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128 results on '"Kenichiro Ito"'

1. Real‐world first‐line treatment with pembrolizumab for non‐small cell lung carcinoma with high PD‐L1 expression: Updated analysis

Author

Yasuyuki Ikezawa, Ryo Morita, Hidenori Mizugaki, Kazunari Tateishi, Keiki Yokoo, Toshiyuki Sumi, Hajime Kikuchi, Yasuo Kitamura, Atsushi Nakamura, Maki Kobayashi, Mari Aso, Nozomu Kimura, Fumiaki Yoshiike, Furuta Megumi, Hisashi Tanaka, Motoki Sekikawa, Tsutomu Hachiya, Keiichi Nakamura, Fumihiro Hommura, Noriaki Sukoh, Kenichiro Ito, Takashi Kikuchi, Toshihiko Agatsuma, and Hiroshi Yokouchi

Subjects
chemotherapy, clinical cancer research, lung cancer, non‐small cell lung cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Background Selecting pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum‐based chemotherapy (COMB) for patients with nonsmall cell lung cancer (NSCLC) and high programmed death‐ligand 1 (PD‐L1) expression is an important issue in clinical practice. We previously conducted a retrospective multicenter observational study of patients with NSCLC and high PD‐L1 expression who received MONO or COMB as a first‐line treatment. Here, we report updated data and evaluate the long‐term outcomes. Methods We performed a retrospective multicenter study of 298 patients with NSCLC and high PD‐L1 expression who received MONO or COMB as first‐line treatment between December 2018 and January 2020. We reviewed the medical records and assessed the clinical efficacy and toxicity using a prolonged data cutoff. Results In total, 164 (median age: 74 years) and 134 (median age: 68 years) patients received MONO and COMB, respectively; patients who received COMB were younger and had better performance statuses (0–1). At the prolonged data cutoff, the median follow‐up was 20.2 (range: 0.1–41.4) months. The median progression‐free survivals were 7.5 and 13.1 months, and overall survivals (OSs) were 17.2 and 33.7 months for MONO and COMB, respectively. Treatment discontinuation rates were 21.9% and 20.1% for the MONO and COMB, respectively. With prolonged follow‐up, although COMB demonstrated an OS benefit and higher objective response rate than MONO, in the propensity score matching analysis COMB didn't demonstrate a significant benefit compared to the MONO. Conclusions COMB may be effective as a first‐line treatment for NSCLC with high PD‐L1 expression in a selected subset of patients.

Published
2024
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2. Real‐world data on the efficacy and safety of immune‐checkpoint inhibitors in elderly patients with non‐small cell lung cancer

Author

Daisuke Morinaga, Hajime Asahina, Shotaro Ito, Osamu Honjo, Hisashi Tanaka, Ryoichi Honda, Hiroshi Yokouchi, Keiichi Nakamura, Kei Takamura, Fumihiro Hommura, Yasutaka Kawai, Kenichiro Ito, Noriaki Sukoh, Keiki Yokoo, Ryo Morita, Toshiyuki Harada, Taichi Takashina, Tomohiro Goda, Hirotoshi Dosaka‐Akita, Hiroshi Isobe, and the Hokkaido Lung Cancer Clinical Study Group Trial

Subjects
elderly patient, immune‐checkpoint inhibitor, non‐small cell lung cancer, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282
Abstract

Abstract Purpose Immune‐checkpoint inhibitors (ICIs) are effective against advanced non‐small cell lung cancer (NSCLC). However, whether the efficacy and safety of ICI treatment in elderly patients are similar to those in younger patients is unclear. This study was designed to address this question. Methods We enrolled patients who received ICI monotherapy in Japan between December 2015 and December 2017; those ≥75 years of age comprised the elderly group. We compared the efficacy and safety of ICI monotherapy in elderly patients with those in younger patients and explored prognostic factors in elderly patients. Results We enrolled 676 patients; 137 (20.3%) were assigned to the elderly group. The median age of the elderly and younger groups was 78 (range, 75–85) and 66 (range, 34–74) years. The median progression‐free survival (4.8 months vs. 3.3 months, p = 0.1589) and median overall survival (12.3 months vs. 13.0 months, p = 0.5587) were similar between the elderly and younger groups. Multivariate analysis revealed that a significantly better OS in the elderly group was associated with better responses to first‐ or second‐line ICI treatment (p = 0.011) and more immune‐related adverse events (irAEs) (p = 0.02). IrAEs that led to ICI discontinuation occurred in 34 of 137 patients (24.8%) in the elderly group, and their survival was significantly higher than that in those who did not have irAEs. Conclusion ICI is also effective in elderly NSCLC patients, and treatment discontinuation due to irAEs may be a good prognostic marker.

Published
2023
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3. Single-chain tandem macrocyclic peptides as a scaffold for growth factor and cytokine mimetics

Author

Kenichiro Ito, Yoshihiko Matsuda, Ayako Mine, Natsuki Shikida, Kazutoshi Takahashi, Kyohei Miyairi, Kazutaka Shimbo, Yoshimi Kikuchi, and Atsushi Konishi

Subjects
Biology (General), QH301-705.5
Abstract

Peptides composed of two or more tandemly linked macrocyclic peptides binding to growth factor/cytokine receptors (STaMPtides) are useful growth factor/cytokine mimetics. The peptides can be produced from bacterial cells and bioactivity is demonstrated (HGF, EPO, TPO).

Published
2022
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4. First-line osimertinib in elderly patients with epidermal growth factor receptor-mutated advanced non-small cell lung cancer: a retrospective multicenter study (HOT2002)

Author

Gaku Yamamoto, Hajime Asahina, Osamu Honjo, Toshiyuki Sumi, Atsushi Nakamura, Kenichiro Ito, Hajime Kikuchi, Fumihiro Hommura, Ryoichi Honda, Keiki Yokoo, Yuka Fujita, Satoshi Oizumi, Ryo Morita, Yasuyuki Ikezawa, Hisashi Tanaka, Nozomu Kimura, Takaaki Sasaki, Noriaki Sukoh, Taichi Takashina, Toshiyuki Harada, Hirotoshi Dosaka-Akita, Hiroshi Isobe, and the Hokkaido Lung Cancer Clinical Study Group Trial

Subjects
Medicine, Science
Abstract

Abstract Osimertinib is a standard of care therapy for previously untreated epidermal growth factor receptor mutation-positive non-small cell lung cancer. However, limited data exist regarding the efficacy and safety of osimertinib as a first-line therapy for elderly patients aged 75 years or older. To assess the potential clinical benefits of osimertinib in this population, this retrospective multi-institutional observational study included 132 patients with non-small cell lung cancer (age ≥ 75 years), who received osimertinib as first-line treatment. The proportion of patients with 1-year progression-free survival was 65.8% (95% confidence interval 57.1–73.5). The median progression-free survival was 19.4 (95% confidence interval 15.9–23.9) months. The median overall survival was not reached (95% confidence interval 24.6–not reached). The frequency of pneumonitis was 17.4%, with a grade 3 or higher rate of 9.1%. More than two-thirds of treatment discontinuations due to pneumonitis occurred within 3 months of starting osimertinib, and the prognosis of patients with pneumonitis was unsatisfactory. Osimertinib is one of the effective first-line therapeutic options for patients aged 75 years or older; however, special caution should be exercised due to the potential development of pneumonitis.

Published
2021
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5. Preface for the special issue on Design, Concurrent Engineering and Smart Manufacturing towards Highly Digitalized Society

Author

Eiji MORINAGA, Masato INOUE, Rei HINO, Koji IWAMURA, Tsuyoshi KOGA, Tetsuro OGI, Koichiro SATO, Sharifu URA, Hideyoshi YANAGISAWA, Kenichiro ITO, Takeo KATO, Tomomi NONAKA, Masashi OKUBO, Tomohisa TANAKA, and Shuho YAMADA

Subjects
Engineering machinery, tools, and implements, TA213-215, Mechanical engineering and machinery, TJ1-1570
Published
2022
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6. Association of body mass index with outcomes in patients with newly diagnosed atrial fibrillation: GARFIELD-AF

