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Ito Takamichi Last modified date:2024.06.03





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Homepage
https://kyushu-u.elsevierpure.com/en/persons/takamichi-ito
 Reseacher Profiling Tool Kyushu University Pure
Phone
092-642-5586
Fax
092-642-5600
Academic Degree
M.D., Ph.D.
Country of degree conferring institution (Overseas)
No
Field of Specialization
Skin tumor, Skin surgery, Skin pathology
Total Priod of education and research career in the foreign country
01years00months
Research
Research Interests
  • Prognostic factors of malignant skin tumors
    keyword : skin tumor, malignant skin tumor, prognostic factor
    2013.04.
  • Pathology and etiology of hair diseases.
    keyword : hair, alopecia, hair growth
    2018.04.
Academic Activities
Reports
1. Hashimoto H, Ito T. , Current Management and Treatment of Extramammary Paget's Disease. , Curr Treat Options Oncol. 2022 Jun;23(6):818-830. , 2022.05.
2. Hashimoto H, Tanaka Y, Murata M, Ito T. , Nectin-4: a Novel Therapeutic Target for Skin Cancers. , Curr Treat Options Oncol. 2022 Apr;23(4):578-593. , 2022.04.
3. Ito T*, Tanaka Y, Murata M, Kaku-Ito Y, Furue K, Furue M. , BRAF heterogeneity of melanoma.

, Curr Treat Option Oncol. 22: 20., 2021, 2021.04.
4. Nakamura Y, Asai J, Igaki H, Inozume T, Namikawa K, Hayashi A, Fukushima S, Fujimura T, Ito T, Imafuku K, Tanaka R, Teramoto Y, Minagawa A, Miyagawa T, Miyashita A, Wada M, Koga H, Sugaya M., Japanese Dermatological Association Guidelines: Outlines of guidelines for cutaneous melanoma 2019., 2020.09.
5. Furue K, Ito T, Tsuji G, Nakahara T, Furue M. , The CCL20 and CCR6 axis in psoriasis.

, Scand J Immunol. 91: e12846, 2020. doi: 10.1111/sji.12846., 2020.04.
6. Furue K, Ulzii D, Tanaka Y, Ito T, Tsuji G, Kido-Nakahara M, Nakahara T, Furue M. , Pathogenic implication of epidermal scratch injury in psoriasis and atopic dermatitis.
, J Dermatol 47: 979-988, 2020., 2020.04.
7. Wada-Ohno M, Ito T, Furue M. , Adjuvant Therapy for Melanoma. , Curr Treat Options Oncol. , 2019.09.
8. Ito T*, Kaku-Ito Y, Furue M., The diagnosis and management of extramammary Paget's disease., Expert Rev Anticancer Ther, 18: 543-553, 2018, 2018.06.
Papers
1. Gaku Tsuji, Ayako Yumine, Kazuhiko Yamamura, Masaki Takemura, Makiko Kido-Nakahara, Takamichi Ito, Takeshi Nakahara, The therapeutic AHR-modulating agent Tapinarof regulates semaphorin 3A expression in human keratinocytes via NRF2., The Journal of Investigative Dermatology, 10.1016/j.jid.2023.10.002, 2023.10.
2. Gaku Tsuji, Kazuhiko Yamamura, Koji Kawamura, Makiko Kido-Nakahara, Takamichi Ito, Takeshi Nakahara, Regulatory Mechanism of the IL-33-IL-37 Axis via Aryl Hydrocarbon Receptor in Atopic Dermatitis and Psoriasis. [Review], International Journal of Molecular Sciences, 10.3390/ijms241914633, 24, 19, 2023.09, Interleukin (IL)-33 and IL-37 have been identified as novel cytokines involved in various inflammatory diseases. However, their specific roles remain largely unknown. Recent studies have shown that IL-33, which triggers inflammation, and IL-37, which suppresses it, cooperatively regulate the balance between inflammation and anti-inflammation. IL-33 and IL-37 are also deeply involved in the pathogenesis of inflammatory skin diseases such as atopic dermatitis (AD) and psoriasis. Furthermore, a signaling pathway by which aryl hydrocarbon receptor (AHR), a receptor for dioxins, regulates the expression of IL-33 and IL-37 has been revealed. Here, we outline recent findings on the mechanisms regulating IL-33 and IL-37 expression in AD and psoriasis. IL-33 expression is partially dependent on mitogen-activated protein kinase (MAPK) activation, and IL-37 has a role in suppressing MAPK in human keratinocytes. Furthermore, IL-33 downregulates skin barrier function proteins including filaggrin and loricrin, thereby downregulating the expression of IL-37, which colocalizes with these proteins. This leads to an imbalance of the IL-33-IL-37 axis, involving increased IL-33 and decreased IL-37, which may be associated with the pathogenesis of AD and psoriasis. Therefore, AHR-mediated regulation of the IL-33-IL-37 axis may lead to new therapeutic strategies for the treatment of AD and psoriasis..
3. Taku Fujimura, Koji Yoshino, Motoki Nakamura, Hiroshi Kato, Takamichi Ito, Takeo Maekawa, Yasuhiro Fujisawa, Shigeto Matsushita, Ryo Amagai, Emi Yamazaki, Manami Takahashi, Erika Tamabuchi, Akira Hashimoto, Yumi Kambayashi, Naoya Yamazaki, Toshio Miyata, Yoshihide Asano, Efficacy and safety of TM5614 in combination with paclitaxel in the treatment of paclitaxel-resistant cutaneous angiosarcoma: Phase II study protocol., Experimental Dermatology, 10.1111/exd.14976, 2023.11, Cutaneous angiosarcoma (CAS) is an endothelial cell-derived, highly aggressive type of vascular tumour. Although chemoradiotherapy with paclitaxel (PTX) is recognized as a first-line therapy for CAS, second-line therapy for CAS remains controversial, and there is no standard therapy for taxane-resistant CAS. Plasminogen activator inhibitor-1 (PAI-1) is associated with poor clinical outcomes, and elevated levels of PAI-1 in both tissue and serum are correlated with poor response to therapy in various cancers, including skin cancers. Since PAI-1 protects endothelial cells from Fas ligand-mediated apoptosis, PAI-1 inhibition might induce apoptosis of endothelial cell-derived tumours such as CAS. This is a single-arm, open-label, multi-institutional, Phase 2 clinical trial to assess the efficacy and safety of PTX in combination with TM5614 (PAI-1 inhibitor) in patients with PTX-resistant CAS. PTX will be administered for 28 weeks, with oral administration of TM5614. The primary endpoint of this study will be the overall response rate (ORR) at 28 weeks after starting treatment (central image evaluation). The secondary endpoint will include the ORR at 28 weeks after starting treatment (investigator evaluation), ORR at 8 weeks and 16 weeks after initiation of treatment (central and investigator evaluation), progression-free survival, overall survival, disease control rate and safety profiles. Assuming the null hypothesis of a response rate of 13.6% and an alternative hypothesis of 45%, a minimum of 15 patients are required to achieve a two-sided, Type I error of 5% and power of 70% based on the exact binomial distribution. Data quality control will be conducted by a combination of centralized (remote) and on-site monitoring. This study will contribute to the development of novel combination therapy for PTX-resistant CAS patients, which remains an unmet clinical need..
4. Takamichi Ito, Yumiko Kaku-Ito, Fumitaka Ohno, Takeshi Nakahara, A real-world study on the safety profile of extended-interval dosing of immune checkpoint inhibitors for melanoma: a single-center analysis in Japan., Frontiers in Medicine, 10.3389/fmed.2023.1293397, 10, 1293397-1293397, 2023.12, BACKGROUND: Anti-programmed death-1 (PD-1) antibodies are the mainstay for the treatment of unresectable or high-risk melanoma. However, real-world data on the safety profile of their extended-interval doses (EDs) are limited, particularly in Asian patients with melanoma. MATERIALS AND METHODS: In this single-center retrospective study, we analyzed the risks of immune-related adverse events (irAEs) among 71 Japanese patients (36 males; mean age, 65.0 years) who received anti-PD-1 monotherapy for melanoma at our institute. Patients who were administered ipilimumab prior to anti-PD-1 monotherapy were excluded. Patients were divided into three groups: canonical-interval dose (CD) group (n = 50, body weight-based dosing or 240 mg Q2W for nivolumab and body weight-based dosing or 200 mg Q3W for pembrolizumab), ED group (n = 14, 480 mg Q4W for nivolumab and 400 mg Q6W for pembrolizumab), and dose-switch (DS) group (n = 7, upfront CD followed by ED). RESULTS: The CD group received nivolumab more frequently in the metastatic setting. There were no significant differences in baseline characteristics among the three groups, including in sex, age, primary tumor site, tumor subtype, and follow-up period. irAEs occurred in 36.6% (26 patients) of all patients (32.0% of the CD group, 35.7% of the ED group, and 71.4% of the DS group), while severe (grade ≥ 3) irAEs occurred in only two patients, both of whom were in the CD group. Most of the irAEs occurred during the first 6 months of anti-PD-1 therapy and, interestingly, all of the irAEs in the DS group occurred before the switch (during the CD). There was no significant difference among the three groups in the probability of irAE estimated by the Kaplan-Meier method. CONCLUSION: These findings may highlight the safety of ED of anti-PD-1 monotherapy in the treatment of Asian patients with melanoma..
