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36 results on '"K. Ligon"'

1. JS04.6.A The landscape of tumor cell states and spatial organization in H3-K27M mutant diffuse midline glioma across age and location

Author

I Liu, L Jiang, E Samuelsson, S Marco Salas, O Hack, D Jeong, M Shaw, B Englinger, J LaBelle, K Ernst, H Palova, P Pokorna, J Sterba, O Slaby, R Geyeregger, D Jones, C Koschmann, J Svedlund, A Resnick, A Diaz, C Haberler, T Czech, I Slavc, J Cotter, K Ligon, S Alexandrescu, W Yung, I Arrillaga-Romany, M Suva, A Beck, J Gojo, M Monje, M Nilsson, and M Filbin

Subjects
Cancer Research, Oncology, Neurology (clinical)
Abstract

Background Histone 3 lysine27-to-methionine mutations (H3-K27M) frequently occur in childhood diffuse midline gliomas (DMGs) of the pons, thalamus and spinal cord, presumed to be driven by the specific spatiotemporal context of these midline locations during postnatal development. While most common in the pons and at mid-childhood ages, the same oncohistone mutation is recurrently detected in adult DMGs and throughout different midline regions. The potential heterogeneity of tumors at different ages and in different anatomical locations of the midline are vastly understudied. Material and Methods Through dissecting the transcriptomic, epigenomic and spatial architectures of a comprehensive cohort of patient H3-K27M DMGs - spanning the age range from 2-68 years and locations from spinal cord to thalamus - at single cell resolution, we delineate how age- and location-dependent contexts shape glioma cell-intrinsic and -extrinsic features in light of the shared driver mutation. Results We identify that oligodendrocyte precursor (OPC)-like cells constitute the stem-like compartment in H3-K27M DMGs across all clinico-anatomical groups, however, depending on location, display varying levels of maturity resembling less differentiated pre-OPCs or more mature OPCs further differentiated along the oligodendroglial lineage. We further demonstrate increased mesenchymal cell states in adult tumors, which we link to age-related differences in glioma-associated immune cell compartments. We for the first time resolve the spatial organization of H3-K27M DMG cell types in intact patient tissues, identifying a local niche of the oligodendroglial lineage. Conclusion Our study provides a powerful resource for rational modeling and therapeutic frameworks taking into account determinants of age and location in this lethal glioma group.

Published
2022

2. Timely preterm-birth prediction among pregnant women in Medicaid without preterm-birth history

Author

Xiao Wang, Hannah K Ligon, Yolande Pengetnze, Barry S. Lachman, Sarah E. Messiah, Weiwei Ouyang, Luyu Xie, and Donna Persaud

Subjects
medicine.medical_specialty, business.industry, Singleton, Obstetrics, Medicaid, Health Policy, Attendance, Psychological intervention, MEDLINE, Infant, Newborn, United States, Cohort Studies, Pregnancy, Cohort, Medicine, Humans, Premature Birth, Female, Pregnant Women, business, Socioeconomic status, Reproductive History, Cohort study, Retrospective Studies
Abstract

Objectives To develop and prospectively validate a novel model incorporating claims and community-level socioeconomic data to predict preterm birth at scale among pregnant Medicaid women with no history of preterm birth (PTB). Study design A longitudinal Texas Medicaid cohort study, with 2-year retrospective model building (October 2015-October 2017) and a 1-year prospective model validation phase (January 2018-December 2018). Methods Inclusion criteria were females aged 11 to 55 years with at least 1 live singleton birth and no history of PTB. The primary outcome was live singleton birth earlier than 35 weeks. Covariates were medical/mental/behavioral comorbidities, obstetric history, sociodemographic characteristics, and health services utilization. Of multiple models built, the most parsimonious was selected to classify pregnancies as very high, high, medium, and low risk. Model performance was evaluated using positive predictive value (PPV), sensitivity, case identification ratio (1 / PPV), and timing of prediction. Results The model was built on 6689 pregnancies and validated on 7855 pregnancies. PTB rate earlier than 35 weeks was approximately 3.3%. Significant risk predictors included prenatal visit attendance, insurance gap days, and medical/obstetrical comorbidities. Model PPV was approximately 4-fold higher for very high-risk women (14.7%) vs cohort (3.3%) and so was the case identification ratio (1:7 vs 1:30, respectively). Sensitivity was good, with 57% of PTBs classified as medium risk or higher. Timing of prediction was clinically relevant, with more than 80% of PTBs risk stratified before 24 weeks. Conclusions We report a novel PTB prediction model among pregnant Medicaid women without PTB history, which is timely, accurate, practical, and scalable. We leverage Medicaid and community data readily accessible by Medicaid plans to support population-level interventions to prevent PTBs.

Published
2021

3. Use of streambed substrate as refuge by steelhead or rainbow trout Oncorhynchus mykiss during simulated freshets

Author

Rodney J. Nakamoto, P. F. Baker, Bret C. Harvey, and F. K. Ligon

Subjects
0106 biological sciences, 010604 marine biology & hydrobiology, Aquatic Science, Biology, Fish measurement, 010603 evolutionary biology, 01 natural sciences, Substrate (marine biology), Fishery, Flume, Water column, Carrying capacity, Rainbow trout, Ecology, Evolution, Behavior and Systematics, Refugium (fishkeeping)
Abstract

A flume was used to estimate the carrying capacity of streambed substrates for juvenile steelhead or rainbow trout Oncorhynchus mykiss seeking refuge from simulated freshets. The simulated freshets had mean water column velocities of c. 1·1 m s(-1). The number of O. mykiss finding cover within the interstices of the substrate was documented for different substrate sizes and levels of embeddedness. The availability of suitable refuges determined the carrying capacity of the substrate for O. mykiss. For the size of the O. mykiss tested [mean ± s.d. fork length (L(F)) = 122 ± 12.6 mm], the number of interstices with depths ≥200 mm measured with a 14.0 mm diameter flexible plastic tube was the best predictor of the number of O. mykiss able to find cover (r(2) = 0.75). Oncorhynchus mykiss seeking refuge from freshets may need deeper interstices than those seeking concealment at autumn or winter base flows. The availability of interstices suitable as refuge from high flows may determine autumn and winter carrying capacity.

Published
2016

4. OMICS AND PROGNSTIC MARKERS

Author

K. Adachi, H. Sasaki, S. Nagahisa, K. Yoshida, N. Hattori, Y. Nishiyama, T. Kawase, M. Hasegawa, M. Abe, Y. Hirose, A. Alentorn, Y. Marie, S. Poggioli, H. Alshehhi, B. Boisselier, C. Carpentier, K. Mokhtari, L. Capelle, D. Figarella-Branger, K. Hoang-Xuan, M. Sanson, J.-Y. Delattre, A. Idbaih, S. Yust-Katz, M. Anderson, A. Olar, A. Eterovic, N. Ezzeddine, K. Chen, H. Zhao, G. Fuller, K. Aldape, J. de Groot, N. Andor, J. Harness, S. G. Lopez, T. L. Fung, H. W. Mewes, C. Petritsch, A. Arivazhagan, K. Somasundaram, K. Thennarasu, P. Pandey, B. Anandh, V. Santosh, B. Chandramouli, A. Hegde, P. Kondaiah, M. Rao, R. Bell, R. Kang, C. Hong, J. Song, J. Costello, R. Nagarajan, B. Zhang, A. Diaz, T. Wang, L. Bie, Y. Li, H. Liu, W. F. C. Luyo, M. H. Carnero, M. E. P. Iruegas, A. R. Morell, M. C. Figueiras, R. L. Lopez, C. F. Valverde, A. K.-Y. Chan, J. C.-S. Pang, N. Y.-F. Chung, K. K.-W. Li, W. S. Poon, D. T.-M. Chan, Y. Wang, H.-a. K. Ng, M. Chaumeil, P. Larson, H. Yoshihara, D. Vigneron, S. Nelson, R. Pieper, J. Phillips, S. Ronen, V. Clark, Z. E. Omay, A. Serin, J. Gunel, B. Omay, C. Grady, M. Youngblood, K. Bilguvar, J. Baehring, J. Piepmeier, P. Gutin, A. Vortmeyer, C. Brennan, M. N. Pamir, T. Kilic, B. Krischek, M. Simon, K. Yasuno, M. Gunel, A. L. Cohen, M. Sato, K. D. Aldape, C. Mason, K. Diefes, L. Heathcock, L. Abegglen, D. Shrieve, W. Couldwell, J. D. Schiffman, H. Colman, Q. G. D'Alessandris, T. Cenci, M. Martini, L. Ricci-Vitiani, R. De Maria, L. M. Larocca, R. Pallini, B. Theeler, F. Lang, G. Rao, M. Gilbert, E. Sulman, R. Luthra, K. Eterovic, M. Routbort, R. Verhaak, G. Mills, J. Mendelsohn, F. Meric-Bernstam, A. Yung, K. MacArthur, S. Hahn, G. Kao, R. Lustig, M. Alonso-Basanta, S. Chandrasekaran, E. P. Wileyto, E. Reyes, J. Dorsey, K. Fujii, K. Kurozumi, T. Ichikawa, M. Onishi, J. Ishida, Y. Shimazu, B. Kaur, E. A. Chiocca, I. Date, C. Geisenberger, A. Mock, R. Warta, C. Schwager, C. Hartmann, A. von Deimling, A. Abdollahi, C. Herold-Mende, O. Gevaert, A. Achrol, S. Gholamin, S. Mitra, E. Westbroek, J. Loya, L. Mitchell, S. Chang, G. Steinberg, S. Plevritis, S. Cheshier, J. Xu, S. Napel, G. Zaharchuk, G. Harsh, D. Gutman, C. Holder, R. Colen, W. Dunn, R. Jain, L. Cooper, S. Hwang, A. Flanders, D. Brat, J. Hayes, A. Droop, H. Thygesen, M. Boissinot, D. Westhead, S. Short, S. Lawler, P. Bady, S. Kurscheid, M. Delorenzi, M. E. Hegi, C. Crosby, C. Faulkner, T. Smye-Rumsby, K. Kurian, M. Williams, K. Hopkins, A. Palmer, H. Williams, C. Wragg, H. R. Haynes, K. M. Kurian, P. White, T. Oka, L. Jalbert, A. Elkhaled, R. Jensen, K. Salzman, M. Schabel, D. Gillespie, M. Mumert, B. Johnson, T. Mazor, M. Barnes, S. Yamamoto, H. Ueda, K. Tatsuno, K. Aihara, A. Bollen, M. Hirst, M. Marra, A. Mukasa, N. Saito, H. Aburatani, M. Berger, B. Taylor, S. Popov, A. Mackay, W. Ingram, A. Burford, A. Jury, M. Vinci, C. Jones, D. T. W. Jones, V. Hovestadt, S. Picelli, W. Wang, P. A. Northcott, M. Kool, G. Reifenberger, T. Pietsch, M. Sultan, H. Lehrach, M.-L. Yaspo, A. Borkhardt, P. Landgraf, R. Eils, A. Korshunov, M. Zapatka, B. Radlwimmer, S. M. Pfister, P. Lichter, A. Joy, I. Smirnov, M. Reiser, W. Shapiro, S. Kim, B. Feuerstein, C. Jungk, S. Friauf, A. Unterberg, T. A. Juratli, J. McElroy, W. Meng, A. Huebner, K. D. Geiger, D. Krex, G. Schackert, A. Chakravarti, T. Lautenschlaeger, B. Y. Kim, W. Jiang, J. Beiko, S. Prabhu, F. DeMonte, R. Sawaya, D. Cahill, I. McCutcheon, C. Lau, L. Wang, K. Terashima, S. Yamaguchi, M. Burstein, J. Sun, T. Suzuki, R. Nishikawa, H. Nakamura, A. Natsume, S. Terasaka, H.-K. Ng, D. Muzny, R. Gibbs, D. Wheeler, X.-q. Zhang, S. Sun, K.-f. Lam, K. M. Y. Kiang, J. K. S. Pu, A. S. W. Ho, G. K. K. Leung, F. Loebel, W. T. Curry, F. G. Barker, N. Lelic, A. S. Chi, D. P. Cahill, D. Lu, J. Yin, C. Teo, K. McDonald, A. Madhankumar, C. Weston, B. Slagle-Webb, J. Sheehan, A. Patel, M. Glantz, J. Connor, C. Maire, J. Francis, C.-Z. Zhang, J. Jung, V. Manzo, V. Adalsteinsson, H. Homer, B. Blumenstiel, C. S. Pedamallu, E. Nickerson, A. Ligon, C. Love, M. Meyerson, K. Ligon, L. E. Jalbert, S. J. Nelson, A. W. Bollen, I. V. Smirnov, J. S. Song, A. B. Olshen, M. S. Berger, S. M. Chang, B. S. Taylor, J. F. Costello, S. Mehta, B. Armstrong, S. Peng, A. Bapat, M. Berens, B. Melendez, M. Mollejo, P. Mur, T. Hernandez-Iglesias, C. Fiano, J. Ruiz, J. A. Rey, V. Stadler, A. Schulte, K. Lamszus, C. Schichor, M. Westphal, J.-C. Tonn, O. Morozova, S. Katzman, M. Grifford, S. Salama, D. Haussler, A. Olshen, S. Fouse, S. Nakamizo, T. Sasayama, H. Tanaka, K. Tanaka, K. Mizukawa, M. Yoshida, E. Kohmura, P. Northcott, D. Jones, S. Pfister, R. Otani, S. Takayanagi, K. Saito, S. Tanaka, M. Shin, T. Ozawa, M. Riester, Y.-K. Cheng, J. Huse, K. Helmy, N. Charles, M. Squatrito, F. Michor, E. Holland, M. Perrech, L. Dreher, G. Rohn, R. Goldbrunner, M. Timmer, B. Pollo, V. Palumbo, C. Calatozzolo, M. Patane, R. Nunziata, M. Farinotti, A. Silvani, S. Lodrini, G. Finocchiaro, E. Lopez, A. Rioscovian, R. Ruiz, G. Siordia, A. P. de Leon, C. Rostomily, R. Rostomily, D. Silbergeld, D. Kolstoe, M. Chamberlain, J. Silber, P. Roth, A. Keller, J. Hoheisel, P. Codo, A. Bauer, C. Backes, P. Leidinger, E. Meese, E. Thiel, A. Korfel, M. Weller, G. Nagae, M. Nagane, J. Z. Sanborn, T. Mikkelsen, S. Jhanwar, L. Chin, M. Nishihara, M. Schliesser, C. Grimm, E. Weiss, R. Claus, D. Weichenhan, M. Weiler, T. Hielscher, F. Sahm, B. Wiestler, A.-C. Klein, J. Blaes, C. Plass, W. Wick, G. Stragliotto, A. Rahbar, C. Soderberg-Naucler, M. Won, R. Ezhilarasan, P. Sun, D. Blumenthal, M. Vogelbaum, R. Jenkins, R. Jeraj, P. Brown, K. Jaeckle, D. Schiff, J. Dignam, J. Atkins, D. Brachman, M. Werner-Wasik, M. Mehta, J. Shen, J. Luan, A. Yu, M. Matsutani, Y. Liang, T.-K. Man, A. Trister, M. Tokita, S. Mikheeva, A. Mikheev, S. Friend, M. van den Bent, L. Erdem, T. Gorlia, M. Taphoorn, J. Kros, P. Wesseling, H. Dubbink, A. Ibdaih, P. French, H. van Thuijl, J. Heimans, B. Ylstra, J. Reijneveld, A. Prabowo, I. Scheinin, H. van Essen, W. Spliet, C. Ferrier, P. van Rijen, T. Veersema, M. Thom, A. S.-v. Meeteren, E. Aronica, H. Kim, S. Zheng, D. J. Brat, S. Virk, S. Amini, C. Sougnez, J. Barnholtz-Sloan, R. G. W. Verhaak, C. Watts, A. Sottoriva, I. Spiteri, S. Piccirillo, A. Touloumis, P. Collins, J. Marioni, C. Curtis, S. Tavare, B. Tews, T. P. C. Yeung, B. Al-Khazraji, L. Morrison, L. Hoffman, D. Jackson, T.-Y. Lee, S. Yartsev, G. Bauman, J. Fu, R. Vegesna, Y. Mao, L. E. Heathcock, W. Torres-Garcia, S. Wang, A. McKenna, C. W. Brennan, W. K. A. Yung, J. N. Weinstein, E. P. Sulman, and D. Koul

