Wiley Acta Medica Okayama 1347-9032 2021 First-line pembrolizumab vs chemotherapy in metastatic non-small-cell lung cancer: KEYNOTE-024 Japan subset EN Miyako Satouchi Department of Thoracic Oncology, Hyogo Cancer Center Kaname Nosaki Department of Thoracic Oncology, National Hospital Organization Kyushu Cancer Center Toshiaki Takahashi Division of Thoracic Oncology, Shizuoka Cancer Center Kazuhiko Nakagawa Department of Medical Oncology, Faculty of Medicine, Kindai University Keisuke Aoe Department of Medical Oncology, National Hospital Organization Yamaguchi Ube Medical Center Takayasu Kurata Department of Thoracic Oncology, Kansai Medical University Hospital Akimasa Sekine Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center Atsushi Horiike Department of Thoracic Medical Oncology, The Cancer Institute Hospital of the Japanese Foundation for Cancer Research Tatsuro Fukuhara Miyagi Cancer Center Shunichi Sugawara Department of Pulmonary Medicine, Sendai Kousei Hospital Shigeki Umemura Department of Thoracic Oncology, National Cancer Center Hospital East Hideo Saka Department of Respiratory Medicine and Medical Oncology, National Hospital Organization Nagoya Medical Center Isamu Okamoto Research Institute for Diseases of the Chest, Graduate School of Medical Sciences, Kyushu University Nobuyuki Yamamoto Internal Medicine III, Wakayama Medical University Hiroshi Sakai Department of Thoracic Oncology, Saitama Cancer Center Kazuma Kishi Department of Respiratory Medicine, Respiratory Center, Toranomon Hospital Nobuyuki Katakami Division of Integrated Oncology, Institute of Biomedical Research and Innovation Hospital Hidehito Horinouchi Department of Thoracic Oncology, National Cancer Center Hospital Toyoaki Hida Department of Thoracic Oncology, Aichi Cancer Center Hiroaki Okamoto Department of Respiratory Medicine and Medical Oncology, Yokohama Municipal Citizen’s Hospital Shinji Atagi Department of Thoracic Oncology, National Hospital Organization Kinki-Chuo Chest Medical Center Tatsuo Ohira Department of Surgery, Tokyo Medical University Shi Rong Han MSD K.K. Kazuo Noguchi MSD K.K. Victoria Ebiana Merck & Co., Inc. Katsuyuki Hotta Center for Innovative Clinical Medicine, Okayama University Hospital This prespecified subanalysis of the global, randomized controlled phase Ill KEYNOTE-024 study of pembrolizumab vs chemotherapy in previously untreated metastatic non-small-cell lung cancer without EGFR/ALK alterations and a programmed death-ligand 1 (PD-L1) tumor proportion score of 50% or greater evaluated clinical outcomes among patients enrolled in Japan. Treatment consisted of pembrolizumab 200 mg every 3 weeks (35 cycles) or platinum-based chemotherapy (four to six cycles). The primary end-point was progression-free survival; secondary end-points included overall survival and safety. Of 305 patients randomized in KEYNOTE-024 overall, 40 patients were enrolled in Japan (all received treatment: pembrolizumab, n = 21; chemotherapy, n = 19). The hazard ratio (HR) for progression-free survival by independent central review (data cut-off date, 10 July 2017) was 0.25 (95% confidence interval [CI], 0.10-0.64; one-sided, nominal P = .001). The HR for overall survival (data cut-off date, 15 February 2019) was 0.39 (95% CI, 0.17-0.91; one-sided, nominal P = .012). Treatment-related adverse events occurred in 21/21 (100%) pembrolizumab-treated and 18/19 (95%) chemotherapy-treated patients; eight patients (38%) and nine patients (47%), respectively, had grade 3-5 events. Immune-mediated adverse events and infusion reactions occurred in 11 patients (52%) and four patients (21%), respectively; four patients (19%) and one patient (5%), respectively, had grade 3-5 events. Consistent with results from KEYNOTE-024 overall, first-line pembrolizumab improved progression-free survival and overall survival vs chemotherapy with manageable safety among Japanese patients with metastatic non-small-cell lung cancer without EGFRIALK alterations and a PD-L1 tumor proportion score of 50% or greater. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 36 2 2002 Cytotoxicity of the Bacillus thuringiensis Crystal Protein against Mammalian Cells 61 66 EN Masashi Yamagiwa Akitoshi Namba Tetsuyuki Akao Eiichi Mizuki Michio Ohba Hiroshi Sakai 10.18926/47026 The crystal proteins produced by Bacillus thuringiensis subsp, israelensis (Bti) and subsp. coreanensis A1519 strain were examined for the cytotoxicity against MOLT-4 and HeLa cells by MTT assay and LDH assay, The A1519 crystal proteins processed by proteinase K exhibited the specific cell-killing activity toward MOLT-4 with little damage to the cell membrane, On the other hand, the Bti crystal proteins processed by proteinase K caused the substantial damage to the cell membrane of both MOLT-4 and HeLa, leading to the cell lysis. The non-digested crystal proteins of both strains exhibited no cytotoxicity, These data suggested that while the Bti crystal proteins caused the colloid-osmotic swelling and cell lysis of MOLT-4 and HeLa, the proteinase K-digested A1519 crystal proteins induced the specific cell death of MOLT-4 through a mechanism other than that of Bti. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 37 2 2003 The role of helices of domain I for the insecticidal activity of Bacillus thuringiensis Cry4A toxin 67 72 EN Masashi Yamagiwa Hiroshi Sakai 10.18926/46981 An active form of Cry4A is a heterodimer of the 20- and 45-kDa fragments that are derived from the 130-kDa Cry4A protoxin. To investigate the function of these two fragments, several deletion mutants were constructed and expressed in E.coli as the GST (glutathione-S-transferase) fusion proteins. The results of the bioassay against Culex pipiens larvae showed that the interaction of two fragments of Cry4A was necessary for the toxicity, and that the C-terminal 67 amino acids of the 20-kDa fragment corresponding to the helices α4 and α5 were involved in determining the insecticidal activity. Surprisingly the lack of helix α5 did not affect the toxicity to C. pipiens, suggesting that the role of helix α5 of Cry4A was different from that postulated in the case of Cry4A toxins. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 38 1-2 2004 The cytotoxicity of Bacillus thuringiensis subsp. coreanensis A2316 strain against the human leukemic T cell 97 100 EN Masashi Yamagiwa Taichi Hirao Masaaki Kiyomi Tetsuyuki Akao Eiichi Mizuki Michio Ohba Hiroshi Sakai 10.18926/46956 Bacillus thuringiensis subsp. coreanensis A2316 is a newly isolated strain from Yonakunijima Island in Japan. It produces the proteinaceous inclusion body (crystal) which has no insecticidal and hemolytic activities. When the crystal proteins were digested by proteinase K, they exhibited the strong cytotoxicity against human leukemic T cell, MOLT-4. The proteinase K-digested A2316 crystal proteins have little damage upon the cell membrane of MOLT-4, suggesting that the cell death of MOLT-4 was induced through a mechanism other than the colloid-osmotic swelling and cell lysis as caused by hitherto known B. thuringiensis crystal proteins. The 29-kDa polypeptide proved to be an active component of the proteinase K-digested A2316 crystal proteins. EC(50) of the purified 29-kDa polypeptide was 0.0579 μg/ml. The N-terminal amino acid sequence of the 29-kDa polypeptide was identical with that of p29 produced by B. thuringiensis A1519 strain and shared no significant homology with all the known proteins, suggesting that this polypeptide belong to a new family of B. thuringiensis crystal proteins. No potential conflict of interest relevant to this article was reported.

