前田　拓 (マエダ　タク)

北海道大学病院　外科講師
Last Updated :2026/04/14

■研究者基本情報

学位

  • 医学博士, 北海道大学

Researchmap個人ページ

ホームページURL

J-Global ID

研究キーワード

  • 腫瘍免疫
  • 移植リンパ節
  • 悪性黒色種
  • 機能的リンパ組織
  • 組織培養・移植学
  • lymph node transfer
  • 機能的リンパ移植法
  • 遊離リンパ節移植
  • リンパ系再構築
  • 血管柄付きリンパ節移植
  • 再生医療
  • 放射線照射
  • 脂肪移植
  • 羊膜
  • 間葉系幹細胞
  • リンパ系機能不全
  • メラノーマ
  • Circulating tumor cells

研究分野

  • ライフサイエンス, 形成外科学

担当教育組織

■経歴

経歴

  • 2018年04月 - 現在
    北海道大学大学院・医学研究院, 形成外科学教室, 助教
  • 2022年04月
    北海道大学病院 形成外科 講師

学歴

  • 2015年04月 - 2018年03月, 北海道大学, 医学研究科 博士課程
  • 2000年04月 - 2006年03月, 神戸大学, 医学部, 医学科

委員歴

  • 2023年03月 - 2025年03月
    日本形成外科学会、評議員
  • 2024年11月
    日本頭蓋顎顔面外科学会、代議員
  • 2023年
    日本皮膚悪性腫瘍学会、評議員
  • 2022年12月
    日本マイクロサージャリー学会、評議員
  • 2022年12月
    日本創傷外科学会、編集委員
  • 2022年12月
    日本創傷外科学会、学術委員
  • 日本皮膚悪性腫瘍学会, 皮膚がん診療ガイドライン作成委員会 委員(メラノーマ)

■研究活動情報

受賞

  • 2023年08月, 第39回日本皮膚悪性腫瘍学会学術大会ポスター賞　　　　　　　　　　　　　　　
  • 2023年04月, Plastic surgery research council 2023, Cleveland, OH, Top Scoring Abstracts.Transplanted lymph node can bring antitumor effects of T cell expansion in tumor immunity.　　　　　　　　　　　　　　　
  • 2016年, 北海道大学形成外科学教室, 北成賞 臨床研究者部門　　　　　　　　　　　　　　　
    前田拓

