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Nishijima, Yoshinori ; 西嶋, 義憲
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金沢大学人間社会研究域経済学経営学系<br />Persons or objects on signs seem to have a culturally preferred direction of facing (Kumakura, 1
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990). Is such a difference in direction also true of pictures on traffic signs between Japan and Germany? People in Japan and Germany drive on the left and the right side of the road, respectively. In this respect, a question arises: Does the difference between left-hand and right-hand traffic in these two countries influence the way the pictures on traffic signs face? The aim of this study is threefold: 1) to collect functionally equivalent traffic signs in Japan and Germany; 2) to compare the pictures on the signs between these countries with respect to their facing directions; and 3) to try to clarify whether and to what extent differences in facing directions are found on the traffic signs. The results are expected to contribute to the study of the relationship between writing directions and facing directions of pictures.
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Nishijima, Yoshinori ; 西嶋, 義憲
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金沢大学人間社会研究域経済学経営学系<br />This study focuses on functionally equivalent, but semantically different sign expressions in Ja
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panese and German, such as o-nori-no-sai-wa tesuri-ni o-tsukamarikudasai [Literally, “when steping on, please grip handrail”], kiiroi-sen-no uchigawani o-tachi-kudasai [please stand inside yellow line], oriru sai-wa o-oashimoto-ni gochūi-kudasai [“when getting off, please pay attention to under foot”], and o-ko-sama tsure-no kata-wa o-ko-sama-no te-o totte o-nori-kudasai [“person with child is asked to ride on taking child’s hand”] in Japanese versus its German counterpart Benutzung auf eigene Gefahr [“using at your own risk”], which are posted near escalators. This example tells us that the Japanese sign consists of four concrete sentences whereas the German one presents a simple and abstract sentence. Such correspondents cannot be adequately explained from only construal and politeness perspectives. In this study, such corresponding expressions in Japanese and German will be contrasted to find out what information is relevant to each society. The results will reveal what communicative behaviors are expected in corresponding situations between Japan and Germany, which can contribute to efficient intercultural communication.
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Nishijima, Yoshinori ; 西嶋, 義憲
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金沢大学人間社会研究域経済学経営学系<br />By comparing some functionally equivalent routine formulas in Japaneseand German in correspondin
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g situations, it is hypothesized that different strategies arereflected in formulation patterns of routine formulas in both languages. For example,different expressions are used by parents in Japanese and German if their childbumps into a post. The two expressions are often used in corresponding situations inboth Japan and Germany and can therefore be regarded as functionally equivalent,although the used strategies differ, i.e., the Japanese expression is based on sharing thedangerous situation between the parent and the child, whereas the German one focuseson providing an appropriate direction to the child. Comparing such functionallyequivalent routine formulas suggests that they reflect different strategies, includingpoliteness, in corresponding situations. This study tested this hypothesis by comparingfunctionally equivalent routine formulas uttered in corresponding apologetic situationsin the socialization process of controlling children’s social behavior in Japan andGermany. The results confirm the hypothesis and suggest that the difference in strategy influences the communicative behaviors of Japanese and German speakers. Concerning politeness, the results reveal the aspects considered polite in corresponding routineformulas of the two languages. Furthermore, the communicative normality of each language is also reflected in its respective routine formulas and focus of attention in interactions. This information may be applied toward more efficient foreign language teaching.
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Nishijima, Yoshinori ; 西嶋, 義憲
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金沢大学人間社会研究域経済学経営学系<br />The aim of this paper is twofold: (1) to compare functionally equivalent English, German, and Ja
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panese sign expressions in public spaces with respect to politeness and (2) to reveal whether and how politeness is formulated in sign expressions in each language in relation to explicitness. A total of 208 Japanese and 198 German sign expressions were collected through fieldwork. Among them, 35 functionally equivalent correspondence pairs between the two languages were confirmed, and they were compared, along with their English equivalents, with respect to politeness. The results showed that English signs tend to use explicit expressions, whereas Japanese signs frequently contain honorific items, and German signs use infinitive phrases to avoid mentioning personal relationships. Based on these findings, it is pointed out that each language has its preferred styles of politeness, even for sign expressions, which are expected to give relevant information or instructions to passengers in a clear, direct manner.
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Nishijima, Yoshinori ; 西嶋, 義憲
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金沢大学人間社会研究域経済学経営学系<br />Interest in the linguistic study of perspectives from which linguistic expressions are formulate
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d has been revived in the past 20 years, due to the recent development of cognitive linguistics. Among the many contributions to the study of such perspectives, Ikegami (2000) clearly showed that Japanese differs from English, through a comparison of a Japanese literary text with its English translation. However, there has been little discussion on the methods employed for comparison in the studies on this topic. The purpose of the present paper is threefold: (1) to describe what methodological problems are recognized in previous contrastive studies on the perspectives, especially in the field of cognitive linguistics; (2) in order to avoid methodological problems, to propose an alternative method for a more objective comparison of the perspectives between two languages; and (3) to demonstrate the validity of the proposed method for contrasting formulation patterns in terms of their perspective by some of the data obtained.
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Nishijima, Yoshinori ; 西嶋, 義憲
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金沢大学人間社会研究域経済学経営学系<br />The present paper discusses the different perspectives from which Japanese and German speakers f
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ormulate utterances. It was hypothesized that these different perspectives are reflected not only in evaluating concepts of communicative behavior, but also in routine formulas for controlling communicative behavior in Japanese and German. This hypothesis was examined by comparing two pairs of functionally equivalent routine formulas in Japanese and German. Furthermore, a questionnaire was administered to compare other Japanese and German routine formulas possibly used in corresponding situations. The results confirmed that in Japanese, linguistic formulation patterns relate to the empathy felt by the speaker toward an interlocutor, arising from the perspective of their situation, whereas in German, these tend to depend on an opposition between the participants involved, characterized by a perspective external to their situation. Because the data employed in the present study are limited, the hypothesis should be verified using extensive data. The results of this study helps clarify the possible misunderstandings between Japanese and German speakers, owing to the different linguistic formulation patterns employed, and could promote more efficient foreign language teaching.
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Nishijima, Yoshinori ; 西嶋, 義憲
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金沢大学人間社会研究域経済学経営学系<br />Research on the perspectives from which linguistic expressions are formulated has increased in t
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he past 20 years due to the development of cognitive linguistics. For example, Ikegami (2000) showed that Japanese and English speakers employ different perspectives by comparing the opening sentence of a Japanese literary text with its English translation. Similarly, Narita (2009) compared sentences from literary texts with their translations in Japanese and German. However, these studies analyzing literary text translations contain little discussion on the validity of the translation-based comparison method, particularly in terms of comparability and objectivity. This paper has three purposes: (1) to claim that the original and translation-based methods are not always appropriate for perspective studies; (2) to propose, as an alternative method, comparing functionally equivalent formulas used on public signs, i.e., Watch your step, Keep out, and Out of Service; and (3) to show how Japanese differs from German in the perspectives from which corresponding expressions in the two languages are formulated. Expressions were collected from signs on buses, trains, and railway stations in Japan and Germany. Examples include Haire-masen/Kein Eingang (‘No entrance’), Senro-ni orite-wa ike-masen/Ausstieg verboten (‘Do not go down to the railway track’), and ishitsubutsu-gakari/Fundbüro (‘Lost and found’). Functionally equivalent expressions were selected for the analysis. For example, a formula telling bus passengers that the bus will stop at the next station is Tsugi tomari-masu (next.TOP stop.HON) in Japanese and Wagen hält (vehicle.NOM stop.PRES) in German. These corresponding expressions can be compared syntactically and semantically. The former has no surface-level subject; it conveys that “I” and “we” or the bus will stop at the next station. The scene is described from the perspective inside the situation, i.e., from within the bus. The latter has a third-person subject, Wagen, signifying that the bus is observed from the perspective outside the situation. These different perspectives and their occurrence distributions are shown through the comparison of corresponding sign expressions. The analysis reveals that Japanese tends to formulate expressions from a perspective inside the scene where the event occurs, whereas German expresses sentences from the perspective outside the scene.<br />19th International Congress of Linguists(19 ICL), 21-27 July 2013 Geneva
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Mukaida, Naofumi ; Nakamoto, Yasunari ; 向田, 直史 ; 中本, 安成
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金沢大学がん進展制御研究所<br />Tumor immunity proceeds through multiple processes, which consist of antigen presentation by antigen
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presenting cells (APCs) to educate effector cells and destruction by the effector cytotoxic cells. However, tumor immunity is frequently repressed at tumor sites. Malignantly transformed cells rarely survive the attack by the immune system, but cells that do survive change their phenotypes to reduce their immunogenicity. The resultant cells evade the attack by the immune system and form clinically discernible tumors. Tumor microenvironments simultaneously contain a wide variety of immune suppressive molecules and cells to dampen tumor immunity. Moreover, the liver microenvironment exhibits immune tolerance to reduce aberrant immune responses to massively-exposed antigens via the portal vein, and immune dysfunction is frequently associated with liver cirrhosis, which is widespread in hepatocellular carcinoma (HCC) patients. Immune therapy aims to reduce tumor burden, but it is also expected to prevent non-cancerous liver lesions from progressing to HCC, because HCC develops or recurs from noncancerous liver lesions with chronic inflammatory states and/or cirrhosis and these lesions cannot be cured and/or eradicated by local and/or systemic therapies. Nevertheless, cancer immune therapy should augment specific tumor immunity by using two distinct measures: enhancing the effector cell functions such as antigen presentation capacity of APCs and tumor cell killing capacity of cytotoxic cells, and reactivating the immune system in immune-suppressive tumor microenvironments. Here, we will summarize the current status and discuss the future perspective on immune therapy for HCC. © The Author(s) 2018.<br />Supported by (in part) Research Programs on the Innovative Development and Application for New Drugs for Hepatitis B (No. 17fk0310116h0001) from the Japan Agency for Medical Research and Development (AMED) and Extramural Collaborative Research Grant of Cancer Research Institute, Kanazawa University.
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Fujisawa, Mieko ; Takemura, Kazuhisa ; Funaki, Yukihiko ; Udo, Nobuyuki ; Takahashi, Ryo ; 藤澤, 美恵子
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金沢大学人間社会研究域経済学経営学系<br />Many countries have implemented an energy labeling system that displays the energy savings perfo
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rmance of buildings. However, previous studies have reported mixed findings on the effectiveness of this system.This study is undertaken in Japan to assess whether energy labels are effective and validate the significance of the label design. We use an online survey to determine the effects of energy labels on target consumers. We choose two energy label designs: one with a stairs rating form design and the second with a rating scale of the energy efficiency. Adopting a within-subjects method, each respondent is shown both designs and asked to evaluate the energy-saving level based on the labels. Cross-tabulation confirms the positive effects of labeling on energy-savings levels, which are amplified by increasing the level of the reference point. The highest insulation performance level in Japan complies with a law enacted back in 1993; the results show that greater effects can be realized by increasing the level of the reference point.A logistic regression analysis shows that energy labels with the stairs rating have a negative influence, while labels with a rating scale are preferred based on ease of understanding by the respondents. This suggests that energy labels that offer a rating scale can contribute to facilitating energy savings, although there are problems with the comprehension of the gradation colors which need to be further examined. These results can act as a guideline towards optimal designs of the upcoming task of modifying the energy labeling system in Japan.<br />許可を得て登録 2021-04-09
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Haryanto ; Mukai, Kanae ; Nakajima, Yukari ; Okuwa, Mayumi ; Cau, Kim Jiu ; Sugama, Junko ; Nakatani, Toshio ; 向井, 加奈恵 ; 中島, 由加里 ; 大桑, 麻由美 ; 須釜, 淳子 ; 中谷, 壽男
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金沢大学医薬保健研究域保健学系<br />The purpose of this study is to evaluate and clarify the effect of Indonesian honey, two types of J
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apanese honey and hydrocolloid dressing on wound healing process. Four groups of male mice were treated to produce two circular full-thickness skin wounds on the dorsum. They were then randomly allocated to receive daily Indonesian honey, Japanese honey (Buckwheat and Acacia honey) or hydrocolloid dressing as a control for treatment application. Macroscopic findings were observed from day 0 to 14 after wounding. Microscopic evaluation was assessed using qualitative analysis. The ratios of wound areas for honey groups on day 3 and 7 were smaller than those of the control group. Wound areas of honey groups gradually decreased to almost the same wound area as the control group on day 14, while the wound area of the control group peaked on day 5 and rapidly decreased until day 14. Microscopic finding that Indonesian honey was different with Japanese honey especially Buckwheat honey.
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Mukai, Kanae ; Komatsu, Emi ; Nakajima, Yukari ; Urai, Tamae ; Nasruddin ; Sugama, Junko ; Nakatani, Toshio ; 向井, 加奈恵 ; 中島, 由加里 ; 須釜, 淳子 ; 中谷, 壽男
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金沢大学医薬保健研究域保健学系<br />Cutaneous wound healing is delayed by protein malnutrition (PM). On the other hand, estrogen promot
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es cutaneous wound healing by its anti-inflammatory and cell proliferation effects. Therefore, we hypothesized that estrogen administration in protein-malnourished ovariectomized (OVX) female mice might improve the inflammatory response and promote cutaneous wound healing as well as normal nutrition. To test this hypothesis, we used full-thickness excisional wounds in Control SHAM, PM SHAM, PM OVX and PM OVX+17β-estradiol mice. The Control diet included 200 g/kg protein and the PM diet included 30 g/kg protein. The ratio of wound area in the Control SHAM group was significantly smaller than those in the three PM groups. In addition, microscopic findings also showed that the ratio of collagen fibers, the ratio of myofibroblasts and the number of new blood vessels in the Control SHAM group were significantly greater than those in the three PM groups. However, the number of Ym1-positive cells as an anti-inflammatory M2-like macrophage marker in the PM OVX+17β-estradiol group was significantly higher than those in the other three groups. These results indicate that the appearance of anti-inflammatory M2-like macrophages was promoted by estrogen administration; however, it could not promote cutaneous wound healing upon a low-protein diet. Therefore, it may be confirmed that nutrition is more important for promoting cutaneous wound healing than estrogen administration.
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Mukai, Kanae ; Komatsu, Emi ; Nakajima, Yukari ; Urai, Tamae ; Nasruddin ; Sugama, Junko ; Nakatani, Toshio ; 向井, 加奈恵 ; 中島, 由加里 ; 浦井, 珠恵 ; 須釜, 淳子 ; 中谷, 壽男
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金沢大学医薬保健研究域保健学系<br />Topical estrogen application to wounds is effective in promoting cutaneous wound healing. However,
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whether it promotes cutaneous wound healing in delayed cutaneous wound healing associated with advanced age remains to be elucidated. This study aimed to evaluate the effect of topical estrogen application to wounds in cutaneous wound healing in 80-week-old female mice. C57BL/6J female mice aged 82–85 and 12 weeks old were submitted to two full-thickness wounds. Mice were divided into four groups: aged group, topical estrogen wound treatment aged group (aged-E), vehicle wound treatment aged group (aged-vehicle), and young group. Wound healing was observed until day 14. In the aged group, wound area ratio (wound area / initial wound area) was significantly higher on days 3–14, ratio of re-epithelialization was significantly lower on day 3 and tended to be lower on day 14, and neutrophil number was significantly higher on day 7 compared with the young group. In contrast, in the aged-E group, wound area ratio was significantly smaller on days 1–14, re-epithelialization ratio was significantly higher on days 3–14, and neutrophil and macrophage number was significantly lower on days 3 and 7 compared with the aged group. These results demonstrate that topical estrogen application to wounds in 80-week-old female mice promoted cutaneous wound healing by reducing wound area and inflammatory response and promoting re-epithelialization.
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Asano, Kimi ; Nakajima, Yukari ; Mukai, Kanae ; Urai, Tamae ; Okuwa, Mayumi ; Sugama, Junko ; Konya, Chizuko ; Nakatani, Toshio ; 浅野, きみ ; 中島, 由加里 ; 向井, 加奈恵 ; 浦井, 珠恵 ; 大桑, 麻由美 ; 須釜, 淳子 ; 紺家, 千津子 ; 中谷, 壽男
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金沢大学医薬保健研究域保健学系<br />Background Previously, we showed that lymphatic vessels (LVs) formed detours after lymphatic obstru
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ction, contributing to preventing lymphedema. In this study, we developed detours using lymphatic ligation in mice and we identified the detours histologically. Methods and results Under anesthesia, both hindlimbs in mice were subcutaneously injected with Evans blue dye to detect LVs. We tied the right collecting LV on the abdomen that passes through the inguinal lymph node (LN) at two points. The right and left sides comprised the operation and sham operation sides, respectively. Lymphography was performed to investigate the lymph flow after lymphatic ligation until day 30, using a near-infrared fluorescence imaging system. Anti-podoplanin antibody and 5-ethynyl-2’-deoxyuridine (EdU) were used to detect LVs and lymphangiogenesis. Within 30 days, detours had developed in 62.5% of the mice. Detours observed between two ligation sites were enlarged and irregular in shape. Podoplanin+ LVs, which were located in the subcutaneous tissue of the upper panniculus carnosus muscle, connected to collecting LVs at the upper portion from the cranial ligation site and at the lower portion from the caudal ligation site. EdU+ cells were not observed in these detours. The sham operation side showed normal lymph flow and did not show enlarged pre-collecting LVs until day 30. Conclusions Detours after lymphatic ligation were formed not by lymphangiogenesis but through an enlargement of pre-collecting LVs that functioned as collecting LVs after lymphatic ligation. Further studies are required to explore the developmental mechanism of the lymphatic detour for treatment and effective care of lymphedema in humans. © 2020 Asano et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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Ikeya, Noriyuki ; Tanaka, Gengo ; Tsukagoshi, Akira ; 田中, 源吾
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金沢大学国際基幹教育院GS教育系
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Tanaka, Gengo ; Ikeya, Noriyuki ; 田中, 源吾
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金沢大学国際基幹教育院GS教育系<br />Eighty-five fossil and Recent species of the genus Loxoconcha (Crustacea : Ostracoda) from East As
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ia are systematically reexamined. On the basis of carapace morphology, the genus Loxoconcha from East Asia is divided into five species groups : L. pulchra, L. optima, L. japonica, L. uranouchiensis and L. japonica species groups. The migration and speciation patterns of four species of the L. japonica species group are as follows. In Late Miocene, L. lilljeborgii and L. tumulosa were distributed over the Paleo-Indian Ocean. In Early Pliocene time, these species migrated to the Western Pacific and L. japonica evolved from populations of L. tumulosa by peramorphic evolution. In the Middle Pleistocene, L. shanhaiensis evolved from populations of L. japonica in the Ryukyu Islands by paedomorphic evolution.
