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1. In Vitro Study of Encapsulation Therapy for Fabry Disease Using Genetically Engineered CHO Cell Line

Author

Y. Naganawa, K. Ohsugi, R. Kase, I. Date, H. Sakuraba, and N. Sakuragawa M.D., Ph.D.

Subjects
Medicine
Abstract

Fabry disease is an X-linked recessive disorder caused by a deficiency of the lysosomal hydrolase α-galac-tosidase A (α-gal). The deficiency of this enzyme leads to the systemic deposition of ceramide trihexoside (CTH) in various tissues and organs. Enzyme replacement using IV doses of recombinant human α-gal produced in CHO cells or in human fibroblasts is currently being evaluated in clinical trials as a potential therapy for this disease. However, it requires lifelong therapy involving a large amount of purified α-gal. As a novel approach for treatment of Fabry disease we used polymer encapsulated Chinese hamster ovary (CHO) cells genetically modified to express α-gal. The secreted high levels of α-gal passed through the semipermeable polymeric membrane. Using coculture system with Fabry fibroblasts, the secreted enzyme was taken up in cells, resulting in reduced accumulation of CTH in Fabry fibroblasts. This in vitro study demonstrated that an encapsulated α-gal-secreting cell line can be used to treat Fabry mice by transplantation in vivo. Judging from the protection against immune rejection by a semipermeable synthetic membrane, this novel approach may be applied to treat patients with Fabry disease and other lysosomal storage diseases.

Published
2002
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2. Neurotrophic Factor-Secreting Cell Grafting for Cerebral Ischemia: Preliminary Report

Author

K. Fujiwara M.D., I. Date, T. Shingo, H. Yoshida, K. Kobayashi, A. Takeuchi, T. Tamiya, and T. Ohmoto

Subjects
Medicine
Abstract

In this experiment, we examined a possible protective effect of encapsulated neurotrophic factor-secreting cell grafting for ischemic injury. We established a basic fibroblast growth factor (bFGF)-secreting cell line by genetic manipulation. We enveloped these cells into polymer capsules, which consist of a semipermeable membrane, and implanted them into the right striatum of rats. At 6 days after implantation, these rats received right middle cerebral artery occlusion (MCAO) using interluminal suture technique. At 24 h after MCAO, rats were sacrificed and their cerebral infarction volume was determined by 2,3,5-triphenyltetrazolium chloride (TTC) staining and image analysis. We found approximately 30% reduction in infarct volume in the encapsulated bFGF-secreting cell grafting groups vs. the encapsulated naive BHK cell grafting group or the without implantation group. We measured bFGF secretion from encapsulated bFGF-secreting cells using enzyme-linked immunosorbent assay (ELISA). The retrieved capsules continued to secrete bFGF. There was no significant difference of bFGF secretion between the capsules before and after transplantation. A large number of viable BHK-bFGF cells was observed within the full length of the retrieved capsule. These results indicate that encapsulated bFGF-secreting cell grafting exerts a protective effect on ischemic injury.

Published
2001
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3. ANGIOGENESIS AND INVASION

Author

H. Abuhusain, A. Matin, Q. Qiao, H. Shen, B. Daniels, M. Laaksonen, C. Teo, A. Don, K. McDonald, A. Jahangiri, M. De Lay, K. Lu, C. Park, S. Carbonell, G. Bergers, M. K. Aghi, M. Anand, C. Tucker-Burden, J. Kong, D. J. Brat, E. Bae, L. Smith, G. Muller-Greven, R. Yamada, M. Nakano-Okuno, X. Feng, D. Hambardzumyan, I. Nakano, C. L. Gladson, M. Berens, S. Jung, S. Kim, J. Kiefer, J. Eschbacher, H. Dhruv, K. Vuori, C. Hauser, R. Oshima, D. Finlay, P. Aza-Blanc, M. Bessarabova, Y. Nikolsky, D. Emig, L. Rivera, J. Chang, K. Burrell, S. Singh, R. Hill, G. Zadeh, C. Li, Y. Chen, X. Mei, K. Sai, Z. Chen, J. Wang, M. Wu, P. Marsden, S. Das, E. Eskilsson, K. M. Talasila, G. V. Rosland, L. Leiss, H. S. Saed, N. Brekka, P. O. Sakariassen, M. Lund-Johansen, P. O. Enger, R. Bjerkvig, H. Miletic, V. Gawrisch, M. Ruttgers, P. Weigell, E. Kerkhoff, M. Riemenschneider, U. Bogdahn, A. Vollmann-Zwerenz, P. Hau, T. Ichikawa, M. Onishi, K. Kurozumi, T. Maruo, K. Fujii, J. Ishida, Y. Shimazu, T. Oka, E. A. Chiocca, I. Date, R. Jain, B. Griffith, K. Khalil, L. Scarpace, T. Mikkelsen, S. Kalkanis, L. Schultz, S. Jalali, C. Chung, W. Foltz, C. Jiang, H. Wang, N. Kijima, N. Hosen, N. Kagawa, N. Hashimoto, Y. Chiba, M. Kinoshita, H. Sugiyama, T. Yoshimine, R. Klank, S. Decker, C. Forster, M. Price, K. SantaCruz, J. McCarthy, J. Ohlfest, D. Odde, B. Kaur, Y. Huang, Q. Lin, H. Mao, Y. Wang, M. Kogiso, P. Baxter, C. Man, Z. Wang, Y. Zhou, X.-N. Li, J. Liang, Y. Piao, J. de Groot, S. McDonell, V. Henry, L. Holmes, S. R. Michaelsen, M.-T. Stockhausen, null Hans, S. Poulsen, R. Jahedi, F. Azuaje, D. Stieber, S. Foerster, J. Varughese, C. Ritter, S. P. Niclou, A. Soentgerath, P. Euskirchen, P. C. Huszthy, L. Prestegarden, K. O. Skaftnesmo, O. Keunen, J. Nigro, O. K. Vintermyr, S. Mork, N. Mohan-Sobhana, B. Hu, J. De Jesus, B. Hollingsworth, M. Viapiano, C. Carlin, C. Gladson, M. Nakada, T. Furuta, H. Sabit, Y. Chikano, Y. Hayashi, H. Sato, T. Minamoto, J.-i. Hamada, F. Fack, H. Espedal, N. Obad, E. Gotlieb, S. Bougnaud, A. Golebiewska, A. Oudin, N. H. C. Brons, P. O'Halloran, T. Viel, K. Schwegmann, L. Wachsmuth, S. Wagner, K. Kopka, P. Dicker, C. Faber, M. Jarzabek, S. Hermann, M. Schafers, D. O'Brien, J. Prehn, A. Jacobs, A. Byrne, S. Inoue, L. S. Olsen, M. Stockhausen, H. S. Poulsen, K. H. Plate, A. Scholz, R. Henschler, P. Baumgarten, P. Harter, M. Mittelbronn, D. Dumont, Y. Reiss, S. Rahimpour, C. Yang, J. Frerich, Z. Zhuang, D. Renner, F. Jin, I. Parney, A. Johnson, R. Rockne, A. Hawkins-Daarud, J. Jacobs, C. Bridge, M. Mrugala, J. Rockhill, K. Swanson, H. Schneider, E. Szabo, K. Seystahl, M. Weller, Y. Takahashi, M. Ouchida, K. Fuji, M. Umakoshi, H. Sim, P. Gruenbacher, L. Jakeman, J. Parker, K. Dionne, P. Canoll, B. DeMasters, and A. Waziri

Subjects
Abstracts, Cancer Research, Oncology, Angiogenesis, Cancer research, Neurology (clinical), Biology
Published
2013

