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Traianou A.,Aristotle University of Thessaloniki | Ulrich M.,Skin Cancer Center Charite | Apalla Z.,Aristotle University of Thessaloniki | De Vries E.,Erasmus University Rotterdam | And 22 more authors.
British Journal of Dermatology | Year: 2012

Summary Background There are limited data regarding the association of actinic keratosis (AK) and other types of nonmelanoma skin cancer (NMSC); studies investigating possible correlation of AK with melanocytic naevi are even scarcer. To our knowledge, there are no data examining the risk of AK in people using specific medications. Objective To investigate constitutional and exposure risk factors leading to AK and the coexistence of AK with NMSC and melanoma. Methods A multicentre hospital-based case-control study was performed in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain, including 343 patients with actinic keratosis (AK), 409 with squamous cell carcinoma (SCC), 602 with basal cell carcinoma (BCC), 360 with invasive melanoma and 119 with in situ melanoma, and 686 control subjects. Exposures were assessed by questionnaires that were partly self-administered and partly filled out by dermatologists. Unconditional logistic regression modelling was used to assess associations including the influence of phenotypic characteristics, presence of naevi, sun-exposure habits and certain drugs on AK risk. Results Differences in hair and eye coloration variably influenced the risk for AK, with red hair signifying a seven times higher risk [odds ratio (OR) 6.9, 95% confidence interval (CI) 4.34-11.00), and brown - compared with blue - eyes, about a 40% reduced risk (OR 0.61, 95% CI 0.13-0.92). The darker the skin phototype, the lower the risk for AK, with phototype IV exhibiting nine times less risk of developing AK. Some and many freckles on the arms were associated with an OR of 1.8 (95% CI 1.08-2.81) and 3.0 (95% CI 1.10-3.54), respectively, while overall number of naevi and high educational level were inversely associated with AK. Sun exposure, thiazide diuretics and cardiac drugs had a higher risk for AK. SCC was the most frequent (58%) skin neoplasm coexisting with AKs, followed by BCC (30%), melanoma in situ (12%) and invasive melanoma (6%). Conclusion In this large case-control study from across Europe the expected associations were confirmed for known risk factors. Some possible new risk factors, including cardiac and diuretic drugs, were identified, creating a new field for further investigation in future studies. © 2012 The Authors.

Stockfleth E.,Skin Cancer Center Charite
Journal of Drugs in Dermatology | Year: 2012

Background: Diclofenac sodium 3% gel (Solaraze®) gained US approval for the treatment of actinic keratosis (AK) more than 10 years ago. Since the publication of the pivotal phase 3 studies, numerous clinical studies have assessed use of this therapy in a variety of body areas, special populations, and novel combinations. Objective: To provide a comprehensive update on clinical data and research on the use of diclofenac sodium 3% gel in AK. Methods: Review of the literature. Results: Accumulating evidence from preclinical research supports that the proposed mechanism of diclofenac sodium 3% gel may include cyclo-oxgenase 2 (COX-2) inhibition, inhibition of angiogenesis, and induction of apoptosis. A literature review identified 17 publications (beyond the 2 pivotal studies) on the use of diclofenac sodium 3% gel for AK. A phase 4 open-label study reported that 58 percent of patients achieved complete clearance of target lesions at the 30-day post-treatment assessment; among patients who were evaluable at 1-year post-treatment, sustained long-term clearance of AK lesions was observed. Active comparator studies demonstrated comparable efficacy of diclofenac sodium 3% gel with 5-fluorouracil 5% and imiquimod 5%. Publications on the efficacy of diclofenac sodium 3% gel for AK of the lip report complete clearance rates comparable to those reported for other body areas. Diclofenac sodium 3% gel has also demonstrated efficacy for clearing AK lesions in immunosuppressed populations. Sequential use of diclofenac sodium 3% gel with cryosurgery or photodynamic therapy has been investigated and may emerge as a useful approach for some patients. Conclusions: Diclofenac sodium 3% gel has a unique proposed mechanism of action in AK that may involve COX-2 inhibition, inhibition of angiogenesis, and induction of apoptosis. In the past decade, numerous clinical studies have demonstrated this topical therapy to be effective and well tolerated for the treatment of AK. © 2012-Journal of Drugs in Dermatology. All Rights Reserved.

