研究活動情報

• Transcanal Endoscopic Ear Surgery for Pediatric Bilateral Congenital Cholesteatoma: A Report of Two Cases.

  Takashi Ueda, Takeshi Fujita, Natsumi Uehara, Jun Yokoi, Mitsuko Yui, Ayu Akazawa, Toshihiko Yamashita, Yukako Goto, Akinobu Kakigi, Ken-Ichi Nibu

  Bilateral congenital cholesteatoma (BCC) is rare among congenital cholesteatoma (CC) cases, and bilateral surgery poses a significant psychophysical burden on pediatric patients. Here, we present 2 pediatric cases of BCC that were successfully managed using simultaneous bilateral transcanal endoscopic ear surgery (TEES). The surgical approach provided clear visualization of the middle ear structures, enabling successful cholesteatoma removal with minimal invasiveness and a short operative time. In both cases, follow-up computed tomography showed no recurrence, and pure-tone audiometry results demonstrated good outcomes. Simultaneous bilateral TEES can be a viable option for pediatric BCC, as it reduces patient burden due to its less invasive procedure and short operative time.

  2024年11月, The journal of international advanced otology, 20(6) (6), 540 - 542, 英語, 国際誌

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• 当院におけるアッシャー症候群の検討

  上原 奈津美, 横井 純, 藤田 岳, 西尾 信哉, 柿木 章伸, 松永 達雄, 宇佐美 真一, 丹生 健一

  (一社)日本耳科学会, 2024年10月, 日本耳科学会総会・学術講演会抄録集, 34回, 185 - 185, 日本語


• 神経線維種症II型(NF2)に対して人工内耳植込術を施行した2症例

  赤座 暁子, 藤田 岳, 上原 奈津美, 横井 純, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2024年10月, 日本耳科学会総会・学術講演会抄録集, 34回, 220 - 220, 日本語


• OTOPLANを用いたFLEXsoft人工内耳電極の周波数ミスマッチに関する検討

  横井 純, 藤田 岳, 上原 奈津美, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2024年10月, 日本耳科学会総会・学術講演会抄録集, 34回, 242 - 242, 日本語


• グロムス腫瘍との鑑別に苦慮した側頭骨内顔面神経鞘腫の1例

  渡辺 啓太, 藤田 岳, 横井 純, 柿木 章伸, 上原 奈津美, 丹生 健一

  (一社)日本耳科学会, 2024年10月, 日本耳科学会総会・学術講演会抄録集, 34回, 272 - 272, 日本語


• 長期抗菌薬投与を継続しながら外来治療に移行した頭蓋底骨髄炎の一例

  水本 真理愛, 上原 奈津美, 小池 雪絵, 藤田 岳, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2024年10月, 日本耳科学会総会・学術講演会抄録集, 34回, 295 - 295, 日本語


• 高度難聴と幻聴を伴う統合失調症症例に対する人工内耳装用効果について

  岩城 忍, 横井 純, 上原 奈津美, 藤田 岳, 柿木 章伸, 丹生 健一

  (一社)日本聴覚医学会, 2024年09月, Audiology Japan, 67(5) (5), 448 - 448, 日本語


• Induction of Immunological Antitumor Effects by the Combination of Adenovirus-Mediated Gene Transfer of B7-1 and Anti-Programmed Cell Death-1 Antibody in a Murine Squamous Cell Carcinoma Model.

  Makiko Hara, Sumiyo Saburi, Natsumi Uehara, Takahiro Tsujikawa, Mie Kubo, Tatsuya Furukawa, Masanori Teshima, Hirotaka Shinomiya, Shigeru Hirano, Ken-Ichi Nibu

  BACKGROUND: The goal of this study was to evaluate the antitumor immune effects of B7-1 gene expression in addition to immune checkpoint inhibitor against squamous cell carcinoma. METHODS: A murine SCC cell line, KLN205, was infected with adenoviral vector carrying B7-1 (AdB7). Infected cells were injected subcutaneously in the flanks of DBA/2 mice. Three weeks after implantation, anti-mouse PD-1 antibody (antiPD1) was intraperitonially administrated twice a week for a total of six times. RESULTS: CD80 was significantly overexpressed in the AdB7-infected tumors. IFN-gamma in the T cells in the spleen was significantly increased and tumor size was significantly reduced in the mice treated with both AdB7 and antiPD1. Targeted tumors treated with both AdB7 and antiPD1 exhibited significantly increased cell densities of total immune cells as well as Ki-67+ CD8+ T cells and decreased regulatory T cells. CONCLUSIONS: These results suggest that the B7-1 gene transfer may enhance the antitumor effect of anti-PD1 antibody against SCC.

  2024年03月, Cancers, 16(7) (7), 英語, 国際誌

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• 耳痛を伴わず診断に難渋した中耳放線菌症の1例

  上原 奈津美, 神澤 真紀, 横井 純, 由井 光子, 井之口 豪, 藤田 岳, 柿木 章伸, 丹生 健一

  日本耳鼻咽喉科免疫アレルギー感染症学会, 2024年03月, 日本耳鼻咽喉科免疫アレルギー感染症学会誌, 4(1) (1), 31 - 36, 日本語


• Expression of EGFR and p16 in Squamous Cell Carcinoma of External Auditory Canal.

  Yasuyuki Kajimoto, Hirotaka Shinomiya, Natsumi Uehara, Masanori Teshima, Takeshi Fujita, Akinobu Kakigi, Yoshinori Imamura, Naomi Kiyota, Daisuke Miyawaki, Ryohei Sasaki, Hidehito Kimura, Ken-Ichi Nibu

  The expression of EGFR and p16 in the external auditory canal squamous cell carcinoma (EACSCC) and their impacts on oncological outcomes were not well studied. Seventeen-one consecutive patients who were treated for EACSCC at Kobe University Hospital from 1995 to 2018 were enrolled in this study. The expression of EGFR, and p16 were evaluated and their impacts on oncological outcomes were statistically analyzed. Positive expression of EGFR was observed in 62 patients (87%). Strong positive expression of p16 were observed in 18 patients (32.4%), and weakly positive expression in 30 patients (42.3%), respectively. While the number of the patients with negative EGFR expression were limited, all the surgically treated patients with negative EGFR expression have been alive without disease. In the patients with T3 & T4a EACSCC, prognosis of the patients with positive p16 expression EACSCC tended to be better than those with negative p16 expression. These results suggest the clinical significance of EGFR and p16 expressions in the patients with advanced EACSCC to predict oncological outcomes.

  2024年01月, The Kobe journal of medical sciences, 69(4) (4), E144-E150, 英語, 国内誌

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• 中耳真珠腫による顔面神経麻痺症例の検討

  上原 奈津美, 下田 光, 横井 純, 藤田 岳, 柿木 章伸, 丹生 健一

  日本顔面神経学会, 2024年01月, Facial Nerve Research, 43, 198 - 200, 日本語


• 中耳真珠腫による顔面神経麻痺症例の検討

  上原 奈津美, 下田 光, 横井 純, 藤田 岳, 柿木 章伸, 丹生 健一

  日本顔面神経学会, 2024年01月, Facial Nerve Research, 43, 198 - 200, 日本語


• 当院で定めた成人両側人工内耳手術の選択基準の妥当性について

  岩城 忍, 柿木 章伸, 藤田 岳, 上原 奈津美, 横井 純, 丹生 健一

  (一社)日本聴覚医学会, 2023年12月, Audiology Japan, 66(6) (6), 544 - 551, 日本語


• 外耳道に挿入する耳科内視鏡ロボットの初期位置を決める画像認識手法

  奥家 拓海, 河合 俊和, 西川 敦, 藤田 岳, 上原 奈津美, 山下 俊彦, 鈴木 寿

  (一社)日本コンピュータ外科学会, 2023年11月, 日本コンピュータ外科学会誌, 25(3) (3), 165 - 165, 日本語


• 内視鏡下耳科手術支援ロボットの自律化に向けた深層学習を用いた複数手術器具検出

  丸川 可南子, 松居 和寛, 厚海 慶太, 藤田 岳, 上原 奈津美, 山下 俊彦, 河合 俊和, 鈴木 寿, 谷口 和弘, 平井 宏明, 西川 敦

  (一社)日本コンピュータ外科学会, 2023年11月, 日本コンピュータ外科学会誌, 25(3) (3), 178 - 178, 日本語


• ピボット点を切り替える斜交関節を備えた耳科用内視鏡マニピュレータ

  伊澤 樹哉, 河合 俊和, 藤田 岳, 上原 奈津美, 山下 俊彦, 西川 敦, 鈴木 寿

  (一社)日本コンピュータ外科学会, 2023年11月, 日本コンピュータ外科学会誌, 25(3) (3), 227 - 227, 日本語


• 内視鏡下耳科手術支援ロボット制御に向けた術者の姿勢・動作の画像解析

  西田 周誠, 松居 和寛, 厚海 慶太, 藤田 岳, 上原 奈津美, 山下 俊彦, 河合 俊和, 鈴木 寿, 谷口 和弘, 平井 宏明, 西川 敦

  (一社)日本コンピュータ外科学会, 2023年11月, 日本コンピュータ外科学会誌, 25(3) (3), 242 - 242, 日本語


• 高齢者における人工内耳の装用効果

  岩城 忍, 横井 純, 上原 奈津美, 藤田 岳, 柿木 章伸, 丹生 健一

  (一社)日本聴覚医学会, 2023年09月, Audiology Japan, 66(5) (5), 330 - 330, 日本語


• Oncological outcomes of concurrent chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil for locally advanced squamous cell carcinoma of the external auditory canal: A single-center study.

