Faculty Profiles - YOSHIOKA Norie

Papers - YOSHIOKA Norie

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Angiogenin-induced Osteoclastogenesis Mediates Bone Destruction in Oral Squamous Carcinoma

KASUMI AOKI, NANA YOSHITANI, NAITO KURIO, NORIE YOSHIOKA, JUMPEI TERAMACHI, MIKA IKEGAME, HIROHIKO OKAMURA, SOICHIRO IBARAGI

Anticancer Research 45 ( 3 ) 1025 - 1033 2025.3

Does the anatomy around the pterygomaxillary suture contribute to the risk of bad fractures in Le Fort I osteotomy? Reviewed International journal

Kyoichi Obata, Hideka Kanemoto, Koki Umemori, Kisho Ono, Norie Yoshioka, Akiyoshi Nishiyama, Joe Iwanaga, Soichiro Ibaragi

Journal of cranio-maxillo-facial surgery : official publication of the European Association for Cranio-Maxillo-Facial Surgery 52 ( 11 ) 1193 - 1198 2024.11

Language：English Publishing type：Research paper (scientific journal)

Le Fort I (LF1) osteotomy, a common orthognathic procedure for the maxilla aimed at achieving maxillary mobility by separating the pterygomaxillary suture, poses a risk of bad fracture that may lead to complications and inadequate mobility. Our study analyzed two- and three-dimensional computed tomography images to identify the anatomical factors associated with bad fractures due to an LF1 osteotomy. Point 'a' is where the lateral pterygomaxillary suture on the axial image aligns with the zygomatic alveolar line near the line used for an LF1 osteotomy, with the base line connecting the bilateral 'a' points.Two risk factors were identified on the pterygoid side: (i) when the distance from point 'a' to the intersection of the base line and the medial pterygoid plate was <6.0 mm; and (ii) when the distance from the piriform aperture margin to the base line was <44.78 mm. Six risk factors were identified on the maxillary side, including the distance between the most anterior and most lateral points of the internal surface of the maxillary sinus being <31.9 mm. Our analyses revealed that fractures that occur during pterygomaxillary suture separation in an LF1 osteotomy are influenced by anatomical factors of the maxilla and pterygoid process, which form the pterygomaxillary suture.

DOI： 10.1016/j.jcms.2024.02.018

Lingual nerve revisited-A comprehensive review Part II: Surgery and radiology. Reviewed International journal

Kisho Ono, Takashi Nishioka, Kyoichi Obata, Yohei Takeshita, Chista Irani, Yuki Kunisada, Norie Yoshioka, Soichiro Ibaragi, R Shane Tubbs, Joe Iwanaga

Clinical anatomy (New York, N.Y.) 2024.8

Language：English Publishing type：Research paper (scientific journal)

The lingual nerve (LN) is a branch of the mandibular division of the fifth cranial nerve, the trigeminal nerve, arising in the infratemporal fossa. It provides sensory fibers to the mucous membranes of the floor of the mouth, the lingual gingiva, and the anterior two-thirds of the tongue. Although the LN should rarely be encountered during routine and basic oral surgical procedures in daily dental practice, its anatomical location occasionally poses the risk of iatrogenic injury. The purpose of this section is to consider this potential LN injury risk and to educate readers about the anatomy of this nerve and how to treat it.

DOI： 10.1002/ca.24211

腓骨による下顎骨再建後にカスタムメイドチタンメッシュと海綿骨骨髄細片による骨造成を行ったインプラント治療の1例 Reviewed

渡辺禎久, 吉岡徳枝, 佐々木朗

Japanese Journal of Maxillo Facial Implants 23 ( 2 ) 73 - 81 2024.8

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(公社)日本顎顔面インプラント学会

下顎歯肉癌切除後の下顎骨再建は血管柄付き骨皮弁が第一選択とされるが,解剖的な限界があり,下顎骨の三次元的形態を正確に再現できない場合がある.インプラントは再建手術後の咀嚼機能回復に重要な役割を果たすが,骨量が不十分な場合は埋入が困難となる可能性がある.今回,われわれは骨量が不十分と診断された腓骨再建後の症例に対して,カスタムメイドチタンメッシュトレーと海綿骨骨髄細片(PCBM)を用いた再建下顎骨の二次的形成術を行った後,インプラント治療を行った症例を経験したのでその概要を報告する.患者は,71歳の男性,下顎歯肉癌の手術後,食事摂取困難のため形成外科から紹介され当科を受診した.術前診断で,インプラント埋入には骨の高径が不足していたため,骨造成が必要と診断した.カスタムメイドチタンメッシュトレーとPCBMによる再建下顎骨の二次的形成術を施行し,形成術から1年1ヵ月後インプラントを5本埋入した.インプラント埋入1年後にインプラント支持ブリッジを用いた咬合再建を行った.現在,腫瘍切除後5年以上経過したが腫瘍の再発はない.インプラント治療後,インプラント周囲の軟組織増殖に対する手術を行った後は炎症の所見はなく,整容面および咀嚼機能面での問題はなく経過良好である.(著者抄録)

Spontaneous Eruption of Permanent Teeth That Had Eruption Disturbances After Extirpation of Odontomas: A Report of Two Cases. Reviewed International journal

Yuki Kunisada, Norie Yoshioka, Kyoichi Obata, Koki Umemori, Soichiro Ibaragi

Cureus 16 ( 5 ) e61460 2024.5

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Odontomas, often found adjacent to impacted teeth, are tumors of abnormal tissue morphology arising from the tooth germ and are usually asymptomatic. They are often found by accident on X-ray images, and the eruption of permanent teeth is often caused by odontomas. In most cases, the tooth is extracted with the permanent tooth or orthodontic treatment is performed after extraction. However, the criteria are not clear. We encountered two cases of dental eruption in which permanent teeth, which originally seemed to be suitable for orthodontic treatment, spontaneously erupted after odontoma removal. It is necessary to examine the indications and timing of tooth extraction.

DOI： 10.7759/cureus.61460

Novel mechanism of cisplatin resistance in head and neck squamous cell carcinoma involving extracellular vesicles and a copper transporter system. Reviewed International journal

Tatsuo Ogawa, Kisho Ono, Shoji Ryumon, Hotaka Kawai, Tomoya Nakamura, Koki Umemori, Kunihiro Yoshida, Hideka Kanemoto, Kyoichi Obata, Norie Yoshioka, Tatsuo Okui, Kuniaki Okamoto, Hitoshi Nagatsuka, Soichiro Ibaragi

Head & neck 46 ( 3 ) 636 - 650 2024.3

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: Cisplatin (CDDP) plays a central role in chemotherapy for head and neck squamous cell carcinoma (HNSCC), but drug resistance in HNSCC chemotherapy remains a problem, and the mechanism of CDDP resistance is unclear. We investigated CDDP-resistance mechanisms mediated by extracellular vesicles (EVs) and ATPase copper transporting beta (ATP7B) in HNSCC. METHODS: We established CDDP-resistant sublines of HNSCC cells and verified their ATP7B expression. We used an EV secretion inhibitor (GW4869) and ATP7B short hairpin (sh)RNA transfection to examine the correlation between EV secretion and ATP7B expression. RESULTS: The CDDP-resistant HNSCC sublines showed decreased CDDP sensitivity and increased ATP7B expression. GW4869 suppressed ATP7B expression, and ATP7B shRNA transfection suppressed EV secretion. The suppressions of EV secretion and ATP7B expression both enhanced CDDP's cell-killing effect. CONCLUSIONS: EVs were involved in the ATP7B-mediated mechanism underlying CDDP resistance. Further clarification of the EV-induced CDDP-resistance mechanism may lead to novel therapeutic strategies for HNSCC.

