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107 results on '"I. Nishisho"'

1. Familial Isolated Hyperparathyroidism Caused by Single Adenoma: A Distinct Entity Different from Multiple Endocrine Neoplasia

Author: Tetsuo Taguchi, Eiichi Shiba, H. Nakazawa, Taeko Shimizu, Tsuyoshi Watanabe, Shin-ichiro Takai, Sugimoto T, Y. Shishiba, Fumine Tsukamoto, and I. Nishisho
Subjects: Adenoma, Adult, Genetic Markers, Male, endocrine system, medicine.medical_specialty, endocrine system diseases, Endocrinology, Diabetes and Metabolism, Polymerase Chain Reaction, Proto-Oncogene Mas, Loss of heterozygosity, Endocrinology, Germline mutation, Proto-Oncogene Proteins, Internal medicine, Multiple Endocrine Neoplasia Type 1, medicine, Drosophila Proteins, Humans, MEN1, Multiple endocrine neoplasia, Germ-Line Mutation, Parathyroid adenoma, Hyperparathyroidism, business.industry, Parathyroid neoplasm, Proto-Oncogene Proteins c-ret, Receptor Protein-Tyrosine Kinases, Middle Aged, medicine.disease, Pedigree, Parathyroid Neoplasms, Haplotypes, Cancer research, Female, business
Abstract: Familial hyperparathyroidism (FHPT) is a hereditary disease where hyperparathyroidism (HPT) is transmitted in an autosomal dominant fashion. FHPT consists of a variety of diseases such as multiple endocrine neoplasia type1 (MEN 1) and type2 (MEN 2), familial isolated hyperparathyroidism (FIHPT) with single adenoma and with multiple adenomas (or hyperplasia), and FHPT with jaw-tumor (FHPT-JT). Isolation of the genes responsible for MEN1, and 2, i.e. MEN1 and RET, respectively, makes it possible to examine the relations among disorders constituting FHPT. We studied germ-line mutations in these 2 genes in a family of FHPT with single parathyroid adenoma. The disorder in this family was proved to be an entity different from MEN1 because no germ-line mutations in MEN1 gene were found in the affected members. The loss of heterozygosity (LOH) at MEN1 gene and PYGM were not found in the abnormal parathyroid in this family, supporting the above conclusion. No mutations in exons 10, and 11 of RET proto-oncogene was found in germ-line DNA of the affected member of the family, suggesting no relation to MEN2A. Linkage study excluded the possibility of FHPT-JT syndrome. PRAD1 was not overexpressed in the parathyroid tumors in this family. The relation of this disorder to FIHPT with multiple enlarged parathyroid glands remains to be clarified. A search for the gene(s) predisposing to FIHPT is needed.
Published: 1998
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2. MDM2 gene amplification and expression in non-small-cell lung cancer: immunohistochemical expression of its protein is a favourable prognostic marker in patients without p53 protein accumulation

Author: Masahiko Higashiyama, S Ishiguro, O Doi, Tsutomu Kasugai, Ken Kodama, I Nishisho, Tomio Nakayama, Koji Takami, and Hideoki Yokouchi
Subjects: Adult, Male, Cancer Research, Pathology, medicine.medical_specialty, Lung Neoplasms, Tumor suppressor gene, Biology, medicine.disease_cause, Gene product, Carcinoma, Non-Small-Cell Lung, Proto-Oncogene Proteins, medicine, Humans, Point Mutation, Postoperative Period, Nuclear protein, Lung cancer, neoplasms, Aged, Aged, 80 and over, Gene Amplification, Nuclear Proteins, Proto-Oncogene Proteins c-mdm2, Middle Aged, Prognosis, medicine.disease, Immunohistochemistry, Survival Analysis, Neoplasm Proteins, enzymes and coenzymes (carbohydrates), Oncology, Cancer research, biology.protein, Adenocarcinoma, Mdm2, Female, Tumor Suppressor Protein p53, Carcinogenesis, Research Article
Abstract: MDM2 is an oncoprotein that inhibits p53 tumour-suppressor protein. Amplification of the MDM2 gene and overexpression of its protein have been observed in some human malignancies, and these abnormalities have a role in tumorigenesis through inactivation of p53 function. To determine the clinicopathological and prognostic value of MDM2 abnormalities in non-small-cell lung cancer (NSCLC), MDM2 gene amplification and its protein expression status were analysed in surgically resected materials. MDM2 gene amplification was detected in only 2 (7%) of the 30 tested patients. MDM2 protein was found immunohistochemically in a total of 48 (24%) of the 201 patients. MDM2 protein was slightly frequently observed in patients with adenocarcinoma, but its presence or absence was not associated with clinicopathological factors such as T-factor, N-factor, stage, tumour size, differentiation or p53 protein status. Overall, MDM2-positive patients tended to have a better prognosis (P = 0.062). In particular, among immunohistochemically p53-negative patients (n = 110), those with positive MDM2 protein expression showed significantly better prognosis (P = 0.039) and, in a multivariate analysis, MDM2 protein status was a favourable prognostic factor (P = 0.037). In contrast, among p53-positive patients (n = 91), there was no difference in prognosis depending on MDM2 protein status. Thus, in the NSCLC patients studied, MDM2 gene amplification was a minor event, but expression of its protein, which was often observed immunohistochemically, was a favourable prognostic marker, especially among patients without p53 protein accumulation. Further study is needed to determine how MDM2 protein expression results in a better prognosis. Images Figure 1 Figure 2
Published: 1997
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3. Fourth meeting of the European Neurological Society 25–29 June 1994 Barcelona, Spain

