論文 - 肥田　時征

Rechallenge With Nivolumab After Vemurafenib Treatment of Initially Nivolumab-Resistant Advanced Melanoma.

Junji Kato, Tokimasa Hida, Takafumi Kamiya, Sayuri Sato, Hitomi Takahashi, Toshihiko Torigoe, Hisashi Uhara

JAMA dermatology   154 ( 5 ) 621 - 622  2018年05月  [査読有り]  [国際誌]

DOI PubMed

Dermoscopic features distinctive for extraocular sebaceous carcinoma.

Kohei Horimoto, Junji Kato, Yasuyuki Sumikawa, Tokimasa Hida, Takafumi Kamiya, Sayuri Sato, Hitomi Takahashi, Masahide Sawada, Toshiharu Yamashita, Hisashi Uhara

The Journal of dermatology   45 ( 4 ) 487 - 490  2018年04月  [査読有り]  [国際誌]

　概要を見る

We examined dermoscopic features of three cases of extraocular sebaceous carcinoma and reviewed the literatures. The yellowish structures, polymorphous vessels and ulceration were common findings in our cases and all cases of the previous reports. The appearance of whitish-pink areas has not been described previously. Our results suggested that the combination of four dermoscopic features, whitish-pink areas, yellowish structures, polymorphous vessels and ulceration might be distinctive in extraocular sebaceous carcinoma.

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Imiquimod 5% cream as a therapeutic option for extramammary Paget's disease.

Masahide Sawada, Junji Kato, Toshiharu Yamashita, Akihiro Yoneta, Tokimasa Hida, Kohei Horimoto, Sayuri Sato, Hisashi Uhara

The Journal of dermatology   45 ( 2 ) 216 - 219  2018年02月  [査読有り]  [国際誌]

　概要を見る

A wide local excision is the standard treatment for extramammary Paget's disease (EMPD), though this treatment often leads to permanent anogenital mutilation and functional impairment. The purpose of our study is to evaluate the efficacy and safety of the topical application of imiquimod 5% cream for non-invasive EMPD. We examined nine patients with EMPD. Eight of the nine patients were treated with imiquimod 5% cream three times per week for 16 weeks; one case was treated for 6 weeks. The response rate was 100% including five complete remissions. Local irritation was observed in three patients, which was controlled by a provisional withdrawal of the treatment. These results suggest that imiquimod 5% cream may be considered an alternative therapeutic option for the treatment of non-invasive EMPD.

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Successful TS-1 monotherapy as the second-line treatment for advanced extramammary Paget's disease: A report of two cases.

Junji Kato, Tokimasa Hida, Toshiharu Yamashita, Shiori Kamiya, Kohei Horimoto, Sayuri Sato, Hitomi Takahashi, Masahide Sawada, Mao Yamada, Hisashi Uhara

The Journal of dermatology   45 ( 1 ) 80 - 82  2018年01月  [査読有り]  [国際誌]

　概要を見る

There is no standard chemotherapeutic treatment for advanced extramammary Paget's disease, though the effectiveness of some chemotherapy regimens, including docetaxel, has been reported. In this report, we report that TS-1 monotherapy was effective in two patients with advanced extramammary Paget's disease after docetaxel treatment failure. TS-1 monotherapy may be useful as the second-line treatment for patients with advanced extramammary Paget's disease.

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Case of diffuse panbronchiolitis developed in a patient with epidermodysplasia verruciformis.

Naomi Kitayama, Satoshi Nakamizo, Yumi Nonomura, Yo Kaku, Yuichiro Endo, Teruki Dainichi, Masae Okura, Tokimasa Hida, Toshiharu Yamashita, Atsushi Otsuka, Kenji Kabashima

The Journal of dermatology ( WILEY )  44 ( 12 ) e363-e364 - e364  2017年12月  [査読有り]  [国際誌]

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An adult case of cardiofaciocutaneous syndrome with BRAF mutation.

