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1. Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

Author

Salluzzi, Marina, Blenkin, Nicole, Dueck, Ashley, Doram, Craig, Zhang, Qiao, Kenney, Carol, Ryckborst, Karla, Bohn, Shelly, Collier, Quentin, Taylor, Frances, Lethebe, B. Cord, Jambula, Anitha, Sage, Kayla, Toussaint, Lana, Save, Supryia, Lee, Jaclyn, Laham, N, Sultan, A.A., Deepak, A., Sitaram, A., Demchuk, Andrew M., Lockey, A., Micielli, A., Wadhwa, A., Arabambi, B., Graham, B., Bogiatzi, Chrysi, Doshi, Darshan, Chakraborty, D., Kim, Diana, Vasquez, D, Singh, D, Tse, Dominic, Harrison, E., Smith, E.E., Teleg, E., Klourfeld, E., Klein, G., Sebastian, I.A., Evans, J, Hegedus, J, Kromm, J, Lin, K, Ignacio, K, Ghavami, Kimia, Ismail, M., Moores, M., Panzini, M.A., Boyko, M., Almekhlafi, M.A., Newcommon, Nancy, Maraj, N., Imoukhuede, O., Volny, O., Stys, Peter, Couillard, Phillipe, Ojha, P., Eswaradass, P., Joundi, Raed, Singh, R., Asuncion, R.M., Muir, R.T., Dey, S., Mansoor, S., Wasyliw, S., Nagendra, S., Hu, Sherry, Althubait, S., Chen, S., Bal, S., Van Gaal, Stephen, Peters, Steven, Ray, Sucharita, Chaturvedi, S., Subramaniam, Suresh, Fu, Vivian, Villaluna, K., Maclean, G., King-Azote, P., Ma, C., Plecash, A., Murphy, C., Gorman, J., Wilson, L., Zhou, L., Benevente, O., Teal, P., Yip, S., Mann, S., Dewar, B., Demetroff, M., Shamloul, R., Beardshaw, R., Roberts, S., Blaquiere, D., Stotts, G., Shamy, M., Bereznyakova, O., Fahed, R., Alesefir, W., Lavoie, Suzy, Hache, A., Collard, K, Mackey, A., Gosselin-Lefebvre, S., Verreault, S., Beauchamp, B., Lambourn, L., Khaw, A., Mai, L., Sposato, L., Bres Bullrich, M., Azarpazhooh, R., Fridman, S., Kapoor, A., Southwell, A., Bardi, E., Fatakdawala, I., Kamra, M, Lopes, K., Popel, N., Norouzi, V., Liu, A., Liddy, A.M., Ghoari, B., Hawkes, C., Enriquez, C.A., Gladstone, D.J., Manosalva Alzate, H.A., Khosravani, H., Hopyan, J.J., Sivakumar, K., Son, M., Boulos, M.I., Hamind, M.A., Swartz, R.H., Murphy, R., Reiter, S., Fitzpatrick, T., Bhandari, V., Good, J., Penn, M., Naylor, M., Frost, S., Cayley, A., Akthar, F., Williams, J., Kalman, L., Crellin, L., Wiegner, R., Singh, R.S., Stewart, T., To, W., Singh, S., Pikula, A., Jaigobin, C., Carpani, F., Silver, F., Janssen, H., Schaafsma, J., del Campo, M., Alskaini, M., Rajendram, P., Fairall, P., Granfield, B., Crawford, D., Jabs, J., White, L., Sivakumar, L., Piquette, L., Nguyen, T., Nomani, A., Wagner, A., Alrohimi, A., Butt, A., D'Souza, A., Gajurel, B., Vekhande, C., Kamble, H., Kalashyan, H., Lloret, M., Benguzzi, M., Arsalan, N., Ishaque, N., Ashayeriahmadabad, R., Samiento, R., Hosseini, S., Kazi, S., Das, S., Sugumar, T., Selchen, D., Kostyrko, P., Muccilli, A., Saposnik, A.G., Vandervelde, C., Ratnayake, K., McMillan, S., Katsanos, A., Shoamanesh, A., Sahlas, D.J., Naidoo, V., Todorov, V., Toma, H., Brar, J., Lee, J., Horton, M., Shand, E., Weatherby, S., Jin, A., Durafourt, B., Jalini, S., Gardner, A., Tyson, C., Junk, E., Foster, K., Bolt, K., Sylvain, N., Maley, S., Urroz, L., Peeling, L., Kelly, M., Whelan, R., Cooley, R., Teitelbaum, J., Boutayeb, A., Moore, A., Cole, E., Waxman, L., Ben-Amor, N., Sanchez, R., Khalil, S., Nehme, A., Legault, C., Tampieri, D., Ehrensperger, E., Vieira, L., Cortes, M., Angle, M., Hannouche, M., Badawy, M., Werner, K., Wieszmuellner, S., Langer, A., Gisold, A., Zach, H., Rommer, P., Macher, S., Blechinger, S., Marik, W., Series, W., Baumgartinger, M., Krebs, S., Koski, J., Eirola, S., Ivanoff, T., Erakanto, A., Kupari, L., Sibolt, G., Panula, J., Tomppo, L., Tiainen, M., Ahlstrom, M., Martinez Majander, N., Suomalainen, O., Raty, S., Levi, C., Kerr, E., Allen, J., Kaauwai, L.P., Belevski, L., Russell, M., Ormond, S., Chew, A., Loiselle, A., Royan, A., Hughes, B., Garcia Esperon, C., Pepper, E., Miteff, F., He, J., Lycett, M., Min, M., Murray, N., Pavey, N., Starling de Barros, R., Gangadharan, S., Dunkerton, S., Waller, S., Canento Sanchez, T., Wellings, T., Edmonds, G., Whittaker, K.A., Ewing, M., Lee, P., Singkang, R., McDonald, A., Dos Santos, A., Shin, C., Jackson, D., Tsoleridis, J., Fisicchia, L., Parsons, N., Shenoy, N., Smith, S., Sharobeam, A., Balabanski, A., Park, A., Williams, C., Pavlin-Premri, D., Rodrigues, E., Alemseged, F., Ng, F., Zhao, H., Beharry, J., Ng, J.L., Williamson, J., Wong, J.Z.W., Li, K., Kwan, M.K., Valente, M., Yassi, N., Yogendrakumar, V., McNamara, B., Buchanan, C., McCarthy, C., Thomas, G., Stephens, K., Chung, M., Chung, M.F., Tang, M., Busch, T., Frost, T., Lee, R., Stuart, N., Pachani, N., Menon, A., Borojevic, B., Linton, C.M., Garcia, G., Callaly, E.P., Dewey, H., Liu, J., Chen, J., Wong, J., Nowak, K., To, K., Lizak, N.S., Bhalala, O., Park, P., Tan, P., Martins, R., Cody, R., Forbes, R., Chen, S.K., Ooi, S., Tu, S., Dang, Y.L., Ling, Z., Cranefield, J., Drew, R., Tan, A., Kurunawai, C., Harvey, J., Mahadevan, J.J., Cagi, L., Palanikumar, L., Chia, L.N., Goh, R., El-Masri, S., Urbi, B., Rapier, C., Berrill, H., McEvoy, H., Dunning, R., Kuriakose, S., Chad, T., Sapaen, V., Sabet, A., Shah, D., Yeow, D., Lilley, K., Ward, K., Mozhy