  Akihiro Yamada, Hirotaka Shinomiya, Natsumi Uehara, Keisuke Iritani, Shun Tatehara, Tatsuya Furukawa, Masanori Teshima, Daisuke Miyawaki, Takeshi Fujita, Akinobu Kakigi, Naomi Kiyota, Ryohei Sasaki, Ken-Ichi Nibu

  BACKGROUND: Squamous cell carcinoma of the external auditory canal (EACSCC) is a rare condition. However, a standard treatment has not yet been established. We retrospectively evaluated the efficacy, adverse events, and feasibility of TPF-CCRT (concomitant chemoradiotherapy with docetaxel, cisplatin, and 5-fluorouracil) in patients with advanced EACSCC. METHODS: Thirty-five consecutive patients with advanced EACSCC (T3, T4) initially treated with TPF-CCRT at Kobe University Hospital were included. T4 diseases with invasion of the brain, internal carotid artery, or internal jugular vein were classified as T4b, and those without these features were classified as T4a. RESULTS: Five-year overall survival rates for T3 and T4 were 100% and 64.2%, respectively. A significant difference was observed between T4a and T4b (82.4% vs. 30%, p = 0.007). Five-year progression-free survival rates of T3, T4a, and T4b were 100%, 68%, and 20% (p = 0.022), respectively. CONCLUSIONS: TPF-CCRT should be considered as a plausible treatment option for advanced EACSCC.

  2023年07月, Head & neck, 英語, 国際誌

  研究論文（学術雑誌）


• Live Imaging of the Dehydration Effect of Isosorbide on the Normal and Hydropic Guinea Pig Cochleae Using Optical Coherence Tomography.

  Akinobu Kakigi, Naoya Egami, Takeshi Fujita, Natsumi Uehara, Jun Yokoi, Kento Koda, Ken-Ichi Nibu, Shinji Yamashita, Tatsuya Yamasoba

  OBJECTIVE: To investigate the isosorbide-induced dehydration effect on the endolymphatic space by intratympanic administration of isosorbide. BACKGROUND: Isosorbide, an osmotic diuretic, is used orally as a typical conservative therapy for Menière's disease (MD) in Japan. The dehydration effect occurs 6 hours after isosorbide ingestion. Intratympanic administration of isosorbide resolves endolymphatic hydrops faster than oral ingestion. In addition, the dehydration effect has never been shown directly. Therefore, we investigated the dehydration effect of intratympanic administration of isosorbide on endolymphatic hydrops using optical coherence tomography. METHODS: We used eight Hartley guinea pigs, divided into normal and hydrops groups. In the hydrops group, the animals underwent endolymphatic sac obliteration to create endolymphatic hydrops. We obtained midmodiolar section images of the cochleae using optical coherence tomography. Then, 50 to 70% isosorbide was sequentially administered intratympanically for 5 minutes, and the apical turn of the cochlea was observed. The relative midmodiolar cross-sectional area of the scala media was calculated for quantitative assessment of the endolymphatic space. RESULTS: In the normal group, 50% isosorbide had a slight but significant dehydration effect on the scala media; at 55 to 70%, Reissner's membrane became flat. In the hydrops group, 50% isosorbide slightly reduced endolymphatic hydrops; 65% flattened Reissner's membrane, and 70% slightly concaved it toward the basilar membrane. CONCLUSION: The results suggest that we could select the concentration of isosorbide according to the stage or severity of MD and relief from acute attack. Intratympanic administration of isosorbide may be a promising treatment for patients with MD.

  2023年07月, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 英語, 国際誌

  研究論文（学術雑誌）


• Genetic variants of cancer‑associated genes analyzed using next‑generation sequencing in small sporadic vestibular schwannomas.

  Takeshi Fujita, Kazuko Sakai, Natsumi Uehara, Yujiro Hoshi, Anjin Mori, Hajime Koyama, Mitsuo Sato, Kazuya Saito, Yasuhiro Osaki, Kazuto Nishio, Katsumi Doi

  Vestibular schwannoma (VS) is the most common tumor of the cerebellopontine angle. Despite the increasing diagnosis of sporadic VS over the past decade, the use of traditional microsurgeries to treat VS has decreased. This is likely a result of the adoption of serial imaging as the most common initial evaluation and treatment strategy, especially for small-sized VS. However, the pathobiology of VSs remains unclear, and elucidating the genetic information of tumor tissue may reveal novel insights. The present study performed a comprehensive genomic analysis of all exons in the key tumor suppressor and oncogenes from 10 small (<15 mm) sporadic VS samples. The evaluations identified NF2, SYNE1, IRS2, APC, CIC, SDHC, BRAF, NUMA1, EXT2, HRAS, BCL11B, MAGI1, RNF123, NLRP1, ASXL1, ADAMTS20, TAF1L, XPC, DDB2 and ETS1 as mutated genes. The current study could not draw any new conclusions about the relationship between VS-related hearing loss and gene mutations; however, it did reveal that NF2 was the most frequently mutated gene in small sporadic VS.

  2023年03月, Oncology letters, 25(3) (3), 121 - 121, 英語, 国際誌

  研究論文（学術雑誌）


• Vestibular function after simultaneous bilateral cochlear implantation in adults.

  Jun Yokoi, Takeshi Fujita, Natsumi Uehara, Shinobu Iwaki, Akinobu Kakigi, Ken-Ichi Nibu

  INTRODUCTION: Binaural hearing enhances speech intelligibility, source localization, and speech comprehension in noisy environments. Although bilateral cochlear implantation (CI) offers several benefits, concerns arise regarding the risk of bilateral postoperative vestibular dysfunction with simultaneous CI. This study aimed to longitudinally evaluate changes in vestibular function in adult patients who underwent simultaneous bilateral CI using minimally invasive electrodes and surgical techniques. METHODS: A retrospective review was conducted on 10 patients who underwent simultaneous bilateral CI at our hospital. Vertigo symptoms and vestibular function test results were examined preoperatively, 1-6 months postoperatively, and 1 year postoperatively. Nystagmus tests, caloric reflex tests, vestibular evoked myogenic potentials (VEMP) measurements, and static stabilometry were performed as vestibular function tests. RESULTS: Although an initial transient decline in vestibular function was observed, no significant long-term decline was observed in the caloric reflex test, ocular VEMP (oVEMP), or cervical VEMP (cVEMP). Moreover, regardless of the presence or absence of abnormalities in caloric reflex, oVEMP, or cVEMP, no significant deterioration was detected in the static stabilometer test. While two patients reported preoperative dizziness, all patients were symptom-free 1 year postoperatively. DISCUSSION: The findings suggest that using current minimally invasive electrodes and surgical techniques in simultaneous bilateral CI leads to temporary vestibular function decline postoperatively. However, most patients experience a recovery in function over time, highlighting the potential safety and efficacy of the procedure. Simultaneous bilateral CI surgery is viable, depending on the patient's auditory needs and burden.

  2023年, Frontiers in neurology, 14, 1304927 - 1304927, 英語, 国際誌

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• 視覚聴覚二重障害を持つ小児の診療における遺伝学的検査の意義

  松永 達雄, 奈良 清光, 務台 英樹, 泉 修司, 山岸 達矢, 堀井 新, 江崎 友子, 土橋 奈々, 中川 尚志, 上原 奈津美, 丹生 健一, 山本 修子, 和佐野 浩一郎, 南 修司郎, 加我 君孝

  日本小児耳鼻咽喉科学会, 2022年06月, 小児耳鼻咽喉科, 43(2) (2), 157 - 157, 日本語


• Case report: Late middle-aged features of FAM111A variant, Kenny-Caffey syndrome type 2-suggestive symptoms during a long follow-up.

  Yuka Ohmachi, Shin Urai, Hironori Bando, Jun Yokoi, Masaaki Yamamoto, Keitaro Kanie, Yuma Motomura, Yasutaka Tsujimoto, Yuriko Sasaki, Yuka Oi, Naoki Yamamoto, Masaki Suzuki, Hiroki Shichi, Genzo Iguchi, Natsumi Uehara, Hidenori Fukuoka, Wataru Ogawa

  Kenny-Caffey syndrome type 2 (KCS2) is an extremely rare skeletal disorder involving hypoparathyroidism and short stature. It has an autosomal dominant pattern of inheritance and is caused by variants in the FAM111 trypsin-like peptidase A (FAM111A) gene. This disease is often difficult to diagnose due to a wide range of more common diseases manifesting hypoparathyroidism and short stature. Herein, we present the case of a 56-year-old female patient with idiopathic hypoparathyroidism and a short stature. The patient was treated for these conditions during childhood. Upon re-evaluating the etiology of KCS2, we suspected that the patient had the disorder because of clinical manifestations, such as cortical thickening and medullary stenosis of the bones, and lack of intellectual abnormalities. Genetic testing identified a heterozygous missense variant in the FAM111A gene (p.R569H). Interestingly, the patient also had bilateral sensorineural hearing loss and vestibular dysfunction, which have been rarely described in previous reports of pediatric cases. In KCS2, inner ear dysfunction due to Eustachian tube dysfunction may progress in middle age or later. However, this disease is now being reported in younger patients. Nevertheless, our case may be instructive of how such cases emerge chronically after middle age. Herein, we also provide a literature review of KCS2.

