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1. Detection of Plasmodium vivax infection in the Republic of Korea by loop-mediated isothermal amplification (LAMP)

Author

Feng Lu, In Bum Suh, Jun Hu Chen, Jung Yeon Kim, Chae Seung Lim, Heui June Ahn, Takafumi Tsuboi, Eun-Taek Han, Jetsumon Sattabongkot, and Satoru Takeo

Subjects
medicine.medical_specialty, Veterinary (miscellaneous), Plasmodium vivax, Loop-mediated isothermal amplification, Context (language use), Sensitivity and Specificity, Apicomplexa, Republic of Korea, parasitic diseases, Malaria, Vivax, RNA, Ribosomal, 18S, medicine, Humans, biology, DNA, Protozoan, medicine.disease, biology.organism_classification, Virology, Infectious Diseases, Insect Science, Tropical medicine, Plasmodium vivax infection, Parasitology, Nucleic Acid Amplification Techniques, Nested polymerase chain reaction, Malaria
Abstract

Loop-mediated isothermal amplification (LAMP) is a novel technique that rapidly amplifies target DNA in isothermal conditions. In a previous study, the sensitivities and specificities of LAMP, microscopy, and nested PCR were compared in the context of rapid malaria detection. In the present study, LAMP detected vivax malaria parasites in 115 of 117 microscopically positive samples (sensitivity, 98.3%; 95% CI, 97.4–100%), which agreed well with the nested PCR results (sensitivity, 99.1%; 95% CI: 96.0–100%). No positive cases of malaria were detected by LAMP or nested PCR in 50 consecutive feverish patients other than malaria from malaria endemic areas. LAMP performed on DNA extracted from heat-treated blood had a sensitivity of 93.3% (28/30, 95% CI: 84.4–100%) and specificity of 100% (30/30, 95% CI: 100%). The present study shows that LAMP based assays have high sensitivity, specificity, and amplification efficiencies for Plasmodium vivax detection. The authors recommend that LAMP can be considered as a rapid nucleic acid amplification assay for the molecular diagnosis of P. vivax in both clinical laboratories and malaria clinics in areas where vivax malaria is endemic.

Published
2010

2. Endometrial signet ring cell metastasis from advanced gastric cancer: case report

Author

Dae-Woon Eom, Taeeun Kim, Yongchel Ahn, Ho Suk Oh, Heui June Ahn, Moon Ho Kim, Dong Seok Lee, and Gil Hyun Kang

Subjects
Oncology, medicine.medical_specialty, business.industry, Signet ring cell, Internal medicine, Cancer research, Medicine, Hematology, Advanced gastric cancer, business, medicine.disease, Metastasis
Published
2015

3. 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

4. Mammalian Target of Rapamycin Inhibitors Versus Vascular Endothelial Growth Factor Tyrosine Kinase Inhibitors (VEGF TKI) as Second-Line Therapy in Patients with Metastatic Renal Cell Carcinoma after Failure of First-Line VEGF TKI: Single Center Retrospective Analysis

Author

K. Park, Yongcheol Ahn, J.H. Hong, Jong-Joon Ahn, Cheryn Song, J.-L. Lee, S.H. Park, Inkeun Park, Heui June Ahn, and Choung Soo Kim

Subjects
Sorafenib, Oncology, medicine.medical_specialty, Everolimus, Sunitinib, business.industry, medicine.drug_class, Hematology, medicine.disease, Temsirolimus, Tyrosine-kinase inhibitor, respiratory tract diseases, Vascular endothelial growth factor, chemistry.chemical_compound, chemistry, Renal cell carcinoma, Internal medicine, medicine, business, PI3K/AKT/mTOR pathway, medicine.drug
Abstract

