JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 18, Issue 2 p. 147-148 Clinical LetterOpen Access Mechanikerhände bei einer Patientin mit isolierten anti-RO52-Antikörpern: Antisynthetase-Syndrom ohne Antisynthetase-Antikörper Peter Korsten, Corresponding Author Peter Korsten peter.korsten@med.uni-goettingen.de Klinik für Nephrologie und Rheumatologie, Universitätsmedizin Göttingen Korrespondenzanschrift Dr. med. Peter Korsten Klinik für Nephrologie und Rheumatologie Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Göttingen E-Mail: peter.korsten@med.uni-goettingen.deSearch for more papers by this authorJens Schmidt, Jens Schmidt Klinik für Neurologie, Universitätsmedizin GöttingenSearch for more papers by this authorJörg Larsen, Jörg Larsen Klinik für diagnostische und interventionelle Radiologie, Universitätsmedizin GöttingenSearch for more papers by this authorCornelia S. Seitz, Cornelia S. Seitz Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin GöttingenSearch for more papers by this author Peter Korsten, Corresponding Author Peter Korsten peter.korsten@med.uni-goettingen.de Klinik für Nephrologie und Rheumatologie, Universitätsmedizin Göttingen Korrespondenzanschrift Dr. med. Peter Korsten Klinik für Nephrologie und Rheumatologie Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Göttingen E-Mail: peter.korsten@med.uni-goettingen.deSearch for more papers by this authorJens Schmidt, Jens Schmidt Klinik für Neurologie, Universitätsmedizin GöttingenSearch for more papers by this authorJörg Larsen, Jörg Larsen Klinik für diagnostische und interventionelle Radiologie, Universitätsmedizin GöttingenSearch for more papers by this authorCornelia S. Seitz, Cornelia S. Seitz Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin GöttingenSearch for more papers by this author First published: 06 February 2020 https://doi.org/10.1111/ddg.13985_gAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume18, Issue2February 2020Pages 147-148 RelatedInformation
Melanoma progression and resistance to therapy are associated with faulty regulation of signalling molecules including the central transcription factor NF-κB. Increased expression of the c-Rel subunit of NF-κB has been described in progressing melanoma, though mechanistic implications of this upregulation remain unclear. To elucidate the functional role of c-Rel in melanoma biology, we have assessed its expression in human melanoma as well as in melanoma cell lines. Suppression of c-Rel expression in four melanoma cell lines resulted in reduced growth and altered cell cycle regulation, namely G2/M and polyploid phase induction. Moreover, mitotic spindle morphology was profoundly altered in three of the cell lines with a predominance of monopolar structures. These findings suggest that c-Rel is involved in G2/M phase regulation, prevention of polyploidy and, consequently, chromosomal stability. Our results highlight a novel tumor-promoting function of c-Rel in human melanoma cells through governing cell cycle regulation.
JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 18, Issue 2 p. 147-148 Clinical LetterOpen Access Mechanic's hands in a patient with isolated anti-Ro52 antibodies: antisynthetase syndrome without antisynthetase antibodies Peter Korsten, Corresponding Author Peter Korsten peter.korsten@med.uni-goettingen.de orcid.org/0000-0001-6065-5680 Department of Nephrology and Rheumatology, University Medical Center Göttingen, Germany Correspondence to Peter Korsten, MD Department of Nephrology and Rheumatology University Medical Center Göttingen Robert-Koch-Strasse 40 37075 Göttingen, Germany E-Mail: peter.korsten@med.uni-goettingen.deSearch for more papers by this authorJens Schmidt, Jens Schmidt Department of Neurology, University Medical Center Göttingen, Göttingen, GermanySearch for more papers by this authorJörg Larsen, Jörg Larsen Department of Diagnostic and Interventional Radiology, University Medical Center Göttingen, Göttingen, GermanySearch for more papers by this authorCornelia S. Seitz, Cornelia S. Seitz Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, GermanySearch for more papers by this author Peter Korsten, Corresponding Author Peter Korsten peter.korsten@med.uni-goettingen.de orcid.org/0000-0001-6065-5680 Department of Nephrology and Rheumatology, University Medical Center Göttingen, Germany Correspondence to Peter Korsten, MD Department of Nephrology and Rheumatology University Medical Center Göttingen Robert-Koch-Strasse 40 37075 Göttingen, Germany E-Mail: peter.korsten@med.uni-goettingen.deSearch for more papers by this authorJens Schmidt, Jens Schmidt Department of Neurology, University Medical Center Göttingen, Göttingen, GermanySearch for more papers by this authorJörg Larsen, Jörg Larsen Department of Diagnostic and Interventional Radiology, University Medical Center Göttingen, Göttingen, GermanySearch for more papers by this authorCornelia S. Seitz, Cornelia S. Seitz Department of Dermatology, Venereology and Allergology, University Medical Center Göttingen, GermanySearch for more papers by this author First published: 19 November 2019 https://doi.org/10.1111/ddg.13985AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume18, Issue2February 2020Pages 147-148 RelatedInformation
ZUSAMMENFASSUNG Gegenstand und Ziel Myositis-Patienten bedürfen einer interdisziplinären Diagnostik und Therapie. Über Konsile erfolgt die Besprechung unsystematisch und zum Teil therapeutisch divergent. Interdisziplinäre Fallkonferenzen bieten potenzielle Vorteile bei Myositiden und anderen Systemerkrankungen. Material und Methoden Narrative Beschreibung des „Göttinger Modells“ und retrospektive Analyse der immunologischen Fallkonferenzen von September 2018 bis Februar 2019. Ergebnisse 30 Patienten wurden vorgestellt, 15 im Rahmen einer Myositis. Weitere Diagnosen umfassten Sarkoidose, Sklerodermie und andere Entitäten. 20 Patienten wiesen positive antinukleäre Antikörper (AK) auf; weitere AK waren Ro52, Antisynthetase, Mi2-β, TIF1-γ, MDA5 und CENP-B/Fibrillarin. Eine CK-Erhöhung lag in 5 Fällen vor. 23 Patienten wurde eine weitere Diagnostik empfohlen. Therapieänderungen erfolgten bei 11 Patienten. Schlussfolgerungen Interdisziplinäre Fallkonferenzen ermöglichen eine systematische diagnostische und therapeutische Strategie. In einer prospektiven Studie sollte untersucht werden, inwieweit sich Fallkonferenzen auf krankheitsassoziierte sowie patientenseitige Outcomes auswirken. Klinische Relevanz Das „Göttinger Modell“ ist gut umsetzbar und führt überwiegend zu diagnostischen und therapeutischen Konsequenzen.
JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 16, Issue 12 p. 1490-1492 Clinical Letter EBV-positives mukokutanes Ulkus am Penis Christina Mitteldorf, Corresponding Author Christina Mitteldorf christina.mitteldorf@med.uni-goettingen.de Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Göttingen Korrespondenzanschrift Priv.-Doz. Dr. med. Christina Mitteldorf Klinik für Dermatologie, Venerologie und Allergologie Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Gßttingen, Deutschland E-Mail: christina.mitteldorf@med.uni-goettingen.deSearch for more papers by this authorPhilipp Ströbel, Philipp Ströbel Institut für Pathologie, Universitätsmedizin GöttingenSearch for more papers by this authorMichael P. Schön, Michael P. Schön Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin GöttingenSearch for more papers by this authorCornelia S. Seitz, Cornelia S. Seitz Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin GöttingenSearch for more papers by this author Christina Mitteldorf, Corresponding Author Christina Mitteldorf christina.mitteldorf@med.uni-goettingen.de Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Göttingen Korrespondenzanschrift Priv.