Yoko Funasaka

• MD, PhD
• Professor at Nippon Medical School

Background: Both ultraviolet B (UVB) phototherapy with 308-nm excimer light and excimer laser devices are widely used to treat vitiligo. While the devices share the 308-nm wavelength, they have distinct characteristics. Notably, the excimer laser exhibits laser properties (monochromatic coherent light) and unique device specifications (a high frequ...

Vitiligo is an autoimmune skin disease with acquired depigmentation. Dietary habits may modulate the pathogenesis of vitiligo. We evaluated dietary habits in adult Japanese patients with nonsegmental vitiligo, and compared their results with those of age‐ and sex‐matched controls. We also examined the relationship between dietary habits and Vitilig...

Background: Modified Kligman's formula (mKF) is the gold standard treatment for melasma; however, its prolonged use is not recommended due to side effects. Cysteamine is a potent, safe, and effective depigmenting agent. Here, we conducted a double-blind, randomized, and placebo-controlled clinical trial to assess the efficacy of cysteamine isobion...

Senile lentigo (SL) is a pigmentary disorder associated with disrupted epidermal turnover. Trace minerals in the skin are known to regulate keratinocyte proliferation and differentiation. To clarify the role of iron in SL, we compared the expression of molecules related to iron metabolism between SL lesion (lesion) and the surrounding normal skin (...

Psoriasis is a chronic skin disease with interleukin (IL)-17-dominated inflammation and hyperproliferation of epidermis. Dietary fiber is fermented by the gut microbiome into short-chain fatty acids (SCFAs) that manifest anti-inflammatory effects. We examined if feeding with an inulin-enriched high-fiber diet (HFD) might improve topical imiquimod-i...

Background: Peutz-Jeghers syndrome (PJS) is a rare disease characterized by the presence of hamartomatous polyposis throughout the gastrointestinal tract, except for the esophagus, along with characteristic mucocutaneous pigmentation. It is caused by germline pathogenic variants of the STK11 gene, which exhibit an autosomal dominant mode of inheri...

Background: We previously reported that pre-irradiation with infrared radiation A (IRA) eliminated ultraviolet B (UVB) -induced cyclobutane pyrimidine dimers (CPDs). Accelerated elimination of CPDs could have resulted from enhanced DNA repair and/or enhanced induction of apoptosis. In this study, we examined whether IRA accelerated the elimination...

SASH1 has been reported as a causal gene of lentiginous phenotypes with and without heredity, including an autosomal dominant type characterized by lentigines predominantly on sun-exposed areas such as the face and limbs. Recently, cases of dyschromatosis with SASH1 mutations have been reported worldwide; however, only one case has been reported fr...

Background Pembrolizumab, an anti-programmed cell death-1 protein monoclonal antibody, is effective for patients with advanced non-small-cell lung cancer. However, immune checkpoint inhibitors such as pembrolizumab induce various immune-related adverse events, involving the lung, liver, gastrointestinal, endocrine system, and skin. Intralymphatic h...

Background: For laser therapy, darker skin types should be carefully treated, however, the precise role of melanin content, subspecies, and the heat effect of the laser has not been well studied in vivo. Methods: We generated three groups of mice that have epidermal melanocytes producing only eumelanin, dominant pheomelanin, and no melanin. Usin...

Psoriasis is a chronic, relapsing, inflammatory keratotic skin disease. To elucidate the medication adherence and treatment satisfaction, we performed a questionnaire survey using the eight-item Morisky Medication Adherence Scale (MMAS-8) and nine-item Treatment Satisfaction Questionnaire for Medication (TSQM-9) of 163 psoriatic patients who regula...

Verrucous carcinoma (VC) is an uncommon, distinct type of well-differentiated squamous cell carcinoma. Here we present two cases of VC, one arising from the lower leg and the other from genital skin. Case 1, a female patient, aged 95 years, had a brownish verrucous plaque on her right lower leg. Histopathologically, epithelial tumor cells grew push...

Giant cell tumors of the tendon sheath (GCT-TS) are one of the most common tumors of the hand, along with ganglions. However, occurrence in the toes is far less common. Here we present a rare case of GCT-TS at the middle phalanx level of the flexor digitorum longus tendon sheath. Magnetic resonance imaging showed low intensity both on T1 and T2 wei...

