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International journal of dermatology 07/2012; · 1.18 Impact Factor
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ABSTRACT: Topical 5-aminolevulinic acid-based photodynamic therapy (ALA-PDT) is an effective treatment for Bowen's disease (BD). In order to compare the efficacy of two different light sources, using either an excimer-dye laser (EDL) (630 nm) or a metal-halide lamp (MHL) (600 to 740 nm) a protocol for topical ALA-PDT for treatment of BD of the extremities was established, and responses during 12 months follow-up were assessed.
From 25 patients a total of 26 lesions that had been histopathologically diagnosed as BD from 2005 to 2010 in the Department of Dermatology at the Aichi Medical University Hospital were randomly selected. The light source used for the topical ALA-PDT was EDL in 17 lesions and MHL in 9 lesions. The photosensitizing protoporphyrin IX that is produced within BD lesions 4 h after application of 20% ALA cream was mostly consumed after exposure to 100 J/cm(2) irradiation using 630 nm EDL. Each lesion was irradiated once a week for 3 weeks, for a total dosage of 300 J/cm(2) (100 mW/cm(2)). Patients were followed up clinically every 3 months for 12 months, and at 1 month after the final treatment lesions were evaluated histopathologically.
Histologically, the complete response (CR) rate at 1-month follow-up was 82% (14/17 lesions) in the EDL treatment group and 100% (9/9 lesions) in the MHL treatment group (P > 0.05). The recurrence rate at 12 months after PDT was 46% (6/13 lesions, one patient lost to follow-up) in the EDL group and 0% in the MHL group (P < 0.05) (χ(2) test with Fisher's exact test). The average period before recurrence after EDL treatment was 6.5 months.
A novel protocol for topical ALA-PDT in Japanese in Asian patients with BD was developed and implemented. The protocol improved the CR rate compared with previous studies. Moreover, the present results indicate that the efficacy of topical ALA-PDT using MHL was superior to that using EDL for BD patients.
Photodermatology Photoimmunology and Photomedicine 06/2012; 28(3):142-6. · 1.30 Impact Factor
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Journal of dermatological science 03/2012; 67(1):69-71. · 3.71 Impact Factor
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European journal of dermatology: EJD 09/2011; 21(6):1021-2. · 2.53 Impact Factor
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European journal of dermatology: EJD 07/2011; 21(5):809-10. · 2.53 Impact Factor
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European journal of dermatology: EJD 06/2011; 21(4):625-6. · 2.53 Impact Factor
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Acta Dermato-Venereologica 03/2010; 90(2):198-200.
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Photodermatology Photoimmunology and Photomedicine 12/2009; 25(6):333-4. · 1.30 Impact Factor
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ABSTRACT: In photodynamic therapy (PDT) for skin cancer, 5-aminolevulinic acid (ALA) is applied topically to the affected area to be absorbed percutaneously through passive diffusion, and typically requires 4-6 h before performing PDT. In this study, we attempted to reduce the absorption period in PDT by ionizing ALA using direct-current pulsed iontophoresis to treat actinic keratosis (AK). Twenty percent ALA solution was applied to AK lesions of five patients using direct-current pulsed iontophoresis. ALA-PDT was repeated three times with a total irradiation of 150 J/cm(2) (50 J/cm(2) per irradiation, weekly). One week after the last PDT, therapeutic results were assessed by skin biopsy. In all subjects, protoporphyrin IX (PpIX) production was confirmed after iontophoresis, and its production levels were comparable to the conventional occlusive dressing technique (ODT). Skin biopsies from the treated lesion showed the disappearance of tumour cells. These results indicated that direct-current pulsed iontophoresis for applying ALA before PDT is useful to treat AK.
Photodermatology Photoimmunology and Photomedicine 10/2009; 25(5):280-2. · 1.30 Impact Factor
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Tomoe Kuhara,
Daisuke Watanabe, Yoichi Akita,
Tomohiro Takeo,
Natsuko Ishida,
Aki Nakano,
Noriko Yamashita,
Yuichiro Ohshima,
Morihiro Kawada,
Takeshi Yanagishita,
Yasuhiko Tamada,
Yoshinari Matsumoto
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ABSTRACT: 5-aminolaevulinic acid-based photodynamic therapy (ALA-PDT) is widely performed in the clinical setting for superficial skin cancers, giving favorable results, but residual tumor and recurrence occur occasionally. Thioredoxin is a common antioxidant that suppresses apoptosis and facilitates cell growth. We investigated the expression of thioredoxin following ALA-PDT in human skin squamous cell carcinoma cell line, HSC-5.
