Gene mutation and 3D-conformation of proteins related to EGFR pathway in head and neck cancer

• Project/Area Number: 24592587
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Hokkaido University
• Principal Investigator: HOMMA Akihiro 北海道大学, 医学(系)研究科(研究院), 准教授 (30312359)
• Co-Investigator(Kenkyū-buntansha): HATAKEYMA Hiromitsu 北海道大学, 北海道大学病院, 助教 (10455652)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2014: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000); Fiscal Year 2013: ¥650,000 (Direct Cost: ¥500,000、Indirect Cost: ¥150,000); Fiscal Year 2012: ¥3,770,000 (Direct Cost: ¥2,900,000、Indirect Cost: ¥870,000)
• Keywords: 頭頸部癌 / gene mutation / EGFR pathway / EGFR / 次世代シーケンサー / SNPアレイ

Outline of Final Research Achievements

DNA, mRNA and protein materials were extracted from normal mucosa and tissue of head and neck squamous cell carcinoma obtained from surgical specimen or biopsied tissue. 3D-conformation of the proteins interactions between drugs and other proteins were analyzed by amino-acid residue sequence and by atomic-level structure.
HB-EGF, a ligand of epidermal growth factor receptor (EGFR), has contained more in the cetuximab-sensitive head and cancer cell line than in the cetuximab-resistant cell line. The increase of HB-EGF activated the EGFR pathway and reduced the efficacy of cetuximab.

Research Products

• [Journal Article] Lymph node metastasis in the suprasternal space from thyroid papillary cancer. (2015)
  • Author(s): Homma A, Hatakeyama H, MD, Mizumachi T, Furusawa J, Kano S, Sakashita S, Fukuda S
  • Journal Title: Int Canc Conf J. Volume: 4 Issue: 1 Pages: 57-60
  • DOI: 10.1007/s13691-014-0171-9
  • NAID: 120005682117
  • Peer Reviewed / Open Access
• [Journal Article] Dose-finding and efficacy confirmation trial of superselective intra-arterial infusion of cisplatin and concomitant radiotherapy for patients with locally advanced maxillary sinus cancer (JCOG1212, RADPLAT-MSC). (2015)
  • Author(s): Homma A, Nakamura K, Matsuura K, Mizusawa J, Onimaru R, Fukuda H, Fujii M
  • Journal Title: Jpn J Clin Oncol Volume: 45 Issue: 1 Pages: 119-122
  • DOI: 10.1093/jjco/hyu169
  • Peer Reviewed / Open Access
• [Journal Article] Oxidative stress regulates IL-4 gene expression in mast cells through the reduction of histone deacetylase (2015)
  • Author(s): Nakamaru, Y., Takagi, D., Homma, A., Hatakeyama, S., Fukuda, S.
  • Journal Title: Otolaryngol. Head Neck Surg. Volume: 152 Issue: 1 Pages: 48-52
  • DOI: 10.1177/0194599814559189
  • Peer Reviewed / Open Access
• [Journal Article] Multi-institutional retrospective study for the evaluation of ocular function-preservation rates in maxillary sinus squamous cell carcinomas with orbital invasion. (2014)
  • Author(s): Sakashita T, Hayashi R, Homma A, Matsuura K, Kato K, Kawabata K, Monden N, Hasegawa Y, Onitsuka T, Fujimoto Y, Iwae S, Okami K, Matsuzuka T, Yoshino K, Fujii M
  • Journal Title: Head Neck. Volume: Epub Issue: 4 Pages: 537-542
  • DOI: 10.1002/hed.23639
  • Peer Reviewed / Open Access
• [Journal Article] Early and long-term morbidity after minimally invasivetotal laryngo-pharyngo-esophagectomy with gastric pull-up reconstruction via thoracoscopy, laparoscopy and cervical incision. (2014)
  • Author(s): Homma A, Nakamaru Y, Hatakeyama H, Mizumachi T, Kano S, Furusawa J, Sakashita T, Shichinohe T, Ebihara Y, Hirano S, Furukawa H, Hayashi T, Yamamoto Y, Fukuda S.