Background Sequential therapy is a standard strategy used to overcome the limitations of targeted agents in metastatic renal cell carcinoma. It remains unclear whether a mammalian target of rapamycin (mTOR) inhibitor is a more effective second-line therapy after first-line VEGF TKI has failed than the alternative, vascular endothelial growth factor tyrosine kinase inhibitor (VEGF TKI). Methods A clinical database was used to identify all patients with mRCC treated with VEGF TKIs in the Asan Medical Center. Medical records were reviewed to identify those patients in whom first-line VEGF TKI failed and who were then treated with second-line VEGF TKI or mTOR inhibitors. Patient medical characteristics, radiological response and survival status were assessed. Results Of the 83 patients who met the inclusion criteria, 41 received second-line VEGF TKI [sunitinib (n = 16) and sorafenib (n = 25)] and 42 were treated with mTOR inhibitors [temsirolimus (n = 11) and everolimus (n = 31)]. After a median follow-up duration of 23.9 months (95% CI: 17.8–30.0), progression-free survival was 3.0 months for both groups [hazard ratio (HR, VEGF TKI versus mTOR inhibitor) = 0.97, 95% CI: 0.59–1.62, P = 0.92]. Overall survival was 10.6 months for the VEGF TKI group and 8.2 months for the mTOR inhibitor group (HR = 0.98, 95% CI: 0.57–1.68, P = 0.94). The two groups did not differ significantly in terms of the disease control rate (51% for VEGF TKI and 59% for mTOR inhibitor, P = 0.75). Conclusions Second-line VEGF TKI seems to be as effective as mTOR inhibitors and may be a viable option as a second-line agent after first-line anti-VEGF agents have failed.

Published
2012

5. RANDOMIZED PHASE II STUDY OF FIRST-LINE EVEROLIMUS (EVE) + BEVACIZUMAB (BEV) VERSUS INTERFERON ALFA-2A (IFN) + BEV IN PATIENTS (PTS) WITH METASTATIC RENAL CELL CARCINOMA (MRCC): RECORD-2

