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9. External validation of a genitourinary cancer-specific prognostic scoring system to predict survival for patients with bone metastasis (modified B-FOM scoring model): Comparison with other scoring models in terms of accuracy

Author

Owari, Takuya, Miyake, Makito, Nakai, Yasushi, Tanaka, Nobumichi, Itami, Yoshitaka, Hirao, Shuya, Momose, Hitoshi, Nakagawa, Yoshinori, Iida, Kouta, Maesaka, Fumisato, Shimizu, Takuto, Iemura, Yusuke, Matsumoto, Yoshihiro, Kuwada, Masaomi, Otani, Takeshi, Otsuka, Kenji, Okajima, Eijiro, Hosokawa, Yukinari, Okamura, Ryosuke, and Fujimoto, Kiyohide

Published
2021
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15. Development of Environmental Public Interest Litigation in China: How can public participation play its role beyond environmental authoritarianism?

Author

Otsuka, Kenji

Subjects
authoritarianism, China, spillover effect, environmental public interest litigation, Environmental governance
Abstract

China is well known as one of the longest-standing authoritarian countries ruled by a Communist party in the world. Nevertheless, both non-participatory and participatory approaches to decision making in environmental governance can be observed under this form of regime. How then can we identify their combinations in China’s environmental governance? In exploring this question, this study focuses on the recent development of environmental public interest litigation (EPIL) cases after the enactment of the revised Environmental Protection Law (EPL) in 2015, and tests the pro-authoritarianism assumption, “non-environmental spillover effects,” as a characteristic of Chinese “environmental authoritarianism” raised by earlier writers. Looking into the recent development of EPIL cases by NGOs and procuratorates carefully, it can be concluded that a kind of division of work between NGOs and procuratorates stipulated in the revised EPL could restrain authoritarian spillover effects, although there are disproportionately increasing numbers of cases by procuratorates than NGOs. Also, there are some cases where NGOs and procuratorates cooperate in EPILs. Furthermore, local NGOs can mobilize numerous volunteers in this process. The experience and knowledge accumulated among the broader group of locals in the country might bring an “environmental spillover effect,” which means a spillover toward pro-environmental democracy, to push EPIL reform toward a more participation-friendly style of involvement.

Published
2023

16. A multicenter, open‐label, phase II trial of pemetrexed plus bevacizumab in elderly patients with previously untreated advanced or recurrent nonsquamous non‐small cell lung cancer

Author

Yabuki, Yohei, primary, Hanibuchi, Masaki, additional, Takeuchi, Eiji, additional, Haku, Takashi, additional, Kanematsu, Takanori, additional, Nishimura, Naoki, additional, Toyoda, Yuko, additional, Mitsuhashi, Atsushi, additional, Otsuka, Kenji, additional, Sato, Seidai, additional, Goto, Hisatsugu, additional, Yoneda, Hiroto, additional, Ogino, Hirokazu, additional, Nokihara, Hiroshi, additional, Tsutomu, Shinohara, additional, and Nishioka, Yasuhiko, additional

Published
2023
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20. Introduction

Author

Terao, Tadayoshi, Otsuka, Kenji, Terao, Tadayoshi, editor, and Otsuka, Kenji, editor

Published
2007
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23. Single-laboratory Validation Study and Surveillance Using an Improved Multiresidue Analytical Method for Veterinary Drugs in Livestock Products by LC-MS/MS

Author

Hayashi, Momoka, primary, Kanda, Maki, additional, Yoshikawa, Souichi, additional, Nakajima, Takayuki, additional, Hayashi, Hiroshi, additional, Matsushima, Yoko, additional, Ohba, Yumi, additional, Koike, Hiroshi, additional, Nagano, Chieko, additional, Otsuka, Kenji, additional, and Sasamoto, Takeo, additional

Published
2023
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25. Blockade of PD-1/PD-L1 Pathway Enhances the Antigen-Presenting Capacity of Fibrocytes

Author

Afroj, Tania, Mitsuhashi, Atsushi, Ogino, Hirokazu, Saijo, Atsuro, Otsuka, Kenji, Yoneda, Hiroto, Tobiume, Makoto, Nguyen, Na Thi, Goto, Hisatsugu, Koyama, Kazuya, Sugimoto, Masamichi, Kondoh, Osamu, Nokihara, Hiroshi, and Nishioka, Yasuhiko

Subjects
PD-1/PD-L1 Blockade, Antigen-presentation, Fibrocytes, CD8+ T-cells, Cancer immunotherapy
Abstract