DOI： 10.1002/hed.27620

顔面軟部組織に発生したランゲルハンス細胞組織球症の1例 Reviewed

増井正典, 吉岡徳枝, 伊原木聰一郎, 小野喜章, 長塚仁, 佐々木朗

日本口腔外科学会雑誌 69 ( 6 ) 298 - 303 2023.6

Authorship：Corresponding author Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(公社)日本口腔外科学会

26歳男性。左側下唇を誤咬した後、滲出液を伴う腫瘤を自覚し、近在病院の歯科を受診した。加療されるも改善なく、腫瘤の増大傾向がみられたため、精査目的で当科へ紹介となった。初診時、左側下唇粘膜には25×12mm大の潰瘍を伴う腫瘤が認められた。造影CT画像では腫瘤は不整な外形を呈するが、明らかな内部性状の異常はみられなかった。アレルギー疾患や梅毒を疑い、血液検査が行われたが否定的で、組織生検によりランゲルハンス細胞組織球症(LCH)と診断された。全身検索の結果、下唇と左側眼瞼皮膚に発生したLCH SM型であり、下唇の病変にはコルチコステロイドを局所注射し、眼瞼の病変にはコルチコステロイド軟膏を塗布した。治療開始8ヵ月後には下唇の病変と左眼瞼皮膚の紅斑は消失し、8年経過現在、再燃や他臓器病変の出現はみられていない。

Other Link： https://search.jamas.or.jp/default/link?pub_year=2023&ichushi_jid=J01073&link_issn=&doc_id=20230630350002&doc_link_id=10.5794%2Fjjoms.69.298&url=https%3A%2F%2Fdoi.org%2F10.5794%2Fjjoms.69.298&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

複合的な要因を有する骨格性下顎骨後退症例に対して下顎骨前方移動術を施行し機能的改善を認めた一治験例 Reviewed

中西泰之, 植田紘貴, 吉岡徳枝, 伊原木聰一郎, 上岡寛

日本顎変形症学会雑誌 33 ( 2 ) 187 - 187 2023.5

癌の骨破壊病変に対する銅のキレートを応用した治療に関する基礎的検討

佐々木朗, 坂本裕美, 中野敬介, 金本栄華, 吉岡徳枝, 竜門省二, 西山明慶, 志茂剛, 伊原木聰一郎

日本口腔内科学会雑誌 28 ( 2 ) 80 - 80 2022.12

Craniomaxillofacial Fibrous Dysplasia Improved Cosmetic and Occlusal Problem by Comprehensive Treatment: A Case Report and Review of Current Treatments. Reviewed International journal

Kisho Ono, Norie Yoshioka, Yuki Kunisada, Tomoya Nakamura, Yuko Nakamura, Kyoichi Obata, Soichiro Ibaragi, Shogo Minagi, Akira Sasaki

Diagnostics (Basel, Switzerland) 12 ( 9 ) 2022.9

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

Fibrous dysplasia (FD) is a fibrous lesion of immature bone, with an incidence of 10-20% in the head and neck region. Most cases are monostotic, but when a lesion occurs on the maxillofacial region and spreads to the surrounding bone, it is classified as polyostotic, despite its localized occurrence. In some cases, surgical intervention is required to improve the cosmetic or functional disturbance of a FD in the maxillofacial region, but it is necessary to confirm symmetry of the maxillofacial region in real time, and a surgical support system is required to compensate. Furthermore, prosthetic intervention is considered when postoperative acquired defects occur or further cosmetic or occlusal function improvement is needed. A comprehensive approach by an oral surgeon and a maxillofacial prosthodontist is necessary for the successful treatment and rehabilitation of such patients. In this article, we describe the case of a craniomaxillofacial FD patient with facial asymmetry and denture incompatibility with improved quality of life measures by integrating surgical treatment using a navigation system and postoperative prosthetic rehabilitation. We also discuss recent diagnostic methods and treatment strategies for craniomaxillofacial FD in the literature.

DOI： 10.3390/diagnostics12092146

The advantages and disadvantages of jaw reconstruction with ULTRA FLEX MESH CUSTOM<sup>®</sup> and autogenous particulate cancellous bone and marrow Invited Reviewed

Norie YOSHIOKA, Akira SASAKI

Japanese Journal of Oral and Maxillofacial Surgery 68 ( 6 ) 244 - 253 2022.6

多数歯欠損を伴う高齢期の下顎前突症患者に対する外科的矯正治療を伴った包括的歯科治療の1例 Reviewed

河野加奈, 中村政裕, 吉岡徳枝, 川邉紀章, 西山明慶, 佐々木朗, 上岡寛

日本顎変形症学会雑誌 32 ( 1 ) 48 - 59 2022.4

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(NPO)日本顎変形症学会

症例は65歳女性で、顎変形症の治療が保険適用となったことを知り、加療を希望し当院口腔外科を受診後、当科を紹介により受診した。機能性反対咬合および下顎骨の右方偏位を伴う下顎前突症と診断し、骨格性の改善を図るため外科的矯正治療を選択した。歯系では下顎骨の後方移動量を確保するため、術前矯正治療にて下顎前歯部に歯科矯正用アンカースクリューを埋入し、小臼歯の近心移動により空隙を閉鎖するとともに前歯部の唇側傾斜および圧下を図ることとした。上顎歯列は補綴処理による咬合獲得を行い、下顎右側臼歯部においても補綴処置による咬合獲得を行った。軟組織ではオトガイを後退させることでEラインに対する上下口唇の後退を改善し、下顎臼歯部が欠損していたため術後の安定性を考慮して下顎枝矢状分割術を選択した。

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2022&ichushi_jid=J03047&link_issn=&doc_id=20220510230006&doc_link_id=%2Fdh5jawdf%2F2022%2F003201%2F007%2F0048-0059%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdh5jawdf%2F2022%2F003201%2F007%2F0048-0059%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

Comparative Study on Epstein-Barr Virus-Positive Mucocutaneous Ulcer and Methotrexate-Associated Lymphoproliferative Disorders Developed in the Oral Mucosa: A Case Series of 10 Patients and Literature Review. Reviewed International journal

Kyoichi Obata, Tatsuo Okui, Sawako Ono, Koki Umemori, Shoji Ryumon, Kisho Ono, Mayumi Yao, Norie Yoshioka, Soichiro Ibaragi, Akira Sasaki

Diagnostics (Basel, Switzerland) 11 ( 8 ) 2021.7

Language：English Publishing type：Research paper (scientific journal)

Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is an iatrogenic immunodeficiency-associated lymphoproliferative disorder that occurs mainly with MTX use. This disorder has been associated with Epstein-Barr virus (EBV) infection. In 2017, the WHO newly defined the disease concept of EBV-positive mucocutaneous ulcer (EBV-MCU) as a good-prognosis EBV-related disease. Here, we report 10 cases of MTX-LPD or EBV-MCU in the oral mucosa. This retrospective, observational study was conducted with MTX-LPD or EBV-MCU in the oral mucosa patients who visited us during the nine year period from 2012 to 2021. We gathered the basic information, underlying disease, histopathological evaluation, treatment and prognosis for the subjects. All were being treated with MTX for rheumatoid arthritis. EBV infection was positive in all cases by immunohistochemistry. A complete or partial response was obtained in all cases with the withdrawal of MTX. Our results suggests that the most common risk factor for developing EBV-MCU is the use of immunosuppressive drugs. The most common site of onset is the oral mucosa, which may be attributed to the mode of EBV infection and the high incidence of chronic irritation of the oral mucosa. A small number of patients had been diagnosed with MTX-LPD, but we consider that these cases were EBV-MCU based on our study.

DOI： 10.3390/diagnostics11081375

A skeletal Class III facial asymmetry case with a canted occlusal plane treated by LeFort I with unilateral horseshoe osteotomy Reviewed

Tomoyo Tanaka, Mitsuhiro Hoshijima, Norie Yoshioka, Hiroshi Kamioka

Orthodontic Waves 80 ( 3 ) 171 - 183 2021.7

A case of intramandibular neurofibroma resembling a radicular cyst in a neurofibromatosis type 1 patient. Reviewed International journal

Yuki Kunisada, Norie Yoshioka, Soichiro Ibaragi, Tatsuo Okui, Hitoshi Nagatsuka, Akira Sasaki

International journal of surgery case reports 82 105883 - 105883 2021.5

Authorship：Corresponding author Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Neurofibromatosis is a disease that causes various abnormalities such as neurofibroma, mainly in the skin and nerves. The common sites in the oral cavity are the palate, gingiva, tongue, buccal mucosa, and lips but, occurrence in the mandible is rare. PRESENTATION OF CASE: A 26-year-old woman was referred to our clinic because of percussion pain. Radiographic findings showed a radiolucent area. The patient was clinically diagnosed with a radicular cyst by a previous doctor. Multiple café-au-lait spots were found disseminated on her body, and she had already been prenatally diagnosed with neurofibromatosis type 1 (NF1). We performed a biopsy and suggested a neurofibroma. Tumor extirpation was performed under general anesthesia. The histopathological diagnosis showed a neurofibroma. CLINICAL DISCUSSION AND CONCLUSION: NF1 is a systemic nevus that causes abnormalities in melanocytes and Schwann cells, and various lesions appear, but intramandibular lesions are extremely rare. Diagnosis of NF1 and radicular cysts in the mandible is difficult due to their image resemblance. However, it should be kept in mind if the underlying disease is NF1. In our case, it was easy to detach and may have originated from small peripheral nerve endings in the mandible.