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Tanaka, Gengo ; Seto, Koji ; Mukuda, Takao ; Nakano, Yusuke ; 田中, 源吾
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金沢大学国際基幹教育院GS教育系<br />Thirty-five ostracod species belonging to 18 genera are recognized from the Middle Miocene Fujina
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Formation (ca. 14-12 Ma), 3km southwest of Matsue City, Shimane Prefecture, Japan. Most of these species are part of the recent Japan Sea proper water fauna; they are also classified into 4 categories, circumpolar, cryophilic, endemic cool-temperate and temperate species. These ostracod assemblages indicate that the Fujina Formation was deposited under a cold-water environment. Ten new species, Ambtonia shimanensis, A. takayasui, Acanthocythereis fujinaensis, A. izumoensis, Cluthia tamayuensis, C. subjaponica, Kotoracythere tsukagoshii, Laperousecythere ikeyai, Palmoconcha irizukii, and Robertsonites yatsukanus are described.
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Tanaka, Gengo ; 田中, 源吾
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金沢大学国際基幹教育院GS教育系<br />島根県,出雲市菅沢の大森層より26属42種の介形虫化石を抽出し,2つの介形虫群(Ambostracon-Argilloecia-Cytheropteron群集およびPaijenborchella-
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Palmoconcha-Urocythereis pohangensis群集)を認めた.これらの群集は冷温〜温暖な公海の下浅海環境を示唆する.大森層および布志名層からの介形虫化石群の主成分分析は,その堆積環境が上部層準に向かってしだいに深くなっていったことを示唆する.5新種(Cytheropteron shimanense, Loxoconcha izumoensis, Paradoxostoma yakumotatsunus, Schizocythere sakanoueiおよびUrocythereis sugesawensis)を記載した.<br />Ostracods from the Omori Formation in Sugesawa (Izumo City, Shimane Prefecture) comprise 42 species belonging to 26 genera. Five new species, Cytheropteron shimanense, Loxoconcha izumoensis, Paradoxostoma yakumotatsunus, Schizocythere sakanouei and Urocythereis sugesawensis are described. Two ostracod assemblages (Ambostracon-Argilloecia-Cytheropteron assemblage and Paijenborchella-Palmoconcha-Urocythereis pohangensis assemblage) are recognized. These assemblages indicate that the uppermost of the Omori Formation was deposited under the environments from cool to warm open sublittoral condition. Principal components analysis of ostracod assemblages from the Omori and Fujina Formations indicates that, in general, the depositional environment becomes deeper and deeper towards the upper horizon.
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Tanaka, Gengo ; Nakase, Hajime ; Yamashita, Shota ; Arai, Kazuno ; 田中, 源吾
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金沢大学国際基幹教育院GS教育系<br />In Rikuzentakata City, Ostracode assemblages in sediment deposited by the Tohoku‐Oki earthquake an
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d tsunami of 11 March 2011 revealed that the sediment was derived from the seafloor from at least 9 m water depth, and was transported inland more than 1 km. The tsunami wave height at this location was higher than 10 m. Four hundred fifty seven modern ostracode assemblages were used in the modern analogue technique to estimate the depth source of the tsunami deposited assemblages. The application of this method to paleo‐tsunami deposits may provide insight into past tsunami wave height and potentially earthquake slip and magnitude.<br />Embargo Period 6 months
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Tanaka, Gengo ; 田中, 源吾
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Sanyuania cuneata Zhao & Whatley, 1992 was reported initially from Late Pleistocene core samples from the northern part
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of the Yellow Sea and Recent sediments collected from supra tidal pools (17 practical salinity unit (psu)) in Xiangshangang Bay, East China Sea (Zhao & Whatley, 1992). Later, specimens were discovered, but not identified, in Lake Nakaumi, Shimane Prefecture, SW Japan (Fig. 1) (as Cytheridae gen. et. sp. indet. by Tanaka et al. (1998) and Sanyuania sp. by Seto et al. (1999)). Further examination of these Japanese specimens has clarified that they are conspecific with the Chinese specimens. This has provided an opportunity to review the distribution (Fig. 1) and potential environmental significance of Sanyuania cuneata and, for the first time, to describe its appendages (Fig. 2).Specimens figured herein were recovered from Lake Nakaumi (35°26′ 50″ N, 133°07′50″ E) at a depth of 0.3–6.0 m and salinity of 8–17 psu on 9 September 1998. The surface of the sediment was covered by the byssus of the mussel Musculista senhousia (Benson, 1842).Sanyuania cuneata is probably endemic to the East China Sea and the southwestern part of the Sea of Japan and is a potentially useful palaeoenvironmental indicator of brackish (steno-haline) environments in the area. By using the oxygen isotopic data from planktonic foraminifers and the estimated value of salinity flowing into the Japan Sea, Matsui et al. (1998) approximated that the salinity of the surface water of Japan Sea declined to about 20 psu during the Last Glacial Maximum . . .
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Tanaka, Gengo ; Parker, Andrew R. ; Hasegawa, Yoshikazu ; Siveter, David J. ; Yamamoto, Ryoichi ; Miyashita, Kiyoshi ; Takahashi, Yuichi ; Ito, Shosuke ; Wakamatsu, Kazumasa ; Mukuda, Takao ; Matsuura, Marie ; Tomikawa, Ko ; Furutani, Masumi ; Suzuki , Kayo ; Maeda, Haruyoshi ; 田中, 源吾
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金沢大学国際基幹教育院GS教育系<br />Vision, which consists of an optical system, receptors and image-processing capacity, has existed
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for at least 520 Myr. Except for the optical system, as in the calcified lenses of trilobite and ostracod arthropods, other parts of the visual system are not usually preserved in the fossil record, because the soft tissue of the eye and the brain decay rapidly after death, such as within 64 days and 11 days, respectively. The Upper Carboniferous Hamilton Formation (300 Myr) in Kansas, USA, yields exceptionally well-preserved animal fossils in an estuarine depositional setting. Here we show that the original colour, shape and putative presence of eumelanin have been preserved in the acanthodii fish Acanthodes bridgei. We also report on the tissues of its eye, which provides the first record of mineralized rods and cones in a fossil and indicates that this 300 Myr-old fish likely possessed colour vision.<br />This work was supported by the Science Research of Education and Science Government of Japan (grant no. 24540501 to G.T. and no. 24340129 to H.M.).
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Tanaka, Gengo ; Smith, Robin J. ; Siveter, David J. ; Parker, Andrew R. ; 田中, 源吾
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金沢大学国際基幹教育院GS教育系<br />Compound eyes are common in decapod crustaceans. Decapods have an abundant post-Palaeozoic fossil
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record, but hitherto morphological information about their eyes has been mainly restricted to Recent material. Here we report the discovery of compound eyes recovered from acetic acid residues of two fish-bearing nodules from the Cretaceous Santana Formation of Brazil; they include what are identified as decapod larval compound eyes. The fossil eyes are comparable to phyllosoma larval eyes because of the following characters: the hemispherical visual surface on a stalked eye; the relatively small-size of the visual surface of the eye; rounded facets are arranged in square arrays in the anterior region; the fact that the neighboring ommatidia are bounded by ridges and/ or grooves; and the more convex inner surface of the cornea lens. This report represents the first description of a three-dimensionally preserved fossil decapod eye. We conclude that the eyes probably represent palinuroid phyllosoma larval eyes and were an adaptation to a planktonic lifestyle. © 2009 Zoological Society of Japan.
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| 22.
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Kobayashi, Mio ; Kakuda, Yuko ; Harada, Kenichi ; Sato, Yasunori ; Sasaki, Motoko ; Ikeda, Hiroko ; Terada, Mitsuhiro ; Mukai, Munenori ; Kaneko, Shuichi ; Nakanuma, Yasuni ; 小林, 水緒 ; 原田, 憲一 ; 佐藤, 保則 ; 佐々木, 素子 ; 池田, 博子 ; 金子, 周一 ; 中沼, 安二
概要:
金沢大学医薬保健研究域医学系<br />AIM: To investigate histological and immunohistochemical differences in hepatitis between autoimmune
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hepatitis (AIH) and primary biliary cirrhosis (PBC) with AIH features. METHODS: Liver needle biopsies of 41 PBC with AIH features and 43 AIH patients were examined. The activity of periportal and lobular inflammation was scored 0 (none or minimal activity) to 4 (severe), and the degree of hepatitic rosette formation and emperipolesis was semiquantatively scored 0-3. The infiltration of mononuclear cells positive for CD20, CD38, CD3, CD4, and CD8 and positive for immunoglobulins (IgG, IgM, and IgA) at the periportal areas (interface hepatitis) and in the hepatic lobules (lobular hepatitis) were semiquantitatively scored in immunostained liver sections (score 0-6). Serum aspartate aminotransferase (AST), immunoglobulins, and autoantibodies at the time of liver biopsy were correlated with the histological and immunohistochemical scores of individual lesions. RESULTS: Lobular hepatitis, hepatitic rosette formation, and emperipolesis were more extensive and frequent in AIH than in PBC. CD3+, CD4+, and CD8+ cell infiltration scores were higher in the hepatic lobules and at the interface in AIH but were also found in PBC. The degree of mononuclear cell infiltration correlated well with the degree of interface and lobular hepatitis in PBC, but to a lesser degree in AIH. CD20+ cells were mainly found in the portal tracts and, occasionally, at the interface in both diseases. Elevated AST correlated well with the hepatocyte necroinflammation and mononuclear cell infiltration, specifically CD38+ cells in PBC. No correlation existed between autoantibodies and inflammatory cell infiltration in PBC or AIH. While most AIH cases were IgG-predominant at the interface, PBC cases were divided into IgM-predominant, IgM/IgGequal, and IgG-predominant types, with the latter sharing several features with AIH. CONCLUSION: These results suggest that the hepatocellular injuries associated with interface and lobular hepatitis in AIH and PBC with interface hepatitis may not be identical. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
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| 23.
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Okazaki, Mitsuyoshi ; Makino, Isamu ; Kitagawa, Hirohisa ; Nakanuma, Shinichi ; Hayashi, Hironori ; Nakagawara, Hisatoshi ; Miyashita, Tomoharu ; Tajima, Hidehiro ; Takamura, Hiroyuki ; Ohta, Tetsuo ; 岡崎, 充善 ; 牧野, 勇 ; 北川, 裕久 ; 中沼, 伸一 ; 林, 泰寛 ; 中川原, 寿俊 ; 宮下, 知治 ; 田島, 秀浩 ; 高村, 博之 ; 太田, 哲生
概要:
金沢大学医薬保健研究域医学系<br />We herein report a case of anaplastic carcinoma of the pancreas with remarkable intraductal tumor gr
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owth into the main pancreatic duct. A 76-year-old male was referred to our hospital for treatment of a pancreatic tumor. Preoperative examinations revealed a poorly defined tumor in the main pancreatic duct in the body of the pancreas, accompanied with severe dilatation of the main pancreatic duct, which was diagnosed as an intraductal papillary-mucinous neoplasm. We performed distal pancreatectomy and splenectomy. The pathological examination revealed that the tumor consisted of a mixture of anaplastic carcinoma (giant cell type) and adenocarcinoma in the pancreas. There was a papillary projecting tumor composed of anaplastic carcinoma in the dilated main pancreatic duct. The patient is now receiving chemotherapy because liver metastasis was detected 12 mo after surgery. In this case, we could observe a remarkable intraductal tumor growth into the main pancreatic duct. We also discuss the pathogenesis and characteristics of this rare tumor with specific tumor growth. © 2014 Baishideng Publishing Group Co., Limited. All rights reserved.
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| 24.
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Sato, Hirohide ; Sato, Yasunori ; Harada, Kenichi ; Sasaki, Motoko ; Hirano, Katsuyasu ; Nakanuma, Yasuni ; 佐藤, 保則 ; 原田, 憲一 ; 佐々木, 素子 ; 中沼, 安二
概要:
金沢大学医薬保健研究域医学系<br />A 77-year-old woman complained of epigastralgia, and a tumor (5 cm in diameter) of the gallbladder n
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eck was detected by image analysis. Following cholecystectomy, the tumor was pathologically diagnosed as intraductal papillary neoplasm (IPN), gastric type, with associated invasive carcinoma. About 10 mo later, intraluminal multiple masses (3 foci, up to 1.8 cm) were noted in the extrahepatic bile duct, and the resected specimen showed that all tumors had similar gross and microscopic features as seen in gallbladder IPN without invasion, and they were synchronous multiple lesions. This case showed a papillary tumor of the gallbladder of gastric phenotype, and confirmed that the gallbladder is a target of IPN in addition to the bile ducts. © 2013 Baishideng. All rights reserved.
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| 25.
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Onishi, Ichiro ; Kitagawa, Hirohisa ; Harada, Kenichi ; Maruzen, Syogo ; Sakai, Seisyo ; Makino, Isamu ; Hayashi, Hironori ; Nakagawara, Hisatoshi ; Tajima, Hidehiro ; Takamura, Hiroyuki ; Fujimura, Takashi ; Kayahara, Masato ; Ikeda, Hiroko ; Ohta, Tetsuo ; Nakanuma, Yasuni ; 北川, 裕久 ; 原田, 憲一 ; 牧野, 勇 ; 林, 泰寛 ; 中川原, 寿俊 ; 田島, 秀浩 ; 高村, 博之 ; 藤村, 隆 ; 萱原, 正都 ; 池田, 博子 ; 太田, 哲生 ; 中沼, 安二
概要:
金沢大学医薬保健研究域医学系<br />We present the first case of an intraductal papillary neoplasm of the bile duct (IPNB) accompanying
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a mixed adenoneuroendocrine carcinoma (MANEC). A 74-yearold woman presented with fever of unknown cause. Laboratory data revealed jaundice and liver injury. Contrast-enhanced computed tomography revealed a 20 mm polypoid tumor in the dilated distal bile duct, which exhibited early enhancement and papillary growth. Upper gastrointestinal endoscopy revealed mucus production from the papilla of Vater, characterized by its protruding and dilated orifice. Endoscopic ultrasonography visualized the polypoid tumor in the distal bile duct, but no invasive region was suggested by diagnostic imaging. Therefore, the initial diagnosis was IPNB. After endoscopic nasobiliary drainage, a pylorus-preserving pancreaticoduodenectomy was performed. Pathological examination of the resected bile duct revealed papillary proliferation of biliary-type cells with nuclear atypia, indicating pancreaticobiliary-type IPNB. In addition, solid portions comprised of tumor cells with characteristic salt-and-pepper nuclei were evident. Immunohistochemistry revealed expression of the neuroendocrine marker synaptophysin in this solid component, diagnosing it as a neuroendocrine tumor (NET). Furthermore, the MIB-1 proliferation index of NET was higher than that of IPNB, and microinvasion of the NET component was found, indicating neuroendocrine carcinoma (NET G3). This unique case of MANEC, comprising IPNB and NET, provides insight into the pathogenesis of biliary NET. © 2013 Baishideng. All rights reserved.
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| 26.
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Hattori, Yuki ; Gabata, Toshifumi ; Matsui, Osamu ; Mochizuki, Kentaro ; Kitagawa, Hirohisa ; Kayahara, Masato ; Ohta, Tetsuo ; Nakanuma, Yasuni ; 蒲田, 敏文 ; 松井, 修 ; 北川, 裕久 ; 萱原, 正都 ; 太田, 哲生 ; 中沼, 安二
概要:
金沢大学医薬保健研究域医学系<br />Aim: To evaluate retrospectively the correlation between enhancement patterns on dynamic computed to
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mography (CT) and angiogenesis and fibrosis in pancreatic adenocarcinoma. Methods: Twenty-three patients with pancreatic adenocarcinoma underwent dynamic CT and tumor resection. In addition to the absolute and relative enhanced value that was calculated by subtracting the attenuation value on pre-contrast from those on contrast-enhanced CT in each phase, we defined one parameter, "tumor-aorta enhancement ratio", which was calculated by dividing enhancement of pancreatic cancer by enhancement of abdominal aorta in each phase. These enhancement patterns were correlated with the level of vascular endothelial growth factor (VEGF), microvessel density (MVD), and extent of fibrosis. Results: The absolute enhanced value in the arterial phase correlated with the level of VEGF and MVD (P = 0.047, P = 0.001). The relative enhanced value in arterial phase and tumor-aorta enhancement ratio (arterial) correlated with MVD (P = 0.003, P = 0.022). Tumor-aorta enhancement ratio (arterial) correlated negatively with the extent of fibrosis (P = 0.004). The tumors with greater MVD and higher expression of VEGF tended to show high enhancement in the arterial dominant phase. On the other hand, the tumors with a larger amount of fibrosis showed a negative correlation with the grade of enhancement during the arterial phase. Conclusion: Enhancement patterns on dynamic CT correlated with angiogenesis and may be modified by the extent of fibrosis. © 2009 The WJG Press and Baishideng. All rights reserved.
