Faculty Profiles - YOSHIOKA Norie

Papers - YOSHIOKA Norie

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Angiogenin-Stimulated rRNA Transcription Is Essential for Initiation and Survival of AKT-Induced Prostate Intraepithelial Neoplasia Reviewed

Soichiro Ibaragi, Norie Yoshioka, Hiroko Kishikawa, Jamie K. Hu, Peter M. Sadow, Ming Li, Guo-fu Hu

MOLECULAR CANCER RESEARCH 7 ( 3 ) 415 - 424 2009.3

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER ASSOC CANCER RESEARCH

Anglogenin (ANG), originally identified as an angiogenic ribonuclease, has recently been shown to play a direct role In prostate cancer cell proliferation by mediating rRNA transcription. ANG Is up-regulated In human prostate cancer and is the most significantly up-regulated gene In AKT-driven prostate Intraepithellal neoplasla (PIN) in mice. Enhanced cell proliferation in the PIN lesions requires Increased ribosome biogenesis, a multistep process Involving an orchestrated production of ribosomal proteins and rRNA. AKT Is known to enhance ribosomal protein production through the mammalian target of rapamycin pathway. However, It was unknown how rRNA Is proportionally Increased. Here, we report that ANG Is essential for AKT-driven PIN formation and survival. We showed that up-regulation of ANG In the AKT-overexpressing mouse prostates is an early and lasting event. It occurs before PIN initiation and lasts beyond PIN is fully developed. Knocking down ANG expression by intraprostate Injection of lentivirus-mediated ANG-specific small Interfering RNA prevents AKT-Induced PIN formation without affecting AKT expression and its signaling through the mammalian target of rapamycin pathway. Neomycin, an aminoglycoside that blocks nuclear translocation of ANG, and N65828, a small-molecule enzymatic inhibitor of the ribonucleolytic activity of ANG, both prevent AKT-Induced PIN formation and reverse established PIN. They also decrease nucleolar organizer region, restore cell size, and normalize luminal architectures of the prostate despite continuous activation of AKT. All three of the prostate luminal epithelial cells and inhibit AKT-induced PIN, indicating an essential role of ANG in AKT-mediated cell proliferation and survival.

DOI： 10.1158/1541-7786.MCR-08-0137

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当科におけるインプラント患者の臨床統計的検討

帆波辰基, 目瀬浩, 西山明慶, 岸本晃治, 塚本剛一, 志茂剛, 吉岡徳枝, 銅前昇平, 中妻加奈子, 辻本紗代子, 伊原木聰一郎, 佐々木朗

岡山歯学会雑誌 28 ( 2 ) 151 - 155 2009

Language：Japanese Publisher：岡山歯学会

2002〜2009年の7年間に著者等の施設でインプラント埋入を施行した162例(男性62例、女性100例、18〜78歳・平均55.3歳)を対象に受診経路、埋入インプラントの種類、埋入本数・部位などについて検討した。その結果、患者の受診経路は院内他科からの紹介141例・他院からの紹介15例・紹介なし7例で、紹介患者が96%を占めた。埋入インプラントの種類はBranemark System;382本・Steri-Oss System;54本・Replace;14本で、埋入本数は2002年(14名34本)から2007年(46名126本)にかけて増加傾向にあった。年齢別患者数とインプラント埋入本数では40〜70歳代の147名に415本と大部分を占めており、埋入部位は上顎235本・下顎215本とほぼ同じであった。前臼歯別では上顎前歯部84本・上顎臼歯部151本、下顎前歯部18本・下顎臼歯部197本であった。経過観察では全例で術後の合併症は認めず、インプラント総残存率は99.5%であった。

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入院加療を要した歯性感染症の臨床統計的検討

目瀬浩, 中山周子, 小山貴弘, 小野達生, 銅前昇平, 吉岡徳枝, 志茂剛, 佐々木朗

岡山歯学会雑誌 26 ( 2 ) 97 - 101 2007.12

Language：Japanese Publisher：岡山歯学会

1982年4月〜2001年3月までの19年間に岡山大学医学部・歯学部附属病院口腔外科(病態系)を受診し入院加療を要した歯性感染症318例(男性185例、女性133例、平均44.9歳)を対象として、その発生原因、背景因子、処置方法などを検討した。入院時の臨床診断は膿瘍231例(72.7%)、蜂窩織炎38例(11.9%)、急性骨髄炎35例(11.0%)、急性歯性上顎洞炎14例(4.4%)で、原因疾患は根尖性歯周炎178例(56.0%)が最多、次いで智歯周囲炎65例(20.4%)、歯根嚢胞11例(3.5%)であった。また318例中81例(25.5%)が糖尿病、肝障害、腎障害など炎症に関連する基礎疾患を有していた。局所的な炎症の増悪要因を分析すると、患者本人が歯性および関連性炎症病変を放置したものが、基礎疾患を有するもので93例(39.2%)、基礎疾患の無いもので28例(34.5%)を占めていた。また基礎疾患を有しておらず、他の局所的な要因も明らかではなかった症例が72例(22.6%)認められた。入院期間は274例(86.2%)が20日以内で、消炎処置のみを行ったものが133例(41.8%)、原因疾患に対する処置まで行ったものが185例(58.2%)であった。

