., Giedraitis V., Deramecourt V., Maier W., Jian X., Pijnenburg Y. A. L., Smith A. D., Saenz A., Bizzarro A., Lauria A., Vacca A., Solomon A., Anastasiou A., Richardson A., Boland A., Koivisto A., Daniele A., Greco A., Marianthi A., McGuinness B., Fin B., Ferrari C., Custodero C., Ferrarese C., Ingino C., Mangone C., Reyes Toso C., Martinez C., Cuesta C., Muchnik C., Joachim C., Ortiz C., Besse C., Johansson C., Zoia C. P., Laske C., Anastasiou C., Palacio D. L., Politis D. G., Janowitz D., Craig D., Mann D. M., Neary D., Jurgen D., Daian D., Belezhanska D., Kohler E., Castano E. M., Koutsouraki E., Chipi E., De Roeck E., Costantini E., Vardy E. R. L. C., Piras F., Roveta F., Prestia F. A., Assogna F., Salani F., Sala G., Lacidogna G., Novack G., Wilcock G., Thonberg H., Kolsch H., Weber H., Boecker H., Etchepareborda I., Piaceri I., Tuomilehto J., Lindstrom J., Laczo J., Johnston J., Deleuze J. -F., Harris J., Schott J. M., Priller J., Bacha J. I., Snowden J., Lisso J., Mihova K. Y., Traykov L., Morelli L., Brusco L. I., Rainer M., Takalo M., Bjerke M., Del Zompo M., Serpente M., Sanchez Abalos M., Rios M., Peltonen M., Herrman M. J., Kohler M., Rojo M., Jones M., Orsini M., Medel N., Olivar N., Fox N. C., Salvadori N., Hooper N. M., Galeano P., Solis P., Bastiani P., Passmore P., Heun R., Antikainen R., Olaso R., Perneczky R., Germani S., Lopez-Garcia S., Love S., Mehrabian S., Bagnoli S., Kochen S., Andreoni S., Teipel S., Todd S., Pickering-Brown S., Natunen T., Tegos T., Laatikainen T., Strandberg T., Polvikoski T. M., Matoska V., Ciullo V., Cores V., Solfrizzi V., Lisetti V., Sevillano Z., Aguilera N., Alarcon E., Boada M., Buendia M., Canabate P., Carracedo A., Diego S., Gailhajenet A., Guitart M., Ibarria M., Lafuente A., Maronas O., Martin E., Martinez M. T., Marquie M., Mauleon A., Moreno M., Orellana A., Pancho A., Peleja E., Preckler S., Real L. M., Ruiz A., Saez M. E., Serrano-Rios M., Tarraga L., Vargas L., Adarmes-Gomez A. D., Alonso M. D., Alvarez V., Amer-Ferrer G., Antequera M., Bernal M., Bullido M. J., Burguera J. A., Carrillo F., Carrion-Claro M., Casajeros M. J., Clarimon J., Cruz-Gamero J. M., de Pancorbo M. M., Escuela R., Garrote-Espina L., Garcia-Alberca J. M., Garcia Madrona S., Garcia-Ribas G., Gomez-Garre P., Hevilla S., Jesus S., Labrador Espinosa M. A., Legaz A., Lleo A., Lopez de Munain A., Macias-Garcia D., Manzanares S., Marin M., Marin-Munoz J., Marin T., Martinez B., Martinez V., Martinez-Lage Alvarez P., Medina M., Mendioroz Iriarte M., Mir P., Molinuevo J. L., Pastor P., Perez Tur J., Perinan-Tocino T., Pineda-Sanchez R., Pinol-Ripoll G., Real de Asua D., Rodrigo S., Sanchez del Valle Diaz R., Sanchez-Juan P., Sastre I., Vicente M. P., Vigo-Ortega R., Vivancos L., Macleod C., McCracken C., Brayne C., Bresner C., Grozeva D., Bellou E., Sommerville E. W., Matthews F., Leonenko G., Menzies G., Windle G., Harwood J., Phillips J., Bennett K., Luckuck L., Clare L., Woods R., Saad S., Burholt V., Kehoe P. G., Scheltens P., Holstege H., Amouyel P., Schellenberg G. D., Williams J., Seshadri S., van Duijn C. M., Mather K. A., Sanchez-Valle R., Blennow K., Huisman M., Andreassen O. A., Posthuma D., van der Flier W. M., Ramirez A., Lambert J. -C., and van der Lee S. J.
- Abstract
The original version of this Article omitted from the author list the 212th author Patrizia Mecocci, who is from the Institute of Gerontology and Geriatrics, Department of Medicine, University of Perugia, Perugia, Italy. Consequently, the “Sample Contribution” section of Author Contributions was updated to add “P.M” between “P.D.” and “R.C.”. Additionally, the original version of this Article contained the incorrect affiliation for author Patrick Gavin Kehoe, which incorrectly read “German Center for Neurodegenerative Diseases (DZNE), Berlin, Germany”. The correct version replaces this affiliation with “Bristol Medical School (THS), University of Bristol, Southmead Hospital, Bristol, UK”. This has been corrected in both the PDF and HTML versions of the Article.
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- 2023
8. OA15.04 Comparison of Digital Vs Manual PD-L1 Tumour Cell Scoring on SP263-Stained Whole Imaging Slides from IMpower110
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Herbst, R.S., primary, Ruderman, D., additional, Conway, J., additional, Prizant, H., additional, Hennek, S., additional, Shamshoian, J., additional, Abel, J., additional, Montalto, M., additional, Beck, A., additional, Wapinski, I., additional, Molinero, L., additional, Amin, R., additional, Hoang, T., additional, Ballinger, M., additional, de Marinis, F., additional, Giaccone, G., additional, Jassem, J., additional, Giltnane, J., additional, Srivastava, M.K., additional, and Spigel, D.R., additional
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- 2023
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9. Randomized open-label controlled study of cancer vaccine OSE2101 versus chemotherapy in HLA-A2-positive patients with advanced non-small-cell lung cancer with resistance to immunotherapy: ATALANTE-1
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Besse, B., primary, Felip, E., additional, Garcia Campelo, R., additional, Cobo, M., additional, Mascaux, C., additional, Madroszyk, A., additional, Cappuzzo, F., additional, Hilgers, W., additional, Romano, G., additional, Denis, F., additional, Viteri, S., additional, Debieuvre, D., additional, Galetta, D., additional, Baldini, E., additional, Razaq, M., additional, Robinet, G., additional, Maio, M., additional, Delmonte, A., additional, Roch, B., additional, Masson, P., additional, Schuette, W., additional, Zer, A., additional, Remon, J., additional, Costantini, D., additional, Vasseur, B., additional, Dziadziuszko, R., additional, Giaccone, G., additional, Zemanová, M., additional, Besse, B., additional, Bonnet, C., additional, Cadranel, J., additional, Chouaid, C., additional, Cortot, A., additional, Delclaux, B., additional, Duchemann, B., additional, El Kouri, C., additional, Ferrand, F.R., additional, Ginoux, M., additional, Mazieres, J., additional, Molinier, O., additional, Moro-Sibilot, D., additional, Pichon, E., additional, Zalcman, G., additional, Schmidtke-Schrezenmeier, G., additional, Urban, L., additional, Gottfried, M., additional, Nechushtan, H., additional, Peled, N., additional, Wollner, M., additional, Bonanno, L., additional, Bonetti, A., additional, Minotti, V., additional, Rea, A., additional, Tassinari, D., additional, Tonini, G., additional, Karaszewska, B., additional, Szczęsna, A., additional, De Castro, J., additional, Garcia Campelo, M.R., additional, Hernández, A., additional, Moran, T., additional, Provencio, M., additional, Dasgupta, A., additional, Gabrail, N., additional, Harshad, A., additional, Liu, S., additional, Oubre, D., additional, Panikkar, R., additional, and Sanborn, R., additional
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- 2023
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10. Clinical evaluation of dacomitinib for the treatment of metastatic non-small cell lung cancer (NSCLC): current perspectives
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Lavacchi D, Mazzoni F, and Giaccone G
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dacomitinib ,non-small cell lung cancer (NSCLC) ,epidermal growth factor receptor (EGFR) ,pan-HER inhibitor ,second-generation TKI. ,Therapeutics. Pharmacology ,RM1-950 - Abstract
Daniele Lavacchi1, Francesca Mazzoni1, Giuseppe Giaccone1,2 1Department of Oncology, Careggi Hospital and University of Florence, Florence, Italy; 2Lombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USACorrespondence: Giuseppe GiacconeLombardi Comprehensive Cancer Center, Georgetown University, Washington, DC, USATel +1 202 687 7072Email gg496@georgetown.eduAbstract: Systemic treatment of advanced non-small cell lung cancer (NSCLC) has undergone remarkable changes in the last decade, with the introduction of targeted therapies and immunotherapy. The identification of activating mutations in the epidermal growth factor receptor (EGFR) gene (deletions in exon 19 [Del19] and point mutation L858R in exon 21) has been the first important step toward molecularly guided precision therapy in lung cancer. Several randomized trials comparing EGFR tyrosine kinase inhibitors (TKIs) (gefitinib, erlotinib, and afatinib) to standard chemotherapy in first-line treatment of advanced EGFR-mutant NSCLC showed significant improvement in progression-free survival (PFS) and in response rate, with lower rates of adverse events (AEs) and better symptom control. However, none of these trials showed significant improvement in overall survival (OS). Despite impressive responses with EGFR-TKI, disease invariably progresses after 9 to 13 months, due to acquired resistance. Dacomitinib is a potent, irreversible, highly selective, second-generation EGFR-TKI, which inhibits the signaling from both heterodimers and homodimers of all the members of the human epidermal growth factor receptor (HER) family. Here, we review the clinical development of dacomitinib from phase I to phase III, with particular attention to its toxicity and on its activity on T790M mutation. Then, we critically examine the results of ARCHER 1050, a study that was crucial for Food and Drug Administration (FDA) approval. ARCHER 1050 was the first randomized phase III study comparing dacomitinib with gefitinib, in first-line treatment of patients with advanced EGFR-mutated NSCLC. Dacomitinib was superior to gefitinib in terms of primary end-point (14.7 vs 9.2 months) and OS (34.1 vs 26.8 months). The incidence of diarrhea, skin rash, mucositis and, consequently, dose reductions was higher with dacomitinib, while hepatic toxicity was higher with gefitinib. Dacomitinib constitutes one of the standard first-line options in patients with advanced EGFR-mutated NSCLC.Keywords: dacomitinib, non-small cell lung cancer, NSCLC, epidermal growth factor receptor, EGFR, pan-HER inhibitor, second-generation TKI
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- 2019
11. Cerebellar and subcortical atrophy contribute to psychiatric symptoms in frontotemporal dementia
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Bussy, A., Levy, J., Best, T., Patel, R., Cupo, L., Van Langenhove, T., Nielsen, J., Pijnenburg, Y., Waldö, M., Remes, A., Schroeter, M., Santana, I., Pasquier, F., Otto, M., Danek, A., Levin, J., Le Ber, I., Vandenberghe, R., Synofzik, M., Moreno, F., de Mendonça, A., Sanchez‐Valle, R., Laforce, R., Langheinrich, T., Gerhard, A., Graff, C., Butler, C., Sorbi, S., Jiskoot, L., Seelaar, H., van Swieten, J., Finger, E., Tartaglia, M., Masellis, M., Tiraboschi, P., Galimberti, D., Borroni, B., Rowe, J., Bocchetta, M., Rohrer, J., Devenyi, G., Chakravarty, M., Ducharme, S., Esteve, A., Nelson, A., Bouzigues, A., Heller, C., Greaves, C., Cash, D., Thomas, D., Todd, E., Benotmane, H., Zetterberg, H., Swift, I., Nicholas, J., Samra, K., Russell, L., Shafei, R., Convery, R., Timberlake, C., Cope, T., Rittman, T., Benussi, A., Premi, E., Gasparotti, R., Archetti, S., Gazzina, S., Cantoni, V., Arighi, A., Fenoglio, C., Scarpini, E., Fumagalli, G., Borracci, V., Rossi, G., Giaccone, G., Di Fede, G., Caroppo, P., Prioni, S., Redaelli, V., Tang‐Wai, D., Rogaeva, E., Castelo‐Branco, M., Freedman, M., Keren, R., Black, S., Mitchell, S., Shoesmith, C., Bartha, R., Rademakers, R., Poos, J., Papma, J., Giannini, L., van Minkelen, R., Nacmias, B., Ferrari, C., Polito, C., Lombardi, G., Bessi, V., Veldsman, M., Andersson, C., Thonberg, H., Öijerstedt, L., Jelic, V., Thompson, P., Lladó, A., Antonell, A., Olives, J., Balasa, M., Bargalló, N., Borrego‐Ecija, S., Verdelho, A., Maruta, C., Ferreira, C., Miltenberger, G., do Couto, F., Gabilondo, A., Gorostidi, A., Villanua, J., Cañada, M., Tainta, M., Zulaica, M., Barandiaran, M., Alves, P., Bender, B., Wilke, C., Graf, L., Vogels, A., Vandenbulcke, M., Van Damme, P., Bruffaerts, R., Poesen, K., Rosa‐Neto, P., Gauthier, S., Camuzat, A., Brice, A., Bertrand, A., Funkiewiez, A., Rinaldi, D., Saracino, D., Colliot, O., Sayah, S., Prix, C., Wlasich, E., Wagemann, O., Loosli, S., Schönecker, S., Hoegen, T., Lombardi, J., Anderl‐Straub, S., Rollin, A., Kuchcinski, G., Bertoux, M., Lebouvier, T., Deramecourt, V., Santiago, B., Duro, D., Leitão, M., Almeida, M., Tábuas‐Pereira, M., Afonso, S., Engel, A., Polyakova, M., Erasmus MC other, Neurology, Radiology & Nuclear Medicine, Clinical Genetics, GENetic Frontotemporal dementia Initiative (GENFI), Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, Verdelho, Ana, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Engel, Annerose, Polyakova, Maryna, Esteve, Aitana Sogorb, Nelson, Annabel, Bouzigues, Arabella, Heller, Carolin, Greaves, Caroline V, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Zetterberg, Henrik, Swift, Imogen J, Nicholas, Jennifer, Samra, Kiran, Russell, Lucy L, Bocchetta, Martina, Shafei, Rachelle, Convery, Rhian S, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Scarpini, Elio, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Bussy, Aurélie [0000-0001-6695-9941], Nielsen, Jørgen E [0000-0003-0453-5582], Borroni, Barbara [0000-0001-9340-9814], Bocchetta, Martina [0000-0003-1814-5024], Devenyi, Gabriel A [0000-0002-7766-1187], Apollo - University of Cambridge Repository, and Amsterdam Neuroscience - Neurodegeneration
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C9orf72 Protein ,Radiological and Ultrasound Technology ,Medizin ,frontotemporal dementia ,Neurology ,Frontotemporal Dementia ,Cerebellum ,Humans ,magnetic resonance imaging ,genetics ,neuropsychiatry ,Radiology, Nuclear Medicine and imaging ,Human medicine ,ddc:610 ,Neurology (clinical) ,Atrophy ,Anatomy ,genetics [Frontotemporal Dementia] ,genetics [C9orf72 Protein] - Abstract
Funder: Alzheimer Society of Canada; Id: http://dx.doi.org/10.13039/501100000143, Funder: Weston Brain Institute; Id: http://dx.doi.org/10.13039/100012479, Funder: Fonds de Recherche du Québec ‐ Santé, Funder: Canadian Institutes of Health Research; Id: http://dx.doi.org/10.13039/501100000024, Funder: NIHR Rare Diseases Translational Research Collaboration, Funder: Deutsche Forschungsgemeinschaft; Id: http://dx.doi.org/10.13039/501100001659, Recent studies have reported early cerebellar and subcortical impact in the disease progression of genetic frontotemporal dementia (FTD) due to microtubule-associated protein tau (MAPT), progranulin (GRN) and chromosome 9 open reading frame 72 (C9orf72). However, the cerebello-subcortical circuitry in FTD has been understudied despite its essential role in cognition and behaviors related to FTD symptomatology. The present study aims to investigate the association between cerebellar and subcortical atrophy, and neuropsychiatric symptoms across genetic mutations. Our study included 983 participants from the Genetic Frontotemporal dementia Initiative including mutation carriers and noncarrier first-degree relatives of known symptomatic carriers. Voxel-wise analysis of the thalamus, striatum, globus pallidus, amygdala, and the cerebellum was performed, and partial least squares analyses (PLS) were used to link morphometry and behavior. In presymptomatic C9orf72 expansion carriers, thalamic atrophy was found compared to noncarriers, suggesting the importance of this structure in FTD prodromes. PLS analyses demonstrated that the cerebello-subcortical circuitry is related to neuropsychiatric symptoms, with significant overlap in brain/behavior patterns, but also specificity for each genetic mutation group. The largest differences were in the cerebellar atrophy (larger extent in C9orf72 expansion group) and more prominent amygdalar volume reduction in the MAPT group. Brain scores in the C9orf72 expansion carriers and MAPT carriers demonstrated covariation patterns concordant with atrophy patterns detectable up to 20 years before expected symptom onset. Overall, these results demonstrated the important role of the subcortical structures in genetic FTD symptom expression, particularly the cerebellum in C9orf72 and the amygdala in MAPT carriers.