Author: H. Hattig, C. Delli Pizzi, M. C. Addonizio, Michelle Davis, A. R. Giovagnoli, L. Florensa, M. Roth, J. de Kruijk, Francisco Lacruz, Ph. Dewailly, A. Toygar, C. Avendano, P.P. De Deyn, J. F. Hurtevent, F. Lomeila, T. W. Wong, Gordon T. Plant, M. Bud, H. J. Willison, DH Miller, D. W. Langdon, R. Cioni, J. Servan, A. Kaygisiz, E. Racadot, D. B. Schens, E. Picciola, L. Falip, C. Bouchard, J. Jotova, A. Jorge-Santamaria, P. Misra, A. Dufour, C. P. Panagopoulos, A. Venneri, B. Sredni, B. Angelard, M. Janelidze, M. Carreno, J. Obenberger, J. Pouget, H. W. Moser, R. Kaufmann, J. A. Molina, D. Linden, A. Martin Urda, E. Uvestad, A. Krone, J. P. Cochin, J. Mallecourt, A. Cambon-Thomsen, K. Violleau, P. Osschmann, A. M. Durocher, E. Bussaglia, D. M. Danielle, H. Efendi, C. Van Broeckhoven, K. G. Jordan, W. Rautenberg, C. Iniguez, J. M. Delgado, Graham Watson, M. Lawden, Gareth J. Barker, K. Stiasny, James T. Becker, G. Campanella, E. Peghi, A. Poli, A. Haddad, T. Yamawaki, Giacomo P. Comi, S. Sotgiu, B. Ersmark, A. Pomes, M. Ziegler, P. Ferrante, P. Ruppi, H. KuÇukoglu, R. Bouton, U. K. Rinne, P. Vieregge, M. Dary, P. Giunti, Peter J. Goadsby, S. Jung, E. Secor, A. Steinberg, N. Vila, M. A. Hernandez, M. Cursi, A. Enqelhardt, A. Engelhardt, J. Veitch, F. Di Silverio, F. Arnaud, B. Neundörfer, R. Brucher, Dominique Caparros-Lefebvre, B. Meyer, Marianne Dieterich, M. H. Snidaro, R. Gomez, R. Cerbo, M. Ragno, J. M. Vance, S. Nemni, A. Caliskan, F. Barros, I. Velcheva, D. Ceballos-Baumann, V. Barak, A. Avila, N. Antonova, F. Resche, S. Pappata, L. Varela, S. R. Silveira Santos, A. Cammarota, L. Naccache, Y. Nara, E. Tournier-Lasserves, R. Mobner, T. Chase, A. Ensenyat, J. Ulrich, G. Giegerich, M. Rother, M. Revilla, N. Nitschke, K. Honczarenko, E. Basart Tarrats, J. Blin, B. Jacob, J. Santamaria, S. Knezevic, J. L. Castillo, M. Antem, J. Colomer, O. Busse, Didier Hannequin, S. Carrier, J. B. Ruidavets, C. Rozman, J. Bogoussslavsky, J. Pascual Calvet, E. Monros, J. M. Polo, M. Zucconl, Javier Muruzabal, R. R. Allen, R. Rivolta, K. Haugaard, A. Nespolo, K. Hoang-Xuang, G. Bussone, T. Avramidis, E. Corsini, Christiana Franke, T. Vinogradova, H. Boot, K. Vestergaard, G. H. Jansen, N. Argentino, M. Raltzig, W. Linssen, Mark B. Pepys, P. Roblot, L. Lauritzen, E. Fainardi, D. Morin, T. X. Arbizu Urdiain, J. Wollenhaupt, S. Bostantjopoulou, G. Pavesi, A. D. Forman, Giovanni Fabbrini, D. Jean, J. J. Archelos, M. I. Blanchs, M. Del Gobbo, Anna Carla Turconi, Ch. Derouesné, Elio Scarpini, A. Visbeck, P. Castejon, J. P. Renou, F. Mounier-Vehier, G. Potagas, Ch. Duyckaerts, A. Filla, R. Schneider, G. Ronen, K. Nagata, J. P. Vedel, A. Henneberg, G. van Melle, C. Baratti, H. Knott, M. C. Prevett, A. Bes, B. Metin, Jos V. Reempts, L. Martorell, Mefkure Eraksoy, H. O. Handwerker, D. S. Younger, O. Oktem, D. Frongillo, C. Soriano-Soriano, L. Niehaus, F. Zipp, A. Tartaro, S Newman, R. H. Browne, P. Davous, R. Sanchez, M. Muros, M. E. Kornhuber, A. Lavarone, M. Mohr, M. R. Garcia, S. Russell, H. Kellar-Wood, M. R. Tola, B. Ostermeyer, Ch. Tzekov, K. Sartor, E. B. Ringelstein, P. P. Gazzaniga, Paul Krack, H. Fidaner, H. Rico, T. Dbaiss, F. Alameda, E. Torchiana, L. Rumbach, I. Charques, J. M. Bogaard, C. D. Frith, L. J. Rappelle, R. Brenner, A. Joutel, K. Fuxe, G. HÄcker, M. J. Blaser, J. Valls-SolÇ, G. Ulm, M. Alberdi, A. Bock, F. W. Bertelsmann, U. Wieshmann, J. Visa, J. R. Lupski, D. D'Amico, L. M. P. Ramos, A. A. Vanderbark, R. Horn, M. Warmuth, Dietmar Kühne, Mark S. Palmer, C. Ehrenheim, E. Canga, S. Viola, O. Scarpino, P. Naldi, R. Almeida, A. A. Raymond, J. Gamez, Stephan Arnold, A. DiGiovanni, J. Dalmau, C. C. Chari, H. F. Beer, J. C. Koetsier, J. Iriarte, E. Yunis, J. Casadevall, E. Le Guern, E. Stenager, S. R. Benbadis, J. M. Warter, F. Burklin, I. Theodorou, L. Johannesen, G. A. Graveland, X. Leclerc, I. Vecchio, L. Ozelius, G. Nicoletti, R. K. Gherardi, E. Esperet, M. L. Delodovici, F. Cattin, F. Paiau, Giorgio Sacilotto, C. A. J. Broere, D. Chavdarov, J. P. Willmer, C. H. Hawkes, Th. Naegele, E. Ellie, E. Dartigues, M. J. Guardiola, S. Hesse, Z. Levic, Marco Rovaris, P. Saugeir-Veber, B. A. Yaqub, H. F. Durwen, R. Larumbe, J. Ballabrina, M. Sendtner, J. Röther, M. Horstink, C. Kluglein, M.P. Montesi, H. Apaydin, J. Montoya, E. Waubant, Ch. Verellen-Dunoulin, A. Nicolai, J. Lopez-Delval, R. Lemon, G. Cantinho, E. Granieri, A. Zeviani, Wolfgang H. Oertel, U. Ficola, V. Di Piero, V. Fragola, K. Sabev, M. V. Guitera, I. Turki, F. Bolgert, P. Ingrand, J. M. Gobernado, L. M. E. Grimaldi, S. Baybas, B. Eymard, Y. Rolland, Y. Robitaille, Ta. Pampols, P. J. Koehler, A. Carroacedo, J. Vilchez, S. Di Vittorio, I. R. Rise, T. Nagy, M. Kuffner, E. Palazzini, A. Ott, J. Pruim, T. X. Arbizu, E. Manetti, C. Cervera, S. Felber, G. Gursoy, J. Scholz, G. A. Buscaino, M. S. Chen, A. Pascual, J. Hazan, J. U. Gajda, J. G. Cea, G. Bottini, G. Damalik, F. Le Doze, G. Bonaldi, J. M. Hew, C. Messina, A. M. Kennedy, J. M. Carney, N. M. F. Murray, M. Parent, M. Koepp, V. Dimova, D. De Leo, K. Jellinger, G. Salemi, S. Mientus, M. L. Hansen, F. Mazzucchelli, J. Vieth, M. Mauri, E. Bartels, L. Johannsen, C. Humphreys, J. Emile, D. N. Landon, E. Kansu, R. Sanchez-Pernaute, Rsj Frackowiak, M. Gonzalez Torres, L. Oller, C. Machedo, J. Kother, M. Billiard, H. Durak, T. Schindler, A. Frank, A. Uncini, A. Sbriccoli, C. Farinas, D. W. Paty, N. Fast, A. T. Zangaladze, A. Kerkhofs, J. M. Pino Garcia, I. De la Fuente, B. Marini, L. Gomez, I. Rubio, Alessandra Bardoni, C. Brodie, P. Acin, U. Sliwka, S. A. Hawkins, S. Tardieu, F. Vitullo, J. M. Pereira Monteino, R. Gagliardi, T. Jezewski, A. Cano, T. Lempert, F. Abad Alegria, G. Rotondo, D. Ince, C. Martinez Parra, Y. Huang, H. Luders, Y. Steinvil, F. G. A. Van Der Meche, R. Bianchi, A. Sanchez, T. Sevilla, J. M. Ketelslegers, A. Domzal-Stryga, M. Pandolfo, M. O. Josse, K. W. Neff, I. Blanco, G. W. Bruyn, O. W. Witte, J. L. Thibault, G. Andersen, J. Pariset, A. Marcone, R. J. M. Lane, A. Hofman, M. Verin, T. Matilla, P. Bedoucha, J. Roche, M. Lai, M. Collard, A. Ugarte, F. Gallecho, D. Silbersweig, C. Kennard, J. P. Azulay, T. W. Ho, P. L. I. Dellemijn, R. Girardello, F. Baas, B. Voss, F. Rozenberg, E. M. Brocker, V. Stanev, A. A. J. Soeterboek, A. Marra, A. Rey, E. Ertem, M. Sawradewicz-Rybak, J. De Keyser, P. Cavallari, F. Proust, Y. Chevalier, H. C. Hansen, D. Leys, C. A. Davie, K. Hoang-Xuan, C. Bairati, H. van Crevel, Thomas T. Warner, B. Bompais, A. Dobbeleir, T Campbell, C. Macko, C. J. M. Klijn, M. Dussallant, T. P. Berlit, W. Rozenbaum, M. J. van den Bent, W. A. Rocca, M. Muller, H. Hundemer, U. Zifko, M. Campera, F. Drislane, D. Ranoux, T. M. Kloss, Anil Kumar, I. Ruolt, C. Bargnani, B. Marescau, N. A. Losseff, S. Notermans, B. Kint, E. T. Burke, C. Aykut, J. Matias Guiu, P. Maquet, T. Drogendijk, M. Leone, K. von Ammon, M. Pepeliarska, C. Prados, L. DiGiamberardino, T. Logtenberg, G. Lenoir, I. Castaldo, Damhaut, M. Radionova, G. Sirabian, R. Navon, Giovanni Antonini, K. Al Moutaery, E. Chamas, R. Schönhuber, M. Giannini, B. Debilly, I. Labatut, H. Henon, J. A. Egido, M. Baudrimont, J. N. Lorenzo, J. E. C. Bromberg, R. Antonacci, J. J. Vilchez, T. Moulin, B. Rautenstrauss, Giovanni Meola, J. Noth, S Mammi, P. Laforet, F. Lopez, C. Gehring, S. Bort, G. Rancurel, D. Decamps, S. Kostadinova, Y. Shapira, B. Neundoerfer, D. Chavrot, M. Solimena, J. P. Salier, W. Deberdt, R. Hoff-Jörgensen, A. Messina, S. Meairs, G. Rosoklija, E. Nelis, I. Bertran, C. Ertekin, J. Lohmeyer, Mitermayer Galvao dos Reis, L. Calo, E. Maccagnano, A. P. Hays, J. Verlooy, M. G. Forno, T. Blanco, L. Bail, Gabriella Silvestri, J. Montero, F. Bertrand, R. T. Ghnassia, C. Besses, T. Sereghy, F. Shalit, G. Bogliun, S. Braghi, St. Baykouchev, C. Franke, A. Lasa, L. C. Archard, J. Kriebel, S. Shaunak, M. Nocito, Alexander Tsiskaridze, E. Manfredini, T. Seigal, David G. Gadian, M. Barlas, J. D. Degos, C. Seeber, J. Caemert, J. L. Mas, R. B. Pepinsky, M. G. D'Angelo, N. Baumann, S. Yorifuji, H. P. Endtz, M. A. Cassatella, R. A. C. Hughes, V. Golzi, A. Bittencourt, A. Ferreira, M. Sanson, C. Alper, M. Vermeulen, M. A. A. van Walderveen, E. Alexiou, C. H. Lucas, M. Fiorelli, Y. N. Debbink, R. Gil, S. Congia, T. Banerjee, J. M. Bouchard, A. N. Pinto, A. Ceballos-Baumann, G. Grollier, P. I. M. Schmitz, M. D. Catata, N. Lahat, N. S. Rao, P. Papathanasopoulos, J. Valls-Solé, D. Claus, G. Schroter, A. Castro, C. Videbaek, R. Martinez Dreke, A. D. Platts, M. Hermesl, A. C. PeÇanha-Martins, M. Cardoso Silva, P. Masnou, M. J. A. Tanner, Ch. Confavreux, B. Mishu, H. Rasmussen, L. Valenciano, Carlo Pozzilli, S. W. Li, V. Salzman, Y. Vashtang, Massimo Franceschi, M. Severo, G. Deuschl, S. Setien, G. Mariani, A. Protti, J. Castillo, M. J. B. Taphoorn, M. Frontali, I. Milonas, D. Decoq, J. A. Navarro, S. Castellvi-Pel, C. Ertikin, M. Urtasun, Y. Lajat, B. E. Kendall, E. Verdu, B. Gueguen, E. Boisen, R. Couderc, A Danek, JM Stevens, F. Nicoli, L. Feltri, M. L. Vazquez-Andre, J. A. Morgan-Hughes, L. D'Angelo, F. Y. Liew, L. F. Pascual, J. Patrignani Ochoa, Vittorio Martinelli, J. Cophignon, L. Zhang, S. Martin, J. F. Meder, H. C. Buschmann, L. Bertin, J. van Gijn, A. Barreiro, A. Cools, C. Leon, A. Berod, E. A. Anllo, E. Zanette, L. Petrov, R. Barona, B. Gallicchio, P. J. Cozzone, N. Diederich, G. Cancel, L. Schelosky, P. Orizaola, K. Yulug, S. Ozer, Valeria A. Sansone, B. Guiraud-Chaumeil, K. Voigt, P. Labauge, M. Eoli, J. Zhu, J. Aguirre, M. Ferrarini, B. Zyluk, E. Planas, A. Cadilha, C. Tortorella, H. Bismuth, C. E. Counsell, A. Laun, A. Ferlini, Rio J. Montalban, N. Biary, L. Becker, M. Fardeau, M. Poloni, V. M. S. de Bruin, C. Fornada, J. Barros, E. Ganzmann, E. Touze, D. Wallach, J. Peila, H. Fujimura, M. T. Iba-Zizen, G. Macchi, C. Villoslada, R. Gouider, Ph. Rondepierre, P. Grummich, P. Chiodi, C. Conte, M. Michels, P. Annunziata, G. Semana, C. Sommer, J. Vajsar, D. Zekin, J. Kulisevsky, David G. Munoz, B. Jacotot, M. Magoni, A. Luxen, T. Garcia-Silva, S. Di Cesare, Christophe Tzourio, M. Gomori, I. Picomell, L. Santoro, F. Villa, Giovanni Pennisi, T. Ribalta, J. M. Molto, L. Marzorati, P. Loiseau, F. Gemignani, A. Gironell, J. Wissel, A. Prusinski, F. Cailloux, P. Villanueva-Hemandez, P. Cozzone, T. Del Ser, J. Sans-Sabrafen, M. Zappia, P. W. A. Willems, G. Tchernia, D. Gardeur, R. Bauer, F. Palomo, H. Metz, S. Lamoureux, C. Chastang, I. Reinhard, A. Goldfarb, S. Harder, Jordi Río, C. Ozkara, E. Tekinsoy, P. Vontobell, J. De Recondo, M. Rabasa, L. Lacomblez, F. Boon, Dgt Thomas, V. Palma, Renato Mantegazza, A. Dervis, M. Nueckel, B. YalÇinerner, I. Duran, G. Dalla Volta, A. Zubimendi, J. Pinheiro, A. Marbini, Xavier Montalban, H. Wekerle, X. Pereira Monteino, F. Crespo, F. Koskas, N. Battistini, C. Ruiz, H. Offner, J. de Pommery, P. Kanovsky, J. Y. Barnett, J. Pardo, G. Tomei, R. Rene, H. M. Lokhorst, P. Thajeb, H. Bilgin, D. McGehee, R. Fahsold, L. Morgante, Katie Sidle, C. Delwaide, M. N. Diaye, P. H. Rice, A. Creange, C. Sabev, K. Stephan, K. WeilBenborn, G. Magnani, L. Grymonprez, F. Cardellach, M. Kaps, N. G. Meco, F. Vega, V. Bonifati, A. Desomer, M. Baldy-Moulinier, G. Kvale, F. J. Authier, B. Yegen, T. Ho, J. M. Rozet, E. A. Cabanis, L. Bruce, L. Ambrosoli, M. A. Petrella, M. Hernandez, P. Timmings, H. B. van der Worp, F. Mahieux, A. Urbano-Marquez, D. A. Krendel, A. A. Garcia, R. Divari, R. Michalowicz, M. R. Piedmonte, M. Bondavalli, M. Zanca, P. F. Ippel, Onofre Combarros, B. Tavitian, E. Hirsch, I. Anastasopoulos, A. Roses, A. Köhler, P. Vienna, V. Timmerman, P. Sergi, F. Cornelio, A. Di Pasquale, R. Verleger, S. Castellvirel, J. Proano, B. van Moll, F. Rubio, W. Hacke, I. Lavenu, L. Zetta, M. W. Tas, N. Bittmann, M. Bonamini, O. R. Hommes, V. Dousset, N. Afsar, S. Belal, R. R. Myers, J. Goes, Giuseppe Vita, E. Clementi, V. G. Karepov, M. Jueptner, A Vincent, P. Emmrich, Th. Heb, A. Caballo, J. Gallego, T. Mokrusch, C. Perla, L. Gebuhrer, O. Titlbach, Alessandro Prelle, A. Czlonkowska, M. Russo, D. Hadjiev, T. S. Chkhikvishvili, M. Oehlschlager, G. Becker, I. Günther, E. N. Stenager, J. Garcia Agundez, J. Casademont, J. Batlle, S. Podobnik-Sarkanji, C. Alonso-Villaverde, B. Delaguillaume, B. Genc, B. Mazoyer, A. Rodriguez-Al-barino, Ch. Hilger, B. Ferrero, R. Price, W. Grisold, L. Fuhry, D. Oulbani, D. Ewing, A. Petkov, W. Walther, A. Gokyigit, John Newsom-Davis, J. Tayot, D. Seliak, G. Pelliccioni, D. Campagne, K. Kessler, F. Boureau, D. Perani, J. P. N'Guyen, N. Tchalucova, B. A. Antin-Ozerkis, C. Lacroix, B. D. Aronovich, I. H. Jenkins, E. A. dos Reis, M. Hortells, H. M. Meinck, H. Ch. Buschmann, S. C. J. M. Jacobs, T. Wetter, P. Creissard, N. Martinez, J. Weidenfeldl, H. J. Sturenburg, G. Damlacik, V. Gracia, J. C. Turpin, A. Pou-Serradell, J. P. Vincent, T. Gagoshidze, U. Ozkutlu, M. McLeod, K. Siegfried, I. Tchaoussoglou, J. Hildebrand, S. Kowalska, M. C. Picot, G. Galardin, L. Crevits, F. Andreetta, S. Larumbe-Lobalde, G. de la Sierra, J. C. Alvarez-Cermeno, R. J. Seitz, P. L. Oey, L. Ptacek, A. M. J. Paans, A. Wirrwar, A. Schmied, J. Uilchez, H. Tounsi, D. Hipola, V. Avoledo, Y. Hirata, P. Vermersch, T. M. Aisonobe, J. Valls-SoIè, H. Staunton, J. Dichgans, R. Karabudak, I. Dones, G. Porta, E. Janssens, Maria Martinez, J. M. Fernandez-Real, R. Villagra, Y. Yoshino, C. Kabus, K. Schimrigk, I. Girard-Buttaz, F. Piccoli, F. Aichner, P. Zuchegna, S. M. Al Deeb, F. Bono, N. Busquets, A. Jobert, Patrizia Ciscato, M. Martin, L. Polman, S. Darbra, V. Le Cam-Duchez, F. Baldissera, B. Baykan-Kurt, D. Guez, M. Bratoeva, H. Matsui, M. Mila, H. Perron, L. Bjorge, G. Husby, Steven T. DeKosky, D. R. Cornblath, J. M. Gabriel, J. J. Poza, Y. Wu, A. Toscano, R. P. Kleyweg, J. Kuhnen, S. O. Confort-Gouny, A. Barcelo, A. M. Conti, C. Fiol, C. Steichen-Wiehn, J. Rodes, M. Cavenaile, C. Vedeler, M. Drlicek, C. Argentino, M. L. Peris, A. Cervello, A. Z. GinaÏ, S. Yancheva, D. Passingham, S. Aoba, D. L. 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Brasic, W. Heide, I. Santilli, W. M. Korn, D. Selcuki, M. J. Barrett, D. Krieger, T. Leon, T. Houallah, M. Tournilhac, C. Nos, D. Chavot, F. Barbieri, F. J. Jimenez-Jimenez, J. Muruzabal, K. Poeck, A. Sennlaub, L. M. Iriarte, L. G. Lazzarino, C. Sanz, P. A. Fischer, S. D. Shorvon, R. Hoermann, F. Delecluse, M. Krams, O. Corabianu, F. H. Hochberg, Christopher J. Mathias, B. Debachy, C. M. Poser, L. Delodovici, A. Jimenez-Escrig, F. Baruzzi, F. Godenberg, D. Cucinotta, P. J. Garcia Ruiz, K. Maier-Hauff, P. R. Bar, R. Mezt, R. Jochens, S. Karakaneva, C. Roberti, E. Caballero, Joseph E. Parisi, M. Zamboni, T. Lacasa, B. Baklan, J. C. Gautier, J. A. Martinez-Matos, W. Pollmann, G. Thomas, L. Verze, E. Chleide, R. Alvarez Sala, I. Noel, E. Albuisson, O. Kastrup, S. I. Rapoport, H. J. Braune, H. Lörler, M. Le Merrer, A. Biraben, S. Soler, S. J. Taagholt, U. Meyding-Lamadé, K. Bleasdale-Barr, Isabella Moroni, Y. Campos, J. Matias-Guiu, G. Edan, M. G. Bousser, John B. Clark, J. Garcia de Yebenes, N. K. Olsen, P. Hitzenberger, S. Einius, Aj Thompson, Ch. J. Vecht, T. Crepin-Leblond, Klaus L. Leenders, A. Di Muzio, L. Georgieva, René Spiegel, K. Sabey, D. Ménégalli, J. Meulstee, U. Liszka, P. Giral, C. Sunol, J. M. Espadaler, A. D. Crockar, K. Varli, G. Giraud, P. J. Hülser, A. Benazzouz, A. Reggio, M. Salvatore, K. Genc, M. Kushnir, S. Barbieri, J. Ph. Azulay, M. Gianelli, N. Bathien, A. AlMemar, F. Hentati, I. Ragueneau, F. Chiarotti, R. C. F. Smits, A. K. Asbury, F. Lacruz, B. Muller, Alan J. Thompson, Gordon Smith, K. Schmidt, C. Daems Monpeun, Juergen Weber, A. Arboix, G. R. Fink, A. M. Cobo, M. Ait Kaci Ahmed, E. Gencheva, Israel-Biet, G. Schlaug, P. De Jonghe, Philip Scheltens, K. Toyka, P. Gonzalez-Porque, A. Cila, J. M. Fernandez, P. Augustin, J. Siclia, S. Medaglini, D. E. Ziogas, A. Feve, L. Kater, G. J. E. Rinkel, D. Leppert, Rüdiger J. Seitz, S. Ried, C. Turc-Carel, G. Smeyers, F. Godinho, M. Czygan, M. Rijntjes, E. Aversa, M. Frigo, Leif Østergaard, J. L. Munoz Blanco, A. Cruz-Matinez, J. De Reuck, C. Theillet, T. Barroso, V. Oikonen, Florence Lebert, M. Kilinc, C. Cordon-Cardon, G. Stoll, E. Thiery, F. Pulcinelli, J. Solski, M. Schmiegelow, L. J. Polman, P. Fernandez-Calle, C. Wikkelso, M. Ben Hamida, M. Laska, E. Kott, W. Sulkowski, C. Lucas, N. M. Bornstein, D. Schmitz, M. W. Lammers, A. de Louw, R. J. S. Wise, P. A. van Darn, C. Antozzi, P. Villanueva, P. H. E. Hilkens, C. Constantin, W. Ricart, A. Wolf, M. Gamba, P. Maguire, Alessandro Padovani, B. M. Patten, Marie Sarazin, H. Ackermann, L. Durelli, S. Timsit, Sebastian Jander, B. W. Scheithauer, G. Demir, J. P. Neau, P. Barbanti, A. Brand, N. AraÇ, V. Fischer-Gagnepain, R. Marchioli, G. Serratrice, C. Maugard-Louboutin, G. T. Spencer, D. Lücke, G. Mainardi, K. Harmant Van Rijckevorsel, G. B. Creel, R. Manzanares, Francesco Fortunato, A. May, J. Workman, K. Johkura, E. Fernandez, Carlo Colosimo, L. Calliauw, L. Bet, Félix F. Cruz-Sánchez, M. Dhib, H. Meinardi, F. Carrara, J. Kuehnen, C. Peiro, H. Lassmann, K. Skovgaard Olsen, A. McDonald, L. Sciulli, A. Cobo, A. Monticelli, B. Conrad, J. Bagunya, J. Benitez, V. Desnizza, B. Dupont, O. Delrieu, D. Moraes, J. J. Heimans, F. Garcia Rio, M. Matsumto, A. Fernandez, R. Nermni, R. Chalmers, M. J. Marchau, F. Aguado, P. Velupillai, P. J. Martin, P. Tassan, V. Demarin, A. Engelien, T. Gerriets, Comar, J. L. Carrasco, J. P. Pruvo, A. Lopez de Munain, D. Pavitt, J. Alarcon, Chris H. Polman, B. Guldin, N. Yeni, Hartmut Brückmann, N. Wilczak, H. Szwed, R. Causaran, G. Kyriazis, M. E. Westarp, M. Gasparini, N. Pecora, J. M. Roda, E. Lang, V. Scaioli, David R. Fish, D. Caputo, O. Gratzl, R. Mercelis, A. Perretti, G. Steimetz, I. Link, C. Rigoletto, A. Catafau, G. Lucotte, M. Buti, G. Fagiolari, A. Piqueras, C. Godinot, J. C. Meurice, Erodriguez J. Dominigo, F. Lionnet, H. Grzelec, David J. Brooks, P. M. G. Munro, F. X. Weilbach, M. Maiwald, W. Split, B. Widjaja-Cramer, V. Ozturk, J. Colas, E. Brizioli, J. Calleja, L. Publio, M. Desi, R. Soffietti, P. Cortinovis-Tourniaire, E. F. Gonano, G. Cavaletti, S. Uselli, K. Westerlind, H. Betuel, C. O. Dhiver, H. Guggenheim, M. Hamon, R. Fazio, P. Lehikoinen, A. Esser, B. Sadzot, G. Fink, Angelo Antonini, D. Bendahan, V. Di Carlo, G. Galardi, A. F. Boller, M. Aksenova, Del Fiore, V. de la Sayette, H. Chabriat, A. Nicoletti, A. Dilouya, M. L. Harpin, E. Rouillet, J. Stam, A. Wolters, M. R. Delgado, Eduardo Tolosa, G. Said, A. J. Lees, L. Rinaldi, A. Schulze-Bonhage, MA Ron, C. Lefebvre, E. W. Radü, R. Alvarez, M. L. Bots, P. Reganati, S. Palazzi, A. Poggi, N. J. Scolding, V. Sazdovitch, T. Moreau, E. Maes, M. A. Estelies, P. Petkova, Jose-Felix Marti-Masso, G De La Meilleure, N. Mullatti, M. Rodegher, N. C. Notermans, T. A. T. Warner, S. Aktan, J. P. Louboutin, L. Volpe, C. Scheidt, W. Aust, C. M. Wiles, U. Schneider, S. K. Braekken, W. R. Willems, K. Usuku, Peter M. Rothwell, C. Talamon, M. L. Sacchetti, A. Codina, M. H. Marion, A. Santoro, J. Roda, A. Bordoni, D. J. Taylor, S. Ertas, H. H. Emmen, J. Vichez, V. BesanÇon, R. E. Passingham, M. L. Malosio, A. Vérier, M. Bamberg, A. W. Hansen, E. Mostacero, G. Gaudriault, Marie Vidailhet, B. Birebent, K. Strijckmans, F. Giannini, T. Kammer, I. Araujo, J. Nowicki, E. Nikolov, A. Hutzelmann, R. Gherardi, J. Verroust, L. Austoni, A. Scheller, A. Vazquez, S. Matheron, H. Holthausen, J. M. Gerard, M. Bataillard, S. Dethy, V. H. Patterson, V. Ivanez, N. P. Hirsch, F. Ozer, M. Sutter, C. Jacomet, M. Mora, Bruno Colombo, A. Sarropoulos, T. H. Papapetropoulos, M. Schwarz, D. S. Dinner, N. Acarin, B. Iandolo, J. O. Riis, P. R. J. Barnes, F. Taroni, J. Kazenwadel, L. Torre, A. Lugaresi, I. L. Henriques, S. Pauli, S. Alfonso, Pedro Quesada, A. S. T. Planting, J. M. Castilla, Thomas Gasser, M. Van der Linden, A. Alfaro, E. Nobile-Orazio, G. Popova, W. Vaalburg, F. G. A. van der Mech, L. Williams, F. Medina, J. P. Vernant, J. Yaouanq, B. Storch-Hagenlocher, A. Potemkowski, R. Riva, M. H. Mahagne, M. Ozturk, Ve. Drory, N. Konic, C. Jungreis, A. Pou Serradell, J. L. Gauvrit, G. J. Chelune, S. Hermandez, T. Dingus, L. Hewer, Ch. Koch, M. N. Metz-Lutz, G. Parlato, M. Sinaki, Charles Pierrot-Deseilligny, H. C. Diener, J. Broeckx, J. Weill-Fulazza, M. L. Villar, M. Rizzo, O. Ganslandt, C. Duran, N. A. Fletcher, G. Di Giovacchino, Susan T. Iannaccone, C. Kolig, N. Fabre, H. A. Crockard, Rita Bella, M. Tazir, E. Papagiannuli, K. Overgaard, Emma Ciafaloni, I. Lorenzetti, F. Viader, P. A. H. Millac, I. Montiel, L. H. Visser, M. Palomar, P. L. Murgia, H. Pedersen, Rafael Blesa, S. Seddigh, W. O. Renier, I. Lemahieu, H. M. L. Jansen, L. Rosin, J. Galofre, K. Mattos, M. Pondal, G. M. Hadjigeorgiou, D. Francis, L. Cantin, D. Stegeman, M. Rango, A. B. M. F. Karim, S. Schraff, B. Castellotti, I. Iriarte, E. Laborde, T. J. Tjan, R. Mutani, D. Toni, B. Bergaasco, J. G. Young, C. Klotzsch, A. Zincone, X. Ducrocq, M. Uchuya, O. J. Kolar, A. Quattrone, T. Bauermann, Nereo Bresolin, J. Vallée, B. C. Jacobs, A. Campos, Werner Poewe, J. A. Villanueva, A. W. Kornhuber, A. Malafosse, E. Diez-Tejedor, G. Jungreia, M. J. A. Puchner, A. Komiyama, O. Saribas, V. Volpini, L. Geremia, S. Bressi, A. Nibbio, Timothy E. Bates, T. z. Tzonev, E. Ideman, G. A. Damlacik, G. Martino, G. Crepaldi, T. Martino, Kjell Någren, E. Idiman, D. Samuel, J. M. Perez Trullen, Y. van der Graaf, J. O. Thorell, M. J. M. Dupuis, E. Sieber, R. D'Alessandro, C. Cazzaniga, J. Faiss, A. Tanguy, A. Schick, I. Hoksergen, A. Cardozo, R. Shakarishvili, G. K. Wennlng, J. L. Marti-Vilalta, J. Weissenbach, I. L. Simone, Amalia C. Bruni, Darius J. Adams, C. Weiller, A. Pietrangeli, F. Croria, C. Vigo-Pelfrey, Patricia Limousin, A. Ducros, G. Conti, O. Lindvall, E. Richter, M. Zuffi, A. Nappo, T. Riise, J. Wijdenes, M. J. Fernandez, J. Rosell, P. Vermersh, S. Servidei, M. S. C. Verdugo, F. Gouttiere, W. Solbach, M. Malbezin, I. S. Watanabe, A. Tumac, W. I. McDonald, D. A. Butterfield, P. P. Costa, F. deRino, F. Bamonti, J. M. Cesar, C. H. Lahoz, I. Mosely, M. Starck, M. H. Lemaitre, K. M. Stephan, S. Tex, R. Bokonjic, I. Mollee, L. Pastena, M. Gutierrez, F. Boiler, M. C. Martinez-Para, M. Velicogna, O. Obuz, A. Grinspan, M. Guarino, L. M. Cartier, E. Ruiz, D. Gambi, S. Messina, M. Villa, Michael G. Hanna, J. Valk, Leone Pascual, M. Clanet, Z. Argov, B. Ryniewicz, E. Magni, B. Berlanga, K. S. Wong, C. Gellera, C. Prevost, F. Gonzalez-Huix, R. Petraroli, J. E. G. Benedikz, I. Kojder, C. Bommelaer, L. Perusse, M. R. Bangioanni, Guy M. McKhann, A. Molina, C. Fresquet, E. Sindern, Florence Pasquier, M. J. Rosas, M. Altieri, O. Simoncini, M. Koutroumanidis, C. A. F. Tulleken, M. Dary-Auriol, S. Oueslati, H. Kruyer, I. Nishisho, C. R. Horning, A. Vital, G. V. Czettritz, J. Ph. Neau, B. Mihout, A. Ameri, M. Francis, S. Quasthoff, D. Taussig, S. Blunt, P. Valentin, C. Y. Gao, O. Heinzlef, H. d'Allens, C. Coudero, M. Erfas, G. Borghero, P. J. Modrego Pardo, M. C. Patrosso, N. L. Gershfeld, P. A. J. M. Boon, O. Sabouraud, M. Lara, J. Svennevig, G. L. Lenzi, A. Barrio, H. Villaroya, JosÇ M. Manubens, O. Boespflug-Tanguy, M. Carreras, D. A. Costiga, J. P. Breux, S. Lynn, C. Oliveras Ley, A. G. Herbaut, J. Nos, C. Tornali, Y. A. Hekster, J. L. Chopard, J. M. Manubens, P. Chemouilli, A. Jovicic, F. Dworzak, S. Smirne, S. E. Soudain, B. Gallano, D. Lubach, G. Masullo, G. Izquierdo, A. Pascual Leone Pascual, A. Sessa, V. Freitas, O. Crambes, L. Ouss, G. W. Van Dijk, P. Marchettini, P. Confalonieri, M. Donaghy, A. Munnich, M. Corbo, and M. E. L. van der Burg
Subjects: Neurology, business.industry, Media studies, Library science, Medicine, Neurology (clinical), business
Published: 1994
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4. Phase I study of docetaxel administered by bi-weekly infusion to patients with metastatic breast cancer

