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2. Hippocampal Sparing Radiotherapy in adults with Primary Brain Tumors: A comparative planning and dosimetric study using IMPT, IMRT and 3DCRT
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Aka, P, Taylor, R, Hugtenburg, R, Lambert, J, Powell, J, Bevolo, T, Gao, M, Gondi, V, Hartsell, W.H, Bolsi, A, Beer, J, Belosi, M.F, Siewert, D, Lomax, A.J, Weber, D.C, Huang, Y.J, Huang, C.C, Chao, P.J, Liu, C, Shang, H, Ding, X, Wang, Y, Mammar, H, Froelich, Sébastien, Alapetite, Claire, Bolle, Stéphanie, Calugaru, Valentin, Feuvret, Loic, Helfre, Sylvie, Champion, Laurence, Goudjil, Farid, Dendal, Remi, Engelholm, S.A, Munck Af Rosenschold, P, Kristensen, I, Smulders, B, Muhic, A, Alkner, S, Jacob, E, Engelholm, S, Aljabab, S, Lui, A, Wong, T, Liao, J, Laramore, G, Parvathaneni, U, Kharouta, M, Pidikiti, R, Jesseph, F, Smith, M, Dobbins, D, Mattson, D, Choi, S, Mansur, D, Machtay, M, Bhatt, A, Lütgendorf-Caucig, C, Dunavölgyi, R, Georg, P, Perpar, A, Fussl, C, Konstantinovic, R, Ulrike, M, Piero, F, Eugen, H, Vidal, M, Gerard, A, Barnel, C, Maneval, D, Herault, J, Claren, A, Doyen, J, Dendale, R, Toutee, A, Pasquie, I, Goudjil, F, Lumbroso Lerouic, L, Levy, C, Desjardins, L, 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Rucinski, A, Olko, P, Badzio, A, Kopec, R, Franceschini, D, Cozzi, L, De Rose, F, Meattini, I, Fogliata, A, Cozzi, S, Becherini, C, Tomatis, S, Livi, L, Scorsetti, M, Garda, A, Fattahi, S, Michel, A, Mutter, R, Yan, E, Park, S, Corbin, K, Giap, H, LAM, W.W, Geng, H, Tang, K.K, Lee, T.Y, Kong, C.W, Yang, B, Chiu, T.L, Cheung, K.Y, Yu, S.K, Ma, M, Gao, X, Zhao, Z, Zhao, B, Mullikin, T, Routman, D, Yu, J, Greco, K, Fagundes, M, Shan, J, Daniels, T, Rule, W, DeWees, T, Hu, Y, Bues, M, Sio, T, Liu, W, chenbin, L, yuehu, P, yuenan, W, Bai, Y, Gao, X.S, Zhao, Z.L, Ma, M.W, Ren, X.Y, Salem, A, Woolf, D, Aznar, M, Azadeh, A, Eccles, C, Charlwood, F, Faivre-Finn, C, Teoh, S, Fiorini, F, George, B, Vallis, K, Van den Heuvel, F, Huang, E.Y, Juang, P.J, Pan, S, Hawkins, M, Clarke, M, Lowe, M, Radhakrishna, G, Schaub, S, Bowen, S, Nyflot, M, Chapman, T, Apisarnthanarax, S, Vitek, P, Kubes, J, Vondracek, V, Vinakurau, S, Zamecnik, L, Vitolo, V, Barcellini, A, Brugnatelli, S, Cobianchi, L, Vanoli, A, 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R, Bradley, J, Lockney, N, Macdonald, S, Liang, X, Mazal, A, Mendenhall, N, Sher, D, Korreman, S.S, Andreasen, S, Petersen, J.B, Offersen, B.V, Gergelis, K, Jethwa, K, Whitaker, T, Shiraishi, S, Shumway, D, Press, R, Shelton, J, Zhang, C, Dang, Q, Tian, S, Shu, T, Seldon, C, Jani, A, Zhou, J, McDonald, M, Gort, E, Beukema, J.C, Spijkerman-Bergsma, M.J, Both, S, Langendijk, J.A, Matysiak, W.P, Brouwer, C.L, Baba, K, Numajiri, H, Murofushi, K, Oshiro, Y, Mizumoto, M, Onishi, K, Nonaka, T, Ishikawa, H, Okumura, T, Dominietto, M, Adam, K, Ahlhelm, F.J, Safai, S, Abdul-Jabbar, L, Song, J, Tseng, Y. D, Rockhill, J, Fink, J, Chang, L, Halasz, L. 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Choy, H, Miyashiro, I, Bush, D, Chuong, M, Kozarek, J, Rubens, M, Larson, G, Vargas, C, Hung, S.P, Hsieh, C.E, Huang, B.S, Tsang, N.M, Smith, N, Viehman, J, Harmsen, W, Elswick, S, Boughey, J, Harless, C, Jimenez, R, Hickey, S, DePauw, N, Ho, A, Taghian, A, MacDonald, S, Meek, A, Hedrick, S, Baliga, S, Gallotto, S, Lewy, J, Patteson, B, Speroni, S, Omsberg, A, Tarbell, N, Musolino, P, Yock, T, Indelicato, D, Rotondo, R, Mailhot, R, Uezono, H, Bradfield, S, Agarwal, V, Gillies, C, Gosling, A, Casares-Magaz, O, Eskildsen, S.F, Lassen, Y, Hasle, H, Tofting-Olesen, K, Alapetite, C, Puget, S, Nauraye, C, Beccaria, K, Bolle, S, Doz, F, Sainte-Rose, C, Bouffet, E, Zerah, M, Wu, J, Qiu, X, Hua, W, Mao, Y, Frakulli, R, Kramer, P.H, Glas, M, Blase, C, Tippelt, S, Konrath, L, Gruber, N, Schallerbauer-Peter, A, Mock, U, Niyazi, M, Niemierko, A, Schapira, E, Kim, V, Oh, K.S, Hwang, W.L, Busse, P.M, Loeffler, J.S, Shih, H.A, Appel, H, Tseng, Y.D, Tsai, H, Sinesi, C, Rossi, C, Badiyan, S, Kotecha, R, Pike, L, Horick, N, Yeap, B, Franck, K, Wang, I, Loeffler, J, McKenna, M, Shih, H, Kountouri, M, Kole, A.J, Murray, F.R, Kliebsch, U, Combescure, C, iannalfi, A, Riva, G, Dougherty, J, Kruse, J, Iott, M, Brown, P, Olivier, K, Brodin, P, Kabarriti, R, Schechter, C, Kalnicki, S, Garg, M, Tomé, W, Lu, J.J, Chen, P.J, Dhanireddy, B, Severo, C, Lee, C.H, Lin, C.R, Rosier, L, Mathis, T, DeLaney, T, Lin, S, O’Meara, E, Powell, T, Hong, T, Hall, D, Liu, A, Ntentas, G, Dedeckova, K, Darby, S, Cutter, D, Zapletalova, S, Chen, Y.L, Miao, R, Lee, H, Hsiao-Ming, L, Choy, E, Cote, G, Eulitz, J, Lutz, B, Enghardt, W, Lühr, A, Mcmahon, S, Prise, K, Sung Hyun, L, Tansho, R, Mizushima, K, Warmenhoven, J.W, Hufnagl, A, Friedrich, T, Deycmar, S, Gruber, S, Dörr, W, Pruschy, M, Waissi, W, Burckel, H, Nicol, A, Noel, G, Yousef, I, Koizumi, M, Santa Cruz, G.A, González, S.J, Longhino, J, Provenzano, L, Oña, P, Rao, M, Cantarelli, M.D.L.Á, Leiras, A, Olivera, M.S, Alessandrini, P, Brollo, F, Boggio, E, Costa, H, Ventimiglia, R, Binia, S, Nievas, S.I, Langle, Y, Eijan, A.M, Colombo, L.L, Kawai, K, Nakamura, H, Natsuko, K, Masaki, H, Nakada, M, Furuse, M, Miyatake, S.I, Koivunoro, H, Kankaanranta, L, González, S, Joensuu, H, Sokol, O, Hild, S, Wiedemann, J, Köthe, A, Perry, D, Batie, M, Mascia, A, Sertorio, M, Luhr, A, Suckert, T, Müller, J, Beyreuther, E, Gotz, M, Haase, R, Schürer, M, Tillner, F, von Neubeck, C, Davis, A, Sishc, B, Saha, J, Ding, L, Story, M, Wagner, S, Kim, S.Y, Geary, S, Woodruff, T, Xu, T, Meng, Q, Gilchrist, S, Perentesis, J.P, Zheng, Y, Wells, S.I, Kong, Y, Liu, Y, Geng, Y, Knoll, M, Schwager, C, Schlegel, J, Schnölzer, M, Ding, L.H, Aroumougame, A, Chen, B, Saha, D, Pompos, A, Carter, R, Nickson, C, Thomson, J, Hill, M, Rodrigues, D, Snider, J, Sharma, A, Zakhary, M, Kara, L, Vujaskovic, Z, Dykstra, M, Best, T, Keane, F, Khandekar, M, Fintelmann, F, Willers, H, Singh, P, Eley, J, Malyapa, R, Mahmood, J, Hårdemark, B, Sandison, G.A, Wootton, L.S, Miyoaka, R.S, Laramore, G.E, Yang, P, van der Weide, H, Maduro, J, Heesters, M, Gawryszuk, A, Davila-Fajardo, R, Langendijk, H, Eckhard, M, Maxwell, A, VanNamen, K, Cashin, M, Jacovic, A, Dunn, M, kim, T, Jung, J, Kim, J, Swerdloff, S, Saunders, A, Thomas, J, Kidani, T, Okada, A, Tomida, K, Pennington, H, Xiaoqiang, L, Weigang, H, An, Q, Di, Y, Craig, S, Inga, G, Peyman, K, Xuanfeng, D, Cunningham, C, de Kock, M, Slabbert, J, Panaino, C.M, Phoenix, B, Regan, P.H, Shearman, R, Collins, S.M, Taylor, M.J, Grayson, M, Kato, K, Choi, H, Jang, J.W, Shin, W.G, Min, C.H, McMahon, S, Padilla Cabal, F, Fragoso, J.A, Resch, A.F, Katsis, A, Girdhani, S, Marshall, A, Jackson, I, Bentzen, S, Parry, R, Gantz, S, Schellhammer, S, Hoffmann, A, Delorme, R, Dos Santos, M, Salmon, R, Öden, J, Bullivant, K, Rucksdashal, R, Ferret, E, Covington, F, Rice, S, Decesaris, C, Siddiqui, O, Kowalski, E, Samanta, S, and Rothwell, B
- Subjects
Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0642 ,Physics: Absolute and Relative DosimetryPTC58-0180 ,Biology: Biology and Clinical InterfacePTC58-0685 ,Physics: Commissioning New FacilitiesPTC58-0385 ,Physics: 4D Treatment and DeliveryPTC58-0546 ,Clinics: EyePTC58-0714 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0528 ,Physics: Quality Assurance and VerificationPTC58-0507 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0661 ,Biology: Translational and Biomarkers Poster Discussion SessionsPTC58-0221 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0531 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0653 ,Biology: Drug and Immunotherapy CombinationsPTC58-0163 ,Clinics: Sarcoma - LymphomaPTC58-0055 ,Biology: Drug and Immunotherapy CombinationsPTC58-0166 ,Clinics: CNS / Skull BasePTC58-0198 ,Physics: Treatment PlanningPTC58-0421 ,Clinics: PediatricsPTC58-0560 ,General: New HorizonsPTC58-0709 ,Physics: Treatment PlanningPTC58-0664 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0286 ,Physics: Treatment PlanningPTC58-0666 ,Biology: Translational and Biomarkers Poster Discussion SessionsPTC58-0346 ,Physics: Treatment PlanningPTC58-0547 ,Physics: Treatment PlanningPTC58-0308 ,Physics: Treatment PlanningPTC58-0549 ,Physics: Beam Delivery and Nozzle Design Poster Discussion SessionsPTC58-0111 ,Physics: Absolute and Relative DosimetryPTC58-0050 ,Biology: Enhanced Biology in Treatment Planning Poster Discussion SessionsPTC58-0587 ,Biology: Biology and Clinical InterfacePTC58-0454 ,Physics: Absolute and Relative DosimetryPTC58-0052 ,Physics: Commissioning New FacilitiesPTC58-0395 ,Physics: 4D Treatment and DeliveryPTC58-0534 ,Physics: Dose Calculation and OptimisationPTC58-0072 ,Physics: 4D Treatment and DeliveryPTC58-0533 ,Physics: 4D Treatment and DeliveryPTC58-0538 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0113 ,Physics: Quality Assurance and VerificationPTC58-0633 ,Physics: Treatment PlanningPTC58-0431 ,Physics: Beam Delivery and Nozzle DesignPTC58-0230 ,Biology: Mathematical Modelling SimulationPTC58-0179 ,Clinics: Head and Neck / EyePTC58-0365 ,Physics: Treatment PlanningPTC58-0319 ,Biology: Translational and Biomarkers Poster Discussion SessionsPTC58-0697 ,Biology: Biology and Clinical InterfacePTC58-0663 ,Physics: Commissioning New FacilitiesPTC58-0240 ,Physics: Adaptive TherapyPTC58-0177 ,Physics: Commissioning New FacilitiesPTC58-0363 ,Physics: Commissioning New FacilitiesPTC58-0487 ,Physics: 4D Treatment and DeliveryPTC58-0209 ,Physics: 4D Treatment and DeliveryPTC58-0206 ,Clinics: CNS / Skull BasePTC58-0294 ,Physics: Commissioning New FacilitiesPTC58-0127 ,Biology: Mathematical Modelling SimulationPTC58-0068 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0062 ,Physics: 4D Treatment and DeliveryPTC58-0692 ,Physics: Quality Assurance and VerificationPTC58-0723 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0494 ,Physics: Treatment PlanningPTC58-0643 ,Physics: Treatment PlanningPTC58-0521 ,Physics: Treatment PlanningPTC58-0402 ,Physics: Treatment PlanningPTC58-0405 ,Clinics: Head and Neck / EyePTC58-0273 ,Clinics: GIPTC58-0397 ,Physics: Treatment PlanningPTC58-0648 ,Biology: Enhanced Biology in Treatment Planning Poster Discussion SessionsPTC58-0489 ,Physics: Quality Assurance and VerificationPTC58-0617 ,Physics: Quality Assurance and VerificationPTC58-0616 ,Physics: Dose Calculation and Optimisation Poster Discussion SessionsPTC58-0668 ,Clinics: CNS / Skull BasePTC58-0188 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0625 ,Physics: Treatment PlanningPTC58-0654 ,Physics: Treatment PlanningPTC58-0655 ,Biology: Drug and Immunotherapy Combinations Poster Discussion SessionsPTC58-0133 ,Clinics: PediatricsPTC58-0313 ,Physics: Treatment PlanningPTC58-0659 ,Poster AbstractsClinics: CNSPTC58-0290 ,Physics: Commissioning New FacilitiesPTC58-0064 ,Physics: Adaptive TherapyPTC58-0396 ,Physics: Dose Calculation and OptimisationPTC58-0281 ,Physics: Quality Assurance and VerificationPTC58-0427 ,Physics: Quality Assurance and VerificationPTC58-0669 ,General: New Horizons SessionPTC58-0191 ,Physics: Dose Calculation and Optimisation Poster Discussion SessionsPTC58-0217 ,Physics: Quality Assurance and VerificationPTC58-0303 ,Physics: Quality Assurance and VerificationPTC58-0665 ,Clinics: Sarcoma - LymphomaPTC58-0495 ,Physics: Dose Calculation and OptimisationPTC58-0398 ,Physics: Quality Assurance and VerificationPTC58-0667 ,Physics: Quality Assurance and VerificationPTC58-0425 ,Physics: Quality Assurance and VerificationPTC58-0541 ,Physics: Treatment PlanningPTC58-0584 ,Physics: Quality Assurance and VerificationPTC58-0540 ,Biology: Drug and Immunotherapy Combinations Poster Discussion SessionsPTC58-0163 ,Physics: Treatment PlanningPTC58-0224 ,Physics: Treatment PlanningPTC58-0229 ,Clinics: PediatricsPTC58-0249 ,Physics: Beam Delivery and Nozzle Design Poster Discussion SessionsPTC58-0555 ,Clinics: PediatricPTC58-0463 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0556 ,Physics: Absolute and Relative DosimetryPTC58-0498 ,Physics: Commissioning New FacilitiesPTC58-0078 ,Physics: Dose Calculation and OptimisationPTC58-0270 ,Physics: Dose Calculation and OptimisationPTC58-0032 ,Physics: Dose Calculation and OptimisationPTC58-0274 ,Physics: 4D Treatment and DeliveryPTC58-0614 ,Physics: Dose Calculation and OptimisationPTC58-0026 ,Clinics: Head and Neck / EyePTC58-0280 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0091 ,Physics: Treatment PlanningPTC58-0593 ,Biology: Drug and Immunotherapy CombinationsPTC58-0012 ,Physics: Dose Calculation and OptimisationPTC58-0025 ,Physics: Dose Calculation and OptimisationPTC58-0146 ,Clinics: Sarcoma - LymphomaPTC58-0261 ,Physics: Treatment PlanningPTC58-0110 ,Clinics: Lung / Sarcoma / LymphomaPTC58-0733 ,Physics: Quality Assurance and VerificationPTC58-0554 ,Physics: Treatment PlanningPTC58-0597 ,Physics: Dose Calculation and Optimisation Poster Discussion SessionsPTC58-0330 ,Physics: Treatment PlanningPTC58-0115 ,Physics: Treatment PlanningPTC58-0598 ,Physics: Absolute and Relative DosimetryPTC58-0040 ,Physics: Absolute and Relative DosimetryPTC58-0282 ,Biology: Enhanced Biology in Treatment Planning Poster Discussion SessionsPTC58-0399 ,Physics: Absolute and Relative DosimetryPTC58-0283 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0569 ,Clinics: GUPTC58-0647 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0506 ,Physics: Commissioning New FacilitiesPTC58-0047 ,Physics: Dose Calculation and OptimisationPTC58-0067 ,Clinics: GUPTC58-0409 ,Physics: Dose Calculation and OptimisationPTC58-0065 ,Biology: BNCT Poster Discussion SessionsPTC58-0586 ,Physics: Absolute and Relative Dosimetry PTC58-0393 ,Physics: Image GuidancePTC58-0712 ,Physics: Quality Assurance and VerificationPTC58-0645 ,Physics: Treatment PlanningPTC58-0683 ,Biology: BNCT Poster Discussion SessionsPTC58-0107 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0266 ,Physics: Monitoring and Modelling MotionPTC58-0530 ,Biology: BNCT Poster Discussion SessionsPTC58-0341 ,Physics: Commissioning New FacilitiesPTC58-0172 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0456 ,Physics: Dose Calculation and OptimisationPTC58-0170 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0458 ,Physics: Absolute and Relative DosimetryPTC58-0034 ,Physics: Quality Assurance and VerificationPTC58-0417 ,Physics: Quality Assurance and VerificationPTC58-0413 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0492 ,Physics: Dose Calculation and OptimisationPTC58-0168 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0724 ,Physics: Treatment PlanningPTC58-0694 ,Physics: Adaptive TherapyPTC58-0005 ,Physics: Treatment PlanningPTC58-0696 ,Physics: Treatment PlanningPTC58-0453 ,Physics: Adaptive TherapyPTC58-0366 ,Clinics: BreastPTC58-0197 ,Physics: Beam Delivery and Nozzle DesignPTC58-0652 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0017 ,Physics: Treatment PlanningPTC58-0338 ,Clinics: Head and Neck / EyePTC58-0539 ,General: New Horizons SessionPTC58-0390 ,Physics: Image Guidance Poster Discussion SessionsPTC58-0651 ,General: New HorizonsPTC58-0660 ,Physics: Dose Calculation and OptimisationPTC58-0360 ,Physics: Image GuidancePTC58-0297 ,Physics: 4D Treatment and DeliveryPTC58-0147 ,Scientific: RTTPTC58-0388 ,Physics: Dose Calculation and OptimisationPTC58-0484 ,General: New HorizonsPTC58-0301 ,Physics: Dose Calculation and OptimisationPTC58-0485 ,General: New HorizonsPTC58-0304 ,Physics: 4D Treatment and Delivery Poster Discussion SessionsPTC58-0532 ,Clinics: GIPTC58-0575 ,General: New HorizonsPTC58-0306 ,Physics: Quality Assurance and VerificationPTC58-0589 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0344 ,Physics: Quality Assurance and VerificationPTC58-0225 ,Physics: Treatment PlanningPTC58-0381 ,Physics: Quality Assurance and VerificationPTC58-0467 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0585 ,Physics: Commissioning New FacilitiesPTC58-0416 ,Physics: Quality Assurance and VerificationPTC58-0228 ,Physics: Quality Assurance and VerificationPTC58-0348 ,Physics: Dose Calculation and OptimisationPTC58-0234 ,Physics: Quality Assurance and VerificationPTC58-0101 ,Physics: Treatment PlanningPTC58-0386 ,Physics: Dose Calculation and OptimisationPTC58-0118 ,Physics: Treatment PlanningPTC58-0265 ,Physics: Dose Calculation and OptimisationPTC58-0119 ,Clinics: GIPTC58-0218 ,Physics: Treatment PlanningPTC58-0267 ,Physics: Treatment PlanningPTC58-0387 ,Clinics: BreastPTC58-0142 ,Physics: Treatment PlanningPTC58-0269 ,Physics: Beam Delivery and Nozzle DesignPTC58-0620 ,Clinics: PediatricsPTC58-0048 ,Physics: Quality Assurance and VerificationPTC58-0220 ,Physics: Quality Assurance and VerificationPTC58-0461 ,Physics: Treatment PlanningPTC58-0029 ,Physics: Absolute and Relative DosimetryPTC58-0571 ,Physics: Image GuidancePTC58-0046 ,Clinics: GUPTC58-0557 ,Physics: Absolute and Relative DosimetryPTC58-0211 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0131 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0373 ,General: New HorizonsPTC58-0411 ,Physics: Dose Calculation and OptimisationPTC58-0595 ,Clinics: CNS / Skull BasePTC58-0361 ,General: New HorizonsPTC58-0414 ,General: New HorizonsPTC58-0537 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0628 ,Physics: Treatment PlanningPTC58-0271 ,Physics: Commissioning New FacilitiesPTC58-0307 ,Physics: Quality Assurance and VerificationPTC58-0359 ,Physics: Quality Assurance and VerificationPTC58-0354 ,General: New HorizonsPTC58-0419 ,Physics: Treatment PlanningPTC58-0035 ,Biology: BNCTPTC58-0474 ,Clinics: GIPTC58-0460 ,Biology: BNCTPTC58-0596 ,Clinics: GIPTC58-0222 ,Physics: Image GuidancePTC58-0193 ,Clinics: PediatricPTC58-0312 ,Clinics: GUPTC58-0441 ,Clinics: LungPTC58-0701 ,Clinics: EyePTC58-0536 ,Clinics: GUPTC58-0205 ,Physics: Dose Calculation and OptimisationPTC58-0140 ,Clinics: GUPTC58-0208 ,Physics: Dose Calculation and OptimisationPTC58-0020 ,Physics: Image GuidancePTC58-0195 ,Poster AbstractsClinics: CNSPTC58-0717 ,Physics: Quality Assurance and VerificationPTC58-0325 ,Physics: Dose Calculation and OptimisationPTC58-0015 ,Physics: Commissioning New FacilitiesPTC58-0634 ,General: New HorizonsPTC58-0646 ,Physics: Quality Assurance and VerificationPTC58-0566 ,Physics: Dose Calculation and OptimisationPTC58-0134 ,Physics: Dose Calculation and OptimisationPTC58-0376 ,Biology: Mathematical Modelling SimulationPTC58-0462 ,Biology: BNCTPTC58-0567 ,General: New HorizonsPTC58-0527 ,Physics: Treatment PlanningPTC58-0482 ,Clinics: GI, GU, BreastPTC58-0693 ,Physics: Commissioning New FacilitiesPTC58-0518 ,Physics: Quality Assurance and VerificationPTC58-0686 ,Physics: Quality Assurance and VerificationPTC58-0202 ,Physics: Quality Assurance and VerificationPTC58-0322 ,Physics: Quality Assurance and VerificationPTC58-0564 ,Physics: Quality Assurance and VerificationPTC58-0680 ,Physics: Treatment PlanningPTC58-0247 ,Physics: Quality Assurance and VerificationPTC58-0682 ,Physics: Quality Assurance and VerificationPTC58-0440 ,Biology: Translational and BiomarkersPTC58-0514 ,Physics: Beam Delivery and Nozzle Design Poster Discussion SessionsPTC58-0178 ,Clinics: EyePTC58-0520 ,Physics: Absolute and Relative DosimetryPTC58-0231 ,Clinics: Head and Neck / EyePTC58-0424 ,Physics: Absolute and Relative DosimetryPTC58-0471 ,Physics: Absolute and Relative DosimetryPTC58-0356 ,Physics: Dose Calculation and OptimisationPTC58-0491 ,Physics: Dose Calculation and OptimisationPTC58-0250 ,Physics: Commissioning New FacilitiesPTC58-0650 ,Biology: Biology and Clinical InterfacePTC58-0719 ,Physics: Absolute and Relative DosimetryPTC58-0232 ,Physics: Absolute and Relative DosimetryPTC58-0353 ,General: New HorizonsPTC58-0511 ,Physics: Quality Assurance and VerificationPTC58-0219 ,Physics: Absolute and Relative DosimetryPTC58-0238 ,General: New HorizonsPTC58-0512 ,Physics: 4D Treatment and Delivery Poster Discussion SessionsPTC58-0401 ,Clinics: PediatricPTC58-0688 ,Physics: Quality Assurance and VerificationPTC58-0457 ,Physics: Quality Assurance and VerificationPTC58-0214 ,Physics: Quality Assurance and VerificationPTC58-0459 ,General: New HorizonsPTC58-0516 ,Physics: Treatment PlanningPTC58-0372 ,Physics: Treatment PlanningPTC58-0011 ,Physics: Treatment PlanningPTC58-0254 ,Physics: Quality Assurance and VerificationPTC58-0332 ,Clinics: CNS / Skull BasePTC58-0468 ,Biology: Mathematical Modelling SimulationPTC58-0357 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0649 ,Physics: Dose Calculation and OptimisationPTC58-0006 ,Physics: Quality Assurance and VerificationPTC58-0212 ,Physics: Image Guidance Poster Discussion SessionsPTC58-0565 ,Physics: Treatment PlanningPTC58-0018 ,Physics: Treatment PlanningPTC58-0019 ,Clinics: BreastPTC58-0576 ,Clinics: Head and Neck / EyePTC58-0335 ,Clinics: Head and Neck / EyePTC58-0577 ,General: New HorizonsPTC58-0621 ,Physics: Absolute and Relative DosimetryPTC58-0426 ,Physics: Commissioning New Facilities Poster Discussion SessionsPTC58-0268 ,Physics: Absolute and Relative DosimetryPTC58-0423 ,Physics: Treatment PlanningPTC58-0184 ,Physics: Quality Assurance and VerificationPTC58-0149 ,Clinics: GIPTC58-0378 ,Clinics: GIPTC58-0257 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0662 ,General: New HorizonsPTC58-0627 ,Physics: Treatment PlanningPTC58-0186 ,Physics: Treatment PlanningPTC58-0185 ,Physics: Quality Assurance and VerificationPTC58-0144 ,Biology: BNCT Poster Discussion SessionsPTC58-0602 ,Physics: Treatment PlanningPTC58-0189 ,Physics: Dose Calculation and OptimisationPTC58-0315 ,Clinics: Head and neckPTC58-0300 ,General: New Horizons SessionPTC58-0347 ,Physics: Image GuidancePTC58-0082 ,Clinics: BreastPTC58-0443 ,Physics: 4D Treatment and Delivery Poster Discussion SessionsPTC58-0629 ,Physics: Adaptive Therapy Poster Discussion SessionsPTC58-0007 ,Physics: Commissioning New FacilitiesPTC58-0472 ,Clinics: GI, GU, BreastPTC58-0515 ,Physics: Dose Calculation and Optimisation Poster Discussion SessionsPTC58-0606 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0450 ,Physics: Absolute and Relative DosimetryPTC58-0657 ,Physics: Dose Calculation and OptimisationPTC58-0551 ,Physics: Treatment PlanningPTC58-0192 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0675 ,Physics: Treatment PlanningPTC58-0194 ,Physics: Dose Calculation and OptimisationPTC58-0544 ,Physics: Treatment PlanningPTC58-0199 ,Physics: Quality Assurance and VerificationPTC58-0037 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0207 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0434 ,Physics: Quality Assurance and VerificationPTC58-0036 ,Physics: Quality Assurance and VerificationPTC58-0278 ,Physics: Quality Assurance and VerificationPTC58-0394 ,Physics: Quality Assurance and VerificationPTC58-0151 ,Physics: Quality Assurance and VerificationPTC58-0154 ,Physics: Dose Calculation and OptimisationPTC58-0428 ,Clinics: BreastPTC58-0116 ,Biology: Enhanced Biology in Treatment Planning Poster Discussion SessionsPTC58-0435 ,Physics: Commissioning New FacilitiesPTC58-0681 ,Physics: Absolute and Relative DosimetryPTC58-0323 ,Physics: Dose Calculation and OptimisationPTC58-0583 ,Physics: Absolute and Relative DosimetryPTC58-0448 ,Clinics: CNS / Skull BasePTC58-0251 ,General: New HorizonsPTC58-0721 ,Physics: Absolute and Relative DosimetryPTC58-0203 ,Physics: Dose Calculation and OptimisationPTC58-0455 ,Physics: 4D Treatment and DeliveryPTC58-0130 ,Physics: Commissioning New FacilitiesPTC58-0679 ,Physics: Absolute and Relative DosimetryPTC58-0329 ,General: New HorizonsPTC58-0604 ,Physics: Absolute and Relative DosimetryPTC58-0449 ,Clinics: CNS / Skull BasePTC58-0132 ,General: New HorizonsPTC58-0607 ,Physics: Quality Assurance and VerificationPTC58-0122 ,Physics: Quality Assurance and VerificationPTC58-0243 ,Physics: Treatment PlanningPTC58-0165 ,Oral AbstractsPhysics: Dose Calculation and OptimisationPTC58-0437 ,Physics: 4D Treatment and DeliveryPTC58-0377 ,Physics: Quality Assurance and VerificationPTC58-0125 ,Physics: Quality Assurance and VerificationPTC58-0245 ,Physics: Dose Calculation and OptimisationPTC58-0337 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0334 ,Physics: Quality Assurance and VerificationPTC58-0121 ,General: New Horizons SessionPTC58-0563 ,General: New Horizons SessionPTC58-0321 ,Clinics: Head and Neck / EyePTC58-0477 ,Physics: Quality Assurance and VerificationPTC58-0480 ,Clinics: GUPTC58-0010 ,Clinics: EyePTC58-0684 ,Clinics: GUPTC58-0496 ,Clinics: Head and neckPTC58-0676 ,Clinics: GUPTC58-0137 ,Physics: Beam Delivery and Nozzle Design Poster Discussion SessionsPTC58-0256 ,Physics: 4D Treatment and DeliveryPTC58-0117 ,Physics: Absolute and Relative DosimetryPTC58-0552 ,Physics: Absolute and Relative DosimetryPTC58-0310 ,Physics: Absolute and Relative DosimetryPTC58-0672 ,Physics: Absolute and Relative DosimetryPTC58-0436 ,Physics: Dose Calculation and OptimisationPTC58-0452 ,Physics: Dose Calculation and OptimisationPTC58-0331 ,Physics: Commissioning New FacilitiesPTC58-0213 ,Biology: Mathematical Modelling SimulationPTC58-0272 ,Clinics: EyePTC58-0326 ,Physics: Commissioning New FacilitiesPTC58-0568 ,Physics: Dose Calculation and OptimisationPTC58-0444 ,Physics: Quality Assurance and VerificationPTC58-0379 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0095 ,Physics: Treatment PlanningPTC58-0053 ,Physics: Absolute and Relative DosimetryPTC58-0438 ,Physics: Absolute and Relative DosimetryPTC58-0317 ,Physics: Quality Assurance and VerificationPTC58-0497 ,Physics: Quality Assurance and VerificationPTC58-0375 ,Physics: Treatment PlanningPTC58-0056 ,Physics: 4D Treatment and DeliveryPTC58-0124 ,Clinics: GIPTC58-0009 ,Physics: Quality Assurance and VerificationPTC58-0014 ,Physics: Quality Assurance and VerificationPTC58-0374 ,Clinics: LungPTC58-0727 ,General: New Horizons SessionPTC58-0578 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0470 ,Clinics: LungPTC58-0204 ,Clinics: Head and neckPTC58-0227 ,Clinics: LungPTC58-0446 ,Physics: Quality Assurance and VerificationPTC58-0190 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0609 ,Clinics: LungPTC58-0689 ,General: New HorizonsPTC58-0021 ,General: New HorizonsPTC58-0262 ,Biology: BNCT Poster Discussion SessionsPTC58-0081 ,Clinics: GIPTC58-0726 ,General: New HorizonsPTC58-0145 ,Physics: Image GuidancePTC58-0573 ,General: New HorizonsPTC58-0027 ,General: New HorizonsPTC58-0028 ,Biology: Mathematical Modelling and SimulationPTC58-0148 ,Physics: Dose Calculation and OptimisationPTC58-0635 ,Physics: Image GuidancePTC58-0215 ,Physics: Image GuidancePTC58-0336 ,Poster AbstractsClinics: CNSPTC58-0535 ,Physics: Quality Assurance and VerificationPTC58-0187 ,Biology: BNCT Poster Discussion SessionsPTC58-0084 ,General: New Investigator SessionPTC58-0339 ,General: New Horizons SessionPTC58-0420 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0523 ,Biology: BNCT Poster Discussion SessionsPTC58-0088 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0112 ,Physics: Quality Assurance and VerificationPTC58-0182 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0615 ,Physics: Quality Assurance and VerificationPTC58-0080 ,Biology: BNCTPTC58-0085 ,Physics: Adaptive Therapy Poster Discussion SessionsPTC58-0722 ,General: New HorizonsPTC58-0253 ,General: New HorizonsPTC58-0255 ,Clinics: PediatricPTC58-0703 ,General: New HorizonsPTC58-0499 ,Physics: Image Guidance Poster Discussion SessionsPTC58-0380 ,General: New HorizonsPTC58-0259 ,Clinics: GI, GU, BreastPTC58-0288 ,Clinics: GI, GU, BreastPTC58-0045 ,Physics: Absolute and Relative DosimetryPTC58-0619 ,Clinics: PediatricPTC58-0707 ,Physics: Quality Assurance and VerificationPTC58-0196 ,Physics: Quality Assurance and VerificationPTC58-0074 ,Physics: Quality Assurance and VerificationPTC58-0077 ,Biology: BNCT Poster Discussion SessionsPTC58-0073 ,Biology: BNCTPTC58-0075 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0093 ,Clinics: GUPTC58-0161 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0371 ,Physics: Monitoring and Modelling MotionPTC58-0181 ,General: New HorizonsPTC58-0120 ,General: New HorizonsPTC58-0362 ,General: New HorizonsPTC58-0364 ,Physics: Image GuidancePTC58-0473 ,Scientific: RTTPTC58-0641 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0296 ,General: New HorizonsPTC58-0004 ,General: New HorizonsPTC58-0128 ,Clinics: BreastPTC58-0316 ,Physics: 4D Treatment and Delivery Poster Discussion SessionsPTC58-0236 ,General: New HorizonsPTC58-0008 ,General: New Investigator SessionPTC58-0673 ,Physics: Quality Assurance and VerificationPTC58-0167 ,Physics: Quality Assurance and VerificationPTC58-0289 ,Physics: Quality Assurance and VerificationPTC58-0284 ,General: New Horizons SessionPTC58-0522 ,Physics: Quality Assurance and VerificationPTC58-0164 ,Physics: Quality Assurance and VerificationPTC58-0285 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0623 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0502 ,Clinics: GUPTC58-0293 ,Biology: Translational and BiomarkersPTC58-0599 ,Biology: BNCTPTC58-0063 ,Clinics: LungPTC58-0656 ,General: New HorizonsPTC58-0592 ,Biology: BNCT Poster Discussion SessionsPTC58-0092 ,Poster AbstractsClinics: CNSPTC58-0302 ,Physics: Image GuidancePTC58-0464 ,General: New HorizonsPTC58-0352 ,Physics: Image GuidancePTC58-0465 ,General: New HorizonsPTC58-0476 ,Physics: Image GuidancePTC58-0100 ,General: New HorizonsPTC58-0235 ,Biology: Mathematical Modelling and SimulationPTC58-0349 ,Physics: Treatment PlanningPTC58-0094 ,Physics: 4D Treatment and Delivery Poster Discussion SessionsPTC58-0367 ,Physics: Dose Calculation and OptimisationPTC58-0400 ,Biology: Translational and BiomarkersPTC58-0244 ,Physics: Dose Calculation and OptimisationPTC58-0640 ,Biology: Mathematical Modelling and SimulationPTC58-0355 ,General: New Investigator SessionPTC58-0320 ,Physics: Quality Assurance and VerificationPTC58-0057 ,Physics: Quality Assurance and VerificationPTC58-0174 ,Physics: Quality Assurance and VerificationPTC58-0295 ,Physics: Dose Calculation and OptimisationPTC58-0529 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0123 ,Physics: Quality Assurance and VerificationPTC58-0171 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0049 ,Clinics: BreastPTC58-0731 ,General: New HorizonsPTC58-0223 ,General: New HorizonsPTC58-0102 ,General: New HorizonsPTC58-0466 ,Scientific: RTTPTC58-0503 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0389 ,General: New HorizonsPTC58-0108 ,General: New HorizonsPTC58-0109 ,Physics: Commissioning New FacilitiesPTC58-0736 ,Biology: Mathematical Modelling and SimulationPTC58-0343 ,Biology: Mathematical Modelling and SimulationPTC58-0342 ,Clinics: GI, GU, BreastPTC58-0237 ,Physics: Dose Calculation and OptimisationPTC58-0711 ,Biology: Mathematical Modelling and SimulationPTC58-0581 ,Clinics: GI, GU, BreastPTC58-0114 ,Clinics: Base of SkullPTC58-0730 ,Clinics: Head and neckPTC58-0383 ,Clinics: CNS / Skull BasePTC58-0559 ,Clinics: Base of SkullPTC58-0613 ,General: New HorizonsPTC58-0691 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0054 ,General: New HorizonsPTC58-0210 ,Clinics: BreastPTC58-0729 ,General: New HorizonsPTC58-0574 ,Clinics: GI, GU, BreastPTC58-0239 ,Scientific: RTTPTC58-0637 ,General: New HorizonsPTC58-0579 ,Clinics: Lung / Sarcoma / LymphomaPTC58-0176 ,General: New HorizonsPTC58-0699 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0156 ,Biology: Mathematical Modelling and SimulationPTC58-0333 ,Biology: Translational and BiomarkersPTC58-0345 ,Physics: Image GuidancePTC58-0369 ,Physics: Commissioning New FacilitiesPTC58-0509 ,Biology: Mathematical Modelling SimulationPTC58-0658 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0051 ,General: New Investigator SessionPTC58-0548 ,Clinics: GI, GU, BreastPTC58-0241 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0412 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0024 ,Clinics: LungPTC58-0226 ,Biology: Biological Differences between Carbon, Proton and Photons Poster Discussion SessionsPTC58-0069 ,General: New HorizonsPTC58-0562 ,General: New HorizonsPTC58-0561 ,General: New HorizonsPTC58-0201 ,Biology: Mathematical Modelling and SimulationPTC58-0439 ,General: New HorizonsPTC58-0445 ,General: New HorizonsPTC58-0324 ,Physics: Image GuidancePTC58-0031 ,Biology: Mathematical Modelling and SimulationPTC58-0558 ,Physics: Image GuidancePTC58-0392 ,Biology: Mathematical Modelling and SimulationPTC58-0678 ,Physics: Beam Delivery and Nozzle DesignPTC58-0090 ,General: New Investigator SessionPTC58-0630 ,Biology: Biological Differences between Carbon / Proton and Photons Carbons / Proton and PhotonPTC58-0524 ,Physics: Commissioning New FacilitiesPTC58-0713 ,Clinics: GI, GU, BreastPTC58-0139 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0248 ,Clinics: CNS / Pediatrics / Lung Poster Discussion SessionsPTC58-0368 ,Biology: Enhanced Biology in Treatment PlanningPTC58-0519 ,General: New Horizons SessionPTC58-0720 ,Physics: Quality Assurance and VerificationPTC58-0083 ,General: New HorizonsPTC58-0311 ,General: New HorizonsPTC58-0674 ,General: New HorizonsPTC58-0553 ,Physics: Image GuidancePTC58-0023 ,Scientific: RTTPTC58-0612 ,General: New HorizonsPTC58-0677 ,Biology: Mathematical Modelling and SimulationPTC58-0545 ,Physics: Dose Calculation and OptimisationPTC58-0601 ,Physics: Dose Calculation and OptimisationPTC58-0725 ,Physics: Quality Assurance and VerificationPTC58-0098 ,Physics: Dose Calculation and OptimisationPTC58-0605 ,Biology: Biological Differences between Carbon / Proton and Photons Carbons / Proton and PhotonPTC58-0517 ,Biology: Translational and Biomarkers Poster Discussion SessionsPTC58-0618 ,Physics: Monitoring and Modelling MotionPTC58-0481 ,Clinics: GI / Sarcoma Poster Discussion SessionsPTC58-0071 ,Physics: Adaptive TherapyPTC58-0351 ,Physics: 4D Treatment and DeliveryPTC58-0702 ,Physics: Image GuidancePTC58-0734 ,Physics: Image GuidancePTC58-0611 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0486 ,Physics: Absolute and Relative Dosimetry Poster Discussion SessionsPTC58-0442 ,Biology: Drug and Immunotherapy CombinationsPTC58-0327 ,Clinics: Head and Neck / EyePTC58-0096 ,Clinics: LungPTC58-0159 ,Physics: Treatment PlanningPTC58-0708 ,General: New HorizonsPTC58-0097 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0350 ,Biology: Biological Differences between Carbon / Proton and Photons Carbons / Proton and PhotonPTC58-0016 ,Physics: Adaptive TherapyPTC58-0104 ,Physics: Absolute and Relative Dosimetry Poster Discussion SessionsPTC58-0433 ,Physics: Image GuidancePTC58-0608 ,Biology: Translational and Biomarkers Poster Discussion SessionsPTC58-0610 ,Clinics: Head and neckPTC58-0058 ,Physics: Treatment PlanningPTC58-0715 ,Clinics: Head and neckPTC58-0298 ,Clinics: EyePTC58-0099 ,General: New HorizonsPTC58-0086 ,General: New HorizonsPTC58-0089 ,Clinics: Lung / Sarcoma / LymphomaPTC58-0200 ,Poster AbstractsClinics: CNSPTC58-0157 ,Clinics: LungPTC58-0141 ,Clinics: LungPTC58-0260 ,Clinics: LungPTC58-0264 ,Physics: Image GuidancePTC58-0513 ,Physics: Image GuidancePTC58-0631 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0469 ,Biology: BNCT Poster Discussion SessionsPTC58-0384 ,Physics: Image GuidancePTC58-0639 ,Clinics: PediatricsPTC58-0700 ,Clinics: LungPTC58-0136 ,Clinics: BreastPTC58-0706 ,General: New HorizonsPTC58-0079 ,Biology: Drug and Immunotherapy Combinations Poster Discussion SessionsPTC58-0406 ,Clinics: Base of SkullPTC58-0382 ,Physics: Image GuidancePTC58-0624 ,Physics: Beam Delivery and Nozzle DesignPTC58-0173 ,Biology: Drug and Immunotherapy CombinationsPTC58-0358 ,Poster AbstractsClinics: CNSPTC58-0690 ,General: New HorizonsPTC58-0061 ,Clinics: Lung / Sarcoma / LymphomaPTC58-0580 ,Physics: Monitoring and Modelling MotionPTC58-0162 ,Physics: Adaptive TherapyPTC58-0550 ,Physics: Adaptive TherapyPTC58-0430 ,Clinics: Lung / Sarcoma / LymphomaPTC58-0103 ,General: New Investigator SessionPTC58-0252 ,Physics: Quality Assurance and VerificationPTC58-0704 ,Physics: Image GuidancePTC58-0418 ,Clinics: Base of SkullPTC58-0572 ,Clinics: Lung / Sarcoma / LymphomaPTC58-0106 ,Physics: Beam Delivery and Nozzle DesignPTC58-0022 ,Physics: Monitoring and Modelling MotionPTC58-0279 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0447 ,Physics: Treatment PlanningPTC58-0622 ,Clinics: PediatricsPTC58-0644 ,Biology: Biology and Clinical InterfacePTC58-0490 ,Clinics: CNS / Skull BasePTC58-0716 ,General: New HorizonsPTC58-0292 ,Biology: Biological Differences between Carbon / Proton and Photons Carbons / Proton and PhotonPTC58-0570 ,General: New HorizonsPTC58-0059 ,Physics: Quality Assurance and VerificationPTC58-0710 ,Biology: Biological Differences between Carbon / Proton and Photons Carbons / Proton and PhotonPTC58-0216 ,Physics: Image GuidancePTC58-0404 ,Physics: Image GuidancePTC58-0525 ,Physics: Image GuidancePTC58-0526 ,Poster AbstractsClinics: CNSPTC58-0328 ,Clinics: LungPTC58-0070 ,Clinics: Eye / Breast / Pelvis Poster Discussion SessionsPTC58-0135 ,Biology: BNCT Poster Discussion SessionsPTC58-0391 ,Physics: Treatment PlanningPTC58-0510 ,Physics: Treatment PlanningPTC58-0636 ,Physics: Treatment PlanningPTC58-0638 ,Physics: Image GuidancePTC58-0408 ,Physics: Absolute and Relative Dosimetry Poster Discussion SessionsPTC58-0632 ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0318 ,Biology: Enhanced Biology in Treatment PlanningPTC58-0246 ,Clinics: PediatricsPTC58-0504 ,General: New HorizonsPTC58-0160 ,Physics: Image Guidance Poster Discussion SessionsPTC58-0076 ,Physics: Monitoring and Modelling MotionPTC58-0143 ,Biology: Mathematical Modelling and SimulationPTC58-0718 ,Physics: Image GuidancePTC58-0671 ,Clinics: LungPTC58-0183 ,Physics: Image GuidancePTC58-0670 ,Report ,Physics: Treatment Planning Poster Discussion SessionsPTC58-0422 ,Biology: Biological Differences between Carbon / Proton and Photons Carbons / Proton and PhotonPTC58-0129 ,Physics: Adaptive Therapy Poster Discussion SessionsPTC58-0705 ,Biology: Enhanced Biology in Treatment PlanningPTC58-0258 ,General: New HorizonsPTC58-0030 ,General: New HorizonsPTC58-0150 ,Biology: Biology and Clinical InterfacePTC58-0479 ,General: New HorizonsPTC58-0153 ,Clinics: PediatricPTC58-0087 ,General: New HorizonsPTC58-0152 ,General: New HorizonsPTC58-0155 ,General: New HorizonsPTC58-0033 ,General: New HorizonsPTC58-0158 ,Physics: Image GuidancePTC58-0429 ,Biology: Translational and BiomarkersPTC58-0287 ,Physics: Adaptive TherapyPTC58-0403 ,Physics: Image GuidancePTC58-0309 - Published
- 2020
3. Chymotrypsin-Like Elastase 1 in Human Emphysema and Age-Related Airspace Simplification
- Author
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Varisco, B.M., primary, Ojha, M., additional, Goodman, E., additional, Joshi, R., additional, Fan, Q., additional, Lewis, J., additional, and Batie, M., additional
- Published
- 2020
- Full Text
- View/download PDF
4. Role for Cela1 in Postnatal Lung Remodeling and Alpha-1 Antitrypsin-Deficient Emphysema
- Author
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Joshi, R., Heinz, A., Fan, Q., Guo, S., Monia, B., Schmelzer, C.E.H., Weiss, A.S., Batie, M., Parameshwaran, H., Varisco, B.M., and Publica
- Abstract
Alpha-1 antitrypsin (AAT) deficiency-related emphysema is the fourth leading indication for lung transplant. Chymotrypsin-like elastase 1 (Cela1) is a digestive protease that is expressed during lung development in association with regions of elastin remodeling, exhibits stretch-dependent expression during lung regeneration, and binds lung elastin in a stretch-dependent manner. AAT covalently neutralizes Cela1 in vitro. We sought to determine the role of Cela1 in postnatal lung physiology, whether it interacted with AAT in vivo, and to detect any effects it may have in the context of AAT deficiency. The lungs of Cela1−/− mice had aberrant lung elastin structure and higher elastance as assessed with the flexiVent system. On the basis of in situ zymography with ex vivo lung stretch, Cela1 was solely responsible for stretch-inducible lung elastase activity. By mass spectrometry, Cela1 degraded mature elastin similarly to pancreatic elastase. Cela1 promoter and protein sequences were phylogenetically distinct in the placental mammal lineage, suggesting an adaptive role for lung-expressed Cela1 in this clade. A 6-week antisense oligonucleotide mouse model of AAT deficiency resulted in emphysema with increased Cela1 mRNA and reduction of approximately 70 kD Cela1, consistent with covalent binding of Cela1 by AAT. Cela1−/− mice were completely protected against emphysema in this model. Cela1 was increased in human AAT-deficient emphysema. Cela1 is important in physiologic and pathologic stretch-dependent remodeling processes in the postnatal lung. AAT is an important regulator of this process. Our findings provide proof of concept for the development of anti-Cela1 therapies to prevent and/or treat AAT-deficient emphysema.
