Faculty Profiles - akihide Tanimoto

Papers - akihide Tanimoto

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Shintaro Yanazume, Shinichi Togami, Masaki Kamio, Ikumi Kitazono, Tsubasa Hiraki, Akihide Tanimoto, Hiroaki Kobayashi . Bulky cervical tumour showing mixed unique cell clusters in cervical cytology. . Cytopathology : official journal of the British Society for Clinical Cytology31 ( 4 ) 345 - 347 2020.7Reviewed International journal

Kake S, Kawaguchi H, Nagasato T, Yamada T, Ito T, Maruyama I, Miura N, Tanimoto A . Association Between HMGB1 and Thrombogenesis in a Hyperlipaemia-induced Microminipig Model of Atherosclerosis. . In vivo (Athens, Greece)34 ( 4 ) 1871 - 1874 2020.7

Seiya Yokoyama, Taiji Hamada, Michiyo Higashi, Kei Matsuo, Kosei Maemura, Hiroshi Kurahara, Michiko Horinouchi, Tsubasa Hiraki, Tomoyuki Sugimoto, Toshiaki Akahane, Suguru Yonezawa, Marko Kornmann, Surinder K Batra, Michael A Hollingsworth, Akihide Tanimoto . Predicted Prognosis of Patients with Pancreatic Cancer by Machine Learning. . Clinical cancer research : an official journal of the American Association for Cancer Research26 ( 10 ) 2411 - 2421 2020.5Reviewed International journal

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

PURPOSE: Pancreatic cancer remains a disease of high mortality despite advanced diagnostic techniques. Mucins (MUC) play crucial roles in carcinogenesis and tumor invasion in pancreatic cancers. MUC1 and MUC4 expression are related to the aggressive behavior of human neoplasms and a poor patient outcome. In contrast, MUC2 is a tumor suppressor, and we have previously reported that MUC2 is a favorable prognostic factor in pancreatic neoplasia. This study investigates whether the methylation status of three mucin genes from postoperative tissue specimens from patients with pancreatic neoplasms could serve as a predictive biomarker for outcome after surgery. EXPERIMENTAL DESIGN: We evaluated the methylation status of MUC1, MUC2, and MUC4 promoter regions in pancreatic tissue samples from 191 patients with various pancreatic lesions using methylation-specific electrophoresis. Then, integrating these results and clinicopathologic features, we used support vector machine-, neural network-, and multinomial-based methods to develop a prognostic classifier. RESULTS: Significant differences were identified between the positive- and negative-prediction classifiers of patients in 5-year overall survival (OS) in the cross-validation test. Multivariate analysis revealed that these prognostic classifiers were independent prognostic factors analyzed by not only neoplastic tissues but also nonneoplastic tissues. These classifiers had higher predictive accuracy for OS than tumor size, lymph node metastasis, distant metastasis, and age and can complement the prognostic value of the TNM staging system. CONCLUSIONS: Analysis of epigenetic changes in mucin genes may be of diagnostic utility and one of the prognostic predictors for patients with pancreatic ductal adenocarcinoma.

DOI： 10.1158/1078-0432.CCR-19-1247

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Eri Inatsu, Kazuyasu Fujii, Miho Hatanaka, Aoi Okubo, Youhei Uchida, Yuko Higashi, Tsubasa Hiraki, Akihide Tanimoto, Takuro Kanekura . Epstein-Barr virus-positive mucocutaneous ulcer in a patient with untreated chronic lymphocytic leukemia and hypogammaglobulinemia. . The Journal of dermatology47 ( 5 ) e204 - e206 2020.5Reviewed International journal

Hirotsugu Noguchi, Ikumi Kitazono, Kazumasa Hamada, Takako Tanaka, Takashi Tasaki, Hiroshi Shirahama, Yoshimasa Yamamoto, Akihide Tanimoto . Verruciform Xanthoma of the Esophagus: Two Case Reports With Review of the Literature. . International journal of surgical pathology28 ( 3 ) 302 - 305 2020.5

