Kazumori Ishiguro

Combination effect of photodynamic and sonodynamic therapy on experimental skin squamous cell carcinoma in C3H/HeN mice

We studied a combination of photodynamic therapy (PDT) and sonodynamic therapy (SDT) for improving tumoricidal effects in a transplantable mouse squamous cell carcinoma (SCC) model. Two sensitizers were utilized: the pheophorbide‐a derivative PH‐1126, which is a newly developed photosensitizer, and the gallium porphyrin analogue ATX‐70, a commonly used sonosensitizer. Mice were injected with either PH‐1126 or ATX‐70 i.p. at doses of 5 or 10 mg/kg.bw. At 24 (ATX‐70) or 36 hr (PH‐1126) (time of optimum drug concentration in the tumor) after injection, SCCs underwent laser light irradiation (88 J/cm2 of 575 nm for ATX‐70; 44 J/cm2 of 650 nm for PH‐1126) (PDT), ultrasound irradiation (0.51 W/cm2 at 1.0 MHz for 10 minutes) (SDT), or a combination of the two treatments. The combination of PDT and SDT using either PH‐1126 or ATX‐70 as a sensitizer resulted in significantly improved inhibition of tumor growth (92–98%) (additive effect) as compared to either single treatment (27–77%). The combination using PH‐1126 resulted in 25% of the treated mice being tumor free at 20 days after treatment. Moreover, the median survival period (from irradiation to death) of PDT + SDT‐treated mice (>120 days) was significantly greater than that in single treatment groups (77–95 days). Histological changes revealed that combination therapy could induce tumor necrosis 2–3 times as deep as in either of the single modalities. The combination of PDT and SDT could be very useful for treatment of non‐superficial or nodular tumors.

The ultrastructural characteristics of eccrine sweat glands in a Fabry disease patient with hypohidrosis

As an investigation of the pathogenetic mechanism of diminished sweating in Fabry disease, an electron microscopy ultrastructural study was conducted on specimens of eccrine sweat glands from a typical patient with Fabry disease who had hypohidrosis, a low skin moisture content, and diminished thermoregulation ability. Numerous characteristic cytoplasmic inclusions were observed in the eccrine sweat glands, the lamellar pattern of which was considerably variable in various types of gland cells. Large vacuolar inclusions predominated in clear cells of secretory coil; lesser vacuoles were also seen in the coiled duct, and the basal cells of the straight duct toward the coiled duct displayed mulberry-like figures. There were some clear cells showing cell damage and necrosis in the secretory coil. Lamellated inclusions were noted in the unmyelinated axons innervating the eccrine sweat glands. The small blood vessels around the eccrine glands were narrowed by swollen endothelial cells with heavy inclusions. These intracytoplasmic deposits may be responsible for the decreased sweating ability in Fabry disease. The factors related to hypohidrosis are also discussed.

The pathogenesis of the transepithelial elimination of the collagen bundles in acquired reactive perforating collagenosis. A light and electron microscopical study.

Two cases of acquired reactive perforating collagenosis with poorly controlled diabetes mellitus were studied by histochemistry and by electron microscopy. In excoriated wounds, the necrotic mass on the bottom of the ulcer contained the collagen bundles which were continuous with the collagen bundles in the reticular layer. In the developing stage, the epidermis regenerated between the necrotic mass and the reticular dermis, and the collagen bundles in the reticular dermis were in continuity with those in the necrotic mass through the epithelial tunnels. The collagen in the epidermal channels did not degenerate ultra‐structurally. In the mature lesion, collagen bundles being eliminated through the epidermis were surrounded by the fibroblasts at the basal cell layer. Collagen fibers were seen in the cytoplasm of these fibroblasts. From these findings, the mechanisms of the formation of the eruption in acquired reactive perforating collagenosis might be as follows: 1) In the developing stage, the regeneration of epidermis progresses between the necrotic mass and the reticular dermis, and among the collagen bundles. As a result, the collagen bundles remain in the channels of the epidermis. And then, 2) the regenerated epidermis makes the thick horny layer. As a result, the necrotic masses are lifted up and the collagen bundles are pulled up from the dermis through the epidermal channels.

The ultrastructural findings of Charcot-Leyden crystals in stroma of mastocytoma.

Charcot-Leyden crystals (CLCs) have been found in many conditions associated with eosinophilia, but their occurrence in skin diseases is very rare. We report ultrastructural observations on the presence of CLCs in the cutaneous lesions of two cases of mastocytoma. Electron microscopy documented CLCs located in phagosomes of morphologically activated macrophages as well as free CLCs in the stromal tissue, close association between CLCs formation and damaged and lysed eosinophils was present. These findings provided evidence that the formation of CLCs in mastocytoma implicated the individual and interrelated biology of mast cells, eosinophils and macrophages. Phagosomes probably acted as the site of CLCs formation. The clinic and pathologic role of CLCs in mastocytoma deserves further investigation.

Pigmented contact cheilitis from dipentaerythritol fatty acid ester.

Pigmented cosmetic dermatitis, which was previously known as melanosis faciei feminae, was first recognized in 1973 (1). Innumerable patients with this pigmentary disorder presented in 1960s and 1970s in Japan (2). After allergen control was performed, the disease became completely preventable and the incidence decreased. However, sporadic cases of this disease continue to be reported in the 1990s and 2000s (3, 4), so it is necessary to recognize the cosmetic allergens that produce hyperpigmentation.