岡山大学環境管理センター Acta Medica Okayama 0917-1533 25 2003 微生物農薬による害虫の防除と環境保全 2 6 EN Hiroshi Sakai Masashi Yamagiwa No potential conflict of interest relevant to this article was reported.

岡山医学会 Acta Medica Okayama 0030-1558 93 5-6 1981 右脚ブロックの体表面心臓電位図（特に心房中隔欠損症を中心として）―超音波検査,右心カテーテル検査との対比― 579 592 EN Hidenori Yoshida Kazuo Ihoriya Haruki Nagahana Masanobu Nishihara Tatsuo Hyodo Toshiaki Uchida Masashi Kimura Kou Takeda Akinobu Fujii Daiji Saito Setsuro Tanatani Toshimasa Kita Hiroshi Sakai Shoichi Haraoka A body surface isopotential map was recorded in 30 cases of ASD and 3 cases of ECD with right bundle branch block in ECG, then analyzed in comparison with results obtained by cardiac catetherization and two dimensional echocardiograms. 1) In all cases of right bundle branch block, breakthrough minimum appeared later and shifted to the left compared with the normal. 2) Breakthrough minimum of ASD and ECD appeared progressively later associated with Qp/Qs ratio and left to right intracardiac shunt ratio obtained with cardiac catetherization and RVDd with echocardiogram. Breakthrough minimum of ASD and ECD moved to the left accompanied by increases in mean RV pressure, mean PA pressure and RVDd. 3) R'max voltage, the maximum positive potential in the late stage of ventricular depolarization on the right precordial area, increased and correlated well with the mean RV pressure and left to right shunt ratio increment. 4) In the case of ASD, breakthrough minimum appeared later and shifted to the left along with age. No potential conflict of interest relevant to this article was reported.

Faculty of Engineering, Okayama University Acta Medica Okayama 0475-0071 35 1-2 2001 The role of interhelical cleavage for insecticidal activityof Bacillus thuringiensis Cry4A toxin 147 154 EN Masashi Yamagiwa Hiroshi Sakai 10.18926/15366 The Cry4A toxin is a dipteran-specific insecticidal protein produced by Bacillus thuringiensis subsp. israelensis as a protoxin of 130 kDa. Its active form is a heterodimer of 20- and 45-kDa fragments which is generated by an interhelical cleavage of a 60-kDa intermediate at the position of Gln236 between α5 and α6 helices in domain I. On the other hand, Cry1Aa, which is also produced as a 130-kDa protoxin but toxic to lepidopteran larvae, was processed into the active 60-kDa fragment with no additional cleavage. To investigate the role of the intramolecular cleavage of Cry4A for its insecticidal activity, the loop between α5 and α6 of Cry4A which includes the cleavage site was substituted for the corresponding region of Cry1Aa. The resulting mutant designated GST-60Loop was expressed as a GST-fusion protein. A difference of the processing profile was observed between GST-60 and GST-60Loop in the in vitro digestion assay by trypsin, and the insecticidal activity of GST-60Loop was two-fold lower than that of GST-60. These results suggested that the interhelical cleavage of Cry4A promoted the toxicity against C. pipiens larvae. No potential conflict of interest relevant to this article was reported.