論文

  • Sclerosing rhabdomyosarcoma of the infratemporal fossa in an adult: A favorable long-term outcome
    Chikako Yura, Wataru Kakuguchi, Naohiro Ogawa, Daigo Matsuyama, Shin Ariga, Koichi Yasuda, Taku Maeda, Aya Yanagawa-Matsuda, Yuichi Ashikaga, Yoichi Ohiro
    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, 38, 1, 82, 87, Elsevier BV, 2026年01月
    研究論文（学術雑誌）
  • Ultra-deep targeted next-generation sequencing with peripheral blood in patients with vascular malformations: a cohort of 40 patients
    Shintaro Mitamura, Kosuke Ishikawa, Kanako C. Hatanaka, Tatsuro Saito, Yuki Sasaki, Takahiro Miura, Taku Maeda, Emi Funayama, Naoki Murao, Satoru Sasaki, Yutaka Hatanaka
    Molecular Biology Reports, 53, 1, Springer Science and Business Media LLC, 2025年12月19日
    研究論文（学術雑誌）
  • Composite Design of In-House Manufactured Patient-Specific Instruments for Precision Mandibular Reconstruction Using Fibula Free Flap
    Risa Yamamoto, Yuki Wakabayashi, Midori Kawamura, Tomohiro Michida, Ken-ichiro Sakata, Masahiro Hojo, Taku Maeda, Keisuke Nakamura, Taku Kimura, Shinichiro Kuroshima, Ikuya Miyamoto
    Cureus, Springer Science and Business Media LLC, 2025年11月04日
    研究論文（学術雑誌）
  • Correction to: Melanoma skin cancer statistics derived from 7442 Japanese patients: Japanese melanoma study.
    Yasuhiro Fujisawa, Shusuke Yoshikawa, Tatsuya Takenouchi, Shoichiro Mori, Jun Asai, Hisashi Uhara, Yuki Ichigosaki, Taku Fujimura, Yoshiyuki Nakamura, Yasuhiro Nakamura, Fumitaka Ohno, Takeshi Fukumoto, Toshiyuki Ozawa, Kenjiro Namikawa, Satoru Sugihara, Toshihiko Hoashi, Takatoshi Shimauchi, Yu Sawada, Hiroaki Iwata, Taku Maeda, Takuya Miyagawa, Yoshitsugu Shibayama, Naohito Hatta, Akiko Kishi, Masashi Ishikawa, Hisao Kawahira, Norito Katoh, Ryuhei Okuyama
    International journal of clinical oncology, 30, 9, 1882, 1883, 2025年09月, ［査読有り］, ［国内誌］
    英語
  • Japanese Dermatological Association Guidelines: Clinical Questions of Guidelines for Melanoma 2025.
    Satoshi Fukushima, Takamichi Ito, Jun Asai, Hiroshi Igaki, Ryota Tanaka, Kenjiro Namikawa, Ayato Hayashi, Akane Minagawa, Takuya Miyagawa, Azusa Miyashita, Dai Ogata, Mao Okumura, Yukiko Kiniwa, Hiroyuki Goto, Takeshi Namiki, Hiroki Hashimoto, Tokimasa Hida, Takero Hirata, Taku Maeda, Takamitsu Matsuzawa, Teruki Yanagi, Kanae Sugimoto, Emi Kimura, Hiroshi Koga, Hiroshi Uchi, Tomomitsu Miyagaki, Yasuhiro Nakamura, Takashi Inozume
    The Journal of dermatology, 52, 8, e666-e697, 2025年08月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, Advancements in melanoma management have underscored the need for periodic guideline updates every few years to reflect current clinical practices. Previous versions of melanoma clinical practice guidelines in Japan have primarily aimed to reflect global standards of care. This focus on international benchmarks was largely attributed to the scarcity of high-quality evidence from East Asia, necessitating reliance on Western references. Recent findings indicate differences in melanoma subtypes and drug efficacy between Western and East Asian populations. Therefore, efforts were made to incorporate data from East Asia in this revision, aiming to develop guidelines that better reflect the region's unique characteristics. This revision was commissioned by the Japanese Dermatological Association (JDA) and Japanese Skin Cancer Society (JSCS) and was undertaken by a committee comprising experts across relevant fields who meticulously reviewed and systematized a wide range of literature on melanoma to develop comprehensive, evidence-based guidelines. Literature searches were conducted by the Japan Medical Library Association. The recommendation statements were determined using the GRADE Grid approach. The guideline was developed in accordance with the Minds Clinical Practice Guideline Creation Manual 2020, ver. 3.0. Twelve clinical questions (CQs) were established, and corresponding recommendation statements were provided for each CQ. For several CQs, the inclusion of data from East Asia resulted in recommendations that differed from those in Western guidelines. Considering that the biology of melanoma has been increasingly recognized to vary by subtype and ethnicity, guidelines should be developed independently for each region based on evidence specific to the melanoma characteristics of that region. We firmly believe that this Japanese clinical guideline for melanoma will contribute to improving melanoma management in East Asia.
  • Successful surgical management of a patient with osteoradionecrosis of the jaw with RET fusion‑positive advanced thyroid cancer: A case report
    Taku Kimura, Ken-Ichiro Sakata, Kazuhito Yoshikawa, Takeshi Munekata, Tatsuki Itagaki, Taku Maeda, Junichi Kanayama, Jun Sato, Aya Matsuda, Yoshimasa Kitagawa
    Experimental and Therapeutic Medicine, 30, 2, 1, 10, Spandidos Publications, 2025年05月29日
    研究論文（学術雑誌）
  • Extracellular matrix modulating effects of amnion-derived mesenchymal stem cells on aging skin wounds in α-Klotho knockout mice.
    Yuki Sasaki, Shunsuke Ohnishi, Hiroko Takahashi, Kosuke Ishikawa, Takahiro Miura, Emi Funayama, Naoto Okubo, Yuhei Yamamoto, Taku Maeda
    Geriatrics & gerontology international, 25, 5, 701, 708, 2025年05月, ［査読有り］, ［責任著者］, ［国内誌］
    英語, 研究論文（学術雑誌）, AIM: Wounds in the elderly are frequently recalcitrant and chronic as a result of the effects of skin aging and associated complications. The objective of this study is to utilize an α-Klotho knockout (KO) mice wound model to assess the capacity of amnion-derived mesenchymal stem cells (AMSCs) to facilitate wound healing in aging skin. METHODS: AMSCs were applied topically to the wound after extraction and gelatinization of the conditioned medium (CM). Animal experiments were performed with two distinct mouse strains: α-Klotho KO mice and wild-type mice. Full-thickness skin defect models with a diameter of 8 mm were created by incising the skin on the left and right sides of the dorsum. On day 8 after wound creation, the mice were sacrificed, and wound tissue was collected for analysis through histological and immunohistochemical evaluations, as well as through quantitative polymerase chain reaction. RESULTS: The topical application of CM gel to wounds of α-Klotho KO mice demonstrated that wound healing was significantly higher than that observed in control, reaching the wound closure rate of wild-type mice on day 8. Additionally, gene expression analysis of wound tissue indicated that AMSC-CM may regulate extracellular matrix formation and fibrosis. Moreover, histological analysis indicated that AMSC-CM may facilitate wound contraction of aging skin wounds of α-Klotho KO mice by inducing myofibroblast differentiation and promoting granulation and collagen formation, which are the primary components of the extracellular matrix. CONCLUSIONS: AMSC-CM may facilitate wound healing in aging skin of α-Klotho KO mice by regulating the extracellular matrix. Geriatr Gerontol Int 2025; 25: 701-708.
  • A novel mouse model for studies of burn wound conversion using a top hat–shaped brass template
    Matsuda N, Sato C, Ishikawa K, Miura T, Funayama E, Yamamoto Y, Fuyama K, Ohnishi S, Maeda T
    Burns, 51, 2, 107348, 2025年03月, ［査読有り］, ［責任著者］
    英語, 研究論文（学術雑誌）
  • 3D scanner’s potential as a novel tool for lymphedema measurement in mouse hindlimb models
    Dongkyung Seo, Riri Ito, Kosuke Ishikawa, Takahiro Miura, Yuhei Yamamoto, Yasuhito Onodera, Soichiro Nishioka, Yoichi M. Ito, Kanako Fuyama, Taku Maeda
    Scientific Reports, 15, 1, 3747, 3747, Springer Science and Business Media LLC, 2025年01月30日, ［査読有り］, ［責任著者］, ［国際誌］
    英語, 研究論文（学術雑誌）, Lymphedema is characterized by persistent swelling due to impaired lymphatic function and presents significant challenges in both research and clinical settings. Traditional contact-based measurement techniques such as paw thickness and circumferential measurements using calipers or silk thread are useful but limited by observer variability and measurement accuracy. Non-contact methods, including various imaging techniques, offer improvements but often at higher cost and complexity. In this study, we address the need for a more reliable, cost-effective, and non-invasive method for assessing lymphedema in mouse models. Here we show that 3D scanning technology can enhance the measurement of lymphedema in a mouse hindlimb model. Our results indicate that 3D scanners provide more consistent measurements with lower variability compared with conventional methods and without the need for direct contact, which could potentially alter the measurement outcomes. The findings of this study suggest that 3D scanning could replace traditional methods, offering a more standardized and less subjective tool for lymphedema research in the near future. This technology would not only improve upon conventional methods but also extend the capabilities for detailed anatomical analyses in small animal models, which could have implications for other areas of biomedical research.
  • A 4-year-old Boy with a Red Nodule on His Hand: A Quiz.
    Riku Ishii, Noriyuki Otsuka, Takashi Anan, Yuhei Yamamoto, Taku Maeda
    Acta dermato-venereologica, 105, adv41071, 2025年01月28日, ［査読有り］, ［責任著者］, ［国際誌］
    英語, 研究論文（学術雑誌）
  • Hypoxia-Inducible Factor Prolyl Hydroxylase Inhibitor Roxadustat Accelerates Wound Healing in a Mouse Hind limb Lymphedema Model.
    Kosuke Ishikawa, Yoshitada Hoshino, Masayuki Osawa, Emi Funayama, Takahiro Miura, Masahiro Hojo, Yuki Sasaki, Satoru Sasaki, Yuhei Yamamoto, Taku Maeda
    Advances in wound care, 2025年01月24日, ［査読有り］, ［責任著者］, ［国際誌］
    英語, 研究論文（学術雑誌）, Objective: Drugs regulating hypoxia-inducible factor (HIF)-1α have not been investigated for wound healing in lymphedema. Therefore, we examined the effects of drug modulation of HIF-1α activity for wound healing in our previously developed mouse model of nonirradiated hind limb lymphedema. Approach: Mouse hind limb lymphedema models (n = 17) and a sham group (n = 6) were created using 8- to 10-week-old male C57BL/6N mice. Mice with hind limb lymphedema were randomized into experimental groups receiving roxadustat, 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole (YC-1), or dimethyl sulfoxide and were given intraperitoneal injections every 2 days for up to 2 weeks. Four days after the surgery, an 8-mm diameter full-thickness skin wound was created in the hind limb. The number of days required for wound closure and the percentage of wounds closed were measured. Skin samples taken at wound creation were evaluated by histological and molecular analysis. Results: Administration of roxadustat accelerated wound healing, whereas YC-1 delayed it, with a significant decrease and increase in skin thickness, respectively. The relative mRNA expression of Hif1α, matrix metalloproteinase-3, and interleukin-6 was significantly higher in the roxadustat group and that of metalloproteinase-9 was significantly lower in the roxadustat group compared with the control group. Innovation: This study is the first to demonstrate delayed wound healing in a mouse model of hind limb lymphedema and the first to demonstrate the promotion of significant wound healing through the use of roxadustat. Conclusion: Roxadustat exerts wound-healing effects and may promote the regulation of extracellular matrix remodeling via gene expression in hind limb lymphedema wound models.
  • Aggressive Orbital Dedifferentiated Liposarcoma With Osseus Components in a Young Woman.
    Satoru Kase, Taku Maeda, Noriyuki Otsuka, Yuka Suimon, Susumu Ishida
    Cancer diagnosis & prognosis, 5, 3, 404, 409, 2025年, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND/AIM: Dedifferentiated liposarcoma (DDLS) is a rare but aggressive subtype of liposarcoma that arises in soft tissues. In orbital liposarcoma, malignant transformation from well-differentiated to DDLS typically takes at least a year. We herein report a case of a young female with an aggressive DDLS, that developed from an orbital lipoma within one year. CASE REPORT: A 25-year-old woman presented with left upper eyelid swelling. MRI revealed abnormal adipose tissue in the medial orbit. The excised tissue was diagnosed as an orbital lipoma. The eyelid swelling recurred three months later, and the orbital tumor enlarged. An additional resection was performed, which again revealed a lipoma without malignant features. Three months later, the swelling worsened, and tumor resection confirmed well differentiated liposarcoma with a Ki-67 labeling index of 10%. Two months later, CT imaging depicted calcified lesions within the tumor. The patient subsequently underwent orbital exenteration followed by proton beam radiation. Histopathological examination of the exenterated tissue revealed DDLS with extensive osseous components. The Ki-67 labeling index exceeded 50%. CONCLUSION: Ocular oncologists should pay attention to the possibility of rapid malignant transformation in DDLS in primary orbital liposarcoma.
  • Synergistic anti-tumor effects of oncolytic virus and anti-programmed cell death protein 1 antibody combination therapy: For suppression of lymph node and distant metastasis in a murine melanoma model
    Sasaki Y, Maeda T, Hojo M, Miura T, Ishikawa K, Funayama E, Okada K, Yamamoto Y
    Biochemical and Biophysical Research Communications, 740, 151011, 2024年12月, ［査読有り］, ［責任著者］
    英語, 研究論文（学術雑誌）
  • Comparison of leg volume ratio between inguinal lymphadenectomy and inguino-pelvic lymphadenectomy in patients with skin cancer of the lower extremity
    Taku Maeda, Kosuke Ishikawa, Toshihiko Hayashi, Hiroshi Furukawa, Takahiro Miura, Masahiro Hojo, Emi Funayama, Yuhei Yamamoto
    Journal of Plastic, Reconstructive & Aesthetic Surgery, 99, 397, 405, Elsevier BV, 2024年12月, ［査読有り］, ［筆頭著者］
    研究論文（学術雑誌）
  • Salivary miRNAs as a novel therapeutic marker in a patient with advanced oral squamous cell carcinoma: A case report
    Taku Kimura, Ken-Ichiro Sakata, Noritaka Ohga, Jun Sato, Tatsuki Itagaki, Takeshi Munekata, Aya Yanagawa‑Matsuda, Taku Maeda, Masahiro Hojo, Kanako Hatanaka, Yutaka Hatanaka, Hisashi Iizasa
    Oncology Letters, 29, 1, Spandidos Publications, 2024年11月11日
    研究論文（学術雑誌）
  • Effective management of continuous salivary flow through a pharyngocutaneous fistula using a negative pressure wound therapy device
    Taku Maeda, Nayuta Tsushima, Kosuke Ishikawa, Yuhei Yamamoto
    JPRAS Open, 43, 74, 78, Elsevier BV, 2024年11月, ［査読有り］, ［筆頭著者］, ［国際誌］
    英語, 研究論文（学術雑誌）, Esophagojejunal anastomotic fistula is difficult to treat because of continuous salivary flow. This report describes the innovative use of a negative pressure wound therapy device with a slit drain to treat an esophagojejunal anastomotic fistula after free jejunal transfer. Insertion of a slit drain was very effective for management of saliva. This device worked as a portable suction machine, allowing earlier healing without the need for surgery. A negative pressure wound therapy device using a slit drain can be useful for recalcitrant esophagojejunal anastomotic fistula with salivary flow after free jejunal transfer.
  • Physiological and Functional Restoration of the Modiolus Using a Double Tendon Sling in Patients With Full-Thickness Oral Defects
    Taku Maeda, Toshihiko Hayashi, Kosuke Ishikawa, Takahiro Miura, Emi Funayama, Yuhei Yamamoto
    Annals of Plastic Surgery, Ovid Technologies (Wolters Kluwer Health), 2024年10月18日, ［査読有り］, ［筆頭著者］
    研究論文（学術雑誌）, Background

    Reconstruction of the oral modiolus should be considered for facial defects involving the lip and cheek. We have performed free flap reconstruction using a novel technique that includes a vertical and a horizontal sling for full-thickness defects involving the oral commissure.

    Patients and Methods

    We used a free radial forearm flap and the palmaris longus tendon to correct lip and cheek defects in 6 patients (3 men, 3 women; age, 55–84 years). The tendon was divided into 2 portions for use as the double sling. One sling was used to connect the upper and lower stumps of the orbicularis oris in the vertical direction and the other to connect the vertical sling and masseter muscle. The outcomes assessed were esthetic appearance and functional results.

    Results

    The facial defects ranged in size from 3.0 cm × 4.0 cm to 7.0 cm × 6.0 cm and the mucosal defects from 1.5 cm × 4.0 cm to 6.5 cm × 5.0 cm. The length of the harvested tendon ranged from 11.5 to 13.5 cm. All flaps survived without complications. Good esthetic outcomes were achieved (excellent facial appearance, n = 1; no lip deviation or drooping, n = 5). Functionally, all patients had acceptable mouth opening and were able to eat a regular diet.

