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1. First-line pembrolizumab with or without chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: 5-year follow-up of the Japanese population of KEYNOTE‑048

Author

Oridate, Nobuhiko, Takahashi, Shunji, Tanaka, Kaoru, Shimizu, Yasushi, Fujimoto, Yasushi, Matsumoto, Koji, Yokota, Tomoya, Yamazaki, Tomoko, Takahashi, Masanobu, Ueda, Tsutomu, Hanai, Nobuhiro, Yamaguchi, Hironori, Hara, Hiroki, Yoshizaki, Tomokazu, Yasumatsu, Ryuji, Nakayama, Masahiro, Shiga, Kiyoto, Fujii, Takashi, Mitsugi, Kenji, Takahashi, Kenichi, Nohata, Nijiro, Gumuscu, Burak, Lerman, Nati, and Tahara, Makoto

Published
2024
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7. Outcomes in biomarker-selected subgroups from the KESTREL study of durvalumab and tremelimumab in recurrent or metastatic head and neck squamous cell carcinoma

Author

Seiwert, Tanguy Y., Wildsmith, Sophie, Fayette, Jérôme, Harrington, Kevin, Gillison, Maura, Ahn, Myung-Ju, Takahashi, Shunji, Weiss, Jared, Machiels, Jean-Pascal, Baxi, Shrujal, Baker, Valerie, Evans, Brent, Morsli, Nassim, Jill Walker, Real, Katia, L’Hernault, Anne, and Psyrri, Amanda

Published
2024
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8. Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial

Author

Rischin, Danny, Hughes, Brett GM, Gao, Bo, McGrath, Margaret, Greil, Richard, Thurnher, Dietmar, Fuereder, Thorsten, Burian, Martin, Rottey, Sylvie, Machiels, Jean-Pascal, Clement, Paul M, Henry, Stéphanie, Deheneffe, Stéphanie, Vasconcelos Alves, Gustavo, Lima, Iane Pinto Figueiredo, Mourão Dias, Josiane, De Marchi, Pedro Rafael Martins, Mak, Milena Perez, Pereira de Santana Gomes, Andrea Juliana, Oliveira de Castro Junior, Dalvaro, Motta, Tatiane Cardoso, Agostinho Padoan, Monica Luciana, Victorina, Ana Paula, de Azevedo, Sergio Jobim, Siu, Lillian L, Brule, Stephanie, Hilton, John, Wang, Chang Shu, Bouganim, Nathaniel, Webster, Marc, Walker, John, Chua, Neil, Zambrano, Angela Regina, Quiroga Echeverri, Alicia, Niño Gomez, Oscar Mauricio, Ortiz, Carlos Alberto, Rojas, Luis, Cardona Zorilla, Andrés, Urrego Meléndez, Olga Marcela, Holečková, Petra Beran, Melichar, Bohuslav, Cvek, Jakub, Prausová, Jana, Vošmik, Milan, Delord, Jean-Pierre, Zasadny, Xavier, Geoffrois, Lionnel, Tao, Yungan, Pointreau, Yoann, Fietkau, Rainer, Haderlein, Marlen, Mueller, Andreas H, Schroeder, Ursula, Wollenberg, Barbara, Laban, Simon, Ivanyi, Philipp, Gruenwald, Viktor, Schafhausen, Philippe, Gutfeld, Orit, Gluck, Iris, Popovtzer, Aron, Meirovitz, Amichay, Billan, Salem, Brenner, Baruch, Limon, Dror, Licitra, Lisa, Perri, Francesco, Caponigro, Francesco, Violati, Martina, Ferrari, Daris, Nole, Franco, Bertolini, Federica, Livi, Lorenzo, Ghi, Maria Grazia, Imarisio, Ilaria, Tahara, Makoto, Homma, Akihiro, Ueda, Tsutomu, Asada, Yukinori, Yamazaki, Tomoko, Matsumoto, Koji, Fujii, Takashi, Ikeda, Sadakatsu, Takahashi, Shunji, Kinoshita, Takashi, Sasaki, Keita, Tsuji, Akihito, Ahn, Myung-Ju, Cho, Byoung Chul, Lee, Keun-Wook, Lee, Ki Hyeong, Choi, Moon Ki, Yun, Hwan Jung, Hendriks, Mathijs P, Oosting, Sjoukje F, Buter, Jan, Van Meerten, Esther, Graham, Jonathan, Kawecki, Andrzej, Debicka, Izabella, Maciejczyk, Adam, Pysz, Maciej, Filarska, Dorota, Hetnał, Marcin, Koralewski, Piotr, Wygoda, Andrzej, Składowski, Krzysztof, Talerczyk, Małgorzata, Berrocal Jaime, Alfonso, Pérez Segura, Pedro, Braña García, Irene, Basté Rotllan, Neus, Mesía Nin, Ricard, Taberna Sanz, Miren, Iglesias Docampo, Lara, Soria Rivas, Ainara, Rueda Domínguez, Antonio, Trigo Pérez, José Manuel, Hong, Ruey-Long, Li, Shau-Hsuan, Wang, Hung-Ming, Yen, Chia-Jui, Yang, Muh-Hwa, Chang, Yi-Fang, Liu, Yi-Chun, Lin, Jin-Ching, Ekenel, Meltem, Harputluoğlu, Hakan, Aksoy, Sercan, Özyilkan, Özgür, Bılıcı, Ahmet, Şendur, Mehmet Alı Nahıt, Arslan, Cagatay, Harrington, Kevin, Ramkumar, Shanmugasundaram, Gujral, Dorothy, Stewart, Simon, Powell, Melanie, Sibtain, Amen, Roques, Tom, Yip, Kent, Mirza, Arafat, Sivaramalingam, Muthiah, Belman, Neil D, Agarwala, Sanjiv, Anderson, Ian, Patel, Arpan, Maggiore, Ronald, Baumgart, Megan, Burtness, Barbara, Fidler, Mary Jo, Kaur, Varinder, Gaughan, Elizabeth, Worden, Francis, Rodriguez, Cristina P, Sukari, Ammar, Wong, Deborah, Yom, Sue, Walsh, William V, Fiorillo, Joseph A, Yorio, Jeffrey T, Obara, Grzegorz S, Alves, Gustavo, Hughes, Brett G M, Mesía, Ricard, Taberna, Miren, Waldron, John N, Simon, Christian, Grégoire, Vincent, Harrington, Kevin J, Swaby, Ramona F, Zhang, Yayan, Gumuscu, Burak, and Bidadi, Behzad