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| 27.
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Sasaki, Motoko ; Araki, Ichiro ; Yasui, Toshiaki ; Kinoshita, Masaru ; Itatsu, Keita ; Nojima, Takayuki ; Nakanuma, Yasuni ; 佐々木, 素子 ; 野島, 孝之 ; 中沼, 安二
概要:
金沢大学医薬保健研究域医学系<br />We report a case of primary localized malignant biphasic mesothelioma of the liver in a 66-year-old
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man associated with asbestosis. The tumor was detected as a hepatic nodule, 4 cm in diameter, in the right lobe (S8 segment) on CT scan. Histopathological examination demonstrated an intrahepatic tumor with central necrosis consisting of a papillary epithelioid pattern on the surface of the liver, microcystic (microglandular or adenomatoid) pattern mainly in the subcapsular area and sarcomatoid pattern intermingled with microcystic pattern in the major part of the hepatic nodular tumor. Tumor cells, especially of epithelioid type, showed distinct immunoreactivity for mesothelial markers (WT-1, calretinin, D2-40, CK5/6, mesothelin, thrombomodulin) and no immunoreactivity for epithelial (adenocarcinoma) markers (CEA, CD15, BerEP4, BG8, MOC31). P53 immunoreactivity was detected focally in papillary epithelioid tumor cells and extensively in microcystic and sarcomatoid components, suggesting that the papillary epithelioid mesothelioma arose on the surface of the liver, and tumor cells showing microcystic and sarcomatoid patterns invaded and grew into the liver. To date, this is the first case of primary localized malignant biphasic mesothelioma of the liver, since all three primary hepatic mesotheliomas reported so far were epithelioid type. © 2009 The WJG Press and Baishideng. All rights reserved.
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| 28.
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Yoshikawa, Seiichi ; Zen, Yoh ; Fujii, Takahiko ; Sato, Yasunori ; Ohta, Tetsuo ; Aoyagi, Yutaka ; Nakanuma, Yasuni ; 全, 陽 ; 佐藤, 保則 ; 太田, 哲生 ; 中沼, 安二
概要:
金沢大学医薬保健研究域医学系<br />AIM: To reveal the characteristics of CD133+ cells in the liver. METHODS: This study examined the hi
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stological characteristics of CD133 + cells in non-neoplastic and neoplastic liver tissues by immunostaining, and also analyzed the biological characteristics of CD133 + cells derived from human hepatocellular carcinoma (HCC) or cholangiocarcinoma cell lines. RESULTS: Immunostaining revealed constant expression of CD133 in non-neoplastic and neoplastic biliary epithelium, and these cells had the immunophenotype CD133+/CK19+/HepPar -1-. A smal l number of CD133+/CK19-/HepPar-1+ cells were also identified in HCC and combined hepatocellular and cholangiocarcinoma. In addition, small ductal structures, resembling the canal of Hering, partly surrounded by hepatocytes were positive for CD133. CD133 expression was observed in three HCC (HuH7, PLC5 and HepG2) and two cholangiocarcinoma cell lines (HuCCT1 and CCKS1). Fluorescence-activated cell sorting (FACS) revealed that CD133+ and CD133-cells derived from HuH7 and HuCCT1 cells similarly produced CD133+ and CD133- cells during subculture. To examine the relationship between CD133+ cells and the side population (SP) phenotype, FACS was performed using Hoechst 33342 and a monoclonal antibody against CD133. The ratios of CD133+/CD133-cells were almost identical in the SP and non-SP in HuH7. In addition, four different cellular populations (SP/CD133+, SP/CD133-, non-SP/CD133+, and non-SP/CD133-) could similarly produce CD133+ and CD133- cells during subculture. CONCLUSION: This study revealed that CD133 could be a biliary and progenitor cell marker in vivo. However, CD133 alone is not sufficient to detect tumor-initiating cells in cell lines. © 2009 The WJG Press and Baishideng. All rights reserved.
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| 29.
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Fujimura, Takashi ; Ohta, Tetsuo ; Oyama, Katsunobu ; Miyashita, Tomoharu ; Miwa, Koichi ; 藤村, 隆 ; 太田, 哲生 ; 尾山, 勝信 ; 宮下, 知治 ; 三輪, 晃一
概要:
金沢大学医薬保健研究域医学系<br />Selective cyclooxygenase (COX)-2 inhibitors (coxibs) were developed as one of the anti-inflammatory
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drugs to avoid the various side effects of non-steroidal anti-inflammatory drugs (NSAIDs). However, coxibs also have an ability to inhibit tumor development of various kinds the same way that NSAIDs do. Many experimental studies using cell lines and animal models demonstrated an ability to prevent tumor proliferation of COX-2 inhibitors. After performing a randomized study for polyp chemoprevention study in patients with familial adenomatous polyposis (FAP), which showed that the treatment with celecoxib, one of the coxibs, significantly reduced the number of colorectal polyps in 2000, the U.S. Food and Drug Administration (FDA) immediately approved the clinical use of celecoxib for FAP patients. However, some coxibs were recently reported to increase the risk of serious cardiovascular events including heart attack and stroke. In this article we review a role of COX-2 in carcinogenesis of gastrointestinal tract, such as the esophagus, stomach and colorectum, and also analyze the prospect of coxibs for chemoprevention of gastrointestinal tract tumors. © 2006 The WJG Press. All rights reserved.
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| 30.
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Nakanuma, Shinichi ; Miyashita, Tomoharu ; Hayashi, Hironori ; Tajima, Hidehiro ; Takamura, Hiroyuki ; Makino, Isamu ; Oyama, Katsunobu ; Nakagawara, Hisatoshi ; Fushida, Sachio ; Ohta, Tetsuo ; 中沼, 伸一 ; 宮下, 知治 ; 高村, 博之 ; 林, 泰寛 ; 田島, 秀浩 ; 牧野, 勇 ; 尾山, 勝信 ; 中川原, 寿俊 ; 伏田, 幸夫 ; 太田, 哲生
概要:
金沢大学附属病院肝胆膵・移植外科<br />Objectives: Continuous thrombocytopenia after liver transplant is associated with a less favorable
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prognosis, but this pathogenesis remains unclear. We focused on the consumption of platelets in the allograft. We assessed platelet consumption in allografts, and evaluated the pathology of platelet aggregation in an allograft tissue and its involve-ment in clinical outcomes.Materials and Methods: We took biopsy specimens from 20 patients. To examine the localization of platelet aggregation, CD42b was assayed immuno-histochemically, and its level of expression correlated with clinical data and outcomes.Results: Platelet aggregation in zone 3 was 70%, compared with 30% in zone 1 and 50% in zone 2. Platelets were found mainly as extravasated platelet aggregates in local microenvironments. Patients were stratified according to the extent of extravasated platelet aggregates in zone 3 into extravasated platelet aggregate-negative and -positive groups. Graft weight/recipient body weight ratio with the extravasated platelet aggregate-positive group was significantly lower than that of the extravasated platelet aggregate-negative group. Platelet count after surgery was lower, while total bilirubin and prothrombin time/international normalized ratio were higher in the extravasated platelet aggregate-positive than they were in the extravasated platelet aggregate-negative group.Conclusions: Extravasated platelet aggregates in the zone 3 of allograft tissue cause the consumption of platelets and continuous thrombocytopenia after transplant, and may be the clinical marker for deterioration of graft function. Platelet activation and degranulation following the release by platelets of some negative regulators may be involved partially in liver damage.
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| 31.
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Nakanuma, Shinichi ; Takamura, Hiroyuki ; Shoji, Masatoshi ; Hayashi, Hironori ; Tajima, Hidehiro ; Nakagawara, Hisatoshi ; Miyashita, Tomoharu ; Kitagawa, Hirohisa ; Tani, Takashi ; Ohta, Tetsuo ; 中沼, 伸一 ; 高村, 博之 ; 林, 泰寛 ; 田島, 秀浩 ; 中川原, 寿俊 ; 宮下, 知治 ; 北川, 裕久 ; 太田, 哲生
概要:
金沢大学附属病院肝胆膵・移植外科<br />Liver transplant is a treatment for familial amyloid polyneuropathy. Few cases of ABO-incompatible
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living-donor liver transplant for familial amyloid polyneuropathy exist. The outcome of an ABO-incompatible living-donor liver transplant has improved recently, using local infusion therapy and rituximab prophylaxis. Here, we describe a successful ABO-incompatible living-donor liver transplant in a patient with familial amyloid polyneuropathy in whom disease progression ceased at 2 years’ follow-up. Additionally, no evidence of acute or chronic rejection, or adverse events of the immuno-suppressive therapy, was seen. As a postoperative complication, fatty changes in the grafted liver because of malnutrition or adverse events of corticosteroids were confirmed by a liver biopsy taken early after transplant. The main cause of malnutrition was considered to be gastrointestinal dysfunction caused by familial amyloid poly-neuropathy. Therefore, before deterioration of digestive function, liver transplants should be considered for familial amyloid polyneuropathy. This case suggests that an ABO-incompatible living-donor liver transplant may provide greater opportunities for familial amyloid polyneuropathy patients.
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| 32.
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Li, Yan ; Kinoshita, Isami
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| 33.
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Long, Chen ; Felkner, John
概要:
The relationship between urban form and sustainable transportation has been extensively explored in the existing literat
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ure, and it is generally accepted that an urban form characterized by higher density, mixed land use pattern and higher accessibility could shorten travel distance and encourage people to choose alternative non-auto travel modes, which in turn reduces the fuel consumption and associated GHG emissions. However, the extensive research on urban form and sustainable transportation has only identified significant correlations between individual urban form variables, such as urban density, land use mix or road connectivity and the one or multiple sustainable transportation outcomes, such as travel mode or vehicle miles travelled (VMT), but very limited empirical studies have been identified to examine the interaction effects that may exist between the urban form attributes. This paper proposes the hypothesis that interaction effects exist between urban form attributes when examining their influences on sustainable transportation. Taking all cities in Florida, U.S. as a case, the interaction effects in the relationship between urban form and sustainable transportation are tested with empirical data. The regression results verified our hypothesis that density shows “threshold negative-to-positive” synergy with other urban form variables, indicating that certain theoretical correlations between urban form variables and sustainable transportation outcomes are conditional depending on the interactions between or among urban form attributes. The results may expand the theoretical framework on the topic of land use and transportation and has considerable policy implications for planning support systems.
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| 34.
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Pan, Haixiao ; Zheng, Yuming ; Wang, Zizhan
概要:
To explore the impact of geographical location, built environment, public transportation service and individual socioeco
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nomic attributes on commuting carbon dioxide (CO2) emissions, a survey was conducted in 27 residential compounds of Shanghai in 2016. In this paper, commuting distance was calculated according to a Baidu map application programming interface (API). CO2 emissions were calculated based on the mode used in each segment of commuting and distance travelled. Through the use of a multiple linear regression model, factors of personal socioeconomic attributes, including gender, occupation and apartment area, were significant to commuting CO2 emissions. In terms of the public transport service, the distance from compounds to the nearest metro station was found to be a significant factor on CO2 emissions, whereas the built environment, such as parking space and employment density, had a weak impact in our study. In addition, even when living near a metro station, the top 20% of travellers’ CO2 emissions can account for approximately 80% of the total CO2 emissions. Hence, policies to reduce those people’s commuting CO2 emissions are worth further exploring.
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| 35.
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Zheng, Lingwei ; Li, Yan
概要:
Bicycle sharing systems (BSSs) have attracted worldwide attention as representatives of the new, green public transportation systems, and many types of research have examined the topic. However, the research so far is relatively
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scattered, because BSS has undergone several technical upgrades and expansions, and the content of some articles may no longer apply to today's society. Therefore, it is necessary to review and summarise the research on BSSs so far. This article aims to collect and summarise the development, characteristics, and impact of BSSs through an extensive review of relevant literature. The article collects and analyses existing academic literature, online materials, and official reports. It is found that BSSs attract people with the same characteristics, and Western and Eastern users have different characteristics; some common factors promote people's use of BSSs in different regions. The government or enterprises introduce BSSs for different purposes: for reducing congestion or for reducing greenhouse gas emissions. Most of the impacts caused by BSSs are positive, but some impacts, such as model substitution and environmental benefits, do not seem to achieve the expected goals. Through a literature review, this article provides references for people who are interested in conducting further research in this area in the future.
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| 36.
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Jittrapirom, Peraphan ; Jaensirisak, Sittha
概要:
Formulating a transport master plan for a regional city in a developing country can be a challenging task. Regional citi
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es are often lacking financial resources or have limited expertise in the field of transport. Consequently, they are more likely to experience transport problems as they undergo expansion. The tradition of transport planning for regional cities in Thailand began as recently as 1994 with the master plan for Chiang Mai city. Since then, there has been a broad implementation of transport planning across the country, driven by the Office of Traffic and Transport Policy and Planning (OTP). As a result, most Thai cities now have a transport master plan. In this paper, we describe Thailand’s process in formulating and implementing its master plans across the regional cities. We provide three case studies to illustrate the process in practice. The study reveals some lessons learned that could be useful to identify critical planning and governance mechanisms for other developing countries, especially those in the same region, such as Vietnam, Cambodia, and Myanmar.
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| 37.
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Metta, Peerat
概要:
Transport poverty is not only a term used to accentuate the fact that some groups of population in the society are unabl
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e to commute as they need, but the concept is being studied by researchers to accurately locate and identify the disadvantaged, who would need to be considered in transport policy and decision making. Due to its complexity, conceptualization and measurement of transport poverty have not always been clear and comprehensive. As measurement of transport poverty usually requires a specific set of data, developing countries are generally regarded as potentially having insufficient data. Thailand’s social and economic context imply that the issue has been present in the country while availability of data required for its measurement is unconfirmed. This paper reviews and discusses how the concept has been defined and measured by some previous research as well as availability of Thailand’s data applicable for various types of measurement. The results show that existing data would permit certain types and degrees of measurement; nonetheless, a more precise and accurate measurement of the issue would require more complete data sets.
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| 38.
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Li, Yuan ; Huang, Jingxiong ; Yang, Linchuan
概要:
Space syntax starts from the ontology of space to quantify the space and uses mathematical logic to reveal and describe
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the logic of the space structure.However, the application of space syntax analysis to museums in China has rarely been explored. In light of this, this study employs space syntax to analyse the Gulangyu Organ Museum (Xiamen, China) and uses the topological depth, visual graph analysis, and agent simulation to describe the structure of the museum space. Accordingly, several suggestions are proposed,including rearranging the layout of the museum’s functions and transforming the museum from functional space to experience space. This study can serve as a valuable reference for the application of space syntax in the design and optimization of space design and functional layout. We believe that the findings of this study can also be applied to other cultural institutions (e.g.,galleries) with similar characteristics.
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| 39.
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Kumar, Sudeshna ; Santara, Anirban ; Banerji, Haimanti
概要:
This paper systematically reviews the current approaches of assessing sustainability of Neighbourhood-level Urban Communities (NLUCs) to identify existing dimensions of sustainability including missing and neglected ones. The
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authors have adopted a systematic literature review (SLR) approach to provide an overview of state-of-the-art literature in urban sustainability assessment and measurement. The novelty of the content analysis is that it has been accomplished using an automated process of keyword extraction from the systematically selected literature using a Python-implementation of the popular Rapid Automatic Keyword Extraction (RAKE) algorithm. Finally, the paper proposes a pentagram that successfully incorporates five dimensions of sustainability: environmental, economic, social, institutional and cultural, with an overarching component of innovation likely to have an impact on each due to technological advancements and future trends. The outcome of this model will be a basic framework within which indicators can be assigned for assessing the sustainability of the NLUCs.
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| 40.
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Liu, Qiang ; Homma, Riken ; Iki, Kazuhisa
概要:
Public bicycle sharing systems for daily use have been effective for increasing cycling in China, which can significantl
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y ease traffic congestion and the production of toxic gasses. Encouraging the development of bicycle transportation has become an important part of cities’ sustainable development policies. This paper explains the relationships among public bicycle trips,public infrastructure, road characteristics, the built environment, and temporal variations. The study area is the Xiasha Education District, which is located in the east of Hangzhou City, China. Using data on the Hangzhou Public Bicycle system, we utilized Pearson correlation analysis and multiple linear regression modelling to analyse how the variables affect public bicycle trip production for different land uses. This paper also analyses the temporal variations for hourly trip production for three land uses. The results show that public infrastructure and road characteristics significantly affect public bicycle trips. In addition,the effects of temporal variation vary across different land uses. Our findings will be helpful for planners and engineers to improve their understanding of public bicycle production.
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| 41.
