研究者詳細 - 立花　宏太

論文 - 立花　宏太

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Author reply. 査読国際誌

Yoshihiro Matsuda, Tomoko Miyake, Hironobu Toda, Kota Tachibana, Hayato Nomura, Yoji Hirai, Yoshio Kawakami, Naoya Sakoda, Shin Morizane

The Journal of dermatology 52 ( 7 ) e663-e665 2025年7月

Local Control of Conjunctival Malignant Melanoma by Proton Beam Therapy in a Patient With No Metastasis in Six Years From in Situ to Nodular Lesions. 国際誌

Toshihiko Matsuo, Takeshi Ogata, Takahiro Waki, Takehiro Tanaka, Kota Tachibana, Tomokazu Fuji, Takuya Adachi, Osamu Yamasaki

Journal of medical cases 16 ( 1 ) 28 - 36 2025年1月

記述言語：英語掲載種別：研究論文（学術雑誌）

Conjunctival malignant melanoma is extremely rare, with no standard of care established at moment. Here we report a 65-year-old woman, as a hepatitis B virus (HBV) carrier, who presented concurrently a liver mass and lower bulbar conjunctival pigmented lesions in the right eye. Needle liver biopsy and excisional conjunctival biopsy showed hepatocellular carcinoma and conjunctival malignant melanoma in situ, respectively. The priority was given to segmental liver resection for hepatocellular carcinoma after transcatheter arterial chemoembolization. In 1 year, she underwent second and third resection of bulbar conjunctival pigmented lesions, and the pathological examinations constantly showed melanoma in situ. In the course, she showed gradual widening of pigmented lesions to upper bulbar conjunctiva and lower palpebral conjunctiva and lower eyelid. About 2.5 years from the initial visit, the lower eyelid lesion was resected for a genomic DNA-based test of BRAF mutations which turned out to be absent, and then, she began to have intravenous anti-programmed cell death-1 (PD-1), nivolumab every 3 or 4 weeks. She developed iritis in the right eye with conjunctival melanoma as an immune-related adverse event, 3 months after the beginning of nivolumab, and so she used daily topical 0.1% betamethasone eye drops to control the intraocular inflammation. She showed no metastasis in 6 years of follow-up, but later in the course, 5 years from the initial visit, she developed abruptly a non-pigmented nodular lesion on the temporal side of the bulbar conjunctiva along the corneal limbus, accompanied by two pigmented nodular lesions in the upper and lower eyelids in a few months. She thus, underwent proton beam therapy toward the conjunctival melanoma and achieved the successful local control. Proton beam therapy is a treatment option in place of orbital exenteration, and multidisciplinary team collaboration is desirable to achieve better cosmetic and functional outcomes in conjunctival malignant melanoma.

DOI： 10.14740/jmc4351

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The treatment effect of endovascular therapy for chronic limb-threatening ischemia with systemic sclerosis. 査読国際誌

Yoshihiro Matsuda, Tomoko Miyake, Hironobu Toda, Kota Tachibana, Hayato Nomura, Yoji Hirai, Yoshio Kawakami, Naoya Sakoda, Shin Morizane

The Journal of dermatology 51 ( 8 ) 1108 - 1112 2024年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

Systemic sclerosis (SSc) is a collagen disease with immune abnormalities, vasculopathy, and fibrosis. Ca blockers and prostaglandins are used to treat peripheral circulatory disturbances. Chronic limb-threatening ischemia (CLTI) is a disease characterized by extremity ulcers, necrosis, and pain due to limb ischemia. Since only a few patients present with coexistence of CLTI and SSc, the treatment outcomes of revascularization in these cases are unknown. In this study, we evaluated the clinical characteristics and treatment outcomes of seven patients with CLTI and SSc, and 35 patients with uncomplicated CLTI who were hospitalized from 2012 to 2022. A higher proportion of patients with uncomplicated CLTI had diabetes and male. There were no significant differences in the age at which ischemic ulceration occurred, other comorbidities, or in treatments, including antimicrobial agents, revascularization and amputation, improvement of pain, and the survival time from ulcer onset between the two subgroups. EVT or amputation was performed in six or two of the seven patients with CLTI and SSc, respectively. Among those who underwent EVT, 33% (2/6) achieved epithelialization and 67% (4/6) experienced pain relief. These results suggest that the revascularization in cases with CLTI and SSc should consider factors such as infection and general condition, since revascularization improve the pain of these patients.

