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Supplementary Figures S1-S4. Figure S1. Limitations of fluorescence staining on melanoma tumor biopsy material. Figure S2. Equivalent circuit model for the tumor micro fragment - microcavity array system. Figure S3. Time and concentration dependent chemotherapeutic response pattern for tumor metastasis 2. Figure S4. Time and concentration dependent chemotherapeutic response pattern for tumor metastasis 2

Die IMspire150 Studie wurde als Phase III Zulassungsstudie konzipiert und sollte prüfen, ob es bei behandlungsnaiven erwachsenen Patienten mit BRAF-V600-mutierten metastasierten Melanomen (nicht resezierbares klinisches Stadium IIIC-IV, AJCC 2009) einen Unterschied macht, wenn die Erstlinientherapie allein mit der Kombination des BRAF-Inhibitors Vemurafenib (Vem) und dem MEK-Inhibitor Cobimetinib (Cobi) erfolgt oder um den PDL-1 Antikörper Atezolizumab ergänzt wird. Patienten mit unbehandelten oder fortschreitenden Melanom-Hirnmetastasen, anderen aktiven Tumorerkrankungen und schwerwiegenden Autoimmunerkrankungen in der Vorgeschichte wurden ausgeschlossen. Die Randomi­sierung erfolgte 1:1. Der LDH Wert wurde zur Stratifizierung verwendet, Nebenwirkungen wurden gemäß CTCAE 4.0 Kriterien erfasst und als primärer statistischer Endpunkt der Studie wurde das vom Studienarzt bewertete progressionsfreie Überleben (progression-free survival, PFS) gewählt. Die Zwischenanalyse des Gesamtüberlebens der Patienten erfolgte gemäß Protokoll zum Zeitpunkt der Primäranalyse des PFS. Sekundäre Endpunkte waren das PFS, bewertet durch ein unabhängiges Komitee, das objektive Ansprechen, die Dauer des Tumoransprechens, das Gesamtüberleben und die Zeit bis zur Verschlechterung des Gesamtbefindens bzw. der Organfunktionen der Patienten. In den 112 Studienzentren wurden 514 Patienten eingeschlossen (n = 256 Vem/Cobi+Atezolizumab; n = 258 Vem/Cobi); 79% aller Patienten wurden in Europa rekrutiert. In beiden Studienarmen waren ca. 77% der Patienten jünger als 65, hatten einen unauffälligen Allgemeinstatus (ECOG = 0), ca. 94% waren jeweils im Stadium IV (hiervon ca. 60% Stadium M1c) und je 33% hatten einen erhöhten LDH Wert. Zunächst erhielten alle Patienten in beiden Gruppen 2 x tgl. 960mg Vem (2 x tgl. jeweils 4 Tabletten mit 240mg Vem) plus 1 x tgl. 60mg Cobi (1 x tgl. 3 Tabletten mit 20mg Cobi) per os für 21 Tage. Dann wurde Vem bei den Patienten, die in den Atezolizumab-Arm randomisiert worden waren, auf 2 x tgl. 720mg reduziert (3 × 240mg Vem plus je eine Placebotablette), im anderen Arm bei 2 x tgl. 960mg belassen. Cobi wurde zulassungsgemäß in der letzten Woche der 28 Tage dauernden Behandlungszyklen pausiert. In der Atezolizumab-Gruppe erhielten die Patienten an Tag 1 und 15 jeweils 840mg Atezolizumab i.v., in der anderen Gruppe eine Placeboinfusion. Dosismodifikationen und –unterbrechungen waren für Vem und Cobi erlaubt, für Atezolizumab waren allein Behandlungsunterbrechungen erlaubt.