Mahizhnan, M., Tan, M., Lynch, C., Coveney, S., Tobin, K., McCabe, J., Marnane, M., Murphy, S., Large, M., Moynihan, B., Boyle, K., Sanjuan, E., Sanchis, M., Boned, S., Pancorbo, O., Sala, V., Garcia, L., Garcia-Tornel, A., Juega, J., Pagola, J., Santana, K., Requena, M., Muchada, M., Olive, M., Lozano, P.J., Rubiera, M., Deck, M., Rodriguez, N., Gomez, B., Reyes Munoz, F.J., Gomez, A.S., Sanz, A.C., Garcia, E.C., Penacoba, G., Ramos, M.E., de Lera Alfonso, M., Feliu, A, Pardo, L., Ramirez, P., Murillo, A., Lopez Dominguez, D., Rodriguez, J., Terceno Izaga, M., Reina, M., Viturro, S.B., Bojaryn, U., Vera Monge, V.A., Silva Blas, Y., R Siew, R., Agustin, S J, Seet, C., Tianming, T., d'Emden, A., Murray, A., Welch, A., Hatherley, K., Day, N., Smith, W., MacRae, E., Mitchell, E.S., Mahmood, A., Elliot, J., Neilson, S., Biswas, V., Brown, C., Lewis, A., Ashton, A., Werring, D., Perry, R., Muhammad, R., Lee, Y.C., Black, A., Robinson, A., Williams, A., Banaras, A., Cahoy, C., Raingold, G., Marinescu, M., Atang, N., Bason, N., Francia, N., Obarey, S., Feerick, S., Joseph, J., Schulz, U., Irons, R., Benjamin, J., Quinn, L., Jhoots, M., Teal, R., Ford, G., Harston, G., Bains, H., Gbinigie, I., Mathieson, P., Sim, C.H., Hayter, E., Kennedy, K., Binnie, L., Priestley, N., Williams, R., Ghatala, R., Stratton, S., Blight, A., Zhang, L., Davies, A., Duffy, H., Roberts, J., Homer, J., Roberts, K., Dodd, K., Cawley, K., Martin, M., Leason, S., Cotgreave, S., Taylor, T., Nallasivan, A., Haider, S., Chakraborty, T., Webster, T., Gil, A., Martin, B., Joseph, B., Cabrera, C., Jose, D., Man, J., Aquino, J., Sebastian, S., Osterdahl, M., Kwan, M., Matthew, M., Ike, N., Bello, P., Wilding, P., Fuentes, R., Shah, R., Mashate, S., Patel, T., Nwanguma, U., Dave, V., Haber, A., Lee, A., O'Sullivan, A., Drumm, B., Dawson, A.C., Matar, T., Roberts, D., Taylor, E., Rounis, E., El-Masry, A., O'Hare, C., Kalladka, D., Jamil, S., Auger, S., Raha, O., Evans, M., Vonberg, F., Kalam, S., Ali Sheikh, A., Jenkins, I.H., George, J., Kwan, J., Blagojevic, J., Saeed, M., Haji-Coll, M., Tsuda, M., Sayed, M., Winterkron, N., Thanbirajah, N., Vittay, O., Karim, R., Smail, R.C., Gauhar, S., Elmamoun, S., Malani, S., Pralhad Kelavkar, S., Hiden, J., Ferdinand, P., Sanyal, R., Varquez, R., Smith, B., Okechukwu, C., Fox, E., Collins, E., Courtney, K., Tauro, S., Patterson, C., McShane, D., Roberts, G., McIImoyle, J., McGuire, K., Fearon, P., Gordon, P., Isaacs, K., Lucas, K., Smith, L., Dews, L., Bates, M., Lawrence, S., Heeley, S., Patel, V., Chin, Y.M., Sims, D., Littleton, E., Khaira, J., Nadar, K., Kieliszkowska, A., Sari, B., Domingos Belo, C., Smith, E., Manolo, E.Y., Aeron-Thomas, J., Doheny, M., Garcia Pardo, M., Recaman, M., Tibajia, M.C., Aissa, M., Mah, Y., Yu, T., Meenakshisundaram, S., Heller, S., Alsukhni, R., Williams, O., Farag, M., Benger, M., Engineer, A., Bayhonan, S., Conway, S., Bhalla, A., Nouvakis, D., Theochari, E., Boyle, F., Teo, J., King-Robson, J., Law, K.Y., Sztriha, L., McGovern, A., Day, D., Mitchell-Douglas, J., Francis, J., Iqbal, A., Punjabivaryani, P., Anonuevo Reyes, J., Anonuevo Reyes, M., Pauls, M., Buch, A., Hedstrom, A., Hutchinson, C., Kirkland, C., Newham, J., Wilkes, G., Fleming, L., Fleck, N., Franca, A., Chwal, B., Oldoni, C., Mantovani, G., Noll, G., Zanella, L., Soma, M., Secchi, T., Borelli, W., Rimoli, B.P., da Cunha Silva, G.H., Machado Galvao Mondin, L.A., Barbosa Cerantola, R., Imthon, A.K., Esaki, A.S., Camilo, M., Vincenzi, O.C., ds Cruz, R.R., Morillos, M.B., Riccioppa Rodrigues, G.G., Santos Ferreira, K., Pazini, A.M., Pena Pereira, M.A., de Albuquerque, A.L.A., Massote Fontanini, C.E., Matinez Rubio, C.F., dos Santos, D.T., Dias, F.A., Alves, F.F.A., Milani, C., Pegorer Santos, B., Winckler, F., De Souza, J.T., Bonome, L.A.M., Cury Silva, V.A., Teodoro, R.S., Modolo, G.P., Ferreira, N.C., Barbosa dos Santos, D.F., dos Santos Moreira, J.C., Cruz Guedes de Morais, A.B., Vieira, J., Mendes, G., de Queiroz, J.P., Coutts, Shelagh B, Ankolekar, Sandeep, Appireddy, Ramana, Arenillas, Juan F, Assis, Zarina, Bailey, Peter, Barber, Philip A, Bazan, Rodrigo, Buck, Brian H, Butcher, Ken S, Camden, Marie-Christine, Campbell, Bruce C V, Casaubon, Leanne K, Catanese, Luciana, Chatterjee, Kausik, Choi, Philip M C, Clarke, Brian, Dowlatshahi, Dar, Ferrari, Julia, Field, Thalia S, Ganesh, Aravind, Ghia, Darshan, Goyal, Mayank, Greisenegger, Stefan, Halse, Omid, Horn, Mackenzie, Hunter, Gary, Imoukhuede, Oje, Kelly, Peter J, Kennedy, James, Kleinig, Timothy J, Krishnan, Kailash, Lima, Fabricio, Mandzia, Jennifer L, Marko, Martha, Martins, Sheila O, Medvedev, George, Menon, Bijoy K, Mishra, Sachin M, Molina, Carlos, Moussaddy, Aimen, Muir, Keith W, Parsons, Mark W, Penn, Andrew M W, Pille, Arthur, Pontes-Neto, Octávio M, Roffe, Christine, Serena, Joaquin, Simister, Robert, Singh, Nishita, Spratt, Neil, Strbian, Daniel, Tham, Carol H, Wiggam, M Ivan, Williams, David J, Willmot, Mark R, Wu, Teddy, Yu, Amy Y X, Zachariah, George, Zafar, Atif, Zerna, Charlotte, and Hill, Michael D