DOI： 10.1111/1346-8138.17334

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四肢体幹に多発した良性対称性脂肪腫症の1例

坂田伽奈子, 村田愛美, 砂川滉, 佐藤由規, 立花宏太, 神野泰輔, 森実真

日本皮膚外科学会誌 28 ( 2 ) 104 - 104 2024年7月

ボーエン病に合併したメルケル細胞癌の1例査読

松本真理, 澤井希望, 別木祐介, 立花宏太, 神野泰輔, 森実真

西日本皮膚科 86 ( 3 ) 320 - 320 2024年6月

Open Treatmentを施行した内眼角部基底細胞癌の2例

立花宏太, 横溝紗佑里, 蓮井謙一, 神野泰輔, 森実真

日本皮膚外科学会誌 28 ( 1 ) 40 - 41 2024年5月

BRAF/MEK阻害薬により左腋窩リンパ節が縮小し手術を施行したが,ぶどう膜炎を合併した左前胸部悪性黒色腫の1例査読

村田愛美, 立花宏太, 神野泰輔, 森実真, 金道寛弥, 荒川謙三

日本皮膚科学会雑誌 134 ( 6 ) 1711 - 1711 2024年5月

Topical application of activator protein-1 inhibitor T-5224 suppresses inflammation and improves skin barrier function in a murine atopic dermatitis-like dermatitis. 査読国際誌

Minori Sasakura, Hitoshi Urakami, Kota Tachibana, Kenta Ikeda, Ken-Ichi Hasui, Yoshihiro Matsuda, Ko Sunagawa, Daisuke Ennishi, Shuta Tomida, Shin Morizane

Allergology international : official journal of the Japanese Society of Allergology 73 ( 2 ) 323 - 331 2024年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: Selective activator protein (AP)-1 inhibitors are potentially promising therapeutic agents for atopic dermatitis (AD) because AP-1 is an important regulator of skin inflammation. However, few studies have investigated the effect of topical application of AP-1 inhibitors in treating inflammatory skin disorders. METHODS: Immunohistochemistry was conducted to detect phosphorylated AP-1/c-Jun expression of skin lesions in AD patients. In the in vivo study, 1 % T-5224 ointment was topically applied for 8 days to the ears of 2,4 dinitrofluorobenzene challenged AD-like dermatitis model mice. Baricitinib, a conventional therapeutic agent Janus kinase (JAK) inhibitor, was also topically applied. In the in vitro study, human epidermal keratinocytes were treated with T-5224 and stimulated with AD-related cytokines. RESULTS: AP-1/c-Jun was phosphorylated at skin lesions in AD patients. In vivo, topical T-5224 application inhibited ear swelling (P < 0.001), restored filaggrin (Flg) expression (P < 0.01), and generally suppressed immune-related pathways. T-5224 significantly suppressed Il17a and l17f expression, whereas baricitinib did not. Baricitinib suppressed Il4, Il19, Il33 and Ifnb expression, whereas T-5224 did not. Il1a, Il1b, Il23a, Ifna, S100a8, and S100a9 expression was cooperatively downregulated following the combined use of T-5224 and baricitinib. In vitro, T-5224 restored the expression of FLG and loricrin (LOR) (P < 0.05) and suppressed IL33 expression (P < 0.05) without affecting cell viability and cytotoxicity. CONCLUSIONS: Topical T-5224 ameliorates clinical manifestations of AD-like dermatitis in mice. The effect of this inhibitor is amplified via combined use with JAK inhibitors.