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-EXPERIMENTAL (PRE-CLINICAL) THERAPEUTICS AND PHARMACOLOGY

Author

F. H. Yang, B. Zhang, D. J. Zhou, L. Bie, M. W. Tom, D. C. Drummond, T. Nicolaides, S. Mueller, A. Banerjee, J. W. Park, M. D. Prados, D. C. James, N. Gupta, R. Hashizume, G. W. Strohbehn, J. Zhou, M. Fu, T. R. Patel, J. M. Piepmeier, W. M. Saltzman, Q. Xie, J. Johnson, R. Bradley, M. L. Ascierto, L. Kang, J. Koeman, F. M. Marincola, M. Briggs, K. Tanner, G. F. Vande Woude, S. Tanaka, L. K. Klofas, H. Wakimoto, D. R. Borger, A. J. Iafrate, T. T. Batchelor, A. S. Chi, A. B. Madhankumar, B. Slagle-Webb, E. Rizk, K. Harbaugh, J. R. Connor, G. Sarkar, G. L. Curran, R. B. Jenkins, K. Kurozumi, T. Ichikawa, M. Onishi, K. Fujii, J. Ishida, Y. Shimazu, I. Date, K. Ebsworth, M. J. Walters, L. S. Ertl, Y. Wang, R. D. Berahovich, P. Zhang, J. P. Powers, S.-C. Liu, R. Al Omran, T. J. Sullivan, J. C. Jaen, M. Brown, T. J. Schall, N. Yusuke, S. Shimizu, Y. Shishido-Hara, Y. Shiokawa, M. Nagane, J. Wang, K. Sai, F.-R. Chen, Z.-P. Chen, Z. Shi, J. Zhang, K. Zhang, L. Han, L. Chen, X. Qian, A. Zhang, G. Wang, Z. Jia, P. Pu, C. Kang, L.-Y. Kong, T. A. Doucette, S. D. Ferguson, J. Hachem, Y. Yang, J. Wei, W. Priebe, G. N. Fuller, W. Qiao, G. Rao, A. B. Heimberger, P.-Y. Chen, T. Ozawa, D. Drummond, R. Santos, J. D. Torre, C. Ng, E. L. Lepe, N. Butowski, M. Prados, K. Bankiewicz, C. D. James, Z. Cheng, Y. Gong, Y. Ma, S. Muller-Knapp, S. Knapp, E. Antonio Chiocca, B. Kaur, J. S. Yu, V. Judkowski, A. Bunying, J. Ji, Z. Li, J. Bender, C. Pinilla, V. Srinivasan, M. Dombovy-Johnson, E. Carson-Walter, K. Walter, Z. Xu, B. Popp, D. Schlesinger, L. Gray, J. Sheehan, S. T. Keir, H. S. Friedman, D. D. Bigner, C. Kut, B. Tyler, E. McVeigh, X. Li, D. Herzka, S. Grossman, J. L. Lasky, E. Panosyan, W. H. Meisen, J. Hardcastle, J. Wojton, E. Wohleb, C. Alvarez-Breckenridge, M. Nowicki, J. Godbout, S. Y. Lee, J. M. Sheehan, S. Yin, S. Kaluz, S. N. Devi, R. de Noronha, K. C. Nicolaou, E. G. Van Meir, J. E. Lachowicz, M. Demeule, C. Che, S. Tripathy, S. Jarvis, J.-C. Currie, A. Regina, T. Nguyen, J.-P. Castaigne, K. Zielinska-Chomej, C. Mohanty, K. Viktorsson, R. Lewensohn, J. J. Driscoll, S. Alsidawi, R. E. Warnick, O. Rixe, A. C. deCarvalho, S. Irtenkauf, L. Hasselbach, H. Xin, T. Mikkelsen, J. H. Sherman, A. Siu, O. Volotskova, M. Keidar, D. M. Gibo, P. Dickinson, J. Robertson, J. Rossmeisl, W. Debinski, S. Nair, R. Schmittling, D. Boczkowski, G. Archer, J. H. Sampson, D. A. Mitchell, I. S. Miller, S. Didier, D. W. Murray, M. Issaivanan, S. J. Coniglio, J. E. Segall, Y. Al-Abed, M. Symons, A. Fotovati, K. Hu, J. Triscott, J. Bacha, D. M. Brown, S. E. Dunn, D. J. Daniels, T. E. Peterson, A. B. Dietz, G. J. Knutson, I. F. Parney, R. J. Diaz, B. Golbourn, D. Picard, C. Smith, A. Huang, J. Rutka, N. Saito, J. Fu, J. Yao, S. Wang, D. Koul, W. K. A. Yung, Y. Yuan, E. P. Sulman, H. Colman, F. F. Lang, E. A. Slat, E. D. Herzog, J. B. Rubin, A. S. Carminucci, B. Amendolara, R. Leung, L. Lei, P. Canoll, J. N. Bruce, J. A. Wojton, Z. Chu, C.-H. Kwon, L. M. Chow, M. Palascak, R. Franco, T. Bourdeau, S. Thornton, X. Qi, G. J. Kitange, A. C. Mladek, D. Su, B. L. Carlson, M. A. Schroeder, J. L. Pokorny, K. K. Bakken, S. K. Gupta, P. A. Decker, W. Wu, J. N. Sarkaria, M. P. Oddou, A. Mollard, L. T. Call, H. Vakayalapati, S. L. Warner, S. Sharma, D. J. Bearss, T. C. Chen, H. Cho, W. Wang, F. M. Hofman, C. T. Flores, D. Snyder, L. Sanchez-Perez, C. Pham, H. Friedman, E. Woolf, M. G. Abdelwahab, G. Turner, M. C. Preul, A. Lynch, J. M. Rho, A. C. Scheck, L. Salphati, T. P. Heffron, B. Alicke, K. Barck, R. A. Carano, J. Cheong, J. Greve, L. B. Lee, M. Nishimura, J. Pang, E. G. Plise, H. B. Reslan, X. Zhang, S. G. GOuld, A. G. Olivero, H. S. Phillips, G. Zadeh, S. Jalali, D. Voce, Z. Wei, K. Shijun, K. Nikolai, W. Josh, C. Clayton, Y. Bakhtiar, R. Alkins, A. Burgess, M. Ganguly, W. Wels, K. Hynynen, Y. M. Li, H. Jun, V. Daniel, H. A. Walter, H. Nakashima, T. T. Nguyen, I. Shalkh, W. F. Goins, E. A. Chiocca, I. V. Pyko, M. Nakada, N. Furuyama, T. Lei, Y. Hayashi, K. Kawakami, T. Minamoto, A. S. Fedulau, and J.-i. Hamada

Subjects
Cancer Research, Microarray analysis techniques, Cell, technology, industry, and agriculture, Pharmacology, Biology, Molecular biology, Abstracts, medicine.anatomical_structure, Oncology, Targeted drug delivery, Apoptosis, Gene expression, Cancer cell, medicine, Neurology (clinical), KEGG, Regulator gene
Abstract

Ginsenoside Rg3 is a natural active ingredient that is extracted from Korean red ginseng root. It elevates the therapeutic effect of radiotherapy and chemotherapy, but previous studies found that the application of Rg3 is heavily limited by its low bioavailability and poor absorption via oral administration. To overcome these problems, Rg3-loaded PEG-PLGA-NPs (Rg3-NPs) were prepared by the modified spontaneous emulsification solvent diffusion (SESD) method, and the physicochemical characteristics of Rg3-NPs were investigated. We treated primary glioblastoma with 50 mM Rg3-NPs for 48h. We then used gene expression arrays (Illumina) for genome-wide expression analysis and validated the results for genes of interest by means of real-time PCR. Functional annotations were then performed using the DAVID and KEGG online tools. The results showed that the Rg3-NPs are slick and uniform, the average diameter of the nanoparticles is 75-90 nm, and their entrapment efficiency is 89.7+1.7%. MTT showed that the growth of cells can be significantly inhibited by Rg3-NPs in a dose-dependent manner. FCM testing showed Rg3-NPs can be released from the conjugate nanoparticle and react with the genes in the cell nuclei, causing changes in the gene molecules. We also found that cancer cells treated with Rg3-NPs undergo cell-cycle arrest at different checkpoints. This arrest was associated with a decrease in the mRNA levels of core regulatory genes BUB1, CDC20, TTK, and CENPE, as determined by microarray analysis and verified by real-time PCR. Furthermore, Rg3-NPs induced the expression of the apoptotic and antimigratory protein p53 in cell lines. The results of the present study, together with the results of earlier studies, show that Rg3-NPs target genes involved in theprogressionoftheM-phaseofthecellcycle.Itisassociatedwithseveralimportant pathways, which include apoptosis (p53). Rg3-NPs may be a potent cell-cycle regulation drug targeting the M-phase in glioblastoma cell lines.

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. Measurement and comparison of individual external doses of high-school students living in Japan, France, Poland and Belarus - The 'D-shuttle' project - The '

Author

N Adachi, V Adamovitch, Y Adjovi, K Aida, H Akamatsu, S Akiyama, A Akli, A Ando, T Andrault, H Antonietti, S Anzai, G Arkoun, C Avenoso, D Ayrault, M Banasiewicz, M Banaśkiewicz, L Bernardini, E Bernard, E Berthet, M Blanchard, D Boreyko, K Boros, S Charron, P Cornette, K Czerkas, M Dameron, I Date, M De Pontbriand, F Demangeau, ł Dobaczewski, L Dobrzyński, A Ducouret, M Dziedzic, A Ecalle, V Edon, K Endo, T Endo, Y Endo, D Etryk, M Fabiszewska, S Fang, D Fauchier, F Felici, Y Fujiwara, C Gardais, W Gaul, L Gurin, R Hakoda, I Hamamatsu, K Handa, H Haneda, T Hara, M Hashimoto, T Hashimoto, K Hashimoto, D Hata, M Hattori, R Hayano, R Hayashi, H Higasi, M Hiruta, A Honda, Y Horikawa, H Horiuchi, Y Hozumi, M Ide, S Ihara, T Ikoma, Y Inohara, M Itazu, A Ito, J Janvrin, I Jout, H Kanda, G Kanemori, M Kanno, N Kanomata, T Kato, S Kato, J Katsu, Y Kawasaki, K Kikuchi, P Kilian, N Kimura, M Kiya, M Klepuszewski, E Kluchnikov, Y Kodama, R Kokubun, F Konishi, A Konno, V Kontsevoy, A Koori, A Koutaka, A Kowol, Y Koyama, M Kozioł, M Kozue, O Kravtchenko, W Kruczała, M Kudła, H Kudo, R Kumagai, K Kurogome, A Kurosu, M Kuse, A Lacombe, E Lefaillet, M Magara, J Malinowska, M Malinowski, V Maroselli, Y Masui, K Matsukawa, K Matsuya, B Matusik, M Maulny, P Mazur, C Miyake, Y Miyamoto, K Miyata, M Miyazaki, M Molȩda, T Morioka, E Morita, K Muto, H Nadamoto, M Nadzikiewicz, K Nagashima, M Nakade, C Nakayama, H Nakazawa, Y Nihei, R Nikul, S Niwa, O Niwa, M Nogi, K Nomura, D Ogata, H Ohguchi, J Ohno, M Okabe, M Okada, Y Okada, N Omi, H Onodera, K Onodera, S Ooki, K Oonishi, H Oonuma, H Ooshima, H Oouchi, M Orsucci, M Paoli, M Penaud, C Perdrisot, M Petit, A Piskowski, A Płocharski, A Polis, L Polti, T Potsepnia, D Przybylski, M Pytel, W Quillet, A Remy, C Robert, M Sadowski, M Saito, D Sakuma, K Sano, Y Sasaki, N Sato, T Schneider, C Schneider, K Schwartzman, E Selivanov, M Sezaki, K Shiroishi, I Shustava, A Śniecińska, E Stalchenko, A Staroń, M Stromboni, W Studzińska, H Sugisaki, T Sukegawa, M Sumida, Y Suzuki, K Suzuki, R Suzuki, H Suzuki, W Świderski, M Szudejko, M Szymaszek, J Tada, H Taguchi, K Takahashi, D Tanaka, G Tanaka, S Tanaka, K Tanino, K Tazbir, N Tcesnokova, N Tgawa, N Toda, H Tsuchiya, H Tsukamoto, T Tsushima, K Tsutsumi, H Umemura, M Uno, A Usui, H Utsumi, M Vaucelle, Y Wada, K Watanabe, S Watanabe, K Watase, M Witkowski, T Yamaki, J Yamamoto, T Yamamoto, M Yamashita, M Yanai, K Yasuda, Y Yoshida, A Yoshida, K Yoshimura, M Żmijewska, E Zuclarelli, Fukushima Medical University (FMU), National Centre for Nuclear Research [Otwock], Narodowe Centrum Badań Jądrowych (NCBJ), Centre d’étude sur l’Evaluation de la Protection dans le domaine Nucléaire (CEPN), and Institut de Radioprotection et de Sûreté Nucléaire (IRSN)

Subjects
Male, student, Republic of Belarus, Range (biology), [SDV]Life Sciences [q-bio], education, FOS: Physical sciences, Electronic Personal Dosimeter, Radiation Dosage, 030218 nuclear medicine & medical imaging, Education, Electronic personal dosimeters, 03 medical and health sciences, 0302 clinical medicine, Annual dose, Radiation Monitoring, Fukushima Nuclear Accident, Humans, human, Fukushima, Students, Waste Management and Disposal, International comparison, comparative study, High school students, Teaching, Public Health, Environmental and Occupational Health, Belarus, General Medicine, Physics - Medical Physics, External dose, Geography, female, 030220 oncology & carcinogenesis, Background radiation, Residence, Individual dose, Medical Physics (physics.med-ph), France, Poland, radiation dose, Demography
Abstract

Twelve high schools in Japan (of which six are in Fukushima Prefecture), four in France, eight in Poland and two in Belarus cooperated in the measurement and comparison of individual external doses in 2014. In total 216 high-school students and teachers participated in the study. Each participant wore an electronic personal dosimeter 'D-shuttle' for two weeks, and kept a journal of his/her whereabouts and activities. The distributions of annual external doses estimated for each region overlap with each other, demonstrating that the personal external individual doses in locations where residence is currently allowed in Fukushima Prefecture and in Belarus are well within the range of estimated annual doses due to the terrestrial background radiation level of other regions/countries. © 2016 IOP Publishing Ltd.