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A therapeutic target for prostate cancer based on angiogenin-stimulated angiogenesis and cancer cell proliferation Reviewed

Norie Yoshioka, Li Wang, Koji Kishimoto, Takanori Tsuji, Guo-fu Hu

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA 103 ( 39 ) 14519 - 14524 2006.9

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：NATL ACAD SCIENCES

Human angiogenin is progressively up-regulated in the prostate epithelial cells during the development of prostate cancer from prostate intraepithelial neoplasia (PIN) to invasive adenocarcinoma. Mouse angiogenin is the most up-regulated gene in AKT-induced PIN in prostate-restricted AKT transgenic mice. These results prompted us to study the role that angiogenin plays in prostate cancer. Here, we report that, in addition to its well established role in mediating angiogenesis, angiogenin also directly stimulates prostate cancer cell proliferation. Angiogenin undergoes nuclear translocation in PC-3 human prostate cancer cells grown both in vitro and in mice. Thus, knocking down angiogenin expression in PC-3 human prostate adenocarcinoma cells inhibits ribosomal RNA transcription, in vitro cell proliferation, colony formation in soft agar, and xenograft growth in athymic mice. Blockade of nuclear translocation of angiogenin by the aminoglycoside antibiotic neomycin inhibited PC-3 cell tumor growth in athymic mice and was accompanied by a decrease in both cancer cell proliferation and angiogenesis. These results suggest that angiogenin has a dual effect, angiogenesis and cancer cell proliferation, in prostate cancer and may serve as a molecular target for drug development. Blocking nuclear translocation of angiogenin could have a combined benefit of antiangiogenesis and chemotherapy in treating prostate cancer.

DOI： 10.1073/pnas.0606708103

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Pathogenic role of connective tissue growth factor (CTGF/CCN2) in osteolytic metastasis of breast cancer Reviewed

T Shimo, S Kubota, N Yoshioka, S Ibaragi, S Isowa, T Eguchi, A Sasaki, M Takigawa

JOURNAL OF BONE AND MINERAL RESEARCH 21 ( 7 ) 1045 - 1059 2006.7

Language：English Publishing type：Research paper (scientific journal) Publisher：AMER SOC BONE & MINERAL RES

Introduction: Connective tissue growth factor (CTGF/CCN2) is a mediator of local angiogenesis induced by breast cancer, but its role in osteolytic metastasis has not been evaluated. PTH-related peptide (PTHrP) is another critical factor in the development of the osteolytic metastasis. Using both in vivo and in vitro approaches, we studied whether/how neutralization of CCN2 prevented bone metastasis and how PTHrP signaling is related.
Materials and Methods: A mouse model of bone metastasis by human breast cancer cell line MDA231 was treated with a CCN2-neutralizing antibody, and osteolytic bone metastases were assessed on radiographs and immunohistochemistry. Ccn2 gene expression and transcription were examined by Northern blot and luciferase analysis. Immunoblot analysis and kinase inhibitors were used to identify the signaling pathways implicated. Anti-angiogenic/osteoclastogenic effects of ccn2 downregulation were also evaluated.
Results: Treatment of mice with a CCN2-neutralizing antibody greatly decreased osteolytic bone metastasis, microvasculature, and osteoclasts involved. The antibody also suppressed the growth of subcutaneous tumor in vivo and proliferation and migration of human umbilical vein endothelial cells (HUVECs) in vitro. Downregulation of ccn2 also repressed osteoclastogenesis. CCN2 expression was specifically observed in cancer cells producing PTHrP and type I PTH/PTHrP receptor (PTH1R) invaded the bone marrow, and PTHrP strongly upregulated ccn2 in MDA231 cells in vitro. Activation of protein kinase C (PKC) and protein kinase A (PKA) was necessary and sufficient for the stimulation of ccn2 by PTHrP. Indeed, inhibition of the extracellular signal-regulated kinase (ERK1/2), PKC, or PKA by specific inhibitors counteracted the stimulation of ccn2 expression. Incubation of MDA231 cells with PTHrP induced the activation of ERK1/2. Consistent with these findings, inhibition of PKC prevented PTHrP-induced ERK1/2 activation, whereas 12-O-tetradecanoylphorbol-13-acetate (TPA), a stimulator of PKC, upregulated it.
Conclusions: CCN2 was critically involved in osteolytic metastasis and was induced by PKA- and PKC-dependent activation of ERK1/2 signaling by PTHrP. Thus, CCN2 may be a new molecular target for anti-osteolytic therapy to shut off the PTHrP-CCN2 signaling pathway.