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Naing, Naidah ; Hadi, Karim
概要:
Purpose: Several studies have been conducted on the concept of Bugis community house construction to understand its macr
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o- and micro-cosmology. This study was, however, conducted to complement the multi-perception research on the relationship between architecture and local wisdom by disclosing the formation of residential space plans. This involved the use of the Bugis house as the subject and the application of the horizontal and vertical philosophies’ perspectives based on the anatomical dimensions of a lying human body as its traditional architectural uniqueness. Research Design & Methodology: The study was conducted qualitatively in Talungeng Village, Bone Regency, Indonesia, for a period of one year, 2018–2019, using the case study approach, phenomenology, and ethnography model. Data were collected through several eligible informants and analyzed using the Discovering Cultural Themes method by associating studies with architecture. Results & Findings: This study showed the horizontal spatial organization and relations in the Bugis house plan derive from the philosophy and function of human body parts in a lying position, which is believed to be a means to provide protection and comfort for residents, while the vertical aspect involves the use of the house frame as the central pillar in proportion to the whole structure. The adoption of the human body as the framework is usually to provide mutual support for the building structure and to ensure it has enough strength to mitigate against earthquakes, floods, and strong winds.
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| 42.
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Yılmaz, Merve ; Terzi, Fatih
概要:
Urban growth patterns are a reflection of how urbanization is affected by physical geography as well as by the economic,
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social, and natural factors of individual cities. Therefore, an analysis of any urban growth pattern triggered by these factors by using measurable variables can make a significant contribution towards the determination of future spatial growth strategies. This paper aims to characterise and evaluate the urban growth pattern of Antalya, a coastal city in Turkey, that occurred between 1987 and 2016. To achieve this, a multi-temporal analysis of satellite images was carried out to determine the city’s urban growth patterns in 1987, 2000, and 2016, and spatial growth indices were then used to identify three urban growth types – sprawl, infill, and leapfrog. The results clearly show that the amount of built-up area in Antalya increased considerably after 2000, and is estimated to have grown by a factor of eight over the period covered by this study, predominantly through the processes of sprawl and leapfrog development.
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| 43.
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Rudiarto, Iwan ; Pamungkas, Dony
概要:
Climate-related disasters such as floods and tidal floods impact livelihood systems in coastal areas everywhere, particu
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larly in developing countries, resulting in a certain degree of livelihood vulnerability. In this paper, we examine the spatial exposure and livelihood vulnerability level of Tegal, a city in Central Java, Indonesia. Data were collected from 100 household samples distributed in the study area. Two types of assessment were performed: a spatial assessment with distance analysis and a vulnerability assessment using the Livelihood Vulnerability Index (LVI). The results of the study show that 33.80% of the settlement area and 22.25% of the fishery area are vulnerable to tidal floods. Climate-related disasters also threaten 32.20% of the households sampled, whose members work mostly as fishermen and rely on coastal resources for their livelihood. A key finding of the study is that the community is highly vulnerable with a low adaptive capacity level. This calls for more decisive policy interventions to enhance the community’s adaptive capacity and reduce its exposure level.
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| 44.
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Zaim, Zaflis ; Rudiarto, Iwan ; Buchori, Imam ; Wahyudi, Ade
概要:
Customary land tenure associated with land administration systems have begun to receive attention through research. A re
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cent study discusses the practice of land release to gain insight into the forces that underpin transformation of customary land rights. However, few studies address the ability to negotiate and adapt to customary land tenure. This study fills this gap, especially the utilisation of Bengkok land as village-owned land and explores the knowledge that drives changes in customary land management rights in Indrokilo sub-village. Data were collected through surveys and interviews addressed to respondents as Bengkok land users and key actors. The results of the study indicate that the change in Bengkok Bayan’s land management rights to collective rights of farmer groups has been affected by four conditions, namely: the vacancy of the village official (Bayan), the village land leasing system, sanitation programme socialisation, and resident participation. The aspirations of the farmer groups are accommodated by the village government in the form of a village head's decree and the terms of land rent compensation. Adaptation of farmers, farmer groups and village government is manifested in the form of land use arrangements as Kandang kawasan (cattle pen), separation of cattle pens and houses, as well as Bengkok land rental systems. Changing the Bengkok land management rights for communal interests requires legal strengthening through regional regulations in order to recognise the existence of farmer groups, promote justice, and reduce poverty for the sustainability of suburban area development.
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| 45.
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Zhan, Qingming ; Gao, Sihang ; Xiao, Yinghui ; Yang, Chen ; Wu, Yihan ; Fan, Zhiyu ; Wu, Jiaqi ; Zhan, Meng
概要:
There has been a growing interest in finding mitigation measures for urban heat islands and urban pollution islands that focus mainly on urban landscape mechanisms. However, relatively little research has considered spatial
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non-stationarity and temporal non-stationarity, which are both intrinsic properties of the environmental system, simultaneously. At the same time, the relevance of and differences between the thermal environment and air pollution has also been rarely discussed, and both issues are of great importance to urban planning. In this study, which is aimed at improving urban ventilation to reduce the urban heat island and urban pollution island effects, an urban ventilation potential evaluation, land surface temperature time-series clustering and air pollution source identification are comprehensively applied to identify the operational areas, compensation areas and ventilation corridors in Xiangyang, China, thus bridging the gap between academic research and urban planning. The specific research areas include: (1) defining the operational areas for urban ventilation corridor planning through an urban ventilation potential evaluation featuring urban morphology indicators, land surface temperature time-series clustering with k-means and an urban air pollution source diffusion analysis via the Hybrid Single-Particle Lagrangian Integrated Trajectory (HYSPLIT) and geographically weighted regression (GWR) methods; (2) identifying urban cold islands through land surface temperatures and delimiting the compensation areas in urban ventilation corridor planning; (3) designating urban ventilation corridors through an urban ventilation potential evaluation and computational fluid dynamics (CFD); and (4) improving urban ventilation corridor planning through defining operational areas, compensation areas and ventilation corridors as well as proposing corresponding control measures.
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| 46.
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Soltani, Sahar ; Gu, Ning ; Ochoa, J. Jorge ; Sivam, Alpana ; Sun, Xuyang
概要:
A large body of research has focused on the various social, environmental and economic ways in which urban density might affect cities. When considering density as one of the elements of urban form, the measurements that studies
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usually apply, such as net or gross building density, do not have any link to the design of the built form. This paper argues that the same building density can yield different design layouts, thereby emphasising the need for developing other measurements of density in close relationship with design factors. To demonstrate this, several cases with various ranges of density (low, medium and high) were explored through spatial analysis and categorised in three clusters for further study with statistical tests. The results confirm meaningful differences between cases with the same density but different spatial design characteristics. The outcomes also indicate that the category of the cases based on conventional density measures, namely population density and building density (which are commonly used in urban studies), fail to capture design differences when density ranges differ. These results should draw attention to this phenomenon, which appears worthy of further investigation in future studies.
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| 47.
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Shi, Peipei ; Xiao, Yinghui ; Zhan, Qingming
概要:
Advanced technologies and big data have brought new visions and methods to urban planning research. Based on the Baidu heat map and POI data of two typical days (a weekend day and a workday) in 2018, this paper analyses the spatial and
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temporal aggregation patterns of crowds in the urban centre of Wuhan using ArcGIS. Aggregation patterns are defined by the intensity of population activities and the places where crowds gather. In terms of time, the daily change of population aggregation intensity is studied by counting the heat value of 24 moments captured throughout the day. The results show that on rest days, people prefer to travel around noon and in the afternoon, reaching the highest peak of the day around 15:00, while on workdays, residents' activities are affected by commuting, with obvious 'morning rush hours' and 'evening rush hours'. Firstly, the spatial correlation between the density of POI distribution and the degree of population aggregation has been studied by the spatial coupling relationship between the Baidu heat map and POI data. Secondly, the index of correlation between the aggregation of different POIs and population (ICPP) are mentioned to analyse the purposes and the degrees of aggregation during weekend and workday rush hours. Based on the ICPP, we analyse activities from three aspects: the different ICPPs between the workday and the weekend; the different ICPPs between the morning, afternoon and evening; and the different ICPPs among different POIs.
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| 48.
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Kawanishi, Takuya ; 川西, 琢也
概要:
金沢大学理工研究域フロンティア工学系<br />In parameter estimation, the maximum-likelihood method (ML) does not work for some distributions
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. In such cases, the maximum product of spacings method (MPS) is used as an alternative. However, the advantages and disadvantages of the MPS, its variants, and the ML are still unclear. These methods are based on the Kullback–Leibler divergence (KLD), and we consider applying the method of weighted residuals (MWR) to it. We prove that, after transforming the KLD to the integral over [0, 1], the application of the collocation method yields the ML, and that of the Galerkin method yields the MPS and Jiang’s modified MPS (JMMPS); and the application of zero boundary conditions yields the ML and JMMPS, and that of non-zero boundary conditions yields the MPS. Additionally, we establish formulas for the approximate difference among the ML, MPS, and JMMPS estimators. Our simulation for seven distributions demonstrates that, for zero boundary condition parameters, for the bias convergence rate, ML and JMMPS are better than the MPS; however, regarding the MSE for small samples, the relative performance of the methods differs according to the distributions and parameters. For non-zero boundary condition parameters, the MPS outperforms the other methods: the MPS yields an unbiased estimator and the smallest MSE among the methods. We demonstrate that from the viewpoint of the MWR, the counterpart of the ML is JMMPS not the MPS. Using this KLD-MWR approach, we introduce a unified view for comparing estimators, and provide a new tool for analyzing and selecting estimators. © 2020, SBMAC - Sociedade Brasileira de Matemática Aplicada e Computacional.
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| 49.
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Saito, Motonobu ; Goto, Akiteru ; Abe, Noriko ; Saito, Katsuharu ; Maeda, Daichi ; Ohtake, Tohru ; Murakami, Yoshinori ; Takenoshita, Seiichi ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Cell adhesion molecule (CADM) genes encode immunoglobulin superfamily molecules, which are involved
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in cell-cell adhesion in a number of human epithelia. Through the maintenance of epithelia, CADM genes protect against malignant conversion and metastasis. Whilst numerous in vitro studies have investigated the molecular characteristics of CADM1 and CADM4 and in vivo studies have investigated CADM1 and CADM4 expression in a number of tumor types, the roles of CADM1 and CADM4 have yet to be elucidated. Therefore, in the present study, CADM1 and CADM4 expression levels were evaluated using immunohistochemistry staining in 208 patients with breast cancer and compared with clinicopathological factors. CADM1 and CADM4 expression levels were negative in 160 (76.9%) and 166 (79.8%) of the 208 cases, respectively. The lack of expression in these cases was associated with advanced tumor stage, suggesting that inactivation of CADM1 and CADM4 promotes breast cancer development. The prognostic role of CADM1 and CADM4 in breast cancer was also evaluated and the expression of CADM1 and CADM4 were not associated with cancer-specific survival or overall survival rate in the cohort of patients in the present study. Whilst these results suggested that CADM1 and CADM4 possess tumor suppressive roles, further functional experiments are required to address the important mechanisms involving CADM1 and CADM4. © 2018, Spandidos Publications. All rights reserved.
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| 50.
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Ikeda, Yuji ; Oda, Katsutoshi ; Hiraike-Wada, Osamu ; Koso, Takahiro ; Miyasaka, Aki ; Kashiyama, Tomoko ; Tanikawa, Michihiro ; Sone, Kenbun ; Nagasaka, Kazunori ; Maeda, Daichi ; Kawana, Kei ; Nakagawa, Shunsuke ; Fukayama, Masashi ; Tetsu, Osamu ; Fujii, Tomoyuki ; Yano, Tetsu ; Kozuma, Shiro ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Cyclin D1 is an important regulator of cell cycle progression. Phosphorylation of cyclin D1 at Thr28
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6 by GSK3β triggers its nuclear export and cytoplasmic proteolysis via the 26S proteasome. Cyclin D1 overexpression is a common event in various types of human cancers; however, reports of mutations are extremely rare. We analyzed mutations of the cyclin D1 gene, CCND1, in 88 endometrial cancer tissue specimens and detected mutations in 2 cases (2.3%). Both were unreported mutations with substitution of threonine to isoleucine at codon 286 (T286I). These two tumors harbored coexisting mutations in K-ras, PIK3CA and/or PTEN and showed accumulation of cyclin D1 in the nucleus by immunohistochemistry. Furthermore, we analyzed the functions of mutant cyclin D1 (T286I) by luciferase assays, immunofluorescence, western blotting and clonogenic cell survival assays in HEK-293T cells. We found that exogenous mutant cyclin D1 (T286I) accumulated in the nuclei in HEK-293T cells, and that it inhibited the expression of pRb. Additionally, the number of colonies was increased by introduction of mutant cyclin D1 (T286I) compared to that of wild-type cyclin D1. In conclusion, we identified an unreported CCND1 mutation (T286I) in two endometrial cancers and revealed that the mutation was functional for inducing cell proliferation in human cells.
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| 51.
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Ohmatsu, Hanako ; Sugaya, Makoto ; Fujita, Hideki ; Miyagaki, Tomomitsu ; Kadono, Takafumi ; Maeda, Daichi ; Takazawa, Yutaka ; Fukayama, Masashi ; Tamaki, Kunihiko ; Sato, Shinichi ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系
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| 52.
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Suzuki, Kensuke ; Nagasaka, Kazunori ; Oda, Katsutoshi ; abe, Hiroyuki ; Maeda, Daichi ; Matsumoto, Yoko ; Arimoto, Takahide ; Kawana, Kei ; Fukayama, Masashi ; Osuga, Yutaka ; Fujii, Tomoyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Background: Lymphangioleiomyomatosis (LAM) is a rare idiopathic disorder that occurs in women of chi
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ldbearing age, and consists of a diffuse proliferation of abnormal smooth muscle cells along the thoracic and abdominal lymphogenous route. Case presentation: We experienced a case of a 47-yo woman with recent history of systemic lupus erythematosus (SLE) diagnosed with endometrial cancer, initially suspected to have metastasized to pelvic and para-aortic lymph nodes based on preoperative diagnostic imaging. Subsequent pathological diagnosis revealed stage IB endometrial cancer without evidence of lymph node involvement. Instead, enlarged pelvic and para-aortic lymph nodes were found to be due to extrapulmonary LAM, from a primary lesion found inside the uterine myometrium. SLE improved after surgery. Conclusion: This is the first reported case of comorbid endometrial cancer, SLE, and aggressive LAM metastasizing to regional lymph nodes, and strengthens the clinical evidence for a common role of mTOR pathway hyperactivity and estrogen responsiveness in the pathophysiology of metastasizing lesions of the genital tract. © 2016 The Author(s).
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| 53.
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Seiki, Takayuki ; Nagasaka, Kazunori ; Kranjec, Christian ; Kawana, Kei ; Maeda, Daichi ; Nakamura, Hiroe ; Taguchi, Ayumi ; Matsumoto, Yoko ; Arimoto, Takahide ; Wada-Hiraike, Osamu ; Oda, Katsutoshi ; Nakagawa, Shunsuke ; Yano, Tetsu ; Fukayama, Masashi ; Banks, Lawrence ; Osuga, Yutaka ; Fujii, Tomoyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Background: The high risk Human Papillomavirus (HPV) E6 oncoproteins play an essential role in the d
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evelopment of cervical malignancy. Important cellular targets of E6 include p53 and the PDZ domain containing substrates such as hScrib and Dlg. We recently showed that hScrib activity was mediated in part through recruitment of protein phosphatase 1γ (PP1γ). Methods: Expression patterns of hScrib and PP1γ were assessed by immunohistochemistry of HPV-16 positive cervical intraepithelial neoplasm (CIN), classified as CIN1 (n=4), CIN2 (n=8), CIN3 (n=8), cervical carcinoma tissues (n=11), and HPV-negative cervical tissues (n=8), as well as by subfractionation assay of the HPV-16 positive cervical cancer cell lines, CaSki and SiHa. To explore the effects of the HPV-16 oncoproteins, we have performed siRNA knockdown of E6/E7 expression, and monitored the effects on the expression patterns of hScrib and PP1γ. Results: We show that PP1γ levels in HPV-16 positive tumour cells are reduced in an E6/E7 dependent manner. Residual PP1γ in these cells is found mostly in the cytoplasm as opposed to the nucleus where it is predominantly found in normal cells. We have found a striking concordance with redistribution in the pattern of expression (9/11; 81.8%) and loss of PP1γ expression in HPV-16 positive cervical tumours (2/11; 18.2%). Furthermore, this loss of PP1γ expression and redistribution in the pattern of expression occurs progressively as the lesions develop (8/8; 100%). Conclusion: Together, these results suggest that PP1γ may be a novel target of the HPV-16 oncoproteins and indicate that it might be a potential novel biomarker for HPV-16 induced malignancy. © Seiki et al.
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| 54.
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Oda, Katsutoshi ; Ikeda, Yuji ; Maeda, Daichi ; Arimoto, Takahide ; Kawana, Kei ; Fukayama, Masashi ; Osuga, Yutaka ; Fujii, Tomoyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Background: Surgical site infections are potential complications following open myomectomy. These in
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fections usually develop immediately after the surgery, and are most often located in the myometrium. Pyogenic cervical cysts are rare and have not been previously reported to occur at the site of myomectomy.Case presentation: A 41-year-old nulligravida Japanese woman was referred to our hospital with a large cervical cyst (>15 cm in diameter). She had undergone a myomectomy 13 years previously, and the surgical site had extended to the endocervical gland. Standard blood tests did not show any evidence of inflammation. The patient underwent a total abdominal hysterectomy, which revealed that the cyst contained multiple components, including Escherichia coli, old blood, and evidence of endometriosis. A pathological review did not show malignant cells within the cyst. The pyogenic cyst originated from the upper anterior cervix, which was one of the sites involved in the previous myomectomy.Conclusion: We reported a huge pyogenic cervical cyst exhibiting signs of endometriosis, in the vicinity of the uterine scar from the open myomectomy. The previous surgery and endometriosis might have contributed to the formation of this rare pyogenic cyst. © 2014 Oda et al.; licensee BioMed Central Ltd.