  • Journal Title: Eur Arch Otorhinolaryngol. Volume: Epub
  • Peer Reviewed / Open Access
• [Journal Article] Hearing Preservation after Lateral Temporal Bone Resection for Early-Stage External Auditory Canal Carcinoma. (2014)
  • Author(s): Morita S, Nakamaru Y, Homma A, Sakashita T, Masuya M, Fukuda S
  • Journal Title: Audiol Neurotol. Volume: 19 Issue: 6 Pages: 351-357
  • DOI: 10.1159/000362781
  • Peer Reviewed / Open Access
• [Journal Article] The potential diagnostic role of the number of ultrasonographic characteristics for patients with thyroid nodules evaluated as bethesdaI-v. (2014)
  • Author(s): Sakashita T, Homma A, Hatakeyama H, Mizumachi T, Kano S, Furusawa J, Iizuka S, Hoshino K, Hatanaka KC, Oba K, Fukuda S.
  • Journal Title: Front Oncol. Volume: 4 Pages: 261-261
  • DOI: 10.3389/fonc.2014.00261
  • Peer Reviewed / Open Access
• [Journal Article] Salvage operations for patients with persistent or recurrent cancer of the maxillary sinus after superselective intra-arterial infusion of cisplatin with concurrent radiotherapy. (2014)
  • Author(s): Sakashita T, Homma A, Hatakeyama H, Kano S, Mizumachi T, Furusawa J, Yoshida D, Fujima N, Onimaru R, Tsuchiya K, Yasuda K, Shirato H, Suzuki F, Fukuda S.
  • Journal Title: Br J Oral Maxillofac Surg Volume: 52 Issue: 4 Pages: 323-328
  • DOI: 10.1016/j.bjoms.2014.01.018
  • NAID: 120005476154
  • Peer Reviewed / Open Access
• [Journal Article] The incidence of late neck recurrence in N0 maxillary sinus squamous cell carcinomas after superselective intra-arterial chemoradiotherapy without prophylactic neck irradiation. (2014)
  • Author(s): Sakashita T, Homma A, Hatakeyama H, Kano S, Mizumachi T, Furusawa J, Yoshida D, Fujima N, Onimaru R, Tsuchiya K, Yasuda K, Shirato H, Fukuda S.
  • Journal Title: Eur Arch Otorhinolaryngol Volume: 271 Issue: 10 Pages: 2767-2770
  • DOI: 10.1007/s00405-013-2806-4
  • NAID: 120005665822
  • Peer Reviewed / Open Access
• [Journal Article] Lymph node metastasis in T4 maxillary sinus squamous cell carcinoma: Incidence and treatment outcome. (2014)
  • Author(s): Homma A, Hayashi R, Matsuura K, Kato K, Kawabata K, Monden N, Hasegawa Y, Onitsuka T, Fujimoto Y, Iwae S, Okami K, Matsuzuka T, Yoshino K, Nibu K, Kato T, Nishino H, Asakage T, Ota I, Kitamura M, Kubota A, Ueda T, Ikebuchi K, Watanabe A, Fujii M
  • Journal Title: Ann Surg Oncol . Volume: 21 Issue: 5 Pages: 1706-1710
  • DOI: 10.1245/s10434-014-3544-6
  • Peer Reviewed / Open Access
• [Journal Article] Effect of local extension sites on survival in locally advanced maxillary sinus cancer. (2014)
  • Author(s): Kano S, Hayashi R, Homma A, Matsuura K, Kato K, Kawabata K, Monden N, Hasegawa Y, Onitsuka T, Fujimoto Y, Iwae S, Okami K, Matsuzuka T, Yoshino K, Fujii M.
  • Journal Title: Head Neck. Volume: 36 Issue: 11 Pages: 1567-1572
  • DOI: 10.1002/hed.23483
  • Peer Reviewed / Open Access
• [Journal Article] Japanese Board Certification System for head and neck surgeons. (2014)
  • Author(s): Yoshimoto S, Nakashima T et al.