  2022年, Frontiers in endocrinology, 13, 1073173 - 1073173, 英語, 国際誌

  神戸大学リポジトリ（Kernel）へのリンク


• Facial nerve palsy as the presenting feature of metastatic prostatic cancer in the temporal bone

  Daichi Fujii, Hikari Shimoda, Natsumi Uehara, Takeshi Fujita, Masanori Teshima, Hirotaka Shinomiya, Akinobu Kakigi, Tomoaki Terakawa, Masato Fujisawa, Ken-ichi Nibu

  Informa {UK} Limited, 2021年12月, Acta Oto-Laryngologica Case Reports, 6(1) (1), 1 - 5

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Genetic background in late-onset sensorineural hearing loss patients.

  Natsumi Uehara, Takeshi Fujita, Daisuke Yamashita, Jun Yokoi, Sayaka Katsunuma, Akinobu Kakigi, Shin-Ya Nishio, Ken-Ichi Nibu, Shin-Ichi Usami

  Genetic testing for congenital or early-onset hearing loss patients has become a common diagnostic option in many countries. On the other hand, there are few late-onset hearing loss patients receiving genetic testing, as late-onset hearing loss is believed to be a complex disorder and the diagnostic rate for genetic testing in late-onset patients is lower than that for the congenital cases. To date, the etiology of late-onset hearing loss is largely unknown. In the present study, we recruited 48 unrelated Japanese patients with late-onset bilateral sensorineural hearing loss, and performed genetic analysis of 63 known deafness gene using massively parallel DNA sequencing. As a result, we identified 25 possibly causative variants in 29 patients (60.4%). The present results clearly indicated that various genes are involved in late-onset hearing loss and a significant portion of cases of late-onset hearing loss is due to genetic causes. In addition, we identified two interesting cases for whom we could expand the phenotypic description. One case with a novel MYO7A variant showed a milder phenotype with progressive hearing loss and late-onset retinitis pigmentosa. The other case presented with Stickler syndrome with a mild phenotype caused by a homozygous frameshift COL9A3 variant. In conclusion, comprehensive genetic testing for late-onset hearing loss patients is necessary to obtain accurate diagnosis and to provide more appropriate treatment for these patients.

  2021年11月, Journal of human genetics, 67(4) (4), 223 - 230, 英語, 国際誌

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Phase I trial of concurrent chemoradiotherapy with docetaxel, cisplatin and 5-fluorouracil (TPF-CRT) for locally advanced squamous cell carcinoma of the external auditory canal.

  Hirotaka Shinomiya, Natsumi Uehara, Takeshi Fujita, Daisuke Miyawaki, Yoshinori Imamura, Masanori Teshima, Akinobu Kakigi, Naomi Kiyota, Ryohei Sasaki, Ken-Ichi Nibu

  PURPOSE: Chemoradiotherapy with docetaxel (DOC), cisplatin (CDDP), and 5-FU (TPF-CRT) for locally advanced external auditory canal cancer (EACC) has favorable oncological and functional outcomes. To establish TPF-CRT as a standard of care for advanced EACC, we conducted this study to determine the maximum tolerated (MTD) and recommended dose (RD) of DOC in TPF-CRT for locally advanced EACC. METHODS: To determine the recommended (RD) and maximum tolerated dose (MTD) of DOC in TPF-CRT for EACC, a phase I trial was conducted using the standard "3 + 3" design for maximum dose finding. DOC was administered twice every 4 weeks, CDDP at 70 mg/m2 and 5-FU at 700 mg/m2; patients were also receiving radiotherapy (66 Gy). Eight patients with T3 or T4 EACC were prospectively enrolled. RESULTS: Two patients treated with DOC, 50 mg/m2, and one out of six patients treated with DOC, 40 mg/m2, had dose-limiting toxicities. Prolonged febrile neutropenia was observed in three patients. Grade 3 non-hematological toxicities were observed in only three patients. At study completion, six patients survived, five of whom were disease free. CONCLUSION: The RD and MTD of DOC in TPF-CRT for locally advanced EACC are 40 mg/m2 when doses of CDDP and 5-FU are 70 mg/m2 and 700 mg/m2, respectively.

  2021年07月, European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery, 279(6) (6), 2805 - 2810, 英語, 国際誌

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• New proposal to revise the classification for squamous cell carcinoma of the external auditory canal and middle ear

  H Shinomiya, N Uehara, T Fujita, K Yoshida, Y Imamura, M Teshima, H Kimura, D Miyawaki, A Kakigi, N Kiyota, N Otsuki, R Sasaki, E Kohmura, K Nibu

  The prognosis of patients with advanced squamous cell carcinoma of the external auditory canal and middle ear has been improved by advances in skull base surgery and multidrug chemoradiotherapy during the last two decades. Ninety-five patients with squamous cell carcinoma of the external auditory canal and middle ear who were treated between 1998 and 2017 were enrolled. The number of patients with tumour stages T₁, T₂, T₃ and T₄ was 15, 22, 24 and 34, respectively. Oncological outcomes and prognostic factors were retrospectively investigated. Among patients with T₄ disease, invasion of the brain (p = 0.024), carotid artery (p = 0.049) and/or jugular vein (p = 0.040) were significant predictors of poor prognosis. The five-year overall survival rate of patients with at least one of these factors (T_4b) was significantly lower than that of patients without these factors (T_4a) (25.5 vs 65.5 per cent, p = 0.049). It is proposed that stage T₄ be subclassified into T_4a and T_4b according to the prognostic factors.

  Cambridge University Press (CUP), 2021年04月, The Journal of Laryngology & Otology, 135(4) (4), 297 - 303

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• 当科における顔面神経鞘腫23例の検討

  下田 光, 柿木 章伸, 横井 純, 上原 奈津美, 藤田 岳, 丹生 健一, 橋川 和信, 甲村 英二

  日本顔面神経学会, 2021年03月, Facial Nerve Research, 40, 197 - 201, 日本語


• 当科における顔面神経鞘腫23例の検討

  下田 光, 柿木 章伸, 横井 純, 上原 奈津美, 藤田 岳, 丹生 健一, 橋川 和信, 甲村 英二

  日本顔面神経学会, 2021年03月, Facial Nerve Research, 40, 197 - 201, 日本語


• Reconstruction of the external auditory canal using full-thickness rolled-up skin graft after lateral temporal bone resection for T1 and T2 external auditory canal cancer.

  Takeshi Fujita, Akinobu Kakigi, Natsumi Uehara, Jun Yokoi, Makiko Hara, Hirotaka Shinomiya, Masanori Teshima, Ken-Ichi Nibu

  OBJECTIVE: To present our results of the external auditory canal (EAC) reconstruction procedure using rolled-up full-thickness skin graft with tympanoplasty after lateral temporal bone resection (LTBR) for early-stage EAC carcinoma. PATIENTS AND METHODS: A retrospective review of 15 patients who had undergone LTBR with reconstruction of the EAC for T1 and T2 EAC cancer between 2016 and 2020. RESULTS: Postoperative mean air-bone gap was 30.7 decibel hearing level. Although a few patients experienced chronic granulation, persistent otorrhea, and/or laterization of the tympanic membrane, most patients showed no serious complications related to the EAC reconstruction. CONCLUSION: EAC reconstruction using a full-thickness skin graft in combination with tympanoplasty is useful for minimizing the hearing loss, maintaining the cosmetic appearance, and facilitating the observation into the ear cavity.

  2021年01月, Auris, nasus, larynx, 英語, 国際誌

  研究論文（学術雑誌）


• Live imaging and functional changes of the inner ear in an animal model of Meniere's disease.

  Akinobu Kakigi, Naoya Egami, Natsumi Uehara, Takeshi Fujita, Ken-Ichi Nibu, Shinji Yamashita, Tatsuya Yamasoba

  The symptoms of Meniere's disease (MD) are generally considered to be related to endolymphatic hydrops (EH). There are many recent reports supporting the possibility that vasopressin (VP) is closely linked to the formation of EH in Meniere's disease. Based on this, we developed a clinically relevant animal model of Meniere's disease in which a VP type 2 receptor agonist was administered after electrocauterization of the endolymphatic sac. We report live imaging of the internal structure, and functional changes of the inner ear after electrocauterization of the endolymphatic sac and administration of a VP type 2 receptor agonist. In this model, the development of EH was visualized in vivo using optical coherence tomography, there was no rupture of Reissner's membrane, and low-tone hearing loss and vertiginous attacks were observed. This study suggested that acute attacks are caused by the abrupt development of EH. This is the first report of live imaging of the development of EH induced by the administration of a VP type 2 receptor agonist.