Verruciform xanthoma is a rare benign verrucopapillary lesion that develops in the oral mucosa and genital skin. Its development in the esophagus is extremely rare, with only 5 reported cases. We present 2 cases of verruciform xanthoma of the esophagus. Case 1 involved a 91-year-old woman, who had hypertension and chronic gastritis with Helicobacter pylori infection, with a 12-year history of a 10-mm white-yellow elevated lesion on the esophagus, 35 cm from the incisor teeth. Case 2 involved a 70-year-old man with fundic gland polyp, hyperlipidemia, and lung cancer, who had a 10-mm whitish granular/verrucoid lesion on the esophagus, 28 cm from the incisor teeth. Microscopically, these lesions show verrucous and papillomatous epithelial hyperplasia with neutrophilic intraepithelial exocytosis. The histological hallmark is the presence of numerous foamy histiocytes infiltrating the elongated squamous epithelial papillae. Although its etiology is unknown, irritation or trauma caused by radiotherapy has been suggested.

DOI： 10.1177/1066896919879495

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Yanazume Shintaro, Fukuda Mika, Togami Shinichi, Kamio Masaki, Kitazono Ikumi, Hiraki Tsubasa, Tanimoto Akihide, Kobayashi Hiroaki . 子宮の印環細胞癌と扁平上皮癌の衝突癌が認められた稀な1例(Rare signet-ring cell and squamous cell carcinoma collision tumor in the cervix) . 鹿児島産科婦人科学会雑誌28 39 - 44 2020.3Reviewed

Language：English Publisher：鹿児島産科婦人科学会

症例は46歳の経産婦で、5年前から不正出血がみられ、38℃を超える発熱があったため来院した。白血球数、血小板数、C反応性蛋白質の上昇とヘモグロビン値の低下が認められた。子宮頸部のPapanicolaou生検で、印環細胞癌(SRCC)様腫瘍細胞と非定形扁平上皮細胞が存在することが明らかになった。子宮頸部腫瘍のパンチ生検により、粘液性SRCCとHPV18型感染が認められた。根治的子宮摘出術と両側付属器切除および腹腔リンパ節郭清を行った。各種検査の結果、最終的に子宮頸部のSRCCと扁平上皮癌の衝突癌(pT1b2N0M0)と診断した。次世代シーケンシングパネルを用いて生殖細胞変異の同定を試みたところ、両病変ともFLT3、BRCA2、R1遺伝子のChr13にヘテロ接合性消失が明らかになった。パクリタキセルとカルボプラチンによる術後化学療法を6コース行った。18ヵ月間の経過観察中、疾患の兆候は認められていない。

赤羽俊章, 北薗育美, 小林裕明, 谷本昭英 . 遺伝子パネル検査を利用した婦人科腫瘍の分子病理統合診断 . 鹿児島産科婦人科学会雑誌28 1 - 4 2020.3Reviewed

Language：Japanese Publisher：鹿児島産科婦人科学会

鹿児島大学病院では、これからのゲノム医療に対応するため、産婦人科学教室と共同で婦人科腫瘍の遺伝子パネル検査の臨床研究を昨年から開始した。高品質のホルマリン固定パラフィン包埋検体を作成する取り組みや、液状処理細胞診検体を使用したパネル検査の基礎研究を行っている。当講座では独自の遺伝子パネル検査を開発し臨床研究に使用している。産婦人科学教室との臨床研究で使用したパネルは、分子標的薬関連・ミスマッチ修復関連・NCCNガイドライン関連遺伝子を含む60遺伝子と17ヶ所のマイクロサテライト領域を標的としたオリジナルの固形腫瘍専用の遺伝子パネル検査である。本稿では以下の項目で解説した。1)遺伝子パネル検査、2)類内膜腺癌で認められる遺伝子異常、3)カスタム遺伝子パネル検査。

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赤羽俊章, 北薗育美, 小林裕明, 谷本昭英 . 遺伝子パネル検査を利用した婦人科腫瘍の分子病理統合診断 . 鹿児島産科婦人科学会雑誌28 1 - 4 2020.3