-Doz. Dr. med. Christina Mitteldorf Klinik für Dermatologie, Venerologie und Allergologie Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Gßttingen, Deutschland E-Mail: christina.mitteldorf@med.uni-goettingen.deSearch for more papers by this authorPhilipp Ströbel, Philipp Ströbel Institut für Pathologie, Universitätsmedizin GöttingenSearch for more papers by this authorMichael P. Schön, Michael P. Schön Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin GöttingenSearch for more papers by this authorCornelia S. Seitz, Cornelia S. Seitz Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin GöttingenSearch for more papers by this author First published: 11 December 2018 https://doi.org/10.1111/ddg.13697_gAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume16, Issue12December 2018Pages 1490-1492 RelatedInformation
JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 16, Issue 12 p. 1490-1492 Clinical Letter EBV-positive mucocutaneous ulcer on the penis Christina Mitteldorf, Corresponding Author Christina Mitteldorf christina.mitteldorf@med.uni-goettingen.de Department of Dermatology, Venereology and Allergology, Göttingen University Medical Center, Göttingen, Germany Correspondence to Priv.-Doz. Dr. med. Christina Mitteldorf Department of Dermatology, Venereology and Allergology Göttingen University Medical Center Robert-Koch-Straße 40 37075 Göttingen, Germany E-mail: christina.mitteldorf@med.uni-goettingen.deSearch for more papers by this authorPhilipp Ströbel, Philipp Ströbel Institute of Pathology, Göttingen University Medical Center, Göttingen, GermanySearch for more papers by this authorMichael P. Schön, Michael P. Schön Department of Dermatology, Venereology and Allergology, Göttingen University Medical Center, Göttingen, GermanySearch for more papers by this authorCornelia S. Seitz, Cornelia S. Seitz Department of Dermatology, Venereology and Allergology, Göttingen University Medical Center, Göttingen, GermanySearch for more papers by this author Christina Mitteldorf, Corresponding Author Christina Mitteldorf christina.mitteldorf@med.uni-goettingen.de Department of Dermatology, Venereology and Allergology, Göttingen University Medical Center, Göttingen, Germany Correspondence to Priv.-Doz. Dr. med. Christina Mitteldorf Department of Dermatology, Venereology and Allergology Göttingen University Medical Center Robert-Koch-Straße 40 37075 Göttingen, Germany E-mail: christina.mitteldorf@med.uni-goettingen.deSearch for more papers by this authorPhilipp Ströbel, Philipp Ströbel Institute of Pathology, Göttingen University Medical Center, Göttingen, GermanySearch for more papers by this authorMichael P. Schön, Michael P. Schön Department of Dermatology, Venereology and Allergology, Göttingen University Medical Center, Göttingen, GermanySearch for more papers by this authorCornelia S. Seitz, Cornelia S. Seitz Department of Dermatology, Venereology and Allergology, Göttingen University Medical Center, Göttingen, GermanySearch for more papers by this author First published: 12 November 2018 https://doi.org/10.1111/ddg.13697Citations: 1AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume16, Issue12December 2018Pages 1490-1492 RelatedInformation
JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 16, Issue 2 p. 201-203 Clinical Letter „Creeping eruption“ und eosinophile Follikulitis: Atypische kutane Larva migrans Anike Lockmann, Anike Lockmann Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin GöttingenSearch for more papers by this authorCornelia S. Seitz, Cornelia S. Seitz Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin GöttingenSearch for more papers by this authorMichael P. Schön, Michael P. Schön Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin GöttingenSearch for more papers by this authorRotraut Mößner, Corresponding Author Rotraut Mößner rmoessn@gwdg.de Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Göttingen Korrespondenzanschrift Prof. Dr. med. Rotraut Mößner Universitätsmedizin Göttingen Klinik für Dermatologie, Venerologie und Allergologie Robert-Koch-Straße 40 37075 Göttingen E-mail: rmoessn@gwdg.deSearch for more papers by this author Anike Lockmann, Anike Lockmann Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin GöttingenSearch for more papers by this authorCornelia