DOI： 10.1016/j.ijscr.2021.105883

Correction to: Duplication of the external jugular vein: a language barrier of database search in classic anatomical studies. Reviewed International journal

Kisho Ono, Norie Yoshioka, Dany Hage, Soichiro Ibaragi, R Shane Tubbs, Joe Iwanaga

Surgical and radiologic anatomy : SRA 43 ( 10 ) 1729 - 1730 2021.4

Duplication of the external jugular vein: a language barrier of database search in classic anatomical studies Reviewed

Kisho Ono, Norie Yoshioka, Dany Hage, Soichiro Ibaragi, R. Shane Tubbs, Joe Iwanaga

Surgical and Radiologic Anatomy 43 ( 10 ) 1721 - 1728 2021.2

Language：English Publishing type：Research paper (scientific journal) Publisher：Springer Science and Business Media LLC

Objective: Many anatomical variations of the superficial veins of the head and neck have been reported throughout the literature. Accordingly, anatomists and surgeons must have a comprehensive understanding of these variations to avoid confusion. Duplication of the external jugular vein (EJV) is occasionally observed during routine cadaveric dissections
however, this variation seems to be reported less often than actual experience suggests. Therefore, to gain a better understanding of its anatomical and clinical implications, an analysis of the available data should be available. Thus, in this article, we reviewed the current available literature for studies reporting duplication of the EJV. Methods: We conducted a search using PubMed and Google Scholar with the following keywords: “duplication of the external jugular vein,” “division of the external jugular vein,” and “fenestration of the external jugular vein,” “double external jugular vein,” and “doubled external jugular vein.” As a case illustration, we also describe a case of a duplicated EJV found during a right neck dissection of a female cadaver. Results: Twenty sides across sixteen different studies were analyzed including the present case. All studies were published between 2009 and 2020. EJV division patterns were classified as either duplication, fenestration, fenestration followed by duplication, or double fenestrations. Conclusions: We have reviewed the literature regarding cases documenting duplication/fenestration of the EJV. As it is often difficult to find recent studies that report on classic anatomical variations, therefore, revisiting older articles and textbooks is necessary for achieving a “comprehensive” review, especially across different languages.

DOI： 10.1007/s00276-021-02717-6

Other Link： https://link.springer.com/article/10.1007/s00276-021-02717-6/fulltext.html

A case of oral cancer with delayed occipital lymph node metastasis: Case report. Reviewed International journal

Kisho Ono, Norie Yoshioka, Masanori Masui, Kyoichi Obata, Yuki Kunisada, Tatsuo Okui, Soichiro Ibaragi, Hotaka Kawai, Hitoshi Nagatsuka, Akira Sasaki

Clinical case reports 8 ( 12 ) 2469 - 2475 2020.12

舌扁平上皮癌における新TNM分類(UICC:第8版)の実用性(第2報) 正誤表に準拠 Reviewed

吉田祥子, 岸本晃治, 村瀬友里香, 伊原木聰一郎, 吉岡徳枝, 奥井達雄, 長塚仁, 佐々木朗

日本口腔腫瘍学会誌 31 ( 3 ) 151 - 156 2019.9

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(一社)日本口腔腫瘍学会

UICCのTNM分類は、口腔癌の進行度評価の基準として使用されている。2016年に公表された第8版TNM分類では、T分類に浸潤の深さ(DOI)、N分類に被膜外進展(ENE)が導入された。そして、われわれは、舌扁平上皮癌の手術症例を対象に、第7版と第8版TNM分類による評価を比較し、後者の実用性を本誌において報告した。さらに、2018年にUICCから正誤表が公表され、T2、T3、T4が訂正された。そこで本研究では、当科で手術を施行した舌扁平上皮癌107例について、正誤表に準拠して改めて検討を行った。正誤表に準拠して評価すると、1例がT3からT2に、3例がT3からT4aに変更された。第7版と比較すると、後発転移率がT1では低下し、T2では増加したが、第8版とは同様の結果であった。生存率は、第8版と同様に、Tの上昇とともに低下した。また、pTの変更に伴って、pStageが変更されたため、stageの上昇とともに生存率が低下した。訂正された第8版TNM分類は、進行度に即したTの細分化を舌扁平上皮癌においても実現し、細分化により進行度を的確に後発転移と生存率へ反映させており、実用的であると考えられた。(著者抄録)

顎変形症治療コンセンサスミーティングにおけるアンケート調査 Reviewed

岩井俊憲, 竹信俊彦, 管野貴浩, 山内健介, 大井一浩, 古賀陽子, 佐藤貴子, 友松伸允, 成田真人, 吉岡德枝, 小林正治

日本顎変形症学会雑誌 29 ( 1 ) 11 - 22 2019

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(NPO)日本顎変形症学会

顎変形症治療コンセンサスミーティングの事前に行ったアンケート調査の概要を報告した。参加予定の36施設36人に対してweb入力方式により画面上にてアンケートを実施した。口腔外科医単独で治療計画を立案している施設はなく、19.4%の施設は矯正歯科医が単独で治療計画を立案しており、80.6%の施設は両者が共同で治療を立案していた。38.9%の施設は口腔外科医単独でスプリントを作製しており、44.4%の施設は矯正歯科医が単独で作製していた。両者が共同で作製している施設は16.7%と少なかった。75.0%の施設は半調節性咬合器を用いてスプリントを作製していたが、25.0%の施設は半調節性咬合器を使用していなかった。また、50%の施設では3Dプランニングを行っておらず、69.4%の施設は3Dプリンターを所有していなかった。30.6%の施設は原則全例に3Dモデルを作製しており、52.8%の施設は必要な症例(非対称症例など)のみに作製していた。

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2019&ichushi_jid=J03047&link_issn=&doc_id=20190507340003&doc_link_id=130007649438&url=https%3A%2F%2Fci.nii.ac.jp%2Fnaid%2F130007649438&type=CiNii&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00003_1.gif

Retinoic Receptor Signaling Regulates Hypertrophic Chondrocyte-specific Gene Expression Reviewed

Tsuyoshi Shimo, Eiki Koyama, Tatsuo Okui, Masanori Masui, Yuki Kunisada, Soichiro Ibaragi, Norie Yoshioka, Naito Kurio, Shoko Yoshida, Akira Sasaki, Masahiro Iwamoto

In Vivo 33 ( 1 ) 85 - 91 2018.12

舌扁平上皮癌における新TNM分類(UICC:第8版)の実用性 Reviewed

吉田祥子, 岸本晃治, 村瀬友里香, 伊原木聰一郎, 吉岡徳枝, 奥井達雄, 長塚仁, 佐々木朗

日本口腔腫瘍学会誌 30 ( 4 ) 151 - 157 2018.12

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(一社)日本口腔腫瘍学会

UICCのTNM分類は、口腔癌の進行度評価の基準にされているが、2016年に第8版へ改訂され、T分類では浸潤の深さ(Depth of Invasion:DOI)が、N分類では被膜外進展(Extra Nodal Extension:ENE)が導入された。本研究では、当科で手術を行った舌扁平上皮癌症例107例において、第7版と第8版TNM分類により評価を行い、TNM分類改訂と頸部リンパ節後発転移(以下後発転移)および生存率との関連について検討を行った。TNM分類改訂により、17例(15.9%)にcTの変更を、6例(5.6%)にpTの変更を認めた。後発転移数・後発転移率は、cT1とpT1では低下し、cT2とpT2では増加した。また、第7版でcT4a、pT4aの2例が、第8版ではcT3、pT3に変更されたため、第8版は第7版と比較してcT3、pT3の生存率が低下した。第7版でpN2bの3例が、第8版ではpN3bに分類され、3例とも経過不良であった。当科の舌扁平上皮癌症例におけるTNM分類の第7版から第8版への見直しは、主にStage上昇につながった。そして、第8版TNM分類は、舌扁平上皮癌の進行度をより的確に後発転移と生存率へ反映させるため、実用的であると考えられた。(著者抄録)

Questionnaire surveys on the female oral surgeons’ consciousness and intention to their careers Reviewed