5. Naohito Hatta, Dai Ogata, Jun Asai, Takeo Maekawa, Takamichi Ito, Tatsuya Takenouchi, Yukiko Kiniwa, Azusa Miyashita, Takuya Miyagawa, Ikko Muto, Yuki Yamamoto, Tohru Nagano, Yoshio Kiyohara, Eiji Nakano, Shuichi Ohe, Buntaro Yamaguchi, Masahiro Fukuyama, Taisuke Matsuya, Arata Tsutsumida, Kenjiro Namikawa, Naoya Yamazaki, Recent treatment and prognosis in 643 patients with extramammary Paget's disease., Experimental Dermatology, 10.1111/exd.15030, 33, 2, e15030, 2024.02, Information about extramammary Paget's (EMPD) treatment is limited because of the rarity of the disease. The prognosis differs between in situ EMPD and invasive EMPD; therefore, therapy should be planned according to the disease stage. We collected data on 643 EMPD cases treated between 2015 and 2019 in Japan and assessed recent trends in EMPD treatment and prognosis based on the EMPD-oriented TNM staging. Among the 643 patients, 317 had stage 0 (49.3%), 185 had stage I (28.8%), 51 had stage II (7.9%), 18 had stage IIIA (2.8%), 48 had stage IIIB (7.5%) and 24 had stage IV (3.7%) disease. Each stage showed a distinct survival curve, with the exception of stages II and IIIA. Curative surgery was most common in patients with stage 0-III disease. Chemotherapy was the first-line therapy, mainly in patients with stage IIIB and IV disease, most commonly with docetaxel (DTX), followed by DTX + tegafur gimeracil oteracil potassium (TS-1) and TS-1. Patients with local disease exhibited a 4.4% recurrence rate. Univariate analysis revealed no prognostic differences according to age, sex or primary tumour site. SLNB was not related to disease-specific survival. In multivariate analysis, female sex significantly predicted local relapse in stage 0-I (HR 3.09; 95% CI, 1.13-8.43), and initial treatment with curative surgery was significantly protective in terms of disease-specific survival in stage II-IIIA (HR, 0.17; 95% CI, 0.04-0.71) and stage IIIB-IV (HR 0.16; 95% CI, 0.05-0.51). Further clinical studies are needed to improve the prognosis of patients with stage II-IV EMPD..
6. Yuka Tanaka, Takamichi Ito, Maho Murata, Keiko Tanegashima, Yumiko Kaku-Ito, Takeshi Nakahara, NECTIN4-targeted antibody-drug conjugate is a potential therapeutic option for extramammary Paget disease., Experimental Dermatology, 10.1111/exd.15049, 33, 3, e15049, 2024.03, Extramammary Paget disease (EMPD) is a rare skin cancer mainly found in areas rich in apocrine sweat glands. Since the effective treatments for advanced and/or metastasized EMPD are limited, there is an urgent need to develop novel therapeutic approaches. Nectin cell adhesion molecule 4 (NECTIN4) is highly expressed in cancers and considered to be a promising therapeutic target. NECTIN4 is also expressed in EMPD, but its role and the efficacy of NECTIN4-targeted therapy in EMPD remain unclear. This study investigated the potential of NECTIN4 as a novel therapeutic target for EMPD. NECTIN4 expression was immunohistochemically analysed in EMPD patients' primary (118 samples) and metastatic (21 samples) lesions. Using an EMPD cell line, KS-EMPD-1, the effects of NECTIN4 inhibition on cell proliferation and migration were investigated. NECTIN4 was expressed in primary and metastatic EMPD lesions, and the H-score of NECTIN4 staining was significantly higher in metastatic lesions than in primary ones. Knockdown of NECTIN4 significantly inhibited cell proliferation and affected cell migration. The cytotoxic effects of NECTIN4-targeted antibody-drug conjugate (ADC) were further evaluated, revealing a significant decrease in EMPD cell viability. In conclusion, NECTIN4 is a potential therapeutic target and NECTIN4-targeted ADC is promising as a therapeutic option for EMPD..
7. Takamichi Ito, Yuka Tanaka, Yumiko Kaku-Ito, Yoshinao Oda, Takeshi Nakahara, FOXM1: a new therapeutic target of extramammary Paget disease., Scientific Reports, 10.1038/s41598-024-54773-8, 14, 1, 4048-4048, 2024.02, Extramammary Paget disease (EMPD) is a rare skin cancer that primarily affects older individuals predominantly in areas with apocrine sweat glands. Although most early EMPD lesions are indolent, patients with metastatic EMPD have a poor prognosis due to the lack of effective systemic treatment. In this study, we investigated the role of forkhead box M1 (FOXM1), a potent transcription factor, in EMPD and assessed the potential of FOXM1 as a therapeutic target. Immunohistochemistry of 112 primary and 17 metastatic EMPD samples revealed that FOXM1 expression increased with tumor progression. Patients in whom FOXM1 was expressed in more than 10% of tumor cells had significantly shorter disease-specific survival than the other patients (p = 0.0397). In in vitro studies using our newly established EMPD cell line, KS-EMPD-1, we found high expression of FOXM1. Knockdown of FOXM1 impaired tumor cell viability, migration, and invasion. Inhibition of FOXM1 using thiostrepton also reduced tumor cell viability in a dose-dependent manner. These findings suggest that FOXM1 is a promising therapeutic target for patients with EMPD..
8. Kenjiro Namikawa, Takamichi Ito, Shusuke Yoshikawa, Koji Yoshino, Yukiko Kiniwa, Shuichi Ohe, Taiki Isei, Tatsuya Takenouchi, Hiroshi Kato, Satoru Mizuhashi, Satoshi Fukushima, Yosuke Yamamoto, Takashi Inozume, Yasuhiro Fujisawa, Osamu Yamasaki, Yasuhiro Nakamura, Jun Asai, Takeo Maekawa, Takeru Funakoshi, Shigeto Matsushita, Eiji Nakano, Kohei Oashi, Junji Kato, Hisashi Uhara, Takuya Miyagawa, Hiroshi Uchi, Naohito Hatta, Keita Tsutsui, Taku Maeda, Taisuke Matsuya, Hiroto Yanagisawa, Ikko Muto, Mao Okumura, Dai Ogata, Naoya Yamazaki, Systemic therapy for Asian patients with advanced BRAF V600-mutant melanoma in a real-world setting: A multi-center retrospective study in Japan (B-CHECK-RWD study)., Cancer Medicine, 10.1002/cam4.6438, 2023.08, BACKGROUND: Anti-PD-1-based immunotherapy is considered a preferred first-line treatment for advanced BRAF V600-mutant melanoma. However, a recent international multi-center study suggested that the efficacy of immunotherapy is poorer in Asian patients in the non-acral cutaneous subtype. We hypothesized that the optimal first-line treatment for Asian patients may be different. METHODS: We retrospectively collected data of Asian patients with advanced BRAF V600-mutant melanoma treated with first-line BRAF/MEK inhibitors (BRAF/MEKi), anti-PD-1 monotherapy (Anti-PD-1), and nivolumab plus ipilimumab (PD-1/CTLA-4) between 2016 and 2021 from 28 institutions in Japan. RESULTS: We identified 336 patients treated with BRAF/MEKi (n = 236), Anti-PD-1 (n = 64) and PD-1/CTLA-4 (n = 36). The median follow-up duration was 19.9 months for all patients and 28.6 months for the 184 pa tients who were alive at their last follow-up. For patients treated with BRAF/MEKi, anti-PD-1, PD-1/CTLA-4, the median ages at baseline were 62, 62, and 53 years (p = 0.03); objective response rates were 69%, 27%, and 28% (p 
9. Yusuke Muto, Yumi Kambayashi, Hiroshi Kato, Satoshi Fukushima, Takamichi Ito, Takeo Maekawa, Ishizuki Shoichiro, Hiroshi Uchi, Shigeto Matsushita, Yuki Yamamoto, Koji Yoshino, Yasuhiro Fujisawa, Ryo Amagai, Kentaro Ohuchi, Akira Hashimoto, Yoshihide Asano, Taku Fujimura, Postoperative adjuvant therapy for 120 melanoma patients, including acral and mucosal subtypes: A multicenter, observational study of two-year follow-up results., The British Journal of Dermatology, 10.1093/bjd/ljad183, 2023.05.
10. Gaku Tsuji, Kazuhiko Yamamura, Koji Kawamura, Makiko Kido-Nakahara, Takamichi Ito, Takeshi Nakahara, Novel Therapeutic Targets for the Treatment of Atopic Dermatitis., Biomedicines, 10.3390/biomedicines11051303, 11, 5, 2023.04, Atopic dermatitis (AD) is a chronic inflammatory skin disease that significantly impacts quality of life. The pathogenesis of AD is a complex combination of skin barrier dysfunction, type II immune response, and pruritus. Progress in the understanding of the immunological mechanisms of AD has led to the recognition of multiple novel therapeutic targets. For systemic therapy, new biologic agents that target IL-13, IL-22, IL-33, the IL-23/IL-17 axis, and OX40-OX40L are being developed. Binding of type II cytokines to their receptors activates Janus kinase (JAK) and its downstream signal, namely signal transduction and activator of transcription (STAT). JAK inhibitors block the activation of the JAK-STAT pathway, thereby blocking the signaling pathways mediated by type II cytokines. In addition to oral JAK inhibitors, histamine H4 receptor antagonists are under investigation as small-molecule compounds. For topical therapy, JAK inhibitors, aryl hydrocarbon receptor modulators, and phosphodiesterase-4 inhibitors are being approved. Microbiome modulation is also being examined for the treatment of AD. This review outlines current and future directions for novel therapies of AD that are currently being investigated in clinical trials, focusing on their mechanisms of action and efficacy. This supports the accumulation of data on advanced treatments for AD in the new era of precision medicine..