Published
2024
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5. CRISPR-based gene editing enables FOXP3 gene repair in IPEX patient cells

Author

Goodwin, M, Lee, E, Lakshmanan, U, Shipp, S, Froessl, L, Barzaghi, F, Passerini, L, Narula, M, Sheikali, A, Lee, CM, Bao, G, Bauer, CS, Miller, HK, Garcia-Lloret, M, Butte, MJ, Bertaina, A, Shah, A, Pavel-Dinu, M, Hendel, A, Porteus, M, Roncarolo, MG, and Bacchetta, R

Subjects
Genetics, Biotechnology, Rare Diseases, Stem Cell Research, Autoimmune Disease, Regenerative Medicine, Pediatric, Aetiology, 5.2 Cellular and gene therapies, Development of treatments and therapeutic interventions, 2.1 Biological and endogenous factors, Inflammatory and immune system, Good Health and Well Being, Child, Forkhead Transcription Factors, Gene Editing, Genetic Diseases, X-Linked, Humans, Mutation, Phenotype, T-Lymphocytes, Regulatory
Abstract

The prototypical genetic autoimmune disease is immune dysregulation polyendocrinopathy enteropathy X-linked (IPEX) syndrome, a severe pediatric disease with limited treatment options. IPEX syndrome is caused by mutations in the forkhead box protein 3 (FOXP3) gene, which plays a critical role in immune regulation. As a monogenic disease, IPEX is an ideal candidate for a therapeutic approach in which autologous hematopoietic stem and progenitor (HSPC) cells or T cells are gene edited ex vivo and reinfused. Here, we describe a CRISPR-based gene correction permitting regulated expression of FOXP3 protein. We demonstrate that gene editing preserves HSPC differentiation potential, and that edited regulatory and effector T cells maintain their in vitro phenotype and function. Additionally, we show that this strategy is suitable for IPEX patient cells with diverse mutations. These results demonstrate the feasibility of gene correction, which will be instrumental for the development of therapeutic approaches for other genetic autoimmune diseases.

Published
2020

11. Gamma-ray Sources Imaging and Test-beam Results with MACACO III Compton Camera

Author

Universidad de Sevilla. Departamento de Física Atómica, Molecular y Nuclear, Ministerio de Ciencia e Innovación (MICIN). España, European Union (UE). H2020, Barrientos, L., Borja Lloret, M., Casaña, J. V., Dendooven, P., García López, Francisco Javier, Hueso González, F., Jiménez Ramos, María del Carmen, Pérez Curbelo, J., Ros, A., Roser, J., Senra, C., Viegas, R., Llosá, G., Universidad de Sevilla. Departamento de Física Atómica, Molecular y Nuclear, Ministerio de Ciencia e Innovación (MICIN). España, European Union (UE). H2020, Barrientos, L., Borja Lloret, M., Casaña, J. V., Dendooven, P., García López, Francisco Javier, Hueso González, F., Jiménez Ramos, María del Carmen, Pérez Curbelo, J., Ros, A., Roser, J., Senra, C., Viegas, R., and Llosá, G.

Abstract

Hadron therapy is a radiotherapy modality which offers a precise energy deposition to the tumors and a dose reduction to healthy tissue as compared to conventional methods. However, methods for real-time monitoring are required to ensure that the radiation dose is deposited on the target. The IRIS group of IFIC-Valencia developed a Compton camera prototype for this purpose, intending to image the Prompt Gammas emitted by the tissue during irradiation. The system detectors are composed of Lanthanum (III) bromide scintillator crystals coupled to silicon photomultipliers. After an initial characterization in the laboratory, in order to assess the system capabilities for future experiments in proton therapy centers, different tests were carried out in two facilities: PARTREC (Groningen, The Netherlands) and the CNA cyclotron (Sevilla, Spain). Characterization studies performed at PARTREC indicated that the detectors linearity was improved with respect to the previous version and an energy resolution of 5.2 % FWHM at 511 keV was achieved. Moreover, the imaging capabilities of the system were evaluated with a line source of 68Ge and a point-like source of 241Am-9Be. Images at 4.439 MeV were obtained from irradiation of a graphite target with an 18 MeV proton beam at CNA, to perform a study of the system potential to detect shifts at different intensities. In this sense, the system was able to distinguish 1 mm variations in the target position at different beam current intensities for measurement times of 1800 and 600 s.

Published
2024

16. Tenecteplase versus standard of care for minor ischaemic stroke with proven occlusion (TEMPO-2): a randomised, open label, phase 3 superiority trial