An external dental fistula is a skin manifestation caused by an underlying dental problem. We report a rare case of external dental fistula associated with a fixed cantilever denture. A 77-year-old Japanese woman presented with an enlarging reddish granulomatous lesion on her right cheek that was diagnosed as an external dental fistula. A fixed can...

A 72-year-old Japanese woman presented in July 2012 with a 5-year history of depigmented areas on the face. On physical examination, she had multiple well-demarcated depigmented areas on the face and neck. She had also experienced increased thirst for the past 3 years. A blood sample was positive for antinuclear and anti-SS-A antibodies. A biopsied...

We present a woman with squamous cell carcinomas on both feet in long-standing eczematous lesions. Histopathological examination of biopsies from the both feet revealed highly atypical cells invading the reticular layer of the dermis in the hyperkeratotic lesion and they were associated with surrounding dermatitis with spongiosis. Although the caus...

Actinic keratosis (AK) is a cutaneous cancer in situ which develops as a result of excessive exposure to ultraviolet (UV). Toll-like receptor (TLR)7 agonist imiquimod is a topical immune response modifier and is effective for the treatment of non-melanoma skin cancers. Recently, the diagnostic role of the dermatoscope has been reported in the cours...

Extranodal natural killer/T-cell lymphoma (ENK/TCL) is most often in the nose or the nasopharynx but can present elsewhere. We report a rare case of ENK/TCL that presented as swelling of an upper eyelid without ocular involvement. A 76-year-old man visited our hospital with a swollen lesion of the left upper eyelid which had appeared 2 months earli...

A 29-year-old Japanese woman presented with a brownish papule, 5×8 mm in size, on the lateral aspect of the right fifth toe, which had developed within 3 years. The papule was asymmetrical with hyperkeratosis on the surface, at the center of the lesion. Dermoscopy showed biphasic features consisting of a starburst pattern and a region of regression...

is missing (Short communication).

A 63-year-old Japanese man with non-Hodgkin B-cell lymphoma presented with erythematous skin lesions on his entire body, with oral, ocular and anal mucosal lesions. The patient was diagnosed with paraneoplastic pemphigus. Immunofluorescence showed both immunoglobulin (Ig)G and IgA antibodies to keratinocyte cell surfaces. Various immunoblot and enz...

Background Acanthosis nigricans (AN) can occur as a cutaneous manifestation of genetic diseases, one of which is associated with activating mutations of the fibroblast growth factor receptor 3 gene (FGFR3). Objective We explored familial AN patients with FGFR3 mutations and examined the effectiveness of glycolic acid (GA) peeling in improving their...

Apocrine poromas are rare and distinctive benign adnexal neoplasms featuring tumor cells differentiating toward folliculo-sebaceous-apocrine units. We report an extremely rare case with multiple apocrine poromas in a single patient. Fifteen tumors were distributed on the head, neck, forearm and axilla of a 74-year-old man. All tumors were mostly co...

To clarify the status of gene mutation and activation of growth signal in melanoma of Japanese patients in vivo, we analyzed the mutation of BRAF exon 15, NRAS exon 2, and KIT exons 9, 11, 13, 17 and 18 in melanoma cells obtained by laser capture microdissection, and performed direct sequencing in 20 cases of acral lentiginous melanoma (ALM) and 17...

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 webs...

Infrared radiation A (IRA) is absorbed by melanin and generates heat. Therefore, the effect of IRA could be well analyzed using skin, which contains melanin in the epidermis. Hairless mice harboring epidermal melanocytes that produce eumelanin, pheomelanin, or non-melanin were generated by backcrossing K14-stem cell factor mice, recessive yellow mi...

A 72-year-old woman with a history of diffuse large B cell lymphoma and recent recurrence visited our department complaining of several painful edematous nodules with blisters on her face. She had iteratively developed cutaneous eruptions after every treatment with granulocyte colony-stimulating factor (G-CSF) for neutropenia, and each time the eru...

Malignant peripheral nerve sheath tumor (MPNST) involving bone is rare. We report a case of MPNST of the fifth toe. The lesion was located in the distal phalanx of the right fifth toe and extended into surrounding subcutaneous tissues. Findings on magnetic resonance imaging and histological features of the case are described and the literature is b...

The majority of malignant melanoma cell types are able to produce melanin and the degree of melanin synthesis in various types of cultured cell line differs. In this study, we evaluated three types of cultured cell line, MNT‑1, HM3KO and G‑361, with differing melanin production levels. The level was greatest in the MNT‑1 cells, lower in the HM3KO c...