11. Takamichi Ito, Yuka Tanaka, Toshio Ichiki, Yumiko Kaku-Ito, Takeshi Nakahara, KS-EMPD-1: a novel cell line of primary extramammary Paget's disease., Human Cell, 10.1007/s13577-023-00951-1, 2023.07, Extramammary Paget's disease (EMPD) is a rare skin cancer that mainly occurs in apocrine sweat gland-rich areas in elderly people. The prognosis of metastatic EMPD is unfavorable because of the lack of fully effective systemic therapies. However, the difficulty in establishing a model of EMPD has hampered basic research for exploring its pathogenesis and optimal treatments. Here, we established for the first time an EMPD cell line (named KS-EMPD-1) from a primary tumor on the left inguinal region of an 86-year-old Japanese male. The cells were successfully maintained for more than 1 year, with a doubling time of 31.2 ± 0.471 h. KS-EMPD-1 exhibited constant growth, spheroid formation, and invasiveness, and was confirmed to be identical to the original tumor by short tandem repeat analyses, whole exome sequencing, and immunohistochemistry (CK7+CK20-GCDFP15+). Western blotting of the cells revealed the protein expression of HER2, NECTIN4, and TROP2, which have recently attracted attention as potential therapeutic targets for EMPD. KS-EMPD-1 was highly sensitive to docetaxel and paclitaxel on chemosensitivity test. The KS-EMPD-1 cell line is a promising resource for basic and preclinical research on EMPD to better define the tumor characteristics and treatment strategy of this rare cancer..
12. Toshio Ichiki, Yuichi Yamada, Takamichi Ito, Takeshi Nakahara, Yasuharu Nakashima, Masafumi Nakamura, Tomoharu Yoshizumi, Akira Shiose, Koichi Akashi, Yoshinao Oda, Histological and immunohistochemical prognostic factors of primary angiosarcoma., Virchow Arch, 10.1007/s00428-023-03572-z, 483, 1, 59-69, 2023.06, Angiosarcoma is a malignant vascular endothelial neoplasm with various histological patterns. Despite its highly malignant potential, histological prognostic prediction has not been adopted for angiosarcoma. This study aimed to establish a method of predicting the prognosis of primary angiosarcoma. Formalin-fixed, paraffin-embedded samples from 104 primary angiosarcomas were prepared. All the cases were reviewed based on histological examinations with H&E staining. Because the French Fédération Nationale des Centres de Lutte Contre Le Cancer system (FNCLCC) is not adopted for angiosarcoma, we experimentally established a modified version of FNCLCC. Immunohistochemical staining for ERG, CD31, CD34, D2-40, HHV-8, p16, C-MYC, and p53 was performed. Fluorescence in situ hybridization (FISH) was performed for 31 cases to assay c-MYC gene amplification. Multivariate analysis revealed that age (> 70 years old) (p = 0.0011), non-cutaneous angiosarcoma (p = 0.0265), metastasis on diagnosis (p 
13. Yusuke Muto, Yumi Kambayashi, Hiroshi Kato, Satoshi Fukushima, Takamichi Ito, Takeo Maekawa, Yasuhiro Fujisawa, Koji Yoshino, Hiroshi Uchi, Shigeto Matsushita, Yuki Yamamoto, Ryo Amagai, Kentaro Ohuchi, Akira Hashimoto, Yoshihide Asano, Taku Fujimura, Adverse events associated with postoperative outcomes of adjuvant anti-PD-1 antibody therapy in both acral and non-acral cutaneous melanomas: A multicenter, observational, post hoc analysis study., The Journal of Dermatology, 10.1111/1346-8138.16912, 2023.07, Since anti-PD-1 Abs can cause irreversible immune-related adverse events (irAEs), the associations between their efficacies and the incidence of irAEs are important to evaluate the use of anti-PD-1Abs for the treatment of melanoma, especially in the adjuvant setting. The purpose of this post hoc analysis study was to retrospectively analyze the associations between recurrence-free survival (RFS) at 12 months and the onset of any irAEs in 31 non-acral cutaneous and 30 acral melanoma cases treated with anti-PD-1 Abs therapy at the adjuvant setting in Asians. There were 20 cases with greater than grade 1 AEs in both the acral and non-acral cutaneous groups. Of the acral melanoma, 10 cases were nails or toes, and 20 cases were soles and heels. The log-rank test showed that RFS was better in cases with AEs than in cases without AEs. The present study suggested that the different profiles of irAEs between non-acral cutaneous and acral melanoma might correlate with the different response to anti-PD1 Abs of melanoma in the adjuvant setting..
14. Yasuhiro Nakamura, Jun Asai, Hiroshi Igaki, Takashi Inozume, Kenjiro Namikawa, Ayato Hayashi, Satoshi Fukushima, Taku Fujimura, Takamichi Ito, Keisuke Imafuku, Ryota Tanaka, Yukiko Teramoto, Akane Minagawa, Takuya Miyagawa, Azusa Miyashita, Makoto Wada, Hiroshi Koga, Makoto Sugaya, Japanese Dermatological Association Guidelines: Outlines of guidelines for cutaneous melanoma 2019., The Journal of dermatology, 10.1111/1346-8138.15151, 47, 2, 89-103, 2020.02, With consideration of the ongoing developments in treatment options for cutaneous melanoma, the Japanese Skin Cancer Society published the first guidelines for cutaneous melanoma in 2007 and later revised them in 2015. Here, we report on an English version of the 2019 Japanese Melanoma Guidelines. In this latest edition, all processes were carried out according to the Grading of Recommendations, Assessment, Development and Evaluation system. A comprehensive published work search, systematic review and determination of recommendations in each clinical question were performed by a multidisciplinary expert panel consisting of dermatologists, a plastic and reconstructive surgeon, and a radiation oncologist. The advent of novel agents, such as immune checkpoint inhibitors and molecular-targeted agents, has drastically changed the nature of treatment for adjuvant and advanced-stage diseases among melanoma patients worldwide. Additionally, recent reports of clinical trials regarding surgical procedures and a better understanding of molecular biology and tumor immunology in clinical types of melanoma have had an impact on clinical practise. Based on these viewpoints, eight relevant clinical questions were raised in this report that aim to help clinicians select the appropriate therapeutic approach..
15. Taku Fujimura, Takeo Maekawa, Hiroshi Kato, Takamichi Ito, Shigeto Matsushita, Koji Yoshino, Yasuhiro Fujisawa, Shoichiro Ishizuki, Kojiro Segawa, Jun Yamamoto, Akira Hashimoto, Yumi Kambayashi, Yoshihide Asano, Treatment for taxane-resistant cutaneous angiosarcoma: A multicenter study of 50 Japanese cases., The Journal of Dermatology, 10.1111/1346-8138.16786, 2023.03, Cutaneous angiosarcoma (CAS) is a rare and highly aggressive type of vascular tumor. Although chemoradiotherapy with taxanes is recognized as a first-line therapy for CAS, second-line therapy for CAS remains controversial. From the above findings, the efficacy and safety profiles of taxane-switch (change paclitaxel to docetaxel or vise), eribulin methylate, and pazopanib regimens in second-line chemotherapy were evaluated retrospectively in 50 Japanese taxane-resistant CAS patients. Although there was no significant difference in progression-free survival (P = 0.3528) among the regimens, the incidence of all adverse events (AEs) (P = 0.0386), as well as severe G3 or more AEs (P = 0.0477) was significantly higher in the eribulin methylate group and pazopanib group than in the taxane-switch group. The present data suggest that switching to another taxane should be considered for the treatment of taxane-resistant CAS in second-line therapy based on the safety profiles..
16. Gaku Tsuji, Akiko Hashimoto-Hachiya, Ayako Yumine, Masaki Takemura, Makiko Kido-Nakahara, Takamichi Ito, Kazuhiko Yamamura, Takeshi Nakahara, PDE4 inhibition by difamilast regulates filaggrin and loricrin expression via keratinocyte proline-rich protein in human keratinocytes., Journal of Dermatological Science, 10.1016/j.jdermsci.2023.04.007, 110, 2, 61-68, 2023.04, BACKGROUND: Difamilast, a topical phosphodiesterase 4 (PDE4) inhibitor, has been shown to be effective for treating atopic dermatitis (AD), but the molecular mechanism involved is unclear. Since skin barrier dysfunction including reduced expression of filaggrin (FLG) and loricrin (LOR) contributes to AD development, difamilast treatment may be able to improve this dysfunction. PDE4 inhibition increases transcriptional activity of cAMP-responsive element binding protein (CREB). Therefore, we hypothesized that difamilast may affect FLG and LOR expression via CREB in human keratinocytes. OBJECTIVE: To elucidate the mechanism by which difamilast regulates FLG and LOR expression via CREB in human keratinocytes. METHODS: We analyzed normal human epidermal keratinocytes (NHEKs) treated with difamilast. RESULTS: We observed increases of intracellular cAMP levels and CREB phosphorylation in difamilast (5 μM)-treated NHEKs. Next, we found that difamilast treatment increased mRNA and protein levels of FLG and LOR in NHEKs. Since reduced expression of keratinocyte proline-rich protein (KPRP) is reported to be involved in skin barrier dysfunction in AD, we examined KPRP expression in difamilast-treated NHEKs. We found that difamilast treatment increased mRNA and protein levels of KPRP in NHEKs. Furthermore, KPRP knockdown using siRNA transfection abolished the upregulation of FLG and LOR in difamilast-treated NHEKs. Finally, CREB knockdown canceled the upregulation of FLG, LOR, and KPRP in difamilast-treated NHEKs, indicating that PDE4 inhibition by difamilast treatment positively regulates FLG and LOR expression via the CREB-KPRP axis in NHEKs. CONCLUSION: These findings may provide further guidance for therapeutic strategies in the treatment of AD using difamilast..