Subjects
Abstracts, Cancer Research, Text mining, Oncology, business.industry, Neurology (clinical), Computational biology, Biology, Omics, business
Published
2013

5. LAB-STEM CELLS

Author

D. Kozono, M. Nitta, O. Sampetrean, N. Kimberly, D. Kushwaha, D. Merzon, K. Ligon, S. Zhu, K. Zhu, T. H. Kim, C.-H. Kwon, O. Becher, H. Saya, C. C. Chen, L. K. Donovan, S. M. Birks, V. Bosak, G. J. Pilkington, P. Mao, J. Li, K. Joshi, B. Hu, S. Cheng, R. W. Sobol, I. Nakano, M. Li, J. S. Hale, J. T. Myers, A. Y. Huang, C. Gladson, A. A. Sloan, J. N. Rich, J. D. Lathia, P. E. Hall, J. Gallagher, Q. Wu, M. Venere, E. Levy, M. S. Rani, P. Huang, E. Bae, J. Selfridge, L. Cheng, H. Guvenc, R. E. McLendon, A. E. Sloan, H. Phillips, A. Lai, M. Bredel, S. Bao, A. Hjelmeland, M. Sinyuk, P. Sathyan, J. Hale, P. Zinn, C. T. Carson, U. Naik, S. Majumder, L. A. Song, A. Vasanji, N. Tenley, A. B. Hjelmeland, P. Peruzzi, A. Bronisz, E. Antonio Chiocca, J. A. Godlewski, O. A. Guryanova, X. Fang, H.-M. C. Christel, C. Benito, G. Zoltan, B. Aline, S. Tilman, B. Josephine, M. Carolin, S. Thomas, G. Violaine, A. Unterberg, V. Capilla-Gonzalez, H. Guerrero-Cazares, A. Cebrian-Silla, J. M. Garcia-Verdugo, A. Quinones-Hinojosa, J. Man, J. Shoemake, J. Rich, J. Yu, X. He, F. DiMeco, A. L. Vescovi, J. A. Heth, K. M. Muraszko, X. Fan, S. A. Nguyen, O. D. Stechishin, H. A. Luchman, J. J. Kelly, J. G. Cairncross, S. Weiss, Y. Kim, E. Kim, O. O. Guryanova, M. Hitomi, J. Lathia, D. Serwanski, J. Robert, J. Lee, A. Nishiyama, J. K. Liu, W. A. Flavahan, N. Fernandez, M. Wu, S. Das, E. Bazzoli, T. Pulvirenti, M. C. Oberstadt, F. Perna, W. Boyoung, N. Schultz, J. T. Huse, E. I. Fomchenko, F. Voza, V. Tabar, C. W. Brennan, L. M. DeAngelis, S. D. Nimer, E. C. Holland, M. Squatrito, Y.-H. Chen, D. H. Gutmann, S.-H. Kim, M. K. Lee, Y.-J. Chwae, B. C. Yoo, K.-H. Kim, A. Soeda, A. Hara, T. Iwama, D. M. Park, A. Golebiewska, S. Bougnaud, D. Stieber, N. H. Brons, L. Vallar, F. Hertel, R. Bjerkvig, S. P. Niclou, P. Hamerlik, R. Rasmussen, D. Fricova, B. Jiri, A. Schulte, A. Kathagen, S. Zapf, H. Meissner, H. S. Phillips, M. Westphal, K. Lamszus, M. Sanzey, S. K. Singh, A. Vartanian, J. Gumin, E. P. Sulman, F. F. Lang, G. Zadeh, N. S. Bayin, A. Dietrich, T. Abel, M. V. Chao, H.-R. Song, C. J. Buchholz, D. Placantonakis, M. Esencay, D. Zagzag, I. V. Balyasnikova, M. S. Prasol, S. D. Ferguson, A. U. Ahmed, Y. Han, M. S. Lesniak, M. E. Barish, C. E. Brown, K. Herrmann, S. Argalian, M. Gutova, Y. Tang, A. Annala, R. A. Moats, L. Y. Ghoda, K. S. Aboody, S. Gadani, J. Adkins, A. Vsanji, R. McLendon, A. Chenn, D. Park, C. Dictus, S. Friauf, N. A. Valous, N. Grabe, B. Muerle, A. W. Unterberg, C. C. Herold-Mende, H. K. Lee, S. Finniss, E. Buchris, A. Ziv-Av, S. Casacu, C. Xiang, K. Bobbit, S. A. Rempel, T. Mikkelsen, S. Slavin, C. Brodie, D.-H. Woo, Y. Oh, M. Kim, D.-H. Nam, Q. Li, S. Salas, C. Pendleton, O. Wijesekera, D. Chesler, J. Wang, C. Smith, A. Levchenko, Q. LaPlant, K. Pitter, A.-M. Bleau, K. Helmy, J. Werbeck, L. Barrett, F. Shimizu, R. Benezra, E. Holland, Q. Chu, E. Bar, B. Orr, C. G. Eberhart, R. S. Schmid, R. E. Bash, A. M. Werneke, K. K. White, C. R. Miller, F. Agasse, N. Jhaveri, F. M. Hofman, T. C. Chen, A. Natsume, T. Wakabayashi, Y. Kondo, N. Chang, E. Moon, R. Kanai, S. Yip, A. Kimura, S. Tanaka, E. Rheinbay, D. Cahill, W. Curry, G. Mohapatra, J. Iafrate, A. Chi, R. Martuza, S. Rabkin, H. Wakimoto, C. Cusulin, J. A. Frank, and A. J. Annala

Subjects
Abstracts, Cancer Research, Oncology, business.industry, Medicine, Neurology (clinical), Stem cell, business, Cell biology
Published
2012

6. LAB-OMICS AND PROGNOSTIC MARKERS

Author

R. L. Jensen, S. Abraham, N. Hu, J.-L. Boulay, S. Leu, S. Frank, E. Vassella, I. Vajtai, S. von Felten, E. Taylor, M. Schulz, G. Hutter, M. Sailer, J. Hench, L. Mariani, H. F. van Thuijl, I. Scheinin, D. F. van Essen, J. J. Heimans, P. Wesseling, B. Ylstra, J. C. Reijneveld, A. R. Borges, P. L. Larrubia, J. M. B. Marques, S. G. Cerdan, P. Brastianos, P. Horowitz, S. Santagata, R. T. Jones, A. McKenna, G. Getz, K. Ligon, E. Palescandolo, P. Van Hummelen, A. Stemmer-Rachamimov, D. Louis, W. C. Hahn, I. Dunn, R. Beroukhim, X. Guan, J. Vengoechea, S. Zheng, A. Sloan, Y. Chen, D. Brat, B. P. O'Neill, M. Cohen, K. Aldape, S. Rosenfeld, H. Noushmehr, R. G. Verhaak, J. Barnholtz-Sloan, E. M. Bahassi, Y.-Q. Li, E. Cross, W. Li, J. Vijg, C. McPherson, R. Warnick, P. Stambrook, O. Rixe, L. Manterola, S. Tejada-Solis, R. Diez-Valle, M. Gonzalez, P. Jauregui, N. Sampron, C. Barrena, I. Ruiz, J. Gallego, J.-Y. Delattre, A. L. de Munain, M. M. Mlonso, K. Saito, A. Mukasa, G. Nagae, K. Aihara, S. Takayanagi, H. Aburatani, N. Saito, X.-T. Kong, B. D. Fu, S. Du, A. N. Hasso, M. E. Linskey, D. Bota, C. Li, Y.-S. Chen, Z.-p. Chen, C. H. Kim, J. H. Cheong, J. M. Kim, N. P. Yelon, E. Jacoby, Z. R. Cohen, J. Ishida, K. Kurozumi, T. Ichikawa, M. Onishi, K. Fujii, Y. Shimazu, I. Date, R. Narayanan, Q. H. Ho, B. S. Levin, M. L. Maeder, J. K. Joung, C. L. Nutt, D. N. Louis, J. Thorsteinsdottir, P. Fu, M. Gehrmann, G. Multhoff, J.-C. Tonn, C. Schichor, K. Thirumoorthy, N. Gordon, S. Walston, D. Patel, M. Okamoto, A. Chakravarti, K. Palanichamy, P. French, L. Erdem, L. Gravendeel, J. de Rooi, P. Eilers, A. Idbaih, W. Spliet, W. den Dunnen, J. Teepen, P. S. Smitt, J. M. Kros, T. Gorlia, M. van den Bent, D. McCarthy, R. W. Cook, K. Oelschlager, D. Maetzold, M. Hanna, W. Wick, C. Meisner, B. Hentschel, M. Platten, M. C. Sabel, S. Koeppen, R. Ketter, M. Weiler, G. Tabatabai, A. Schilling, A. von Deimling, D. Gramatzki, M. Westphal, G. Schackert, M. Loeffler, M. Simon, G. Reifenberger, M. Weller, L. Moren, M. Johansson, T. Bergenheim, H. Antti, E. P. Sulman, L. D. Goodman, K. M. Wani, F. DeMonte, K. D. Aldape, B. Krischek, I. Gugel, D. Aref, C. Marshall, S. Croul, G. Zadeh, C. L. Nilsson, E. Sulman, H. Liu, C. Wild, C. F. Lichti, M. R. Emmett, F. F. Lang, C. Conrad, A. Alentorn, Y. Marie, B. Boisselier, C. Carpetier, K. Mokhtari, K. Hoang-Xuan, L. Capelle, T. Lautenschlaeger, A. Huebner, J. B. McIntyre, T. Magliocco, M. Hamilton, J. Easaw, B. Pollo, C. Calatozzolo, R. Vuono, S. Guzzetti, M. Eoli, A. Silvani, F. Di Meco, G. Filippini, G. Finocchiaro, A. Joy, A. Ramesh, I. Smirnov, M. Reiser, W. Shapiro, G. Mills, S. Kim, B. Feuerstein, D. D. Gonda, J. Li, N. McCabe, S. Walker, N. Goffard, K. Wikstrom, E. McLean, C. Greenan, T. Delaney, M. McCarthy, F. McDyer, K. E. Keating, I. F. James, T. Harrison, P. Mullan, D. P. Harkin, B. S. Carter, R. D. Kennedy, C. C. Chen, A. S. Patel, J. E. Allen, D. T. Dicker, K. Rizzo, J. M. Sheehan, M. J. Glantz, W. S. El-Deiry, B. Salhia, J. T. Ross, J. Kiefer, C. Van Cott, R. Metpally, A. Baker, Z. Sibenaller, S. Nasser, T. Ryken, R. Ramanathan, M. E. Berens, J. Carpten, N. L. Tran, Y. Bi, S. Pal, Z. Zhang, R. Gupta, L. Macyszyn, H. Fetting, D. O'Rourke, R. V. Davuluri, A. M. Ezrin, K. Moore, W. Stummer, C. G. Hadjipanayis, D. P. Cahill, J. Beiko, D. Suki, S. Prabhu, J. Weinberg, F. Lang, R. Sawaya, G. Rao, I. McCutcheon, F. G. Barker, A. D. Trister, B. Bot, K. Fontes, C. Bridge, A. L. Baldock, J. K. Rockhill, M. M. Mrugala, R. R. Rockne, E. Huang, K. R. Swanson, H. R. Underhill, J. Zhang, M. Shi, X. Lin, A. Mikheev, R. C. Rostomily, A. C. Scheck, P. Stafford, A. Hughes, Z. Cichacz, S. W. Coons, S. A. Johnston, L. Mainwaring, J. Craig, D. Garcia, G. Bergthold, M. Burns, B. Rich, S. Ramkissoon, C. Eberhart, A. Ligon, L. Goumnerova, C. Stiles, M. Kieran, W. Hahn, K. H. Olausson, J. Correia, E. Gafni, M. Theisen, M. Hayashi, S. Haidar, C. Maire, L. A. Mainwaring, A. Norden, P. Wen, A. Kung, B. Alexander, P. Tonellato, and K. L. Ligon

Subjects
Cancer Research, business.industry, Brain tumor, Cancer, Biology, medicine.disease, Omics, Bioinformatics, Abstracts, Cell and molecular biology, Text mining, Oncology, Glioma, medicine, Cancer research, Neurology (clinical), business
Abstract

High-grade glioma is the most common brain tumor in adults, and the prognosis for patients diagnosed with this type of cancer is still poor. The biological behavior of the tumors is correlated to t ...