Background: The PROspective Cutaneous Lymphoma International Prognostic Index (PROCLIPI) study is a prospective analysis of an international database. Here we examine front-line treatments and quality of life (QoL) in patients with newly diagnosed mycosis fungoides (MF). Objectives: To identify (i) differences in first-line approaches according to tumour-nodes-metastasis-blood (TNMB) staging; (ii) parameters related to a first-line systemic approach and (iii) response rates and QoL measures. Methods: In total, 395 newly diagnosed patients with early-stage MF (stage IA–IIA) were recruited from 41 centres in 17 countries between 1 January 2015 and 31 December 2018 following central clinicopathological review. Results: The most common first-line therapy was skin-directed therapy (SDT) (322 cases, 81·5%), while a smaller percentage (44 cases, 11·1%) received systemic therapy. Expectant observation was used in 7·3%. In univariate analysis, the use of systemic therapy was significantly associated with higher clinical stage (IA, 6%; IB, 14%; IIA, 20%; IA–IB vs. IIA, P < 0·001), presence of plaques (T1a/T2a, 5%; T1b/T2b, 17%; P < 0·001), higher modified Severity Weighted Assessment Tool (> 10, 15%; ≤ 10, 7%; P = 0·01) and folliculotropic MF (FMF) (24% vs. 12%, P = 0·001). Multivariate analysis demonstrated significant associations with the presence of plaques (T1b/T2b vs. T1a/T2a, odds ratio 3·07) and FMF (odds ratio 2·83). The overall response rate (ORR) to first-line SDT was 73%, while the ORR to first-line systemic treatments was lower (57%) (P = 0·027). Health-related QoL improved significantly both in patients with responsive disease and in those with stable disease. Conclusions: Disease characteristics such as presence of plaques and FMF influence physician treatment choices, and SDT was superior to systemic therapy even in patients with such disease characteristics. Consequently, future treatment guidelines for early-stage MF need to address these issues.

The article deals with the exact measurement of wavelength intensities in the vicinity of the frequency of the light source at the output of the polarizing optic fiber sensor. A functional polarizing fiber optic temperature sensor is used as the measuring element, and the frequency variations are induced by a birefringence change in the fiber retaining polarization due to temperature changes. Different speed of light propagation in the two polarization planes of the polarization maintaining optical fiber was used to excite the birefringence. Highly detailed measurements show that the intensity peaks vary depending on the changing temperature of the optical fiber due to the changing birefringence. Thanks to accurate measuring instruments, the dependence between the instantaneous change in the polarization state and the change in the maximum intensity at given wavelengths were observed. The described measurement determines whether wavelength variations may be a suitable alternative to evaluating polarization changes, which in some situations is difficult and costly.

The aim of this work is to point out the current possibilities of using polarized light in sensor technology. Furthermore, the aim is to demonstrate the possibility of using the fiber sensor of thermal field disturbance as a truly feasible biomedical sensor applicable in medicine and especially to analyse different ways of measuring polarization changes. This paper concludes theoretical and experimental study deal with temperature response of birefringent fiber. It is supposed to use it for design of sensor of temperature disturbance. The paper follows up on the previous works, where the response of the birefringent PANDA fiber to thermal exposure in the temperature range from 0 to 48 °C was studied. These experiments analyzed the dynamic sensitivity characteristic of birefringent fiber for the process of thermal source apposition. The present paper brings a detailed comparative analysis of fiber response to the processes of apposition and the removal of thermal source, which are evaluated from the point of view of the system’s response after the ending of the thermal exposure. For practical use in fiber recovery analyses, the phase development rotation senses are described on the observable Poincare sphere.

The treatment of allergic reactions to red tattoo dye is challenging in most cases, as local therapy often does not offer long-term improvement and laser therapy is considered relatively contraindicated by many authors owing to the risk of generalized side effects. Therefore, surgical removal of these tattoos is favored; shave excision is the method of choice, particularly for the removal of the entire dye.The aim of this article was to retrospectively analyze the best post-operative outcome after surgical removal of allergic tattoo reactions using different excision techniques.We compared the different surgical procedures performed on seven patients with single and multiple allergic tattoo reactions treated between 2013 and 2018.The best aesthetic results were achieved by superficial ablation of the inflammatory reaction, partially leaving tattoo remains in the skin.Based on our experience with this small number of patients, a superficial removal of the tattoo without complete removal of the dye is, in most cases, sufficient to achieve healing. The remaining dye residues seem to be better tolerated by the immune system afterwards. Furthermore, the tattoo is often preserved in large parts.