- Published
- 2018
5. Hexavalent chromium uptake by sensitive and tolerant mutants of Schizosaccharomyces pombe
- Author
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Czakó-Vér, Klára, Batie, M., Raspor, P., Sipiczki, Mátyás, and Pesti, M.
- Subjects
Természettudományok ,Genetics ,Biológiai tudományok ,Molecular Biology ,Microbiology - Published
- 1999
6. High prevalence of hepatitis G virus (HGV) infection in renal transplantation
- Author
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Berthoux, P., primary, Dejean, C., additional, Cecillon, S., additional, Batie, M., additional, and Berthoux, F., additional
- Published
- 1998
- Full Text
- View/download PDF
7. Original article. High prevalence of hepatitis G virus (HGV) infection in renal transplantation.
- Author
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Berthoux, P, Dejean, C, Cecillon, S, Batie, M, and Berthoux, F
- Abstract
Introduction: The newly discovered (1995) hepatitis G virus (HGV) is an RNA virus from the Flaviviridae family with 85% genomic homology to GB virus C (GBV-C). We studied the prevalence of HGV infection among a cohort of 398 renal transplant recipients (PT), all of whom had previously received blood transfusions, been grafted between August 1984 and December 1991, and been treated by cyclosporin A (CsA) as the main immunosuppressant. [ABSTRACT FROM PUBLISHER]
- Published
- 1998
- Full Text
- View/download PDF
8. Comparison of ELISA method versus MEIA method for daily practice in the therapeutic monitoring of tacrolimus.
- Author
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Dietemann, J, Berthoux, P, Gay-Montchamp, J P, Batie, M, and Berthoux, F
- Abstract
For the adequate management of transplant patients on tacrolimus therapy, it is important to obtain optimal blood concentrations. The purpose of this study was to determine the most appropriate method for daily practice of tacrolimus determination in whole blood. We compared enzyme-linked immunosorbent assay (ELISA) with microparticle enzyme immunoassay (MEIA), using European controls and blood samples from organ graft recipients treated with tacrolimus. Time, practicability and cost were considered also.
- Published
- 2001
- Full Text
- View/download PDF
9. Oxygen-regulated post-translation modifications as master signalling pathway in cells.
- Author
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Batie M, Fasanya T, Kenneth NS, and Rocha S
- Subjects
- Animals, Humans, Protein Processing, Post-Translational, Chromatin, Hypoxia metabolism, Mammals metabolism, Oxygen metabolism, Lysine metabolism
- Abstract
Oxygen is essential for viability in mammalian organisms. However, cells are often exposed to changes in oxygen availability, due to either increased demand or reduced oxygen supply, herein called hypoxia. To be able to survive and/or adapt to hypoxia, cells activate a variety of signalling cascades resulting in changes to chromatin, gene expression, metabolism and viability. Cellular signalling is often mediated via post-translational modifications (PTMs), and this is no different in response to hypoxia. Many enzymes require oxygen for their activity and oxygen can directly influence several PTMS. Here, we review the direct impact of changes in oxygen availability on PTMs such as proline, asparagine, histidine and lysine hydroxylation, lysine and arginine methylation and cysteine dioxygenation, with a focus on mammalian systems. In addition, indirect hypoxia-dependent effects on phosphorylation, ubiquitination and sumoylation will also be discussed. Direct and indirect oxygen-regulated changes to PTMs are coordinated to achieve the cell's ultimate response to hypoxia. However, specific oxygen sensitivity and the functional relevance of some of the identified PTMs still require significant research., (© 2023 The Authors. Published under the terms of the CC BY 4.0 license.)
- Published
- 2023
- Full Text
- View/download PDF
10. Fixed Cell Immunofluorescence for Quantification of Hypoxia-Induced Changes in Histone Methylation.
- Author
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Shakir D, Batie M, and Rocha S
- Subjects
- Humans, Methylation, Protein Processing, Post-Translational, Fluorescent Antibody Technique, DNA Methylation, Histones metabolism, Hypoxia metabolism
- Abstract
Hypoxia and its signalling pathway play a key role in human physiology and a variety of diseases. Alterations in histone methylation coordinate transcriptional responses to hypoxia. Here, we detail a fixed cell immunofluorescence method for quantifying hypoxia-induced changes in histone methylation, exemplified by the measurement of H3K27me3., (© 2023. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)
- Published
- 2023
- Full Text
- View/download PDF
11. Regulation of chromatin accessibility by hypoxia and HIF.
- Author
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Batie M, Frost J, Shakir D, and Rocha S
- Subjects
- Cell Hypoxia genetics, Gene Expression Regulation, Humans, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Oxygen metabolism, Chromatin genetics, Hypoxia genetics, Hypoxia metabolism
- Abstract
Reduced oxygen availability (hypoxia) can act as a signalling cue in physiological processes such as development, but also in pathological conditions such as cancer or ischaemic disease. As such, understanding how cells and organisms respond to hypoxia is of great importance. The family of transcription factors called Hypoxia Inducible Factors (HIFs) co-ordinate a transcriptional programme required for survival and adaptation to hypoxia. However, the effects of HIF on chromatin accessibility are currently unclear. Here, using genome wide mapping of chromatin accessibility via ATAC-seq, we find hypoxia induces loci specific changes in chromatin accessibility are enriched at a subset hypoxia transcriptionally responsive genes, agreeing with previous data using other models. We show for the first time that hypoxia inducible changes in chromatin accessibility across the genome are predominantly HIF dependent, rapidly reversible upon reoxygenation and partially mimicked by HIF-α stabilisation independent of molecular dioxygenase inhibition. This work demonstrates that HIF is central to chromatin accessibility alterations in hypoxia, and has implications for our understanding of gene expression regulation by hypoxia and HIF., (© 2022 The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
12. Systems approaches to understand oxygen sensing: how multi-omics has driven advances in understanding oxygen-based signalling.
- Author
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Batie M, Kenneth NS, and Rocha S
- Subjects
- Animals, Chromatin genetics, Chromatin metabolism, Humans, Metabolome genetics, Proteome genetics, Proteome metabolism, Transcription Factors genetics, Transcription Factors metabolism, Cell Hypoxia genetics, Gene Expression Regulation, Oxygen metabolism, Signal Transduction genetics, Transcriptome genetics
- Abstract
Hypoxia is a common denominator in the pathophysiology of a variety of human disease states. Insight into how cells detect, and respond to low oxygen is crucial to understanding the role of hypoxia in disease. Central to the hypoxic response is rapid changes in the expression of genes essential to carry out a wide range of functions to adapt the cell/tissue to decreased oxygen availability. These changes in gene expression are co-ordinated by specialised transcription factors, changes to chromatin architecture and intricate balances between protein synthesis and destruction that together establish changes to the cellular proteome. In this article, we will discuss the advances of our understanding of the cellular oxygen sensing machinery achieved through the application of 'omics-based experimental approaches., (© 2022 The Author(s).)
- Published
- 2022
- Full Text
- View/download PDF
13. Oxygen-dependent changes in binding partners and post-translational modifications regulate the abundance and activity of HIF-1α/2α.
