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| 1.
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山田, 外史
概要:
Cancer is the most deadly disease in the world today. There is a variety of different treatment methods for cancer, incl
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uding radiotherapy and chemotherapy with anticancer drugs that have been in use over a long period of time. Hyperthermia is one of the cancer treatment methods that utilizes the property that cancer cells are more sensitive to temperature than normal cells. The control of temperature is an important task in achieving success using this treatment method. This paper reports the development of a novel needle-type nanosensor based on the spin-valve giant magnetoresistive (SV-GMR) technique to measure the magnetic flux density inside the body via pricking the needle. The sensor has been fabricated. The modeling and experimental results of flux density measurement have been reported. From the information of flux density, the temperature rise can be estimated to permit the delivery of controlled heating to precisely defined locations in controlled hyperthermia cancer treatment. The actual experiment with human is under investigation. © 2007, IEEE. All rights reserved.<br />Proceedings of the 1997 2nd International Conference on Power Electronics and Drive Systems, PEDS. Part 2 (of 2); Singapore, Singapore; ; 26 May 1997 through 29 May 1997; Code 47014
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| 2.
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Funasaka, Tatsuyoshi ; Nakano, Hiroshi ; Wu, Yu ; Hashizume, Chieko ; Gu, Ling ; Nakamura, Takuro ; Wang, Wei ; Zhou, Pengbo ; Moore, Malcolm AS ; Sato, Hiroshi ; Wong, Richard W.
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金沢大学フロンティアサイエンス機構<br />Chromosomal translocations involving chimeric fusions of the nucleoporin NUP98 protein have often
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been described in acute myelogenous leukemia (AML). All the fusion proteins have an identical NUP98 N terminus, which contains the GLEBS motif for interaction with the mRNA export factor RAE1 and FG repeats that associate with the transcription factors HDAC1 and p300. It is virtually unknown whether these interaction partners affect leukemogenesis. We previously showed that RAE1 depletion caused aneuploidy, which enhanced tumorigenesis. We speculated that RAE1 may also be directly involved in NUP98 fusion-mediated leukemogenesis. We show here that RNA interference (RNAi)-mediated knockdown of NUP98 caused severe chromosome segregation defects and disrupted RAE1 but not HDAC1 expression and localization. Next, we performed rescue experiments to confirm that the RAE1-NUP98 complex orchestrates proper chromosome segregation. Interestingly, we found diverse behaviors of NUP98 and the leukemogenic fusion protein NUP98-HOXA9 throughout the cell cycle. Strikingly, in NUP98-HOXA9-transfected cells, RAE1 protein were reduced and mis-localized. Our cellular interpretations were further confirmed by NUP98-HOXA9 transgenic mice and the NUP98-HOXA9 AML patient. These data suggest that RAE1 orchestrates NUP98-mediated leukemogenesis and raise the possibility that targeting this negative feedback loop may provide a new strategy for the therapy of aggressive leukemias. © 2011 Landes Bioscience.
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| 3.
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柳原, 清子
概要:
本研究は、成人期にがんできょうだいと死別した人の悲嘆と、家族システムの変化を明ら かにするものである。対象者は20 ～ 50 歳代の男女7 名で、半構成面接をし、質的研究手法 でまとめた。 結果として、9 カテゴリー、12 サブカテゴリー、
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28 概念が抽出された。きょうだいは家族 システムのサブシステムであり、【育ち合い】の関係で成長し、結婚で互いが生殖家族を持っ て分離する。一方で成人期での発病と死別は、家族システムおよびきょうだいシステムの凝 集性を高め、【一身で世話する】ことになる。患者のがん発病は、【微妙な位置の身びいき意識】 という、小姑の立場からの身びいき意識を生み出し、定位家族、生殖家族メンバー間の軋轢 や葛藤を生み出した。 また、きょうだいの悲嘆は【一様でない哀しみ】であった。それは育ち合ってきたコンボ イ（護送船団＝立場の弱い者に配慮しながら助け合う）としての関係性の喪失であり、自己 存在を証明してくれる人を喪うことであった。この悲嘆は社会的に認知されにくく、さらに きょうだい自身が【老親の取り持ち役】を優先して自分の悲嘆を封印してしまうことから、 2 重の意味で悲嘆を見えにくいものにしていた。一方で、老親への気配りは、新たな役割獲 得であり、それが、悲嘆を癒している面があった。さらに、きょうだいは遺伝子を共有して おり、がんの発病への危惧としての【血の怯え】も見出された。 全体として、きょうだいへの看病と死別の過程は、成人し分離し生殖家族が中心だったきょ うだいの家族への視座を、生殖家族から定位家族へ回帰させるものであった。それは老親へ のコミット、きょうだいの絆の再凝集の形であらわれていた。
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| 4.
