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Start Over Author "T. Shiroyama" Journal annals of oncology
4 results on '"T. Shiroyama"'

1. Extension of Surgical Indication for Gastric Cancer with Peritoneal Metastasis by Intraperitoneal Chemotherapy

Author

F. Imamura, Daisuke Makiura, Y. Goda, Y. Hashiguchi, M. Mizuta, N. Sugimoto, S. Fujita, Shinya Ueda, S. Ozaki, M. Kawayama, M. Niimi, Kojiro Futagami, N. Matsubara, T. Tamaki, M. Fukushima, K. Hirokaga, Won Seog Kim, A. Koyama, K. Matsumoto, H. Kusumoto, Y. Yoshida, T. Sasatomi, H. Akamatsu, A. Ohtsu, I. Sasaki, X. Liu, T. Ura, Chandra P. Belani, H. Yamamoto, K. Watanabe, N. Hokamura, H. Fukushima, H. Nishizaki, K. Yonesaka, Noriaki Ohuchi, S. Takao, H.-J. Tsai, Dimitri Pchejetski, K. Sunami, H. Fujimoto, J. Zhang, H. Samura, Tomoko Oku, M. Mori, Eiji Oki, T. Yano, N. Yamamoto, J. Tsukada, Yasutaka Sukawa, Kazuyoshi Yanagihara, A. Goy, J. Inoue, Kazuto Nishio, Y-C Chang, L. Wang, N. Kotani, M. Inomata, T. Nishimura, C.-C. Lin, N. Aisu, R. Saura, M. Makino, Hideki Shimodaira, Y. Fujishima, Satoshi Watanabe, H. Tanaka, Akiko Hisamoto, Koichi Akashi, J. E. Jang, T. Nobuoka, Chihiro Makimura, Taichi Isobe, T. Takahashi, C. Morizane, S.-M. Chang, N. Takigawa, F. Lv, N. Katagami, A. Kumagai, Takahide Komori, Koichi Hirata, N. Okamoto, A. Makiyama, Y. Takahashi, Hideyuki Hayashi, S. Iwasa, J.-C. Lin, J. S. Kim, K. Eguchi, A. Yokoyama, H. Kunimoto, M. Inoue, L. Sauer, H. Ueno, M. Nakano, A.-H. Kwon, Kiyoshi Ando, H. Nishimura, M. Kaibori, S. Arita, K. Tauchi, Erina Hatashita, H. Yoshioka, Ikuo Sekine, S. Iida, S.-F. Lin, J. Cao, H. Horinouchi, S. Atagi, H. Harashima, Hironori Ishigami, H. Isobe, Yoshimitsu Kobayashi, Shinichi Nishina, M. Motonaga, Tokuzo Arao, M. Edagawa, Kazuo Shirouzu, Kei Kawana, A. Kitamura, Emiko Sakaida, T. Ozaki, H. Fukada, Hiromichi Ishiyama, A. Tsuya, Manabu Muto, K. Takizawa, Satoru Kitazono, H. Uemura, T. Nakagawa, S. Kondo, Naoto Takahashi, Hisato Kawakami, M. D. Galsky, Shigeki Ito, Yoshihiko Maehara, S. Negoro, H. Matsushita, M. Kashiwa-Motoyama, Yoshinori Imamura, Kunio Okamoto, T. Ecke, Miyako Takahashi, T. Matsuno, K. Itoh, K. Tanaka, Kazuo Tamura, Y. Suzuki, A. Iwashima, K. Katayama, Tsuyoshi Shirakawa, M. Ohtsu, Ryohei Sasaki, M. Hayashi, M. Egyed, M. Tateyama, M. Munakata, T. Nomizu, T. Muta, T. Terauchi, Shin Takahashi, Y. Kohjimoto, I. Kawase, L. Qiu, Nozomi Niitsu, Y. Nishida, Hironori Yamaguchi, T. Sawai, T. Nakajima, Takanori Ishida, Tatsuo Oyake, M. Nagase, T. Yoshinami, Y. Sakata, Chiaki Imai, M. Kitazono, W. K. Oh, H. Kataoka, Y. Kakechi, Y. Terasaki, T. Miyagishima, Akira Yamada, A. Ono, R. Konno, M. Higashiguchi, Y. Namba, Hiroshi Kagamu, Eiki Ichihara, H. Nakasa, T. Yagi, Y. Tamaki, T. Onoe, N. Sonoda, Kazuhiko Nakagawa, H. Yamana, M. Sasaki, Yoji Ishida, K. Kaira, S. Yokoyama, W. Li, M. Tanioka, Eishi Baba, Hitoshi Kusaba, H. Suzuki, Sung Yong Oh, N. M. Hahn, Tomoko Kataoka, M. Mikami, Chikatoshi Katada, Y. Narita, J. Leach, T. Uehara, K. Miura, S. Yamamoto, O. Kobayashi, Kentaro Yamanaka, Katsuyuki Kiura, S. Hua, H. Miyao, Y. Kodama, Isamu Okamoto, K. Mikami, T. Hirashima, E. Konno, Naoko Chayahara, Junta Tanaka, Chang Fang Chiu, Hironobu Minami, Tadashi Hasegawa, Atsuo Okamura, T. Okusaka, K.-I. Nishiyama, M. Satouchi, Y. Maekawa, T. Kato, Rei Ono, F. Hongo, Mamoru Watanabe, T. Miki, M. Ogura, Masato Komoda, S. Natsugoe, Yuichi Takiguchi, I. Iwanaga, Hiroshi Soeda, Y. Fujiwara, M. Endo, H. Yasui, S. Katano, Satoshi Yuki, K. Nagai, H. Tsukuda, Jun Koshio, I. Hara, J. Tomomatsu, M. Kudo, Kenichi Yoshimura, T. Esaki, Satoshi Morita, R. Udagawa, M. Nakamura, S. Miura, K. Iwata, W. Su, N. Nonomura, S. J. Kim, Y. Omori, T. Shukuya, S. Y. Hyun, H. Hara, Yasunori Emi, M. Nezu, S. Tanimura, Koji Wada, Y. H. Min, D. Y. Hwang, Yoshito Komatsu, S. Takaishi, Kazuhiko Kobayashi, Mayumi Ono, K. Sato, Yuka Kato, T. Mine, S. Egawa, J. Li, N. Matsumura, Y. Tsuji, Hiroyuki Hata, Hirohisa Yoshizawa, S. Sogabe, Y. Guo, D. Kuroda, Chih-Cheng Chen, T. Takano, X. Hong, Y. D. Kim, K. Oda, Shoji Tokunaga, Masahiro Nozawa, Takeshi Sugawara, T. Fukui, Y. Saito, T. Fukuda, Yasuhisa Shinomura, Y. Yamashita, T. Minami, H. Mukai, Y. Ito, Ayumu Hosokawa, Hiroshi Nakatsumi, Y. Ohoka, S. Matsuyama, H. Takase, T. Akimoto, M. Ishizaki, T. Nakamura, Masahiro Tabata, T. Shimada, K. Shitara, Kimiharu Uozumi, T. Shiroyama, A. Umeta, N. Akakura, T.-Y. Chen, Kiyoko Kuwata, S. Emoto, Y. Naito, O. Muto, Cheolwon Suh, H. Oda, S. Fujii, Kenichiro Kudo, H. Hino, N. Morishita, Hiromichi Matsuoka, Y. Adachi, K. Minato, W.-Y. Kao, K. Hatake, Kosuke Ichikawa, Wataru Okamoto, S. H. Yoon, N. Wada, K. Uchida, U. Fujii, Ih-Jen Su, E. Vandendries, H. Ootsuka, Mitsuaki Tatsumi, K. Hatanaka, K. Matsui, M. Saijo, Fumihiko Fujita, W.-L. Hwang, Y. Negoro, M. Asanabe, Aya Kita, Hideo Baba, H. C. Chung, H. Igaki, J. Hashimoto, Yohei Funakoshi, Ukihide Tateishi, Masanori Toyoda, T. Feldman, Y. Kimura, T. Kondo, Yoshito Akagi, T. Kojima, A. Bamias, D. Takahari, Katsuyuki Hotta, K. Tobinai, K. Yamazaki, A. Volkert, T. Miyake, Hiroharu Yamashita, H. Iishi, Kazunori Murai, Y. Hata, M. Ri, H. Tomioka, S. Kato, M. Fukuoka, Y. Nakamura, Naomi Kiyota, Yee Soo Chae, T. Kimura, N. Gondo, Hiroshi Saeki, G. Sonpavde, H. S. Eom, K. Tane, Yasuo Ohashi, Yasuyuki Kawamoto, T. Beppu, T. Naito, M. Iwasaku, T. Ueda, R. Nakatake, Y. Umeyama, Takayasu Kurata, H. Kenmotsu, Hironori Ashinuma, Y. Miura, Ken-ichi Nibu, Y. Ogata, Toshihiro Miyamoto, N. Uike, K. Muro, S. Goya, Yasushi Takamatsu, Ichiei Narita, Chikashi Ishioka, T. Sueta, Satoshi Takeuchi, M.-C. Chang, Y. Iwanami, Yasuo Hamamoto, H. Kashihara, Yoshikazu Kotani, H. Daiko, Y. Kakugawa, J.-W. Cheong, T. Oochi, Joji Kitayama, K. Matsuo, M. Tamiya, Tzeon Jye Chiou, T. Sugiura, K. Kato, S. Krege, Masatomo Otsuka, A. Kitao, Y. Tanaka, Toru Mukohara, Masataka Taguri, Y. Hattori, T. Harada, Y. Hasegawa, S. Hoshino, K. Yoneyama, M. Ikeda, Shingo Tamura, H. Murakami, M. Kitada, K. Yanase, K. Nosho, and C. S. Chim