Published
2016

8. 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

10. Adult neural stem and progenitor cells modified to secrete GDNF can protect, migrate and integrate after intracerebral transplantation in rats with transient forebrain ischemia

Author

M, Kameda, T, Shingo, K, Takahashi, K, Muraoka, K, Kurozumi, T, Yasuhara, T, Maruo, T, Tsuboi, T, Uozumi, T, Matsui, Y, Miyoshi, H, Hamada, and I, Date

Subjects
Male, Neurons, Middle Cerebral Artery, Behavior, Animal, Stem Cells, Genetic Vectors, Green Fluorescent Proteins, Long-Term Potentiation, Cell Differentiation, Enzyme-Linked Immunosorbent Assay, Fibroblasts, Transfection, Immunohistochemistry, Magnetic Resonance Imaging, Adenoviridae, Rats, Bromodeoxyuridine, Cell Movement, Ischemic Attack, Transient, In Situ Nick-End Labeling, Animals, Glial Cell Line-Derived Neurotrophic Factor, Rats, Wistar, Cells, Cultured, Stem Cell Transplantation
Abstract

Adult neural stem and progenitor cells (NSPCs) are important autologous transplantation tools in regenerative medicine, as they can secrete factors that protect the ischemic brain. We investigated whether adult NSPCs genetically modified to secrete more glial cell line-derived neurotrophic factor (GDNF) could protect against transient ischemia in rats. NSPCs were harvested from the subventricular zone of adult Wistar rats and cultured for 3 weeks in the presence of epidermal growth factor. The NSPCs were treated with fibre-mutant Arg-Gly-Asp adenovirus containing the GDNF gene (NSPC-GDNF) or enhanced green fluorescent protein (EGFP) gene (NSPC-EGFP; control group). In one experiment, cultured cells were transplanted into the right ischemic boundary zone of Wistar rat brains. One week later, animals underwent 90 min of intraluminal right middle cerebral artery occlusion followed by magnetic resonance imaging and behavioural tests. The NSPC-GDNF group had higher behavioural scores and lesser infarct volume than did controls at 1, 7 and 28 days postocclusion. In the second experiment, we transplanted NSPCs 3 h after ischemic insult. Compared to controls, rats receiving NSPC-GDNF had decreased infarct volume and better behavioural assessments at 7 days post-transplant. Animals were killed on day 7 and brains were collected for GDNF ELISA and morphological assessment. Compared to controls, more GDNF was secreted, more NSPC-GDNF cells migrated toward the ischemic core and more NSPC-GDNF cells expressed immature neuronal marker. Moreover, the NSPC-GDNF group showed more effective inhibition of microglial invasion and apoptosis. These findings suggest that NSPC-GDNF may be useful in treatment of cerebral ischemia.

Published
2007

11. Differential diagnosis of the infundibular dilation and aneurysm of internal carotid artery: assessment with fusion imaging of 3D MR cisternography/angiography

Author

T, Satoh, M, Omi, C, Ohsako, K, Fujiwara, K, Tsuno, W, Sasahara, K, Onoda, K, Tokunaga, K, Sugiu, and I, Date

Subjects
Adult, Carotid Artery Diseases, Posterior Cerebral Artery, Interventional, Angiography, Digital Subtraction, Intracranial Aneurysm, Middle Aged, Magnetic Resonance Imaging, Sensitivity and Specificity, Cerebral Angiography, Diagnosis, Differential, Imaging, Three-Dimensional, Pituitary Gland, Posterior, Image Processing, Computer-Assisted, Feasibility Studies, Humans, Female, cardiovascular diseases, Pneumoencephalography, Algorithms, Carotid Artery, Internal, Magnetic Resonance Angiography, Aged, Dilatation, Pathologic
Abstract

SUMMARY: Fusion imaging of 3D MR cisternography/angiography was used for the assessment of the vascular bulging finding detected by MR angiography from the viewpoint of the outer wall configuration of the corresponding internal carotid artery depicted by MR cisternography. With a fusion image, useful information was obtained to distinguish an infundibular dilation and enlarged origin of the normal posterior communicating artery from an aneurysm. This imaging technique can be a feasible addition to a noninvasive screening of cerebrovascular lesions with MR angiography alone.

Published
2006

12. Endovascular treatment for elderly patients with ruptured aneurysm

Author

K, Sugiu, K, Tokunaga, K, Watanabe, W, Sasahara, M, Tagawa, N, Tamesa, S, Ono, K, Onoda, and I, Date

Subjects
Adult, Aged, 80 and over, Male, Intracranial Aneurysm, Aneurysm, Ruptured, Middle Aged, Prognosis, Embolization, Therapeutic, Risk Assessment, Severity of Illness Index, Neurosurgical Procedures, Age Distribution, Postoperative Complications, Treatment Outcome, Risk Factors, Prevalence, Humans, Female, Vascular Surgical Procedures, Aged, Retrospective Studies
Abstract

We report our results of endovascular treatment for elderly patients with ruptured aneurysm and discuss the indication for treatment. One hundred and thirty four consecutive patients with ruptured aneurysm treated in our institute during the last 4 years were retrospectively evaluated. Fifty eight patients were included in group A (over 70 years old), and 76 patients in group B (under 69 years old). In both groups, the outcome was strongly related to the preoperative HuntKosnik grade. However, significant risk factors (i.e. pneumonia, rupture of extracranial aneurysm) which make prognosis poor were more common in group A. Group A showed poor outcome in grade III patients, although there were no outcome differences between the two groups in patients of other grades. Endovascular treatment for elderly patients with ruptured aneurysms seemed to be useful. Their outcome was strongly related to their preoperative condition. General risk factors should be evaluated before treatment, especially in elderly patients. Patients with low HuntKosnik grade seem to be most suitable for endovascular treatment. On the other hand, outcome of patients with poor preoperative grade was worse despite the less invasive nature of endovascular treatment. An improvement of outcome in grade III patients is desirable.

Published
2005

13. The role of dopamine in manganese-induced oxidative injury in rat pheochromocytoma cells

Author

Ak K. Agrawal, Kavita Seth, I. Date, and Pk K. Seth

Subjects
0301 basic medicine, medicine.medical_specialty, Cell Survival, Health, Toxicology and Mutagenesis, Dopamine, PC12 cell line, Pheochromocytoma, Toxicology, medicine.disease_cause, Tritium, PC12 Cells, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Chlorides, Internal medicine, medicine, Animals, 030102 biochemistry & molecular biology, biology, Superoxide Dismutase, Neurotoxicity, General Medicine, Glutathione, medicine.disease, Catalase, Genetically modified organism, Enzymes, Mitochondria, Rats, Oxidative Stress, Endocrinology, chemistry, Mechanism of action, Manganese Compounds, 030220 oncology & carcinogenesis, biology.protein, medicine.symptom, Oxidative stress, medicine.drug, Thymidine
Abstract

Reactive dopamine (DA) metabolites have been implicated in both Parkinson's disease and manganese (Mn) neurotoxicity. Rat PC12 and genetically modified PC12 (PC12M) cells capable of producing higher DA content, on exposure to MnCl2 (10¡ 6 M) for 72 hours, exhibited a significant decrease in glutathione content. Activity of antioxidant enzyme catalase was also inhibited following 24 and 72-hour MnCl2 exposure. MnCl2 caused a concentration dependent (10¡ 7 to 10¡3 M) loss in mitochondrial activity after 24 and 72 hours and an impaired DNA synthesis after 72 hours with changes being more marked in PC12M cells. The results indicate that the free-radical-mediated toxicity of Mn at cellular level involves down-regulation of anti oxidants in normal and DA-rich PC12 cells. PC12M cells appeared to be more sensitive than PC12 cells.

Published
2002

15. [Linkage of gene expression with cerebral vasospasm]

Author

S, Ono, I, Date, and T, Ohmoto

Subjects
Mice, Knockout, Mice, Calcitonin Gene-Related Peptide, Endothelins, Animals, Gene Expression, Humans, Vasospasm, Intracranial, Mice, Transgenic, RNA, Messenger, Muscle, Smooth, Vascular, Signal Transduction
Published
2001

16. [Use of the GDC for embolization of a tumor fed by a cavernous branch of the internal carotid artery]

Author

A, Katsumata, N, Kusaka, K, Sugiu, H, Nakashima, I, Date, and T, Ohmoto

Subjects
Cranial Fossa, Posterior, Meningeal Neoplasms, Humans, Female, Middle Aged, Meningioma, Embolization, Therapeutic, Carotid Artery, Internal, Craniotomy, Petrous Bone
Abstract

Currently, embolization of small branches of the internal carotid artery (ICA) can be embolized through superselective microcatheterization, followed by the injection of liquid or particulate embolic materials. Often, however, a microcatheter cannot be placed in a stable enough position to allow an endovascular surgeon to perform a safe embolization, and the reflux of embolic agents into the main trunk of the ICA is a major concern. Meticulous technique and a detailed knowledge of the vascular anatomy of the cavernous sinus region are necessary to maximize devascularization of the lesion and to minimize the risk of complications. This report describes the case of a patient with a hypervascular tumor whose feeding vessel from the cavernous ICA was successfully occluded with polyvinyl alcohol (PVA) combined with a regular Guglielmi detachable coil (GDC). A 62-year-old woman had a left-sided petroclival meningioma, which was diagnosed based on computed tomography and magnetic resonance studies. Transfemoral angiographic studies demonstrated that the tumor was fed by intracavernous branches of the left ICA. We believed that another embolic agent would have presented a risk of reflux into the ICA, with possible unwanted occlusion of normal intracranial arteries. A single GDC was sufficient to occlude the feeding artery, and the patient underwent successful surgery 3 days after the endovascular procedure. The GDC can eliminate the ICA supply to hypervascular tumors safely when liquid or particle embolic materials would present a risk of reflux into normal arteries. This device can be positioned and repositioned and can be detached without mechanical force. It may also decrease the risk of unwanted embolization of normal intracranial arteries.