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Ogiwara, Shimpachiro ; Ikezawa, Yoko
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金沢大学大学院医学系研究科<br />PURPOSE: To demonstrate attitudes of health science students towards clients with cancer (ATC). The o
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bjective was three-fold: 1) to describe health science students' ATC, 2) to compare ATC amongst health science students according to their professional discipline, academic seniority and gender, 3) to note whether their ATC differed according to: a) their experience with cancer clients during clinical placement; and/or b) their acquired perception through their class-work of the need for psychological support for cancer clients. RELEVANCE: To show how important a student's prior classroom instruction and positive experience in clinical placement is to the establishment of an empathic attitude to clients with cancer. PARTICIPANTS: A total of 860 students participated from five professional disciplines of the School of Health Sciences at the University of Kanazawa, Japan. Five hundred and sixty-eight responded appropriately with the rate of response being 66 per cent. METHOD: The ATC scale consisted of 30 statements with six responses (+3, +2, +1, -1, -2, -3) for each statement. Two additional questions were provided on the questionnaire: a) whether or not a need for psychological support for such clients was perceived necessary as was instructed through their class-work; and b) students' experience with cancer clients during clinical placements. ANALYSIS: Descriptive analysis of student demographics, the Fisher's PLSD post-hoc test followed by multiple comparisons and the Mann-Whitney U test to determine any statistically significant difference in the ATC scores. RESULTS: Student nurses scored significantly high on the ATC scale, followed by laboratory science, physiotherapy, radiological technology and occupational therapy students. It was also found that all fourth year students scored significantly high on the ATC scale. The student nurses showed that they dealt with significantly large numbers of cancer clients during their clinical placements. The students who were affirmative to the two additional questions were found to have significantly higher ATC scores than those who were negative. CONCLUSION: Senior students' ATC was found to be more positive. Student nurses' approach to cancer clients was on a more person-to-person basis. Having experience alone with cancer clients was not sufficient to promote a positive ATC, but additional structured classroom instruction was found to play a necessary role in ATC.
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Mizukoshi, Eishiro ; Fushimi, Kazumi ; Arai, Kuniaki ; Yamashita, Tatsuya ; Honda, Masao ; Kaneko, Shuichi
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Background & Aims: Chondroitin-glucuronate C5-epimerase is an enzyme that converts D-glucuronic acid to L-iduronic acid
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residues in dermatan sulphate biosynthesis. It is also identified to be a tumour-associated antigen recognized by cytotoxic T cells (CTLs) and its enhanced expression in many cancers has been reported. In the present study, we investigated the usefulness of this molecule as an immunotherapeutic target in hepatocellular carcinoma (HCC). Methods: The expression of chondroitin-glucuronate C5-epimerase in hepatoma cell lines and HCC tissues was confirmed by immunofluorescence and immunohistochemical analysis. CTL responses were investigated by several immunological techniques using peripheral blood mononuclear cells (PBMCs) or tumour-infiltrating lymphocytes. To determine the safety of immunotherapy using chondroitin-glucuronate C5-epimerase-derived peptide, 12 patients with HCC were administered s.c. vaccinations of the peptides and analysed. Results: Chondroitin-glucuronate C5-epimerase was expressed in HCC cell lines and human tissues including alpha-foetoprotein (AFP)-negative individuals. Chondroitin-glucuronate C5-epimerase-specific CTLs could be generated by stimulating PBMCs of HCC patients with peptides and they showed cytotoxicity against HCC cells expressing the protein. The frequency of CTL precursors investigated by enzyme-linked immunospot (ELISPOT) assay was 0-34 cells/3 × 10 5 PBMCs and the infiltration of interferon-gamma-producing CTLs into the tumour site was confirmed. In the vaccination study, no severe adverse events were observed and the peptide-specific CTLs were induced in 4 of 12 patients tested. Conclusions: Chondroitin-glucuronate C5-epimerase is a potential candidate for tumour antigen with immunogenicity and the peptides derived from this antigen could be useful in HCC immunotherapy. © 2012 John Wiley & Sons A/S.