Fibrocytes, a distinct population of collagen-producing, monocyte-derived cells, are involved in wound healing as well as fibrotic diseases. Recently, fibrocytes have been revealed to play a role in the tumor microenvironment, particularly under antiangiogenic therapy. In addition, combination cancer immunotherapy with immune checkpoint inhibitor and antiangiogenic agents have been developed for various cancers in the clinical setting, although the immunological background is not clear. In the current study, we aimed to determine the function of fibrocytes in tumor immunity induced by immune checkpoint inhibitor therapy. Human and murine fibrocytes were generated from PBMCs and lungs, respectively. The expression of costimulatory and inhibitory molecules on fibrocytes was examined by flow cytometry. The stimulation of CD8+ T cells by fibrocytes was examined in MLRs with a 3H-thymidine incorporation assay. Fibrocytes expressed CD80low and CD86high as a costimulatory molecule, and expressed PD-L1high, but not PD-L2, as a coinhibitory molecule.Without any stimulation, fibrocytes strongly enhanced the proliferation of CD8+ T cells in mice and humans. Treatment with anti-CD86 and -CD54 Abs inhibited the growth of CD8+ T cells induced by fibrocytes. Anti–PD-L1 Ab further enhanced the proliferation of CD8+ T cells, even in the OVA-specific MLR with OT-1Rag-/- mice. Importantly, fibrocytes derived from PBMCs of patients with lung adenocarcinoma or murine MC38 tumors augmented the proliferation of CD8+ T cells with PD-L1 blockade. These results suggest that fibrocytes infiltrating tumor sites may play a role in the antitumor immunity mediated by CD8+ T cells when the activity is further enhanced by PD-L1/PD-1 blockade.

Published
2021

27. 抗PD-1抗体への化学療法の併用はmyeloid-derived suppressor cellsを減少させることにより中皮腫の増殖を抑制する

Author

Otsuka, Kenji, Mitsuhashi, Atsushi, Goto, Hisatsugu, Hanibuchi, Masaki, Koyama, Kazuya, Ogawa, Hirohisa, Ogino, Hirokazu, Saijo, Atsuro, Kozai, Hiroyuki, Yoneda, Hiroto, Tobiume, Makoto, Kishuku, Masatoshi, Ishizawa, Keisuke, and Nishioka, Yasuhiko

Subjects
PD-1, MDSC, Malignant pleural mesothelioma, Lung cancer, VEGF
Abstract

Background: The combination of anti-PD-1/PD-L1 antibody with chemotherapy has been approved for the first-line therapy of lung cancer. However, the effects against malignant mesothelioma (MPM) and the immunological mechanisms by which chemotherapy enhances the effect of targeting PD-1/PD-L1 in MPM are poorly understood. Materials and Methods: We utilized syngeneic mouse models of MPM and lung cancer and assessed the therapeutic effects of anti-PD-1 antibody and its combination with cisplatin (CDDP) and pemetrexed (PEM). An immunological analysis of tumor-infiltrating cells was performed with immunohistochemistry. Results: We observed significant therapeutic effects of anti-PD-1 antibody against MPM. Although the effect was associated with CD8+ and CD4+ T cells in tumors, the number of Foxp3+ cells was not reduced but rather increased. Consequently, combination with CDDP/PEM significantly enhanced the antitumor effects of anti-PD-1 antibody by decreasing numbers of intratumoral myeloid-derived suppressor cells (MDSCs) and vessels probably through suppression of VEGF expression by CDDP+PEM. Conclusions: The combination of anti-PD-1 antibody with CDDP+PEM may be a promising therapy for MPM via inhibiting the accumulation of MDSCs and vessels in tumors.

Published
2020

28. External validation of a genitourinary cancer-specific prognostic scoring system to predict survival for patients with bone metastasis (modified B-FOM scoring model): Comparison with other scoring models in terms of accuracy.

Author

Owari, Takuya, Miyake, Makito, Nakai, Yasushi, Tanaka, Nobumichi, Itami, Yoshitaka, Hirao, Shuya, Momose, Hitoshi, Nakagawa, Yoshinori, Iida, Kouta, Maesaka, Fumisato, Shimizu, Takuto, Iemura, Yusuke, Matsumoto, Yoshihiro, Kuwada, Masaomi, Otani, Takeshi, Otsuka, Kenji, Okajima, Eijiro, Hosokawa, Yukinari, Okamura, Ryosuke, Fujimoto, Kiyohide, Owari, Takuya, Miyake, Makito, Nakai, Yasushi, Tanaka, Nobumichi, Itami, Yoshitaka, Hirao, Shuya, Momose, Hitoshi, Nakagawa, Yoshinori, Iida, Kouta, Maesaka, Fumisato, Shimizu, Takuto, Iemura, Yusuke, Matsumoto, Yoshihiro, Kuwada, Masaomi, Otani, Takeshi, Otsuka, Kenji, Okajima, Eijiro, Hosokawa, Yukinari, Okamura, Ryosuke, and Fujimoto, Kiyohide