  2020年07月, Scientific reports, 10(1) (1), 12271 - 12271, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Cover Image

  Natsumi Uehara, Naoki Otsuki, Mie Kubo, Junko Kitamoto, Yasutaka Kojima, Masanori Teshima, Hirotaka Shinomiya, Toshiro Shirakawa, Ken‐ichi Nibu

  2020年06月, Cancer Reports

  研究論文（学術雑誌）


• Clinical Characteristics and In Vitro Analysis of MYO6 Variants Causing Late-Onset Progressive Hearing Loss.

  Shin-Ichiro Oka, Timothy F Day, Shin-Ya Nishio, Hideaki Moteki, Maiko Miyagawa, Shinya Morita, Shuji Izumi, Tetsuo Ikezono, Satoko Abe, Jun Nakayama, Misako Hyogo, Nobuhiko Okamoto, Natsumi Uehara, Chie Oshikawa, Shin-Ichiro Kitajiri, Shin-Ichi Usami

  MYO6 is known as a genetic cause of autosomal dominant and autosomal recessive inherited hearing loss. In this study, to clarify the frequency and clinical characteristics of hearing loss caused by MYO6 gene mutations, a large-scale genetic analysis of Japanese patients with hearing loss was performed. By means of massively parallel DNA sequencing (MPS) using next-generation sequencing for 8074 Japanese families, we found 27 MYO6 variants in 33 families, 22 of which are novel. In total, 2.40% of autosomal dominant sensorineural hearing loss (ADSNHL) in families in this study (32 out of 1336) was found to be caused by MYO6 mutations. The present study clarified that most cases showed juvenile-onset progressive hearing loss and their hearing deteriorated markedly after 40 years of age. The estimated hearing deterioration was found to be 0.57 dB per year; when restricted to change after 40 years of age, the deterioration speed was accelerated to 1.07 dB per year. To obtain supportive evidence for pathogenicity, variants identified in the patients were introduced to MYO6 cDNA by site-directed mutagenesis and overexpressed in epithelial cells. They were then assessed for their effects on espin1-induced microvilli formation. Cells with wildtype myosin 6 and espin1 co-expressed created long microvilli, while co-expression with mutant constructs resulted in severely shortened microvilli. In conclusion, the present data clearly showed that MYO6 is one of the genes to keep in mind with regard to ADSNHL, and the molecular characteristics of the identified gene variants suggest that a possible pathology seems to result from malformed stereocilia of the cochlear hair cells.

  2020年03月, Genes, 11(3) (3), 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Prevalence and clinical features of hearing loss caused by EYA4 variants.

  Jun Shinagawa, Hideaki Moteki, Shin-Ya Nishio, Kenji Ohyama, Koshi Otsuki, Satoshi Iwasaki, Shin Masuda, Chie Oshikawa, Yumi Ohta, Yasuhiro Arai, Masahiro Takahashi, Naoko Sakuma, Satoko Abe, Yuika Sakurai, Hirofumi Sakaguchi, Takashi Ishino, Natsumi Uehara, Shin-Ichi Usami

  Variants in the EYA4 gene are known to lead to autosomal dominant non-syndromic hereditary hearing loss, DFNA10. To date, 30 variants have been shown to be responsible for hearing loss in a diverse set of nationalities. To better understand the clinical characteristics and prevalence of DFNA10, we performed genetic screening for EYA4 mutations in a large cohort of Japanese hearing loss patients. We selected 1,336 autosomal dominant hearing loss patients among 7,408 unrelated Japanese hearing loss probands and performed targeted genome enrichment and massively parallel sequencing of 68 target genes for all patients. Clinical information of cases with mutations in EYA4 was gathered and analyzed from medical charts. Eleven novel EYA4 variants (three frameshift variants, three missense variants, two nonsense variants, one splicing variant, and two single-copy number losses) and two previously reported variants were found in 12 probands (0.90%) among the 1,336 autosomal dominant hearing loss families. The audiometric configuration of truncating variants tends to deteriorate for all frequencies, whereas that of non-truncating variants tends to show high-frequency hearing loss, suggesting a new correlation between genotype and phenotype in DFNA10. The rate of hearing loss progression caused by EYA4 variants was considered to be 0.63 dB/year, as found in this study and previous reports.

  2020年02月, Scientific reports, 10(1) (1), 3662 - 3662, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Oncolytic effect of Midkine promoter-based conditionally replicating adenoviruses expressing EGFR siRNA in head and neck squamous cancer cell line T891

  Natsumi Uehara, Naoki Otsuki, Mie Kubo, Junko Kitamoto, Yasutaka Kojima, Masanori Teshima, Hirotaka Shinomiya, Toshiro Shirakawa, Ken-ichi Nibu

  2020年02月, Cancer Reports, 3(3) (3), 英語

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• A case of extrusion of the internal magnet of a cochlear implant after MRI

  Masahiro Matsumoto, Hideaki Ogita, Ayana Komurasaki, Koji Ushiro, Kiyohiro Fujino, Akinobu Kakigi, Shinobu Iwaki, Natsumi Uehara, Juichi Ito

  Society of Practical Otolaryngology, 2020年, Practica Oto-Rhino-Laryngologica, 113(4) (4), 235 - 240, 日本語

  研究論文（学術雑誌）


• Traumatic perilymphatic fistula caused by a camellia branch: A case report

  Natsumi Uehara, Takeshi Fujita, Ken-ichi Nibu, Akinobu Kakigi

  2020年, ACTA OTO-LARYNGOLOGICA CASE REPORTS, 5(1) (1), 101 - 105, 英語

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Clinical management for T1 and T2 external auditory canal cancer.

  Hirotaka Shinomiya, Natsumi Uehara, Masanori Teshima, Akinori Kakigi, Naoki Otsuki, Ken-Ichi Nibu

  OBJECTIVE: The purpose of this study was to clarify the impact of superficial parotidectomy and postoperative radiotherapy (PORT) for the surgical treatment of early stage squamous cell carcinoma (SCC) in external auditory canal (EAC). MATERIALS AND METHODS: Thirty-seven patients with T1 (n = 14) or T2 (n = 19) SCC in EAC treated between 2000 and 2016 at Kobe University Hospital were enrolled in this study. Thirty-three patients were operated with sleeve resection or lateral temporal bone resection. RESULTS: The 5-year overall survival and disease-specific survival rates were 95% and 100%, respectively. Surgical margin was positive in 4 patients, who were treated by PORT and have been alive without disease. Prophylactic superficial parotidectomy was simultaneously performed at the time of initial surgery in 15 patients, in whom no lymph node (LN) metastasis was observed. Among the other 22 patients, regional recurrence in parotid LN was observed in one patient, who was successfully salvaged by total parotidectomy. Potential parotid lymph node metastasis rates of T1 and T2 SCC in EAC was 0% (0/14) and 5% (1/19) respectively. CONCLUSIONS: Complete resection without positive surgical margins is essential for the treatment of the patients with T1 and T2 ear cancers. Prophylactic superficial parotidectomy or neck dissection is not mandatory for T1 and T2 diseases, as long as precisely extent of disease is assessed preoperatively. PORT should be performed for the patients with positive surgical margins. LEVELS OF EVIDENCE: 4.

  2019年10月, Auris, nasus, larynx, 46(5) (5), 785 - 789, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Endocytosis of CF in marginal cells of stria vascularis regulated by ROCK and MLCK signaling cascade, but not G-proteins.

  Akinobu Kakigi, Teruhiko Okada, Taizo Takeda, Natsumi Uehara, Ken-Ichi Nibu

  Objective The endocytosis of cationized feritin (CF) via a clathrin-mediated pathway is regulated by a signaling network. Marginal cells showed the active endocytosis of CF via a clathrin-mediated pathway. The internalization of receptors through this clathrin-mediated pathway is an important regulatory event in signal transduction. Numerous kinases are involved in endocytosis, and each endocytic route is subjected to high-order regulation by cellular signaling mechanisms. In this study, we investigated whether ROCK and MLCK signaling cascades and G-proteins regulate the endocytosis of CF in marginal cells of the stria vascularis. Methods CF was infused into the cochlear duct with pertussis toxin (PTX),Clostridium botulinum C3 toxin (BTX), guanosine(g-thio)-triphosphate (GTP-γS), ML-7, Y-27632. Endocytic activity was measured at 30 min after the start of infusion under an electron microscope. Results In marginal cells, CF was internalized via a clathrin-mediated pathway that depends on F-actin and microtubules (MT). Its processes were controlled by myosin light chain kinase (MLCK) and Rho-associated kinase (ROCK), but not affected by G-protein-coupled receptor (GPCR) or the RhoA signaling cascade. Conclusion Our previous study showed that the main endocytotic pathway of microperoxidase (MPO) did not depend on the Rho/ROCK molecular switch or actin/myosin motor system, but was mainly regulated by the RhoA signaling cascade. The present study results indicate that these signaling cascades regulating CF internalization completely differ from the cascades for MPO internalization.

  2019年10月, Auris, nasus, larynx, 46(5) (5), 790 - 796, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Mutational Spectrum and Clinical Features of Patients with LOXHD1 Variants Identified in an 8074 Hearing Loss Patient Cohort.