- Author
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Daly LA, Brownridge PJ, Batie M, Rocha S, Sée V, and Eyers CE
- Subjects
- Humans, Oxygen, Protein Isoforms, Protein Processing, Post-Translational, Basic Helix-Loop-Helix Transcription Factors genetics, Basic Helix-Loop-Helix Transcription Factors metabolism, Hypoxia, Hypoxia-Inducible Factor 1, alpha Subunit genetics
- Abstract
Cellular adaptation to low-oxygen environments is mediated in part by the hypoxia-inducible factors (HIFs). Like other transcription factors, the stability and transcriptional activity of HIFs-and consequently, the hypoxic response-are regulated by post-translational modifications (PTMs) and changes in protein-protein interactions. Our current understanding of PTM-mediated regulation of HIFs is primarily based on in vitro protein fragment-based studies typically validated in fragment-expressing cells treated with hypoxia-mimicking compounds. Here, we used immunoprecipitation-based mass spectrometry to characterize the PTMs and binding partners for full-length HIF-1α and HIF-2α under normoxic (21% oxygen) and hypoxic (1% oxygen) conditions. Hypoxia substantially altered the complexity and composition of the HIFα protein interaction networks, particularly for HIF-2α, with the hypoxic networks of both isoforms being enriched for mitochondrial proteins. Moreover, both HIFα isoforms were heavily covalently modified. We identified ~40 PTM sites composed of 13 different types of modification on both HIFα isoforms, including multiple cysteine modifications and an unusual phosphocysteine. More than 80% of the PTMs identified were not previously known and about half exhibited oxygen dependency. We further characterized an evolutionarily conserved phosphorylation of Ser
31 in HIF-1α as a regulator of its transcriptional function, and we propose functional roles for Thr406 , Thr528 , and Ser581 in HIF-2α. These data will help to delineate the different physiological roles of these closely related isoforms in fine-tuning the hypoxic response., (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)- Published
- 2021
- Full Text
- View/download PDF
14. PBRM1 Cooperates with YTHDF2 to Control HIF-1α Protein Translation.
- Author
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Shmakova A, Frost M, Batie M, Kenneth NS, and Rocha S
- Subjects
- A549 Cells, HeLa Cells, Humans, Protein Biosynthesis, Signal Transduction, Cell Hypoxia, DNA-Binding Proteins physiology, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, RNA-Binding Proteins metabolism, Transcription Factors physiology
- Abstract
PBRM1, a component of the chromatin remodeller SWI/SNF, is often deleted or mutated in human cancers, most prominently in renal cancers. Core components of the SWI/SNF complex have been shown to be important for the cellular response to hypoxia. Here, we investigated how PBRM1 controls HIF-1α activity. We found that PBRM1 is required for HIF-1α transcriptional activity and protein levels. Mechanistically, PBRM1 is important for HIF-1α mRNA translation, as absence of PBRM1 results in reduced actively translating HIF-1α mRNA. Interestingly, we found that PBRM1, but not BRG1, interacts with the m6A reader protein YTHDF2. HIF-1α mRNA is m6A-modified, bound by PBRM1 and YTHDF2. PBRM1 is necessary for YTHDF2 binding to HIF-1α mRNA and reduction of YTHDF2 results in reduced HIF-1α protein expression in cells. Our results identify a SWI/SNF-independent function for PBRM1, interacting with HIF-1α mRNA and the epitranscriptome machinery. Furthermore, our results suggest that the epitranscriptome-associated proteins play a role in the control of hypoxia signalling pathways.
- Published
- 2021
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15. Roles of HIF and 2-Oxoglutarate-Dependent Dioxygenases in Controlling Gene Expression in Hypoxia.
- Author
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Frost J, Frost M, Batie M, Jiang H, and Rocha S
- Abstract
Hypoxia-reduction in oxygen availability-plays key roles in both physiological and pathological processes. Given the importance of oxygen for cell and organism viability, mechanisms to sense and respond to hypoxia are in place. A variety of enzymes utilise molecular oxygen, but of particular importance to oxygen sensing are the 2-oxoglutarate (2-OG) dependent dioxygenases (2-OGDs). Of these, Prolyl-hydroxylases have long been recognised to control the levels and function of Hypoxia Inducible Factor (HIF), a master transcriptional regulator in hypoxia, via their hydroxylase activity. However, recent studies are revealing that dioxygenases are involved in almost all aspects of gene regulation, including chromatin organisation, transcription and translation. We highlight the relevance of HIF and 2-OGDs in the control of gene expression in response to hypoxia and their relevance to human biology and health.
- Published
- 2021
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16. Use of ChIP-qPCR to Study the Crosstalk Between HIF and NF-κB Signaling in Hypoxia and Normoxia.
- Author
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Shakir D, Batie M, and Rocha S
- Subjects
- Gene Expression Regulation, Humans, Hypoxia genetics, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Inflammation, NF-kappa B genetics, NF-kappa B metabolism, Signal Transduction
- Abstract
Hypoxia and inflammation are intensely connected in a functional crosstalk. Within this crosstalk, two major transcription factors take center stage: HIF and NF-κB. To investigate transcription factor function, an important aspect is its ability to bind DNA. The most appropriate method to study this property in cells is the use of chromatin immunoprecipitation followed by qPCR and/or next generation sequencing. This allows identification of potentially directly regulated genes as well as enhancer regions. Here we describe the ChIP-qPCR method in detail, including key aspects important for the success of the technique.
- Published
- 2021
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17. Oxygen-sensing mechanisms in cells.
- Author
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Wilson JW, Shakir D, Batie M, Frost M, and Rocha S
- Subjects
- Animals, Dioxygenases genetics, Dioxygenases metabolism, Humans, Jumonji Domain-Containing Histone Demethylases genetics, Jumonji Domain-Containing Histone Demethylases metabolism, Models, Biological, Transcription, Genetic, Adenosine Triphosphate metabolism, Mitochondria metabolism, Oxygen metabolism, Signal Transduction
- Abstract
The importance of oxygen for the survival of multicellular and aerobic organisms is well established and documented. Over the years, increased knowledge of its use for bioenergetics has placed oxygen at the centre of research on mitochondria and ATP-generating processes. Understanding the molecular mechanisms governing cellular oxygen sensing and response has allowed for the discovery of novel pathways oxygen is involved in, culminating with the award of the Nobel Prize for Medicine and Physiology in 2019 to the pioneers of this field, Greg Semenza, Peter Ratcliffe and William Kaelin. However, it is now beginning to be appreciated that oxygen can be a signalling molecule involved in a vast array of molecular processes, most of which impinge on gene expression control. This review will focus on the knowns and unknowns of oxygen as a signalling molecule, highlighting the role of 2-oxoglutarate-dependent dioxygenases as central players in the cellular response to deviations in oxygen tension., (© 2020 The Authors. The FEBS Journal published by John Wiley & Sons Ltd on behalf of Federation of European Biochemical Societies.)
- Published
- 2020
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18. Violet-light suppression of thermogenesis by opsin 5 hypothalamic neurons.
- Author
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Zhang KX, D'Souza S, Upton BA, Kernodle S, Vemaraju S, Nayak G, Gaitonde KD, Holt AL, Linne CD, Smith AN, Petts NT, Batie M, Mukherjee R, Tiwari D, Buhr ED, Van Gelder RN, Gross C, Sweeney A, Sanchez-Gurmaches J, Seeley RJ, and Lang RA
- Subjects
- Adipose Tissue, Brown innervation, Adipose Tissue, Brown metabolism, Adipose Tissue, Brown radiation effects, Animals, Body Temperature, Cold Temperature, Cyclic AMP metabolism, Female, Male, Membrane Proteins deficiency, Membrane Proteins genetics, Mice, Opsins deficiency, Opsins genetics, Thermogenesis genetics, Color, Light, Membrane Proteins metabolism, Neurons metabolism, Neurons radiation effects, Opsins metabolism, Preoptic Area cytology, Thermogenesis radiation effects
- Abstract
The opsin family of G-protein-coupled receptors are used as light detectors in animals. Opsin 5 (also known as neuropsin or OPN5) is a highly conserved opsin that is sensitive to visible violet light
1,2 . In mice, OPN5 is a known photoreceptor in the retina3 and skin4 but is also expressed in the hypothalamic preoptic area (POA)5 . Here we describe a light-sensing pathway in which POA neurons that express Opn5 regulate thermogenesis in brown adipose tissue (BAT). We show that Opn5 is expressed in glutamatergic warm-sensing POA neurons that receive synaptic input from several thermoregulatory nuclei. We further show that Opn5 POA neurons project to BAT and decrease its activity under chemogenetic stimulation. Opn5-null mice show overactive BAT, increased body temperature, and exaggerated thermogenesis when cold-challenged. Moreover, violet photostimulation during cold exposure acutely suppresses BAT temperature in wild-type mice but not in Opn5-null mice. Direct measurements of intracellular cAMP ex vivo show that Opn5 POA neurons increase cAMP when stimulated with violet light. This analysis thus identifies a violet light-sensitive deep brain photoreceptor that normally suppresses BAT thermogenesis.- Published
- 2020
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19. Gene transcription and chromatin regulation in hypoxia.
- Author
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Batie M and Rocha S
- Subjects
- Animals, Cell Hypoxia, Gene Expression Profiling, Gene Expression Regulation, Homeostasis, Humans, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Methylation, Oxygen metabolism, Protein Processing, Post-Translational, RNA, Untranslated metabolism, Transcription Factors metabolism, Chromatin metabolism, Hypoxia metabolism, Transcription, Genetic
- Abstract
Oxygen sensing is an essential feature of metazoan biology and reductions in oxygen availability (hypoxia) have both physiological and pathophysiological implications. Co-ordinated mechanisms have evolved for sensing and responding to hypoxia, which involve diverse biological outputs, with the main aim of restoring oxygen homeostasis. This includes a dynamic gene transcriptional response, the central drivers of which are the hypoxia-inducible factor (HIF) family of transcription factors. HIFs are regulated in an oxygen-dependent manner and while their role in hypoxia is well established, it is apparent that other key players are required for gene expression control in hypoxia. In this review, we highlight the current understanding of the known and potential molecular mechanisms underpinning gene transcriptional responses to hypoxia in mammals, with a focus on oxygen-dependent effects on chromatin structure., (© 2020 The Author(s).)
- Published
- 2020
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20. HIF-1β Positively Regulates NF-κB Activity via Direct Control of TRAF6.
- Author
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D'Ignazio L, Shakir D, Batie M, Muller HA, and Rocha S
- Subjects
- Animals, Aryl Hydrocarbon Receptor Nuclear Translocator genetics, Biomarkers, Cell Line, Cell Survival genetics, Drosophila Proteins genetics, Gene Expression Regulation, Gene Knockdown Techniques, Humans, Hypoxia genetics, Hypoxia metabolism, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Promoter Regions, Genetic, Protein Binding, RNA, Small Interfering, Signal Transduction, TNF Receptor-Associated Factor 6 genetics, Aryl Hydrocarbon Receptor Nuclear Translocator metabolism, Drosophila Proteins metabolism, NF-kappa B metabolism, TNF Receptor-Associated Factor 6 metabolism
- Abstract
NF-κB signalling is crucial for cellular responses to inflammation but is also associated with the hypoxia response. NF-κB and hypoxia inducible factor (HIF) transcription factors possess an intense molecular crosstalk. Although it is known that HIF-1α modulates NF-κB transcriptional response, very little is understood regarding how HIF-1β contributes to NF-κB signalling. Here, we demonstrate that HIF-1β is required for full NF-κB activation in cells following canonical and non-canonical stimuli. We found that HIF-1β specifically controls TRAF6 expression in human cells but also in Drosophila melanogaster . HIF-1β binds to the TRAF6 gene and controls its expression independently of HIF-1α. Furthermore, exogenous TRAF6 expression is able to rescue all of the cellular phenotypes observed in the absence of HIF-1β. These results indicate that HIF-1β is an important regulator of NF-κB with consequences for homeostasis and human disease.
- Published
- 2020
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21. Adaptive Thermogenesis in Mice Is Enhanced by Opsin 3-Dependent Adipocyte Light Sensing.
- Author
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Nayak G, Zhang KX, Vemaraju S, Odaka Y, Buhr ED, Holt-Jones A, Kernodle S, Smith AN, Upton BA, D'Souza S, Zhan JJ, Diaz N, Nguyen MT, Mukherjee R, Gordon SA, Wu G, Schmidt R, Mei X, Petts NT, Batie M, Rao S, Hogenesch JB, Nakamura T, Sweeney A, Seeley RJ, Van Gelder RN, Sanchez-Gurmaches J, and Lang RA
- Subjects
- Animals, Cold Temperature, Energy Metabolism radiation effects, Gene Expression Profiling, Lipolysis radiation effects, Mice, Inbred C57BL, Phenotype, Photons, Thermogenesis genetics, Adipocytes, Brown metabolism, Adipocytes, Brown radiation effects, Adipocytes, White metabolism, Adipocytes, White radiation effects, Light, Rod Opsins metabolism, Thermogenesis radiation effects
- Abstract
Almost all life forms can detect and decode light information for adaptive advantage. Examples include the visual system, in which photoreceptor signals are processed into virtual images, and the circadian system, in which light entrains a physiological clock. Here we describe a light response pathway in mice that employs encephalopsin (OPN3, a 480 nm, blue-light-responsive opsin) to regulate the function of adipocytes. Germline null and adipocyte-specific conditional null mice show a light- and Opn3-dependent deficit in thermogenesis and become hypothermic upon cold exposure. We show that stimulating mouse adipocytes with blue light enhances the lipolysis response and, in particular, phosphorylation of hormone-sensitive lipase. This response is Opn3 dependent. These data establish a key mechanism in which light-dependent, local regulation of the lipolysis response in white adipocytes regulates energy metabolism., Competing Interests: Declaration of Interests R.J.S. receives research support from Novo Nordisk, Zafgen, Kallyope, Pfizer, and Ironwood Pharmaceuticals., (Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.)