    Conclusions

    Good physiological and functional results can be achieved using a double tendon sling for reconstruction of the modiolus in patients with full-thickness defects involving the oral commissure.
  • Hypoxic culture enhances the antimicrobial activity of amnion-derived mesenchymal stem cells, thereby reducing bacterial load and promoting wound healing in diabetic mice
    Riku Ishii, Shunsuke Ohnishi, Masahiro Hojo, Kosuke Ishikawa, Emi Funayama, Takahiro Miura, Naoto Okubo, Kazufumi Okada, Yuhei Yamamoto, Taku Maeda
    Biochemical and Biophysical Research Communications, 150903, 150903, Elsevier BV, 2024年10月, ［査読有り］, ［責任著者］
    研究論文（学術雑誌）
  • Distinct Roles of Omental and Latissimus Dorsi Flaps for Blocking Infection Pathways and Protecting A Left Ventricular Assist Device
    Dongkyung Seo, Taku Maeda, Tomonori Ooka, Takahiro Miura, Kosuke Ishikawa, Emi Funayama, Satoru Wakasa, Yuhei Yamamoto
    The Heart Surgery Forum, 27, 9, E998, E1002, Forum Multimedia Publishing LLC, 2024年09月10日, ［査読有り］, ［責任著者］
    研究論文（学術雑誌）, Left ventricular assist devices (LVADs) are vital for managing severe heart failure in transplant-ineligible patients, but device exposure and infection pose significant challenges. This report details a 42-year-old man with dilated cardiomyopathy and bronchial asthma who presented with an externalized LVAD following a HeartMate II to HeartMate III exchange due to malfunction. Our tailored surgical strategy treated the LVAD driveline and main body as two distinct parts. This distinction is crucial, as major upstream infections typically originate from the driveline. We applied flaps to these parts for different purposes, maximizing their unique characteristics. The omental flap, chosen for its flexibility, blood supply, and immunological activation upon foreign body contact, covered the driveline. The latissimus dorsi flap provided vascularity and mechanical protection for the LVAD. Additionally, we review the omentum's basic physiological aspects, which are often unfamiliar to clinicians. Infection has not recurred in 6 months postoperatively, demonstrating the approach's effectiveness.
  • Leukocytoclastic Vasculitis-Induced Lower Leg Ulceration in the Course of Immune Checkpoint Inhibitor Therapy for Advanced Malignant Melanoma: A Case Report
    Dongkyung Seo, Shin Ariga, Kosuke Ishikawa, Takahiro Miura, Rika Moku, Emi Funayama, Yuhei Yamamoto, Taku Maeda
    Journal of Wound Management and Research, 20, 2, 168, 172, Korean Wound Management Society, 2024年06月30日, ［査読有り］, ［責任著者］
    研究論文（学術雑誌）, Immune checkpoint inhibitors (ICIs) have expanded therapeutic options for advanced malignancies, offering new hope for conditions once deemed untreatable. However, the advent of ICIs has introduced a spectrum of immune-related adverse events (irAEs), including leukocytoclastic vasculitis (LCV), a rare but significant complication. This case report describes development of LCV after treatment with nivolumab and ipilimumab in a 70-year-old man with malignant melanoma, highlighting the diagnostic and management challenges of such irAEs. Despite extensive investigation, conventional pathology failed to identify the immune complexes typically associated with LCV. The clinical presentation, alongside a detailed medical history and the exclusion of infections, medications, and autoimmune diseases, was crucial in establishing a diagnosis. Ulcer resolution following discontinuation of ICI therapy and initiation of steroids further support the conclusion that LCV was an irAE in this patient. This case underscores the need for vigilant monitoring for irAEs for the variable onset after ICI therapy and the importance of thorough history-taking to guide diagnosis and treatment. With ICIs becoming increasingly prevalent in oncology, the incidence of ICI-induced ulcers like LCV is expected to rise, necessitating heightened awareness and multidisciplinary approaches to patient care.
  • Fluoroscopy- and endoscopy-guided transoral sclerotherapy using foamed polidocanol for oropharyngolaryngeal venous malformations in a hybrid operation room: A case series
    Ishikawa K, Maeda T, Funayama E, Murao N, Miura T, Sasaki Y, Seo D, Mitamura S, Oide S, Yamamoto Y, Sasaki S
    Journal of Clinical Medicine, 13, 8, 2369, 2024年04月18日, ［査読有り］, ［招待有り］
    英語, 研究論文（学術雑誌）
  • Lymphatic drainage patterns of malignant skin tumors in the head and neck region: a single-center retrospective study
    Nishio T, Maeda T, Ishikawa K, Murao N, Fuyama K, Yamamoto Y, Hayashi T
    International Journal of Clinical Oncology, 2024年03月30日, ［査読有り］, ［国内誌］
    英語, 研究論文（学術雑誌）
  • Refinement of Surgery for Postaxial Polysyndactyly of the Toes
    Kosuke Ishikawa, Hiroshi Furukawa, Yuhei Yamamoto, Emi Funayama, Takahiro Miura, Taku Maeda
    Annals of Plastic Surgery, Ovid Technologies (Wolters Kluwer Health), 2024年03月27日, ［査読有り］
    研究論文（学術雑誌）, Purpose

    Treatment for polysyndactyly of the toes aims at cosmetic improvement but the lateroplantar rotation of the new fifth toe remains challenging. This study evaluated our novel surgical procedure for postaxial polysyndactyly of the toes.

    Materials and Methods

    Patients with postaxial polysyndactyly involving the fourth, fifth, and sixth toes treated in 2007 to 2017 with a minimum follow-up duration of 1 year were retrospectively investigated. Our aims of surgery for this condition were to avoid excessive lateroplantar rotation of the new fifth toe by using a proximally elongated plantar “shark-fin flap” and to make the tip of this toe appear to be naturally pointing inward by using the dog-ear component of the flap on the tip of the toe. The excess skin of the shark-fin flap was grafted onto the lateral surface of the fourth toe. Lateroplantar rotation of the fifth toe in these patients was compared with that in photographs of the feet of 96 normal 4-year-old children.

    Results

    A total of 11 feet in 10 patients (6 male, 4 female; mean age 1.3 years) were analyzed. Syndactyly between the fourth and fifth toes was complete in 3 feet, incomplete at the level of the distal interphalangeal joint of the fifth toe in 5, and incomplete at the level of the proximal interphalangeal joint of the fifth toe in 3. Lateroplantar rotation of the fifth toe, evaluated by the mean angle between 2 intersecting lines extending from the proximal nail fold of the third and fifth toes, was 25 ± 10° in normal feet and 0 ± 12° in operated feet with polysyndactyly. The absolute left-right difference in this angle was 7 ± 5° in normal children and 22 ± 12° in patients with polysyndactyly. Valgus deformity of the new fifth toe improved in all patients during a mean postoperative follow-up of 3.8 years.

    Conclusions

    Using our procedure, no excessive lateroplantar rotation has been observed when the tip of the fifth toe is inclined inward using a dog-ear flap component. This procedure could be useful in patients in whom the cosmetic outcome is a priority.
  • Negative Pressure Wound Therapy with Instillation and Dwell Time in Patients on Hemodialysis
    Erika Guilpain Kusajima, Kosuke Ishikawa, Emi Funayama, Takahiro Miura, Katsumi Horiuchi, Suguru Matsui, Tatsuya Saito, Hotaka Matsui, Yuhei Yamamoto, Taku Maeda
    International Journal of Surgical Wound Care, 5, 1, 1, 7, Japan Society for Surgical Wound Care, 2024年03月01日, ［査読有り］
    研究論文（学術雑誌）
  • Intranodal lymphangiography with lipiodol as a diagnostic and therapeutic approach for spontaneous cervical chyle leak
    Yuki Sasaki, Yusuke Sakuhara, Satoru Sasaki, Taku Maeda, Yuhei Yamamoto, Kosuke Ishikawa
    Clinical Case Reports, 11, 12, Wiley, 2023年12月19日, ［査読有り］
    研究論文（学術雑誌）, Key Clinical Message

    We present a case of spontaneous cervical chyle leak that showed as left‐sided neck swelling. Spontaneous chyle leak is extremely rare. Lymphangiography with lipiodol is useful as a diagnostic and therapeutic approach for chyle leak.
  • Burn conversion possibly caused by COVID-19 infection: A case report
    Dongkyung Seo, Taku Maeda, Yuhei Yamamoto, Emi Funayama, Takahiro Miura, Norifumi Matsuda, Kosuke Ishikawa
    Burns Open, Elsevier BV, 2023年12月, ［査読有り］
    研究論文（学術雑誌）
  • Partially involuting congenital hemangioma with pyogenic granuloma‐induced rapid progression following incisional biopsy in infancy: A case report
    Yuki Sasaki, Kosuke Ishikawa, Takahiro Miura, Emi Funayama, Yuhei Yamamoto, Taku Maeda
    Clinical Case Reports, 11, 10, Wiley, 2023年10月17日, ［査読有り］
    研究論文（学術雑誌）, Key Clinical Message

    We present a case of partially involuting congenital hemangioma (PICH) that showed rapid growth with ulceration after incisional biopsy. PICH does not typically grow after birth. However, if growth occurs due to stimuli like biopsy, it is essential to consider the possibility of pyogenic granuloma complication.
  • Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel–Trenaunay syndrome in an Asian population
    Yuki Sasaki, Kosuke Ishikawa, Kanako C. Hatanaka, Yumiko Oyamada, Yusuke Sakuhara, Tadashi Shimizu, Tatsuro Saito, Naoki Murao, Tomohiro Onodera, Takahiro Miura, Taku Maeda, Emi Funayama, Yutaka Hatanaka, Yuhei Yamamoto, Satoru Sasaki
    Orphanet Journal of Rare Diseases, 18, 1, Springer Science and Business Media LLC, 2023年09月04日, ［査読有り］
    研究論文（学術雑誌）, Abstract

    Background

    Klippel–Trenaunay syndrome (KTS) is a rare slow-flow combined vascular malformation with limb hypertrophy. KTS is thought to lie on the PIK3CA-related overgrowth spectrum, but reports are limited. PIK3CA encodes p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) that plays an essential role in the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. We aimed to demonstrate the clinical utility of targeted next-generation sequencing (NGS) in identifying PIK3CA mosaicism in archival formalin-fixed paraffin-embedded (FFPE) tissues from patients with KTS.