Die Publikation von Dummer et al. beschreibt die Daten zur Effektivität und Sicherheit des Hedgehog pathway Inhibitors (HPI) Sonidegib in der abschließenden 42-Monatsanalyse der BOLT (basal cell carcinoma outcomes with LDE225 (sonidegib) treatment) Studie. Ursprünglich wurden 230 erwachsene, nicht systemisch mit HPI vorbehandelte Patienten mit Basalzellkarzinomen (BCC), die nicht für eine kurative chirurgische Behandlung oder eine Bestrahlung in Frage kamen, in 58 Zentren aus 12 Ländern zwischen dem 20. Juli 2011 und dem 10. Januar 2013 eingeschlossen. Die primäre Datenanalyse fand 6 Monate nach der Randomisierung des letzten Patienten statt. Diese wurden im Verhältnis 1:2 für die Behandlung mit 200mg (n = 79) oder 800mg (n = 151) Sonidegib pro Tag per os randomisiert. Auf eine zweckmäßige Vergleichstherapie wurde verzichtet, weil bei diesen Patienten mit lokal fortgeschrittenem Basalzellkarzinom (locally advanced Basal Cell Carcinoma, laBCC) oder metastasiertem Basalzellkarzinom (mBCC) keine Spontanremission zu erwarten sei und bei Beginn der Studie kein geeigneter Komparator zur Verfügung stand (die Zulassung von Vismodegib als HPI beim BCC erfolgte 2013). Die Behandlung erfolgte bis zum Fortschreiten der Erkrankung, dem Auftreten von nicht tolerabler Toxizität, bis zum Studienende, dem Rückzug des Einverständnisses oder dem Versterben der Patienten. In Bezug auf die Effektivität wurde das objektivierbare Tumoransprechen (Objective Response Rate, ORR) bei laBCC anhand von modifizierten RECIST (mRECIST) Kriterien durch ein zentrales Gutachterboard bewertet oder mithilfe der RECIST Kriterien bei mBCC. Die Sicherheitsanalyse wurde über die kontinuierliche Dokumentation und Überwachung der unerwünschten Ereignisse (adverse events, AE) vorgenommen.

Alexander Eggermont und Mitarbeiter haben die EORTC 1325/KEYNOTE-054 Studie [1] als Ausgangspunkt für weitere Untersuchungen gewählt. Sie gingen der Frage nach, ob das tumorfreie Überleben (relaps-free survival, RFS) bei Stadium III Melanom Patienten vom Auftreten immunologisch vermittelter unerwünschter Nebenwirkungen (immun-related adverse events, irAE) beeinflusst wird. Die EORTC 1325/KEYNOT-054 Studie vergleicht die Therapie mit dem Immuncheckpoint-Inhibitor (ICI) Pembrolizumab (Pem) zu Placebo. Eingeschlossen wurden nicht vorbehandelte Patienten im Stadium III (AJCC 2009) ohne bekannte Autoimmunerkrankungen, die mindestens eine Mikrometastase von 1mm Durchmesser im Sentinel-Lymphknoten hatten, eine komplettierende regionäre Lymphadenektomie erhalten hatten und bei Studieneinschluss tumorfrei waren. Pembrolizumab (200mg) wurde i.v. alle 3 Wochen für maximal 18 Gaben verabreicht. Von 1011 Patienten begannen 509 mit Pem und 505 mit Placebo , wobei Alter, Body-Mass-Index, Tumorstadien (IIIA, IIIB und IIIC), BRAF-Mutationsstatus und PD-L1 Expression in den Gruppen ohne signifikante Unterschiede waren [1]. Die irAE wurden in 3 Gruppen eingeteilt: 1.) endokrine AE (Hypo- oder Hyperthyreoidismus, Thyreoiditis, Hypophysitis, Diabetes mellitus Typ I, Niereninsuffizienz), 2.) Vitiligo und 3.) alle irAE (endokrine AE, Pneumonitis/interstitielle Lungenerkrankung, Sarcoidose, Vitiligo, schwere Hautreaktionen, Kolitis, Pankreatitis, Hepatitis, Nephritis, Uveitis, Myositis oder Myocarditis). Verschiedene statistische Rechenmodelle (z.B. Cox Regressionsmethode mit ergänzenden zeitvariablen Indikatoren) wurden zur Abschätzung der Assoziation vom Auftreten von irAE und RFS bei Patienten im Pem- und Placebo-Arm sowie zur Betrachtung des Einflusses einer systemischen Steroidgabe auf die Zielvariablen verwendet.

The paper deals with the analytical description of the sensitivity and dynamic characteristics of the birefringent fiber temperature response usable for realization of thermal field disturbance sensors. The response is given by changing the phase shift development between two polarization modes in birefringent fiber, caused by body heat transfer of different temperatures. The aim is to analyze sensitivity and dynamic behaviors, which are significant when optical fiber is used as a sensor of temperature field disturbance. The result shows a very good match with measured time responses, especially due to a specific arrangement for suppressing the influence of conduction and convection.