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| 55.
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Inoue, Tomoko ; Oda, Katsutoshi ; Arimoto, Takahide ; Samejima, Taiki ; Takazawa, Yutaka ; Maeda, Daichi ; Fukayama, Masashi ; Kawana, Kei ; Osuga, Yutaka ; Fujii, Tomoyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Background: Xanthogranulomatous inflammation is an uncommon form of chronic inflammation that is des
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tructive to the normal tissue of affected organs. Although xanthogranulomatous endometritis and xanthogranulomatous salpingitis of the female genital tract has been described previously, to the best of our knowledge, this is the first report of xanthogranulomatous inflammation with infiltration into the uterine myometrium from the perimetrium without endometritis.Case presentation: A 68-year-old Japanese woman with intermittent lower abdominal pain and low-grade fever who was initially treated with antibiotics underwent hysterectomy due to abscess formation in the posterior wall of the myometrium and perimetrium (the outer serosal layer of the uterus). Histopathological findings revealed that the abscess was caused by xanthogranulomatous inflammation with the granulation tissue and chronic inflammatory cells that consisted of focal and sheets of foam cells. The inflammation destroyed the perimetrial elastic lamina, and the myometrium was deeply infiltrated by the xanthoma cells. Neither endometritis nor salpingitis was coexistent with the xanthogranulomatous inflammation.Conclusion: The patient was diagnosed as xanthogranulomatous inflammation, most likely arising from the perimetrium. Our findings suggest that the perimetrium, as well as the endometrium and adnexae, is one of the origins of xanthogranulomatous inflammation in female genital tract. © 2014 Inoue et al.; licensee BioMed Central Ltd.
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| 56.
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Matsumoto, Yoko ; Miyamoto, Yuichiro ; Cabral, Horacio ; Matsumoto, Yu ; Nagasaka, Kazunori ; Nakagawa, Shunsuke ; Yano, Tetsu ; Maeda, Daichi ; Oda, Katsutoshi ; Kawana, Kei ; Nishiyama, Nobuhiro ; Kataoka, Kazunori ; Fujii, Tomoyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Treatment of recurrent or advanced cervical cancer is still limited, and new therapeutic choices are
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needed for improving prognosis and quality of life of patients. Because human papilloma virus (HPV) infection is critical in cervical carcinogenesis, with the E6 and E7 oncogenes of HPV degrading tumor suppressor proteins through the ubiquitin proteasome system, the inhibition of the ubiquitin proteasome system appears to be an ideal target to suppress the growth of cervical tumors. Herein, we focused on the ubiquitin proteasome inhibitor MG132 (carbobenzoxy-Leu-Leu-leucinal) as an anticancer agent against cervical cancer cells, and physically incorporated it into micellar nanomedicines for achieving selective delivery to solid tumors and improving its in vivo efficacy. These MG132-loaded polymeric micelles (MG132/m) showed strong tumor inhibitory in vivo effect against HPV-positive tumors from HeLa and CaSki cells, and even in HPV-negative tumors from C33A cells. Repeated injection of MG132/m showed no significant toxicity to mice under analysis by weight change or histopathology. Moreover, the tumors treated with MG132/m showed higher levels of tumor suppressing proteins, hScrib and p53, as well as apoptotic degree, than tumors treated with free MG132. This enhanced efficacy of MG132/m was attributed to their prolonged circulation in the bloodstream, which allowed their gradual extravasation and penetration within the tumor tissue, as determined by intravital microscopy. These results support the use of MG132 incorporated into polymeric micelles as a safe and effective therapeutic strategy against cervical tumors. © 2016 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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| 57.
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Nishimura, Riki ; Takita, Junko ; Sato-Otsubo, Aiko ; Kato, Motohiro ; Koh, Katsuyoshi ; Hanada, Ryoji ; Tanaka, Yukichi ; Kato, Keisuke ; Maeda, Daichi ; Fukayama, Masashi ; Sanada, Masashi ; Hayashi, Yasuhide ; Ogawa, Seishi ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Rhabdomyosarcoma (RMS) is a common solid tumor in childhood divided into two histological subtypes,
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embryonal (ERMS) and alveolar (ARMS). The ARMS subtype shows aggressive clinical behavior with poor prognosis, while the ERMS subtype has a more favorable outcome. Because of the rarity, diagnostic diversity and heterogeneity of this tumor, its etiology remains to be completely elucidated. Thus, to identify genetic alterations associated with RMS development, we performed single nucleotide polymorphism array analyses of 55 RMS samples including eight RMS-derived cell lines. The ERMS subtype was characterized by hyperploidy, significantly associated with gains of chromosomes 2, 8 and 12, whereas the majority of ARMS cases exhibited near-diploid copy number profiles. Loss of heterozygosity of 15q was detected in 45.5% of ARMS that had been unrecognized in RMS to date. Novel amplifications were also detected, including IRS2 locus in two fusion-positive tumors, and KRAS or NRAS loci in three ERMS cases. Of note, gain of 13q was significantly associated with good patient outcome in ERMS. We also identified possible application of an ALK inhibitor to RMS, as ALK amplification and frequent expression of ALK were detected in our RMS cohort. These findings enhance our understanding of the genetic mechanisms underlying RMS pathogenesis and support further studies for therapeutic development of RMS. © 2013 Japanese Cancer Association.
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| 58.
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Hiraike, Haruko ; Wada-Hiraike, Osamu ; Nakagawa, Shunsuke ; Saji, Shigehira ; Maeda, Daichi ; Miyamoto, Yuichiro ; Sone, Kenbun ; Tanikawa, Michihiro ; Oda, Katsutoshi ; Nakagawa, Keiichi ; Yano, Tetsu ; Fukayama, Masashi ; Taketani, Yuji ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />DBC1/KIAA1967 (deleted in breast cancer 1) is a putative tumor-suppressor gene cloned from breast ca
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ncer specimens and is reported to regulate p53-dependent apoptosis through its specific inhibition of SIRT1 deacetylase. Although SIRT1 plays a pivotal role in carcinogenesis by regulating cellular proliferation, survival and death, its role in breast cancer remains controversial. Therefore, we aimed to investigate the expression status and clinicopathological significance of DBC1 and SIRT1 in breast cancer tissues. We evaluated the expression of DBC1 and SIRT1 in breast core-needle biopsy specimens from 48 primary breast cancer patients between 2005 and 2008. These patients were treated with primary systemic chemotherapy and subsequent surgical resection of the lesions. Immunohistochemical expression scores of DBC1 and SIRT1 were evaluated, and the relationship between their expression levels and clinicopathological features of breast cancer was analyzed. The expression was observed exclusively in the nuclei of normal and neoplastic ductal cells. In breast biopsy specimens, positive expression of DBC1 and SIRT1 was noted in 85 and 98% of patients, respectively. Expression of DBC1 was significantly associated with the tumor nuclear grade (P=0.019). DBC1 and SIRT1 expression was inversely correlated with HER2 expression (P=0.026 and 0.003, respectively). Lower expression of DBC1 and SIRT1 indicated a tendency for a favorable pathological response to chemotherapy, although this was not statistically significant. Our results reveal that the expression of DBC1 and SIRT1 in breast tissues is associated with tumor characteristics. © 2011 Spandidos Publications Ltd.
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| 59.
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Nomura, Yusuke ; Tamura, Daisuke ; Horie, Masafumi ; Sato, Masakazu ; Sasaki, Shinya ; Yamamoto, Yohei ; Kudo-Asabe, Yukitsugu ; Umakoshi, Michinobu ; Koyama, Kei ; Makino, Kenichi ; Takashima, Shinogu ; Imai, Kazuhiro ; Minamiya, Yoshihiro ; Munakata, Satoru ; Yachida, Shinichi ; Terada, Yukihiro ; Goto, Akiteru ; Maeda, Daichi ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Endometrial stromal nodule (ESN) and low-grade endometrial stromal sarcoma (LG-ESS) are rare uterine
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tumors known as endometrial stromal tumors (ESTs). In addition to their similarity in morphological features, recent studies have shown that these two tumors share common genetic alterations. In particular, JAZF1-SUZ12 fusion is found with high frequency in both ESN and LG-ESS. In LG-ESS, some minor fusions have also been described, which include rearrangements involving PHF1 and its partner genes, such as JAZF1, EPC1, MEAF6, BRD8, EPC2, and MBTD1. Because of the rarity of ESN, genetic alterations other than JAZF1 fusion have not been investigated in detail. In this study, we performed a next-generation sequencing-based analysis in a case of ESN with peripheral metaplastic bone formation and detected MEAF6-PHF1 fusion, which has been reported in a small subset of uterine LG-ESSs and soft tissue ossifying fibromyxoid tumors. The finding that MEAF6-PHF1 fusion is a background genetic abnormality detected both in ESN and LG-ESS, along with JAZF1-SUZ12, provides further support for the similarity and continuum between these two types of ESTs. Furthermore, the association between metaplastic bone formation and MEAF6-PHF1 fusion may not be limited to soft tissue tumors. © 2020 Wiley Periodicals LLC
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| 60.
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Tamura, Daisuke ; Maeda, Daichi ; Sato, Toshiharu ; Sugawara, Tae ; Shirasawa, Hiromitsu ; Shimizu, Dai ; Sato, Naoki ; Goto, Akiteru ; Terada, Yukihiro ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />An extragonadal yolk sac tumor (YST) is a rare malignant germ cell tumor that usually occurs in chil
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dhood. The pathogenesis of extragonadal YST remains largely unknown, especially with regards to its cell of origin. Herein, we report a case of extragonadal YST arising in the uterine round ligament. A 31-year-old Japanese woman, para 2, underwent partial resection of a left-sided, 5-cm, solid inguinal mass. Intraoperative findings showed enlargement of the uterine round ligament in the inguinal canal. Pathological evaluation diagnosed the mass as YST with a mature teratoma (MT) component. The preoperative α-fetoprotein level was markedly elevated, at 24 790 ng/mL. Postoperative magnetic resonance imaging revealed a right ovarian MT and a 3-cm mass remaining in the left lower abdominal wall. The patient underwent total abdominal hysterectomy, bilateral adnexectomy, and left inguinal mass resection. We sampled three frozen tissues (YST, right ovarian MT, and left normal ovary) and performed a single nucleotide polymorphism (SNP) array. Pathological evaluation revealed remnant extragonadal YST in the left inguinal region. The SNP array demonstrated a completely homozygous YST genotype. Copy number variations were gains of 1p, 1q, 2p, 3p, 7p, 8p, 10q, 14q, 18p, 20q, Xp, and Xq and losses of 12q, 20p, and Xq. The right ovarian MT and left normal ovary were partially homozygous and heterozygous, respectively. The evidence suggests that this neoplasm is presumed to be a postmeiotic germ cell origin. © 2019 Wiley Periodicals, Inc.
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| 61.
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Uni, Masahiro ; Yoshimi, Akihide ; Maki, Hiroaki ; Maeda, Daichi ; Nakazaki, Kumi ; Nakamura, Fumihiko ; Fukayama, Masashi ; Kurokawa, Mineo ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />We report here a 47-year-old male with the diagnosis of high-grade B-cell lymphoma and hemophagocyto
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sis accompanying disseminated intravascular coagulation (DIC). Lymphoma-associated hemophagocytic syndrome (LAHS) is a life-threatening disorder, and LAHS secondary to B-cell lymphoma is relatively rare compared to that secondary to T- or NK/T-cell lymphoma in Western countries. T- or NK/T-cell LAHS is sometimes combined with DIC, which makes patients' outcomes even worse, but few reports of B-cell LAHS accompanying DIC has been published so far. We successfully treated a patient with this condition with recombinant thrombomodulin (rTM), a novel agent for DIC. We believe that rTM is a therapeutic option in cases with B-cell LAHS accompanying DIC.
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| 62.
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Maeda, Daichi ; Tsui-Lien, Mao ; Fukayama, Masashi ; Nakagawa, Shunsuke ; Yano, Tetsu ; Taketani, Yuji ; Shih, Ie-Ming ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Recent genome-wide analysis has demonstrated that somatic mutations in ARID1A (BAF250) are the most
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common molecular genetic changes in ovarian clear cell carcinoma (OCCC). ARID1A mutations, which occur in approximately half of OCCC cases, lead to deletion of the encoded protein and inactivation of the putative tumor suppressor. In this study, we determined the significance of loss of ARID1A immunoreactivity with respect to several clinicopathological features in a total of 149 OCCCs. First, we demonstrated that ARID1A immunohistochemistry showed concordance with the mutational status in 91% of cases with 100% sensitivity and 66% specificity. Specifically, among 12 OCCC cases for which ARIDA mutational status was known, ARIDIA immunoreactivity was undetectable in all 9 cases harboring ARID1A mutations and was undetectable in one of 3 cases with wild-type ARID1A. With respect to the entire cohort, ARID1A immunoreactivity was undetectable in 88 (59%) of 149 OCCCs. There was no significant difference between ARID1A negative and positive cases in terms of histopathologic features, age, clinical stage, or overall survival. In conclusion, this study provides further evidence that mutations in ARID1A resulted in loss of ARID1A protein expression in OCCC, although no significant differences between ARID1A positive and negative cases were observed with respect to any clinicopathological features examined. © 2010 by the authors.
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| 63.
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Shiraishi, Kouya ; Okada, Yukinori ; Takahashi, Atsushi ; Kamatani, Yoichiro ; Momozawa, Yukihide ; Ashikawa, Kyota ; Kunitoh, Hideo ; Matsumoto, Shingo ; Takano, Atsushi ; Shimizu, Kimihiro ; Goto, Akiteru ; Tsuta, Koji ; Watanabe, Shun-ichi ; Ohe, Yuichiro ; Watanabe, Yukio ; Goto, Yasushi ; Nokihara, Hiroshi ; Furuta, Koh ; Yoshida, Akihiko ; Goto, Koichi ; Hishida, Tomoyuki ; Tsuboi, Masahiro ; Tsuchihara, Katsuya ; Miyagi, Yohei ; Tanaka, Kazumi ; Nakayama, Haruhiko ; Yokose, Tomoyuki ; Nagashima, Toshiteru ; Ohtaki, Yoichi ; Maeda, Daichi ; Imai, Kazuhiro ; Minamiya, Yoshihiro ; Sakamoto, Hiromi ; Saito, Akira ; Shimada, Yoko ; Sunami, Kuniko ; Saito, Motonobu ; Inazawa, Johji ; Nakamura, Yusuke ; Yoshida, Teruhiko ; Yokota, Jun ; Matsuda, Fumihiko ; Matsuo, Keitaro ; Daigo, Yataro ; Kubo, Michiaki ; Kohno, Takashi ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Lung adenocarcinoma driven by somatic EGFR mutations is more prevalent in East Asians (30-50%) than
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in European/Americans (10-20%). Here we investigate genetic factors underlying the risk of this disease by conducting a genome-wide association study, followed by two validation studies, in 3,173 Japanese patients with EGFR mutation-positive lung adenocarcinoma and 15,158 controls. Four loci, 5p15.33 (TERT), 6p21.3 (BTNL2), 3q28 (TP63) and 17q24.2 (BPTF), previously shown to be strongly associated with overall lung adenocarcinoma risk in East Asians, were re-discovered as loci associated with a higher susceptibility to EGFR mutation-positive lung adenocarcinoma. In addition, two additional loci, HLA class II at 6p21.32 (rs2179920; P =5.1 × 10 '17, per-allele OR=1.36) and 6p21.1 (FOXP4) (rs2495239; P=3.9 × 10 '9, per-allele OR=1.19) were newly identified as loci associated with EGFR mutation-positive lung adenocarcinoma. This study indicates that multiple genetic factors underlie the risk of lung adenocarcinomas with EGFR mutations.
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| 64.
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Oki, Shinya ; Sone, Kenbun ; Oda, Katsutoshi ; Hamamoto, Ryuji ; Ikemura, Masako ; Maeda, Daichi ; Takeuchi, Makoto ; Tanikawa, Michihiro ; Mori-Uchino, Mayuyo ; Nagasaka, Kazunori ; Miyasaka, Aki ; Kashiyama, Tomoko ; Ikeda, Yuji ; Arimoto, Takahide ; Kuramoto, Hiroyuki ; Wada-Hiraike, Osamu ; Kawana, Kei ; Fukayama, Masashi ; Osuga, Yutaka ; Fujii, Tomoyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />The histone methyltransferase EZH2, a key epigenetic modifier, is known to be associated with human
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tumorigenesis. However, the physiological importance of EZH2 and its clinical relevance in endometrial cancer remain unclear. Hence, in the present study, we investigated the expression and function of EZH2 in endometrial cancer. In a quantitative real-time PCR analysis of 11 endometrial cancer cell lines and 52 clinical endometrial cancer specimens, EZH2 was significantly overexpressed in cancer cells and tissues compared to that in corresponding normal control cells and tissues. Kaplan-Meier survival analysis using data of the TCGA RNA-seq database and tissue microarrays (TMAs) indicated that EZH2 overexpression is associated with endometrial cancer prognosis. In addition, knockdown of EZH2 using specific siRNAs resulted in growth suppression and apoptosis induction of endometrial cancer cells, accompanied by attenuation of H3K27 trimethylation. Consistent with these results, treatment with GSK126, a specific EZH2 inhibitor, suppressed endometrial cancer cell growth and decreased the number of cancer cell colonies. Furthermore, GSK126 showed additive effects with doxorubicin or cisplatin, which are conventional drugs for treatment of endometrial cancer. Further studies should explore the therapeutic potential of inhibiting EZH2 in patients with endometrial cancer. © Oki et al.