17. Takamichi Ito, Hiroki Hashimoto, Yumiko Kaku-Ito, Yuka Tanaka, Takeshi Nakahara, Nail Apparatus Melanoma: Current Management and Future Perspectives. [Review], Journal of Clinical Medicine, 10.3390/jcm12062203, 12, 6, 2023.03, Nail apparatus melanoma (NAM) is a rare type of cutaneous melanoma that belongs to the acral melanoma subtype. NAM is managed principally in accordance with the general treatment for cutaneous melanoma, but there is scarce evidence in support of this in the literature. Acral melanoma is genetically different from non-acral cutaneous melanoma, while recently accumulated data suggest that NAM also has a different genetic background from acral melanoma. In this review, we focus on recent advances in the management of NAM. Localized NAM should be surgically removed; amputation of the digit and digit-preserving surgery have been reported. Sentinel lymph node biopsy can be considered for invasive NAM for the purpose of accurate staging. However, it is yet to be clarified whether patients with metastatic sentinel lymph nodes can be safely spared completion lymph node dissection. Similar to cutaneous melanoma, immune checkpoint inhibitors and BRAF/MEK inhibitors are used as the first-line treatment for metastatic NAM, but data on the efficacy of these therapies remain scarce. The therapeutic effects of immune checkpoint inhibitors could be lower for NAM than for cutaneous melanoma. This review highlights the urgent need to accumulate data to better define the optimal management of this rare melanoma..
18. Yuka Tanaka, Takamichi Ito, Yumiko Kaku-Ito, Keiko Tanegashima, Gaku Tsuji, Makiko Kido-Nakahara, Yoshinao Oda, Takeshi Nakahara, Human epidermal growth factor receptor 3 serves as a novel therapeutic target for acral melanoma., Cell Death Discovery, 10.1038/s41420-023-01358-5, 9, 1, 54-54, 2023.02, Acral melanoma (AM) is a rare, life-threatening skin cancer. Since AM bears unique features, existing therapies for other types of malignant melanomas have limited effects and the establishment of effective treatments for AM is strongly desired. Human epidermal growth factor receptor 3 (HER3) is a receptor tyrosine kinase that is frequently elevated in tumors and contributes to tumor progression, so it is considered a promising therapeutic target for tumors. This study was established to evaluate the potential of HER3-targeted therapy to treat AM by investigating the expression and function of HER3. HER3 expression was immunohistochemically analyzed in AM lesions of 72 patients and in AM cell lines. To investigate function of HER3, effects of HER3 inhibition on cell proliferation, apoptosis/survival, anchorage-independent growth, and underlying signals were assessed. HER3 was expressed in patients' AM tissues with various intensities and HER3 expression was significantly correlated with patient's disease-free survival. In vitro analyses revealed that HER3 is more highly expressed in AM cells than in normal epidermal melanocytes. AM cells were also shown to be sensitive to the cytotoxic part of a HER3-targeted antibody-drug conjugate. Inhibition of HER3 did not affect cell proliferation, whereas it decreased the anchorage-independent growth of AM cells likely through affecting the nuclear translocation of Yes-associated protein. It is implied that HER3 may serve as a novel therapeutic target for AM..
19. Taku Fujimura, Sadanori Furudate, Takeo Maekawa, Hiroshi Kato, Takamichi Ito, Shigeto Matsushita, Koji Yoshino, Akira Hashimoto, Yusuke Muto, Kentaro Ohuchi, Ryo Amagai, Yumi Kambayashi, Yasuhiro Fujisawa, Cutaneous angiosarcoma treated with taxane-based chemoradiotherapy: A multicenter study of 90 Japanese cases., Skin Health and Disease, 10.1002/ski2.180, 3, 1, e180, 2023.02, Cutaneous angiosarcoma (CAS) is rare and most previous studies of CAS have been small case series, and randomized, phase II studies of CAS are limited. Since treatment options for CAS are controversial, and because only paclitaxel should be recommended based on high-level evidence, it is important to evaluate the efficacy of another taxane-derived agents, docetaxel, in real-world practice. The efficacy and safety profiles of chemoradiotherapy using taxane-based agents, docetaxel and paclitaxel, were retrospectively examined in the maintenance setting in 90 Japanese CAS patients, including 35 docetaxel-treated cases and 55 paclitaxel-treated cases. Overall survival and dose duration time of the patient group treated with docetaxel was equivalent to that with paclitaxel, even in the cohorts with metastasis. Adverse events due to docetaxel and paclitaxel were observed in 77.1% and 69.1% of cases, respectively. The incidence ratio of total severe adverse events tended to be higher in the docetaxel-treated group (40.0%) than in the paclitaxel-treated group (23.6%). Peripheral neuropathy occurred only in the paclitaxel-treated group, whereas high-grade interstitial pneumonia developed only in the docetaxel-treated group. In addition, we also evaluate 19 patients selected other taxanes, 17 patients selected eribulin methylate, 11 patients pazopanib, and 2 patients selected nivolumab as second-line chemotherapy. The efficacy of a monthly docetaxel regimen is equivalent to a three-weekly paclitaxel regimen evaluated by Overall survival and DDT, even in the cohorts with metastasis, and it is a tolerable protocol for CAS as a maintenance therapy in the Japanese population..
20. Yasuhiro Fujisawa, Kenjiro Namikawa, Koji Yoshino, Yukiko Kiniwa, Takamichi Ito, Hiroshi Kato, Shigeto Matsushita, Toshihiko Hoashi, Yasuhiro Nakamura, Shusuke Yoshikawa, Takuya Miyagawa, Jun Asai, Taisuke Matsuya, Satoshi Fukushima, Jyunji Kato, Tatsuya Takenouchi, Hiroshi Uchi, Mamiko Masuzawa, Teruki Yanagi, Takeo Maekawa, Combined use of nivolumab and ipilimumab among Japanese melanoma patients: Multi-center, retrospective study of 111 cases., The British Journal of Dermatology, 10.1093/bjd/ljad114, 2023.04.
21. Takashi Inozume, Kenjiro Namikawa, Hiroshi Kato, Shusuke Yoshikawa, Yukiko Kiniwa, Koji Yoshino, Satoru Mizuhashi, Takamichi Ito, Tatsuya Takenouchi, Shigeto Matsushita, Yasuhiro Fujisawa, Takamitsu Matsuzawa, Satoru Sugihara, Jun Asai, Hiroshi Kitagawa, Takeo Maekawa, Taiki Isei, Masahito Yasuda, Naoya Yamazaki, Hisashi Uhara, Yasuhiro Nakamura, Analyzing the relationship between the efficacy of first-line immune checkpoint inhibitors and cumulative sun damage in Japanese patients with advanced BRAF wild-type nonacral cutaneous melanoma: A retrospective real-world, multicenter study., Journal of Dermatological Science, 10.1016/j.jdermsci.2023.03.008, 110, 1, 19-26, 2023.03, BACKGROUND: Efficacy of anti-PD-1 antibody monotherapy (PD1) or anti-PD-1 plus anti-CTLA-4 combination therapy (PD1 +CTLA4) for melanoma is affected by its clinical subtype. The amount of tumor mutation burden (TMB) caused by cumulative sun damage (CSD) is occasionally used to explain this; however, their relationship in Japanese nonacral cutaneous melanoma (NACM) is still unclear. OBJECTIVE: To analyze the ICI efficacy and its relationship with CSD of the primary lesion in Japanese patients with NACM. METHODS: Japanese patients with advanced BRAF wild-type NACM who received first-line ICIs were recruited. Objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), and the degree of solar elastosis (SE) were evaluated. RESULTS: A total of 146 patients (PD1 group 113 and PD1 +CTLA4 group 33) were included. No significant differences in ORR were observed between the PD1 and PD1 +CTLA4 groups (35 % vs. 36 %; P = 0.67) or PFS and OS (median PFS 6.1 months vs. 8.5 months; P = 0.46, median OS 28.1 months vs. not reached; P = 0.59). Multivariate survival analysis revealed that PD1 +CTLA4 did not prolong the PFS and OS. The SE score had no effect on either PFS or OS. CONCLUSIONS: ICI efficacy was not as high as those reported in Western countries, and PD1 +CTLA4 did not present better clinical efficacy compared to PD1. Indicators of CSD did not serve as a predictor for clinical advantage. These findings may partially support the theory that ICI efficacy is affected by CSD; however, other unrecognized factors may also exist..
22. Yuka Tanaka, Maho Murata, Keiko Tanegashima, Yoshinao Oda, Takamichi Ito, Nectin cell adhesion molecule 4 regulates angiogenesis through Src signaling and serves as a novel therapeutic target in angiosarcoma, Scientific Reports, 10.1038/s41598-022-07727-x, 12, 1, 2022.12, Angiosarcoma is a rare, life-threatening soft tissue sarcoma with malignant endothelial cells that is mainly found in the skin. Multidisciplinary approaches are used to treat patients with unresectable metastasized lesions; considering the cellular origin of angiosarcoma, anti-angiogenic therapy has also been used recently. However, these treatments have limited efficacy, and the survival rate remains low. Thus, more effective treatments need to be developed. Nectin cell adhesion molecule 4 (NECTIN4) is highly expressed in malignant tumors and promotes tumor progression. Thus, NECTIN4 is expected to be a novel therapeutic target for cancer. However, the significance of NECTIN4 in angiosarcoma remains unknown. Using immunohistochemistry, we investigated NECTIN4 expression in 74 tissue samples from angiosarcoma patients, finding variable NECTIN4 expression. In addition, we investigated NECTIN4 expression and function in human angiosarcoma cell lines. NECTIN4 expression was higher in angiosarcoma cells than normal endothelial cells, and angiosarcoma cells were sensitive to monomethyl auristatin E, the cytotoxic part of a NECTIN4-targetting antibody–drug conjugate. NECTIN4 knockdown inhibited the proliferation and angiogenesis of angiosarcoma cells, and Src kinase signaling was shown to be involved in NECTIN4 function, at least in part. NECTIN4-targeted therapy has the potential to be a novel treatment strategy for angiosarcoma..