  Karuna Maekawa, Shin-Ya Nishio, Satoko Abe, Shin-Ichi Goto, Yohei Honkura, Satoshi Iwasaki, Yukihiko Kanda, Yumiko Kobayashi, Shin-Ichiro Oka, Mayuri Okami, Chie Oshikawa, Naoko Sakuma, Hajime Sano, Masayuki Shirakura, Natsumi Uehara, Shin-Ichi Usami

  Variants of the LOXHD1 gene, which are expressed in hair cells of the cochlea and vestibule, have been reported to cause a progressive form of autosomal recessive non-syndromic hereditary hearing loss, DFNB77. In this study, genetic screening was conducted on 8074 Japanese hearing loss patients utilizing massively parallel DNA sequencing to identify individuals with LOXHD1 variants and to assess their phenotypes. A total of 28 affected individuals and 21 LOXHD1 variants were identified, among which 13 were novel variants. A recurrent variant c.4212 + 1G > A, only reported in Japanese patients, was detected in 18 individuals. Haplotype analysis implied that this variation occurred in a mutational hot spot, and that multiple ancestors of Japanese population had this variation. Patients with LOXHD1 variations mostly showed early onset hearing loss and presented different progression rates. We speculated that the varying severities and progression rates of hearing loss are the result of environmental and/or other genetic factors. No accompanying symptoms, including vestibular dysfunction, with hearing loss were detected in this study. Few studies have reported the clinical features of LOXHD1-gene associated hearing loss, and this study is by far the largest study focused on the evaluation of this gene.

  2019年09月, Genes, 10(10) (10), 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Frequency and clinical features of hearing loss caused by STRC deletions.

  Yoh Yokota, Hideaki Moteki, Shin-Ya Nishio, Tomomi Yamaguchi, Keiko Wakui, Yumiko Kobayashi, Kenji Ohyama, Hiromitsu Miyazaki, Rina Matsuoka, Satoko Abe, Kozo Kumakawa, Masahiro Takahashi, Hirofumi Sakaguchi, Natsumi Uehara, Takashi Ishino, Tomoki Kosho, Yoshimitsu Fukushima, Shin-Ichi Usami

  2019年03月, Scientific reports, 9(1) (1), 4408 - 4408, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Mucosa-associated lymphoid tissue lymphoma of parotid gland with involvement of subglottis and trachea

  NUehara, NOtsuki, HShinomiya, KUehara, KNibu

  2018年12月, ACTA OTO-LARYNGOLOGICA CASE REPORTS, 英語

  [査読有り]

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• 研究者の最新動向 制限増殖型アデノウイルスベクターを用いた頭頸部癌に対する新たな治療法の開発

  上原奈津美, 丹生健一

  2018年10月, Precision Medicine, 1(1号) (1号), 93 - 97, 日本語

  [査読有り][招待有り]

  研究論文（学術雑誌）


• Adenovirus-mediated transfer of HPV 16 E6/E7 antisense RNA combined with cisplatin inhibits cellular growth and induces apoptosis in HPV-positive head and neck cancer cells.

  Yasutaka Kojima, Naoki Otsuki, Mie Kubo, Junko Kitamoto, Eri Takata, Hiroki Saito, Kyoko Kosaka, Naoya Morishita, Natsumi Uehara, Toshiro Shirakawa, Ken-Ich Nibu

  Human papillomavirus (HPV) infection has been identified as an etiologic factor of head and neck cancers (HNCs). We explored the potential use of antisense HPV RNA transcripts for gene therapy and its effect in combination with cisplatin (CDDP) for HPV-positive HNCs. We introduced the antisense RNA transcripts of the E6 and E7 genes of HPV type 16 into UM-SCC-47 cells harboring HPV 16 and YCU-T892 cells that were HPV-negative using a recombinant adenoviral vector, Ad-E6/E7-AS. We then analyzed the effects of the introduction of Ad-E7-AS on cell and tumor growth and the synergistic effect with CDDP in vitro and in vivo. After infection of Ad-E6/E7-AS, the cellular growth of UM-SCC-47 cells were suppressed, but not that of YCU-T892 cells. E7 protein expression was suppressed, and p53 and pRb protein expression increased after infection of Ad-E7-AS. Cell growth and tumorigenicity were greatly suppressed in combination with CDDP compared with Ad-E7-AS or CDDP treatment alone in vitro. Ad-E7-AS combined with CDDP treatment significantly reduced the volumes of established subcutaneous tumors. Transfection with HPV 16 E7 antisense RNA combined with CDDP treatment might be a potentially useful approach to the therapy of HPV 16-positive HNC.

  2018年10月, Cancer gene therapy, 25(9-10) (9-10), 274 - 283, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• POU4F3 mutation screening in Japanese hearing loss patients: Massively parallel DNA sequencing-based analysis identified novel variants associated with autosomal dominant hearing loss

  Tomohiro Kitano, Maiko Miyagawa, Shin-ya Nishio, Hideaki Moteki, Kiyoshi Oda, Kenji Ohyama, Hiromitsu Miyazaki, Hiroshi Hidaka, Ken-ichi Nakamura, Takaaki Murata, Rina Matsuoka, Yoko Ohta, Nobuhiro Nishiyama, Kozo Kumakawa, Sakiko Furutate, Satoshi Iwasaki, Takechiyo Yamada, Yumi Ohta, Natsumi Uehara, Yoshihiro Noguchi, Shin-ichi Usami

  2017年05月, PLOS ONE, 12(5) (5), 英語

  研究論文（学術雑誌）

  神戸大学リポジトリ（Kernel）へのリンク


• Isosorbide-Induced Decompression Effect on the Scala Media: Participation of Plasma Osmolality and Plasma Arginine Vasopressin.

  Taizo Takeda, Setsuko Takeda, Natsumi Uehara, Shungaku Yanagisawa, Tatsuya Furukawa, Ken-Ichi Nibu, Akinobu Kakigi

  OBJECTIVE: The correlation between the isosorbide-induced decompression effect on the endolymphatic space and plasma osmolality (p-OSM) or plasma arginine vasopressin (p-AVP) was investigated on comparing two different dosages of isosorbide (2.8 and 1.4 g/kg) to elucidate why the decompression effect is delayed with a large dose of isosorbide. MATERIALS AND METHODS: Two experiments were performed using 80 guinea pigs. Experiment 1 was designed to morphologically investigate the sequential influence of the oral intake of 1.4- and 2.8-g/kg doses of isosorbide on the endolymphatic volume. The animals used were 50 guinea pigs (control: 10, experimental: 40). All animals underwent surgical obliteration of the endolymphatic sac of the left ear. One month after the surgery, control animals were sacrificed 3 hours after the intake of distilled water, and experimental animals were sacrificed 3 and 6 hours after the isosorbide intake. All of the left temporal bone served for the quantitative assessment of changes in the endolymphatic space, and the cross-sectional area of the scala media was measured from the mid-modiolar sections of the cochlea.Experiment 2 was designed to investigate changes in p-OSM and p-AVP levels 3 hours after the oral intake of isosorbide. Animals used were 15 guinea pigs (control: 5, experimental: 10). The control group received the oral administration of distilled water (4 ml/kg), and the experimental animals were subdivided into two groups consisting of 10 animals each by the dosage of isosorbide (1.4 or 2.8 g/kg). All animals were sacrificed for the measurement of p-OSM and p-AVP concentrations 3 hours after the intake of water or 70% isosorbide solution. RESULTS: Morphologically, an isosorbide-induced decompression effect was noted in animals with both 1.4- and 2.8-g/kg doses of isosorbide. According to the regression analysis, however, the volumetric decrease of the endolymphatic space was more evident in cases with the small dose (1.4 g/kg) 3 hours after the intake (analysis of covariance [ANCOVA], p < 0.001). Six hours after, the decompression effect was significantly greater in cases with the large dose (2.8 g/kg) (ANCOVA, p < 0.001).Isosorbide intake caused a rise in p-OSM levels dose-dependently. The Cochran-Cox test revealed that the differences in the mean values among control and isosorbide groups were significant (p < 0.01). Regarding the p-AVP level, a significant increase was evident in cases with the large dose (2.8 g/kg) (p < 0.01, Cochran-Cox test), and not in cases with the small dose (1.4 g/kg). CONCLUSION: An isosorbide-induced decompression effect of the endolymphatic space was evident in spite of two different dosages of isosorbide (2.8 and 1.4 g/kg). Three hours after the isosorbide intake, however, the decompression effect was more marked in the group with the small dose (1.4 g/kg). Since significant rises in p-OSM and p-AVP were evident in the group with the large dose, this early rise of p-AVP due to dehydration seems to be the major reason for the delayed decompression effect in cases with a large isosorbide intake.

  2017年04月, Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology, 38(4) (4), 599 - 605, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• 内耳障害を来した中耳非結核性抗酸菌症の1例

  上原奈津美, 後藤友佳子, 山本沙織

  2015年12月, Otology Japan, 25(5号) (5号), 823 - 827, 日本語

  [査読有り]

  研究論文（学術雑誌）


• A high-fat diet delays age-related hearing loss progression in C57BL/6J mice.