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| 65.
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Goto, Akiteru ; Masamitsu, Tanaka ; Yoshida, Makoto ; Umakoshi, Michinobu ; Nanjo, Hiroshi ; Shiraishi, Kouya ; Saito, Motonobu ; Kohno, Takashi ; Kuriyama, Sei ; Konno, Hayato ; Imai, Kazuhiro ; Hajime, Saito ; Minamiya, Yoshihiro ; Maeda, Daichi ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Purpose miR-451 is a tumor suppressive microRNA with several target genes, including Macrophage migr
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ation inhibitory factor (MIF). As little is known about the expression and clinicopathological significance of mir-451 in NSCLC, we performed a clinicopathological study of 370 NSCLC cases to clarify them. Cell biological experiments were also performed on NSCLC cell lines to confirm the tumor-suppressive role of miR-451 and whether or not MIF is targeted by miR-451. Methods We analyzed 370 NSCLC cases for the miR-451 expression by quantitative real-time polymerase chain reaction and the MIF expression by immunohistochemistry. Eighty-four background lung tissue samples were also evaluated for the miR-451 expression. The clinicopathological and genetic factors surveyed were the disease-free survival, smoking status, histological type, disease stage, EGFR gene mutations and ALK rearrangements. In 286 adenocarcinoma cases, the invasive status (adenocarcinoma in situ, minimally invasive adenocarcinoma and invasive adenocarcinoma) was also evaluated. Five NSCLC cell lines (H23, H441, H522, H1703, and H1975) were cultured and evaluated for their miR-451 and MIF expression. The cell lines with lower miR-451 and higher MIF expressions were then selected and transfected with miR-451-mimic to observe its effects on MIF expression, Akt and Erk status, cell proliferation, and cell migration. Results The miR-451 expression was down-regulated in cancer tissues compared with background lung tissues (P<0.0001). Factors such as advanced disease stage, positive pleural invasion and nodal status and being a smoker were significantly correlated with a lower expression of miR-451 (P<0.05 each), while EGFR gene mutations and ALK rearrangements were not. In adenocarcinoma, invasive and minimally invasive adenocarcinoma showed lower expression of miR-451 than adenocarcinoma in situ (P<0.0005, respectively). A survival analysis showed that a lower expression of miR-451 was an independent predictor of a poor prognosis for NSCLC (P<0.05). The MIF expression was inversely correlated with the miR-451 expression. Out of 5 NSCLC cell lines examined, H441 and H1975 showed higher MIF and lower miR-451 expressions. After the transfection of miR-451-mimic, the MIF expression and phosphorylated Akt expression of these cell lines was suppressed, as were cell proliferation and cell migration. Conclusion This clinicopathological study of 370 NSCLC cases and the cell biological studies of NSCLC cell lines clarified the tumor-suppressive role of miR-451 and its prognostic value. We also validated MIF as a target of miR-451 in NSCLC. © 2017 Goto et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 66.
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Kito, Masahiko ; Maeda, Daichi ; Kudo-Asabe, Yukitsugu ; Sato, Naoki ; Ie-Ming, Shih ; Wang, Tian-Li ; Tanaka, Masamitsu ; Terada, Yukihiro ; Goto, Akiteru ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />In Table 1, the values in the Case column should be listed from 1 to 18. Please see the corrected Ta
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ble 1 here. © 2016 Kito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.<br />Correction to: PLoS ONE https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156069
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| 67.
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Kito, Masahiko ; Maeda, Daichi ; Kudo-Asabe, Yukitsugu ; Sato, Naoki ; Ie-Ming, Shih ; Wang, Tian-Li ; Tanaka, Masamitsu ; Terada, Yukihiro ; Goto, Akiteru ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />There is a growing body of evidence regarding cell competition between normal and mutant mammalian c
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ells, which suggest that it may play a defensive role in the early phase of carcinogenesis. In vitro study in the past has shown that overexpression of vimentin in normal epithelial cells at the contact surface with transformed cells is essential for the cell competition involved in epithelial defense against cancer. In this study, we attempted to examine cell competition in human tissue in vivo by investigating surgically resected human fallopian tubes that contain p53 signatures and serous tubal intraepithelial lesions (STILs), a linear expansion of p53-immunopositive/TP53 mutant tubal epithelial cells that are considered as precursors of pelvic high grade serous carcinoma. Immunofluorescence double staining for p53 and the cell competition marker vimentin was performed in 21 sections of human fallopian tube tissue containing 17 p53 signatures and 4 STILs. The intensities of vimentin expression at the interface between p53-positive cells at the end of the p53 signature/STIL and adjacent p53-negative normal tubal epithelial cells were compared with the background tubal epithelium. As a result, the average vimentin intensity at the interfaces relative to the background intensity was 1.076 (95% CI, 0.9412-1.211 for p53 signature and 0.9790 (95% CI, 0.7206-1.237) for STIL. Thus, it can be concluded that overexpression of the cell competition marker vimentin are not observed in human tissue with TP53 alterations. © 2016 Kito et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 68.
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Maeda, Daichi ; Yoshiyuki, Akiyama ; Morikawa, Teppei ; Kunita, Akiko ; Ota, Yasunori ; Katoh, Hiroto ; Niimi, Aya ; Nomiya, Akira ; Ishikawa, Shumpei ; Goto, Akiteru ; Igawa, Yasuhiko ; Fukayama, Masashi ; Homma, Yukio ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Interstitial cystitis (IC) is a chronic bladder disease with urinary frequency, bladder discomfort o
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r bladder pain of unknown etiology. Based on cystoscopic findings, patients with IC are classified as either Hunner-type/classic IC (HIC), presenting with a specific Hunner lesion, or non-Hunner-type IC (NHIC), presenting with no Hunner lesion, but post-hydrodistension mucosal bleeding. Inflammatory cell infiltration, composed predominantly of lymphocytes, plasma cells and epithelial denudation, has in the past been documented as a major pathological IC finding. However, the significance of the pathological evaluation of IC, especially with regard to the difference between HIC and NHIC, has been downplayed in recent years. In this study, we performed immunohistochemical quantification of infiltrating T-lymphocytes, B-lymphocytes and plasma cells, and measured the amount of residual epithelium in urinary bladder biopsy specimens taken from patients with HIC and NHIC, and those with no IC, using image analysis software. In addition, in situ hybridization of the light chains was performed to examine clonal B-cell expansion. Lymphoplasmacytic infiltration was significantly more severe in HIC specimens than in NHIC specimens (P <0.0001). Substantial lymphoplasmacytic inflammation (≥200 cells/mm2) was observed in 93% of HIC specimens, whereas only 8% of NHIC specimens were inflamed. Plasmacytic infiltration was more prominent in HIC specimens compared with NHIC and non-IC cystitis specimens (P <0.005). Furthermore, expansion of light-chain-restricted B-cells was observed in 31% of cases of HIC. The amount of residual epithelium was decreased in HIC specimens compared with NHIC specimens and non-IC cystitis specimens (P <0.0001). These results suggest that NHIC and HIC are distinct pathological entities, with the latter characterized by pancystitis, frequent clonal B-cell expansion and epithelial denudation. An abnormality in the B-cell population may be involved in the pathogenesis of HIC. © 2015 Maeda et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 69.
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Uehara, Yuriko ; Oda, Katsutoshi ; Ikeda, Yuji ; Koso, Takahiro ; Tsuji, Shingo ; Yamamoto, Shogo ; Asada, Kayo ; Sone, Kenbun ; Kurikawa, Reiko ; Makii, Chinami ; Hagiwara, Otoe ; Tanikawa, Michihiro ; Maeda, Daichi ; Hasegawa, Kosei ; Nakagawa, Shunsuke ; Wada-Hiraike, Osamu ; Kawana, Kei ; Fukayama, Masashi ; Fujiwara, Keiichi ; Yano, Tetsu ; Osuga, Yutaka ; Fujii, Tomoyuki ; Aburatani, Hiroyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Correction to: PLoS ONE https://journals.plos.org/plosone/article?id=10.1371/journal.pone.0128066
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| 70.
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Uehara, Yuriko ; Oda, Katsutoshi ; Ikeda, Yuji ; Koso, Takahiro ; Tsuji, Shingo ; Yamamoto, Shogo ; Asada, Kayo ; Sone, Kenbun ; Kurikawa, Reiko ; Makii, Chinami ; Hagiwara, Otoe ; Tanikawa, Michihiro ; Maeda, Daichi ; Hasegawa, Kosei ; Nakagawa, Shunsuke ; Wada-Hiraike, Osamu ; Kawana, Kei ; Fukayama, Masashi ; Fujiwara, Keiichi ; Yano, Tetsu ; Osuga, Yutaka ; Fujii, Tomoyuki ; Aburatani, Hiroyuki ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Ovarian clear cell carcinoma (CCC) is generally associated with chemoresistance and poor clinical ou
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tcome, even with early diagnosis; whereas high-grade serous carcinomas (SCs) and endometrioid carcinomas (ECs) are commonly chemosensitive at advanced stages. Although an integrated genomic analysis of SC has been performed, conclusive views on copy number and expression profiles for CCC are still limited. In this study, we performed single nucleotide polymorphism analysis with 57 epithelial ovarian cancers (31 CCCs, 14 SCs, and 12 ECs) and microarray expression analysis with 55 cancers (25 CCCs, 16 SCs, and 14 ECs). We then evaluated PIK3CA mutations and ARID1A expression in CCCs. SNP array analysis classified 13% of CCCs into a cluster with high frequency and focal range of copy number alterations (CNAs), significantly lower than for SCs (93%, P < 0.01) and ECs (50%, P = 0.017). The ratio of whole-arm to all CNAs was higher in CCCs (46.9%) than SCs (21.7%; P < 0.0001). SCs with loss of heterozygosity (LOH) of BRCA1 (85%) also had LOH of NF1 and TP53, and LOH of BRCA2 (62%) coexisted with LOH of RB1 and TP53. Microarray analysis classified CCCs into three clusters. One cluster (CCC-2, n = 10) showed more favorable prognosis than the CCC-1 and CCC-3 clusters (P = 0.041). Coexistent alterations of PIK3CA and ARID1A were more common in CCC-1 and CCC-3 (7/11, 64%) than in CCC-2 (0/10, 0%; P < 0.01). Being in cluster CCC-2 was an independent favorable prognostic factor in CCC. In conclusion, CCC was characterized by a high ratio of whole-arm CNAs; whereas CNAs in SC were mainly focal, but preferentially caused LOH of well-known tumor suppressor genes. As such, expression profiles might be useful for sub-classification of CCC, and might provide useful information on prognosis. © 2015 Uehara et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
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| 71.
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Takai, Erina ; Maeda, Daichi ; Li, Zhuo ; Kudo-Asabe, Yukitsugu ; Totoki, Yasushi ; Nakamura, Hiromi ; Nakamura, Akiko ; Rumi Nakamura ; Kirikawa, Misato ; Ito, Yukinobu ; Yoshida, Makoto ; Inoue, Takamitsu ; Habuchi, Tomonori ; Ikoma, Shohei ; Katoh, Hiroto ; Kato, Mamoru ; Shibata, Tatsuhiro ; Ishikawa, Shumpei ; Yachida, Shinichi ; Goto, Akiteru ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Recent genomic studies on cancer tissues obtained during rapid autopsy have provided insights into t
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he clonal evolution and heterogeneity of cancer. However, post-mortem blood has not been subjected to genetic analyses in relation to cancer. We first confirmed that substantial quantities of cell-free DNA were present in the post-mortem plasma of 12 autopsy cases. Then, we focused on a pilot case of prostate cancer with multiple metastases for genetic analyses. Whole-exome sequencing of post-mortem plasma-derived cell-free DNA and eight frozen metastatic cancer tissues collected during rapid autopsy was performed, and compared their mutational statuses. The post-mortem plasma cell-free DNA was successfully sequenced and 344 mutations were identified. Of these, 160 were detected in at least one of the metastases. Further, 99% of the mutations shared by all metastases were present in the plasma. Sanger sequencing of 30 additional formalin-fixed metastases enabled us to map the clones harboring mutations initially detected only in the plasma. In conclusion, post-mortem blood, which is usually disposed of during conventional autopsies, can provide valuable data if sequenced in detail, especially regarding cancer heterogeneity. Furthermore, post-mortem plasma cell-free DNA sequencing (liquid autopsy) can be a novel platform for cancer research and a tool for genomic pathology. © 2020, The Author(s).
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| 72.
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Ito, Yukinobu ; Yoshida, Makoto ; Maeda, Daichi ; Takahashi, Masato ; Nanjo, Hiroshi ; Masuda, Hirotake ; Gopto, Akiteru ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Arteriovenous malformations consist of tangles of arteries and veins that are often connected by a f
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istula. The causes and mechanisms of these clinical entities are not fully understood. We discovered that suturing an arterial patch into the common jugular vein of rabbits led to spontaneous neovascularization, the formation of an arteriovenous fistula and the development of an arteriovenous shunt. An arterial patch excised from the common carotid artery was sutured into the common jugular vein. Within a month, a dense nidus-like neovasculature formed around the patch. Angiography and pulse-oximeter analyses showed that the blood flowing into the neovasculature was arterial blood. This indicated that an arteriovenous shunt had formed. Fluorescence in situ hybridization with a Y chromosome probe in female rabbits that received an arterial patch from male rabbits showed that the vessels close to the graft bore the Y chromosome, whereas the vessels further away did not. Enzyme-linked immunosorbent assays and cDNA microarray analysis showed that multiple angiogenic factors were upregulated after patch transplantation. This is the first in vivo model of spontaneous arteriovenous fistula formation. Further research on these differences may help to improve understanding of human vascular anomaly diseases and the basic principles underlying vasculogenesis and/or angiogenesis. © 2018 The Author(s).
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| 73.
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Takahashi, Kenichi ; Mashima, Hirosato ; Miura, Kouichi ; Maeda, Daichi ; Goto, Akiteru ; Gotio, Takashi ; Sun-Wada, Ge-Hong ; Wada, Yoh ; Ohnishi, Hirohide ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Although aberrations of intracellular vesicle transport systems towards lysosomes including autophag
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y and endocytosis are involved in the onset and progression of acute pancreatitis, the molecular mechanisms underlying such aberrations remain unclear. The pathways of autophagy and endocytosis are closely related, and Rab7 plays crucial roles in both. In this study, we analyzed the function of Rab7 in acute pancreatitis using pancreas-specific Rab7 knockout (Rab7Δpan) mice. In Rab7Δpan pancreatic acinar cells, the maturation steps of both endosomes and autophagosomes were deteriorated, and the lysosomal functions were affected. In experimental models of acute pancreatitis, the histopathological severity, serum amylase concentration and intra-pancreatic trypsin activity were significantly higher in Rab7Δpan mice than in wild-type mice. Furthermore, the autophagy process was blocked in Rab7Δpan pancreas compared with wild-type mice. In addition, larger autophagic vacuoles that colocalize with early endosome antigen 1 (EEA1) but not with lysosomal-associated membrane protein (LAMP)-1 were much more frequently formed in Rab7Δpan pancreatic acinar cells. Accordingly, Rab7 deficiency exacerbates the severity of acute pancreatitis by impairing the autophagic and endocytic pathways toward lysosomes.
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| 74.
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Akiyama, Yoshiyuki ; Morikawa, Teppei ; Maeda, Daichi ; Shintani, Yukako ; Niimi, Aya ; Nomiya, Akira ; Nakayama, Atsuhito ; Igawa, Yasuhiko ; Fukayama, Masashi ; Homma, Yukio ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />An up-regulated CXCR3 pathway and affluent plasma cell infiltration are characteristic features of H
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unner type interstitial cystitis (HIC). We further examined these two features using bladder biopsy samples taken from 27 patients with HIC and 15 patients with non-IC cystitis as a control. The number of CD3-positive T lymphocytes, CD20-positive B lymphocytes, CD138-positive plasma cells, and CXCR3-positive cells was quantified by digital image analysis. Double-immunofluorescence for CXCR3 and CD138 was used to detect CXCR3 expression in plasma cells. Correlations between CXCR3 positivity and lymphocytic and plasma cell numbers and clinical parameters were explored. The density of CXCR3-positive cells showed no significant differences between HIC and non-IC cystitis specimens. However, distribution of CXCR3-positivity in plasma cells indicated co-localization of CXCR3 with CD138 in HIC specimens, but not in non-IC cystitis specimens. The number of CXCR3-positive cells correlated with plasma cells in HIC specimens alone. Infiltration of CXCR3-positive cells was unrelated to clinical parameters of patients with HIC. These results suggest that infiltration of CXCR3-positive plasma cells is a characteristic feature of HIC. The CXCR3 pathway and specific immune responses may be involved in accumulation/retention of plasma cells and pathophysiology of the HIC bladder.
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| 75.