Subjects
medicine.medical_specialty, Chemotherapy, medicine.diagnostic_test, Colorectal cancer, business.industry, medicine.medical_treatment, Cancer, Hematology, medicine.disease, Gastroenterology, Chemotherapy regimen, Surgery, Metastasis, Oncology, Pancreatic fistula, Internal medicine, medicine, Gastrectomy, business, Laparoscopy
Abstract

Background The prognosis of gastric cancer with peritoneal metastasis is extremely poor. Neither systemic chemotherapy nor surgery alone prolongs survival of patients significantly. Methods Patients diagnosed with advanced gastric cancer underwent staging laparoscopy and received chemotherapy when peritoneal dissemination and/or cancer cells on peritoneal cytology were confirmed. The chemotherapy regimen consisted of S-1, weekly intravenous and intraperitoneal paclitaxel, which was verified in our phase II trial (Ann Oncol 2009). S-1 was administered at 80 mg/m2/day for 14 consecutive days, followed by 7 days rest. Paclitaxel was administered intravenously at 50 mg/m2 and intraperitoneally at 20 mg/m2 on days 1 and 8. Clinical response of chemotherapy was assessed by computed tomography, gastroendoscopy, peritoneal cytology and second-look laparoscopy. Radical gastrectomy was carried out when macroscopic curative resection was made achievable by chemotherapy. Chemotherapy was restarted after operation as soon as possible. Overall survival, relapse free survival, morbidity and mortality of gastrectomy were evaluated. Results Out of 100 patients with peritoneal metastasis who received chemotherapy, 60 patients underwent gastrectomy after response to chemotherapy, including 54 with macroscopic metastasis and 6 with positive peritoneal cytology only. A median of three courses were administered preoperatively (range 1–16). Total or distal gastrectomy with lymphnode dissection was carried out in 54 or 6 patients, respectively. The median survival time was 34.5 months. The median relapse-free survival was 16.7 months. The first site of relapse was the peritoneum in 24 patients and the other organ site in 17 patients. Postoperative complications included anastomotic leakage and pancreatic fistula in two patients each, which were healed conservatively. There were no treatment-related deaths. Conclusions Gastrectomy combined with S-1, intravenous and intraperitoneal paclitaxel is safe and active for gastric cancer patients with peritoneal metastasis.