Published
2001

17. [Surgical therapy for Parkinson's disease]

Author

S, Tomita, I, Date, and T, Ohmoto

Subjects
Hypothalamus, Motor Cortex, Brain, Electric Stimulation Therapy, Nerve Tissue Proteins, Parkinson Disease, Thalamus, Animals, Humans, Brain Tissue Transplantation, Fibroblast Growth Factor 2, Ciliary Neurotrophic Factor, Glial Cell Line-Derived Neurotrophic Factor, Nerve Growth Factors
Published
2001

18. [Neurosurgical therapy for parkinson's disease]

Author

S, Tomita, I, Date, and T, Ohmoto

Subjects
Antiparkinson Agents, Levodopa, Stereotaxic Techniques, Adrenal Medulla, Cell Transplantation, Subthalamic Nucleus, Humans, Electric Stimulation Therapy, Female, Parkinson Disease, Peripheral Nerves, Middle Aged, Globus Pallidus
Abstract

Stereotactic surgery and neuronal transplantation are considered to be effective surgical therapies for advanced Parkinson's disease with wearing off phenomenon. As a stereotactic surgery, posteroventral pallidotomy and chronic pallidal or subthalamic stimulation with inhibitory parameters were performed. Flattening of the motor fluctuations were obtained with improving general motor symptoms especially at "off" time. Therapeutic l-dopa dose could not reduced following pallidotomy and pallidal stimulation, whereas subthalamic stimulation saved 30-50% of l-dopa dose. By the constant supply of dopamine, neuronal transplantation was effective on wearing off. Chromaffin cells of adrenal medulla and pretransected peripheral nerve were cografted into the bilateral caudate nuclei. After the transplantation significant reduction of % time off and l-dopa dose was observed.

Published
2000

19. Neural transplantation for Parkinson's disease

Author

I, Date and T, Ohmoto

Subjects
Neurons, Disease Models, Animal, Animals, Humans, Brain Tissue Transplantation, Parkinson Disease
Abstract

1. Neural transplantation is one promising approach for the treatment of Parkinson's disease. Fetal substantia nigra cells are a good source of dopamine, but in order to avoid ethical and immunological problems, adrenal medullary chromaffin cells have been investigated as an alternative source. 2. Grafted adrenal medullary chromaffin cells can provide dopamine as well as several neurotrophic factors that affect dopaminergic neurons in the brain. 3. We review experimental studies for application of neural transplantation techniques in Parkinson's disease, including immunological studies, cryopreservation, microvasculature, donor tissue, and direct gene delivery studies performed in our laboratory. Our clinical experience and new approach involving a polymer-encapsulated cell grafting procedure are also described.

Published
1999

21. [Extradural temporopolar approach for giant pituitary adenomas invading the cavernous sinus and parasellar regions]

Author

T, Tamiya, Y, Ono, I, Date, M, Kawauchi, K, Matsumoto, and T, Ohmoto

Subjects
Adenoma, Adult, Microsurgery, Humans, Cavernous Sinus, Female, Neoplasm Invasiveness, Pituitary Neoplasms, Middle Aged, Skull Base Neoplasms, Vascular Neoplasms, Hypophysectomy
Abstract

An extradural temporopolar approach has recently been used in the treatment of the parasellar, infrachiasmatic, or intracavernous regions. In this approach, the temporal (superficial) dural layer is separated from the deep layer (inner cavernous membrane) to expose the cavernous sinus extradurally. We report our experiences with 5 cases in which a giant pituitary adenoma invading the cavernous sinus and parasellar regions was resected via the extradural temporopolar approach.Between January 1995 and December 1997, 60 patients with pituitary adenomas were operated on at Okayama University Hospital. The extradural temporopolar approach was used for 5 patients who had a giant pituitary adenoma invading the cavernous sinus and parasellar regions. The 5 patients were women aged from 32 to 62 years and presented with a visual dysfunction. Four patients had hormonally non-functioning pituitary adenomas and one had a growth-hormone secreting pituitary adenoma.The operations resulted in 1 total, 3 subtotal and 1 partial removal. There was no operative mortality or major morbidity. Transient oculomotor palsy occurred in 2 cases postoperatively. This approach provided excellent exposure of the tumor, relevant cranial nerves and arteries in and around the cavernous sinus through extradural retraction of the temporal lobe, allowing for sufficient resection of the intracavernous and parasellar portion of the tumor. Tumors invading the inferior portion of the clivus or the contralateral cavernous sinus could not be removed through this approach.Our findings suggest that the extradural temporopolar approach is useful for resection of giant pituitary adenomas invading the cavernous sinus and parasellar regions.

Published
1998

22. [Encapsulated dopamine-secreting cells transplanted into the brain: a possible therapy for Parkinson's disease]

Author

Y, Miyoshi, I, Date, T, Ono, T, Imaoka, S, Asari, T, Ohmoto, and H, Iwata

Subjects
Cell Transplantation, Dopamine, Guinea Pigs, Adrenal Gland Neoplasms, Tumor Cells, Cultured, Animals, Brain, Capsules, Parkinson Disease, Pheochromocytoma, Chromatography, High Pressure Liquid, Rats
Abstract

Encapsulation of neurosecretory cells within a semipermeable membrane may possibly isolate the enclosed cells from the host immune system and allow inward diffusion of nutrients and outward diffusion of neurotransmitters. Moreover, the encapsulation procedure may prevent the tumor formation of enclosed cells, when they are derived from tumor cells. In the present study, PC12 cells, a dopaminergic cell line derived from a rat pheochromocytoma, were enclosed within an agarose/poly (styrene sulfonic acid) (agarose/PSSa) mixture and transplanted into the brains of rats (allogeneic transplantation) or guinea pigs (xenogeneic transplantation). Tyrosine hydroxylase (TH) immunoreactive PC12 cells within the microcapsules were observed in all rats and guinea pigs at least up to five weeks after transplantation. PC12 cells were round in shape and of relatively uniform small size. Although PC12 cells occasionally formed cell clusters, the formation of a tumor was not observed. The host reaction to agarose/PSSa microcapsules was minimum. The degree of glial fibrillary acidic protein (GFAP) positive astrocyte density around the microcapsules was similar to that around injection tracks. There was no apparent immunological rejection around the capsules. High-performance liquid chromatography with electrochemical detection (HPLC-EC) showed basal and potassium-evoked release of dopamine from the PC12 cell-enclosed microcapsules in vitro. Although our data is preliminary, we believe that agarose/PSSa microcapsules are promising for producing semipermeable membranes that enable allo-and xenotransplantation of neurosecretory cells into the brain in the absence of systemic immunosuppression. This approach is expected to be applied in Parkinson's disease in the near future.

Published
1996

23. [Intrathecal dissemination of meningiomas; a case report]

Author

T, Satoh, T, Kageyama, Y, Yoshimoto, I, Kamata, I, Date, and M, Motoi

Subjects
Adult, Male, Cisterna Magna, Meningeal Neoplasms, Humans, Spinal Cord Neoplasms, Meningioma, Magnetic Resonance Imaging, Spinal Canal, Subarachnoid Space, Cerebrospinal Fluid
Abstract

A case of the cytologically verified intrathecal dissemination of benign meningiomas was reported. A 36-year-old man was admitted to our hospital because trans-sphenoidal surgery was planned for the repair of CSF rhinorrhea caused by a recurrent pituitary adenoma. The CT scan demonstrated incidental multiple tumors spread throughout in the pontomedullary and ambient cisterns. The head and spinal MRI showed more than fifteen small tumors in the posterior fossa and the thoracic spinal canal. CSF cytology revealed benign fibroblastic or meningotheliomatous meningioma with whorl formation and psammoma body. Several comments were made on the mechanism of the intrathecal dissemination of the meningiomas.

Published
1992

24. [Cool storage of fetal rat brain for neural transplantation]

Author

Y, Yoshimoto, I, Date, K, Sakai, T, Furuta, S, Asari, and T, Ohmoto

Subjects
Cryopreservation, Fetal Tissue Transplantation, Mesencephalon, Graft Survival, Animals, Brain Tissue Transplantation, Tissue Preservation, Rats, Inbred F344, Rats
Abstract

The availability, storage and transportation of donor tissue are major practical problems associated with the potential use of grafted neural cell replacements in neurodegenerative diseases. The capacity to collect and maintain viable fetal neural tissue would facilitate possible clinical applications, and provide opportunities to study various neural diseases. In the present study, we examined the effect of cool storage on the survivability of intraventricular rat fetal ventral mesencephalic grafts (gestational days 15). In all experiments, fetal ventral mesencephalons were dissected out under a dissecting microscope in calcium-free magnesium-free buffer (CMF: 0.15 M NaCl, 0.008 M Na2HPO4, 0.0027 M KCl, 0.0015 M KHPO4, 0.026 M NaHCO3, with 0.1% glucose, 100 micrograms/ml streptomycin, 2.5 micrograms/ml fungizone). Fetal mesencephalic tissue was grafted into the lateral ventricle following pregraft refrigeration in calcium-free magnesium-free buffer at 4 degrees C. Fetal mesencephalic tissue was hibernated for 5, 12, 16, 20, 24, 28, 32 hours (group A, B, C, D, E, F and G, respectively). As a control group, fetal mesencephalic tissue was grafted into the lateral ventricle immediately after dissection. Grafted fetal mesencephalic tissue which had been hibernated for 16 hours or less survived well. There were no significant decreases in the size of grafts among group A, B, C and the control group. In group A, B, C and the control group, clusters of TH-positive neurons and dense networks of neuritic profiles within the grafts provided a morphological appearance reminiscent of the dendritic bundles that characterize the zone reticulate of the substantia nigra in situ.(ABSTRACT TRUNCATED AT 250 WORDS)

Published
1992

25. [Cografting technique in the treatment of Parkinson's disease]

Author

I, Date, S, Asari, A, Nishimoto, and D, Felten

Subjects
Mice, Inbred C57BL, Aging, Disease Models, Animal, Mice, Adrenal Medulla, Animals, Brain Tissue Transplantation, Chromaffin Granules, Parkinson Disease, Sciatic Nerve, Corpus Striatum, Tissue Donors
Abstract

Intracerebral grafting of dopamine containing adrenal chromaffin cells to the brain of experimental animals can ameliorate the symptoms of experimentally induced Parkinson's disease. Clinical trials of adrenal autograft to the patients with Parkinson's disease are on-going with variable results and autopsy cases show poor survivability of grafted chromaffin cells. The present study was performed to determine if transected peripheral nerve could provide sufficient nerve growth factor to enhance the survivability of grafted chromaffin cells. Survivability of grafted chromaffin cells increased when cografts with sciatic nerve were performed, and host dopaminergic fiber recovery was more prominent in mice with cografts than in mice with adrenal grafts alone. Although this enhanced survivability and recovery of host fibers were seen in cografted mice from aging donors, the degree of these effects was greater in cografted mice from young donors. Considering these results, we suggest that methods to increase the survivability of grafted chromaffin cells be explored more deeply because such survivability might be closely related to the functional recovery of patients with Parkinson's disease, using this grafting procedure.