Author

Rickard Sandin, Javier Diaz, David Smith, investigators, H. Pandha, A. Damato, M. Del Prete, M. Reckova, E. Korbenfeld, A. Seth, Cristina Suarez, P. Celiz, S. Liskova, R.K. Sahoo, A. Felici, A. Suder, Francesco Cognetti, P. Gronesova, G. Martignoni, M. Jebali, E. Fernández-Parra, C. Bokemeyer, Yingwei Peng, M.C. Sebastia, H. Mullot, Daniele Raggi, D. Urosa Velasco, Begoña Mellado, J. Chester, Corina Andresen, Sally Ellis, N. Nicolai, A. Omar, A. Ambavane, Georg A. Bjarnason, Frank Priou, A. Vieillefond, T. Wahlgren, U. Harmenberg, H. Nemeth, M. Rivoire, Guru Sonpavde, C. Binder, V. Prati, M. Witkowski, R. Delva, J.F. Rodríguez-Moreno, L. Stern, V. Calderero, O. Bauduceau, Andrea Viqueira, K. Kaiser, Maurizio Colecchia, M.P. López Martí, M.E. Lampron, J.T. Hartmann, D. Tunali, Reza Elaidi, V. Galvis, Z. Sycova-Mila, Veg Team, R. von Moos, Jose Carlos Benitez, Simon Chowdhury, H. Mergenthaler, F. Arpaci, S. Cascinu, G. Erdem, A. Comte, J.M. Sepulveda Sanchez, K. Slimane, Mustafa Benekli, Paul Nathan, S. Van Belle, B. Metzner, Hussein M. Khaled, Q. Wang, Denice D. Tsao-Wei, J. Jin, H. Cortes-Funes, N. Clottens, P. Wilson, G. Procopio, A.L. Gentile, L. Burattini, Robert E. Hawkins, R. Montironi, G.R. Pond, Viorel Jinga, B. Ceccaldi, Tanya B. Dorff, S. Lata, Sergio Bracarda, P. Palacka, N. Karadurmus, S. Tumolo, Mario Sznol, A. Guillot, H. Spliid, C. Kahl, Cora N. Sternberg, K. Nagyivanyi, N. Sarwar, G. Krekeler, G. Fischer, S. Le Moulec, Brian I. Rini, R. Casciano, Derek Raghavan, F. Mehmud, N.V. Jensen, Suleyman Buyukberber, J.P. Fusco, Kim Edmonds, C. Messina, H.G. Sayer, Sanjiv S. Agarwala, R.J. Jones, J. Ribeiro, T. Geldart, A. González del Alba, E. López Juarez, G. Mead, Ben Challacombe, I. Brindel, T. M-H, F. Lumachi, S.M. M. Basso, E.Q. Bergan, R. Morales-Barrera, J.L. Perez Gracia, P. Cislo, I. Victoria, B. Sarsık, M. Cakar, S. Lee, Marc Campayo, R. Roy, A. Necchi, M. Ozturk, Hai T. Tran, R. Mondéjar Solís, M. Schmidt, N. Dalal, J. Coombs, Danka Cholujova, Ashok Kumar Gupta, C. Poehlein, S. Ozkan, B. Maughan, W.E. Berdel, C. Masini, F. Pili, A. Vuillemin, R. Martínez-Monge, J.J. Zudaire, F. Orlandi, C. Cianci, J. Bay, J. Thompson, C. Theodore, L. McCann, Anne Gold, N. Muzaffar, A. Houlgatte, L. Bergmann, X. Ren, G.B. Chiara, M. Ktiouet, Muhammad A. Khattak, J. Eymard, N. Nagaraj, J. Yu, Alfredo Falcone, Oezlem Anak, C. Korn, Karim Fizazi, P. Biron, V. Usakova, E. Gökmen, A. Flechon, R.R. Prasad, R. Bianco, M.E. Zudaire, S.J. Park, U. De Giorgi, Brad Rosbrook, F. Selle, A. Zurita-Saavedra, E. Verzoni, Günter Niegisch, J.L. Álvarez-Ossorio, Börje Ljungberg, N. Lainez, T.M. Kim, Irina Proskorovsky, C. Rodriguez-Antona, L. Maute, Komel Khabra, F. Algaba, A.C. Palozzo, L. Bodnar, O. Etxaniz, L. Galli, J.