    Results

    Participants were 9 female and 5 male patients with KTS diagnosed as capillaro-venous malformation (CVM) or capillaro-lymphatico-venous malformation (CLVM). Median age at resection was 14 years (range, 5–57 years). Median archival period before DNA extraction from FFPE tissues was 5.4 years (range, 3–7 years). NGS-based sequencing of PIK3CA achieved an amplicon mean coverage of 119,000x. PIK3CA missense mutations were found in 12 of 14 patients (85.7%; 6/8 CVM and 6/6 CLVM), with 8 patients showing the hotspot variants E542K, E545K, H1047R, and H1047L. The non-hotspot PIK3CA variants C420R, Q546K, and Q546R were identified in 4 patients. Overall, the mean variant allele frequency for identified PIK3CA variants was 6.9% (range, 1.6–17.4%). All patients with geographic capillary malformation, histopathological lymphatic malformation or macrodactyly of the foot had PIK3CA variants. No genotype–phenotype association between hotspot and non-hotspot PIK3CA variants was found. Histologically, the vessels and adipose tissues of the lesions showed phosphorylation of the proteins in the PI3K/AKT/mTOR signaling pathway, including p-AKT, p-mTOR, and p-4EBP1.

    Conclusions

    The PI3K/AKT/mTOR pathway in mesenchymal tissues was activated in patients with KTS. Amplicon-based targeted NGS could identify low-level mosaicism from low-input DNA extracted from FFPE tissues, potentially providing a diagnostic option for personalized medicine with inhibitors of the PI3K/AKT/mTOR signaling pathway.
  • Development of a simultaneous and noninvasive measuring method using high-frame rate videography and motion analysis software for the assessment of facial palsy recovery in a rat model
    Takahiro Miura, Yuhei Yamamoto, Emi Funayama, Kosuke Ishikawa, Taku Maeda
    Journal of Plastic, Reconstructive & Aesthetic Surgery, 82, 211, 218, Elsevier BV, 2023年07月, ［査読有り］
    研究論文（学術雑誌）
  • Utility of Color Doppler Ultrasonography in Monitoring of a Free Jejunal Flap
    Taku Maeda, Kosuke Ishikawa, Yoichiro Oda, Satoshi Kano, Nayuta Tsushima, Tomohiro Sakashita, Akihiro Homma, Yuhei Yamamoto, Emi Funayama
    The Laryngoscope, Wiley, 2023年06月29日, ［査読有り］, ［筆頭著者］
    研究論文（学術雑誌）
  • Therapeutic Potential of the Prolyl Hydroxylase Inhibitor Roxadustat in a Mouse Hindlimb Lymphedema Model
    Yoshitada Hoshino, Masayuki Osawa, Emi Funayama, Kosuke Ishikawa, Takahiro Miura, Masahiro Hojo, Yuhei Yamamoto, Taku Maeda
    Lymphatic Research and Biology, 21, 4, 372, 380, Mary Ann Liebert Inc, 2023年03月07日, ［査読有り］, ［責任著者］
    研究論文（学術雑誌）
  • Refinements in the reconstruction of bisphosphonate-related osteonecrosis of the jaw.
    Taku Maeda, Yuhei Yamamoto, Akira Satoh, Toshihiko Hayashi
    JPRAS open, 35, 1, 5, 2023年03月, ［査読有り］, ［筆頭著者］, ［国際誌］
    英語, 研究論文（学術雑誌）, The recommended treatment strategy for stage 3 bisphosphonate-related osteonecrosis of the jaw (BRONJ) is currently rigid plate fixation without bone reconstruction. However, a recent systematic review indicated the utility of microsurgical reconstruction after resection of BRONJ. Several types of flaps have been described but their applications are controversial. Here we present a detailed reconstruction plan for obtaining better outcomes in patients with maxillary and mandibular BRONJ. Given that progressive maxillary BRONJ is often invasive to the skin, including the eyelid, leading to functional loss such as leakage of discharge and ectropion, several revision surgeries are needed to increase the volume in the defect after the free flap transfer. For progressive mandibular BRONJ, hemi-mandibulectomy to subtotal mandibulectomy with an adequate margin from the necrotic bone is necessary, followed by a well-designed fibular free flap.
  • Effectiveness and safety of percutaneous sclerotherapy using absolute ethanol and/or polidocanol for maxillofacial venous malformations involving the masticatory muscles: A case series
    Kosuke Ishikawa, Satoru Sasaki, Hiroshi Furukawa, Taku Maeda, Takahiro Miura, Yuki Sasaki, Yuhei Yamamoto, Emi Funayama
    Oral Surgery, Oral Medicine, Oral Pathology and Oral Radiology, 135, 3, 355, 362, Elsevier BV, 2023年03月, ［査読有り］
    研究論文（学術雑誌）
  • Efficacy of hyperbaric oxygen after microtia reconstruction using costal cartilage: A retrospective case-control study
    Naoki Murao, Akihiko Oyama, Yuhei Yamamoto, Emi Funayama, Kosuke Ishikawa, Taku Maeda
    Undersea and Hyperbaric Medicine, Undersea and Hyperbaric Medical Society (UHMS), 2023年01月01日, ［査読有り］, ［責任著者］
    研究論文（学術雑誌）, Introduction: Microtia reconstruction with autologous costal cartilage framework grafting is challenging because the three-dimensional structure of the ear is highly complex, and meeting the high aesthetic demands of patients can be difficult. If the skin flap overlying the framework is thinned to achieve a smooth and accentuated outline, a poor blood supply in the thin skin flap may lead to skin necrosis, exposure of the framework, and poor surgical results. Hyperbaric oxygen (HBO2) therapy can promote the healing of complex wounds and flaps. This study sought to determine the effectiveness of HBO2 therapy for prevention of postoperative complications after framework grafting in microtia reconstruction. Methods: We retrospectively evaluated postoperative complications and compared outcomes in pediatric patients who underwent costal cartilage grafting for microtia reconstruction at our institution between 2011 and 2015 according to whether or not they received postoperative HBO2 therapy. HBO2 therapy was applied once daily for a total of 10 sessions starting on the first postoperative day. Results: During the study period, eight patients received HBO2 therapy after costal cartilage grafting and 12 did not. There was no significant difference in the incidence of postoperative ulcers. However, the incidence of framework exposure was lower and the healing time was shorter in patients who received HBO2 therapy than in those who did not. Discussion: HBO2 therapy can be used safely in pediatric patients to reduce postoperative complications and improve the aesthetic outcome of microtia reconstruction. After costal cartilage grafting, HBO2 therapy should be considered as adjuvant therapy.
  • Sentinel node restoration by vascularized lymph node transfer in mice
    Erika G. Kusajima, Yuhei Yamamoto, Kosuke Ishikawa, Takahiro Miura, Emi Funayama, Masayuki Osawa, Ryo Takagi, Taku Maeda
    Microsurgery, Wiley, 2022年11月02日, ［査読有り］
    研究論文（学術雑誌）
  • Restoration of lymph flow by flap transfer can prevent severe lower extremity lymphedema after inguino-pelvic lymphadenectomy
    Taku Maeda, Yuhei Yamamoto, Toshihiko Hayashi, Hiroshi Furukawa, Kosuke Ishikawa, Takahiro Miura, Masahiro Hojo, Emi Funayama
    Surgery Today, 53, 5, 588, 595, Springer Science and Business Media LLC, 2022年10月29日, ［査読有り］, ［筆頭著者］
    研究論文（学術雑誌）
  • Streptococcal Toxic Shock Syndrome in a Pediatric Patient With Intramuscular Venous Malformation in the Neck
    Norifumi Matsuda, Kosuke Ishikawa, Emi Funayama, Shintaro Mitamura, Satoru Sasaki, Yuhei Yamamoto, Taku Maeda
    The Journal of Emergency Medicine, Elsevier BV, 2022年10月, ［査読有り］
    研究論文（学術雑誌）
  • Temporoparietal fascia flap was useful for the open surgery of temporomandibular joint mobilization
    Hiroyuki Hato, Noritaka Ohga, Chiharu Satoh, Ken-ichiro Sakata, Takuya Asaka, Taku Maeda, Taihiko Yamaguhi, Toshihiko Hayashi, Yoshimasa Kitagawa
    Journal of Oral and Maxillofacial Surgery, Medicine, and Pathology, Elsevier BV, 2021年10月
    研究論文（学術雑誌）
  • Combined internal and external negative pressure wound therapy: breakthrough treatment for lymphocutaneous intractable fistula
    Takahiro Miura, Yuhei Yamamoto, Naoki Murao, Taku Maeda, Masayuki Osawa, Toshihiko Hayashi, Emi Funayama
    Surgery Today, 51, 10, 1630, 1637, Springer Science and Business Media LLC, 2021年10月, ［査読有り］
    研究論文（学術雑誌）
  • Breast reconstruction via fat grafting for a patient with bilateral congenital amastia ( Finlay‐Marks syndrome)
    Riri Ito, Yuhei Yamamoto, Taku Maeda, Kosuke Ishikawa, Emi Funayama
    Congenital Anomalies, 61, 4, 142, 143, Wiley, 2021年07月, ［査読有り］
    研究論文（学術雑誌）
  • Topical Application of Conditioned Medium from Hypoxically Cultured Amnion-Derived Mesenchymal Stem Cells Promotes Wound Healing in Diabetic Mice.
    Hiroko Takahashi, Shunsuke Ohnishi, Yuhei Yamamoto, Toshihiko Hayashi, Naoki Murao, Masayuki Osawa, Taku Maeda, Kosuke Ishikawa, Naoya Sakamoto, Emi Funayama