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- 2023
12. Design and conduct of early clinical studies of immunotherapy agent combinations: recommendations from the task force on Methodology for the Development of Innovative Cancer Therapies
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Atkins, M., Banerji, U., Bates, S., Bogaerts, J., Calvo, E., De Braud, F., Douillard, J.Y., Giaccone, G., Keegan, P., Kumar, R., LoRusso, P., Marabelle, A., Perrone, A., Pignatti, F., Plummer, R., Seymour, L., Schwartz, G., Shalabi, A., Shapiro, G., Siu, L.L., Smoragiewicz, M., Tabernero, J., Therasse, P., and Yang, A.
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- 2018
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13. First-in-human phase 1 study of margetuximab (MGAH22), an Fc-modified chimeric monoclonal antibody, in patients with HER2-positive advanced solid tumors
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Bang, Y.J., Giaccone, G., Im, S.A., Oh, D.Y., Bauer, T.M., Nordstrom, J.L., Li, H., Chichili, G.R., Moore, P.A., Hong, S., Stewart, S.J., Baughman, J.E., Lechleider, R.J., and Burris, H.A.
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- 2017
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14. Motor symptoms in genetic frontotemporal dementia: developing a new module for clinical rating scales
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Samra, K, MacDougall, AM, Peakman, G, Bouzigues, A, Bocchetta, M, Cash, DM, Greaves, CV, Convery, RS, van Swieten, JC, Jiskoot, L, Seelaar, H, Butler, CR, Fenoglio, C, Rohrer, JD, Gerhard, A, Ducharme, S, Le Ber, I, Tiraboschi, P, Santana, I, Pasquier, F, Levin, J, Shoesmith, C, Otto, M, Russell, LL, Nelson, A, Cash, D, Thomas, DL, Todd, E, Ferrari, C, Benotmane, H, Timberlake, C, Gabilondo, A, Cope, T, Rittman, T, Benussi, A, Premi, E, Gasparotti, R, Thompson, P, Archetti, S, Fumagalli, G, do Couto, FS, Borracci, V, Polito, C, Rossi, G, Giaccone, G, Di Fede, G, Caroppo, P, Ferreira, CB, Prioni, S, Langheinrich, T, Redaelli, V, Lladó, A, Bartha, R, Tang-Wai, D, Rogaeva, E, Castelo-Branco, M, Freedman, M, Keren, R, Black, S, Mitchell, S, Miltenberger, G, Rademakers, R, Poos, J, Papma, JM, Giannini, L, van Minkelen, R, Pijnenburg, Y, Gauthier, S, Nacmias, B, Lombardi, G, Bessi, V, Veldsman, M, Andersson, C, Thonberg, H, Öijerstedt, L, Prix, C, Jelic, V, Antonell, A, Graff, C, Olives, J, Balasa, M, Bargalló, N, Borrego-Ecija, S, Verdelho, A, Kuchcinski, G, Maruta, C, Gorostidi, A, Laforce, R, Villanua, J, Wlasich, E, Cañada, M, Tainta, M, Zulaica, M, Barandiaran, M, Moreno, F, Alves, P, Bender, B, Bertoux, M, Wilke, C, Lebouvier, T, Camuzat, A, Graf, L, Vogels, A, Vandenbulcke, M, Van Damme, P, Bruffaerts, R, Poesen, K, Rosa-Neto, P, Sanchez-Valle, R, Brice, A, Bertrand, A, Funkiewiez, A, Rinaldi, D, Saracino, D, Colliot, O, Sorbi, S, Sayah, S, Wagemann, O, Loosli, S, Schönecker, S, Hoegen, T, Lombardi, J, Anderl-Straub, S, Nicholas, J, Rollin, A, Deramecourt, V, Arighi, A, Santiago, B, Duro, D, Leitão, MJ, Almeida, MR, Tábuas-Pereira, M, Gazzina, S, Afonso, S, Masellis, M, Tartaglia, C, Shafei, R, Rowe, JB, Borroni, B, Finger, E, Synofzik, M, Galimberti, D, Vandenberghe, R, de Mendonça, A, Cantoni, V, Genetic FTD Initiative (GENFI), Samra, Kiran [0000-0002-3105-7099], Apollo - University of Cambridge Repository, Maruta, Carolina, Ferreira, Catarina B, Miltenberger, Gabriel, do Couto, Frederico Simões, Gabilondo, Alazne, Gorostidi, Ana, Villanua, Jorge, Cañada, Marta, Tainta, Mikel, Zulaica, Miren, Barandiaran, Myriam, Alves, Patricia, Bender, Benjamin, Wilke, Carlo, Graf, Lisa, Vogels, Annick, Vandenbulcke, Mathieu, Van Damme, Philip, Bruffaerts, Rose, Poesen, Koen, Rosa-Neto, Pedro, Gauthier, Serge, Camuzat, Agnès, Brice, Alexis, Bertrand, Anne, Funkiewiez, Aurélie, Rinaldi, Daisy, Saracino, Dario, Colliot, Olivier, Sayah, Sabrina, Prix, Catharina, Wlasich, Elisabeth, Wagemann, Olivia, Loosli, Sandra, Schönecker, Sonja, Hoegen, Tobias, Lombardi, Jolina, Anderl-Straub, Sarah, Rollin, Adeline, Kuchcinski, Gregory, Bertoux, Maxime, Lebouvier, Thibaud, Deramecourt, Vincent, Santiago, Beatriz, Duro, Diana, Leitão, Maria João, Almeida, Maria Rosario, Tábuas-Pereira, Miguel, Afonso, Sónia, Nelson, Annabel, Bocchetta, Martina, Cash, David, Thomas, David L, Todd, Emily, Benotmane, Hanya, Nicholas, Jennifer, Samra, Kiran, Shafei, Rachelle, Timberlake, Carolyn, Cope, Thomas, Rittman, Timothy, Benussi, Alberto, Premi, Enrico, Gasparotti, Roberto, Archetti, Silvana, Gazzina, Stefano, Cantoni, Valentina, Arighi, Andrea, Fenoglio, Chiara, Fumagalli, Giorgio, Borracci, Vittoria, Rossi, Giacomina, Giaccone, Giorgio, Di Fede, Giuseppe, Caroppo, Paola, Tiraboschi, Pietro, Prioni, Sara, Redaelli, Veronica, Tang-Wai, David, Rogaeva, Ekaterina, Castelo-Branco, Miguel, Freedman, Morris, Keren, Ron, Black, Sandra, Mitchell, Sara, Shoesmith, Christen, Bartha, Robart, Rademakers, Rosa, Poos, Jackie, Papma, Janne M, Giannini, Lucia, van Minkelen, Rick, Pijnenburg, Yolande, Nacmias, Benedetta, Ferrari, Camilla, Polito, Cristina, Lombardi, Gemma, Bessi, Valentina, Veldsman, Michele, Andersson, Christin, Thonberg, Hakan, Öijerstedt, Linn, Jelic, Vesna, Thompson, Paul, Langheinrich, Tobias, Lladó, Albert, Antonell, Anna, Olives, Jaume, Balasa, Mircea, Bargalló, Nuria, Borrego-Ecija, Sergi, and Verdelho, Ana
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Progranulin ,Clinical Neurology ,C9ORF72 ,tau Proteins ,AMYOTROPHIC-LATERAL-SCLEROSIS ,diagnosis [Frontotemporal Dementia] ,C9orf72 ,Tremor ,Genetics ,Humans ,ddc:610 ,genetics [Frontotemporal Dementia] ,genetics [C9orf72 Protein] ,MUTATION ,Science & Technology ,C9orf72 Protein ,HERITABILITY ,Amyotrophic Lateral Sclerosis ,PROGRESSIVE SUPRANUCLEAR PALSY ,COGNITIVE IMPAIRMENT ,REPEAT EXPANSION ,genetics [tau Proteins] ,Motor ,PATHOLOGICAL FEATURES ,Neurology ,FOS: Biological sciences ,Frontotemporal Dementia ,Mutation ,Human medicine ,Neurosciences & Neurology ,Neurology (clinical) ,Tau ,TAU ,Life Sciences & Biomedicine ,Frontotemporal dementia ,PARKINSONISM - Abstract
Funder: CIBERNED, Funder: Canadian Institutes of Health Research; doi: http://dx.doi.org/10.13039/501100000024, Funder: Lemaire Family Foundation, Funder: Swedish Frontotemporal Dementia Initiative, Funder: Italian Ministry of Health, Funder: Weston Brain Institute; doi: http://dx.doi.org/10.13039/100012479, Funder: Mady Browaaeys Fund, Funder: Miriam Marks Brain Research UK, Funder: Bluefield Project, OBJECTIVE: To investigate the optimal method of adding motor features to a clinical rating scale for frontotemporal dementia (FTD). METHODS: Eight hundred and thirty-two participants from the international multicentre Genetic FTD Initiative (GENFI) study were recruited: 522 mutation carriers (with C9orf72, GRN and MAPT mutations) and 310 mutation-negative controls. A standardised clinical questionnaire was used to assess eight motor symptoms (dysarthria, dysphagia, tremor, slowness, weakness, gait disorder, falls and functional difficulties using hands). Frequency and severity of each motor symptom was assessed, and a principal component analysis (PCA) was performed to identify how the different motor symptoms loaded together. Finally, addition of a motor component to the CDR® plus NACC FTLD was investigated (CDR® plus NACC FTLD-M). RESULTS: 24.3% of mutation carriers had motor symptoms (31.7% C9orf72, 18.8% GRN, 19.3% MAPT) compared to 6.8% of controls. Slowness and gait disorder were the commonest in all genetic groups while tremor and falls were the least frequent. Symptom severity scores were similar to equivalent physical motor examination scores. PCA revealed that all motor symptoms loaded together so a single additional motor component was added to the CDR® plus NACC FTLD to form the CDR® plus NACC FTLD-M. Individual global scores were more severe with the CDR® plus NACC FTLD-M, and no patients with a clinically diagnosed motor disorder (ALS/FTD-ALS or parkinsonism) were classified anymore as asymptomatic (unlike the CDR® plus NACC FTLD alone). CONCLUSIONS: Motor features are present in mutation carriers at all disease stages across all three genetic groups. Inclusion of motor symptoms in a rating scale that can be used in future clinical trials will not only ensure a more accurate severity measure is recorded but that a wider spectrum of FTD phenotypes can be included in the same trial.
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- 2022
15. Avelumab plus axitinib in unresectable or metastatic type B3 thymomas and thymic carcinomas (CAVEATT): a single-arm, multicentre, phase 2 trial
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Conforti, F, Zucali, P, Pala, L, Catania, C, Bagnardi, V, Sala, I, Della Vigna, P, Perrino, M, Zagami, P, Corti, C, Stucchi, S, Barberis, M, Guerini-Rocco, E, Di Venosa, B, De Vincenzo, F, Cordua, N, Santoro, A, Giaccone, G, Martino De Pas, T, Conforti F., Zucali P. A., Pala L., Catania C., Bagnardi V., Sala I., Della Vigna P., Perrino M., Zagami P., Corti C., Stucchi S., Barberis M., Guerini-Rocco E., Di Venosa B., De Vincenzo F., Cordua N., Santoro A., Giaccone G., Martino De Pas T., Conforti, F, Zucali, P, Pala, L, Catania, C, Bagnardi, V, Sala, I, Della Vigna, P, Perrino, M, Zagami, P, Corti, C, Stucchi, S, Barberis, M, Guerini-Rocco, E, Di Venosa, B, De Vincenzo, F, Cordua, N, Santoro, A, Giaccone, G, Martino De Pas, T, Conforti F., Zucali P. A., Pala L., Catania C., Bagnardi V., Sala I., Della Vigna P., Perrino M., Zagami P., Corti C., Stucchi S., Barberis M., Guerini-Rocco E., Di Venosa B., De Vincenzo F., Cordua N., Santoro A., Giaccone G., and Martino De Pas T.