Author

Daniela Poli, Sophie Testa, Corrado Lodigiani, Toon Wei Lim, Kevin Jones, Kangning Chen, Hui Li, Hilary Pinnock, Grzegorz Bilo, Hack-Lyoung Kim, Andrew Murray, Bernard J Gersh, Kurt Huber, Robin Fox, Sarah Davies, James Rogers, Morten Schou, Xin Li, Vira Tseluyko, Sergey Popov, Rajeev Gupta, Grzegorz Opolski, Preeti Pandya, Bronte Ayres, Milan Gupta, Peter Hutchinson, Phil Simmons, Andrew Gallagher, Michel Galinier, Franck Paganelli, Jens Kilian, Adam Blenkhorn, Mohamed Ibrahim, Fernando Lanas, Karen Pieper, Eivind Berge, M Clark, Agneta Andersson, Karim Ladha, Bijoy Sinha, Torstein Hole, Dan Atar, Hywel Jones, R Smith, Andrew Ross, Emmanuel Ellie, Paul Evans, Yong Wang, Hiroshi Ono, Tadashi Nakamura, Paul MacDonald, Stephen Rogers, Igor Sibon, Simon Dobson, David Fitzmaurice, Jiyan Chen, Neil Roberts, Pierre Amarenco, Nigel Hart, Giancarlo Agnelli, Georges Mairesse, Pekka Raatikainen, Oleg Sychov, Yasuyuki Suzuki, Bo Liu, Mathieu Zuber, John French, Yuejin Yang, Myeong-Chan Cho, Julian Thompson, Michael Stokes, John W Eikelboom, Mark Richardson, John Matthews, Will Murdoch, Jean-Philippe Neau, Freek Verheugt, Ajay K Kakkar, Giuseppe Ambrosio, Marcin Gruchała, Keith A A Fox, Sunil Kumar, Ruiping Zhao, Patrick Carroll, Masanori Kaneko, Thanh Phan, Ping Yang, Sung-Won Jang, Claire Jones, Mårten Rosenqvist, Johan Engdahl, Debabrata Roy, John Cairns, Ping Chen, Michael Olsen, Paul Angaran, David Russell, Helena Dominguez, Béla Merkely, Joseph Berlingieri, James Bennett, Hugo ten Cate, Hiroshi Yamaguchi, Masahiro Minamoto, Hiroyuki Oda, Toshihiko Shiraiwa, Jonathan Webster, Yukihiro Koretsune, Kotaro Obunai, R Thompson, Yong Seog Oh, Giuliana Guazzaloca, Giuliana Martini, Marc Bonnefoy, Michael Cox, András Nagy, Kazuki Sato, Richard Davies, Daisuke Ikeda, Susumu Suzuki, Hiroki Teragawa, Koji Matsushita, Ying Guo, Catherine Neden, Mark Pugsley, Simon Cartwright, Polly Jacobs, Xiaoshu Cheng, Daniel Nishijima, Sylvia Haas, Vinay Kumar, Saverio Virdone, Jean-Pierre Bassand, Samuel Z Goldhaber, Shinya Goto, Frank Misselwitz, Alexander G G Turpie, Alison Macleod, Karen Forshaw, Mark Boon, Stephen Miller, Simon Wetherell, Moustafa Moustafa, Gaetano Serviddio, Renato Lopes, Kazuo Takei, Hiroaki Nishioka, Mykola Stanislavchuk, C Ramesh, R Kamath, Stuart J Connolly, Nooshin Bazargani, Kevin Douglas, Werner Hacke, Gloria Kayani, Ali Oto, Hiroshi Watanabe, Walter Hermans, Kazuya Murata, Christian Fielder Camm, Marco Moia, Niraj Sharma, Jaeyoung Kim, Walter Abhayaratna, Andriy Yagensky, Hosen Kiat, Wilhelm Haverkamp, Yang Jiao, Hitoshi Kato, Jindrich Spinar, Daniel Theodoro, Philip Cooke, Paolo Golino, Tetsuro Yoshida, Prakash Chandwani, Christine A'Court, Brian Ramjattan, Torbjørn Øien, Toshiyuki Kobayashi, Richard West, Petr Jansky, Seil Oh, Jan Steffel, Martin van Eickels, Hyung-Wook Park, Nam-Ho Kim, Søren Rasmussen, Kazuo Suzuki, David Colquhoun, Hiroshi Ando, Simon Franklin, Tae-Joon Cha, Sang Cheol Bae, Guosheng Fu, Yoshihiro Saito, Heinz Drexel, Michel Martelet, Joseph Mouallem, Nicolas Delarche, Sylvain Destrac, Neil Macey, Andreas Kopf, Masayuki Nakano, Olga Barbarash, Takeshi Inoue, Taro Minagawa, Weihua Li, John Eikelboom, Hiroshi Kubo, Lars Andersson, D Burns, Andrea Podczeck-Schweighofer, Megumi Okada, Massimo Volpe, Takuma Aoyama, Karsten Mueller, Carlos Astudillo, Hiroshi Takeda, Peter Mayer, Jung Hoon Sung, Dinesh Jain, Jung Han Yoon, Alessandro Capucci, Dongryeol Ryu, Kelvin Wong, Hong Euy Lim, Xiaowei Yan, Yusheng Zhao, Yuehui Yin, YUKIHIRO SETA, Taek Jong Hong, MASAKI SHIMOYAMA, Dayi Hu, Junichi Minami, Yuriy Mostovoy, David Foo, Ramazan Topsakal, Zhi-Cheng Jing, Dipen Shah, Kenichi Yamamoto, David Coulshed, Olivier Piot, Ramón Corbalán, Silva Severi, Waldemar Myszka, Mehmet Birhan Yilmaz, Gi-Byoung Nam, Jun Kim, Harald Darius, Jan-Erik Karlsson, PETER VANDERGOTEN, Nasser Taha, Shuta Toru, Jörn Nielsen, Tsutomu Takagi, Koji Higuchi, Steen Husted, Tomohiro Katsuya, Frank Cools, Iveta Petrova, Songkwan Silaruks, GÜNTER LEHMANN, Frederic Casassus, Bernard Crousillat, Bernard Doucet, Jean-Joseph Muller, Grzegorz Raczak, Kazuyuki Saito, Anders Ostrem, Chi Keong Ching, KUNIHIKO YAMAMOTO, John Camm, Carmine Mazzone, Jaemin Shim, Jadwiga Nessler, Jan Vercammen, Marc Delforge, Chong-Jin Kim, Pierre Nazeyrollas, Louise Lumley, Paul Roome, Helen Stoddart, Mark Rickenbach, Paul Mullen, Noriyuki Nakanishi, Gordon Irvine, Paul Conn, Kurt Lenz, Richard Coates, E Fisher, Warwick Coulson, Jiri Lastuvka, Pablo García Pavía, P Jhittay, Philip Saunders, Peter Bernhardt, Wanwarang Wongcharoen, Kentaro Yamamoto, Hector Lucas Luciardi, Harry Gibbs, Marianne Brodmann, Jørn Dalsgaard Nielsen, Hany Ragy, Matyas Keltai, Jitendra Pal Singh Sawhney, Janina Stepinska, Elizaveta Panchenko, Barry Jacobson, Xavier Viñolas, Pantep Angchaisuksiri, Alex Parkhomenko, Huaiqin Zhang, Shiping Cao, Daowen Wang, Guizhou Tao, Yingmin Chen, Shenghu He, Tongguo Wu, Moshui Chen, Longgen Xiong, Praveen Jadhavm, Raghava Sarma, Govind Kulkarni, Rasesh Atulbhai Pothiwala, Mohanan Padinhare Purayil, Kamaldeep Chawla, Veerappa Annasaheb Kothiwale, Bagirath Raghuraman, Vinod Madan Vijan, Jitendra Sawhney, Ganapathi Bantwal, Aziz Khan, Ramdhan Meena, Manojkumar Chopada, Sunitha Abraham, Vikas Bisne, Govindan Vijayaraghavan, Rajashekhar Durgaprasad, Kartikeya Bhargava, Udigala Madappa Nagamalesh, Rajeeve Kumar Rajput, Seishu Kanamori, Koichiro Kumagai, Yosuke Katsuda, Keiki Yoshida, Fumitoshi Toyota, Yuji Mizuno, Ikuo Misumi, Hiroo Noguchi, Shinichi Ando, Tetsuro Suetsugu, Susumu Adachi, Kei Chiba, Hiroaki Norita, Makoto Tsuruta, Takeshi Koyanagi, Takayuki Higashi, Shiro Azakami, Shinichiro Komaki, Kenshi Kumeda, Takashi Murayama, Jun Matsumura, Yurika Oba, Ryuji Sonoda, Kazuo Goto, Kotaro Minoda, Yoshikuni Haraguchi, Hisakazu Suefuji, Hiroo Miyagi, Tsugihiro Nakamura, Hidekazu Nandate, Ryuji Zaitsu, Yoshihisa Fujiura, Akira Yoshimura, Hiroyuki Numata, Jun Ogawa, Yasuyuki Kamogawa, Kinshiro Murakami, Yutaka Wakasa, Masanori Yamasawa, Hiromitsu Maekawa, Sumihisa Abe, Hajime Kihara, Satoru Tsunoda, Katsumi Saito, Hiroki Tachibana, Ichiro Oba, Takashi Kuwahata, Satoshi Higa, Masamichi Gushiken, Takuma Eto, Hidetoshi Chibana, Kazuaki Fujisawa, Yuhei Shiga, Hirokuni Sumi, Toshihisa Nagatomo, Yoshihiko Atsuchi, Toshiro Nagoshi, Kazuhisa Sanno, Fumihiro Hoshino, Naoto Yokota, Masahiro Kameko, Toshifumi Tabuchi, Munesumi Ishizawa, Yoshitake Fujiura, Taku Seto, Tetsu Iwao, Norio Ishioka, Koichi Oshiro, Keizo Tsuchida, Yutaka Hatori, Motoshi Takeuchi, Hiroto Takezawa, Shinjiro Nagano, Masaaki Iwaki, Yuichiro Nakamura, Naomasa Miyamoto, Toshifumi Taguchi, Ko Ashida, Naoto Yoshizawa, Jun Agata, Seishiro Matsukawa, Osamu Arasaki, Shuji Fukuoka, Hirofumi Murakami, Kazuya Mishima, Yoshiki Hata, Ichiro Sakuma, Ichiro Takamura, Mitsuyuki Akutsu, Toshihide Unoki, Yoshinori Go, Makoto Ikemura, Shoji Morii, Shigeru Marusaki, Hideo Doi, Mitsuru Tanaka, Takaaki Kusumoto, Shigeo Kakinoki, Chiga Ogurusu, Masami Nakatsuka, Yutaka Kitami, Yoichi Nakamura, Hiroshi Oda, Rikimaru Oyama, Masato Ageta, Teruaki Mita, Kazuhiko Nagao, Takafumi Mito, Mitsunori Abe, Masako Fujii, Makoto Okawa, Tsuneo Fujito, Toshiya Taniguchi, Tenei Ko, Mizuho Imamaki, Masahiro Akiyama, Takashi Ueda, Hironori Odakura, Masahiko Inagaki, Yoshiki Katsube, Atsuyuki Nakata, Shinobu Tomimoto, Mitsuhiro Shibuya, Kenichiro Ito, Masahiro Matsuta, Motoyuki Ishiguro, Masamichi Wada, Hiroaki Mukawa, Masato Mizuguchi, Fumio Okuda, Teruaki Kimura, Kuniaki Taga, Masaaki Techigawara, Morio Igarashi, Toshihiko Seo, Shinya Hiramitsu, Hiroaki Hosokawa, Mitsumoto Hoshiai, Michitaka Hibino, Koichi Miyagawa, Hideki Horie, Nobuyoshi Sugishita, Yukio Shiga, Akira Soma, Kazuo Neya, Kunio Akahane, Saori Matsui, Hirofumi Kanda, Shiro Nagasaka, Atsushi Taguchi, Akiko Miyashita, Hiroki Sasaguri, Jin Nariyama, Taketo Hatsuno, Takash Iwase, Kazuya Kawai, Tomobumi Kotani, Tsuyoshi Tsuji, Hirosumi Sakai, Kiyoshi Nishino, Kenichi Ikeda, Kazuo Maeda, Tomohiro Shinozuka, Koichi Kawakami, Hiromichi Kitazumi, Mamoru Hamaoka, Jisho Kojima, Akitoshi Sasaki, Yoshihiro Tsuchiya, Tetsuo Betsuyaku, Masaaki Honda, Koichi Hasegawa, Takao Baba, Kazuaki Mineoi, Toshihiko Koeda, Kunihiko Hirasawa, Toshihide Kumazaki, Akira Nakagomi, Eiji Otaki, Takashi Shindo, Hiroyoshi Hirayama, Chikako Sugimoto, Takashi Yamagishi, Ichiro Mizuguchi, Kazunori Sezaki, Isamu Niwa, Ken Takenaka, Osamu Iiji, Koichi Taya, Hitoshi