Norie YOSHIOKA, Akira SASAKI, Toshiyuki SHIBATA, Kenichi KURITA, Mikihiko KOGO

Japanese Journal of Oral and Maxillofacial Surgery 64 ( 9 ) 516 - 527 2018.9

逆行性超選択的動注化学放射線療法中に腫瘍栄養動脈が閉塞し吻合枝から急速動注した舌癌の1例 Reviewed

伊原木聰一郎, 吉岡徳枝, 奥井達雄, 國定勇希, 志茂剛, 光藤健司, 藤内祝, 佐々木朗

日本口腔腫瘍学会誌 30 ( 1 ) 23 - 27 2018.3

Language：Japanese Publishing type：Research paper (scientific journal) Publisher：(一社)日本口腔腫瘍学会

今回われわれは、舌癌に対して逆行性超選択的動注化学放射線療法を施行中に腫瘍栄養動脈が閉塞したため、腫瘍栄養動脈の吻合枝から急速動注療法を施行した舌癌の1例を経験したので報告する。症例:43歳女性。2012年7月に当科を受診し、左側舌癌・両側頸部リンパ節転移(T4aN2cM0、扁平上皮癌)と診断した。原発巣は逆行性超選択的動注化学放射線療法を行い、頸部リンパ節転移に対しては照射後に頸部郭清術を施行する予定とした。2012年8月に患側は浅側頭動脈から舌動脈と顔面動脈の共通幹に、健側は浅側頭動脈から舌動脈に、それぞれカテーテルを留置した。定期的にインジゴカルミン染色でカテーテル脱落の有無を検査していたが、46Gy照射後から、患側の舌動脈と顔面動脈の共通幹の支配領域が染色されなくなった。Seldinger法で患側の外頸動脈にカテーテルを留置し外頸動脈分枝を造影すると、舌動脈と顔面動脈は造影されず、顎動脈分枝の頬動脈および下歯槽動脈から顔面動脈への吻合枝が描出された。下歯槽動脈をコイルで塞栓し頬動脈からシスプラチンを急速動注した。2012年10月に70Gy照射を終了した。2012年11月に両側頸部郭清術を行った。治療終了から現在までに約5年経過しているが再発および転移なく経過良好である。(著者抄録)

Other Link： https://search-tp.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2018&ichushi_jid=J02382&link_issn=&doc_id=20180322250004&doc_link_id=%2Fdy8ortum%2F2018%2F003001%2F004%2F0023-0027%26dl%3D0&url=https%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdy8ortum%2F2018%2F003001%2F004%2F0023-0027%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

The Prognostic Implications of Bone Invasion in Gingival Squamous Cell Carcinoma. Reviewed International journal

Shoko Yoshida, Tsuyoshi Shimo, Yurika Murase, Kiyofumi Takabatake, Koji Kishimoto, Soichiro Ibaragi, Norie Yoshioka, Tatsuo Okui, Hitoshi Nagatsuka, Akira Sasaki

Anticancer research 38 ( 2 ) 955 - 962 2018.2

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND/AIM: This study evaluated the associations between bone invasion of gingival squamous cell carcinoma (SCC) and clinicopathological manifestations, and aimed to determine whether bone invasion is an independent prognostic factor in gingival SCC. PATIENTS AND METHODS: The study was a retrospective review of 78 patients with gingival SCC who underwent surgery with curative intent. The level of bone invasion was pathologically categorized as medullary, cortical or no bone invasion. RESULTS: Cortical and medullary bone invasion was present in 29 and 22 patients, respectively. There was a significant association between medullary bone invasion and tumor size (p=0.017), pathological N classification (p<0.001), differentiation (p=0.017) and lymphovascular invasion (p=0.007). Medullary bone invasion and lymphovascular invasion were independent predictors of reduced overall survival (p=0.015, 0.048); medullary bone invasion was also an independent predictor of reduced disease-specific survival (p=0.018). CONCLUSION: Pathologically-proven medullary bone invasion and lymphovascular invasion were found to be key prognostic factors in gingival SCC. The results suggest that it is necessary to consider adjuvant therapy in patients with medullary bone invasion.

Maxillofacial Fractures in Elderly Patients Reviewed

Hiroaki Takakura, Tsuyoshi Shimo, Norie Yoshioka, Mayumi Yao, Kyoichi Obata, Soichiro Ibaragi, Tatsuo Okui, Yuki Kunisada, Ayaka Morisawa, Akane Shibata, Shoko Yoshida, Yurika Murase, Koji Kishimoto, Akiyoshi Nishiyama, Hiroshi Mese, Akira Sasaki

International Journal of Surgery & Surgical Procedures 2 ( 128 ) 1 - 5 2017.11

下顎に発生した顎放線菌症の1例本邦における顎放線菌症の過去集計と現状との比較検討 Reviewed

小畑協一, 伊原木聰一郎, 矢尾真弓, 柴田茜, 吉岡徳枝, 志茂剛, 佐々木朗

日本口腔内科学会雑誌 23 ( 1 ) 23 - 27 2017.6

Language：Japanese Publisher：(一社)日本口腔内科学会

顎放線菌症は開口障害や板状硬結、多発性膿瘍といった特徴的な症状を有する特異性炎である。しかし近年典型的な症状を示す症例が減少していることから診断が困難となっている。症例は85歳の女性で、左側頬部の腫脹と開口障害で当院を受診した。X線写真検査で下顎骨の破壊と融解を認めた。悪性腫瘍を疑ったが、病理組織学的診断は放線菌症であった。外科的掻爬を行い、ベンジルペニシリンとアモキシシリンの投与を行った。(著者抄録)

セツキシマブ投与にてアナフィラキシー様のinfusion reactionを発症したマダニ咬傷既往のある口腔癌患者の1例

矢尾真弓, 志茂剛, 柴田茜, 小畑協一, 吉岡徳枝, 伊原木聰一郎, 藤井由起子, 岸本晃治, 佐々木朗

岡山歯学会雑誌 36 ( 1 ) 1 - 6 2017.6

Language：Japanese Publisher：岡山歯学会

症例は69歳男性で、左側口底癌にて顎下部を含めた口底部分切除術を施行したが、その後、左側上内頸静脈リンパ節の後発転移と節外浸潤を認めた。左側根治的頸部郭清術変法と術後化学放射線療法で頸部腫瘍は一旦縮小したものの再度増大し、さらに右肺下葉に転移を認めたため、多剤併用化学療法の施行目的で入院した。セツキシマブ・シスプラチン・5-FUの多剤併用化学療法を計画した。しかし、セツキシマブ投与開始5分後より意識消失と全身の浮腫が出現し、infusion reaction(IR)と判断して即座にセツキシマブの投与を中止した。IR発症から30分後には循環動態と呼吸状態が安定したため、集中治療室に搬入となった。約8時間後には全身皮膚に皮疹と四肢の浮腫および皮膚そう痒感を認めており、d-クロルフェニラミンマレイン酸塩の静脈内注射を施行した。発症翌日には四肢の浮腫と皮疹は改善し、意識障害等の有害事象もなく一般病棟に帰室した。発症翌日に再度既往歴を問診したところ、マダニ咬傷の既往があることが判明し、IRの原因としてマダニとの関連があることが疑われた。

Examination of Diseases Requiring Oral Surgery Treated via Medical-Dental Cooperation in the Department of Oral and Maxillofacial Surgery (Biopathology), Okayama University Hospital Reviewed

Masanori Masui, Tsuyoshi Shimo, Norie Yoshioka, Soichiro Ibaragi, Tatsuo Okui, Yuki Kunisada, Mayumi Yao, Shoko Yoshida, Yurika Murase, Koji Kishimoto, Akiyoshi Nishiyama, Yoshihiko Soga, Akira Sasaki

2 ( 115 ) 1 - 7 2017.5

Endoscope-Assisted Transoral Reduction and Internal Fixation of a Mandibular Subcondylar Fracture with a 3D - Shaped Plate Reviewed

Soichiro Ibaragi, Norie Yoshioka, Koji Kishimoto, Akira Sasaki

International Journal of Contemporary Medical Research 4 ( 2 ) 575 - 577 2017.2

Endoscope-assisted transoral reduction and internal fixation of a mandibular subcondylar with a 3D-shaped plate: Report of a Case. Reviewed

Ibaragi S, Yoshioka N, Kishimoto K, Sasaki A

International Society for Contemporary Medical Research 4 ( 2 ) 574 - 576 2017.2

Semaphorin 4D promotes bone invasion in head and neck squamous cell carcinoma. Reviewed