  Takeshi Fujita, Daisuke Yamashita, Natsumi Uehara, Go Inokuchi, Shingo Hasegawa, Naoki Otsuki, Ken-ichi Nibu

  OBJECTIVE: Age-related hearing loss (AHL), or presbycusis, is the most common sensory disorder among the elderly. We used C57BL/6J mice as an AHL model to determine a possible association between AHL and a high-fat diet (HFD). METHODS: Forty C57BL/6J mice were randomly assigned to a control or HFD group. Each group was divided into the following subgroups: 1-, 3-, 5- and 12-month groups (HFD, n = 5/subgroup; control, n = 5/subgroup). Nine CBA/N-slc mice were also used as a 12-month control (n = 5) or 12-month HFD (n = 4) group. The mice were fed a HFD or normal (control) diet throughout this study. Hearing function was evaluated at 1, 3, 5 and 12 months using auditory evoked brainstem responses (ABRs). Spiral ganglion cells (SGCs) were also counted. RESULTS: The elevation of ABR thresholds (at 4 and 32 kHz) at 3 and 5 months was significantly suppressed in the HFD group compared with the control groups for C57BL/6J mice. After 12 months, the elevation of ABR thresholds was significantly suppressed in the HFD group at all frequencies for C57BL/6J mice. In contrast, CBA/N-slc mice displayed opposite outcomes, as ABR thresholds at all frequencies at 12 months were significantly elevated in the HFD group compared with the control group. For the C57BL/6J mice at 12 months, SGC numbers significantly decreased in all parts of the cochleae in the control group compared with the HFD groups. In contrast, for the CBA/N-slc mice, SGC numbers significantly decreased, particularly in the upper parts of the cochleae in the HFD group compared with the control groups. CONCLUSIONS: The elevation in ABR thresholds and SGC loss associated with aging in the HFD-fed C57BL/6J mice were significantly suppressed compared with those in the normal diet-fed mice. These results suggest that HFD delays AHL progression in the C57B/6J mice.

  2015年, PloS one, 10(1) (1), e0117547, 英語, 国際誌

  [査読有り]

  神戸大学リポジトリ（Kernel）へのリンク


• New MT-ND6 and NDUFA1 mutations in mitochondrial respiratory chain disorders.

  Natsumi Uehara, Masato Mori, Yoshimi Tokuzawa, Yosuke Mizuno, Shunsuke Tamaru, Masakazu Kohda, Yohsuke Moriyama, Yutaka Nakachi, Nana Matoba, Tetsuro Sakai, Taro Yamazaki, Hiroko Harashima, Kei Murayama, Keisuke Hattori, Jun-Ichi Hayashi, Takanori Yamagata, Yasunori Fujita, Masafumi Ito, Masashi Tanaka, Ken-Ichi Nibu, Akira Ohtake, Yasushi Okazaki

  OBJECTIVE: Mitochondrial respiratory chain disorder (MRCD) is an intractable disease of infants with variable clinical symptoms. Our goal was to identify the causative mutations in MRCD patients. METHODS: The subjects were 90 children diagnosed with MRCD by enzyme assay. We analyzed whole mitochondrial DNA (mtDNA) sequences. A cybrid study was performed in two patients. Whole exome sequencing was performed for one of these two patients whose mtDNA variant was confirmed as non-pathogenic. RESULTS: Whole mtDNA sequences identified 29 mtDNA variants in 29 patients (13 were previously reported, the other 13 variants and three deletions were novel). The remaining 61 patients had no pathogenic mutations in their mtDNA. Of the 13 patients harboring unreported mtDNA variants, we excluded seven variants by manual curation. Of the remaining six variants, we selected two Leigh syndrome patients whose mitochondrial enzyme activity was decreased in their fibroblasts and performed a cybrid study. We confirmed that m.14439G>A (MT-ND6) was pathogenic, while m.1356A>G (mitochondrial 12S rRNA) was shown to be a non-pathogenic polymorphism. Exome sequencing and a complementation study of the latter patient identified a novel c.55C>T hemizygous missense mutation in the nuclear-encoded gene NDUFA1. INTERPRETATION: Our results demonstrate that it is important to perform whole mtDNA sequencing rather than only typing reported mutations. Cybrid assays are also useful to diagnose the pathogenicity of mtDNA variants, and whole exome sequencing is a powerful tool to diagnose nuclear gene mutations as molecular diagnosis can provide a lead to appropriate genetic counseling.

  2014年05月, Annals of clinical and translational neurology, 1(5) (5), 361 - 9, 英語, 国際誌

  [査読有り]

  研究論文（学術雑誌）


• Vestibular dysfunction and compensation after removal of acoustic neuroma.

  Natsumi Uehara, Hitoshi Tanimoto, Tasuku Nishikawa, Kiyoshi Doi, Sayaka Katsunuma, Hidehito Kimura, Eiji Kohmura, Ken-ichi Nibu

  OBJECTIVE: To evaluate vestibular function after unilateral acoustic neuroma surgery via a retrosigmoid approach. METHODS: Thirty-eight patients were tested using caloric irrigation, static posturography, and the Dizziness Handicap Inventory (DHI) before, and one week to nine months after surgery. RESULTS: Twenty-six patients were categorized as a response group and 12 as a no-response group on the basis of preoperative caloric irrigation findings. The posturographic parameters and DHI scores at one week after surgery showed significant deterioration in the response group, but not in the no-response group. However, they recovered to the preoperative baseline at 3 months after surgery. The posturographic parameters and DHI scores for older patients tended to be worse than those for younger patients at 6 and 9 months after surgery. CONCLUSION: Patients in whom caloric responses are retained preoperatively show a temporary disturbance of balance after removal of acoustic neuroma. Disequilibrium after surgery ameliorates to the preoperative baseline within three months due to vestibular compensation, regardless of preoperative vestibular function. It is possible that poorer vestibular compensation may facilitate incomplete recovery in older patients after surgery.

  2011年, Journal of vestibular research : equilibrium & orientation, 21(5) (5), 289 - 95, 英語, 国際誌

  [査読有り]

• 耳科手術支援ロボットの開発

  藤田 岳, 上原 奈津美, 山下 俊彦, 西川 敦, 河合 俊和, 鈴木 寿, 横井 純, 柿木 章伸, 丹生 健一

  頭頸部外科領域にロボット手術が保険適応となり, 耳鼻咽喉科医にとってもロボット手術は身近な存在となってきた. しかし泌尿器・消化器領域で発展してきた手術ロボットを, そのまま耳や鼻の手術に応用することはまだ難しい. 私達は経外耳道的内視鏡下耳科手術 (Trans-canal Endoscopic Ear Surgery: TEES) を支援するロボットの研究・開発を複数の大学の工学部と共同で行っている. 手術ロボットの研究を通して, 自分たちの手術の特徴や問題点を改めて見直す機会が得られている. 本稿では, これまでの耳科手術用ロボットや内視鏡保持ロボットについて概略を述べ, 現在研究中の TEES 支援ロボットのコンセプトと試作機について述べる. また, 将来ロボット自身が自律的に手術を行うことを目標とした, ロボットの自律レベル向上に向けた研究についても紹介する.

  日本耳鼻咽喉科頭頸部外科学会, 2023年03月20日, 日本耳鼻咽喉科頭頸部外科学会会報, 126(3) (3), 181 - 184, 日本語, 国内誌, 国際共著していない


• 遅発性感音難聴患者における聴力型から見た遺伝学的背景の検討

  上原 奈津美, 藤田 岳, 横井 純, 西尾 信哉, 宇佐美 真一, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2022年10月, 日本耳科学会総会・学術講演会抄録集, 32回, 138 - 138, 日本語


• ミトコンドリアDNA7445A>G変異による難聴及び掌蹠角化症を認めた2例

  稲田 幸歩, 上原 奈津美, 横井 純, 藤田 岳, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2022年10月, 日本耳科学会総会・学術講演会抄録集, 32回, 170 - 170, 日本語


• 中耳髄膜腫の一例

  庄司 夢, 上原 奈津美, 横井 純, 藤田 岳, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2022年10月, 日本耳科学会総会・学術講演会抄録集, 32回, 309 - 309, 日本語


• 経外耳道的内視鏡下手術(TEES)で摘出し得たグロムス腫瘍症例

  小西池 佑一, 藤田 岳, 横井 純, 上原 奈津美, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2022年10月, 日本耳科学会総会・学術講演会抄録集, 32回, 310 - 310, 日本語


• 手術とデノスマブによるアジュバント療法を施行した側頭骨骨巨細胞腫の1例

  横井 純, 柿木 章伸, 上原 奈津美, 藤田 岳, 丹生 健一

  (一社)日本耳科学会, 2022年10月, 日本耳科学会総会・学術講演会抄録集, 32回, 393 - 393, 日本語


• 成人における両側人工内耳手術の適応に関する検討(第一報)

  岩城 忍, 横井 純, 上原 奈津美, 藤田 岳, 柿木 章伸, 丹生 健一

  (一社)日本聴覚医学会, 2022年09月, Audiology Japan, 65(5) (5), 430 - 430, 日本語


• 内視鏡下耳科手術支援ロボット制御のための深層学習を用いた手術器具セグメンテーション

  堀ノ内 琢磨, 松居 和寛, 厚海 慶太, 藤田 岳, 上原 奈津美, 山下 俊彦, 河合 俊和, 鈴木 寿, 谷口 和弘, 平井 宏明, 西川 敦

  (一社)日本コンピュータ外科学会, 2022年06月, 日本コンピュータ外科学会誌, 24(2) (2), 126 - 126, 日本語


• 側頭骨内に広範に破壊・浸潤を来した若年成人顔面神経鞘腫の1例-根治切除の戦略と課題-

  下田光, 柿木章伸, 横井純, 上原奈津美, 藤田岳, 橋川和信, 木村英仁, 丹生健一

  2022年, Facial Nerve Research Japan, 41


• 外耳道内を直動する内視鏡テレオペレーションシステム

  伊澤 樹哉, 河合 俊和, 藤田 岳, 上原 奈津美, 西川 敦, 鈴木 寿

  By introducing locally operated surgical assistant robots in a sterilized area, a surgeon can perform safe and accurate robotically assisted transcanal endoscopic ear surgery. A new endoscopic teleoperation system with linear motion that can be used by the surgeon’s hand in the external auditory canal has been developed. The manipulator system consists of a master device using a ratchet gear and a follower device using a constant spring for safety. The manually control when the power is shut off to the follower motor leads to high speed drive outside. The motion scaling control can produce precise drive in the ear canal. Task required time and position error are shorter in reduced scale.