Published
2024
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12. First-line pembrolizumab ± chemotherapy for recurrent/metastatic head and neck cancer: Japanese subgroup of KEYNOTE-048

Author

Takahashi, Shunji, Oridate, Nobuhiko, Tanaka, Kaoru, Shimizu, Yasushi, Fujimoto, Yasushi, Matsumoto, Koji, Yokota, Tomoya, Yamazaki, Tomoko, Takahashi, Masanobu, Ueda, Tsutomu, Hanai, Nobuhiro, Yamaguchi, Hironori, Hara, Hiroki, Yoshizaki, Tomokazu, Yasumatsu, Ryuji, Nakayama, Masahiro, Shiga, Kiyoto, Fujii, Takashi, Mitsugi, Kenji, Takahashi, Kenichi, Nohata, Nijiro, Gumuscu, Burak, Swaby, Ramona F., and Tahara, Makato

Published
2022
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14. Efficacy and Safety of Pembrolizumab in Previously Treated Advanced Neuroendocrine Tumors: Results From the Phase II KEYNOTE-158 Study

Author

Strosberg, Jonathan, Mizuno, Nobumasa, Doi, Toshihiko, Grande, Enrique, Delord, Jean-Pierre, Shapira-Frommer, Ronnie, Bergsland, Emily, Shah, Manisha, Fakih, Marwan, Takahashi, Shunji, Piha-Paul, Sarina A, O'Neil, Bert, Thomas, Sajeve, Lolkema, Martijn P, Chen, Menghui, Ibrahim, Nageatte, Norwood, Kevin, and Hadoux, Julien

Subjects
Digestive Diseases, Clinical Research, Cancer, Adult, Aged, Aged, 80 and over, Antibodies, Monoclonal, Humanized, Antineoplastic Agents, Immunological, B7-H1 Antigen, Disease Progression, Drug Resistance, Neoplasm, Female, Humans, Male, Middle Aged, Neuroendocrine Tumors, Programmed Cell Death 1 Receptor, Survival Rate, Oncology and Carcinogenesis, Oncology & Carcinogenesis
Abstract