DOI： 10.1016/j.alit.2023.12.006

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Perineal Squamous Cell Carcinoma Arising in an Epidermal Cyst. 査読

Fuminori Teraishi, Yuki Matsumi, Kota Tachibana, Toshiyuki Watanabe, Toshiyoshi Fujiwara

Acta medica Okayama 78 ( 2 ) 197 - 200 2024年4月

記述言語：英語

A 90-year-old Japanese woman who had been aware of a subcutaneous mass on the right perineal region for 5 years was referred to our hospital for further examination and treatment because of the rapid growth of the mass and bleeding that began 3 months earlier. A biopsy of the mass revealed a diagnosis of well-differentiated squamous cell carcinoma. On preoperative examination, the tumor was 90×40 mm in size and was suspected to have partially invaded the levator ani muscle and external sphincter. Since a preoperative cardiac evaluation indicated severe aortic stenosis, we performed transcatheter aortic valve implantation. A radical resection was then performed with general anesthesia. The skin and subcutaneous tissue defects were reconstructed with a posterior gluteal-thigh propeller flap, and a sigmoid colostomy was created. The patient had a good postoperative course and was transferred to a rehabilitation facility 28 days after the surgery. Epidermal cysts are a common benign tumor, and clinicians should keep in mind that these cysts can become malignant.

DOI： 10.18926/AMO/66930

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A method for measuring serum levels of melanin-associated indole metabolites using LC-MS/MS and its application to malignant melanoma. 査読国際誌

Masaki Takiwaki, Hiroshi Umemura, Yoshikuni Kikutani, Seketsu Fukuzawa, Kentaro Abe, Kiyotaka Fujino, Satoru Sugihara, Kota Tachibana, Shin Morizane, Mamoru Satoh, Tomohiro Nakayama, Osamu Yamasaki

Clinica chimica acta; international journal of clinical chemistry 117873 - 117873 2024年3月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND AND AIMS: With the development of novel therapies for advanced malignant melanoma (MM), biomarkers that can accurately reflect the progression of MM are needed. Serum levels of melanin-related indole metabolites such as 5-hydroxy-6-methoxyindole-2-carboxylic acid (5H6MI2C) and 6-hydroxy-5-methoxyindole-2-carboxylic acid (6H5MI2C) are potential biomarkers for MM. Here, we describe the development of a mass spectrometry (MS)-based assay to determine serum levels of 5H6MI2C and 6H5MI2C. MATERIALS AND METHODS: We developed a stable isotope dilution-selective reaction monitoring-MS protocol using liquid chromatography tandem mass spectrometry (LC-MS/MS) to measure human serum 5H6MI2C and 6H5MI2C levels. Analytical evaluations of the method were performed and the method was applied to serum samples from MM patients (n = 81). RESULTS: The method established in this study showed high reproducibility and linearity. This novel method also found that serum 6H5MI2C levels were significantly elevated in patients with metastatic MM compared to those with non-metastatic MM. Unfortunately, 5H6MI2C did not show a comparable significant difference. CONCLUSION: We successfully established measurement methods for serum 5H6MI2C and 6H5MI2C levels using LC-MS/MS. Serum 6H5MI2C levels offer a potential marker for MM.

