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BACKGROUND: Recently, 5-aminolevulinic acid (5-ALA)-induced protoporphyrin IX fluorescence was reported to be a useful tool during total surgical resection of high-grade gliomas. However, the labeling efficacy of protoporphyrin IX fluorescence is lower in metastatic brain tumors compared to that in high-grade gliomas, and the mechanism underlying protoporphyrin IX fluorescence in metastatic brain tumors remains unclear. Lung cancer, particularly non-small cell lung cancer (NSCLC), is the most common origin for metastatic brain tumor. Therefore, we investigated the mechanism of protoporphyrin IX fluorescence in NSCLC and associated metastatic brain tumors. METHODS: Western blotting and quantitative real-time polymerase chain reaction (qRT-PCR) was employed to evaluate the protein and mRNA levels of five transporters and enzymes involved in the porphyrin biosynthesis pathway: peptide transporter 1 (PEPT1), hydroxymethylbilane synthase (HMBS), ferrochelatase (FECH), ATP-binding cassette 2 (ABCG2), and heme oxygenase 1 (HO-1). The correlation between protein, mRNA, and protoporphyrin IX levels in NSCLC cells were evaluated in vitro. Immunohistochemistry was used to determine proteins that played a key role in intraoperative protoporphyrin IX fluorescence in clinical samples from patients with NSCLC and pathologically confirmed metastatic brain tumors. RESULTS: A significant correlation between PEPT1 expression and protoporphyrin IX accumulation in vitro was identified by western blotting (P = 0.003) and qRT-PCR (P = 0.04). Immunohistochemistry results indicated that there was a significant difference in PEPT1 between the intraoperative protoporphyrin IX fluorescence-positive and protoporphyrin IX fluorescence-negative groups (P = 0.009). CONCLUSION: Expression of PEPT1 was found to be positively correlated with 5-ALA-induced protoporphyrin IX accumulation detected by photodynamic reaction in metastatic brain tumors originating from NSCLC., 博士（医学）・甲第714号・令和元年年6月26日, Copyright © 2019 Elsevier B.V. All rights reserved.

Background/Aim: Natural killer (NK) cells are considered potential antitumor effector cells. The aim of this study was toestablish a novel type of a chimeric antigen receptor (CAR) NK cell line (CAR-KHYG-1) specific for epidermal growth factorreceptor variant III (EGFRvIII)-expressing tumors and investigate the anti-tumor activity of EGFRvIII-specific-CAR-KHYG-1(EvCAR-KHYG-1). Materials and Methods: EvCAR-KHYG-1 was established by self-inactivated lentiviral-based transduction of theEvCAR gene and magnetic bead-based purification of EvCAR-expressing NK cells. The anti-tumor effects of EvCAR-KHYG-1 wereevaluated using growth inhibition and apoptosis detection assays in glioblastoma (GBM) cell lines (EGFRvIII-expressing andnon-expressing U87MG). Results: The findings demonstrated that EvCAR-KHYG-1 inhibited GBM cell-growth via apoptosis in anEGFRvIII-expressing specific manner. Conclusion: This is the first study to establish a CAR NK cell line based on the humanNK cell line KHYG-1. Therapy with EvCAR-KHYG-1 may be an effective treatment option for GBM patients., 博士（医学）・甲第726号・令和2年3月16日, Copyright© 2018, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved., 発行元の規定により、本文の登録不可。本文は以下のURLを参照 "http://dx.doi.org/10.21873/anticanres.12824"（※全文閲覧は学内限定）

Glioblastoma is the leading malignant glioma with a poor prognosis. This study aimed to investigate the antitumor effects of natural killer cells in combination with temozolomide as the standard chemotherapeutic agent for glioblastoma. Using a simple, feeder-less, and chemically defined culture method, we expanded human peripheral blood mononuclear cells and assessed the receptor expression, natural killer cell activity, and regulatory T cell frequency in expanded cells. Next, using the standard human glioblastoma cell lines (temozolomide-sensitive U87MG, temozolomide-resistant T98G, and LN-18), we assessed the ligand expressions of receptors on natural killer cells. Furthermore, the antitumor effects of the combination of the expanded natural killer cells and temozolomide were assessed using growth inhibition assays, apoptosis detection assays, and senescence-associated β-galactosidase activity assays in the glioblastoma cell lines. Novel culture systems were sufficient to attain highly purified (>98%), expanded (>440-fold) CD3-/CD56+ peripheral blood-derived natural killer cells. We designated the expanded population as genuine induced natural killer cells. Genuine induced natural killer cells exhibited a high natural killer activity and low regulatory T cell frequency compared with lymphokine-activated killer cells. Growth inhibition assays revealed that genuine induced natural killer cells inhibited the glioblastoma cell line growth but enhanced temozolomide-induced inhibition effects in U87MG. Apoptosis detection assays revealed that genuine induced natural killer cells induced apoptosis in the glioblastoma cell lines. Furthermore, senescence-associated β-galactosidase activity assays revealed that temozolomide induced senescence in U87MG. Genuine induced natural killer cells induce apoptosis in temozolomide-sensitive and temozolomide-resistant glioblastoma cells and enhances temozolomide-induced antitumor effects in different mechanisms. Hence, the combination of genuine induced natural killer cells and temozolomide may prove to be a promising immunochemotherapeutic approach in patients with glioblastoma if the antitumor effects in vivo can be demonstrated., 博士（医学）・甲第715号・令和元年6月26日, Copyright: © 2019 Tanaka et al. This is an open access article distributed under the terms of the Creative Commons Attribution License(https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

The class of the school is one of the most important chances for schoolchildren who learn the name of living things. Indeed, various living things appear on textbooks. In the present study, 36 textbooks of 7 subjects for all grades at one elementary school in Hiroshima Pref. were examined. Names of living things described on them were picked out and classified. As the results, the names picked out were total of 583 kinds (animal: 312, plants: 263 and others: 8), and 349 kinds could be classified to the species level. “Cats” appeared on most textbooks. 13 kinds that include “dogs”, “mosses” and “cherry” appeared on a textbook in at least one subject of every grade. The most 323 kinds appeared on the textbook of Japanese. The 58.5 kinds that appeared on textbooks of science were the greatest by the mean value of kinds per one textbook. The chances, which schoolchildren learn about living things, are not only in science classes. Therefore, it was suggested that by cooperation between subjects based on the names of living things, schoolchildren deepen their knowledge about living things, and also it leads deeper understanding of the contents of other various subjects.

The addition of 2.5 at% Si or Al to Fe_2Tb causes the formation of an amorphous single phase and the glass formation range extends up to 15 at% Si or Al which is the maximum additional amount in the present study. The amorphous (Fe_2Tb)_M_ (M=Si or Al) alloys crystallize through two stages consisting of Am→Fe_2Tb+Am→Fe_2Tb+unknown compound. The Fe_2Tb phase in coexistent with the amorphous phase has a very fine spherical morphology with a particle size of 5 to 20 nm. The additional Si or Al element is enriched into the unknown compounds. The coexistent state of the nanocrystalline Fe_2Tb and amorphous phases extends over the temperature region of about 300 K because of the high thermal stability of the remaining amorphous phase. The high thermal stability of the amorphous phase and the formation of the nanoscale Fe_2Tb grains are presumably due to the necessity of the redistribution of Si or Al into the remaining amorphous phase. The best magnetostrictive properties of high σ_, low H_c, high λ_s and high λ/H were obtained in the coexistent nanocrystalline Fe_2Tb and amorphous phases and the phase transition into Fe_2Tb and unknown compounds caused the depression of the magnetostrictive properties.