Kitazawa, Samu Ueda, Hirokazu Kakuda, Takuya Ono, Seizo Oriso, Junya Kamata, Toshihiko Nanke, Itaru Maeda, Yoshifusa Matsuura, Yasuyuki Maruyama, Hajime Horie, Tetsutaro Kito, Hiroshi Asano, Masaichi Nakamura, Takashi Washizuka, Tomoki Yoshida, Masato Sawano, Shinichi Arima, Hidekazu Arai, Hisanori Shinohara, Hiroyuki Takai, Nobufusa Furukawa, Akira Ota, Kenji Aoki, Taku Yamamoto, Takeaki Kasai, Shunji Suzuki, Shu Suzuki, Nitaro Shibata, Masayuki Watanabe, Yosuke Nishihata, Toru Arino, Masaki Okuyama, Tetsushi Wakiyama, Tomoko Kato, Yasuo Sasagawa, Takeshi Tana, Yoshihito Hayashi, Shinichi Hirota, Yukihiko Abe, Hirohide Uchiyama, Shuichi Tohyo, Naoto Hanazono, Seiichi Miyajima, Hisashi Shimono, Yasunobu Shozawa, Yawara Niijima, Osamu Murai, Hideko Inaba, Katsumasa Nomura, Masatsugu Nozoe, Toshiyuki Furukawa, Nobuhisa Ito, Shunichi Nagai, Kiyoharu Sato, Shiro Nakahara, Yujin Shimoyama, Naoko Ohara, Teruhiko Kozuka, Hideaki Okita, Masato Endo, Tsutomu Goto, Makoto Hirose, Emiko Nagata, Toshizumi Mori, Shuichi Seki, Katsuhiro Okamoto, Osamu Moriai, Yoko Emura, Tsuyoshi Fukuda, Haruhiko Date, Shuichi Kawakami, Sho Nagai, Yuya Ueyama, Tetsuro Fudo, Mitsuru Imaizumi, Takuo Ogawa, Shunsuke Take, Hideo Ikeda, Norihiko Sakamoto, Kiyomitsu Ikeoka, Nobuo Wakaki, Masatake Abe, Junji Doiuchi, Tetsuya Kira, Masato Tada, Ken Tsuzaki, Naoya Miura, Yasuaki Fujisawa, Wataru Furumoto, Akinori Fujisawa, Ryosai Nakamura, Hiroyasu Komatsu, Rei Fujiki, Shuichi Kawano, Keijiro Nishizawa, Yoji Kato, Junya Azuma, Kiyoshi Yasui, Toshio Amano, Yasuhiro Sekine, Tatsuo Honzawa, Yuichiro Koshibu, Yasuhide Sakamoto, Shingo Miyaguchi, Kojuro Morishita, Yasuko Samejima, Toyoshi Sasaki, Fumiko Iseki, Hiroshi Kano, Yoichi Takagi, Yoko Onuki Pearce, Takayuki Fukui, Toru Nakayama, Hideaki Kanai, Yoshiyuki Kawano, Tetsuji Ino, Hironori Miyoshi, Yasufumi Miyamoto, Masahito Shigekiyo, Shimato Ono, Yutaka Okamoto, Satoshi Ubukata, Kojiro Kodera, Tatsuo Oriuchi, Naoki Matsumoto, Koichi Inagaki, Atsushi Iseki, Tomohiro Yoshida, Toshihiro Goda, Tsukasa Katsuki, Atsushi Sato, Etsuo Mori, Toshio Tsubokura, Hiroshi Shudo, Shunichi Fujimoto, Yoshiyuki Furukawa, Hiroshi Hosokawa, Jun Narumi, Kiichiro Yamamoto, Masaki Owari, Takuya Inakura, Takafumi Anno, Kazuyuki Shirakawa, Tan Yuyang, Hui Nam Park, Woo-Shik Kim, HyeYoung Lee, Dae Hyeok Kim, Dae-Kyeong Kim, Dong Ju Choi, Hui-Kyung Jeon, Dong-Gu Shin, Sang Weon Park, Hoon Ki Park, Sang-Jin Han, Young Keun On, JaeJin Kwak, Seong Hoon Park, Kee-Sik Kim, Byung Chun Jung, Gyo-Seung Hwang, Sakda Rungaramsin, Peerapat Katekangplu, Porames Khunrong, Thanita Bunyapipat, Pinij Kaewsuwanna, Khanchai Siriwattana, Waraporn Tiyanon, Supalerk Pattanaprichakul, Khanchit Likittanasombat, Doungrat Cholsaringkarl, Warangkana Boonyapisit, Sirichai Cheewatanakornkul, Pisit Hutayanon, Seksan Chawanadelert, Pairoj Chattranukulchai, Boonsert Chatlaong, Yingsak Santanakorn, Khompiya Kanokphatcharakun, Piya Mongkolwongroj, Sasivimon Jai-Aue, Ongkarn Komson, Armagan Altun, Ali Aydinlar, Zeki Ongen, Sadik Acikel, Durmus Yildiray Sahin, Ozcan Yilmaz, Hasan Pekdemir, Mesut Demir, Murat Sucu, Levent Sahiner, Murat Ersanli, Ertugrul Okuyan, Dursun Aras, Florencia Rolandi, Adrian Cesar Ingaramo, Gustavo Alberto Sambadaro, Vanina Fernandez Caputi, Hector Luciardi, Sofia Graciela Berman, Pablo Dragotto, Andres Javier Kleiban, Nestor Centurion, Ricardo Dario Dran, Javier Egido, Matias Jose Fosco, Victor Alfredo Sinisi, Luis Rodolfo Cartasegna, Oscar Gomez Vilamajo, Jose Luis Ramos, Sonia Sassone, Gerardo Zapata, Diego Conde, Guillermo Giacomi, Alberto Alfredo Fernandez, Mario Alberto Berli, Fabian Ferroni, Jefferson Jaber, Luciana Vidal Armaganijan, André Steffens, José Márcio Ribeiro, Marcelo Silveira Teixeira, Paulo Rossi, Leonardo Pires, Daniel Moreira, Luiz Bodanese, Marcelo Westerlund Montera, Jamil Abdalla Saad, Euler Roberto Manenti, Alexandre Negri, Carlos Moncada, Dalton Precoma, Fernando Roquette, Gilmar Reis, Estêvão Lanna Figueiredo, Roberto Vieira Botelho, Helius Carlos Finimundi, Adriano Kochi, Fábio Alban, Rogério Tadeu Tumelero, Lilia Maia, Humberto Montecinos, Martín Larico Gómez, Carlos Conejeros, Patricio Marin Cuevas, Alejandro Forero, Claudio Bugueño Gutiérrez, Juan Aguilar, Sergio Potthoff Cardenas, German Eggers, Cesar Houzvic, Carlos Rey, Germán Arriagada, Gustavo Charme Vilches, Raul Leal Cantu, Ricardo Cabrera Jardines, Nilda Espinola Zavaleta, Enrique Lopez Rosas, Gerardo Pozas, Ernesto Cardona Muñoz, Norberto Matadamas Hernandez, Adolfo Leyva Rendon, Norberto Garcia Hernandez, David Lopez Villezca, Carlos Hernandez Herrera, Rodolfo Gaona Rodriguez, Efrain Villeda Espinosa, David Flores Martinez, Jose Velasco Barcena, Omar Fierro Fierro, Ignacio Rodriguez Briones, Humberto Alvarez Lopez, Rafael Olvera Ruiz, Roxana Reyes Sanchez, Roberto Arriaga Nava, Pedro Fajardo Campos, Mario Benavides Gonzalez, Claus Hagn, Johannes Foechterle, Michael Winkler, Bruno Schneeweiss, Alfons Gegenhuber, Wilfried Lang, Sabine Eichinger-Hasenauer, Peter Kaserer, Josef Sykora, Heribert Rasch, Bernhard Strohmer, Luc Capiau, Geert Vervoort, Bart Wollaert, Geert Hollanders, Dirk Faes, Yohan Balthazar, Olivier Xhaet, Harry Striekwold, John Thoeng, Kurt Hermans, Wim Anné, Ivan Blankoff, Michel Beutels, Stefan Verstraete, Philippe Purnode, Pascal Godart, Tim Boussy, Philippe Desfontaines, Alex Heyse, Joeri Voet, Eva Zidkova, Rudolf Spacek, Vilma Machova, Ondrej Ludka, Josef Olsr, Lubos Kotik, Blazej Racz, Richard Ferkl, Jan Hubac, Ilja Kotik, Zdenek Monhart, Hana Burianova, Ondrej Jerabek, Jana Pisova, Vratislav Dedek, Michaela Honkova, Petr Podrazil, Petr Reichert, Miroslav Novak, Vaclav Durdil, Katarina Plocova, Ulrik Hintze, Næstved Sygehus, Arne Bremmelgaard, John Markenvard, Jan Børger, Jorgen Solgaard, Ebbe Eriksen, Thomas Løkkegaard, Michael Bruun, Jacob Mertz, Joël Ohayon, Yannick Gottwalles, Philippe Loiselet, Mohamed Bassel Koujan, André Marquand, Jean-Pierre Cebron, Maxime Guenoun, Dominique Guedj-Meynier, A G Lokesh, James Kadouch, Pierre-Yves Fournier, Jean-Pierre Huberman, Nestor Lemaire, Gilles Rodier, Xavier Vandamme, Marie Hélène Mahagne, Antoine Mielot, Jean-Baptiste Churet, Vincent Navarre, Frederic Sellem, Gilles Monniot, Jean-Paul Boyes, Désiré Obadia, Etienne Bearez, Jean Philippe Brugnaux, Alain Fedorowsky, Jean-Baptiste Berneau, Frédéric Chemin, Sebastien Schellong, Georg Koeniger, Uwe Gerbaulet, Bernd-Thomas Kellner, Thomas Schaefer, Jan Purr, Enno Eißfeller, Heinz-Dieter Zauzig, Peter Riegel, Christoph Axthelm, Gerd-Ulrich Heinz, Holger Menke, Andreas Pustelnik, Stefan Zutz, Wolfgang Eder, Guenter Rehling, Dirk Glatzel, Norbert Ludwig, Petra Sandow, Henning Wiswedel, Cosmas Wildenauer, Steffen Schoen, Toralf Schwarz, Adyeri Babyesiza, Maximilian Kropp, Hans-Hermann Zimny, Friedhelm Kahl, Andreas Caspar, Sabine Omankowsky, Torsten Laessig, Hermann-Josef Hartmann, Hans-Walter Bindig, Gunter Hergdt, Dietrich Reimer, Joachim Hauk, Holger Michel, Praxis Dres, Werner Erdle, Wilfried Dorsch, Janna Dshabrailov, Karl-Albrecht Rapp, Reinhold Vormann, Thomas Mueller, Uwe Horstmeier, Volker Eissing, Heinz Hey, Heinz Leuchtgens, Volker Lilienweiss, Heiner Mueller, Christian Schubert, Herrmann Lauer, Thomas Buchner, Gunter Brauer, Susanne Kamin, Sylvia Baumbach, Muwafeg Abdel-Qader, Hans-Holger Ebert, Carsten Schwencke, Laszlo Karolyi, Britta Sievers, Jens-Uwe Roehnisch, Andras Vertes, Gabor Szantai, Andras Matoltsy, Nikosz Kanakaridisz, Zoltan Boda, Erno Kis, Balazs Gaszner, Ferenc Juhasz, Gizella Juhasz, Sandor Kancz, Zoltan Laszlo, Zsolt May, Ebrahim Noori, Tamas Habon, Peter Polgar, Gabriella Szalai, Sandor Vangel, Gabriella Engelthaler, Judit Ferenczi, Mihaly Egyutt, Leone Maria Cristina, Eros Tiraferri, Rita Santoro, Teresa Maria Caimi, Maria Tessitori, Roberto Cappelli, Roberto Quintavalla, Franco Cosmi, Raffaele Fanelli, Vincenzo Oriana, Raffaele Reggio, Roberto Santi, Leonardo Pancaldi, Jorge Salerno Uriate, Flavia Lillo, Enrico Maria Pogliani, Michele Accogli, Antonio Mariani, Mauro Feola, Arturo Raisaro, Luciano Fattore, Andrea Mauric, Fabrizio Germini, Luca Tedeschi, Maria Settimi, Sergio Nicoli, Paolo Ricciarini, Antonio Argena, Paolo Ronchini, Claudio Bulla, Filippo Tradati, Maria Grazia Bongiorni, Enrico Salomone, Claudio Tondo, Saverio Iacopino, Andreas Lucassen, Henk Adriaansen, Maarten Bongaerts, Mathijs Pieterse, Johannes Herrman, Pieter Hoogslag, Cees Buiks, Per