- Published
- 2020
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22. IL-13-induced intestinal secretory epithelial cell antigen passages are required for IgE-mediated food-induced anaphylaxis.
- Author
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Noah TK, Knoop KA, McDonald KG, Gustafsson JK, Waggoner L, Vanoni S, Batie M, Arora K, Naren AP, Wang YH, Lukacs NW, Munitz A, Helmrath MA, Mahe MM, Newberry RD, and Hogan SP
- Subjects
- Allergens metabolism, Anaphylaxis metabolism, Animals, Food Hypersensitivity metabolism, Humans, Immunoglobulin E immunology, Interleukin-13 metabolism, Intestinal Mucosa metabolism, Mast Cells immunology, Mice, Mice, Inbred BALB C, Mice, Inbred NOD, Mice, SCID, Allergens immunology, Anaphylaxis immunology, Food Hypersensitivity immunology, Interleukin-13 immunology, Intestinal Mucosa immunology
- Abstract
Background: Food-induced anaphylaxis (FIA) is an IgE-dependent immune response that can affect multiple organs and lead to life-threatening complications. The processes by which food allergens cross the mucosal surface and are delivered to the subepithelial immune compartment to promote the clinical manifestations associated with food-triggered anaphylaxis are largely unexplored., Objective: We sought to define the processes involved in the translocation of food allergens across the mucosal epithelial surface to the subepithelial immune compartment in FIA., Methods: Two-photon confocal and immunofluorescence microscopy was used to visualize and trace food allergen passage in a murine model of FIA. A human colon cancer cell line, RNA silencing, and pharmacologic approaches were used to identify the molecular regulation of intestinal epithelial allergen uptake and translocation. Human intestinal organoid transplants were used to demonstrate the conservation of these molecular processes in human tissues., Results: Food allergens are sampled by using small intestine (SI) epithelial secretory cells (termed secretory antigen passages [SAPs]) that are localized to the SI villous and crypt region. SAPs channel food allergens to lamina propria mucosal mast cells through an IL-13-CD38-cyclic adenosine diphosphate ribose (cADPR)-dependent process. Blockade of IL-13-induced CD38/cADPR-dependent SAP antigen passaging in mice inhibited induction of clinical manifestations of FIA. IL-13-CD38-cADPR-dependent SAP sampling of food allergens was conserved in human intestinal organoids., Conclusion: We identify that SAPs are a mechanism by which food allergens are channeled across the SI epithelium mediated by the IL-13/CD38/cADPR pathway, regulate the onset of FIA reactions, and are conserved in human intestine., (Copyright © 2019 American Academy of Allergy, Asthma & Immunology. Published by Elsevier Inc. All rights reserved.)
- Published
- 2019
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23. JmjC histone demethylases act as chromatin oxygen sensors.
- Author
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Batie M and Rocha S
- Abstract
Oxygen sensing is important in physiology but also in disease. We find that hypoxia (oxygen deficiency) triggers rapid and hypoxia-inducible factor (HIF)-independent histone methylation changes which are reversible upon reoxygenation. Hypoxia-induced histone methylation genomic distribution precedes transcriptional changes and is mimicked by specific Jumonji-C (JmjC) histone demethylase depletion. Oxygen sensing by JmjC histone demethylases is required for the cellular response to hypoxia.
- Published
- 2019
- Full Text
- View/download PDF
24. An opsin 5-dopamine pathway mediates light-dependent vascular development in the eye.
- Author
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Nguyen MT, Vemaraju S, Nayak G, Odaka Y, Buhr ED, Alonzo N, Tran U, Batie M, Upton BA, Darvas M, Kozmik Z, Rao S, Hegde RS, Iuvone PM, Van Gelder RN, and Lang RA
- Subjects
- Animals, Dopamine Plasma Membrane Transport Proteins antagonists & inhibitors, Dopamine Plasma Membrane Transport Proteins chemistry, Dopamine Plasma Membrane Transport Proteins metabolism, Endothelium, Vascular metabolism, Eye enzymology, Eye growth & development, Eye metabolism, Membrane Proteins genetics, Mice, Mice, Knockout, Opsins genetics, Retinal Ganglion Cells metabolism, Retinal Ganglion Cells radiation effects, Threonine metabolism, Vesicular Inhibitory Amino Acid Transport Proteins physiology, Vitreous Body metabolism, Dopamine metabolism, Eye blood supply, Light, Membrane Proteins metabolism, Opsins metabolism
- Abstract
During mouse postnatal eye development, the embryonic hyaloid vascular network regresses from the vitreous as an adaption for high-acuity vision. This process occurs with precisely controlled timing. Here, we show that opsin 5 (OPN5; also known as neuropsin)-dependent retinal light responses regulate vascular development in the postnatal eye. In Opn5-null mice, hyaloid vessels regress precociously. We demonstrate that 380-nm light stimulation via OPN5 and VGAT (the vesicular GABA/glycine transporter) in retinal ganglion cells enhances the activity of inner retinal DAT (also known as SLC6A3; a dopamine reuptake transporter) and thus suppresses vitreal dopamine. In turn, dopamine acts directly on hyaloid vascular endothelial cells to suppress the activity of vascular endothelial growth factor receptor 2 (VEGFR2) and promote hyaloid vessel regression. With OPN5 loss of function, the vitreous dopamine level is elevated and results in premature hyaloid regression. These investigations identify violet light as a developmental timing cue that, via an OPN5-dopamine pathway, regulates optic axis clearance in preparation for visual function.
- Published
- 2019
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25. Hypoxia induces rapid changes to histone methylation and reprograms chromatin.
- Author
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Batie M, Frost J, Frost M, Wilson JW, Schofield P, and Rocha S
- Subjects
- Amino Acids, Dicarboxylic pharmacology, Animals, Cell Hypoxia, Fibroblasts, HeLa Cells, Histones metabolism, Humans, Lysine metabolism, Methylation, Protein Domains, Retinoblastoma-Binding Protein 2 antagonists & inhibitors, Retinoblastoma-Binding Protein 2 chemistry, Retinoblastoma-Binding Protein 2 genetics, Chromatin metabolism, Oxygen metabolism, Retinoblastoma-Binding Protein 2 metabolism
- Abstract
Oxygen is essential for the life of most multicellular organisms. Cells possess enzymes called molecular dioxygenases that depend on oxygen for activity. A subclass of molecular dioxygenases is the histone demethylase enzymes, which are characterized by the presence of a Jumanji-C (JmjC) domain. Hypoxia can alter chromatin, but whether this is a direct effect on JmjC-histone demethylases or due to other mechanisms is unknown. Here, we report that hypoxia induces a rapid and hypoxia-inducible factor-independent induction of histone methylation in a range of human cultured cells. Genomic locations of histone-3 lysine-4 trimethylation (H3K4me3) and H3K36me3 after a brief exposure of cultured cells to hypoxia predict the cell's transcriptional response several hours later. We show that inactivation of one of the JmjC-containing enzymes, lysine demethylase 5A (KDM5A), mimics hypoxia-induced cellular responses. These results demonstrate that oxygen sensing by chromatin occurs via JmjC-histone demethylase inhibition., (Copyright © 2019 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2019
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26. TNFSF14/LIGHT, a Non-Canonical NF-κB Stimulus, Induces the HIF Pathway.
- Author
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D'Ignazio L, Batie M, and Rocha S
- Abstract
Non-canonical NF-κB signalling plays important roles in the development and function of the immune system but it also is deregulated in a number of inflammatory diseases. Although, NF-κB and HIF crosstalk has been documented, this has only been described following canonical NF-κB stimulation, involving RelA/p50 and the HIF-1 dimer. Here, we report that the non-canonical inducer TNFSF14/LIGHT leads to HIF induction and activation in cancer cells. We demonstrate that only HIF-2α is induced at the transcriptional level following non-canonical NF-κB activation, via a mechanism that is dependent on the p52 subunit. Furthermore, we demonstrate that p52 can bind to the HIF-2α promoter in cells. These results indicate that non-canonical NF-κB can lead to HIF signalling implicating HIF-2α as one of the downstream effectors of this pathway in cells., Competing Interests: The authors declare no conflict of interest.
- Published
- 2018
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27. Role for Cela1 in Postnatal Lung Remodeling and Alpha-1 Antitrypsin-Deficient Emphysema.
- Author
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Joshi R, Heinz A, Fan Q, Guo S, Monia B, Schmelzer CEH, Weiss AS, Batie M, Parameshwaran H, and Varisco BM
- Subjects
- Animals, Biomechanical Phenomena, Elastin metabolism, Fibroblasts metabolism, Humans, Lung growth & development, Mice, Knockout, Pancreatic Elastase genetics, Emphysema genetics, Gene Expression Regulation, Enzymologic genetics, Pancreatic Elastase metabolism, alpha 1-Antitrypsin genetics
- Abstract
Alpha-1 antitrypsin (AAT) deficiency-related emphysema is the fourth leading indication for lung transplant. Chymotrypsin-like elastase 1 (Cela1) is a digestive protease that is expressed during lung development in association with regions of elastin remodeling, exhibits stretch-dependent expression during lung regeneration, and binds lung elastin in a stretch-dependent manner. AAT covalently neutralizes Cela1 in vitro. We sought to determine the role of Cela1 in postnatal lung physiology, whether it interacted with AAT in vivo, and to detect any effects it may have in the context of AAT deficiency. The lungs of Cela1
-/- mice had aberrant lung elastin structure and higher elastance as assessed with the flexiVent system. On the basis of in situ zymography with ex vivo lung stretch, Cela1 was solely responsible for stretch-inducible lung elastase activity. By mass spectrometry, Cela1 degraded mature elastin similarly to pancreatic elastase. Cela1 promoter and protein sequences were phylogenetically distinct in the placental mammal lineage, suggesting an adaptive role for lung-expressed Cela1 in this clade. A 6-week antisense oligonucleotide mouse model of AAT deficiency resulted in emphysema with increased Cela1 mRNA and reduction of approximately 70 kD Cela1, consistent with covalent binding of Cela1 by AAT. Cela1-/- mice were completely protected against emphysema in this model. Cela1 was increased in human AAT-deficient emphysema. Cela1 is important in physiologic and pathologic stretch-dependent remodeling processes in the postnatal lung. AAT is an important regulator of this process. Our findings provide proof of concept for the development of anti-Cela1 therapies to prevent and/or treat AAT-deficient emphysema.- Published
- 2018
- Full Text
- View/download PDF
28. SINHCAF/FAM60A and SIN3A specifically repress HIF-2α expression.
- Author
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Biddlestone J, Batie M, Bandarra D, Munoz I, and Rocha S
- Subjects
- A549 Cells, Basic Helix-Loop-Helix Transcription Factors genetics, DNA-Binding Proteins genetics, HeLa Cells, Histone Deacetylase 1 genetics, Histone Deacetylase 1 metabolism, Humans, Promoter Regions, Genetic, RNA, Messenger genetics, Repressor Proteins genetics, Sin3 Histone Deacetylase and Corepressor Complex, Basic Helix-Loop-Helix Transcription Factors biosynthesis, DNA-Binding Proteins metabolism, Gene Expression Regulation, RNA, Messenger biosynthesis, Repressor Proteins metabolism
- Abstract
The SIN3A-HDAC (histone deacetylase) complex is a master transcriptional repressor, required for development but often deregulated in disease. Here, we report that the recently identified new component of this complex, SINHCAF (SIN3A and HDAC-associated factor)/FAM60A (family of homology 60A), links the SIN3A-HDAC co-repressor complex function to the hypoxia response. We show that SINHCAF specifically represses HIF-2α mRNA and protein expression, via its interaction with the transcription factor SP1 (specificity protein 1) and recruitment of HDAC1 to the HIF-2α promoter. SINHCAF control over HIF-2α results in functional cellular changes in in vitro angiogenesis and viability. Our analysis reveals an unexpected link between SINHCAF and the regulation of the hypoxia response., (© 2018 The Author(s).)