    Plastic and reconstructive surgery, 147, 6, 1342, 1352, 2021年06月01日, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: Mesenchymal stem cells or their conditioned medium improve chronic wound healing, and their effect is enhanced by hypoxia. Diabetic foot ulcers are chronic wounds characterized by abnormal and delayed healing, which frequently require amputation. The authors evaluated the effect of topical application of conditioned medium from hypoxically cultured amnion-derived mesenchymal stem cells on wound healing in diabetic mice. METHODS: Amnion-derived mesenchymal stem cells were cultured under 21% oxygen to prepare normoxic conditioned medium and under 1% oxygen to prepare hypoxic conditioned medium. Hydrogels containing standard medium, normoxic conditioned medium, or hypoxic conditioned medium were topically applied to excisional wounds of mice with streptozotocin-induced diabetes. Ulcer tissues were harvested on day 9; immunohistochemical and quantitative polymerase chain reaction analyses were performed to analyze angiogenesis, inflammatory cell infiltration, and expression levels of inflammation-related genes. RESULTS: Hypoxic conditioned medium significantly enhanced wound closure, increased capillary density and epithelization, and reduced macrophage infiltration. It also tended to reduce the infiltration of neutrophils and enhance the infiltration of regulatory T cells; it showed a tendency to downregulate the expression of the inflammation-related genes interleukin-1β, interleukin-6, chemokine ligand 1, and chemokine ligand 2. Normoxic conditioned medium exhibited similar effects, although they were of lesser magnitude than those of hypoxic conditioned medium. CONCLUSIONS: Hydrogels containing hypoxically cultured, amnion-derived mesenchymal stem cell conditioned medium accelerated wound healing in diabetic mice by enhancing angiogenesis, accelerating epithelization, and suppressing inflammation. Therefore, topical application of amnion mesenchymal stem cell-derived hypoxic conditioned medium could be a novel treatment for diabetic foot ulcers.
  • Cleft lip in oto-palato-digital syndrome type I.
    Erika Guilpain Kusajima, Taku Maeda, Naoki Murao, Emi Funayama, Yuhei Yamamoto
    Congenital anomalies, 61, 3, 103, 104, 2021年05月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）
  • Iatrogenic third-degree burn caused by off-label use of an infrared radiant heat lamp in a patient with accidental hypothermia
    Kosuke Ishikawa, Taku Maeda, Toshihiko Hayashi, Ryuji Shichinohe, Naoki Murao, Masahiro Hojo, Riri Ito, Masayuki Osawa, Yuhei Yamamoto, Emi Funayama
    Burns Open, 5, 1, 21, 24, Elsevier BV, 2021年01月
    研究論文（学術雑誌）
  • Maggot debridement therapy in critical limb ischaemia: a case study.
    Taku Maeda, Yuhei Yamamoto, Naoki Murao, Toshihiko Hayashi, Chu Kimura, Suguru Matsui, Tatsuya Saito, Hotaka Matsui, Masayuki Osawa, Emi Funayama
    Journal of wound care, 29, Sup12, S28-S32, 2020年12月01日, ［査読有り］, ［筆頭著者］, ［国際誌］
    英語, 研究論文（学術雑誌）, OBJECTIVE: In critical limb ischaemia (CLI), first-line therapy is revascularisation, but alternative treatment options are needed in certain cases. Maggot debridement therapy (MDT) is historically considered to be contraindicated in ischaemic ulcers. Wound care in patients with CLI is becoming increasingly diverse with the development of novel revascularisation strategies; therefore, CLI now needs to be reconsidered as an indication for MDT. METHOD: We retrospectively reviewed five legs with CLI (five male, one female) treated with MDT between January 2013 and December 2017. Changes in skin perfusion pressure (SPP) around the ulcer before and after MDT were evaluated. One or two cycles of MDT were performed (eight in total). We also evaluated the proportion of necrotic tissue in the ulcer and the presence of exposed necrotic bone. The proportion of necrotic tissue in the ulcer was classified as NT 1+ (<25%), NT 2+ (25-50%), NT 3+ (50-75%) or NT 4+ (>75%). RESULTS: When the proportion of necrotic tissue was >50%, with no exposed necrotic bone in the wound, an increase in SPP was observed after five (62.5%) of eight cycles of MDT. And with a proportion of necrotic tissue of <25% and/or exposed necrotic bone in the wound, a decrease in SPP was observed after three (37.5%) of eight cycles. Wound healing was accelerated in the presence of increased SPP. CONCLUSION: Effective MDT with increased SPP requires an ulcerative state of necrotic tissue grade > NT 3+, with no exposed necrotic bone.
  • Long-term outcomes and recurrence-free interval after the treatment of keloids with a standardized protocol.
    T Maeda, E Funayama, Y Yamamoto, N Murao, M Osawa, K Ishikawa, T Hayashi
    Journal of tissue viability, 2020年11月30日, ［査読有り］, ［筆頭著者］, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: Recurrence rates of keloids have generally been reported at one time point. However, the longer the duration after treatment, the greater the likelihood that such lesions will recur. In this study, we analysed the time to recurrence during long-term follow-up. MATERIAL AND METHODS: We retrospectively reviewed recurrence-free interval in 52 patients with keloid (age 8-79 years) who had been treated between June 2006 and January 2011 using a standardised protocol developed by our group. RESULTS: Mean duration of follow-up was 37.5 (range, 7-120) months in patients with keloid. Kaplan-Meier survival curves revealed a statistically significant difference in recurrence-free interval between ear keloids and keloids excluding ear keloids. Recurrence rate for keloids was high in the first 2 years after treatment. CONCLUSIONS: Kaplan-Meier analysis was useful for understanding the tendency of recurrence of keloids after treatment using a standardised protocol.
  • A Comparison of Outcomes After Palatoplasty in Patients With Non-Syndromic Pierre Robin Sequence Versus Patients With Non-Syndromic Isolated Cleft Palate
    Maeda Taku, Yuhei Yamamoto, Akihiko Oyama, Satoru Sasaki, Toshihiko Hayashi, Naoki Murao, Masayuki Osawa, Emi Funayama
    The Journal of craniofacial surgery, 31, 8, 2231, 2234, NLM (Medline), 2020年11月01日, ［査読有り］, ［筆頭著者］
    英語, 研究論文（学術雑誌）
  • A Comparison of Outcomes After Palatoplasty in Patients With Non-Syndromic Pierre Robin Sequence Versus Patients With Non-Syndromic Isolated Cleft Palate.
    Maeda Taku, Yuhei Yamamoto, Akihiko Oyama, Satoru Sasaki, Toshihiko Hayashi, Naoki Murao, Masayuki Osawa, Emi Funayama
    The Journal of craniofacial surgery, 2020年10月13日, ［査読有り］, ［筆頭著者］, ［国際誌］
    英語, 研究論文（学術雑誌）, The purpose of this retrospective study was to compare outcomes of cleft palate repair in patients with non-syndromic Pierre Robin sequence (NS-PRS) versus those with non-syndromic isolated cleft palate (NS-ICP). Pierre Robin sequence (PRS) was defined as a diagnosis of the triad of microretrognathia, glossoptosis, and cleft palate, and the severity of PRS was assessed based on the presence of respiratory and feeding problems. All patients underwent palatoplasty between January 2000 and December 2011. The authors examined age at palatoplasty, type of cleft palate, fistula rate, velopharyngeal (VP) function, nasal emission, hypernasality, and need for secondary speech surgery, in addition to PRS severity in the NS-PRS patients. A total of 15 NS-PRS patients and 40 NS-ICP patients were reviewed. The incidence of VP dysfunction, nasal emission, hypernasality, and secondary speech surgery was not significantly different between the NS-PRS patients and NS-ICP patients. Age at palatoplasty was significantly different between the 2 groups (P = 0.012) but type of CP was not (P = 1.00). Only 2 NS-PRS patients were classified as category III (severe), and all of the NS-PRS patients who had VP insufficiency were classified as PRS severity category I (not severe). The findings of this study indicate that NS-PRS patients may not have worse outcomes than NS-ICP patients.
  • Ulcerated Infantile Hemangioma of the Hard Palate: Diagnostic Treatment With Oral Propranolol
    Kosuke Ishikawa, Munezumi Fujita, Tomohiro Takeda, Shintaro Mitamura, Takuya Nishio, Emi Funayama, Toshihiko Hayashi, Masayuki Osawa, Taku Maeda, Yuhei Yamamoto, Satoru Sasaki
    The Journal of craniofacial surgery, 31, 6, e600, e602, NLM (Medline), 2020年09月01日
    英語, 研究論文（学術雑誌）
  • Application of negative-pressure wound therapy after radical excision of soft tissue malignancy
    Taku Maeda, Naoki Murao, Toshihiko Hayashi, Emi Funayama, Masayuki Osawa, Kosuke Ishikawa, Yuhei Yamamoto
    International Journal of Surgical Wound Care, 1, 2, 47, 52, Japan Society for Surgical Wound Care, 2020年09月01日, ［査読有り］, ［筆頭著者］
    研究論文（学術雑誌）
  • Wound Care for Calciphylaxis
    Erika Guilpain Kusajima, Yuhei Yamamoto, Naoki Murao, Toshihiko Hayashi, Masayuki Osawa, Taku Maeda, Kosuke Ishikawa, Katsumi Horiuchi, Suguru Matsui, Tatsuya Saito, Hotaka Matsui, Emi Funayama
    International Journal of Surgical Wound Care, 1, 1, 20, 26, Japan Society for Surgical Wound Care, 2020年
    研究論文（学術雑誌）
  • Combination laser therapy as a non-surgical method for treating congenital melanocytic nevi from cosmetically sensitive locations on the body.
    Emi Funayama, Yuhei Yamamoto, Akihiko Oyama, Naoki Murao, Toshihiko Hayashi, Taku Maeda, Hiroshi Furukawa, Masayuki Osawa
    Lasers in medical science, 34, 9, 1925, 1928, 2019年12月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）
  • Advancement Flap Using Excess Skin for Upper Eyelid Full-Thickness Defects.
    Ito R, Maeda T, Yamamoto Y, Funayama E, Murao N, Osawa M, Ishikawa K, Ikeda M, Hayashi T
    The Journal of craniofacial surgery, 30, 8, 2614, 2616, 2019年11月, ［査読有り］
  • Squamous cell carcinoma arising in a chronic leg ulcer in Klippel-Trenaunay syndrome after the Charles procedure: A case with 40 years of follow up.
    Kosuke Ishikawa, Emi Funayama, Yuhei Yamamoto, Hiroshi Furukawa, Toshihiko Hayashi, Naoki Murao, Masayuki Osawa, Taku Maeda, Munezumi Fujita, Satoru Sasaki
    The Journal of dermatology, 46, 11, e403-e405, 2019年11月, ［査読有り］, ［国際誌］