- Abstract
Background: Patients with advanced type B3 thymoma and thymic carcinoma resistant to chemotherapy have few treatment options. We report the efficacy and safety results of the combination of the anti-PD-L1 inhibitor avelumab with the anti-angiogenesis drug axitinib in patients with advanced type B3 thymoma and thymic carcinoma. Methods: CAVEATT was a single-arm, multicentre, phase 2 trial, conducted in two Italian centres (the European Instituteof Oncology and the Humanitas Institute, Milan) in patients with histologically confirmed type B3 thymoma or thymic carcinoma, with advanced stage of disease who had progressed after at least one line of platinum-based chemotherapy. Previous treatment with an anti-angiogenesis drug was allowed but not with immune checkpoint inhibitors. Other inclusion criteria were age 18 years or older, an Eastern Cooperative Oncology Group performance status of 0–2, progressive disease, and presence of measurable disease according to Response Evaluation Criteria In Solid Tumours (RECIST) version 1.1. Patients received avelumab 10 mg/kg intravenously every 2 weeks and axitinib 5 mg orally twice daily until disease progression or unacceptable toxicity. The primary endpoint was the centrally assessed overall response rate according to RECIST version 1.1. Patients who received at least one cycle of treatment and had at least one CT scan after treatment start at scheduled time point by protocol were judged assessable for response and were included in efficacy and safety analyses. This study is registered with EUDRACT, 2017–004048–38; enrolment is completed and follow-up is ongoing. Findings: Between April 22, 2019, and June 30, 2021, 32 patients were enrolled. 27 patients had a thymic carcinoma, three a type B3 thymoma, and two a mixed type B3 thymoma and thymic carcinoma. 29 (91%) of 32 patients had stage IVB disease and 13 (41%) of 32 had been pretreated with an anti-angiogenesis drug. 11 of 32 patients had an overall response; thus the overall
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- 2022
16. In Situ Tissue Labeling of Cerebral Amyloid Using HIV-Related Tat Peptide
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Maderna, E., Colombo, L., Cagnotto, A., Di Fede, G., Indaco, A., Tagliavini, F., Salmona, M., and Giaccone, G.
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- 2018
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17. Randomized phase 2 study of gemcitabine and cisplatin with or without vitamin supplementation in patients with advanced esophagogastric cancer
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van Zweeden, A. A., van Groeningen, C. J., Honeywell, R. J., Giovannetti, E., Ruijter, R., Smorenburg, C. H., Giaccone, G., Verheul, H. M. W., Peters, G. J., and van der Vliet, Hans J.
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- 2018
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18. Effectiveness of Anthracycline Against Experimental Prion Disease in Syrian Hamsters
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Tagliavini, F., McArthur, R. A., Canciani, B., Giaccone, G., Porro, M., Bugiani, M., Bugiani, O., Peri, E., Dall'Ara, P., Rocchi, M., Poli, G., Forloni, G., Bandiera, T., Varasi, M., Suarato, A., Cassutti, P., Cervini, M. A., Lansen, J., Salmona, M., and Post, C.
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- 1997
19. Selumetinib with and without erlotinib in KRAS mutant and KRAS wild-type advanced nonsmall-cell lung cancer
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Carter, C.A., Rajan, A., Keen, C., Szabo, E., Khozin, S., Thomas, A., Brzezniak, C., Guha, U., Doyle, L.A., Steinberg, S.M., Xi, L., Raffeld, M., Tomita, Y., Lee, M.J., Lee, S., Trepel, J.B., Reckamp, K.L., Koehler, S., Gitlitz, B., Salgia, R., Gandara, D., Vokes, E., and Giaccone, G.
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- 2016
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20. Why has active immunotherapy not worked in lung cancer?
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Thomas, A. and Giaccone, G.
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- 2015
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21. 172P Phase I study of JTX-8064, a LILRB2 (ILT4) inhibitor, as monotherapy and combination with pimivalimab (pimi), a PD-1 inhibitor (PD-1i), in patients (pts) with advanced solid tumors
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Papadopoulos, K., primary, Li, T., additional, Lakhani, N., additional, Powderly, J., additional, George, T., additional, Teoh, D.G.K., additional, Kilari, D., additional, Giaccone, G., additional, Sanborn, R.E., additional, Ghamande, S., additional, LoRusso, P., additional, Gibney, G., additional, Ma, V.T-L., additional, Yalamanchili, K., additional, Brown, J., additional, Mota, N., additional, Tasillo Kadra, C., additional, Umiker, B., additional, Xiao, X., additional, and Trehu, E., additional
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- 2022
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22. KEYNOTE-867: Phase 3, Randomized, Placebo-Controlled Study of Stereotactic Body Radiotherapy (SBRT) with or without Pembrolizumab in Patients with Unresected Stage I or II Non–Small-Cell Lung Cancer (NSCLC)
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Jabbour, S.K., primary, Houghton, B., additional, Robinson, A.G., additional, Quantin, X., additional, Wehler, T., additional, Kowalski, D., additional, Ahn, M.J., additional, Erman, M., additional, Giaccone, G., additional, Borghaei, H., additional, McLean, J., additional, Xu, Y., additional, Souza, F., additional, and Pall, G., additional
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- 2022
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23. 492TiP A phase I study of synthetic lethal, IDE397 (MAT2A inhibitor) as a monotherapy and in combination with chemotherapy in advanced solid tumors harboring MTAP deletion
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Johnson, M.L., primary, Rodon, J., additional, Aljumaily, R., additional, Villalona-Calero, M., additional, Borazanci, E., additional, Pishvaian, M., additional, Turk, A., additional, Carvajal, R.D., additional, Mantia, C., additional, Giaccone, G., additional, Mounir, Z., additional, Patel, A., additional, Maurer, M., additional, Neilan, C., additional, Rajendran, D., additional, Ganesan, U., additional, Hinkle, J., additional, and Tolcher, A.W., additional
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- 2022
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24. 1019P Pattern of clinical activity of anticancer vaccine OSE2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO) in phase III Atalante-1 randomized trial
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Garcia Campelo, M.R., primary, Felip, E., additional, Besse, B., additional, Cobo Dols, M., additional, Quoix, E., additional, Madroszyk Flandin, A-C., additional, Cappuzzo, F., additional, Denis, F., additional, Hilgers, W., additional, Romano, G., additional, Debieuvre, D., additional, Galetta, D., additional, Baldini, E., additional, Viteri Ramirez, S., additional, Duc Phan, M., additional, Schuette, W., additional, Zer, A., additional, Vasseur, B., additional, Dziadziuszko, R., additional, and Giaccone, G., additional
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- 2022
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25. 1024P Net treatment benefit of OSE2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO) in phase III Atalante-1 randomized trial
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Buyse, M.E., primary, Montestruc, F., additional, Chiem, J-C., additional, Deltuvaite-Thomas, V., additional, Salvaggio, S., additional, Garcia Campelo, M.R., additional, Cobo Dols, M., additional, Quoix, E., additional, Madroszyk Flandin, A-C., additional, Cappuzzo, F., additional, Romano, G., additional, Viteri Ramirez, S., additional, Schuette, W., additional, Zer, A., additional, Comis, S., additional, Vasseur, B., additional, Dziadziuszko, R., additional, Giaccone, G., additional, Besse, B., additional, and Felip, E., additional
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- 2022
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26. Sex-based differences in response to anti-PD-1 or PD-L1 treatment in patients with non-small-cell lung cancer expressing high PD-L1 levels. A systematic review and meta-analysis of randomized clinical trials
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Conforti, F, Pala, L, Pagan, E, Corti, C, Bagnardi, V, Queirolo, P, Catania, C, De Pas, T, Giaccone, G, Conforti, F., Pala, L., Pagan, E., Corti, C., Bagnardi, V., Queirolo, P., Catania, C., De Pas, T., Giaccone, G., Conforti, F, Pala, L, Pagan, E, Corti, C, Bagnardi, V, Queirolo, P, Catania, C, De Pas, T, Giaccone, G, Conforti, F., Pala, L., Pagan, E., Corti, C., Bagnardi, V., Queirolo, P., Catania, C., De Pas, T., and Giaccone, G.
- Abstract
Background: In our previous works, we demonstrated that patients’ sex affects the efficacy of immune checkpoint inhibitors (ICIs) in patients with several advanced solid tumors. Here, we assessed the sex-based heterogeneity of efficacy of anti-programmed cell death protein 1 (anti-PD-1)/anti-programmed death-ligand 1 (anti-PD-L1) given as monotherapy, for advanced non-small-cell lung cancer (NSCLC) expressing high PD-L1 levels, to evaluate if available evidence supports this therapeutic option for both women and men. Methods: We carried out a systematic review and meta-analysis including all randomized, controlled trials testing anti-PD-1/anti-PD-L1 drugs in monotherapy, as first-line treatment of advanced NSCLC expressing high PD-L1 levels. The primary endpoint was the difference in efficacy of anti-PD-1/anti-PD-L1 drugs versus chemotherapy, between men and women, measured in terms of the difference in overall survival (OS) log [hazard ratio (HR)] reported in male and female study participants. Results: We analyzed four randomized, controlled trials, including 1672 patients, of whom 1224 (73.2%) were men and 448 (26.8%) were women. The pooled OS-HR comparing anti-PD-1/anti-PD-L1 versus chemotherapy was 0.59 [95% confidence interval (CI), 0.50-0.69] for men and only 0.84 (95% CI, 0.64-1.10) for women. The pooled ratio of the OS-HRs reported in men versus women was 0.71 (95% CI, 0.52-0.98; P-heterogeneity: 0.04), indicating a significantly greater effect for men. No heterogeneity among single-study estimates was observed in either male patients (Q = 2.39, P = 0.50, I2 = 0%) or in female patients (Q = 1.13, P = 0.50, I2 = 0%). Conclusion: Evidence available indicates anti-PD-1/anti-PD-L1 monotherapy as highly effective in men but not in women, even in NSCLCs expressing high PD-L1 levels. Prospective trials testing sex-based tailored immunotherapy strategies are needed.
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- 2021
27. Neuro-telehealth for fragile patients in a tertiary referral neurological institute during the COVID-19 pandemic in Milan, Lombardy
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Pareyson, D, Pantaleoni, C, Eleopra, R, De Filippis, G, Moroni, I, Freri, E, Zibordi, F, Bulgheroni, S, Pagliano, E, Sarti, D, Silvani, A, Grazzi, L, Tiraboschi, P, Didato, G, Anghileri, E, Bersano, A, Valentini, L, Piacentini, S, Muscio, C, Leonardi, M, Mariotti, C, Eoli, M, Nuzzo, S, Tagliavini, F, Confalonieri, P, De Giorgi, F, Antozzi, C, Ardissone, A, Bersano, E, Boncoraglio, G, Bonvegna, S, Botturi, A, Brambilla, L, Canafoglia, L, Caputi, L, Caroppo, P, Carriero, M, Casali, C, Casazza, M, Catania, A, Ciaccio, C, Cilia, R, Dallabella, E, D'Amico, D, Danti, F, D'Arrigo, S, Decurtis, M, Deleo, F, Devigili, G, Difede, G, Digiacomo, R, Elia, A, Esposito, S, Estienne, M, Fenu, S, Fichera, M, Finocchiaro, G, Frangiamore, R, Gatti, M, Gaviani, P, Giaccone, G, Giani, L, Giovagnoli, A, Andreasi, N, Granata, T, Granocchio, E, Lamperti, C, Lamperti, E, Leone, M, Masson, R, Nanetti, L, Nardocci, N, Pastori, C, Pisciotta, C, Cecchini, A, Ragona, F, Redaelli, V, Saletti, V, Salsano, E, Scelzo, E, Solazzi, R, Tozzo, A, Usai, S, Zorzi, G, Arnoldi, M, Foscan, M, Marchi, A, Pedrinelli, I, Zanin, R, Gazzola, S, Magazu, S, Scopelliti, M, Casalino, T, Desalvatore, M, Mazzanti, S, Taddei, M, Fedeli, A, Sattin, D, Galimberti, L, Zagari, R, Bombonato, M, Fonte, L, Floridia, S, Pareyson D., Pantaleoni C., Eleopra R., De Filippis G., Moroni I., Freri E., Zibordi F., Bulgheroni S., Pagliano E., Sarti D., Silvani A., Grazzi L., Tiraboschi P., Didato G., Anghileri E., Bersano A., Valentini L., Piacentini S., Muscio C., Leonardi M., Mariotti C., Eoli M., Nuzzo S., Tagliavini F., Confalonieri P., De Giorgi F., Antozzi C., Ardissone A., Bersano E., Boncoraglio G., Bonvegna S., Botturi A., Brambilla L., Canafoglia L., Caputi L., Caroppo P., Carriero M. R., Casali C., Casazza M., Catania A., Ciaccio C., Cilia R., DallaBella E., D'Amico D., Danti F. R., D'Arrigo S., DeCurtis M., Deleo F., Devigili G., DiFede G., DiGiacomo R., Elia A., Esposito S., Estienne M., Fenu S., Fichera M., Finocchiaro G., Frangiamore R., Gatti M., Gaviani P., Giaccone G., Giani L., Giovagnoli A. R., Andreasi N. G., Granata T., Granocchio E., Lamperti C., Lamperti E., Leone M., Masson R., Nanetti L., Nardocci N., Pastori C., Pisciotta C., Cecchini A. P., Ragona F., Redaelli V., Saletti V., Salsano E., Scelzo E., Solazzi R., Tozzo A., Usai S., Zorzi G., Arnoldi M. T., Foscan M., Marchi A., Pedrinelli I., Zanin R., Gazzola S., Magazu S., Scopelliti M. R., Casalino T., DeSalvatore M., Mazzanti S., Taddei M., Fedeli A., Sattin D., Galimberti L., Zagari R., Bombonato M., Fonte L., Floridia S., Pareyson, D, Pantaleoni, C, Eleopra, R, De Filippis, G, Moroni, I, Freri, E, Zibordi, F, Bulgheroni, S, Pagliano, E, Sarti, D, Silvani, A, Grazzi, L, Tiraboschi, P, Didato, G, Anghileri, E, Bersano, A, Valentini, L, Piacentini, S, Muscio, C, Leonardi, M, Mariotti, C, Eoli, M, Nuzzo, S, Tagliavini, F, Confalonieri, P, De Giorgi, F, Antozzi, C, Ardissone, A, Bersano, E, Boncoraglio, G, Bonvegna, S, Botturi, A, Brambilla, L, Canafoglia, L, Caputi, L, Caroppo, P, Carriero, M, Casali, C, Casazza, M, Catania, A, Ciaccio, C, Cilia, R, Dallabella, E, D'Amico, D, Danti, F, D'Arrigo, S, Decurtis, M, Deleo, F, Devigili, G, Difede, G, Digiacomo, R, Elia, A, Esposito, S, Estienne, M, Fenu, S, Fichera, M, Finocchiaro, G, Frangiamore, R, Gatti, M, Gaviani, P, Giaccone, G, Giani, L, Giovagnoli, A, Andreasi, N, Granata, T, Granocchio, E, Lamperti, C, Lamperti, E, Leone, M, Masson, R, Nanetti, L, Nardocci, N, Pastori, C, Pisciotta, C, Cecchini, A, Ragona, F, Redaelli, V, Saletti, V, Salsano, E, Scelzo, E, Solazzi, R, Tozzo, A, Usai, S, Zorzi, G, Arnoldi, M, Foscan, M, Marchi, A, Pedrinelli, I, Zanin, R, Gazzola, S, Magazu, S, Scopelliti, M, Casalino, T, Desalvatore, M, Mazzanti, S, Taddei, M, Fedeli, A, Sattin, D, Galimberti, L, Zagari, R, Bombonato, M, Fonte, L, Floridia, S, Pareyson D., Pantaleoni C., Eleopra R., De Filippis G., Moroni I., Freri E., Zibordi F., Bulgheroni S., Pagliano E., Sarti D., Silvani A., Grazzi L., Tiraboschi P., Didato G., Anghileri E., Bersano A., Valentini L., Piacentini S., Muscio C., Leonardi M., Mariotti C., Eoli M., Nuzzo S., Tagliavini F., Confalonieri P., De Giorgi F., Antozzi C., Ardissone A., Bersano E., Boncoraglio G., Bonvegna S., Botturi A., Brambilla L., Canafoglia L., Caputi L., Caroppo P., Carriero M. R., Casali C., Casazza M., Catania A., Ciaccio C., Cilia R., DallaBella E., D'Amico D., Danti F. R., D'Arrigo S., DeCurtis M., Deleo F., Devigili G., DiFede G., DiGiacomo R., Elia A., Esposito S., Estienne M., Fenu S., Fichera M., Finocchiaro G., Frangiamore R., Gatti M., Gaviani P., Giaccone G., Giani L., Giovagnoli A. R., Andreasi N. G., Granata T., Granocchio E., Lamperti C., Lamperti E., Leone M., Masson R., Nanetti L., Nardocci N., Pastori C., Pisciotta C., Cecchini A. P., Ragona F., Redaelli V., Saletti V., Salsano E., Scelzo E., Solazzi R., Tozzo A., Usai S., Zorzi G., Arnoldi M. T., Foscan M., Marchi A., Pedrinelli I., Zanin R., Gazzola S., Magazu S., Scopelliti M. R., Casalino T., DeSalvatore M., Mazzanti S., Taddei M., Fedeli A., Sattin D., Galimberti L., Zagari R., Bombonato M., Fonte L., and Floridia S.
