1.

その他

その他
池田, 博子 ; Ikeda, Hiroko ; イケダ, ヒロコ
出版情報: 博士学位論文要旨 論文内容の要旨および論文審査結果の要旨/金沢大学大学院医学研究科.  平成20年7月  pp.8-,  2008-07-01.  金沢大学
URL: http://hdl.handle.net/2297/19235
概要: 取得学位 : 博士(医学), 学位授与番号 : 医博甲第1878号 , 学位授与年月日 : 平成19年6月30日, 学位授与大学 : 金沢大学, 主査教授 : 大井 章史, 副査教授 : 金子 周一 , 清水 徹
2.

論文

論文
池田, 博子 ; Ikeda, Hiroko
出版情報: 平成23(2011)年度 科学研究費補助金 若手研究(B) 研究成果報告書 = 2011 Fiscal Year Final Research Report.  2010-2011  pp.4p.-,  2012-05-21.  金沢大学附属病院
URL: http://hdl.handle.net/2297/00051410
概要: ラットやマウスなどの動物研究ではDelta-like protein(DLK)-1が肝プロジェニター/ステム細胞に発現していると報告されており,一方で肝線維化に関連することが知られている肝星細胞でのDLK1発現が文献的に報告されている.ヒト 肝組織におけるDLK1発現を分子病理学的に解析した.その結果, DLK1はステム細胞関連と推察される腫瘍で発現しており, DLK1が肝癌ステム細胞のマーカーとなりうる分子であることを解明した.<br />The expression of Delta-like protein(DLK)-1 in hepatic progenitor/stem cell has been known in animal experiments, whereas the upregulation of DLK1 in hepatic stellate cells has been reported and implied relation to fibrosis. I examined the expression of DLK1 in human tissue. As results, The expression of DLK1 was demonstrated in liver cancer associated with stem-cell origin. It was suggested that DLK1 could be cancer stem-cell marker of the liver.<br />研究課題/領域番号:22790341, 研究期間(年度):2010-2011 続きを見る
3.

論文

論文
池田, 博子 ; Ikeda, Hiroko
出版情報: 平成21(2009)年度 科学研究費補助金 若手研究(B) 研究成果報告書 = 2009 Fiscal Year Final Research Report.  2008-2009  pp.4p.-,  2010-05-17.  金沢大学附属病院
URL: http://hdl.handle.net/2297/00051411
概要: 細胞老化は不可逆的な細胞周期の停止として定義されており、前癌病変におけるセネッセンス細胞の出現およびセネッセンスからの回避機序は腫瘍発生初期段階での重要なステップであると考えられている。分子病理学的に検討の結果、ヒト肝組織では肝硬変でセネッ センス関連マーカー発現細胞が出現し、肝ディスプラジア結節では消失していた。肝硬変は肝細胞癌の前癌病変である可能性が示唆された。<br />Cellular senescence is defined as the irreversible arrest of cell cycle. Senescence in premalignant lesion and escape from senescence are thought to be important the early stage of tumoriogenesis. Senescence-associated markers are observed in cirrhotic liver and the markers disappear in dysplastic nodules. The results imply that the cirrhotic state already might to be premalignancy. 続きを見る
4.

論文

論文
池田, 博子 ; Ikeda, Hiroko
出版情報: 金沢大学十全医学会雑誌 = Journal of the Juzen Medical Society.  127  pp.103-107,  2018-11.  金沢大学十全医学会 — The Juzen Medical Society Kanazawa University
URL: http://hdl.handle.net/2297/00053874
概要: 近年,日本国民の約2人に1人は生涯のうちにがんに罹患すると推計されている.日本ではがん対策基本法に基づき,癌に対する取り組みが進められている.1990年に始まったヒトゲノム計画ではヒト1人分の全ゲノム解析に,13年の歳月と30億ドルの費用を 要していたが,目覚ましい技術進歩により,2016年には解析期間は1週間以下にまで短縮し,費用は約1000ドルにまで低廉化してきた.こうした技術革新により,次世代シークエンシング法 (next-generation sequencing; NGS) を用いたゲノム解析が,研究のみならず,患者の診断・治療といった診療にも拡がってきている.政府はがんゲノム医療の計画的な推進を提唱し,2017年には厚生労働省主導のがんゲノム医療推進コンソーシアム懇談会が立ち上げられ,当該医療の推進に必要な薬事承認や保険適用の制度設計などが議論されている1). 悪性腫瘍の病理組織・細胞検体を用いた体細胞遺伝子検査は急増しており,今後は次世代シークエンシング法 (NGS) などの新規技術を用いたゲノム診断 (遺伝子パネル検査) の臨床導入が見込まれている.日常の病理組織診断では,生検もしくは手術などにより採取・切除された組織のホルマリン固定パラフィン包埋 (formalin-fixed, paraffin-embedded; FFPE) 検体が主として用いられ,形態診断に加え,核酸やタンパクなどの検索を目的とした分子診断に供される.ゲノム解析では生体内環境に近い新鮮検体の利用が望ましいが,現況では治療法選択などにおいて腫瘍の病理診断は必須である.今後は形態診断,免疫組織化学法を用いた分子診断,ゲノム診断,いずれの利用にも耐えうる一定水準以上の病理検体の品質が求められるようになり,病理検査室ではその対応が急務となっている. 本稿では,がんゲノム医療の国内動向と遺伝子パネル検査の現状を概説し,ゲノム診療,研究のための病理組織検体取扱い規定を紹介する. 続きを見る
5.