Author

Coutts, Shelagh B, Ankolekar, Sandeep, Appireddy, Ramana, Arenillas, Juan F, Assis, Zarina, Bailey, Peter, Barber, Philip A, Bazan, Rodrigo, Buck, Brian H, Butcher, Ken S, Camden, Marie-Christine, Campbell, Bruce C V, Casaubon, Leanne K, Catanese, Luciana, Chatterjee, Kausik, Choi, Philip M C, Clarke, Brian, Dowlatshahi, Dar, Ferrari, Julia, Field, Thalia S, Ganesh, Aravind, Ghia, Darshan, Goyal, Mayank, Greisenegger, Stefan, Halse, Omid, Horn, Mackenzie, Hunter, Gary, Imoukhuede, Oje, Kelly, Peter J, Kennedy, James, Kenney, Carol, Kleinig, Timothy J, Krishnan, Kailash, Lima, Fabricio, Mandzia, Jennifer L, Marko, Martha, Martins, Sheila O, Medvedev, George, Menon, Bijoy K, Mishra, Sachin M, Molina, Carlos, Moussaddy, Aimen, Muir, Keith W, Parsons, Mark W, Penn, Andrew M W, Pille, Arthur, Pontes-Neto, Octávio M, Roffe, Christine, Serena, Joaquin, Simister, Robert, Singh, Nishita, Spratt, Neil, Strbian, Daniel, Tham, Carol H, Wiggam, M Ivan, Williams, David J, Willmot, Mark R, Wu, Teddy, Yu, Amy Y X, Zachariah, George, Zafar, Atif, Zerna, Charlotte, Hill, Michael D, Salluzzi, Marina, Blenkin, Nicole, Dueck, Ashley, Doram, Craig, Zhang, Qiao, Kenney, Carol, Ryckborst, Karla, Bohn, Shelly, Collier, Quentin, Taylor, Frances, Lethebe, B. Cord, Jambula, Anitha, Sage, Kayla, Toussaint, Lana, Save, Supryia, Lee, Jaclyn, Laham, N, Sultan, A.A., Deepak, A., Sitaram, A., Demchuk, Andrew M., Lockey, A., Micielli, A., Wadhwa, A., Arabambi, B., Graham, B., Bogiatzi, Chrysi, Doshi, Darshan, Chakraborty, D., Kim, Diana, Vasquez, D, Singh, D, Tse, Dominic, Harrison, E., Smith, E.E., Teleg, E., Klourfeld, E., Klein, G., Sebastian, I.A., Evans, J, Hegedus, J, Kromm, J, Lin, K, Ignacio, K, Ghavami, Kimia, Ismail, M., Moores, M., Panzini, M.A., Boyko, M., Almekhlafi, M.A., Newcommon, Nancy, Maraj, N., Imoukhuede, O., Volny, O., Stys, Peter, Couillard, Phillipe, Ojha, P., Eswaradass, P., Joundi, Raed, Singh, R., Asuncion, R.M., Muir, R.T., Dey, S., Mansoor, S., Wasyliw, S., Nagendra, S., Hu, Sherry, Althubait, S., Chen, S., Bal, S., Van Gaal, Stephen, Peters, Steven, Ray, Sucharita, Chaturvedi, S., Subramaniam, Suresh, Fu, Vivian, Villaluna, K., Maclean, G., King-Azote, P., Ma, C., Plecash, A., Murphy, C., Gorman, J., Wilson, L., Zhou, L., Benevente, O., Teal, P., Yip, S., Mann, S., Dewar, B., Demetroff, M., Shamloul, R., Beardshaw, R., Roberts, S., Blaquiere, D., Stotts, G., Shamy, M., Bereznyakova, O., Fahed, R., Alesefir, W., Lavoie, Suzy, Hache, A., Collard, K, Mackey, A., Gosselin-Lefebvre, S., Verreault, S., Beauchamp, B., Lambourn, L., Khaw, A., Mai, L., Sposato, L., Bres Bullrich, M., Azarpazhooh, R., Fridman, S., Kapoor, A., Southwell, A., Bardi, E., Fatakdawala, I., Kamra, M, Lopes, K., Popel, N., Norouzi, V., Liu, A., Liddy, A.M., Ghoari, B., Hawkes, C., Enriquez, C.A., Gladstone, D.J., Manosalva Alzate, H.A., Khosravani, H., Hopyan, J.J., Sivakumar, K., Son, M., Boulos, M.I., Hamind, M.A., Swartz, R.H., Murphy, R., Reiter, S., Fitzpatrick, T., Bhandari, V., Good, J., Penn, M., Naylor, M., Frost, S., Cayley, A., Akthar, F., Williams, J., Kalman, L., Crellin, L., Wiegner, R., Singh, R.S., Stewart, T., To, W., Singh, S., Pikula, A., Jaigobin, C., Carpani, F., Silver, F., Janssen, H., Schaafsma, J., del Campo, M., Alskaini, M., Rajendram, P., Fairall, P., Granfield, B., Crawford, D., Jabs, J., White, L., Sivakumar, L., Piquette, L., Nguyen, T., Nomani, A., Wagner, A., Alrohimi, A., Butt, A., D'Souza, A., Gajurel, B., Vekhande, C., Kamble, H., Kalashyan, H., Lloret, M., Benguzzi, M., Arsalan, N., Ishaque, N., Ashayeriahmadabad, R., Samiento, R., Hosseini, S., Kazi, S., Das, S., Sugumar, T., Selchen, D., Kostyrko, P., Muccilli, A., Saposnik, A.G., Vandervelde, C., Ratnayake, K., McMillan, S., Katsanos, A., Shoamanesh, A., Sahlas, D.J., Naidoo, V., Todorov, V., Toma, H., Brar, J., Lee, J., Horton, M., Chen, S., Shand, E., Weatherby, S., Jin, A., Durafourt, B., Jalini, S., Gardner, A., Tyson, C., Junk, E., Foster, K., Bolt, K., Sylvain, N., Maley, S., Urroz, L., Peeling, L., Kelly, M., Whelan, R., Cooley, R., Teitelbaum, J., Boutayeb, A., Moore, A., Cole, E., Waxman, L., Ben-Amor, N., Sanchez, R., Khalil, S., Nehme, A., Legault, C., Tampieri, D., Ehrensperger, E., Vieira, L., Cortes, M., Angle, M., Hannouche, M., Badawy, M., Werner, K., Wieszmuellner, S., Langer, A., Gisold, A., Zach, H., Rommer, P., Macher, S., Blechinger, S., Marik, W., Series, W., Baumgartinger, M., Krebs, S., Koski, J., Eirola, S., Ivanoff, T., Erakanto, A., Kupari, L., Sibolt, G., Panula, J., Tomppo, L., Tiainen, M., Ahlstrom, M., Martinez Majander, N., Suomalainen, O., Raty, S., Levi, C., Kerr, E., Allen, J., Kaauwai, L.P., Belevski, L., Russell, M., Ormond, S., Chew, A., Loiselle, A., Royan, A., Hughes, B., Garcia Esperon, C., Pepper, E., Miteff, F., He, J., Lycett, M., Min, M., Murray, N., Pavey, N., Starling de Barros, R., Gangadharan, S., Dunkerton, S., Waller, S., Canento Sanchez, T., Wellings, T., Edmonds, G., Whittaker, K.A., Ewing, M., Lee, P., Singkang, R., McDonald, A., Dos