The morphology of common warts depends on the inducing human papillomavirus (HPV) type. In order to assess the impact of the virus type on wart epidemiology we determined the virus type by PCR and recorded anamnestic data of 238 patients with common warts. Warts induced by the related HPV types 2, 27 and 57 predominated in the study population (n = 202). These warts mostly occurred as multiple verrucae vulgares, mosaic warts or endophytic warts. Patients aged between 10 and 30 years were most affected and they typically displayed a long disease history (mean duration of warts at the time of first clinical examination, 22 months). A different age distribution was observed in HPV 1-induced warts, most of which occurred in children 6-10 years of age. HPV 2-related warts responded only modestly to treatment, as they persisted in approximately 50% of all patients for more than 6 additional months. No sex preference was detected, but an association with atopic diseases was noted as 39.8% of patients with warts containing HPV 2-related viruses showed a history of atopic eczema, pollinosis or asthma as compared with 20.6% of the control population without a history of warts or with short-duration wart disease. Thus, our results indicate that the epidemiology, as well as morphology, of common warts is closely linked to the virus type.
PDT, a new therapeutic procedure for the management of many malignant conditions including skin cancer, involves the administration of a photosensitizing compound followed by illumination of the lesion with visible light. We earlier showed an involvement of: (i) WAF1/ p21-cyclins (D1 and E)-cdk (2 and 6) network; and (ii) Rb/E2F-DP machinery during silicon phthalocyanine (Pc4)-PDT-mediated cell cycle dysregulation and apoptosis of human epidermoid carcinoma (A431) cells. Here, we investigated the involvement of EGFR-pathway during antiproliferative responses of Pc4-PDT in A431 cells and during ablation of murine skin papillomas. Pc4-PDT of A431 cells was found to result in a timedependent down-modulation of the protein expression and phosphorylation of EGFR and Shc (an immediate downstream molecule in EGFR-pathway), during progressive increase in apoptotic response. To establish the relevance of these in vitro ®ndings to in vivo situations, we subjected chemically-as well as ultraviolet B radiation-induced squamous papillomas in SENCAR and SKH-1 hairless mice, respectively, to Pc4-PDT, and assessed its e ect on EGFR-pathway during ablation of these tumors. Pc4-PDT was found to result in a timedependent: (i) inhibition of protein expressions of EGFR; and (ii) tyrosine phosphorylation of EGFR and Shc; and (iii) induction of apoptosis, during the regression of these tumors. These data suggest the involvement of EGFRpathway during the antiproliferative e ects of PDT. It is tempting to speculate that inhibitors of EGFR could enhance the therapeutic e cacy of PDT. Oncogene (2001) 20, 2314 ± 2317.Keywords: PDT; EGFR; Shc; cell cycle; apoptosis Photodynamic therapy (PDT), relatively a new therapeutic procedure, is used for the management of a variety of solid tumors including skin cancer, and is showing promise for the treatment of many nonmalignant diseases including many dermatological disorders (Dougherty et al., 1998;Oleinick and Evans, 1998;Kalka et al., 2000b). PDT involves a selective uptake of a porphyrin based photosensitizing chemical in the tumor relative to the surrounding normal tissue followed by irradiation of the tumor with visible or near infrared light that is typically derived through a laser (Dougherty et al., 1998;Oleinick and Evans, 1998;Kalka et al., 2000b). This causes a photoactivation leading to an oxidative damage to a variety of cellular targets that subsequently results in the death of cancerous cells and thereby ablation of the tumor. The mechanism(s) of the PDT-mediated cell killing is not fully understood.Many studies have shown that PDT is associated with apoptotic death of cancer cells in vitro and in vivo (Dougherty et al., 1998;Oleinick and Evans, 1998;Kalka et al., 2000b). Studies from this laboratory have shown the involvement of apoptosis as an early event in ablation of: (i) RIF-1 implanted tumors in C3H mice (Zaidi et al., 1993); (ii) ovarian cancer (OVCAR-3) tumor xenografts (Colussi et al., 1999) and SW480 human colon cancer xenografts in nude mice (Whitacre et al., 2000); and ...
Acute adverse effects of ultraviolet (UV) radiation in humans include sunburn, photosensitivity reactions and immunological suppression. Chronic exposure to UV light, particularly the UVB (290–320 nm) component of the UV radiation, and certain environmental chemicals increase the risk of nonmelanoma skin cancer and play a major role in cutaneous aging. The lipid peroxidation (LPO) of biomembranes, mediated by reactive oxygen species and free radicals, is one of the major causes of cellular damage induced by UV radiation and toxins. Antioxidants, such as vitamin E, vitamin C and melanins, are reactive oxygen and radical scavengers, thereby minimizing the light- and toxin-induced tissue destruction. We examined the influence of 8 biotechnically produced polyphenolic melanins on the LPO of microsomal membranes in comparison with α-tocopherol, ascorbate and synthetic melanin. All biomelanins showed better inhibition of peroxidative damage than synthetic melanin. Three of the 8 tested drugs inhibited the LPO at least as effectively as vitamin C and vitamin E. The combination of the most effective biomelanin with both vitamin C and vitamin E resulted in greater LPO inhibition than caused by each agent alone. Our data show that biomelanins are potent inhibitors of the peroxidative destruction of biomembranes, indicating that these compounds may be useful antioxidative agents in cosmetic preparations.
Atopic dermatitis (AD) patients with predominantly head and neck involvement react to patch tests of the yeast Malassezia sympodialis (Ms). Protein patch testing methods and interpretation are controversial, but subgroups of AD patients may have unique triggers for disease activity. The aim of the study was to identify clinical characteristics of patients who are patch test-positive to Dermatophagoides farinae/pteronyssinus (Df) and Ms and characterize cutaneous cytokine profiles of the atopy patch tests (APTs). 25 AD patients and 27 control dermatitis patients were patch tested with Ms and Df. Qualitative analysis of Th-1 and Th-2 cytokines by RT-PCR mRNA was obtained from positive APTs. Atopic dermatitis patients with a textile pattern or head and neck involvement demonstrated more positive APTs to Ms than control patients. Early positive APTs (<6 hr) did not exhibit a Th-1 type cytokine profile. The subgroup of adult AD patients with head, neck and upper torso pattern of dermatitis seems most likely to react to Ms (and Df). The immune mechanism of protein patch tests includes a Th-1 cell-mediated component after 6 hr or more.
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