@article{Karavasili2019,

title = {Synergistic antitumor potency of a self-assembling peptide hydrogel for the local co-delivery of doxorubicin and curcumin in the treatment of head and neck cancer.},

author = {Christina Karavasili and Dimitrios A. Andreadis and Orestis L. Katsamenis and Emmanuel Panteris and Pinelopi Anastasiadou and Zacharias Kakazanis and Vasilis Zoumpourlis and Catherine K. Markopoulou and Sotirios Koutsopoulos and Ioannis S. Vizirianakis and Dimitrios G. Fatouros},

url = {https://pubs.acs.org/doi/10.1021/acs.molpharmaceut.8b01221},

doi = {10.1021/acs.molpharmaceut.8b01221},

issn = {1543-8392},

year  = {2019},

date = {2019-06-01},

journal = {Molecular pharmaceutics},

volume = {16},

number = {6},

issue = {6},

pages = {2326–2341},

publisher = {American Chemical Society (ACS)},

abstract = {Combination therapy has been conferred with manifold assets leveraging the synergy of different agents to achieve a sufficient therapeutic outcome with lower administered drug doses and reduced side effects. The therapeutic potency of a self-assembling peptide hydrogel for the co-delivery of doxorubicin and curcumin was assessed against head and neck cancer cells. The dual loaded peptide hydrogel enabled control over the rate of drug release based on drug's aqueous solubility. A significantly enhanced cell growth inhibitory effect was observed after treatment with the combination drug-loaded hydrogel formulations compared to the respective combination drug solution. The synergistic pharmacological effect of selected hydrogel formulations was further confirmed with enhanced apoptotic cell response, interference in cell cycle progression, and significantly altered apoptotic/anti-apoptotic gene expression profiles obtained in dose levels well below the half-maximal inhibitory concentrations of both drugs. The in vivo antitumor efficacy of the drug-loaded peptide hydrogel formulation was confirmed in HSC-3 cell-xenografted severe combined immunodeficient mice and visualized with μCT imaging. Histological and terminal deoxynucleotidyl transferase dUTP nick end labeling assay analyses of major organs were implemented to assess the safety of the topically administered hydrogel formulation. Overall, results demonstrated the therapeutic utility of the dual drug-loaded peptide hydrogel as a pertinent approach for the local treatment of head and neck cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Katsamenis2019,

title = {X-ray micro-computed tomography for non-destructive 3D X-ray histology},

author = {Orestis L Katsamenis and Michael Olding and Jane A Warner and David S Chatelet and Mark G Jones and Giacomo Sgalla and Bennie Smit and Oliver J Larkin and Ian Haig and Luca Richeldi and others},

url = {https://www.sciencedirect.com/science/article/pii/S0002944019302068},

doi = {https://doi.org/10.1016/j.ajpath.2019.05.004},

year  = {2019},

date = {2019-05-01},

journal = {The American journal of pathology},

publisher = {Elsevier},

abstract = {Historically, micro-computed tomography has been considered unsuitable for histological analysis of unstained formalin-fixed and paraffin-embedded (FFPE) soft tissue biopsies due to a lack of image contrast between the tissue and the paraffin. However, we recently demonstrated that μCT can successfully resolve microstructural detail in routinely prepared tissue specimens. Here, we illustrate how μCT imaging of standard FFPE biopsies can be seamlessly integrated into conventional histology workflows, enabling non-destructive three-dimensional (3D) X-ray histology, the use and benefits of which we showcase for the exemplar of human lung biopsy specimens. This technology advancement was achieved through manufacturing a first-of-kind μCT scanner for X-ray histology and developing optimised imaging protocols, which do not require any additional sample preparation. 3D X-ray histology allows for non-destructive 3D imaging of tissue microstructure, resolving structural connectivity and heterogeneity of complex tissue networks, such as the vascular or the respiratory tract. We also demonstrate that 3D X-ray histology can yield consistent and reproducible image quality, enabling quantitative assessment of tissue’s 3D microstructures, which is inaccessible to conventional two-dimensional histology. Being non-destructive the technique does not interfere with histology workflows, permitting subsequent tissue characterisation by means of conventional light microscopy-based histology, immunohistochemistry, and immunofluorescence. 3D X-ray histology can be readily applied to a plethora of archival materials, yielding unprecedented opportunities in diagnosis and research of disease.},

note = {In Press, Accepted Manuscript},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{karavasili2019synergistic,

title = {Synergistic anti-tumour potency of a self-assembling peptide hydrogel for the local co-delivery of doxorubicin and curcumin in the treatment of head and neck cancer},

author = {Christina Karavasili and Dimitrios A Andreadis and Orestis L Katsamenis and Emmanuel Panteris and Pinelopi Anastasiadou and Zacharias Kakazanis and Vasilis Zoumpourlis and Catherine K Markopoulou and Sotirios Koutsopoulos and Ioannis S Vizirianakis and others},