ALA-PDT was performed in HSC-5 cells using low-dose (5 J/cm(2), 100 mW/cm(2)) or high-dose (30 J/cm(2), 100 mW/cm(2)) irradiation, and the expression of thioredoxin was measured by Western blotting. An MTT assay was used to assess cell growth following a low dose of multiple irradiations. Cell death was examined by Western blotting for caspase-3 and PARP. Immunofluorescence double staining using annexin V and propidium iodine was also performed.
Expression of thioredoxin was only observed following low-dose exposure ALA-PDT. Multiple low-dose exposure ALA-PDT significantly proliferated cell growth. With high-dose exposure ALA-PDT, caspase-3 and PARP expression were seen, and cell death due to apoptosis and/or necrosis was observed, but thioredoxin was barely detected.
Low-dose exposure ALA-PDT increased the expression of thioredoxin and facilitated the growth of HSC-5 cells.
Photodermatology Photoimmunology and Photomedicine 07/2008; 24(3):142-6. · 1.30 Impact Factor
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Archives of dermatology 02/2008; 144(1):19-21. · 4.76 Impact Factor
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ABSTRACT: Although actinic cheilitis is a common disease, it should be treated carefully because it can undergo malignant transformation. We report a case of actinic cheilitis treated with photodynamic therapy (PDT) using 5-aminolevulinic acid (ALA), with satisfactory outcome in both clinical and pathological aspects. Actinic cheilitis is a pathologic condition affecting mainly the lower lip caused by long-term exposure of the lips to the UV radiation in sunlight. Analogous to actinic keratosis of the skin, actinic cheilitis is considered as a precancerous lesion and it may develop into squamous cell carcinoma. We report a case of actinic cheilitis treated with PDT using ALA, with satisfactory outcome in both clinical and pathological aspects.
Photodermatology Photoimmunology and Photomedicine 11/2007; 23(5):209-10. · 1.30 Impact Factor
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ABSTRACT: There have been several attempts to make granuloma model to clarify the mechanism of granulomatous diseases like sarcoidosis. However, a unique in vitro model that generates multinucleated giant cell (MGC) through epithelioid cells resembled to human granuloma, has not yet been clearly established. In this study, the generation of granuloma model that forms MGC via epithelioid cells from the mouse macrophage cell line was investigated. A RAW 246.7 mouse macrophage cell line was cultured with lipopolysaccharide (LPS) and concanavalin A (Con A) in various concentrations either alone or both. We found that separate treatment of LPS and Con A induced around 35 and 20% MGC respectively whereas cotreatment of these chemicals drastically accelerated granuloma formation rate and it was around 80%. The highest fusion index (MGC formation rate) was observed at days 7. A gradual increase of tumor necrosis factor alpha (TNF-alpha) production in the culture supernatant was analyzed by enzyme-linked immunosorbent assay (ELISA). And the neutralization of the elevated level of TNF-alpha production by its monoclonal antibody leads to significant decrease of MGC formation. Interestingly, we found that the RAW cells were changed into spindle cells, which morphologically resembled to epithelioid cells and eventually MGC was formed from these spindle cells. Our in vitro granuloma model appeared to be similar with in vivo epithelioid cell granulomas like sarcoidosis. Thus, our model would be useful as in vitro epithelioid granuloma model for analyzing the mechanisms and screening the effective drugs of granulomatous diseases in future.
Archives for Dermatological Research 11/2007; 299(8):399-403. · 2.28 Impact Factor
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Kazuo Uchida, Yoichi Akita,
Keitaro Matsuo,
Shigeyoshi Fujiwara,
Atsuko Nakagawa,
Yoshiaki Kazaoka,
Hiroshi Hachiya,
Yoshiyuki Naganawa,
Ichiro Oh-Iwa,
Kiyoshi Ohura,
Shinsuke Saga,
Tatsushi Kawai,
Yoshinari Matsumoto,
Kazuo Shimozato,
Ken-Ichi Kozaki
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ABSTRACT: We carried out SEREX (serological analysis of antigens by recombinant cDNA expression cloning) using sera from patients with Sjögren's syndrome (SjS) and investigated the frequencies of autoantibodies against autoantigens identified by SEREX in the sera of healthy individuals (HI) and patients with SjS, rheumatoid arthritis (RA) and systemic lupus erythematosus (SLE). IFI16 and two kelch-like proteins, KLHL12 and KLHL7, were found to be novel autoantigens in SjS by SEREX. A markedly high frequency of anti-IFI16 autoantibodies was observed in the sera of SjS (SjS, 70%; RA, 13%; SLE, 33%; HI, 0%). Interestingly, all serum samples from SjS demonstrated immunoreactivity against one or both of IFI16 and SS-B/La. The presence of autoantibodies against KLHL12 and KLHL7 in the sera was significantly specific to SjS (23% and 17%, respectively), as they were not detected in RA, SLE or HI. Furthermore, we confirmed that transcripts of these autoantigens were expressed preferentially in the salivary glands and immuno-privileged testes. Our results suggest these autoantigens may be useful as serological markers for the clinical diagnosis of SjS and may play a crucial role as organ-specific autoantigens in the aetiopathogenesis of SjS. This study warranted clinical evaluations of autoantibodies against IFI16, KLHL12 and KLHL7 in combination with anti-SS-B/La autoantibodies.