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Baba, Satoshi ; Taguchi, Ayumi ; Kawata, Akira ; Hara, Konan ; Eguchi, Satoko ; Mori, Mayuyo ; Adachi, Katsuyuki ; Mori, Seiichiro ; Iwata, Takashi ; Mitsuhashi, Akira ; Maeda, Daichi ; Komatsu, Atsushi ; Nagamatsu, Takeshi ; Oda, Katsutoshi ; Kukimoto, Iwao ; Osuga, Yutaka ; Fujii, Tomoyuki ; Kawana, Kei ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />Background: Human papillomavirus (HPV) infection is a primary cause of cervical cancer. Although epi
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demiologic study revealed that carcinogenic risk differs according to HPV genotypes, the expression patterns of HPV-derived transcripts and their dependence on HPV genotypes have not yet been fully elucidated. Methods: In this study, 382 patients with abnormal cervical cytology were enrolled to assess the associations between HPV-derived transcripts and cervical intraepithelial neoplasia (CIN) grades and/or HPV genotypes. Specifically, four HPV-derived transcripts, namely, oncogenes E6 and E6*, E1^E4, and viral capsid protein L1 in four major HPV genotypes-HPV 16, 18, 52, and 58-were investigated. Results: The detection rate of E6/E6*increased with CIN progression, whereas there was no significant change in the detection rate of E1^E4 or L1 among CIN grades. In addition, we found that L1 gene expression was HPV type-dependent. Almost all HPV 52-positive specimens, approximately 50% of HPV 58-positive specimens, around 33% of HPV 16-positive specimens, and only one HPV18-positive specimen expressed L1. Conclusions: We demonstrated that HPV-derived transcripts are HPV genotype-dependent. Especially, expression patterns of L1 gene expression might reflect HPV genotype-dependent patterns of carcinogenesis. © 2020 The Author(s).
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Inagaki, Chiaki ; Maeda, Daichi ; Kimura, Akie ; Otsuru, Toru ; Iwagami, Yoshifumi ; Nishida, Naohiro ; Sakai, Daisuke ; Shitotsuki, Ryo ; Yachida, Shinichi ; Doki, Yuichiro ; Satoh, Taroh ; 前田, 大地
概要:
金沢大学医薬保健研究域医学系<br />BACKGROUND Bile duct cancer constitutes gallbladder cancer (GBC), intrahepatic cholangiocarcinoma (I
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CA), and extrahepatic cholangiocarcinoma (ECA). These three entities show morphological and immunohistochemical resemblance so that it is difficult to differentiate between primary ICA and liver metastasis of GBC, which sometimes becomes a point of discussion in clinical practice. Although these cancers demonstrate significant differences in their mutational landscape, several reports demonstrated shared genomic alteration in paired primary and metastatic site aids in distinguishing metastatic recurrence from second primary cancers. CASE SUMMARY We present a 73-year-old female patient who underwent curative resection for GBC harboring epidermal growth factor receptor 2 (ERBB2) activating mutation on next-generation sequencing (NGS)-based genomic testing. One year later, a hepatic lesion was observed on follow-up imaging and she underwent surgical resection for a pathological diagnosis. The histological findings of the hepatic lesion were similar to those of the primary lesion. Additionally, using NGS panel testing, the hepatic lesion was found to have ERBB2 activating mutation, which is the identical mutation detected in the sequencing result of the primary site. ERBB2 activating mutation occurs more frequently in GBC than ICA and ECA. Therefore, in the present case, we think this molecular finding potentiated the diagnosis of the liver mass toward a metastatic recurrence. Additionally, this patient underwent HER2-targeted treatment with lapatinib in combination with capecitabin and obtained clinical benefit. CONCLUSION This case illustrated NGS panel usefulness in distinguishing GBC recurrence from second primary cancer and HER2-targeted agent efficacy on ERBB2 mutated GBC. © The Author(s) 2019.
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| 77.
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Tsuda, Takeaki ; 津田, 武明
概要:
金沢大学先端科学・社会共創推進機構<br />One-dimensional flow equations were derived for non-Newtonian fluids in slot coating and a simple
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numerical method was proposed to solve the equations. We investigated non-Newtonian effects on coating performance and coating quality in slot coating. In some cases, computational results and experimental data were compared and both agreed well. A series of numerical computations showed that the one-dimensional approach can describe non-Newtonian flow under lips in a few minutes and that a pressure field equation proposed by Higgins can determine the location of an upstream meniscus. Moreover, it was found that the non-Newtonian characteristics of coating liquids affect both coating performance and coating quality. Because each non-Newtonian effect is quite different, we should optimize the conditions of slot coating and die geometries according to the target problem. © 2010 The Society of Rheology, Japan.
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| 78.
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Asano, Tetsuo ; Bose, Prosenjit ; Carmi, Paz ; Maheshwari, Anil ; Shu, Chang ; Smid, Michiel H. M. ; Wuhrer, Stefanie ; 浅野, 哲夫
概要:
金沢大学<br />The distance preserving graph embedding problem is to embed vertices of a given weighted graph into points in
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2-dimensional Euclidean space so that for each edge the distance between their corresponding endpoints is as close to the weight of the edge as possible. If the given graph is complete, that is, if distance constraints are given as a full matrix, then principal coordinate analysis can solve it in polynomial time. A serious disadvantage is its quadratic space requirement. In this paper we develop linear-space algorithms for this problem. A key idea is to partition a set of n objects into disjoint subsets (clusters) of size O(√n) such that the minimum inter cluster distance is maximized among all possible such partitions.<br />CCCG2007 The 19th Canadian Conference on Computational Geometry, August 20-22, 2007
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Asano, Tetsuo ; Mulzer, Wolfgang ; Wang, Yajun ; 浅野, 哲夫
概要:
金沢大学<br />Constant-work-space algorithms model computation when space is at a premium: the input is given as a read-only
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array that allows random ac- cess to its entries, and the algorithm may use constantly many additional registers of O(logn) bits each, where n denotes the input size. We present such algorithms for two restricted variants of the shortest path problem. First, we describe how to report a simple path between two arbitrary nodes in a given tree. Using a technique called "computing instead of storing", we obtain a naive algorithm that needs quadratic time and a constant number of additional registers. We then show how to improve the running time to linear by applying a technique named "simulated parallelization". Second, we show how to compute a shortest geodesic path between two points in a simple polygon in quadratic time and with constant work-space.
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| 80.
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Asano, Tetsuo ; Demaine, Erik D. ; Demaine, Martin L. ; Uehara, Ryuhei ; 浅野, 哲夫
概要:
金沢大学<br />Kaboozle is a puzzle consisting of several square cards, each annotated with colored paths and dots drawn on b
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oth sides and holes drilled. The goal is to join two colored dots with paths of the same color (and fill all holes) by stacking the cards suitably. The freedoms here are to reflect, rotate, and order the cards arbitrarily, so it is not surprising that the problem is NP-complete (as we show). More surprising is that any one of these freedoms-reflection, rotation, and order-is alone enough to make the puzzle NP-complete. Furthermore, we show NP-completenessof a particularly constrained form of Kaboozle related to 1D paper folding. Specifically, we suppose that the cards are glued together into a strip, where each glued edge has a specified folding direction (mountain or valley). This variation removes the ability to rotate and reflect cards, and restricts the order to be a valid folded state of a given 1D mountain-valley pattern. © 2012 Information Processing Society of Japan.
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| 81.
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Higuchi, Akihiro ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />Dry eye syndrome is a multifactorial condition on the tear and ocular surface. Autologous serum e
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ye drop is an effective method for treating dry eye. Autologous serum eye drops are now widely used by specialists since a first report in 1975. The results of a systematic study showed that the efficacy of autologous serum eye drops remains ambiguous because its preparation methods and clinical application have not been standardized. To elucidate the efficacy of autologous serum eye drops, well-designed, large-scale, high-quality randomized controlled trials need to be conducted with standardized treatment and use. Since serum components are partially similar to tear components, autologous serum eye drops improve dry eye by supplying tear components such as growth factors, proteins, and vitamins. Adding to the evidence based on the treatment of dry eye, we have found a new treatment candidate from serum: selenoprotein P (SeP). The efficacy of SeP as a treatment for dry eye was revealed by applying SeP eye drops to a dry eye rat model. Compared with phosphate-buffered saline treatment, SeP eye drops significantly reduced the fluorescein score of the cornea and suppressed the oxidative stress in the cornea, which is related to onset of dry eye, leading to improved corneal disorder. We have developed a new dry eye model caused by oxidative stress that will be used to screen candidate molecules for antioxidative activity. © 2018 The Authors.
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| 82.
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Higuchi, Akihiro ; Erina Oonishi ; Kawakita, Tetsuya ; Tsubota, Kazuo ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />Purpose: 2-hydroxy estradiol (2-OHE2) is a catechol derivative of 17β -Estradiol (E2) and it is s
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ynthesized from E2 catalyzed by cytochrome P4501A1. Previous studies reported that 2-OHE2 is a physiologic antioxidant in lipoproteins, liver microsomes, and the brain. Catechol derivatives show an anti-inflammatory effect through the inhibition of prostaglandin endoperoxide synthase (PGS) activity. Corneal erosion caused by dry eye is related to an increase in oxidative stress and inflammation in ocular surface cells. We investigated the therapeutic effects of 2-OHE2 on corneal damage caused by dry eye. Methods: Steroidal radical scavenging activity was confirmed through the electron spin resonance (ESR) method. PGS activity was measured using the COX Fluorescent Activity Assay Kit. To evaluate the effect of 2-OHE2 on the treatment for dry eye, 2-OHE2 was applied as an eye drop experiment using dry eye model rats. Results: 2-OHE2 scavenged tyrosyl radical and possibly suppressed oxidative stress in corneal epithelial cells. In addition, 2-OHE2 inhibited PGS activity, and 2-OHE2 is probably a competitive inhibitor of PGS. Corneal PGS activity was upregulated in the dry eye group. Therefore, 2-OHE2 eye drops improved corneal erosion in dry eye model rats. Conclusions: 2-OHE2 is a candidate for the treatment of dry eye through the suppression of inflammation and oxidative stress in the cornea. © 2016 Molecular Vision.
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| 83.
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Higuchi, Akihiro ; Kawakita, Tetsuya ; Tsubota, Kazuo ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />Purpose: To investigate the effect of desiccation on secretion of inflammatory cytokines in corne
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al epithelial cells and in the rat desiccation model. Methods: A human corneal epithelial cell line (CEPI) was grown in keratinocyte growth medium 2 (KGM2) to approximately 80% confluence. The medium was aspirated and dishes were left for 0 to 30 min with the cover left open to dry the cells (short-term desiccation). After desiccation, KGM2 was added to the dishes and collected from the dishes 15 min later to measure the concentrations of cytokines in the medium by sandwich enzyme immunoassay (ELISA). Viability of the cells was estimated with alamer blue. To study the effect of long-term desiccation, cultivated cells on transwells were used. After dessiccation for up to 8 h, the viability of the cells and levels of cytokines in the culture medium were examined. The expression of cytokines in the cornea of the dry eye model rat was measured by real-time PCR. Results: Short-term dessication of CEPI cells significantly increased the interleukin (IL)-6 level and slightly increased the tumor necrosis factor (TNF)-α level. Anti-IL-6 antibody partially suppressed cell death caused by desiccation. Upon long-term desiccation, IL-6 and IL-8 levels were increased. In the dry eye model rats, the IL-6 mRNA level in the cornea significantly increased, whereas TNF-α mRNA level slightly increased. Conclusions: Desiccation induced IL-6 expression in corneal epithelial cells, suggesting that IL-6 participates in desiccation-induced cell death. © 2011 Molecular Vision.
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| 84.
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Higuchi, Akihiro ; Inoue, Hiroyoshi ; Kawakita, Tetsuya ; Ogishima, Tadashi ; Tsubota, Kazuo ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />The ocular surface is strongly affected by oxidative stress, and anti-oxidative systems are maint
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ained in corneal epithelial cells and tear fluid. Dry eye is recognized as an oxidative stress-induced disease. Selenium compound eye drops are expected to be a candidate for the treatment of dry eye. We estimated the efficacy of several selenium compounds in the treatment of dry eye using a dry eye rat model. All of the studied selenium compounds were uptaken into corneal epithelial cells in vitro. However, when the selenium compounds were administered as eye drops in the dry eye rat model, most of the selenium compounds did not show effectiveness except for Se-lactoferrin. Se-lactoferrin is a lactoferrin that we prepared that binds selenium instead of iron. Se-lactoferrin eye drops suppressed the up-regulated expression of heme oxygenase-1, cyclooxygenase-2, matrix metallopeptidase-9, and interleukin-6 and also suppressed 8-OHdG production in the cornea induced by surgical removal of the lacrimal glands. Compared with Se-lactoferrin, apolactoferrin eye drops weakly improved dry eye in high dose. The effect of Se-lactoferrin eye drops on dry eye is possibly due to the effect of selenium and also the effect of apolactoferrin. Se-lactoferrin is a candidate for the treatment of dry eye via regulation of oxidative stress in the corneal epithelium. © 2012 Higuchi et al.
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| 85.
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Higuchi, Akihiro ; Takahashi, Kazuhiko ; Hirashima, Masaki ; Kawakita, Tetsuya ; Tsubota, Kazuo ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />The ocular surface is always attacked by oxidative stress, and cornea epithelial cells are suppos
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ed to have their own recovery system against oxidative stress. Therefore we hypothesized that tears supply key molecules for preventing oxidative stress in cornea. The potential target key molecule we focused is selenoprotein P (SeP). SeP is a carrier of selenium, which is an essential trace element for many animals, for oxidative stress metabolism in the organism, and was extremely expressed in lacrimal gland. An experiment was performed with SeP eye drops in a rat dry eye model, prepared by removing the lacrimal glands. The anticipated improvement in corneal dry eye index and the suppression of oxidative stress markers were observed in SeP eye drop group. Furthermore, the concentration of SeP was significantly higher in dry eye patients compared with normal volunteers. Collectively, we concluded that tear SeP is a key molecule to protect the ocular surface cells against environmental oxidative stress. © 2010 Higuchi et al.
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| 86.
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Higuchi, Akihiro ; Inoue, Hiroyoshi ; Kaneko, Yoshio ; Oonishi, Erina ; Tsubota, Kazuo ; 樋口, 明弘
概要:
金沢大学先端科学・社会共創推進機構<br />The ocular surface is strongly affected by oxidative stress, which causes many ocular diseases in
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cluding dry eye. Previously, we showed that selenium compounds, e.g., selenoprotein P and Se-lactoferrin, were candidates for treatment of dry eye. This paper shows the efficacy of Se-lactoferrin for the treatment of dry eye compared with Diquas as a control drug using two dry eye models and incorporation of lactoferrin into corneal epithelial cells via lactoferrin receptors. We show the efficacy of Se-lactoferrin eye drops in the tobacco smoke exposure rat dry eye model and short-term rabbit dry eye model, although Diquas eye drops were only effective in the short-term rabbit dry eye model. These results indicate that Se-lactoferrin was useful in the oxidative stress-causing dry eye model. Se-lactoferrin was taken into corneal epithelium cells via lactoferrin receptors. We identified LRP1 as the lactoferrin receptor in the corneal epithelium involved in lactoferrin uptake. Se-lactoferrin eye drops did not irritate the ocular surface of rabbits. Se-lactoferrin was an excellent candidate for treatment of dry eye, reducing oxidative stress by a novel mechanism. © 2016 The Author(s).
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| 87.
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論文
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Yamaguchi, Naoya ; Ishii, Fumiyuki ; 山口, 直也 ; 石井, 史之
概要:
金沢大学ナノマテリアル研究所<br />We investigate the effect of tensile strain on spin splitting at the n-type interface of LaAlO3/SrTi
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O3 in terms of spin–orbit coupling coefficient α and spin texture in the momentum space using first-principles density-functional calculations. Our results show that α could be controlled by the tensile strain, and can be enhanced by up to 5 times for a tensile strain of 7%, and the effect of the tensile strain leads to a persistent spin helix, which has a long spin lifetime. The strain effect on the LaAlO3/SrTiO3 interface is important for various applications such as spin field-effect transistors and spin-to-charge conversion.
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| 88.
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Naito, Hisamichi ; Takara, Kazuhiro ; Wakabayashi, Taku ; Kawahara, Hiroki ; Kidoya, Hiroyasu ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />It is widely accepted that blood vessels in the tumor microenvironment are immature because mural ce
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ll (MC) adhesion to endothelial cells (ECs) is broadly lacking. Hyperpermeability of the tumor vasculature then results in interstitial hypertension that mitigates against penetration of anticancer drugs into the depths of the tumor. It has been suggested that treatment with angiogenesis inhibitors normalizes blood vessels, resulting in restoration of normal permeability and improved drug delivery. However, recent reports suggest that cancer cell invasion is induced from the edge of the tumor into peripheral areas after treatment with angiogenesis inhibitors. Therefore, it is important to assess the status of blood vessels in the fibrous cap at the tumor rim after antiangiogenesis therapy. In the present study, we found that mature blood vessels in which ECs are covered with MCs are present in the fibrous cap. After treatment with angiogenesis inhibitors, immature blood vessels were destroyed and vascular function was significantly improved, but maturing blood vessels in which ECs were covered with MCs remained visible. These maturing blood vessels showed a less dilated character after treatment with the angiogenesis inhibitors. It is widely accepted that well-matured blood vessels are sheathed in extracellular matrix (ECM) and that cancer cells migrate along tracks made of ECM collagen fibers. Therefore, our data indicate the importance of destroying maturing blood vessels outside the tumor parenchyma to prevent cancer cell invasion. © 2011 Japanese Cancer Association.
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| 89.
