Representation of skin carcinomas in public awareness - Awareness worldwide and in Germany.

BACKGROUND AND OBJECTIVES: In recent years, there has been an increase in skin cancer. The aim of this study was therefore to investigate the representation of skin cancer in public awareness worldwide and in Germany, and to determine whether Skin Cancer Awareness Month is represented in the search interests of the Internet-using population in the same way as Breast Cancer Awareness Month worldwide. DATA AND METHODS: In this study, Google Trends data were used to track levels of public awareness for different tumor entities and skin cancer types worldwide and for Germany. RESULTS: The results of this analysis clearly showed a high level of relative public search interest in breast cancer worldwide in the awareness month of October. Worldwide and in Germany, there was a certain increase in search interest and a certain seasonal effect around the May awareness month for skin cancer. For example, the analysis showed a search interest in May and during the summer months in Germany. CONCLUSIONS: It is likely that the population, for example in Germany, may benefit further from an even greater emphasis on the topic of skin cancer.

Multi-wavelength, handheld laser speckle imaging for skin evaluation.

OBJECTIVE: A handheld device was developed and qualified for in vivo human skin evaluation using laser speckle imaging technology. METHODS: Each laser speckle device prototype allows the choice of up to three different laser wavelengths in the range of 400 nm to 800 nm in total. Speckle pattern analysis gives various speckle parameters, for example, speckle contrast, speckle size, speckle modulation or fractal dimension. The developed laser speckle device prototypes were evaluated investigating three skin issues. RESULTS: We receive reproducible results from the speckle imaging device. For skin ageing, we found significant changes within three age groups. The effect of a methyl nicotinate treatment was clearly visible and quantifiable using a moorFLPI device as well as our speckle imaging device. In terms of basal cell carcinoma diagnosis, we found significant differences between normal and diseased skin, even though the number of samples was limited. CONCLUSION: As shown with first application examples, it was possible to demonstrate the potential of the method for skin evaluation in vivo.

Improving Post-Operative Outcomes in Aged and Diabetic Obese Mice.

Due to their small size, high metabolic rate, and large surface to volume ratio, mice are a challenge to work with surgically and pre-operatively. Working with mice that are more susceptible to anesthetic agents, aged, or obese (e.g., diabetic mice), provides even more challenges. In two separate studies, we found simple that supportive care measures during and after surgery improved post-operative outcomes.

Skin Regeneration Using Dermal Substrates that Contain Autologous Cells and Silver Nanoparticles to Promote Antibacterial Activity: In Vitro Studies.

We hypothesized that the addition of silver nanoparticles (AgNP) to a dermal substrate would impart antibacterial properties without inhibiting the proliferation of contained cells. Our in vitro model was based on the commercial substrate, Integra. The substrate was prepared by simple immersion into 0 to 1% suspension of AgNP (75 or 200 nm diameter) followed by rinsing for 20 minutes and sterilization under an ultraviolet C lamp. A total of 107 human adipose stem cells per cubic centimeter were injected and after 1 hour, 6 × 105 keratinocytes/cm2 were seeded and cultured for up to 14 days. Constructs were evaluated using a metabolic assay (WST-1), and hematoxylin and eosin and immunoperoxidase staining. Bactericidal activity was measured using a log reduction assay against bacteria that are prevalent in burns. The presence of AgNP did not significantly change the metabolic activity of constructs after 14 days of culture, and the distribution of cells within the substrate was unchanged from the controls that did not have AgNP. Antibacterial activity of Integra containing AgNP (75 nm diameter) was concentration dependent. In conclusion, the addition of AgNP to the dermal substrate suppressed bacterial growth but did not significantly affect cell proliferation, and may represent an important property to incorporate into a future clinical skin regeneration system.

Distinct Effects of Adipose-Derived Stem Cells and Adipocytes on Normal and Cancer Cell Hierarchy.