Anton Sirnes, Erik Gjertsen, Knut Erga, Arne Hallaråker, Gunnar Skjelvan, Beraki Ghezai, Arne Svilaas, Peter Christersson, Svein Høegh Henrichsen, Jan Erik Otterstad, Jan Berg-Johansen, Andrzej Gieroba, Malgorzata Biedrzycka, Michal Ogorek, Beata Wozakowska-Kaplon, Krystyna Loboz-Grudzien, Jerzy Kuzniar, Roman Zaluska, Jaroslaw Hiczkiewicz, Lucyna Swiatkowska-Byczynska, Lech Kucharski, Piotr Minc, Maciej Olszewski, Grzegorz Kania, Malgorzata Krzciuk, Zbigniew Lajkowski, Bozenna Ostrowska-Pomian, Jerzy Lewczuk, Elzbieta Zinka, Agnieszka Karczmarczyk, Malgorzata Chmielnicka-Pruszczynska, Iwona Wozniak-Skowerska, Marek Bronisz, Marcin Ogorek, Grazyna Glanowska, Piotr Ruszkowski, Grzegorz Skonieczny, Ryszard Sciborski, Boguslaw Okopien, Piotr Kukla, Krzysztof Galbas, Krzysztof Cymerman, Jaroslaw Jurowiecki, Pawel Miekus, Stanislaw Mazur, Roman Lysek, Jacek Baszak, Teresa Rusicka-Piekarz, Ewa Domanska, Jozef Lesnik, Gadel Kamalov, Dmitry Belenky, Liudmila Egorova, Alexander Khokhlov, Eduard Yakupov, Dmitry Zateyshchikov, Olga Miller, Evgeniy Mazur, Konstantin Zrazhevskiy, Tatyana Novikova, Yulia Moiseeva, Elena Polkanova, Konstantin Sobolev, Maria Rossovskaya, Yulia Shapovalova, Alla Kolesnikova, Konstantin Nikolaev, Oksana Zemlianskaia, Anna Zateyshchikova, Victor Kostenko, Maria Poltavskaya, Anton Edin, Elena Aleksandrova, Oksana Drapkina, Alexander Vishnevsky, Oleg Nagibovich, Petr Chizhov, Svetlana Rachkova, Mikhail Sergeev, Borys Kurylo, Alexey Ushakov, Pere Alvarez Garcia, Luis Tercedor Sanchez, Salvador Tranche Iparraguirre, Pere Toran Monserrat, Emilio Marquez Contreras, Jordi Isart Rafecas, Juan Motero Carrasco, Casimiro Gomez Pajuelo, Angel Grande Ruiz, Jordi Merce Klein, Ines Monte Collado, Herminia Palacin Piquero, Carles Brotons Cuixart, Esther Fernandez Escobar, Cecilia Corros Vicente, Manuel Vida Gutierrez, Francisco Epelde Gonzalo, Encarnacion Martinez Navarro, Maria Barreda Gonzalez, Jose Iglesias Sanmartin, Mercedes Jimenez Gonzalez, Juan Herreros Melenchon, Tomas Ripoll Vera, Manuel Jimenez Navarro, Maria Vazquez Caamano, Gonzalo Marcos Gomez, Andres Iniguez Romo, Alexander Wirdby, Kerstin Henriksson, Micael Elmersson, Arnor Egilsson, Ulf Börjesson, Gunnar Svärd, Anders Lindh, Lars-Bertil Olsson, Mikael Gustavsson, Lars Benson, Claes Bothin, Ali Hajimirsadeghi, Björn Martinsson, Marianne Ericsson, Åke Ohlsson, Håkan Lindvall, Peter Svensson, Katarina Thörne, Hans Händel, Pyotr Platonov, Fredrik Bernsten, Ingar Timberg, Milita Crisby, Lennart Malmqvist, Jörgen Thulin, Aida Hot-Bjelak, Steen Jensen, Per Stalby, Johann Debrunner, Iurii Rudyk, Oleksandr Karpenko, Svitlana Zhurba, Igor Kraiz, Oleksandr Parkhomenko, Iryna Kupnovytska, Nestor Seredyuk, Oleksiy Ushakov, Olena Koval, Igor Kovalskiy, Yevgeniya Svyshchenko, Susanna Tykhonova, Ivan Fushtey, Naresh Chauhan, Daryl Goodwin, Ramila Patel, Bennett Wong, Alex Cameron, Niranjan Patel, M S Kainth, Gill Pickavance, Joanna McDonnell, Laura Handscombe, Trevor Gooding, Helga Wagner, Catherine Bromham, Shoeb Suryani, Bhupinder Sarai, W Willcock, S Sircar, A Gilliand, Roman Bilas, E Strieder, Anne Wakeman, Graham Kirby, Bhaskhar Vishwanathan, Nigel Bird, John Bisatt, Jennifer Litchfield, Tim Fooks, Richard Kelsall, Neil Paul, Elizabeth Alborough, Michael Aziz, Pete Wilson, Sue Fairhead, Hasan Chowan, Gary Taylor, Dawn Tragen, Matt Parfitt, Claire Seamark, Carolyn Paul, Angus Jefferies, Helen Sharp, Claire Giles, Matthew Bramley, Philip Williams, Jehad Aldegather, William Lumb, Phil Evans, Frances Scouller, Yvette Stipp, Philip Pinney, Paul Wadeson, T Railton, Emyr Davies, Jonathan McClure, Marc Jacobs, Claire Hutton, Keith Butter, Susan Barrow, Helen Little, Ulka Choudhary, Ikram Haq, Paul Ainsworth, Phil Weeks, Jane Eden, Lisa Gibbons, Janet Glencross, K Poland, Conor Mulolland, A Warke, Ian Hodgins, Stephen Vercoe, Jayesh Patel, Amar Ali, Nigel De-Sousa, Mark Danielsen, Purnima Sharma, Sophia Galloway, Charlotte Hawkins, Raife Oliver, Martin Aylward, Mira Pattni, Shahid Ahmad, Catherine Rothwell, Fiaz Choudhary, Sabrina Khalaque, Stephanie Short, Sharon Peters, Amy Butler, Steven Coates, Steve Walton, Diane Shepherd, Toh Wong, Melanie Deacon, David Cornelius, Henry Choi, Jon Sumner, Tim Myhill, Salah Estifanos, Diane Geatch, Justin Wilkinson, Richard Veale, Rob Hirst, Kashif Zaman, Catherine Liley, Rebecca Wastling, Paul McEleny, Andre Beattie, Mike Wong, Chaminda Dooldeniya, Greg Rogers, Rajesh Muvva, Matthew Adam, Nicolas Thomas, Rory Reed, Simon Randfield, Ann Flynn, Andrew Halpin, Louise Lomax, Minnal Nadaph, Iain Munro, Jane Goram, John Shewring, Emma Bowen-Simpkins, Bhuwanendu Singh, Penny Astridge, Philip Thomson, Ron Lehman, Andrei Catanchin, David Eccleston, Peter Blombery, Greg Starmer, Margaret Arstall, Maurits Binnekamp, Astin Lee, Robert Luton, Amritanshu Shekhar Pandey, Stephen Cheung, Rolland Leader, Philippe Beaudry, Félix Ayala-Paredes, John Heath, Germain Poirier, Bradley Schweitzer, Reginald Nadeau, Ripple Dhillon, Tomasz Hruczkowski, Andrea Lavoie, Ratika Parkash, James Cha, Benoit Coutu, Jorge Bonet, Saul Vizel, Sameh Fikry, Ahmed Mowafy, Azza Katta, Mazen Tawfik, Moustafa Nawar, Mohamed Sobhy, Tarek Khairy, Ahmed Abd El-Aziz, Ashraf Reda, Atef Elbahry, Mohamed Setiha, Magdi Elkhadem, Adel El-Etreby, David Kettles, Junaid Bayat, Heidi Siebert, Adrian Horak, Ynez Kelfkens, Riaz Garda, Thayabran Pillay, Michele Guerra, Hendrik Theron, Rikus Louw, Deon Greyling, Pindile Mntla, Siddique Ismail, Fayzal Ahmed, Johannes Engelbrecht, Shambu Maharajh, Veronica Ueckermann, Ghazi Yousef, Munther AlOmairi, Rajan Maruthanayagam, Rupesh Singh, Ahmed Naguib, Amrish Agrawal, Mukesh Nathani, Adel Wassef, Scott Beach, Peter Duffy, Stephen Falkowski, Kevin Ferrick, Miguel Franco, Annette Quick, Vance Wilson, Mark Alberts, Edwin Blumberg, Roddy Canosa, Ted Gutowski, Rodney Ison, Jorge Garcia, Howard Noveck, Pamela Rama, Rajneesh Reddy, Marcus Williams, Keith Ferdinand, Ihsan Haque, Robert Mendelson, Sridevi Pitta, Charles Treasure, Cas Cader, Walter Pharr, Alisha Oropallo, George Platt, Jaspal Gujral, James Welker, Firas Koura, Ajay K. Kakkar, A. John Camm, David A. Fitzmaurice, Keith A.A. Fox, Bernard J. Gersh, Samuel Z. Goldhaber, Lorenzo G. Mantovani, Karen S. Pieper, Alexander G.G. Turpie, Freek W.A. Verheugt, Antonio Carlos PereiraBarretto, Stuart J. Connolly, Jean-Yves Le Heuzey, Jitendra Pal SinghSawhney, Carlos JerjesSánchez Díaz, Hugo Ten Cate, Wael Al Mahmeed, Zhiming Yang Li Xue, A.G. Ravi Shankar, Chiei Takanaka Sen Adachi, Rodolfo AndresAhuad Guerrero, Leonel Adalberto Di Paola, DárioCelestino Sobral Filho, Costantino RobertoFrack Costantini, Weimar Kunz SebbaBarrosodeSouzaem, João David deSouzaNeto, José Carlos MouraJorge, Adalberto MenezesLorga Filho, Carlos Henrique DelCarlo, FernandoAugustoAlves da Costa, Gilson Robertode Araújo, Jose FranciscoKerr Saraiva, João CarlosFerreira Braga, Roberto Álvaro RamosFilho, Cláudio MunhozdaFontoura Tavares, CésarCássio Broilo França, Guido BernardoAranha Rosito, João BatistadeMouraXavierMoraes Junior, Roberto Simõesde Almeida, Ney CarterdoCarmo Borges, LuísGustavo Gomes Ferreira, Benjamin AleckJosehStockins Fernandez, CarlosJerjes Sanchez Diaz, Jesus JaimeIllescas Diaz, Maria GuadalupeRamos Zavala, GuillermoAntonio Llamas Esperón, Manuel delosRios Ibarra, LuisRamon Virgen Carrillo, JuanJose Lopez Prieto, Jose LuisLeiva Pons, Carlos GerardoCantu Brito, EduardoJulianJose Roberto ChuquiureValenzuela, Alberto EstebanBazzoni Ruiz, Oscar MartinLopez Ruiz, Jesus DavidMorales Cerda, Axel De Wolf, Carmela Viitanen, Giovanni Di Minno, Raimondo De Cristofaro, Angelo De Blasio, Maria D'Avino, J.H. Ruiter, Coen van Guldener, P.R. Nierop S.H.K., B.E. Groenemeijer, W. Terpstra, L.V.A. Boersma, Wieslaw Supinski Jaroslaw, Roman Libis Vera Eltishcheva, Maria FernandaLopez Fernandez, Luis MiguelRincon Diaz, Luis FernandoIglesias Alonso, Jose RamonGonzalez Juanatey, Joan Bayo iLlibre, Carlos AlexandreAlmeida Fernandez, Juan JoseMontero Alia, Maria AngelsMoleiro Oliva, Maria delMarRodriguez Alvarez, Maria FeArcocha Torres, Miguel AngelPrieto Diaz, Jan Lindén Centrumkliniken, Juerg H. Beer, Colin Bradshaw Cumberlidge, Daniel Jackson Ben Ward, Nick Hargreaves Ben Frankel, William van Gaal, David O'Donnell, Miranda du Preez, Seif Kamal Abou Seif, Mohamed Gamal El Din, Louis van Zyl, Rehana Loghdey Wessel Oosthuysen, Abdullah Al Naeemi, Ehab M. Esheiba, and W. Michael Kutayli