Abstract

Objective: We previously developed genitourinary (GU) cancer-specific scoring system for prediction of survival in patients with bone metastasis (the Bone-Fujimoto-Owari-Miyake [B-FOM] scoring model) based on five prognostic factors: the type of primary tumor (prostate cancer (PCa) vs renal cell carcinoma (RCC) and PCa vs urothelial carcinoma (UC)), poor performance status (PS), visceral metastasis, high Glasgow-prognostic score (GPS), elevated neutrophil-to-lymphocyte ratio (NLR). The aim of this study was to externally validate and further improve the performance of the B-FOM score. Methods: The external validation cohort comprised 309 patients with GU cancer with bone metastasis from multiple institutions. Clinical factors were analyzed using Kaplan-Meier method and COX regression hazard model. Performance of a modified B-FOM score was compared to that of other scoring models by the Kaplan-Meier method and the area under the curve (AUC) of receiver operating characteristic curves. Results: The median follow-up period of development and validation cohort were 25 and 17 months, respectively. Kaplan-Meier curve demonstrated that the type of primary tumor (RCC and UC vs PCa), poor PS, presence of visceral metastasis, high GPS, elevated NLR were significantly associated with shorter cancer-specific survival. Risk groups were successfully stratified by the modified B-FOM score classification. Moreover, the AUC of the modified B-FOM scoring model for predicting mortality at 6, 12, and 24 months were 0.895, 0.856, and 0.815, respectively, which were the highest among evaluated models. Conclusions: The B-FOM scoring model is a simple and accurate prediction tool. By using this scoring model at the time of the diagnosis of bone metastasis in patients with GU cancers, an individualized optimal treatment strategy can be selected., © 2020 The Authors. Published by Elsevier GmbH. This is an open access article under the CC BY-NC-ND license(https://creativecommons.org/licenses/by-nc-nd/4.0/).

Published
2022

29. Radiation therapy induces an abscopal effect and upregulates programmed death-ligand 1 expression in a patient with non-small cell lung cancer

Author

Morita, Yutaka, Saijo, Atsuro, Nokihara, Hiroshi, Mitsuhashi, Atsushi, Yoneda, Hiroto, Otsuka, Kenji, Ogino, Hirokazu, Bando, Yoshimi, Nishioka, Yasuhiko, Morita, Yutaka, Saijo, Atsuro, Nokihara, Hiroshi, Mitsuhashi, Atsushi, Yoneda, Hiroto, Otsuka, Kenji, Ogino, Hirokazu, Bando, Yoshimi, and Nishioka, Yasuhiko

Abstract

Radiation therapy (RT) activates the antigen presentation of dendritic cells and priming of cancer-specific cytotoxic CD8+ T cells, occasionally resulting in a systemic immune response to the tumor outside of the treatment field. The phenomenon of tumor regression at the site distant from irradiated fields is known as the abscopal effect. Several case reports have indicated a potential role of RT in overcoming primary and acquired resistance against immune checkpoint inhibitors in non-small cell lung cancer (NSCLC) and melanoma patients. We herein report an NSCLC patient who developed acquired resistance to an RT-induced abscopal effect and subsequently experienced reactivation of the systemic antitumor immune response by pembrolizumab, an antiprogrammed death 1 antibody. In this case, RT not only induced an abscopal effect but also upregulated the programmed death-ligand 1 expression outside of the irradiated field when the patient developed resistance to the abscopal effect. This case can facilitate our understanding of the mechanism underlying the RT-induced systemic immune response against cancer cells and adaptive resistance mechanism of cancer cells from immune surveillance. These findings highlight the promising results of current clinical trials combining RT and immune checkpoint inhibitors. Ongoing clinical trials will further establish evidence supporting combination therapy with RT and immune checkpoint inhibitors.

Published
2022

30. Surveillance of Acaricides in Honey

Author

Ohba, Yumi, primary, Nakajima, Takayuki, additional, Kanda, Maki, additional, Hayashi, Hiroshi, additional, Nagano, Chieko, additional, Yoshikawa, Souichi, additional, Matsushima, Youko, additional, Koike, Hiroshi, additional, Hayashi, Momoka, additional, Otsuka, Kenji, additional, and Sasamoto, Takeo, additional

Published
2022
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35. A case of pulmonary pleomorphic carcinoma with preexisting interstitial pneumonia successfully treated with pembrolizumab

Author

Sako, Masahiro, primary, Nokihara, Hiroshi, additional, Kondo, Kensuke, additional, Mitsuhashi, Atsushi, additional, Ozaki, Ryohiko, additional, Yabuki, Yohei, additional, Abe, Akane, additional, Yoneda, Hiroto, additional, Ogino, Hirokazu, additional, Otsuka, Kenji, additional, Uehara, Hisanori, additional, and Nishioka, Yasuhiko, additional