Language：Japanese Publisher：鹿児島産科婦人科学会

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Takuro Hirano, Yoshinari Shinsato, Kan Tanabe, Nayuta Higa, Muhammad Kamil, Kohichi Kawahara, Masatatsu Yamamoto, Kentaro Minami, Michiko Shimokawa, Takaaki Arigami, Shigehiro Yanagita, Daisuke Matushita, Yoshikazu Uenosono, Sumiya Ishigami, Yuko Kijima, Kosei Maemura, Ikumi Kitazono, Akihide Tanimoto, Tatsuhiko Furukawa, Shoji Natsugoe . FARP1 boosts CDC42 activity from integrin αvβ5 signaling and correlates with poor prognosis of advanced gastric cancer. . Oncogenesis9 ( 2 ) 13 - 13 2020.2Reviewed International journal

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

Considering the poor prognosis of most advanced cancers, prevention of invasion and metastasis is essential for disease control. Ras homologous (Rho) guanine exchange factors (GEFs) and their signaling cascade could be potential therapeutic targets in advanced cancers. We conducted in silico analyses of The Cancer Genome Atlas expression data to identify candidate Rho-GEF genes showing aberrant expression in advanced gastric cancer and found FERM, Rho/ArhGEF, and pleckstrin domain protein 1 (FARP1) expression is related to poor prognosis. Analyses in 91 clinical advanced gastric cancers of the relationship of prognosis and pathological factors with immunohistochemical expression of FARP1 indicated that high expression of FARP1 is significantly associated with lymphatic invasion, lymph metastasis, and poor prognosis of the patients (P = 0.025). In gastric cancer cells, FARP1 knockdown decreased cell motility, whereas FARP1 overexpression promoted cell motility and filopodium formation via CDC42 activation. FARP1 interacted with integrin β5, and a potent integrin αvβ5 inhibitor (SB273005) prevented cell motility in only high FARP1-expressing gastric cancer cells. These results suggest that the integrin αvβ5-FARP1-CDC42 axis plays a crucial role in gastric cancer cell migration and invasion. Thus, regulatory cascade upstream of Rho can be a specific and promising target of advanced cancer treatment.

DOI： 10.1038/s41389-020-0190-7

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Tsubasa Hiraki, Miho Hatanaka, Akiko Arimura, Hisao Kawahira, Mari Kirishima, Ikumi Kitazono, Michiko Horinouchi, Michiyo Higashi, Takuro Kanekura, Akihide Tanimoto . Granulomatous/sarcoid-like reactions in the setting of programmed cell death-1 inhibition: a potential mimic of disease recurrence. . Journal of cutaneous pathology47 ( 2 ) 154 - 160 2020.2

Nivolumab and pembrolizumab are humanized IgG4 monoclonal antibodies against programmed cell death 1 (PD-1). Although these agents are effective in treating advanced melanoma, non-small-cell lung carcinoma, and other types of cancers, various adverse events have been reported. Cutaneous adverse events are particularly prevalent and, while granulomatous/sarcoid-like reactions are uncommon, they are increasingly recognized as immune-related adverse events associated with immune checkpoint inhibitors. Herein, we report two cases of granulomatous/sarcoid-like reaction with foreign material, mimicking metastatic malignancy after PD-1 inhibitor treatment. Clinicians should be aware of the existence of cutaneous lesions and perform biopsy if needed to prevent misdiagnosis and unnecessary adjustments to immunotherapy.

DOI： 10.1111/cup.13569

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Takashi Kijima, Takaaki Arigami, Yoshikazu Uenosono, Tsubasa Hiraki, Shigehiro Yanagita, Daisuke Matsushita, Keishi Okubo, Masataka Shimonosono, Sumiya Ishigami, Kosei Maemura, Akihide Tanimoto, Shoji Natsugoe . Comparison of HER2 Status Before and After Trastuzumab-based Chemotherapy in Patients With Advanced Gastric Cancer. . Anticancer research40 ( 1 ) 75 - 80 2020.1

BACKGROUND/AIM: The aim of the present study was to compare human epidermal growth factor receptor 2 (HER2) expression before and after trastuzumab-based chemotherapy in patients with advanced HER2-positive gastric cancer. MATERIALS AND METHODS: We assessed HER2 expression using immunohistochemistry and/or fluorescence in situ hybridization in pre-treatment biopsied specimens and post-treatment resected specimens obtained from seven patients with advanced HER2-positive gastric cancer receiving trastuzumab-based chemotherapy. RESULTS: Four patients maintained the HER2-positive status and three patients had a change in HER2 expression from positive to negative. In patients showing the loss of HER2 expression after treatments, HER2-positive tumor cells with a dominant histological type disappeared, and HER2-negative tumor cells with another dominant histological type were identified. CONCLUSION: HER2 expression can change after trastuzumab-based chemotherapy in patients with advanced HER2-positive gastric cancer. Continuous monitoring of HER2 expression after treatments may be utilized to determine whether the continued use of trastuzumab is advisable.