De Vries E.,Erasmus Medical Center | Arnold M.,Erasmus Medical Center | Altsitsiadis E.,Skin Cancer Center Charite | Altsitsiadis E.,Catholic University of Leuven | And 4 more authors.
British Journal of Dermatology | Year: 2012

Summary Background Behavioural interventions to reduce exposure to ultraviolet radiation (UVR) can reduce risk of skin cancer. Objectives To integrate the data and to evaluate the impact of interventions to limit exposure to UVR on skin cancer incidence in four selected countries. Methods Using PREVENT, a dynamic simulation model, we modelled the potential for skin cancer prevention in four European countries under various scenarios to avoid damage by UVR. Results In general, the most effective interventions were those aimed at protecting people during outdoor work and outdoor hobbies against the harmful effects of UVR, and combinations of several interventions. These could in theory lead to reductions of up to 45% in skin cancer cases projected for the year 2050. Conclusions The scope for prevention depends on the prevalence of the risk factors in the different countries, as well as the associated risk factors and time lags modelled. © 2012 The Authors.

Stover L.A.,Skin Cancer Center Charite | Hinrichs B.,Skin Cancer Center Charite | Hinrichs B.,European Skin Cancer Foundation | Petzold U.,Barmer GEK | And 6 more authors.
British Journal of Dermatology | Year: 2012

Summary Background Skin neoplasms are the most frequent types of neoplasms in white populations, and their incidence is increasing. Epidemiological studies have shown that the major environmental aetiological factor for their development is sunlight exposure. Sun protection programmes are urgently needed to raise awareness of the health hazards of ultraviolet radiation. In 2010 the 'SunPass' project was implemented at 55 kindergartens in Germany. This is the first nationwide environmental education programme for sun safety designed to teach children in kindergartens and their caregivers how to protect themselves from overexposure to the sun. Objectives An interventional lecture, site inspections and a certification were part of the programme. Effects of these interventions were studied. Methods The gain in knowledge and changed sun-behavioural attributes were quantified by questionnaires administered before and after the 'SunPass' interventions. Results The total number of children was 5424. Sun-protection behaviour after the intervention improved significantly (P < 0.001). Among parents, 22.2% reported one to five sunburns of their child since birth. There was a significant increase in hat use by children in kindergartens (P = 0.029), as well as some significantly improved shade practices. There was a significantly increased demand for protective clothing for children (P < 0.001). The change in sunscreen use in kindergartens was not significant. Conclusions Although some aims of the 'SunPass' project were not fulfilled, such as the precise knowledge of skin types and a change of sunscreen use, the study had some positive outcomes in increasing the awareness of skin cancer and its prevention possibilities. The findings of the present study suggest that relatively brief interventions in kindergartens lead to improved sun protection of children. The whole investigation reaching over 5400 children and their parents underlines the importance of learning appropriate sun-protective behaviour in early childhood in order to decrease the risk for skin cancer. © 2012 The Authors.

PubMed | Skin Cancer Center Charite and University of Heidelberg
Type: Journal Article | Journal: Archives of gynecology and obstetrics | Year: 2016

The prognosis of patients with non-platinum-sensitive recurrent ovarian cancer is poor. There is a need for salvage therapies with anti-tumor activity and acceptable toxicity for maintaining quality of life. Pegylated liposomal doxorubicin (PLD, Caelyx()) is a promising drug fulfilling these demands. We present retrospective data of patients with advanced epithelial ovarian cancer (EOC) who were treated with pegylated liposomal doxorubicin at the University of Heidelberg between 2007 and 2009.Eligible patients for this retrospective study had advanced ovarian cancer and were treated in a palliative setting with PLD at the university hospital of Heidelberg, Germany. Primary objectives were toxicity and efficacy of PLD. 34 patients were included in this study between November 2007 and December 2009; one patient received PLD twice as palliative treatment.The median age of the 34 patients enrolled in this study was 59.9years (range 27-77years). The median weight of the patients was 69kg (range 47-109kg), the median height 164cm (range 140-176cm). Pegylated liposomal doxorubicin was administered every 4weeks with a dosage of 40mg/m(2) body surface. PLD was administered for three cycles in median (range 1-9 cycles). Dose reduction was necessary in only four patients. In our study time to progression and overall survival was 8.74 and 14.23months.In conclusion, this retrospective study showed the efficacy and low toxicity of pegylated liposomal doxorubicin in patients with advanced EOC. Further observations are needed to confirm these preliminary experiences on a larger number of patients.