DOI： 10.1016/j.cca.2024.117873

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Successful treatment with secukinumab in a patient with generalized pustular psoriasis preceded by palmoplantar lesions. 査読国際誌

Nozomi Sawai, Yoshio Kawakami, Kota Tachibana, Hayato Nomura, Tomoko Miyake, Emi Yokoyama, Yoji Hirai, Shin Morizane

The Journal of dermatology 50 ( 12 ) e413-e414 2023年8月

Clinicopathologic and genetic characterization of invasive melanoma with BRAF V600K mutation: A study of 16 cases. 査読国際誌

Keisuke Goto, Shusuke Yoshikawa, Toshihiro Takai, Kota Tachibana, Keiichiro Honma, Taiki Isei, Yoji Kukita, Takuma Oishi

Journal of cutaneous pathology 50 ( 8 ) 739 - 747 2023年8月

記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND: The clinicopathologic and genetic features of cutaneous melanoma with a BRAF V600K mutation are not well-known. We aimed to evaluate these characteristics in comparison with those associated with BRAF V600E. METHODS: Real-time polymerase chain reaction (PCR) and/or the MassARRAY® system were used to detect BRAF V600K in 16 invasive melanomas and confirm BRAF V600E in another 60 cases. Immunohistochemistry and panel next-generation sequencing were used to evaluate protein expression and tumor mutation burden, respectively. RESULTS: The median age of melanoma patients harboring the BRAF V600K mutation (72.5 years) was higher than those with the BRAF V600E (58.5 years). The two groups also differed in sex (13/16 [81.3%] male in the V600K group vs. 23/60 [38.3%] in V600E) and in the frequency of scalp involvement (8/16 [50.0%] in V600K vs. 1/60 [1.6%] in V600E). The clinical appearance was similar to a superficial spreading melanoma. Histopathologically, non-nested lentiginous intraepidermal spread and subtle solar elastosis were observed. One patient (1/13, 7.7%) had a pre-existing intradermal nevus. Diffuse PRAME immunoexpression was seen in only one (14.3%) of seven tested cases. Loss of p16 expression was observed in all 12 cases (100%) analyzed. The tumor mutation burden was 8 and 6 mutations/Mb in the two tested cases. CONCLUSIONS: Melanoma carrying the BRAF V600K mutation showed the predominance on the scalp of elderly men, lentiginous intraepidermal growth, subtle solar elastosis, possible existence of intradermal nevus component, frequent loss of p16 immunoexpression, limited immunoreactivity for PRAME, and intermediate tumor mutation burden.

DOI： 10.1111/cup.14470

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Precision laparoscopic sentinel node navigation surgery for femoral skin cancer. 査読

Shunya Hanzawa, Fuminori Teraishi, Yuki Matsumi, Kota Tachibana, Toshiyoshi Fujiwara

Asian journal of endoscopic surgery 16 ( 3 ) 523 - 527 2023年7月

記述言語：英語

Navigation surgery using indocyanine green (ICG) fluorescence imaging has been used in thoracoabdominal surgery, and its usefulness has been reported in many cases. In this study, laparoscopic lateral lymph node dissection was performed using ICG fluorescence imaging in a patient with left femoral spinous cell carcinoma with inguinal and external iliac lymph node metastases. Spinous cell carcinoma is classified as a rare cancer in Japan, and there is a scarcity of evidence for pelvic lymph node dissection, as well as a lack of studies that mention the dissection area. We hypothesized that visualization of lymph nodes and lymph flow using intraoperative ICG fluorescence imaging would indicate the area of dissection and lead to more efficient dissection. In conclusion, intraoperative ICG fluorescence imaging may be useful in this area where there is limited evidence, although there are some limitations.

DOI： 10.1111/ases.13159

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Cutaneous Pseudolymphoma Caused by an Injury with a Metallic Piece of a Mowing Machine Containing Tungsten. 査読国際誌

Mayu Tokuda, Yoshio Kawakami, Yoji Hirai, Kota Tachibana, Yuki Nakagawa, Satoru Sugihara, Tomoko Miyake, Osamu Yamasaki, Keiko Manabe, Shin Morizane

Indian journal of dermatology 68 ( 4 ) 468 - 470 2023年

"Input/output cytokines" in epidermal keratinocytes and the involvement in inflammatory skin diseases. 査読国際誌