Sayuri Sato, Tokimasa Hida, Masae Okura, Aki Ishikawa, Toshiharu Yamashita

European journal of dermatology : EJD ( JOHN LIBBEY EUROTEXT LTD )  27 ( 4 ) 412 - 413  2017年08月  [査読有り]  [国際誌]

担当区分：   責任著者

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Psoriasiform mycosis fungoides masquerading as tumourous plaques.

Yasuyuki Yamaguchi, Yasuyuki Fujita, Yu Hirata, Machiko Nishimura, Satoru Shinkuma, Ken Natsuga, Toshifumi Nomura, Tokimasa Hida, Naoko Kato, Hiroshi Shimizu

European journal of dermatology : EJD ( JOHN LIBBEY EUROTEXT LTD )  27 ( 3 ) 295 - 296  2017年06月  [査読有り]  [国際誌]

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Serum cytokeratin 19 fragment 21-1 is a useful tumor marker for the assessment of extramammary Paget's disease.

Junji Kato, Yasuyuki Sumikawa, Tokimasa Hida, Takafumi Kamiya, Kohei Horimoto, Shiori Kamiya, Sayuri Sato, Hitomi Takahashi, Masahide Sawada, Toshiharu Yamashita

The Journal of dermatology ( WILEY )  44 ( 6 ) 666 - 670  2017年06月  [査読有り]  [国際誌]

　概要を見る

Cytokeratin 19 fragment 21-1 (CYFRA 21-1) has been used as a tumor marker for several malignancies. However, to date, no studies have assessed whether CYFRA 21-1 could be a useful marker for extramammary Paget's disease (EMPD). The present study aimed to evaluate the significance of CYFRA 21-1 as a serum tumor marker for EMPD progression. Concentrations of serum CYFRA 21-1 and carcinoembryonic antigen (CEA) in 13 cases of EMPD were measured prior to undergoing treatment at Sapporo Medical University Hospital from January 2014 to May 2016. Four of the 13 patients had lymph node metastases at diagnosis, but none had distant metastases. Immunohistochemistry indicated that all 13 primary tumors and four metastatic tumors in lymph nodes were positive for cytokeratin 19. Although none of the 13 patients showed high serum CEA levels, six patients (46.2%) had elevated serum CYFRA 21-1. Furthermore, CYFRA 21-1 was reduced in association with post-treatment tumor reduction in all six patients. Among these six patients, four developed recurrence and metastasis during the follow-up period. CYFRA 21-1 was re-elevated in all four of these patients; however, serum CEA was elevated only in the patient with distant metastasis. These results suggest that CYFRA 21-1 is more sensitive compared with CEA, and can be useful as a tumor marker for evaluating tumor progression and treatment efficacy in patients with EMPD.

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Clinical and epidemiological analysis in 149 cases of rhododendrol-induced leukoderma.

Momoko Yoshikawa, Yasuyuki Sumikawa, Tokimasa Hida, Takafumi Kamiya, Kimi Kase, Yasue Ishii-Osai, Junji Kato, Yuji Kan, Shiori Kamiya, Yuki Sato, Toshiharu Yamashita

The Journal of dermatology ( WILEY )  44 ( 5 ) 582 - 587  2017年05月  [査読有り]  [国際誌]

　概要を見る

Rhododendrol-induced leukoderma is an acquired depigmentation that develops mainly at the contact site after repeated use of skin-whitening cosmetics containing rhododendrol. In most cases, cessation of further depigmentation or occurrence of repigmentation is observed after discontinuing the use of cosmetics. However, some patients develop vitiligo vulgaris through the spread of depigmentation into the non-exposed areas. Our study aims to investigate the patient-specific factors that may affect the extent of depigmentation or repigmentation, as well as development of vitiligo vulgaris. The degree of depigmentation of the face, neck and hands where exposed to rhododendrol was scored using photographs over time. The relationships between depigmentation score at first visit/improvement rate of depigmentation score and patient demographics were evaluated and three important clinical observations were made. First, repigmentation of the face was superior compared with that of the hands and neck, suggesting a possible role for the migration and differentiation of melanocyte stem cells from hair follicles, as a mechanism of repigmentation. Second, the intensity of rhododendrol exposure did not contribute to differences in the severity of depigmentation. This suggested a possibility of underlying genetic susceptibility to melanocyte cytotoxicity or immune reaction. Third, depigmentation score at first visit and past history of atopic dermatitis were significantly high in patients who developed vitiligo vulgaris. This suggested that severe chemical damage of melanocytes by rhododendrol leads to a higher risk of developing vitiligo vulgaris through the possible involvement of an immune reaction. These clinical observations may help to further understand the pathogenesis of rhododendrol-induced leukoderma.