DOI： 10.21873/anticanres.13927

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Tomoko Hanada, Ryosuke Hanaya, Fauziah Chaira Ummah, Taro Kamisasanuki, Mari Kirishima, Akihide Tanimoto, Kazunori Arita, Koji Yoshimoto . Combined Transcranial-supraorbital and Transconjunctival Approach for Optic Nerve Coloboma with Ophthalmic Dysplasia Associated with Rheumatoid Arthritis. . NMC case report journal7 ( 1 ) 1 - 4 2020.1Reviewed

Language：English Publisher：The Japan Neurosurgical Society

We report a 59-year-old woman with optic nerve coloboma and ophthalmic dysplasia associated with rheumatoid arthritis. She experienced progressive visual dysfunction over the course of several years and presented with headache and pain in the left eye. Since infancy the visual acuity of her left eye had been compromised and her eyesight worsened gradually until she was blind in the left eye. Macroscopic observation showed a reddish lesion on the sclera thought to be due to rheumatoid arthritis (RA). Magnetic resonance imaging and computed tomography disclosed a well-defined cystic lesion at the left retro-bulbar optic nerve within the optic nerve sheath. We selected the combined transcranial-supraorbital and transconjunctival approach to remove the eyeball after detaching the optic nerve. This technique was successful and the placement of an ocular prosthetic was cosmetically acceptable.

DOI： 10.2176/nmccrj.cr.2018-0302

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Hanada Tomoko, Hanaya Ryosuke, Ummah Fauziah Chaira, Kamisasanuki Taro, Kirishima Mari, Tanimoto Akihide, Arita Kazunori, Yoshimoto Koji . 関節リウマチを伴う眼形成不全合併視神経コロボーマに対する経頭蓋眼窩上アプローチと経結膜アプローチの併用(Combined Transcranial-supraorbital and Transconjunctival Approach for Optic Nerve Coloboma with Ophthalmic Dysplasia Associated with Rheumatoid Arthritis) . NMC Case Report Journal7 ( 1 ) 1 - 4 2020.1Reviewed

Language：English Publisher：(一社)日本脳神経外科学会

症例は59歳女性で、左眼の視力障害と重度疼痛をきたして近医を受診した。関節リウマチの既往を有し、メトトレキサートとNSAIDsにてコントロールされていた。受診時、左眼の強膜炎を認め、MRIにて左眼窩に嚢胞性病変がみられたため、当院眼科紹介となった。MRIと超音波検査で左眼球と交通する嚢胞性病変を認め、強膜炎、網膜剥離および水疱性角膜症を伴うコロボーマと診断し、有痛性水疱性角膜症の治療目的に神経外科に転科となった。著明な強膜充血と浮腫のほか、肥厚化した嚢胞性視神経と左眼球の変性が認められ、眼球摘出と義眼挿入の適応と判断し、神経外科医と眼科医の協働のもと球後手術を行う方針とした。経頭蓋眼窩上アプローチと経結膜アプローチを選択し、開頭術と眼窩切開術によって視神経鞘を切離後、顕微鏡下に経結膜眼球摘出術を施行した。術後の病理所見では嚢胞性病変は視神経に付着し、嚢胞壁は線維性結合組織で構成されていた。また、網膜萎縮と視神経変性が認められ、コロボーマに一致する所見が得られた。術後MRIでは眼球とコロボーマの摘出が確認され、整容的にも満足が得られる結果となった。