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Kitahara, Masaaki ; Mizukoshi, Eishiro ; Nakamoto, Yasunari ; Mukaida, Naofumi ; Matsushima, Kouji ; Kaneko, Shuichi
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Background & aims Immunotherapy using dendritic cells (DCs) is a promising cancer therapy. The success of this therapy d
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epends on the function of induced DCs. However, there has been no consensus on optimal conditions for DC preparation in vitro for immunotherapy of hepatocellular carcinoma (HCC) patients. To address relevant issues, we evaluated the procedures to induce DCs that efficiently function in hepatitis C virus (HCV)-related HCC. Methods We studied immunological data from 14 HCC patients. The DC preparation and the surface markers were assessed by flow cytometric analysis. Four different additional activation stimuli (Method I, medium alone; Method II, with OK-432; Method III, with IL-1β + IL-6 + TNF-α; Method IV, with IL-1β + IL-6 + TNF-α + PGE2) were tested and the functions of DCs were confirmed by examination of the ability of phagocytosis, cytokine production and allogeneic mixed lymphocyte reaction (MLR). Results The numbers of DCs induced and their cytokine production ability were not different between healthy controls and HCC patients. T-cell stimulatory activity of DCs in MLR was significantly lower in HCC patients than in healthy controls. The maturation of DCs with OK-432 boosted production of cytokines and chemokines, such as IL-2, IL-12p70, IFN-γ, TNF-α, IL-13 and MIP1α, and restored T-cell stimulatory activity of DCs in MLR. Conclusions The clinically approved compound OK-432 is a candidate for highly immunocompetent DC preparation and may be considered as a key drug for immunotherapy of HCV-related HCC patients. © 2014 Published by Elsevier B.V.
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| 7.
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Mizukoshi, Eishiro ; Yamashita, Tatsuya ; Arai, Kuniaki ; Terashima, Takeshi ; Kitahara, Masaaki ; Nakagawa, Hidetoshi ; Iida, Noriho ; Fushimi, Kazumi ; Kaneko, Shuichi
概要:
Hepatic arterial infusion chemotherapy (HAIC) has been employed as an alternative therapy to sorafenib for the patients
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with advanced hepatocellular carcinoma (HCC). In this study, we performed a comparative analysis of various immune cell responses including tumor-associated antigen (TAA)-specific T cells, regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) in advanced HCC patients treated with HAIC. Thirty-six HCC patients were examined in the study. Interferon gamma enzyme-linked immunospot assays were performed to examine the frequency of TAA-specific T cells. The frequencies of Tregs and MDSCs were examined by multicolor fluorescence-activated cell sorting analysis. The treatment with HAIC using interferon (IFN)/5-fluorouracil (FU) or IFN/FU + cisplatin modulated the frequencies of various immune cells. In 22.2 % of patients, the frequency of TAA-specific T cells increased after HAIC. Although the frequency of Tregs decreased after HAIC, it was not associated with the prognosis of patients. An analysis of prognostic factors for overall survival identified diameter of the tumor (<3.0 cm), absence of major portal vein invasion, absence of distant metastasis, Union Internationale Contre Le Cancer tumor lymph node metastasis stage (I or II), neutrophil lymphocytic ratio (<2.1) and the frequency of MDSCs (<30.5 %) as factors that prolonged overall survival time after HAIC. Even in the group adjusted with progressive levels of tumors, patients with a low frequency of MDSCs had a significantly longer overall survival time. In conclusion, the frequency of MDSCs before the treatment is a prognostic factor in HAIC against HCC. © 2016 Springer-Verlag Berlin Heidelberg
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| 8.