Introduction: Lentigo maligna (LM) is a rare form of in situ melanoma, frequently seen as a large patch in elderly patients. The aim of this study was to assess clinical and dermoscopic features of LM. Material and Methods: A retrospective study of LM patients presenting to our center between July 2007 and July 2017 was performed. Demographic data, anatomical location, laterality, diameter, Clark level, Breslow stage, ‘ABCD' signs and dermoscopic features were registered. Facial versus extrafacial LM were compared. Results: We found 21 LM, of which 12 had an extrafacial location and 9 a facial location. Half of the extrafacial lesions were located on an upper limb. The median age at diagnosis was 63 years (ranging from 38 to 84 years). Most LM cases were female (16/21) with phototype II (13/21). More than half of the patients (11/21) had a history of a skin neoplasm or actinic keratosis. The median diameter found was 6 mm (interquartile range = 4.5 mm), ranging from 1 to 15 mm. Five lesions were invasive (median Breslow depth of 0.2 mm), and 4 of them were extrafacial. Discussion: In this study LM was more frequently found in an extrafacial location and as a small patch with a 6-mm diameter medium. The epidemiology of LM/LM melanoma might be changing. Full body examination and dermoscopy are of the utmost importance for the diagnosis. Dermatologists should be aware and search for small lesions outside the face and neck, particularly in middle-aged female patients with photo-damaged skin.

Introduction: Lentigo maligna (LM) is a rare form of in situ melanoma, frequently seen as a large patch in elderly patients. The aim of this study was to assess clinical and dermoscopic features of LM. Material and Methods: A retrospective study of LM patients presenting to our center between July 2007 and July 2017 was performed. Demographic data, anatomical location, laterality, diameter, Clark level, Breslow stage, ‘ABCD' signs and dermoscopic features were registered. Facial versus extrafacial LM were compared. Results: We found 21 LM, of which 12 had an extrafacial location and 9 a facial location. Half of the extrafacial lesions were located on an upper limb. The median age at diagnosis was 63 years (ranging from 38 to 84 years). Most LM cases were female (16/21) with phototype II (13/21). More than half of the patients (11/21) had a history of a skin neoplasm or actinic keratosis. The median diameter found was 6 mm (interquartile range = 4.5 mm), ranging from 1 to 15 mm. Five lesions were invasive (median Breslow depth of 0.2 mm), and 4 of them were extrafacial. Discussion: In this study LM was more frequently found in an extrafacial location and as a small patch with a 6-mm diameter medium. The epidemiology of LM/LM melanoma might be changing. Full body examination and dermoscopy are of the utmost importance for the diagnosis. Dermatologists should be aware and search for small lesions outside the face and neck, particularly in middle-aged female patients with photo-damaged skin.

Stage III/IV melanoma remains incurable in most cases due to chemotherapeutic resistance. Thus, predicting and monitoring chemotherapeutic responses in this setting offer great interest. To overcome limitations of existing assays in evaluating the chemosensitivity of dissociated tumor cells, we developed a label-free monitoring system to directly analyze the chemosensitivity of undissociated tumor tissue. Using a preparation of tumor micro-fragments (TMF) established from melanoma biopsies, we characterized the tissue organization and biomarker expression by immunocytochemistry. Robust generation of TMF was established successfully and demonstrated on a broad range of primary melanoma tumors and tumor metastases. Organization and biomarker expression within the TMF were highly comparable with tumor tissue, in contrast to dissociated, cultivated tumor cells. Using isolated TMF, sensitivity to six clinically relevant chemotherapeutic drugs (dacarbazine, doxorubicin, paclitaxel, cisplatin, gemcitabine, and treosulfan) was determined by impedance spectroscopy in combination with a unique microcavity array technology we developed. In parallel, comparative analyses were performed on monolayer tumor cell cultures. Lastly, we determined the efficacy of chemotherapeutic agents on TMF by impedance spectroscopy to obtain individual chemosensitivity patterns. Our results demonstrated nonpredictable differences in the reaction of tumor cells to chemotherapy in TMF by comparison with dissociated, cultivated tumor cells. Our direct impedimetric analysis of melanoma biopsies offers a direct ex vivo system to more reliably predict patient-specific chemosensitivity patterns and to monitor antitumor efficacy. Cancer Res; 74(22); 6408–18. ©2014 AACR.

Den Sicherheitsanalysen von Sznol und Koautoren liegen die Daten von 448 Patienten der Dosiseskalations-Studie CA209-004 (Phase I) sowie der Phase-II- und III-Studien CheckMate 067 und CheckMate 069 zugrunde. Schadendorf und Koautoren wählten dagegen die 407 behandelten Patienten der CheckMate 067 und 069 Studien aus. In allen Studien war eine Induktionstherapie mit Nivolumab plus Ipilimumab sowie eine Konsolidierungstherapie nur mit Nivolumab vorgesehen. Sznol und Koautoren legen den Fokus auf die Häufigkeit, Schwere, Art und den zeitlichen Verlauf der Nebenwirkungen (NW) der immunonkologischen (I-O) Therapie. Sie unterscheiden allgemeine und vermutet immunologische NW. Schadendorf und Koautoren analysieren die Daten in Bezug auf die therapeutische Effektivität (progressionsfreies Überleben und Gesamtüberleben) und unterscheiden nach Patienten, welche die Therapie aufgrund von NW abbrachen versus diejenigen, die die I-O-Therapie fortführten.