-P. Lotz, S.S. Sridhar, Yongchel Ahn, G. El Hussiny, E. Paze, M. Bianconi, E. Esteban, I. Fernandes, Omid Hamid, V. Kruse, P.F. Geertsen, Laurence Albiges, Joseph C. Cappelleri, M. Gaulet, Mayer Fishman, W. Kong, Aslam Sohaib, L. Formisano, B. Biswas, Heui June Ahn, C. Nicolau, G. Ye, P. Beuzeboc, C. Arqueros, A. Bair, H. Abdel Azim, F. Riet, T. Turker, J. Fouque, John D. Powderly, G. Velasco, J. Areal, G. Papiani, B. Wittig, D.R. Siemens, U. Anido, G. Anguera, J. Medioni, K. Pennert, G.G. Hermann, Igor Puzanov, D. Herchenhorn, James Larkin, B. Bui, P. Srinivasan, I. Waxman, J. Garcia-Donas, M. Ermani, J. Malet, R. Buzzoni, C. Emmanouilides, L. Kumar, Xin-Yun Huang, J. Beaumont, M. Bragagni, F. Fabbri, M. Santoni, A. Castillo, A. Pantuck, S. Imbevaro, G. Chahine, K. Zhang, D. Ondrus, Parminder Singh, Francesco Massari, S. Spanik, Svetozar Gogov, J. Kowalski, N. Pardo, J.M. Miclea, Dae Ho Lee, P. Gerletti, P. Rocca Cossu, H.J. Choi, Stéphane Oudard, J. Guo, A. Berkenblit, Pablo Maroto, A.R. Jazeih, L. Hodge, D. Ye, Daniel Castellano, David Cella, I.G. Sullivan, Vsevolod Matveev, I. Temby, Gwenaelle Gravis, J. Khalil, R. Fougeray, M. Wheater, G. Di Lorenzo, P. Landsman-Blumberg, A.J. Birtle, S. Zanetta, M. Harza, Y. Su, A. Badran, A. Alcaraz, K. Wood, S. Weikert, D. Chen, M. Bonomi, B. Paño, E. Garanzini, L. Ciuffreda, Lisa Derosa, D.J. George, L. Cerbone, J-H Ahn, A.J. McPartlin, E. Barsoum, J. Droz, Antonin Levy, T. Brechenmacher, J. Kim, A. Ozet, S Songül Yalçin, P.A. Zucali, F. Brusa, L. Steelman, J.J. Sánchez, O.E. Carranza, I. Bodrogi, Alain Ravaud, E. Boleti, L. Santomé, I. Chaib, J.V. Heymach, B. Sanchez, E. Matczak, Ying Chen, E. Castanon Alvarez, C. Farfan, J-P. Machiels, J. P. Maroto, J.H. Hong, S. Babakulov, G. Elhussiny, D. Santeufemia, L. Chen, A. Shamseddine, Jacek Pinski, S. Stergiopoulos, J.L. Cuadra Urteaga, A. Boeckenhoff, Viktor Grünwald, P. Sandström, C. Ketchens, S. Rudman, L. Costa, I. Cañamares, Shaowen Qin, M.C. Lopez Lopez, Darrel P. Cohen, A. Cappetta, R. De Vivo, M.J. Méndez-Vidal, Georgia Kollia, U. Kube, K.M. Boucher, Tim O'Brien, Z. Küronya, A.M. Molina, Y.-N. Wong, C. Ferrario, A.M. Gianni, M.D. Michaelson, R. Salvioni, Walter M. Stadler, M. Taron, S. Sarker, B. Kopf, L. Wang, B. Lutiger, Jon M. Wigginton, C. Sacco, J. Shanks, Sarvendra Kumar, C. Buges, L. Wood, M. Domenech, Riccardo Giampieri, M.P. Trojniak, R. Sabbatini, N. Leonhartsberger, R. Lewis, L. Anton-Aparicio, A.J. Zurita Saavedra, Yohann Loriot, D. Giannarelli, M. Cichowicz, M. Aglietta, E. Horn, N. Bonnin, J. Wang, M. Nicodemo, A. Bamias, X. Xiao, M. Calderon, P. Giannatempo, K. Dykstra, Lisa Pickering, Patricia A. English, G. Rosti, J. Ma, G. Guderian, Jean Jacques Patard, Andrew G. Bushmakin, N. Siddqui, P. Sabin Domínguez, C. Chevreau, J. Carles, D. Muskett, I.F. Tannock, A. Scarpa, G. Deplanque, Emilio Bria, L. Védrine, C. Chen, H. Villavicencio, S. Pan, Bohuslav Melichar, J. Palou, W. Kozłowski, Michal Mego, E. Jones, H. Ozturk, J.A. Arranz Arija, A. Benedict, C. Helissey, R. González Beca, G. Kooiman, Yuan Liu, C. May, K. Bíró, E. Hall, S. Vazquez-Estevez, M. Morente, R. Rosa, Raika Durusoy, A. Caty, R. Keyser, A. Shablak, J.A. Williams, D. Burcoveanu, M. Tschaika, S. Navruzov, E. Weith, F. de Braud, R. Kockelbergh, Begoña Perez-Valderrama, A.V. Soerensen, J.A. Peña, Christophe Massard, A. Chandra, M. Staehler, L.E. Abella, W. Arafat, G. Fargues, A. Darwish, E. De