Published
2012

7. Estimating Habitat-Specific Abundances of PIT-Tagged Juvenile Salmonids Using Mobile Antennas: A Comparison with Standard Electrofishing Techniques in a Small Stream

Author

Peter Fritz Baker, Matthew R. Sloat, and Franklin K. Ligon

Subjects
endocrine system, Ecology, biology, Range (biology), Mobile antennas, Regression analysis, Management, Monitoring, Policy and Law, Aquatic Science, biology.organism_classification, Fishery, Electrofishing, Habitat, Abundance (ecology), Oncorhynchus, Juvenile, Environmental science, Ecology, Evolution, Behavior and Systematics
Abstract

The use of passive integrated transponder (PIT) tags in ecological studies is increasingly common, but evaluations of their performance and range of application in the field are still emerging. Here, we compare habitat unit–scale abundance estimates of PIT-tagged juvenile coho salmon Oncorhynchus kisutch and steelhead O. mykiss derived from multiple-pass surveys with a submersible pole-mounted PIT antenna and backpack electrofishing in a small coastal California stream. We found high concordance of methods for coho salmon and age-0 steelhead and moderate concordance for age-1 and older steelhead. Regression analysis of PIT antenna estimates on electrofishing estimates indicated an approximately one-to-one relationship between methods. Regression intercepts for coho salmon and age-0 steelhead were significantly greater than zero, but the differences were small (with an effect equivalent to less than one fish). We found no evidence that pool area, cover area, or cover complexity influenced the rela...

Published
2011

8. Cell Biology and Signaling

Author

M. Agarwal, R. Nitta, S. Dovat, G. Li, H. Arita, Y. Narita, S. Fukushima, K. Tateishi, Y. Matsushita, A. Yoshida, Y. Miyakita, M. Ohno, V. P. Collins, N. Kawahara, S. Shibui, K. Ichimura, S. A. Kahn, S. Gholamin, M.-P. Junier, H. Chneiweiss, I. Weissman, S. Mitra, S. Cheshier, T. Avril, A. Hamlat, P.-J. Le Reste, J. Mosser, V. Quillien, C. Carrato, A. Munoz-Marmol, L. Serrano, L. Pijuan, C. Hostalot, S. l. Villa, A. Ariza, O. Etxaniz, C. Balana, E. T. Benveniste, Y. Zheng, B. McFarland, D. Drygin, S. Bellis, M. Bredel, D. Lotsch, C. Engelmaier, S. Allerstorfer, M. Grusch, J. Pichler, S. Weis, J. Hainfellner, C. Marosi, S. Spiegl-Kreinecker, W. Berger, A. Bronisz, M. O. Nowicki, Y. Wang, K. Ansari, E. A. Chiocca, J. Godlewski, K. Brown, M. Kwatra, T. Bui, S. Zhu, D. Kozono, J. Li, D. Kushwaha, B. Carter, C. Chen, J. Schulte, M. Srikanth, S. Das, J. Zhang, J. Lathia, L. Yin, J. Rich, E. Olson, J. Kessler, A. Chenn, A. Cherry, B. Haas, Y. H. Lin, S.-E. Ong, N. Stella, C. P. Cifarelli, R. J. Griffin, D. Cong, W. Zhu, Y. Shi, P. Clark, J. Kuo, S. Hu, D. Sun, M. Bookland, N. Darbinian, A. Dey, M. Robitaille, M. Remke, D. Faury, C. Maier, A. Malhotra, N. Jabado, M. Taylor, S. Angers, A. Kenney, X. Ren, H. Zhou, M. Schur, A. Baweja, M. Singh, A. Erdreich-Epstein, J. Fu, D. Koul, J. Yao, N. Saito, S. Zheng, R. Verhaak, Z. Lu, W. K. A. Yung, G. Gomez, S. Volinia, C. Croce, C. Brennan, W. Cavenee, F. Furnari, S. G. Lopez, D. Qu, C. Petritsch, M. Gonzalez-Huarriz, G. Aldave, D. Ravi, A. Rubio, R. Diez-Valle, M. Marigil, P. Jauregi, B. Vera, A. A. d. l. Rocha, S. Tejada-Solis, M. M. Alonso, U. Gopal, J. Isaacs, M. Gruber-Olipitz, S. Dabral, S. Ramkissoon, A. Kung, E. Pak, J. Chung, M. Theisen, Y. Sun, V. Monrose, Y. Franchetti, D. Shulman, N. Redjal, B. Tabak, R. Beroukhim, J. Zhao, S. Buonamici, K. Ligon, J. Kelleher, R. Segal, D. Canton, P. Diaz, J. Scott, K. Hara, T. Kageji, Y. Mizobuchi, K. Kitazato, T. Okazaki, T. Fujihara, K. Nakajima, H. Mure, K. Kuwayama, T. Hara, S. Nagahiro, L. Hill, H. Botfield, K. Hossain-Ibrahim, A. Logan, G. Cruickshank, Y. Liu, M. Gilbert, N. Kyprianou, V. Rangnekar, C. Horbinski, Y. Hu, C. Vo, Z. Li, C. Ke, N. Ru, K. R. Hess, M. E. Linskey, Y.-a. H. Zhou, F. Hu, K. Vinnakota, S. Wolf, H. Kettenmann, P. J. Jackson, J. D. Larson, D. A. Beckmann, B. S. Moriarity, D. A. Largaespada, S. Jalali, S. Agnihotri, S. Singh, K. Burrell, S. Croul, G. Zadeh, S.-H. Kang, M. O. Yu, N.-H. Song, K.-J. Park, S.-G. Chi, Y.-G. Chung, S. K. Kim, J. W. Kim, J. Y. Kim, J. E. Kim, S. H. Choi, T. M. Kim, S.-H. Lee, S.-K. Kim, S.-H. Park, I. H. Kim, C.-K. Park, H.-W. Jung, M. Koldobskiy, I. Ahmed, G. Ho, A. Snowman, E. Raabe, C. Eberhart, S. Snyder, I. Gugel, A. Bornemann, G. Pantazis, S. Mack, D. Shih, N. Sabha, M. Tatagiba, B. Krischek, A. Schulte, K. Liffers, A. Kathagen, S. Riethdorf, M. Westphal, K. Lamszus, J. S. Lee, J. Xiao, P. Patel, J. Schade, J. Wang, B. Deneen, H.-R. Song, L. Leiss, C. Gjerde, H. Saed, A. Rahman, M. Lellahi, P. O. Enger, R. Leung, O. Gil, L. Lei, P. Canoll, S. Sun, D. Lee, A. S. W. Ho, J. K. S. Pu, X.-q. Zhang, N. P. Lee, P. J. R. Dat, G. K. K. Leung, D. Loetsch, E. Steiner, K. Holzmann, C. Pirker, J. Hlavaty, H. Petznek, B. Hegedus, T. Garay, T. Mohr, W. Sommergruber, W. J. Lukiw, B. M. Jones, Y. Zhao, S. Bhattacharjee, F. Culicchia, N. Magnus, D. Garnier, B. Meehan, S. McGraw, M. Hashemi, T. H. Lee, C. Milsom, N. Gerges, J. Trasler, R. Pawlinski, N. Mackman, J. Rak, Z. Maherally, A. Thorne, Q. An, E. Barbu, H. Fillmore, G. Pilkington, S. L. Tan, S. Tan, S. Choi, C. Potts, D. A. Ford, Z. Nahle, A. M. Kenney, L. Matlaf, S. Khan, A. Zider, E. Singer, C. Cobbs, L. Soroceanu, B. C. McFarland, S. W. Hong, R. Rajbhandari, G. B. Twitty, G. K. Gray, H. Yu, E. N. Benveniste, S. E. Nozell, M. Minata, S. Kim, P. Mao, J. Kaushal, I. Nakano, T. Mizowaki, T. Sasayama, K. Tanaka, K. Mizukawa, M. Nishihara, S. Nakamizo, H. Tanaka, M. Kohta, K. Hosoda, E. Kohmura, S. Moeckel, K. Meyer, P. Leukel, U. Bogdahn, M. J. Riehmenschneider, A. K. Bosserhoff, R. Spang, P. Hau, A. Mukasa, A. Watanabe, H. Ogiwara, H. Aburatani, J. Mukherjee, S. Obha, W. See, R. Pieper, R. Otsuka, D. Kung, T. Sinha, G. Meares, S. Nozell, M. Ott, U. Litzenburger, K. Rauschenbach, L. Bunse, S. Pusch, K. Ochs, F. Sahm, C. Opitz, A. von Deimling, W. Wick, M. Platten, P. Peruzzi, R. Read, T. Fenton, J. Wykosky, S. Vandenberg, I. Babic, A. Iwanami, H. Yang, P. Mischel, J. Thomas, M. W. Ronellenfitsch, A. L. Thiepold, P. N. Harter, M. Mittelbronn, J. P. Steinbach, Y. Rybakova, A. Kalen, E. Sarsour, P. Goswami, J. Silber, G. Harinath, B. Aldaz, A. W. M. Fabius, S. Turcan, T. A. Chan, J. T. Huse, A. M. Sonabend, M. Bansal, P. Guarnieri, C. Soderquist, J. Yun, B. Kennedy, J. Sisti, S. Bruce, R. Bruce, R. Shakya, T. Ludwig, S. Rosenfeld, P. A. Sims, J. N. Bruce, A. Califano, M.-T. Stockhausen, K. Kristoffersen, L. S. Olsen, H. S. Poulsen, B. Stringer, B. Day, G. Barry, M. Piper, P. Jamieson, K. Ensbey, Z. Bruce, L. Richards, A. Boyd, A. Sufit, T. Burleson, J. P. Le, A. K. Keating, T. Sundstrom, J. K. Varughese, P. Harter, L. Prestegarden, K. Petersen, F. Azuaje, C. Tepper, E. Ingham, L. Even, S. Johnson, K. O. Skaftnesmo, M. Lund-Johansen, R. Bjerkvig, K. Ferrara, F. Thorsen, H. Takeshima, S. Yamashita, K. Yokogami, S. Mizuguchi, H. Nakamura, J. Kuratsu, T. Fukushima, K. Morishita, Y. Tang, D. Vaka, S. Chen, A. Ponnuswami, Y.-J. Cho, M. Monje, T. Nakamura, D. Cahill, K. Tiemann, H. Hedman, S. P. Niclou, M. Timmer, R. Tjiong, G. Rohn, R. Goldbrunner, P. Stavrinou, M. Perrech, M. Tokita, S. Mikheev, D. Sellers, A. Mikheev, Y. Kosai, R. Rostomily, I. Tritschler, K. Seystahl, J. J. Schroeder, M. Weller, A. Wade, A. E. Robinson, J. J. Phillips, Y. Gong, Y. Ma, Z. Cheng, R. Thompson, Q.-W. Fan, C. Cheng, W. Gustafson, E. Charron, P. Zipper, R. Wong, J. Chen, J. Lau, C. Knobbe-Thosen, N. Jura, G. Reifenberger, K. Shokat, W. Weiss, S. Wu, J. Hu, T. Taylor, G. R. Villa, P. S. Mischel, S. L. Gonias, D. Yamashita, T. Kondo, H. Takahashi, A. Inoue, S. Kohno, H. Harada, S. Ohue, T. Ohnishi, P. Li, J. Ng, L. Yuelling, F. Du, T. Curran, Z.-j. Yang, D. Zhu, R. C. Castellino, E. G. Van Meir, G. Begum, Q. Wang, S.-S. Yang, S.-H. Lin, and K. Kahle

Subjects
Cancer Research, Tumor suppressor gene, Central nervous system, 030204 cardiovascular system & hematology, Biology, urologic and male genital diseases, Abstracts, 03 medical and health sciences, 0302 clinical medicine, medicine, Progenitor cell, Transcription factor, 030304 developmental biology, 0303 health sciences, urogenital system, Cell growth, medicine.disease, nervous system diseases, 3. Good health, Cell biology, medicine.anatomical_structure, NFIB, Oncology, Cell culture, Neurology (clinical), Glioblastoma
Abstract

The phylogenetically-conserved vertebrate transcription factor, NFIB, is an orchestrator of glial differentiation in the developing mammalian central nervous system. We found NFIB expression to be reduced in glioblastoma (GBM), the commonest and most lethal primary adult brain cancer, so investigated what effect increased expression of NFIB had on GBM. Increased expression of NFIB in primary GBM cell lines induced expression of markers of glial differentiation, inhibited cell proliferation, reduced stem/progenitor cell growth, altered cell cycle progression and inhibited tumor growth in murine models of GBM. We thus identified NFIB to be a novel tumor suppressor gene in GBM.

Published
2010

9. Use of streambed substrate as refuge by steelhead or rainbow trout Oncorhynchus mykiss during simulated freshets

Author

F K, Ligon, R J, Nakamoto, B C, Harvey, and P F, Baker

Subjects
Behavior, Animal, Refugium, Rivers, Oncorhynchus mykiss, Water Movements, Animals, Seasons, Ecosystem
Abstract

A flume was used to estimate the carrying capacity of streambed substrates for juvenile steelhead or rainbow trout Oncorhynchus mykiss seeking refuge from simulated freshets. The simulated freshets had mean water column velocities of c. 1·1 m s(-1). The number of O. mykiss finding cover within the interstices of the substrate was documented for different substrate sizes and levels of embeddedness. The availability of suitable refuges determined the carrying capacity of the substrate for O. mykiss. For the size of the O. mykiss tested [mean ± s.d. fork length (L(F)) = 122 ± 12.6 mm], the number of interstices with depths ≥200 mm measured with a 14.0 mm diameter flexible plastic tube was the best predictor of the number of O. mykiss able to find cover (r(2) = 0.75). Oncorhynchus mykiss seeking refuge from freshets may need deeper interstices than those seeking concealment at autumn or winter base flows. The availability of interstices suitable as refuge from high flows may determine autumn and winter carrying capacity.