Objectives: This study was aimed at investigating the prognostic role of multiple lymph node basin drainage (MLBD) in patients with positive sentinel lymph node (SLN) biopsy. Background: MLBD is frequently observed in patients with trunk melanoma undergoing SLN. The prognostic value of MLBD in SLN-positive patients is still debated. Methods: Retrospective data from 312 trunk melanoma patients with positive SLN biopsy (1991-2012) at 6 Italian referral centres were gathered in a multicentre database. MLBD was defined at preoperative lymphoscintigraphy. Clinical and pathological data were analysed for their association with disease-free interval (DFI) and disease-specific (DSS) survival. Results: MLBD was identified in 34.6% of patients (108/312) and was significantly associated with >1 positive SLN (37 vs. 15.2%; p < 0.001) and with >1 positive lymph node (LN) after complete lymph node dissection (CLND) (50.9 vs. 34.8%; p = 0.033). No differences were observed according to drainage pattern in patients who had negative and positive non-SLN at CLND. MLBD was not associated with either DFI or DSS. Multivariate analyses showed that tumour thickness, ulceration, and number of metastatic LNs were associated with worse DFI and DSS, while regression confirmed its protective role in survival. Conclusion: In positive SLN patients, MLBD has no association with survival, which is mainly related to American Joint Committee on Cancer (AJCC) prognostic factors. Since the overall number of positive LNs drives the prognosis, the importance of a CLND in all the positive basins is confirmed.

Long-wavelength UVA (340-400 nm UVA-1) phototherapy has been reported to be effective in atopic dermatitis, localized scleroderma and T-cell-derived skin diseases. We retrospectively investigated 70 patients with acute cutaneous GVHD after allogeneic haematopoietic cell transplantation or donor lymphocyte infusion. Complete and partial responses with a median duration of 10 months were achieved in 49 (70%) and 17 (24.3%) patients, respectively. Overall, 47 (67.1%) patients were not treated with systemic steroids. Furthermore, immunosuppression could be tapered in 24 (34.3%) patients while they were receiving UVA-1 treatment. Responses were seen irrespective of age or type of conditioning. Treatment was very well tolerated. After a median follow-up of 18 (range 10-60) months, three patients developed epithelial skin neoplasia. We conclude that UVA-1 therapy is feasible, well tolerated and can be an effective treatment for acute GVHD of the skin, thereby avoiding the use of systemic steroids and/or allowing a more rapid tapering of systemic immunosuppression in a substantial number of patients. The results of this retrospective analysis warrant larger, prospective studies and the effectiveness of UVA-1 therapy should be compared with other established treatment modalities.

Summary Background Basal cell carcinoma (BCC) is the most common malignant skin carcinoma. Fluorescence diagnosis (FD) has been suggested as a promising method for noninvasive detection of subclinical tumour cell dissemination in BCC. Objectives In this prospective study, we evaluated the clinical performance of a preoperative definition of the lateral borders of BCC by FD in comparison with its definition by purely clinical diagnosis (CD). The fluorescence intensity on the skin was recorded using a digital light-emitting diode-based fluorescence imaging system. Methods Twenty-six patients with BCC (22 with nodular subtype) of the H-zone were included. The tumour area was determined 3 h after application of methyl aminolaevulinate by inspection and photographic documentation (CD) and FD. Subsequently, BCCs were excised according to the complete area defined by CD and FD with a security margin of 3 mm; surgical specimens were sectioned horizontally and subjected to meticulous histological mapping. The tumour areas as determined by FD, CD and histology were superimposed to map the entire lateral tumour margin. Results The tumour area could be visualized by FD in 24 of 26 patients. The mean tumour area as determined by FD was significantly smaller than the tumour area as determined by CD [80 mm2, 95% confidence interval (CI) 50–110 mm2 vs. 101 mm2, 95% CI 76–125 mm2; P

Summary Basal cell carcinoma is the most common tumor in Central Europe, the U.S. and Australia. The increasing incidence of basal cell carcinoma presents the health care system, especially dermatology, with great challenges. In recent years new options for treating basal cell carcinoma have become available, enriching our therapeutic options. We review the current status of each of these treatment approaches.