- Abstract
Background: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. Methods: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. Results: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March–September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. Conclusions: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.
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- 2021
28. Effectiveness of intensive clinical and radiological follow-up in patients with surgically resected NSCLC. Analysis of 2661 patients from the prospective MAGRIT trial
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Conforti, F, Pala, L, Pagan, E, Bagnardi, V, Zagami, P, Spaggiari, L, Catania, C, Vansteenkiste, J, Giaccone, G, De Pas, T, Conforti F., Pala L., Pagan E., Bagnardi V., Zagami P., Spaggiari L., Catania C., Vansteenkiste J., Giaccone G., De Pas T., Conforti, F, Pala, L, Pagan, E, Bagnardi, V, Zagami, P, Spaggiari, L, Catania, C, Vansteenkiste, J, Giaccone, G, De Pas, T, Conforti F., Pala L., Pagan E., Bagnardi V., Zagami P., Spaggiari L., Catania C., Vansteenkiste J., Giaccone G., and De Pas T.
- Abstract
Background: Limited evidence is available on effectiveness of clinicoradiological follow-up of early-stage NSCLC patients. MAGRIT was a phase III adjuvant RCT conducted in surgically resected stage IB-IIIA NSCLC patients, in which all participants had a prospectively defined intensive clinicoradiological follow-up. Methods: At patient-level data, we analyzed detection modality of disease recurrences and new primary lung cancer (i.e. detected by clinicoradiological scheduled exams versus by interim unscheduled exams), features associated with higher risk of locoregional and/or distant recurrence, and recurrence rates over time. Results: In the 2261 patients studied, there was a significant association between the type of recurrence and the modality of detection: 88.4% (95% CI, 84%–91%) of the locoregional recurrences and 93.2% (95% CI, 84%–99%) of the new primary lung cancers were detected by scheduled exams, whereas this was only 68.7% (95% CI, 65%–73%) for distant metastases (p < 0.001). Survival of patients with locoregional recurrence or new primary lung cancer detected by scheduled exams was significantly better as compared with those detected by unscheduled exams (HR 0.56, 95% CI 0.36–0.87; p = 0.01). Survival was similarly poor in patients with distant recurrences, both with scheduled and unscheduled detection (3-year survival after recurrence 22.0% and 21.8%, respectively). Recurrence rate was the highest in the first 18 months after surgery—with a peak between month 6 and 12—decreasing thereafter. The hazard of a second primary lung cancer was constant over time. Conclusion: Intensive follow-up is effective in detecting locoregional recurrences and second primary lung cancers, with impact on patients’ survival but did not influence the detection of distant recurrences.
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- 2020
29. Modelling the cascade of biomarker changes in GRN-related frontotemporal dementia
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Panman, J. L., Venkatraghavan, V., Van Der Ende, E. L., Steketee, R. M. E., Jiskoot, L. C., Poos, J. M., Dopper, E. G. P., Meeter, L. H. H., Kaat, L. D., Rombouts, S. A. R. B., Vernooij, M. W., Kievit, A. J. A., Premi, E., Cosseddu, M., Bonomi, E., Olives, J., Rohrer, J. D., Sanchez-Valle, R., Borroni, B., Bron, E. E., Van Swieten, J. C., Papma, J. M., Klein, S., Afonso, S., Almeida, M. R., Anderl-Straub, S., Andersson, C., Antonell, A., Archetti, S., Arighi, A., Balasa, M., Barandiaran, M., Bargallo, N., Bartha, R., Bender, B., Black, S., Butler, C., Bocchetta, M., Borrego-Ecija, S., Bras, J., Bruffaerts, R., Caroppo, P., Cash, D., Castelo-Branco, M., Convery, R., Cope, T., Danek, A., De Arriba, M., De Mendonca, A., Di Fede, G., Diaz, Z., Ducharme, S., Duro, D., Fenoglio, C., Ferreira, C. B., Finger, E., Flanagan, T., Fox, N., Freedman, M., Fumagalli, G., Gabilondo, A., Galimberti, D., Gasparotti, R., Gauthier, S., Gazzina, S., Gerhard, A., Giaccone, G., Gorostidi, A., Graff, C., Greaves, C., Guerreiro, R., Heller, C., Hoegen, T., Indakoetxea, B., Jelic, V., Karnath, H. -O., Keren, R., Laforce, R., Leitao, M. J., Levin, J., Llado, A., Loosli, S., Maruta, C., Masellis, M., Mead, S., Miltenberger, G., Van Minkelenm Sara Mitchell, R., Moore, K., Moreno, F., Nicholas, J., Oijerstedt, L., Otto, M., Ourselin, S., Padovani, A., Peakman, G., Pijnenburg, Y., Polito, C., Prioni, S., Prix, C., Rademakers, R., Redaelli, V., Rittman, T., Rogaeva, E., Rosa-Neto, P., Rossi, G., Rosser, M., Rowe, J., Santana, I., Santiago, B., Scarpini, E., Schonecker, S., Shafei, E. S. R., Shoesmith, C., Synofzik, M., Tabuas-Pereira, M., Tagliavini, F., Tartaglia, C., Tainta, M., Taipa, R., Tang-Wai, D., Thomas, D. L., Thonberg, H., Timberlake, C., Tiraboschi, P., Todd, E., Vandamme, P., Vandenberghe, R., Vandenbulcke, M., Veldsman, M., Verdelho, A., Villanua, J., Warren, J., Wilkeione, C., Elisabeth, W., Henrik, W., Zulaica, Z. M., Neurology, Physics and medical technology, Radiology & Nuclear Medicine, Clinical Genetics, and Medical Research Council
- Subjects
Male ,Oncology ,Disease ,Neuropsychological Tests ,GENFI consortium investigators ,Primary progressive aphasia ,Cognition ,Progranulins ,0302 clinical medicine ,Neurofilament Proteins ,BEHAVIORAL VARIANT ,HETEROGENEITY ,Gray Matter ,11 Medical and Health Sciences ,Language ,Psychiatry ,0303 health sciences ,Brain ,Middle Aged ,Magnetic Resonance Imaging ,White Matter ,17 Psychology and Cognitive Sciences ,ALZHEIMERS-DISEASE ,Psychiatry and Mental health ,Phenotype ,medicine.anatomical_structure ,Frontotemporal Dementia ,Disease Progression ,Biomarker (medicine) ,Female ,Life Sciences & Biomedicine ,Frontotemporal dementia ,medicine.medical_specialty ,Clinical Neurology ,EVENT-BASED MODEL ,Grey matter ,Lateralization of brain function ,White matter ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Internal medicine ,NEUROFILAMENT LIGHT-CHAIN ,medicine ,Humans ,LOBAR DEGENERATION ,PROGRANULIN ,Aged ,030304 developmental biology ,Science & Technology ,Neurology & Neurosurgery ,business.industry ,DISEASE PROGRESSION ,medicine.disease ,Mutation ,WHITE-MATTER INTEGRITY ,Surgery ,Neurosciences & Neurology ,Neurology (clinical) ,business ,GENFI ,Biomarkers ,030217 neurology & neurosurgery ,Progressive disease - Abstract
ObjectiveProgranulin-related frontotemporal dementia (FTD-GRN) is a fast progressive disease. Modelling the cascade of multimodal biomarker changes aids in understanding the aetiology of this disease and enables monitoring of individual mutation carriers. In this cross-sectional study, we estimated the temporal cascade of biomarker changes for FTD-GRN, in a data-driven way.MethodsWe included 56 presymptomatic and 35 symptomatic GRN mutation carriers, and 35 healthy non-carriers. Selected biomarkers were neurofilament light chain (NfL), grey matter volume, white matter microstructure and cognitive domains. We used discriminative event-based modelling to infer the cascade of biomarker changes in FTD-GRN and estimated individual disease severity through cross-validation. We derived the biomarker cascades in non-fluent variant primary progressive aphasia (nfvPPA) and behavioural variant FTD (bvFTD) to understand the differences between these phenotypes.ResultsLanguage functioning and NfL were the earliest abnormal biomarkers in FTD-GRN. White matter tracts were affected before grey matter volume, and the left hemisphere degenerated before the right. Based on individual disease severities, presymptomatic carriers could be delineated from symptomatic carriers with a sensitivity of 100% and specificity of 96.1%. The estimated disease severity strongly correlated with functional severity in nfvPPA, but not in bvFTD. In addition, the biomarker cascade in bvFTD showed more uncertainty than nfvPPA.ConclusionDegeneration of axons and language deficits are indicated to be the earliest biomarkers in FTD-GRN, with bvFTD being more heterogeneous in disease progression than nfvPPA. Our data-driven model could help identify presymptomatic GRN mutation carriers at risk of conversion to the clinical stage.
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- 2021
30. Association of Anticancer Immune Checkpoint Inhibitors with Patient-Reported Outcomes Assessed in Randomized Clinical Trials: A Systematic Review and Meta-Analysis
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Pala, L, Sala, I, Oriecuia, C, De Pas, T, Queirolo, P, Specchia, C, Cocorocchio, E, Ferrucci, P, Patane, D, Saponara, M, Pennacchioli, E, Coppola, S, Viale, G, Giaccone, G, Gelber, R, Bagnardi, V, Conforti, F, Pala, L, Sala, I, Oriecuia, C, De Pas, T, Queirolo, P, Specchia, C, Cocorocchio, E, Ferrucci, P, Patane, D, Saponara, M, Pennacchioli, E, Coppola, S, Viale, G, Giaccone, G, Gelber, R, Bagnardi, V, and Conforti, F
- Abstract
Importance: The association of immune checkpoint inhibitors (ICIs) with patient quality of life has been poorly explored. Objective: To evaluate patient-reported outcomes (PROs) assessed in randomized clinical trials (RCTs) of immunotherapy-based treatments. Data Sources: This systematic review and random-effects meta-Analysis used RCTs identified in PubMed, MEDLINE, Embase, and Scopus from database inception to June 1, 2021. Study Selection: A total of 2259 RCTs were identified that assessed ICIs as monotherapy or in combination with chemotherapy or combined with another ICI and/or targeted therapy vs control groups not containing immunotherapy in patients with advanced solid tumors. Studies were reviewed independently by 2 authors. Data Extraction and Synthesis: This meta-Analysis followed the PRISMA guidelines and recommendations of the Setting International Standards in Analyzing Patient-Reported Outcomes and Quality of Life Endpoints Data Consortium. Main Outcomes and Measures: The coprimary aims of the meta-Analysis were (1) pooled differences between treatment groups in the mean change of PRO score from baseline to 12 and 24 weeks of follow-up and (2) pooled differences between treatment groups in the time to deterioration of PRO score. For each end point, RCTs have been analyzed according to the type of treatment administered in the experimental group: ICIs given as monotherapy, ICIs combined with chemotherapy, or ICIs in association with another ICI and/or with targeted therapies. Results: Of the 2259 identified RCTs, 34 (18709 patients) met the selection criteria and were analyzed. In the group of 19 RCTs testing ICIs as monotherapy, the pooled between-groups difference of mean change from baseline to 12 weeks of follow-up was 4.6 (95% CI, 2.8-6.4), and the mean change from baseline to 24 weeks of follow-up was 6.1 (95% CI, 4.2-8.1), significantly favoring ICIs. The pooled difference was 1.4 (95% CI,-0.4 to 3.2) at week 12 and 2.5 (95% CI,-0.8 to 5.9) at w
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- 2022
31. Genetic architecture of sporadic frontotemporal dementia and overlap with Alzheimerʼs and Parkinsonʼs diseases
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Ferrari, Raffaele, Wang, Yunpeng, Vandrovcova, Jana, Guelfi, Sebastian, Witeolar, Aree, Karch, Celeste M, Schork, Andrew J, Fan, Chun C, Brewer, James B, Momeni, Parastoo, Schellenberg, Gerard D, Dillon, William P, Sugrue, Leo P, Hess, Christopher P, Yokoyama, Jennifer S, Bonham, Luke W, Rabinovici, Gil D, Miller, Bruce L, Andreassen, Ole A, Dale, Anders M, Hardy, John, Desikan, Rahul S, Hernandez, D G, Nalls, M A, Rohrer, J D, Ramasamy, A, Kwok, J B J, Dobson-Stone, C, Schofield, P R, Halliday, G M, Hodges, J R, Piguet, O, Bartley, L, Thompson, E, Haan, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, N J, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Landqvist Waldö, M, Nilsson, K, Nilsson, C, Mackenzie, I R A, Hsiung, G-Y R, Mann, D M A, Grafman, J, Morris, C M, Attems, J, Griffiths, T D, McKeith, I G, Thomas, A J, Pietrini, P, Huey, E D, Wassermann, E M, Baborie, A, Jaros, E, Tierney, M C, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, J B, Schlachetzki, J C M, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, V M, Grossman, M, Trojanowski, J Q, van der Zee, J, Cruts, M, Van Broeckhoven, C, Cappa, S F, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, J E, Hjermind, L E, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, M N, Fox, N C, Warren, J D, Spillantini, M G, Morris, H R, Rizzu, P, Heutink, P, Snowden, J S, Rollinson, S, Richardson, A, Gerhard, A, Bruni, A C, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Conidi, M E, Smirne, N, Rademakers, R, Baker, M, Dickson, D W, Graff-Radford, N R, Petersen, R C, Knopman, D, Josephs, K A, Boeve, B F, Parisi, J E, Seeley, W W, Karydas, A M, Rosen, H, van Swieten, J C, Dopper, E G P, Seelaar, H, Pijnenburg, Y A L, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, A A, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, H-H, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, and Singleton, A B