UNLABELLED: Adipose-derived stem cells (ASC) have received considerable attention in oncology because of the known direct link between obesity and cancer as well as the use of ASCs in reconstructive surgery after tumor ablation. Previous studies have documented how cancer cells commandeer ASCs to support their survival by altering extracellular matrix composition and stiffness, migration, and metastasis. This study focused on delineating the effects of ASCs and adipocytes on the self-renewal of stem/progenitor cells and hierarchy of breast epithelial cells. The immortalized breast epithelial cell line MCF10A, ductal carcinoma in situ (DCIS) cell lines MCF10DCIS.com and SUM225, and MCF10A-overexpressing SRC oncogene were examined using a mammosphere assay and flow cytometry for the effects of ASCs on their self-renewal and stem-luminal progenitor-differentiated cell surface marker profiles. Interestingly, ASCs promoted the self-renewal of all cell types except SUM225. ASC coculture or treatment with ASC conditioned media altered the number of CD49f(high)/EpCAM(low) basal/stem-like and CD49f(medium)/EpCAM(medium) luminal progenitor cells. Among multiple factors secreted by ASCs, IFNγ and hepatocyte growth factor (HGF) displayed unique actions on epithelial cell hierarchy. IFNγ increased stem/progenitor-like cells while simultaneously reducing the size of mammospheres, whereas HGF increased the size of mammospheres with an accompanying increase in luminal progenitor cells. ASCs expressed higher levels of HGF, whereas adipocytes expressed higher levels of IFNγ. As luminal progenitor cells are believed to be prone for transformation, IFNγ and HGF expression status of ASCs may influence susceptibility for developing breast cancer as well as on outcomes of autologous fat transplantation on residual/dormant tumor cells. IMPLICATIONS: This study suggests that the ratio of ASCs to adipocytes influences cancer cell hierarchy, which may impact incidence and progression. Mol Cancer Res; 14(7); 660-71. ©2016 AACR.

Proteomic analysis of endothelial cold-adaptation.

BACKGROUND: Understanding how human cells in tissue culture adapt to hypothermia may aid in developing new clinical procedures for improved ischemic and hypothermic protection. Human coronary artery endothelial cells grown to confluence at 37°C and then transferred to 25°C become resistant over time to oxidative stress and injury induced by 0°C storage and rewarming. This protection correlates with an increase in intracellular glutathione at 25°C. To help understand the molecular basis of endothelial cold-adaptation, isolated proteins from cold-adapted (25°C/72 h) and pre-adapted cells were analyzed by quantitative proteomic methods and differentially expressed proteins were categorized using the DAVID Bioinformatics Resource. RESULTS: Cells adapted to 25°C expressed changes in the abundance of 219 unique proteins representing a broad range of categories such as translation, glycolysis, biosynthetic (anabolic) processes, NAD, cytoskeletal organization, RNA processing, oxidoreductase activity, response-to-stress and cell redox homeostasis. The number of proteins that decreased significantly with cold-adaptation exceeded the number that increased by 2:1. Almost half of the decreases were associated with protein metabolic processes and a third were related to anabolic processes including protein, DNA and fatty acid synthesis. Changes consistent with the suppression of cytoskeletal dynamics provided further evidence that cold-adapted cells are in an energy conserving state. Among the specific changes were increases in the abundance and activity of redox proteins glutathione S-transferase, thioredoxin and thioredoxin reductase, which correlated with a decrease in oxidative stress, an increase in protein glutathionylation, and a recovery of reduced protein thiols during rewarming from 0°C. Increases in S-adenosylhomocysteine hydrolase and nicotinamide phosphoribosyltransferase implicate a central role for the methionine-cysteine transulfuration pathway in increasing glutathione levels and the NAD salvage pathway in increasing the reducing capacity of cold-adapted cells. CONCLUSIONS: Endothelial adaptation to mild-moderate hypothermia down-regulates anabolic processes and increases the reducing capacity of cells to enhance their resistance to oxidation and injury associated with 0°C storage and rewarming. Inducing these characteristics in a clinical setting could potentially limit the damaging effects of energy insufficiency due to ischemia and prevent the disruption of integrated metabolism at low temperatures.

Reduced artefacts and improved assessment of hyperintense brain lesions with BLADE MR imaging in patients with neurofibromatosis type 1.

BACKGROUND: Assessment of small brain lesions in children is often compromised by pulsation, flow or movement artefacts. MRI with a rotating blade-like k-space covering (BLADE, PROPELLER) can compensate for these artefacts. OBJECTIVE: We compared T2-weighted FLAIR images that were acquired with different k-space trajectories (conventional Cartesian and BLADE) to evaluate the impact of BLADE technique on the delineation of small or low-contrast brain lesions. MATERIALS AND METHODS: The subject group comprised 26 children with neurofibromatosis type 1 (NF 1), who had been routinely scanned at 1.5 T for optic pathway gliomas with both techniques and who had the typical hyperintense brain lesions seen in NF 1. Four experienced radiologists retrospectively compared unlabelled 4-mm axial images with respect to the presence of artefacts, visibility of lesions, quality of contour and contrast. RESULTS: Both techniques were comparable in depicting hyperintense lesions as small as 2 mm independent of contrast and edge definition. Pulsation and movement artefacts were significantly less common with BLADE k-space trajectory. In 7 of 26 patients (27%), lesions and artefacts were rated as indistinguishable in conventional FLAIR, but not in BLADE FLAIR images. CONCLUSION: BLADE imaging significantly improved the depiction of lesions in T2-W FLAIR images due to artefact reduction especially in the posterior fossa.