In vivo reflectance confocal microscopy (RCM) provides high-resolution, real-time optical sections of the skin in a non-invasive manner, allowing visualization of the skin in its native state. Highly reflective skin components including melanin, collagen and keratin appear bright (white) in RCM images. RCM examination of solar lentigines is known t...

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. However, it needs to be clarified whether the repetitive procedure of chemical peeling on photodamaged skin is safe and whether the different chemicals used for peeling results in...

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. However, it needs to be clarified whether the repetitive procedure of chemical peeling on photodamaged skin is safe and whether the different chemicals used for peeling results in...

Heterotrimeric G protein is composed of a Gα-subunit and a Gβγ-dimer. Previous studies have revealed that Gβγ-dimers including the Gγ2 subunit (Gng2/GNG2) are associated with cell proliferation, differentiation, invasion and angiogenesis. At present, however, there is no information on the expression level of Gng2/GNG2 alone in any kind of tumor. I...

Chemical peeling may be defined as the therapies, procedures and techniques used for the treatment of certain cutaneous diseases or conditions, and for aesthetic improvement. The procedures include the application of one or more chemical agents to the skin. Chemical peeling has been very popular in both medical and aesthetic fields. Because neither...

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photoaged skin. We assessed the photochemopreventive effect of several clinically used chemical peeling agents on the ultraviolet (UV)-irradiated skin of hairless mice. Chemical peeling was done u...

Chemical peeling is one of the dermatological treatments available for certain cutaneous diseases and conditions or improvement of cosmetic appearance of photo-aged skin. We assessed the photo-chemopreventive effect of several clinically used chemical peeling agents on the ultraviolet-irradiated skin of hairless mice. Chemical peeling was done usin...

A 55-year-old woman was admitted for evaluation of progressive generalized oedema and mild kidney dysfunction (serum creatinine 1.12 mg/dL; blood urea nitrogen 45 mg/dL). On admission, generalized oedema, transudative pleural effusion, collapsed inferior vena cava and low fractional excretion of sodium (0.14%) suggested severe volume depletion due...

We have previously shown that ectopic expression of metabotropic glutamate receptor subtype 1 in melanocytes is essential for both development and in vivo growth of melanoma using newly developed transgenic mice which conditionally express metabotropic glutamate receptor subtype 1 (mGluR1). In this study, we developed conditional transgenic mice, w...

Skin hyperpigmentation disorders due to abnormal melanin production induced by ultraviolet (UV) irradiation are both a clinical and cosmetic problem. UV irradiation stimulates melanin production in melanocytes by increasing intracellular cAMP. Expression of heat shock proteins (HSPs), especially HSP70, is induced by various stressors, including UV...

A 63-year-old man had first noticed a dark nodular growth on his left leg about10 years previously, but reported that it seemed to have grown rapidly over the past few years. He consulted our clinic on June 9, 2008, and was diagnosed as having basal cell carcinoma, solid type, forming a polypoid nodular lesion based on skin biopsy findings. The les...

Key Features: Acquired chronic hypermelanosis on the face occurring mainly in women with Fitzpatrick skin types IV-V

We present herein a case of right axillary accessory breast associated with galactorrhea in an adolescent girl. A 14-year-old Japanese girl presented with an 11-month history of a tender, subcutaneous lesion in the right axillary fossa. Seven months later, she experienced menarche. Subsequently, the patient noticed pressure-induced galactorrhea fro...

Fusion of cancer cells with migratory bone-marrow-derived cells such as macrophages can produce cancer cells with increased metastatic potential. To study this, we fused mouse macrophages with weakly metastatic mouse melanoma cells and generated a panel of hybrid clones. About half of these showed increased metastatic potential in mice. These hybri...

Irradiation with UV light, especially UVB, causes epidermal damage via the induction of apoptosis, inflammatory responses, and DNA damage. Various stressors, including UV light, induce heat shock proteins (HSPs) and the induction, particularly that of HSP70, provides cellular resistance to such stressors. The anti-inflammatory activity of HSP70, su...

This prospective study, in the very early phase after initiation of glucocorticoid (GC) treatment, showed that alendronate was effective in suppressing accelerated bone resorption and subsequent decrease in bone mineral density (BMD) at the lumbar spine of patients with high-dose GC treatment. How bisphosphonates affect bone metabolism and BMD of p...