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Muir-Torre syndrome caused by exonic deletion of MLH1 due to homologous recombination.

Mirei Shiki, Tokimasa Hida, Kokichi Sugano, Rie Kaneko, Takafumi Kamiya, Akihiro Sakurai, Toshiharu Yamashita

European journal of dermatology : EJD ( JOHN LIBBEY EUROTEXT LTD )  27 ( 1 ) 54 - 58  2017年02月  [査読有り]  [国際誌]

　概要を見る

BACKGROUND: Muir-Torre syndrome (MTS) is characterized by sebaceous neoplasms with internal malignancies and regarded as a variant of hereditary nonpolyposis colorectal cancer (HNPCC). Pathogenic variations of MTS have been identified in the MSH2, MLH1, and MSH6 genes, with the majority of variations located in MSH2. OBJECTIVES: To present an MTS patient who was the only individual with skin malignancies within a cancer-prone pedigree and to show the usefulness of RNA-based genetic analysis in the investigation of MTS. MATERIALS & METHODS: A 77-year-old man who had operated X-ray equipment at his workplace in his twenties was clinically diagnosed with MTS and investigated by RNA-based analysis, multiplex ligation-dependent probe amplification, and genomic DNA sequencing. RESULTS: The patient had suffered from sebaceous tumours, squamous cell carcinomas of the skin, and colon cancer. The patient's family history was remarkable for visceral malignant diseases. Genetic analysis revealed homologous recombination between two Alu elements within intron 4 and 5 of the MLH1 gene. The rearrangement caused a 1,222-bp deletion, including the entire exon 5. Deletion of exon 5 has previously been reported only in two patients with HNPCC, and not in patients with MTS. CONCLUSION: For the genetic analysis of MTS, the possibility of rare copy number variations of MLH1, as well as MSH2 variations, should be considered. RNA-based screening using puromycin is recommended in order to identify such variations. It remains unclear why only the proband among the pedigree had skin malignancies, however, the skin carcinogenesis might have been related to occupational radiation exposure.

DOI PubMed

Diagnosis of eight groups of xeroderma pigmentosum by genetic complementation using recombinant adenovirus vectors.

Toshiharu Yamashita, Masae Okura, Yasue Ishii-Osai, Tokimasa Hida

The Journal of dermatology   43 ( 10 ) 1167 - 1173  2016年10月  [査読有り]  [国際誌]

　概要を見る

Because patients with xeroderma pigmentosum (XP) must avoid ultraviolet (UV) light from an early age, an early diagnosis of this disorder is essential. XP is composed of seven genetic complementation groups, XP-A to -G, and a variant type (XP-V). To establish an easy and accurate diagnosis of the eight disease groups, we constructed recombinant adenoviruses that expressed one of the XP cDNA. When fibroblasts derived from patients with XP-A, -B, -C, -D, -F or -G were infected with the adenovirus expressing XPA, XPB, XPC, XPD, XPF or XPG, respectively, and UV-C at 5-20 J/m2 was irradiated, cell viability was clearly recovered by the corresponding recombinant adenoviruses. In contrast, XP-E and XP-V cells were not significantly sensitive to UV irradiation and were barely complemented by the matched recombinant adenoviruses. However, co-infection of Ad-XPA with Ad-XPE increased survival rate of XP-E cells after UV-C exposure. When XP-V cell strains, including one derived from a Japanese patient, were infected with Ad-XPV, exposed to UV-B and cultured with 1 mmol/L of caffeine, flow cytometry detected a characteristic decrease in the S phase in all the XP-V cell strains. From these results, the eight groups of XP could be differentiated by utilizing a set of recombinant adenoviruses, indicating that our procedure provides a convenient and correct diagnostic method for all the XP groups including XP-E and XP-V.