  • Journal Title: Auris Nasus Larynx. Volume: 41 Issue: 4 Pages: 1175-81
  • DOI: 10.1016/j.anl.2013.10.019
  • Peer Reviewed / Open Access
• [Journal Article] 中央咽頭扁平上皮癌症例に対するWeekly CDDP併用 化学放射線療法の臨床的検討 (2014)
  • Author(s): 水町貴諭, 本間明宏, 坂下智博, 加納里志, 畠山博充, 土屋和彦, 安田耕一, 鬼丸力也, 白土博樹, 福田 諭
  • Journal Title: 頭頸部癌 Volume: 40 Pages: 66-70
  • Peer Reviewed
• [Journal Article] 頸部腫瘤摘出・生検後に中咽頭癌と診断された症例の検討 (2014)
  • Author(s): 水町貴諭, 加納里志, 坂下智博, 畠山博充, 本間明宏, 福田 諭
  • Journal Title: 日本耳鼻咽喉科学会会報 Volume: 117 Pages: 1463-1470
  • NAID: 130004913865
  • Peer Reviewed
• [Journal Article] The role of initial neck dissection for patients with node-positive oropharyngeal squamous cell carcinomas (2014)
  • Author(s): T. Sakashita, A. Homma, R. Hayashi, K. Kawabata, K. Yoshino, S. Iwae, Y. Hasegawa, K. Nibu, T. Kato, K. Shiga, K. Matsuura, N. Monden, M. Fuji
  • Journal Title: Oral Oncology Volume: 40 Issue: 7 Pages: 211-215
  • DOI: 10.1016/j.oraloncology.2014.03.003
  • NAID: 120005464719
  • Peer Reviewed
• [Journal Article] Matched-pair analysis in patients with advanced oropharyngeal cancer: surgery versus concurrent chemoradiotherapy. (2013)
  • Author(s): Kano S, Homma A, Hayashi R, Kawabata K, Yoshino K, Iwae S, Hasegawa Y, Nibu K, Kato T, Shiga K, Matsuura K, Monden N, Fujii M.
  • Journal Title: Oncology Volume: 84 Issue: 5 Pages: 290-298
  • DOI: 10.1159/000346908
  • Peer Reviewed
• [Journal Article] Prognostic value of cyclin D1 expression in tumor-free surgical margins in head and neck squamous cell carcinomas. (2013)
  • Author(s): Sakashita T, Homma A, Suzuki S, Hatakeyama H, Kano S, Mizumachi T, Oridate N, Fukuda S
  • Journal Title: Acta Otolaryngol Volume: 133 Issue: 9 Pages: 984-981
  • DOI: 10.3109/00016489.2013.795287
  • NAID: 120005476151
  • Peer Reviewed
• [Journal Article] Superselective intra-arterial cisplatin infusion and concomitant radiotherapy for maxillary sinus cancer. (2013)
  • Author(s): Homma A, Sakashita T, Yoshida D, Onimaru R, Tsuchiya K, Suzuki F, Yasuda K, Hatakeyama H, Furusawa J, Mizumachi T, Kano S, Inamura N, Taki S, Shirato H, Fukuda S.
  • Journal Title: Br J Cancer Volume: 109 Issue: 12 Pages: 2980-2986
  • DOI: 10.1038/bjc.2013.663
  • NAID: 120005438253
  • Peer Reviewed
• [Journal Article] Improved survival of Japanese patients with human papillomavirus-positive oropharyngeal squamous cell carcinoma (2012)
  • Author(s): Mizumachi T, Kano S, Sakashita T, Hatakeyama H, Suzuki S, Homma A, Oridate N, Fukuda S
  • Journal Title: Int J Clin Oncol Volume: online 31 Issue: 5 Pages: 0-0
  • DOI: 10.1007/s10147-012-0469-6
  • Peer Reviewed
• [Journal Article] Salvage surgery for recurrent oropharyngeal cancer after chemoradiotherapy. (2012)
  • Author(s): Kano S, Homma A, Hayashi R, Kawabata K, Yoshino K, et al.
  • Journal Title: Int J Clin Oncol Volume: Epub ahead of print Issue: 5 Pages: 817-823
  • DOI: 10.1007/s10147-012-0449-x
  • Peer Reviewed
• [Journal Article] Rapid superselective high-dose cisplatin infusion with concomitant radiotherapy for squamous cell carcinoma of the nasal vestibule: a report of two cases. (2012)
  • Author(s): Homma A, Suzuki F, Hatakeyama H, Sakashita T, Yoshida D, et al.