23. Yusuke Muto, Yumi Kambayashi, Hiroshi Kato, Satoshi Fukushima, Takamichi Ito, Takeo Maekawa, Yasuhiro Fujisawa, Koji Yoshino, Hiroshi Uchi, Shigeto Matsushita, Yuki Yamamoto, Ryo Amagai, Kentaro Ohuchi, Akira Hashimoto, Taku Fujimura, Adjuvant Anti-PD-1 Antibody Therapy for Advanced Melanoma: A Multicentre Study of 78 Japanese Cases., Acta Dermato-Venereologica, 10.2340/actadv.v102.678, 102, adv00756, 2022.08, Anti-PD-1 antibodies (Abs) are among the optimal adjuvant therapies for melanoma at high risk of recurrence, especially BRAF wild-type melanoma, but the anti-tumour effects of anti-PD-1 Abs in the adjuvant setting for acral melanoma have not been evaluated previously. The aim of this study was to analyse the efficacy and safety profiles of anti-PD-1 Ab monotherapy in the adjuvant setting in an Asian population including a high ratio of acral melanoma. The efficacy and safety profiles of anti-PD-1 Ab monotherapy in the adjuvant setting were retrospectively analysed in 78 Japanese patients with advanced melanoma, including 31 cases (40%) of acral melanoma. Overall relapse-free survival was 60.3% (47 of 78 cases, 95% confidence interval (CI) 49.2–70.4%), and 39.7% of patients (31 of 78 patients, 95% CI 29.6–50.8%) relapsed during the adjuvant PD-1 Ab treatment. Six cases (7.9%) discontinued the protocol due to serious adverse events. One case (1.3%) discontinued the protocol due to trauma. The relapse-free survival of acral melanoma was 25.8%, whereas that of high cumulative sun damage was 60.0%, and that of low cumulative sun damage was 57.1%. The acral type had a significantly lower 12-month relapse-free survival than other cutaneous types (p = 0.029). The acral type appeared to be an independent prognostic factor on multivariate analysis (p = 0.015). Adverse events due to anti-PD-1 antibody were observed in 37.1% overall. The results of this study suggest that anti-PD-1 Ab therapy in the adjuvant setting is less effective for acral melanoma than for other cutaneous types..
24. Hiroki Hashimoto, Takamichi Ito, Current Management and Treatment of Extramammary Paget's Disease. [review], Current Treatment Options in Oncology, 10.1007/s11864-021-00923-3, 23, 6, 818-830, 2022.06, OPINION STATEMENT: Extramammary Paget's disease (EMPD) is a rare neoplastic disease affecting areas rich in apocrine glands in the elderly. EMPD clinically resembles a benign inflammatory skin disease, and ill-defined tumor borders can lead to misdiagnosis and incomplete excision. Several prognostic factors have been reported, including nodule formation, tumor thickness, tumor invasion, lymphovascular invasion, and a perianal location, which are characteristic of primary tumors. EMPD typically presents as an in situ tumor spreading horizontally within the epidermis and then invading into the dermis as it transitions to a vertical growth phase. For this reason, tumor thickness, rather than tumor size, is correlated with patient prognosis. The best treatment for resectable EMPD is complete surgical removal of the tumor. EMPD sometimes has unclear tumor borders, and it can unexpectedly spread beyond its clinical boundaries. Surgical resection in such cases is often associated with tumor-positive margins, which can result in recurrence. However, surgical excision with wide margins may deteriorate patients' organ functions and quality of life. Mohs micrographic surgery may be ideal for controlling the surgical margins and minimizing the sacrifice of normal tissue, but this technique is not always feasible because of constraints associated with the medical environment. No standard treatment for unresectable or metastatic EMPD has been established. Although conventional chemotherapy has been used as the first-line treatment, it frequently causes adverse events, and consequently, targeted therapy will become more valuable in the near future..
25. Hiroki Hashimoto, Yuka Tanaka, Maho Murata, Takamichi Ito, Nectin-4: a Novel Therapeutic Target for Skin Cancers. [review], Current Treatment Options in Oncology, 10.1007/s11864-022-00940-w, 23, 4, 578-593, 2022.04, OPINION STATEMENT: Nectin-4 is a tumor-associated antigen that is highly expressed on various cancer cells, and it has been further proposed to have roles in tumor development and propagation ranging from cellular proliferation to motility and invasion. Nectin-4 blockade reduces tumor proliferation and induces apoptosis in several malignancies. Nectin-4 has been used as a potential target in antibody-drug conjugate (ADC) development. Enfortumab vedotin, an ADC against Nectin-4, has demonstrated efficacy against solid tumor malignancies. Enfortumab vedotin has received US Food and Drug Administration approval for treating urothelial cancer. Furthermore, the efficacy of ADCs against Nectin-4 against solid tumors other than urothelial cancer has been demonstrated in preclinical studies, and clinical trials examining the effects of enfortumab vedotin are ongoing. Recently, Nectin-4 was reported to be highly expressed in several skin cancers, including malignant melanoma, cutaneous squamous cell carcinoma, and extramammary Paget's disease, and involved in tumor progression and survival in retrospective studies. Nectin-4-targeted therapies and ADCs against Nectin-4 could therefore be novel therapeutic options for skin cancers. This review highlights current knowledge on Nectin-4 in malignant tumors, the efficacy of enfortumab vedotin in clinical trials, and the prospects of Nectin-4-targeted agents against skin cancers..
26. Ito T, Hashimoto H, Tanaka Y, Tanegashima K, Murata M, Ichiki T, Iwasaki T, Oda Y, Kaku-Ito Y., TROP2 Expression in Sebaceous and Sweat Gland Carcinoma., J Clin Med. 2022 Jan 25;11(3):607., 2022.01.
27. Chi-Che Hsieh, Yue-Chiu Su, Kuan-Ying Jiang, Takamichi Ito, Ting-Wei Li, Yumiko Kaku-Ito, Shih-Tsung Cheng, Li-Tzong Chen, Daw-Yang Hwang, Che-Hung Shen, TRPM1 promotes tumor progression in acral melanoma by activating the Ca2+/CaMKIIδ/AKT pathway., Journal of Advanced Research, 10.1016/j.jare.2022.03.005, 43, 45-57, 2023.01, Introduction: Acral melanoma is a predominant and aggressive subtype of melanoma in non-Caucasian populations. There is a lack of genotype-driven therapies for over 50% of patients. TRPM1 (transient receptor potential melastatin 1), a nonspecific cation channel, is mainly expressed in retinal bipolar neurons and skin. Nonetheless, the function of TRPM1 in melanoma progression is poorly understood. Objectives: We investigated the association between TRPM1 and acral melanoma progression and revealed the molecular mechanisms by which TRPM1 promotes tumor progression and malignancy. Methods: TRPM1 expression and CaMKII phosphorylation in tumor specimens were tested by immunohistochemistry analysis and scored by two independent investigators. The functions of TRPM1 and CaMKII were assessed using loss-of-function and gain-of-function approaches and examined by western blotting, colony formation, cell migration and invasion, and xenograft tumor growth assays. The effects of a CaMKII inhibitor, KN93, were evaluated using both in vitro cell and in vivo xenograft mouse models. Results: We revealed that TRPM1 protein expression was positively associated with tumor progression and shorter survival in patients with acral melanoma. TRPM1 promoted AKT activation and the colony formation, cell mobility, and xenograft tumor growth of melanoma cells. TRPM1 elevated cytosolic Ca2+ levels and activated CaMKIIδ (Ca2+/calmodulin-dependent protein kinase IIδ) to promote the CaMKIIδ/AKT interaction and AKT activation. The functions of TRPM1 in melanoma cells were suppressed by a CaMKII inhibitor, KN93. Significant upregulation of phospho-CaMKII levels in acral melanomas was related to increased expression of TRPM1. An acral melanoma cell line with high expression of TRPM1, CA11, was isolated from a patient to show the anti-tumor activity of KN93 in vitro and in vivo. Conclusions: TRPM1 promotes tumor progression and malignancy in acral melanoma by activating the Ca2+/CaMKIIδ/AKT pathway. CaMKII inhibition may be a potential therapeutic strategy for treating acral melanomas with high expression of TRPM1..
28. Ito T, Tanegashima K, Tanaka Y, Hashimoto H, Murata M, Oda Y, Kaku-Ito Y., Trop2 Expression in Extramammary Paget's Disease and Normal Skin., Int J Mol Sci. 2021 Jul 19;22(14):7706., 2021.06.
29. Hashimoto H, Kaku-Ito Y, Oda Y, Ito T., CDK4: A Novel Therapeutic Target for Extramammary Paget's Disease., Front Oncol. 2021 Jul 29;11:710378., 10.3389/fonc.2021.710378, 11, 710378-710378, 2021.06, BACKGROUND: The outcome of extramammary Paget's disease (EMPD) is poor when it progresses to metastasis because of the lack of effective systemic therapies. Recently, CDK4-targeted therapy has attracted attention as a potential therapeutic target for some cancers. The aim of this study was to analyze the impact of CDK4 expression on the survival of patients with EMPD. METHODS: We retrospectively reviewed 110 patients with EMPD. We conducted immunohistochemical analysis of CDK4 and cyclin D1 expression, and assessed the association between their expression and survival. RESULTS: Most EMPD lesions (108/110, 98.2%) were positive for CDK4 staining and there was a positive correlation between CDK4 expression and cyclin D1 expression (r = 0.54, p
30. Fujisawa Y, Ito T, Kato H, Irie H, Kaji T, Maekawa T, Asai J, Yamamoto Y, Fujimura T, Nakai Y, Yasuda M, Matsuyama K, Muto I, Matsushita S, Uchi H, Nakamura Y, Uehara J, Yoshino K., Outcome of combination therapy using BRAF and MEK inhibitors among Asian patients with advanced melanoma: An analysis of 112 cases., Eur J Cancer 145: 210-220, 2021, 2021.04.