Hypothermic preconditioning of endothelial cells attenuates cold-induced injury by a ferritin-dependent process.

Hypothermia for myocardial protection or storage of vascular grafts may damage the endothelium and impair vascular function upon reperfusion/rewarming. Catalytic iron pools and oxidative stress are important mediators of cold-induced endothelial injury. Because endothelial cells are highly adaptive, we hypothesized that hypothermic preconditioning (HPC) protects cells at 0 degrees C by a heme oxygenase-1 (HO-1) and ferritin-dependent mechanism. Storage of human coronary artery endothelial cells at 0 degrees C caused the release of lactate dehydrogenase, increases in bleomycin-detectible iron (BDI), and increases in the ratio of oxidized/reduced glutathione, signifying oxidative stress. Hypoxia increased injury at 0 degrees C but did not increase BDI or oxidative stress further. HPC at 25 degrees C for 15-72 h attenuated these changes by an amount achievable by pretreating cells with 10-20 microM deferoxamine, an iron chelator, and protected cell viability. Treating cells with hemin chloride at 37 degrees C transiently increased intracellular heme, HO-1, BDI, and ferritin. Elevated heme/iron sensitized cells to 0 degrees C but ferritin was protective. HPC increased iron maximally after 2 h at 25 degrees C and ferritin levels peaked after 15 h. HO-1 was not induced. When HPC-mediated increases in ferritin were blocked by deferoxamine, protection at 0 degrees C was diminished. We conclude that HPC-mediated endothelial protection from hypothermic injury is an iron- and ferritin-dependent process.

Endothelial cell preservation at 10 degrees C minimizes catalytic iron, oxidative stress, and cold-induced injury.

There is growing evidence that oxidative stress plays an important role in mediating the injury induced by hypothermia during the preservation of cells and tissues for clinical or research use. In cardiovascular allografts, endothelial cell loss or injury may lead to impaired control of vascular permeability and tone, thrombosis, and inflammation. We hypothesized that hypothermia-induced damage to the endothelium is linked to increases in intracellular catalytic iron pools and oxidative stress. In this study, bovine aortic endothelial cells and cell culture methods were used to model the response of the endothelium of cardiovascular tissues to hypothermia. Confluent cells were stored at 0 degrees C to 25 degrees C and cell damage was measured by lipid peroxidation (LPO) and lactate dehydrogenase release. Varying the bleomycin-detectible iron (BDI) in cells modulated cold-induced LPO and cell injury. In untreated cells, injury was highest at 0 degrees C and a minimum at 10 degrees C. A similar temperature-dependent trend was found in BDI levels and cell plating efficiencies. Arrhenius plots of cell killing and iron accumulation rates showed biphasic temperature dependence, with minima at 10 degrees C and matching activation energies above and below 10 degrees C. These findings imply that the mechanisms underlying the hypothermic increase in catalytic iron, oxidative stress, and cell killing are the same and that preservation of the endothelium may be optimized at temperatures above those routinely used.

Lung preservation: pulmonary flush route affects bronchial mucosal temperature and expression of IFN-gamma and Gro in regional lymph nodes.

Optimal lung preservation via flush of the pulmonary vasculature minimizes early graft failure post-lung transplantation. We hypothesized that the route of pulmonary flush has differential effects on thermal gradients in the lung and expression of inflammatory mediators. Swine underwent antegrade flush (AG) via pulmonary artery; AG/RG: antegrade + retrograde flush via pulmonary veins or AG/BA: antegrade + bronchial artery flush via bronchial artery. Temperatures were recorded in bronchial mucosa and peribronchial lymph nodes. RT-PCR was utilized to detect cytokine gene expression in the nodes. AG/BA flush resulted in greatest cooling of bronchial mucosa and lymph nodes (p < 0.001). The route of flush did not affect expression of RANTES, MCP-1, IL-8, IL-1beta, TNF-alpha or IL-6. However, expression of Gro was reduced 4-h post-preservation in all groups. Only AG/BA resulted in decreased IFN-gamma transcripts. These data show that, compared to AG or AG/RG, AG/BA flush results in the greatest cooling of lung compartments and down regulates lymph node expression of a cytokine and chemokine that have key roles in inflammation and immunity. These data suggest that pulmonary flush via AG/BA during donor harvest may be optimal to decrease the risk of early graft failure.