  一般社団法人 日本機械学会, 2022年, ロボティクス・メカトロニクス講演会講演概要集, 2022, 1A1-S06, 日本語


• 超音波モータとギアレス直流モータで構成する耳科手術支援内視鏡直動システム

  横山 健太, 河合 俊和, 西川 敦, 藤田 岳, 上原 奈津美, 鈴木 寿

  By introducing locally operated surgical assistant robots in a sterilized area, a surgeon can perform safe and accurate robotically assisted endoscopic ear surgery. A new locally operated endoscope manipulator with dual linear motion that can be used by the surgeon’s left hand during endoscopic ear surgery has been developed. The linear motion of the endoscope is driven by selectable two motors. An ultrasonic motor using a rack and pinion with a linear guide leads to precise and safe motion in the ear canal. A gearless DC motor using a belt pulley with the shared linear guide leads to high speed motion outside. The dimensions of the linear motion device are 155 mm * 282 mm * 77 mm.

  一般社団法人 日本機械学会, 2022年, ロボティクス・メカトロニクス講演会講演概要集, 2022, 1A1-S02, 日本語


• 一側性聴神経腫瘍症例における蝸牛内のMRI信号強度

  藤田 岳, 横井 純, 上原 奈津美, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2021年10月, 日本耳科学会総会・学術講演会抄録集, 31回, 187 - 187, 日本語


• 当科におけるグロムス腫瘍18例の治療方針の検討

  横井 純, 藤田 岳, 上原 奈津美, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2021年10月, 日本耳科学会総会・学術講演会抄録集, 31回, 199 - 199, 日本語


• ミトコンドリアDNA3243A>G変異によるミトコンドリア病の1家系

  上原 奈津美, 横井 純, 藤田 岳, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2021年10月, 日本耳科学会総会・学術講演会抄録集, 31回, 265 - 265, 日本語


• キヌタ骨が乳突洞内に脱出した外傷性耳小骨離断の1例

  遠藤 侑未, 上原 奈津美, 横井 純, 藤田 岳, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2021年10月, 日本耳科学会総会・学術講演会抄録集, 31回, 385 - 385, 日本語


• 高齢者における人工内耳装用後の聴取成績の経過について

  岩城 忍, 横井 純, 上原 奈津美, 藤田 岳, 柿木 章伸, 丹生 健一

  (一社)日本聴覚医学会, 2021年09月, Audiology Japan, 64(5) (5), 466 - 466, 日本語


• 色素性乾皮症の聴力障害

  藤田 岳, 上原 奈津美, 柿木 章伸, 丹生 健一

  日本小児耳鼻咽喉科学会, 2021年06月, 小児耳鼻咽喉科, 42(2) (2), 163 - 163, 日本語


• Pseudo-dominant遺伝形式を示すGJB2遺伝子変異が検出された先天性難聴児の1例

  橋本 裕依子, 上原 奈津美, 岩城 忍, 藤田 岳, 柿木 章伸, 丹生 健一

  日本小児耳鼻咽喉科学会, 2021年06月, 小児耳鼻咽喉科, 42(2) (2), 190 - 190, 日本語


• 好酸球中耳炎の中耳貯留液における脂質メディエーターの解析

  藤田 岳, 横井 純, 上原 奈津美, 井之口 豪, 後藤 友佳子, 土井 勝美, 柿木 章伸, 篠原 正和, 丹生 健一

  (一社)日本耳鼻咽喉科頭頸部外科学会, 2021年04月, 日本耳鼻咽喉科学会会報, 124(4) (4), 605 - 605, 日本語


• ミトコンドリア病による成人難聴症例の検討

  上原 奈津美, 藤田 岳, 横井 純, 柿木 章伸, 丹生 健一

  (一社)日本耳鼻咽喉科頭頸部外科学会, 2021年04月, 日本耳鼻咽喉科学会会報, 124(4) (4), 639 - 639, 日本語


• 外側側頭骨切除術時に皮膚管を用いた一期的外耳道・伝音再建

  藤田 岳, 横井 純, 上原 奈津美, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2020年11月, 日本耳科学会総会・学術講演会抄録集, 30回, 164 - 164, 日本語


• 色素性乾皮症の聴力障害とモデルマウスの聴覚解析

  藤田 岳, 上原 奈津美, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2019年10月, 日本耳科学会総会・学術講演会抄録集, 29回, 471 - 471, 日本語


• 両側同時人工内耳植え込み術を施行した両側内耳破壊の一症例

  岩城 忍, 上原 奈津美, 藤田 岳, 柿木 章伸, 丹生 健一

  (一社)日本聴覚医学会, 2019年10月, Audiology Japan, 62(5) (5), 502 - 502, 日本語


• MRI検査後に人工内耳インプラント磁石の変位・排出をきたした1症例

  柿木 章伸, 上原 奈津美, 丹生 健一

  耳鼻咽喉科臨床学会, 2019年06月, 耳鼻咽喉科臨床 補冊, (補冊154) (補冊154), 74 - 74, 日本語


• 急速に進行し半規管瘻孔をきたした小児後天性真珠腫症例のCT値による検討

  上原 奈津美, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2018年09月, Otology Japan, 28(4) (4), 574 - 574, 日本語


• 同時に手術を施行した両側先天性真珠腫の一例

  山下 俊彦, 上原 奈津美, 吉田 亜由, 後藤 友佳子, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2018年09月, Otology Japan, 28(4) (4), 580 - 580, 日本語


• 椿の枝で受傷した外傷性外リンパ瘻の1例

  上原 奈津美, 柿木 章伸, 丹生 健一

  耳鼻咽喉科臨床学会, 2018年06月, 耳鼻咽喉科臨床 補冊, (補冊153) (補冊153), 70 - 70, 日本語


• 先天性真珠腫術後の再形成性真珠腫により外耳道後壁が広汎に破壊された1例

  横井 純, 上原 奈津美, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2017年10月, Otology Japan, 27(4) (4), 423 - 423, 日本語


• 難聴を契機に診断されたCat Eye症候群の1例

  上原 奈津美, 長谷川 信吾, 柿木 章伸, 丹生 健一

  (一社)日本耳科学会, 2017年10月, Otology Japan, 27(4) (4), 665 - 665, 日本語


• 頭頸部癌に対する遺伝子診断

  丹生健一, 大月直樹, 四宮弘隆, 四宮瞳, 上原奈津美

  耳鼻咽喉科臨床学会, 2017年06月, 耳鼻咽喉科臨床, 110(6) (6), 367 - 374, 日本語

  記事・総説・解説・論説等（学術雑誌）


• 頭頸部癌に対する遺伝子診断

  丹生 健一, 大月 直樹, 四宮 弘隆, 四宮 瞳, 上原 奈津美

  耳鼻咽喉科臨床学会, 2017年, 耳鼻臨床, 110(6) (6), 367 - 374, 日本語

  [査読有り]