Author: E, Shin, M, Ishitobi, M, Hiraoia, F, Kazumasa, M, Hideyuki, I, Nishisho, S, Toshiro, H, Yasunori, and T, Tosimasa
Subjects: Adult, Neutropenia, Dose-Response Relationship, Drug, Paclitaxel, Breast Neoplasms, Docetaxel, Middle Aged, Antineoplastic Agents, Phytogenic, Drug Administration Schedule, Recombinant Proteins, Asthenia, Lymphatic Metastasis, Granulocyte Colony-Stimulating Factor, Edema, Humans, Female, Taxoids, Neoplasm Metastasis, Infusions, Intravenous, Fatigue, Aged, Neoplasm Staging
Abstract: To find a more convenient and tolerable schedule than the tri-weekly or weekly schedules, we conducted a dose escalation study of bi-weekly docetaxel.Between March 1998 and June 1999, 16 patients entered this phase I study. The starting dose was 40 mg/m2, with planned dose escalation to 45, 50 and 55 mg/m2, in consecutive patient cohorts. Patients continued to receive the assigned treatment at the same dose level bi-weekly, provided that they did not develop progressive disease, refuse further treatment, or experience unacceptable toxicity.Grade 4 neutropenia lasting for more 4 days was seen at dose level 3 in all three patients. Only one patient who had previously received intensive chemotherapy required granulocyte colony stimulating factor (G-CSF) to prevent neutropenic fever and there were no actual episodes of neutropenic fever. Grade 3 asthenia and Grade 3 elevation of serum glutamic oxaloacetic transaminase were noted in only one patient treated at a dose of 40 mg/m2. Grade 3 skin toxicity and grade 2 elevation of serum glutamic oxaloacetic transaminase were seen in only one patient treated at a dose of 55 mg/m. Cumulative toxicity was not severe in all patients. Although grade 3 and/or grade 4 neutropenia were noted in eight patients (50%), all except one who received treatment at dose of 55 mg/m2 did not need G-CSF. Nail toxicity and peripheral edema seemed to be related to the number of treatment cycles. Severe fatigue and asthenia were never seen in all patients.1) The maximum-tolerated dose of docetaxel when administered by this bi-weekly schedule was 55 mg/m2; 2) Docetaxel administered on a bi-weekly basis well tolerated.
Published: 2001