Satoru Kake, Hiroaki Kawaguchi, Tomoka Nagasato, Tomonobu Yamada, Takashi Ito, Ikuro Maruyama, Naoki Miura, Akihide Tanimoto . Association Between HMGB1 and Thrombogenesis in a Hyperlipaemia-induced Microminipig Model of Atherosclerosis. . In vivo34 ( 4 ) 1871 - 1874 2020

Hiroto Tokumoto, Takao Setoguchi, Yoshinobu Saitoh, Hiromi Sasaki, Satoshi Nagano, Shingo Maeda, Akihide Tanimoto, Noboru Taniguchi . Neurotensin receptor 1 is a new therapeutic target for human undifferentiated pleomorphic sarcoma growth. . Molecular carcinogenesis58 ( 12 ) 2230 - 2240 2019.12

Undifferentiated pleomorphic sarcoma (UPS) is the second most common soft tissue sarcoma. For patients with unresectable or metastatic disease, chemotherapies are considered, but in many cases they are not curative. There is a need to identify specific molecular dysregulations that can be therapeutic targets. We focused on neurotensin receptor 1 (NTSR1), which belongs to the G-protein-coupled receptor. NTSR1 expression was upregulated in specimens from patients with UPS. Real-time polymerase chain reaction showed that expression of NTSR1 messenger RNA was 5- to 7-fold increased in UPS cells compared with myoblasts. Western blot showed a high expression of NTSR1 protein in UPS cell lines. Knockdown of NTSR1 prevented UPS cell proliferation and invasion. We confirmed that SR48692, an inhibitor of NTSR1, exhibited antitumor activities in UPS cells. The combination index showed that SR48692 and standard chemotherapeutic drugs prevented UPS cell proliferation synergistically. Mouse xenograft models showed that SR48692 inhibited extracellular signal-regulated kinase phosphorylation and enhanced the response to standard chemotherapeutic drugs. Inhibition of NTSR1 improved the effect of standard chemotherapeutic drugs for UPS. SR48692 may be a new drug for targeted UPS therapy.

DOI： 10.1002/mc.23111

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Toshinobu Imashioya, Yuichi Kodama, Tadasuke Ooka, Shunsuke Nakagawa, Takuro Nishikawa, Takayuki Tanabe, Yasuhiro Okamoto, Naoko Imuta, Mari Kirishima, Akihide Tanimoto, Toyoyasu Koriyama, Junichiro Nishi, Yoshifumi Kawano . Liver abscess due to Sterigmatomyces halophilus in a boy with acute lymphoblastic leukemia. . Journal of infection and chemotherapy : official journal of the Japan Society of Chemotherapy25 ( 12 ) 1047 - 1049 2019.12Reviewed International journal

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

We report the first case of liver abscess due to Sterigmatomyces halophilus. Because this pathogen grows poorly in culture medium without added salts, it was identified by sequencing analysis targeting the rRNA gene internal transcribed spacer (ITS) region. This method could be useful for pathogens that cannot be cultured using standard methods.

DOI： 10.1016/j.jiac.2019.05.021

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Takuro Kanekura, Akiko Arimura, Mari Kirishima, Akihide Tanimoto . Eruptive squamous cell carcinoma in a patient treated with concomitant pembrolizumab and imiquimod. . The Journal of dermatology46 ( 12 ) 1202 - 1204 2019.12

Pembrolizumab, a humanized monoclonal antibody against programmed cell death 1, is used for various malignant neoplasms. Toll-like receptor (TLR) agonists, specifically targeting the TLR9 subfamily (TLR7-9), are treatment options for solid tumors and hematological malignancies. We experienced a case of eruptive squamous cell carcinoma (SCC) in a patient treated concomitantly with pembrolizumab and imiquimod, a TLR7 agonist. A 75-year-old woman who was given a diagnosis of bladder cancer with lung metastasis received pembrolizumab for 3 months when she was referred to our department for the evaluation of skin rashes on her hands. Her skin lesions were diagnosed as well-differentiated SCC and treated with topical imiquimod. Two months after the start of imiquimod, more than 10 reddish papules appeared on her hands. The histological diagnosis of a new plaque was the same as an earlier biopsy. We herein describe this case in detail and provide a published work review.