Published
2015

10. Mutations in LRRK2 other than G2019S are rare in a north american–based sample of familial Parkinson's disease

Author

S. Chouinard, A. Kaczmarek, Susan Mendick, Sharon Evans, P. M. Conneally, Roberta Winnick, Andrew Feigin, L. Elmer, Nathan Pankratz, Barbara Shannon, E. Aiken, T. Ajax, C. Horn, Christine Hunter, J. Mannetter, Margaret F. Turk, Donald S. Higgins, Miodrag Velickovic, C. Dingmann, Maryan DeAngelis, Kapil D. Sethi, M. Marotta-Kollarus, L. Woodward, M. Stacy, Cheyl A. Halter, Karen Williams, Carolyn Peterson, Nestor Galvez-Jimenez, Margaret C. Lannon, C. Schell, Kelvin L. Chou, Tatyana Simuni, H. Poiffaut, Stewart A. Factor, H. Shill, Joseph Jankovic, Michel Panisset, Tatiana Foroud, Juliette Harris, Deborah Judd, A. Podichetty, S. Phipps, Kathy Davis, Joann Belden, V. E. Elsaesser, S. Narayan, J. Fraser, Clifford W. Shults, K. Williamson, Aileen Shinaman, S. Wilson, William C. Nichols, L. Marlor, John M. Bertoni, Joanne Wojcieszek, Cheryl Halter, Kenneth Marek, P. Ryan, Alice Rudolph, Christopher F. O'Brien, Karen Blindauer, Karyn Boyar, Jayaraman Rao, Kelly E. Lyons, Becky Dunlop, C. Costan-Toth, Lauren Seeberger, Ryan J. Uitti, Karen Marder, Stephen G. Reich, David Oakes, Lisa Scollins, Jean Hall, Joanna Hamann, Mandar Jog, Eric Siemers, E. Ohmann, E. Licari, Frederick J. Marshall, Mark Forrest Gordon, Maureen Cook, Peter A. LeWitt, Vincent Calabrese, Jeannine Petit, Diane K. Marek, Rachel Saunders-Pullman, Peggy Roberge, C. Joubert, Hubert H. Fernandez, K. Ligon, J. Carpenter, Lewis Sudarsky, J. Danielson, William C. Koller, David Simon, Michael W. Pauciulo, Danna Jennings, Joseph H. Friedman, and Cliff Shults

Subjects
Adult, Male, Pathology, medicine.medical_specialty, Parkinson's disease, Adolescent, Glycine, Pedigree chart, Disease, Protein Serine-Threonine Kinases, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, medicine.disease_cause, Central nervous system disease, Degenerative disease, Serine, medicine, Humans, Genetic Testing, Aged, Aged, 80 and over, Family Health, Genetics, Mutation, business.industry, Parkinson Disease, Middle Aged, medicine.disease, LRRK2, nervous system diseases, Neurology, North America, Cohort, Female, Neurology (clinical), business
Abstract

A total of 956 individuals with Parkinson's disease (PD) from 430 multiplex PD pedigrees were screened for 12 previously reported, pathogenic LRRK2 mutations: R793M, L1114L, I1371V, R1441C, R1441G, R1441H, Y1699C, M1869T, I2012T, I2020T, G2385R, and IVS31 +3G > A. Previous screening identified the LRRK2 G2019S mutation in 5% of our families. Only 1 of the 12 newly screened mutations, R1441C, was detected in a single family in our patient cohort. These results indicate that, although the G2019S mutation remains the most common mutation identified in familial PD patients, other mutations in LRRK2 are infrequent.

Published
2006

11. IMMUNE CHECKPOINT BLOCKADE FOR GLIOBLASTOMA: PRECLINICAL ACTIVITY OF SINGLE AGENT AND COMBINATORIAL THERAPY

Author

D. A. Reardon, P. Gokhale, K. Ligon, X. Liao, S. Rodig, J. Zhou, L. Win, F. S. Hodi, N. E. Kohl, and G. Freeman

Subjects
Cancer Research, Oncology, Neurology (clinical), abstracts
Abstract

BACKGROUND: Outcome for glioblastoma (GBM) remains dismal and innovative treatment strategies are desperately needed. Growing data support the contribution of local and systemic immune checkpoint molecules to regulating immunosuppression by GBM tumors. METHODS: Luciferized GL261 cells (GL261-Luc) were stereotactically implanted intracranially in albino C57BL/6 mice. Cohorts of mice with growing tumors (increasing bioluminescence) were treated with murine monoclonal antibodies (MAb) against PD-L1, PD-L2, CTLA-4 and combinations thereof every 3 days X 8 doses beginning 6 days following tumor implantation. Treated mice and appropriate controls were followed for overall survival and subsets of mice underwent magnetic resonance imaging (MRI) as well as analysis of tumor infiltrating immune cells, and evaluation of systemic immune cells and immunocytokines. Tumor re-challenge experiments were performed among long-term surviving treated mice. RESULTS: Improved survival was noted among mice treated with immune checkpoint blockade compared to appropriate controls. The most robust survival benefit was noted among mice treated with combinatorial therapy. MRI imaging among long-term surviving animals demonstrated clear evidence of initial tumor growth followed by regression and eradication of tumors. Long-term surviving mice appeared fully intact neurologically and exhibited no evidence of tumor growth following re-challenge of GL261-Luc cells injected subcutaneously. Characterization of tumor infiltrating immune cells as well as systemic immune cells and immunocytokines is ongoing. CONCLUSIONS: Immune checkpoint blockade provides significant survival benefit and appears safe in this immunocompetent, orthotopic GBM model. Re-challenge experiments demonstrate evidence of long-term immunologic memory and further elucidation of underlying mechanisms of immune-mediated anti-tumor activity is ongoing. These data strongly support the evaluation of immune checkpoint inhibitors among patients with GBM. SECONDARY CATEGORY: Preclinical Experimental Therapeutics.

Published
2014

12. EXPERIMENTAL THERAPEUTICS AND PHARMACOLOGY

Author

C. Aaberg-Jessen, L. Fogh, B. Halle, V. Jensen, N. Brunner, B. W. Kristensen, T. Abe, Y. Momii, J. Watanabe, I. Morisaki, A. Natsume, T. Wakabayashi, M. Fujiki, B. Aldaz, A. W. M. Fabius, J. Silber, G. Harinath, T. A. Chan, J. T. Huse, S. Anai, T. Hide, H. Nakamura, K. Makino, S. Yano, J.-i. Kuratsu, I. V. Balyasnikova, M. S. Prasol, D. K. Kanoija, K. S. Aboody, M. S. Lesniak, T. Barone, C. Burkhart, A. Purmal, A. Gudkov, K. Gurova, R. Plunkett, K. Barton, K. Misuraca, F. Cordero, E. Dobrikova, H. Min, M. Gromeier, D. Kirsch, O. Becher, L. B. Pont, J. Kloezeman, M. van den Bent, R. Kanaar, A. Kremer, S. Swagemakers, P. French, C. Dirven, M. Lamfers, S. Leenstra, R. Balvers, A. Kleijn, S. Lawler, X. Gong, A. Andres, J. Hanson, J. Delashaw, D. Bota, C.-C. Chen, N.-W. Yao, W.-J. Chuang, C. Chang, P.-Y. Chen, C.-Y. Huang, K.-C. Wei, Y. Cheng, Q. Dai, R. Morshed, Y. Han, B. Auffinger, D. Wainwright, L. Zhang, A. Tobias, E. Rincon, B. Thaci, A. Ahmed, C. He, M. Lesniak, Y. A. Choi, H. Pandya, D. M. Gibo, I. Fokt, W. Priebe, W. Debinski, Y. Chornenkyy, S. Agnihotri, P. Buczkowicz, P. Rakopoulos, A. Morrison, M. Barszczyk, C. Hawkins, S. Chung, S. Decollogne, P. Luk, H. Shen, W. Ha, B. Day, B. Stringer, P. Hogg, P. Dilda, K. McDonald, S. Moore, M. Hayden-Gephart, J. Bergen, Y. Su, H. Rayburn, M. Edwards, M. Scott, J. Cochran, A. Das, A. K. Varma, G. C. Wallace, Y. N. Dixon-Mah, W. A. Vandergrift, P. Giglio, S. K. Ray, S. J. Patel, N. L. Banik, T. Dasgupta, A. Olow, X. Yang, S. Mueller, M. Prados, C. D. James, D. Haas-Kogan, N. D. Dave, P. B. Desai, G. A. Gudelsky, L. M. L. Chow, K. LaSance, X. Qi, J. Driscoll, K. Ebsworth, M. J. Walters, L. S. Ertl, Y. Wang, R. D. Berahovic, J. McMahon, J. P. Powers, J. C. Jaen, T. J. Schall, Z. Eroglu, J. Portnow, A. Sacramento, E. Garcia, A. Raubitschek, T. Synold, S. Esaki, S. Rabkin, R. Martuza, H. Wakimoto, S. Ferluga, C. L. Tome, H. E. Forde, I. A. Netland, L. Sleire, B. Skeie, P. O. Enger, D. Goplen, M. Giladi, A. Tichon, R. Schneiderman, Y. Porat, M. Munster, M. Dishon, U. Weinberg, E. Kirson, Y. Wasserman, Y. Palti, D. Gramatzki, M. Staudinger, K. Frei, M. Peipp, M. Weller, C. Grasso, L. Liu, N. Berlow, L. Davis, M. Fouladi, A. Gajjar, E. Huang, E. Hulleman, M. Hutt, C. Keller, X.-N. Li, P. Meltzer, M. Quezado, M. Quist, E. Raabe, P. Spellman, N. Truffaux, D. van Vurden, N. Wang, K. Warren, R. Pal, J. Grill, M. Monje, A. L. Green, S. Ramkissoon, D. McCauley, K. Jones, J. A. Perry, L. Ramkissoon, C. Maire, S. Shacham, K. L. Ligon, A. L. Kung, K. Zielinska-Chomej, V. Grozman, J. Tu, K. Viktorsson, R. Lewensohn, S. Gupta, A. Mladek, K. Bakken, B. Carlson, F. Boakye-Agyeman, S. Kizilbash, M. Schroeder, J. Reid, J. Sarkaria, P. Hadaczek, T. Ozawa, L. Soroceanu, Y. Yoshida, L. Matlaf, E. Singer, E. Fiallos, C. S. Cobbs, R. Hashizume, M. Tom, Y. Ihara, R. Santos, J. D. L. Torre, E. Lepe, T. Waldman, D. James, X. Huang, L. Yu-Jen, N. Gupta, D. Solomon, Z. Zhang, T. Hayashi, K. Adachi, S. Nagahisa, M. Hasegawa, Y. Hirose, M. H. Gephart, Y. S. Su, S. Hingtgen, R. Kasmieh, I. Nesterenko, J.-L. Figueiredo, R. Dash, D. Sarkar, P. Fisher, K. Shah, E. Horne, P. Diaz, N. Stella, C. Huang, H. Yang, K. Wei, T. Huang, J. Hlavaty, D. Ostertag, F. L. Espinoza, B. Martin, H. Petznek, M. Rodriguez-Aguirre, C. Ibanez, N. Kasahara, W. Gunzburg, H. Gruber, D. Pertschuk, D. Jolly, J. Robbins, B. Hurwitz, J. Y. Yoo, C. Bolyard, J.-G. Yu, J. Wojton, J. Zhang, Z. Bailey, D. Eaves, T. Cripe, M. Old, B. Kaur, L. Serwer, N. Le Moan, S. Ng, N. Butowski, A. Krtolica, S. P. L. Cary, T. Johns, S. Greenall, J. Donoghue, T. Adams, G. Karpel-Massler, M.-A. Westhoff, R. E. Kast, A. Dwucet, C. R. Wirtz, K.-M. Debatin, M.-E. Halatsch, N. Merkur, F. Kievit, Z. Stephen, K. Wang, D. Kolstoe, R. Ellenbogen, M. Zhang, G. Kitange, E. Haefner, K. Knubel, B. M. Pernu, A. Sufit, A. M. Pierce, S. K. Nelson, A. K. Keating, S. S. Jensen, J. Lachowicz, M. Demeule, A. Regina, S. Tripathy, J.-C. Curry, T. Nguyen, J.-P. Castaigne, T. Davis, A. Davis, K. Tanaka, T. Keating, J. Getz, G. T. Kapp, J. M. Romero, S. Lee, S. Ramisetti, B. Slagle-Webb, A. Sharma, J. Connor, W.-S. Lee, M. Kluk, J. C. Aster, K. Ligon, S. Sun, D. Lee, A. S. W. Ho, J. K. S. Pu, Z.-q. Zhang, N. P. Lee, P. J. R. Day, G. K. K. Leung, Z. Liu, X. Liu, A. B. Madhankumar, P. Miller, B. Webb, J. R. Connor, Q. X. Yang, M. Lobo, S. Green, M. Schabel, Y. Gillespie, R. Woltjer, M. Pike, Y.-J. Lu, H. A. Luchman, O. Stechishin, S. Nguyen, J. G. Cairncross, S. Weiss, X. Lun, J. C. Wells, X. Hao, N. Grinshtein, D. Kaplan, A. Luchman, D. Senger, S. Robbins, A. Madhankumar, E. Rizk, R. Payne, A. Park, M. Pang, K. Harbaugh, A. Wilisch-Neumann, D. Pachow, E. Kirches, C. Mawrin, S. McDonell, J. Liang, Y. Piao, N. Nguyen, A. Yung, R. Verhaak, E. Sulman, C. Stephan, F. Lang, J. de Groot, Y. Mizobuchi, T. Okazaki, T. Kageji, K. Kuwayama, K. T. Kitazato, H. Mure, K. Hara, R. Morigaki, K. Matsuzaki, K. Nakajima, S. Nagahiro, S. Kumala, M. Heravi, S. Devic, T. Muanza, K. H. Knubel, A. Neuwelt, Y. J. Wu, A. Donson, R. Vibhakar, S. Venkatamaran, V. Amani, E. Neuwelt, L. Rapkin, N. Foreman, F. Ibrahim, P. New, K. Cui, H. Zhao, D. Chow, W. Stephen, K. Nozue-Okada, M. Nagane, K. L. McDonald, D. Ogawa, E. Chiocca, J. Godlewski, A. Patel, N. Pasupuleti, F. Gorin, A. Valenzuela, L. Leon, K. Carraway, C. Ramachandran, S. Nair, K.-W. Quirrin, Z. Khatib, E. Escalon, S. Melnick, A. Phillips, E. Boghaert, K. Vaidya, P. Ansell, D. Shalinsky, Y. Zhang, M. Voorbach, S. Mudd, K. Holen, R. Humerickhouse, E. Reilly, S. Parab, O. Diago, T. Ryken, S. Agarwal, M. Al-Keilani, M. Alqudah, Z. Sibenaller, M. Assemolt, K. Sai, W.-y. Li, W.-p. Li, Z.-p. Chen, R. Saito, Y. Sonoda, M. Kanamori, Y. Yamashita, T. Kumabe, T. Tominaga, G. Sarkar, G. Curran, R. Jenkins, R. Scharnweber, Y. Kato, J. Lin, R. Everson, H. Soto, C. Kruse, L. Liau, R. Prins, S. Semenkow, Q. Chu, C. Eberhart, R. Sengupta, J. Marassa, D. Piwnica-Worms, J. Rubin, R. Shai, T. Pismenyuk, I. Moshe, T. Fisher, S. Freedman, A. Simon, N. Amariglio, G. Rechavi, A. Toren, M. Yalon, Y. Shimazu, K. Kurozumi, T. Ichikawa, K. Fujii, M. Onishi, J. Ishida, T. Oka, M. Watanabe, Y. Nasu, H. Kumon, I. Date, R. W. Sirianni, R. L. McCall, J. Spoor, M. van der Kaaij, M. Geurtjens, O. Veiseh, C. Fang, M. Leung, G. Strohbehn, K.-K. Atsina, T. Patel, J. Piepmeier, J. Zhou, W. M. Saltzman, M. Takahashi, G. Valdes, A. Inagaki, S. Kamijima, K. Hiraoka, E. Micewicz, W. H. McBride, K. S. Iwamoto, H. E. Gruber, J. M. Robbins, D. J. Jolly, C. McCully, J. Bacher, T. Thomas, R. Murphy, E. Steffen-Smith, R. McAllister, D. Pastakia, B. Widemann, P. Chen, M. Hua, H. Liu, E. C. Woolf, M. G. Abdelwahab, K. E. Fenton, Q. Liu, G. Turner, M. C. Preul, A. C. Scheck, W. Shen, D. Brown, H. Pedersen, S. Hariono, T.-W. Yao, A. Sidhu, W. A. Weiss, T. P. Nicolaides, and T. Olusanya