Coene, H. Sun, C. Martin Lorente, Robin Wiltshire, Cyrus Chargari, A. Louveau, E. Aitini, L. van Bortel, A. Onofri, A.A. Patel, I. Chirivella Gonzalez, F. Villacampa, J. Rajec, D. Biasoni, C. Szczylik, J. Schmitz, U. Mueller, P.F. Conte, M. Carducci, G. Tapia Rico, Anne Schuckman, Xun Lin, I. Alemany, A. Farnesi, E. Arevalo, Meral Kurt, M.O. Giganti, C. Song, I.G. Schmidt-Wolf, J. Pan, M. De Fromont, M. Schmidinger, K. Das, M. Yaman, C. Teghom, C. Boni, I. Ozer-Stillman, F. Maines, B. Moya Ortega, T.B. Powles, S. Pusceddu, I. Barista, I. Duran, S. Cierniak, M.E. Gore, R. Rosell, Jamal Tarazi, E. Kurt, D. Svetlovska, G. Li, F. Gyergyay, W. Yin, C. Porta, I. Park, M. Smoter, G. Rottenberg, S. Crabb, M. Rizzo, G. Gravis-Mescam, A. Spencer-Shaw, David M. Berman, R. Janciauskiene, F. Pons Valladares, I. Testa, E. Bajetta, Olga Valota, M. Lazaro, B. Esteves, Mario Scartozzi, M. Catanzaro, M. Arzoz, David F. McDermott, E. Sevin, Charles G. Drake, L. Ye, Ugur Coskun, A. Lorch, D. Pelov, D. Xanthaki, L. Nappi, G. Lo Re, Giampaolo Tortora, L. Ruiz, Kolette D. Fly, P. Mendez, M. Johnson, M. Jakobsson, Y. Lin, Sinil Kim, J.Y. Yuan, I. Chiappino, I.A. Muazzam, Xudong Zhang, K.J. Park, Stéphane Culine, C. Papandreou, S. Hauser, B. Paolini, O. Fernandez, D. Kalanovic, L. León, C. De La Piedra, R. Iacovelli, S. Provent, P.D. Simmonds, Michele Milella, D. Jäger, K. Massopust, G. Miolo, J. Neves, D. Amadori, F.L. Lim, M. Ramos Vazquez, A. De Both, S. Ozaydin, O. Reig Torras, E. Villa, G. Mickisch, T. Nguyen, R. Stec, M. Schroff, Cristina Suarez Rodriguez, S. Rottey, Boris Alekseev, O. Rick, D. Condori, W.J. Mackillop, J. Gligorov, Christopher M. Booth, A. Fontana, A.S. Ataergin, L. Capdevila, J.-F. Martini, M. Jimenez, J. Loewy, Piotr Tomczak, J. Hu, K.L. Baker-Neblett, M. Pastorek, P. Rescigno, V. Miskovska, F. Atzori, Thomas Gauler, K. Fode, Ü.E. Bagriacik, D. Nosov, Y. Kim, P.C. Lara, Frede Donskov, Michael B. Atkins, L. Géczi, V. Lorusso, Kiruthikah Thillai, F. Zhou, A.M. Aparicio, B. González, Susan Groshen, M. Aieta, R. Cathomas, E. Calvo, A. Lopez, S. Hernando, D.S. Heo, F. Goldwasser, F. Boccardo, Carlos H. Barrios, V. Damiano, Toni K. Choueiri, L.N. Pandite, F.J. Afonso, Jonathan Shamash, Fiona C Thistlethwaite, G.R. Hudes, Mellar P. Davis, D. Macedo, A. Font, Joaquim Bellmunt, S. Lundstam, Ignacio Gil-Bazo, T. Eisen, J. Qiu, Siamak Daneshmand, David I. Quinn, Ashok Panneerselvam, S. De Placido, L. Jacobasch, M. Climent, Luca Faloppi, Petri Bono, B.K. Mohanti, F. Valduga, Y. Huang, M. Zemanova, M. Fehr, E. Biasco, A. Kaprin, T. Montella, Cristian Loretelli, O. Ekinci, S. S¸en, C. Bailly, Sylvie Negrier, L. Ozkan, Beata Korytowsky, T. de Revel, A. Somers, B. Escudier, Umut Demirci, K. Stauch, Helen Boyle, A. Jirillo, C. Kim, R.A. Figlin, N. Shi, Joseph K. T. Lee, A. Jouinot, G. Abdel Metaal, R. Marconcini, C. Dubot, A. Pinto, L. Crino, T.E. Hutson, Thomas Powles, J. Mardiak, D. Cesic, Sook Ryun Park, D. Kim, S. Cetintas, Subramanian Hariharan, Alessandro Bittoni, M. Cotreau, J. Donovan, J. Obertova, Robert J. Motzer, and T. Steiner