S. Seitz, Cornelia S. Seitz Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin GöttingenSearch for more papers by this authorMichael P. Schön, Michael P. Schön Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin GöttingenSearch for more papers by this authorRotraut Mößner, Corresponding Author Rotraut Mößner rmoessn@gwdg.de Klinik für Dermatologie, Venerologie und Allergologie, Universitätsmedizin Göttingen Korrespondenzanschrift Prof. Dr. med. Rotraut Mößner Universitätsmedizin Göttingen Klinik für Dermatologie, Venerologie und Allergologie Robert-Koch-Straße 40 37075 Göttingen E-mail: rmoessn@gwdg.deSearch for more papers by this author First published: 08 February 2018 https://doi.org/10.1111/ddg.13414_gAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume16, Issue2February 2018Pages 201-203 RelatedInformation
JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 16, Issue 2 p. 202-204 Clinical Letter Creeping eruption and eosinophilic folliculitis: Atypical cutaneous larva migrans Anike Lockmann, Anike Lockmann Department of Dermatology, Venereology, and Allergology, University Medical Center GöttingenSearch for more papers by this authorCornelia S. Seitz, Cornelia S. Seitz Department of Dermatology, Venereology, and Allergology, University Medical Center GöttingenSearch for more papers by this authorMichael P. Schön, Michael P. Schön Department of Dermatology, Venereology, and Allergology, University Medical Center GöttingenSearch for more papers by this authorRotraut Mößner, Corresponding Author Rotraut Mößner rmoessn@gwdg.de Department of Dermatology, Venereology, and Allergology, University Medical Center Göttingen Correspondence to Rotraut Mößner, MD Department of Dermatology, Venereology, and Allergology University Medical Center Göttingen Robert-Koch-Strasse 40 37075 Göttingen, Germany E-mail: rmoessn@gwdg.deSearch for more papers by this author Anike Lockmann, Anike Lockmann Department of Dermatology, Venereology, and Allergology, University Medical Center GöttingenSearch for more papers by this authorCornelia S. Seitz, Cornelia S. Seitz Department of Dermatology, Venereology, and Allergology, University Medical Center GöttingenSearch for more papers by this authorMichael P. Schön, Michael P. Schön Department of Dermatology, Venereology, and Allergology, University Medical Center GöttingenSearch for more papers by this authorRotraut Mößner, Corresponding Author Rotraut Mößner rmoessn@gwdg.de Department of Dermatology, Venereology, and Allergology, University Medical Center Göttingen Correspondence to Rotraut Mößner, MD Department of Dermatology, Venereology, and Allergology University Medical Center Göttingen Robert-Koch-Strasse 40 37075 Göttingen, Germany E-mail: rmoessn@gwdg.deSearch for more papers by this author First published: 12 January 2018 https://doi.org/10.1111/ddg.13414Citations: 7AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article.Citing Literature Volume16, Issue2February 2018Pages 202-204 RelatedInformation
Konfokale Laserscanmikroskopie (Reflectance confocal microscopy; RCM) kann eine nützliche Methode für die genaue, schnelle und nicht‐invasive Diagnose für vesikullobullöse Hauterkrankungen (VSD) am Krankenbett sein. Das primäre Ergebnis dieser Studie war eine deskriptive statistische Analyse von RCM‐Merkmalen, die mit einer ausgewählten Gruppe an VSD einhergehen.
To maintain proper skin barrier function, epidermal homeostasis requires a subtly governed balance of proliferating and differentiating keratinocytes. While differentiation takes place in the suprabasal layers, proliferation, including mitosis, is usually restricted to the basal layer. Only recently identified as an important regulator of epidermal homeostasis, c-Rel, an NF-kappa B transcription factor subunit, affects the viability and proliferation of epidermal keratinocytes. In human keratinocytes, decreased expression of c-Rel causes a plethora of dysregulated cellular functions including impaired cell viability, increased apoptosis, and abnormalities during mitosis and cell cycle regulation. On the other hand, c-Rel shows aberrant expression in many epidermal tumors. Here, in the context of its role in different cell types and compared with other NF-kappa B subunits, we discuss the putative function of c-Rel as a regulator of epidermal homeostasis and mitotic progression. In addition, implications for disease pathophysiology with perturbed c-Rel function and abnormal homeostasis, such as epidermal carcinogenesis, will be discussed.