PurposeKEYNOTE-158 (ClinicalTrials.gov identifier: NCT02628067) investigated the efficacy and safety of pembrolizumab across multiple cancers. We present results from patients with previously treated advanced well-differentiated neuroendocrine tumors (NET).Patients and methodsPembrolizumab 200 mg was administered every 3 weeks for 2 years or until progression, intolerable toxicity, or physician/patient decision. Tumor imaging was performed every 9 weeks for the first year and then every 12 weeks. Endpoints included objective response rate (ORR) per RECIST v1.1 by independent central radiologic review (primary) and duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety (secondary).ResultsA total of 107 patients with NETs of the lung, appendix, small intestine, colon, rectum, or pancreas were treated. Median age was 59.0 years (range, 29-80), 44.9% had ECOG performance status 1, 40.2% had received ≥3 prior therapies for advanced disease, and 15.9% had PD-L1-positive tumors (combined positive score ≥1). Median follow-up was 24.2 months (range, 0.6-33.4). ORR was 3.7% (95% CI, 1.0-9.3), with zero complete responses and four partial responses (three pancreatic and one rectal) all in patients with PD-L1-negative tumors. Median DOR was not reached, with one of four responses ongoing after ≥21 months follow-up. Median PFS was 4.1 months (95% CI, 3.5-5.4); the 6-month PFS rate was 39.3%. Median OS was 24.2 months (95% CI, 15.8-32.5). Treatment-related adverse events (AE) occurred in 75.7% of patients, 21.5% of whom had grade 3-5 AEs.ConclusionsPembrolizumab monotherapy showed limited antitumor activity and manageable safety in patients with previously treated advanced well-differentiated NETs.

Published
2020

17. Preliminary safety, pharmacokinetics and clinical activity of DFF332, an oral HIF2α inhibitor, as monotherapy in a phase 1 dose escalation study in patients with advanced clear cell renal cell carcinoma.

Author

Pal, Sumanta Kumar, primary, Tannir, Nizar M., additional, Grell, Peter, additional, Gao, Xin, additional, Kotecha, Ritesh R, additional, Picus, Joel, additional, De Braud, Filippo G., additional, Takahashi, Shunji, additional, Wong, Alvin, additional, Suárez, Cristina, additional, Otero, Javier A, additional, Kundamal, Nicole, additional, Yang, Xin, additional, Sharaby, Sherif, additional, Roy, Mike, additional, Barzaghi-Rinaudo, Patrizia, additional, and Albiges, Laurence, additional

Published
2024
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18. Tucatinib and trastuzumab for previously treated HER2−mutated metastatic breast cancer (SGNTUC−019): A phase 2 basket study.

Author

Okines, Alicia Frances Clare, primary, Curigliano, Giuseppe, additional, Mizuno, Nobumasa, additional, Oh, Do-Youn, additional, Rorive, Andree, additional, Soliman, Hatem Hussein, additional, Takahashi, Shunji, additional, Bekaii-Saab, Tanios S., additional, Hamilton, Erika P., additional, Monk, Bradley J., additional, Nakamura, Yoshiaki, additional, Nguyen, Danny, additional, O'Malley, David M., additional, Reck, Martin, additional, Yu, Evan Y., additional, Ramos, Jorge, additional, Tan, Sherry, additional, Stinchcombe, Tom, additional, and Pohlmann, Paula R, additional

Published
2024
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23. Pembrolizumab for previously treated advanced anal squamous cell carcinoma: results from the non-randomised, multicohort, multicentre, phase 2 KEYNOTE-158 study

Author

Marabelle, Aurelien, Cassier, Philippe A, Fakih, Marwan, Kao, Steven, Nielsen, Dorte, Italiano, Antoine, Guren, Tormod Kyrre, van Dongen, Marloes G J, Spencer, Kristen, Bariani, Giovanni Mendonca, Ascierto, Paolo A, Santoro, Armando, Shah, Manisha, Asselah, Jamil, Iqbal, Syma, Takahashi, Shunji, Piha-Paul, Sarina A, Ott, Patrick A, Chatterjee, Arkendu, Jin, Fan, Norwood, Kevin, and Delord, Jean-Pierre

Published
2022
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29. Fusobacterium nucleatum, immune responses, and metastatic organ diversity in colorectal cancer liver metastasis.