  • Journal Title: Int Canc Conf J Volume: 1 Issue: 4 Pages: 215-219
  • DOI: 10.1007/s13691-012-0044-z
  • NAID: 120005451604
  • Peer Reviewed
• [Journal Article] Otolaryngologic Manifestations of Antineutrophil Cytoplasmic Antibody-Associated Vasculitis. (2012)
  • Author(s): Nakamaru Y, Takagi D, Oridate N, Homma A, Fukuda S.
  • Journal Title: Otolaryngol Head Neck Surg Volume: 146 Issue: 1 Pages: 119-12
  • DOI: 10.1177/0194599811424044
  • Peer Reviewed
• [Journal Article] Combined modality therapy for laryngeal cancer with superselective intra-arterial cisplatin infusion and concomitant radiotherapy. (2012)
  • Author(s): ④ Taki S, Homma A, Suzuki F, Oridate N, Hatakeyama H, Mizumachi T, Kano S, et al.
  • Journal Title: Int J Clin Oncol Volume: 17 Issue: 5 Pages: 441-446
  • DOI: 10.1007/s10147-011-0308-1
  • NAID: 10031144330
  • Peer Reviewed
• [Journal Article] Evaluation of nodal response after intra-arterial chemoradiation for node-positive head and neck cancer (2012)
  • Author(s): Sakashita T, Homma A, Oridate N, Hatakeyama H, Kano S, Mizumachi T, Fukuda S
  • Journal Title: Eur Arch Otorhinolaryngol Volume: 269 Issue: 6 Pages: 1671-1676
  • DOI: 10.1007/s00405-011-1814-5
  • NAID: 120005946626
  • Peer Reviewed
• [Journal Article] Platinum concentration in sentinel lymph nodes after preoperative intra-arterial cisplatin chemotherapy targeting primary tongue cancer (2012)
  • Author(s): Sakashita T, Homma A, Oridate N, Suzuki S, Hatakeyama H, Kano S, Mizumachi T, Yoshida D, Fujima N, Fukuda S
  • Journal Title: Acta Otolaryngol Volume: 132 Issue: 10 Pages: 1121-1125
  • DOI: 10.3109/00016489.2012.680494
  • NAID: 10031131102
  • Peer Reviewed
• [Journal Article] 今日の治療指針 (2012)
  • Author(s): 本間明宏
  • Journal Title: 耳鼻咽喉科疾患 Volume: 25 Pages: 1260-1260
  • Peer Reviewed
• [Journal Article] 特集：頭頸部扁平上皮癌に対する新しい治療戦略「化学療法ー同時放射線治療と超選択的動注療法」. (2012)
  • Author(s): 本間明宏
  • Journal Title: JOHNS Volume: 28 Pages: 1181-1184
  • Peer Reviewed
• [Journal Article] 大量シスプラチンの超選択的動注療法と照射の同時併用療法の現状. (2012)
  • Author(s): 本間明宏
  • Journal Title: 頭頸部外科 Volume: 22 Pages: 29-31
  • NAID: 10031170465
  • Peer Reviewed
• [Journal Article] 腫瘍性疾患診療NAVI 「1.鼻副鼻腔腫瘍」 (2012)
  • Author(s): 本間明宏
  • Journal Title: 耳喉頭頸 Volume: 84 Pages: 249-253
  • Peer Reviewed
• [Journal Article] 切除可能T3、T4上顎洞扁平上皮癌における手術の位置付けー当院における治療戦略ー. (2012)
  • Author(s): 本間明宏, 折舘伸彦, 鈴木清護, 鈴木章之, 畠山博充他.
  • Journal Title: 耳鼻 Volume: 58
  • NAID: 130004555582
  • Peer Reviewed
• [Journal Article] 喉頭癌T3症例の治療成績の検討. (2012)
  • Author(s): 水町貴諭, 折舘伸彦, 本間明宏, 坂下智博, 加納里志他.
