Effective photodynamic therapy of actinic keratoses on the head and face with a novel, self‐adhesive 5‐aminolaevulinic acid patch

Hauschild, Axel; Popp, Georg; Stockfleth, Eggert; Meyer, Karl‐Gustav; Imberger, Dirk; Mohr, Peter; Itschert, G.; Kaufmann, Roland; Neuber, Karsten; Frambach, Yvonne; Gollnick, Harald; Brunnert, Marcus; Stocker, Marcus; Ortland, C.; Karrer, Sigrid

doi:10.1111/j.1600-0625.2008.00770.x

Cited by 41 publications

(38 citation statements)

References 27 publications

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“…Four SCC cells lines have been used in this study as model for epithelial skin cancer, because of a general lack of AK cell lines. Furthermore, AK is frequently assessed as an early stage of invasive SCC (Quatresooz et al, 2008;Hauschild et al, 2009), and similar pathway aberrations have been reported in AK and SCC, particularly including the COX-2 pathway Muller-Decker and Furstenberger, 2007). The SCC cell lines investigated here have been used in many other laboratories and are generally accepted as representative for cutaneous skin cancer (Rheinwald and Beckett, 1981;Tilgen et al, 1983;Schon et al, 2003).…”

Section: Discussionmentioning

confidence: 93%

“…AK lesions, which derive from neoplastic epidermal keratinocytes, are primarily restricted to the epidermis; however, they may proceed to invasive squamous cell carcinoma (SCC). Therefore, and due to histological and molecular correspondence, AK is considered by some researchers a carcinoma in situ and an early stage of invasive SCC (Quatresooz et al, 2008;Hauschild et al, 2009). Topical 3% diclofenac sodium in 2.5% hyaluronic acid solution (diclofenac/hyaluronic acid (HA), Solaraze) has been approved as a new treatment for AK and has shown significant efficacy (Merk, 2007;Stockfleth et al, 2008).…”

Section: Introductionmentioning

confidence: 97%

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Enhanced Death Ligand-Induced Apoptosis in Cutaneous SCC Cells by Treatment with Diclofenac/Hyaluronic Acid Correlates with Downregulation of c-FLIP

Fecker

Stockfleth

Braun

et al. 2010

Journal of Investigative Dermatology

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Actinic keratosis (AK) occurs on sun-exposed skin and may progress to invasive squamous cell carcinoma (SCC). As for its topical treatment, diclofenac/hyaluronic acid (HA) has been recently approved. The NSAID diclofenac is an inhibitor of COX-2; however, its mode of action in cutaneous epithelial cancer cells is largely unknown. Here, the effects of diclofenac/HA were investigated in relation to death ligand-mediated apoptosis (TNF-alpha, TRAIL, and CD95 activation). Whereas diclofenac/HA only moderately induced apoptosis by itself, it resulted in pronounced enhancement of death ligand-mediated apoptosis in sensitive SCC cell lines (3/4). Apoptosis was associated with activation of initiator caspases of the extrinsic pathway (caspase-8/caspase-10). Furthermore, death ligand and diclofenac/HA-mediated apoptosis were blocked by the same caspase inhibitors, indicating related pathways. The proapoptotic effects of diclofenac/HA appeared independent of the p53 pathway. Also, upregulation of death receptors appeared less important; however, strong downregulation of c-FLIP isoforms was seen after diclofenac/HA treatment. The crucial role of c-FLIP was proven through overexpression and knockdown experiments. Thus, induction of apoptosis appears to be highly characteristic of the mode of action of diclofenac/HA, and the therapeutic effect may be related to sensitization of neoplastic keratinocytes for death ligand-induced apoptosis.

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Section: Discussionmentioning

confidence: 93%

Section: Introductionmentioning

confidence: 97%

Enhanced Death Ligand-Induced Apoptosis in Cutaneous SCC Cells by Treatment with Diclofenac/Hyaluronic Acid Correlates with Downregulation of c-FLIP

Fecker

Stockfleth

Braun

et al. 2010

Journal of Investigative Dermatology

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“…One randomized controlled study found that complete clearance of actinic keratoses 8 weeks after treatment occurred with 4-hour incubation of the self-adhesive ALA patch (86% of actinic keratosis lesions) and red light therapy. Shorter incubation times at 2 hours (73%), one hour (72%), and half an hour (51%) proved to be subpar 59. In one Phase III study, the 5-ALA patch-PDT without crust removal proved superior (82% and 89%) to placebo-PDT (19% and 29%, P <0.001) and cryosurgery (77%) in improvement of actinic keratosis lesions on the scalp 60…”