論文

論文
Kakuda, Yuko ; Harada, Kenichi ; Sawada-Kitamura, Seiko ; Ikeda, Hiroko ; Sato, Yasunori ; Sasaki, Motoko ; Okafuji, Hirofumi ; Mizukoshi, Eishiro ; Terasaki, Shuichi ; Ohta, Hajime ; Kasashima, Satomi ; Kawashima, Atsuhiro ; Kaizaki, Yasuharu ; Kaneko, Shuichi ; Nakanuma, Yasuni
出版情報: Human Pathology.  44  pp.1107-1117,  2013-06-01.  Elsevier
URL: http://hdl.handle.net/2297/33483
概要: Recently, our research team proposed a new histologic staging and grading system for primary biliary cirrhosis (PBC) that takes into account necroinflammatory activity and histologic heterogeneity. The present study aimed to confirm the usefulness of the new evaluation system. A total of 152 liver biopsy specimens and clinical data (including outcomes in patients with PBC before treatment with ursodeoxycholic acid) were analyzed with respect to the new system. Staging was evaluated on the basis of 3 histologic components (fibrosis, bile duct loss, and deposition of orcein-positive granules), and grading was assessed on the basis of chronic cholangitis activity and hepatitis activity. Concurrently, the classical systems, that is, the Scheuer and Ludwig staging systems, were also assessed and compared with our new system. PBC cases showed different distributions in each stage of the 3 systems. The new staging and grading system reflected liver dysfunctions before specific treatment. This was on a par with the results obtained using the classical systems. Development of cirrhosis-related conditions correlated well with the new staging system compared with the 2 classical staging systems, and in particular, the amount of deposition of orcein-positive granules could reflect development of cirrhosis-related conditions (scores 0-1 versus scores 2-3 groups, P < .0001). In conclusion, the new PBC staging system was demonstrated to reflect clinicolaboratory features, and its progression was associated with the development of cirrhosis-related conditions. © 2013 Elsevier Inc. All rights reserved. 続きを見る
6.

論文

論文
Harada, Kenichi ; Sato, Yasunori ; Ikeda, Hiroko ; Maylee, Hsu ; Igarashi, Saya ; Okamura, Atsushi ; Masuda, Shinji ; Nakanuma, Yasuni
出版情報: Virchows Archiv : an international journal of pathology.  460  pp.281-289,  2012-03-01.  Springer Verlag (Germany)
URL: http://hdl.handle.net/2297/31405
概要: Neuroendocrine neoplasms in hepatobiliary organs are very rare, but several cases of mixed adenoneuroendocrine carcinoma (MANEC) have been reported. In this study, we characterized the neuroendocrine component of biliary MANEC. A total of 274 cases of biliary cancer including 17 intrahepatic cholangiocarcinomas (CCs), 15 hepatic hilar CCs without preceding hepatobiliary disease, 55 hepatic hilar CCs with hepatolithiasis, 49 gallbladder cancers, 53 extrahepatic CCs, and 85 hepatocellular carcinomas were examined for a neuroendocrine component using immunohistochemistry with neuroendocrine markers (chromogranin A and synaptophysin). In the MANEC cases, in addition to a close histological examination, the proliferative activity and the expression of somatostatin receptor 2A were also evaluated. In addition to an ordinary adenocarcinoma, a neuroendocrine component occupying more than 30% of the entire tumor was also found in 4% (2/55 cases) of hepatic hilar cholangiocarcinomas with hepatolithiasis, 10% (5/49 cases) of gallbladder cancers, and 4% (2/53 cases) of extrahepatic cholangiocarcinomas, but not in the intrahepatic cholangiocarcinomas, hilar cholangiocarcinomas without preceding hepatobiliary disease, and hepatocellular carcinomas. Two cases were positive for somatostatin receptor 2A. The adenocarcinoma components were predominately located at the surface of the tumors, and the majority of stromal and vascular invasion and lymph node metastasis involved neuroendocrine components, showing the features of neuroendocrine tumor G2 or neuroendocrine carcinomas (NECs). NEC components showed higher proliferative activity on Ki67 immunostaining, compared to the adenocarcinoma components. Biliary MANECs are found in hepatic hilar cholangiocarcinomas with hepatolithiasis, gallbladder cancers, and extrahepatic cholangiocarcinomas and show a characteristic histology. Since the neuroendocrine component in biliary MANEC defines the prognosis, it is important to identify it and consider the indications for adjunctive therapy with somatostatin analogues. 続きを見る
7.