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- 2017
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32. Neuro-telehealth for fragile patients in a tertiary referral neurological institute during the COVID-19 pandemic in Milan, Lombardy
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Pareyson D., Pantaleoni C., Eleopra R., De Filippis G., Moroni I., Freri E., Zibordi F., Bulgheroni S., Pagliano E., Sarti D., Silvani A., Grazzi L., Tiraboschi P., Didato G., Anghileri E., Bersano A., Valentini L., Piacentini S., Muscio C., Leonardi M., Mariotti C., Eoli M., Nuzzo S., Tagliavini F., Confalonieri P., De Giorgi F., Antozzi C., Ardissone A., Bersano E., Boncoraglio G., Bonvegna S., Botturi A., Brambilla L., Canafoglia L., Caputi L., Caroppo P., Carriero M. R., Casali C., Casazza M., Catania A., Ciaccio C., Cilia R., DallaBella E., D'Amico D., Danti F. R., D'Arrigo S., DeCurtis M., Deleo F., Devigili G., DiFede G., DiGiacomo R., Elia A., Esposito S., Estienne M., Fenu S., Fichera M., Finocchiaro G., Frangiamore R., Gatti M., Gaviani P., Giaccone G., Giani L., Giovagnoli A. R., Andreasi N. G., Granata T., Granocchio E., Lamperti C., Lamperti E., Leone M., Masson R., Nanetti L., Nardocci N., Pastori C., Pisciotta C., Cecchini A. P., Ragona F., Redaelli V., Saletti V., Salsano E., Scelzo E., Solazzi R., Tozzo A., Usai S., Zorzi G., Arnoldi M. T., Foscan M., Marchi A., Pedrinelli I., Zanin R., Gazzola S., Magazu S., Scopelliti M. R., Casalino T., DeSalvatore M., Mazzanti S., Taddei M., Fedeli A., Sattin D., Galimberti L., Zagari R., Bombonato M., Fonte L., Floridia S., Pareyson, D, Pantaleoni, C, Eleopra, R, De Filippis, G, Moroni, I, Freri, E, Zibordi, F, Bulgheroni, S, Pagliano, E, Sarti, D, Silvani, A, Grazzi, L, Tiraboschi, P, Didato, G, Anghileri, E, Bersano, A, Valentini, L, Piacentini, S, Muscio, C, Leonardi, M, Mariotti, C, Eoli, M, Nuzzo, S, Tagliavini, F, Confalonieri, P, De Giorgi, F, Antozzi, C, Ardissone, A, Bersano, E, Boncoraglio, G, Bonvegna, S, Botturi, A, Brambilla, L, Canafoglia, L, Caputi, L, Caroppo, P, Carriero, M, Casali, C, Casazza, M, Catania, A, Ciaccio, C, Cilia, R, Dallabella, E, D'Amico, D, Danti, F, D'Arrigo, S, Decurtis, M, Deleo, F, Devigili, G, Difede, G, Digiacomo, R, Elia, A, Esposito, S, Estienne, M, Fenu, S, Fichera, M, Finocchiaro, G, Frangiamore, R, Gatti, M, Gaviani, P, Giaccone, G, Giani, L, Giovagnoli, A, Andreasi, N, Granata, T, Granocchio, E, Lamperti, C, Lamperti, E, Leone, M, Masson, R, Nanetti, L, Nardocci, N, Pastori, C, Pisciotta, C, Cecchini, A, Ragona, F, Redaelli, V, Saletti, V, Salsano, E, Scelzo, E, Solazzi, R, Tozzo, A, Usai, S, Zorzi, G, Arnoldi, M, Foscan, M, Marchi, A, Pedrinelli, I, Zanin, R, Gazzola, S, Magazu, S, Scopelliti, M, Casalino, T, Desalvatore, M, Mazzanti, S, Taddei, M, Fedeli, A, Sattin, D, Galimberti, L, Zagari, R, Bombonato, M, Fonte, L, and Floridia, S
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Adult ,medicine.medical_specialty ,Telemedicine ,Neurology ,Referral ,Dermatology ,Telehealth ,03 medical and health sciences ,0302 clinical medicine ,Pandemic ,medicine ,Humans ,Outpatient clinic ,030212 general & internal medicine ,Medical prescription ,Child ,Pandemics ,Referral and Consultation ,SARS-CoV-2 ,business.industry ,Teleneurorehabilitation ,COVID-19 ,General Medicine ,medicine.disease ,Televisit ,Psychiatry and Mental health ,Italy ,Neuro-telehealth ,Neurology (clinical) ,Neurosurgery ,Medical emergency ,business ,030217 neurology & neurosurgery - Abstract
Background: Lombardy was severely hit by the COVID-19 pandemic since February 2020 and the Health System underwent rapid reorganization. Outpatient clinics were stopped for non-urgent patients: it became a priority to manage hundreds of fragile neurological patients who suddenly had less reference points. In Italy, before the pandemic, Televisits were neither recognized nor priced. Methods: At the Fondazione IRCCS Istituto Neurologico C. Besta, we reorganized outpatient clinics to deliver Neuro-telemedicine services, including Televisits and Teleneurorehabilitation, since March 2020. A dedicated Working Group prepared the procedure, tested the system, and designed satisfaction questionnaires for adults and children. Results: After a pilot phase, we prepared a procedure for Telemedicine outpatient clinics which was approved by hospital directions. It included prescription, booking, consenting, privacy and data protection, secure connection with patients (Teams Microsoft 365), electronic report preparation and delivery, reporting, and accountability of the services. During the March–September 2020 period, we delivered 3167 Telemedicine services, including 1618 Televisits, to 1694 patients (972 adults, 722 children) with a wide range of chronic neurological disorders. We successfully administered different clinical assessment and scales. Satisfaction among patients and caregivers was very high. Conclusions: During the dramatic emergency, we were able to take care of more than 1600 patients by organizing Neuro-telehealth in a few weeks, lessening the impact of the pandemic on fragile patients with chronic neurological disorders; this strategy is now stably embedded in our care pathways. In Italy, Telehealth is at present recognized and priced and is becoming a stable pillar of the health system.
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- 2021
33. Clinical, Pathological, and Molecular Characterization of Gerstmann-Sträussler-Scheinker Disease in the Indiana Kindred (PRNP F198S)
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Ghetti, B., Tagliavini, F., Dlouhy, S. R., Piccardo, P., Young, K., Yee, R. D., Hutchins, G. D., Giaccone, G., Prelli, F., Frangione, B., Unverzagt, F., Bugiani, O., Farlow, M. R., and Morrison, Douglas R. O., editor
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- 1998
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34. Clinical Pharmacology of Carboplatin Administered in Alternating Sequence with Paclitaxel in Patients with Non-Small Cell Lung Cancer: A European Cancer Centre (ECC) Study
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van Warmerdam, L. J. C., Huizing, M. T., Giaccone, G., Bakker, P. J. M., Vermorken, J. B., Postmus, P. E., van Zandwijk, N., Koolen, M. G. J., ten Bokkel Huinink, W. W., Maes, R. A. A., van der Vijgh, W. J. F., Veenhof, C. H. N., Beijnen, J. H., Pinedo, H. M., editor, and Schornagel, J. H., editor
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- 1996
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35. Phase I trial of SU14813 in patients with advanced solid malignancies
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Fiedler, W., Giaccone, G., Lasch, P., van der Horst, I., Brega, N., Courtney, R., Abbattista, A., Shalinsky, D.R., Bokemeyer, C., and Boven, E.
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- 2011
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36. IGNYTE: A Phase 1/2 Multi-Cohort Clinical Trial of RP1 ± Nivolumab in Patients with Non-Small Cell Lung Cancer and Other Solid Tumors
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Emamekhoo, H., primary, Patel, S., additional, Rodriguez, E., additional, Riaz, M.K., additional, Giaccone, G., additional, Furqan, M., additional, Sacco, J.J., additional, Bommareddy, P., additional, Raza, S., additional, He, S., additional, Harrington, K., additional, and Middleton, M.R., additional
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- 2022
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37. 61P IMpower110: Exploratory analyses of the impact of first-line (1L) atezolizumab on the efficacy of next-line of therapy in PD-L1–selected NSCLC
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Patel, S.P., primary, Reuss, J.E., additional, Scilla, K., additional, Giaccone, G., additional, Spigel, D.R., additional, Ngiam, C., additional, Zhu, Q., additional, Bara, I., additional, Ding, B., additional, and Herbst, R.S., additional
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- 2021
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38. Clinical relevance of drug resistance: Where do we stand now and where are we going to ?
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Linn, S. C., Giaccone, G., Pinedo, H. M., Banzet, P., editor, Holland, J. F., editor, Khayat, D., editor, and Weil, M., editor
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- 1994
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39. HSP-90 inhibitor ganetespib is synergistic with doxorubicin in small cell lung cancer
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Lai, C-H, Park, K-S, Lee, D-H, Alberobello, A T, Raffeld, M, Pierobon, M, Pin, E, Petricoin III, E F, Wang, Y, and Giaccone, G
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- 2014
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40. New Chemotherapeutic Agents: A Selection of Some of the Most Promising New Drugs
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Pinedo, H. M., Smorenburg, C. H., Giaccone, G., Azzi, A., editor, Packer, L., editor, Cittadini, A., editor, Baserga, R., editor, Pinedo, H. M., editor, Galeotti, T., editor, and Corda, D., editor
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- 1993
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41. A C6orf10/LOC101929163 locus is associated with age of onset in C9orf72 carriers
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Zhang M1, 2 3, Ferrari R4, Tartaglia MC3, 5 6, Keith J7, Surace EI8, Wolf U9, Sato C3, Grinberg M3, Liang Y3, Xi Z3, Dupont K3, McGoldrick P3, Weichert A3, McKeever PM3, Schneider R3, 6 7, McCorkindale MD4, Manzoni C10, Rademakers R11, Graff-Radford NR12, Dickson DW11, Parisi JE13, Boeve BF14, Petersen RC14, Miller BL15, Seeley WW16, van Swieten JC17, van Rooij J17, Pijnenburg Y18, van der Zee J19, Van Broeckhoven C19, Le Ber I21, Van Deerlin V23, Suh E23, Rohrer JD24, Mead S25, Graff C26, Öijerstedt L26, Pickering-Brown S28, Rollinson S28, Rossi G29, Tagliavini F30, Brooks WS31, Dobson-Stone C32, Halliday GM32, Hodges JR32, Piguet O34, Binetti G36, Benussi L37, Ghidoni R37, Nacmias B38, Sorbi S38, Bruni AC40, Galimberti D41, Scarpini E41, Rainero I42, Rubino E42, Clarimon J43, Lleó A43, Ruiz A45, Hernández I45, Pastor P46, Diez-Fairen M46, Borroni B48, Pasquier F49, Deramecourt V49, Lebouvier T49, Perneczky R50, 51 52, Diehl-Schmid J50, Grafman J53, Huey ED55, Mayeux R55, Nalls MA57, Hernandez D57, Singleton A57, Momeni P58, Zeng Z59, Hardy J4, Robertson J3, Zinman L6, 7, Rogaeva E3, 6, International FTD-Genomics Consortium (IFGC), Ferrari R, Hernandez DG, Nalls MA, Rohrer JD, Ramasamy A, Kwok JBJ, Dobson-Stone C, Brooks WS, Schofield PR, Halliday GM, Hodges JR, Piguet O, Bartley L, Thompson E, Hernández I, Ruiz A, Boada M, Borroni B, Padovani A, Cruchaga C, Cairns NJ, Benussi L, Binetti G, Ghidoni R, Forloni G, Albani D, Galimberti D, Fenoglio C, Serpente M, Scarpini E, Clarimón J, Lleó A, Blesa R, Wald Ouml ML, Nilsson K, Nilsson C, Mackenzie IRA, Hsiung GR, Mann DMA, Grafman J, Morris CM, Attems J, Griffiths TD, McKeith IG, Thomas AJ, Pietrini P, Huey ED, Wassermann EM, Baborie A, Jaros E, Tierney MC, Pastor P, Razquin C, Ortega-Cubero S, Alonso E, Perneczky R, Diehl-Schmid J, Alexopoulos P, Kurz A, Rainero I, Rubino E, Pinessi L, Rogaeva E, St George-Hyslop P, Rossi G, Tagliavini F, Giaccone G, Rowe JB, Schlachetzki JCM, Uphill J, Collinge J, Mead S, Danek A, Van Deerlin VM, Grossman M, Trojanowski JQ, van der Zee J, Van Broeckhoven C, Cappa SF, Leber I, Hannequin D, Golfier V, Vercelletto M, Brice A, Nacmias B, Sorbi S, Bagnoli S, Piaceri I, Nielsen JE, Hjermind LE, Riemenschneider M, Mayhaus M, Ibach B, Gasparoni G, Pichler S, Gu W, Rossor MN, Fox NC, Warren JD, Grazia Spillantini M, Morris HR, Rizzu P, Heutink P, Snowden JS, Rollinson S, Richardson A, Gerhard A, Bruni AC, Maletta R, Frangipane F, Cupidi C, Bernardi L, Anfossi M, Gallo M, Elena Conidi M, Smirne N, Rademakers R, Baker M, Dickson DW, Graff-Radford NR, Petersen RC, Knopman D, Josephs KA, Boeve BF, Parisi JE, Seeley WW, Miller BL, Karydas AM, Rosen H, van Swieten JC, Dopper EGP, Seelaar H, Pijnenburg YAL, Scheltens P, Logroscino G, Capozzo R, Novelli V, Puca AA, Franceschi M, Postiglione A, Milan G, Sorrentino P, Kristiansen M, Chiang HH, Graff C, Pasquier F, Rollin A, Deramecourt V, Lebouvier T, Kapogiannis D, Ferrucci L, Pickering-Brown S, Singleton AB, Hardy J, Momeni P, Human genetics, Amsterdam Neuroscience - Neurodegeneration, Neurology, Divisions, Zhang, M1, 