31. Matsukane R, Watanabe H, Minami H, Hata K, Suetsugu K, Tsuji T, Masuda S, Okamoto I, Nakagawa T, Ito T, Eto M, Mori M, Nakanishi Y, Egashira N., Continuous monitoring of neutrophils to lymphocytes ratio for estimating the onset, severity, and subsequent prognosis of immune related adverse events., Sci Rep 11: 1324., 2021, 2021.04.
32. Hashimoto H, Ito T, Yamada Y, Oda Y, Furue M., Eosinophilic infiltration discriminates lichen-planus-like eruption caused by an immune checkpoint inhibitor from ordinary lichen planus., J Dermatol 48: e102-103, 2021., 2021.04.
33. Tanaka Y, Murata M, Shen CH, Furue M, Ito T*., NECTIN4: A novel therapeutic target for melanoma., Int J Mol Sci 22: 976., 2021., 2021.04.
34. Ide T, Ito T, Wada-Ohno M, Furue M., Preoperative screening CT/PET(-CT) scans for acral melanoma: Is it necessary?, J Clin Med 10: 811., 2021, 2021.04.
35. Fujimura T, Yoshino K, Kato H, Fujisawa Y, Nakamura Y, Yamamoto Y, Kurimoto K, Ito T, Matsushita S, Maekawa T, Ohuchi K, Amagai R, Muto Y, Kambayashi Y, Hashimoto A, Aiba S., Case series of BRAF mutated advanced melanoma treated with encorafenib plus binimetinib combined therapy., J Dermatol 48: 397-400, 2021., 2021.04.
36. Hashimoto H, Ito T, Ichiki T, Yamada Y, Oda Y, Furue M., The clinical and histopathological features of cutaneous immune-related adverse events and their outcomes., J Clin Med 10: 728., 2021, 2021.04.
37. Hashimoto H, Kaku-Ito Y, Furue M, Ito T., The outcome of chemotherapy for metastatic extramammary Paget’s disease., J Clin Med 10: 739., 2021, 2021.04.
38. Yuka Tanaka, Maho Murata, Yoshinao Oda, Masutaka Furue, Takamichi Ito, Nectin cell adhesion molecule 4 (Nectin4) expression in cutaneous squamous cell carcinoma: A new therapeutic target?, Biomedicines, 10.3390/biomedicines9040355, 9, 4, 2021.04, Cutaneous squamous cell carcinoma (cSCC) is the second most common skin cancer, and its incidence is rising because of the aging population. Nectin cell adhesion molecule 4 (NECTIN4) is involved in the progression of tumors and has attracted interest as a potential therapeutic target. However, little is known about the expression and significance of NECTIN4 in cSCC. The aim of this study was to determine the expression and function of NECTIN4 in cSCC. Immunohistological NECTIN4 expression was investigated in tissues from 34 cSCC patients. Using an A431 human SCC cell line, the role of NECTIN4 in the regulation of cell–cell attachment and migration and proliferation was assessed. NECTIN4 was expressed in most cSCC tissues and on the plasma membrane of A431 cells. Silencing of NECTIN4 prevented cell–cell attachment and induced the expression migration-related molecules, leading to an increase in cell migration. Knockdown of NECTIN4 downregulated extracellular signal-regulated kinase signaling, decreased cyclin D1 expression, and inhibited cell proliferation. These results show that NECTIN4 is expressed in cSCC and functions in the regulation of cell–cell interactions, as well as in the migration and proliferation of SCC cells. NECTIN4-targeted therapy may serve as a novel and promising treatment for cSCC..
39. Hiroki Hashimoto, Yumiko Kaku-Ito, Masutaka Furue, Takamichi Ito, Mucosal Invasion, but Not Incomplete Excision, Has Negative Impact on Long-Term Survival in Patients With Extramammary Paget’s Disease, Frontiers in Oncology, 10.3389/fonc.2021.642919, 11, 2021.04, Background: Extramammary Paget’s disease (EMPD) sometimes spreads from the skin to mucosal areas, and curative surgical excision of these areas is challenging. The aim of this study is to analyze the impact of mucosal involvement and surgical treatment on the survival of patients with EMPD. Methods: We conducted a retrospective review of 217 patients with EMPD. We also assessed the associations between tumor involvement in boundary areas (anal canal, external urethral meatus, vaginal introitus), prognostic factors, and survival in 198 patients treated with curative surgery. Results: Of 217 patients, 75 (34.6%) had mucosal boundary area involvement. Lesions in these areas were associated with frequent lymphovascular invasion (p = 0.042), lymph node metastasis (p = 0.0002), incomplete excision (p
40. Takamichi Ito, Yuka Tanaka, Maho Murata, Yumiko Kaku-Ito, Kazuhisa Furue, Masutaka Furue, BRAF Heterogeneity in Melanoma. [review], Current treatment options in oncology, 10.1007/s11864-021-00818-3, 22, 3, 20-20, 2021.02, OPINION STATEMENT: In the era of molecular targeted therapy, the accurate detection of BRAF mutation in melanoma has become increasingly important. With the advances of molecular analyses and immunohistochemistry, the presence of BRAF mutational heterogeneity in melanoma has been widely recognized. Although most patients with melanoma have a homogeneous BRAF mutation status because the BRAF mutation occurs at an early stage of melanoma development and acts as a driver gene mutation, BRAF mutational heterogeneity does exist, among different tumor sites of a single patient (intertumor heterogeneity) and/or even within a single tumor (intratumor heterogeneity). To summarize the published reports, about 10% of melanoma patients may show intertumorally discordant BRAF status and about 15% of BRAF-mutated melanomas may have intratumor BRAF heterogeneity, although the reported results vary strikingly among the studies and methods used. Considering the BRAF heterogeneity of melanoma, a single biopsy from a single tumor may not be sufficient to uncover the entire BRAF status of a patient. Multiple samples from different sites may be preferable to assess the indication of BRAF/MEK inhibitors, as recommended by the current clinical guidelines. The impact of BRAF heterogeneity on patient survival or the response to treatment with BRAF/MEK inhibitors is an interesting issue, but requires further investigation..
41. Tanaka Y, Ito T, Tsuji G, Furue M., Baicalein inhibits benzo[a]pyrene-induced toxic response by downregulating Src phosphorylation and by upregulating NRF2-HMOX1 system., Antioxidants (Basel) 9: 507., 2020, 2020.04.
42. Ito T*, Kaku-Ito Y, Wada-Ohno M, Furue M., Narrow margin excision for acral melanoma: Is it acceptable?, J Clin Med 9: 2266., 2020, 2020.04.
43. Furue K, Ito T, Tsuji G, Nakahara T, Furue M., Scratch wound-induced CXCL8 upregulation is EGFR-dependent in keratinocytes., J Dermatol Sci 99: 209-212, 2020, 2020.04.
44. Murata M, Ito T*, Tanaka Y, Kaku-Ito Y, Furue M., NECTIN4 Expression in Extramammary Paget's Disease: Implication of a New Therapeutic Target., Int J Mol Sci 21:5891., 2020, 2020.04.
45. Furue K, Ulzii D, Tanaka Y, Ito T, Tsuji G, Kido-Nakahara M, Nakahara T, Furue M., Pathogenic implication of epidermal scratch injury in psoriasis and atopic dermatitis.[Review], 2020.04.
46. Furue K, Ito T, Tsuji G, Nakahara T, Furue M., The CCL20 and CCR6 axis in psoriasis.[Review], 2020.04.
47. Ito T*, Kaku-Ito Y, Murata M, Furue K, Shen CH, Oda Y, Furue M., Immunohistochemical BRAF V600E expression and intratumor BRAF V600E heterogeneity in acral melanoma: Implication in melanoma-specific survival., J Clin Med., 10.3390/jcm9030690, 9, 3, 2020.03, Acral melanoma, a distinct form of cutaneous melanoma originating in the glabrous skin of the palms, soles, and nail beds, has a different genetic background from other subtypes of cutaneous melanoma. The roles of oncogenic BRAF mutations of acral melanoma in pathogenesis and patient outcomes have not been fully elucidated. We retrieved a total of 112 patients with primary acral melanoma and checked their BRAF V600E status using immunohistochemical staining of VE1 antibody. Among these cases, 21 acral melanoma samples (18.8%) showed positive BRAF V600E staining, and of those, 11 samples (9.8%) showed a heterogeneous staining pattern, with a mixture of VE1-positive and VE1-negative cells. BRAF V600E positivity was significantly associated with thicker melanoma (p = 0.0015). There was no significant difference in clinicopathological factors between homogeneous and heterogeneous VE1-positive acral melanoma. Both patients with BRAF V600E-positive acral melanoma and those with heterogeneous BRAF V600E had significantly shorter melanoma-specific survival than those with BRAF V600E-negative melanoma in Kaplan-Meier analysis (p = 0.0283 and p = 0.0065, respectively). These findings provide novel insights into the pathobiology of acral melanoma..
48. Tsuji G, Hashimoto-Hachiya A, Yen V, Miake S, Takemura M, Mitamura Y, Ito T, Murata M, Furue M, Nakahara T., Aryl hydrocarbon receptor activation downregulates IL-33 expression in keratinocytes via ovo-like 1., J Clin Med., 2020.03.
