Thomas Vogt

Universität des Saarlandes, Saarbrücken, Saarland, Germany

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Publications (255)825.55 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Varicella zoster virus (VZV) establishes lifelong persistence and may reactivate in individuals with impaired immune function. To investigate immunologic correlates of protection and VZV-reactivation, specific immunity was characterized in 207 non-symptomatic immunocompetent and 132 immunocompromised individuals and compared to patients with acute herpes-zoster. VZV-specific CD4-T-cells were quantified flow-cytometrically after stimulation and characterized for expression of IFNγ, IL-2, and TNFα and surface-markers for differentiation (CD127) and anergy (CTLA-4, PD-1). IgG- and IgA-levels were quantified using ELISA. In healthy individuals, VZV-specific antibody- and T-cell-levels were age-dependent with highest median VZV-specific CD4-T-cell-frequencies of 0.108% (IQR 0.121%) during adolescence. VZV-specific T-cell-profiles were multifunctional with predominant expression of all three cytokines, CD127-positivity and low expression of CTLA-4 and PD-1. Non-symptomatic immunocompromised patients had similar VZV-specific immunological properties except for lower T-cell-frequencies (p<0.001) and restricted cytokine-expression. In contrast, significantly elevated antibody- and VZV-specific CD4-T-cell-levels were found in zoster-patients. Their specific T-cells showed a shift in cytokine-expression towards IFNγ-single-positivity, an increase in CTLA-4- and PD-1-, and a decrease in CD127-expression (all p<0.0001). This phenotype normalized after resolution of symptoms. In conclusion, VZV-specific CD4-T-cells in zoster-patients bear typical features of anergy. This phenotype is reversible and may serve as adjunct tool for monitoring VZV-reactivations in high-risk-patients.
    The Journal of infectious diseases. 09/2014;
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    ABSTRACT: Spontaneous melanoma phenotype switching is controlled by unknown environmental factors and may determine melanoma outcome and responsiveness to anti-cancer therapy. We show that Orai1 and STIM2 are highly expressed and control store operated Ca(2+) entry in human melanoma. Lower extracellular Ca(2+) or silencing of Orai1/STIM2 caused a decrease in intracellular Ca(2+) , which correlated with enhanced proliferation and increased expression of microphtalmia-associated-transcription-factor, a marker for proliferative melanoma phenotype. In contrast, the invasive and migratory potential of melanoma cells was reduced upon silencing of Orai1 and/or STIM2. Accordingly, markers for a non-proliferative, tumor-maintaining phenotype such as JARID1B and Brn2 decreased. Immunohistochemical staining of primary melanomas and lymph node metastases revealed a heterogeneous distribution of Orai1 and STIM2 with elevated expression in the invasive rim of the tumor. In summary, our results support a dynamic model in which Orai1 and STIM2 inversely control melanoma growth and invasion. Pharmacological tuning of Orai1 and particularly STIM2 might thus prevent metastatic spread and render melanomas more susceptible to conventional therapy. This article is protected by copyright. All rights reserved.
    Pigment Cell & Melanoma Research 01/2014; · 5.84 Impact Factor
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    ABSTRACT: Drug delivery via the hair follicle (HF) especially with nanoparticles (NP) recently gained attention due to a depot effect and facilitated absorption conditions within the lower HF. With the prospect of transdermal drug delivery, it is of interest to optimize the follicular uptake of NP. In this study, a method was developed to quantify NP uptake into HF and applied in vitro in a pig ear model and in vivo in human volunteers. The influence of NP material on HF uptake was investigated using fluorescence-labeled NP based on poly(d,l-lactide-co-glycolide) (PLGA). All NP had similar hydrodynamic sizes (163-170nm) but different surface modifications: (i) plain PLGA, (ii) chitosan-coated PLGA (Chit.-PLGA), and (iii) Chit.-PLGA coated with different phospholipids (PL) (DPPC (100), DPPC:Chol (85:15), and DPPC:DOTAP (92:8). Differential stripping was performed, including complete mass balance. The samples were extracted for fluorescence quantification. An effect of the PL coating on follicular uptake was observed as DPPC (100) and DPPC:DOTAP (92:8) penetrated into HF to a higher extent than the other tested NP. The effect was observed both in the pig ear model as well as in human volunteers, although it was statistically significant only in the in vitro model. An excellent in vitro-in vivo correlation (IVIVC, r(2)=0.987) between both models was demonstrated, further supporting the suitability of the pig ear model as a surrogate for the in vivo situation in humans for quantifying NP uptake into HF. These findings may help to optimize NP for targeting the HF and to improve transdermal delivery.