Published
2012

2. SRPX2 is a Novel Chondroitin Sulfate Proteoglycan that is Overexpressed in Gastrointestinal Cancer

Author

T. Hirashima, Y. Omuro, C. Kondo, T. Kanematsu, K. Muraki, Po-Chuan Wang, K. Ishiguro, Young-Ae Park, C.-Y. Lu, C.-C. Liao, H. Tei, H. Takeyama, M. Toishi, A. D. Abdullah, M. Terada, K. Yamamoto, N. Yamamoto, K. Fujii, M. Sugimoto, H. Kakizaki, K. Shinozaki, Y. Okada, Yoko Inaguma, S. Shimizu, Shigeki Ito, H. Y. Lim, N. Nogami, N. Awata, M. Nishioka, H. Ueoka, Tomoya Ishii, Y. Ahn, Kazumichi Kawakubo, Y. Aoyagi, C. Nishijima, R. Kameda, A. Okamoto, Y. Yamashita-Kashima, H. Suzuki, K. Yamao, A. Yonemori, H. Fukuda, H. Katayama, K. Honoki, T. Nomura, Y. Tono, T. Shimoyama, J. Nagano, H. Miyamoto, Y. Takeda, M. Fukutake, N. Katsumata, S. Fujita, K. Fujimoto-Ouchi, D. Tamura, H. Obaishi, S. Mitsunaga, J.-H. Baek, Yuichiro Tada, K. Uno, S. Oura, M. Nakamura, Y. Imanura, Atsushi Kumanogoh, M. Manabe, Kaoru Tanaka, T. Yokota, K. Saito, K. Tamura, Yukihiko Fujii, T. Lim, Toshihiko Tomita, C. Seki, Masafumi Taniwaki, Tomohide Sugiyama, N. Kunami, T. Yoshino, Y. Takeoka, T. Yoshikawa, Won-Suk Lee, M. Hattori, H. Yasui, T. Motoya, T. Nishizaki, N. Kouge, E. Sato, S.H. Park, J.H. Hong, N. Mori, M. Tajika, K. Yasuda, Mika Nakamae, Kazuya Fukuoka, T. Shimomura, A. Suzuki, M. Arima, Hideo Koh, S. Tokunaga, N. Miyamoto, Masao Nakata, T. Ueda, Hideharu Kimura, H. Nakano, Kimikazu Yakushijin, M. Hayashi, K. Ishitani, K. Yoshida, T. Takeuchi, Shohei Yokota, K. Hirano, N. Horikawa, S. Bandoh, G. Naka, Y. Seki, M. A. De Velasco, F. Tanikawa, S. Hirano, S. Ohkawa, S. Kadowaki, M. Sakurai, R. Kaji, J.-I. Lee, K. Kitahara, K. Nihei, T. Sumi, Meiki Fukuda, S. Park, K. Nosaka, T. Maeda, O. Morimura, G. Sano, H.-L. Wu, Haruhiko Hirata, Mizuki Aimoto, Y. Igeta, K. Itoh, Y. Ikari, Kentaro Iwanaga, K. Itatsu, Akira Ueda, C. Oabata, H. Fujiwara, T. W. Kim, K. Misu, H. Mikayama, K. Morise, K. Nagata, M. Sato, Takashi Kijima, Kazuo Kasahara, Takahiro Mori, N. Mizuno, Y. Fujitani, Abdul Aziz Baba, K. Takashima, Kazuhide Higuchi, J.-C. Jo, G. Tamaki, S. Magoshi, R. Watanabe, A. Abe, M. Iino, H. Goto, Junji Tsurutani, Y. Katashiba, K. Kato, K. Hosono, L. Y. Kwan, Y. Okabe, N. Takeuchi, Chih-Hsin Tang, I. Kawase, Takayuki Kii, D. Kishino, K. Matsuura, K. Isobe, K. Monden, H. Udagawa, K. Kim, M. Tada, Kazuyoshi Yanagihara, Cheryn Song, T. Terui, Yasuhito Fujisaka, I. Yamaguchi, Hirokazu Fukui, K. Naito, T. Suzumura, H. A. Jung, N. Ureshino, Wataru Okamoto, H. Miyawaki, N. Nakamura, T. Tsukazaki, K. Furuta, K. Matsuda, S. J. Lee, Y. Ishiura, J.-L. Lee, Y. Kato, Shinichiro Hayashi, Y. Horita, J. H. Kim, Y. Tsutsumi, M. Inaoki, K.-P. Kim, Y. Ishigatsubo, T. Mikawa, M. Yamane, A. Husin, Yasufumi Takeshita, S. Kobayashi, N. Kubo, N. Hosono, Yeong-Shiau Pu, M. Ando, Keita Kudo, Hitoshi Nishitani, M. Mori, H. Daga, T. Fukuda, A. Nakaya, N. Fuse, I. Miki, W. Yamamoto, M. Fukushima, T. Ikezoe, H. Ueno, J.