Author

Shigematsu, Yasuyuki, Saito, Rumiko, Amori, Gulanbar, Kanda, Hiroaki, Takahashi, Yu, Takeuchi, Kengo, Takahashi, Shunji, and Inamura, Kentaro

Abstract

The presence of Fusobacterium nucleatum is associated with an immunosuppressive tumor immune microenvironment (TIM) in primary colorectal cancer (CRC), contributing to tumor progression. Its persistence in CRC liver metastasis tissues raises questions about its role in modulating local and systemic immune responses and influencing recurrence patterns. This retrospective cohort study of 218 patients with CRC liver metastasis investigated the association of F. nucleatum in CRC liver metastasis tissues with systemic inflammation, TIM alterations, and the number of metastatic organs involved in recurrence. Two‐step polymerase chain reaction (PCR), including digital PCR, detected F. nucleatum in 42% (92/218) of fresh‐frozen specimens of CRC liver metastases. Compared with the F. nucleatum‐none group, the F. nucleatum‐high group showed higher C‐reactive protein levels (0.82 vs. 0.22 mg/dL; Ptrend = 0.02), lower numbers of CD8+ cells (33.2 vs. 65.3 cells/mm2; Ptrend = 0.04) and FOXP3+ cells (11.3 vs. 21.7 cells/mm2; Ptrend = 0.01) in the TIM, and a greater number of metastatic organs involved in recurrence (1.6 vs. 1.1; p < 0.001). The presence of F. nucleatum in CRC liver metastasis tissues was associated with increased systemic inflammation, TIM alterations, and a greater number of metastatic organs involved in recurrence. These findings suggest a potential contribution of F. nucleatum to the metastatic propensity of CRC cells and could inform future research to enhance understanding of the interaction between tumor, host, and microbes in the metastatic process. [ABSTRACT FROM AUTHOR]

Published
2024
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30. Cemiplimab monotherapy in Japanese patients with recurrent or metastatic cervical cancer.

Author

Hasegawa, Kosei, Takahashi, Shunji, Ushijima, Kimio, Okadome, Masao, Yonemori, Kan, Yokota, Harushige, Vergote, Ignace, Monk, Bradley J., Tewari, Krishnansu S., Fujiwara, Keiichi, Li, Jingjin, Jamil, Shaheda, Paccaly, Anne, Takehara, Kazuhiro, Usami, Tomoka, Aoki, Yoichi, Suzuki, Nao, Kobayashi, Yoichi, Yoshida, Yoshio, and Watari, Hidemichi

Subjects
*CANCER chemotherapy, *JAPANESE people, *CEMIPLIMAB, *CERVICAL cancer, *OVERALL survival
Abstract

Background: In the phase 3 EMPOWER‐Cervical 1/GOG‐3016/ENGOT‐cx9 study, cemiplimab significantly improved overall survival (OS) versus chemotherapy for patients with recurrent or metastatic cervical cancer who progressed after first‐line platinum‐based chemotherapy. We present a post hoc subgroup analysis of patients enrolled in Japan. Methods: Patients were enrolled regardless of programmed cell death‐ligand 1 status and randomized 1:1 to cemiplimab 350 mg intravenously every 3 weeks or investigator's choice single‐agent chemotherapy for up to 96 weeks. Primary endpoint was OS. Key secondary endpoints were progression‐free survival (PFS) and objective response rate (ORR). Results: Overall, 608 patients were randomized, of whom 56 (9.2%) were in Japan (cemiplimab, n = 29; chemotherapy, n = 27). The median (range) duration of follow‐up was 13.6 (6.0–25.3) versus 18.2 (6.0–38.2) months for patients in Japan and for the overall population, respectively. Median OS (95% confidence interval [CI]) was 8.4 (7.0‐not evaluable) and 9.4 (5.4–14.9) months for cemiplimab versus chemotherapy (hazard ratio [HR]: 0.86; 95% CI: 0.43–1.68). Median PFS (95% CI) was 4.0 (1.4–8.2) versus 3.7 (1.8–4.2) months with cemiplimab and chemotherapy (HR: 0.90; 95% CI: 0.50–1.61), respectively. ORR was 17.2% for cemiplimab and 7.4% for chemotherapy (odds ratio, 2.47; 95% CI, 0.44–13.99). Incidence of treatment‐emergent adverse events at any grade was 79.3% for cemiplimab and 100% for chemotherapy. Grade ≥3 adverse events were 37.9% versus 66.7% with cemiplimab and chemotherapy, respectively. Discussion: While acknowledging limitations inherent to a small subgroup analysis, the HR of 0.86 observed in Japanese patients suggests an emerging survival benefit despite a 4.6‐month shorter median duration of follow‐up versus the overall study population. [ABSTRACT FROM AUTHOR]