Subjects
Cancer Research, Abstracts, Oncology, business.industry, Medicine, Neurology (clinical), Pharmacology, business
Published
2013

13. R1514Q substitution in Lrrk2 is not a pathogenic Parkinson's disease mutation

Author

Karen Williams, Carolyn Peterson, S. Narayan, Margaret F. Turk, Julie H. Carter, C. Schell, Carlos Singer, Chad W. Christine, Paul J. Tuite, Robyn Schacherer, J. Whetteckey, S. Phipps, Diane K. Marek, William C. Nichols, John M. Bertoni, A. H. Rajput, Kenneth Marek, An Tran, P. Ryan, J. Hevezi, Joan Werner, Kelvin L. Chou, S. Chouinard, James Sutton, Margaret C. Lannon, T. Ajax, Joan Young, Deborah Judd, L. Zelaya, David Grimes, Magali Fernandez, Theresa A. Zesiewicz, Mark Stacy, Peggy Gray, Debra Berry, Michael J. Aminoff, C. Horn, C. Costan-Toth, J. Mannetter, Patricia Simpson, Susan Rolandelli, Tatiana Foroud, T. Tra, S. Wilson, Judith Dobson, Nestor Galvez-Jimenez, Donna Schwieterman, Shirley Uy, K. Price, J. Wojcieszek, Anette Nieves, Paul Atchison, Susan Bennett, L. Klassen, A. Podichetty, Vincent Calabrese, Becky Dunlop, D. Kamp, Holly Delgado, Sandra Roque, Maureen A. Leehey, Richard Camicioli, Julie So, Jayaraman Rao, Kelly E. Lyons, Kapil D. Sethi, A. Wang, Lynn Marlor, David Oakes, S. Culver, Juan Sanchez-Ramos, L. Woodward, J. Danielson, Jeannine Petit, Joann Belden, E. Licari, M. Meacham, Deborah Fontaine, Sharon Evans, C. Stone, S. Morehouse, Christopher F. O'Brien, G. Podskalny, J. Fraser, Anthony E. Lang, W.R. Wayne Martin, Carmen Serrano, H. Poiffaut, Stewart A. Factor, Joanne Wojcieszek, S. Belber, L. Davis, C. Allen, J. Hall, Judy Richman, Joseph Jankovic, Carson Reider, Stephen G. Reich, Stephanie Thomas, Kathy Davis, Richard B. Dewey, Karen Marder, T. Demarcaida, A. Kaczmarek, Lauren Seeberger, C. Halter, Mary Lou Klimek, Donald S. Higgins, Miodrag Velickovic, Joanna Hamann, Eric Siemers, E. Ohmann, C. Dingmann, Galit Kleiner-Fisman, Shari Niswonger, Theresa Derian, Maryan DeAngelis, Aileen Shinaman, Tilak Mendis, M. Rundle, Susan Mendick, L. Giffin, Karen Blindauer, Paul Gordon, Andrew Feigin, L. Shulman, Maureen Cook, Brian Wulbrecht, Rajesh Pahwa, T. Foroud, Un Jung Kang, Arthur Watts, Oksana Suchowersky, C. Joubert, J. Vo, Mandar Jog, M. Panisset, Roberta Winnick, Ronald F. Pfeiffer, Barbara Shannon, Jean P. Hubble, Clifford W. Shults, T. Gales, Tanya Simuni, M. Wolff, Hubert H. Fernandez, Pam Andrews, Karyn Boyar, Brad A. Racette, Vicki Hunt, Christine Hunter, Daniel D. Truong, L. Good, Robert L. Rodnitzky, P. Rodriguez, Sandra K. Kostyk, T. Shirley, Cheryl Halter, Peter A LeWitt, W. Weiner, Ryan J. Uitti, Lisa Scollins, Marc L. Gordon, J. Carpenter, Alice Rudolph, Lewis Sudarsky, Robert A. Hauser, Cliff Shults, Bala V. Manyam, Francis O. Walker, Juliette Harris, Marguerite Wieler, K. Dustin, Kelli Williamson, Brenda Pfeiffer, William C. Koller, Frederick J. Marshall, V. Hagen, A. Campbell, B. Hutchinson, L. Elmer, Anja Rudolph, K. Haas, Tori Ross, Rachel Saunders-Pullman, Nathan Pankratz, E. Aiken, Mariann DiMinno, Peggy Roberge, Arif Dalvi, B. Hayward, Mayank Pathak, David Simon, Michael W. Pauciulo, Holly A. Shill, M. Marotta-Kollarus, K. Ligon, Alok Sahay, Joseph H. Friedman, Neal Hermanowicz, E. Julian-Baros, Irenita Gardiner, N. Luong, Danna Jennings, R. Kurlan, and P. M. Conneally

Subjects
Adult, Male, Parkinson's disease, Adolescent, Genotype, Arginine, Guanine, Protein Serine-Threonine Kinases, Biology, Leucine-Rich Repeat Serine-Threonine Protein Kinase-2, medicine.disease_cause, Diagnosis, Differential, chemistry.chemical_compound, Degenerative disease, medicine, Humans, Point Mutation, Aged, Aged, 80 and over, Genetics, Mutation, Substitution (logic), Adenine Nucleotide Translocator 1, Genetic Variation, Parkinson Disease, Middle Aged, medicine.disease, LRRK2, nervous system diseases, Amino Acid Substitution, Neurology, chemistry, Female, Neurology (clinical), Carrier Proteins
Abstract

Mutations in LRRK2 were first reported as causing Parkinson's disease (PD) in late 2004. Since then, approximately a dozen LRRK2 substitutions have been identified that are believed to be pathogenic mutations. The substitution of adenine for guanine at nucleotide 4541 (4541G>A) in LRRK2 was recently reported. This substitution resulted in the replacement of an arginine at position 1514 with a glutamine (R1514Q). Although this substitution was not found in a large cohort of controls, its pathogenicity could not be verified. We have now genotyped the R1514Q substitution in a sample of 954 PD patients from 429 multiplex PD families. This substitution was identified in 1.8% of the PD patients; however, the majority of the PD sibships segregating this substitution were discordant for this putative mutation. In addition, the R1514Q substitution was detected in 1.4% of neurologically evaluated, control individuals. These data suggest that the R1514Q variant is not a pathogenic LRRK2 mutation. We believe it is imperative that the causative nature of any newly identified genetic variant be determined before it is included in any panel for diagnostic testing.

Published
2007

14. Estimating the influence of temperature on the survival of chinook salmon smolts (Oncorhynchus tshawytscha) migrating through the Sacramento – San Joaquin River Delta of California

Author

Peter Fritz Baker, Franklin K. Ligon, and Terence P. Speed

Subjects
Delta, Chinook wind, geography, River delta, geography.geographical_feature_category, biology, Aquatic Science, biology.organism_classification, Confidence interval, Fishery, Water temperature, Oncorhynchus, Environmental science, %22">Fish , San Joaquin, Ecology, Evolution, Behavior and Systematics
Abstract

Data from the U.S. Fish and Wildlife Service are used to investigate the relationship between water temperature and survival of hatchery-raised fall-run chinook salmon (Oncorhynchus tshawytscha) smolts migrating through the Sacramento – San Joaquin Delta of California. A formal statistical model is presented for the release of smolts marked with coded-wire tags (CWTs) in the lower Sacramento River and the subsequent recovery of marked smolts in midwater trawls in the Delta. This model treats survival as a logistic function of water temperature, and the release and recovery of different CWT groups as independent mark–recapture experiments. Iteratively reweighted least squares is used to fit the model to the data, and simulation is used to establish confidence intervals for the fitted parameters. A 95% confidence interval for the upper incipient lethal temperature, inferred from the trawl data by this method, is 23.01 ± 1.08 °C This is in good agreement with published experimental results obtained under controlled conditions (24.3 ± 0.1 and 25.1 ± 0.1 °C for chinook salmon acclimatized to 10 and 20 °C, respectively): this agreement has implications for the applicability of laboratory findings to natural systems.

Published
1995

15. Downstream Ecological Effects of Dams

Author

Franklin K. Ligon, William E. Dietrich, and William J. Trush

Subjects
geography, geography.geographical_feature_category, Floodplain, business.industry, Ecology, Sediment, Biota, Ecological relationship, Hydroelectricity, Environmental science, Ecosystem, General Agricultural and Biological Sciences, business, Hydropower, Channel (geography)
Abstract

The damming of a river changes the flow of water, sediment, nutrients, energy, and biota, interrupting and altering most of a river`s ecological processes. This article discusses the importance of geomorphological analysis in river conservation and management. To illustrate how subtle geomorphological adjustments may profoundly influence the ecological relationships downstream from dames, three case studies are presented. Then a geomorphically based approach for assessing and possibly mitigating some of the environmental effects of dams by tailoring dam designed and operation is outlined. The cases are as follows: channel simplification and salmon decline on the McKenzie River in Oregon; Channel incision and reduced floodplain inundation on the Oconee river in Georgia; Increased stability of a braided river in New Zealand`s south island. 41 refs., 10 figs., 1 tab.

Published
1995

16. Long-term outcome of early versus delayed rasagiline treatment in early Parkinson's disease

Author

Micki McCollister, Julie Hevezi, Naomi Santoni, Tracey Tam, Rajesh Pahwa, Cynthia Alcorn-Costa, Barbara Fussell, Xiaoming Lu, Cheryl Armstrong, Peggy Gray, Patricia Dyches, Jovianna N. Wellinghoff, Shaunna Caouette, James B. Osborne, William C. Koller, Tilak Mendis, Shantelle Coe, Jacqueline Nash, Shirley Uy, Howard I. Hurtig, Susan Rolli, Tracy Stewart, Judy Richman, Susan Rolandelli, William G. Ondo, Cathi A. Thomas, Melodie Moterson, Maryan DeAngelis, Sheila Everett, Mary Mathews, Linda L. Mann, Eric Molho, Lorette J. Jenkins, Jessie Roth, Sandra K. Kostyk, Deborah L. Caputo, Ali H. Rajput, Jean Ayan, Un Jung Kang, Paul Atchison, Jo Belden, Julie So, Andew Feigin, Lisa Johnston, Lawrence I. Golb, Howard H. Hurtig, Larisa I. Skrypnik, Michael J. Aminoff, J. Carpenter, Patricia Seuffert, Carlos Singer, Amy Parsons, Kapil D. Sethi, Mark Forrest Gordon, Pam King, Mary Lloyd, Katherine B. Hawthorne, Linda Klassen, Shoba Narayan, Cathy R. Anderson, Patricia Kaminski, Karen Caplan, Robert A. Hauser, Dinorah Bateman, Erica Barnabei, Cheryl Fitzer-Attas, Kellie Gelles, Tamara Gales, Joanne Wojcieszek, Robert Hauser, Teri Radam, Karen Stavris, Carolyn C. Weeks, Marlene Gerow, Connie Kawai, Tracey Borst, Caroline M. Tanner, Charles H. Adler, Mickie Welsh, Nancy Pearson, Anita Lopez, Georgia Germain, Cathy W. Allen, Marianne Ewasnishin, Lisa Tagg, Brenda Ebbitt, Myrna Schear, Jean A. Jaglin, Roberta Winnick, Dawn Miller, Nancy Saton, Suzanne W. Schuman, Davoud Mohtat, Barbara Shannon, Vincent Calabrese, Mark F. Lew, Janis M. Miyasaki, William J. Weiner, Jody Lowery, Christine Hunter, Diane Brown, Keely Haas, Paul J. Tuite, Peter A. LeWitt, Mirann DiMinno, Cheryl Cooper, Peter Novak, Robert G. Feldman, Joanne Hamann, Sharon Evans, W.R. Wayne Martin, Mark Stacy, Debra Berry, Sharon Wortzel, John M. Bertoni, Kenneth Marek, Kelli Williamson, Lisa Gauger, Cheryl Newcomb, Carolyn Peterson, K. Ligon, Stephanie Newman, Vanessa Patterson, Peggy Roberge, Arif Dalvi, Laura Sutherland, Frederick J. Marshall, Scott Cradr, Karen Betcher, Carolyn Deloa, Jean P. Hubble, Kathleen M. Shannon, Sharyn Parness, Neila Mendis, Germanine McInnes, Adrienne Baranauskas, and Irenita Gardiner

Subjects
Adult, Male, medicine.medical_specialty, Parkinson's disease, Monoamine Oxidase Inhibitors, Time Factors, Placebo, Severity of Illness Index, Drug Administration Schedule, law.invention, Central nervous system disease, Antiparkinson Agents, Levodopa, chemistry.chemical_compound, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Severity of illness, medicine, Humans, Longitudinal Studies, Aged, Retrospective Studies, Rasagiline, Dose-Response Relationship, Drug, Reproducibility of Results, Retrospective cohort study, Parkinson Disease, Middle Aged, medicine.disease, Surgery, Clinical trial, Treatment Outcome, Neurology, chemistry, Indans, Quality of Life, Female, Neurology (clinical), Psychology
Abstract

The purpose of this study to compare the long-term clinical outcome of early versus delayed rasagiline treatment in early Parkinson's disease (PD). Subjects (N = 404) were randomly assigned to initial treatment with rasagiline (early-start group) or placebo for 6 months followed by rasagiline (delayed-start group) in the TEMPO study. Subjects who chose to participate in an open-label extension (N = 306) continued to receive rasagiline as well as other PD medications as needed. Average (+/-SD) duration in the study was 3.6 +/- 2.1 years; 177 subjects received rasagiline for > or =5.0 years. Over the entire 6.5-year follow-up period, the adjusted mean difference in change from baseline in total UPDRS scores was 2.5 units (SE 1.1; P = 0.021) or 16% (SE 5.7; P = 0.006) in favor of the early-start versus delayed-start rasagiline group. Although the interaction between treatment and time was significant, values for the early-start group were better than the delayed-start group across all time points. Significantly less worsening (percent change) in total UPDRS scores was observed in the early-start group at the time points 0.5, 1.5, 2.0, 3.0, 4.5, 5.0, and 5.5 years (P < 0.05). Compared to delayed start, early initiation of rasagiline provided long-term clinical benefit, even in the face of treatment with other dopaminergic agents. This might reflect enduring benefits due to neuroprotection or effects on compensatory mechanisms in early PD.