2, 3, Ferrari, R4, Tartaglia, Mc3, 5, 6, Keith, J7, Surace, Ei8, Wolf, U9, Sato, C3, Grinberg, M3, Liang, Y3, Xi, Z3, Dupont, K3, Mcgoldrick, P3, Weichert, A3, Mckeever, Pm3, Schneider, R3, 6, 7, Mccorkindale, Md4, Manzoni, C10, Rademakers, R11, Graff-Radford, Nr12, Dickson, Dw11, Parisi, Je13, Boeve, Bf14, Petersen, Rc14, Miller, Bl15, Seeley, Ww16, van Swieten, Jc17, van Rooij, J17, Pijnenburg, Y18, van der Zee, J19, Van Broeckhoven, C19, Le Ber, I21, Van Deerlin, V23, Suh, E23, Rohrer, Jd24, Mead, S25, Graff, C26, Öijerstedt, L26, Pickering-Brown, S28, Rollinson, S28, Rossi, G29, Tagliavini, F30, Brooks, Ws31, Dobson-Stone, C32, Halliday, Gm32, Hodges, Jr32, Piguet, O34, Binetti, G36, Benussi, L37, Ghidoni, R37, Nacmias, B38, Sorbi, S38, Bruni, Ac40, Galimberti, D41, Scarpini, E41, Rainero, I42, Rubino, E42, Clarimon, J43, Lleó, A43, Ruiz, A45, Hernández, I45, Pastor, P46, Diez-Fairen, M46, Borroni, B48, Pasquier, F49, Deramecourt, V49, Lebouvier, T49, Perneczky, R50, 51, 52, Diehl-Schmid, J50, Grafman, J53, Huey, Ed55, Mayeux, R55, Nalls, Ma57, Hernandez, D57, Singleton, A57, Momeni, P58, Zeng, Z59, Hardy, J4, Robertson, J3, Zinman, L6, Rogaeva, E3, International FTD-Genomics Consortium, (IFGC), Ferrari, R, Hernandez, Dg, Nalls, Ma, Rohrer, Jd, Ramasamy, A, Kwok, Jbj, Dobson-Stone, C, Brooks, W, Schofield, Pr, Halliday, Gm, Hodges, Jr, Piguet, O, Bartley, L, Thompson, E, Hernández, I, Ruiz, A, Boada, M, Borroni, B, Padovani, A, Cruchaga, C, Cairns, Nj, Benussi, L, Binetti, G, Ghidoni, R, Forloni, G, Albani, D, Galimberti, D, Fenoglio, C, Serpente, M, Scarpini, E, Clarimón, J, Lleó, A, Blesa, R, Wald Ouml, Ml, Nilsson, K, Nilsson, C, Mackenzie, Ira, Hsiung, Gr, Mann, Dma, Grafman, J, Morris, Cm, Attems, J, Griffiths, Td, Mckeith, Ig, Thomas, Aj, Pietrini, P, Huey, Ed, Wassermann, Em, Baborie, A, Jaros, E, Tierney, Mc, Pastor, P, Razquin, C, Ortega-Cubero, S, Alonso, E, Perneczky, R, Diehl-Schmid, J, Alexopoulos, P, Kurz, A, Rainero, I, Rubino, E, Pinessi, L, Rogaeva, E, St George-Hyslop, P, Rossi, G, Tagliavini, F, Giaccone, G, Rowe, Jb, Schlachetzki, Jcm, Uphill, J, Collinge, J, Mead, S, Danek, A, Van Deerlin, Vm, Grossman, M, Trojanowski, Jq, van der Zee, J, Van Broeckhoven, C, Cappa, Sf, Leber, I, Hannequin, D, Golfier, V, Vercelletto, M, Brice, A, Nacmias, B, Sorbi, S, Bagnoli, S, Piaceri, I, Nielsen, Je, Hjermind, Le, Riemenschneider, M, Mayhaus, M, Ibach, B, Gasparoni, G, Pichler, S, Gu, W, Rossor, Mn, Fox, Nc, Warren, Jd, Grazia Spillantini, M, Morris, Hr, Rizzu, P, Heutink, P, Snowden, J, Rollinson, S, Richardson, A, Gerhard, A, Bruni, Ac, Maletta, R, Frangipane, F, Cupidi, C, Bernardi, L, Anfossi, M, Gallo, M, Elena Conidi, M, Smirne, N, Rademakers, R, Baker, M, Dickson, Dw, Graff-Radford, Nr, Petersen, Rc, Knopman, D, Josephs, Ka, Boeve, Bf, Parisi, Je, Seeley, Ww, Miller, Bl, Karydas, Am, Rosen, H, van Swieten, Jc, Dopper, Egp, Seelaar, H, Pijnenburg, Yal, Scheltens, P, Logroscino, G, Capozzo, R, Novelli, V, Puca, Aa, Franceschi, M, Postiglione, A, Milan, G, Sorrentino, P, Kristiansen, M, Chiang, Hh, Graff, C, Pasquier, F, Rollin, A, Deramecourt, V, Lebouvier, T, Kapogiannis, D, Ferrucci, L, Pickering-Brown, S, Singleton, Ab, Hardy, J, Momeni, P, and Int FTD-Genomics Consortium IFGC
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Male ,Heterozygote ,amyotrophic lateral sclerosis ,Genotype ,genetic association ,Age of onset ,Polymorphism, Single Nucleotide ,frontotemporal dementia ,age of onset ,C9orf72 ,Humans ,amyotrophic lateral sclerosi ,Aged ,C9orf72 Protein ,Original Articles ,DNA Methylation ,Middle Aged ,Amyotrophic lateral sclerosis ,Gene Expression Regulation ,Genetic association ,CpG Islands ,Female ,Human medicine ,Neurology (clinical) ,Frontotemporal dementia - Abstract
Discovery of disease age-of-onset modifiers is important for clinical trials and drug design. Zhang et al. perform a genome-wide analysis of epigenetic functional polymorphisms and identify an association between the C6orf10/LOC101929163 locus and age of FTD/ALS onset. The risk allele may be associated with a pro-inflammatory state in the brain., The G4C2-repeat expansion in C9orf72 is the most common known cause of amyotrophic lateral sclerosis and frontotemporal dementia. The high phenotypic heterogeneity of C9orf72 patients includes a wide range in age of onset, modifiers of which are largely unknown. Age of onset could be influenced by environmental and genetic factors both of which may trigger DNA methylation changes at CpG sites. We tested the hypothesis that age of onset in C9orf72 patients is associated with some common single nucleotide polymorphisms causing a gain or loss of CpG sites and thus resulting in DNA methylation alterations. Combined analyses of epigenetic and genetic data have the advantage of detecting functional variants with reduced likelihood of false negative results due to excessive correction for multiple testing in genome-wide association studies. First, we estimated the association between age of onset in C9orf72 patients (n = 46) and the DNA methylation levels at all 7603 CpG sites available on the 450 k BeadChip that are mapped to common single nucleotide polymorphisms. This was followed by a genetic association study of the discovery (n = 144) and replication (n = 187) C9orf72 cohorts. We found that age of onset was reproducibly associated with polymorphisms within a 124.7 kb linkage disequilibrium block tagged by top-significant variation, rs9357140, and containing two overlapping genes (LOC101929163 and C6orf10). A meta-analysis of all 331 C9orf72 carriers revealed that every A-allele of rs9357140 reduced hazard by 30% (P = 0.0002); and the median age of onset in AA-carriers was 6 years later than GG-carriers. In addition, we investigated a cohort of C9orf72 negative patients (n = 2634) affected by frontotemporal dementia and/or amyotrophic lateral sclerosis; and also found that the AA-genotype of rs9357140 was associated with a later age of onset (adjusted P = 0.007 for recessive model). Phenotype analyses detected significant association only in the largest subgroup of patients with frontotemporal dementia (n = 2142, adjusted P = 0.01 for recessive model). Gene expression studies of frontal cortex tissues from 25 autopsy cases affected by amyotrophic lateral sclerosis revealed that the G-allele of rs9357140 is associated with increased brain expression of LOC101929163 (a non-coding RNA) and HLA-DRB1 (involved in initiating immune responses), while the A-allele is associated with their reduced expression. Our findings suggest that carriers of the rs9357140 GG-genotype (linked to an earlier age of onset) might be more prone to be in a pro-inflammatory state (e.g. by microglia) than AA-carriers. Further, investigating the functional links within the C6orf10/LOC101929163/HLA-DRB1 pathway will be critical to better define age-dependent pathogenesis of frontotemporal dementia and amyotrophic lateral sclerosis.
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- 2018
42. LBA47 Activity of OSE-2101 in HLA-A2+ non-small cell lung cancer (NSCLC) patients after failure to immune checkpoint inhibitors (IO): Final results of phase III Atalante-1 randomised trial
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Besse, B., primary, Garcia Campelo, M.R., additional, Cobo Dols, M.A., additional, Quoix, E., additional, Madroszyk, A., additional, Felip, E., additional, Cappuzzo, F., additional, Denis, F., additional, Hilgers, W., additional, Romano, G., additional, Debieuvre, D., additional, Baldini, E., additional, Galetta, D., additional, Viteri, S., additional, Phan, M., additional, Schuette, W., additional, Zer, A., additional, Costantini, D., additional, Dziadziuszko, R., additional, and Giaccone, G., additional
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- 2021
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43. Efficacy of everolimus (RAD001) in patients with advanced NSCLC previously treated with chemotherapy alone or with chemotherapy and EGFR inhibitors
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Soria, J.-C., Shepherd, F.A., Douillard, J.-Y., Wolf, J., Giaccone, G., Crino, L., Cappuzzo, F., Sharma, S., Gross, S.H., Dimitrijevic, S., Di Scala, L., Gardner, H., Nogova, L., and Papadimitrakopoulou, V.
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- 2009
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44. Phase Ib safety and pharmacokinetic evaluation of daily and twice daily oral enzastaurin in combination with pemetrexed in advanced/metastatic cancer
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Hanauske, A.-R., Lahn, M., Musib, L.C., Weigang-Köhler, K., Yilmaz, E., Graefe, T., Kuenen, B., Thornton, D., McNealy, P., and Giaccone, G.
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- 2009
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45. Targeting HER2 aberrations as actionable drivers in lung cancers: phase II trial of the pan-HER tyrosine kinase inhibitor dacomitinib in patients with HER2-mutant or amplified tumors
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Kris, M. G., Camidge, D. R., Giaccone, G., Hida, T., Li, B. T., OʼConnell, J., Taylor, I., Zhang, H., Arcila, M. E., Goldberg, Z., and Jänne, P. A.
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- 2015
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46. Gemcitabine uptake in glioblastoma multiforme: potential as a radiosensitizer
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Sigmond, J., Honeywell, R.J., Postma, T.J., Dirven, C.M.F., de Lange, S.M., van der Born, K., Laan, A.C., Baayen, J.C.A., Van Groeningen, C.J., Bergman, A.M., Giaccone, G., and Peters, G.J.
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- 2009
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47. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
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de Rojas, I. Moreno-Grau, S. Tesi, N. Grenier-Boley, B. Andrade, V. Jansen, I.E. Pedersen, N.L. Stringa, N. Zettergren, A. Hernández, I. Montrreal, L. Antúnez, C. Antonell, A. Tankard, R.M. Bis, J.C. Sims, R. Bellenguez, C. Quintela, I. González-Perez, A. Calero, M. Franco-Macías, E. Macías, J. Blesa, R. Cervera-Carles, L. Menéndez-González, M. Frank-García, A. Royo, J.L. Moreno, F. Huerto Vilas, R. Baquero, M. Diez-Fairen, M. Lage, C. García-Madrona, S. García-González, P. Alarcón-Martín, E. Valero, S. Sotolongo-Grau, O. Ullgren, A. Naj, A.C. Lemstra, A.W. Benaque, A. Pérez-Cordón, A. Benussi, A. Rábano, A. Padovani, A. Squassina, A. de Mendonça, A. Arias Pastor, A. Kok, A.A.L. Meggy, A. Pastor, A.B. Espinosa, A. Corma-Gómez, A. Martín Montes, A. Sanabria, Á. DeStefano, A.L. Schneider, A. Haapasalo, A. Kinhult Ståhlbom, A. Tybjærg-Hansen, A. Hartmann, A.M. Spottke, A. Corbatón-Anchuelo, A. Rongve, A. Borroni, B. Arosio, B. Nacmias, B. Nordestgaard, B.G. Kunkle, B.W. Charbonnier, C. Abdelnour, C. Masullo, C. Martínez Rodríguez, C. Muñoz-Fernandez, C. Dufouil, C. Graff, C. Ferreira, C.B. Chillotti, C. Reynolds, C.A. Fenoglio, C. Van Broeckhoven, C. Clark, C. Pisanu, C. Satizabal, C.L. Holmes, C. Buiza-Rueda, D. Aarsland, D. Rujescu, D. Alcolea, D. Galimberti, D. Wallon, D. Seripa, D. Grünblatt, E. Dardiotis, E. Düzel, E. Scarpini, E. Conti, E. Rubino, E. Gelpi, E. Rodriguez-Rodriguez, E. Duron, E. Boerwinkle, E. Ferri, E. Tagliavini, F. Küçükali, F. Pasquier, F. Sanchez-Garcia, F. Mangialasche, F. Jessen, F. Nicolas, G. Selbæk, G. Ortega, G. Chêne, G. Hadjigeorgiou, G. Rossi, G. Spalletta, G. Giaccone, G. Grande, G. Binetti, G. Papenberg, G. Hampel, H. Bailly, H. Zetterberg, H. Soininen, H. Karlsson, I.K. Alvarez, I. Appollonio, I. Giegling, I. Skoog, I. Saltvedt, I. Rainero, I. Rosas Allende, I. Hort, J. Diehl-Schmid, J. Van Dongen, J. Vidal, J.-S. Lehtisalo, J. Wiltfang, J. Thomassen, J.Q. Kornhuber, J. Haines, J.L. Vogelgsang, J. Pineda, J.A. Fortea, J. Popp, J. Deckert, J. Buerger, K. Morgan, K. Fließbach, K. Sleegers, K. Molina-Porcel, L. Kilander, L. Weinhold, L. Farrer, L.A. Wang, L.