49. Furue K, Ito T, Tanaka Y, Hashimoto-Hachiya A, Takemura M, Murata M, KIdo-Nakahara M, Tsuji G, Nakahara T, Furue M., The EGFR-ERK/JNK-CCL20 Pathway in Scratched Keratinocytes May Underpin Koebnerization in Psoriasis Patients., Int J Mol Sci, 2020.02.
50. Murata M, Ito T*, Yamamura K, Hashimoto-Hachiya A, Furue K, Furue M., OVOL2-mediated ZEB1 downregulation may prevent promotion of actinic keratosis to squamous cell carcinoma., J Clin Med, 10.3390/jcm9030618, 9, 3, 2020.02, Progression of actinic keratosis (AK) to cutaneous squamous cell carcinoma (cSCC) is rare. Most cases of AK remain as intraepidermal lesions, owing to the suppression of the epithelial-to-mesenchymal transition (EMT). Ovo-like transcriptional repressor 1 (OVOL1) and ovo-like zinc finger 2 (OVOL2) are important modulators of EMT in some tumors, but their roles in skin tumors remain elusive. This study elucidated the roles of OVOL1/2 in AK and cSCC using 30 AK/30 cSCC clinical samples, and an A431 human SCC cell line using immunohistochemistry and molecular biological approaches. Immunohistochemically, OVOL1/2 were upregulated in AK and downregulated in cSCC. Meanwhile, EMT-related factors, vimentin and zinc finger E-box binding homeobox 1 (ZEB1) were downregulated in AK and upregulated in cSCC. Moreover, ZEB1 expression was higher in tumors in which OVOL2 expression was low. Thus, we observed an inverse association between OVOL2 and ZEB1 expression in AK and cSCC. Although knockdown of OVOL1 or OVOL2 increased the mRNA and protein levels of ZEB1, only OVOL2 knockdown increased the invasive ability of A431. In conclusion, OVOL2 inhibits ZEB1 expression and may inhibit the promotion of AK into cSCC. OVOL2/ZEB1 axis may be a potential target for preventing the development of cSCC..
51. Ito T*, Kaku-Ito Y, Murata M, Ichiki T, Kuma Y, Tanaka Y, Ide T, Ohno F, Wada-Ohno M, Yamada Y, Oda Y, Furue M., Intra- and Inter-Tumor BRAF Heterogeneity in Acral Melanoma: An Immunohistochemical Analysis., Int J Mol Sci., 10.3390/ijms20246191, 20, 24, 2019.12, The current development of BRAF inhibitors has revolutionized the treatment of unresectable melanoma. As the potential heterogeneity of BRAF mutations in melanoma has been reported, accurate detection of BRAF mutations are important. However, the genetic heterogeneity of acral melanoma-a distinct type of melanoma with a unique genetic background-has not fully been investigated. We conducted a retrospective review of our acral melanoma patients. Of the 196 patients with acral melanoma, we retrieved 31 pairs of primary and matched metastatic melanomas. We immunostained the 31 pairs with VE1, a BRAFV600E-mutation-specific monoclonal antibody. Immunohistochemistry with VE1 showed a high degree of sensitivity and specificity for detecting BRAFV600E mutations compared with the real-time polymerase chain reaction method. A total of nine primary (29.0%) and eight metastatic (25.8%) acral melanomas were positive for VE1. In three patients (9.7%), we observed a discordance of VE1 staining between the primary and metastatic lesions. Of note, VE1 immunohistochemical staining revealed a remarkable degree of intra-tumor genetic heterogeneity in acral melanoma. Our study reveals that VE1 immunostaining is a useful ancillary method for detecting BRAFV600E mutations in acral melanoma and allows for a clear visualization of intra- and inter-tumor BRAF heterogeneity..
52. Furue K, Ito T, Tsuji G, Ulzii D, Vu YH, Kido-Nakahara M, Nakahara T, Furue M., The IL-13-OVOL1-FLG axis in atopic dermatitis.[Review], 2019.11.
53. Tanaka Y, Uchi H, Ito T, Furue M., Indirubin-pregnane X receptor-JNK axis accelerates skin wound healing., Sci Rep., 2019.10.
54. Furue K, Ito T, Tsuji G, Esaki H, Kido-Nakahara M, Nakahara T, Furue M., Does mechanical scratching cause the recruitment of T-helper 17 cells in atopic dermatitis?[Review], 2019.10.
55. Furue K, Ito T, Tanaka Y, Yumine A, Hashimoto-Hachiya A, Takemura M, Murata M, Yamamura K, Tsuji G, Furue M., Cyto/chemokine profile of in vitro scratched keratinocyte model: Implications of significant upregulation of CCL20, CXCL8 and IL36G in Koebner phenomenon., J Dermatol Sci, 10.1016/j.jdermsci.2019.04.002, 94, 1, 244-251, 2019.09, BACKGROUND: Scratch injury induces Koebner phenomenon in psoriasis. Smoking is also a risk factor for psoriasis. Keratinocytes can produce various psoriasis-related molecules including TNF, IL1 A, IL1B, IL6, IL12B, IL17C, IL23 A, IL36 A, IL36B, IL36 G, CXCL1, CXCL2, CXCL8, CXCL9, CXCL10, CCL20, IFNB, and CAMP. However, the scratch-induced molecular profiling remains elusive. OBJECTIVE: To profile the induction pattern of above-mentioned psoriasis-related and keratinocyte-derived molecules by scratch injury in the presence or absence of anti-psoriatic drugs or benzo[a]pyrene, a major environmental pollutant of tobacco smoke. METHODS: Confluent normal human keratinocytes were scratched and molecules were assayed by qRT-PCR, ELISA and Western blotting with or without drugs and benzo[a]pyrene. RESULTS: Among the 18 molecules, the scratch injury on a confluent keratinocyte sheet significantly and selectively upregulated the mRNA expression of four cyto/chemokines, CXCL8, CCL20, IL36G, and TNF, in a scratch-line-number-dependent manner under either low- or high-calcium condition. However, significant protein secretion was only demonstrated for CXCL8 and CCL20. The IL36 G protein was not secreted, but its intracellular level was significantly upregulated by scratch injury, whereas neither the secretion nor the intracellular level of TNF protein was affected by scratch injury. Dexamethasone, but not maxacalcitol nor the phosphodiesterase 4 inhibitor apremilast, partially inhibited the CXCL8 and CCL20 secretion. Benzo[a]pyrene significantly and synergistically enhanced the scratch-induced CCL20 secretion that may explain why smoking is a risk factor for psoriasis. CONCLUSION: CCL20 and to a less extent CXCL8 may play a key role in triggering the Koebner phenomenon after scratch injury to keratinocytes..
56. Wada-Ohno M, Ito T, Furue M., Adjuvant Therapy for Melanoma.[Review], 2019.09.
57. Kaku-Ito Y, Ito T (co-first), Tsuji G, Nakahara T, Uchi H, Hagihara A, Furue M., Evaluation of mapping biopsies for extramammary Paget's disease: a retrospective study., J Am Acad Dermatol, 76: 1171-1177, 2018, 2018.06.
58. Ito T*, Kaku-Ito Y, Furue M., The diagnosis and management of extramammary Paget's disease.[Review], 2018.06.
59. Furue K, Ito T, Tsuji G, Kadono T, Furue M., Autoimmuity and autoimmune comorbidities in psoriasis.[Review], 2018.04.
60. Furue M, Ito T, Wada M, Wada N, Kadono T, Uchi H., Melanoma and immune checkpoint inhibitors.[Review], 2018.04.
61. Tsuji G, Ito T, Chiba T, Mitoma C, Nakahara T, Uchi H, Furue M., The role of the OVOL1-OVOL2 axis in normal and diseased human skin.[Review], 2018.04.
62. Kuma Y, Yamada Y, Yamamoto H, Kohashi K, Ito T, Furue M, Oda Y., A Novel Fusion Gene CRTC3-MAML2 in Hidradenoma: Clinicopathological and Histopathological Significance., Hum Pathol, Hum Pathol 70: 55-61, 2017, 2017.12.
63. Chang CH, Kuo CJ, Ito T, Su YY, Jiang ST, Chiou MH, Lin YH, Memberg M, Stiewe T, Ito S, Wakamatsu K, Alkalay I, Ben-Neriah Y., CK1α ablation in keratinocytes induces p53-dependent, sunburn-protective skin hyperpigmentation., Proc Natl Acad Sci USA, 114: E8035-E8044, 2017, 2017.09.
64. Hiraki-Hotokebuchi Y, Yamada Y, Kohashi K, Yamamoto H, Endo M, Setsu N, Yuki K, Ito T, Iwamoto Y, Furue M, Oda Y., Alteration of PDGFRβ-Akt-mTOR Pathway Signaling in Fibrosarcomatous Transformation of Dermatofibrosarcoma Protuberans., Hum Pathol, Hum Pathol 67: 60-68, 2017, 2017.09.
65. Wada M, Ito T, Tsuji G, Nakahara T, Uchi H, Hagihara A, Furue M., Acral lentiginous melanoma versus other melanoma: a single-center analysis in Japan., J Dermatol, J Dermatol 44: 932-8, 2017, 2017.08.
66. Tsuji G, Hashimoto-Hachiya A, Kiyomatsu-Oda M, Takemura M, Ohno F, Ito T, Morino-Koga S, Mitoma C, Nakahara T, Uchi H, Furue M., Aryl hydrocarbon receptor activation restores filaggrin expression via OVOL1 in atopic dermatitis., Cell Death Dis, Cell Death Dis 8: e2931, 2017, 2017.07.