-H. Ahn, T. Matsumoto, A. Kuwahara, T. Ogura, N. Hirai, S. Mizuta, A. Ochiai, N. Masumori, S. Kim, Y. Ohki, Yoshinori Imamura, T. Tamaki, K. Nishino, Y. Aoyama, T. Ogawa, T. Koyama, M. Morise, K. Kawada, T. Masaki, Keishi Yamashita, S. Yamamoto, K. Tanimoto, M. Hori, Atsuo Okamura, Masataka Ikeda, K. Oishi, H. Hashimoto, Y. Ohe, M. Yasui, Y. Akatsuka, F. Imamura, Y. Hirayama, Ho Young Kim, S. Kishi, M. Jung, Y. Inukai, K. Miwa, S.-H. Nam, T. Hishima, T. Okusaka, Y. Horiuchi, A. Ioka, W. Fukushima, M. Yamauchi, N. Hokamura, K. Hirata, Y. Katou, K. Tada, K. Suzuki, K. Teramoto, Syusai Yamada, M. Iikura, Takeo Shimasaki, Y. Inoue, K. Kawahara, T. Kitani, H. Sawai, T. Terashima, K. Honda, Hitomi Umeguchi, Masataka Okamoto, M. Kita, Y. Yatabe, Y.-M. Cho, Sojiro Kusumoto, K. Hokkoku, Takaaki Sasaki, Masayuki Hino, M. Omi, H. Tanaka, S. Kawazoe, M. Sakai, H. Tsuchihashi, Kazushi Endo, R. Mauchi, K. Ohashi, H. Takasaki, N. Naganobu, K. Aoe, S.Y. Oh, C. Honma, Takahiro Miyamoto, K. Yamazaki, M. Fujii, T. Fujisawa, S. Morikawa, T. Yamauchi, Masayoshi Kobune, K. Kuwano, T. Onikubo, M. Kuyama, M. Asayama, T. Kozuki, M. Kanie, Masahiko Shibuya, Y. Yamamoto, N. Morishita, Y. Yoshii, Toru Mukohara, K. Izumi, Y.S. Park, N.-R. Lee, Y. Horio, K. Nakamura, M. Matsuda, K. Sugino, S.H. Lee, S. Ueno, Tsutomu Sato, Y. Hasumi, H. Yamamoto, T. Karasuno, Yong Chan Ahn, M. Kitamura, Y. Namba, K. Karasawa, S. Hayasi, K. Hashimoto, Y. Ozaki, Takayuki Takahama, A. Todaka, M. Inoue, S. Boku, A. Ohtsu, Tadashi Matsunaga, K. Togitani, H.-H. Wu, Hirofumi Kogure, H. Kitamura, T. Matsuzaki, M. Gouchi, Hyun-Jin Kim, T. Shiroyama, K. Okada, Y. Terasaki, K. Park, H. Katou, N. Kobayashi, D. Mohri, Y. Hasegawa, T. Yoshimasu, Masahiro Tabata, S. Hijioka, Y.-Y. Chen, Shinji Nakao, M. Kodaira, Akihiko Gemma, T. Yoshida, Hiroya Takiuchi, Masaki Fujimura, A. Shimoda, Hiroyuki Isayama, K. Ohta, T.-L. Chen, T. Maruyama, K. Maruyama, K.-W. Lee, Takashi Hirose, Y. Fujita, H. Kato, Maya Watanabe, S. Iwasa, H. Okuyama, Cherry Wu, A. Hata, K. Myo, M. Takase, Y. Urasaki, K. Shingu, Shingo Nishikawa, M. Tsuzuki, I. Hoshi, T. Maruo, Hiroki Yoshita, Hirohisa Nakamae, Shigeru Hatabe, Hideko Ikeda, Hayato Koba, Y. Hata, S. Matsushima, M. Yunokawa, S. Tamaru, J. S. Ahn, T. Funakoshi, S.-J. Jang, S. Kageyama, K. Nakagawa, H. Nishimori, Eizaburo Sueoka, K. Hashidume, S. H. Hong, Atsushi Kawaguchi, Tomomi Nakamura, H. Kaneko, A. Seki, K.-L. Tan, T. Ichimura, Y. Matsuda, M. Nezu, M. Kudo, H. Fujii, K. Shibata, S. J. Sym, K. Takeuchi, Chiharu Tabata, M. Takeshita, Y. Ueda, A. Nakayama, N. Nishiyama, Sang We Kim, Y. S. Kim, H. Suzushima, S. Soma, K. Miura, H. Gonda, D. Gomi, A. Mogi, K. Ishizuka, T. Mizutani, Y. Yamada, A. Sato, G. Kaneko, T. Samejima, R. Shimabukuro, Masahide Fujita, K. Horie, R. Ohhashi, T. Wakasa, H. Nomura, K. Sato, T. Hamaguchi, S. Horiguchi, M. Ootsuka, S. Kawabata, Y. Okamoto, A. Yoshida, H. Takeda, M. Sugiyama, Y. S. Hong, Y. Yanagita, Yasushi Ichikawa, K. Tomii, T. Enokida, Tzyh-Chyuan Hour, Y. Takeyama, Y. Matsuura, Y. Kakehi, S. Kanazawa, S. Kimura, T. Yamada-Murano, D. Abe, Nagio Takigawa, T. Yana, A. Ogino, R. Sakai, S. Watanabe, K. A. Kwon, Y. Nakai, O. Watanabe, Naokatsu Nakada, Masanori Toyoda, H. Inomata, R. Sekine, J. S. Lee, T. Shukuya, O. Ishiko, Y. Ikeda, K. Nakase, S. Kuzu, H. Mukai, K. Ozaki, R. Koyama, Takashi Nakano, K. Hashizume, E. Noguchi, N. Hida, Y. Takamatsu, Tomoko Yamagishi, H. Agatsuma, S. Miyamoto, D.H. Lee, H. Kunimoto, H. Ogino, T. Miya, Naoki Sasahira, A. Yamane, T. Takami, N. Imai, Y. Fukui, Tae Min Kim, T. Kita, Jiro Watari, H. Kawabata, N. Motohashi, K. Aomatsu, T. Obayashi, H. Hayashi, S.