Published
2024
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31. Inverse Correlation between pks -Carrying Escherichia coli Abundance in Colorectal Cancer Liver Metastases and the Number of Organs Involved in Recurrence.

Author

Shigematsu, Yasuyuki, Saito, Rumiko, Kanda, Hiroaki, Takahashi, Yu, Takeuchi, Kengo, Takahashi, Shunji, and Inamura, Kentaro

Subjects
LIVER tumors, POLYKETIDES, RESEARCH funding, T cells, COLORECTAL cancer, BIOCHIPS, METASTASIS, ESCHERICHIA coli, GENES, IMMUNOHISTOCHEMISTRY, DISEASE relapse, CARCINOGENESIS, C-reactive protein
Abstract

Simple Summary: This study explores whether Escherichia coli carrying the polyketide synthetase (pks) gene cluster in colorectal cancer (CRC) liver metastasis tissues influence immune responses and cancer recurrence patterns. Analyzing tissues from 239 patients, we found that pks+ E. coli was present in 66.7% of liver metastasis cases. Higher levels of pks+ E. coli were associated with lower levels of the serum C-reactive protein, fewer densities of CD4+ cells and CD163+ cells in the tumor microenvironment, and a reduction in the number of organs affected by recurrent metastasis. These findings suggest that pks+ E. coli may influence both systemic and local immune responses, potentially reducing the diversity of affected metastatic organs. Colibactin, a genotoxin produced by Escherichia coli strains harboring the polyketide synthetase (pks) gene cluster, causes DNA damage and somatic mutations. pks+ E. coli is enriched in primary colorectal cancer (CRC) and is associated with clonal driver mutations, but its role in CRC liver metastasis is unclear. We assessed the association of pks+ E. coli in CRC liver metastasis tissues with systemic and local immune responses and the number of organs involved in recurrence using specimens and clinicopathological data from 239 patients with CRC liver metastasis who underwent metastasectomy. The levels of pks+ E. coli in fresh-frozen specimens were quantified as "very low" (<50th percentile), "low" (50th to 75th percentiles), and "high" (>75th percentile) using a digital PCR. Immunohistochemical analysis of tumor-infiltrating immune cells was performed using tissue microarrays. Systemic inflammation was evaluated using serum C-reactive protein (CRP) levels. pks+ E. coli was detected in 66.7% (157 of 239) liver metastasis tissues. Higher levels of pks+E. coli were associated with decreased serum CRP levels and reduced densities of CD4+ cells and CD163+ cells in the tumor-immune microenvironment. The "high" pks+ E. coli group had fewer metastatic organs involved than the "very low" pks+ E. coli group (mean number of organs: 1.00 vs. 1.23). These findings suggest that pks+ E. coli play a modulating role in CRC metastasis. [ABSTRACT FROM AUTHOR]

Published
2024
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32. Outcomes of long-term nivolumab and subsequent chemotherapy in Japanese patients with head and neck cancer: 2-year follow-up from a multicenter real-world study

Author

Yasumatsu, Ryuji, Shimizu, Yasushi, Hanai, Nobuhiro, Kariya, Shin, Yokota, Tomoya, Fujii, Takashi, Tsukahara, Kiyoaki, Ando, Mizuo, Hanyu, Kenji, Ueda, Tsutomu, Hirakawa, Hitoshi, Takahashi, Shunji, Ono, Takeharu, Sano, Daisuke, Yamauchi, Moriyasu, Watanabe, Akihito, Omori, Koichi, Yamazaki, Tomoko, Monden, Nobuya, Kudo, Naomi, Arai, Makoto, Yonekura, Syuji, Asakage, Takahiro, Nekado, Takahiro, Yamada, Takayuki, and Homma, Akihiro