Immunology 10/2005; 116(1):53-63. · 3.32 Impact Factor
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ABSTRACT: Sezary syndrome and mycosis fungoides are forms of cutaneous T-cell lymphoma, and in the early stage of these diseases psoralen plus ultraviolet A (PUVA) is one of the treatments of choice. Photodynamic therapy using 5-aminolevulinic acid (ALA-PDT) is an effective, non-invasive, and safe treatment for most superficial skin cancers. In order to obtain greater efficacy of PUVA, we investigated the synergistic anti-tumor effects of ALA-PDT and PUVA using 8-methoxypsoralen (8-MOP) and a UVA lamp.
The in vitro effects of PUVA and ALA-PDT and their combination in HUT-78 cell line from human SS were determined by MTT assay.
In our results, cell proliferation compared with controls was inhibited to 53.2% with UVA alone, 52.3% with 1 microM 8-MOP, 43.8% with 100 microM ALA, and 19.2% with combined 8-MOP and ALA.
Combined use of ALA and PUVA using 8-MOP and UVA lamps, which are widespread in Japan, had a strong anti-tumor effect in vitro. Combined treatment with ALA-PDT and PUVA using a UVA lamp appears to have a strong treatment effect.
Photodermatology Photoimmunology and Photomedicine 23(2-3):95-7. · 1.30 Impact Factor
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Yoichi Akita,
Ken-ichi Kozaki,
Tomohiro Takeo,
Motonobu Ohmura,
Atsuko Nakagawa,
Takeshi Yanagishita,
Yoshiaki Kazaoka,
Tadashige Nozaki,
Kazuhisa Yokoo,
Mitsuko Shinohara,
Daisuke Watanabe,
Tatsushi Kawai,
Shiro Yamada,
Yasuhiko Tamada,
Kiyoshi Ohura,
Yoshinari Matsumoto
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ABSTRACT: Background5-Aminolaevulinic acid (ALA)-based photodynamic therapy (PDT) for patients with skin and oral diseases is a highly sophisticated procedure, but the incidence of disease recurrence after treatment with ALA-based PDT is somewhat alarming. Calcipotriol, an analogue of 1,25-dihydroxyvitamin D3 (1,25(OH)2D3), has been reported to regulate the proliferation and differentiation of keratinocytes.ObjectiveIn order to obtain even greater efficacy of ALA-based PDT, we investigated the synergistic effects of calcipotriol as an adjunct to ALA-based PDT for human oral squamous cell carcinoma (SCC) cell lines.MethodsIntracellular protoporphyrin IX (PpIX) converted from exogenous ALA in SCC cell lines treated with/without calcipotriol was measured by a fluorescencemeter. Then, the in vitro effects of calcipotriol, the cyclooxygenase (COX)-2 selective inhibitor (nimesulide), ALA-based PDT and their combination on two SCC cell lines, HSC-2 (a COX-2 high expresser) and HSC-4 (a COX-2 non-expresser), were determined by MTT assay and double-staining for annexin V and propidium iodide.ResultsThe concentration of intracellular PpIX was increased in four of the eight SCC cell lines (50%) treated with calcipotriol. The greatest alteration of intracellular PpIX was found in HSC-4 (1.9-fold). The combination of calcipotriol and ALA-based PDT remarkably inhibited cellular proliferation and induced cellular death of both HSC-2 and HSC-4. Whereas, this morphological damage was more serious in HSC-4 than in HSC-2. Furthermore, these effects were almost equivalent to the synergistic effect of the combination of nimesulide and ALA-based PDT on HSC-2.ConclusionsThe present study suggests that treatment with calcipotriol enhances the photodynamic effects on SCC via the accumulation of exogenous ALA-dependent PpIX.
Journal of Dermatological Science Supplement.