Takada H, Ibaragi S, Eguchi T, Okui T, Obata K, Masui M, Morisawa A, Takabatake K, Kawai H, Yoshioka N, Hassan NMM, Shimo T, Hu GF, Nagatsuka H, Sasaki A

Int J Oncol 51 ( 2 ) 625 - 632 2017

Oral squamous cell carcinoma-derived sonic hedgehog promotes angiogenesis. Reviewed

Kuroda H, Kurio N, Shimo T, Matsumoto K, Masui M, Takabatake K, Okui T, Ibaragi S, Kunisada Y, Obata K, Yoshioka N, Kishimoto K, Nagatsuka H, Sasaki A

Anticancer Res 37 6731 - 6737 2017

Role of Neurokinin 3 receptor signaling in oral squamous cell carcinoma. Reviewed

Obata K, Shimo T, Okui T, Matsumoto K, Takada H, Takabatake K, Kunisada Y, Ibaragi S, Yoshioka N, Kishimoto K, Nagatsuka H, Sasaki A

Anticancer Res 37 6119 - 6123 2017

Orthognathic surgery during breast cancer treatment—A case report

Tsuyoshi Shimo, Norie Yoshioka, Masahiro Nakamura, Soichiro Ibaragi, Tatsuo Okui, Yuki Kunisada, Masanori Masui, Mayumi Yao, Koji Kishimoto, Shoko Yoshida, Akiyoshi Nishiyama, Hiroshi Kamioka, Akira Sasaki

International Journal of Surgery Case Reports 31 30 - 34 2017

Analysis of Pathological Activities of CCN Proteins in Bone Metastasis Reviewed

Tsuyoshi Shimo, Norie Yoshioka, Masaharu Takigawa, Akira Sasaki

Methods in Molecular Biology 1489 505 - 512 2016.10

A Case of Severe Open-bite due to Macroglossia Associated with Beckwith-Wiedemann Syndrome Treated by Orthognathic Surgery Reviewed

NORIE YOSHIOKA, AKIYOSHI NISHIYAMA, TAKUMI TAKAHASHI, SOICHIRO IBARAGI, SHOHEI DOMAE, TSUYOSHI SHIMO, AKIRA SASAKI

The Japanese Journal of Jaw Deformities 26 ( 3 ) 228 - 236 2016.8

口腔疾患に続発した内頸静脈血栓症の2例

銅前昇平, 岸本晃治, 吉田祥子, 栗尾奈愛, 松本憲一, 村瀬友里香, 吉岡徳枝, 志茂剛, 佐々木朗

岡山歯学会雑誌 35 ( 1 ) 23 - 28 2016.6

Language：Japanese Publisher：岡山歯学会

症例1は68歳女で、左側頬部から頸部の腫脹と開口障害を主訴とした。左側扁桃周囲膿瘍および両側頸部蜂窩織炎の診断で、両側深頸部膿瘍切開ドレナージを2回施行した。再ドレナージの3日後の造影CTにて壊死組織・膿瘍は減少傾向を認めたが、左側内頸静脈内が血栓により頭蓋底付近で閉塞していたためヘパリン点滴静脈内投与を開始した。11日後の造影CTにて血栓は消失し、その後ワルファリン経口投与を退院後4ヵ月間継続投与した。症例2は74歳男で、左側上顎歯肉の疼痛を主訴とした。左側上顎悪性黒色腫・両側頸部リンパ節転移の診断で、左側上顎骨部分切除術を施行後、両側機能的頸部郭清術を施行した。郭清後23日目の造影CTにて左側内頸静脈内に血栓を認めたため、ヘパリン点滴静脈内投与とワルファリン投与を開始し、20日後に血栓は消失した。郭清後28日目より化学療法を1コース施行して退院したが、転倒により硬膜下血腫を発症しワルファリン投与を中止した。

Detection of sonic hedgehog in patients undergoing orthognathic surgery Reviewed

Kunisada Y, Shimo T, Masui M, Yoshioka N, Ibaragi S, Matsumoto K, Okui T, Kurio N, Domae S, Kishimoto K, Nishiyama A, Sasaki A

Int J Surg 5 1 - 4 2016

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

Purpose: Sonic Hedgehog (SHH) is a regulatory protein involved in bone fracture healing. Orthognathic surgery involves surgical osteotomy of the mandible or maxilla to restore the proper anatomic and functional position in patients with dentofacial deformity. The purpose of this study was to analyze SHH local blood serum concentrations after osteotomy to gain further understanding of the molecular regulation of the initial stage of osteotomy healing.Methods: Serum samples (local drainage and peripheral venous) of 34 patients (24 females and 10 males, mean age was 23.4 (16-42) years) who underwent orthognathic surgery were isolated from patients at different time points during the perioperative period. The levels of SHH, soluble receptor activator of nuclear factor-kappa B ligand (sRANKL) and osteoprotegerin (OPG) were measured using ELISA.Results: SHH was detected in the local drainage immediately after osteotomy (309.5 +/- 58.2 pg/ml), and decreased for 2 days after the operation (197.5 +/- 43.6 pg/ml). The sRANKL local serum concentrations were at the maximum level immediately after the operation (141.4 +/- 22.6 pg/ml) and decreased for 2 days (110.1 +/- 23.4 pg/ml). On the other hand, the OPG concentration in the local serum was at a minimum after osteotomy (59.4 +/- 4.6 pg/ml) and reached its maximum (181.5 +/- 17.8 pg/ml, P < 0.01) at 2 days after osteotomy. SHH and OPG local serum levels on day 2 were associated with the amount of bleeding during the operation. The local drainage serum level of SHH of maxillary/mandibular osteotomy had a tendency to be higher than that of mandible-only osteotomy at 2 days after operation.Conclusions: Elevated levels of SHH in local serum after osteotomy, especially during the initial stage of healing, indicates its importance in osteotomy healing. (c) 2016 The Authors. Published by Elsevier Ltd on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI： 10.1016/j.ijso.2016.09.002

Autologous blood injection for the treatment of recurrent temporomandibular joint dislocation. Reviewed

Yoshioka N, Shimo T, Ibaragi S, Sasaki A

Acta Med Okayama. 70 291 - 294 2016

Familial adenoid cystic carcinoma of sublingual salivary glands Reviewed

Norie Yoshioka, Hiroshi Mese, Tatsuo Okui, Soichiro Ibaragi, Akira Sasaki

JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY MEDICINE AND PATHOLOGY 27 ( 3 ) 353 - 356 2015.5

Authorship：Lead author Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCIENCE INC

Tumors of the sublingual salivary gland are extremely rare. Most of the sublingual tumors are malignant, adenoid cystic carcinoma (ACC) and mucoepidermoid carcinoma being the most common histological types. Here we report the first case of a familial occurrence of ACC in a family in which the father and daughter were treated for ACC of the sublingual salivary gland. A 75-year-old man was referred with a swelling of the floor of the mouth on his right side and diagnosed as ACC of sublingual salivary gland synchronous with adenocarcinoma of the lung. One year later, his daughter presented, at the age of 46 years, with a swelling of the floor of the mouth on her right side, which was also diagnosed as ACC. This is the first case of familial recurring ACC of sublingual salivary gland worldwide. (C) 2014 Asian AOMS, ASOMP, JSOP, JSOMS, JSOM, and JAMI. Published by Elsevier Ltd. All rights reserved.(star)

DOI： 10.1016/j.ajoms.2014.03.008

Expression pattern of sonic hedgehog signaling and calcitonin gene related peptide in the socket healing process after tooth extraction Reviewed

Pang P, Shimo T, Takada H, Matsumoto K, Yoshioka N, Ibaragi S, Sasaki A

BBRC 467 21 - 26 2015

Expression and roles of CCN2 in dental epithelial cells Reviewed

Shimo T, Koyama E, Kurio N, Matsumoto K, Okui T, Ibaragi S, Yoshioka N, Sasaki A

In vivo 9 189 - 195 2015

Installing an original sleeve for rod unaccessible pain from a distraction device in a hemifacial microsomia patient

Tsuyoshi Shimo, Akiyoshi Nishiyama, Norie Yoshioka, Akira Sasaki

INTERNATIONAL JOURNAL OF SURGERY CASE REPORTS 12 137 - 139 2015

Language：English Publishing type：Research paper (scientific journal) Publisher：ELSEVIER SCI LTD