Published
1991

26. [Mobile neurinoma of the cauda equina; a case report]

Author

T, Satoh, T, Kageyama, I, Kamata, and I, Date

Subjects
Male, Cauda Equina, Peripheral Nervous System Neoplasms, Humans, Myelography, Neurilemmoma, Aged
Abstract

A case of mobile tumor of the cauda equina was presented with a brief review of factors relating to the mobility. A 66-year-old man was admitted to our hospital complaining of left lumbago aggravated by coughing or assuming the supine position. However, neurological examination failed to reveal any abnormalities. The initial myelography showed complete obstruction above the superior border of the L1 vertebra, while the second myelography showed the same obstruction, but it had moved upwards to the superior border of T12. Surgery revealed an elastic, soft tumor and cystic dilatation of the subarachnoid space above and below the tumor. The tumor was mobile but originated from a single elongated and tortuous nerve of the cauda equina. Pathologic examination revealed neurinoma.

Published
1991

27. [Cografts of adrenal medulla and peripheral nerve in a mouse model of Parkinson's disease]

Author

I, Date, S, Asari, A, Nishimoto, and D, Felten

Subjects
Mice, Inbred C57BL, Aging, Disease Models, Animal, Mice, Adrenal Medulla, Cell Survival, Dopamine, Graft Survival, Animals, Brain Tissue Transplantation, Parkinson Disease, Sciatic Nerve, Corpus Striatum
Abstract

Systemic injection of MPTP damages the nigrostriatal dopaminergic system in C57B1/6 mice. Since transected peripheral nerve segments are known to produce nerve growth factor, we performed adrenal medullary grafts or cografts of adrenal medulla and sciatic nerve into the striatum of MPTP-treated mice, and compared the survivability of grafted chromaffin cells and the recovery of intrinsic host dopaminergic fibers. Survivability of grafted chromaffin cells increased when cografts with sciatic nerve were made, and host dopaminergic fiber recovery was more prominent in mice with cografts than in mice with adrenal grafts alone. The degree of recovery of host intrinsic dopaminergic fibers was greater in younger host striatum than in older host striatum. We conclude that cografts of adrenal medulla and sciatic nerve increase the survivability of grafted chromaffin cells better than adrenal medullary grafts alone, and that survivability of grafted chromaffin cells promotes host dopaminergic fiber recovery.

Published
1991

28. [The effect of a new immunosuppressive agent, FK-506, on xenogeneic neural transplantation in rodents--comparison with cyclosporin A]

Author

K, Sakai, I, Date, Y, Yoshimoto, T, Arisawa, H, Nakashima, T, Furuta, S, Asari, and A, Nishimoto

Subjects
Graft Rejection, Male, Mice, Mice, Inbred C3H, Mesencephalon, Graft Survival, Transplantation, Heterologous, Cyclosporine, Animals, Brain Tissue Transplantation, Rats, Inbred Strains, Tacrolimus, Rats
Abstract

The present study was performed to compare the immunosuppressive effect of FK-506 (FK) with cyclosporin A (CyA) in xenogeneic neural transplantation in rodents. The solid grafts of embryonic ventral mesencephalic tissue from 14-day rat embryos were transplanted into the right lateral ventricle of 20 mature male mice using a stereotactic approach, and the mice were sacrificed 14 days after transplantation. The removed brains, which were sectioned coronally, were stained with antibodies against glial fibrillary acidic protein (GFAP), Lyt-2 or tyrosine hydroxylase (TH) in addition to hematoxylin-eosin and Nissl stainings. The subcutaneous (s.c.) administration of FK at a dose of 10.0 mg/kg daily for 14 days enabled the neural xenografts to survive and grow (n = 5), although all of the neural xenografts treated with CyA at a dose of 10.0 mg/kg s.c. (n = 5) or FK at a dose of 1.0 mg/kg s.c. (n = 5) daily for 14 days and ones treated without such an immunosuppressive agent (n = 5) were rejected by immunological reactions. We conclude that FK is a more powerful immunosuppressive agent than CyA in xenogeneic neural transplantation as well as in cardiac and renal allograftings.

Published
1991

29. [Adrenal medullary graft induces recovery of the host nigrostriatal dopaminergic system in MPTP-induced mouse model of Parkinson's disease]

Author

I, Date, S, Asari, A, Nishimoto, and D L, Felten

Subjects
Mice, Inbred C57BL, Mice, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Adrenal Medulla, Dopamine, Chromaffin System, Image Processing, Computer-Assisted, Animals, Parkinson Disease, Secondary, Corpus Striatum, Tissue Donors
Abstract

C57BL/6 mice show decreased dopaminergic fibers and dopamine concentration in the striatum following systemic injection of 1-methyl-4-phenyl-1, 2, 3, 6-tetrahydropyridine (MPTP). We have investigated the effect of adrenal medullary grafts into the striatum of young mice treated with MPTP. Enhanced recovery of the host nigrostriatal dopaminergic system was observed in those adrenal medullary grafted mice. However, this recovery was influenced by the survivability of grafted chromaffin cells and adrenal chromaffin cells from younger donors survived better than those from older donors. Since adrenal chromaffin cells contain several kinds of neurotrophic factors such as basic fibroblast growth factor and gangliosides, survivability of those grafted chromaffin cells may play an important role concerning recovery of the host intrinsic dopaminergic fibers. Adrenal medullary grafts to the patients with Parkinson's disease are currently under way in a large number of hospitals and we suggest more consideration be given to methods which lead to enhance the grafted chromaffin cell survival, since those survivability might be closely related to the functional recovery of these patients.

Published
1990

30. [Recovery of nigrostriatal and mesolimbic dopaminergic system following administration of ganglioside in MPTP-treated mice]

Author

I, Date, S, Asari, A, Nishimoto, and D L, Felten

Subjects
Mice, Inbred C57BL, Substantia Nigra, Disease Models, Animal, Mice, 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine, Dopamine, Age Factors, Limbic System, Animals, G(M1) Ganglioside, Parkinson Disease, Secondary, Adrenergic Fibers, Corpus Striatum
Abstract

The effects of systemic injection of GM 1 ganglioside on dopaminergic (DA) nigrostriatal and mesolimbic system following 1-methyl-4-phenyl-1, 2,3,6-tetrahydropyridine (MPTP) have been studied in C 57 BL/6 mice. MPTP treatment (4 x 20 mg/kg i.p. given 12 hr apart) resulted in significant depletion of DA concentration in the major terminal fields of the nigrostriatal and mesolimbic DA systems, i.e. dorsal striatum, ventral striatum, nucleus accumbens and olfactory tubercle 5 weeks after treatment in young (2 month old) mice. In aging (12 month old) mice treated with MPTP, significant depletion of DA concentration was observed in the cell body regions, i.e. substantia nigra and ventral tegmental area in addition to the major terminal fields, suggesting that the effect of MPTP is more widespread in aging mice. Although GM 1 ganglioside treatment (30 mg/kg, i.p. daily for 5 weeks) partially restored DA concentration in every major terminal field in young mice, such an apparent recovery was not seen in aging mice. GM 1 ganglioside treatment also reduced the increased 3,4-dihydroxyphenylacetic acid (DOPAC)/DA ratio following MPTP injection in the striatum of young mice, but such an effect was not observed in aging mice. We conclude that DA nigrostriatal and mesolimbic system in aging mice demonstrates reduced regenerative capacity following MPTP depletion compared with young mice, and the beneficial effect of GM 1 ganglioside for the recovery of DA nigrostriatal and mesolimbic system neurons declines with age.

Published
1990

31. [Hypothalamic hamartoma with precocious puberty--a case report]

Author

I, Date, Y, Yagyu, S, Mino, and T, Ohhashi

Subjects
Gonadotropin-Releasing Hormone, Immunoassay, Male, Radiography, Hypothalamus, Posterior, Hamartoma, Humans, Puberty, Precocious, Testosterone, Postoperative Period, Hypothalamic Neoplasms, Luteinizing Hormone, Child
Abstract

A case of hypothalamic hamartoma with precocious puberty is presented and the literature of reported cases is reviewed. An 8-year-old boy was admitted to our hospital because of precocious puberty and mental retardation. His genital development was Tanner's stage 4 and pubic hair was Tanner's stage 3. Bone age was 11 years. Plain CT showed an isodense mass in the suprasellar cistern which was not enhanced following contrast administration. Metrizamide CT cisternography showed a filling defect in the suprasellar cistern. Endocrinological evaluation revealed high levels of serum luteinizing hormone (LH) and testosterone with a marked response of LH to LH-RH injection. A left frontotemporal craniotomy was performed and the tumor was partially removed. The tumor was gray, firm and well-circumscribed with poor vascularity. Postoperatively, a right oculomotor palsy and transient diabetes insipidus developed. He was discharged ambulatory one month later. Serum LH and testosterone returned to normal and the response of LH to LH-RH injection became normal. Hamartoma was diagnosed on histological examination. Electron micrographic study showed numerous dense granules with approximately 0.1 mu in diameter, in which Judge proved LH-RH by immunofluorescent study in 1977. Our case supports the hypothesis that hypothalamic hamartoma may cause precocious puberty by autonomous secretion of LH-RH and we consider that neurosurgical treatment is recommended.