Subjects
Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Objective While greater body mass index (BMI) is associated with increased risk of developing atrial fibrillation (AF), the impact of BMI on outcomes in newly diagnosed AF is unclear. We examine the influence of BMI on outcomes and whether this is modified by sex and evaluate the effect of non-vitamin K oral anticoagulants (NOACs) in patients with high BMI.Methods GARFIELD-AF is a prospective registry of 52 057 newly diagnosed AF patients. The study population comprised 40 482 participants: 703 underweight (BMI

Published
2022
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7. Evaluation of the information presentation timing for motorcycle head-up display

Author

Kenichiro ITO, Hidekazu NISHIMURA, and Tetsuro OGI

Subjects
head-up display, immersive cave, virtual reality, motorcycle simulator, navigation system, human interface, Mechanical engineering and machinery, TJ1-1570, Engineering machinery, tools, and implements, TA213-215
Abstract

Navigation systems are nowadays widely used for cars though it is yet to be able to say popularized for motorcycles. While motorcycle navigation systems are not popularized yet, previous research indicates motorcyclist's high demand against a useful navigation system. The absence of useful motorcycle navigation system is an issue of current products not capable of providing navigation information efficiently. To work with the issue, information presentation design is necessary to consider the motorcyclist's characterful viewpoint movement of looking at the road surface carefully in a vertical movement. As a solution to this issue, we propose the use of head-up display for information presentation. Previous studies have revealed the amount and positions suitable to present information for motorcyclist while riding, although the timing of information presentation is yet to be discussed. Thus, in this paper, the information presentation timing to provide navigation information has been evaluated. Experiment using an immersive CAVE motorcycle simulator was conducted with the configuration of five timings between 25 m to 85 m prior to the intersection under conditions of urban street with 30 km/h speed limit. Durations of motorcyclist's viewpoint movement and five scale subjective ratings were used for evaluation. The experimental results from 10 subjects showed a statistically significant difference in subjective ratings. In conclusion, suitable information presentation timing of riding in urban streets with 30 km/h speed limit is around 40 m to 55 m prior to the target intersection.