67. Yamada Y, Kuda M, Kohashi K, Yamamoto H, Takemoto J, Ishii T, Iura K, Maekawa A, Bekki H, Ito T, Otsuka H, Kuroda M, Honda Y, Sumiyoshi S, Inoue T, Kinoshita N, Nishida A, Yamashita K, Ito I, Komune S, Taguchi T, Iwamoto Y, Oda Y., Histological and immunohistochemical characteristics of undifferentiated small round cell sarcomas associated with CIC-DUX4 and BCOR-CCNB3 fusion genes., Virchows Arch, Virchows Arch 470: 373-380, 2017, 2017.07.
68. Yamada Y, Kinoshita I, Kohashi K, Yamamoto H, Kuma Y, Ito T, Koda K, Kisanuki A, Kurosawa M, Yoshimura M, Furue M, Oda Y., HIF-1α, MDM2, CDK4, and p16 expression in ischemic fasciitis, focusing on its ischemic condition., Virchows Arch, Virchows Arch 471: 117-122, 2017, 2017.07.
69. Ito T*, Tsuji G, Ohno F, Nakahara T, Uchi H, Furue M., Potential role of the OVOL1-OVOL2 axis and c-Myc in the progression of cutaneous squamous cell carcinoma., Mod Pathol, 30: 919-927, 2017, 2017.06.
70. Itoh E, Nakahara T, Murata M, Ito T, Onozuka D, Furumura M, Hagihara A, Furue M., Chronic spontaneous urticaria: implications of subcutaneous inflammatory cell infiltration in an intractable clinical course., J Allergy Clin Immunol, J Allergy Clin Immunol 139: 363-366, 2017, 2017.01.
71. Ito T*, Uchi H, Nakahara T, Tsuji G, Oda Y, Hagihara A, Furue M., Cutaneous angiosarcoma of the head and face: a single-center analysis of treatment outcomes in 43 patients in Japan., J Cancer Res Clin Oncol, J Cancer Res Clin Oncol 142: 1387-1394, 2016, 2016.06.
72. Ito T, Kohashi K, Yamada Y, Maekawa A, Kuda M, Furue M, Oda Y, Prognostic significance of forkhead box M1 (FoxM1) expression and antitumor effect of FoxM1 inhibition in melanoma., Histopathology, 69: 63–71, 2016, 2016.06.
73. Ito T*, Tsuji G, Uchi H, Nakahara T, Hashimoto-Hachiya A, Yoshida Y, Yamamoto O, Oda Y, Furue M., Activation of the OVOL1-OVOL2 Axis in the Hair Bulb and in Pilomatricoma., Am J Pathol, 186: 1036-1043, 2016, 2016.04.
74. Ito T, Kohashi K, Yamada Y, Iwasaki T, Maekawa A, Kuda M, Hoshina D, Abe R, Furue M, Oda Y., Prognostic Significance of Forkhead Box M1 (FOXM1) Expression and Antitumor Effect of FOXM1 Inhibition in Angiosarcoma., J Cancer, J Cancer 7: 823-830, 2016, 2016.04.
75. Ito T*, Inatomi Y, Nagae K, Nakano-Nakamura M, Nakahara T, Furue M, Uchi H., Narrow-margin excision is a safe, reliable treatment for well-defined, primary pigmented basal cell carcinoma: an analysis of 288 lesions in Japan., J Eur Acad Dermatol Venereol, J Eur Acad Dermatol Venereol 29: 1828-31, 2015, 2015.09.
76. Ito T*, Wada M, Nagae K, Nakano-Nakamura M, Nakahara T, Furue M, Uchi H., Triple-marker PCR assay of sentinel lymph node as a prognostic factor in melanoma., J Eur Acad Dermatol Venereol, J Eur Acad Dermatol Venereol 29: 912-918, 2015., 2015.05.
77. Sakaizawa K, Ashida A, Uchiyama A, Ito T, Fujisawa Y, Ogata D, Matsushita S, Fujii K, Fukushima S, Shibayama Y, Hatta N, Takenouchi T, Uehara J, Okuyama R, Yamazaki N, Uhara H., Clinical characteristics associated with BRAF, NRAS and KIT mutations in Japanese melnoma patients., J Dermatol Sci, J Dermatol Sci 80: 33–7, 2015, 2015.04.
78. Ito T*, Kaku Y, Nagae K, Nakano-Nakamura M, Nakahara T, Oda Y, Hagihara A, Furue M, Uchi H., Tumor thickness as a prognostic factor in extramammary Paget's disease., J Dermatol, J Dermatol 42: 269-75, 2015, 2015.03.
79. Ito T*, Wada M, Nagae K, Nakano-Nakamura M, Nakahara T, Hagihara A, Furue M, Uchi H., Acral lentiginous melanoma: Who benefits from sentinel lymph node biopsy?, J Am Acad Dermatol, 72: 71-77, 2015, 2015.01.
80. Mitoma C, Nakahara T, Uchi H, Ito T, Inatomi Y, Ide T, Jinnai S, Jinnai N, Iwasaki N, Sakamoto K, Kimura N, Maeda A, Kuma Y, Maehara E, Tsutsumi M, Kido-Nakahara M, Hirota T, Tamari M, Furue M., Preferential expression of OVOL1 in inner root sheath of hair, sebaceous gland, eccrine duct and their neoplasms in human skin., Fukuoka Acta Med, 105, 8, 166-173, Fukuoka Acta Med 105: 166-173, 2014, 2014.08, OVOL1は表皮細胞の増殖を抑制し角化を推進させる転写因子と考えられている。最近のgenome-wide association studyでは、アトピー性皮膚炎の疾患感受性遺伝子の一つとしても注目を浴びている。マウスではOvol1は皮膚及び毛嚢に発現していることが報告されているがヒトでの研究はこれまで報告されていない。本研究では、ヒト健常皮膚および皮膚疾患で、OVOL1の発現を免疫組織学的に明らかにした。健常皮膚では、OVOL1は基底層上層の表皮細胞、毛嚢の内毛根鞘、成熟した脂腺細胞、エクリン汗腺の導管部に優位に発現していた。炎症性皮膚疾患のOVOL1の発現は健常皮膚に比べ変化を認めなかった。OVOL1の発現はeccrine poromaとhidradenomaで亢進していた。ボーエン病と脂腺腫ではOVOL1の発現は亢進していたが、有棘細胞癌や脂腺癌ではむしろ減少していた。OVOL1はヒト皮膚の器官形成や腫瘍発生に重要な役割をになっているのではないかと考えた。(著者抄録).
81. Zhu L, Kohda F, Nakahara T, Chiba T, Tsuji G, Hachisuka J, Ito T, Tu Y, Moroi Y, Uchi H, Furue M., Aberrant expression of S100A6 and matrix metalloproteinase 9, but not S100A2, S100A4, and S100A7, is associated with epidermal carcinogenesis., J Dermatol Sci, J Dermatol Sci 72:311-9, 2013, 2013.12.
82. Zhu L, Ito T, Nakahara T, Nagae K, Fuyuno Y, Nakao M, Akahosi M, Nakagawa R, Tu Y, Uchi H, Furue M., Upregulation of S100P, receptor for advanced glycation end products and ezrin in malignant melanoma., J Dermatol, J Dermatol 40: 973-979, 2013, 2013.12.
83. Ito T*, Moroi Y, Oba J, Nakahara T, Takeuchi S, Uchi H, Takahara M, Masuda T, Furue M., The prognostic value of RT-PCR assay of sentinel lymph node biopsy for patients with cutaneous melanoma: A single center analysis in Japan., Melanoma Res, Melanoma Res 22: 38-44, 2012, 2012.01.
Presentations
1. [Invited Lecture] Nail apparatus melanoma: Current management and future perspectives..
2. Ito T, Kohashi K, Yamada Y, Furue M, Oda Y., Prognostic significance of forkhead box M1 (FOXM1) expression and antitumor effect of FOXM1 inhibition in melanoma., International Investigative Dermatology 2018, 2018.05.
3. Ito T, Tsuji G, Ohno F, Nakahara T, Uchi H, Furue M., Potential role of the OVOL1-OVOL2 axis and c-Myc in the progression of cutaneous squamous cell carcinoma from Bowen's disease., The 76th Annual Meeting of the Society for Investigative Dermatology., 2017.04.
4. Ito T., 【The 17th Galderma Award】Acral lentiginous melanoma: Who benefits from sentinel lymph node biopsy?, The 41st Annual Meeting of the Japanese Society for Investigative Dermatology, 2016.12.
5. Ito T, Yamamoto O, Oda Y, Furue M., Interesting educational cases: a red nodule on the forehead of an 83-year-old woman., The 3rd Eastern Asia Dermatology Congress. 2014/09/24-26. Jeju, Korea, 2014.09.
6. Ito T, Yoshida Y, Furue M, Yamamoto O, Yellow plaque on the chest., The 12th Korean Dermatopathology Symposium, 2013.05.
Membership in Academic Society
  • The Japanese Dermatological Association [Representative]
  • The Japanese Skin Cancer Society
  • The Japanese Society of Plastic and Reconstructive Surgery
  • The Japan Dermatohistopathology Society [Trustee]
  • The Japanese Society for Investigative Dermatology [Councilor]
  • The Japanese Society of Pathology
  • The Japanese Cancer Association
  • The Japanese Society for Pressure Ulcers [Manager of Kyushu Okinawa Block]
  • The Japanese Society for Burn Injuries
Awards
  • Research Grant Award. Fukuoka Foundation for Sound Health Cancer Research Fund
  • Japanese Dermatological Association Research Grant for Fundamental Medicine (SHISEIDO donation)
  • GlaxoSmithKlein Japan Research Grant
  • Research Grant in Medicine
  • Society Award
  • The 17th Galderma Award
  • Best Presentation Award
  • Best Poster Award
  • Best Abstract Award
  • Best Poster Award