Background and objectives: Reflectance confocal microscopy (RCM) may be a useful method for accurate, rapid, and noninvasive bedside diagnosis of vesiculobullous skin diseases (VSD). The main outcome measure of this study was a descriptive statistical analysis of RCM features associated with selected group of VSD.Patients and methods: Single-center, observational study at a university-based dermatology department. Forty skin lesions in 24 patients with bullous pemphigoid (BP), varicella zoster virus infection (VZI), or allergic contact dermatitis (ACD) were assessed.Results: Patients with BP, VZI, and ACD were assessed for the presence of a large spectrum of RCM features, among others including histopathological correlates for spongiosis, vesicles/blisters, epidermal necrosis, pleomorphic ballooned keratinocytes, and inflammatory infiltrate. The three conditions showed distinct patterns of occurrence with respect to these RCM features. Using a multivariate regression model, we identified sets of morphologic features in BP (vesicles/blisters at the dermoepidermal junction, inflammatory infiltrate within blisters and basal epidermal layers, spongiosis in basal epidermal layers), VZI (acantholysis in the stratum spinosum, epidermal necrosis, pleomorphic ballooned keratinocytes, multinucleated giant cells), and ACD (microvesicles, spongiosis, and prominent inflammatory infiltrate in the stratum granulosum/spinosum).Conclusions: RCM seems to be a useful tool in the evaluation and differentiation of a selected group of VSD, and offers a good correlation with histopathological findings.
JDDG: Journal der Deutschen Dermatologischen GesellschaftVolume 14, Issue 12 p. 1201-1202 Editorial Haut und Rheuma Susann Patschan, Corresponding Author Susann Patschan susann.patschan@med.uni-goettingen.de Korrespondenzanschrift PD Dr. Susann Patschan Klinik für Nephrologie und Rheumatologie Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Göttingen E-mail: susann.patschan@med.uni-goettingen.de Prof. Dr. Cornelia S. Seitz Klinik für Dermatologie, Venerologie und Allergologie Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Göttingen E-mail: cseitz@med.uni-goettingen.deSearch for more papers by this authorCornelia S. Seitz, Corresponding Author Cornelia S. Seitz cseitz@med.uni-goettingen.de Korrespondenzanschrift PD Dr. Susann Patschan Klinik für Nephrologie und Rheumatologie Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Göttingen E-mail: susann.patschan@med.uni-goettingen.de Prof. Dr. Cornelia S. Seitz Klinik für Dermatologie, Venerologie und Allergologie Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Göttingen E-mail: cseitz@med.uni-goettingen.deSearch for more papers by this author Susann Patschan, Corresponding Author Susann Patschan susann.patschan@med.uni-goettingen.de Korrespondenzanschrift PD Dr. Susann Patschan Klinik für Nephrologie und Rheumatologie Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Göttingen E-mail: susann.patschan@med.uni-goettingen.de Prof. Dr. Cornelia S. Seitz Klinik für Dermatologie, Venerologie und Allergologie Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Göttingen E-mail: cseitz@med.uni-goettingen.deSearch for more papers by this authorCornelia S. Seitz, Corresponding Author Cornelia S. Seitz cseitz@med.uni-goettingen.de Korrespondenzanschrift PD Dr. Susann Patschan Klinik für Nephrologie und Rheumatologie Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Göttingen E-mail: susann.patschan@med.uni-goettingen.de Prof. Dr. Cornelia S. Seitz Klinik für Dermatologie, Venerologie und Allergologie Universitätsmedizin Göttingen Robert-Koch-Straße 40 37075 Göttingen E-mail: cseitz@med.uni-goettingen.deSearch for more papers by this author First published: 19 December 2016 https://doi.org/10.1111/ddg.13162Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. Volume14, Issue12December 2016Pages 1201-1202 RelatedInformation