DOI： 10.1359/JBMR.060416

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口腔扁平上皮癌におけるVEGF,PD-ECGF,VEGF-Cの発現とその臨床病理学的意義 Reviewed

岸本晃治, 吉濱泰斗, 万代とし子, 大山和彦, 吉岡徳枝, 中山周子, 志茂剛, 佐々木朗

日本口腔外科学会雑誌 51 ( 5 ) 218 - 225 2005.5

Language：Japanese Publisher：(公社)日本口腔外科学会

口腔扁平上皮癌切除術症例62例を対象に,血管内皮細胞増殖因子(VEGF),血小板由来血管内皮細胞増殖因子(PD-ECGF),VEGF-Cの発現と臨床病理学的諸因子の関連について比較検討した.間接酵素抗体法による免疫組織化学的検索および統計学的解析を行った結果,VEGF,PD-ECGF,VEGF-Cは,腫瘍の細胞および核に発現した.腫瘍内微小血管は,抗CD31抗体により褐色に染色された.VEGFはリンパ節転移,分化度,浸潤様式と有意に相関し,PD-ECGFは年齢,浸潤様式と相関し,VEGF-Cはリンパ節転移と強く相関した.統計学的解析を行った結果,リンパ節転移は浸潤様式,VEGF-Cが規定因子で,予後はVEGF,リンパ節転移が規定因子であった.血管新生因子と腫瘍内微小血管密度(MVD)は,VEGF,PD-ECGF,VEGF-Cの発現陽性例は陰性例より増加傾向を示し,PD-ECGFの発現のみが有意に相関した.以上より,血管新生はPD-ECGF,リンパ節転移はVEGF-C,予後はVEGFが最も関連していることが判明した

DOI： 10.5794/jjoms.51.218

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固有鼻腔内逆生歯牙の1例．

銅前昇平, 西山明慶, 吉岡徳枝, 小野達生, 目瀬浩, 佐々木朗

岡山歯学会雑誌 24 ( 2 ) 81 - 84 2005

Language：Japanese Publisher：岡山歯学会

8歳女児.右鼻腔内に白色の硬固物を指摘された.パノラマ,PAにて右鼻腔内にX線不透過像を認めた.上顎咬合法では未萠出の右側上顎犬歯根尖部近心側に過剰歯を認め,鼻腔付近かつ口蓋側に位置した.右側鼻腔内萠出過剰歯と診断した.鼻内所見,X線所見より,口腔内よりも鼻腔内アプローチの方が外科的侵襲が少なく,また硬固物に可動性があったため鼻腔内アプローチでの摘出が可能と判断し,表面麻酔後,浸潤麻酔を行い,モスキート鉗子にて歯牙様硬固物を摘出した.創面は上皮化し現在術後経過は良好である

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悪性腫瘍に伴う高カルシウム血症に対する血管新生阻害剤TNP-470の効果に関する基礎的研究

吉岡德枝

岡山歯学会雑誌 2 53 - 68 2003.12

Combination chemotherapy of paclitaxel and cisplatin induces apoptosis with Bcl-2 phosphorylation in a cisplatin-resistant human epidermoid carcinoma cell line Reviewed

S Sawada, H Mese, A Sasaki, N Yoshioka, T Matsumura

CANCER CHEMOTHERAPY AND PHARMACOLOGY 51 ( 6 ) 505 - 511 2003.6

Language：English Publishing type：Research paper (scientific journal) Publisher：SPRINGER-VERLAG

Purpose. Paclitaxel (Taxol, TXL) is an antimicrotubule agent that stabilizes microtubules, arrests the cell cycle at the G(2)/M phase and induces apoptosis. In vitro drug sensitivity assays have shown that the combination of TXL and CDDP is more effective in CDDP-resistant ovarian carcinoma cell lines, with different cytotoxicities depending on the sequence of drug exposure. CDDP also shows poor results in human epidermoid carcinoma particularly of the head and neck region. Methods. We investigated the effects and the molecular mechanisms of combination chemotherapy with TXL and CDDP in the CDDP-resistant cell line A431/CDDP2, and in its parental human epidermoid cell line A431/P. Drug sensitivity was determined using the MTS assay and cell cycle perturbation was analyzed using flow cytometry. DNA fragmentation was then analyzed and the protein levels of caspase-3 and Bcl-2, and phosphorylated of Bcl-2 were determined by Western blotting. Results. In the drug sensitivity assay, exposure to CDDP prior to TXL was more effective than exposure TXL prior to CDDP in A431/P cells. In A431/CDDP2 cells, exposure to TXL prior to CDDP was more effective than exposure to CDDP prior to TXL. Exposure to TXL arrested the cells in the G(2)/M phase in both cell lines. In A431/CDDP2 cells, exposure to TXL prior to CDDP arrested the cells in the G(2)/M phase, an effect caused by either CDDP or TXL. Analysis of DNA fragmentation showed similar results to the drug sensitivity assay. Expression of caspase-3 protein active form was detected following exposure to TXL only and to the TXL/CDDP combination in both A431/P and A431/CDDP2 cells, but phosphorylation of Bcl-2 protein was detected only following exposure to TXL and only in A431/CDDP2 cells. Conclusions. These results indicate that exposure to TXL prior to CDDP plays a key role in circumventing CDDP resistance by phosphorylating Bcl-2 protein in the human epidermoid carcinoma cell line A431/CDDP2.