論文

論文
Ooi, Akishi ; Inokuchi, Masafumi ; Harada, Shinichi ; Inazawa, Johji ; Tajiri, Ryousuke ; Sawada-Kitamura, Seiko ; Ikeda, Hiroko ; Kawashima, Hiroko ; Dobashi, Yoh
出版情報: Journal of Pathology.  227  pp.8-16,  2012-05-01.  John Wiley and Sons
URL: http://hdl.handle.net/2297/30345
概要: Oestrogen receptor-alpha (ERα), encoded by the ESR1 gene located on 6q25, is a nuclear transcription factor. Since it was reported in 2007 that more than 20% of breast cancers show ESR1 gene amplification, there has been considerable controversy about its frequency and clinical significance. We set out to assess the frequency and levels of ESR1 amplification in breast cancers. In a total of 106 breast needle biopsy specimens examined by immunohistochemistry, 78 tumours contained more than 10% ERα-positive cancer cells. In fluorescence in situ hybridization (FISH) analysis with an ESR1-specific probe, variously extended ESR1 signals were found in ERα-expressing cells. Some of these were indistinguishable from large clustered signals generally accepted to mean high-level gene amplification in homogeneously staining regions (HSRs), and could be considered to represent gene amplification. However, with RNase treatment, the 'HSR-like' signals changed to small compact signals, and are thus thought to represent concentrated RNA. FISH using two differently labelled probes corresponding to the non-overlapping 5'- and 3'-end portions of the ESR1 gene on touch smears showed a preserved spatial relationship of the 3' to 5' sequence of ESR1, therefore strongly suggesting that the RNA consisted of primary transcripts. Using touch smears obtained from 51 fresh tumours, precise enumeration of ESR1 signals with a correction by the number of centromere 6 on FISH after RNase A treatment revealed that three tumours (5.9%) had tumour cells with one to three additional copies of ESR1 as predominant subpopulations. This infrequent and low level of gene amplification of ESR1 was also detected as a 'gain' of the gene by analysis with multiplex ligation-dependent probe amplification (MLPA). The consistent results from immunohistochemistry, FISH, and MLPA in the present study settle the long-standing debate concerning gene amplification of ESR1 in breast carcinoma. © 2012 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd 続きを見る
8.

論文

論文
Funada, Akira ; Masuta, Eiichi ; Fujino, Noboru ; Hayashi, Kenshi ; Ino, Hidekazu ; Kita, Yoshihito ; Ikeda, Hiroko ; Fujii, Takahiko ; Nakanuma, Yasuni ; Yamagishi, Masakazu
出版情報: International Heart Journal.  51  pp.214-217,  2010-01-01.  International Heart Journal Association
URL: http://hdl.handle.net/2297/31473
概要: Hypertrophic cardiomyopathy (HCM) is associated with gene mutations that encode sarcomeric proteins. However, the relationship between genotype and histopathologic fndings is unclear. We report on two autopsy cases with advanced HCM associated with deletion of lysine 183 mutation in the cardiac troponin I gene. One case, a 74-year-old female exhibited dilated cardiomyopathy-like features. Transmural scarring was diffuse and circumferential, involving the whole left ventricle, especially the ventricular septum which was replaced with extensive fbrosis and showed marked wall thinning. The other case, a 92-year-old male revealed typical HCM fndings. Patchy scars which corresponded to replacement fbrosis were found extending from the septum to the anterior wall. These two autopsy cases indicate the clinical heterogeneity of HCM even within the same disease-causing mutation and suggest that the degree and extent of fbrosis determine differences in the clinical manifestations of HCM. This is the frst autopsy report that demonstrates identical sarcomeric gene mutations causing different clinical manifestations and histologic fndings. The fndings suggest that additional genetic or environmental factors infuence the phenotypic expressions and clinical courses of HCM caused by genetic mutation of sarcomeric proteins. 続きを見る
9.

