Atsushi Tanemura

Osaka University

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Data from CpG Island Methylator Phenotype Predicts Progression of Malignant Melanoma

Atsushi Tanemura Alicia M. Terando Myung‐Shin Sim Anneke Q. van Hoesel Michiel F.G. de Maat

<div>AbstractPurpose: The CpG island methylator phenotype (CIMP) may be associated with development of malignancy through coordinated inactivation of tumor suppressor and tumor-related genes (TRG) and methylation of multiple noncoding, methylated-in-tumor (MINT) loci. These epigenetic changes create a distinct CIMP pattern that has been linked to recurrence and survival in gastrointestinal cancers. Because epigenetic inactivation of TRGs also has been shown in malignant melanoma, we hypothesized the existence of a clinically significant CIMP in cutaneous melanoma progression.Experimental Design: The methylation status of the CpG island promoter region of TRGs related to melanoma pathophysiology (WIF1, TFPI2, RASSF1A, RARβ2, SOCS1, and GATA4) and a panel of MINT loci (MINT1, MINT2, MINT3, MINT12, MINT17, MINT25, and MINT31) in primary and metastatic tumors of different clinical stages (n = 122) was assessed.Results: Here, we show an increase in hypermethylation of the TRGs WIF1, TFPI2, RASSF1A, and SOCS1 with advancing clinical tumor stage. Furthermore, we find a significant positive association between the methylation status of MINT17, MINT31, and TRGs. The methylation status of MINT31 is associated with disease outcome in stage III melanoma.Conclusions: These findings show the significance of a CIMP pattern that is associated with advancing clinical stage of malignant melanoma. Future prospective large-scale studies may determine if CIMP-positive primary melanomas are at high risk of metastasis or recurrence.</div>

CpG site

10.1158/1078-0432.c.6517740

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Citations (0)

Dysregulation of autophagy in melanocytes contributes to hypopigmented macules in tuberous sclerosis complex

Journal of Dermatological Science (2017)

Fei Yang Lingli Yang Mari Wataya‐Kaneda Junya Hasegawa Tamotsu Yoshimori

Hypopigmentation

TSC2

Melanocyte

10.1016/j.jdermsci.2017.11.002

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Citations (23)

Successful Treatment of Multiple Bursal Cysts in Systemic Sclerosis

Dermatologic Surgery (2002)

Atsushi Tanemura Yuji Yamaguchi Tateki Kubo Kenji Yano Satoshi Itami

BACKGROUND Bursitis frequently occurs in the various conditions of autoimmune disorders including rheumatoid arthritis, but there have been few cases of effusive bursitis in systemic sclerosis. OBJECTIVE To present a case of systemic sclerosis with multiple bursitis on upper, lower extremities, and trunk with or without joint involvement. METHODS Case report and review of the literature. RESULTS Multiple asymptomatic cystic masses contained yellow and chalky sterile fluid, all of which were diagnosed as effusive bursitis. Most of them were treated with a surgical resection, a continuous drainage, and an injection of highly concentrated ethanol into their internal spaces. However, an intrabursal injection of emulsified triamcinolone acetonide was the only effective treatment for the giant mass that occurred on the right chest wall. CONCLUSION Successful treatment of multiple bursal cysts with systemic sclerosis was presented.

Bursitis

10.1097/00042728-200212000-00017

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Citations (0)

Aggressive Squamous Cell Carcinoma in a Case of Epidermodysplasia Verruciformis Carrying a TMC6 Splice-site Mutation

Acta Dermato Venereologica (2023)

Kazunori Yokoi Noriko Arase Takashi Shimbo Manabu Fujimoto Atsushi Tanemura

Abstract is missing (Short communication)

Epidermodysplasia verruciformis

10.2340/actadv.v103.4550

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Citations (1)

Human High Molecular Weight–Melanoma-Associated Antigen: Utility for Detection of Metastatic Melanoma in Sentinel Lymph Nodes

Clinical Cancer Research (2008)