Objective. Vasculopathy is a key factor in the pathophysiology of systemic sclerosis (SSc) and the main cause for Raynaud phenomenon (RP), digital ulcers (DU), and/or pulmonary arterial hypertension (PAH). It is so far unknown how patients with SSc are treated with vasoactive agents in daily practice. To determine to which extent patients with SSc were treated with different vasoactive agents, we used data from the German Network for Systemic Scleroderma registry. Methods. The data of 3248 patients with SSc were analyzed. Results. Patients were treated with vasoactive drugs in 61.1% of cases (1984/3248). Of these, 47.6% received calcium channel inhibitors, followed by 34.2% treated with angiotensin-converting enzyme (ACE) inhibitors, 21.1% treated with intravenous (IV) prostanoids, 10.1% with pentoxifylline, 8.8% with angiotensin 1 receptor antagonists (AT1RA), 8.7% with endothelin 1 receptor antagonists (ET1RA), 4.1% with phosphodiesterase type 5 (PDE5) inhibitors, and 5.3% with others. Patients with RP received vasoactive therapy in 63.3% of cases, with DU in 70.1%, and with PAH in 78.2% of cases. Logistic regression analysis revealed that patients with PAH were significantly more often treated with PDE5 inhibitors and ET1RA, and those with DU with ET1RA and IV prostanoids. In addition, 41.8% of patients were treated with ACE inhibitors and/or AT1RA. Patients registered after 2009 received significantly more often ET1RA, AT1RA, and IV prostanoids compared with patients registered prior to 2005. Conclusion. These data clearly indicate that many patients with SSc do not yet receive sufficient vasoactive therapy. Further, in recent years, a marked change of treatment regimens can be observed.
The transcription factor NF-κB exerts key functions in epidermal homeostasis and carcinogenesis. Its c-Rel subunit is expressed in squamous cell carcinoma, and c-Rel down-regulation results in increased apoptosis, G2/M cell cycle delay with reduced proliferation and aberrant mitotic spindle formation. To further study the impact of c-Rel on essential keratinocyte features such as migration and epithelial morphology, c-Rel was down-regulated in HaCaT keratinocytes by a siRNA approach. This inhibition of c-Rel impaired the keratinocyte-typical clustered growth leading to a more scattered appearance of the cultures. The cells were more spindle-shaped and elongated, albeit without expression changes of markers characteristic for epithelial mesenchymal transition. In addition, wound healing-related migration and adhesion to type I collagen, fibronectin, laminin and vitronectin were significantly impaired. On the sub-cellular level, these functional features were not associated with quantitatively altered adhesion receptor or Rho-GTPase expression, but rather with a significantly reduced length of cell-matrix adhesion complexes and altered appearance of filamentous actin. Thus, our studies support a role for c-Rel in processes crucial for keratinocyte integrity and malignant transformation such as adhesion and migration.
Due to its almost universal resistance to chemotherapy, metastasized melanoma remains a major challenge in clinical oncology. Given that phosphatidyl inositol‐3 kinase (PI3K) activation in melanoma cells is associated with poor prognosis, disease progression and resistance to chemotherapy, the PI3K‐Akt signalling pathway is a promising therapeutic target for melanoma treatment. We analysed six human melanoma cell lines for their constitutive activation of Akt and then tested two representative lines, A375 and LOX, for their susceptibility to PI3K‐inhibition by the highly specific small molecule inhibitor, BAY 80‐6946. In addition, the effect of BAY 80‐6946 on A375 and LOX melanoma cells was assessed in vivo in a xenotransplantation mouse model. We provide experimental evidence that specifically inhibiting the PI3K pathway and phosphorylation of Akt by this novel compound results in antitumoral activities including inhibition of proliferation, induction of apoptosis and cell cycle arrest in vitro and in vivo . However, the susceptibility did not show a clear‐cut pattern and differed between the melanoma cell lines tested, resulting in in vivo growth inhibition of A375 but not LOX melanoma cells. Thus, in some cases BAY 80‐6946 or related compounds may be a valuable addition to the therapeutic armamentarium.