INTRODUCTION: Lengthening of the mandible by distraction osteogenesis using an internal device is the preferred method for the treatment of hemifacial microsomia. Despite its advantages, this technique can lead to various complications after the surgery.PRESENTATION OF CASE: We report the case of an 8-yr-old Japanese girl whose case presented practical difficulties in device activation because of rod unaccessible pain after the initial mandibular distraction with an internal device, and this complication was addressed with the installation of an original sleeve.DISCUSSION: In the present patient, the region of the bend rod was located at the inferior border of the right mandible, causing rod unaccessible pain by contacting the surrounding tissue including a sensory nerve. Careful vertical ramus distractor position planning and tools to resolve complications are the key factors for accomplishing the scheduled elongation.CONCLUSION: Alternative techniques using a sleeve for safer and gentle distraction for rod unaccessible pain on activation should be considered. (C) 2015 The Authors. Published by Elsevier Ltd. on behalf of Surgical Associates Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

DOI： 10.1016/j.ijscr.2015.05.037

岡山大学病院口腔がん専門外来と岡山市歯科医師会の連携による口腔がん検診研修会の概要とアンケート結果について

岸本晃治, 岡崎景, 西山明慶, 居樹秀明, 松村達志, 伊原木聰一郎, 銅前昇平, 吉岡徳枝, 栗尾奈愛, 矢尾真弓, 小畑協一, 尾野裕子, 志茂剛, 壺内智郎, 飯田征二, 佐々木朗

岡山歯学会雑誌 33 ( 2 ) 23 - 28 2014.12

Language：Japanese Publisher：岡山歯学会

口腔癌検診研修会基礎コースを修了した歯科医師を対象に、研修会終了後にアンケート調査を行った。2013年に行われた3回の研修会の研修者の合計は46人(3人が2回研修)であった。臨床経験年数は10〜42年(平均23.6年、中央値25年)に比較的長い研修者が多かった。口腔癌症例経験ありは70%に認められ、経験症例数は1〜3例が多かった。口腔癌症例経験者の中で癌の疑いがあると診断して専門機関に紹介した症例が93%と大部分を占めた。しかし、その中で早期癌を診断できた症例は45%に過ぎず、初診時に進行していた症例も46例に認められた。また、紹介が少し遅くなった症例が9%認められたが患者が専門機関をなかなか受診してくれなかった例も1例あった。癌の部位は舌が最も多く41%認められ、下顎歯肉32%、口底13%と続いた。研修会の時間・レベルは概ね適切で、講義・実習・テキストもためになり、今後の臨床に役立つとの回答が得られた。再研修の必要性は91%と多かったが、アドバンスコースの希望者は69%に留まり、ベーシックコースの希望者も22%認められた。また、再研修までの期間は1年の35%を前後にばらつきが認められた。研修者はより実践的に役立つ研修内容を希望していた。

骨髄移植後の慢性GVHD患者に発生した多発性口腔扁平上皮癌の1例

奥井達雄, 目瀬浩, 伊原木聰一郎, 吉岡徳枝, 志茂剛, 佐々木朗

日本口腔外科学会雑誌 60 ( 3 ) 151 - 155 2014.3

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

症例は42歳男性で、全身倦怠感を主訴に受診し、慢性骨髄性白血病と診断された。HLAが一致する弟をドナーとした骨髄移植を受け、移植直後に移植片対宿主病(GVHD)を発症し、慢性GVHDによる肝機能低下、GVHDに対するプレドニゾロン長期投与による軽度の腎機能低下を認めた。骨髄移植直後より口内炎を自覚していたが、右側頬粘膜に腫瘤を自覚するようになり、血液腫瘍内科より紹介受診した。体格中等度、栄養状態良好で、顔面、四肢皮膚に慢性GVHDによる色素逸脱を認めた。右側頬粘膜に22×16mmの弾性軟、周囲に硬結を触知する腫瘤を認めた。MR画像で右側頬粘膜に前後径20mm、厚み4mmの境界明瞭なSTIR高信号域を認め、左側下顎小臼歯部舌側歯肉に前後径10mmの境界明瞭なSTIR高信号域を認めた。骨髄移植によるGVHDを伴った二次性多発性口腔癌、白板症の疑いと臨床診断し、全身麻酔下に腫瘍切除術を施行した。左側下顎生検を行い、舌背中央部は軽度上皮異形成、左側下顎大臼歯歯肉頬移行部は高分化扁平上皮癌と病理組織学的に診断され、左側下顎歯肉癌に対し腫瘍切除術を施行した。術後12ヵ月再発を認めず、厳重な経過観察を行っている。

DOI： 10.5794/jjoms.60.151

Expression and roles of CCN2 in dental mesenchymal cells in primary culture-With findings in a case of odontogenic myxofibroma

Tsuyoshi Shimo, Eiki Koyama, Yuu Horikiri, Tatsuo Okui, Naito Kurio, Naoki Katase, Shoko Yoshida, Yuichiro Takebe, Koji Kishimoto, Norie Yoshioka, Hitoshi Nagatsuka, Akira Sasaki

Oral Science International 11 ( 1 ) 8 - 14 2014.1

Language：English Publishing type：Research paper (scientific journal)

Purpose of the research: Tooth germ development involves multiple events, including cell proliferation and cell differentiation. Connective tissue growth factor (CTGF/CCN2) is a signaling protein involved in tooth germ development, and we investigated how it is expressed and what roles it may have in primary cultures of mesenchymal cells derived from the developing tooth germ. We also examined the expression of CCN2 in a human odontogenic myxofibroma, a benign tumor of odontogenic mesenchymal origin, and considered the possible roles of CCN2 in the development of myxofibromas. Materials and methods: Mesenchymal cells of early bell-stage tooth germs were isolated from Day-90 bovine embryos and placed in primary culture. A resected specimen from a patient with odontogenic myxofibroma was prepared for immunohistochemical studies. Principal results: The CCN2 expression level in proliferating odontogenic mesenchymal cells freshly isolated from the early bell stage of developing bovine tooth germs and placed in primary culture was 3 times higher than that in the confluent non-proliferating cells. Recombinant CCN2 significantly increased the proliferation and type I collagen expression in odontogenic mesenchymal cells in primary culture. Immunohistochemical analysis on myxofibroma case revealed that CCN2 was detectable in MIB-1, a cellular marker of proliferation-positive odontogenic mesenchymal cells adjacent to capillary blood vessels and in the endothelial cells of the vessels in the tumor. Major conclusion: CCN2 signaling would influence the proliferation of and extracellular matrix production by dental mesenchymal cells. Our results suggest that the same mechanisms of CCN2 action toward dental mesenchymal cells would also be operative in the odontogenic myxofibroma microenvironment. © 2013 Japanese Stomatological Society.

DOI： 10.1016/S1348-8643(13)00008-6

Neamine inhibits oral cancer progression bysuppressing angiogenin-mediated angiogenesis and cancer cell proliferation. Reviewed

Kishimoto K, Yoshida S, Ibaragi S, Yoshioka N, Okui T, Hu GF, Sasaki A

Anticancer Res 34 2113 - 2121 2014

Oral infection control to assist infliximab therapy in a Behçet's disease patient with severe eye inflammation in response to dental treatment: a case report. International journal

Chieko Kudo, Hiroshi Wakabayashi, Masayuki Shimoe, Hiroya Kobayashi, Takashi Ito, Toshinori Ohkawa, Arisa Isoshima-Nakamura, Junji Mineshiba, Norie Yoshioka, Kumiko Nawachi, Hiroshi Maeda, Toshihiko Matsuo, Hirofumi Makino, Shogo Takashiba

Clinical case reports 2 ( 6 ) 274 - 280 2014

エナメル上皮腫摘出後に骨移植と骨延長により骨増量を行ったインプラント治療の1例

伊原木聰一郎, 目瀬浩, 中山周子, 兒玉真一, 奥井達雄, 吉岡徳枝, 岸本晃治, 中妻可奈子, 志茂剛, 佐々木朗

Japanese Journal of Maxillo Facial Implants 12 ( 2 ) 53 - 57 2013.8

Language：Japanese Publisher：(公社)日本顎顔面インプラント学会

59歳女。右側頬部の腫脹を主訴に受診し、パノラマX線写真で右側下顎骨にX線透過像を認めた。CT写真では、腫瘍直下に下顎管が存在していた。局研麻酔下で生検を行い、エナメル上皮腫と診断した。全身麻酔下に腫瘍摘出術および抜歯を施行した。病理組織学的所見からエナメル上皮腫と診断した。腫瘍摘出術後3年3ヵ月後にインプラント治療に先立ち、下歯槽神経血管束移動術と右側下顎枝からの骨移植を行った。4ヵ月の治癒期間の後、骨延長を行った。頬側の骨量が不十分であったため、オトガイ部からの骨移植を再度行い、1年2ヵ月後にインプラント体を埋入した。現在、上部構造装着から4年が経過しているが、腫瘍の再発や、インプラント周囲粘膜組織の炎症徴候もなく、正常な咬合・咀嚼機能が維持されている。さらにパノラマX線写真においてもインプラント周囲の異常な骨吸収はなく、歯槽骨頂の骨レベルは維持され、経過は良好である。