Photoaging could be induced by accumulated DNA damage on skin cells. Photoaged skin has such characteristics as a nodular leathery surface with fine and coarse wrinkles, blotches and yellowing, dryness, and teleangiectasia, and finally skin cancer formation. For this condition, chemical peeling, iontophoresis, laser and phototherapy are used with s...

Thioredoxin, a redox-regulating protein that scavenges reactive oxygen species, appears to show an excellent antiinflammatory effect in treating animal models of various human inflammatory diseases. The aim of this study was to clarify whether thioredoxin is useful for treating inflammatory skin diseases, such as contact dermatitis, caused by epicu...

Ectopic expression of metabotropic glutamate receptor subtype 1 (mGluR1) in mouse melanocytes induces melanoma formation. Although requirement of mGluR1 for development of melanoma in the initial stage has been demonstrated, its role in melanoma growth in vivo remains unclear. In this study, we developed novel transgenic mice that conditionally exp...

We evaluated the efficacy and safety of Besoften® Lotion (heparinoid preparation) in 17 patients with atopic dermatitis after 8 weeks of application on their dry skin. The amount of water content of stratum corneum showed a tendency to increase, but this tendency was not significant statistically. The transepidermal water loss decreased significant...

Synopsis Oxidative stress caused by ultraviolet (UV) radiation generates reactive oxygen species (ROS) in the skin, induces the secretion of melanocyte growth and activating factors from keratinocytes, which results in the formation of cutaneous hyper‐pigmentation. Thus, increasing the anti‐oxidative ability of skin cells is expected to be a good s...

BackgroundHeat shock protein 47 (HSP47) is a specific chaperone of procollagen. It is important to elucidate the effects of heat on collagen synthesis both in vitro and in vivo.ObjectivesWe examined the effects of heat on collagen synthesis and the role of HSP47 using an in vitro system, and we also characterized the efficacy of wrinkle removal by...

Beta1,6-acetylglucosaminyltransferase V (GnT-V) forms beta1,6 branching on the trimannosyl terminus of N-glycans, allowing for the production of beta1,6Glc-NAc-bearing oligosaccharides. These are used by healthy myeloid cells and cancer cells alike for systemic migration. GnT-V has multiple glycoprotein substrates and thereby exerts global effects...

Ultraviolet B (UVB) radiation in the skin induces pigmentation that protects cells from further UVB damage and reduces photocarcinogenesis. Although the mechanisms are not well understood, our laboratory has shown that UVB radiation causes increased MSH receptor activity by redistributing MSH receptors from internal pools to the external surface, w...

Chronic ultraviolet (UV) radiation from sunlight induces wrinkle formation. Retinoic acid (RA) can markedly improve wrinkles, although RA does have some side-effects, such as skin irritation. As the efficacy and cytotoxicity of RA has been traced to its free carboxylic acid, we synthesized a new molecule, N-retinoyl-D-glucosamine (GRA), in which a...

Two clinical studies using different types of iontophoresis equipment was performed to confirm the effects of vitamin C derivatives on pigmented macules such as solar lentigines and ephelides by a controlled half face study. In the first study, iontophoresis with 5% sodium L-ascorbyl-2-phosphate was performed on one side of the face using an in-hos...

In order to investigate the mechanism of glycolic acid (GA) function in human stratum corneum, we monitored changes in cathepsin D-like (CD) and chymotrypsin-like (SCCE) proteinases for 3 weeks following topical GA application (50% w/v, pH 0.9) for 30 min to human skin. In the early phase, weakened stratum corneum cohesion in the lower layers was o...

Fatty acids are common components of biological membranes that are known to play important roles in intracellular signaling. We report here a novel mechanism by which fatty acids regulate the degradation of tyrosinase, a critical enzyme associated with melanin biosynthesis in melanocytes and melanoma cells. Linoleic acid (unsaturated fatty acid, C1...

Clinical evaluation of a sunscreen cream (AK-UV®) containing glycoceramide was performed in 36 patients with sensitive skin found in atopic dermatitis or contact dermatitis. The sunscreen has been developed as hypo-irritant and hypo-allergic for the sensitive skin such as atopic dermatitis. The products were evaluated for the safety and the usefuln...