Notch is a highly conserved transmembrane receptor that determines cell fate. Notch signaling denotes cleavage of the Notch intracellular domain, its translocation to the nucleus, and subsequent activation of target gene transcription. Involvement of Notch signaling in several cancers is well known, but its role in melanoma remains poorly characterized. Here we show that the Notch1 pathway is activated in human melanoma. Blocking Notch signaling suppressed whereas constitutive activation of the Notch1 pathway enhanced primary melanoma cell growth both in vitro and in vivo yet had little effect on metastatic melanoma cells. Activation of Notch1 signaling enabled primary melanoma cells to gain metastatic capability. Furthermore, the oncogenic effect of Notch1 on primary melanoma cells was mediated by β-catenin, which was upregulated following Notch1 activation. Inhibiting β-catenin expression reversed Notch1-enhanced tumor growth and metastasis. Our data therefore suggest a β-catenin-dependent, stage-specific role for Notch1 signaling in promoting the progression of primary melanoma.

In addition to producing sebum, sebocytes link lipid metabolism with inflammation at a cellular level and hence, greatly resemble adipocytes. However, so far no analysis was performed to identify and characterize the adipocyte-associated inflammatory proteins, the members of the adipokine family in sebocytes. Therefore, we determined the expression profile of adipokines (adiponectin, interleukin [IL]

Background Allergen immunotherapy (AIT) is considered a curative treatment in some atopic diseases, but in AD contradictory clinical results exist and the action of AIT has not been elucidated. In the literature, there is no evidence for parallel investigations of permeability barrier, cutaneous and blood immune responses after AIT in AD.Objectives The objective was to investigate immune parameters in the blood and skin and to detect clinical and barrier changes after AIT in AD.Methods Mild-to-moderate AD patients (n = 14) with concomitant allergic rhinitis to house dust mites were selected.All patients received topical treatment, while eight patients were randomly selected for adjuvant AIT also. At baseline and after 6 months, clinical, barrier and immunological investigations (serum and skin tests) were performed. In selected patients, biopsies from atopy patch tests (APTs) were analysed by immunohistochemistry for AD-relevant immune cells and mediators. ResultsIn the adjuvant AIT group, clinical parameters and barrier functions improved significantly. Blood immune parameters displayed no significant changes. Post-AIT APT became negative in all patients in the AIT group, but remained positive in the non-AIT group. Cutaneous dendritic cell and T-cell recruitment decreased significantly after allergen challenge in the AIT group, but no significant changes in skin or serum immunoglobulin E levels or prick test (SPT) reactivity were detected. Conclusions Allergen immunotherapy is a beneficial adjuvant treatment for sensitized AD patients. AIT improves not only clinical symptoms, but also permeability barrier functions. The effect of AIT on sensitization should be detected by APT, not by SPT.

Nijmegen breakage syndrome (NBS) is a rare autosomal recessive chromosomal instability syndrome characterized by severe immunodeficiency, growth retardation, microcephaly, a distinct facial appearance, and a high predisposition to lymphoid malignancy. We report a 7-year-old white girl with NBS associated with cutaneous tuberculosis. The patient presented with multiple red-brown, centrally scaring plaques on the leg and had neither pulmonary nor systemic manifestation of tuberculosis. Polymerase chain reaction testing using Mycobacterium genus- and Mycobacterium tuberculosis species-specific primers confirmed the clinical diagnosis of cutaneous tuberculosis. This is the first report describing the simultaneous presentation of NBS and cutaneous tuberculosis.

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