Published
2022
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35. Expression of Syo_1.56 SARP Regulator Unveils Potent Elasnin Derivatives with Antibacterial Activity

Author

A. Abdelhakim, Islam, primary, Futamura, Yushi, additional, Asami, Yukihiro, additional, Hanaki, Hideaki, additional, Kito, Naoko, additional, Masuda, Sachiko, additional, Shibata, Arisa, additional, Muranaka, Atsuya, additional, Koshino, Hiroyuki, additional, Shirasu, Ken, additional, Osada, Hiroyuki, additional, Ishikawa, Jun, additional, and Takahashi, Shunji, additional

Published
2024
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36. A Prospective Cohort Study Exploring the Effect of Lenvatinib Planned Drug Holidays in Treatment of Differentiated Thyroid Cancer

Author

Tahara, Makoto, primary, Takami, Hiroshi, additional, Ito, Yasuhiro, additional, Okamoto, Takahiro, additional, Sugitani, Iwao, additional, Sugino, Kiminori, additional, Takahashi, Shunji, additional, Takeyama, Hiroshi, additional, Tsutsui, Hidemitsu, additional, Hara, Hisato, additional, Mitsuma, Ayako, additional, Yamashita, Hiroyuki, additional, Ohashi, Yasuo, additional, and Imai, Tsuneo, additional

Published
2024
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38. Pembrolizumab plus concurrent chemoradiotherapy versus placebo plus concurrent chemoradiotherapy in patients with locally advanced squamous cell carcinoma of the head and neck (KEYNOTE-412): a randomised, double-blind, phase 3 trial