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Iba, Tomohiro ; Naito, Hisamichi ; Shimizu, Shota ; Rahmawati, Fitriana Nur ; Wakabayashi, Taku ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
Background: During sprouting angiogenesis, stalk cells, localized behind tip cells, generate endothelial cells (ECs) for
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the elongation of new vessels. We hypothesized that stalk cells may have endothelial progenitor cell properties because of their highly proliferative ability. We conducted Hoechst dye DNA staining in ECs of preexisting blood vessels from hind limb muscle and found that endothelial-side population (E-SP) cells, which efflux Hoechst rapidly with abundant ABC transporters, show highly producing ability of ECs. We previously showed the existence of E-SP cells in hind limb muscle, retina, and liver, but not in other tissues such as adipose tissue, skin, and placenta. Methods: We investigated the existence of E-SP cells and analyzed their proliferative ability among CD31+CD45- ECs from adipose tissue, skin, and placenta of adult mice. We also analyzed the neovascular formation of E-SP cells from adipose tissue in vivo. Results: We detected E-SP cells in all tissues examined. However, by in vitro colony formation analysis on OP9 cells, we found that E-SP cells from adipose tissue and skin, but not from placenta, have highly proliferative ability. Moreover, E-SP cells from adipose tissue could contribute to the neovascular formation in hind limb ischemia model. Conclusion: The adipose tissue and skin are available sources to obtain endothelial stem cells for conducting therapeutic angiogenesis in regenerative medicine. © 2019 The Author(s).
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| 90.
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Wakabayashi, Taku ; Naito, Hisamichi ; Takara, Kazuhiro ; Kidoya, Hiroyasu ; Sakimoto, Susumu ; Oshima, Yusuke ; Nishida , Kohji ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
Purpose. The neovascular form of age-related macular degeneration (AMD) is characterized by the growth of abnormal new b
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lood vessels from the choroid, termed choroidal neovascularization (CNV). The origin of the new vessels in CNV, however, has not been elucidated fully to our knowledge. The purpose of this study is to identify vascular endothelial side population (SP) cells in the preexisting choroidal vessels, and investigate their potential role in AMD. Methods. We made single cell suspensions of freshly isolated mouse choroidal, retinal, and brain tissue by enzymatic digestion. Vascular endothelial SP cells were isolated using flow cytometry based on the ability to efflux the DNA-binding dye, Hoechst 33342, via ATP-binding cassette (ABC) transporters. Results. In the choroid, 2.8% of CD31+CD45- vascular endothelial cells (ECs) showed a typical SP staining pattern. They were not bone marrow-derived and possessed high colony-forming capacity in vitro. They proliferated during laser-induced CNV in vivo. In contrast, stereotypic SP staining pattern was not observed in retinal and brain ECs. Retinal and brain EC-SP cells included increased SP populations with less colony-forming capacity within the SP compartment, because they contained cells with and without proliferative potential. The latter still could efflux the dye due to high levels of ABC transporters, such as ABCB1a, ABCC4, and ABCC6. Conclusions. The EC-SP cells in the choroid may represent vessel-residing endothelial stem/progenitor cells contributing mainly to angiogenesis, and may be useful for augmenting vascular regeneration or for developing new antiangiogenic therapy in AMD. © 2013 The Association for Research in Vision and Ophthalmology, Inc.
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| 91.
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Yamakawa, Daishi ; Kidoya, Hiroyasu ; Sakimoto, Susumu ; Jia, Weizhen ; Naito, Hisamichi ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Tie2 is a receptor tyrosine kinase expressed on vascular endothelial cells (ECs). It has dual roles
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in promoting angiogenesis and stabilizing blood vessels, and it has been suggested that Tie2 forms dimers and/or oligomers in the absence of angiopoietin-1 (Ang1); however, the mechanism of ligand-independent dimerization of Tie2 and its biological significance have not been clarified. Using a bimolecular fluorescence complementation assay and a kinase-inactive Tie2 mutant, we show here that ligand-independent Tie2 dimerization is induced without Tie2 phosphorylation. Moreover, based on the fact that Tie1 never forms heterodimers with Tie2 in the absence of Ang1 despite having high amino acid sequence homology with Tie2, we searched for ligand-independent dimerization domains of Tie2 by reference to the difference with Tie1. We found that the YIA sequence of the intracellular domain of Tie2 corresponding to the LAS sequence in Tie1 is essential for this dimerization. When the YIA sequence was replaced by LAS in Tie2 (Tie2YIA/LAS), ligand-independent dimer was not formed in the absence of Ang1. When activation of Tie2YIA/LAS was induced by a high dose of Ang1, phosphorylation of Tie2 was limited compared with wild-type Tie2, resulting in retardation of activation of Erk downstream of Tie2. Therefore, these data suggest that ligand-independent dimerization of Tie2 is essential for a strong response upon stimulation with high dose Ang1. © 2013 by The American Society for Biochemistry and Molecular Biology, Inc.
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| 92.
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Kidoya, Hiroyasu ; Muramatsu, Fumitaka ; Shimamura, Teppei ; Jia, Weizhen ; Satoh, Takashi ; Hayashida, Yumiko ; Naito, Hisamichi ; Kunisaki, Yuya ; Arai, Fumio ; Seki, Masahide ; Suzuki, Yutaka ; Osawa , Tsuyoshi ; Akira , Shizuo ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />The balance between self-renewal and differentiation of hematopoietic stem and progenitor cells (HSP
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Cs) maintains hematopoietic homeostasis, failure of which can lead to hematopoietic disorder. HSPC fate is controlled by signals from the bone marrow niche resulting in alteration of the stem cell transcription network. Regnase-1, a member of the CCCH zinc finger protein family possessing RNAse activity, mediates post-transcriptional regulatory activity through degradation of target mRNAs. The precise function of Regnase-1 has been explored in inflammation-related cytokine expression but its function in hematopoiesis has not been elucidated. Here, we show that Regnase-1 regulates self-renewal of HSPCs through modulating the stability of Gata2 and Tal1 mRNA. In addition, we found that dysfunction of Regnase-1 leads to the rapid onset of abnormal hematopoiesis. Thus, our data reveal that Regnase-1-mediated post-transcriptional regulation is required for HSPC maintenance and suggest that it represents a leukemia tumor suppressor. © 2019, The Author(s).
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| 93.
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Kawahara, Hiroki ; Naito, Hisamichi ; Takara, Kazuhiro ; Wakabayashi, Taku ; Kidoya, Hiroyasu ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Background:A drug delivery system specifically targeting endothelial cells (ECs) in tumors is requir
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ed to prevent normal blood vessels from being damaged by angiogenesis inhibitors. The purpose of this study was to investigate whether apelin, a ligand for APJ expressed in ECs when angiogenesis is taking place, can be used for targeting drug delivery to ECs in tumors.Methods and Results:Uptake of apelin via APJ stably expressed in NIH-3T3 cells was investigated using TAMRA (fluorescent probe)-conjugated apelin. Both long and short forms of apelin (apelin 36 and apelin 13) were taken up, the latter more effectively. To improve efficacy of apelin- liposome conjugates, we introduced cysteine, with its sulfhydryl group, to the C terminus of apelin 13, resulting in the generation of apelin 14. In turn, apelin 14 was conjugated to rhodamine-encapsulating liposomes and administered to tumor-bearing mice. In the tumor microenvironment, we confirmed that liposomes were incorporated into the cytoplasm of ECs. In contrast, apelin non-conjugated liposomes were rarely found in the cytoplasm of ECs. Moreover, non-specific uptake of apelin-conjugated liposomes was rarely detected in other normal organs.Conclusions:ECs in normal organs express little APJ; however, upon hypoxic stimulation, such as in tumors, ECs start to express APJ. The present study suggests that apelin could represent a suitable tool to effectively deliver drugs specifically to ECs within tumors. © 2013 Kawahara et al.
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| 94.
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Sakimoto, Susumu ; Kidoya, Hiroyasu ; Kamei, Motohiro ; Naito, Hisamichi ; Yamakawa, Daishi ; Sakaguchi, Hirokazu ; Wakabayashi, Taku ; Nishida, Kohji ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Purpose: Adrenomedullin (ADM) has been shown to take part in physiological and pathological angiogen
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esis. The purpose of this study was to investigate whether ADM signaling is involved in choroidal neovascularization (CNV) using a mouse model. Methods and Results: CNV was induced by laser photocoagulation in 8-week-old C57BL/6 mice. ADM mRNA expression significantly increased following treatment, peaking 4 days thereafter. The expression of ADM receptor (ADM-R) components (CRLR, RAMP2 and RAMP 3) was higher in CD31+CD45- endothelial cells (ECs) than CD31-CD45- non-ECs. Inflammatory stimulation upregulated the expression of ADM not only in cell lines but also in cells in primary cultures of the choroid/retinal pigment epithelium complex. Supernatants from TNFα-treated macrophage cell lines potentiated the proliferation of ECs and this was partially suppressed by an ADM antagonist, ADM (22-52). Intravitreous injection of ADM (22-52) or ADM neutralizing monoclonal antibody (mAb) after laser treatment significantly reduced the size of CNV compared with vehicle-treated controls (p<0.01). Conclusions: ADM signaling is involved in laser-induced CNV formation, because both an ADM antagonist and ADM mAb significantly inhibited it. Suppression of ADM signaling might be a valuable alternative treatment for CNV associated with age-related macular degeneration. © 2013 Sakimoto et al.
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| 95.
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Ryu Kanzaki, ; Naito, Hisamichi ; Kise, Kazuyoshi ; Takara, Kazuhiro ; Eino, Daisuke ; Minami, Masato ; Shintani, Yasushi ; Funaki, Soichiro ; Kawamura, Tomohiro ; Kimura, Toru ; Okumura, Meinoshin ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Alterations to the tumor stromal microenvironment induced by chemotherapy could influence the behavi
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or of cancer cells. In the tumor stromal microenvironment, cancer-associated fibroblasts (CAFs) play an important role. Because the receptor tyrosine kinase Axl and its ligand Gas6 could be involved in promoting non-small cell lung cancer (NSCLC), we investigated the role of Gas6 secreted by CAFs during chemotherapy in NSCLC. In a murine model, we found that Gas6 expression by CAFs was upregulated following cisplatin treatment. Gas6 expression might be influenced by intratumoral hypoperfusion during chemotherapy, and it increased after serum starvation in a human lung CAF line, LCAFhTERT. Gas6 is associated with LCAFhTERT cell growth. Recombinant Gas6 promoted H1299 migration, and conditioned medium (CM) from LCAFhTERT cells activated Axl in H1299 cells and promoted migration. Silencing Gas6 in LCAFhTERT reduced the Axl activation and H1299 cell migration induced by CM from LCAFhTERT. In clinical samples, stromal Gas6 expression increased after chemotherapy. Five-year disease-free survival rates for patients with tumor Axl- and stromal Gas6-positive tumors (n = 37) was significantly worse than for the double negative group (n = 12) (21.9% vs 51.3%, p = 0.04). Based on these findings, it is presumed that Gas6 derived from CAFs promotes migration of Axl-expressing lung cancer cells during chemotherapy and is involved in poor clinical outcome. © 2017 The Author(s).
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| 96.
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Yoshida, Mari ; Ishioka, Yukichi ; Ozawa, Takamasa ; Okuyama, Hirohisa ; Iguchi, Motofumi ; Ota, Takeshi ; Ito, Takaomi ; Nagira, Morio ; Morita, Atsushi ; Tanaka, Hidekazu ; Naito, Hisamichi ; Kidoya, Hiroyasu ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Partner of sld five 1 (PSF1) is an evolutionary conserved DNA replication factor involved in DNA rep
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lication in lower species, which is strongly expressed in normal stem cell populations and progenitor cell populations. Recently, we have investigated PSF1 functions in cancer cells and found that PSF1 plays a significant role in tumour growth. These findings provide initial evidence for the potential of PSF1 as a therapeutic target. Here, we reveal that PSF1 contains an immunogenic epitope suitable for an antitumour vaccine. We analysed PSF1 peptides eluted from affinity-purified human leukocyte antigen (HLA) by mass spectrometry and identified PSF179-87 peptide (YLYDRLLRI) that has the highest prediction score using an in silico algorithm. PSF179-87 peptide induced PSF1-specific cytotoxic T lymphocyte responses such as the production of interferon-γ and cytotoxicity. Because PSF1 is expressed in cancer cell populations and highly expressed in cancer stem cell populations, these data suggest that vaccination with PSF179-87 peptide may be a novel therapeutic strategy for cancer treatment. © 2017 The Author(s).
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| 97.
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Matsushita, Jun ; Inagaki, Shigenori ; Nishie, Tomomi ; Sakasai, Tomoki ; Tanaka, Junko ; Watanabe, Chisato ; Mizutani, Ken-ichi ; Miwa, Yoshihiro ; Matsumoto, Ken ; Takara, Kazuhiro ; Naito, Hisamichi ; Kidoya, Hiroyasu ; Takakura, Nobuyuki ; Nagai, Takeharu ; Takahashi, Satoru ; Ema, Masatsugu ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Angiogenesis is important from normal development as well as from tumour growth. However, the molecu
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lar and cellular mechanisms underlying angiogenesis are not fully understood, partly because of the lack of a good animal model from imaging. Here, we report the generation of a novel transgenic (Tg) mouse that expresses a bioluminescent reporter protein, Nano-lantern, under the control of Fetal liver kinase 1 (Flk1). Flk1-Nano-lantern BAC Tg mice recapitulated endogenous Flk1 expression in endothelial cells and lymphatic endothelial cells during development and tumour growth. Importantly, bioluminescence imaging of endothelial cells from the aortic rings of Flk1-Nano-lantern BAC Tg mice enabled us to observe endothelial sprouting from 18 hr without any detectable phototoxicity. Furthermore, Flk1-Nano-lantern BAC Tg mice achieved time-lapse luminescence imaging of tumour angiogenesis in freely moving mice with implanted tumours. Thus, this transgenic mouse line contributes a unique model to study angiogenesis within both physiological and pathological contexts.
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| 98.
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Yamane, Keitaro ; Naito, Hisamichi ; Wakabayashi, Taku ; Yoshida, Hironori ; Muramatsu, Fumitaka ; Iba, Tomohiro ; Kidoya, Hiroyasu ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />SLD5 is a member of the GINS complex, essential for DNA replication in eukaryotes. It has been repor
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ted that SLD5 is involved in early embryogenesis in the mouse, and cell cycle progression and genome integrity in Drosophila. SLD5 may be involved in malignant tumor progression, but its relevance in human cancer has not been determined. Here, we found strong SLD5 expression in both human bladder cancer tissues from patients and cell lines. Knockdown of SLD5 using small interfering RNA resulted in reduction of cell growth both in vitro and an in vivo xenograft model. Moreover, we found that high levels of SLD5 in bladder cancer cells result from downregulation of microRNA (miR)-370 that otherwise suppresses its expression. High level expression of DNA-methyltransferase (DNMT) 1 and IL-6 were also observed in bladder cancer cells. Knockdown of IL-6 led to downregulation of DNMT1 and SLD5 expression, suggesting that IL-6-induced overexpression of DNMT1 suppresses miR-370, resulting in high SLD5 expression. Our findings could contribute to understanding tumorigenic processes and progression of human bladder cancer, whereby inhibition of SLD5 could represent a novel strategy to prevent tumor growth.
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| 99.
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論文
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Sakimoto, Susumu ; Kidoya, Hiroyasu ; Naito, Hisamichi ; Kamei, Motohiro ; Sakaguchi, Hirokazu ; Goda, Nobuhito ; Fukamizu, Akiyoshi ; Nishida , Kohji ; Takakura, Nobuyuki ; 内藤, 尚道 ; 高倉, 伸幸
概要:
金沢大学医薬保健研究域医学系<br />Interactions between astrocytes and endothelial cells (ECs) are crucial for retinal vascular formati
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on. Astrocytes induce migration and proliferation of ECs via their production of vascular endothelial growth factor (VEGF) and, conversely, ECs induce maturation of astrocytes possibly by the secretion of leukemia inhibitory factor (LIF). Together with the maturation of astrocytes, this finalizes angiogenesis. Thus far, the mechanisms triggering LIF production in ECs are unclear. Here we show that apelin, a ligand for the endothelial receptor APJ, induces maturation of astrocytes mediated by the production of LIF from ECs. APJ (Aplnr)- and Apln-deficient mice show delayed angiogenesis; however, aberrant overgrowth of endothelial networks with immature astrocyte overgrowth was induced. When ECs were stimulated with apelin, LIF expression was upregulated and intraocular injection of LIF into APJ-deficient mice suppressed EC and astrocyte overgrowth. These data suggest an involvement of apelin/APJ in the maturation process of retinal angiogenesis. © 2012. Published by The Company of Biologists Ltd.
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論文
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Nagao, Seiya ; Kanamori, Masaki ; Ochiai, Shinya ; Tomihara, S. ; Fukushi, Keisuke ; Yamamoto, Masayoshi ; 長尾, 誠也 ; 落合, 伸也 ; 福士, 圭介 ; 山本, 政儀
概要:
金沢大学環日本海域環境研究センター<br />At stations on the Natsui River and the Same River in Fukushima Prefecture, Japan, effects of a h
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eavy rain event on radiocesium export were studied after Typhoon Roke during 21-22 September 2011, six months after the Fukushima Dai-ichi Nuclear Power Plant accident. Radioactivity of 134Cs and 137Cs in river waters was 0.009-0.098 Bq L-1 in normal flow conditions during July-September 2011, but it increased to 0.85 Bq L -1 in high flow conditions because of heavy rains occurring with the typhoon. The particulate fractions of 134Cs and 137Cs were 21-56% of total radiocesium in the normal flow condition, but were close to 100% after the typhoon. These results indicate that the pulse input of radiocesium associated with suspended particles from land to coastal ocean occurred because of the heavy rain event. Export flux of 134Cs and 137Cs attributable to the heavy rain accounts for 30-50% of the annual radiocesium flux from inland to coastal ocean region in 2011. Results show that rain events are one factor contributing to the transport and dispersion of radiocesium in river watersheds and coastal marine environments. © 2013 Author(s).
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