    英語
  • New video fluoroscopic chewing examination for patients who use dentures after mandibular reconstruction.
    T Hayashi, K Kuribayashi, T Maeda, Y Yamamoto
    The British journal of oral & maxillofacial surgery, 57, 7, 697, 698, 2019年09月, ［国際誌］
    英語, 研究論文（学術雑誌）
  • Oculo-Auriculo-Fronto-Nasal Syndrome With Duane Retraction Syndrome and Dysplastic Bony Structure in the Midline of Nose.
    Riri Ito, Masayuki Osawa, Yuhei Yamamoto, Naoki Murao, Toshihiko Hayashi, Taku Maeda, Kosuke Ishikawa, Akihiko Oyama, Emi Funayama
    The Journal of craniofacial surgery, 30, 6, e576-e578, 2019年09月, ［国際誌］
    英語, 研究論文（学術雑誌）, Oculo-auriculo-fronto-nasal syndrome (OAFNS) is a rare anomaly characterized by features overlapping those of frontonasal dysplasia (FND) and the oculo-auriculo-vertebral spectrum (OAVS). The FND features malformation of frontonasal process-derived structures, characterized by anomalies in the central portion of the face. The OAVS is characterized by developmental anomalies of the first and second pharyngeal arches. The OAFNS is a condition with clinical features of both FND and OAVS.Here, the authors present the case of a male with OAFNS who not only exhibited typical OAFNS symptoms but also a dysplastic bony structure that bridged the anterior nasal spine and inferior nasal bones, and unilateral type 3 Duane retraction syndrome (absence of right-eye abduction). Abnormal nasal bones are characteristic of OAFNS; such abnormalities are absent from FND and OAVS. The authors reduced the dysplastic nasal bony structure via open external rhinoplasty, followed by lateral nasal osteotomy when he was 16 years of age. The nasal dorsum appeared natural after surgery and he was satisfied with the result.
  • Chondrocutaneous Bilateral Advancement Flap with Postoperative Radiation Therapy for a Helical Rim Keloid.
    Maeda T, Hayashi T, Murao N, Yamamoto Y
    Aesthetic plastic surgery, 43, 3, 658, 662, 2019年06月, ［査読有り］, ［筆頭著者］, ［国際誌］
    英語, 研究論文（学術雑誌）, Keloids can be recalcitrant, and a well-planned treatment strategy is essential. Multiple ear piercings have recently become popular, particularly among younger age groups. Management of keloids that develop after piercing of the ear cartilage may be particularly problematic. Helical rim keloids are difficult to excise because of the complex, three-dimensional, cartilaginous structure of the helix and its thin and tightly adherent covering layer of skin. The chondrocutaneous advancement flap introduced by Antia and Buch may be a useful reconstructive option for a helical rim keloid after marginal loss of a segment of the helix as a result of trauma, a burn, or excision of a malignant tumor. However, this technique is limited to wounds that involve only the helix. In this technical note, we describe the use of a chondrocutaneous bilateral advancement flap with postoperative radiation therapy to treat a more invasive and relatively large keloid on the scapha. This technique is straightforward and safe in terms of preserving the blood supply. The addition of adjuvant radiation therapy can help to decrease the risk of recurrence and preserve the morphological structure of the ear and patient satisfaction.Level of Evidence IV This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
  • Changes in high endothelial venules in lymph nodes after vascularized and nonvascularized lymph node transfer in a murine autograft model.
    Kosuke Ishikawa, Emi Funayama, Taku Maeda, Toshihiko Hayashi, Naoki Murao, Masayuki Osawa, Riri Ito, Hiroshi Furukawa, Akihiko Oyama, Yuhei Yamamoto
    Journal of surgical oncology, 119, 6, 700, 707, 2019年05月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, BACKGROUND AND OBJECTIVES: Vascularized lymph node transfer (LNT) is gaining popularity in the treatment of lymphedema. However, it is unclear whether the vascularization of transferred lymph nodes (LNs) contributes to functional improvement. High endothelial venules (HEVs) are specialized vessels that allow lymphocytes to enter LNs. In this study, we compared the numbers of HEVs and lymphocytes in LNs after vascularized and nonvascularized LNT. METHODS: Fifty mice were divided into three groups (group 1, pedicled vascularized LNT; group 2, pedicled nonvascularized LNT; group 3, free nonvascularized LNT). Afferent lymphatic reconnection was confirmed by patent blue staining. The transferred LNs were harvested 4 weeks after surgery. HEVs, B-cells, and T-cells were subjected to immunohistochemical staining and quantified. RESULTS: Afferent lymphatic reconnection was observed in 13 of 20 transferred LNs in group 1, 11 of 15 in group 2, and 7 of 15 in group 3. The ratio of dilated/total HEVs in transferred LNs with afferent lymphatic reconnection was significantly higher in group 1 than in groups 2 and 3. No significant differences in numbers of B-cells and T-cells were found in the transferred LNs. CONCLUSIONS: We found that more functional HEVs were preserved in cases with successful afferent lymphatic reconnection after vascularized LNT than after nonvascularized LNT.
  • Feasibility of pedicled vascularized inguinal lymph node transfer in a mouse model: A preliminary study.
    Kosuke Ishikawa, Taku Maeda, Emi Funayama, Toshihiko Hayashi, Naoki Murao, Masayuki Osawa, Hiroshi Furukawa, Akihiko Oyama, Yuhei Yamamoto
    Microsurgery, 39, 3, 247, 254, 2019年03月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, PURPOSE: Vascularized lymph node transfer is becoming more common in the treatment of lymphedema, but suitable small animal models for research are lacking. Here, we evaluated the feasibility of pedicled vascularized inguinal lymph node transfer in mice. METHODS: Twenty-five mice were used in the study. An inguinal lymph node-bearing flap with a vascular pedicle containing the superficial caudal epigastric vessels was transferred into the ipsilateral popliteal fossa after excision of the popliteal lymph node. Indocyanine green (ICG) angiography was used to confirm vascularity of the flap. ICG lymphography was performed to evaluate lymphatic flow at 3 and 4 weeks postoperatively. Patent blue dye was injected into the ipsilateral hind paw to observe staining of the transferred lymph node at 4 weeks postoperatively. All transferred lymph nodes were then harvested and histologically evaluated by hematoxylin and eosin staining. RESULTS: In 16 of the 25 mice, ICG lymphography showed reconnection between the transferred lymph node and the afferent lymphatic vessels, as confirmed by patent blue staining. Histologically, these transferred lymph nodes with afferent lymphatic reconnection significantly regressed in size (0.37 ± 0.24 mm2 ) and showed clear follicle formation, whereas those without afferent lymphatic reconnection showed less size regression (1.31 ± 1.17 mm2 ); the cell population was too dense to allow identification of follicles. CONCLUSIONS: We established a mouse model of vascularized lymph node transfer with predictable afferent lymphatic reconnection. Both the vascularization and reconnection might be necessary for functional regeneration of the transferred lymph node.
  • NEDD4 Is Involved in Inflammation Development during Keloid Formation.
    Munezumi Fujita, Yuhei Yamamoto, Jing-Jing Jiang, Toru Atsumi, Yuki Tanaka, Takuto Ohki, Naoki Murao, Emi Funayama, Toshihiko Hayashi, Masayuki Osawa, Taku Maeda, Daisuke Kamimura, Masaaki Murakami
    The Journal of investigative dermatology, 139, 2, 333, 341, 2019年02月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, Keloids mark a chronic inflammatory disease characterized by a fibroproliferative disorder of the skin. A genome-wide association study showed that single-nucleotide polymorphism rs8032158 in the neural precursor cell-expressed NEDD4 gene, which has six protein-coding transcript variants (TVs), is genetically linked to keloids. Here, we show that the high frequency of risk allele C in rs8032158 in keloid patients is associated with a selectively higher expression of TV3 of NEDD4 to activate the NF-κB pathway. Comparisons of keloid scars with normal skin samples that do not have the single-nucleotide polymorphism allele and were derived from different anatomical sites showed stronger expressions of NEDD4 TV3 and activated forms of NF-κB and STAT3 in keloid scars. Forced expression or selective knockdown of NEDD4 TV3 increased or decreased NF-κB activation in vitro. Furthermore, NEDD4 knockdown suppressed NF-κB-dependent inflammation development in vivo. Mechanistic analysis showed that NEDD4 TV3 is involved in NF-κB activation through its association with the adaptor protein RIP. These results suggest that NEDD4 TV3 is a potential diagnostic marker and therapeutic target for chronic skin diseases, including keloid.
  • Comparison of Nasal Symmetry Between Presurgical Nasal Stenting and Postsurgical Nasal Retainer Placement in Unilateral Clefts.
    Emi Funayama, Yuhei Yamamoto, Akihiko Oyama, Hiroshi Furukawa, Naoki Murao, Toshihiko Hayashi, Taku Maeda, Masayuki Osawa
    The Journal of craniofacial surgery, 30, 1, 133, 136, 2019年01月, ［査読有り］, ［国際誌］