Published
2008

17. Pramipexole in levodopa-treated Parkinson disease patients of African, Asian, and Hispanic heritage

Author

Mickie Welsh, Daniel Truong, Rajesh Pahwa, K. Ligon, Cynthia L. Comella, Kenneth Marek, William C. Koller, Kimberly Janko, Brenda Pfeiffer, Andrea Freimuth, Sara Rast, Lori McGee-Minnich, An Hao Tran, Cheryl H. Waters, Karl Kieburtz, Kapil D. Sethi, Howard I. Hurtig, Cindy Casaceli, Sheila Everett, Ronald F. Pfeiffer, C.D. Wood, Carmen Serrano Ramos, Sam Goldman, Jayaraman Rao, Andrew Feigin, Marian L. Evatt, Arthur Watts, Carolyn C. Weeks, Richard Trosch, David Oakes, Giselle Petzinger, Caroline M. Tanner, Janet S. Cellar, Julie H. Carter, Cornelia Kamp, Kathleen M. Shannon, Denni Day, Kathie Mistura, Susan Broshjeit, Clare Das, George W. Paulson, Adelma Rivera Cruz, Alicia Brocht, Karen Hodgeman, Carson Reider, Frederick J. Marshall, Karen Thompson, Mary Matthews, Ira Shoulson, Mariella Fernandez, Joel S. Perlmutter, Lisa M. Shulman, and Dinorah Rodriguez

Subjects
Cross-Cultural Comparison, Male, medicine.medical_specialty, Levodopa, Time Factors, Disease, Severity of Illness Index, law.invention, Antiparkinson Agents, Pramipexole, Randomized controlled trial, Double-Blind Method, law, Internal medicine, Medicine, Humans, Pharmacology (medical), Benzothiazoles, Aged, Retrospective Studies, Pharmacology, African american, Asian, business.industry, Parkinson Disease, Hispanic or Latino, Middle Aged, Black or African American, Treatment Outcome, Physical therapy, Female, Neurology (clinical), business, medicine.drug
Abstract

Little is known regarding the effects of antiparkinsonian drugs in US racial or ethnic minorities.: To evaluate the safety, tolerability, and efficacy of adjunctive pramipexole in Parkinson disease (PD) patients of African, Asian, or Hispanic heritage stably treated with levodopa.Multicenter, parallel-group, double-blind, randomized, placebo-controlled trial.: Seventeen Parkinson Study Group sites in the United States and Puerto Rico.One hundred forty-four PD patients of African, Asian, or Hispanic heritage enrolled from January 1997 to August 1998 and observed until October 1998.Subjects received pramipexole or placebo (3:1 ratio), 0.375 mg/d to a maximum tolerated dose (or=4.5 mg/d) over a 6-week period, achieving optimum levels (0.375, 1.5, 3.0, or 4.5 mg/d) in the 4-week maintenance period.Change in the sum of the Unified Parkinson's Disease Rating Scale parts 2 (activities of daily living) and 3 (motor) from baseline to week 10.Parkinsonism improved (mean [SD] reduction in Unified Parkinson's Disease Rating Scale activities of daily living + motor score at 10 weeks, 10.27 [11.96] pramipexole vs 6.54 [13.58] placebo, P = 0.012) and was similar in each group. Adverse events occurred in 85.3% on pramipexole and 68.6% on placebo. Hallucinations and insomnia were more common on pramipexole than placebo (18 vs 0, P = 0.023, and 15 vs 0, P = 0.045, respectively).Pramipexole is an effective adjunctive antiparkinsonian therapy in PD patients of African, Asian, and Hispanic heritage. Tolerability and safety overall were similar among the groups, but differences in profiles of adverse effects and tolerability were suggested.

Published
2007

18. Effects of discharge fluctuation and the addition of fine sediment on stream fish and macroinvertebrates below a water-filtration facility

Author

Don C. Erman and Franklin K. Ligon

Subjects
Hydrology, Global and Planetary Change, Ecology, biology, Backwashing, Sediment, Sedimentation, biology.organism_classification, Pollution, Hatchery, Benthic zone, Environmental science, Salmo, Bay, Cottus asper
Abstract

A small, coastal stream in the San Francisco Bay area of California, USA, received the discharges from a drinking-water filtration plant. Two types of discharges were present. Discharges from filter backwashing were 3–4 times base stream flow, occurred 10–60 times per day, contained fine sediments, and each lasted about 10 min. The other discharge was a large, steady flow of relatively sediment-free water from occasional overflow of the delivery aqueduct which generally lasted several hours a day. Samples of invertebrates from natural substrates had significantly fewer taxa and lower density at the two stations below the backwash than at the two above. However, when stable artificial substrates were used, there were no significant differences among all four stations. The aqueduct apparently had no effect because the. invertebrate community at the station upstream of the backwash but downstream of the aqueduct was statistically similar to the station above the aqueduct. To test for acute toxicity, we exposed additional artificial substrates to short-term simulated backwash conditions. These exposures had no effect on invertebrate density or drift. Three-spine stickleback (Gasterosteus aculeatus) populations were also significantly reduced at the two downstream stations and were made up mostly of larger, adult fish. Prickly sculpins (Cottus asper), restricted to the most downstream station, were emaciated and had poor growth, probably as a result of scarce benthic food organisms. Artificial redds with eggs of rainbow trout (Salmo gairdneri) had significantly lower survival at two stations below the plant backwash (30.7% and 41.8%) than at the one above it (61.4%). Hatchery rainbow trout held in cages below the treatment plant from 7 to 37 days survived and continued to feed. Thus, the major effect of the water treatment plant on fish and invertebrates probably was not from acute toxicity in the discharges or the occasionally large discharge of clean water from the aqueduct, but was from the fluctuating backwash flows containing fine sediment that displaced small fish downstream and created unstable benthic substrates for invertebrates. The filter plant that we studied is a direct-feed type (that is, no sedimentation before filtration). These generally require greater frequencies of backwashing than do conventional plants and may therefore have greater biological impacts. Direct-feed plants are becoming increasingly popular throughout the world, for the most part because they are cheaper to build and operate. But if the associated biological problems are mitigated, then the cost savings of direct-feed compared to conventional plants may be lost.

Published
1988

19. Noninvasive molecular subtyping of pediatric low-grade glioma with self-supervised transfer learning.

Author

Tak D, Ye Z, Zapaishchykova A, Zha Y, Boyd A, Vajapeyam S, Chopra R, Hayat H, Prabhu S, Liu KX, Elhalawani H, Nabavizadeh A, Familiar A, Resnick A, Mueller S, Aerts HJWL, Bandopadhayay P, Ligon K, Haas-Kogan D, Poussaint T, and Kann BH

Abstract

Purpose: To develop and externally validate a scan-to-prediction deep-learning pipeline for noninvasive, MRI-based BRAF mutational status classification for pLGG., Materials and Methods: We conducted a retrospective study of two pLGG datasets with linked genomic and diagnostic T2-weighted MRI of patients: BCH (development dataset, n=214 [60 (28%) BRAF fusion, 50 (23%) BRAF V600E, 104 (49%) wild-type), and Child Brain Tumor Network (CBTN) (external validation, n=112 [60 (53%) BRAF-Fusion, 17 (15%) BRAF-V600E, 35 (32%) wild-type]). We developed a deep learning pipeline to classify BRAF mutational status (V600E vs. fusion vs. wildtype) via a two-stage process: 1) 3D tumor segmentation and extraction of axial tumor images, and 2) slice-wise, deep learning-based classification of mutational status. We investigated knowledge-transfer and self-supervised approaches to prevent model overfitting with a primary endpoint of the area under the receiver operating characteristic curve (AUC). To enhance model interpretability, we developed a novel metric, COMDist, that quantifies the accuracy of model attention around the tumor., Results: A combination of transfer learning from a pretrained medical imaging-specific network and self-supervised label cross-training (TransferX) coupled with consensus logic yielded the highest macro-average AUC (0.82 [95% CI: 0.70-0.90]) and accuracy (77%) on internal validation, with an AUC improvement of +17.7% and a COMDist improvement of +6.4% versus training from scratch. On external validation, the TransferX model yielded AUC (0.73 [95% CI 0.68-0.88]) and accuracy (75%)., Conclusion: Transfer learning and self-supervised cross-training improved classification performance and generalizability for noninvasive pLGG mutational status prediction in a limited data scenario., Competing Interests: Competing Interests All the authors declare no competing interests.

Published
2023
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20. Clinical trial links oncolytic immunoactivation to survival in glioblastoma.

Author

Ling AL, Solomon IH, Landivar AM, Nakashima H, Woods JK, Santos A, Masud N, Fell G, Mo X, Yilmaz AS, Grant J, Zhang A, Bernstock JD, Torio E, Ito H, Liu J, Shono N, Nowicki MO, Triggs D, Halloran P, Piranlioglu R, Soni H, Stopa B, Bi WL, Peruzzi P, Chen E, Malinowski SW, Prabhu MC, Zeng Y, Carlisle A, Rodig SJ, Wen PY, Lee EQ, Nayak L, Chukwueke U, Gonzalez Castro LN, Dumont SD, Batchelor T, Kittelberger K, Tikhonova E, Miheecheva N, Tabakov D, Shin N, Gorbacheva A, Shumskiy A, Frenkel F, Aguilar-Cordova E, Aguilar LK, Krisky D, Wechuck J, Manzanera A, Matheny C, Tak PP, Barone F, Kovarsky D, Tirosh I, Suvà ML, Wucherpfennig KW, Ligon K, Reardon DA, and Chiocca EA

Subjects
Humans, Nestin genetics, Reproducibility of Results, Survival Analysis, T-Lymphocytes cytology, T-Lymphocytes immunology, Treatment Outcome, Tumor Microenvironment immunology, Brain Neoplasms immunology, Brain Neoplasms pathology, Glioblastoma immunology, Glioblastoma pathology, Oncolytic Virotherapy adverse effects, Oncolytic Viruses genetics, Oncolytic Viruses immunology, Oncolytic Viruses physiology, Herpesvirus 1, Human genetics, Herpesvirus 1, Human immunology, Herpesvirus 1, Human physiology
Abstract

Immunotherapy failures can result from the highly suppressive tumour microenvironment that characterizes aggressive forms of cancer such as recurrent glioblastoma (rGBM) 1,2 . Here we report the results of a first-in-human phase I trial in 41 patients with rGBM who were injected with CAN-3110-an oncolytic herpes virus (oHSV) 3 . In contrast to other clinical oHSVs, CAN-3110 retains the viral neurovirulence ICP34.5 gene transcribed by a nestin promoter; nestin is overexpressed in GBM and other invasive tumours, but not in the adult brain or healthy differentiated tissue 4 . These modifications confer CAN-3110 with preferential tumour replication. No dose-limiting toxicities were encountered. Positive HSV1 serology was significantly associated with both improved survival and clearance of CAN-3110 from injected tumours. Survival after treatment, particularly in individuals seropositive for HSV1, was significantly associated with (1) changes in tumour/PBMC T cell counts and clonal diversity, (2) peripheral expansion/contraction of specific T cell clonotypes; and (3) tumour transcriptomic signatures of immune activation. These results provide human validation that intralesional oHSV treatment enhances anticancer immune responses even in immunosuppressive tumour microenvironments, particularly in individuals with cognate serology to the injected virus. This provides a biological rationale for use of this oncolytic modality in cancers that are otherwise unresponsive to immunotherapy (ClinicalTrials.gov: NCT03152318 )., (© 2023. The Author(s).)

Published
2023
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21. The Alliance AMBUSH Trial: Rationale and Design.

Author

Mahajan A, Shih H, Penas-Prado M, Ligon K, Aldape K, Hu LS, Loughan AR, Basso MR, Leeper HE, Nahed BV, Stott SL, Geyer S, Giannini C, and Galanis E

Abstract

Unlike medulloblastoma (MB) in children, robust prospective trials have not taken place for older patients due to the low incidence of MB in adults and adolescent and young adults (AYA). Current MB treatment paradigms for older patients have been extrapolated from the pediatric experience even though questions exist about the applicability of these approaches. Clinical and molecular classification of MB now provides better prognostication and is being incorporated in pediatric therapeutic trials. It has been established that genomic alterations leading to activation of the sonic hedgehog (SHH) pathway occur in approximately 60% of MB in patients over the age of 16 years. Within this cohort, protein patched homolog (PTCH) and smoothened (SMO) mutations are commonly found. Among patients whose tumors harbor the SHH molecular signature, it is estimated that over 80% of patients could respond to SHH pathway inhibitors. Given the advances in the understanding of molecular subgroups and the lack of robust clinical data for adult/AYA MB, the Alliance for Clinical Trial in Oncology group developed the AMBUSH trial: Comprehensive Management of AYA and Adult Patients with Medulloblastoma or Pineal Embryonal Tumors with a Randomized Placebo Controlled Phase II Focusing on Sonic Hedgehog Pathway Inhibition in SHH Subgroup Patients (Adult & Adolescent MedulloBlastoma Using Sonic Hedgehog Trial). This trial will enroll patients 18 years of age or older with MB (any molecular subgroup and risk stratification) or pineal embryonal tumor. Patients will be assigned to one of three cohorts: (1) average risk non-SHH-MB, (2) average risk SHH-MB, and (3) high risk MB or pineal embryonal tumors. All patients will receive protocol-directed comprehensive treatment with radiation therapy and chemotherapy. Patients with SHH-MB in cohort 1 will be randomized to a smoothened inhibitor or placebo as maintenance therapy for one year.