- Published
- 2018
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29. Hypoxia and Chromatin: A Focus on Transcriptional Repression Mechanisms.
- Author
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Batie M, Del Peso L, and Rocha S
- Abstract
Hypoxia or reduced oxygen availability has been studied extensively for its ability to activate specific genes. Hypoxia-induced gene expression is mediated by the HIF transcription factors, but not exclusively so. Despite the extensive knowledge about how hypoxia activates genes, much less is known about how hypoxia promotes gene repression. In this review, we discuss the potential mechanisms underlying hypoxia-induced transcriptional repression responses. We highlight HIF-dependent and independent mechanisms as well as the potential roles of dioxygenases with functions at the nucleosome and DNA level. Lastly, we discuss recent evidence regarding the involvement of transcriptional repressor complexes in hypoxia., Competing Interests: The authors declare no conflict of interest.
- Published
- 2018
- Full Text
- View/download PDF
30. Detection of Fetal Arrhythmia Using Optically-Pumped Magnetometers.
- Author
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Batie M, Bitant S, Strasburger JF, Shah V, Alem O, and Wakai RT
- Subjects
- Electrocardiography, Female, Humans, Pregnancy, Signal-To-Noise Ratio, Arrhythmias, Cardiac diagnosis, Fetal Diseases diagnosis, Magnetocardiography methods, Prenatal Diagnosis methods, Signal Processing, Computer-Assisted
- Published
- 2018
- Full Text
- View/download PDF
31. Hypoxia and Inflammation in Cancer, Focus on HIF and NF-κB.
- Author
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D'Ignazio L, Batie M, and Rocha S
- Abstract
Cancer is often characterised by the presence of hypoxia and inflammation. Paramount to the mechanisms controlling cellular responses under such stress stimuli, are the transcription factor families of Hypoxia Inducible Factor (HIF) and Nuclear Factor of κ-light-chain-enhancer of activated B cells (NF-κB). Although, a detailed understating of how these transcription factors respond to their cognate stimulus is well established, it is now appreciated that HIF and NF-κB undergo extensive crosstalk, in particular in pathological situations such as cancer. Here, we focus on the current knowledge on how HIF is activated by inflammation and how NF-κB is modulated by hypoxia. We summarise the evidence for the possible mechanism behind this activation and how HIF and NF-κB function impacts cancer, focusing on colorectal, breast and lung cancer. We discuss possible new points of therapeutic intervention aiming to harness the current understanding of the HIF-NF-κB crosstalk., Competing Interests: The authors declare no conflict of interest.
- Published
- 2017
- Full Text
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32. KDM2 Family Members are Regulated by HIF-1 in Hypoxia.
- Author
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Batie M, Druker J, D'Ignazio L, and Rocha S
- Abstract
Hypoxia is not only a developmental cue but also a stress and pathological stimulus in many human diseases. The response to hypoxia at the cellular level relies on the activity of the transcription factor family, hypoxia inducible factor (HIF). HIF-1 is responsible for the acute response and transactivates a variety of genes involved in cellular metabolism, cell death, and cell growth. Here, we show that hypoxia results in increased mRNA levels for human lysine (K)-specific demethylase 2 (KDM2) family members, KDM2A and KDM2B, and also for Drosophila melanogaster KDM2, a histone and protein demethylase. In human cells, KDM2 family member's mRNA levels are regulated by HIF-1 but not HIF-2 in hypoxia. Interestingly, only KDM2A protein levels are significantly induced in a HIF-1-dependent manner, while KDM2B protein changes in a cell type-dependent manner. Importantly, we demonstrate that in human cells, KDM2A regulation by hypoxia and HIF-1 occurs at the level of promoter, with HIF-1 binding to the KDM2A promoter being required for RNA polymerase II recruitment. Taken together, these results demonstrate that KDM2 is a novel HIF target that can help coordinate the cellular response to hypoxia. In addition, these results might explain why KDM2 levels are often deregulated in human cancers.
- Published
- 2017
- Full Text
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33. Stretch regulates expression and binding of chymotrypsin-like elastase 1 in the postnatal lung.
- Author
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Joshi R, Liu S, Brown MD, Young SM, Batie M, Kofron JM, Xu Y, Weaver TE, Apsley K, and Varisco BM
- Subjects
- Amino Acid Sequence, Animals, Biomechanical Phenomena, Cells, Cultured, Chymases, Elastin metabolism, Fibroblasts metabolism, Kidney cytology, Kidney embryology, Lung cytology, Mice, Pancreatic Elastase genetics, Thy-1 Antigens genetics, Thy-1 Antigens metabolism, alpha 1-Antitrypsin genetics, alpha 1-Antitrypsin metabolism, Gene Expression Regulation, Enzymologic physiology, Lung physiology, Pancreatic Elastase metabolism
- Abstract
Lung stretch is critical for normal lung development and for compensatory lung growth after pneumonectomy (PNX), but the mechanisms by which strain induces matrix remodeling are unclear. Our prior work demonstrated an association of chymotrypsin-like elastase 1 (Cela1) with lung elastin remodeling, and that strain triggered a near-instantaneous elastin-remodeling response. We sought to determine whether stretch regulates Cela1 expression and Cela1 binding to lung elastin. In C57BL/6J mice, Cela1 protein increased 176-fold during lung morphogenesis. Cela1 was covalently bound to serpin peptidase inhibitor, clade A, member 1, resulting in a higher molecular mass in lung homogenate compared to pancreas homogenate. Post-PNX, Cela1 mRNA increased 6-fold, protein 3-fold, and Cela1-positive cells 2-fold. Cela1 was expressed predominantly in alveolar type II cells in the embryonic lung and predominantly in CD90-positive lung fibroblasts postnatally. During compensatory lung growth, Cela1 expression was induced in nonproliferative mesenchymal cells. In ex vivo mouse lung sections, stretch increased Cela1 binding to lung tissue by 46%. Competitive inhibition with soluble elastin completely abrogated this increase. Areas of stretch-induced elastase activity and Cela1 binding colocalized. The stretch-dependent expression and binding kinetics of Cela1 indicate an important role in stretch-dependent remodeling of the peripheral lung during development and regeneration., (© FASEB.)
- Published
- 2016
- Full Text
- View/download PDF
34. Chromatin and oxygen sensing in the context of JmjC histone demethylases.
- Author
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Shmakova A, Batie M, Druker J, and Rocha S
- Subjects
- Chromatin ultrastructure, Histones metabolism, Humans, Transcription, Genetic drug effects, Cell Hypoxia, Chromatin physiology, Jumonji Domain-Containing Histone Demethylases physiology, Oxygen metabolism
- Abstract
Responding appropriately to changes in oxygen availability is essential for multicellular organism survival. Molecularly, cells have evolved intricate gene expression programmes to handle this stressful condition. Although it is appreciated that gene expression is co-ordinated by changes in transcription and translation in hypoxia, much less is known about how chromatin changes allow for transcription to take place. The missing link between co-ordinating chromatin structure and the hypoxia-induced transcriptional programme could be in the form of a class of dioxygenases called JmjC (Jumonji C) enzymes, the majority of which are histone demethylases. In the present review, we will focus on the function of JmjC histone demethylases, and how these could act as oxygen sensors for chromatin in hypoxia. The current knowledge concerning the role of JmjC histone demethylases in the process of organism development and human disease will also be reviewed.
- Published
- 2014
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35. PITX1, a specificity determinant in the HIF-1α-mediated transcriptional response to hypoxia.
- Author
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Mudie S, Bandarra D, Batie M, Biddlestone J, Moniz S, Ortmann B, Shmakova A, and Rocha S
- Subjects
- Aryl Hydrocarbon Receptor Nuclear Translocator chemistry, Aryl Hydrocarbon Receptor Nuclear Translocator metabolism, Cell Hypoxia, Cell Line, Tumor, Cell Proliferation, Cell Survival, HEK293 Cells, HeLa Cells, Histone Demethylases metabolism, Humans, Hypoxia-Inducible Factor 1, alpha Subunit genetics, Paired Box Transcription Factors antagonists & inhibitors, Paired Box Transcription Factors genetics, Photobleaching, Protein Binding, RNA Interference, RNA, Messenger metabolism, RNA, Small Interfering metabolism, Transcription, Genetic, Hypoxia-Inducible Factor 1, alpha Subunit metabolism, Paired Box Transcription Factors metabolism
- Abstract
Hypoxia is an important developmental cue for multicellular organisms but it is also a contributing factor for several human pathologies, such as stroke, cardiovascular diseases and cancer. In cells, hypoxia activates a major transcriptional program coordinated by the Hypoxia Inducible Factor (HIF) family. HIF can activate more than one hundred targets but not all of them are activated at the same time, and there is considerable cell type variability. In this report we identified the paired-like homeodomain pituitary transcription factor (PITX1), as a transcription factor that helps promote specificity in HIF-1α dependent target gene activation. Mechanistically, PITX1 associates with HIF-1β and it is important for the induction of certain HIF-1 dependent genes but not all. In particular, PITX1 controls the HIF-1α-dependent expression of the histone demethylases; JMJD2B, JMJD2A, JMJD2C and JMJD1B. Functionally, PITX1 is required for the survival and proliferation responses in hypoxia, as PITX1 depleted cells have higher levels of apoptotic markers and reduced proliferation. Overall, our study identified PITX1 as a key specificity factor in HIF-1α dependent responses, suggesting PITX1 as a protein to target in hypoxic cancers.
- Published
- 2014
- Full Text
- View/download PDF
36. Impact of corticosterone treatment on spontaneous seizure frequency and epileptiform activity in mice with chronic epilepsy.
- Author
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Castro OW, Santos VR, Pun RY, McKlveen JM, Batie M, Holland KD, Gardner M, Garcia-Cairasco N, Herman JP, and Danzer SC
- Subjects
- Animals, Anti-Inflammatory Agents blood, Anti-Inflammatory Agents metabolism, Corticosterone blood, Corticosterone metabolism, Male, Mice, Mice, Inbred C57BL, Pilocarpine, Status Epilepticus blood, Stress, Physiological, Anti-Inflammatory Agents pharmacology, Corticosterone pharmacology, Seizures drug therapy, Status Epilepticus chemically induced, Status Epilepticus physiopathology
- Abstract
Stress is the most commonly reported precipitating factor for seizures in patients with epilepsy. Despite compelling anecdotal evidence for stress-induced seizures, animal models of the phenomena are sparse and possible mechanisms are unclear. Here, we tested the hypothesis that increased levels of the stress-associated hormone corticosterone (CORT) would increase epileptiform activity and spontaneous seizure frequency in mice rendered epileptic following pilocarpine-induced status epilepticus. We monitored video-EEG activity in pilocarpine-treated mice 24/7 for a period of four or more weeks, during which animals were serially treated with CORT or vehicle. CORT increased the frequency and duration of epileptiform events within the first 24 hours of treatment, and this effect persisted for up to two weeks following termination of CORT injections. Interestingly, vehicle injection produced a transient spike in CORT levels - presumably due to the stress of injection - and a modest but significant increase in epileptiform activity. Neither CORT nor vehicle treatment significantly altered seizure frequency; although a small subset of animals did appear responsive. Taken together, our findings indicate that treatment of epileptic animals with exogenous CORT designed to mimic chronic stress can induce a persistent increase in interictal epileptiform activity.
- Published
- 2012
- Full Text
- View/download PDF
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