Immunohistochemical analysis of the mechanistic target of rapamycin and hypoxia signalling pathways in basal cell carcinoma and trichoepithelioma

Background: Basal cell carcinoma (BCC) is the most common cancer in Caucasians. Trichoepithelioma (TE) is a benign neoplasm that strongly resembles BCC. Both are hair follicle (HF) tumours. HFs are hypoxic microenvironments, therefore we hypothesized that hypoxia-induced signalling pathways could be involved in BCC and TE as they are in other human malignancies. Hypoxia-inducible factor 1 (HIF1) and mechanistic/mammalian target of rapamycin (mTOR) are key players in these pathways. Objectives: To determine whether HIF1/mTOR signalling is involved in BCC and TE. Methods: We used immunohistochemical staining of formalin-fixed paraffin-embedded BCC (n = 45) and TE (n = 35) samples to assess activity of HIF1, mTORC1 and their most important target genes. The percentage positive tumour cells was assessed manually in a semi-quantitative manner and categorized (0%, 80%). Results: Among 45 BCC and 35 TE examined, expression levels were respectively 81% and 57% (BNIP3), 73% and 75% (CAIX), 79% and 86% (GLUT1), 50% and 19% (HIF1 alpha), 89% and 88% (pAKT), 55% and 61% (pS6), 15% and 25% (pMTOR), 44% and 63% (PHD2) and 44% and 49% (VEGF-A). CAIX, Glut1 and PHD2 expression levels were significantly higher in TE when only samples with at least 80% expression were included. Conclusions: HIF and mTORC1 signalling seems active in both BCC and TE. There are no appreciable differences between the two with respect to pathway activity. At this moment immunohistochemical analyses of HIF, mTORC1 and their target genes does not provide a reliable diagnostic tool for the discrimination of BCC and TE

the prevention of chronic diseases through ehealth a practical overview

Disease prevention is an umbrella term embracing individual-based or population-based interventions aimed at preventing the manifestation of diseases (primary prevention), reducing the impact of a disease that has arisen (secondary prevention), or mitigating the impact of an ongoing illness (tertiary prevention). Digital health has the potential to improve prevention of chronic diseases. Its application ranges from effective mHealth weight-loss intervention to prevent or delay the onset of diabetes in overweight adults to the cost-effective intervention on the provision of mental-health care via mobile-based or Internet-based programs to reduce the incidence or the severity of anxiety. The present contribution focuses on the effectiveness of eHealth preventive interventions and on the role of digital health in improving health promotion and disease prevention. We also give a practical overview on how eHealth interventions have been effectively implemented, developed, and delivered for the primary, secondary, and tertiary prevention of chronic diseases

Maligne melanoom en voorstadia:Diagnostiek, behandeling en nazorg

Het meanoom is een van de meest agressieve vormen van huiskanker. Deze bijdrage geeft een overzicht van de verschillende typen melanoom en het klinische herkennen ervan, de diagnostiek, therapie en nazorg. Daarnaast komen potentiële voorlopers, zoals atypische/dysplastische en congenitale naevi, aan bod. Deze uiteenzetting heeft als doel huisartsen handvatten aan te reiken voor het herkennen en het behandelen dan wel tijdig verwijzen van patiënten met melanomen naar een dermatoloog. Deze vroege detectie met daaropvolgende behandeling is essentieel voor de te verwachten prognose

PpIX fluorescence kinetics and increased skin damage after intracutaneous injection of 5-aminolevulinic acid and repeated illumination

Photodynamic therapy with topically applied 5-aminolevulinic acid is used successfully for superficial skin lesions. The results for thicker, nodular lesions are less favorable. The method of aminolevulinic acid administration, the concentrations of aminolevulinic acid, and the irradiation schemes used so far have not been investigated thoroughly. As aminolevulinic acid photodynamic therapy has high potential for the increasing problem of skin cancer, we investigated both visually and histopathologically the photodynamic-therapy-induced skin damage after intracutaneous administration of aminolevulinic acid in normal porcine skin. We also investigated the kinetics of the aminolevulinic-acid-induced photosensitizer protoporphyrin IX fluorescence after irradiation in relation to fluence and irradiance. Finally we investigated the effect on photodynamic-therapy-induced damage of a fractionated irradiation. This study demonstrates that intracutaneous administration of aminolevulinic acid leads to higher fluorescence levels and thus to formation of higher protoporphyrin IX concentrations than topical application of aminolevulinic acid cream. The peak level of protoporphyrin IX after intracutaneous administration of aminolevulinic acid is reached earlier than after topical administration. The comeback of fluorescence, indicating re-synthesis of protoporphyrin IX after irradiation, is inhibited with increasing fluence. Photodynamic-therapy-induced damage increases with increasing fluence, but is independent of the irradiance. Finally, the photodynamic-therapy-induced skin damage seems to be greater after fractionated irradiations with two equal light fractions of 15 J per cm2 separated by a dark interval of 2 h