5. [Efficacy of combination therapy for multiple liver metastases of colorectal cancer]

Author: Y, Kurokawa, Y, Hasuike, H, Mishima, Y, Takeda, K, Fujitani, E, Shin, T, Sawamura, I, Nishisho, T, Tsujinaka, and N, Kikkawa
Subjects: Male, Antimetabolites, Antineoplastic, Liver Neoplasms, Hepatectomy, Humans, Infusions, Intra-Arterial, Female, Fluorouracil, Colorectal Neoplasms, Combined Modality Therapy, Survival Analysis, Carcinoembryonic Antigen, Retrospective Studies
Abstract: In our hospital, combination therapy, mainly intra-arterial infusion, is performed for multiple liver metastases of colorectal cancer. The median survival time of the combination group (n = 18), the hepatectomy only group (n = 3) and the best supportive care group (n = 7) were 21.7, 12.5 and 6.1 months, respectively. The prognosis of the combination group was significantly better than that in the other groups (p0.0001). Univariate analysis against the combination group revealed that serum CEA was a significant prognostic factor (p = 0.0196). Moreover, we divided the combination group into two groups on the basis of serum CEA either below or above 50 ng/ml. The prognosis of the low CEA group (n = 11), whose median survival time was 25.9 months, was significantly better than the high CEA group (n = 7), whose median survival time was 17.8 months (p = 0.0031). It therefore appears that combination therapy may be of no benefit when serum CEA is above 50 ng/ml.
Published: 2000

6. [Case report--efficacy of short-term intraarterial 5-fluorouracil for liver metastasis from colorectal cancer]

Author: Y, Takeda, Y, Hasuike, H, Mishima, I, Nishisho, and N, Kikkawa
Subjects: Antimetabolites, Antineoplastic, Liver Neoplasms, Humans, Infusions, Intra-Arterial, Female, Fluorouracil, Adenocarcinoma, Middle Aged, Colorectal Neoplasms, Combined Modality Therapy, Drug Administration Schedule
Abstract: Hepatectomy has the highest cure rate among the various methods for treating liver metastasis from colorectal cancer. We previously reported that continuous hepatic arterial infusion (HAI) of 5-FU is effective for improving the prognosis of patients with liver metastasis. In this study, we examined the efficacy of short-term continuous HAI of 5-FU for treating liver metastasis from colorectal cancer. A 57-year-old woman with a solitary liver metastasis from rectal cancer was treated by continuous HAI of 5-FU (1,000 mg/day) for 6 days. Her elevated serum CEA level (20.7 ng/ml) then returned to normal. Computed tomography revealed a decrease of 55.6% in the size of the liver tumor. Partial segmentectomy (S7) was subsequently performed. Histological examination of the resected tumor showed marked degeneration, necrosis, fibrosis, and calcification with viable moderately differentiated adenocarcinoma cells. These results suggest that preoperative HAI of 5-FU is safe and worth trying in patients with liver metastasis from colorectal cancer.
Published: 2000

7. [A late phase II study of raltitrexed (ZD 1694) in chemotherapy-naive patients with advanced colorectal cancer]

Author: I, Nishisho, N, Kikkawa, T, Ebata, H, Osanai, S, Ujiie, Y, Mitachi, M, Tsutsui, K, Sawai, Y, Nishiguchi, K, Yasutake, H, Wakasugi, and A, Wakui
Subjects: Adult, Male, Antimetabolites, Antineoplastic, Rectal Neoplasms, Leukopenia, Thiophenes, Thymidylate Synthase, Middle Aged, Drug Administration Schedule, Colonic Neoplasms, Quinazolines, Humans, Female, Enzyme Inhibitors, Aged
Abstract: A multicenter co-operative late phase II study of raltitrexed (ZD1694), a specific thymidylate synthase (TS) inhibitor, was conducted in chemotherapy-naive patients with advanced colorectal cancer. Raltitrexed was infused intravenously over 15 minutes once every three weeks. Between April 1996 and September 1998, 61 patients were enrolled and 58 were eligible. Fourteen patients experienced a partial response (PR), 22 no change (NC), 20 progressive disease (PD) and 2 no evaluable (NE). The overall response rate was 24.1% (95% CI: 13.9-37.2%). Responses were seen in lung (22.7%), liver (22.9%) and deep lymph nodes (10.0%). Median survival was 11.6 months. Grade 3 or 4 toxicities were: leukopenia (13.8%), neutropenia (24.1%), hemoglobin decrease (15.5%), FBC decrease (6.9%), hematocrit decrease (6.9%), thrombocytopenia (6.9%), transient SGPT increase (6.9%), nausea/vomiting (20.7%), anorexia (15.5%), and asthenia (6.9%). These adverse reactions were considered to be manageable. Only one death was associated with drug treatment. These results suggest that raltitrexed provides an effective and convenient treatment for patients with advanced and previously untreated colorectal cancer.
Published: 2000

8. [Efficacy and side effect of continuous intra-arterial infusion of high-dose 5-FU for liver metastases of colorectal cancer]

Author: Y, Kurokawa, Y, Hasuike, T, Hattori, S, Hayashi, K, Fujitani, E, Shin, H, Mishima, T, Sawamura, I, Nishisho, K, Kobayashi, T, Kobayashi, and N, Kikkawa
Subjects: Adult, Male, Antimetabolites, Antineoplastic, Liver Neoplasms, Middle Aged, Prognosis, Combined Modality Therapy, Survival Rate, Hepatic Artery, Hepatectomy, Humans, Infusions, Intra-Arterial, Female, Fluorouracil, Colorectal Neoplasms, Aged
Abstract: Fifteen patients with liver metastases of colorectal cancer were entered in our study, and 5-FU was given continuously by hepatic intra-arterial route at 1 g/day over 6 days. No leukopenia (3,000/mm3), anemia (10 g/dl), or thrombocytopenia (75,000/mm3) occurred, and no elevation of serum AST (150 IU/l) or serum T-Bil (2 mg/ml) appeared. One patient (4.2%) had nausea with vomiting 1-5 per day, and another (4.2%) had mucositis requiring treatment. In patients with multiple liver metastases, survival of the continuous infusion group [total dose of 5-FUor = 12 g] (n = 5) seems to be longer than those of the hepatectomy only group (n = 3) or the control group (n = 7). We suggest that this continuous intra-arterial infusion of high-dose 5-FU is a useful chemotherapy with few side effects or complications.
Published: 1999

9. Microchimerism in thymus is associated with up-regulated T helper type 1 cytokine transcription during cardiac allograft rejection in rats

Author: H, Ota, M, Gotoh, H, Ohzato, L, He, T, Tanigawa, H, Nagano, K, Dono, Y, Takeda, M, Okuyama, J, Shimizu, K, Umeshita, S, Nakamori, M, Sakon, I, Nishisho, and M, Monden
Subjects: Graft Rejection, Male, Transcription, Genetic, Cell Transplantation, Chimera, Rats, Inbred Strains, T-Lymphocytes, Helper-Inducer, Thymus Gland, Th1 Cells, Polymerase Chain Reaction, Rats, Th2 Cells, Animals, Cytokines, Heart Transplantation, RNA, Messenger, Rats, Wistar, Erythrocyte Transfusion, Spleen
Abstract: Intrathymic microchimerism (MC) is thought to be responsible for inducing allograft tolerance. However, the role of MC in the thymus gland after transplantation, particularly in the rejection response, is unknown. We investigated serial changes in intrathymic cytokine production associated with MC and allograft rejection.Donor-specific cell injection (DSI) and heterotopic heart transplantation (HTx) were performed in the fully allogeneic combination using DA rats (RT1a) as donors and WS rats (RT1k)as recipients. MC was checked by polymerase chain reaction (PCR) using a donor RT1.Bbeta domain 1 region sequence-specific primers. Reverse transcription (RT)-PCR analysis of cytokine (interleukin [IL]-2, interferon-gamma, IL-4, and IL-10) profiles of the thymus was performed in animals given DSI, HTx, or DSI/HTx.DSI alone resulted in an immediate development of MC, detected by PCR, in various organs including the thymus, spleen, liver, and blood, of most rats, lasting for over 2 months. However, DSI-induced MC selectively disappeared in the thymus on day 7 after grafting, several days before the rejection of cardiac allograft. RT-PCR analysis of cytokine profiles showed that the levels of Th1 (IL-2 and interferon-gamma) cytokines transcribed in the thymus were higher than in the spleen. MC reappeared in the thymus on day 21 after grafting, but was not associated with elevation of Th1 cytokine transcription when allograft was replaced by fibrosis.Intrathymic MC does not always confer unresponsiveness to alloantigen, but can be eliminated after anti-donor response.
Published: 1999

10. [Features of colorectal cancer with fecal-occult-blood tests--comparison with colorectal cancer with no screening]

Author: I, Takemasa, N, Kikkawa, M, Yasui, I, Nishisho, K, Fujitani, H, Mishima, Y, Hasuike, and K, Kobayashi
Subjects: Male, Survival Rate, Japan, Lymphatic Metastasis, Occult Blood, Humans, Mass Screening, Female, Colorectal Neoplasms, Prognosis
Abstract: There is now evidence from three randomized controlled trials (from Minnesota, Nottingham and Funen) that screening average-risk individuals for colorectal cancer (CRC) with fecal-occult-blood tests (FOBT) can reduce mortality from CRC. In Japan, mortality rates from CRC have increased and mass screening with FOBT has been performed since 1992. Although there is growing proportion of CRC with FOBT, there is no conclusive evidence that they reduce mortality from this cause. We evaluated the feature of CRC with FOBT, as one of the methods for evaluation of the efficacy of screening with this test.Between January, 1982 and December, 1996, 2071 cases with CRC resected in our hospital were considered. We evaluated the clinicopathological findings about age, sex, location of tumor, size depth, incidence of lymph node metastasis, stage and prognosis of CRC with FOBT (376) compared with CRC with no screening (controls; 1695).CRC with FOBT were earlier stage and smaller-sized cancers than controls. No significant difference was found in the incidence of lymph node metastasis at each depth and prognosis in each stage.By screening with FOBT, we can detect at an earlier stage and with a smaller cancer, with the same biological behavior as controls. Now, we must encourage colon screening, continuing to research ways to improve identification of high-risk subgroups and increase complicance.
Published: 1998

11. [Growth and development of colorectal cancer with subclassification on submucosa and proper muscle infiltrating cancer]

Author: I, Takemasa, I, Nishisho, K, Fujitani, E, Shin, H, Mishima, Y, Hasuike, K, Kobayashi, T, Kobayashi, N, Kikkawa, and M, Takeda
Subjects: Adenoma, Male, Carcinoma, Humans, Female, Neoplasm Invasiveness, Intestinal Mucosa, Middle Aged, Colorectal Neoplasms, Cell Division
Abstract: Colorectal cancer (CRC) infiltrating the submucosa (sm cancer) and the proper muscle (mp cancer) represent an early and an intermediate stage in the development of CRC, and sm and mp cancer are therefore appropriate to discuss the natural history of CRC. A total of 337 sm cancers and 291 mp cancers resected in our series were evaluated. We divided sm and mp cancers into three categories, respectively, sm 1, sm 2, sm 3, mp 1, mp 2, and mp 3, according to the depth of infiltration of the submucosa or the proper muscle. The deeper the invasion, the larger of the tumor size, and the proportion of depressed type in their configuration increases. On the contrary, the proportion of tumors with adenomatous component decreases. A larger proportion of tumors in all categories of infiltration showed PG more of ten than that of NPG in their marginal structure. In this study, 17% of sm cancer and 23% of mp cancer might develop not via the adenoma-carcinoma sequence.
Published: 1998

12. Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features

Author: T, Yamada, S, Nakamori, H, Ohzato, S, Oshima, T, Aoki, N, Higaki, K, Sugimoto, K, Akagi, Y, Fujiwara, I, Nishisho, M, Sakon, M, Gotoh, and M, Monden
Subjects: Adult, Male, Base Sequence, Palliative Care, DNA, Adenocarcinoma, Middle Aged, Polymerase Chain Reaction, Pancreatic Neoplasms, Genes, ras, Pancreatectomy, Pancreatitis, Reference Values, Chronic Disease, Humans, Point Mutation, Female, Codon, Aged, DNA Primers, Neoplasm Staging
Abstract: We investigated the presence of K-ras gene mutation in plasma DNA and assessed its clinical value in patients with pancreatic adenocarcinoma. Mutations in codon 12 of the K-ras gene were examined by mutant allele-specific amplification method using DNA extracted from surgical specimens and plasma samples of 21 patients with pancreatic adenocarcinoma. K-ras gene mutation was detected in 15 of 21 (71%) primary tumors. In 9 of 15 (60%) patients with K-ras gene mutation-positive tumors, an identical mutation was detected in the plasma DNA. None of four patients with chronic pancreatitis or five healthy subjects had such mutations in plasma DNA. Tumors positive for K-ras gene mutation in plasma DNA were significantly larger (P = 0.04) and less likely to result in a curative cure after surgical resection (P = 0.09) than those negative for the mutation. Other clinicopathological features, including age, sex, histological type, mode of invasion, and metastasis, did not correlate with K-ras gene mutations in plasma DNA. Treatment resulted in disappearance of K-ras gene mutations in plasma DNA in six of nine (67%) patients. Three patients with a persistently positive K-ras gene mutation in pre- and post-treatment plasma samples were likely to show early recurrence or have a progressive disease. Our findings suggest that K-ras gene mutation can be detected in plasma DNA of patients with pancreatic adenocarcinoma. Detection of K-ras mutations in plasma may be clinically useful for evaluating tumor burden and efficacy of treatment.
Published: 1998

13. [A new two-part therapy for multiple bilobar liver metastases of colorectal cancer--treatment of one lobe with partial hepatectomy and the other with arterial chemotherapy]