ZusammenfassungDie Therapie von Varizen und der chronisch-venösen Insuffizienz ist multimodal. Neben der Kompressionstherapie und der systemischen medikamentösen Therapie gehören die Möglichkeiten der refluxausschaltenden invasiven Behandlungen der Varikose dazu. Wir berichten über einen Patienten, bei dem in einem einzeitigen, ambulanten Vorgehen drei insuffiziente Stammvenen mittels endovenöser Radiofrequenzablation (ClosureFAST ®) behandelt wurden.

Focal epithelial hyperplasia (FEH) or Heck disease is a rare skin disease caused by human papilloma viruses (HPV). The case of a 9-year old boy is presented to demonstrate the successful treatment of massive FEH with 5% imiquimod cream. Initially, the patient had noticed several separate papules, which spread and developed into multiple peri- and intraoral papillomatous nodules. The lesions were treated with carbon dioxide laser destruction. However, multiple, skin-coloured papillomatous nodules were found on the tongue, buccal mucosa and lips 1.5 years later. Treatment with imiquimod was initiated, because the patient suffered tremendously from the disease. 5 % imiquimod cream was applied 3 times per week. Regression of lesions was obvious after 1 month of treatment. Complete clearance was achieved after 2 additional months of treatment and no recurrence was detected over a follow-up period of 5 months. Our case points out the clinical value of imiquimod for the non-traumatic and almost painless therapy of HPV-induced skin diseases in children.

Background: Mutations of the stem cell factor receptor C-KIT play a major pathogenetic role in the development of different malignant diseases like human mastocytosis, myeloproliferative disorders, gastrointestinal stromal tumors, acute myelogenous leukemia, and sinonasal lymphomas. Furthermore, the expression of C-KIT has been described in Hodgkin's disease and nodal CD30+ anaplastic large cell lymphomas (ALCLs). As it is possible to inhibit C-KIT by innovative kinase inhibitors like STI571, it may be an attractive target for new therapeutical approaches. Therefore, we screened more than 50 different types of cutaneous T-cell lymphomas (TCLs) for the presence of C-KIT. Immunohistochemical stainings were performed on paraffin-embedded tissue sections using a polyclonal rabbit anti-human C-KIT antibody. Naphtol-ASD-chloroacetate esterase (NASDCE)-control stainings were performed on every positive sample to distinguish C-KIT-positive lymphoma cells from C-KIT-positive mast cells. Results: We found weak expression of C-KIT in seven of 18 patients with primary cutaneous CD30+ ALCL, two of eight patients with primary cutaneous pleomorphic TCL, six of 18 patients suffering from mycosis fungoides, and three of five patients with Sezary's syndrome. Generally, only a very small population of the lymphoma cells expressed C-KIT. This finding indicates a difference to the systemic variant of CD30+ ALCL. The potential use of C-KIT targeting new therapeutical approaches is therefore discussed critically, because C-KIT expression is very rare in all investigated types of primary cutaneous lymphoma.

Background Topical immunomodulatory therapy with imiquimod has been recently used for the treatment of actinic keratoses, intraepithelial carcinoma, and small basal cell carcinoma (BCC) besides the licensed indication of extragenital warts (condyloma). Methods We treated several patients with particular epidermal neoplasias such as squamous cell cancer (SCC) and basal cell cancer of sclerodermiform type three times per week for 4 to 12 weeks. Results We report several novel aspects of the treatment of epidermal cancers with self-applied, nonpainful, immunomodulatory therapy. First, we treated—for the first time—two immunosuppressed renal transplant patients for invasive SCC with imiquimod. Interestingly, systemic immunosuppression did not adversely affect the response to therapy. Second, one patient with the high-risk and aggressive growth pattern of basal cell cancer (sclerodermiform histology) was cured from his disease at a particular location in the face, suggesting sufficient penetration despite scarring. No recurrence was detected in another patient who suffered from 29 BCCs until almost 2-years follow-up. Third, the treatment of actinic keratoses in the face is substantially shorter (in the order of 4 to 6 weeks) as opposed to other skin cancers. Immunomodulatory treatment with imiquimod led to the demarcation of in situ actinic keratosis lesions that could not be identified using the dermatologist's experience, probably because of the existence of exclusive alterations on the molecular level. Conclusion Several novel aspects of immunomodulatory treatment with imiquimod and new indications such as selected cases of sclerodermiform BCC and SCC have been described. The texture of the skin at various different body locations may explain the varying sensitivities to imiquimod when facial skin is compared with skin on the extremities.