Published
1985

32. Hyperplasia of Gums with Epanutin Therapy. Two Cases

Author

A. I. Date

Subjects
medicine.medical_specialty, business.industry, Medicine, Library science, Hyperplasia, business, medicine.disease, Section for the Study of Disease in Children, Dermatology
Published
1945

33. Assessment of morphology and hemodynamics in a surgically clipped neck of a cerebral aneurysm: illustrative case.

Author

Satoh T, Ichikawa T, Fujii K, and Date I

Abstract

Background: Silent magnetic resonance angiography reduces metal artifacts, enabling clear visualization of the clipped neck following surgical clipping of cerebral aneurysms. This study aimed to delineate the morphology of the clipped neck complex in cerebral aneurysms using three-dimensional (3D) multifusion imaging of silent magnetic resonance angiography and fast spin echo magnetic resonance cisternography. Additionally, computational fluid dynamics analysis was utilized to evaluate the hemodynamics of the parent vessel at the clipped neck, allowing for a detailed assessment of hemodynamics at the clipped neck., Observations: The 3D multifusion image enabled visualization of the orientation and shape of the clip within the clipped neck complex, alongside the morphology of the parent vessel. In the hemodynamic analysis of the parent vessel at the clipped neck, areas of high-intensity magnitude of wall shear stress (WSSm) variation corresponding to the clip's contour, along with significant vector of wall shear stress (WSSv) variation related to vector directionality, were visualized in 3D. The intentional residual neck, coated with muscle grafts, was depicted as an area with low WSSm variation values and high WSSv variation values., Lessons: Three-dimensional multifusion imaging, along with computational fluid dynamics analysis of the parent vessels, facilitated both the morphological and hemodynamic visualization and assessment of the clipped neck complex following neck clipping surgery for cerebral aneurysms. https://thejns.org/doi/10.3171/CASE24194.

Published
2024
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34. State-of-the-Art and New Treatment Approaches for Spinal Cord Tumors.

Author

Kumawat C, Takahashi T, Date I, Tomita Y, Tanaka M, Arataki S, Komatsubara T, Flores AOP, Yu D, and Jain M

Abstract

Spinal cord tumors, though rare, present formidable challenges in clinical management due to their intricate nature. Traditional treatment modalities like surgery, radiation therapy, and chemotherapy have been the mainstay for managing these tumors. However, despite significant advancements, challenges persist, including the limitations of surgical resection and the potential side effects associated with radiation therapy. In response to these limitations, a wave of innovative approaches is reshaping the treatment landscape for spinal cord tumors. Advancements in gene therapy, immunotherapy, and targeted therapy are offering groundbreaking possibilities. Gene therapy holds the potential to modify the genes responsible for tumor growth, while immunotherapy harnesses the body's own immune system to fight cancer cells. Targeted therapy aims to strike a specific vulnerability within the tumor cells, offering a more precise and potentially less toxic approach. Additionally, novel surgical adjuncts are being explored to improve visualization and minimize damage to surrounding healthy tissue during tumor removal. These developments pave the way for a future of personalized medicine for spinal cord tumors. By delving deeper into the molecular makeup of individual tumors, doctors can tailor treatment strategies to target specific mutations and vulnerabilities. This personalized approach offers the potential for more effective interventions with fewer side effects, ultimately leading to improved patient outcomes and a better quality of life. This evolving landscape of spinal cord tumor management signifies the crucial integration of established and innovative strategies to create a brighter future for patients battling this complex condition.

Published
2024
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35. Cervical spinal cord stimulation exerts anti-epileptic effects in a rat model of epileptic seizure through the suppression of CCL2-mediated cascades.

Author

Okazaki Y, Sasaki T, Hosomoto K, Tanimoto S, Kawai K, Nagase T, Sugahara C, Yabuno S, Kin K, Sasada S, Yasuhara T, Tanaka S, and Date I

Subjects
Animals, Rats, Male, Kainic Acid, Hippocampus metabolism, Neuroglia metabolism, Rats, Sprague-Dawley, Electroencephalography, Chemokine CCL2 metabolism, Chemokine CCL2 genetics, Disease Models, Animal, Spinal Cord Stimulation methods, Seizures therapy, Seizures metabolism, Epilepsy therapy, Epilepsy metabolism
Abstract

Epidural spinal cord stimulation (SCS) is indicated for the treatment of intractable pain and is widely used in clinical practice. In previous basic research, the therapeutic effects of SCS have been demonstrated for epileptic seizure. However, the mechanism has not yet been elucidated. In this study, we investigated the therapeutic effect of SCS and the influence of epileptic seizure. First, SCS in the cervical spine was performed. The rats were divided into four groups: control group and treatment groups with SCS conducted at 2, 50, and 300 Hz frequency. Two days later, convulsions were induced by the intraperitoneal administration of kainic acid, followed by video monitoring to assess seizures. We also evaluated glial cells in the hippocampus by fluorescent immunostaining, electroencephalogram measurements, and inflammatory cytokines such as C-C motif chemokine ligand 2 (CCL2) by quantitative real-time polymerase chain reaction. Seizure frequency and the number of glial cells were significantly lower in the 300 Hz group than in the control group. SCS at 300 Hz decreased gene expression level of CCL2, which induces monocyte migration. SCS has anti-seizure effects by inhibiting CCL2-mediated cascades. The suppression of CCL2 and glial cells may be associated with the suppression of epileptic seizure., (© 2024. The Author(s).)

Published
2024
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36. Organized Chronic Subdural Hematoma (OCSDH) Mimicking Meningioma.

Author

Hirano S, Otani Y, Fujii K, and Date I

Subjects
Humans, Male, Adult, Diagnosis, Differential, Tomography, X-Ray Computed, Magnetic Resonance Imaging, Meningioma diagnostic imaging, Meningioma surgery, Hematoma, Subdural, Chronic diagnostic imaging, Hematoma, Subdural, Chronic surgery, Hematoma, Subdural, Chronic diagnosis, Meningeal Neoplasms diagnostic imaging, Meningeal Neoplasms diagnosis, Meningeal Neoplasms surgery
Abstract

Organized chronic subdural hematoma (OCSDH) is a relatively rare condition that forms over a longer period of time compared to chronic subdural hematoma and is sometimes difficult to diagnose with preoperative imaging. We resected an intracranial lesion in a 37-year-old Japanese man; the lesion had been increasing in size for >17 years. The preoperative diagnosis based on imaging findings was meningioma; however, pathological findings revealed OCSDH. Clinicians should be aware that OCSDH mimics other tumors and consider surgical strategies for this disease., Competing Interests: No potential conflict of interest relevant to this article was reported.

Published
2024
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37. Genomic landscape of glioblastoma without IDH somatic mutation in 42 cases: a comprehensive analysis using RNA sequencing data.

Author

Okamoto T, Mizuta R, Takahashi Y, Otani Y, Sasaki E, Horio Y, Kuroda H, Matsushita H, Date I, Hashimoto N, and Masago K

Subjects
Humans, Male, Female, Middle Aged, Aged, Adult, Sequence Analysis, RNA methods, Biomarkers, Tumor genetics, Genomics methods, Young Adult, Aged, 80 and over, Prognosis, Glioblastoma genetics, Isocitrate Dehydrogenase genetics, Brain Neoplasms genetics, Brain Neoplasms pathology, Mutation
Abstract

Purpose: Glioblastoma is a malignant brain tumor with a poor prognosis. Genetic mutations associated with this disease are complex are not fully understood and require further elucidation for the development of new treatments. The purpose of this study was to comprehensively analyze genetic mutations in glioblastomas and evaluate the usefulness of RNA sequencing., Patients and Methods: We analyzed 42 glioblastoma specimens that were resected in routine clinical practice and found wild-type variants of the IDH1 and IDH2 genes. RNA was extracted from frozen specimens and sequenced, and genetic analyses were performed using the CLC Genomics Workbench., Results: The most common genetic alterations in the 42 glioblastoma specimens were TP53 mutation (28.6%), EGFR splicing variant (16.7%), EGFR mutation (9.5%), and FGFR3 fusion (9.5%). Novel genetic mutations were detected in 8 patients (19%). In 12 cases (28.6%), driver gene mutations were not detected, suggesting an association with PPP1R14A overexpression. Our findings suggest the transcription factors SOX10 and NKX6-2 are potential markers in glioblastoma., Conclusion: RNA sequencing is a promising approach for genotyping glioblastomas because it provides comprehensive information on gene expression and is relatively cost-effective., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Published
2024
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38. Evaluation of the shrinkage process of a neck remnant after stent-coil treatment of a cerebral aneurysm using silent magnetic resonance angiography and computational fluid dynamics analysis: illustrative case.

Author

Satoh T, Sugiu K, Hiramatsu M, Haruma J, and Date I

Abstract

Background: Silent magnetic resonance angiography (MRA) mitigates metal artifacts, facilitating clear visualization of neck remnants after stent and coil embolization of cerebral aneurysms. This study aims to scrutinize hemodynamics at the neck remnant by employing silent MRA and computational fluid dynamics., Observations: The authors longitudinally tracked images of a partially thrombosed anterior communicating artery aneurysm's neck remnant, which had been treated with stent-assisted coil embolization, using silent MRA over a decade. Computational fluid dynamics delineated the neck remnant's reduction process, evaluating hemodynamic parameters such as flow rate, wall shear stress magnitude and vector, and streamlines. The neck remnant exhibited diminishing surface area, volume, neck size, dome depth, and aspect ratio. Its reduction correlated with a decline in the flow rate ratio of the remnant dome to the inflow parent artery. Analysis delineated regions within the contracting neck remnant characterized by consistently low average wall shear stress magnitude and variation, accompanied by notable variations in wall shear stress vector directionality., Lessons: Evaluation of neck remnants after stent-coil embolization is possible through silent MRA and computational fluid dynamics. Predicting the neck remnant reduction may be achievable through hemodynamic parameter analysis.

Published
2024
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39. Midline invasion predicts poor prognosis in diffuse hemispheric glioma, H3 G34-mutant: an individual participant data review.