Santos, A., Shin, C., Jackson, D., Tsoleridis, J., Fisicchia, L., Parsons, N., Shenoy, N., Smith, S., Sharobeam, A., Balabanski, A., Park, A., Williams, C., Pavlin-Premri, D., Rodrigues, E., Alemseged, F., Ng, F., Zhao, H., Beharry, J., Ng, J.L., Williamson, J., Wong, J.Z.W., Li, K., Kwan, M.K., Valente, M., Yassi, N., Cooley, R., Yogendrakumar, V., McNamara, B., Buchanan, C., McCarthy, C., Thomas, G., Stephens, K., Chung, M., Chung, M.F., Tang, M., Busch, T., Frost, T., Lee, R., Stuart, N., Pachani, N., Menon, A., Borojevic, B., Linton, C.M., Garcia, G., Callaly, E.P., Dewey, H., Liu, J., Chen, J., Wong, J., Nowak, K., To, K., Lizak, N.S., Bhalala, O., Park, P., Tan, P., Martins, R., Cody, R., Forbes, R., Chen, S.K., Ooi, S., Tu, S., Dang, Y.L., Ling, Z., Cranefield, J., Drew, R., Tan, A., Kurunawai, C., Harvey, J., Mahadevan, J.J., Cagi, L., Palanikumar, L., Chia, L.N., Goh, R., El-Masri, S., Urbi, B., Rapier, C., Berrill, H., McEvoy, H., Dunning, R., Kuriakose, S., Chad, T., Sapaen, V., Sabet, A., Shah, D., Yeow, D., Lilley, K., Ward, K., Mozhy Mahizhnan, M., Tan, M., Lynch, C., Coveney, S., Tobin, K., McCabe, J., Marnane, M., Murphy, S., Large, M., Moynihan, B., Boyle, K., Sanjuan, E., Sanchis, M., Boned, S., Pancorbo, O., Sala, V., Garcia, L., Garcia-Tornel, A., Juega, J., Pagola, J., Santana, K., Requena, M., Muchada, M., Olive, M., Lozano, P.J., Rubiera, M., Deck, M., Rodriguez, N., Gomez, B., Reyes Munoz, F.J., Gomez, A.S., Sanz, A.C., Garcia, E.C., Penacoba, G., Ramos, M.E., de Lera Alfonso, M., Feliu, A, Pardo, L., Ramirez, P., Murillo, A., Lopez Dominguez, D., Rodriguez, J., Terceno Izaga, M., Reina, M., Viturro, S.B., Bojaryn, U., Vera Monge, V.A., Silva Blas, Y., R Siew, R., Agustin, S J, Seet, C., Tianming, T., d'Emden, A., Murray, A., Welch, A., Hatherley, K., Day, N., Smith, W., MacRae, E., Mitchell, E.S., Mahmood, A., Elliot, J., Neilson, S., Biswas, V., Brown, C., Lewis, A., Ashton, A., Werring, D., Perry, R., Muhammad, R., Lee, Y.C., Black, A., Robinson, A., Williams, A., Banaras, A., Cahoy, C., Raingold, G., Marinescu, M., Atang, N., Bason, N., Francia, N., Obarey, S., Feerick, S., Joseph, J., Schulz, U., Irons, R., Benjamin, J., Quinn, L., Jhoots, M., Teal, R., Ford, G., Harston, G., Bains, H., Gbinigie, I., Mathieson, P., Irons, R., Sim, C.H., Hayter, E., Kennedy, K., Binnie, L., Priestley, N., Williams, R., Ghatala, R., Stratton, S., Blight, A., Zhang, L., Davies, A., Duffy, H., Roberts, J., Homer, J., Roberts, K., Dodd, K., Cawley, K., Martin, M., Leason, S., Cotgreave, S., Taylor, T., Nallasivan, A., Haider, S., Chakraborty, T., Webster, T., Gil, A., Martin, B., Joseph, B., Cabrera, C., Jose, D., Man, J., Aquino, J., Sebastian, S., Osterdahl, M., Kwan, M., Matthew, M., Ike, N., Bello, P., Wilding, P., Fuentes, R., Shah, R., Mashate, S., Patel, T., Nwanguma, U., Dave, V., Haber, A., Lee, A., O'Sullivan, A., Drumm, B., Dawson, A.C., Matar, T., Biswas, V., Roberts, D., Taylor, E., Rounis, E., El-Masry, A., O'Hare, C., Kalladka, D., Jamil, S., Auger, S., Raha, O., Evans, M., Vonberg, F., Kalam, S., Ali Sheikh, A., Jenkins, I.H., George, J., Kwan, J., Blagojevic, J., Saeed, M., Haji-Coll, M., Tsuda, M., Sayed, M., Winterkron, N., Thanbirajah, N., Vittay, O., Karim, R., Smail, R.C., Gauhar, S., Elmamoun, S., Malani, S., Pralhad Kelavkar, S., Hiden, J., Ferdinand, P., Sanyal, R., Varquez, R., Smith, B., Okechukwu, C., Fox, E., Collins, E., Courtney, K., Tauro, S., Patterson, C., McShane, D., Kerr, E., Roberts, G., McIImoyle, J., McGuire, K., Fearon, P., Gordon, P., Isaacs, K., Lucas, K., Smith, L., Dews, L., Bates, M., Lawrence, S., Heeley, S., Patel, V., Chin, Y.M., Sims, D., Littleton, E., Khaira, J., Nadar, K., Kieliszkowska, A., Sari, B., Domingos Belo, C., Smith, E., Manolo, E.Y., Aeron-Thomas, J., Doheny, M., Garcia Pardo, M., Recaman, M., Tibajia, M.C., Aissa, M., Mah, Y., Yu, T., Patel, V., Meenakshisundaram, S., Heller, S., Alsukhni, R., Williams, O., Farag, M., Benger, M., Engineer, A., Aissa, M., Bayhonan, S., Conway, S., Bhalla, A., Nouvakis, D., Theochari, E., Boyle, F., Teo, J., King-Robson, J., Law, K.Y., Sztriha, L., Ismail, M., McGovern, A., Day, D., Mitchell-Douglas, J., Francis, J., Iqbal, A., Punjabivaryani, P., Anonuevo Reyes, J., Anonuevo Reyes, M., Pauls, M., Buch, A., Hedstrom, A., Hutchinson, C., Kirkland, C., Newham, J., Wilkes, G., Fleming, L., Fleck, N., Franca, A., Chwal, B., Oldoni, C., Mantovani, G., Noll, G., Zanella, L., Soma, M., Secchi, T., Borelli, W., Rimoli, B.P., da Cunha Silva, G.H., Machado Galvao Mondin, L.A., Barbosa Cerantola, R., Imthon, A.K., Esaki, A.S., Camilo, M., Vincenzi, O.C., ds Cruz, R.R., Morillos, M.B., Riccioppa Rodrigues, G.G., Santos Ferreira, K., Pazini, A.M., Pena Pereira, M.A., de Albuquerque, A.L.A., Massote Fontanini, C.E., Matinez Rubio, C.F., dos Santos, D.T., Dias, F.A., Alves, F.F.A., Milani, C., Pegorer Santos, B., Winckler, F., De Souza, J.T., Bonome, L.A.M., Cury Silva, V.A., Teodoro, R.S., Modolo, G.P., Ferreira, N.C., Barbosa dos Santos, D.F., dos Santos Moreira, J.C., Cruz Guedes de Morais, A.B., Vieira, J., Mendes, G., and de Queiroz, J.P.