Ferrandiz L.,Hospital Universitario Virgen Macarena | Ruiz-De-Casas A.,Hospital Universitario Virgen Macarena | Trakatelli M.,General Hospital Papageorgiou | De Vries E.,Erasmus Medical Center | And 15 more authors.
British Journal of Dermatology | Year: 2012

Summary Background A wide variety of both surgical and nonsurgical therapies is currently available for patients with skin cancer. Objectives This part of the EPIDERM (European Prevention Initiative for Dermatological Malignancies) project is aimed at the evaluation of the treatment preferences for skin cancer in eight countries of the European Union. Methods A multicentre hospital-based case-control study was carried out at dermatology departments in Finland, Germany, Greece, Italy, Malta, Poland, Scotland and Spain. Patients with skin cancer (basal cell carcinoma, actinic keratosis, squamous cell carcinoma, cutaneous malignant melanoma and Bowen disease) were consecutively enrolled between July 2008 and July 2010. Information on the study variables (sex, age, country, tumour type, anatomical location and treatment) was obtained from questionnaires designed by the EPIDERM project. Results In total, 1708 patients with skin cancer were included. Surgery was the first treatment option in 76.5% of the patients (P = 0.001). Actinic keratosis was the only tumour type in which nonsurgical treatment was more frequent than surgery (91.4%). Tumours on the head were less likely to be surgically excised than those at other locations (odds ratio 0.25, P = 0.001). Simple excision or curettage was the most common surgical procedure (65.4%), followed by graft and flaps (22.4%). Cryotherapy was the most common nonsurgical option (52.4%), followed by imiquimod (18.0%), photodynamic therapy (PDT; 12.0%), 5-fluorouracil (5-FU; 5.7%), and diclofenac with hyaluronic acid (4.0%). Conclusions Surgery remains the first-choice treatment of skin cancer. Regarding nonsurgical treatments, the conservative treatments available (imiquimod, 5-FU, PDT and diclofenac gel) have not yet exceeded the use of ablative options such as cryotherapy despite their accepted benefit of treating field cancerization. © 2012 The Authors.

Plotz M.,Skin Cancer Center Charite | Gillissen B.,Charité - Medical University of Berlin | Quast S.-A.,Skin Cancer Center Charite | Berger A.,Skin Cancer Center Charite | And 2 more authors.
Cancer Letters | Year: 2013

Melanoma cells are characterized by apoptosis deficiency coinciding with reduced expression of the proapoptotic Bcl-2 protein Bim. An adenoviral vector was constructed with the BimL cDNA controlled by an inducible promoter. Highly efficient apoptosis induction and abrogated cell proliferation was seen in melanoma cells upon BimL overexpression. Loss of mitochondrial membrane potential, release of mitochondrial apoptogenic factors and caspase-9 processing indicated the activation of mitochondrial apoptosis pathways. BimL activated both Bax and Bak, as shown by siRNA knockdown and activation-specific antibodies. Of note, BimL overrode the apoptosis blockade by Bcl-2 overexpression or by Bax/Bak single knockdown. The high efficacy correlated to BimL interaction with all antiapoptotic Bcl-2 family members in melanoma cells, shown by co-immunoprecipitation analyses for Bcl-2, Bcl-xL, Mcl-1 and Bcl-w. Thus, BimL reveals an outstanding proapoptotic potential in melanoma cells, and strategies for its re-expression appear of interest. These have been reported for B-Raf inhibitors, and their efficacy may be partly attributed to BimL. © 2013.

Franke J.C.,Skin Cancer Center Charite | Franke J.C.,Free University of Berlin | Plotz M.,Skin Cancer Center Charite | Prokop A.,University of Cologne | And 3 more authors.
Biochemical Pharmacology | Year: 2010

Chemotherapy resistance and related defects in apoptotic signaling are crucial for the high mortality of melanoma. Effective drugs are lacking, also due to the fact that apoptosis regulation in this tumor is essentially not understood. The cytosine analogue ferropoptoside (N69), which contains an iron carbonyl complex, resulted in strong induction of apoptosis in melanoma cells starting already after 2 h, whereas cytotoxicity remained at a low level. Surprisingly, there was no indication for any caspase activation at early times, although cytochrome c was released from mitochondria. Indicative for new proapoptotic pathways was the production of reactive oxygen species (ROS) as an early effect, and the inhibition of apoptosis by the antioxidant vitamin E. Apoptosis was also blocked by exogenous Bcl-2 overexpression and by the pan-protease inhibitor zVAD. However, only zVAD also prevented ROS production, for which Bcl-2 remained without an effect. Thus, new proapoptotic pathways are described here for melanoma cells clearly related to ROS production. A cascade enclosing enhanced levels of intracellular iron, which lead to enhanced ROS production in a Fenton reaction, appears as suggestive. Whereas off-target effects of zVAD appear as upstream, Bcl-2 may exert its inhibitory activity downstream of ROS. New proapoptotic pathways are of particular interest for melanoma as they may open new options for targeting this highly therapy-refractory tumor. © 2009 Elsevier Inc. All rights reserved.

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