-H. Li, S. Sakata, H. Okada, K. Masa, T. Iwata, H. Yoshida, Tokuzo Arao, R. Hassan, H. Imaoka, M. Kobayashi, H. Iwasaki, K. Nomura, H. Harada, T. Watanabe, K. Kaneko, H. Nakagawa, K. Sakamoto, A. Hiasa, Katsuyuki Hotta, Nobuhiko Emi, S. Maruyama, M. Yonemura, H. Tsurumi, Takuhiro Yamaguchi, M. Nagata, T. Nakai, Motoki Yoshida, S. Motomura, A. Sakai, H. Inoue, Toshimitsu Yamaoka, T. Morikita, S. Hirokawa, Hideaki Ijichi, Namiki Masayuki, Meiko Nishimura, Y. Ishii, A. Shimatani, Jong-Hyeok Kim, M. Ujihara, Yuko Kanbayashi, Y. Nakashima, T. Hosoda, K. Sanada, S. Kondo, Y. Honma, S. Sakamoto, H. Kubo, M. Kondo, F. Nomura, M. Hashizume, T. Shiraishi, B.-S. Kim, T. Kouno, T. Maki, H. Akaike, Z. Saito, Junya Fukuoka, T. Ohnishi, C. H. Maeng, M. Wada, Jong-Mu Sun, C. Morizane, Y. Matsumoto, K. Migita, Y. Okamura, Sun Young Rha, Hiroyoshi Ichihara, J. Kato, N. Yoshimura, W.-J. Wu, N. Wada, M. Yoshihara, K. Hamai, Kazuhiko Koike, Woo Kyun Bae, Y. Maeda, S. Mimura, Y. Sakai, H. Wakasugi, H. Nishimoto, M. Nagano, K. Taira, I. Park, T. Inokuma, Katsuhiko Shimizu, Y. Nakahara, S. Okamura, K. Ogawa, F. Saito, Y. Miura, Hyo Jin Lee, K. Fujita, K. Takagi, T. Shiina, Charny Park, Shin Kuwakado, N. Moto, Y.-C. Chiu, S. Saji, T. Araya, J. Takeshita, H. Iwase, Naoe Goto, H. Murakami, T. Hayashi, K. Otsuka, Rishu Takimoto, H. Nakahama, C.-C. Shih, Naoko Aragane, S. Hamauchi, H. K. Ahn, N. Tomita, N. Chyayahara, T. Hida, K. Watanabe, Y. Kokubo, N. Katusmata, L. K. Chi, M. Okumura, T. Kusakabe, S. Homma, H. Nakagomi, Hiroo Katsuya, D. B. Shin, Naoko Chayahara, F. Fukuta, Kazutoshi Shibuya, Ayumu Hosokawa, F. Ota, R. Yoshino, M. Goto, Y. Shibata, J. E. Kim, H. Watanabe, K. Mandai, T. Shimamura, S. Inoue, M. Fujimoto, S. Mitsuoka, Kunio Okamoto, M.-J. Kim, E. Chung, H. Moriwaki, Y. Misumi, S. Ogawa, K. C. Lee, J.-O. Lee, H. Hirosawa, Yoshiki Terada, A. Kinoshita, J. Hong, Y. J. Kim, A. Kido, M. Kijima, Y. Shiota, H. Hayase, A. Sekikawa, M. Ahn, K. Komuta, M. Sasaki, T. Murakami, M. Okuda, N. Matsubara, R. Saitou, R. Nakamura, K. Masuo, Kazuko Matsumoto, K. Mouri, Y. Ookuma, Kazutoshi Komiya, K. Sakai, N. Yogo, Takahiko Nakane, M. Mukai, Isao Tachibana, Shiro Kimbara, Kentaro Okuda, T. Fujisaki, S.-J. Chuang, Y. Niwa, H. Oda, Y. Nishida, T. Ando, Yuichi Ando, J. Tong, C. Shimizu, J. Choi, Satoshi Iyama, H. Imai, K. H. Park, T. Misao, Yohei Funakoshi, Chang-Sik Yu, Tadashi Kimura, J. Hori, M. Itoh, S. Ebihara, S.-H. Gan, T. Yano, H. Okamoto, E. Fukutani, U. Tateishi, T. Ishihara, Takuro Yoshimura, T. Shinkai, A. Yokoyama, T. Kikuchi, Y. Yamashita, K. Hagiwara, Y. Noda, Y. Oyama, K. Okuno, Naomi Kiyota, K. Yonemori, K. Kuramoto, T. Shimoi, H. Hong, Ryuya Yamanaka, E. Matsuki, O. Kondo, H. Gondou, Yusuke Nakamura, M.