Author: Y, Hasuike, T, Yagyu, E, Shin, H, Mishima, I, Nishisho, K, Kobayashi, T, Kobayashi, N, Kikkawa, and T, Hosoki
Subjects: Antineoplastic Combined Chemotherapy Protocols, Liver Neoplasms, Hepatectomy, Humans, Infusions, Intra-Arterial, Female, Fluorouracil, Cisplatin, Colorectal Neoplasms, Combined Modality Therapy, Drug Administration Schedule, Aged
Abstract: We studied a new two-part therapy for patients of multiple (more than five) bilobar liver metastases from colorectal cancer, in which one lobe is treated with partial hepatectomy and the other with arterial chemotherapy. The patient was a 72-year-old woman who had undergone sigmoidectomy and partial hepatectomy on March 9, 1995, for advanced sigmoid cancer with liver metastasis. In December 1995, new foci were detected in the remaining liver. Intraoperative echography during reoperation revealed 6 foci in the right lobe, 2 in the left lobe and 1 in the caudate lobe. During reoperation, we performed partial hepatectomy at the left lobe metastases and microwave coagulation in the caudate lobe. A catheter was inserted into the right hepatic artery, and the right hepatic artery was ligated with the catheter. From 2 weeks after operation, CDDP (20 mg) and 5-FU (1,500 mg) were given weekly by infusion from the arterial root. As a result, the serum CEA level fell to 3.6 ng/ml on June 26, 1996, and 1.9 mg/ml on August 14, 1996. A right lobectomy would have been performed if no metastasis appeared in the remainder of the left lobe over a one-year period. However, no foci were detected on a CT scan on March 26, 1997. This new two-part therapy warrants detailed investigation for bilobar bilateral liver metastases of colorectal cancer.
Published: 1997

14. The relationship between specific RET proto-oncogene mutations and disease phenotype in multiple endocrine neoplasia type 2. International RET mutation consortium analysis

Author: C, Eng, D, Clayton, I, Schuffenecker, G, Lenoir, G, Cote, R F, Gagel, H K, van Amstel, C J, Lips, I, Nishisho, S I, Takai, D J, Marsh, B G, Robinson, K, Frank-Raue, F, Raue, F, Xue, W W, Noll, C, Romei, F, Pacini, M, Fink, B, Niederle, J, Zedenius, M, Nordenskjöld, P, Komminoth, G N, Hendy, and L M, Mulligan
Subjects: Hyperparathyroidism, Proto-Oncogene Proteins c-ret, Receptor Protein-Tyrosine Kinases, Multiple Endocrine Neoplasia Type 2a, Pheochromocytoma, Proto-Oncogene Mas, Phenotype, Carcinoma, Medullary, Proto-Oncogene Proteins, Mutation, Drosophila Proteins, Humans, Cysteine, Hirschsprung Disease, Thyroid Neoplasms, Codon
Abstract: Multiple endocrine neoplasia type 2 (MEN 2) is an autosomal dominant disorder. The 3 recognized subtypes include MEN 2A, characterized by medullary thyroid carcinoma (MTC), pheochromocytoma (pheo), and hyperparathyroidism (HPT); MEN 2B, by MTC, pheo, and characteristic stigmata; and familial MTC (FMTC), by the presence of MTC only. The purpose of this study was to establish the relationship between specific mutations and the presence of certain disease features in MEN 2 which could help in clinical decision making.Correlative survey study of 477 MEN 2 families.Eighteen tertiary referral centers worldwide.A total of 477 independent MEN 2 families.Association between the position and type of germline mutation in the RET proto-oncogene and the presence or absence of MTC, pheo, HPT, and/or other features in a family.There is a statistically significant association between the presence of any mutation at a specific position (codon 634) and the presence of pheo and HPT. The presence of a specific mutation, CGC at codon 634, has yet to be associated with FMTC. Conversely, mutations at codons 768 and 804 are thus far seen only with FMTC, while codon 918 mutation is MEN 2B--specific. Rare families with both MEN 2 and Hirschsprung disease were found to have MEN 2-specific codon mutations. Patients with Hirschsprung disease presenting with such mutations should be monitored for the possible development of MEN 2 tumors.This consortium analysis suggests that genotype-phenotype correlations do exist and, if made reliably absolute, could prove useful in the future in clinical management with respect to screening, surveillance, and prophylaxis, as well as provide insight into the genetic effects of particular mutations.
Published: 1996

15. Mutations of the transforming growth factor beta type II receptor gene and microsatellite instability in gastric cancer

Author: M, Ohue, N, Tomita, T, Monden, Y, Miyoshi, T, Ohnishi, H, Izawa, Y, Kawabata, M, Sasaki, M, Sekimoto, I, Nishisho, H, Shiozaki, and M, Monden
Subjects: Male, Stomach Neoplasms, Adenine, DNA Mutational Analysis, Humans, Female, DNA, Neoplasm, Frameshift Mutation, Receptors, Transforming Growth Factor beta, Microsatellite Repeats
Abstract: Forty-three sporadic gastric cancers were analyzed with regard to whether mutations of simple repeated sequences in the transforming growth factor beta type II receptor (TbetaR-II) gene are associated with microsatellite instability (MSI) and gastric carcinogenesis. In 12 of the 43 cancers (28%), MSI was observed at least at 1 of the 2 microsatellite loci. Frameshift mutations of the TbetaR-II gene, all of which were 1 base deletion of 10 adenine repeats, were detected in 3 of 6 cancers, with MSI at 2 loci. However, mutations were not detected in 6 cancers, with MSI only at 1 locus and 31 cancers without MSI. Moreover, microanalysis in these cases revealed that the mutant-type alleles of TbetaR-II were invariably common in different areas within the tumor, in contrast to the markedly variable alleles of microsatellite loci. Our results suggest that frameshift mutation of the TbetaR-II gene may be a critical event associated with MSI and may contribute to carcinogenesis of the stomach. One of the possible mechanisms of escape from growth control by TGFbeta during gastric carcinogenesis could involve frameshift mutations of the TbetaR-II gene caused by DNA replication errors.
Published: 1996

16. A family of multiple endocrine neoplasia type 2A: genetic analysis and clinical features

Author: H, Morita, H, Daidoh, K, Nagata, Y, Okano, Y, Sudoh, T, Maruyama, H, Sarui, T, Ishizuka, K, Akagi, I, Nishisho, and K, Yasuda
Subjects: Adult, Aged, 80 and over, Calcitonin, Male, Heterozygote, Base Sequence, Molecular Sequence Data, Proto-Oncogene Proteins c-ret, Receptor Protein-Tyrosine Kinases, Multiple Endocrine Neoplasia Type 2a, Exons, Sequence Analysis, DNA, Middle Aged, Polymerase Chain Reaction, Proto-Oncogene Mas, Pedigree, Parathyroid Hormone, Proto-Oncogene Proteins, Drosophila Proteins, Humans, Female, Child, Aged
Abstract: Since a heterozygous missense mutation of the RET proto-oncogene in the germline was found to cause multiple endocrine neoplasia type 2A (MEN 2A) in 1993, some 20 different mutations of this gene have been identified in MEN 2A kindreds. We report an MEN 2A family in which serine (AGC) substitutes for cysteine (TGC) at codon 618 in exon 10 of the RET proto-oncogene. The mutation was identified by sequencing PCR products of exons 10 and 11 in the proband. Since this mutation results in creation of a new cleavage site for Alu I restriction enzyme, most of the other members of the family were screened by digestion of the PCR product of exon 10 with this enzyme. Eleven of 20 subjects across four generations examined have the mutation of the RET proto-oncogene, and all of the adult gene carriers except one woman had MTC. Characteristics of this family are 1) pheochromocytoma has been found in only the proband, 2) no obvious hyperparathyroidism has been observed, and 3) the prognosis is favorable, with nobody dying of MEN 2A itself. Genetic analysis of MEN 2A is definitely useful and essential for screening of a MEN 2A family. It is very important to accumulate cases with MEN 2A and investigate the phenotype and the prognosis in each mutation.
Published: 1996

17. Biallelic inactivation of the APC gene in hepatoblastoma

Author: H, Kurahashi, K, Takami, T, Oue, T, Kusafuka, A, Okada, A, Tawa, S, Okada, and I, Nishisho
Subjects: Gene Expression Regulation, Neoplastic, Hepatoblastoma, Blotting, Southern, Genes, APC, Base Sequence, Liver Neoplasms, Molecular Sequence Data, Humans, Point Mutation, Polymerase Chain Reaction, Alleles
Abstract: Familial adenomatous polyposis (FAP) is an inherited disorder caused by germline mutation of the adenomatous polyposis coli (APC) gene. Increased risk of hepatoblastoma (HBL) in FAP kindreds has been reported. To determine whether inactivation of the APC gene plays a role in development of HBL, 13 sporadic infantile hepatic tumors were analyzed for genetic alterations in the APC gene. A PCR-mediated RNase protection analysis was performed to detect subtle genetic alterations in the mutation cluster region and in exons 3 and 4 of the APC gene. The results showed that a G to T transversion at the splice acceptor site of the intron 3-exon 4 junction had occurred in one HBL. Sequence analysis of normal tissue of the patient proved the mutation to be germinal. Southern blot analysis at the APC locus revealed that the tumor had lost the opposite allele and was isodisomic at this locus. RNA analysis indicated that the tumor contained only the small APC transcript, from which exon 4 was entirely absent. Since abnormal splicing causes termination due to frameshift, it was hypothesized that only the truncated APC protein was expressed in this tumor. These findings suggest that inactivation of the APC gene is closely related to tumorigenesis of HBLs in FAP patients.
Published: 1995

18. Multistep carcinogenesis in colorectal cancers

Author: K, Takami, I, Yana, H, Kurahashi, and I, Nishisho
Subjects: Male, Genes, APC, Base Sequence, Molecular Sequence Data, Oncogenes, Genes, p53, Colorectal Neoplasms, Hereditary Nonpolyposis, Pedigree, Cell Transformation, Neoplastic, Genes, ras, Adenomatous Polyposis Coli, Mutation, Humans, Point Mutation, Female, Genes, Tumor Suppressor, Colorectal Neoplasms
Abstract: Recent advances in molecular genetics have revealed that multiple genetic alterations including activation of oncogenes and inactivation of tumor suppressor genes are required for tumor development and progression. Tumorigenesis of colorectal cancer, in which most cancers are considered to arise from preceding benign adenomas, has been well documented at the molecular level. Familial adenomatous polyposis (FAP), which is characterized by the development of hundreds to thousands of adenomatous polyps in the colon and rectum, one or more of which can progress to cancer if left without surgical treatment, is a good model for elucidation of genetic alterations involved in colorectal tumorigenesis. The adenomatous polyposis coli (APC) gene responsible for FAP was isolated in 1991, and germinal and somatic mutations of the APC gene have been identified. Moreover, activation of K-ras oncogene and inactivation of several tumor suppressor genes such as MCC, p53, and DCC are supposed to play important roles at specific stages of colorectal tumorigenesis. More recently, two genes, MSH2 and MLH1, responsible for hereditary non-polyposis colorectal cancer (HNPCC) have been identified. Thus the molecular mechanism of colorectal tumorigenesis now seems to be more complicated than has been supposed.
Published: 1995

19. Existence of microchimerism in the spleen after intraportal injection in molecular-biological and immunofluorescence study

Author: H, Nagano, M, Monden, M, Gotoh, T, Tanigawa, Y, Hasuike, K, Akagi, T, Yoshida, H, Ota, I, Nishisho, and T, Mori
Subjects: Male, Transplantation, Heterotopic, Cell Transplantation, Chimera, Lymphoid Tissue, Fluorescent Antibody Technique, DNA, Polymerase Chain Reaction, Rats, Rats, Inbred ACI, Portal System, Rats, Inbred Lew, Animals, Transplantation, Homologous, Deoxyribonucleases, Type II Site-Specific, Polymorphism, Restriction Fragment Length, Spleen
Published: 1994

20. Restriction fragment length polymorphism analysis to detect microchimerism at the DNA level in rats

Author: H, Nagano, M, Monden, M, Gotoh, T, Tanigawa, Y, Hasuike, K, Akagi, T, Yoshida, H, Ota, I, Nishisho, and T, Mori
Subjects: Male, Base Sequence, Chimera, Molecular Sequence Data, Polymerase Chain Reaction, Rats, Rats, Inbred ACI, Major Histocompatibility Complex, Lymphocyte Transfusion, Animals, Transplantation, Homologous, Rats, Wistar, Polymorphism, Restriction Fragment Length, Spleen, DNA Primers
Published: 1994

21. Disruption of the APC gene by a retrotransposal insertion of L1 sequence in a colon cancer

Author: Y, Miki, I, Nishisho, A, Horii, Y, Miyoshi, J, Utsunomiya, K W, Kinzler, B, Vogelstein, and Y, Nakamura
Subjects: Base Sequence, Molecular Sequence Data, DNA, DNA, Neoplasm, Exons, Blotting, Southern, Mutagenesis, Insertional, Retroviridae, Adenomatous Polyposis Coli, Sequence Homology, Nucleic Acid, Colonic Neoplasms, DNA Transposable Elements, Humans, Genes, Tumor Suppressor, Intestinal Mucosa, Repetitive Sequences, Nucleic Acid
Abstract: The APC gene is responsible for familial adenomatous polyposis and is considered to be a tumor suppressor gene associated with development of sporadic colorectal tumors. Here we report the disruption of the APC gene caused by somatic insertion of a long interspersed repetitive element (LINE-1 sequence) into the last exon of the APC gene in a colon cancer. The inserted sequence was composed of a 3' portion of the LINE-1 consensus sequence and nearly 180 base pairs of polyadenylate tract. Furthermore, since an 8-base pair target site duplication was observed, retrotranscriptional insertion of an active LINE-1 sequence is suspected as the cause of this insertion event. This is the first report of the disruption of a tumor suppressor gene caused by somatic insertion of a mobile genetic element.
Published: 1992

22. [Cytomolecular aspects of colorectal carcinoma]

Author: Y, Miki, I, Nishisho, Y, Miyoshi, and Y, Nakamura
Subjects: Oncogene Proteins, Genes, ras, Adenomatous Polyposis Coli, Humans, DNA, Neoplasm, Colorectal Neoplasms, Polymerase Chain Reaction
Abstract: This report reviewed recent remarkable progresses on the cytomolecular mechanisms in colorectal carcinogenesis. Colorectal carcinoma is a good model for the study of multi-step progression, because we can obtain adenomatous polyps which are considered as a precancerous form. Furthermore, a familial syndrome, which is characterized by numerous adenomas of the colon, is available for linkage analysis. Recently, the p53 and DCC genes have been identified as candidate tumor suppressor genes on chromosome 17p and 18q respectively. In this paper, we present the multiple genetic alterations in colorectal carcinoma, including activation of K-ras gene and inactivation of tumor suppressor gene such as p53 and DCC genes as well as loss of heterozygosity and approach to the gene responsible for adenomatous polyposis coli by reverse genetics.
Published: 1991

23. Mutations of the adenomatous polyposis coli gene in familial polyposis coli patients and sporadic colorectal tumors

Author: Y, Nakamura, I, Nishisho, K W, Kinzler, B, Vogelstein, Y, Miyoshi, Y, Miki, H, Ando, A, Horii, and H, Nagase
Subjects: Genes, APC, Adenomatous Polyposis Coli, Base Sequence, Molecular Sequence Data, Mutation, Humans, Gardner Syndrome, Colorectal Neoplasms, Genes, MCC
Abstract: We have isolated several genes in the chromosome 5q21 region tightly linked to hereditary familial polyposis coli (FAP) and Gardner's syndrome (GS). Two of these genes (MCC and APC) were found to be somatically altered by point mutation, deletion or insertion in tumors of sporadic colorectal cancer patients. One of them (adenomatous polyposis coli; APC) was also found to mutate in the germ-line of both APC and GS patients. The identification of these genes has significant implications for understanding the pathogenesis of colorectal neoplasia and for the diagnosis and counseling of individuals with inherited predispositions to colorectal cancer. Furthermore, in one colon carcinoma, we identified an interesting mechanism causing dysfunction of the APC gene. This gene was disrupted by a somatic insertion of a long interspersed repetitive element (LINE-1 sequence: L1) into the last exon. As an insertional sequence contains a 3' portion of the L1 consensus sequence including the poly(A) tract and an 8 bp target-site duplication was observed, this insertion is suspected to be caused by a retrotranscriptional insertion of one of the L1 sequences. This is the first case of the disruption of a tumor suppressor gene by the insertion of a movable genetic element.
Published: 1991

24. Sequential Treatment with Irinotecan and Doxifluridine: Optimal Dosing Schedule in Murine Models and in a Phase I Study for Metastatic Colorectal Cancer.