Author

Machiels, Jean-Pascal, primary, Tao, Yungan, additional, Licitra, Lisa, additional, Burtness, Barbara, additional, Tahara, Makoto, additional, Rischin, Danny, additional, Alves, Gustavo, additional, Lima, Iane Pinto Figueiredo, additional, Hughes, Brett G M, additional, Pointreau, Yoann, additional, Aksoy, Sercan, additional, Laban, Simon, additional, Greil, Richard, additional, Burian, Martin, additional, Hetnał, Marcin, additional, Delord, Jean-Pierre, additional, Mesía, Ricard, additional, Taberna, Miren, additional, Waldron, John N, additional, Simon, Christian, additional, Grégoire, Vincent, additional, Harrington, Kevin J, additional, Swaby, Ramona F, additional, Zhang, Yayan, additional, Gumuscu, Burak, additional, Bidadi, Behzad, additional, Siu, Lillian L, additional, Hughes, Brett GM, additional, Gao, Bo, additional, McGrath, Margaret, additional, Thurnher, Dietmar, additional, Fuereder, Thorsten, additional, Rottey, Sylvie, additional, Machiels, Jean-Pascal, additional, Clement, Paul M, additional, Henry, Stéphanie, additional, Deheneffe, Stéphanie, additional, Vasconcelos Alves, Gustavo, additional, Mourão Dias, Josiane, additional, De Marchi, Pedro Rafael Martins, additional, Mak, Milena Perez, additional, Pereira de Santana Gomes, Andrea Juliana, additional, Oliveira de Castro Junior, Dalvaro, additional, Motta, Tatiane Cardoso, additional, Agostinho Padoan, Monica Luciana, additional, Victorina, Ana Paula, additional, de Azevedo, Sergio Jobim, additional, Brule, Stephanie, additional, Hilton, John, additional, Wang, Chang Shu, additional, Bouganim, Nathaniel, additional, Webster, Marc, additional, Walker, John, additional, Chua, Neil, additional, Zambrano, Angela Regina, additional, Quiroga Echeverri, Alicia, additional, Niño Gomez, Oscar Mauricio, additional, Ortiz, Carlos Alberto, additional, Rojas, Luis, additional, Cardona Zorilla, Andrés, additional, Urrego Meléndez, Olga Marcela, additional, Holečková, Petra Beran, additional, Melichar, Bohuslav, additional, Cvek, Jakub, additional, Prausová, Jana, additional, Vošmik, Milan, additional, Zasadny, Xavier, additional, Geoffrois, Lionnel, additional, Fietkau, Rainer, additional, Haderlein, Marlen, additional, Mueller, Andreas H, additional, Schroeder, Ursula, additional, Wollenberg, Barbara, additional, Ivanyi, Philipp, additional, Gruenwald, Viktor, additional, Schafhausen, Philippe, additional, Gutfeld, Orit, additional, Gluck, Iris, additional, Popovtzer, Aron, additional, Meirovitz, Amichay, additional, Billan, Salem, additional, Brenner, Baruch, additional, Limon, Dror, additional, Perri, Francesco, additional, Caponigro, Francesco, additional, Violati, Martina, additional, Ferrari, Daris, additional, Nole, Franco, additional, Bertolini, Federica, additional, Livi, Lorenzo, additional, Ghi, Maria Grazia, additional, Imarisio, Ilaria, additional, Homma, Akihiro, additional, Ueda, Tsutomu, additional, Asada, Yukinori, additional, Yamazaki, Tomoko, additional, Matsumoto, Koji, additional, Fujii, Takashi, additional, Ikeda, Sadakatsu, additional, Takahashi, Shunji, additional, Kinoshita, Takashi, additional, Sasaki, Keita, additional, Tsuji, Akihito, additional, Ahn, Myung-Ju, additional, Cho, Byoung Chul, additional, Lee, Keun-Wook, additional, Lee, Ki Hyeong, additional, Choi, Moon Ki, additional, Yun, Hwan Jung, additional, Hendriks, Mathijs P, additional, Oosting, Sjoukje F, additional, Buter, Jan, additional, Van Meerten, Esther, additional, Graham, Jonathan, additional, Kawecki, Andrzej, additional, Debicka, Izabella, additional, Maciejczyk, Adam, additional, Pysz, Maciej, additional, Filarska, Dorota, additional, Koralewski, Piotr, additional, Wygoda, Andrzej, additional, Składowski, Krzysztof, additional, Talerczyk, Małgorzata, additional, Berrocal Jaime, Alfonso, additional, Pérez Segura, Pedro, additional, Braña García, Irene, additional, Basté Rotllan, Neus, additional, Mesía Nin, Ricard, additional, Taberna Sanz, Miren, additional, Iglesias Docampo, Lara, additional, Soria Rivas, Ainara, additional, Rueda Domínguez, Antonio, additional, Trigo Pérez, José Manuel, additional, Hong, Ruey-Long, additional, Li, Shau-Hsuan, additional, Wang, Hung-Ming, additional, Yen, Chia-Jui, additional, Yang, Muh-Hwa, additional, Chang, Yi-Fang, additional, Liu, Yi-Chun, additional, Lin, Jin-Ching, additional, Ekenel, Meltem, additional, Harputluoğlu, Hakan, additional, Özyilkan, Özgür, additional, Bılıcı, Ahmet, additional, Şendur, Mehmet Alı Nahıt, additional, Arslan, Cagatay, additional, Harrington, Kevin, additional, Ramkumar, Shanmugasundaram, additional, Gujral, Dorothy, additional, Stewart, Simon, additional, Powell, Melanie, additional, Sibtain, Amen, additional, Roques, Tom, additional, Yip, Kent, additional, Mirza, Arafat, additional, Sivaramalingam, Muthiah, additional, Belman, Neil D, additional, Agarwala, Sanjiv, additional, Anderson, Ian, additional, Patel, Arpan, additional, Maggiore, Ronald, additional, Baumgart, Megan, additional, Fidler, Mary Jo, additional, Kaur, Varinder, additional, Gaughan, Elizabeth, additional, Worden, Francis, additional, Rodriguez, Cristina P, additional, Sukari, Ammar, additional, Wong, Deborah, additional, Yom, Sue, additional, Walsh, William V, additional, Fiorillo, Joseph A, additional, Yorio, Jeffrey T, additional, and Obara, Grzegorz S, additional