Subjects
medicine.medical_specialty, medicine.medical_treatment, Gastroenterology, 03 medical and health sciences, 0302 clinical medicine, Prostate, Internal medicine, medicine, Stomatitis, Objective response, 030304 developmental biology, 0303 health sciences, Proteinuria, Genitourinary system, business.industry, Treatment options, Hematology, medicine.disease, Nephrectomy, 3. Good health, medicine.anatomical_structure, Oncology, Tolerability, 030220 oncology & carcinogenesis, medicine.symptom, business
Abstract

Background Study results demonstrated that IFN augments BEV activity and improves median PFS in pts with mRCC. Thus, combination BEV + IFN is a standard first-line treatment option for mRCC. Combining BEV with the mTOR inhibitor EVE may be an efficacious and well-tolerated treatment option. The open-label, phase II RECORD-2 trial compared first-line EVE + BEV and IFN + BEV in mRCC. Patients and methods: Therapy-naive pts with clear cell mRCC and prior nephrectomy were randomized 1:1 to BEV 10 mg/kg IV every 2 weeks with either EVE 10 mg oral daily or IFN (9 MIU SC 3 times/week, if tolerated). Tumour assessments were every 12 weeks. Primary objective was treatment effect on progression-free survival (PFS) per central review based on an estimate of the chance of a subsequent phase III trial success (50% threshold for phase II success). Results In EVE + BEV (n = 182) and IFN + BEV (n = 183) arms, median age was 60/60 years, 76/72% of pts were men, MSKCC risk was favourable/intermediate/poor in 36/57/7% and 36/57/7% of pts, and 43/46% of pts had >2 organs involved, respectively. For EVE + BEV and IFN + BEV, median treatment duration was 8.5/8.3 months, respectively; 23/26% of pts discontinued due to AEs. In EVE + BEV and IFN + BEV arms, median PFS by central review was 9.3/10.0 months (HRIFN/EVE, 0.91; 95% CI, 0.69-1.19; P =0.485), respectively; probability of subsequent phase III success was 5.1%. Results of central and local PFS analysis were consistent. Objective response rate was 27/28% in EVE + BEV and IFN + BEV arms, respectively. Median overall survival (OS) was not reached in the EVE + BEV arm and was 25.9 months (95% CI: 21.1, 30.2) in the IFN + BEV arm. Most frequent AEs (%) were stomatitis (63), proteinuria (49), diarrhoea (39), hypertension (38), and epistaxis (35) in EVE + BEV arm and decreased appetite (45), fatigue (41), proteinuria (37), and pyrexia (35) in IFN + BEV arm. Conclusions In RECORD-2, PFS and tolerability were similar for first-line EVE + BEV and IFN + BEV. Final OS analysis will occur after 2-year follow-up. Disclosure A. Ravaud: Alain Ravaud is a member of global, European, and/or French boards on urological tumors for Pfizer, Novartis, GlaxoSmithKline, Bayer-Schering, and Dendreon, and has received institutional grant support from Pfizer, Novartis, and Roche. O. Anak: Ozlem Anak is an employee of Novartis Pharma AG. D. Pelov: Diana Pelov is an employee of Novartis Pharmaceuticals Corporation. A. Louveau: Anne-Laure Louveau is an employee of Novartis Pharma S.A.S. T. M-H: Tay M-H is a speaker for an advisory board for Novartis Pharmaceuticals Corporation. B. Melichar: Bohuslav Melichar has received honoraria from Novartis and Roche and served on an advisory board for Roche. All other authors have declared no conflicts of interest.

Published
2012

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