Author

Kegoya Y, Otani Y, Inoue Y, Mizuta R, Higaki F, Washio K, Koizumi S, Kurozumi K, Ishida J, Fujii K, Yamamoto N, Tanaka Y, and Date I

Subjects
Humans, Male, Child, Young Adult, Adult, Histones genetics, Mutation, Prognosis, Brain Neoplasms diagnostic imaging, Brain Neoplasms genetics, Brain Neoplasms pathology, Glioma diagnostic imaging, Glioma genetics
Abstract

Introduction: Diffuse hemispheric glioma, H3 G34-mutant (DHGs), is a newly categorized tumor in pediatric-type diffuse high-grade gliomas, World Health Organization grade 4, with a poor prognosis. Although prognostic factors associated with genetic abnormalities have been reported, few reports have examined the clinical presentation of DHGs, especially from the viewpoint of imaging findings. In this study, we investigated the relationship between clinical factors, including imaging findings, and prognosis in patients with DHGs., Methods: We searched Medline through the PubMed database using two search terms: "G34" and "glioma", between 1 April 2012 and 1 July 2023. We retrieved articles that described imaging findings and overall survival (OS), and added one DHG case from our institution. We defined midline invasion (MI) as invasion to the contralateral cerebrum, brainstem, corpus callosum, thalamus, and basal ganglia on magnetic resonance imaging. The primary outcome was 12-month survival, estimated using Kaplan-Meier curves and logistic regression., Results: A total of 96 patients were included in this study. The median age was 22 years, and the proportion of male patients was 48.4%. Lesions were most frequently located in the frontal lobe (52.6%). MI was positive in 39.6% of all patients. The median OS was 14.4 months. Univariate logistic regression analysis revealed that OS was significantly worse in the MI-positive group compared with the MI-negative group. Multivariate logistic regression analysis revealed that MI was an independent prognostic factor in DHGs., Conclusions: In this study, MI-positive cases had a worse prognosis compared with MI-negative cases., Previous Presentations: No portion of this study has been presented or published previously., (© 2024. The Author(s).)

Published
2024
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40. Power suppression in EEG after the onset of SAH is a significant marker of early brain injury in rat models.

Author

Takasugi Y, Hishikawa T, Shimizu T, Murai S, Haruma J, Hiramatsu M, Tokunaga K, Takeda Y, Sugiu K, Morimatsu H, and Date I

Subjects
Rats, Animals, Electroencephalography methods, Disease Models, Animal, Neurons pathology, Subarachnoid Hemorrhage pathology, Brain Injuries pathology
Abstract

We analyzed the correlation between the duration of electroencephalogram (EEG) recovery and histological outcome in rats in the acute stage of subarachnoid hemorrhage (SAH) to find a new predictor of the subsequent outcome. SAH was induced in eight rats by cisternal blood injection, and the duration of cortical depolarization was measured. EEG power spectrums were given by time frequency analysis, and histology was evaluated. The appropriate frequency band and recovery percentage of EEG (defined as EEG recovery time) to predict the neuronal damage were determined from 25 patterns (5 bands × 5 recovery rates) of receiver operating characteristic (ROC) curves. Probit regression curves were depicted to evaluate the relationships between neuronal injury and duration of depolarization and EEG recovery. The optimal values of the EEG band and the EEG recovery time to predict neuronal damage were 10-15 Hz and 40%, respectively (area under the curve [AUC]: 0.97). There was a close relationship between the percentage of damaged neurons and the duration of depolarization or EEG recovery time. These results suggest that EEG recovery time, under the above frequency band and recovery rate, may be a novel marker to predict the outcome after SAH., (© 2024. The Author(s).)

Published
2024
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41. Neurogenesis impairment with glial activation in the hippocampus-connected regions of intracerebroventricular streptozotocin-injected mice.

Author

Masai K, Nakayama Y, Shin K, Sugahara C, Miyazaki I, Yasuhara T, Date I, and Asanuma M

Subjects
Mice, Animals, Streptozocin, Neurogenesis physiology, Neuroglia, Brain, Hippocampus
Abstract

Adult neurogenesis in the hippocampus and subventricular zone (SVZ) is impaired by intracerebroventricular administration of streptozotocin (icv-STZ) to rodents. Although neural cells in the several brain regions which connect with the hippocampus or SVZ is thought to be involved in the adult neurogenesis, few studies have investigated morphological alterations of glial cells in these areas. The present study revealed that icv-STZ induces reduction of neural progenitor cells and a dramatic increase in reactive astrocytes and microglia especially in the hippocampus and various hippocampus-connected brain areas. In contrast, there was no significant neuronal damage excluding demyelination of the stria medullaris. The results indicate the hippocampal neurogenesis impairment of this model might be occurred by activated glial cells in the hippocampus, or hippocampus-connected regions., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Published
2024
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42. Low frequency of intracranial progression in advanced NSCLC patients treated with cancer immunotherapies.

Author

Kemmotsu N, Ninomiya K, Kunimasa K, Ishino T, Nagasaki J, Otani Y, Michiue H, Ichihara E, Ohashi K, Inoue T, Tamiya M, Sakai K, Ueda Y, Dansako H, Nishio K, Kiura K, Date I, and Togashi Y

Subjects
Humans, Animals, Mice, Programmed Cell Death 1 Receptor, Prognosis, Immunotherapy methods, B7-H1 Antigen, Lung Neoplasms pathology, Carcinoma, Non-Small-Cell Lung drug therapy, Brain Neoplasms therapy
Abstract

Intracranial metastases are common in nonsmall-cell lung cancer (NSCLC) patients, whose prognosis is very poor. In addition, intracranial progression is common during systemic treatments due to the inability to penetrate central nervous system (CNS) barriers, whereas the intracranial effects of cancer immunotherapies remain unclear. We analyzed clinical data to evaluate the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies compared with those treated without PD-1 blockade therapies, and found that the frequency of intracranial progression in advanced NSCLC patients treated with PD-1 blockade therapies was significantly lower than that in patients treated with cytotoxic chemotherapies. In murine models, intracranial rechallenged tumors after initial rejection by PD-1 blockade were suppressed. Accordingly, long-lived memory precursor effector T cells and antigen-specific T cells were increased by PD-1 blockade in intracranial lesions. However, intracranial rechallenged different tumors are not suppressed. Our results indicate that cancer immunotherapies can prevent intracranial progression, maintaining long-term effects intracranially as well as systemically. If intracranial recurrence occurs during the treatment with PD-1 blockade therapies, aggressive local therapies could be worthwhile., (© 2023 UICC.)

Published
2024
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43. Effective Epilepsy Surgery for Post-Traumatic West Syndrome Following Abusive Head Trauma.

Author

Tsuchiya H, Shibata T, Sasaki T, Inoue T, Date I, Akiyama T, and Kobayashi K

Subjects
Humans, Female, Infant, Seizures, Electroencephalography, Spasms, Infantile complications, Spasms, Infantile drug therapy, Epilepsy, Craniocerebral Trauma complications, Craniocerebral Trauma surgery, Brain Injuries, Traumatic complications
Abstract

West syndrome, an infantile developmental and epileptic encephalopathy with a deleterious impact on long-term development, requires early treatment to minimize developmental abnormality; in such cases, epilepsy surgery should be considered a powerful therapeutic option. We describe a 10-month-old female admitted with West syndrome associated with a hemispheric lesion following abusive head trauma. Her seizures were suppressed by hemispherotomy at 12 months of age, leading to developmental improvement. Surgical treatment of West syndrome following traumatic brain injury has not been reported previously but is worth considering as a treatment option, depending on patient age and brain plasticity., Competing Interests: No potential conflict of interest relevant to this article was reported.

Published
2023
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44. Combination therapy with hydrogen peroxide and irradiation promotes an abscopal effect in mouse models.

Author

Kemmotsu N, Zhu L, Nagasaki J, Otani Y, Ueda Y, Dansako H, Fang Y, Date I, and Togashi Y

Abstract

Hydrogen peroxide (H 2 O 2 ) induces oxidative stress and cytotoxicity, and can be used for treating cancers in combination with radiotherapy. A product comprising H 2 O 2 and sodium hyaluronate has been developed as a radiosensitizer. However, the effects of H 2 O 2 on antitumor immunity remain unclear. To investigate the effects of H 2 O 2 , especially the abscopal effect when combined with radiotherapy (RT), we implanted murine tumor cells simultaneously in two locations in mouse models: the hind limb and back. H 2 O 2 mixed with sodium hyaluronate was injected intratumorally, followed by irradiation only at the hind limb lesion. No treatment was administered to the back lesion. The H 2 O 2 /RT combination significantly reduced tumor growth at the noninjected/nonirradiated site in the back lesion, whereas H 2 O 2 or RT individually did not reduce tumor growth. Flow cytometric analyses of the tumor-draining lymph nodes in the injected/irradiated areas showed that the number of dendritic cells increased significantly with maturation in the H 2 O 2 /RT combination group. In addition, analyses of tumor-infiltrating lymphocytes showed that the number of CD8 + (cluster of differentiation 8) T cells and the frequency of IFN-γ + (interferon gamma) CD8 + T cells were higher in the noninjected/nonirradiated tumors in the H 2 O 2 /RT group compared to those in the other groups. PD-1 (programmed death receptor 1) blockade further increased the antitumor effect against noninjected/nonirradiated tumors in the H 2 O 2 /RT group. Intratumoral injection of H 2 O 2 combined with RT therefore induces an abscopal effect by activating antitumor immunity, which can be further enhanced by PD-1 blockade. These findings promote the development of H 2 O 2 /RT therapy combined with cancer immunotherapies, even for advanced cancers., (© 2023 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.)

Published
2023
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45. Age is a major determinant for poor prognosis in patients with pilocytic astrocytoma: a SEER population study.