Author: H. Mishima, T. Kato, M. Yanagisawa, T. Tsujinaka, I. Nishisho, M. Tsujie, K. Fujimoto-Ouchi, Y. Tanaka, and N. Kikkawa
Subjects: COLON cancer, DRUGS, DIARRHEA, CANCER treatment, THERAPEUTICS
Abstract: Background: Irinotecan (CPT-11) and doxifluridine (5'-DFUR) are active agents against colorectal cancer. Each drug, however, has the possibility of causing diarrhea. Methods and Results: First, we determined the optimal dosing regimen in murine models. CPT-11 (i.v., q2d ×3) and 5'-DFUR (p.o., qd ×14) were administered to mice bearing a human colorectal cancer xenograft model. Diarrhea was stronger in the simultaneously administered schedule but not much stronger in the sequentially administered schedule compared with monotherapies. Both schedules yielded similar antitumor efficacies. Next, we conducted a phase I study combining CPT-11 on days 1 and 15, and 5'-DFUR on days 314 and 1728 every 5 weeks in 19 patients with metastatic colorectal cancer. The doses of CPT-11 ranged from 80 to 150 mg/m2 and those of 5'-DFUR from 800 to 1,200 mg. Diarrhea of grade 3/4 developed in only 1 patient at 100 mg/m2/800-mg doses. Dose-limiting toxicities were hyperbilirubinemia and skipping doses due to fatigue at 150 mg/m2/1,200-mg doses. Conclusion: For the phase II study, the recommended dose was set at CPT-11 150 mg/m2 and 5'-DFUR 800 mg.Copyright © 2005 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]
Published: 2005
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25. D10S20, a previously unmapped RFLP (OS-3), is located on 10q near D10S4

Author: I. Nishisho, Yuan-Tsong Chen, S. Takai, Jingshi Wu, Frank H. Ruddle, A.J. Pakstis, J.R. Kidd, Kenneth K. Kidd, H. Tateishi, T. Miki, and Dimitrina D. Pravtcheva
Subjects: congenital, hereditary, and neonatal diseases and abnormalities, Linkage disequilibrium, TaqI, Genetic Linkage, Somatic cell, Locus (genetics), Biology, Cell Line, chemistry.chemical_compound, Gene Frequency, Genetic linkage, Genetics, Humans, Alleles, Southern blot, Polymorphism, Genetic, Chromosomes, Human, Pair 10, Chromosome Mapping, Molecular biology, Blotting, Southern, genomic DNA, Haplotypes, chemistry, Lod Score, Restriction fragment length polymorphism, Polymorphism, Restriction Fragment Length
Abstract: The locus recognized by the probe OS-3 is assigned to chromosome 10 both by Southern blot analysis of a panel of somatic cell hybrid DNAs and by genetic linkage to markers already assigned to chromosome 10. In Caucasians this probe recognizes a three-allele TaqI RFLP as well as two-allele BanII and RsaI RFLPs which are both in strong linkage disequilibrium with each other and with the TaqI RFLP. The D10S20 locus defined by this probe maps 5.5 cM distal to D10S4 on the long arm of chromosome 10. Because this human clone hybridizes with mouse genomic DNA, it will be useful in comparative mapping studies.
Published: 1988
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26. An anonymous single copy chromosome 18 probe associated with a frequent RFLP (D18S5)

Author: Tetsuro Miki, Shin-ichiro Takai, I. Nishisho, H. Tateishi, and Tasuku Honjo
Subjects: Genetics, Polymorphism, Genetic, Chromosome, DNA Restriction Enzymes, Single copy, Biology, Molecular biology, Gene Frequency, Chromosome 18, Humans, Restriction fragment length polymorphism, Cloning, Molecular, Allele frequency, Chromosomes, Human, 16-18
Published: 1986

27. Loss of genes on the long arm of chromosome 22 in human meningiomas

Author: M, Okazaki, I, Nishisho, H, Tateishi, K, Motomura, M, Yamamoto, T, Miki, T, Hayakawa, S, Takai, T, Honjo, and T, Mori
Subjects: Male, Polymorphism, Genetic, Chromosomes, Human, Pair 22, Genetic Carrier Screening, Leukocytes, Meningeal Neoplasms, Humans, Nucleic Acid Hybridization, Female, DNA Restriction Enzymes, Chromosome Deletion, Meningioma, Polymorphism, Restriction Fragment Length
Abstract: It has been proposed that loss of genes at specific chromosomal loci leads to tumorigenesis in some human tumors. This type of oncogenesis was first demonstrated in retinoblastoma and Wilms' tumor. Recently, it has been reported that acoustic neuroma, ductal breast tumor, and renal cell carcinoma may be caused by the same mechanism. Cytogenetic studies demonstrated that some meningiomas have monosomy of chromosome 22. In addition, human meningiomas are often associated with bilateral acoustic neuroma in which specific loss of alleles on chromosome 22 has been demonstrated. Then, we compared constitutional and tumor genotypes from 14 cases of sporadic human meningiomas, using four polymorphic DNA probes on chromosome 22 (SIS, D22S1, D22S9, IGLC). Loss of constitutional heterozygosity was found in three of 11 informative cases. Two of the three meningiomas maintained constitutional heterozygosity at the IGLC locus and another one showed no loss of heterozygosity at IGLC or D22S9. These results suggest that loss of genes on chromosome 22 caused by either a partial deletion or a mitotic recombination at a locus distal to D22S9 plays an important role in tumorigenesis of the human meningioma.
Published: 1988

28. [Multiple endocrine neoplasia type 2: mapping of the gene predisposing and alteration of genotypes in tumor]

Author: I, Nishisho, S, Takai, H, Tateishi, K, Motomura, M, Okazaki, M, Yamamoto, and T, Miki
Subjects: Genetic Markers, Heterozygote, Genotype, Chromosomes, Human, Pair 1, Chromosomes, Human, Pair 22, Multiple Endocrine Neoplasia, Mutation, Chromosome Mapping, Humans, Chromosome Deletion, Cloning, Molecular
Published: 1988

29. Studies of multiple endocrine neoplasia type 2A syndrome: linkage analyses and comparison of constitutional and tumor genotypes

Author: H, Tateishi, S, Takai, I, Nishisho, T, Miki, K, Motomura, M, Okazaki, A, Miyauchi, T, Ikeuchi, K, Yamamoto, and T, Hattori
Subjects: Genetic Markers, Polymorphism, Genetic, Genotype, Japan, Genetic Linkage, Multiple Endocrine Neoplasia, Chromosomes, Human, Pair 20, Humans, Chromosome Deletion, Lod Score
Published: 1987

30. [Revolution in human gene mapping: linkage analysis using DNA polymorphisms as genetic markers]

Author: S, Takai, I, Nishisho, K, Motomura, H, Tateishi, and T, Miki
Subjects: Genetic Markers, Polymorphism, Genetic, Base Sequence, Genetic Diseases, Inborn, Chromosome Mapping, Humans
Published: 1986

31. Loss of genes on chromosome 22 in medullary thyroid carcinoma and pheochromocytoma

Author: S, Takai, H, Tateishi, I, Nishisho, T, Miki, K, Motomura, A, Miyauchi, M, Kato, T, Ikeuchi, K, Yamamoto, and M, Okazaki
Subjects: Chromosomes, Human, Pair 22, Genetic Carrier Screening, Adrenal Gland Neoplasms, Chromosome Mapping, Humans, Pheochromocytoma, Thyroid Neoplasms, Chromosome Deletion, Polymorphism, Restriction Fragment Length
Abstract: Using polymorphic DNA markers, we compared the constitutional and tumor genotypes of patients with multiple endocrine neoplasia type 2A (MEN2 A). We found loss of constitutional heterozygosity at the D22S9 locus in one out of 9 medullary thyroid carcinomas (MTCs). No loss of heterozygosity was detected at 12 other loci in any of the MTCs tested. Loss of heterozygosity at D22S9 and/or D22S1 was also demonstrated in 2 out of 5 pheochromocytomas tested. These results suggest that loss or mutation of a gene on chromosome 22 may play an important role in tumorigenesis in MEN2A.
Published: 1987

32. [Hepatectomy with microwave coagulation therapy for multiple liver metastases of rectal carcinoid--a case report].

Author: Hashimoto K, Sasaki Y, Yokoyama S, Naitou A, Hiraki M, Matsumoto S, Matsuyama J, Morita S, Morimoto T, Fukushima Y, Nishisho I, Nomura T, and Takeda M
Subjects: Combined Modality Therapy, Female, Humans, Middle Aged, Carcinoid Tumor pathology, Electrocoagulation methods, Hepatectomy, Liver Neoplasms secondary, Liver Neoplasms therapy, Microwaves therapeutic use, Rectal Neoplasms pathology
Abstract: A woman in her 50s was admitted to our hospital for the evaluation of liver masses. Low density areas at S5, S6 and S8 of the liver were revealed by enhanced abdominal CT scan. While exploring for the primary site, we observed a flat tumor, 10 mm in diameter, in the rectum at 10 cm from the anal ring, and local resection of the tumor was performed transanally. It was histologically diagnosed as a rectal carcinoid. During surgery, ultrasonography revealed eight hypoechoic masses at S4, S5, S6 and S8 of the liver. We conducted a partial hepatectomy (S8, S5/6) and microwave coagulation therapy. Histologically, the masses were diagnosed as liver metastases of rectal carcinoid. As of 27 months since surgery, liver metastases control is favorable, and no local recurrence has been observed. Hepatectomy with microwave coagulation therapy is believed to be locally effective in multiple liver metastases of rectal carcinoid tumor.
Published: 2009

33. The significance of the intraoperative repeated dosing of antimicrobials for preventing surgical wound infection in colorectal surgery.

Author: Morita S, Nishisho I, Nomura T, Fukushima Y, Morimoto T, Hiraoka N, and Shibata N
Subjects: Aged, Cefazolin administration & dosage, Cefmetazole administration & dosage, Cefotiam administration & dosage, Cephalosporins administration & dosage, Female, Humans, Intraoperative Care, Logistic Models, Male, Middle Aged, Retrospective Studies, Risk Factors, Statistics, Nonparametric, Cefozopran, Antibiotic Prophylaxis methods, Colorectal Neoplasms surgery, Surgical Wound Infection prevention & control
Abstract: Purpose: It is widely accepted that antimicrobial prophylaxis is useful for the prevention of surgical wound infection, especially in colorectal surgery. While many reports support the finding that the first dose should be administered immediately before surgery, there is less evidence concerning the ideal timing for the second dose. The purpose of this study is to examine the significance of intraoperative repeated dosing., Methods: A surgical series of 131 patients with primary colorectal cancer was retrospectively analyzed for 14 parameters, including the protocols of antimicrobial administration to determine the clinical risk factors for surgical wound infection., Results: The overall surgical wound infection rate of the 131 patients was 16.0% (21/131). When the operation finished within 4 h after the first dose (n = 29), wound infection was observed in only one patient (3.4%). In a prolonged operation exceeding 4 h after the first dose, the surgical wound infection rates were 8.5% and 26.5%, respectively, for those with (n = 47) and without (n = 49) intraoperative repeated dosing, which were significantly different based on both a univariate analysis (P = 0.031) and a multivariate analysis (P = 0.0079)., Conclusion: Intraoperative repeated antimicrobial dosing is therefore recommended to prevent the surgical wound infection for prolonged colorectal surgery.
Published: 2005
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34. A phase II Japanese study of a modified capecitabine regimen for advanced or metastatic colorectal cancer.