    英語, 研究論文（学術雑誌）, The timing of cleft lip nose surgery remains controversial. The less invasive the procedure at the time of primary cleft lip repair, the less the growth and development of the nose is affected. Therefore, the nasal-stenting component of presurgical nasoalveolar molding has increasingly been used. However, not all cleft centers use such treatment. Conventional postsurgical placement of silicone nasal retainers remains popular. No report has yet compared presurgical nasal stenting (preNS) and postsurgical nasal retainer placement (postNR). In this study, postoperative nasal form outcomes after primary lip repair using preNS or postNR in patients with complete unilateral cleft lips, alveoli, and palates were compared. Patients in whom preNS alone was used for 6 months (group I) were compared with those receiving postNR (no preNS) for 6 months after primary nasal cartilage dissection (group II) and controls with no appliance (group III). Nasal anthropometric distances and angular relationships were measured photographically to assess nasal symmetry at 4 years of age in all groups. Compared to group III, groups I and II exhibited significantly greater nostril heights (P = 0.0075, P = 0.0015 respectively) and columellar deviation angles (P = 0.0020, P = 0.0221). Groups I and II did not differ significantly. No significant between-treatment difference in terms of nasal symmetry between preNS and postNR was observed. However, both treatments afforded significantly better results than no treatment. Since older infants tend to resist the placement of nasal devices, preNS is more feasible in this age group.
  • Immune-mediated antitumor effect of a transplanted lymph node.
    Maeda T, Hayashi T, Furukawa H, Iwasaki D, Ishikawa K, Funayama E, Murao N, Osawa M, Oyama A, Yamamoto Y
    International journal of cancer, 143, 5, 1224, 1235, 2018年09月, ［査読有り］, ［筆頭著者］, ［国際誌］
    英語, 研究論文（学術雑誌）, Lymph node (LN) transplantation is a recognized method for reconstruction of the lymphatic system and is used in the clinical setting to treat lymphedema. However, it is unclear whether transplanted LNs contribute to immune surveillance. In our study, we investigated whether a single transplanted non-vascularized LN, defined as a tumor-draining transplanted lymph node (TDTLN), could exert an immune-mediated antitumor effect. LN and lung metastases and primary tumor enlargement were evaluated in mice that were inoculated with B16-F10-luc2 melanoma cells in a hind limb footpad without (group 1) and with (group 2) popliteal lymph node (PLN) resection and in mice that underwent LN transplantation after PLN resection (group 3). The function of a TDTLN (group 3) and a tumor-draining popliteal lymph node (TDPLN; group 1) was evaluated in the context of cancer. LN and lung metastases were significantly aggravated by PLN resection but were significantly decreased by LN transplantation. Immunohistochemistry showed that the TDTLNs retained T-cells and B-cells and fluorescence-activated cell sorting analysis confirmed expansion of lymphocytes in these nodes; however, the degree of expansion in TDTLNs was different from that in TDPLNs. Expression of cytokines associated with immunostimulation was confirmed in the TDTLNs as well as in the TDPLNs. One of the differences in the immune-mediated antitumor effect of the TDPLNs and TDTLNs was ascribed to a difference in the site of lymphocyte homing to peripheral LNs through high endothelial venules. Non-vascularized LN transplantation had an immune-mediated antitumor effect.
  • Lymphatic Reconnection and Restoration of Lymphatic Flow by Nonvascularized Lymph Node Transplantation: Real-Time Fluorescence Imaging Using Indocyanine Green and Fluorescein Isothiocyanate-Dextran
    Taku Maeda, Yuhei Yamamoto, Daisuke Iwasaki, Toshihiko Hayashi, Emi Funayama, Akihiko Oyama, Naoki Murao, Hiroshi Furukawa
    Lymphatic Research and Biology, 16, 2, 165, 173, Mary Ann Liebert Inc., 2018年04月01日, ［査読有り］, ［筆頭著者］
    英語, 研究論文（学術雑誌）
  • Dominant lymph drainage patterns in the occipital and parietal regions: evaluation of lymph nodes in patients with skin cancer of the head
    Taku Maeda, Yuhei Yamamoto, Hiroshi Furukawa, Akihiko Oyama, Emi Funayama, Naoki Murao, Toshihiko Hayashi
    INTERNATIONAL JOURNAL OF CLINICAL ONCOLOGY, 22, 4, 774, 779, 2017年08月, ［査読有り］, ［筆頭著者］
    英語, 研究論文（学術雑誌）
  • Review and proposal of regional surgical management for melanoma: revisiting of integumentectomy and incontinuity dissection in treatment of skin melanoma.
    Toshihiko Hayashi, Hiroshi Furukawa, Takashi Kitamura, Ryuji Shichinohe, Naoki Murao, Akihiko Oyama, Emi Funayama, Taku Maeda, Yuhei Yamamoto
    International journal of clinical oncology, 22, 3, 569, 576, 2017年06月, ［査読有り］, ［国内誌］
    英語, 研究論文（学術雑誌）, BACKGROUND: Past studies showed that integumentectomy and incontinuity could be effective procedures in the surgical management of melanoma patients. The present study reports on the historical background of these procedures. In addition, we analyze the ICG assisted integumentectomy and incontinuity techniques and algorithms that we had created when performing this procedure. METHOD: In accordance with our algorithm, we performed ICG assisted integumentectomy/incontinuity procedures on 17 patients with stage III melanomas between 2008 and 2016. We also investigated the locoregional recurrence rate in a control group comprising 60 patients at stage III without using the algorithm. RESULTS: The former group exhibited a tendency of locoregional recurrence rate suppression. Melanoma cells in the dissected intervening tissue were microscopically identified in 2 out of 17 cases. CONCLUSIONS: Our ICG assisted integumentectomy or incontinuity procedures could be effective in controlling locoregional recurrence rates in melanoma cases. Moreover, our method can be generally applied because the dissection is only performed within the lymphatic pathway region identified using indocyanine green.
  • Application of vacuum-assisted closure therapy and hyperbaric oxygen therapy for an exposed titanium plate after mandible reconstruction: a case report
    Toshihiko Hayashi, Yuichi Ashikaga, Y. Ohiro, Kanchu Tei, S. Tanaka, Taku Maeda, R. Yoshitatsu, Kazuyo Kuribayashi
    International Journal of Oral and Maxillofacial Surgery, 46, 336, Elsevier BV, 2017年03月01日
  • Application of Vacuum-Assisted Closure Therapy and Hyperbaric Oxygen Therapy for an Exposed Titanium Plate After Mandible Reconstruction
    Taku Maeda, Yuhei Yamamoto, Soichi Tanaka, Toshihiko Hayashi
    JOURNAL OF CRANIOFACIAL SURGERY, 27, 7, E601, E604, 2016年10月, ［査読有り］, ［筆頭著者］
    英語, 研究論文（学術雑誌）
  • Reconstruction of low hairline microtia of Treacher Collins syndrome with a hinged mastoid fascial flap
    T. Maeda, A. Oyama, E. Funayama, Y. Yamamoto
    INTERNATIONAL JOURNAL OF ORAL AND MAXILLOFACIAL SURGERY, 45, 6, 731, 734, 2016年06月, ［査読有り］, ［筆頭著者］
    英語, 研究論文（学術雑誌）
  • Promising long-term outcomes of the reused skin-graft technique for chronic gluteal hidradenitis suppurativa
    Taku Maeda, Chu Kimura, Naoki Murao, Kikuko Takahashi
    JOURNAL OF PLASTIC RECONSTRUCTIVE AND AESTHETIC SURGERY, 68, 9, 1268, 1275, 2015年09月, ［査読有り］, ［筆頭著者］
    英語, 研究論文（学術雑誌）
  • Successful Conservative Management of a Large Congenital Scalp and Skull Defect
    Taku Maeda, Akihiko Oyama, Emi Funayama, Hiroshi Furukawa, Kazutoshi Cho, Yuhei Yamamoto
    JOURNAL OF CRANIOFACIAL SURGERY, 26, 3, E275, E277, 2015年05月, ［査読有り］, ［筆頭著者］
    英語, 研究論文（学術雑誌）
  • Increase in skin perfusion pressure after maggot debridement therapy for critical limb ischaemia
    T. Maeda, C. K. Kimura, K. T. Takahashi, K. I. Ichimura
    CLINICAL AND EXPERIMENTAL DERMATOLOGY, 39, 8, 911, 914, 2014年12月, ［査読有り］, ［筆頭著者］
    英語, 研究論文（学術雑誌）
  • Combination of Tessier clefts 3 and 4: Case report of a rare anomaly with 12 years' follow-up
    Taku Maeda, Akihiko Oyama, Toru Okamoto, Emi Funayama, Hiroshi Furukawa, Toshihiko Hayashi, Naoki Murao, Yoshiaki Sato, Yuhei Yamamoto
    JOURNAL OF CRANIO-MAXILLOFACIAL SURGERY, 42, 8, 1985, 1989, 2014年12月, ［査読有り］, ［筆頭著者］
    英語, 研究論文（学術雑誌）
  • Utility of the method using the tsukisui device to control intraoperative bleeding applied to neurofibroma resection
    Taku Maeda, Chu Kimura, Kikuko Takahashi, Kimihito Ichimura
    Plastic and Reconstructive Surgery, 1, 9, e85, Lippincott Williams and Wilkins, 2013年12月19日, ［査読有り］, ［筆頭著者］
    英語, 研究論文（学術雑誌）
  • Correction of anophthalmic enophthalmos with a three-staged procedure: two case reports.
    Tomohiro Minagawa, Ryuta Shioya, Takeshi Yamao, Chigusa Sato, Taku Maeda
    Case reports in surgery, 2011, 731259, 731259, 2011年, ［国際誌］
    英語, Surgical correction of an anophthalmic enophthalmos secondary to inappropriate repair of the eye socket involves several difficult aesthetic issues associated with long-term use of a poorly fitting prosthetic eye. In this paper, we present two cases of anophthalmic enophthalmos. During the treatment of the first patient, unsatisfactory cosmetic problems including lower eyelid retraction, hypoglobus, and severe upper eyelid ptosis were revealed. Accordingly, a three-staged procedure was performed on the second patient, including autologous augmentation of the eye socket, correction of lower eyelid retraction with a cartilage graft, and a frontalis sling procedure to correct upper eyelid ptosis.