DOI PubMed

Biochemical effects of the flavanol-rich lychee fruit extract on the melanin biosynthesis and reactive oxygen species.

Kazuya Hagiwara, Masae Okura, Yasuyuki Sumikawa, Tokimasa Hida, Atsushi Kuno, Yoshiyuki Horio, Toshiharu Yamashita

The Journal of dermatology   43 ( 10 ) 1174 - 1183  2016年10月  [査読有り]  [国際誌]

　概要を見る

An ingredient of fruit polyphenol, resveratrol, is known to have an inhibitory effect on melanogenesis. In order to examine the functional differences between resveratrol and other fruit polyphenols, we compared biochemical effects of a resveratrol-free polyphenol, flavanol-rich lychee fruit extract (FRLFE), with other phenolic compounds including resveratrol. FRLFE as well as hydroquinone and resveratrol suppressed growth of B16F1 melanoma cells more significantly than rhododendrol or arbutin. Resveratrol suppressed mushroom tyrosinase at the lowest concentration (23.0 μmol/L) among the compounds tested. FRLFE and hydroquinone suppressed tyrosinase at almost the same concentration (half maximal inhibitory concentration [IC50 ], 83.5 and 94.6 μmol/L, respectively), which was higher than rhododendrol, ascorbic acid and arbutin (IC50 , 245, 345 and 421 μmol/L, respectively). Western blot analysis revealed that although resveratrol decreased expressions of tyrosinase and tyrosinase-related protein 1, FRLFE did not affect their expressions. Both FRLFE and resveratrol suppressed antimycin A-mediated reactive oxygen species (ROS) production in melanocytic cells. Resveratrol-mediated ROS suppression was inhibited by nicotinamide, a SIRT1 inhibitor. However, FRLFE-mediated suppression was not affected by nicotinamide. Moreover, FRLFE directly decreased superoxide in vitro, as detected by superoxide dismutase-like scavenging activity assay. These results suggest that FRLFE can protect melanocytes from cytotoxicity caused by an excess amount of melanin and ROS in a different manner from resveratrol.

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Circulating melanoma cells as a potential biomarker to detect metastasis and evaluate prognosis.

Tokimasa Hida, Akihiro Yoneta, Kazumasa Wakamatsu, Kenji Yanagisawa, Yasue Ishii-Osai, Yuji Kan, Junji Kato, Toshiharu Yamashita

The Australasian journal of dermatology   57 ( 2 ) 145 - 9  2016年05月  [査読有り]  [国際誌]

　概要を見る

TNM staging is mainly used to evaluate the prognosis of melanoma patients. Serum biomarkers such as 5-S-cysteinyldopa (5-S-CD) have occasionally been used but most do not respond until the tumour burden becomes high. Recently, circulating melanoma cells (CMC) have been reported as a possible new biomarker to detect metastasis, monitor treatment response and predict prognosis. The object of this exploratory study was to evaluate the efficacy of CMC to detect metastasis and predict prognosis by cross-sectional and prospective observational analyses, respectively. Altogether 15 patients with stages II-IV melanoma were enrolled and CMC were enumerated by CellSearch system with cut-off values of two cells/7.5 mL. Serum 5-S-CD and lactate dehydrogenase (LDH) were also measured. The sensitivity of CMC and 5-S-CD for the detection of metastasis was 33 and 50%, respectively. The combination of CMC and 5-S-CD showed a sensitivity of 67%, the best performance among CMC, 5-S-CD, LDH and any combination of two of the markers. Additionally, a 30-month prospective observation showed that CMC could segregate patients with poorer prognosis. The median survival time for the patients with <2 CMC and those with ≥2 CMC was 19.5 and 4.5 months, respectively. The limitation of this study is the small sample size. These preliminary results indicate CMC may complement the efficacy of 5-S-CD to detect metastasis and can be a prognostic marker. Although there is still room for improvement to maximise the sensitivity, the CellSearch system is reproducible, standardised and suitable for multi-centre studies.