論文

論文
Nakanuma, Yasuni ; Harada, Kenichi ; Sato, Yasunori ; Ikeda, Hiroko
出版情報: Histology and Histopathology.  25  pp.223-235,  2010-02-01.  Histology and Histopathology
URL: http://hdl.handle.net/2297/31474
概要: Recent progress in elucidating the etiopathogenesis of pediatric biliary diseases, particularly Caroli's disease with congenital hepatic fibrosis (CHF) and biliary atresia (BA), is reviewed. The former is characterized by multiple saccular dilatations of the intrahepatic bile ducts. An animal model of this disease, the PCK rat, is being extensively studied. PCK rats and Calori's disease with CHF belong to autosomal recessive polycystic kidney disease (ARPKD) with ductal plate malformation. Mutations of PKHD1 have been identified in ARPKD, and fibrocystin, a product of PKHD1 located in the cilia of bile ducts is lacking in the pathologic intrahepatic bile ducts of ARPKD. Disordered cell kinetics, including apoptosis of biliary epithelial cells (BECs), may be significantly related to ductal plate malformation, and laminin and type IV collagen were immunohistochemically reduced in the basement membrane of intrahepatic bile ducts of ARPKD, and such a reduction is an additional factor for the dilatation of bile ducts. Abundant connective tissue growth factor retained diffusely in heparan sulfate proteoglycan in the fibrous portal tracts are responsible for non-resolving hepatic fibrosis. In addition, pathologic BECs of ARPKD may acquire mesenchymal features and participate in progressive hepatic fibrosis by producing extracellular matrix molecules. In an animal model of BA, an initial virus-induced, T-cell mediated autoimmune-mediated cholangiopathy has been reported. In human BA, virus-induced apoptosis of BECs by a TNF-related apoptosis-inducing ligand followed by the progressive obliteration of bile ducts is also suggested, and epithelial mesenchymal transition of BECs induced by viral infection may be involved in the fibrotic process in sclerosing cholangitis. However, the role of viral infections in the affected tissues is controversial. Comprehensive and analytical studies of ARPKD and BA using human materials and animal models may lead to the clarification of their etiopathogenesis and open the way for new therapeutic strategies. 続きを見る
10.

論文

論文
Harada, Kenichi ; Kakuda, Yuko ; Sato, Yasunori ; Ikeda, Hiroko ; Nakanuma, Yasuni
出版情報: Journal of Clinical Pathology.  67  pp.566-572,  2014-07-01.  BMJ Publishing Group
URL: http://hdl.handle.net/2297/37762
概要: Aims Oestrogen has been speculated to play an important role in the pathogenesis of primary biliary cirrhosis (PBC), which mainly affects middle-aged and old-aged females because biliary epithelial cells (BECs) are known to express oestrogen receptors (ERs). Oestrogen-related receptors (ERRs) are constitutively active without oestrogen and competitively inhibit the ER-dependent effects of oestrogen. We clarified the effects of oestrogen and the significance of ERRs along with their association with the pathogenesis of cholangiopathy in PBC. Methods We investigated the expression of ERs and ERRs and the apoptosis-related cell kinetics in BECs using cultured human BECs and human liver specimens. Results Although cultured human BECs and the interlobular bile ducts in the liver expressed ERβ, in cultured BECs, oestrogen treatment did not induce significant cell proliferation but increased the expression of a negative cell proliferation regulator (14-3-3σ protein). The cultured BECs constantly expressed ERRα and ERβ, and oestrogen downregulated the ERRγ expression. Furthermore, the ERβ expression was determined in the intrahepatic bile ducts and was stronger in the middle-aged and old-aged females, particularly those with PBC, than in the younger females. The ERβ ligand activated a transcription factor, SP1, and enhanced the expression of the pro-apoptotic Bcl-2 family molecules and Bcl-2 inhibitor-induced apoptosis in cultured BECs. Conclusions Although oestrogen downregulates the ERRγ expression, the increased ERRγ expression under oestrogen-deficient conditions increases the susceptibility to Bcl-2 family-mediated apoptosis in cultured human BECs of females, particularly those with PBC. Understanding the oestrogen-mediated cell kinetics is important for elucidating the pathogenesis of cholangiopathy in PBC. © 2014 by the BMJ Publishing Group Ltd & Association of Clinical Pathologists. 続きを見る