Published
2022
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22. BPTF regulates growth of adult and pediatric high-grade glioma through the MYC pathway.

Author

Green AL, DeSisto J, Flannery P, Lemma R, Knox A, Lemieux M, Sanford B, O'Rourke R, Ramkissoon S, Jones K, Perry J, Hui X, Moroze E, Balakrishnan I, O'Neill AF, Dunn K, DeRyckere D, Danis E, Safadi A, Gilani A, Hubbell-Engler B, Nuss Z, Levy JMM, Serkova N, Venkataraman S, Graham DK, Foreman N, Ligon K, Jones K, Kung AL, and Vibhakar R

Abstract

High-grade gliomas (HGG) afflict both children and adults and respond poorly to current therapies. Epigenetic regulators have a role in gliomagenesis, but a broad, functional investigation of the impact and role of specific epigenetic targets has not been undertaken. Using a two-step, in vitro/in vivo epigenomic shRNA inhibition screen, we determine the chromatin remodeler BPTF to be a key regulator of adult HGG growth. We then demonstrate that BPTF knockdown decreases HGG growth in multiple pediatric HGG models as well. BPTF appears to regulate tumor growth through cell self-renewal maintenance, and BPTF knockdown leads these glial tumors toward more neuronal characteristics. BPTF's impact on growth is mediated through positive effects on expression of MYC and MYC pathway targets. HDAC inhibitors synergize with BPTF knockdown against HGG growth. BPTF inhibition is a promising strategy to combat HGG through epigenetic regulation of the MYC oncogenic pathway.

Published
2020
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23. Correction: BPTF regulates growth of adult and pediatric high-grade glioma through the MYC pathway.

Author

Green AL, DeSisto J, Flannery P, Lemma R, Knox A, Lemieux M, Sanford B, O'Rourke R, Ramkissoon S, Jones K, Perry J, Hui X, Moroze E, Balakrishnan I, O'Neill AF, Dunn K, DeRyckere D, Danis E, Safadi A, Gilani A, Hubbell-Engler B, Nuss Z, Levy JMM, Serkova N, Venkataraman S, Graham DK, Foreman N, Ligon K, Jones K, Kung AL, and Vibhakar R

Abstract

The original version of this Article omitted the following from the Acknowledgements: This work was supported by the Luke's Army Pediatric Cancer Research Fund St. Baldrick's Scholar Award. This has now been corrected in both the PDF and HTML versions of the Article.

Published
2020
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24. Phase II trial of ponatinib in patients with bevacizumab-refractory glioblastoma.

Author

Lee EQ, Muzikansky A, Duda DG, Gaffey S, Dietrich J, Nayak L, Chukwueke UN, Beroukhim R, Doherty L, Laub CK, LaFrankie D, Fontana B, Stefanik J, Ruland S, Caruso V, Bruno J, Ligon K, Reardon DA, and Wen PY

Subjects
Adult, Aged, Biomarkers blood, Brain Neoplasms blood, Brain Neoplasms mortality, Cytokines blood, Drug Resistance, Neoplasm drug effects, Female, Glioblastoma blood, Glioblastoma mortality, Humans, Imidazoles adverse effects, Imidazoles pharmacology, Karnofsky Performance Status, Male, Middle Aged, Progression-Free Survival, Protein Kinase Inhibitors adverse effects, Pyridazines adverse effects, Pyridazines pharmacology, Receptor, TIE-2 blood, Vascular Endothelial Growth Factor A blood, Vascular Endothelial Growth Factor Receptor-1 blood, Vascular Endothelial Growth Factor Receptor-2 blood, Angiogenesis Inhibitors therapeutic use, Bevacizumab therapeutic use, Brain Neoplasms drug therapy, Glioblastoma drug therapy, Imidazoles therapeutic use, Protein Kinase Inhibitors therapeutic use, Pyridazines therapeutic use
Abstract

Background: Responses to bevacizumab in glioblastoma (GBM) are not durable. Plasma levels of basic fibroblast growth factor (bFGF) increase at the time of tumor progression. By targeting vascular endothelial growth factor receptor (VEGFR), platelet-derived growth factor receptor, Src, and FGF receptor pathways, ponatinib may potentially help to overcome some of the putative mechanisms of adaptive resistance., Methods: We performed a phase II trial of ponatinib in patients with bevacizumab-refractory GBM and variants. Adult patients with Karnofsky performance score (KPS) ≥60, measurable disease, and normal organ and marrow function received 45 mg ponatinib daily. No limit on the number of prior therapies but only one prior bevacizumab-containing regimen was allowed. Primary endpoint was 3-month progression-free survival. Plasma biomarkers of angiogenesis and inflammation were evaluated before and after treatment., Results: The study closed after the first stage. Fifteen patients enrolled: median age 61 [27-74]; median KPS 80 [70-90]; median number of prior relapses 2 [2-4]. Three-month progression-free survival rate was 0, median overall survival was 98 days [95% CI 56, 257], and median PFS was 28 days [95% CI 27, 30]. No responses were seen. The most common grade ≥3 adverse events included fatigue (n = 3), hypertension (2), and lipase elevation (2). Ponatinib treatment significantly increased plasma VEGF, soluble (s)VEGFR1, sVEGFR2, sTIE2, interferon gamma (IFNγ), tumor necrosis factor alpha (TNF-α), interleukin (IL)-6, IL-8, and IL-10 and decreased sVEGFR2., Conclusions: Ponatinib was associated with minimal activity in bevacizumab-refractory GBM patients. Circulating biomarker data confirmed pharmacodynamic changes and suggested that resistance to ponatinib may be related to an increase in inflammatory cytokines., (© 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.)

Published
2019
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25. Clinical Importance of CDKN2A Loss and Monosomy 10 in Pilocytic Astrocytoma.

Author

Cagney DN, Miller MB, Dubuc A, Delalle I, Ligon AH, Chukwueke U, Al-Mefty O, Aizer A, Ligon K, and Wen P

Abstract

This case of a radiation-naive patient with pilocytic astrocytoma highlights how deletions of CDKN2A (cyclin-dependent kinase Inhibitor 2A) and PTEN (phosphatase and tensin homolog) portended a poor clinical outcome. Pilocytic astrocytomas are grade 1 tumors usually occurring in children and young adults with KIAA1549-BRAF fusion defining the majority of pilocytic astrocytomas. The presence of CDKN2A and PTEN loss may be associated with aggressive biology in pilocytic astrocytoma and further studies should include comprehensive genomics in a larger series of adult pilocytic astrocytoma to evaluate this previously unreported finding. Providers need to be aware of this possibility given the potential for poor outcomes., Competing Interests: The authors have declared that no competing interests exist.

Published
2019
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26. Residual Convolutional Neural Network for the Determination of IDH Status in Low- and High-Grade Gliomas from MR Imaging.

Author

Chang K, Bai HX, Zhou H, Su C, Bi WL, Agbodza E, Kavouridis VK, Senders JT, Boaro A, Beers A, Zhang B, Capellini A, Liao W, Shen Q, Li X, Xiao B, Cryan J, Ramkissoon S, Ramkissoon L, Ligon K, Wen PY, Bindra RS, Woo J, Arnaout O, Gerstner ER, Zhang PJ, Rosen BR, Yang L, Huang RY, and Kalpathy-Cramer J

Subjects
Adult, Aged, Aged, 80 and over, Brain diagnostic imaging, Brain pathology, Brain surgery, Brain Neoplasms genetics, Brain Neoplasms mortality, Brain Neoplasms surgery, Datasets as Topic, Female, Glioma genetics, Glioma mortality, Glioma surgery, Humans, Magnetic Resonance Imaging methods, Male, Middle Aged, Mutation, Neoplasm Grading, Predictive Value of Tests, Preoperative Period, Retrospective Studies, Young Adult, Brain Neoplasms diagnostic imaging, Glioma diagnostic imaging, Image Processing, Computer-Assisted methods, Isocitrate Dehydrogenase genetics, Neural Networks, Computer
Abstract

Purpose: Isocitrate dehydrogenase ( IDH ) mutations in glioma patients confer longer survival and may guide treatment decision making. We aimed to predict the IDH status of gliomas from MR imaging by applying a residual convolutional neural network to preoperative radiographic data. Experimental Design: Preoperative imaging was acquired for 201 patients from the Hospital of University of Pennsylvania (HUP), 157 patients from Brigham and Women's Hospital (BWH), and 138 patients from The Cancer Imaging Archive (TCIA) and divided into training, validation, and testing sets. We trained a residual convolutional neural network for each MR sequence (FLAIR, T2, T1 precontrast, and T1 postcontrast) and built a predictive model from the outputs. To increase the size of the training set and prevent overfitting, we augmented the training set images by introducing random rotations, translations, flips, shearing, and zooming. Results: With our neural network model, we achieved IDH prediction accuracies of 82.8% (AUC = 0.90), 83.0% (AUC = 0.93), and 85.7% (AUC = 0.94) within training, validation, and testing sets, respectively. When age at diagnosis was incorporated into the model, the training, validation, and testing accuracies increased to 87.3% (AUC = 0.93), 87.6% (AUC = 0.95), and 89.1% (AUC = 0.95), respectively. Conclusions: We developed a deep learning technique to noninvasively predict IDH genotype in grade II-IV glioma using conventional MR imaging using a multi-institutional data set. Clin Cancer Res; 24(5); 1073-81. ©2017 AACR ., (©2017 American Association for Cancer Research.)

Published
2018
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27. Intracranial myxoid mesenchymal tumors with EWSR1-CREB family gene fusions: myxoid variant of angiomatoid fibrous histiocytoma or novel entity?

Author

Bale TA, Oviedo A, Kozakewich H, Giannini C, Davineni PK, Ligon K, and Alexandrescu S

Subjects
Adolescent, Brain Neoplasms diagnostic imaging, Brain Neoplasms genetics, Child, Diagnosis, Differential, Female, Histiocytoma, Malignant Fibrous diagnosis, Histiocytoma, Malignant Fibrous genetics, Histiocytoma, Malignant Fibrous pathology, Humans, Male, Myxoma diagnostic imaging, Myxoma genetics, Brain Neoplasms pathology, Cyclic AMP Response Element-Binding Protein genetics, Gene Fusion, Mesenchymal Stem Cells pathology, Myxoma pathology, Oncogene Proteins, Fusion genetics, RNA-Binding Protein EWS genetics
Abstract

Intracranial myxoid mesenchymal tumor harboring EWSR1 fusions with CREB family of genes was recently described, and it resembles the myxoid variant of angiomatoid fibrous histiocytoma. We present three pediatric patients with intracranial EWSR1-rearranged myxoid mesenchymal neoplasm and provide a molecular genetic characterization of these tumors. Clinical histories and imaging results were reviewed. Histology, immunohistochemistry, EWSR1, FUS, NR4A3 fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS) were performed. A 12-year-old male (case 1), 14-year-old female (case 2), and 18-year-old male (case 3), presented with headaches, emesis, and seizures, respectively. The magnetic resonance images demonstrated tumors abutting the dura (cases 1 and 3) and in the third ventricle (case 2). All tumors were vascular, with solid sheets of monomorphic oval cells in a prominent myxoid/microcystic matrix. A thin fibrous pseudocapsule was present in all lesions, but definitive lymphocytic cuffing was absent. Morphologically, they closely resembled myxoid variant of angiomatoid fibrous histiocytoma. Mitoses were rare, and necrosis was absent. All tumors expressed desmin and GLUT1, and focal EMA and CD99. The proliferation index was low. FISH and NGS showed EWSR1-CREB1 fusion (cases 1 and 2), and EWSR1-CREM fusion (case 3). There were no FUS (16p11.2) or NR4A3 (9q22.33) rearrangements in case 3. Gains of 5q (including KCNIP1) and 11q (including CCND1) were present in cases 1 and 2. There were no common pathogenic genomic changes other than EWSR1 rearrangements across cases. CNS myxoid mesenchymal neoplasms with histological and immunophenotypic similarities to myxoid variant of AFH are rare, diagnostically challenging, and harbor EWSR1-CREB1 and also a novel EWSR1-CREM fusion not yet described in AFH. Therefore, it is uncertain if these tumors represent variants of AFH or a new entity. The copy number and mutational changes presented here provide support for future studies to further clarify this issue., (© 2017 International Society of Neuropathology.)

Published
2018
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28. Landscape care of urban vacant properties and implications for health and safety: Lessons from photovoice.

Author

Sampson N, Nassauer J, Schulz A, Hurd K, Dorman C, and Ligon K

Subjects
Focus Groups, Humans, Michigan, Safety, Volunteers, Community Participation, Environment, Photography methods, Residence Characteristics statistics & numerical data, Urban Health
Abstract

Care of vacant properties in urban environments is of particular interest to planners and residents alike. We report on a photovoice project completed by community leaders, researchers, and residents in two Detroit neighborhoods experiencing longtime systemic disinvestment. Participants photographed and discussed examples of care in a series of three focus groups in each neighborhood. Analyses highlight how acts of landscape care and visible cues to care contribute to changes in physical and social environments, and explore various links to health. We suggest theoretical and practical applications of residents' perspectives on landscape care and identify implications for well-being and neighborhood stability., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Published
2017
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29. Multi-omics analysis of primary glioblastoma cell lines shows recapitulation of pivotal molecular features of parental tumors.