Abstract

Individuals with minor ischaemic stroke and intracranial occlusion are at increased risk of poor outcomes. Intravenous thrombolysis with tenecteplase might improve outcomes in this population. We aimed to test the superiority of intravenous tenecteplase over non-thrombolytic standard of care in patients with minor ischaemic stroke and intracranial occlusion or focal perfusion abnormality.

Published
2024
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18. From MACACOp to FALCON, characterization and in-beam tests

Author

Viegas, R., primary, Barrientos, L., additional, Borja-Lloret, M., additional, Brzezinski, K., additional, Casaña, J. V., additional, Hueso-González, F., additional, Mazal, A., additional, Pérez-Curbelo, J., additional, Ros, A., additional, Roser, J., additional, Senra, C., additional, Vera-Sánchez, J.A., additional, and Llosá, G., additional

Published
2023
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20. Improvement studies of Compton cameras over gamma cameras in nuclear medicine treatments

Author

Roser, J., primary, Barrientos, L., additional, Bello, P., additional, Borja-Lloret, M., additional, Calatayud, J. M., additional, Casaña, J. V., additional, Hueso-González, F., additional, Lozano, P., additional, Pérez-Curbelo, J., additional, Prado, S., additional, Ros, A., additional, Senra, C., additional, Viegas, R., additional, Torres-Espallardo, I., additional, and Llosá, G., additional

Published
2023
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26. Characterization of a Compton Camera Based on the TOFPET2 ASIC

Author

Universidad de Sevilla. Departamento de Física Atómica, Molecular y Nuclear, Universidad de Sevilla. Departamento de Física Aplicada II, Generalitat Valenciana. España, Ministerio de Ciencia e Innovación (MICIN). España, Viegas, R., Roser, J., Barrientos, L., Borja Lloret, M., Casaña, J. V., García López, Francisco Javier, Jiménez Ramos, María del Carmen, Hueso González, F., Ros, A., Llosá, G., Universidad de Sevilla. Departamento de Física Atómica, Molecular y Nuclear, Universidad de Sevilla. Departamento de Física Aplicada II, Generalitat Valenciana. España, Ministerio de Ciencia e Innovación (MICIN). España, Viegas, R., Roser, J., Barrientos, L., Borja Lloret, M., Casaña, J. V., García López, Francisco Javier, Jiménez Ramos, María del Carmen, Hueso González, F., Ros, A., and Llosá, G.

Abstract

The use of Compton cameras for medical imaging and its interest as a hadron therapy treatment monitoring has increased in the last decade with the development of silicon photomultipliers. MACACOp is a Compton camera prototype designed and assembled at the IRIS group of IFIC-Valencia. This Compton camera is based on monolithic Lanthanum (III) Bromide crystals and silicon photomultipliers, and employs the novel TOFPET2 ASIC as readout electronics. This system emerged as an alternative to MACACO II prototype, with the aim of improving its limited time resolution. To test the performance of the ASIC in a Compton camera setup, the prototype was characterized, both in laboratory and in-beam. A time resolution of 1.5 ns was obtained after time corrections, which improves greatly the performance of the MACACO II. Moreover, the results obtained at high photon energies demonstrate the ability of the system to obtain 1 mm displacements of the reconstructed spots. The results reinforce the potential of the system as a monitoring device for hadron therapy.

Published
2023

30. Enhancing CO2 plasma conversion using metal grid catalysts.

Author

Devid, E. J., Ronda-Lloret, M., Zhang, D., Schuler, E., Wang, D., Liang, C.-H., Huang, Q., Rothenberg, G., Shiju, N. R., and Kleyn, A. W.

Subjects
*METAL catalysts, *PLASMA chemistry, *METAL mesh, *CHEMICAL reactions, *CHEMICAL yield
Abstract

The synergy between catalysis and plasma chemistry often enhances the yield of chemical reactions in plasma-driven reactors. In the case of CO2 splitting into CO and O2, no positive synergistic effect was observed in earlier studies with plasma reactors, except for dielectric barrier discharges, that do not have a high yield and a high efficiency. Here, we demonstrate that introducing metal meshes into radio frequency-driven plasma reactors increases the relative reaction yield by 20%–50%, while supported metal oxide catalysts in the same setups have no effect. We attribute this to the double role of the metal mesh, which acts both as a catalyst for direct CO2 dissociation as well as for oxygen recombination. [ABSTRACT FROM AUTHOR]

Published
2021
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33. The Role of Vacancies in a Ti 2 CT x MXene‐Derived Catalyst for Butane Oxidative Dehydrogenation

Author

Ronda-Lloret, M., Slot, T. K., van Leest, N. P., de Bruin, B., Sloof, W.G., Batyrev, E., Sepúlveda-Escribano, A., Ramos-Fernandez, E. V., Rothenberg, G., Shiju, N. R., Universidad de Alicante. Departamento de Química Inorgánica, Universidad de Alicante. Instituto Universitario de Materiales, Materiales Avanzados, HCSC+ (HIMS, FNWI), and Homogeneous and Supramolecular Catalysis (HIMS, FNWI)

Subjects
Inorganic Chemistry, Química Inorgánica, Oxygen vacancy, TiO, Organic Chemistry, TiO2, Defects, Lower olefins, Physical and Theoretical Chemistry, MXene, Catalysis
Abstract

MXenes are a new family of 2D carbides or nitrides that have attracted attention due to their layered structure, tunable surface groups and high electrical conductivity. Here, we report for the first time that Ti 2 CT x MXene catalyses the selective oxidative dehydrogenation of n -butane to butenes and 1,3-butadiene. This catalyst showed higher intrinsic activity compared to commercial TiC and TiO 2 samples in terms of C 4 olefin formation rate. We propose that the stabilisation of structural vacancies and the change in composition (from a carbide to a mixed phase oxide) in the MXene causes its higher catalytic activity. These vacancies can lead to a higher concentration of unpaired electrons in the MXene-derived material, enhancing its nucleophilic properties and favouring the production of olefins. We thank the Netherlands Organization for Scientific Research (NWO) for the grant “Developing novel catalytic materials for converting CO2, methane and ethane to high-value chemicals in a hybrid plasma-catalytic reactor” (China.15.119). EVRF thanks the “Ministerio de Ciencia e innovación” grant (PID2020-116998RB-I00).

Published
2022

36. The Role of Vacancies in a Ti2CTx MXene-Derived Catalyst for Butane Oxidative Dehydrogenation

Author

Ronda-Lloret, M. (author), Slot, T. K. (author), van Leest, N. P. (author), de Bruin, B. (author), Sloof, W.G. (author), Batyrev, E. (author), Sepúlveda-Escribano, A. (author), Ramos-Fernandez, E. V. (author), Rothenberg, G. (author), Shiju, N. R. (author), Ronda-Lloret, M. (author), Slot, T. K. (author), van Leest, N. P. (author), de Bruin, B. (author), Sloof, W.G. (author), Batyrev, E. (author), Sepúlveda-Escribano, A. (author), Ramos-Fernandez, E. V. (author), Rothenberg, G. (author), and Shiju, N. R. (author)

Abstract

MXenes are a new family of 2D carbides or nitrides that have attracted attention due to their layered structure, tunable surface groups and high electrical conductivity. Here, we report for the first time that the Ti2CTx MXene catalyses the selective oxidative dehydrogenation of n-butane to butenes and 1,3-butadiene. This catalyst showed higher intrinsic activity compared to a commercial TiC and TiO2 samples in terms of C4 olefin formation rate. We propose that the stabilisation of structural vacancies and the change in composition (from a carbide to a mixed phase oxide) in the MXene causes its higher catalytic activity. These vacancies can lead to a higher concentration of unpaired electrons in the MXene-derived material, enhancing its nucleophilic properties and favouring the production of olefins., Team Jilt Sietsma

Published
2022
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37. Virtual worlds and second language acquisition.