-J. Ahn, Yoshiki Hayashi, Shiro Koh, S. Kosaka, Masahiro Gotoh, S. Mizuno, H. Nakamura, S. Okazaki, E. Ichiki, M. Ishizu, K. Ishikawa, Hiroyasu Kaneda, R. Yamamura, Tomonobu Koizumi, R. Ankathil, T. Takahashi, S. Nakatsuka, A. Kamuro, M. Ueno, T. Eguchi, S. Hirai, G. Saito, S. Kudoh, Masanao Nakashima, N. Okamoto, K. Akiyoshi, Hironobu Minami, K. Kubota, K. Okafuji, M. Aoe, T. Ito, K. Nishimura, S. Ota, C. Wong, A. Ooki, Takao Shirai, Wen-Yi Chou, M. Tamiya, H. Tabuse, Y. Kaneko, Y. Shimizu, Y. Murata, A. Okada, S. Sasada, Y. Takagi, A. Naitou, N. Katayama, Kaori Ito, T. Araki, Y. Fujiwara, H. Yokota, Shinya Kajiura, M. Imano, T. Iwai, T. Kobayashi, T. Kubota, N. Kanaji, M. Ohdate, T. Tsukamoto, S. Zenda, A. Fukutomi, T. Kumura, R. Ogawa, K. Shintaku, Kazuto Nishio, T. Morimoto, W. Shioyama, E. K. Cho, H.-I. Lu, Y. Suginoshita, K. Yamaguchi, Y. Shindo, N. Hirokami, J. Shimizu, Chihiro Makimura, K. Araki, T. Taniyama, T. Tanaka, Y. Tanbo, Hiroto Miwa, Y. Hirai, J. Park, Asao Hirose, M. Doi, A. Goto, S. Nomura, S. Ikegaya, A. Yoshii, M. Akahane, T. Kakuma, K. Miyabayashi, S. Y. Kim, H. Kitade, B. Han, K. Yamada, Tadayuki Oshima, J. Ishizawa, M. Miyata, E. Sasak, R. Aibara, N. Takahara, S. Kanno, T. Kojima, I. Ohno, E. Sasaki, E. Tone, A. Morita, R. Suzuki, Yukio Hosomi, Hiroo Ishida, T. Akimoto, N. Hashimoto, T. Takakuwa, K. Umekawa, A. Toyoshima, K. Hara, J. Kitagawa, H. Taniguchi, T. Kamiya, M. Takai, Y. Watanabe, Yasuhito Tanaka, A. Sawada, T. Yasui, Y. Onozawa, Akihiro Hirakawa, S. Okamoto, K. K. Kim, Y.-M. Wang, Y. Takai, T. Tsumura, H. Hirama, Shigeo Horiike, K. Kawasumi, N. Shimeno, Junya Kuroda, C.-Y. Huang, Y.-H. Chen, H. Ogata, S. Matsumoto, I. Takahashi, Hideo Tomioka, I. Okamoto, Itaru Endo, T. M. S. Kam, K. Sekihara, C.-T. Liu, K. Chikamori, N. Hirota, K. Hiramatsu, D. Hamaguchi, T. Nishii, N. Ohmiya, T. Shimizu, T. Sakaizawa, Hiromichi Matsuoka, K. Kawa, J. H. Ji, S. Izumi, T. Hara, Y. Tsuyumu, T. Oguri, T. Akiyama, Y. Ichida, A. Simoyama, T. Hirakata, Y. Yoshimitsu, Y. Sasaki, T. Yamazaki, T. Tsushima, R. Okamoto, Y. Tsukioka, Nobuhiko Seki, S.-M. Bang, Y. Kubota, N. Harada, C.-H. Huang, J. Y. Hong, T. Andou, T. Shimada, T. Doi, Yoshihiro Ono, S. Nanjo, H. Hara, Y. Kikukawa, M. K. Choi, K.-M. Rau, Y. Tomizawa, O. Maeda, K. Ishida, Y. Naito, N. Machida, T. Otsuka, T. Hase, H. Morishita, K. Fukuhara, M. Yoshino, M. Takahashi, H. Takahashi, Heui June Ahn, M. Nisimoto, Y. Sunakawa, Y. Miyakawa, Choung Soo Kim, S.-W. Wang, Takashi Sone, M. Iguchi, T. Shimokawa, Tomoyuki Nagai, K. Morioka, A. Numata, R. Toyozawa, R. Miyahara, Y. M. Ahn, Hyo Song Kim, D. W. Hwang, H. Takamori, Shin-Hee Lee, Narikazu Boku, T. Mizuno, N. Katakami, J. H. Lee, Y. Okuma, Koji Kurokawa, K. Takeda, N. Sakiyama, R. Tachikawa, Satoshi Morita, T. K. Fai, K. H. Seong, K. Yorozu, T. Okamura, Ryo Takahashi, T. Kotake, Y. Arai, T. Kawamura, K. Yakushijinn, Y. Shimada, H. Sugiyama, S. Kamachi, A. Mugitani, T. Yasue, Y. Sugihara, S. Shu, Y. Osaki, Kazuhisa Takahashi, Y. Hashiguchi, K. Funasaka, Y. S. Koo, Tohru Ohmori, S. J. Koh, N. Kanemura, H. Kotani, M. Hsin, T. Kagoo, and A. Inoue