Published
2017
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8. Direct Light-up of cAMP Derivatives in Living Cells by Click Reactions

Author

Yan Xu, Hongshan Liu, Tetsuya Hayashi, Makoto Komiyama, and Kenichiro Ito

Subjects
click chemistry, cAMP, fluorescence, cAMP localization in living cells, Organic chemistry, QD241-441
Abstract

8-Azidoadenosine 3′,5′-cyclic monophosphate (8-azido cAMP) was directly detected in living cells, by applying Cu-free azide-alkyne cycloaddition to probe cAMP derivatives by fluorescence light-up. Fluorescence emission was generated by two non-fluorescent molecules, 8-azido cAMP as a model target and difluorinated cyclooctyne (DIFO) reagent as a probe. The azide-alkyne cycloaddition reaction between 8-azido cAMP and DIFO induces fluorescence in 8-azido cAMP. The fluorescence emission serves as a way to probe 8-azido cAMP in cells.

Published
2013
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9. MET Activation by a Macrocyclic Peptide Agonist that Couples to Biological Responses Differently from HGF in a Context-Dependent Manner

Author

Wenyu Miao, Katsuya Sakai, Ryu Imamura, Kenichiro Ito, Hiroaki Suga, Tetsushi Sakuma, Takashi Yamamoto, and Kunio Matsumoto

Subjects
HGF, MET receptor, surrogate agonist, partial activation, signal transduction, Biology (General), QH301-705.5, Chemistry, QD1-999
Abstract

Non-native ligands for growth factor receptors with distinct chemical properties and different biological activities have the potential to become therapeutic applications. We previously generated MET/hepatocyte growth factor (HGF) receptor agonists using bivalent macrocyclic peptides. The highest MET-activating agonists exhibited biological activity that was indistinguishable from the effects of HGF. In this study, we investigated MET activation, signal characteristics, and biological responses induced by a macrocyclic peptide partial agonist known as aML5-PEG11. aML5-PEG11 induced weak tyrosine phosphorylation of MET while enhancing cell migration with potency comparable to HGF. aML5-PEG11 induced marked AKT (protein kinase B) and ERK (extracellular signal-regulated kinase) activation at a comparable potency and time-dependency to HGF, which suggests that enhancement of cell motility is attributable to activation of these molecules. In a 3-D culture of bile duct cancer cells in collagen gel, HGF induced robust activation of MET, ERK, and AKT, which was associated with enhanced expression of genes involved in bile duct development and subsequent branching of tubulogenesis. In contrast, aML5-PEG11 induced marginal activation of MET, ERK, and AKT (levels near the detection limits), which was associated with failure to enhance the expression of genes involved in bile duct development and a lack of tubulogenic response. Thus, MET activation by aML5-PEG11 couples to biological responses differently from HGF in an extracellular context-dependent manner.

Published
2018
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10. Technologies for the Synthesis of mRNA-Encoding Libraries and Discovery of Bioactive Natural Product-Inspired Non-Traditional Macrocyclic Peptides

Author

Hiroaki Suga, Toby Passioura, and Kenichiro Ito

Subjects
non-standard macrocyclic peptides, non-canonical amino acids, flexizyme, Random non-standard Peptide Integration Discovery (RaPID) system, peptide inhibitors, Organic chemistry, QD241-441
Abstract

In this review, we discuss emerging technologies for drug discovery, which yields novel molecular scaffolds based on natural product-inspired non-traditional peptides expressed using the translation machinery. Unlike natural products, these technologies allow for constructing mRNA-encoding libraries of macrocyclic peptides containing non-canonical sidechains and N-methyl-modified backbones. The complexity of sequence space in such libraries reaches as high as a trillion (>1012), affording initial hits of high affinity ligands against protein targets. Although this article comprehensively covers several related technologies, we discuss in greater detail the technical development and advantages of the Random non-standard Peptide Integration Discovery (RaPID) system, including the recent identification of inhibitors against various therapeutic targets.

Published
2013
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12. Evaluation of information amount to present for motorcycle head-up display

Author

Kenichiro ITO, Yoshisuke TATEYAMA, Hidekazu NISHIMURA, and Tetsuro OGI

Subjects
head-up display, immersive cave, virtual reality, motorcycle simulator, navigation system, human interface, Mechanical engineering and machinery, TJ1-1570, Engineering machinery, tools, and implements, TA213-215
Abstract

Car navigation systems have recently become a popular assist system for automobiles. On the other hand, lack of dedicated motorcycle navigation system is still an issue. This is because currently provided navigation system utilizable for motorcycle has difficulties for riders to obtain information while driving. Recent research propose of using the head-up display technology is considered to solve this issue. Although, topics about the amount of information to provide using the head-up display has not yet been discussed. Since providing too much information distracts driving behaviors, amount of information control is required to prevent inattentive driving behaviors. To evaluate the preferable amount of information, we conducted an experiment using the immersive motorcycle simulator integrated with a head-up display. The experiment measured motorcycle riders' viewpoint movements using the eye-mark recorder to observe the duration spent against the information provided using the head-up display. Through the experiment, we presented different length of Japanese syllabary characters (Hiragana) on the head-up display to 10 subjects. Experiments results indicate presenting 5 Japanese syllabary characters is the preferable amount of information to the motorcycle rider while driving. Applying information theories, we conclude that the preferable information transmission rate is approximately 16 bits per seconds.

Published
2015
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40. First-line osimertinib in elderly patients with epidermal growth factor receptor-mutated advanced non-small cell lung cancer: a retrospective multicenter study (HOT2002)

Author

Noriaki Sukoh, Osamu Honjo, Yasuyuki Ikezawa, Hisashi Tanaka, Atsushi Nakamura, Ryoichi Honda, Hiroshi Isobe, Gaku Yamamoto, Ryo Morita, Hajime Asahina, Kenichiro Ito, Hirotoshi Akita, Takaaki Sasaki, Nozomu Kimura, Hajime Kikuchi, Keiki Yokoo, Toshiyuki Sumi, Satoshi Oizumi, Toshiyuki Harada, Yuka Fujita, Taichi Takashina, Hirotoshi Dosaka-Akita, and Fumihiro Hommura

Subjects
Oncology, Male, medicine.medical_specialty, Lung Neoplasms, Science, Population, Antineoplastic Agents, Kaplan-Meier Estimate, Article, Targeted therapies, Internal medicine, Carcinoma, Non-Small-Cell Lung, Medicine, Humans, Osimertinib, Epidermal growth factor receptor, education, Lung cancer, Protein Kinase Inhibitors, Pneumonitis, Aged, Retrospective Studies, Aged, 80 and over, education.field_of_study, Acrylamides, Multidisciplinary, Aniline Compounds, biology, business.industry, Oncogenes, Exons, medicine.disease, Prognosis, Confidence interval, Progression-Free Survival, ErbB Receptors, Treatment Outcome, Mutation, biology.protein, Observational study, Female, Non small cell, business, Non-small-cell lung cancer, Follow-Up Studies
Abstract

Osimertinib is a standard of care therapy for previously untreated epidermal growth factor receptor mutation-positive non-small cell lung cancer. However, limited data exist regarding the efficacy and safety of osimertinib as a first-line therapy for elderly patients aged 75 years or older. To assess the potential clinical benefits of osimertinib in this population, this retrospective multi-institutional observational study included 132 patients with non-small cell lung cancer (age ≥ 75 years), who received osimertinib as first-line treatment. The proportion of patients with 1-year progression-free survival was 65.8% (95% confidence interval 57.1–73.5). The median progression-free survival was 19.4 (95% confidence interval 15.9–23.9) months. The median overall survival was not reached (95% confidence interval 24.6–not reached). The frequency of pneumonitis was 17.4%, with a grade 3 or higher rate of 9.1%. More than two-thirds of treatment discontinuations due to pneumonitis occurred within 3 months of starting osimertinib, and the prognosis of patients with pneumonitis was unsatisfactory. Osimertinib is one of the effective first-line therapeutic options for patients aged 75 years or older; however, special caution should be exercised due to the potential development of pneumonitis.

Published
2021

41. Bacterially Secretable Single‐Chain Tandem Macrocyclic Peptides for High Affinity and Inhibitory Activity

Author

Kenichiro Ito, Yoshihiko Matsuda, Ayako Mine, Kyohei Miyairi, Yoshimi Kikuchi, and Atsushi Konishi

Subjects
Organic Chemistry, Molecular Medicine, Molecular Biology, Biochemistry
Abstract

The inhibition of protein-protein interactions (PPIs) is an effective approach for therapy. Owing to their large binding surface areas to target proteins, macrocyclic peptides are suitable molecules for PPI inhibition. In this study, we developed single-chain tandem macrocyclic peptides (STaMPtides) that inhibits the vascular endothelial growth factor (VEGF) receptor 2 (VEGFR2). They were artificially designed to comprise two different VEGFR2-binding macrocyclic peptides linked in tandem by peptide linkers and secreted by Corynebacterium glutamicum. Most potent VEGFR2-inhibitory STaMPtides with length-optimized linkers exhibited1000 times stronger inhibitory activity than their parental monomeric peptides, possibly due to the avidity effect of heterodimerization. Our approach of using STaMPtides for PPI inhibition may be used to inhibit other extracellular factors, such as growth factors and cytokines.