Shin Morizane, Tomoyuki Mukai, Ko Sunagawa, Kota Tachibana, Yoshio Kawakami, Mamoru Ouchida

Frontiers in immunology 14 1239598 - 1239598 2023年

記述言語：英語掲載種別：研究論文（学術雑誌）

Considering the role of epidermal keratinocytes, they occupy more than 90% of the epidermis, form a physical barrier, and also function as innate immune barrier. For example, epidermal keratinocytes are capable of recognizing various cytokines and pathogen-associated molecular pattern, and producing a wide variety of inflammatory cytokines, chemokines, and antimicrobial peptides. Previous basic studies have shown that the immune response of epidermal keratinocytes has a significant impact on inflammatory skin diseases. The purpose of this review is to provide foundation of knowledge on the cytokines which are recognized or produced by epidermal keratinocytes. Since a number of biologics for skin diseases have appeared, it is necessary to fully understand the relationship between epidermal keratinocytes and the cytokines. In this review, the cytokines recognized by epidermal keratinocytes are specifically introduced as "input cytokines", and the produced cytokines as "output cytokines". Furthermore, we also refer to the existence of biologics against those input and output cytokines, and the target skin diseases. These use results demonstrate how important targeted cytokines are in real skin diseases, and enhance our understanding of the cytokines.

DOI： 10.3389/fimmu.2023.1239598

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ペムブロリズマブ投与後IFNβ局注,イミキモド外用を併用した悪性黒色腫in-transit転移の1例査読

山崎修, 杉原悟, 立花宏太, 三宅智子, 森実真, 柳井広之, 荒川謙三

西日本皮膚科 84 ( 6 ) 570 - 571 2022年12月

Flare-up of generalized pustular psoriasis following Pfizer-BioNTech BNT162b2 mRNA COVID-19 vaccine: Two cases without mutations of IL36RN and CARD14 genes. 査読国際誌

Kota Tachibana, Yoshio Kawakami, Mayu Tokuda, Shiho Sato, Satoru Sugihara, Tomoko Miyake, Kazumitsu Sugiura, Shin Morizane

The Journal of dermatology 49 ( 10 ) e393-e394 2022年10月

The expression of keratan sulfate in malignant melanoma enhances the adhesion and invasion activity of melanoma cells. 査読国際誌

Kota Tachibana, Yuki Ohkawa, Noriko Kanto, Kento Maeda, Shuichi Ohe, Taiki Isei, Yoichiro Harada, Naoyuki Taniguchi

The Journal of dermatology 49 ( 10 ) 1027 - 1036 2022年10月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

Mammals express a wide variety of glycans that include N-glycans, O-glycans, proteoglycans, glycolipids, etc. Glycan expression can modulate the cellular functions, and hence is strongly involved in the onset and progression of numerous diseases. Here, we report the relevance of the ectopic expression of keratan sulfate (KS) glycan chains in human malignant melanomas. Using a human melanoma cell line, we found that the KS enhanced the invasiveness of the cells but caused no change in the growth rate of the cells. The phosphorylation of paxillin, a focal adhesion-associated adaptor protein, was strong at the region where KS was expressed in the melanoma tissues, indicating that KS stimulated the phosphorylation of paxillin. We also observed that KS enhanced the adhesion of melanoma cells and this was accompanied by a greatly increased level of phosphorylation of paxillin. These data suggest that the expression of KS contributes to the development of malignant phenotypes such as strong cell adhesion and the invasiveness of melanoma cells.