-S. Kleineidam, L. Farotti, L. Parnetti, L. Tremolizzo, L. Hausner, L. Benussi, L. Froelich, L. Ikram, M.A. Deniz-Naranjo, M.C. Tsolaki, M. Rosende-Roca, M. Löwenmark, M. Hulsman, M. Spallazzi, M. Pericak-Vance, M.A. Esiri, M. Bernal Sánchez-Arjona, M. Dalmasso, M.C. Martínez-Larrad, M.T. Arcaro, M. Nöthen, M.M. Fernández-Fuertes, M. Dichgans, M. Ingelsson, M. Herrmann, M.J. Scherer, M. Vyhnalek, M. Kosmidis, M.H. Yannakoulia, M. Schmid, M. Ewers, M. Heneka, M.T. Wagner, M. Scamosci, M. Kivipelto, M. Hiltunen, M. Zulaica, M. Alegret, M. Fornage, M. Roberto, N. van Schoor, N.M. Seidu, N.M. Banaj, N. Armstrong, N.J. Scarmeas, N. Scherbaum, N. Goldhardt, O. Hanon, O. Peters, O. Skrobot, O.A. Quenez, O. Lerch, O. Bossù, P. Caffarra, P. Dionigi Rossi, P. Sakka, P. Hoffmann, P. Holmans, P.A. Fischer, P. Riederer, P. Yang, Q. Marshall, R. Kalaria, R.N. Mayeux, R. Vandenberghe, R. Cecchetti, R. Ghidoni, R. Frikke-Schmidt, R. Sorbi, S. Hägg, S. Engelborghs, S. Helisalmi, S. Botne Sando, S. Kern, S. Archetti, S. Boschi, S. Fostinelli, S. Gil, S. Mendoza, S. Mead, S. Ciccone, S. Djurovic, S. Heilmann-Heimbach, S. Riedel-Heller, S. Kuulasmaa, T. del Ser, T. Lebouvier, T. Polak, T. Ngandu, T. Grimmer, T. Bessi, V. Escott-Price, V. Giedraitis, V. Deramecourt, V. Maier, W. Jian, X. Pijnenburg, Y.A.L. Smith, A.D. Saenz, A. Bizzarro, A. Lauria, A. Vacca, A. Solomon, A. Anastasiou, A. Richardson, A. Boland, A. Koivisto, A. Daniele, A. Greco, A. Marianthi, A. McGuinness, B. Fin, B. Ferrari, C. Custodero, C. Ferrarese, C. Ingino, C. Mangone, C. Reyes Toso, C. Martínez, C. Cuesta, C. Muchnik, C. Joachim, C. Ortiz, C. Besse, C. Johansson, C. Zoia, C.P. Laske, C. Anastasiou, C. Palacio, D.L. Politis, D.G. Janowitz, D. Craig, D. Mann, D.M. Neary, D. Jürgen, D. Daian, D. Belezhanska, D. Kohler, E. Castaño, E.M. Koutsouraki, E. Chipi, E. De Roeck, E. Costantini, E. Vardy, E.R.L.C. Piras, F. Roveta, F. Piras, F. Prestia, F.A. Assogna, F. Salani, F. Sala, G. Lacidogna, G. Novack, G. Wilcock, G. Thonberg, H. Kölsch, H. Weber, H. Boecker, H. Etchepareborda, I. Piaceri, I. Tuomilehto, J. Lindström, J. Laczo, J. Johnston, J. Deleuze, J.-F. Harris, J. Schott, J.M. Priller, J. Bacha, J.I. Snowden, J. Lisso, J. Mihova, K.Y. Traykov, L. Morelli, L. Brusco, L.I. Rainer, M. Takalo, M. Bjerke, M. Del Zompo, M. Serpente, M. Sanchez Abalos, M. Rios, M. Peltonen, M. Herrman, M.J. Kosmidis, M.H. Kohler, M. Rojo, M. Jones, M. Orsini, M. Medel, N. Olivar, N. Fox, N.C. Salvadori, N. Hooper, N.M. Galeano, P. Solis, P. Bastiani, P. Mecocci, P. Passmore, P. Heun, R. Antikainen, R. Olaso, R. Perneczky, R. Germani, S. López-García, S. Love, S. Mehrabian, S. Bagnoli, S. Kochen, S. Andreoni, S. Teipel, S. Todd, S. Pickering-Brown, S. Natunen, T. Tegos, T. Laatikainen, T. Strandberg, T. Polvikoski, T.M. Matoska, V. Ciullo, V. Cores, V. Solfrizzi, V. Lisetti, V. Sevillano, Z. Abdelnour, C. Aguilera, N. Alarcon, E. Alegret, M. Benaque, A. Boada, M. Buendia, M. Cañabate, P. Carracedo, A. Corbatón-Anchuelo, A. Diego, S. Espinosa, A. Gailhajenet, A. Gil, S. Guitart, M. Hernández, I. Ibarria, M. Lafuente, A. Macias, J. Maroñas, O. Martín, E. Martínez, M.T. Marquié, M. Mauleón, A. Montrreal, L. Moreno-Grau, S. Moreno, M. Orellana, A. Ortega, G. Pancho, A. Pelejá, E. Pérez-Cordon, A. Pineda, J.A. Preckler, S. Quintela, I. Real, L.M. Rosende-Roca, M. Ruiz, A. Sáez, M.E. Sanabria, A. Serrano-Rios, M. Sotolongo-Grau, O. Tárraga, L. Valero, S. Vargas, L. Adarmes-Gómez, A.D. Alarcón-Martín, E. Alonso, M.D. Álvarez, I. Álvarez, V. Amer-Ferrer, G. Antequera, M. Antúnez, C. Baquero, M. Bernal, M. Blesa, R. Boada, M. Buiza-Rueda, D. Bullido, M.J. Burguera, J.A. Calero, M. Carrillo, F. Carrión-Claro, M. Casajeros, M.J. Clarimón, J. Cruz-Gamero, J.M. de Pancorbo, M.M. del Ser, T. Diez-Fairen, M. Escuela, R. Garrote-Espina, L. Fortea, J. Franco-Macías, E. Frank-García, A. García-Alberca, J.M. Garcia Madrona, S. Garcia-Ribas, G. Gómez-Garre, P. Hernández, I. Hevilla, S. Jesús, S. Labrador Espinosa, M.A. Lage, C. Legaz, A. Lleó, A. Lopez de Munain, A. López-García, S. Macias-García, D. Manzanares, S. Marín, M. Marín-Muñoz, J. Marín, T. Marquié, M. Martín Montes, A. Martínez, B. Martínez, C. Martínez, V. Martínez-Lage Álvarez, P. Medina, M. Mendioroz Iriarte, M. Mir, P. Molinuevo, J.L. Pastor, P. Pérez Tur, J. Periñán-Tocino, T. Pineda-Sanchez, R. Piñol-Ripoll, G. Rábano, A. Real de Asúa, D. Rodrigo, S. Rodríguez-Rodríguez, E. Royo, J.L. Ruiz, A. Sanchez del Valle Díaz, R. Sánchez-Juan, P. Sastre, I. Valero, S. Vicente, M.P. Vigo-Ortega, R. Vivancos, L. Macleod, C. McCracken, C. Brayne, C. Bresner, C. Grozeva, D. Bellou, E. Sommerville, E.W. Matthews, F. Leonenko, G. Menzies, G. Windle, G. Harwood, J. Phillips, J. Bennett, K. Luckuck, L. Clare, L. Woods, R. Saad, S. Burholt, V. Jansen, I.E. Rongve, A. Kehoe, P.G. Garcia-Ribas, G. Sánchez-Juan, P. Pastor, P. Pérez-Tur, J. Piñol-Ripoll, G. Lopez de Munain, A. García-Alberca, J.M. Bullido, M.J. Álvarez, V. Lleó, A. Real, L.M. Scheltens, P. Holstege, H. Marquié, M. Sáez, M.E. Carracedo, Á. Amouyel, P. Schellenberg, G.D. Williams, J. Seshadri, S. van Duijn, C.M. Mather, K.A. Sánchez-Valle, R. Serrano-Ríos, M. Orellana, A. Tárraga, L. Blennow, K. Huisman, M. Andreassen, O.A. Posthuma, D. Clarimón, J. Boada, M. van der Flier, W.M. Ramirez, A. Lambert, J.-C. van der Lee, S.J. Ruiz, A. EADB contributors The GR@ACE study group DEGESCO consortium IGAP (ADGC, CHARGE, EADI, GERAD) PGC-ALZ consortia
- Abstract
Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a large genetic association study by merging all available case-control datasets and by-proxy study results (discovery n = 409,435 and validation size n = 58,190). Here, we add six variants associated with Alzheimer’s disease risk (near APP, CHRNE, PRKD3/NDUFAF7, PLCG2 and two exonic variants in the SHARPIN gene). Assessment of the polygenic risk score and stratifying by APOE reveal a 4 to 5.5 years difference in median age at onset of Alzheimer’s disease patients in APOE ɛ4 carriers. Because of this study, the underlying mechanisms of APP can be studied to refine the amyloid cascade and the polygenic risk score provides a tool to select individuals at high risk of Alzheimer’s disease. © 2021, The Author(s).
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- 2021
48. Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores
- Author
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de Rojas, I., Moreno-Grau, S., Tesi, N., Grenier-Boley, B., Andrade, V., Jansen, I. E., Pedersen, N. L., Stringa, N., Zettergren, A., Hernandez, I., Montrreal, L., Antunez, C., Antonell, A., Tankard, R. M., Bis, J. C., Sims, R., Bellenguez, C., Quintela, I., Gonzalez-Perez, A., Calero, M., Franco-Macias, E., Macias, J., Blesa, R., Cervera-Carles, L., Menendez-Gonzalez, M., Frank-Garcia, A., Royo, J. L., Moreno, F., Huerto Vilas, R., Baquero, M., Diez-Fairen, M., Lage, C., Garcia-Madrona, S., Garcia-Gonzalez, P., Alarcon-Martin, E., Valero, S., Sotolongo-Grau, O., Ullgren, A., Naj, A. C., Lemstra, A. W., Benaque, A., Perez-Cordon, A., Benussi, A., Rabano, A., Padovani, A., Squassina, A., de Mendonca, A., Arias Pastor, A., Kok, A. A. L., Meggy, A., Pastor, A. B., Espinosa, A., Corma-Gomez, A., Martin Montes, A., Sanabria, A., DeStefano, A. L., Schneider, A., Haapasalo, A., Kinhult Stahlbom, A., Tybjaerg-Hansen, A., Hartmann, A. M., Spottke, A., Corbaton-Anchuelo, A., Rongve, A., Borroni, B., Arosio, B., Nacmias, B., Nordestgaard, B. G., Kunkle, B. W., Charbonnier, C., Abdelnour, C., Masullo, C., Martinez Rodriguez, C., Munoz-Fernandez, C., Dufouil, C., Graff, C., Ferreira, C. B., Chillotti, C., Reynolds, C. A., Fenoglio, C., Van Broeckhoven, C., Clark, C., Pisanu, C., Satizabal, C. L., Holmes, C., Buiza-Rueda, D., Aarsland, D., Rujescu, D., Alcolea, D., Galimberti, D., Wallon, D., Seripa, D., Grunblatt, E., Dardiotis, E., Duzel, E., Scarpini, E., Conti, E., Rubino, E., Gelpi, E., Rodriguez-Rodriguez, E., Duron, E., Boerwinkle, E., Ferri, E., Tagliavini, F., Kucukali, F., Pasquier, F., Sanchez-Garcia, F., Mangialasche, F., Jessen, F., Nicolas, G., Selbaek, G., Ortega, G., Chene, G., Hadjigeorgiou, G., Rossi, G., Spalletta, G., Giaccone, G., Grande, G., Binetti, G., Papenberg, G., Hampel, H., Bailly, H., Zetterberg, H., Soininen, H., Karlsson, I. K., Alvarez, I., Appollonio, I., Giegling, I., Skoog, I., Saltvedt, I., Rainero, I., Rosas Allende, I., Hort, J., Diehl-Schmid, J., Van Dongen, J., Vidal, J. -S., Lehtisalo, J., Wiltfang, J., Thomassen, J. Q., Kornhuber, J., Haines, J. L., Vogelgsang, J., Pineda, J. A., Fortea, J., Popp, J., Deckert, J., Buerger, K., Morgan, K., Fliessbach, K., Sleegers, K., Molina-Porcel, L., Kilander, L., Weinhold, L., Farrer, L. A., Wang, L. -S., Kleineidam, L., Farotti, L., Parnetti, L., Tremolizzo, L., Hausner, L., Benussi, L., Froelich, L., Ikram, M. A., Deniz-Naranjo, M. C., Tsolaki, M., Rosende-Roca, M., Lowenmark, M., Hulsman, M., Spallazzi, M., Pericak-Vance, M. A., Esiri, M., Bernal Sanchez-Arjona, M., Dalmasso, M. C., Martinez-Larrad, M. T., Arcaro, M., Nothen, M. M., Fernandez-Fuertes, M., Dichgans, M., Ingelsson, M., Herrmann, M. J., Scherer, M., Vyhnalek, M., Kosmidis, M. H., Yannakoulia, M., Schmid, M., Ewers, M., Heneka, M. T., Wagner, M., Scamosci, M., Kivipelto, M., Hiltunen, M., Zulaica, M., Alegret, M., Fornage, M., Roberto, N., van Schoor, N. M., Seidu, N. M., Banaj, N., Armstrong, N. J., Scarmeas, N., Scherbaum, N., Goldhardt, O., Hanon, O., Peters, O., Skrobot, O. A., Quenez, O., Lerch, O., Bossu, P., Caffarra, P., Dionigi Rossi, P., Sakka, P., Hoffmann, P., Holmans, P. A., Fischer, P., Riederer, P., Yang, Q., Marshall, R., Kalaria, R. N., Mayeux, R., Vandenberghe, R., Cecchetti, R., Ghidoni, R., Frikke-Schmidt, R., Sorbi, S., Hagg, S., Engelborghs, S., Helisalmi, S., Botne Sando, S., Kern, S., Archetti, S., Boschi, S., Fostinelli, S., Gil, S., Mendoza, S., Mead, S., Ciccone, S., Djurovic, S., Heilmann-Heimbach, S., Riedel-Heller, S., Kuulasmaa, T., del Ser, T., Lebouvier, T., Polak, T., Ngandu, T., Grimmer, T., Bessi, V., Escott-Price, V., Giedraitis, V., Deramecourt, V., Maier, W., Jian, X., Pijnenburg, Y. A. L., Smith, A. D., Saenz, A., Bizzarro, A., Lauria, A., Vacca, A., Solomon, A., Anastasiou, A., Richardson, A., Boland, A., Koivisto, A., Daniele, A., Greco, A., Marianthi, A., McGuinness, B., Fin, B., Ferrari, C., Custodero, C., Ferrarese, C., Ingino, C., Mangone, C., Reyes Toso, C., Martinez, C., Cuesta, C., Muchnik, C., Joachim, C., Ortiz, C., Besse, C., Johansson, C., Zoia, C. P., Laske, C., Anastasiou, C., Palacio, D. L., Politis, D. G., Janowitz, D., Craig, D., Mann, D. M., Neary, D., Jurgen, D., Daian, D., Belezhanska, D., Kohler, E., Castano, E. M., Koutsouraki, E., Chipi, E., De Roeck, E., Costantini, E., Vardy, E. R. L. C., Piras, F., Roveta, F., Prestia, F. A., Assogna, F., Salani, F., Sala, G., Lacidogna, G., Novack, G., Wilcock, G., Thonberg, H., Kolsch, H., Weber, H., Boecker, H., Etchepareborda, I., Piaceri, I., Tuomilehto, J., Lindstrom, J., Laczo, J., Johnston, J., Deleuze, J. -F., Harris, J., Schott, J. M., Priller, J., Bacha, J. I., Snowden, J., Lisso, J., Mihova, K. Y., Traykov, L., Morelli, L., Brusco, L. I., Rainer, M., Takalo, M., Bjerke, M., Del Zompo, M., Serpente, M., Sanchez Abalos, M., Rios, M., Peltonen, M., Herrman, M. J., Kohler, M., Rojo, M., Jones, M., Orsini, M., Medel, N., Olivar, N., Fox, N. C., Salvadori, N., Hooper, N. M., Galeano, P., Solis, P., Bastiani, P., Mecocci, P., Passmore, P., Heun, R., Antikainen, R., Olaso, R., Perneczky, R., Germani, S., Lopez-Garcia, S., Love, S., Mehrabian, S., Bagnoli, S., Kochen, S., Andreoni, S., Teipel, S., Todd, S., Pickering-Brown, S., Natunen, T., Tegos, T., Laatikainen, T., Strandberg, T., Polvikoski, T. M., Matoska, V., Ciullo, V., Cores, V., Solfrizzi, V., Lisetti, V., Sevillano, Z., Aguilera, N., Alarcon, E., Boada, M., Buendia, M., Canabate, P., Carracedo, A., Diego, S., Gailhajenet, A., Guitart, M., Ibarria, M., Lafuente, A., Maronas, O., Martin, E., Martinez, M. T., Marquie, M., Mauleon, A., Moreno, M., Orellana, A., Pancho, A., Peleja, E., Preckler, S., Real, L. M., Ruiz, A., Saez, M. E., Serrano-Rios, M., Tarraga, L., Vargas, L., Adarmes-Gomez, A. D., Alonso, M. D., Alvarez, V., Amer-Ferrer, G., Antequera, M., Bernal, M., Bullido, M. J., Burguera, J. A., Carrillo, F., Carrion-Claro, M., Casajeros, M. J., Clarimon, J., Cruz-Gamero, J. M., de Pancorbo, M. M., Escuela, R., Garrote-Espina, L., Garcia-Alberca, J. M., Garcia Madrona, S., Garcia-Ribas, G., Gomez-Garre, P., Hevilla, S., Jesus, S., Labrador Espinosa, M. A., Legaz, A., Lleo, A., Lopez de Munain, A., Macias-Garcia, D., Manzanares, S., Marin, M., Marin-Munoz, J., Marin, T., Martinez, B., Martinez, V., Martinez-Lage Alvarez, P., Medina, M., Mendioroz Iriarte, M., Mir, P., Molinuevo, J. L., Pastor, P., Perez Tur, J., Perinan-Tocino, T., Pineda-Sanchez, R., Pinol-Ripoll, G., Real de Asua, D., Rodrigo, S., Sanchez del Valle Diaz, R., Sanchez-Juan, P., Sastre, I., Vicente, M. P., Vigo-Ortega, R., Vivancos, L., Macleod, C., McCracken, C., Brayne, C., Bresner, C., Grozeva, D., Bellou, E., Sommerville, E. W., Matthews, F., Leonenko, G., Menzies, G., Windle, G., Harwood, J., Phillips, J., Bennett, K., Luckuck, L., Clare, L., Woods, R., Saad, S., Burholt, V., Kehoe, P. G., Perez-Tur, J., Scheltens, P., Holstege, H., Amouyel, P., Schellenberg, G. D., Williams, J., Seshadri, S., van Duijn, C. M., Mather, K. A., Sanchez-Valle, R., Blennow, K., Huisman, M., Andreassen, O. A., Posthuma, D., van der Flier, W. M., Ramirez, A., Lambert, J. -C., and van der Lee, S. J.