Author

Rosenberg S, Verreault M, Schmitt C, Guegan J, Guehennec J, Levasseur C, Marie Y, Bielle F, Mokhtari K, Hoang-Xuan K, Ligon K, Sanson M, Delattre JY, and Idbaih A

Subjects
Aged, Brain Neoplasms pathology, Female, Gene Expression Profiling, Glioblastoma pathology, High-Throughput Nucleotide Sequencing methods, Humans, Male, Middle Aged, RNA, Messenger genetics, Real-Time Polymerase Chain Reaction, Reverse Transcriptase Polymerase Chain Reaction, Tumor Cells, Cultured, Biomarkers, Tumor genetics, Brain Neoplasms genetics, DNA Copy Number Variations genetics, Exome genetics, Glioblastoma genetics, Point Mutation genetics, Polymorphism, Single Nucleotide genetics
Abstract

Background: Glioblastoma (GBM) is the deadliest primary brain cancer in adults. Emerging innovative therapies hold promise for personalized cancer treatment. Improving therapeutic options depends on research relying on relevant preclinical models. In this line we have established in the setting of the GlioTex project (GBM and Experimental Therapeutics) a GBM patient-derived cell line (GBM-PDCL) library. A multi-omic approach was used to determine the molecular landscape of PDCL and the extent to which they represent GBM tumors., Methods: Single nucleotide polymorphism array, expression arrays, exome sequencing, and RNA sequencing were used to measure and compare the molecular landscapes of 20 samples representing 10 human GBM tumors and paired GBM-PDCLs., Results: Copy number variations were similar for a median of 85% of the genome and for 59% of the major focal events. Somatic point mutations were similar in a median of 41%. Mutations in GBM driver and "druggable" genes were maintained in 67% of events. Mutations that were not conserved in the PDCL were mainly low allelic fraction and/or non-driver mutations. Based on RNA expression profiling, PDCLs cluster closely to their parental tumor with overexpression of pathways associated with cancer progression in PDCL., Conclusions: Overall, PDCLs recapitulate pivotal molecular alterations of paired-parental tumors supporting their use as a preclinical model of GBM. However, some driver aberrations are lost or gained in the passage from tumor to PDCL. Our results support using PDCL as a relevant preclinical model of GBM. Further investigations of changes between PDCLs and their parental tumor may provide insights into GBM biology., (© The Author(s) 2016. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2017
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30. Disseminated glioneuronal tumors occurring in childhood: treatment outcomes and BRAF alterations including V600E mutation.

Author

Dodgshun AJ, SantaCruz N, Hwang J, Ramkissoon SH, Malkin H, Bergthold G, Manley P, Chi S, MacGregor D, Goumnerova L, Sullivan M, Ligon K, Beroukhim R, Herrington B, Kieran MW, Hansford JR, and Bandopadhayay P

Subjects
Adolescent, Biomarkers, Tumor genetics, Brain Neoplasms diagnostic imaging, Brain Neoplasms drug therapy, Brain Neoplasms pathology, Child, Child, Preschool, Female, Glioma diagnostic imaging, Glioma drug therapy, Glioma pathology, Humans, Male, Meningeal Neoplasms diagnostic imaging, Meningeal Neoplasms drug therapy, Meningeal Neoplasms pathology, Proto-Oncogene Mas, Proto-Oncogene Proteins c-raf genetics, Retrospective Studies, Spinal Cord, Treatment Outcome, Brain Neoplasms genetics, Genetic Predisposition to Disease, Glioma genetics, Meningeal Neoplasms genetics, Mutation, Proto-Oncogene Proteins B-raf genetics
Abstract

Disseminated glioneuronal tumors of childhood are rare. We present a retrospective IRB-approved review of the clinical course and frequency of BRAF mutations in disseminated glioneuronal tumors at two institutions. Defining features of our cohort include diffuse leptomeningeal-spread, often with a discrete spinal cord nodule and oligodendroglioma-like histologic features. Patients were identified through a pathology database search of all cases with disseminated low-grade neoplasms with an oligodendroglioma-like component. De-identified clinical information was collected by chart review and all imaging was reviewed. We retrieved the results of targeted genomic analyses for alterations in BRAF. Ten patients (aged 2-14 years) were identified from the Dana-Farber/Boston Children's Hospital and the Royal Children's Hospital, Melbourne pathology databases. Nine patients received chemotherapy. Eight patients are alive, although three have had episodes of progressive disease. We identified genomic alterations affecting the MAPK pathway in six patients. One patient had a germline RAF1 mutation and a clinical diagnosis of cardio-facio-cutaneous syndrome. BRAF duplications were identified in four and BRAF V600E mutation was identified in one. These data support the presence of targetable genomic alterations in this disease.

Published
2016
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31. Phase II trial of sunitinib for recurrent and progressive atypical and anaplastic meningioma.

Author

Kaley TJ, Wen P, Schiff D, Ligon K, Haidar S, Karimi S, Lassman AB, Nolan CP, DeAngelis LM, Gavrilovic I, Norden A, Drappatz J, Lee EQ, Purow B, Plotkin SR, Batchelor T, Abrey LE, and Omuro A

Subjects
Adult, Aged, Aged, 80 and over, Antineoplastic Agents adverse effects, Cohort Studies, Disease-Free Survival, Female, Humans, Indoles adverse effects, Kaplan-Meier Estimate, Male, Meningeal Neoplasms mortality, Meningioma mortality, Middle Aged, Pyrroles adverse effects, Sunitinib, Treatment Outcome, Antineoplastic Agents therapeutic use, Indoles therapeutic use, Meningeal Neoplasms drug therapy, Meningioma drug therapy, Pyrroles therapeutic use
Abstract

Background: No proven effective medical therapy for surgery and radiation-refractory meningiomas exists. Sunitinib malate (SU011248) is a small-molecule tyrosine kinase inhibitor that targets vascular endothelial growth factor receptor (VEGFR) and platelet-derived growth factor receptor, abundant in meningiomas., Methods: This was a prospective, multicenter, investigator-initiated single-arm phase II trial. The primary cohort enrolled patients with surgery and radiation-refractory recurrent World Health Organization (WHO) grades II-III meningioma. An exploratory cohort enrolled patients with WHO grade I meningioma, hemangiopericytoma, or hemangioblastoma. Sunitinib was administered at 50 mg/d for days 1-28 of every 42-day cycle. The primary endpoint was the rate of 6-month progression-free survival (PFS6), with secondary endpoints of radiographic response rate, safety, PFS, and overall survival. Exploratory objectives include analysis of tumoral molecular markers and MR perfusion imaging., Results: Thirty-six patients with high-grade meningioma (30 atypical and 6 anaplastic) were enrolled. Patients were heavily pretreated (median number of 5 recurrences, range 2-10). PFS6 rate was 42%, meeting the primary endpoint. Median PFS was 5.2 months (95% CI: 2.8-8.3 mo), and median overall survival was 24.6 months (95% CI: 16.5-38.4 mo). Thirteen patients enrolled in the exploratory cohort. Overall toxicity included 1 grade 5 intratumoral hemorrhage, 2 grade 3 and 1 grade 4 CNS/intratumoral hemorrhages, 1 grade 3 and 1 grade 4 thrombotic microangiopathy, and 1 grade 3 gastrointestinal perforation. Expression of VEGFR2 predicted PFS of a median of 1.4 months in VEGFR2-negative patients versus 6.4 months in VEGFR2-positive patients (P = .005)., Conclusion: Sunitinib is active in recurrent atypical/malignant meningioma patients. A randomized trial should be performed., (© The Author(s) 2014. Published by Oxford University Press on behalf of the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Published
2015
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33. Integrative genomic analysis of medulloblastoma identifies a molecular subgroup that drives poor clinical outcome.

Author

Cho YJ, Tsherniak A, Tamayo P, Santagata S, Ligon A, Greulich H, Berhoukim R, Amani V, Goumnerova L, Eberhart CG, Lau CC, Olson JM, Gilbertson RJ, Gajjar A, Delattre O, Kool M, Ligon K, Meyerson M, Mesirov JP, and Pomeroy SL

Subjects
Algorithms, Child, Gene Expression Regulation, Neoplastic, Genomics, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Polymorphism, Single Nucleotide, Predictive Value of Tests, Prognosis, RNA, Neoplasm genetics, Cerebellar Neoplasms genetics, Cerebellar Neoplasms pathology, DNA-Binding Proteins genetics, Medulloblastoma genetics, Medulloblastoma pathology, Transcription Factors genetics
Abstract

Purpose: Medulloblastomas are heterogeneous tumors that collectively represent the most common malignant brain tumor in children. To understand the molecular characteristics underlying their heterogeneity and to identify whether such characteristics represent risk factors for patients with this disease, we performed an integrated genomic analysis of a large series of primary tumors., Patients and Methods: We profiled the mRNA transcriptome of 194 medulloblastomas and performed high-density single nucleotide polymorphism array and miRNA analysis on 115 and 98 of these, respectively. Non-negative matrix factorization-based clustering of mRNA expression data was used to identify molecular subgroups of medulloblastoma; DNA copy number, miRNA profiles, and clinical outcomes were analyzed for each. We additionally validated our findings in three previously published independent medulloblastoma data sets., Results: Identified are six molecular subgroups of medulloblastoma, each with a unique combination of numerical and structural chromosomal aberrations that globally influence mRNA and miRNA expression. We reveal the relative contribution of each subgroup to clinical outcome as a whole and show that a previously unidentified molecular subgroup, characterized genetically by c-MYC copy number gains and transcriptionally by enrichment of photoreceptor pathways and increased miR-183∼96∼182 expression, is associated with significantly lower rates of event-free and overall survivals., Conclusion: Our results detail the complex genomic heterogeneity of medulloblastomas and identify a previously unrecognized molecular subgroup with poor clinical outcome for which more effective therapeutic strategies should be developed.

Published
2011
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34. Epidermal growth factor receptor gene amplification in atypical adenomatous hyperplasia of the lung.

Author

McIntire MG, Santagata S, Ligon K, and Chirieac LR

Abstract

Atypical adenomatous hyperplasia (AAH) is postulated to be the earliest morphologic precursor lesion in lung carcinogenesis. The epidermal growth factor receptor (EGFR), one of the members of the Erb-2 family of receptors, is commonly expressed in non-small cell lung carcinoma (NSCLC). A subset of the patients with NSCLC has molecular abnormalities in the EGFR gene, including missense mutations and deletions and/or abnormal gene copy numbers, and the relative importance of each of these for patient outcome is an area of great interest. Recent reports show that EGFR mutations are rare or absent in AAH and are rare in bronchioloalveolar carcinoma (BAC). However, the EGFR gene copy number status in AAH is unknown. In this study, we examined the EGFR gene copy number status in lung adenocarcinomas, synchronous AAH, and BAC in surgical pathology resection specimens. EGFR gene copy number was analyzed by chromogenic in situ hybridization (CISH) using formalin fixed paraffin embedded tissue sections and EGFR probes as recommended by the manufacturer. A known positive case of high-grade glioma was used as a positive control. The results indicate that four of eight adenocarcinomas (50%) had more than five EGFR signals per nucleus, suggesting a gain in copy number. Interestingly, in four of nine cases of AAH (44.4%) more than three EGFR signals per nucleus were noted, with scattered cells showing up to 6 signals per nucleus. In addition, in five of 12 cases of BAC (42%), more than three EGFR signals per nucleus were noted. In the remaining cases two to three intranuclear dot-like peroxidase positive signals were present consistent with non-amplification of the gene. Our study reveals an abnormal EGFR gene copy gain in several cases of AAH. In our cohort, the rate of EGFR gene copy abnormalities in AAH appears similar to BAC and lower than in lung adenocarcinomas. These findings suggest that although EGFR gene copy abnormalities may be an early event in lung carcinogenesis, they are associated with tumor progression to invasive cancer and highlight the complexity of tumor morphogenesis.

Published
2010

35. Meningioangiomatosis associated with meningioma: a case report.

Author

Saad A, Folkerth R, Poussaint T, Smith E, and Ligon K

Subjects
Angiomatosis diagnostic imaging, Angiomatosis pathology, Child, Preschool, Female, Humans, Meningeal Neoplasms diagnostic imaging, Meningeal Neoplasms pathology, Meningioma diagnostic imaging, Meningioma pathology, Radiography, Angiomatosis diagnosis, Meningeal Neoplasms diagnosis, Meningioma diagnosis
Abstract

Background: Meningioangiomatosis is a meningovascular disorder that only rarely occurs in association with a meningioma. Occasionally, as in this case, imaging studies do not readily identify this disorder as a benign process. In addition, this disorder may infiltrate the underlying cerebral cortex, simulating, intraoperatively, a malignant infiltrative process. To allow better recognition of this disorder, we report a case with emphasis on the unique cytologic features of the 2 components (meningioangiomatosis and meningioma) and potential pitfalls in diagnosis., Case: A 3-year-old girl was examined in the neurosurgery service for history of refractory seizure. Neuroimaging showed an ill-defined signal abnormality in the left frontal lobe suggestive of a high-grade tumor. Tumor resection was performed, and intraoperative smear preparation showed meningioangiomatosis associated with meningioma., Conclusion: Familiarity with cytologic preparations of this rare variant is very important in providing accurate intraoperative consultation. To our knowledge, this is the first description of the cytologic features on smear preparation of meningioangiomatosis occurring in association with meningioma.

Published
2009
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36. Detection of p53 alterations in human astrocytomas using frozen tissue sections for the polymerase chain reaction.

Author

Aka K, Bruner JM, Bondy ML, Ligon K, Nishi T, del Giglio A, Moser RP, Levin VA, and Saya H

Subjects
Base Sequence, Frozen Sections, Humans, Immunoenzyme Techniques, Molecular Sequence Data, Polymerase Chain Reaction, Polymorphism, Restriction Fragment Length, Astrocytoma genetics, Genes, Tumor Suppressor, Genetic Carrier Screening methods
Abstract

The polymorphism of amino acid residue 72 on the human p53 tumor-suppressor gene is a useful marker for detecting intragenic loss of heterozygosity (LOH). We examined the LOH of the p53 gene in human malignant astrocytomas by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) analysis using DNA extracted from frozen tissue sections under histologic examination. Eleven of 16 informative cases (69%) of the malignant astrocytomas were found to have LOH in the p53 gene. Sequential frozen sections were analyzed by immunohistochemistry using anti-p53 antibody PAb1801 to detect overexpression of the p53 protein, which is presumably altered if it is detectable. Ten of the 11 cases that had LOH of the p53 gene overexpressed the p53 protein. Moreover, 4 of the 11 patients with LOH of the p53 gene developed a second neoplasm in addition to an astrocytoma, possibly indicating genetic instability in these patients. These data suggest that alterations of the p53 gene may play an important role in the genesis of malignant astrocytoma. The combination of the PCR-RFLP method and immunohistochemical analysis using frozen tissue sections is a practical diagnostic tool for examination of human malignancies, including astrocytomas. astrocytomas.

Published
1993
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