Angiogenin mediates androgen-stimulated prostate cancer growth and enables castration resistance. Reviewed International journal

Li S, Hu MG, Sun Y, Yoshioka N, Ibaragi S, Sheng J, Sun G, Kishimoto K, Hu GF

Mol Cancer Res. 11 ( 10 ) 1203 - 1214 2013

Language：English Publishing type：Research paper (scientific journal)

UNLABELLED: The androgen receptor (AR) is a critical effector of prostate cancer development and progression. Androgen-dependent prostate cancer is reliant on the function of AR for growth and progression. Most castration-resistant prostate cancer (CRPC) remains dependent on AR signaling for survival and growth. Ribosomal RNA (rRNA) is essential for both androgen-dependent and castration-resistant growth of prostate cancer cells. During androgen-dependent growth of prostate cells, androgen-AR signaling leads to the accumulation of rRNA. However, the mechanism by which AR regulates rRNA transcription is unknown. Here, investigation revealed that angiogenin (ANG), a member of the secreted ribonuclease superfamily, is upregulated in prostate cancer and mediates androgen-stimulated rRNA transcription in prostate cancer cells. Upon androgen stimulation, ANG undergoes nuclear translocation in androgen-dependent prostate cancer cells, where it binds to the rDNA promoter and stimulates rRNA transcription. ANG antagonists inhibit androgen-induced rRNA transcription and cell proliferation in androgen-dependent prostate cancer cells. Interestingly, ANG also mediates androgen-independent rRNA transcription through a mechanism that involves its constitutive nuclear translocation in androgen-insensitive prostate cancer cells, resulting in a constant rRNA overproduction and thereby stimulating cell proliferation. Critically, ANG overexpression in androgen-dependent prostate cancer cells enables castration-resistant growth of otherwise androgen-dependent cells. Thus, ANG-stimulated rRNA transcription is not only an essential component for androgen-dependent growth of prostate cancer but also contributes to the transition of prostate cancer from androgen-dependent to castration-resistant growth status. IMPLICATIONS: The ability of angiogenin to regulate rRNA transcription and prostate cancer growth makes it a viable target for therapy.

DOI： 10.1158/1541-7786.MCR-13-0072

Hypoxia-induced up-regulation of angiogenin, besides VEGF, is related to progression of oral cancer Reviewed International journal

Koji Kishimoto, Shoko Yoshida, Soichiro Ibaragi, Norie Yoshioka, Tatsuo Okui, Guo-fu Hu, Akira Sasaki

Oral Oncology 48 ( 11 ) 1120 - 1127 2012.11

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier BV

OBJECTIVES: Angiogenin (ANG) is a prominent angiogenic factor that has been shown to have a dual effect on tumor progression by inducing both angiogenesis and cancer cell proliferation through stimulating ribosomal RNA transcription in both endothelial cells and cancer cells. In the present study, we investigated the expression profiles of ANG and vascular endothelial growth factor (VEGF) in oral cancer and their correlation with hypoxia and evaluated the possible value of ANG as a therapeutic target for oral cancer. MATERIALS AND METHODS: Immunohistochemistry (IHC), ELISA, real-time RT-PCR and Western blotting were used to examine the expression of ANG, VEGF, and hypoxia-inducible factor 1α (HIF-1α) in oral squamous cell carcinoma (OSCC) specimens and human OSCC cell lines. In order to examine the role of ANG, we knocked down ANG expression in HSC-2 cells by means of plasmid-mediated RNA interference. RESULTS: IHC showed that the expression of ANG was significantly correlated with that of HIF-1α in 50 OSCC specimens (P = 0.031). However, no significant correlation between VEGF and HIF-1α expression was found (P = 0.243). Consistently, ANG secretion increased under hypoxia in all of the 10 OSCC cell lines tested; and a significant increase was observed in 6 of them. In contrast, there was no noticeable increase in VEGF secretion under hypoxia in any of these cell lines. In HSC-2 and SAS OSCC cells, the increase in ANG mRNA expression correlated very well with that of HIF-1α protein expression after hypoxia onset. However, no noticeable increase in VEGF mRNA expression was observed even after 12 h of hypoxia. Down-regulation of ANG expression in HSC-2 cells highly expressing and secreting VEGF inhibited ribosome biogenesis, cell proliferation, tumor angiogenesis, and xenograft growth in athymic mice. CONCLUSION: These results suggest that ANG is up-regulated in the hypoxic environment of oral cancers and that its inhibition can have a therapeutic implication.

DOI： 10.1016/j.oraloncology.2012.05.009

幼児の上顎歯肉に発生した巣状口腔粘液症の1例 Reviewed

伊原木聰一郎, 西山明慶, 吉岡徳枝, 片瀬直樹, 長塚仁, 佐々木朗

日本口腔外科学会雑誌 58 ( 9 ) 546 - 549 2012.9

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

1歳7ヵ月女児。左側上顎歯肉の腫瘤を主訴とした。左側上顎歯肉に弾性軟の有茎性腫瘤を認め、腫瘤の先端は分葉状で正常歯肉色であったが、腫瘤基部は血管が豊富で赤色を呈していた。デンタルX線で同部の骨吸収は認めなかった。左側上顎歯肉腫瘍と診断し、腫瘍切除術を行った。腫瘤は有茎性で基部は歯肉と歯槽粘膜の境界部に存在しており、基部から約5mmの安全域を設定し直下の骨膜も切除した。同部の骨面は正常であった。切除部は開放創にして手術を終了した。切除した腫瘍の病理診断は巣状口腔粘液症であった。術後経過は良好で、術後1年の現在、再発は認めていない。

DOI： 10.5794/jjoms.58.546

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2012&ichushi_jid=J01073&link_issn=&doc_id=20121003390008&doc_link_id=10.5794%2Fjjoms.58.546&url=https%3A%2F%2Fdoi.org%2F10.5794%2Fjjoms.58.546&type=J-STAGE&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00007_3.gif

Beckwith-Wiedemann症候群による巨舌に起因する著明な開咬に対して顎矯正手術を施行した1例 Reviewed

吉岡徳枝, 西山明慶, 伊原木聰一郎, 奥井達雄, 高橋巧, 佐々木朗

日本顎変形症学会雑誌 22 ( 2 ) 112 - 112 2012.5

A clinical study of patients aged 75 and older with oral squamous cell carcinoma Reviewed

YOSHIDA Shoko, KISHIMOTO Koji, IBARAGI Soichiro, DOMAE Shohei, YOSHIOKA Norie, SHIMO Tsuyoshi, NISHIYAMA Akiyoshi, MESE Hiroshi, SASAKI Akira

Journal of Japanese Society of Oral Oncology 24 ( 3 ) 103 - 111 2012

Language：Japanese Publisher：Japanese Society of Oral Oncology

As the aging society is advancing in our country, it is expected that the opportunity to treat oral cancer in elderly patients is increasing. In this report, 64 patients (23 male and 41 female) aged 75 and older with oral squamous cell carcinoma (OSCC) were clinically evaluated as compared with 60 patients (32 male and 28 female) aged 65-74 years old, and 63 patients (46 male and 17 female) aged 64 and younger with OSCC who were treated at our clinic between 2000 and 2008.<br>The ratio of Performance Status (PS) grade 0·1 patients in the group aged 75 and older was significantly lower than that in the groups aged 65-74 and those aged 64 and younger. The number of patients aged 75 and older are divided into the radical cure treatment group, palliative treatment group and no treatment group, which accounts for 45 (70.3%), 9 (14.1%), and 10 (15.6%) cases, respectively. The ratio of the radical cure treatment patients in the group aged 75 and older was lower than that in the group aged 65-74. The 5-year cause-specific survival rates of radical cure treatment in the groups aged 75 and older, 65-74 and 64 and younger were 81.3%, 88.6% and 80.9%, respectively. The survival rate of the group aged 75 and older was lower than that aged 65-74. We could not follow up with the patients who underwent no treatment. Therefore, it is necessary to consider a solution to this problem in the future.