Subjects
biology, Molecular mass, business.industry, Angiogenesis, Hematology, Cell biology, chemistry.chemical_compound, Oncology, chemistry, Proteoglycan, Chondroitin sulfate proteoglycan, Cancer cell, medicine, biology.protein, Hepatocyte growth factor, Antibody, Cell adhesion, business, medicine.drug
Abstract

SRPX2 (Sushi repeat-containing protein, X-linked 2) has recently emerged as a multifunctional protein that is involved in seizure disorders, angiogenesis and cellular adhesion. Here, we analyzed this protein biochemically. SRPX2 protein was secreted with a highly post-translational modification. Chondroitinase ABC treatment completely decreased the molecular mass of purified SRPX2 protein to its predicted size, whereas heparitinase, keratanase and hyaluroinidase did not. Secreted SRPX2 protein was also detected using an anti-chondroitin sulfate antibody. These results indicate that SRPX2 is a novel chondroitin sulfate proteoglycan (CSPG). Furthermore, a binding assay revealed that hepatocyte growth factor dose-dependently binds to SRPX2 protein, and a ligand–glycosaminoglycans interaction was speculated to be likely in proteoglycans. Regarding its molecular architecture, SRPX2 has sushi repeat modules similar to four other CSPGs/lecticans; however, the molecular architecture of SRPX2 seems to be quite different from that of the lecticans. Taken together, we found that SRPX2 is a novel CSPG that is overexpressed in gastrointestinal cancer cells. Our findings provide key glycobiological insight into SRPX2 in cancer cells and demonstrate that SRPX2 is a new member of the cancer-related proteoglycan family.

Published
2012

3. A Phase I Dose-Escalation Study of emd 1214063, an Oral Selective CMET Inhibitor, in Patients with Advanced Solid Tumors

Author

M. Boyer, Masahiro Tsuboi, M. Laniado, T. Nukiwa, Kazuhiko Nakagawa, Hirohisa Yoshizawa, S. Kobayashi, Filip Janku, M. Takeda, Manfred B. Klevesath, Jun Sakakibara-Konishi, W. Uhl, K. Arakawa, Akihiko Gemma, N. Omachi, T. Tsuji, A. Tamiya, T. Yoshino, Yoshiki Ishii, N. Yamamoto, G. Falchook, T. Kawaguchi, Satoshi Oizumi, Luis Paz-Ares, Gerald S. Falchook, Andreas Johne, Y-L. Wu, J-C. Soria, Isamu Okamoto, P. Rougier, S. Atagi, A. Campbell, H. Lannert, Razelle Kurzrock, T. Shiroyama, Siquing Fu, K. Asami, H. Isobe, A. Ohtsu, V. Antic, S.-Y. Lee, K. Park, H. Crane, C.-M. Tsai, Sojiro Morita, Ralph Zinner, Jennifer J. Wheler, M. Wirth, Stephen P. Letrent, Sarina Anne Piha-Paul, Pasi A. Jänne, N. Yoshizuka, M. Tamiya, Tony Mok, K. Takeda, Motoki Yoshida, M. D. Rutstein, J.J. Wheler, H. Suzuki, Thierry Gil, H. Tada, S. Ballal, A. Grothey, S. Zastrow, N. Okamoto, Akira Inoue, Y. Ichinose, K. Sugio, S. Minomo, Aung Naing, Ian Taylor, S. Nakamura, Yoichi Nakanishi, Joe O'Connell, Y. Saijyo, J. T.abernero, Jane Q. Liang, F. Nasroulah, Suresh S. Ramalingam, K. O'Byrne, T. Mitsudomi, Axel Heidenreich, N. Morishita, V. Jego, K. Okishio, K. Yamazaki, Jürgen E. Gschwend, T. Hirashima, David S. Hong, M. Zühlsdorf, T. Yamanaka, D.S. Hong, X. Zhang, Apostolia-Maria Tsimberidou, J. Gerloff, A. Miao, Koichi Hagiwara, Kazuhiko Kobayashi, and Hesham M. Amin