Author

Tomita Y, Hibler EA, Suruga Y, Ishida J, Fujii K, Satomi K, Ichimura K, Hirotsune N, Date I, Tanaka Y, and Otani Y

Subjects
Child, Adult, Humans, Aged, Infant, Newborn, Infant, Child, Preschool, Adolescent, Young Adult, Aged, 80 and over, Middle Aged, SEER Program, Incidence, Prognosis, Astrocytoma epidemiology, Central Nervous System Neoplasms
Abstract

Background Pilocytic astrocytomas (PAs) are central nervous system tumors with variable prognosis and poorly understood risk factors. Little evidence exists regarding the effect of age on mortality in PA. Therefore, we conducted a thorough characterization of PA in the US. Methods We queried the Surveillance, Epidemiology, and End Results (SEER) database between 2000 and 2018 to extract age-adjusted incidence rate (AAIR), age-adjusted mortality rate (AAMR), and survival data on PA. The age group comparisons for each measure varied depending on available SEER data. We compared trends in AAIR and AAMR by two age groups (children, 0-19 years; adults, 20 + years) and by sex. The cumulative incidence function and the Fine-Gray competing risk model were applied by 0-19, 20-39, 40-59, and 60 + years of age groups. Results This study included 5211 incident PA and 462 PA-specific deaths between 2000 and 2018. Trends in AAIRs and AAMRs were almost constant between 2000 and 2018. Average AAIRs had a sharp peak in 1-4 years of age groups, whereas AAMRs had a gradual peak in 80-84 years of age groups. Age groups, tumor location, and race/ethnicity were significantly associated with PA-specific death, whereas only age was associated with other cause of deaths. Conclusions Trends in AAIRs and AAMRs were constant regardless of age. PAs in older populations, especially over 60 years old, have higher incidence of death than those in younger populations., (© 2022. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)

Published
2023
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46. Subtyping of Group 3/4 medulloblastoma as a potential prognostic biomarker among patients treated with reduced dose of craniospinal irradiation: a Japanese Pediatric Molecular Neuro-Oncology Group study.

Author

Fukuoka K, Kurihara J, Shofuda T, Kagawa N, Yamasaki K, Ando R, Ishida J, Kanamori M, Kawamura A, Park YS, Kiyotani C, Akai T, Keino D, Miyairi Y, Sasaki A, Hirato J, Inoue T, Nakazawa A, Koh K, Nishikawa R, Date I, Nagane M, Ichimura K, and Kanemura Y

Subjects
Child, Humans, East Asian People, Prognosis, Biomarkers, Tumor, DNA Methylation, Cerebellar Neoplasms classification, Cerebellar Neoplasms pathology, Cerebellar Neoplasms radiotherapy, Cerebellar Neoplasms surgery, Craniospinal Irradiation adverse effects, Medulloblastoma classification, Medulloblastoma pathology, Medulloblastoma radiotherapy, Medulloblastoma surgery
Abstract

Background: One of the most significant challenges in patients with medulloblastoma is reducing the dose of craniospinal irradiation (CSI) to minimize neurological sequelae in survivors. Molecular characterization of patients receiving lower than standard dose of CSI therapy is important to facilitate further reduction of treatment burden., Methods: We conducted DNA methylation analysis using an Illumina Methylation EPIC array to investigate molecular prognostic markers in 38 patients with medulloblastoma who were registered in the Japan Pediatric Molecular Neuro-Oncology Group and treated with reduced-dose CSI., Results: Among the patients, 23 were classified as having a standard-risk and 15 as high-risk according to the classic classification based on tumor resection rate and presence of metastasis, respectively. The median follow-up period was 71.5 months (12.0-231.0). The median CSI dose was 18 Gy (15.0-24.0) in both groups, and 5 patients in the high-risk group received a CSI dose of 18.0 Gy. Molecular subgrouping revealed that the standard-risk cohort included 5 WNT, 2 SHH, and 16 Group 3/4 cases; all 15 patients in the high-risk cohort had Group 3/4 medulloblastoma. Among the patients with Group 3/4 medulloblastoma, 9 of the 31 Group 3/4 cases were subclassified as subclass II, III, and V, which were known to an association with poor prognosis according to the novel subtyping among the subgroups. Patients with poor prognostic subtype showed worse prognosis than that of others (5-year progression survival rate 90.4% vs. 22.2%; p < 0.0001). The result was replicated in the multivariate analysis (hazard ratio12.77, 95% confidence interval for hazard ratio 2.38-99.21, p value 0.0026 for progression-free survival, hazard ratio 5.02, 95% confidence interval for hazard ratio 1.03-29.11, p value 0.044 for overall survival)., Conclusion: Although these findings require validation in a larger cohort, the present findings suggest that novel subtyping of Group 3/4 medulloblastoma may be a promising prognostic biomarker even among patients treated with lower-dose CSI than standard treatment., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Published
2023
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47. A Case of High-Grade Glioma in an Eloquent Area Treated with Awake Craniotomy in an 85-year-old Patient.

Author

Fujii K, Hirano S, Kurozumi K, and Date I

Subjects
Female, Humans, Aged, Aged, 80 and over, Wakefulness, Monitoring, Intraoperative methods, Brain Mapping methods, Craniotomy, Brain Neoplasms surgery, Brain Neoplasms diagnosis, Brain Neoplasms pathology, Glioma surgery, Glioma pathology
Abstract

An 85-year-old woman presented with aphasia due to an occupying lesion in the left frontal lobe near the language area. Complete resection of the contrast-enhancing lesion was performed under awake conditions. The pathological diagnosis was anaplastic astrocytoma, and postoperative radiochemotherapy was administered. Awake surgery is a useful technique to reduce postoperative neurological sequelae and to maximize surgical resection. Although the patient was elderly, which is generally considered high risk, she did not have any severe neurological deficits and had a good outcome. Even in the extreme elderly, awake surgery can be useful for gliomas in language cortices., Competing Interests: No potential conflict of interest relevant to this article was reported.

Published
2023
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48. Angioarchitecture of the Normal Lateral Spinal Artery and Craniocervical Junction Arteriovenous Fistula Using Contrast-enhanced Cone-beam CT.

Author

Hiramatsu M, Sugiu K, Yasuhara T, Hishikawa T, Haruma J, Nishi K, Yamaoka Y, Ebisudani Y, Edaki H, Kimura R, and Date I

Subjects
Humans, Spinal Cord diagnostic imaging, Spinal Cord blood supply, Spine, Vertebral Artery diagnostic imaging, Arteriovenous Fistula diagnostic imaging, Arteriovenous Fistula surgery, Intracranial Aneurysm
Abstract

Background and Purpose: The lateral spinal artery (LSA) perfuses the dorsolateral part of the spinal cord at the craniocervical junction (CCJ). We analyzed the angioarchitecture of the normal LSA and CCJ arteriovenous fistula (AVF)., Methods: The first study included 26 patients with a cerebral aneurysm of the posterior circulation. Using slab maximum intensity projection (MIP) images from three-dimensional rotational angiography (3D-RA) and contrast-enhanced cone-beam CT (CE-CBCT), we analyzed the origin of the LSA, its anastomosis with the posterior inferior cerebellar artery (PICA), the point where it reaches the spinal cord, and the visualized range. In the second study, we analyzed the angioarchitecture and treatment results of 7 CCJAVF lesions treated in our department between 2016 and 2021., Results: We visualized the normal LSA for all patients. In 23 patients with an intradural origin PICA, all LSAs originated from the C1 or C2 radicular artery, and 8 patients had an anastomosis with the PICA. In three patients with a C1 level origin PICA, all LSAs originated from the PICA. All LSAs reached the dorsolateral part of the spinal cord. The mean visualized range of the LSA was 27.4 mm. The LSA was involved in five of seven CCJAVF lesions (71%). There was one lesion with a spinal infarction after LSA embolization. Other lesions were treated by direct interruption of the AVF, and the ASA and LSA were preserved., Conclusion: This is the first report that visualized the LSA's normal anatomy using slab MIP images from 3D-RA and CE-CBCT. Knowledge of LSA anatomy is critical to avoid complications during the treatment of CCJAVF., (© 2022. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany.)

Published
2023
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49. Utility of Comprehensive Genomic Profiling for Precise Diagnosis of Pediatric-Type Diffuse High-Grade Glioma.

Author

Makino K, Otani Y, Fujii K, Ishida J, Hirano S, Suruga Y, Washio K, Nishida K, Yanai H, Tomida S, Ennishi D, and Date I

Subjects
Male, Humans, Child, Adolescent, Temozolomide, Mutation, Genomics, Glioma diagnosis, Glioma genetics, Brain Neoplasms diagnosis, Brain Neoplasms genetics, Brain Neoplasms pathology
Abstract

In the current World Health Organization classification of central nervous system tumors, comprehensive genetic and epigenetic analyses are considered essential for precise diagnosis. A 14-year-old male patient who presented with a cerebellar tumor was initially diagnosed with glioblastoma and treated with radiation and concomitant temozolomide chemotherapy after resection. During maintenance temozolomide therapy, a new contrast-enhanced lesion developed in the bottom of the cavity formed by the resection. A second surgery was performed, but the histological findings in specimens from the second surgery were different from those of the first surgery. Although genome-wide DNA methylation profiling was conducted using frozen tissue for a precise diagnosis, the proportion of tumor cells was insufficient and only normal cerebellum was observed. We then performed comprehensive genetic analysis using formalin-fixed paraffin-embedded sections, which revealed MYCN amplification without alteration of IDH1, IDH2, or Histone H3. Finally, the patient was diagnosed with pediatric-type diffuse high-grade glioma, H3-wildtype and IDH-wildtype. In conclusion, comprehensive genetic and epigenetic analysis should be considered in pediatric brain tumor cases., Competing Interests: No potential conflict of interest relevant to this article was reported.

Published
2023
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50. Trigeminal neuralgia caused by a persistent primitive trigeminal artery: preoperative three-dimensional multifusion imaging and computational fluid dynamics analysis. Illustrative case.

Author

Satoh T, Yasuhara T, Umakoshi M, and Date I

Abstract

Background: Trigeminal neuralgia (TN) is caused by trigeminal nerve compression by colliding vessels. Preoperative three-dimensional (3D) multifusion images are useful for surgical simulations. Moreover, computational fluid dynamics (CFD) analysis of colliding vessels may be useful for hemodynamic evaluation at the site of neurovascular contact (NVC)., Observations: A 71-year-old woman had TN due to compression of the trigeminal nerve by the superior cerebellar artery (SCA) fused with the persistent primitive trigeminal artery (PTA). Preoperative 3D multifusion simulation images of silent magnetic resonance (MR) angiography and MR cisternography depicted the NVC, including the trigeminal nerve, SCA, and PTA. CFD analysis revealed the hemodynamic condition of the NVC, including the SCA and PTA. The wall shear stress magnitude (WSSm) at the NVC showed a local elevation due to flow confluence from the SCA and PTA. High WSSm was observed in the NVC., Lessons: Preoperative simulation images of MR angiography and MR cisternography may depict the NVC. CFD analysis can provide the hemodynamic condition at the NVC.

Published
2023
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