VOC pattern recognition of lung cancer: a comparative evaluation of different dog- and eNose-based strategies using different sampling materials.

Background: It has been reported that canine scent tests offer the possibility to screen for cancer. Assuming that breath samples can be collected with carrier materials, we tested the practicability of different carrier materials to be presented to dogs and validated and compared results with an electronic nose (eNose). Moreover, we hypothesized that cancer detection ability of dogs differs according to their working experience. Methods: In a methodological approach, two dog teams participated, one using experienced working dogs and the other ordinary household dogs to find the most qualified dogs and training method. To find best carrier material for breath sampling we compared charcoal containing glass tubes and fleece masks. In a second validating part, experienced working dogs were trained with improved training strategies. For breath sampling, two different, previously successfully tested fleece-based carrier materials were used: one was used with the dog team and both materials were compared with eNose. Results: In the methodological approach, it turned out that the charcoal-based sampling strategy qualified not sufficiently for VOC-detection. Moreover, we could determine that using experienced working dogs provided several advantages. Overall results of dogs in the validating part regarding specificity were 83%, regarding sensitivity 56%, but with great variability among dogs. Using eNose for breath analysis collected with both fleece carrier materials, specificity was 97% and sensitivity 89-100%. Conclusion: Our data confirmed that the diagnostic accuracy of dogs depended on the type of dog training and on the carrier materials. A comparison of breath samples analysis with an eNose achieved better results for both, sensitivity and specificity than for dogs. The use of fleece masks or fleeces in glass tubes as a sampling material can be recommended as successful VOC carriers, encouraging their use for clinical screenings.

Western diet in ApoE-LDLR double-deficient mouse model of atherosclerosis leads to hepatic steatosis, fibrosis, and tumorigenesis.

Nonalcoholic fatty liver disease has been linked to cardiovascular diseases and atherosclerosis. The aim of the current study was to characterize the hepatic pathology leading to fibrosis and tumors in a murine model of atherosclerosis. Male apolipoprotein E/low-density lipoprotein receptor double-knockout mice (AL) mice were fed with a high fat and high cholesterol western diet for 35 weeks (AL mice on WD). Protein and mRNA analysis as well as micro-computed tomography (micro-CT) were performed to assess oxidative stress, liver damage, inflammation, fibrosis, signaling pathways, vascularization, and tumorigenesis. Controls were chosen to distinguish between genetically and dietary effects in steatohepatitis and associated tumorigenesis. Hepatic inflammation and dyslipidemia were increased in AL mice on WD compared with wild-type mice on WD. Uniquely, AL mice on WD showed a spontaneous development of tumors (30% of cases) and thickening of intrahepatic vessel walls. Functionally relevant underlying signaling pathways such as NF-κB, Stat3, JNK, and AKT were differentially regulated between AL and wild-type mice on WD. Micro-CT was capable of visualizing and quantitatively distinguishing tumor neovascularization from vascularization in non-neoplastic liver tissue. AL mice on WD diet represent a novel model combining atherosclerosis and nonalcoholic fatty liver disease. Signaling pathways of liver cell damage and compensatory liver regeneration in combination with enhanced inflammation appear to be crucial for the spontaneous development of tumors in AL mice on WD. Micro-CT represents a new and powerful technique for the ultrastructural and three-dimensional assessment of the vascular architecture of liver tumors.