- Subjects
Age of Onset ,Aged ,Aged, 80 and over ,Alzheimer Disease ,Amyloid beta-Protein Precursor ,Apolipoproteins E ,Case-Control Studies ,Cohort Studies ,Datasets as Topic ,Female ,Follow-Up Studies ,Genetic Predisposition to Disease ,Genome-Wide Association Study ,Heterozygote ,Humans ,Male ,Middle Aged ,Polymorphism, Single Nucleotide ,Risk Assessment ,Risk Factors ,Multifactorial Inheritance - Published
- 2021
49. PD-L1 quantification across tumor types using the reverse phase protein microarray: implications for precision medicine
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Baldelli, E., Hodge, K.A., Bellezza, G., Shah, N.J., Gambara, G., Sidoni, A., Mandarano, M., Ruhunusiri, C., Dunetz, B., Abu-Khalaf, M., Wulfkuhle, J., Gallagher, R.I., Liotta, L., Bono, J. de, Mehra, N., Riisnaes, R., Ravaggi, A., Odicino, F., Sereni, M.I., Blackburn, M., Zupa, A., Improta, G., Demsko, P., Crino, L., Ludovini, V., Giaccone, G., Petricoin, E.F., Pierobon, M., Baldelli, E., Hodge, K.A., Bellezza, G., Shah, N.J., Gambara, G., Sidoni, A., Mandarano, M., Ruhunusiri, C., Dunetz, B., Abu-Khalaf, M., Wulfkuhle, J., Gallagher, R.I., Liotta, L., Bono, J. de, Mehra, N., Riisnaes, R., Ravaggi, A., Odicino, F., Sereni, M.I., Blackburn, M., Zupa, A., Improta, G., Demsko, P., Crino, L., Ludovini, V., Giaccone, G., Petricoin, E.F., and Pierobon, M.
- Abstract
Contains fulltext : 244665.pdf (Publisher’s version ) (Open Access), BACKGROUND: Anti-programmed cell death protein 1 and programmed cell death ligand 1 (PD-L1) agents are broadly used in first-line and second-line treatment across different tumor types. While immunohistochemistry-based assays are routinely used to assess PD-L1 expression, their clinical utility remains controversial due to the partial predictive value and lack of standardized cut-offs across antibody clones. Using a high throughput immunoassay, the reverse phase protein microarray (RPPA), coupled with a fluorescence-based detection system, this study compared the performance of six anti-PD-L1 antibody clones on 666 tumor samples. METHODS: PD-L1 expression was measured using five antibody clones (22C3, 28-8, CAL10, E1L3N and SP142) and the therapeutic antibody atezolizumab on 222 lung, 71 ovarian, 52 prostate and 267 breast cancers, and 54 metastatic lesions. To capture clinically relevant variables, our cohort included frozen and formalin-fixed paraffin-embedded samples, surgical specimens and core needle biopsies. Pure tumor epithelia were isolated using laser capture microdissection from 602 samples. Correlation coefficients were calculated to assess concordance between antibody clones. For two independent cohorts of patients with lung cancer treated with nivolumab, RPPA-based PD-L1 measurements were examined along with response to treatment. RESULTS: Median-center PD-L1 dynamic ranged from 0.01 to 39.37 across antibody clones. Correlation coefficients between the six antibody clones were heterogeneous (range: -0.48 to 0.95) and below 0.50 in 61% of the comparisons. In nivolumab-treated patients, RPPA-based measurement identified a subgroup of tumors, where low PD-L1 expression equated to lack of response. CONCLUSIONS: Continuous RPPA-based measurements capture a broad dynamic range of PD-L1 expression in human specimens and heterogeneous concordance levels between antibody clones. This high throughput immunoassay can potentially identify subgroups of tumors in wh
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- 2021
50. Disease-related cortical thinning in presymptomatic granulin mutation carriers
- Author
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Borrego-Écija, S. (Sergi), Sala-Llonch, R. (Roser), Swieten, J.C. (John) van, Borroni, B. (Barbara), Moreno, F. (Fermin), Masellis, M. (Mario), Tartaglia, C. (Carmela), Graff, C. (Caroline), Galimberti, D. (Daniela), Laforce, R. (Robert), Rowe, J.B. (James), Finger, E. (Elizabeth), Vandenberghe, R. (Rik), Tagliavini, F. (Fabrizio), De Mendonça, A. (Alexandre), Santana, I. (Isabel), Synofzik, M. (Matthis), Ducharme, S. (Simon), Levin, J. (Johannes), Danek, A. (Adrian), Gerhard, A. (Alex), Otto, M. (Markus), Butler, C. (Chris), Frisoni, G.B. (Giovanni B.), Sorbi, S. (Sandro), Heller, C. (Carolin), Bocchetta, M. (Martina), Cash, D.M. (David M), Convery, R.S. (Rhian S), Moore, K.M. (Katrina M), Rohrer, J.D. (Jonathan), Sánchez-Valle, R. (Raquel), Rossor, M.N. (Martin N.), Fox, N.C. (Nick), Woollacott, I.O.C. (Ione O.C.), Shafei, R. (Rachelle), Greaves, C. (Caroline), Neason, M. (Mollie), Guerreiro, R. (Rita), Bras, J. (Jose), Thomas, D.L. (David L), Nicholas, J. (Jennifer), Mead, S. (Simon), Meeter, L.H.H. (Lieke), Panman, J.L. (Jessica), Papma, J.M. (Janne), Thornton, A.S. (Andrew), Pijnenburg, Y.A.L. (Yolande), Indakoetxea, B. (Begoña), Gabilondo, A. (Alazne), TaintaMD, M. (Mikel), de Arriba, M. (Maria), Gorostidi, A. (Ana), Zulaica, M. (Miren), Villanua, J. (Jorge), Diaz, Z. (Zigor), Olives, J. (Jaume), Lladó, A. (Albert), Balasa, M. (Mircea), Antonell, A. (Anna), Bargallo, N. (Nuria), Premi, E. (Enrico), Cosseddu, M. (Maura), Gazzina, S. (Stefano), Padovani, A. (Alessandro), Gasparotti, R. (Roberto), Archetti, S. (Silvana), Black, S. (Sandra), Mitchell, S. (Sara), Rogaeva, E. (Ekaterina), Freedman, M. (Morris), Keren, R. (Ron), Tang-Wai, D. (David), Öijerstedt, L. (Linn), Andersson, C. (Christin), Jelic, S. (Svetislav Svetislav), Thonberg, H. (Håkan), Arighi, A. (Andrea), Fenoglio, C. (Chiara), Scarpini MD, E. (Elio), Fumagalli, G. (Giorgio), Cope, T. (Thomas), Timberlake, C. (Carolyn), Rittman, T. (Timothy), Shoesmith, C. (Christen), Bartha, R. (Robart), Rademakers, S. (Suzanne), Wilke, C. (Carlo), Bender, B. (Benjamin), Bruffaerts, R. (Rose), Vandamme, P. (Philip), Vandenbulcke, M. (Mathieu), Maruta, C. (Carolina), Ferreira, C.B. (Catarina B.), Miltenberger, G. (Gabriel), Verdelho, A. (Ana), Afonso, S. (Sónia), Taipa, R. (Ricardo), Caroppo, P. (Paola), Di Fede, G. (Giuseppe), Giaccone, G. (Giorgio), Prioni, S. (Sara), Redaelli, V. (Veronica), Rossi, G. (Giacomina), Tiraboschi, P. (Pietro), Duro, D. (Diana), Rosario Almeida, M. (Maria), Castelo-Branco, M. (Miguel), João Leitão, M. (Maria), Tabuas-Pereira, M. (Miguel), Santiago, B. (Beatriz), Gauthier, S. (Serge), Rosa-Neto, P. (Pedro), Veldsman, M. (Michele), Flanagan, T. (Toby), Prix, C. (Catharina), Hoegen, T. (Tobias), Wlasich, E. (Elisabeth), Loosli, S. (Sandra), Schonecker, S. (Sonja), Semler, E. (Elisa), Anderl-Straub, S. (Sarah), Borrego-Écija, S. (Sergi), Sala-Llonch, R. (Roser), Swieten, J.C. (John) van, Borroni, B. (Barbara), Moreno, F. (Fermin), Masellis, M. (Mario), Tartaglia, C. (Carmela), Graff, C. (Caroline), Galimberti, D. (Daniela), Laforce, R. (Robert), Rowe, J.B. (James), Finger, E. (Elizabeth), Vandenberghe, R. (Rik), Tagliavini, F. (Fabrizio), De Mendonça, A. (Alexandre), Santana, I. (Isabel), Synofzik, M. (Matthis), Ducharme, S. (Simon), Levin, J. (Johannes), Danek, A. (Adrian), Gerhard, A. (Alex), Otto, M. (Markus), Butler, C. (Chris), Frisoni, G.B. (Giovanni B.), Sorbi, S. (Sandro), Heller, C. (Carolin), Bocchetta, M. (Martina), Cash, D.M. (David M), Convery, R.S. (Rhian S), Moore, K.M. (Katrina M), Rohrer, J.D. (Jonathan), Sánchez-Valle, R. (Raquel), Rossor, M.N. (Martin N.), Fox, N.C. (Nick), Woollacott, I.O.C. (Ione O.C.), Shafei, R. (Rachelle), Greaves, C. (Caroline), Neason, M. (Mollie), Guerreiro, R. (Rita), Bras, J. (Jose), Thomas, D.L. (David L), Nicholas, J. (Jennifer), Mead, S. (Simon), Meeter, L.H.H. (Lieke), Panman, J.L. (Jessica), Papma, J.M. (Janne), Thornton, A.S. (Andrew), Pijnenburg, Y.A.L. (Yolande), Indakoetxea, B. (Begoña), Gabilondo, A. (Alazne), TaintaMD, M. (Mikel), de Arriba, M. (Maria), Gorostidi, A. (Ana), Zulaica, M. (Miren), Villanua, J. (Jorge), Diaz, Z. (Zigor), Olives, J. (Jaume), Lladó, A. (Albert), Balasa, M. (Mircea), Antonell, A. (Anna), Bargallo, N. (Nuria), Premi, E. (Enrico), Cosseddu, M. (Maura), Gazzina, S. (Stefano), Padovani, A. (Alessandro), Gasparotti, R. (Roberto), Archetti, S. (Silvana), Black, S. (Sandra), Mitchell, S. (Sara), Rogaeva, E. (Ekaterina), Freedman, M. (Morris), Keren, R. (Ron), Tang-Wai, D. (David), Öijerstedt, L. (Linn), Andersson, C. (Christin), Jelic, S. (Svetislav Svetislav), Thonberg, H. (Håkan), Arighi, A. (Andrea), Fenoglio, C. (Chiara), Scarpini MD, E. (Elio), Fumagalli, G. (Giorgio), Cope, T. (Thomas), Timberlake, C. (Carolyn), Rittman, T. (Timothy), Shoesmith, C. (Christen), Bartha, R. (Robart), Rademakers, S. (Suzanne), Wilke, C. (Carlo), Bender, B. (Benjamin), Bruffaerts, R. (Rose), Vandamme, P. (Philip), Vandenbulcke, M. (Mathieu), Maruta, C. (Carolina), Ferreira, C.B. (Catarina B.), Miltenberger, G. (Gabriel), Verdelho, A. (Ana), Afonso, S. (Sónia), Taipa, R. (Ricardo), Caroppo, P. (Paola), Di Fede, G. (Giuseppe), Giaccone, G. (Giorgio), Prioni, S. (Sara), Redaelli, V. (Veronica), Rossi, G. (Giacomina), Tiraboschi, P. (Pietro), Duro, D. (Diana), Rosario Almeida, M. (Maria), Castelo-Branco, M. (Miguel), João Leitão, M. (Maria), Tabuas-Pereira, M. (Miguel), Santiago, B. (Beatriz), Gauthier, S. (Serge), Rosa-Neto, P. (Pedro), Veldsman, M. (Michele), Flanagan, T. (Toby), Prix, C. (Catharina), Hoegen, T. (Tobias), Wlasich, E. (Elisabeth), Loosli, S. (Sandra), Schonecker, S. (Sonja), Semler, E. (Elisa), and Anderl-Straub, S. (Sarah)
- Abstract
Mutations in the granulin gene (GRN) cause familial frontotemporal dementia. Understanding the structural brain changes in presymptomatic GRN carriers would enforce the use of neuroimaging biomarkers for early diagnosis and monitoring. We studied 100 presymptomatic GRN mutation carriers and 94 noncarriers from the Genetic Frontotemporal dementia initiative (GENFI), with MRI structural images. We analyzed 3T MRI structural images using the FreeSurfer pipeline to calculate the whole brain cortical thickness (CTh) for each subject. We also perform a vertex-wise general linear model to assess differences between groups in the relationship between CTh and diverse covariables as gender, age, the estimated years to onset and education. We also explored differences according to TMEM106B genotype, a possible disease modifier. Whole brain CTh did not differ between carriers and noncarriers. Both groups showed age-related cortical thinning. The group-by-age interaction analysis showed that this age-related cortical thinning was significantly greater in GRN carriers in the left superior frontal cortex. TMEM106B did not significantly influence the age-related cortical thinning. Our results validate and expand previous findings suggesting an
- Published
- 2021
- Full Text
- View/download PDF
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