  書評論文,書評,文献紹介等


• 当科における難聴遺伝子解析の検討

  上原 奈津美, 山下 大介, 堀地 祐人, 勝沼 紗矢香, 柿木 章伸, 丹生 健一, 西尾 信哉, 宇佐美 真一

  (一社)日本耳科学会, 2016年09月, Otology Japan, 26(4) (4), 624 - 624, 日本語


• 外耳道後壁削除型鼓室形成術に併施した骨パテによる乳突腔部分充填術後症例の検討

  上原 奈津美, 後藤 友佳子, 長谷川 信吾, 香山 智佳子, 越智 尚樹, 藤田 岳, 小嶋 康隆, 山本 沙織

  (一社)日本耳科学会, 2015年09月, Otology Japan, 25(4) (4), 635 - 635, 日本語


• 【みみ・はな・のどの局所薬物療法】 咽頭・扁桃疾患に対する局所薬物療法

  上原奈津美, 後藤友佳子

  2014年06月, ENTONI, (168号) (168号), 40 - 45, 日本語

  記事・総説・解説・論説等（学術雑誌）


• ピルビン酸ナトリウムを投与したミトコンドリア病の3症例

  荒尾 正人, 酒井 哲郎, 武者 育麻, 山崎 太郎, 雨宮 伸, 上原 奈津美, 岡崎 康司, 村山 圭, 森 雅人, 大竹 明

  (公社)日本小児科学会, 2014年02月, 日本小児科学会雑誌, 118(2) (2), 404 - 404, 日本語


• ミトコンドリア呼吸鎖異常症(MRCD)のミトコンドリアDNA変異の検索

  森 雅人, 上原 奈津美, 水野 洋介, 村山 圭, 岡崎 康司, 大竹 明

  (一社)日本小児神経学会, 2012年05月, 脳と発達, 44(Suppl.) (Suppl.), S324 - S324, 日本語

• 施行しHRMで評価した1例

  古川 竜也, 手島 直則, 上原 奈津美, 森本 浩一, 藤尾 久美, 小松 弘和, 四宮 弘隆, 大月 直樹, 柿木 章伸, 丹生 健一

  第29回 日本頭頸部外科学会, 2019年01月, 日本語, 仙台, 国内会議

  口頭発表（一般）


• 外耳道癌術後の嚥下障害に段階的に嚥下機能改善手術を

  古川 竜也, 手島 直則, 上原 奈津美, 森本 浩一, 藤尾 久美, 小松 弘和, 四宮 弘隆, 大月 直樹, 柿木 章伸, 丹生 健一

  第29回 日本頭頸部外科学会, 2019年01月, 日本語, 仙台, 国内会議

  口頭発表（一般）


• 成人症例における難聴遺伝子解析の検討

  上原 奈津美, 藤田 岳, 勝沼 紗矢香, 柿木 章伸, 丹生 健一

  日本人類遺伝学会第63回大会, 2018年10月, 日本語, 横浜, 国内会議

  口頭発表（一般）


• 急速に進行し半規管瘻孔をきたした小児後天性真珠腫症例のCT値による検討

  上原 奈津美, 柿木 章伸, 丹生 健一

  第28回日本耳科学会総会・学術講演会, 2018年10月, 日本語, 大阪, 国内会議

  ポスター発表


• 当科における内視鏡下輪状咽頭筋切断術の経験

  古川 竜也, 森本 浩一, 小松 弘和, 藤尾 久美, 茂木 千聡, 上原 奈津美, 四宮 弘隆, 大月 直樹, 丹生 健一, 岩城 忍, 高橋 美貴, 上岡 美和, 千年 俊一

  第189回日耳鼻兵庫県地方部会, 2018年07月, 日本語, 神戸, 国内会議

  口頭発表（一般）


• 成人症例における難聴遺伝子解析の検討

  上原 奈津美, 藤田 岳, 勝沼 紗矢香, 柿木 章伸, 丹生 健一

  第189回日耳鼻兵庫県地方部会学術講演, 2018年07月, 日本語, 神戸, 国内会議

  口頭発表（一般）


• 椿の枝で受傷した外傷性外リンパ瘻の1例

  上原 奈津美, 柿木 章伸, 丹生 健一

  第80回耳鼻咽喉科臨床学会総会・学術講演会, 2018年06月, 日本語, 横浜, 国内会議

  口頭発表（一般）


• TRAUMATIC PERILYMPHATIC FISTULA CAUSED BY A CAMELLIA BRANCH

  Natsumi UEHARA, Akinobu KAKIGI, Kenichi NIBU

  the 6th East Asian Symposium on Otology, 2018年05月, 英語, ソウル, 国際会議

  口頭発表（一般）


• 難聴を契機に診断されたCat Eye症候群の1例

  上原奈津美, 池田真理子, 柿木章伸, 飯島一誠, 戸田達史, 丹生健一

  日本人類遺伝学会 第62回大会, 2017年11月, 日本語, 日本人類遺伝学会, 神戸, 国内会議

  ポスター発表


• 当科における難聴遺伝子解析の検討

  上原 奈津美, 山下 大介, 堀地 祐人, 勝沼 紗矢香, 柿木 章伸, 丹生 健一, 西尾 信哉, 宇佐美 真一

  第26回日本耳科学会総会・学術講演会, 2016年10月, 日本語, 日本耳科学会, 長野市, 国内会議

  ポスター発表


• 当科における難聴遺伝子の解析の検討

  上原 奈津美, 山下 大介, 堀地 祐人, 勝沼 紗矢香, 柿木 章伸, 丹生 健一, 西尾 信哉, 宇佐美 真一

  第26回 日本耳科学会総会・学術講演会, 2016年10月, 日本語, 日本耳科学会, 長野市, 国内会議

  口頭発表（一般）


• Evaluation of the dehydration effect of isosorbide on the hydropic guinea pig cochleae using optical coherence tomography in vivo

  Akinobu Kakigi, Natsumi Uehara, Naoya Egami, Shinji Yamashita, Tatsuya Yamasoba, Ken-chi Nibu

  53rd Workshop Inner Ear Biology, 2016年09月, 英語, Inner Ear Biology, Monpellier, France, 国際会議

  口頭発表（一般）

• 免疫チェックポイント阻害剤と遺伝子治療の併用による頭頸部癌に対する治療法の開発

  丹生 健一, 井之口 豪, 上原 奈津美

  日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 神戸大学, 2022年04月01日 - 2026年03月31日


• ミトコンドリア病モデル内耳細胞を用いたミトコンドリア難聴の病態解明

  上原 奈津美

  日本学術振興会, 科学研究費助成事業 若手研究, 若手研究, 神戸大学, 2022年04月01日 - 2025年03月31日


• 免疫チェックポイント阻害剤における共刺激分子遺伝子導入および放射線治療の併用効果

  丹生 健一, 井之口 豪, 大月 直樹, 上原 奈津美

  日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 神戸大学, 2019年04月01日 - 2022年03月31日

  我々はこれまでの研究において、B7分子(CD80)の遺伝子をマウス扁平上皮癌モデルに導入し、腫瘍特異的CTLが効率的に増幅され、B7分子(CD 80)を発現した腫瘍細胞のみならず、導入されていない腫瘍細胞にも増殖抑制効果を示すことを報告した。本研究では、マウス扁平上皮癌モデルを用いて、免疫チェックポイント阻害剤と共刺激分子B7分子(CD80)の遺伝子導入の併用効果を検討した。両者の併用により、マウスに移植された腫瘍はほぼ完全に消失し有意な併用効果が得られた。


• メニエール病における抗利尿ホルモンによるアクアポリン２の細胞内局在に関する研究

  上原 奈津美

  日本学術振興会, 科学研究費助成事業 若手研究, 若手研究, 神戸大学, 2019年04月01日 - 2022年03月31日

  メニエール病における内リンパ水腫形成の機序に抗利尿ホルモン（VP）とそれに制御されるアクアポリン2（AQP2）が深く関与することが明らかになってきた。本研究では、マウスを用いて蝸牛でのVP制御によるAQP2発現局在の変化と内リンパ水腫形成機序の解明を試みた。免疫染色及びin-situ hybrydazation法で蝸牛全体にAQP2の弱発現が見られた。抗利尿ホルモン投与で血管条基底細胞側にAQP２の発現が増強しリチウム投与ではその発現減弱の傾向が見られた。さらなる検討が必要だがAQP2は蝸牛全体に発現分布し、抗利尿ホルモンなどの要因で発現局在が変化し内リンパ水腫形成に関与している可能性がある。


• 増殖制限型アデノウイルスベクターを用いた頭頸部癌に対する新たな治療法の開発

  丹生 健一, 大月 直樹, 上原 奈津美, 白川 利朗

  日本学術振興会, 科学研究費助成事業 基盤研究(B), 基盤研究(B), 神戸大学, 2016年04月01日 - 2019年03月31日

  MidkineはHeparin-binding growth factorの一種で、頭頸部扁平上皮癌を含め多くの癌で高発現しているが、成人の正常組織ではほとんど発現がみられない。この特性を活かし、今回、我々はMidkineをプロモータとしてウイルスの増殖に必要なE1A・E1B遺伝子を組み込んだ制限増殖型アデノウイルスを作成し、更に、このウイルスに頭頸部扁平上皮癌に高発現している上皮成長因子受容体Epidermal growth factor receptor (EGFR)に対するsmall interfering RNA (siRNA)の遺伝子を組み込んだ。

  競争的資金


• エクソソームを用いた新たな頭頸部癌のバイオマーカーの開発

  丹生 健一, 藤田 岳, 上原 奈津美, 大月 直樹

  日本学術振興会, 科学研究費助成事業 挑戦的萌芽研究, 挑戦的萌芽研究, 神戸大学, 2015年04月01日 - 2017年03月31日

  頭頸部癌培養細胞株を用いてエクソソームの単離とマイクロRNAの抽出法を確立した。この技術を利用して、頭頸部癌患者を対象とした臨床研究の計画を作成し、本施設の臨床研究倫理審査委員会の承認を得た。本臨床研究では、腫瘍組織及び腫瘍組織の流出静脈から得られた血液、健側正常組織および健側正常組織の流出静脈から得られた血液から、エクソソームを単離してマイクロRNAを抽出する。現在、症例を集積中であり、得られた結果を比較検討することにより頭頸部癌に特異的なマーカーを見出す予定である。得られた腫瘍特異的なマーカーをプロモーターとして組み込んだアデノウルスベクターによる遺伝子治療の開発に利用する