Author

LS Spaanse letterkunde en cultuur, ICON - Modern and Contemporary Literature, ILS L&E, Jauregi Ondarra, Kristi, Canto, Silvia, Melchor-Couto, S., Ziegler, N., González-Lloret, M., LS Spaanse letterkunde en cultuur, ICON - Modern and Contemporary Literature, ILS L&E, Jauregi Ondarra, Kristi, Canto, Silvia, Melchor-Couto, S., Ziegler, N., and González-Lloret, M.

Published
2022

39. Virtual worlds and second language acquisition

Author

Jauregi Ondarra, Kristi, Canto, Silvia, Melchor-Couto, S., Ziegler, N., González-Lloret, M., LS Spaanse letterkunde en cultuur, ICON - Modern and Contemporary Literature, and ILS L&E

Published
2022

40. Estudio del valor pronóstico de los receptores catecolaminérgicos en cáncer de endometrio : contribución a la progresión tumoral

Author

Español Lloret, M. Pia, Céspedes Navarro, María Virtudes, Porta Roda, Oriol, and Llurba Olivé, Elisa

Subjects
Oncologia, Oncology, Endometrial cancer, Càncer d'endometri, Cáncer de endometrio, Receptores catecolaminérgicos, Catecholaminergic receptors, Receptors catecolaminèrgics, Ciències de la Salut, Oncología
Abstract

El càncer d'endometri és la neoplàsia ginecològica més freqüent a la nostra població. La majoria de pacients són diagnosticades en estadis inicials i tenen pronòstics favorables. Tot i així, un percentatge de pacients situat entre un 10% i un 20%, poden presentar recidives o diagnosticar-se en fases més avançades de la neoplàsia, per tant, la investigació en aquesta patologia ha centrar-se en desenvolupar noves estratègies per precisar el pronòstic i millorar les opcions terapèutiques. Les catecolamines, que intervenen com a neurotransmissors en resposta a l'estrès físic o emocional, s'han perfilat com un dels principals mediadors de la relació entre l'estrès crònic i la progressió del càncer. El treball que es planteja en aquesta tesi doctoral sorgeix de la investigació amb mostres de pacients, amb models in vivo i amb línies cel·lulars de càncer d'endometri per tal de caracteritzar el paper dels receptors catecolaminèrgics en la progressió d'aquest tipus tumoral. L'anàlisi dels nivells d'expressió a nivell de ARNm per als diferents subtipus de receptors catecolaminèrgics, associat a la revisió de resultats de la literatura, ha permès escollir ADRβ2, DRD1 i DRD2 com a principals dianes a ser avaluades mitjançant la tècnica immunohistoquímica. Les nostres dades suggereixen que el receptor adrenèrgic ADRβ2 no determina el pronòstic de les pacients avaluades, a diferència del que s'ha descrit en altres neoplàsies. Per la seva banda DRD1 presenta una expressió reduïda al tumor respecte al teixit endometrial sa. L'anàlisi de l'associació del receptor amb les variables clinico-patològiques suggereix que la seva expressió podria tenir una relació inversa en referència a la mida del tumor i a l'estadi tumoral. Finalment, l'anàlisi de DRD2 s'associa significativament al tipus histològic de càncer d'endometri no endometrioide, a tumors d'alt grau histològic i també a una pitjor supervivència lliure de malaltia i global en la cohort de pacients estudiada. A més, hem establert dos models xenògrafs derivats de mostres de pacient implantats a nivell ortotòpic en ratolí. Aquests models presenten una major rellevància traslacional i clínica. El model generat a partir del tumor END 17 presenta una progressió més ràpida i un pes mitjà tumoral final superior al model END 19, alhora que una supervivència menor; definint-se per tant com un potencial model de CE agressiu. A més, s'ha confirmat en tots dos models la conservació de les característiques del tumor original a partir del perfil immunohistoquímic i del patró d'expressió dels receptors catecolaminèrgics al tumor generat. D'altra banda, l'experimentació in vitro ens ha permès avaluar l'efecte de la neuromodulació de les vies de senyalització adrenèrgica i dopaminèrgica en línies cel·lulars representatives de CE i la seva potencial utilització en teràpia antitumoral. La combinació de l'agonisme de DRD1 i de l'antagonisme de DRD2 ha induït una reducció significativament superior en la capacitat de proliferació cel·lular de la línia AN3CA, comparat amb el seu tractament en monoteràpia, representant una nova estratègia terapèutica. La informació obtinguda en aquest projecte aporta a la comunitat científica nou coneixement sobre el paper dels receptors catecolaminèrgics en càncer d'endometri. La seva aplicació a nivell pronòstic i/o terapèutic podria contribuir a millorar el maneig clínic de les pacients que el pateixen. A partir d'aquest punt, es poden definir dues vies d'actuació. En primer lloc, prosseguir l'experimentació per caracteritzar més detalladament, la contribució nerviosa al microentorn tumoral i els mecanismes implicats en aquesta contribució. En segon lloc, avaluar l'efectivitat terapèutica de la combinació d'agonistes i antagonistes a nivell preclínic, i valorar el reposicionament d'alguns fàrmacs ja aprovats i que podrien tenir noves aplicacions a nivell oncològic. El cáncer de endometrio (CE) es la neoplasia ginecológica más frecuente en nuestra población. La mayoría de pacientes son diagnosticadas en estadios tempranos y tienen pronósticos favorables. Aun así, un porcentaje de pacientes situado entre un 10% y un 20%, pueden presentar recidivas o diagnosticarse en fases más avanzadas de la neoplasia, por lo que la investigación en esta patología debe colaborar en el desarrollo de nuevas estrategias para precisar el pronóstico y las opciones terapéuticas. Las catecolaminas, que intervienen como neurotransmisores en respuesta al estrés físico o emocional, se han perfilado como uno de los principales mediadores de la relación entre el estrés crónico y la progresión del cáncer. El trabajo que se plantea en esta tesis doctoral surge de la investigación con muestras de pacientes, modelos in vivo y líneas celulares de cáncer de endometrio con el objetivo de caracterizar el papel de los receptores catecolaminérgicos en la progresión de este tipo tumoral. El análisis de los niveles de expresión a nivel de ARNm para los distintos subtipos de receptores catecolaminérgicos, asociado a la revisión de resultados de la literatura, ha permitido escoger ADRβ2, DRD1 y DRD2 como principales dianas a evaluar por la técnica inmunohistoquímica. Nuestros datos sugieren el receptor adrenérgico ADRβ2 no determina el pronóstico de las pacientes evaluadas, a diferencia de lo que se ha descrito en otras neoplasias. Por su parte DRD1 presenta una expresión reducida en el tumor con respecto al tejido endometrial sano. El análisis de la asociación del receptor con las variables clínico-patológicas sugiere que su expresión podría tener una relación inversa en referencia al tamaño y al estadio tumoral. Finalmente, el análisis de DRD2, se asocia significativamente al tipo histológico de cáncer de endometrio no endometrioide, a tumores de alto grado histológico y también a una peor supervivencia libre de enfermedad y global en la cohorte de pacientes estudiada. Además, hemos establecido dos modelos xenógrafos derivados de muestras de paciente implantados a nivel ortotópico en ratón. Estos modelos presentan una mayor relevancia traslacional y clínica. El modelo generado a partir del tumor END 17 presenta una progresión más rápida y un peso medio tumoral final superior al modelo END 19, a la vez que una supervivencia menor; definiéndose como potencial modelo de CE agresivo. Además, se ha confirmado en ambos modelos la conservación de las características del tumor original a partir del perfil inmunohistoquímico y del patrón de expresión de los receptores catecolaminérgicos en el tumor generado. Por otra parte, la experimentación in vitro, nos ha permitido evaluar el efecto de la neuromodulación de las vías de señalización adrenérgica y dopaminérgica en líneas celulares representativas de CE, y su potencial utilización en terapia antitumoral. La combinación del agonismo de DRD1 y del antagonismo de DRD2 ha inducido una reducción significativamente mayor en la capacidad de proliferación celular de la línea AN3CA, comparado con su tratamiento en monoterapia, representando una novedosa estrategia terapéutica. La información obtenida de este proyecto aporta a la comunidad científica nuevo conocimiento sobre el papel de los receptores catecolaminérgicos en cáncer de endometrio. Su aplicación a nivel pronóstico y/o terapéutico, podría contribuir a mejorar el manejo clínico de las pacientes. A partir de este punto, se pueden definir dos vías de actuación. En primer lugar, proseguir la experimentación para caracterizar más en detalle, la contribución nerviosa al microentorno tumoral y los mecanismos implicados en dicha contribución. En segundo lugar, evaluar la efectividad terapéutica de la combinación de agonistas y antagonistas a nivel preclínico, y valorar el reposicionamiento de algunos fármacos ya aprobados que podrían tener nuevas aplicaciones a nivel oncológico. Endometrial cancer is the most common gynecologic malignancy in our population. Most patients are diagnosed in early stages and have favorable prognoses. However, somewhere between 10% and 20% of those patients may present recurrences or be diagnosed in more advanced stages. Therefore, researchers must make a concerted effort to develop new strategies to optimize the prognosis and offer new therapeutic options for this pathology. Catecholamines, which act as neurotransmitters in response to physical or emotional stress, have emerged as one of the main mediators of the relationship between chronic stress and cancer progression. There are data suggesting that tumor cells use neurotransmitters and their neuroreceptors to activate the mechanisms of tumor growth and metastasis via nerve fibers that are part of the so-called tumor microenvironment. The project proposed in this doctoral thesis arises from research based on patient samples, in vivo models and established cell lines of endometrial cancer to characterize the role of catecholaminergic receptors in the progression of this tumor. The analysis of the mRNA expression levels for the different subtypes of catecholaminergic receptors along with the results seen in a review of the literature, has made it possible to choose ADRβ2, DRD1 and DRD2 as the main targets to be evaluated by means of the immunohistochemical technique. Our data suggest that ADRβ2 does not determine the prognosis of the patients evaluated, unlike what has been described in other tumor types. On the other hand, DRD1 has a reduced expression in the tumor tissue compared to healthy endometrial tissue. The analysis of the association of the receptor with clinicopathological variables suggests that its expression may have an inverse relationship with tumor size and stage. Finally, DRD2 expression analysis is significantly associated with non-endometrioid endometrial cancer, high grade FIGO classification tumors and worse disease-free and overall survival in the cohort of patients studied. In addition, we have established two patient-derived xenograft models from patient samples implanted orthotopically in mice. These models have greater translational and clinical relevance. Initially, its viability as well as its capacity for tumor implantation and dissemination have been verified. The model generated from the END 17 tumor shows a more rapid progression and a greater tumor weight as well as shorter survival than the END 19 model, thereby defining itself as a potential model of aggressive endometrial cancer. In addition, the conservation of the characteristics of the original tumor has been confirmed in both models based on the immunohistochemical profile and the expression pattern of the catecholaminergic receptors in the generated tumor. In the end, in vitro experimentation has made it possible to evaluate the effect of neuromodulation of adrenergic and dopaminergic signaling pathways in cell lines representative of EC and its potential use in antitumor therapy. The combination of DRD1 agonism and DRD2 antagonism induce a significantly greater reduction in the cell proliferation capacity of the AN3CA cell line, compared to its monotherapy treatment, representing a new therapeutic strategy. The information obtained from this project provides new knowledge to the scientific community on the role of catecholaminergic receptors play in endometrial cancer. Its application as a prognostic and/or therapeutic tools may well contribute to improving the clinical management of affected patients. From this point, two courses of action can be defined. First, continued experimentation to further characterize the nervous contribution to the tumor microenvironment and the mechanisms involved in endometrial cancer is called for. Second, there is a need to evaluate the therapeutic effectiveness of the combination of agonists and antagonists at a preclinical level and to assess the repositioning of some drugs already approved that might have new applications for oncological treatment.

