Increased peri-ductal collagen micro-organization may contribute to raised mammographic density

BACKGROUND: High mammographic density is a therapeutically modifiable risk factor for breast cancer. Although mammographic density is correlated with the relative abundance of collagen-rich fibroglandular tissue, the causative mechanisms, associated structural remodelling and mechanical consequences remain poorly defined. In this study we have developed a new collaborative bedside-to-bench workflow to determine the relationship between mammographic density, collagen abundance and alignment, tissue stiffness and the expression of extracellular matrix organising proteins. METHODS: Mammographic density was assessed in 22 post-menopausal women (aged 54–66 y). A radiologist and a pathologist identified and excised regions of elevated non-cancerous X-ray density prior to laboratory characterization. Collagen abundance was determined by both Masson’s trichrome and Picrosirius red staining (which enhances collagen birefringence when viewed under polarised light). The structural specificity of these collagen visualisation methods was determined by comparing the relative birefringence and ultrastructure (visualised by atomic force microscopy) of unaligned collagen I fibrils in reconstituted gels with the highly aligned collagen fibrils in rat tail tendon. Localised collagen fibril organisation and stiffness was also evaluated in tissue sections by atomic force microscopy/spectroscopy and the abundance of key extracellular proteins was assessed using mass spectrometry. RESULTS: Mammographic density was positively correlated with the abundance of aligned periductal fibrils rather than with the abundance of amorphous collagen. Compared with matched tissue resected from the breasts of low mammographic density patients, the highly birefringent tissue in mammographically dense breasts was both significantly stiffer and characterised by large (>80 μm long) fibrillar collagen bundles. Subsequent proteomic analyses not only confirmed the absence of collagen fibrosis in high mammographic density tissue, but additionally identified the up-regulation of periostin and collagen XVI (regulators of collagen fibril structure and architecture) as potential mediators of localised mechanical stiffness. CONCLUSIONS: These preliminary data suggest that remodelling, and hence stiffening, of the existing stromal collagen microarchitecture promotes high mammographic density within the breast. In turn, this aberrant mechanical environment may trigger neoplasia-associated mechanotransduction pathways within the epithelial cell population. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s13058-015-0664-2) contains supplementary material, which is available to authorized users

Economic importance and application options of some industrial sludge conditioned by different treatment methods

Industrial sludge was obtained from four industries: aluminium extrusion, brewery, pharmaceutical and textile processing factory and treated by aerobic, anaerobic, physicochemical, combinedaerobic/physicochemical and combined anaerobic/physicochemical methods. The results showed that the final destination of the sludge would determine the type and degree of treatment required for thesludge. Physicochemical method generally increases the quantity of sludge solids, thus making the sludge suitable for land reclamation; also, the firmer and denser floc characteristics of the physicochemicallly treated sludge makes the methods a better alternative if conditioned sludge are to be used to reinforce cement for brick making. Biological treatment methods (aerobic and anaerobic)can be used to reduce the quantity of sludge before disposal. Solids destruction is closely related to biogas production. If using sludge as a source of fuel is the focus, the anaerobic biological system maybe the best option. Aerobic biological method and the combined aerobic/physicochemical methods are good options for ammonia reduction. Anaerobic biological method is best for improving the nitrogen content and hence the protein content of sludge so as to use the waste sludge as feeds for poultry birds and livestock. Economic values, application and disposal options of the various sludge arediscussed