DOI： 10.1007/s00280-003-0614-z

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III. 骨転移に対する薬物治療のターゲットー2. Angiogenetic factorー.

佐々木朗, 吉岡徳枝, 志茂剛

THE BONE 17,2,155-159 2003

A clinical and radiological analysis of simple bone cysts Reviewed

MATSUMURA Shinsuke, TSUKAMOTO Goichi, YOSHIOKA Norie, KISHIMOTO Koji, SASAKI Akira, MATSUMURA Tomohiro

J.Jpn.Stomatol.Soc 52 ( 4 ) 170 - 175 2003

Language：Japanese Publisher：Japanese Stomatological Society

Twenty-four simple bone cysts (SBC) in 20 patients were analyzed clinically and radiologically. Seven were male and 13 were female. The mean patient age was 29.5 years and 10 patients were in the ages between ten and 19. Six patients complained of some symptoms like pain or uncomfortable feeling.<BR>Two patients had multiple cysts. One cyst was in the maxilla and 23 in the mandible. Relationships between the lesions and teeth apices were divided into three types: ten were the scalloped type, 13 were the involved type and none were the separated type. One was in the edentulous area. The mean age of the scalloped type was significantly younger than that of the involved type. Four among 40 teeth that contacted with SBCs were not vital.<BR>Six patients showed fibro-osseous lesions (FOL). All of them were female and the mean age was significantly older than that of the group that showed no FOL.<BR>The most common treatment course in our depart mentwas localized removal of cortical bone and drainage with inside exploration and biopsy.<BR>There were two recurrent cases, one of which was related with FOL, and the other had multiple cysts that recurred repeatedly.

DOI： 10.11277/stomatology1952.52.170

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Prognostic significance of heat shock protein 27 (HSP27) in patients with oral squamous cell carcinoma Reviewed

H Mese, A Sasaki, S Nakayama, N Yoshioka, Y Yoshihama, K Kishimoto, T Matsumura

ONCOLOGY REPORTS 9 ( 2 ) 341 - 344 2002.3

Language：English Publishing type：Research paper (scientific journal) Publisher：PROFESSOR D A SPANDIDOS

Heat shock proteins (HSPs) have been defined as proteins induced by heat shock and other environmental and pathophysiologic stress. Heat shock protein 27 (HSP27) is one of the small heat shock proteins. HSP27 is implicated in protein-protein interactions such as folding, translocation, and prevention of inappropriate protein aggregation. Many of their functions suggest that they play important roles in cancers. Archival tissues from 40 patients with oral squamous cell carcinoma who received primary surgical resection were examined for HSP27 by immunohistochemistry and correlated with clinical stage, lymph node metastasis, histological grade and survival period. HSP27 expression was positive staining (+) in 20 (50%), weak or negative staining (-) in 20 (50%) of total 40 cases. There was no correlation between HSP27 expression and clinical stage, lymph node metastasis and histological grade. However, when compared with clinicopathological features, the expression of HSP27 correlated inversely with survival period. This study suggests that the expression of HSP27 is frequently promoted in patients with oral squamous cell carcinoma and should be considered an independent prognostic factor of oral squamous cell carcinoma patients.

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ヒト口腔扁平上皮癌骨転移モデルの性状．

佐々木朗, 横山尚史, 吉岡徳枝, 目瀬浩, 中山周子, 西山明慶, 石川徹, Lim J. Dowin, 松村智弘

骨転移病態・診断・治療 16 ( 1 ) 27 - 31 2000

嚢胞摘出術を施行した上顎洞粘液嚢胞の３例．

吉岡徳枝, 新谷悟, 上山吉哉, 清田章之, 三原真理子, 小野桂一郎, 山田庸介, 岸本晃治, 佐々木朗, 松村智弘

岡山歯学会雑誌 2000

Florid cemento-osseous dysplasia with concomitant simple bone cyst Reviewed

SASAKI A.

Asian J Oral Maxillofac Surg 12 217 - 224 2000

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