Yasufumi Goto Soldano Ferrone Takaaki Arigami Minoru Kitago Atsushi Tanemura

Abstract Purpose: Detection of micrometastasis in melanoma-draining lymph nodes is important for staging and prognosis. Immunohistochemical staining (IHC) using S-100p-HMB-45–, and MART-1–specfic antibodies is used for detecting metastases in sentinel lymph nodes (SLN). However, improvement in IHC is needed for melanoma micrometastasis detection. Experimental Design: Paraffin-embedded archival tissue (PEAT) specimens were obtained from 42 non-SLN macrometastases, 42 SLN metastases, and 16 tumor-negative SLNs of 100 melanoma patients who underwent SLN biopsy. PEAT specimens were assessed by IHC with high molecular weight−melanoma-associated antigen (HMW-MAA)–specific monoclonal antibodies (mAb) and with S-100p-, HMB-45–, and MART-1–specific antibodies. Quantitative real-time reverse-transcriptase PCR assay was used for HMW-MAA and MART-1 mRNA detection. Results: Expression frequency and immunostaining intensity were higher for HMW-MAA than MART-1 in nodal macrometastases (P < 0.0001 and P < 0.0001, respectively) and micrometastases (P < 0.0001 and P = 0.004, respectively). All 52 (100%) macrometastases were positive with HMW-MAA–specific mAbs, whereas 43 (83%) were positive with MART-1–specific mAbs. In a comparison analysis, 23 of 23 (100%) micrometastases were HMW-MAA–positive, whereas 21 (91%) and 18 (78%) specimens were S-100p– and HMB-45–positive, respectively. Quantitative real-time reverse-transcriptase PCR analysis of 48 nodal metastases showed HMW-MAA mRNA detection in SLNs with metastases. Conclusions: HMW-MAA is more sensitive and specific than MART-1, S-100p, and HMB-45 for IHC-based detection of SLN micrometastases. SLN PEAT–based detection specificity of melanoma micrometastases can be improved by IHC with HMW-MAA–specific mAbs.

Micrometastasis

Immunostaining

10.1158/1078-0432.ccr-07-1842

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Citations (36)

Guide for medical professionals (i.e. dermatologists) for the management of Rhododenol‐induced leukoderma

The Journal of Dermatology (2015)

Chikako Nishigori Yumi Aoyama Akiko Ito Kayoko Suzuki Tamio Suzuki

Abstract Because some users develop depigmentation after the use of melanogenesis‐inhibiting products containing the quasi‐drug ingredient Rhododenol, Japanese Dermatological Association (JDA) established a Special Committee on the Safety of Cosmetics Containing Rhododenol on July 17, 2013 and management guide for dermatologists has been updated on the website in order to delineate the diagnostic criteria for Rhododenol‐induced leukoderma and provides a broad guide for standard treatment based on current knowledge. This guide is produced on the basis of the guide (version 7) updated on June 20, 2014 in the website. Rhododenol‐induced leukoderma refers to depigmentation of varying severity that develops after the use of cosmetics containing Rhododenol, mainly at the site of use. In most cases, repigmentation of part or all the affected area is evident after discontinuation. Histopathologically cellular infiltration around the hair follicles and melanophages are present in most cases. The number of melanocytes in the lesion is declined but not totally absent in most cases. Rhododenol itself is a good substrate for tyrosinase, resulting in the formation of Rhododenol metabolites (e.g., Rhododenol quinone). Melanocytes are damaged by Rhododenol metabolites during the subsequent metabolic process. The continued use of cosmetics containing Rhododenol thus induces tyrosinase activity‐dependent cytotoxicity in melanocytes in the epidermis at application sites, resulting in decreasing the amount of melanin produced by melanocytes; the addition of some other factor to this process is believed to subsequently cause the decrease or disappearance of melanocytes themselves from the epidermis.

Depigmentation

Epidermis (zoology)

Discontinuation

10.1111/1346-8138.12744

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Citations (58)

Instantly evaluating bacterial infections on skin ulcers in an Asian population using a fluorescence‐emitting device

Journal of Cutaneous Immunology and Allergy (2023)

Yu Kurokami Yukiho Kurosaki Chigusa Yamashita Kazunori Yokoi Kyoko Tonomura

Abstract MolecuLight i:X® is a handy instrument capable of visualizing the bacterial adhesion over 10,000 CFU/g by recognizing porphyrin and pyoverdine as fluorescence. We took a total of 55 clinical photographs and fluorescence images (20 cases) from May 2021 to December 2021, after which the correlation between fluorescence observation and culture results was investigated. In addition, the course of fluorescent and ulcer status was shown in representative cases. The results suppose that MolecuLight i:X® is in real‐time use and would be helpful in determining the range of collection of bacterial cultures as well as in judging therapeutic necessity for intractable skin ulcers.