    Journal of Controlled Release 01/2014; · 7.63 Impact Factor
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    [Show abstract] [Hide abstract]
    ABSTRACT: Drug delivery via the hair follicle (HF) especially with nanoparticles (NP) recently gained attention due to a depot effect and facilitated absorption conditions within the lower HF. With the prospect of transdermal drug delivery it is of interest to optimize follicular uptake of NP. In this study a method was developed to quantify NP uptake into HF and applied in vitro in a pig ear model and in vivo in human volunteers. The influence of NP material on HF uptake was investigated using fluorescence labeled NP based on poly(D,L-lactide-co-glycolide) (PLGA). All NP had similar hydrodynamic sizes (163–170 nm) but different surface modifications: i) plain PLGA; ii) chitosan coated PLGA (Chit.-PLGA); and iii) Chit.-PLGA coated with different phospholipids (PL) (DPPC (100), DPPC: Chol (85: 15), DPPC: DOTAP (92: 8). Differential stripping was performed including complete mass balance. The samples were extracted for fluorescence quantification. An effect of the PL coating on follicular uptake was observed as DPPC (100) and DPPC: DOTAP (92: 8) penetrated into HF to a higher extent than the other tested NP. The effect was observed both in pig ear as well as in human volunteers, although it was statistically significant only in the in vitro model. An excellent in vitro in vivo correlation (IVIVC, r2 = 0.987) between both models was demonstrated, further supporting the suitability of the pig ear model as a surrogate for the in vivo situation in humans for quantifying NP uptake into HF. These findings may help to optimize NP for targeting the HF and to improve transdermal delivery.
    Journal of Controlled Release 01/2014; · 7.63 Impact Factor
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    ABSTRACT: P53 and its family members have been implicated in the direct regulation of the vitamin D receptor (VDR). Vitamin D- and p53-signaling pathways have a significant impact on spontaneous or carcinogen-induced malignant transformation of cells, with VDR and p53 representing important tumor suppressors. VDR and the p53/p63/p73 proteins all function typically as receptors or sensors that turn into transcriptional regulators upon stimulus, with the main difference being that the nuclear VDR is activated as a transcription factor after binding its naturally occurring ligand 1,25-dihydroxyvitamin D with high affinity while the p53 family of transcription factors, mostly in the nucleoplasm, responds to a large number of alterations in cell homeostasis commonly referred to as stress. An increasing body of evidence now convincingly demonstrates a cross-talk between vitamin D- and p53-signaling that occurs at different levels, has genome-wide implications and that should be of high importance for many malignancies, including non-melanoma skin cancer. One interaction involves the ability of p53 to increase skin pigmentation via POMC derivatives including alpha-MSH and ACTH. Pigmentation protects the skin against UV-induced DNA damage and skin carcinogenesis, yet on the other hand reduces cutaneous synthesis of vitamin D. A second level of interaction may be through the ability of 1,25-dihydroxyvitamin D to increase the survival of skin cells after UV irradiation. UV irradiation-surviving cells show significant reductions in thymine dimers in the presence of 1,25-dihydroxyvitamin D that are associated with increased nuclear p53 protein expression, and significantly reduced NO products. A third level of interaction is documented by the ability of vitamin D compounds to regulate the expression of the murine double minute 2 (MDM2) gene in dependence of the presence of wild-type p53. MDM2 has a well-established role as a key negative regulator of p53 activity. Finally, p53 and family members have been implicated in the direct regulation of VDR. This overview summarizes some of the implications of the cross-talk between vitamin D- and p53-signaling for carcinogenesis in the skin and other tissues.
    Frontiers in physiology. 01/2014; 5:166.
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    ABSTRACT: Abstract The β-blocker propranolol has become a valuable and effective drug for the treatment of infantile hemangiomas. Its therapeutic action probably results from vasoconstriction, blocking of angiogenesis through effects on vascular endothelial growth factor and induction of apoptosis. It is reasonable to suggest that propranolol can also be used effectively in the treatment of other vascular abnormalities. This case report describes propranolol treatment of vascular malformations such as Klippel-Trénaunay syndrome or Parkes-Weber syndrome in adults.