  • Journal Title: 頭頸部外科 Volume: 22 Pages: 317-321
  • NAID: 10031170514
  • Peer Reviewed
• [Journal Article] ＜第13回耳鼻咽喉科手術支援システム･ナビ研究会＞早期舌癌におけるセンチネルリンパ節の領域分布に関する検討. (2012)
  • Author(s): 坂下智博, 本間明宏, 折舘伸彦, 鈴木清護, 畠山博充他
  • Journal Title: 耳展 Volume: 55 Pages: 364-368
  • Peer Reviewed
• [Journal Article] 頭頸部癌化学放射線療法における経管栄養の役割に関する検討. (2012)
  • Author(s): 倉本倫之介, 折舘伸彦, 本間明宏, 及川敬太, 藤田 香他.
  • Journal Title: 嚥下医学 Volume: 1 Pages: 359-363
  • NAID: 40019505696
  • Peer Reviewed
• [Journal Article] オピオイドによる難治性の嘔気とめまいに対してヒスタミンH1受容体拮抗薬とペロスピロンの併用が有効であった2症例. (2012)
  • Author(s): 長田貴之, 柴山良彦, 熊井正貴, 山田武宏, 笠師久美子, 倉本倫之介, 洲崎真吾, 赤澤 茂, 真栄田裕行, 坂下智博, 折舘伸彦, 本間明宏他.
  • Journal Title: 医療薬学 Volume: 38 Pages: 51-55
  • NAID: 130004502708
  • Peer Reviewed
• [Journal Article] 【Best articles of the year】舌根癌における放射線同時併用超選択的動注化学療法. (2012)
  • Author(s): 加納里志, 本間明宏, 折舘伸彦, 鈴木章之, 畠山博充他.
  • Journal Title: 北海道医誌 Volume: 87 Pages: 208-208
• [Journal Article] 【Best articles of the year】口腔癌における超選択的シスプラチン動注化学療法後のセンチネルリンパ節内プラチナ濃度測定. (2012)
  • Author(s): 坂下智博, 本間明宏, 折舘伸彦, 鈴木清護, 畠山博充他.
  • Journal Title: 北海道医誌 Volume: 87 Pages: 261-261
• [Presentation] 超選択的動注化学療法の実際と今後の展望 (2015)
  • Author(s): 本間 明宏
  • Organizer: 頭頸部がん化学療法症例検討会.
  • Place of Presentation: 群馬ロイヤルホテル（群馬県前橋市）
  • Year and Date: 2015-03-04
  • Invited
• [Presentation] 進行頭頸部がんに対する治療戦略. (2014)
  • Author(s): 本間 明宏
  • Organizer: 第3回北摂頭頸部がん治療研究会.
  • Place of Presentation: 大阪新阪急ホテル（大阪府大阪市）
  • Year and Date: 2014-12-04
  • Invited
• [Presentation] 頭頸部がんの化学療法～臨床試験から日常臨床へ～ (2014)
  • Author(s): 本間 明宏
  • Organizer: 第27回日本口腔・咽頭科学会総会 学術講演会
  • Place of Presentation: ホテルライフォート札幌（北海道札幌市）
  • Year and Date: 2014-09-11 – 2014-09-12
  • Invited
• [Presentation] 上顎洞原発扁平上皮癌T4症例の頸部転移について-多施設後ろ向き観察研究- (2014)
  • Author(s): 本間 明宏
  • Organizer: 第52回日本癌治療学会学術集会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
  • Year and Date: 2014-08-28 – 2014-08-30
• [Presentation] Early and long-term morbidity after total laryngo-pharyngo-esophagectomy with gastic pull-up reconstruction (2014)
  • Author(s): Homma A, Hatakeyama H, Mizumachi T, Kano S, Furusawa J, Sakashita T, Shichinohe T, Ebihara Y, Hirano S, Furukawa H, Yamamoto Y, Fukuda S.