DOI： 10.5843/jsot.24.103

Other Link： http://search.jamas.or.jp/link/ui/2013021703

口腔癌切除後の創部に対してポリグリコール酸フェルトとフィブリン糊を併用した被覆法の使用経験

伊原木聰一郎, 岸本晃治, 吉岡徳枝, 銅前昇平, 志茂剛, 中妻可奈子, 辻本紗代子, 栗尾奈愛, 兒玉真一, 武部祐一郎, 堀切優, 柴田茜, 西山明慶, 目瀬浩, 佐々木朗

岡山歯学会雑誌 29 ( 2 ) 107 - 112 2010.12

Language：Japanese Publisher：岡山歯学会

口腔癌切除後の創部に対してポリグリコール酸フェルトとフィブリン糊を併用した被覆法を用いて治療を行った4例を経験した。症例1は80歳女で、右側舌癌に対して舌部分切除術を行った。術後21日目においてほぼPGAフェルトは吸収し、舌の瘢痕拘縮は軽度であった。症例2は65歳女で、左側頬粘膜悪性黒色腫に対して頬粘膜腫瘍切除術と上顎骨部分切除術を行った。術後28日目においてPGAフェルトは吸収しており、瘢痕拘縮は軽度で開口障害もなかった。症例3は78歳女で、左側下顎歯肉癌に対して下顎骨辺縁切除術と頸部郭清術を行った。術後31日目において、骨露出は認めず肉芽で覆われている。症例4は88歳女で、左側頬粘膜癌に対して原発巣は密封小線源治療、頸部リンパ節転移は頸部郭清術を行うこととした。術後44日目において肉芽の新生は十分でなく、頬粘膜は陥凹している。

臼後部に発生した嚢胞腺癌の1例 Reviewed

岸本晃治, 吉田祥子, 銅前昇平, 吉岡徳枝, 志茂剛, 佐々木朗

日本口腔外科学会雑誌 56 ( 12 ) 720 - 724 2010.12

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

症例は90歳男性で、右側下顎臼後部歯肉の違和感、義歯による痛みが出現し、近医の義歯調節で痛みは消失したが、同部に腫瘤を指摘され紹介受診した。右側下顎臼後部に弾性硬、表面がカリフラワー状の境界明瞭な18×16mm大の外向性腫瘤を認めた。CTで同部に12×11×14mm大の類円形病巣と骨髄に達する下掘れ状の骨吸収像を認めた。生検で腫瘍細胞の増殖による嚢胞腔形成と乳頭状構造、一部に細胞異型や分裂像を認め、低悪性の嚢胞腺癌を疑って下顎骨辺縁切除術を行った。病理所見では腫瘍は大小の嚢胞腔を形成して外向性に増殖し、一方で下顎骨内に嚢胞腔を形成して下掘れ状の骨吸収像を認めた。腫瘍は嚢胞腔内に乳頭状増殖を示し、間質に線維性結合組織の増生と硝子化を認め、嚢胞を裏層する腫瘍細胞は円形の核と好酸性の細胞質を有する円柱状細胞からなり、一部に異型や分裂像を認めた。病理診断は低悪性嚢胞腺癌であった。術後2年経過で再発や転移は認めていない。

DOI： 10.5794/jjoms.56.720

エナメル上皮腫に対する外科療法の治療成績と再発に関する臨床的検討 Reviewed

吉田祥子, 塚本剛一, 吉岡徳枝, 志茂剛, 岸本晃治, 西山明慶, 大山和彦, 目瀬浩, 長塚仁, 佐々木朗

日本口腔腫瘍学会誌 22 ( 1 ) 37 - 43 2010.3

Language：Japanese Publisher：(一社)日本口腔腫瘍学会

エナメル上皮腫の治療法については論議のあるところである。当科においては、周囲骨の穿孔がないかもしくはわずかであれば、保存的外科療法-骨面削除と凍結療法を併用した摘出術-を基本的に選択している。当論文では、当科開設の1982年から2007年までの25年間に経験したエナメル上皮腫50例、特に再発症例について検討を行った。50例の手術の内訳は、摘出術12例、摘出と骨面削除または骨面削除および凍結療法(摘出+補助療法)が21例、顎骨切除(辺縁切除と区域切除)が17例であった。再発は6例であり(再発率:12%)、摘出術に5例(再発率:42%)、摘出+補助療法に1例(再発率:5%)認めた。顎骨切除術は再発を認めなかった。摘出と顎骨切除との間および、摘出と摘出+補助療法との間に再発率に関し有意差を認めた。以上より、エナメル上皮腫の保存的外科療法において、骨面削除と凍結療法は有用であることが示唆された。(著者抄録)

DOI： 10.5843/jsot.22.37

Other Link： https://search.jamas.or.jp/index.php?module=Default&action=Link&pub_year=2010&ichushi_jid=J02382&link_issn=&doc_id=20100318180005&doc_link_id=%2Fdy8ortum%2F2010%2F002201%2F006%2F0037-0043%26dl%3D0&url=http%3A%2F%2Fwww.medicalonline.jp%2Fjamas.php%3FGoodsID%3D%2Fdy8ortum%2F2010%2F002201%2F006%2F0037-0043%26dl%3D0&type=MedicalOnline&icon=https%3A%2F%2Fjk04.jamas.or.jp%2Ficon%2F00004_2.gif

当科における口腔扁平上皮癌の治療成績(第1報)

岸本晃治, 吉田祥子, 伊原木聰一郎, 銅前昇平, 吉岡徳枝, 志茂剛, 塚本剛一, 西山明慶, 目瀬浩, 松村智弘, 佐々木朗

岡山歯学会雑誌 28 ( 1 ) 43 - 50 2009.6

Language：Japanese Publisher：岡山歯学会

根治的治療を施行した口腔扁平上皮癌一次症267例において、臨床病理学的諸因子ならびに治療法別の治療成績を評価した。Stage分類、T分類、N分類、原発巣分化度、浸潤様式、再発・転移の因子が、有意に生存率に影響を及ぼした。頬粘膜癌が他の癌に比べ有意に予後不良であった。手術群、術前照射群、術前化学療法群、組織内照射群、放射線動注化学療法群、放射線療法群の5年疾患特異的累積生存率は、それぞれ74.1%、77.1%、100%、97.2%、91.7%.100%であった。根治的治療群における5年累積生存率は全症例77.4%、再発・転移群46.7%であった。N分類および分化度が独立した予後規定因子となった。治療後に評価できる因子である再発・転移(あり/なし)の項目を加え、生存率について多変量解析を行い、再発・転移の因子のみが独立した予後規定因子となった。

Neamine Inhibits Prostate Cancer Growth by Suppressing Angiogenin-Mediated rRNA Transcription Reviewed

Soichiro Ibaragi, Norie Yoshioka, Shuping Li, Miaofen G. Hu, Saori Hirukawa, Peter M. Sadow, Guo-fu Hu

CLINICAL CANCER RESEARCH 15 ( 6 ) 1981 - 1988 2009.3

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

Purpose: Angiogenin (ANG) undergoes nuclear translocation and stimulates rRNA transcription in both prostate cancer cells and endothelial cells. The purpose of this study is to assess the antitumor activity of neamine, a nontoxic degradation product of neomycin that blocks nuclear translocation of ANG.
Experimental Design: The anti-prostate cancer activity of neamine was first evaluated in a xenograft animal model. It was then examined in the murine prostate-restricted AKT transgenic mice that develop prostate intraepithelial neoplasia (PIN) owing to AKT transgene overexpression.
Results: Neamine inhibits xenograft growth of PC-3 human prostate cancer cells in athymic mice. It blocks nuclear translocation of ANG and inhibits rRNA transcription, cell proliferation, and angiogenesis. Neamine also prevents AKT-induced PIN formation as well as reverses fully developed PIN in murine prostate-restricted AKT mice, accompanied by a decrease in rRNA synthesis, cell proliferation, and angiogenesis and an increase in prostate epithelial cell apoptosis.
Conclusion: We confirmed that ANG is a molecular target for cancer drug development and that blocking nuclear translocation of ANG is an effective means to inhibit its activity. Our results also suggested that neamine is a lead compound for further preclinical evaluation.

DOI： 10.1158/1078-0432.CCR-08-2593

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

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。

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。

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

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

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

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

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

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

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.

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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