    Journal of Dermatological Treatment 12/2013; · 1.50 Impact Factor
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    ABSTRACT: : To present and define diagnostic criteria for primary cutaneous carcinosarcomas (CSs). Neoplasms of 6 patients with primary cutaneous CSs were retrospectively analyzed. A panel of histopathologic parameters and immunophenotypic expression of distinct markers of differentiation were investigated. All cases had medium-to-poorly differentiated squamous cell carcinoma representing the epithelial component intermingled with a variable amount of malignant sarcomatous tissue proliferation. The authors identified 3 distinct morphological criteria for the diagnosis of primary cutaneous CSs with features of (1) a clearly defined dual neoplasm with explicit morphological characterization using histology and immunohistochemistry with distinct marker panels while, (2) metastases from distant sites and true collision neoplasms must be excluded, and (3) recognition of the neoplasm as a solid coherent proliferation with careful exclusion of sarcomatous stromal changes in the surrounding neoplasm stroma has to be assured. The low incidence of this entity and a plethora of different synonymous terms in the dermatopathologic literature often cause diagnostic problems and hamper the accurate comparative analysis of cases published previously. Herein, the authors propose defining criteria and a clearly defined morphological approach to contribute to more accurate dermatopathologic diagnoses and provide an unprecedented summary on this neoplastic entity.
    The American Journal of dermatopathology 12/2013; · 1.30 Impact Factor
  • Journal der Deutschen Dermatologischen Gesellschaft 11/2013; 11(11). · 1.40 Impact Factor
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    ABSTRACT: Tumor-associated macrophages (TAMs) play essential roles in tumor progression and metastasis. Tumor cells recruit myeloid progenitors and monocytes to the tumor site, where they differentiate into TAMs; however, this process is not well studied in humans. Here we show that human CD7, a T cell and NK cell receptor, is highly expressed by monocytes and macrophages. Expression of CD7 decreases in M-CSF differentiated macrophages and in Melanoma-conditioned Medium Induced Macrophages (MCMI/Mφ) in comparison to monocytes. A ligand for CD7, SECTM1 (Secreted and transmembrane protein 1), is highly expressed in many tumors, including melanoma cells. We show that SECTM1 binds to CD7 and significantly increases monocyte migration by activation of the PI3K pathway. In human melanoma tissues, tumor-infiltrating macrophages expressing CD7 are present. These melanomas, with CD7-positive inflammatory cell infiltrations, frequently highly express SECTM1, including an N-terminal, soluble form, which can be detected in the sera of metastatic melanoma patients but not in normal sera. Taken together, our data demonstrate that CD7 is present on monocytes and tumor macrophages, and that its ligand, SECTM1, is frequently expressed in corresponding melanoma tissues, possibly acting as a chemoattractant for monocytes to modulate the melanoma microenvironment.Journal of Investigative Dermatology accepted article preview online, 24 October 2013; doi:10.1038/jid.2013.437.
    Journal of Investigative Dermatology 10/2013; · 6.19 Impact Factor
  • Journal der Deutschen Dermatologischen Gesellschaft 10/2013; 11(10). · 1.40 Impact Factor
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    ABSTRACT: Phlebologic diseases have become extremely common and have major socio-economic impact. However, the percentage of dermatologists working in phlebology appears to be decreasing according to the data of the German Society of Phlebology (DGP). To investigate the reasons for this development, we-on behalf of the DGP-sent a questionnaire to 120 German Departments of Dermatology in autumn 2012. In 76 returned questionnaires, the number of physicians with additional fellowship training in phlebology averaged 1.5; the average number of those who fulfill the criteria for training fellows in phlebology was 0.9. In 71.1 % of the departments there was a phlebologist. A special phlebologic outpatient clinic existed in 73.7 % of the departments. Sonography with Doppler (89.5 %) and duplex (86.8 %) was used as the most frequent diagnostic tool. For therapy, compression (94.7 %), sclerotherapy (liquid 78.9 %, foam 63.2 %, catheter 18.4 %), endoluminal thermic procedures (radio wave 28.9 %, laser 17.1 %) and surgery (especially crossectomy and stripping 67.1 %, phlebectomy of tributaries 75 %) were used. The average number of treatments was very heterogenous in the different departments. Phlebology definitely plays an important role in dermatology. Most departments fulfill the formal criteria for the license to conduct advanced training in phlebology. A wide spectrum of phlebological diagnostic and therapeutic procedures is available.
    Der Hautarzt 09/2013; 64(9):685-94. · 0.50 Impact Factor
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    ABSTRACT: With the number of tattoos increasing, a rising number of complications have also been reported, such as allergic and foreign body reactions or the development of malignant tumors. We discuss 19 patients with alterations in skin tattoos, define clinicopathologic characteristics and give a brief review of the literature. Biopsy specimens were obtained in 13 of 19 patients. In all cases, staining was performed with hematoxylin-eosin, periodic acid-Schiff, CD68, CD123, and CD163. The inflammatory infiltrate was classified according to the pattern analysis of Ackerman. Three of 19 patients (15.8%) had temporary tattoos with henna and 16 (84.2%) had permanent tattoos. Histologically, among the 13 biopsy specimens we found signs of acute contact dermatitis in 2 (15.3%), lupus-like patterns in 2 (15.3%), foreign body dermatitis in 5 (38.4%), deposition of pigment without inflammation or simple scarring in 2 (15.3%), and tumors in 2 patients (15.2%), 1 of which was a malignant melanoma. Clinical presentation frequently, but not always, correlates with the histologic pattern. Obtaining a biopsy can be helpful in determining further investigations, for example allergy testing or a search for systemic involvement in cases of tattoo sarcoidosis.