Subjects
medicine.medical_specialty, business.industry, Nausea, Cmax, Hematology, Neutropenia, medicine.disease, Asymptomatic, Gastroenterology, Regimen, Oncology, Pharmacokinetics, Pharmacodynamics, Internal medicine, medicine, Carcinoma, medicine.symptom, business
Abstract

Background The cell surface receptor tyrosine kinase c-Met and its ligand, the hepatocyte growth factor (HGF), are implicated in tumor cell migration, invasion, survival and proliferation. EMD 1214063 is a novel potent and highly selective reversible, ATP-competitive small molecule c-Met inhibitor. Methods This is a phase I, first in human (FIH) clinical trial with escalating doses of EMD 121406(NCT 01014936). The primary objective is to determine the MTD. Secondary objectives include evaluation of safety, pharmacokinetics, anti-tumor effect and pharmacodynamics (Pd). Eligible patients had advanced solid tumors not amenable to standard therapies. Following a classical 3 + 3 dose escalation scheme, successive cohorts of patients were treated with once daily oral EMD 1214063 according to two 21-day-cycle schedules, either days 1-14 followed by a 7-day rest(regimen 1, R1), or continuous three times weekly administration (regimen 2, R2). Pd markers were evaluated in paired tumor biopsies. Results As of 30 March 2011, a total of 41 patients had been enrolled, 21 in R1 and 20 in R2. The dose was escalated from 30 mg/day to 115 mg/day in R2 and to 230 mg/day in R1. One DLT was reported in R1 at 115 mg/day, an asymptomatic, grade 4 lipase and G3 amylase elevation. No other DLTs or treatment-related SAEs were observed. The remaining treatment-related AEs of grade 2 or higher included nausea (n = 1), vomiting (n = 1), anorexia (n = 1), diarrhea (n = 1), and fatigue (n = 1) in R1, and neutropenia (n = 1) in R2. 37 patients (90%) had no drug-related toxicity greater than grade 1. At the dose levels investigated, median Cmax and AUC values increased with dose. Immunohistochemical analysis of a patient with pre- and on-treatment biopsies showed a decrease in phospho-c-Met staining intensity under treatment. Preliminary anti-tumor activity has been observed, including an unconfirmed PR in one patient and stable disease lasting for at least 4 months in 5 patients. One patient with sarcomatoid bladder carcinoma and multiple MET copies due to polysomy of chromosome 7 achieved SD for 16+ months. Conclusions The MTD has not yet been reached and dose escalation of EMD 1214063 continues. Updated results of this FIH study will be presented.

Published
2012

4. The Clinical Significance of the Serum Cross-Linked N-Telopeptide of Type I Collagen as a Prognostic Marker for Non-Small-Cell Lung Cancer

Author

T. Shiroyama, M. Tamiya, T. Hirashima, S. Morita, O. Morimura, K. Okafuji, N. Morishita, H. Suzuki, N. Okamoto, M. Kobayashi, and I. Kawase

Subjects
medicine.medical_specialty, Performance status, business.industry, Hazard ratio, Cancer, Hematology, medicine.disease, Gastroenterology, Oncology, N-terminal telopeptide, Internal medicine, medicine, Carcinoma, Adenocarcinoma, business, Lung cancer, human activities, Survival rate
Abstract

The clinical significance of the serum crosslinked N-telopeptide of type I collagen (NTx) as a prognostic marker for non-small-cell lung cancer (NSCLC) was evaluated. We have revealed that a high serum NTx level (>22 nmol bone collagen equivalents (BCE)/L) appears to be a risk factor for a reduction in overall survival in patients with NSCLC. Introduction: Lung cancer is the leading cause of cancer-related death. Many patients with lung cancer are in its advanced stages at the time of diagnosis. The 5-year survival rate for lung cancer is 10% to 20%, and the prognosis for patients with lung cancer is still poor. The crosslinked N-terminal telopeptide of type I collagen (NTx) is a metabolite of type I collagen, the main constituent of bone matrix. Patients and Methods: We measured serum NTx levels in patients who underwent staging during hospitalization for the initial treatment of lung cancer in our department. We examined whether serum NTx levels would be relevant to the prognosis of non-small-cell lung cancer (NSCLC). Results: This study included 176 patients with lung cancer (125 men and 51 women), including 109 with adenocarcinoma, 53 with squamous cell carcinoma, 6 with large-cell carcinoma, and 8 with other cancer types. Univariate and multivariate analysis using the Cox proportional hazards model revealed a particularly close associ- ation between sex, performance status, disease stage, and serum NTx levels and overall survival (OS). A median OS of 368 days was observed for patients with a serum NTx level 22 nmol BCE/L, which was significantly longer than the 197 days for patients with a serum NTx level 22 nmol BCE/L (hazard ratio (HR), 2.02; 95% confidence interval (CI), 1.36-2.99; log-rank P.00037). Conclusions: We have revealed that a high serum NTx level ( 22 nmol BCE/L) appears to be a risk factor for a reduction in OS in patients with NSCLC.

Published
2012

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