Colocalization of basic fibroblast growth factor and CD44 isoforms containing the variably spliced exon v3 (CD44v3) in normal skin and in epidermal skin cancers.

Previous in vitro studies have shown CD44 isoforms containing the alternatively spliced exon v3 (CD44v3) to be modified with heparan sulphate (HS) and to bind HS-binding basic fibroblast growth factor (bFGF). Here, we demonstrate that exogenously added bFGF is also bound in vivo by CD44v3-positive keratinocytes in normal skin and by tumour cells in basal cell carcinoma and squamous cell carcinoma (SCC), two skin cancers of keratinocyte origin. bFGF binding and CD44v3 expression were colocalized in cultured human normal keratinocytes (HNK) and on the SCC cell line A431. By contrast, benign or malignant tumours of melanocyte origin failed to express CD44v3 and bound no bFGF. The bFGF binding to normal or transformed keratinocytes in vivo and in vitro was dependent on HS modification, as it was completely eliminated by pretreatment with heparitinase or by blocking with free heparin, whereas chondroitinase had no effect. In addition, specific removal of CD44v3 by antibody-induced shedding also diminished bFGF binding to keratinocytes. Furthermore, bFGF stimulated the proliferation of CD44v3-positive HNK and A431 in a dose-dependent fashion. This bFGF effect was again completely abolished by heparitinase or free heparin, but not by chondroitinase. In aggregate, our results suggest that a function of HS-modified CD44 isoforms such as CD44v3 in skin is to present the HS-binding growth factor bFGF, thereby stimulating the proliferation of normal or transformed keratinocytes.

Focal dermal hypoplasia (Goltz-Gorlin syndrome) associated with obstructive papillomatosis of the larynx and hypopharynx.

A 14-year-old girl with focal dermal hypoplasia (Goltz-Gorlin-syndrome) presented with dysphagia, hoarseness, inspiratory stridor, intermittent dry cough and a 10% weight loss. Endoscopy showed that these symptoms were caused by papillomatosis of the hypopharynx and the larynx. The papillomatous masses were resected subtotally by endoscopic laser treatment. Residual papillomas were left in the subglottic space but tracheotomy could be avoided. Complete clinical recovery with adequate weight gain as well as, resolution of dyspnoe and dysphagia resulted after the intervention. Histological examination did not show morphological signs of human papilloma virus as an etiological agent.

Metastasizing porocarcinoma of the head with lethal outcome.

Porocarcinoma is a very rare malignant tumor arising from the duct of eccrine sweat glands. Its prognosis is variable. We report on a patient who developed lymph node and multiple distant metastases, and who died of this malignancy only 6 months after the initial diagnosis.

[Phytotherapy in chronic dermatoses and wounds: what is the evidence?]. / Phytotherapie bei chronischen Dermatosen und Wunden: Was ist gesichert?

Phytotherapeutic preparations and synthetic derivatives of plant origin have been used in conventional dermatology for a long time. A further spectrum of phytotherapeutic agents for the treatment of dermatological diseases and wounds is known from alternative medical treatment. To the efficacy of these phytotherapeutic agents only few data from studies are available. Own studies and studies published in the specialist literature, especially on chamomile, arnica, calendula, hamamelis, Aloe vera, cardiospermum, Mahonia aquifolium, oak bark, bittersweet stalk, and capsaicin indicate that these plants may be of value in selected dermatological indications. Other controlled clinical efficacy studies and pharmacological studies are needed to prove the assumed effects, to record the spectrum of side effects, and to clarify the mechanisms of action.

Effects of Mahonia aquifolium ointment on the expression of adhesion, proliferation, and activation markers in the skin of patients with psoriasis.

OBJECTIVE: To examine the effects of topical therapy with Mahonia aquifolium on the expression of pathogenetically relevant molecules in psoriatic skin by immunohistochemistry. STUDY DESIGN: Prospective-randomized, half-side comparison study with subsequent immunohistochemical assessment of biopsies. METHODS: The study areas were treated with Mahonia aquifolium ointment 3( daily and with dithranol in rising concentrations 1( daily, respectively. Biopsies of lesional skin from the test areas were carried out in 49 patients a) prior to therapy and b) 4 weeks after the start of therapy. Immunohistochemical stainings were performed with the following monoclonal antibodies: anti-ICAM-1, -CD3, -HLA-DR, -keratin 6, -keratin 16, -Ki-67. Evaluation of staining was made by two independent examiners using established semiquantitative scores. RESULTS: Marked staining with all of the cited monoclonal antibodies was observed in the lesional skin prior to therapy. After 4 weeks of therapy there was a marked reduction in the expressions of ICAM-1, CD 3, HLA-DR and keratin 6 and 16. There were significantly greater reductions of ICAM-1, CD3, and HLA-DR at sites treated with dithranol. The expression of Ki-67 was not reduced by either therapy. CONCLUSIONS: These results indicate efficacy of Mahonia aquifolium and dithranol in psoriatic skin both on cellular cutaneous immune mechanisms and on the hyperproliferation of keratinocytes. The effect of dithranol appears to be more potent than that of Mahonia aquifolium.

Dacarbazine and interferon alpha for stage IV malignant melanoma.

Based on encouraging reports of improved response rates with the use of dacarbazine (DTIC) in combination with recombinant interferon alpha-2a (rIFN-alpha-2a) in patients with metastatic malignant melanoma, we conducted a phase II study to determine the efficacy and feasibility of this treatment regimen. 31 patients were treated with an induction dose of rIFN-alpha-2a at 15 MIU/ m2 intravenously (i.v.) daily for 5 days per week for 3 consecutive weeks followed by a continuous maintenance dose of 10 MIU/m2 subcutaneously (s.c.) given 3 days per week; starting on day 22, in conjunction with rIFN-alpha-2a s.c., DTIC was started at a dose of 200 mg/m2 i.v. for 5 continuous days completing a 28-day cycle. Therapy was continued until progression was evidenced. Of the 29 evaluable patients, 7 (24.1%) achieved an objective response (complete plus partial remission) with the highest responses occurring in those patients assessed with pulmonary metastases. The median duration to treatment failure was 2.6 months, while the median survival was 6.9 months. Our data reveal that using rIFN-alpha-2a plus DTIC in combination does not yield better results than those achieved when using DTIC alone. However, 3 of the 7 responders experienced long-term survival ranging up to 42 months. Whether this benefit is achieved by the addition of rIFN-alpha-2a can only be answered by large randomized clinical trials. Conflicting results with some of the current literature are discussed.

[Malignant melanoma of the skin]. / Das maligne Melanom der Haut.

The incidence of malignant melanoma (MM) of the skin is on the increase. If the mortality of this disease is to be reduced, the identification of persons at risk, and early clinical diagnosis are of decisive importance. The prognosis depends on the stage of the disease and has improved over the last few decades. The present article provides an overview of the risk factors and discusses the latest guidelines for the diagnosis, treatment and follow-up, the aim of which is to make possible a uniform approach to the management of malignant melanoma.