Keratinocytes have the ability to take up oligodeoxynucleotides (ODN) and plasmid DNA probably by receptor-mediated endocytosis. Despite the use of DNA for antisense and gene therapy little is known about the regulation of genes following exposure to nucleic acids. To systematically identify gene regulation in keratinocytes upon exposure to ODN we screened human cytokine DNA arrays containing 383 different genes and found interleukin (IL) 1alpha, IL-1beta, integrin-beta(1), alpha-tubulin, and follistatin highly induced, while most genes were unaffected. The time course and concentration dependence for IL-1alpha and follistatin expression were analyzed by standard northern blot technique. ODN of different length and sequence induced comparable amounts of IL-1alpha and follistatin. Their induction was independent of negative charge and of several proinflammatory compounds such as lipopolysaccharides, IL-1beta, and interferon-gamma but was partly inhibited by activin A. In summary, our study revealed several genes of the acute phase protein family that are induced in a non-sequence-specific manner following the exposure of normal human keratinocytes to ODN. Therefore it is tempting to speculate that upon internalization ODN bind to an intracellular receptor (e.g., Toll-like receptor 9) which mediates signaling.

Keratinocytes have the ability to take up oligonucleotides (ODN) and plasmid DNA probably by receptor-mediated endocytosis or macropinocytosis. Despite the use of DNA for antisense and gene therapy, little is known about the regulation of genes following exposure to nucleic acids. To systematically identify gene regulation in keratinocytes upon exposure to ODN, we screened human cytokine DNA arrays containing 383 different genes and found interleukin-1 alpha (IL-1 alpha), IL-1 beta, integrin beta1, alpha-tubulin and follistatin greatly induced, while most genes were unaffected. The time course and concentration dependence for IL-1 alpha and follistatin was confirmed by the standard Northern blot technique and found to be induced by picomolar or femtomolar concentrations of ODN. ODN of different length and sequence induced comparable amounts of IL-1 alpha and follistatin. Their induction was independent of the negative charge and of several proinflammatory compounds and proteins such as lipopolysaccharides, IL-1 beta or IFN-gamma, but was partly inhibited by activin A. In summary, our study revealed several genes of the acute phase protein family that were induced in a non-sequence-specific manner following the exposure of normal human keratinocytes to ODN. Therefore, it is tempting to speculate that, upon internalization, ODN bind to an intracellular receptor (e.g. Toll-like receptor 9), which mediates signaling.

This paper continues previous research work dealing with the study of sensor of thermal field disturbance. The utilization of polarization maintaining fiber (PMF) birefringence high sensitivity upon the temperature is taken in advantage. The effect of laser source wavelength and optical fiber beat length upon the fiber response invoked by disturbing temperature field is theoretically analyzed. The sensitivity of optical fiber response upon the temperature disturbing is experimentally verified. The optical fibers for wavelength 633 nm and 1550 nm with its beat length 2 mm and 5 mm are used in experiment. The experimental work was conducted for different lengths of disturbing temperature radiation sources from fiber-optic sensor and for different length of sensor exposed to the radiation. The relation of fiber response for the wavelength of 633 nm upon different magnitude of disturbing temperature radiation was also investigated. The particular results of experimental work are presented in this paper. The construction of sensor system with desired sensitivity and selection of its parameters can be done based on the obtained results.

Paper presents some results obtained by the measurement of polarization properties of fibers in the incidence of different external effects as temperature, torsion and magnetic field. To emphasize applied physical effect rare earth (Nd 3+ ) fiber has been used. Study of polarization is important from the polarization dispersion point of view for communication systems and also in the area of interferometric and polarization sensors, distributed sensors or general interferometric measurements. Analysis of individual effects is solved theoretically and practically in the series of works. Our contribution solves a relatively short part of fiber, where additionally fluctuation of power between both polarization modes could affect.

