Histological changes and involvement of apoptosis after photodynamic therapy for actinic keratoses

被引:44
作者
Nakaseko, H [1 ]
Kobayashi, M [1 ]
Akita, Y [1 ]
Tamada, Y [1 ]
Matsumoto, Y [1 ]
机构
[1] Aichi Med Univ, Dept Dermatol, Aichi 4801195, Japan
关键词
5-aminolaevulinic acid; actinic keratoses; apoptosis; caspase-3; photodynamic therapy; terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling method;
D O I
10.1046/j.1365-2133.2003.04898.x
中图分类号
R75 [皮肤病学与性病学];
学科分类号
100206 ;
摘要
Background Photodynamic therapy (PDT), which employs a combination of a tumour-localizing photosensitizer and visible light, has been used to treat superficial malignancies in the epidermis. Objectives To examine histological changes and the role of apoptosis in lesions of actinic keratosis (AK) after PDT using 5-aminolaevulinic acid (ALA) and excimer dye laser. Methods After topical ALA-PDT, biopsy specimens were collected from 18 skin lesions in 15 patients with AK. Paraffin-embedded sections of the skin specimens were stained with haematoxylin and eosin. The detection of apoptosis was performed using a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labelling (TUNEL) method, antiactivated caspase-3 antibody and anti-Fas antibody. Results One hour after PDT, cells with eosinophilic cytoplasm and markedly stained nuclei were found, and vacuolation of some tumour cells was noted in the lower layer of the epidermis. An infiltrate of lymphocytes and neutrophils was observed in the upper layer of the dermis. One day after PDT, all layers of the epidermis exhibited slightly degenerative necrosis, with shadow cell formation and chromatin condensation around the nuclear membrane in the lower layer of the epidermis. Necrosis in all layers of the epidermis and lymphocyte infiltration in the dermis were found 3 days after PDT. Tumour cells had disappeared and regenerative thickening of the epidermis was observed 7 days after PDT. TUNEL staining revealed apoptosis-positive cells in the epidermis in 8 of 11 specimens obtained 1 day after PDT. Activated caspase-3 expression was noted in the lower layer of the epidermis in four of these eight TUNEL-positive specimens. Conclusions Results suggested that apoptosis is involved in tumour cell death after PDT in patients with AK, and that it occurs within 1 day after PDT.
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页码:122 / 127
页数:6
相关论文
共 15 条
[1]  
AGARWAL ML, 1991, CANCER RES, V51, P5993
[2]   Involvement of Fas (APO-1/CD-95) during photodynamic-therapy-mediated apoptosis in human epidermoid carcinoma A431 cells [J].
Ahmad, N ;
Gupta, S ;
Feyes, DK ;
Mukhtar, H .
JOURNAL OF INVESTIGATIVE DERMATOLOGY, 2000, 115 (06) :1041-1046
[3]   1993 SYNTEX-AWARD LECTURE - PHOTOMEDICINE AND PHOTODYNAMIC THERAPY [J].
DOLPHIN, D .
CANADIAN JOURNAL OF CHEMISTRY-REVUE CANADIENNE DE CHIMIE, 1994, 72 (04) :1005-1013
[4]   Photodynamic therapy in dermatology [J].
Fritsch, C ;
Goerz, G ;
Ruzicka, T .
ARCHIVES OF DERMATOLOGY, 1998, 134 (02) :207-214
[5]   IDENTIFICATION OF PROGRAMMED CELL-DEATH INSITU VIA SPECIFIC LABELING OF NUCLEAR-DNA FRAGMENTATION [J].
GAVRIELI, Y ;
SHERMAN, Y ;
BENSASSON, SA .
JOURNAL OF CELL BIOLOGY, 1992, 119 (03) :493-501
[6]   Light and death: Photons and apoptosis [J].
Godar, DE .
JOURNAL OF INVESTIGATIVE DERMATOLOGY SYMPOSIUM PROCEEDINGS, 1999, 4 (01) :17-23
[7]  
GOLD R, 1994, LAB INVEST, V71, P219
[8]  
GORCZYCA W, 1993, LEUKEMIA, V7, P659
[9]   Mitochondrial release of apoptosis-inducing factor and cytochrome c during smooth muscle cell apoptosis [J].
Granville, DJ ;
Cassidy, BA ;
Ruehlmann, DO ;
Choy, JC ;
Brenner, C ;
Kroemer, G ;
van Breemen, C ;
Margaron, P ;
Hunt, DW ;
McManus, BM .
AMERICAN JOURNAL OF PATHOLOGY, 2001, 159 (01) :305-311
[10]   Photodynamic therapy in dermatology [J].
Kalka, K ;
Merk, H ;
Mukhtar, H .
JOURNAL OF THE AMERICAN ACADEMY OF DERMATOLOGY, 2000, 42 (03) :389-413