DOI： 10.1111/1346-8138.15101

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米盛圭一, 日高敬文, 吉留伸郎, 原口優清, 谷本昭英, 夏越祥次 . 子宮内膜症を伴った成人Nuck管水腫の1例 . 診断と治療107 ( 12 ) 1547 - 1549 2019.12

Publisher：(株)診断と治療社

26歳女。右下腹部腫瘤を主訴とした。右鼠径部に4cm大の弾性軟の腫瘤を認め、腫瘤は立位で膨隆し、仰臥位または圧迫で縮小した。自発痛や圧痛は認められなかった。腹部CTおよび腹部超音波検査にて、右鼠径部に35mm×37.4mm大の多房性嚢胞性腫瘤を認め、血液検査では異常を認めなかった。以上より、Nuck管水腫と診断し、鼠径ヘルニア根治術の前方アプローチに準じて手術を施行した。病理組織学的検査では、悪性所見を認めず、Nuck管水腫と診断した。嚢胞壁内には子宮内膜症の所見を認めた。術後は経過良好で、術後6日目には退院し、術後1年の時点で、再発は認めなかった。

Kanekura Takuro, Arimura Akiko, Kirishima Mari, Tanimoto Akihide . ペンブロリズマブとイミキモド併用療法を行った患者における発疹性扁平上皮癌(Eruptive squamous cell carcinoma in a patient treated with concomitant pembrolizumab and imiquimod) . The Journal of Dermatology46 ( 12 ) 1202 - 1204 2019.12Reviewed

Language：English Publisher：John Wiley & Sons Australia, Ltd

症例は75歳女性で、手の皮疹評価のため紹介された。15ヵ月前に肺転移を伴う膀胱癌と診断され、3ヵ月間のペンブロリズマブによる治療歴があった。身体検査では両手背部に僅かに隆起した赤色調斑と不規則な色素沈着が見られた。高分化扁平上皮癌(SCC)と診断しイミキモドによる局所治療を開始したが、治療開始2ヵ月後に赤色調丘疹数が増加し、当初よりも斑の大型化とさらなる隆起が認められた。またいくつかの斑では潰瘍化も見られた。患者希望によりイミキモドおよびペンブロリズマブの治療は中止とし、発疹性SCCに対する経口エトレチナートの治療を提案したが同意は得られなかった。2ヵ月後潰瘍は上皮化したが丘疹は持続しており、注意深い観察を行っている。

Imashioya Toshinobu, Kodama Yuichi, Ooka Tadasuke, Nakagawa Shunsuke, Nishikawa Takuro, Tanabe Takayuki, Okamoto Yasuhiro, Imuta Naoko, Kirishima Mari, Tanimoto Akihide, Koriyama Toyoyasu, Nishi Junichiro, Kawano Yoshifumi . 急性リンパ性白血病の小児におけるSterigmatomyces halophilusによる肝膿瘍(Liver abscess due to Sterigmatomyces halophilus in a boy with acute lymphoblastic leukemia) . Journal of Infection and Chemotherapy25 ( 11-12 ) 1047 - 1049 2019.12Reviewed

Language：English Publisher：エルゼビア・ジャパン(株)

6歳男児。急性リンパ性白血病にて同種骨髄移植(allo-BMT)を予定していた。導入療法にて完全寛解が得られ、大量化学療法後に発熱性好中球減少症を発症した(day 0)。抗菌薬による治療を行ったが、発熱が続き、day 28に腹部CTで肝膿瘍がみられた。真菌による肝膿瘍を疑い、アムホテリシンBリポソーム製剤を投与したが、発熱が続いた。day 37に腹腔鏡下肝生検を行い、類上皮細胞肉芽腫および酵母様真菌を認めた。真菌rRNA遺伝子のITS領域のPCR増幅により単一DNAバンドが得られ、塩基配列はSterigmatomyces halophilus CBS4609株と100%一致した。イトラコナゾールおよびフルシトシンの併用療法によりday 100頃に解熱し、day 106の腹部CTでは肝膿瘍は認められなかった。day 150にきょうだいからallo-BMTを行ったところ、急性リンパ性白血病を再発した。化学療法と父親からの造血幹細胞移植にて寛解し、肝膿瘍の再発は認めなかった。

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Papers - akihide Tanimoto