We are analyzing https://link.springer.com/article/10.1186/s13058-015-0664-2.

Title:
Increased peri-ductal collagen micro-organization may contribute to raised mammographic density | Breast Cancer Research
Description:
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.
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collagen, breast, pubmed, tissue, article, google, scholar, cancer, cas, density, high, central, patients, low, mammographic, study, proteins, analysis, fibrils, human, fig, data, force, cell, microscopy, matrix, tendon, ecm, afm, periductal, identified, regions, sections, abundance, risk, expression, assessed, tissues, samples, manchester, fibrillar, tumour, res, biol, staining, mass, content, extracellular, birefringence, fibril,

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differential gelc-ms/ms analysis her2-amplified breast cancers atomic force microscopy/spectroscopy computer-assisted mr imaging article download pdf x-ray imaging combined full size image twist1–g3bp2 mechanotransduction pathway custom-written rule sets e-stained paraffin section peri-ductal breast tissue long-term endocrine therapy contact-point-based model rat-tail tendon cryosections localised micro-mechanical stiffening comprising cell-rich epithelial larger-scale remodelling events e-stained breast biopsies peri-ductal collagen fibrils full-field digital mammograms radio-dense breast tissue liquid chromatography–mass spectrometry peri-ductal collagen remodelling plasma c-reactive protein 25-μm2 peri-ductal regions local micro-stiffness aromatase inhibitor-induced modulation cell-matrix research inter- -trypsin inhibitor filter-aided sample preparation psr/polarised light microscopy cd44+/cd24-/low cells glucose-6-phosphate isomerase nested case–control study heparin-binding glycoprotein periostin research tissue bank atomic force microscopy tumor-stromal collagen features large-scale tissue remodelling micro-mechanical stiffness collagen-rich fibroglandular tissue psr-stained cryosections cut o'brien rachael waddington & jane rogan utilised 5-μm-thick cryosections age-matched postmenopausal women 5 μm thick cryo-sections tumor extracellular matrices afm-derived collagen periodicity birefringent-positive tendon fibrils

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Genomic aberrations in normal tissue adjacent to HER2-amplified breast cancers: field cancerization or contaminating tumor cells?

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WebPage:
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         headline:Increased peri-ductal collagen micro-organization may contribute to raised mammographic density
         description: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. 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. 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. 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.
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            Mammographic density
            Collagen organisation
            Tissue micro-stiffness
            Atomic force microscopy
            Breast cancer
            Cancer risk
            Cancer Research
            Oncology
            Surgical Oncology
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      headline:Increased peri-ductal collagen micro-organization may contribute to raised mammographic density
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         Mammographic density
         Collagen organisation
         Tissue micro-stiffness
         Atomic force microscopy
         Breast cancer
         Cancer risk
         Cancer Research
         Oncology
         Surgical Oncology
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      affiliation:
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            address:
               name:Institute of Cancer Sciences, Manchester Academic Health Sciences Centre, University Hospital of South Manchester, University of Manchester, Manchester, UK
               type:PostalAddress
            type:Organization
      name:Michael J. Sherratt
      affiliation:
            name:University of Manchester
            address:
               name:Centre for Tissue Injury & Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
               type:PostalAddress
            type:Organization
      email:[email protected]
      name:Charles H. Streuli
      affiliation:
            name:University of Manchester
            address:
               name:Wellcome Trust Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Life Sciences, University of Manchester, Manchester, UK
               type:PostalAddress
            type:Organization
PostalAddress:
      name:Centre for Tissue Injury & Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
      name:Wellcome Trust Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Life Sciences, University of Manchester, Manchester, UK
      name:Wellcome Trust Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Life Sciences, University of Manchester, Manchester, UK
      name:Wellcome Trust Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Life Sciences, University of Manchester, Manchester, UK
      name:University Hospital of South Manchester, Manchester, UK
      name:University Hospital of South Manchester, Manchester, UK
      name:Wellcome Trust Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Life Sciences, University of Manchester, Manchester, UK
      name:Wellcome Trust Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Life Sciences, University of Manchester, Manchester, UK
      name:University Hospital of South Manchester, Manchester, UK
      name:Manchester Cancer Research Centre Tissue Biobank, University of Manchester, Manchester, UK
      name:Manchester Cancer Research Centre Tissue Biobank, University of Manchester, Manchester, UK
      name:Manchester Cancer Research Centre Tissue Biobank, University of Manchester, Manchester, UK
      name:Centre for Imaging Sciences, Institute of Population Health, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
      name:University Hospital of South Manchester, Manchester, UK
      name:Institute of Cancer Sciences, Manchester Academic Health Sciences Centre, University Hospital of South Manchester, University of Manchester, Manchester, UK
      name:Centre for Tissue Injury & Repair, Faculty of Medical and Human Sciences, University of Manchester, Manchester, UK
      name:Wellcome Trust Centre for Cell-Matrix Research and Manchester Breast Centre, Faculty of Life Sciences, University of Manchester, Manchester, UK

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