Published
2022

42. Comparison of efficiency and activity recovery coefficients of Compton and Anger cameras in Nuclear Medicine

Author

Etxebeste, Ane, Muñoz, Enrique, Dauvergne, Denis, Letang, J M, Borja-Lloret, M., Llosá, G, Maxim, Voichita, Sarrut, David, Testa, Etienne, Imagerie Tomographique et Radiothérapie, Centre de Recherche en Acquisition et Traitement de l'Image pour la Santé (CREATIS), Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Jean Monnet [Saint-Étienne] (UJM)-Hospices Civils de Lyon (HCL)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Laboratoire de Physique Subatomique et de Cosmologie (LPSC), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes (UGA)-Institut polytechnique de Grenoble - Grenoble Institute of Technology (Grenoble INP ), and Université Grenoble Alpes (UGA)

Subjects
[PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2021

43. Efficiency enhancement studies in a scintillator-based Compton camera for hadrontherapy

Author

Borja-Lloret, M., Etxebeste, A., Llosá, G., Muñoz, Enrique, Ros, Ana, Testa, Etienne, Instituto de Fisica Corpuscular (IFIC), Consejo Superior de Investigaciones Científicas [Madrid] (CSIC)-Universitat de València (UV), Institut de Physique des 2 Infinis de Lyon (IP2I Lyon), Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), and Etxebeste, Ane

Subjects
[PHYS.PHYS.PHYS-MED-PH] Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [PHYS.PHYS.PHYS-MED-PH]Physics [physics]/Physics [physics]/Medical Physics [physics.med-ph], [INFO.INFO-MO] Computer Science [cs]/Modeling and Simulation, [INFO.INFO-MO]Computer Science [cs]/Modeling and Simulation, ComputingMilieux_MISCELLANEOUS
Abstract

International audience

Published
2021

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