Mutations of the stem cell factor receptor C-KIT play a major pathogenetic role in the development of different malignant diseases like human mastocytosis, myeloproliferative disorders, gastrointestinal stromal tumors, acute myelogenous leukemia, and sinonasal lymphomas. Furthermore, the expression of C-KIT has been described in Hodgkin's disease and nodal CD30+ anaplastic large cell lymphomas (ALCLs). As it is possible to inhibit C-KIT by innovative kinase inhibitors like STI571, it may be an attractive target for new therapeutical approaches. Therefore, we screened more than 50 different types of cutaneous T-cell lymphomas (TCLs) for the presence of C-KIT. Immunohistochemical stainings were performed on paraffin-embedded tissue sections using a polyclonal rabbit anti-human C-KIT antibody. Naphtol-ASD-chloroacetate esterase (NASDCE)-control stainings were performed on every positive sample to distinguish C-KIT-positive lymphoma cells from C-KIT-positive mast cells.We found weak expression of C-KIT in seven of 18 patients with primary cutaneous CD30+ ALCL, two of eight patients with primary cutaneous pleomorphic TCL, six of 18 patients suffering from mycosis fungoides, and three of five patients with Sezary's syndrome. Generally, only a very small population of the lymphoma cells expressed C-KIT. This finding indicates a difference to the systemic variant of CD30+ ALCL. The potential use of C-KIT targeting new therapeutical approaches is therefore discussed critically, because C-KIT expression is very rare in all investigated types of primary cutaneous lymphoma.

A new software package, suitable for performing polarization analysis in optical networks is presented. The user can input any initial state of polarization using Jones and Stokes vectors, the polarization ellipse and the density matrix. Each device and optical network can be defined using Jones and Muller matrices, and the quaternions , which represents the device in terms of the four Pauli matrices. The final state of polarization is calculated, and presented using the methods mentioned above, as well as the graphical representation of the polarization ellipse and the Poincare sphere. The extension to first-order component defects in general ellipsometry is included. It can be used for educational and research purposes.

Except of specialists, dealing with different photonics areas, the education of all technical professionals about basic photonics principles, components, applications and system solutions is necessary. Paper deals with the place of photonics in the basic range of education and also in other facultative subjects developing the basic photonics knowledge to the area of systems solution. Photonics education is carried in the three steps: in electrical engineering subjects, in the facultative subjects and in the professional subjects. Basic professional spheres of electrical engineering student education could be as follows: theory of field, theory of signals, theory of information, electronic signals and systems, and electronic measurements. In Electrical Engineering and Electronics Department we offer two facultative subjects for different professions: Opto-electronics, and Fiber Optics. Both subjects are based on the lectures and also on the laboratory practice.

The aim of this paper is contribution to understanding of coupling between the polarization modes on the resultant transfer properties of single mode fiber given by the Jones matrix. In the case of ideal fiber it is possible to describe a propagation of the polarized optical wave by the Jones matrix and corresponding polarization eigenmodes with different propagation described by the Jones matrix are given not by the eigenmodes but by the principal states of polarization. Defined disturbance by the Jones matrix are given not by the eigenmodes but by the principal states of polarization. Defined disturbance along the whole fiber and also relatively defined variable coupling between the polarization modes it is possible to obtain by the torsion of fiber. Experimental evaluation of torsion effect by the Jones matrix elements can define the boundaries of application theory of polarization eigenmodes and principal states of polarization. These results can also contribute to understanding of conditions for polarization preserving of fiber and the development of polarization dispersion during disturbance of propagation conditions. Jones matrix elements have been measured on the working place published before and calculation and optimization of result are done by the use of software made for this purpose with the application of quaternions.

The infection of woodchucks with woodchuck hepatitis virus (WHV) provides an experimental model to study early immune responses during hepadnavirus infection that cannot be tested in patients. The T-cell response of experimentally WHV-infected woodchucks to WHsAg, rWHcAg, and WHcAg peptides was monitored by observing 5-bromo-2′-deoxyuridine and [2- 3 H]adenine incorporation. The first T-cell responses were directed against WHsAg 3 weeks after infection; these were followed by responses to rWHcAg including the immunodominant T-cell epitope of WHcAg (amino acids 97 to 110). Maximal proliferative responses were detected when the animals seroconvered to anti-WHs and anti-WHc (week 6). A decrease in the T-cell response to viral antigens coincided with clearance of viral DNA. Polyclonal rWHcAg-specific T-cell lines were established 6, 12, 18, and 24 weeks postinfection, and their responses to WHcAg peptides were assessed. Five to seven peptides including the immunodominant epitope were recognized throughout the observation period (6 months). At 12 months after infection, T-cell responses to antigens and peptides were not detected. Reactivation of T-cell responses to viral antigens and peptides occurred within 7 days after challenge of animals with WHV. These results demonstrate that a fast and vigorous T-cell response to WHsAg, rWHcAg, and amino acids 97 to 110 of the WHcAg occurs within 3 weeks after WHV infection. The peak of this response was associated with viral clearance and may be crucial for recovery from infection. One year after infection, no proliferation of T cells in response to antigens was observed; however, the WHV-specific T-cell response was reactivated after challenge of woodchucks with WHV and may be responsible for protection against WHV reinfection.