Published
2024
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45. Effectiveness of nivolumab affected by prior cetuximab use and neck dissection in Japanese patients with recurrent or metastatic head and neck cancer: results from a retrospective observational study in a real-world setting

Author

Kariya, Shin, Shimizu, Yasushi, Hanai, Nobuhiro, Yasumatsu, Ryuji, Yokota, Tomoya, Fujii, Takashi, Tsukahara, Kiyoaki, Yoshida, Masafumi, Hanyu, Kenji, Ueda, Tsutomu, Hirakawa, Hitoshi, Takahashi, Shunji, Ono, Takeharu, Sano, Daisuke, Yamauchi, Moriyasu, Watanabe, Akihito, Omori, Koichi, Yamazaki, Tomoko, Monden, Nobuya, Kudo, Naomi, Arai, Makoto, Yonekura, Shuji, Asakage, Takahiro, Fujiwara, Akinori, Yamada, Takayuki, and Homma, Akihiro

Published
2021
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46. A crotonyl-CoA reductase-carboxylase independent pathway for assembly of unusual alkylmalonyl-CoA polyketide synthase extender units.

Author

Ray, Lauren, Valentic, Timothy R, Miyazawa, Takeshi, Withall, David M, Song, Lijiang, Milligan, Jacob C, Osada, Hiroyuki, Takahashi, Shunji, Tsai, Shiou-Chuan, and Challis, Gregory L

Subjects
Streptomyces, Acyl Coenzyme A, Carbon-Carbon Ligases, Polyketide Synthases, Acyl-CoA Dehydrogenases, Bacterial Proteins, Crystallography, X-Ray, Molecular Structure, Amino Acid Sequence, Protein Conformation, Sequence Homology, Amino Acid, Substrate Specificity, Models, Molecular, Polyketides
Abstract

Type I modular polyketide synthases assemble diverse bioactive natural products. Such multienzymes typically use malonyl and methylmalonyl-CoA building blocks for polyketide chain assembly. However, in several cases more exotic alkylmalonyl-CoA extender units are also known to be incorporated. In all examples studied to date, such unusual extender units are biosynthesized via reductive carboxylation of α, β-unsaturated thioesters catalysed by crotonyl-CoA reductase/carboxylase (CCRC) homologues. Here we show using a chemically-synthesized deuterium-labelled mechanistic probe, and heterologous gene expression experiments that the unusual alkylmalonyl-CoA extender units incorporated into the stambomycin family of polyketide antibiotics are assembled by direct carboxylation of medium chain acyl-CoA thioesters. X-ray crystal structures of the unusual β-subunit of the acyl-CoA carboxylase (YCC) responsible for this reaction, alone and in complex with hexanoyl-CoA, reveal the molecular basis for substrate recognition, inspiring the development of methodology for polyketide bio-orthogonal tagging via incorporation of 6-azidohexanoic acid and 8-nonynoic acid into novel stambomycin analogues.

Published
2016

48. Real-world safety and effectiveness of radium-223 in Japanese patients with castration-resistant prostate cancer (CRPC) and bone metastasis: exploratory analysis, based on the results of post-marketing surveillance, according to prior chemotherapy status and in patients without concomitant use of second-generation androgen-receptor axis-targeted agents

Author

Uemura, Hirotsugu, Masumori, Naoya, Takahashi, Shunji, Hosono, Makoto, Kinuya, Seigo, Sunaya, Toshiyuki, Horio, Tomoyo, Okayama, Yutaka, and Kakehi, Yoshiyuki

Published
2021
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49. Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study

Author

Hanai, Nobuhiro, Shimizu, Yasushi, Kariya, Shin, Yasumatsu, Ryuji, Yokota, Tomoya, Fujii, Takashi, Tsukahara, Kiyoaki, Yoshida, Masafumi, Hanyu, Kenji, Ueda, Tsutomu, Hirakawa, Hitoshi, Takahashi, Shunji, Ono, Takeharu, Sano, Daisuke, Yamauchi, Moriyasu, Watanabe, Akihito, Omori, Koichi, Yamazaki, Tomoko, Monden, Nobuya, Kudo, Naomi, Arai, Makoto, Sakurai, Daiju, Asakage, Takahiro, Doi, Issei, Yamada, Takayuki, and Homma, Akihiro

Published
2021
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