Microbiological culture

10.1002/cia2.12293

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Citations (0)

CpG Island Methylator Phenotype Predicts Progression of Malignant Melanoma

Clinical Cancer Research (2009)

Atsushi Tanemura Alicia M. Terando Myung‐Shin Sim Anneke Q. van Hoesel Michiel F.G. de Maat

Abstract Purpose: The CpG island methylator phenotype (CIMP) may be associated with development of malignancy through coordinated inactivation of tumor suppressor and tumor-related genes (TRG) and methylation of multiple noncoding, methylated-in-tumor (MINT) loci. These epigenetic changes create a distinct CIMP pattern that has been linked to recurrence and survival in gastrointestinal cancers. Because epigenetic inactivation of TRGs also has been shown in malignant melanoma, we hypothesized the existence of a clinically significant CIMP in cutaneous melanoma progression. Experimental Design: The methylation status of the CpG island promoter region of TRGs related to melanoma pathophysiology (WIF1, TFPI2, RASSF1A, RARβ2, SOCS1, and GATA4) and a panel of MINT loci (MINT1, MINT2, MINT3, MINT12, MINT17, MINT25, and MINT31) in primary and metastatic tumors of different clinical stages (n = 122) was assessed. Results: Here, we show an increase in hypermethylation of the TRGs WIF1, TFPI2, RASSF1A, and SOCS1 with advancing clinical tumor stage. Furthermore, we find a significant positive association between the methylation status of MINT17, MINT31, and TRGs. The methylation status of MINT31 is associated with disease outcome in stage III melanoma. Conclusions: These findings show the significance of a CIMP pattern that is associated with advancing clinical stage of malignant melanoma. Future prospective large-scale studies may determine if CIMP-positive primary melanomas are at high risk of metastasis or recurrence.

CpG site

10.1158/1078-0432.ccr-08-1361

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Citations (199)

Case of granuloma annulare after using tocilizumab

The Journal of Dermatology (2020)

K Katsuda Noriko Arase Yukinobu Nakagawa Atsushi Tanemura Manabu Fujimoto

Post graduate

10.1111/1346-8138.15252

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Citations (5)

A phase I dose-escalation, safety/tolerability, and preliminary efficacy study of the intratumoral administration of GEN0101 in patients with advanced melanoma

Cancer Immunology Immunotherapy (2022)

Eiji Kiyohara Atsushi Tanemura Kazuma Sakura Toshihiro Nakajima Akira Myoui

Despite recent advance in immunotherapy agents, safe new therapies that enhance the effects of immune checkpoint inhibitors are still required to develop. We previously demonstrated that hemagglutinating virus of Japan-envelope (HVJ-E) induced not only direct tumor cell death but also antitumor immunity through the activation of T and natural killer (NK) cells, thereafter, developed a manufacturing process of HVJ-E (GEN0101) for clinical use. We here performed a phase Ia clinical trial of intratumoral GEN0101 administration in six patients with stage IIIC or IV malignant melanoma. The primary aim was to evaluate the safety and tolerability of GEN0101, and the secondary aim was to examine the objective tumor response. Patients were separated into two groups (n = 3 each) and received a low dose of 30,000 and high dose of 60,000 mNAU of GEN0101. All patients completed a two-week follow-up evaluation without severe adverse events. The overall response rate was 33% (2 of 6), with 2 partial responses in the high-dose group and 2 with stable disease, and 2 with progressive disease in the low-dose group. Local complete or partial responses were observed in 11 of 18 (61%) target lesions. One patient demonstrated shrinkage of lung metastases after the treatment. The activity of NK cells and interferon-γ levels were increased in the circulation, indicating augmentation of antitumor immunity by GEN0101. This trial showed not only the safety and tolerability but also the significant antitumor effect of GEN0101, suggesting that GEN0101 might be a promising new drug for patients with advanced melanoma.

Tolerability

10.1007/s00262-021-03122-z

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Citations (4)