Published
2021
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36. Programmed death (PD)‐1/PD‐ligand 1 blockade mediates antiangiogenic effects by tumor‐derived CXCL10/11 as a potential predictive biomarker

Author

Mitsuhashi, Atsushi, primary, Kondoh, Kensuke, additional, Horikawa, Kazuki, additional, Koyama, Kazuya, additional, Nguyen, Na Thi, additional, Afroj, Tania, additional, Yoneda, Hiroto, additional, Otsuka, Kenji, additional, Ogino, Hirokazu, additional, Nokihara, Hiroshi, additional, Shinohara, Tsutomu, additional, and Nishioka, Yasuhiko, additional

Published
2021
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39. A case of pulmonary pleomorphic carcinoma with preexisting interstitial pneumonia successfully treated with pembrolizumab

Author

Sako, Masahiro, Nokihara, Hiroshi, Kondo, Kensuke, Mitsuhashi, Atsushi, Ozaki, Ryohiko, Yabuki, Yohei, Abe, Akane, Yoneda, Hiroto, Ogino, Hirokazu, Otsuka, Kenji, Uehara, Hisanori, Nishioka, Yasuhiko, Sako, Masahiro, Nokihara, Hiroshi, Kondo, Kensuke, Mitsuhashi, Atsushi, Ozaki, Ryohiko, Yabuki, Yohei, Abe, Akane, Yoneda, Hiroto, Ogino, Hirokazu, Otsuka, Kenji, Uehara, Hisanori, and Nishioka, Yasuhiko

Abstract

Pulmonary pleomorphic carcinoma is often refractory to chemotherapy and follows an aggressive clinical course. Immune checkpoint inhibitors (ICIs) have revolutionized the treatment of advanced lung cancer, and a few cases with pleomorphic carcinoma have been reported to show tumor shrinkage after therapy with ICIs. When treating patients with ICIs, patient selection is essential, and monitoring and management of immune-related adverse events, including pneumonitis, are needed. We herein report a case of pulmonary pleomorphic carcinoma with preexisting interstitial pneumonia treated with pembrolizumab, antiprogrammed cell death 1 antibody. Our report highlights important considerations necessary when treating advanced pleomorphic carcinoma patients complicated with interstitial pneumonia. We also review the literature regarding the use of ICIs in such patients.

Published
2021

45. Monitoring of residual antibacterial agents in animal and fishery products in Tokyo from 2003 to 2019: application and verification of a screening strategy based on microbiological methods

Author

Koike, Hiroshi, primary, Kanda, Maki, additional, Hayashi, Hiroshi, additional, Matsushima, Yoko, additional, Nakajima, Takayuki, additional, Yoshikawa, Souichi, additional, Ohba, Yumi, additional, Hayashi, Momoka, additional, Nagano, Chieko, additional, Sekimura, Kotaro, additional, Otsuka, Kenji, additional, Hashimoto, Tsuneo, additional, and Sasamoto, Takeo, additional

Published
2021
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46. Validation of a Method for Determining Multiple Residual Pesticides in Dried Red Pepper Using LC-MS/MS

Author

Watanabe, Shui, primary, Yamaki, Yumiko, additional, Tomizawa, Sanae, additional, Masubuchi, Tamako, additional, Kamijo, Kyoko, additional, Nakajima, Takayuki, additional, Yoshikawa, Souichi, additional, Yamamoto, Kazuoki, additional, Takada, Tomomi, additional, Kokaji, Yoshie, additional, Ohsawa, Yoshihiro, additional, Otsuka, Kenji, additional, and Hashimoto, Tsuneo, additional

Published
2020
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49. Determination of Antibacterial Agents for Animals in Swine Muscles by Microbiological Screening and LC-MS/MS

Author

Sekimura, Kotaro, primary, Kanda, Maki, additional, Hayashi, Hiroshi, additional, Matsushima, Yoko, additional, Yoshikawa, Souichi, additional, Ohba, Yumi, additional, Koike, Hiroshi, additional, Hayashi, Momoka, additional, Nagano, Chieko, additional, Otsuka, Kenji, additional, Hashimoto, Tsuneo, additional, and Sasamoto, Takeo, additional

Published
2020
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50. Comparison of Validation Results Obtained by GC-MS/MS and LC-MS/MS for the Analysis of Residual Pesticides in Agricultural Products

Author

Nakajima, Takayuki, primary, Otsuka, Kenji, additional, Tomizawa, Sanae, additional, Masubuchi, Tamako, additional, Yamaki, Yumiko, additional, Kamijo, Kyoko, additional, Yoshikawa, Souichi, additional, Takada, Tomomi, additional, Kokaji, Yoshie, additional, Watanabe, Shui, additional, Ohsawa, Yoshihiro, additional, and Hashimoto, Tsuneo, additional

Published
2020
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