Section: Pdt In Neoplastic Diseasementioning

confidence: 99%

Current evidence and applications of photodynamic therapy in dermatology

Wan¹,

Lin²

2014

CCID

114

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In photodynamic therapy (PDT) a photosensitizer – a molecule that is activated by light – is administered and exposed to a light source. This leads both to destruction of cells targeted by the particular type of photosensitizer, and immunomodulation. Given the ease with which photosensitizers and light can be delivered to the skin, it should come as no surprise that PDT is an increasingly utilized therapeutic in dermatology. PDT is used commonly to treat precancerous cells, sun-damaged skin, and acne. It has reportedly also been used to treat other conditions including inflammatory disorders and cutaneous infections. This review discusses the principles behind how PDT is used in dermatology, as well as evidence for current applications of PDT.

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“…PDT mit Methyl-aminolävulinsäure (MAL) und 5-Aminolävulinsäure (ALA) wurde als effektiv bei der Behandlung von AK und Feldkanzerisierung beurteilt [26,28,29]. Durch die Applikation photosensitivierender Stoffe wie 5-Aminolävulin-säure (5-ALA), einer physiologischen Vorstufe des Porphyrins, und nachfolgende Bestrahlung mit Licht geeigneter Wellenlänge werden reaktive Sauerstoffspezies (ROS) produziert, die primär zytotoxische Effekte induzieren [24].…”

Section: Introductionunclassified

Sekundärprävention von Hauttumoren

et al. 2011

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Nichtmelanozytäre Hauttumoren (NMSC) und das maligne Melanom (MM) stellen derzeit die häufigsten Tumorentitäten in der weißhäutigenBevölkerung dar. Beide Tumorentitä-ten zeigen starke Anstiege der Inzidenzraten. Dennoch steigt die Mortalitätsrate nicht parallel; bei vielen Patientengruppen zeigt sich sogar eine stabile oder abnehmende Mortalitätsrate [1]. Die rohe Inzidenzrate des MM beträgt 18,6 bzw. 19,4/100.000 Einwohner/Jahr für Männer bzw. Frauen. Die Inzidenzraten für epitheliale Hauttumoren sind deutlich höher und betragen 199,6 bzw. 177,7/100.000 Einwohner/Jahr für Männer bzw. Frauen (Krebsregister Schleswig-Holstein 2010). Es wird erwartet, dass sich die Inzidenzraten sowohl für das Melanom als auch für NMSC in den nächsten 20 Jahren verdoppeln werden [2]. Daher sind primäre und sekundäre Präventions-maßnahmen von entscheidender, auch wirtschaftlicher Bedeutung. Im Folgenden werden Möglichkeiten zur sekundären Prävention aufgezeigt. Bedeutung der Sekundärprävention von Hauttumoren Das MM stellt eine große Herausforderung für die Früherkennung dar, da Melanome in situ sowie MM mit einer Tumordicke <1 mm meist kurativ behandelbar sind. Deshalb sollte das primäre Ziel sein, ein Melanom in einem Stadium zu diagnostizieren, in dem es durch eine Exzision therapiert werden kann [3]. Obwohl die Inzidenzrate dünner Melanome mit entsprechend guter Prognose zunimmt, bleibt die Inzidenzrate von dicken Melanomen konstant [4]. Dies zeigt, dass weiterhin an der Verbesserung der Sekundär-prävention gearbeitet werden muss. Eine italienische Studie untersuchte die Faktoren, welche mit der Diagnose des Melanoms in frühen Stadien zusammenhän-gen [5]. Unter anderem zeigte sich bei Patienten, welche ihre Haut regelmäßig selbst untersuchten, eine geringere Melanomdicke. Aus diesem Grund sollte die Selbstuntersuchung der Haut unbedingt als eine effiziente präventive Maßnahme empfohlen werden.

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Effective photodynamic therapy of actinic keratoses on the head and face with a novel, self‐adhesive 5‐aminolaevulinic acid patch

Abstract: The results of this first clinical efficacy study suggest excellent therapeutic outcomes with a single PD P 506 A PDT with a 4-h application.

Cited by 41 publications

References 27 publications

Enhanced Death Ligand-Induced Apoptosis in Cutaneous SCC Cells by Treatment with Diclofenac/Hyaluronic Acid Correlates with Downregulation of c-FLIP

Enhanced Death Ligand-Induced Apoptosis in Cutaneous SCC Cells by Treatment with Diclofenac/Hyaluronic Acid Correlates with Downregulation of c-FLIP

Current evidence and applications of photodynamic therapy in dermatology

Sekundärprävention von Hauttumoren

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