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Mizukoshi, Eishiro ; Nakagawa, Hidetoshi ; Kitahara, Masaaki ; Yamashita, Tatsuya ; Arai, Kuniaki ; Sunagozaka, Hajime ; Iida, Noriho ; Fushimi, Kazumi ; Kaneko, Shuichi
概要:
Multidrug resistance-associated protein 3 (MRP3) is a carrier-type transport protein belonging to the ABC transporters.
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In this study, we investigated the safety and immunogenicity of a MRP3-derived peptide (MRP3765) as a vaccine and characterized the MRP3-specific T cell responses induced. Twelve hepatocellular carcinoma (HCC) patients treated with hepatic arterial infusion chemotherapy (HAIC) were enrolled. The MRP3-derived peptide was emulsified in incomplete Freund's adjuvant and administered via subcutaneous immunization three times weekly. No serious adverse drug reactions to the peptide vaccine were observed, and the vaccination was well tolerated. The vaccination induced MRP3-specific immunity in 72.7% of the patients. In a phenotypic analysis, the largest post-vaccinated increase in MRP3-specific T cells was due to an increase in cells with the effector memory phenotype. Among the 12 patients, one patient showed a partial response, nine showed a stable disease, and two showed a progressive disease. The median overall survival time was 14.0 months. In conclusion, the safety, effects of immune boosting, and possible prolongation of overall survival by the MRP3-derived peptide demonstrate the potential of the peptide to provide clinical benefit in HCC patients. © 2015.
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Mizukoshi, Eishiro ; Kaneko, Shuichi
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Hepatocellular carcinoma (HCC) is the sixth most common type of cancer globally. Although many different kinds of treatm
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ent are performed for HCC according to the practical guidelines, the prognosis of patients is not still satisfactory because the effects of treatments are limited for advanced tumors and the recurrence rate of HCC, even in early stages, is very high. Therefore, immunotherapy is highly anticipated as a new treatment method for HCC. For the development of a new HCC therapy, we attempted to establish immunotherapy using dendritic cells (DCs) and peptide vaccine. In several clinical trials that we performed, we confirmed that the immunotherapy was safe and well-tolerated by HCC patients. We observed that DC therapy prolonged the recurrence-free survival of patients compared with that of patients without DC infusion, as well as observing the radiological anti-tumor effect in HCC patients with peptide vaccine. In this chapter, we summarize the results of previous studies using DC and peptide vaccine, including our own data, and describe the prospects of immunotherapy for HCC. © 2015, Springer Japan. All rights reserved.<br />[Book Chapter]
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Sakamoto, Takeharu ; Seiki, Motoharu
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Membrane-type 1 matrix metalloproteinase (MT1-MMP) is expressed in different types of invasive and proliferative cells,
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including cancer cells and stromal cells. MT1-MMP cleaves extracellular matrix proteins, membrane proteins and other pericellular proteins, thereby changing the cellular microenvironment and regulating signal activation. Critical roles of protease activity in cancer cell proliferation, invasion and metastasis have been demonstrated by many groups. MT1-MMP also has a non-protease activity in that it inhibits the oxygen-dependent suppression of hypoxia-inducible factors (HIFs) via Munc18-1-interacting protein 3 (Mint3) and thereby enhances the expression of HIF target genes. Elevated HIF activity in MT1-MMP-expressing cancer cells is a fundamental mechanism underlying the Warburg effect, a well-known phenomenon where malignant cancer cells exhibit a higher rate of glucose metabolism. Because specific intervention of HIF activation by MT1-MMP suppresses tumor formation by cancer cells in mice, both the proteolytic and non-proteolytic activities of MT1-MMP are important for tumor malignancy and function in an integrated manner. In this review, we summarize recent findings relating to how MT1-MMP activates HIF and its effects on cancer cells and stromal cells. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.
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