DOI： 10.1111/1346-8138.16506

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BRAF Immunoexpression Can Be Intralesionally Heterogeneous but BRAF V600E Mutation Status Is Intralesionally Homogeneous and Interlesionally Concordant in Melanoma: A Study of 140 Lesions From 98 Patients. 査読国際誌

Kota Tachibana, Keisuke Goto, Yoji Kukita, Keiichiro Honma, Taiki Isei, Satoru Sugihara, Kohei Taniguchi, Osamu Yamasaki

The American Journal of dermatopathology 44 ( 7 ) 478 - 487 2022年7月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

This study sought to confirm the homogeneity of BRAF V600E mutation status in melanoma. BRAF immunohistochemistry was performed on 102 lesions from 60 patients of melanoma with BRAF V600E mutation and 38 negative-control melanoma lesions from 38 patients, both of which were confirmed by real-time PCR or the MassARRAY System. In the positive-control lesions, 9 lesions from 7 patients with preceding BRAF-inhibitor therapy were included. Of the 102 BRAF-mutant lesions, 101 (99.0%) showed diffuse BRAF immunoexpression, but 39 (38.2%) of them showed various heterogeneous intensities. The heterogeneous intensity of immunostaining was due to necrosis (n = 10), minimal or clear cytoplasm (n = 5), tissue crush (n = 8), insufficient fixation (n = 24), or technical error (n = 4). Only 1 lesion (1.0%) with nondiffuse immunoexpression harbored 80% weakly BRAF-positive tumor area and 20% BRAF-negative area with tissue damage. Sanger sequencing performed on the weak or negative regions in 7 lesions revealed BRAF V600E mutation in all the tested lesions. By contrast, all 38 negative-control lesions demonstrated no BRAF immunoexpression. This study demonstrated intralesional homogeneity and interlesional concordance for BRAF V600E mutation status and intralesional frequent heterogeneity for BRAF immunoexpression. The abovementioned 5 phenomena caused substantial reduction in BRAF immunostaining intensity. In 9 lesions within this study, BRAF immunoexpression and BRAF V600E point mutation status were not affected by preceding BRAF inhibitor therapy. Our data would also support the position that it does not matter whether we select primary or metastatic samples for BRAF mutation analysis.

DOI： 10.1097/DAD.0000000000002146

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Obesity and Dyslipidemia Synergistically Exacerbate Psoriatic Skin Inflammation. 査読国際誌

Kenta Ikeda, Shin Morizane, Takahiko Akagi, Sumie Hiramatsu-Asano, Kota Tachibana, Ayano Yahagi, Masanori Iseki, Hideaki Kaneto, Jun Wada, Katsuhiko Ishihara, Yoshitaka Morita, Tomoyuki Mukai

International journal of molecular sciences 23 ( 8 ) 2022年4月

記述言語：英語掲載種別：研究論文（学術雑誌）

Patients with psoriasis are frequently complicated with metabolic syndrome; however, it is not fully understood how obesity and dyslipidemia contribute to the pathogenesis of psoriasis. To investigate the mechanisms by which obesity and dyslipidemia exacerbate psoriasis using murine models and neonatal human epidermal keratinocytes (NHEKs), we used wild-type and Apoe-deficient dyslipidemic mice, and administered a high-fat diet for 10 weeks to induce obesity. Imiquimod was applied to the ear for 5 days to induce psoriatic dermatitis. To examine the innate immune responses of NHEKs, we cultured and stimulated NHEKs using IL-17A, TNF-α, palmitic acid, and leptin. We found that obesity and dyslipidemia synergistically aggravated psoriatic dermatitis associated with increased gene expression of pro-inflammatory cytokines and chemokines. Treatment of NHEKs with palmitic acid and leptin amplified pro-inflammatory responses in combination with TNF-α and IL-17A. Additionally, pretreatment with palmitic acid and leptin enhanced IL-17A-mediated c-Jun N-terminal kinase phosphorylation. These results revealed that obesity and dyslipidemia synergistically exacerbate psoriatic skin inflammation, and that metabolic-disorder-associated inflammatory factors, palmitic acid, and leptin augment the activation of epidermal keratinocytes. Our results emphasize that management of concomitant metabolic disorders is essential for preventing disease exacerbation in patients with psoriasis.

DOI： 10.3390/ijms23084312

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