  • Organizer: IFHNOS 5th World Congress and AHNS 2014 Annual Meeting
  • Place of Presentation: The Marriott Marquis Time Square（NY,USA)
  • Year and Date: 2014-07-26 – 2014-07-30
• [Presentation] Lymph node metastasis in burns space (2014)
  • Author(s): 29.Homma A, Hatakeyama H, Mizumachi T, Furusawa J, Kano S, Sakashita T, Fukuda F
  • Organizer: 18th World congress joint meeting of the world association for bronchology and interventional pulmonology & the international bronchoesophagology society
  • Place of Presentation: 京都国際会館（京都府京都市）
  • Year and Date: 2014-04-13 – 2014-04-16
• [Presentation] The efficacy of superselective intra-arterial infusion of cisplatin and concomitant radiotherapy for patients with locally advanced maxillary sinus cancer: a single institution experience. (2014)
  • Author(s): 28.Homma A, Sakashita T, Hatakeyama H, Furusawa J, Mizumachi T, Kano S, Inamura N, Taki S, Suzuki F, Yoshida D, Onimaru R, Tsuchiya K, Yasuda K, Nishikawa N, Shirato H, Fukuda F
  • Organizer: 15th Korea-Japan Joint Meeting of Otorhinolaryngology - Head and Neck Surgery,
  • Place of Presentation: Lotte Hotel Seoul (Seoul, Korea）
  • Year and Date: 2014-04-03 – 2014-04-05
• [Presentation] Cervical lymph node metastasis of head and neck squamous carcinoma after chemoradiotherapy. (2013)
  • Author(s): Akihiro HOMMA, Tomohiro SAKASHITA, Hiromitsu HATAKEYAMA, Satoshi KANO, Takatsugu MIZUMACHI, Nobuhiko ORIDATE, Satoshi FUKUDA
  • Organizer: 20th IFOS World Congress
  • Place of Presentation: COEX Convention Center(Seoul, Korea)
• [Presentation] Updates in oral and oropharyngeal cancers「Surgery versus Concomitant Chemoradiotherapy: A Matched-Pair Analysis in Patients with Advanced Oropharyngeal Cancer (2013)
  • Author(s): Homma A, Kano S, Hayashi R, Kawabata K, Yoshino K, Iwae S, Hasegawa Y, Nibu K, Kato T, Shiga K, Matsuura K, Monden N, Fujii M
  • Organizer: The 12th Taiwan-Japan Conference on Otolaryngology Head and Neck Surgery(招待講演）
  • Place of Presentation: NTUH International Convention Center(Taipei, Taiwan)
  • Invited
• [Presentation] ＜Symposium＞head and neck cancer「Superselective intra-arterial chemotherapy with concurrent radiotherapy for sinonasal malignant tumors.
  • Author(s): Homma A, Oridate N, Sakashita T, Yoshida D, Onimaru R, Tsuchiya K, Hatakeyama H, Mizumachi T, Kano S, Shirato H, Fukuda S
  • Organizer: The 14th Japan-Korea Joint Meeting of Otorhinolaryngology-Head and Neck Surgery
  • Place of Presentation: 京都ホテルオークラ（京都市）
• [Presentation] 中咽頭癌に対する治療の現状～多施設による後ろ向き観察研究
  • Author(s): 本間 明宏
  • Organizer: 第113回日本耳鼻咽喉科学会総会・学術講演会
  • Place of Presentation: 朱鷺メッセ(新潟コンベンションセンター)（新潟市）
• [Presentation] 進行上顎洞癌症例の多施設による後ろ向き観察研究
  • Author(s): 本間 明宏
  • Organizer: 第36回日本頭頸部癌学会
  • Place of Presentation: 島根県民会館 （松江市）
• [Presentation] The efficacy of superselective intra-arterial infusion with concomitant radiotherapy for adenoid cystic carcinoma of the head and neck.
  • Author(s): Homma A, Oridate N, Sakashita T, Suzuki S, Hatakeyama H,et al.
  • Organizer: 8th International Conference on Head & Neck Cancer
  • Place of Presentation: Metro Toronto Convention Center（カナダ）
• [Presentation] 局所進行上顎洞原発扁平上皮癌に対するCDDPの超選択的動注療法と放射線同時併用療法の第I/II相試験について.
  • Author(s): 本間明宏
  • Organizer: 平成24年度第1回JCOG頭頸部がんグループ班会議
  • Place of Presentation: 財団法人がん研究振興財団 国際研究交流会館 （東京都中央区)
  • Invited
• [Book] 藤間憲幸, 本間明宏: 画像診断パーフェクトガイド 画像診断6 鼻・副鼻腔癌[耳鼻咽喉86） (2014)
  • Author(s): 藤間憲幸, 本間明宏
  • Publisher: 医学書院