Paraneoplastic pemphigus with widespread mucosal involvement [6]

Mami Wakahara, Takahiro Kiyohara, Masanobu Kumakiri, Takanori Ueda, Kazumori Ishiguro, Tomozo Fujita, Masayuki Amagai and Takashi Hashimoto Department of Dermatology and 1st Internal Medicine, Faculty of Medical Sciences, University of Fukui, 23-3 Shimoaizuki, Matsuoka-cho, Yoshida-gun, Fukui 910-1193 Fujita Memorial Hospital, Fukui, Department of Dermatology, School of Medicine, Keio University, Tokyo and Department of Dermatology, School of Medicine, Kurume University, Fukuoka, Japan. E-mail: kinari@yo.mitene.or.jp Accepted February 21, 2005.

Fasciitis-panniculitis syndrome and advanced gastric adenocarcinoma in association with antibodies to single-stranded DNA.

tol 1968; 80:86–9. 7 Barnes BE. Dermatomyositis and malignancy. A review of the literature. Ann Intern Med 1976; 84:68–76. 8 Grando SA. Autoimmunity to keratinocyte acetylcholine receptors in pemphigus. Dermatology 2000; 201:290–5. 9 Suzuki N, Sugawara M, Sugimoto M et al. Gene expression of human chromosome 8 in mouse cell lines. Biochem Biophys Res Commun 1997; 230:315–19. 10 Beletskaya LV, Gnezditzkaya EV. Reaction of sera of patients with pemphigus vulgaris with antigens of the cementing substance from epithelium of Hassall’s corpuscles of human and animal thymus. Bull Exp Biol Med 1974; 77:678–81.

Combined effects of photodynamic and sonodynamic treatment on experimental skin cancer on C3H mice

In recent years, the effect of ultrasound (US) in combination with porphyrins such as a gallium-porphyrin complex (ATX-70) has been reported in the treatment of experimental cancers. Before clinical application of this method, further studies are needed. The transplanted squamous cell carcinomas (5CC) on C3H/He mice were irradiated by a tunable optical parametric oscillator (OPO) laser light or ultrasound, in the presence of several different photosensitizers. The tumor size and survival of mice after treatment were observed. Furthermore, we compared antitumor effects of combined irradiation of laser light and ultrasound with those of single laser light or ultrasound, in the presence of ATX-70 or a pheoforbide derivative (PH-1126). Besides PH-i 126 and ATX-70, the following sensitizers were tested: Photofrin II (Pf-II), hematoporphyrin oligomer (HpO). 5-aminolevulinic acid (5-ALA) and aluminum phthalocyanine tetrasuiphonate (AIPcS4). In the results, it was good effects of antitumor by the laser light treatment in the case of PH-1126 and AIPcS4, ATX-70, HpO nsd AIPcS4 produced betterantitumor effeets by irradiation with ultrasound. The antitumor effects of combined use of laser fight and ultrasound were stronger than those of single laser light or ultrasound in both cases of PH-i 126 and ATX-70. Key words: OPO laser light, ultrasound, PH-1126. ATX-70

Microfluorocytometric Detection of Nuclear DNA Damage to Cancer Cells in Squamous Cell Carcinoma after Hyperthermia

An 84‐year‐old woman had a squamous cell carcinoma on her left thigh. Before operation, half of the tumor mass was irradiated with a microwave at 43°C for an hour. After the hyperthermia, the tumor mass was removed, and the DNA instability was investigated by microfluorocytometric measurement of the cells stained with pararosaniline‐Feulgen after hydrolysis with 2N HCl at 30°C. The kinetic parameters k1, which is the rate constant for the generation of an apurinic acid, k2, which is the rate constant for the depolymerization of the apurinic acid and which reflects the degree of DNA instability for acid hydrolysis, and y0, which is the theoretical value of the single‐stranded DNA present initially and reflects the degree of DNA damage, were determined by a computer fitting of the Bateman function to the hydrolysis curve plotting of the fluorescence intensity of the pararosaniline‐Feulgen staining the apurinic acid against the different hydrolysis times. The parameter values y0 and k2 of the cells treated by hyperthermia were much higher than those of the cells treated without hyperthermia. It is our conclusion that this microfluorometric detection would be valuable as an evaluation method for a cancer therapy, although more data from other cancers and treatments will be needed.

An evaluation of phthalocyanines as photosensitizer in photodynamic therapy

The spectroscopic properties and the sensitizing efficiency of phthalocyanine derivatives as photosensitizers were investigated to performe for photodynamic therapy(PDT) with a ruby laser. In the results, the absorbances at longer wavelength corresponded to the monomer increased in order of PcS<Zn-Pc<A1-Pc. The Fluorescence intensity increased as following order: PcS<ZnPc<A1-Pc. The fluorescence lifetime in 10mM-CTAB were long as following order: Zn-Pc<PcS<A1Pc. The delay of tumor growth was observed in either group of laser treatment with or without photosensitizer, but its tendency was remarkable in groups of laser treatment with photosensitizers, especially with Zn-Pc or Al-Pc. The histological changes of tumor by PDT were severe edema and bleeding immediately after irradiation and necrosis expanded gradually. It is considered that phthalocyanine can be useful sensitizer of ruby laser treatment.