Published
2022

42. Real-world outcomes of chemotherapy for lung cancer patients undergoing hemodialysis: A multicenter retrospective cohort study (NEJ-042)

Author

Yuji Minegishi, Tomoe Akagami, Makoto Arai, Ryota Saito, Daisuke Arai, Kyoko Murase, Keita Miura, Satoshi Watanabe, Hiroyuki Sakashita, Takao Miyabayashi, Ryoichi Honda, Daisuke Jingu, Takamasa Hotta, Kazutoshi Isobe, kensuke Nakazawa, Kenichiro Ito, Kei Takamura, Minehiko Inomata, Toshiyuki Harada, Rie Sakakibara, Taku Nakagawa, Hideki Shibuya, Kiyoshi Takenaka, Kunihiko Kobayashi, and Masahiro Seike

Subjects
Pulmonary and Respiratory Medicine, ErbB Receptors, Cancer Research, Lung Neoplasms, Oncology, Renal Dialysis, Carcinoma, Non-Small-Cell Lung, Mutation, Humans, Multicenter Studies as Topic, Protein Kinase Inhibitors, Retrospective Studies
Abstract

Malignant tumors are the major cause of death in hemodialysis patients. Management of these patients remains challenging as there is no evidence that chemotherapy is beneficial, and a lack of information about actual clinical practice.This multicenter retrospective study included hemodialysis patients who were diagnosed with lung cancer from January 2002 to June 2018. We reviewed their clinical information including patient characteristics associated with lung cancer and end-stage renal disease, regimen, efficacy and safety of chemotherapy, and outcomes.A total of 162 patients from 22 institutions in Japan were registered. Of 158 eligible patients, 91 received chemotherapy (80 as palliative chemotherapy and 11 as chemoradiotherapy) and 67 received best supportive care only regardless of cancer stage. In small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) patients who received cytotoxic chemotherapy, the objective response rates (ORR) and median overall survival (OS) were 68.1 %, 12.3 months and 37.0 %, 8.5 months, respectively. The ORR and median OS in patients with EGFR-mutant NSCLC treated with EGFR-tyrosine kinase inhibitors (TKI) were 44.4 % and 38.6 months. The treatment-related adverse events (Grade 3 or higher) induced by cytotoxic chemotherapy were myelosuppression and febrile neutropenia; treatment-related death (TRD) was observed in one patient. TRD occurred in 3 of 18 patients who received EGFR-TKI.Chemotherapy should be considered for hemodialysis patients with EGFR-mutant NSCLC and SCLC. However, the survival benefits of chemotherapy for NSCLC patients with EGFR-wild type are unclear; physicians should carefully consider whether to offer chemotherapy to this patient subset.

Published
2022

44. A Two-Step Model for Encouraging the General Public to Exhibit Helping Behaviors Toward People Living With Dementia

Author

Hiroshige Matsumoto, Ayumi Igarashi, Mariko Sakka, Manami Takaoka, Haruna Kugai, Kenichiro Ito, and Noriko Yamamoto-Mitani

Subjects
Health (social science), Life-span and Life-course Studies, Health Professions (miscellaneous)
Abstract

Background and Objectives Dementia awareness initiatives aim to promote helping behaviors toward people living with dementia. We applied the bystander intervention process model in the context of the general public’s helping behaviors toward people living with dementia, and we sought to identify the mechanisms underlying the association between dementia knowledge and helping behaviors. Research Design and Methods In a survey featuring vignettes for the general public in Japan (N = 904), we presented four situations in which people could exhibit helping behaviors toward a person with dementia. Guttman scale analysis was used to test this sequential ordering of the bystander intervention process model: (a) interpreting the need to help, (b) perceiving personal responsibility, and (c) intention to provide help. Mediation analysis was used to examine whether the effects of knowledge on helping behaviors were mediated by attitude toward people living with dementia and the bystander intervention process. Results The results support the two-step model in which interpreting the situation as one where assistance is required is a prerequisite of helping behavior. Dementia knowledge had a significant total effect on intention to provide help (β = 0.136, p < .001). Interpretation (indirect effect: β = 0.092, p < .001), as well as attitude (indirect effect: β = 0.044, p < .001), was found to completely mediate the effect of dementia knowledge on intention to provide help. Discussion and Implications Dementia awareness initiatives designed to promote helping behaviors should focus on knowledge transfer, improving the general public’s attitudes toward people living with dementia, and their ability to interpret when such people need assistance.

Published
2021

45. Pathotypes and Drug Susceptibility of Escherichia coli Isolated from Companion Dogs in Japan

Author

Satowa Suzuki, Kenichiro Ito, Hirotaka Takagi, Mari Matsui, and Kunikazu Yamane

Subjects
0301 basic medicine, Microbiology (medical), Cefotaxime, 030106 microbiology, Ceftazidime, General Medicine, Drug resistance, biochemical phenomena, metabolism, and nutrition, Fosfomycin, Biology, bacterial infections and mycoses, medicine.disease_cause, Microbiology, 03 medical and health sciences, 0302 clinical medicine, Infectious Diseases, Cefalexin, polycyclic compounds, medicine, Enrofloxacin, 030212 general & internal medicine, Escherichia coli, Norfloxacin, medicine.drug
Abstract

Considering the possibility that Escherichia coli carried by companion dogs could infect owners and human society, we investigated their pathogenicity and drug resistance. E. coli was isolated from stool samples of companion dogs (n = 90) to examine the O-serogroup, virulence genes, and drug susceptibility. The age of dogs ranged from 4 months to 16 years, and they were mainly treated with cefalexin, enrofloxacin, or amoxicillin. A total of 69 samples were positive for E. coli (76% of examined dogs), and the most common O-serogroup was O18 (n = 13). Nine diarrheagenic E. coli, including enteropathogenic E. coli (n = 3), enteroaggregative E. coli (n = 1), and astA-carrying E. coli (n = 5), were isolated. In addition, we isolated 28 E. coli strains resistant to at least one of six antimicrobials, including cephalothin (CET), ceftazidime (CAZ), cefotaxime (CTX), chloramphenicol (CP), fosfomycin (FOM), and norfloxacin (NLFX). The resistance pattern was as follows: CET, n = 16; NLFX, n = 3; CET/CP (resistance to both CET and CP), n = 1; CET/NLFX, n = 1; CET/CAZ/CTX, n = 3; CET/CTX/NLFX, n = 2; CET/CP/NLFX, n = 1; and CET/CAZ/CTX/NLFX, n = 1. Moreover, ten E. coli isolates were found to produce extended-spectrum β-lactamase (ESBL), including AmpC (n = 4; OUT, O18, O74, and O166), CTX-M-1 (n = 1; O25), CTX-M-9 (n = 4; OUT, O18, O18, and O125), and AmpC/CTX-M-9 (n = 1; OUT) groups. The AmpC-producing E. coli strains included enteropathogenic and astA-carrying E. coli. Our results showed that the human-infectious diarrheagenic E. coli was isolated from some dogs, and some strains exhibited ESBL. Therefore, future studies are needed to investigate the possibility of transmission of these E. coli strains to humans.

Published
2020

46. One-step construction of ferritin encapsulation drugs for cancer chemotherapy

Author

Yuichi Nakahara, Uno Tagami, Ippei Inoue, Yuta Endo, Yasuyo Suga, Yoriko Okamatsu, Naofumi Okamoto, Mayumi Chiba, Kazutoshi Takahashi, Kenichiro Ito, and Yoshiro Kitahara

Subjects
Drug, media_common.quotation_subject, Size-exclusion chromatography, 02 engineering and technology, 03 medical and health sciences, Drug Delivery Systems, Dynamic light scattering, Neoplasms, Zeta potential, medicine, General Materials Science, Doxorubicin, 030304 developmental biology, media_common, 0303 health sciences, biology, Chemistry, 021001 nanoscience & nanotechnology, Ferritin, Pharmaceutical Preparations, Drug delivery, Apoferritins, Ferritins, Biophysics, biology.protein, Nanomedicine, 0210 nano-technology, medicine.drug
Abstract

Conventionally, a disassembly and reassembly method has been used for encapsulation of drug molecules in ferritin protein nano-cages. However, clinical applications of ferritin have been greatly restricted by its limited drug-loading capacity and process complexity. Here, we establish a simple high yield process for preparing high drug-loaded ferritin nanomedicine for industrial production. A complex of ferritin and a target drug was obtained by incubating the mixture at an appropriate pH. An electrostatic charge potential and small ferritin cavity facilitates the passage of drug molecules through the pores, traversing the ferritin shell and enabling deposition of the drug in the ferritin cavity. Compared to the disassembly/reassembly method, the loading capacity of a doxorubicin-loaded ferritin heavy chain (DOX-FTH), constructed by our novel method, was over 3-fold higher, while doxorubicin recovery was 10-fold higher. Results of transmission electron microscopy, size exclusion chromatography, dynamic light scattering, and zeta potential indicate that DOX-FTH exhibits the same physicochemical characteristics of natural apo-ferritin. Moreover, DOX-FTH can be taken up and induce apoptosis of cancer cells overexpressing TfR1. Here, we have demonstrated the successful introduction of more than ten drug molecule types into ferritin nano-cages using a novel method. These results demonstrate that this one-step method is a powerful production process to construct a drug-loading ferritin drug delivery system carrier.