その他活動・業績

共同研究・競争的資金等の研究課題

  • 低侵襲な頭蓋顎顔面骨再法の開発：間葉系幹細胞とM2マクロファージによる細胞治療
    科学研究費助成事業
    2025年04月 - 2028年03月
    三浦 隆洋, 舟山 恵美, 前田 拓, 石川 耕資, 佐々木 雄輝, 大澤 昌之
    日本学術振興会, 基盤研究(C), 北海道大学, 25K12903
  • 続発性リンパ浮腫における急性期重症化を防ぐ！レグネース１を標的とした新たな治療法
    科学研究費助成事業
    2024年04月01日 - 2027年03月31日
    佐藤 千草, 舟山 恵美, 松田 識郁, 石川 耕資, 前田 拓
    日本学術振興会, 基盤研究(C), 北海道大学, 24K12817
  • 幹細胞によるM１/M２マクロファージ調整作用はリンパ浮腫線維化を抑制しうるか？
    科学研究費助成事業
    2024年04月01日 - 2027年03月31日
    前田 拓, 石川 耕資, 山本 有平, 村尾 尚規
    日本学術振興会, 基盤研究(C), 北海道大学, 24K12818
  • HIF-1α安定化薬によるlymphatic basinの再構築
    科学研究費助成事業
    2024年04月01日 - 2027年03月31日
    草島 英梨香, 石川 耕資, 前田 拓, 三浦 隆洋, 北條 正洋, 徐 東經
    日本学術振興会, 基盤研究(C), 北海道大学, 24K12841
  • 男性型脱毛症治療のゲームチェンジャー；NPWTの毛周期・毛髪成長への影響
    科学研究費助成事業
    2023年04月01日 - 2026年03月31日
    大澤 昌之, 山本 有平, 前田 拓, 石井 浩子, 林 利彦
    禿髪は、様々な原因で毛髪が脱落することで頭皮が露出した状態であり、整容的および心理的に大きな懸念事項となる。その中でも男性型脱毛症(Androgenic alopecia: AGA)は、円形脱毛症、瘢痕性脱毛症等と並ぶ禿髪の原因疾患である。AGAでは、5α還元酵素によりテストステロンから変換されたジヒドロテストステロンがTransforming growth factor(TGF)-βの発現を誘導し、退行期への移行が促進され、脱毛が生じるとされる。現在治療として提供されているフィナステリド(5α還元酵素阻害薬)内服やミノキシジル（血管拡張薬）内服および外用は長期の継続使用が必要であり、毛髪移植は定着率が低く複数回の手術が必要である等の課題があり、より低侵襲に発毛・育毛を促進する治療法の開発が望まれている。
    一方、局所陰圧閉鎖療法（negative pressure wound therapy:NPWT）は、血流改善や細胞に対する物理的刺激等の効果により創傷治癒を促進し、形成外科領域で頻用されている。近年、NPWTを適用した創部において、毛髪の成長が促進されるという副次的な発見が報告された。しかし、現象の報告にとどまっており、その詳細の機序に関しては未解明である。本研究は、NPWTを用いて毛周期・毛髪成長に対する陰圧負荷の影響を基礎的に検証することを目的とし、毛髪治療領域において新たな治療法の確立に至る可能性がある研究である。
    初年度は、C57BL/6マウスに陰圧負荷を行った際の毛周期の変化を観察し、モデル作成を行った。次年度以降は上記モデルでの遺伝子発現解析や免疫組織化学染色、および圧設定のさらなる調整を進めていく予定である。
    日本学術振興会, 基盤研究(C), 北海道大学, 23K09093
  • 光老化のSASP制御～幹細胞エクソソームによるSkin Rejuvenation
    科学研究費助成事業
    2023年04月01日 - 2026年03月31日
    高橋 周子, 山本 有平, 前田 拓, 石川 耕資
    日本学術振興会, 基盤研究(C), 北海道大学, 23K09073
  • リキッドバイオプシーによる脈管奇形の遺伝子診断と個別化医療への応用
    科学研究費助成事業
    2023年04月01日 - 2026年03月31日
    石川 耕資, 山本 有平, 舟山 恵美, 前田 拓
    日本学術振興会, 基盤研究(C), 北海道大学, 23K09072
  • メラノーマ免疫療法の賦活化 - 抗PD-1抗体と腫瘍溶解性ウイルスの併用療法
    科学研究費助成事業 若手研究
    2021年04月01日 - 2023年03月31日
    前田 拓
    悪性黒色腫はメラノサイト由来の悪性腫瘍であり、その転移率の高さから進行期の予後は極めて不良である。近年、免疫チェックポイント阻害薬や分子標的薬などの登場によって、メラノーマの薬物療法は飛躍的に進歩した。これらの薬剤は術後補助療法のみならず、これまで有効な治療法のなかった遠隔転移に対しても一定の効果が認められ、その重要性は今後もますます高まっていくと考えられる。薬物療法の奏効率を高めるために、最適な併用療法が模索される一方で、薬剤の副作用は解決すべき大きな問題である。
    いま新たな癌治療法として注目を集めている腫瘍溶解性ウイルスは、癌細胞選択的に感染・増殖し、内部から細胞を破壊する。正常細胞内では増殖しないため、重大な副作用がないとされる。さらに、宿主の抗腫瘍免疫活性を賦活化させることで、直接ウイルスを投与していない腫瘍に対しても治療効果を発揮することが示唆されている。2017年には腫瘍溶解性ウイルスと抗Programmed cell death protein 1 (PD-1)抗体の併用療法の有用性が報告された。腫瘍溶解性ウイルスは、併用療法の副作用の問題を軽減しつつ、抗腫瘍効果を高めることができる新たな治療の選択肢として大きな期待が寄せられている。
    本研究は、腫瘍溶解性ウイルスと抗PD-1抗体の併用により、センチネルリンパ節や脾臓においてどのような変化が生じるかを検証し、腫瘍溶解性ウイルスの免疫賦活化の機序を詳細に検討することを目的とする。マウスにメラノーマを播種したモデルに各種薬剤を投与し、腫瘍のサイズ、肺・鼠径リンパ節・腋窩リンパ節への遠隔転移、膝窩リンパ節・脾臓のリンパ球分布・遺伝子発現の変化を解析することで、腫瘍溶解性ウイルスと免疫チェックポイント阻害薬の併用療法による免疫賦活化を証明する。
    日本学術振興会, 若手研究, 北海道大学, 21K16219
  • 低酸素応答システム活性化薬剤を用いた下肢慢性創傷の新治療
    科学研究費助成事業
    2020年04月01日 - 2023年03月31日
    大澤 昌之, 舟山 恵美, 山本 有平, 前田 拓, 石川 耕資, 林 利彦
    創傷治癒過程において酸素環境は重要である。生体は低酸素状態に対する適応応答としてHIF-1α (hypoxia inducible factor-1 alpha) を発現することで、血管新生などの創傷治癒の多段階で作用し、創傷治癒を促進するとされる。
    本研究は、リンパ浮腫・虚血・糖尿病を念頭に置いたマウス下肢慢性創傷モデルを用いてHIF-1α調整薬剤の創傷治癒に与える影響を検証し、生体が本来もつ低酸素応答システムを利用した、新たな慢性創傷に対する治療法の開発を目的とした。
    本年度は、２年目の計画に従い、初年度で行ったマウス後肢リンパ浮腫モデルを利用した創傷モデルの作成、Roxadustat（HIF-1α安定化薬）およびYC-１（HIF-1α阻害薬）の容量用法の検討に基づき、薬剤投与群と非投与群の間で創傷治癒期間および各タイムポイントでの創傷閉鎖割合に差があるかどうかを検討した。
    作成した群は、①皮膚切開のみのコントロール（手術なし・薬剤非投与群）②リンパ浮腫モデル（薬剤非投与群）③リンパ浮腫モデル（Roxadustat投与群）④リンパ浮腫モデル（YC-1投与群）の4群であり、それぞれ大腿部に創傷を作成した。
    皮膚切開のみのコントロール（手術なし・薬剤非投与群）に比してリンパ浮腫モデル（薬剤非投与群）は有意に創傷治癒期間が遅延した。また、通常のリンパ浮腫モデル（薬剤非投与群）に比して、Roxadustat（HIF-1α安定化薬）を使用した群で、創傷治癒期間の短縮および創閉鎖割合が促進し、YC-１（HIF-1α阻害薬）を使用した群で、創傷治癒期間の延長および創閉鎖割合が減少する傾向が見られた。また、薬剤を投与したリンパ浮腫モデル群間で後肢の周径の差および皮膚厚の差を認めた。これにより、リンパ浮腫の動態に対しても薬剤による影響がある可能性が示唆された。
    日本学術振興会, 基盤研究(C), 北海道大学, 20K09841
  • 低酸素応答システムからケロイド病態を斬る！～局所免疫の正常化と炎症・線維化の抑制
    科学研究費助成事業
    2020年04月01日 - 2023年03月31日
    村尾 尚規, 山本 有平, 林 利彦, 舟山 恵美, 前田 拓, 石川 耕資
    ケロイドは創傷治癒過程の異常により炎症と線維化が亢進した状態である。抗原とサイトカインの刺激を受けたCD4陽性T細胞、制御性T細胞とTh17細胞は相互に制御しバランスを保っており、炎症性疾患の発症や病態は制御性T細胞とTh17細胞のバランスにより影響される。われわれは既報でケロイド内では制御性T細胞の発現が低下し、免疫バランスの破綻により 炎症が遷延し線維化が亢進することを報告した。一方、近年ケロイド内は、低酸素状態であることがわかってきた。低酸素誘導因子(hypoxia-inducible factor、HIF)は、酸素供給が滞った組織内の細胞で活性化し 様々な遺伝子の発現を誘導し、生体の環境への適応を促す転写因子である。HIFは低酸素適応応答だけでなく、炎症や悪性腫瘍の病態にも関与する。HIFのサブタイプの中でも、ケロイド内ではHIF-1αの発現が亢進しており、低酸素状態を反映していると考えられる。HIF-1αはTh17細胞への分化を促進するが、制御性T細胞への分化を抑制し、免疫バランスを破綻させる。ケロイドにおいても持続的なHIF-1αの発現亢進が制御性T細胞とTh17細胞の免疫バランスを破綻させることで、ケロイド病態を悪化させている可能性があると仮定し、本研究を計画した。本年度は、文書による同意を得て、17例のケロイド患者からケロイド組織の採取を行い、そのうち15例から血液サンプルを採取することができた。採取した組織の部位別内訳は、耳垂7例、耳介6例、頚部1例、肩部1例、臍部2例であった。パラフィンブロック作成及び初代培養を行い、線維芽細胞を凍結保存した。また、採取した血液検体からLeucosep管を用いて末梢血単核球を分離し、凍結保存した。今後はこれらの検体を使用して共培養を行う予定である。
    日本学術振興会, 基盤研究(C), 北海道大学, 20K09858
  • 内臓脂肪の潜在能力：循環と免疫賦活におけるhyper 2-way player　　　　　　　　　　　　　　　
    科学研究費 基盤研究B
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    山本 有平
    日本学術振興会, 競争的資金
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    舟山 恵美
    日本学術振興会, 競争的資金
  • メラノーマの転移機序をCirculating tumor cellsから捉える　　　　　　　　　　　　　　　
    科学研究費 若手研究
    2018年04月 - 2020年03月
    前田 拓
    日本学術振興会, 研究代表者, 競争的資金
  • 機能的リンパ組織移植法の開発!　　　　　　　　　　　　　　　
    科学研究費 基盤研究B
    2016年04月 - 2019年03月
    山本 有平
    日本学術振興会, 競争的資金

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