    Journal der Deutschen Dermatologischen Gesellschaft 08/2013; · 1.40 Impact Factor
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    ABSTRACT: The role of maspin has been discussed controversially in different tumors. In the majority of malignant tumors, maspin seems to act as a tumor suppressor. However, data about maspin expression as well as its function in melanoma are very inconsistent. To investigate the expression of maspin in melanomas and to correlate the intensity of maspin staining with prognostic parameters of the tumor and with progression-free and overall survival. Primary melanomas from 47 patients were investigated for maspin expression using immunohistochemistry. Maspin was heterogeneously expressed predominantly in the cytoplasm of melanoma cells. Maspin staining intensity in the invasive part of the tumor correlated with parameters of prognosis such as Clark level (p = 0.05), tumor thickness (p = 0.002) and stage of disease (p = 0.023). Maspin staining intensity in the invasive front of the tumor significantly correlated with death from disease (p = 0.007) and shortened overall survival (p = 0.007). In accordance with data concerning maspin expression in colorectal cancers, the expression of this protein in the invasive front of primary melanomas seems to correlate with local infiltration and tumor aggressiveness. Strong maspin expression in the invasive margin of primary melanomas therefore might reflect an aggressive tumor phenotype.
    Journal der Deutschen Dermatologischen Gesellschaft 07/2013; · 1.40 Impact Factor
  • Journal der Deutschen Dermatologischen Gesellschaft 07/2013; 11(7):686-688. · 1.40 Impact Factor
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    ABSTRACT: Despite success with BRAFV600E inhibitors, therapeutic responses in patients with metastatic melanoma are short-lived because of the acquisition of drug resistance. We identified a mechanism of intrinsic multidrug resistance based on the survival of a tumor cell subpopulation. Treatment with various drugs, including cisplatin and vemurafenib, uniformly leads to enrichment of slow-cycling, long-term tumor-maintaining melanoma cells expressing the H3K4-demethylase JARID1B/KDM5B/PLU-1. Proteome-profiling revealed an upregulation in enzymes of mitochondrial oxidative-ATP-synthesis (oxidative phosphorylation) in this subpopulation. Inhibition of mitochondrial respiration blocked the emergence of the JARID1B(high) subpopulation and sensitized melanoma cells to therapy, independent of their genotype. Our findings support a two-tiered approach combining anticancer agents that eliminate rapidly proliferating melanoma cells with inhibitors of the drug-resistant slow-cycling subpopulation.
    Cancer cell 06/2013; 23(6):811-25. · 25.29 Impact Factor
  • Journal der Deutschen Dermatologischen Gesellschaft 06/2013; 11(6). · 1.40 Impact Factor
  • Journal der Deutschen Dermatologischen Gesellschaft 06/2013; 11 Suppl 3:2-10. · 1.40 Impact Factor
  • Journal der Deutschen Dermatologischen Gesellschaft 06/2013; 11 Suppl 3:2-9. · 1.40 Impact Factor
  • Clinical and Experimental Dermatology 05/2013; · 1.33 Impact Factor
  • Journal der Deutschen Dermatologischen Gesellschaft 04/2013; · 1.40 Impact Factor

Publication Stats

3k Citations
825.55 Total Impact Points

Institutions

  • 2010–2014
    • Universität des Saarlandes
      • Department of Pharmacy
      Saarbrücken, Saarland, Germany
  • 2010–2013
    • Universitätsklinikum des Saarlandes
      Homburg, Saarland, Germany
  • 2012
    • Universitätsmedizin Göttingen
      • Department of Dermatology, Venereology and Allergology
      Göttingen, Lower Saxony, Germany
  • 2003–2012
    • University Hospital Regensburg
      • Klinik für Dermatologie
      Regensburg, Bavaria, Germany
  • 1995–2010
    • Universität Regensburg
      • Lehrstuhl für Dermatologie und Venerologie
      Regensburg, Bavaria, Germany
  • 1992
    • University of Wuerzburg
      Würzburg, Bavaria, Germany