Published
2021

47. Prognostic factors in patients with advanced non-small cell lung cancer after long-term Anti-PD-1 therapy (HOT1902)

Author

Tomohiro Goda, Satoshi Oizumi, Kei Takamura, Yasutaka Kawai, Ryo Morita, Taichi Takashina, Hirotoshi Dosaka-Akita, Ryoichi Honda, Noriaki Sukoh, Toshiyuki Harada, Osamu Honjo, Shotaro Ito, Keiichi Nakamura, Keiki Yokoo, Hajime Asahina, Fumihiro Hommura, Kenichiro Ito, Hiroshi Isobe, and Hisashi Tanaka

Subjects
0301 basic medicine, Pulmonary and Respiratory Medicine, Cancer Research, medicine.medical_specialty, Lung Neoplasms, Population, Pembrolizumab, Immune checkpoint inhibitor, 03 medical and health sciences, 0302 clinical medicine, Non-small cell lung cancer, Japan, Internal medicine, Carcinoma, Non-Small-Cell Lung, Medicine, Humans, Lung cancer, education, Retrospective Studies, education.field_of_study, business.industry, Medical record, medicine.disease, Prognosis, Discontinuation, 030104 developmental biology, Nivolumab, Oncology, 030220 oncology & carcinogenesis, Observational study, Neoplasm Recurrence, Local, business, ICI rechallenge, Progressive disease
Abstract

Objectives: Limited information is available on the appropriate treatment duration of immune checkpoint inhibitors (ICIs). We aimed to identify candidates who would benefit from ICI discontinuation after one year of treatment for metastatic non-small cell lung cancer (NSCLC). Materials and methods: This retrospective multi-institutional observational study examined medical records of all consecutive patients with advanced or recurrent NSCLC, who started ICI monotherapy at 15 institutions in Japan between December 2015 and December 2017. Patients who received initial ICI therapy for >1 year without progressive disease were defined as the long-term treatment (LT) group; others were defined as the non -longterm treatment (NLT) group. Primary outcomes included the prognostic factors in the LT group, whereas secondary outcomes included efficacy of ICI rechallenge, safety, and survival outcomes in the overall population. Results: In total, 676 patients were enrolled, and 114 (16.9 %) were assigned to the LT group. The median time interval from the start of initial ICI administration to data cutoff was 34.3 months (range, 24.1 & ndash;47.8); thus, all surviving patients were followed-up for at least 2 years from the start of initial ICI. Median progression-free survival (PFS) was longer in the LT than in the NLT group (33.6 months vs. 2.7 months; p < 0.001). On multivariate analysis, significantly better PFS was associated with smoking (hazard ratio [HR]=0.36, p = 0.04), and complete response (CR; HR=uncomputable, p < 0.001) in the LT group. Thirty-seven patients (5.5 %) received ICI rechallenge, including 10 in the LT group. Among patients receiving rechallenge treatment, the median PFS was 2.2 months, with no difference between the LT and NLT groups. Conclusions: In the LT group, smoking and achieving CR were significantly associated with better PFS. Since rechallenge treatment was not effective, careful consideration is required for discontinuing ICI. However, these prognostic factors are helpful in considering candidates for ICI discontinuation. Trial Registration: UMIN ID, UMIN000041403

Published
2021

48. Evaluation of IoT-Setting Method Among Senior Citizens in Japan

Author

Kenichiro Ito, Ken-ichiro Yabu, Takahiro Miura, Reina Yoshizaki, Koki Nakano, Hiroki Kogami, Yuriki Sakurai, Ikuko Sugawara, Daisuke Yoshioka, SooIn Kang, Tohru Ifukube, Mahiro Fujisaki-Sueda-Sakai, and Jiang Wu

Subjects
Focus (computing), business.industry, Computer science, Interface (Java), media_common.quotation_subject, System usability scale, Internet privacy, Information technology, Gerontechnology, ComputerSystemsOrganization_MISCELLANEOUS, The Internet, User interface, business, Function (engineering), media_common
Abstract

To develop methods for supporting senior citizens is critical because the number of senior citizens is growing globally. Recently, the focus is on supporting senior citizens using information technology (IT), including the Internet of Things (IoT). In the IoT system, IoT tools such as cameras and sensors are connected and interacted by the Internet. Furthermore, we can customize their function easily using smartphones to modulate the function we want. Therefore, senior citizens should customize IoT products and help themselves. However, it is challenging to customize IoT product functions for senior citizens because they had fewer chances to use smartphones or computers than young people. Therefore, other customizing methods for IoT products are needed for senior citizens. In this study, we design a workshop to test, where the setting of the user interface (UI) is suitable for senior citizens. We develop three UIs, namely, voice, touch, and camera. To explore which method is suitable for senior citizens, we evaluate the setting time for each method. Consequently, the setting time of the voice interface is shorter than the others. Furthermore, the system usability scale (SUS) score was higher than 68, indicating that the setting method using the voice interface is acceptable for senior citizens. These results indicate that the voice interface is a suitable setting method for senior citizens.

Published
2021

49. Incorporation of Halogenated Amino Acids into Antibody Fragments at Multiple Specific Sites Enhances Antigen Binding

Author

Haruna Sato, Kensaku Sakamoto, Akiko Hayashi, Takuhiro Ito, Kenichiro Ito, Haruna Kenichi, and Chisato Makino

Subjects
Models, Molecular, Halogenation, Constant domain, 010402 general chemistry, 01 natural sciences, Biochemistry, Antibody fragments, Antigen-Antibody Reactions, Antigen, Molecule, Amino Acids, Antigens, Molecular Biology, chemistry.chemical_classification, Binding Sites, biology, 010405 organic chemistry, Chemistry, Organic Chemistry, Antibodies, Monoclonal, Antigen binding, 0104 chemical sciences, Amino acid, biology.protein, Molecular Medicine, Antibody
Abstract

Expansion of the amino-acid repertoire with synthetic derivatives introduces novel structures and functionalities into proteins. In this study, we improved the antigen binding of antibodies by incorporating halogenated tyrosines at multiple selective sites. Tyrosines in the Fab fragment of an anti-EGF-receptor antibody 059-152 were systematically replaced with 3-bromo- and 3-chlorotyrosines, and simultaneous replacements at four specific sites were found to cause a tenfold increase in the affinity toward the antigen. Structure modeling suggested that this effect was due to enhanced shape complementarity between the antigen and antibody molecules. On the other hand, we showed that chlorination in the constant domain, far from the binding interface, of Rituximab Fab also increased the affinity significantly (up to 17-fold). Our results showed that antigen binding is tunable with the halogenation in and out of the binding motifs.

Published
2020

50. Improved Stability of siRNA-Loaded Lipid Nanoparticles Prepared with a PEG-Monoacyl Fatty Acid Facilitates Ligand-Mediated siRNA Delivery

Author

Yuki Goto, Kazuhiro Iwasaki, Hiroaki Suga, Wataru Mizumura, Yu Sakurai, Takayuki Katoh, Hideyoshi Harashima, and Kenichiro Ito

Subjects
Small interfering RNA, Pharmaceutical Science, Nanoparticle, Peptide, 02 engineering and technology, Mice, SCID, Ligands, 030226 pharmacology & pharmacy, Polyethylene Glycols, 03 medical and health sciences, chemistry.chemical_compound, Mice, 0302 clinical medicine, Drug Delivery Systems, Cell Line, Tumor, Drug Discovery, PEG ratio, Gene silencing, Animals, Humans, Gene Silencing, RNA, Small Interfering, chemistry.chemical_classification, Ovarian Neoplasms, Peptide modification, Mice, Inbred ICR, Fatty Acids, 021001 nanoscience & nanotechnology, Ligand (biochemistry), Epithelial Cell Adhesion Molecule, HCT116 Cells, Lipids, chemistry, Biophysics, Molecular Medicine, Nanoparticles, Female, 0210 nano-technology, Peptides, Ethylene glycol
Abstract

Peptide modification is a popular strategy for developing an active targeting lipid nanoparticle (LNP). In modifying the surface of an LNP with a peptide, the sequence and structure of the peptide strongly affects the formation of the LNP. Specifically, a peptide with a high hydrophobicity can induce coarsening and aggregation of the LNP. In an attempt to prevent this from occurring, we incorporated monoacyl and diacyl group-conjugated poly(ethylene glycol) (PEG) into a LNP. We previously developed an original LNP, a multifunctional envelope type nanodevice (MEND) modified with an Epi-1 peptide, a ligand with a high affinity for the epithelial cell adhesion molecule (EpCAM). Using this peptide-modified MEND, the efficiency of delivery of a small interfering RNA (siRNA) encapsulated in the MEND was significantly improved. Although increasing the ratio of modification enhanced cellular uptake, the increase also induced aggregation of the LNP, particularly in the case of a large scale preparation. Our results indicate that a monoacyl PEG-lipid can prevent aggregation, even when the LNP is modified with higher molar ratios of peptide, but that this also results in a decrease in delivery efficiency. Moreover, the Epi-1-modified MEND exhibited a strong silencing effect in an ovarian cancer peritoneal dissemination model. Our results suggest that the simple incorporation of a monoacyl derivative into the PEG-lipid resulted in the formation of a peptide-modified LNP with improved characteristics.

Published
2020

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