Author: Sakamoto J, Kondo Y, Takemiya S, Sakamoto N, and Nishisho I
Subjects: Administration, Oral, Adult, Aged, Capecitabine, Colorectal Neoplasms diagnosis, Colorectal Neoplasms secondary, Deoxycytidine administration & dosage, Deoxycytidine adverse effects, Disease Progression, Fluorouracil analogs & derivatives, Foot Dermatoses chemically induced, Foot Dermatoses complications, Guideline Adherence, Hand Dermatoses chemically induced, Hand Dermatoses complications, Humans, Hyperbilirubinemia blood, Japan, Lymphopenia blood, Middle Aged, Patient Selection, Survival Rate, Syndrome, Time Factors, Treatment Outcome, Colorectal Neoplasms drug therapy, Deoxycytidine analogs & derivatives, Deoxycytidine therapeutic use, Drug Administration Schedule
Abstract: This phase II study evaluated a modified Japanese capecitabine regimen as first-line treatment for advanced/metastatic colorectal cancer. Sixty patients received oral capecitabine 828 mg/m(2) twice daily for 3 weeks every 4 weeks. In the 56 efficacy-evaluable patients, the overall response rate was 26.8% (95% CI 15.8-40.3%) and 21 patients (37.5%) had stable disease. The median duration of response and overall survival times were 7.4 months (range 4.3-13.8) and 17.6 months (95% CI 14.1-20.5), respectively. The most frequent non-hematological treatment-related adverse events (all grades) were hand-foot syndrome (62.7%), anorexia (28.8%), diarrhea (22.0%) and fever (22.0%). There was no grade 3/4 diarrhea. The most common grade 3/4 laboratory abnormalities were lymphocytopenia (30.5%) and hyperbilirubinemia (35.6%). We conclude that the modified Japanese intermittent regimen of capecitabine is effective and well tolerated as first-line treatment for advanced colorectal cancer, and is worthy of further study in larger phase III studies.
Published: 2004
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35. Use of microsatellite analysis in young patients with colorectal cancer to identify those with hereditary nonpolyposis colorectal cancer.

Author: Ikenaga M, Tomita N, Sekimoto M, Ohue M, Yamamoto H, Miyake Y, Mishima H, Nishisho I, Kikkawa N, and Monden M
Subjects: Adult, Aged, Base Pair Mismatch, DNA Mutational Analysis, DNA Repair, DNA, Neoplasm analysis, Family Health, Female, Humans, Male, Middle Aged, Colorectal Neoplasms genetics, Colorectal Neoplasms, Hereditary Nonpolyposis genetics, Medical Records, Microsatellite Repeats genetics
Abstract: Background and Objectives: The frequency of microsatellite instability (MSI) in young patients with colorectal cancer was evaluated, including reexamination of the medical and family history of each patient, and interviews with the patients to determine any possible new occurrence of hereditary nonpolyposis colorectal cancer (HNPCC) in the patients themselves or their family members., Methods: Fifty-three young patients (younger than 40 years of age) with colorectal cancer were selected and investigated. DNA was extracted from paraffin sections and microsatellite analysis was performed., Results: The frequency of MSI among the young patients with colorectal cancer was 50.9%, which was significantly higher than the rate of 12-21% noted in older patients with colorectal cancer (P < 0.001). For the 24 young patients with colorectal cancer who did not have MSI, only one case of HNPCC kindred and two cases with a family history of cancer were identified. In contrast, among the 20 young patients with colorectal cancer who had MSI, five cases of HNPCC kindred, two cases with metachronous patients with colorectal cancer, and three cases with a family history of cancer were identified., Conclusion: Our results suggest that a defect in the DNA mismatch repair system may play some role in carcinogenesis in young patients with colorectal cancer. Microsatellite analysis and subsequent interviews regarding medical and family history are useful tools for efficiently identifying possible cases of HNPCC among young patients with colorectal cancer., (Copyright 2002 Wiley--Liss, Inc.)
Published: 2002
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36. Appendix penetrating into the sigmoid colon: report of a case.

Author: Kurokawa Y, Nishisho I, Mishima H, Yukawa K, and Kikkawa N
Subjects: Appendectomy, Colon, Sigmoid surgery, Humans, Male, Middle Aged, Appendix pathology, Colon, Sigmoid pathology
Published: 2000
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37. Phase I study of docetaxel administered by bi-weekly infusion to patients with metastatic breast cancer.

Author: Shin E, Ishitobi M, Hiraoia M, Kazumasa F, Hideyuki M, Nishisho I, Toshiro S, Yasunori H, and Tosimasa T
Subjects: Adult, Aged, Antineoplastic Agents, Phytogenic administration & dosage, Asthenia chemically induced, Breast Neoplasms pathology, Docetaxel, Dose-Response Relationship, Drug, Drug Administration Schedule, Edema chemically induced, Fatigue chemically induced, Female, Granulocyte Colony-Stimulating Factor therapeutic use, Humans, Infusions, Intravenous, Lymphatic Metastasis, Middle Aged, Neoplasm Metastasis, Neoplasm Staging, Neutropenia chemically induced, Paclitaxel administration & dosage, Recombinant Proteins, Antineoplastic Agents, Phytogenic adverse effects, Breast Neoplasms drug therapy, Paclitaxel adverse effects, Paclitaxel analogs & derivatives, Taxoids
Abstract: Background: To find a more convenient and tolerable schedule than the tri-weekly or weekly schedules, we conducted a dose escalation study of bi-weekly docetaxel., Materials and Methods: Between March 1998 and June 1999, 16 patients entered this phase I study. The starting dose was 40 mg/m2, with planned dose escalation to 45, 50 and 55 mg/m2, in consecutive patient cohorts. Patients continued to receive the assigned treatment at the same dose level bi-weekly, provided that they did not develop progressive disease, refuse further treatment, or experience unacceptable toxicity., Results: Grade 4 neutropenia lasting for more 4 days was seen at dose level 3 in all three patients. Only one patient who had previously received intensive chemotherapy required granulocyte colony stimulating factor (G-CSF) to prevent neutropenic fever and there were no actual episodes of neutropenic fever. Grade 3 asthenia and Grade 3 elevation of serum glutamic oxaloacetic transaminase were noted in only one patient treated at a dose of 40 mg/m2. Grade 3 skin toxicity and grade 2 elevation of serum glutamic oxaloacetic transaminase were seen in only one patient treated at a dose of 55 mg/m. Cumulative toxicity was not severe in all patients. Although grade 3 and/or grade 4 neutropenia were noted in eight patients (50%), all except one who received treatment at dose of 55 mg/m2 did not need G-CSF. Nail toxicity and peripheral edema seemed to be related to the number of treatment cycles. Severe fatigue and asthenia were never seen in all patients., Conclusion: 1) The maximum-tolerated dose of docetaxel when administered by this bi-weekly schedule was 55 mg/m2; 2) Docetaxel administered on a bi-weekly basis well tolerated.
Published: 2000

38. [Case report--efficacy of short-term intraarterial 5-fluorouracil for liver metastasis from colorectal cancer].

Author: Takeda Y, Hasuike Y, Mishima H, Nishisho I, and Kikkawa N
Subjects: Adenocarcinoma surgery, Combined Modality Therapy, Drug Administration Schedule, Female, Humans, Infusions, Intra-Arterial, Liver Neoplasms surgery, Middle Aged, Adenocarcinoma drug therapy, Adenocarcinoma secondary, Antimetabolites, Antineoplastic administration & dosage, Colorectal Neoplasms pathology, Fluorouracil administration & dosage, Liver Neoplasms drug therapy, Liver Neoplasms secondary
Abstract: Hepatectomy has the highest cure rate among the various methods for treating liver metastasis from colorectal cancer. We previously reported that continuous hepatic arterial infusion (HAI) of 5-FU is effective for improving the prognosis of patients with liver metastasis. In this study, we examined the efficacy of short-term continuous HAI of 5-FU for treating liver metastasis from colorectal cancer. A 57-year-old woman with a solitary liver metastasis from rectal cancer was treated by continuous HAI of 5-FU (1,000 mg/day) for 6 days. Her elevated serum CEA level (20.7 ng/ml) then returned to normal. Computed tomography revealed a decrease of 55.6% in the size of the liver tumor. Partial segmentectomy (S7) was subsequently performed. Histological examination of the resected tumor showed marked degeneration, necrosis, fibrosis, and calcification with viable moderately differentiated adenocarcinoma cells. These results suggest that preoperative HAI of 5-FU is safe and worth trying in patients with liver metastasis from colorectal cancer.
Published: 2000

39. [Efficacy of combination therapy for multiple liver metastases of colorectal cancer].

Author: Kurokawa Y, Hasuike Y, Mishima H, Takeda Y, Fujitani K, Shin E, Sawamura T, Nishisho I, Tsujinaka T, and Kikkawa N
Subjects: Antimetabolites, Antineoplastic administration & dosage, Carcinoembryonic Antigen blood, Combined Modality Therapy, Female, Fluorouracil administration & dosage, Hepatectomy, Humans, Infusions, Intra-Arterial, Male, Retrospective Studies, Survival Analysis, Colorectal Neoplasms pathology, Liver Neoplasms drug therapy, Liver Neoplasms secondary, Liver Neoplasms surgery
Abstract: In our hospital, combination therapy, mainly intra-arterial infusion, is performed for multiple liver metastases of colorectal cancer. The median survival time of the combination group (n = 18), the hepatectomy only group (n = 3) and the best supportive care group (n = 7) were 21.7, 12.5 and 6.1 months, respectively. The prognosis of the combination group was significantly better than that in the other groups (p < 0.0001). Univariate analysis against the combination group revealed that serum CEA was a significant prognostic factor (p = 0.0196). Moreover, we divided the combination group into two groups on the basis of serum CEA either below or above 50 ng/ml. The prognosis of the low CEA group (n = 11), whose median survival time was 25.9 months, was significantly better than the high CEA group (n = 7), whose median survival time was 17.8 months (p = 0.0031). It therefore appears that combination therapy may be of no benefit when serum CEA is above 50 ng/ml.
Published: 2000

40. Gastrointestinal stromal tumor of the rectum with activating mutation of c-kit: report of a case.

Author: Kurokawa Y, Nishisho I, Kawahara K, Mishima H, Hirota S, and Kikkawa N
Subjects: Female, Humans, Middle Aged, Mutation, Proto-Oncogene Mas, Rectal Neoplasms pathology, Sarcoma pathology, Proto-Oncogene Proteins c-kit genetics, Rectal Neoplasms genetics, Sarcoma genetics
Abstract: Nonepithelial malignancies of the large bowel are rare. A new disease entity, gastrointestinal stromal tumors, has attracted attention among primary mesenchymal tumors of the gastrointestinal tract. Here we present a case of spindle-cell sarcoma of the rectum, lacking either smooth muscle cells or neural elements. Immunohistochemical findings and sequencing of the c-kit proto-oncogene diagnosed this tumor as a malignant gastrointestinal stromal tumor of the rectum.
Published: 2000
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41. PTEN / MMAC1 mutation and frequent loss of heterozygosity identified in chromosome 10q in a subset of hepatocellular carcinomas.

Author: Fujiwara Y, Hoon DS, Yamada T, Umeshita K, Gotoh M, Sakon M, Nishisho I, and Monden M
Subjects: DNA Mutational Analysis, Genetic Markers, Humans, PTEN Phosphohydrolase, Carcinoma, Hepatocellular genetics, Chromosomes, Human, Pair 10 genetics, Gene Deletion, Genes, Tumor Suppressor genetics, Liver Neoplasms genetics, Loss of Heterozygosity, Microsatellite Repeats genetics, Phosphoric Monoester Hydrolases genetics, Tumor Suppressor Proteins
Abstract: Frequent allelic losses on chromosome 10q have been reported in several types of cancers, suggesting the presence of a putative tumor suppressor gene(s) on the chromosomal arm. We examined loss of heterozygosity (LOH) on chromosome 10q in 37 hepatocellular carcinomas (HCC) using eleven dinucleotide microsatellite markers, spanning the entire chromosome arm of 10q. Twelve (32%) out of 37 informative cases showed allelic losses of at least one locus on 10q and eight tumors showed a partial deletion of 10q. Analysis of deletion mapping of these eight cases identified two commonly deleted regions within the distal part of 10q (10q24-q26), a 20-cM interval flanked by D10S597 and D10S216 and a 24-cM interval flanked by D10S216 and D10S590. Moreover, we detected a somatic missense mutation (Met --> Val) of a candidate tumor suppressor gene PTEN / MMAC1, located at 10q23.3, in one HCC with LOH of 10q. Our findings indicated the presence of putative tumor suppressor gene(s) in the distal region of 10q that might be involved in the development and progression of HCC. Inactivation of PTEN / MMAC1 gene located outside the commonly deleted region of 10q might also play an important role in a subset of HCCs.
Published: 2000
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42. Correlation between clinical features and prognosis of local recurrence after breast-conserving therapy.

Author: Shin E, Takatsuka Y, Okamura Y, Nishisho I, Kawahara K, Kurata A, and Kikkawa N
Abstract: Background. In patients with early stage breast cancer who have breast-conserving therapy (BCT), the impact of local recurrence on the risk of distant metastasis is still controversial. Local recurrence after BCT is an uncommon event, so it is impossible to determine a standard treatment method by a clinical trial because not enough patients can be enrolled. Methods. Between February 1988 and December 1997, 399 patients with clinical stage I and II breast cancer underwent BCT in our department. Of these 399 patients, 22 developed local recurrence during this period. To assess the relationship between their clinical characteristics and prognosis, we performed a retrospective review of these 22 patients. Results. The 5-year overall survival rate after local recurrence was 66.7%. All four patients who had cutaneous or inflammatory type recurrence developed distant metasta-sis after salvage treatment. Of three patients with multiple recurrence, two developed disseminated disease after salvage treatment. Two of four patients treated by repeat lumpectomy developed further local recurrence after salvage lumpectomy. Conclusion. To improve prognosis in patients with multiple, cutaneous, or inflammatory recurrence, aggressive adjuvant systemic therapy may be required after salvage surgery.
Published: 2000
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43. Prognostic significance of c-erb B-2 protein status using an enzyme immunoassay in breast cancer.

Author: Shin E, Takatsuka Y, Nishisho I, Fujitani K, Mishima H, Sawamura T, Hasuike Y, Kobayashi K, Tsujinaka T, and Kikkawa N
Abstract: Background. The prognostic significance of c-erb B-2 in breast cancer remains controversial. The aim of this study was to determine the practical prognostic significance of c-erb B-2 protein status in breast cancer extracts, using an enzyme immunoassay. Methods. An enzyme immunoassay was used to measure levels of c-erb B-2 protein prospectively in 360 patients with breast cancer, using cytosol fractions prepared for steroid receptor assay. The status of c-erb B-2 protein was assessed using a cut-off value for positivity of 18 ng/mg protein. Univariate and multivariate analyses were performed. To evaluate the prognostic significance of c-erb B-2 protein status. Results. Levels of c-erb B-2 protein in tumor tissue extract ranged from 0 to 213.0 ng/mg protein (mean, 15.5 ng/mg protein). In 52 tumors (14.4 %) more than 18.0 ng/mg protein was detected, and these tumors were regarded as c-erb B-2 protein-positive. Correlations were found between c-erb B-2 protein positivity and large tumor size (>3 cm; P = 0.0095), higher histological grade (P < 0.0001), estrogen receptor negativity (P < 0.0001), and progesterone receptor negativity (P < 0.0001). There was also a marginally significant correlation between c-erb B-2 protein positivity and lymph node positivity. Multivariate analysis showed that c-erb B-2 protein status was a significant independent prognostic factor for disease-free survival, being strongly significant in patients with positive lymph nodes. Conclusion. c-erb B-2-positive breast cancers are biologically more aggressive and c-erb B-2 protein status could be a candidate as a prognostic factor for patients with breast cancer, being particularly valuable in patients with positive lymph nodes.
Published: 2000
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44. [A late phase II study of raltitrexed (ZD 1694) in chemotherapy-naive patients with advanced colorectal cancer].