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Nagashima-type palmoplantar keratosis caused by compound heterozygous mutations in SERPINB7.

Tokimasa Hida, Masae Okura, Takafumi Kamiya, Toshiharu Yamashita

European journal of dermatology : EJD   25 ( 2 ) 202 - 3  2015年04月  [査読有り]  [国際誌]

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A case of oculocutaneous albinism type 4: aberrant expression of SLC45A2 transcript with exon skipping.

Tokimasa Hida, Masae Okura, Toju Tanaka, Toshiharu Yamashita

The Journal of dermatology ( WILEY-BLACKWELL )  41 ( 11 ) 1019 - 21  2014年11月  [査読有り]  [国際誌]

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Pigmented mammary Paget's disease presenting with dermoscopic features of multiple dots.

Tokimasa Hida, Toshiharu Yamashita

The Australasian journal of dermatology ( WILEY-BLACKWELL )  55 ( 4 ) 260 - 2  2014年11月  [査読有り]  [国際誌]

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Development of sarcoidosis during β-interferon therapy for melanoma.

Shiki M, Hida T, Yamashita T

The Journal of dermatology ( WILEY-BLACKWELL )  41 ( 9 ) 862 - 3  2014年09月  [査読有り]  [国際誌]

担当区分：   責任著者

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Ankyloblepharon-ectodermal defects-cleft lip/palate syndrome: a case with a novelp63 mutation associated with abnormal keratohyalin granules

Tokimasa Hida, Kimi Kase, Takahiro Hamada, Mitsuhiro Matsuda, Takashi Hashimoto, Toshiharu Yamashita

EUROPEAN JOURNAL OF DERMATOLOGY ( JOHN LIBBEY EUROTEXT LTD )  24 ( 4 ) 495 - 497  2014年07月  [査読有り]

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Influence of isoflavone intake and equol-producing intestinal flora on prostate cancer risk.

Yukiko Sugiyama, Naoya Masumori, Fumimasa Fukuta, Akihiro Yoneta, Tokimasa Hida, Toshiharu Yamashita, Machiko Minatoya, Yoshie Nagata, Mitsuru Mori, Hirokazu Tsuji, Hideyuki Akaza, Taiji Tsukamoto

Asian Pacific journal of cancer prevention : APJCP   14 ( 1 ) 1 - 4  2013年  [査読有り]  [国際誌]

　概要を見る

BACKGROUND: The age-adjusted incidence rate of prostate cancer (PCa) has been reported to be lower among Asians than Western populations. A traditional Japanese meal, high in soybean products or isoflavones, may be associated with a decreased risk of PCa. Equol, which is converted from daidzein by human intestinal flora, is biologically more active than any other isoflavone aglycone. MATERIALS AND METHODS: We reviewed not only recent epidemiological studies on association of isoflavones with PCa risk, but also recent research on human intestinal bacteria responsible for converting daidzein into equol. Studies were systematically searched from the database published within the last 5 years of from 2008-2012. RESULTS: Five out of 6 articles showed significant association of isoflavones with a decreased risk of PCa, and two of them consistently showed that equol-producers carry a significantly reduced risk of PCa. Furthermore, 5 human intestinal bacteria that can convert daidzein into equol were identified in the last 5 years. CONCLUSIONS: If equol can reduce risk of PCa, a possible strategy for reducing the risk of PCa may be to increase the proportion of equol-producers by changing the intestinal flora to carrying an equol-producing bacterium with dietary alteration or probiotic technology.

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Etanercept-induced lichen planus-like eruptions following the lines of Blaschko

Momoko Utsu, Tokimasa Hida, Hiroki Takahashi, Toshiharu Yamashita

EUROPEAN JOURNAL OF DERMATOLOGY ( JOHN LIBBEY EUROTEXT LTD )  22 ( 4 ) 544 - 545  2012年07月  [査読有り]

担当区分：   責任著者

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