Author: Nishisho I, Kikkawa N, Ebata T, Osanai H, Ujiie S, Mitachi Y, Tsutsui M, Sawai K, Nishiguchi Y, Yasutake K, Wakasugi H, and Wakui A
Subjects: Adult, Aged, Antimetabolites, Antineoplastic adverse effects, Colonic Neoplasms mortality, Drug Administration Schedule, Enzyme Inhibitors adverse effects, Female, Humans, Leukopenia chemically induced, Male, Middle Aged, Quinazolines adverse effects, Rectal Neoplasms mortality, Thiophenes adverse effects, Thymidylate Synthase antagonists & inhibitors, Antimetabolites, Antineoplastic therapeutic use, Colonic Neoplasms drug therapy, Enzyme Inhibitors therapeutic use, Quinazolines therapeutic use, Rectal Neoplasms drug therapy, Thiophenes therapeutic use
Abstract: A multicenter co-operative late phase II study of raltitrexed (ZD1694), a specific thymidylate synthase (TS) inhibitor, was conducted in chemotherapy-naive patients with advanced colorectal cancer. Raltitrexed was infused intravenously over 15 minutes once every three weeks. Between April 1996 and September 1998, 61 patients were enrolled and 58 were eligible. Fourteen patients experienced a partial response (PR), 22 no change (NC), 20 progressive disease (PD) and 2 no evaluable (NE). The overall response rate was 24.1% (95% CI: 13.9-37.2%). Responses were seen in lung (22.7%), liver (22.9%) and deep lymph nodes (10.0%). Median survival was 11.6 months. Grade 3 or 4 toxicities were: leukopenia (13.8%), neutropenia (24.1%), hemoglobin decrease (15.5%), FBC decrease (6.9%), hematocrit decrease (6.9%), thrombocytopenia (6.9%), transient SGPT increase (6.9%), nausea/vomiting (20.7%), anorexia (15.5%), and asthenia (6.9%). These adverse reactions were considered to be manageable. Only one death was associated with drug treatment. These results suggest that raltitrexed provides an effective and convenient treatment for patients with advanced and previously untreated colorectal cancer.
Published: 2000

45. [Efficacy and side effect of continuous intra-arterial infusion of high-dose 5-FU for liver metastases of colorectal cancer].

Author: Kurokawa Y, Hasuike Y, Hattori T, Hayashi S, Fujitani K, Shin E, Mishima H, Sawamura T, Nishisho I, Kobayashi K, Kobayashi T, and Kikkawa N
Subjects: Adult, Aged, Antimetabolites, Antineoplastic adverse effects, Combined Modality Therapy, Female, Fluorouracil adverse effects, Hepatectomy methods, Hepatic Artery, Humans, Infusions, Intra-Arterial, Liver Neoplasms mortality, Male, Middle Aged, Prognosis, Survival Rate, Antimetabolites, Antineoplastic administration & dosage, Colorectal Neoplasms pathology, Fluorouracil administration & dosage, Liver Neoplasms drug therapy, Liver Neoplasms secondary
Abstract: Fifteen patients with liver metastases of colorectal cancer were entered in our study, and 5-FU was given continuously by hepatic intra-arterial route at 1 g/day over 6 days. No leukopenia (< 3,000/mm3), anemia (< 10 g/dl), or thrombocytopenia (< 75,000/mm3) occurred, and no elevation of serum AST (> 150 IU/l) or serum T-Bil (> 2 mg/ml) appeared. One patient (4.2%) had nausea with vomiting 1-5 per day, and another (4.2%) had mucositis requiring treatment. In patients with multiple liver metastases, survival of the continuous infusion group [total dose of 5-FU > or = 12 g] (n = 5) seems to be longer than those of the hepatectomy only group (n = 3) or the control group (n = 7). We suggest that this continuous intra-arterial infusion of high-dose 5-FU is a useful chemotherapy with few side effects or complications.
Published: 1999

46. A Retrospective Study of Breast Cancer Patients Treated with Quadrantectomy without Radiation Therapy.

Author: Shin E, Takatsuka Y, Okamura Y, Takeda M, Kobayashi T, Nishisho I I, Kawahara K, Kurata A, and Kikkawa N
Abstract: BACKGROUND: Radiation therapy after breast-conserving surgery (BCS) reduces the risk of local recurrence. However, whether radiation therapy is necessary forall patients undergoing BCS remains unclear. METHODS: In order to determine the selection criteria for patients who can safely omit radiation therapy and to confirm the survival benefit of quadrantectomy without radiation therapy, we reviewed 107 patients who underwent quadrantectomy without radiation therapy between February 1988 and July 1995. RESULTS: The 5-year overall survival, disease-free survival and cumulative local recurrence rates were 93.7%, 80.7% and 12.1% respectively. There were no significant differences of 5-year overall survival (94.0% vs 94.1%) and disease-free survival rates (83.1% vs 70.0%) between patients with or without tamoxifen. The 5-year cumulative local recurrence rate of patients with tamoxifen, however, tended to be lower (p = 0.0810) than that of patients without tamoxifen. The 5-year cumulative local recurrence rate of the patients aged 45 or less was significantly higher than that of patients aged from 45 to 55 years and those over 55 (p= 0.0090 and 0.0089, respectively). In ER positive patients, the 5-year cumulative local recurrence rate of patients with tamoxifen tended to be lower (p= 0.0791) than that of patients without tamoxifen. CONCLUSION: The survival rate of quadrantectomy without radiation therapy wasacceptable. While the risk of local recurrence following quadrantectomy withoutradiation therapy is substantial, radiation therapy following quadrantectomy might not be necessary in elderly ER positive women receiving adjuvant tamoxifen therapy.
Published: 1999
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47. Microchimerism in thymus is associated with up-regulated T helper type 1 cytokine transcription during cardiac allograft rejection in rats.

Author: Ota H, Gotoh M, Ohzato H, He L, Tanigawa T, Nagano H, Dono K, Takeda Y, Okuyama M, Shimizu J, Umeshita K, Nakamori S, Sakon M, Nishisho I, and Monden M
Subjects: Animals, Cell Transplantation, Erythrocyte Transfusion, Male, Polymerase Chain Reaction, RNA, Messenger metabolism, Rats, Rats, Inbred Strains, Rats, Wistar, Spleen metabolism, Spleen pathology, Th1 Cells metabolism, Th2 Cells metabolism, Thymus Gland cytology, Thymus Gland metabolism, Thymus Gland pathology, Chimera physiology, Cytokines genetics, Graft Rejection genetics, Heart Transplantation, T-Lymphocytes, Helper-Inducer physiology, Thymus Gland physiology, Transcription, Genetic physiology
Abstract: Background: Intrathymic microchimerism (MC) is thought to be responsible for inducing allograft tolerance. However, the role of MC in the thymus gland after transplantation, particularly in the rejection response, is unknown. We investigated serial changes in intrathymic cytokine production associated with MC and allograft rejection., Methods: Donor-specific cell injection (DSI) and heterotopic heart transplantation (HTx) were performed in the fully allogeneic combination using DA rats (RT1a) as donors and WS rats (RT1k)as recipients. MC was checked by polymerase chain reaction (PCR) using a donor RT1.Bbeta domain 1 region sequence-specific primers. Reverse transcription (RT)-PCR analysis of cytokine (interleukin [IL]-2, interferon-gamma, IL-4, and IL-10) profiles of the thymus was performed in animals given DSI, HTx, or DSI/HTx., Results: DSI alone resulted in an immediate development of MC, detected by PCR, in various organs including the thymus, spleen, liver, and blood, of most rats, lasting for over 2 months. However, DSI-induced MC selectively disappeared in the thymus on day 7 after grafting, several days before the rejection of cardiac allograft. RT-PCR analysis of cytokine profiles showed that the levels of Th1 (IL-2 and interferon-gamma) cytokines transcribed in the thymus were higher than in the spleen. MC reappeared in the thymus on day 21 after grafting, but was not associated with elevation of Th1 cytokine transcription when allograft was replaced by fibrosis., Conclusions: Intrathymic MC does not always confer unresponsiveness to alloantigen, but can be eliminated after anti-donor response.
Published: 1999
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48. [Features of colorectal cancer with fecal-occult-blood tests--comparison with colorectal cancer with no screening].

Author: Takemasa I, Kikkawa N, Yasui M, Nishisho I, Fujitani K, Mishima H, Hasuike Y, and Kobayashi K
Subjects: Colorectal Neoplasms mortality, Colorectal Neoplasms pathology, Female, Humans, Japan epidemiology, Lymphatic Metastasis, Male, Mass Screening, Prognosis, Survival Rate, Colorectal Neoplasms diagnosis, Occult Blood
Abstract: Background: There is now evidence from three randomized controlled trials (from Minnesota, Nottingham and Funen) that screening average-risk individuals for colorectal cancer (CRC) with fecal-occult-blood tests (FOBT) can reduce mortality from CRC. In Japan, mortality rates from CRC have increased and mass screening with FOBT has been performed since 1992. Although there is growing proportion of CRC with FOBT, there is no conclusive evidence that they reduce mortality from this cause. We evaluated the feature of CRC with FOBT, as one of the methods for evaluation of the efficacy of screening with this test., Methods: Between January, 1982 and December, 1996, 2071 cases with CRC resected in our hospital were considered. We evaluated the clinicopathological findings about age, sex, location of tumor, size depth, incidence of lymph node metastasis, stage and prognosis of CRC with FOBT (376) compared with CRC with no screening (controls; 1695)., Results: CRC with FOBT were earlier stage and smaller-sized cancers than controls. No significant difference was found in the incidence of lymph node metastasis at each depth and prognosis in each stage., Conclusions: By screening with FOBT, we can detect at an earlier stage and with a smaller cancer, with the same biological behavior as controls. Now, we must encourage colon screening, continuing to research ways to improve identification of high-risk subgroups and increase complicance.
Published: 1998

49. [Growth and development of colorectal cancer with subclassification on submucosa and proper muscle infiltrating cancer].

Author: Takemasa I, Nishisho I, Fujitani K, Shin E, Mishima H, Hasuike Y, Kobayashi K, Kobayashi T, Kikkawa N, and Takeda M
Subjects: Adenoma pathology, Carcinoma pathology, Cell Division physiology, Colorectal Neoplasms classification, Female, Humans, Male, Middle Aged, Neoplasm Invasiveness, Colorectal Neoplasms pathology, Intestinal Mucosa pathology
Abstract: Colorectal cancer (CRC) infiltrating the submucosa (sm cancer) and the proper muscle (mp cancer) represent an early and an intermediate stage in the development of CRC, and sm and mp cancer are therefore appropriate to discuss the natural history of CRC. A total of 337 sm cancers and 291 mp cancers resected in our series were evaluated. We divided sm and mp cancers into three categories, respectively, sm 1, sm 2, sm 3, mp 1, mp 2, and mp 3, according to the depth of infiltration of the submucosa or the proper muscle. The deeper the invasion, the larger of the tumor size, and the proportion of depressed type in their configuration increases. On the contrary, the proportion of tumors with adenomatous component decreases. A larger proportion of tumors in all categories of infiltration showed PG more of ten than that of NPG in their marginal structure. In this study, 17% of sm cancer and 23% of mp cancer might develop not via the adenoma-carcinoma sequence.
Published: 1998

50. Detection of K-ras gene mutations in plasma DNA of patients with pancreatic adenocarcinoma: correlation with clinicopathological features.

Author: Yamada T, Nakamori S, Ohzato H, Oshima S, Aoki T, Higaki N, Sugimoto K, Akagi K, Fujiwara Y, Nishisho I, Sakon M, Gotoh M, and Monden M
Subjects: Adenocarcinoma blood, Adenocarcinoma surgery, Adult, Aged, Base Sequence, Chronic Disease, Codon, DNA Primers, Female, Humans, Male, Middle Aged, Neoplasm Staging, Palliative Care, Pancreatectomy, Pancreatic Neoplasms blood, Pancreatic Neoplasms surgery, Pancreatitis blood, Pancreatitis genetics, Pancreatitis pathology, Polymerase Chain Reaction, Reference Values, Adenocarcinoma genetics, Adenocarcinoma pathology, DNA blood, Genes, ras, Pancreatic Neoplasms genetics, Pancreatic Neoplasms pathology, Point Mutation
Abstract: We investigated the presence of K-ras gene mutation in plasma DNA and assessed its clinical value in patients with pancreatic adenocarcinoma. Mutations in codon 12 of the K-ras gene were examined by mutant allele-specific amplification method using DNA extracted from surgical specimens and plasma samples of 21 patients with pancreatic adenocarcinoma. K-ras gene mutation was detected in 15 of 21 (71%) primary tumors. In 9 of 15 (60%) patients with K-ras gene mutation-positive tumors, an identical mutation was detected in the plasma DNA. None of four patients with chronic pancreatitis or five healthy subjects had such mutations in plasma DNA. Tumors positive for K-ras gene mutation in plasma DNA were significantly larger (P = 0.04) and less likely to result in a curative cure after surgical resection (P = 0.09) than those negative for the mutation. Other clinicopathological features, including age, sex, histological type, mode of invasion, and metastasis, did not correlate with K-ras gene mutations in plasma DNA. Treatment resulted in disappearance of K-ras gene mutations in plasma DNA in six of nine (67%) patients. Three patients with a persistently positive K-ras gene mutation in pre- and post-treatment plasma samples were likely to show early recurrence or have a progressive disease. Our findings suggest that K-ras gene mutation can be detected in plasma DNA of patients with pancreatic adenocarcinoma. Detection of K-ras mutations in plasma may be clinically useful for evaluating tumor burden and efficacy of treatment.
Published: 1998

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