url = {https://pubs.acs.org/doi/abs/10.1021/acs.molpharmaceut.8b01221},

doi = {https://doi.org/10.1021/acs.molpharmaceut.8b01221},

year  = {2019},

date = {2019-01-01},

journal = {Molecular pharmaceutics},

publisher = {ACS Publications},

abstract = {Combination therapy has been conferred with manifold assets leveraging the synergy of different agents to achieve a sufficient therapeutic outcome with lower administered drug doses and reduced side effects. The therapeutic potency of a self-assembling peptide hydrogel for the co-delivery of doxorubicin and curcumin was assessed against head and neck cancer cells. The dual loaded peptide hydrogel enabled control over the rate of drug release based on drug’s aqueous solubility. A significantly enhanced cell growth inhibitory effect was observed after treatment with the combination drug-loaded hydrogel formulations compared to the respective combination drug solution. The synergistic pharmacological effect of selected hydrogel formulations was further confirmed with enhanced apoptotic cell response, interference in cell cycle progression, and significantly altered apoptotic/anti-apoptotic gene expression profiles obtained in dose levels well below the half-maximal inhibitory concentrations of both drugs. The in vivo antitumor efficacy of the drug-loaded peptide hydrogel formulation was confirmed in HSC-3 cell-xenografted severe combined immunodeficient mice and visualized with μCT imaging. Histological and terminal deoxynucleotidyl transferase dUTP nick end labeling assay analyses of major organs were implemented to assess the safety of the topically administered hydrogel formulation. Overall, results demonstrated the therapeutic utility of the dual drug-loaded peptide hydrogel as a pertinent approach for the local treatment of head and neck cancer.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Robinson2019,

title = {Correlative 3D Imaging and Microfluidic Modelling of Human Pulmonary Lymphatics using Immunohistochemistry and High-resolution μCT},

author = {Stephanie K. Robinson and Jonathan J. Ramsden and Jane Warner and Peter M. Lackie and Tiina Roose},

url = {https://www.nature.com/articles/s41598-019-42794-7#Ack1},

doi = {https://doi.org/10.1038/s41598-019-42794-7},

year  = {2019},

date = {2019-01-01},

journal = {Scientific reports},

volume = {9},

number = {1},

pages = {6415},

publisher = {Nature Publishing Group},

abstract = {Lung lymphatics maintain fluid homoeostasis by providing a drainage system that returns fluid, cells and metabolites to the circulatory system. The 3D structure of the human pulmonary lymphatic network is essential to lung function, but it is poorly characterised. Image-based 3D mathematical modelling of pulmonary lymphatic microfluidics has been limited by the lack of accurate and representative image geometries. This is due to the microstructural similarity of the lymphatics to the blood vessel network, the lack of lymphatic-specific biomarkers, the technical limitations associated with image resolution in 3D, and sectioning artefacts present in 2D techniques. We present a method that combines lymphatic specific (D240 antibody) immunohistochemistry (IHC), optimised high-resolution X-ray microfocus computed tomography (μCT) and finite-element mathematical modelling to assess the function of human peripheral lung tissue. The initial results identify lymphatic heterogeneity within and between lung tissue. Lymphatic vessel volume fraction and fractal dimension significantly decreases away from the lung pleural surface (p < 0.001},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Koo2018,

title = {Small airways disease in mild and moderate chronic obstructive pulmonary disease: a cross-sectional study.},

author = {Hyun-Kyoung Koo and Dragoş M Vasilescu and Steven Booth and Aileen Hsieh and Orestis L Katsamenis and Nick Fishbane and W Mark Elliott and Miranda Kirby and Peter Lackie and Ian Sinclair and Jane A Warner and Joel D Cooper and Harvey O Coxson and Peter D Paré and James C Hogg and Tillie-Louise Hackett},

doi = {10.1016/S2213-2600(18)30196-6},

issn = {2213-2619},

year  = {2018},

date = {2018-08-01},

journal = {The Lancet. Respiratory medicine},

volume = {6},

issue = {8},

pages = {591–602},

abstract = {The concept that small conducting airways less than 2 mm in diameter become the major site of airflow obstruction in chronic obstructive pulmonary disease (COPD) is well established in the scientific literature, and the last generation of small conducting airways, terminal bronchioles, are known to be destroyed in patients with very severe COPD. We aimed to determine whether destruction of the terminal and transitional bronchioles (the first generation of respiratory airways) occurs before, or in parallel with, emphysematous tissue destruction. In this cross-sectional analysis, we applied a novel multiresolution CT imaging protocol to tissue samples obtained using a systematic uniform sampling method to obtain representative unbiased samples of the whole lung or lobe of smokers with normal lung function (controls) and patients with mild COPD (Global Initiative for Chronic Obstructive Lung Disease [GOLD] stage 1), moderate COPD (GOLD 2), or very severe COPD (GOLD 4). Patients with GOLD 1 or GOLD 2 COPD and smokers with normal lung function had undergone lobectomy and pneumonectomy, and patients with GOLD 4 COPD had undergone lung transplantation. Lung tissue samples were used for stereological assessment of the number and morphology of terminal and transitional bronchioles, airspace size (mean linear intercept), and alveolar surface area. Of the 34 patients included in this study, ten were controls (smokers with normal lung function), ten patients had GOLD 1 COPD, eight had GOLD 2 COPD, and six had GOLD 4 COPD with centrilobular emphysema. The 34 lung specimens provided 262 lung samples. Compared with control smokers, the number of terminal bronchioles decreased by 40% in patients with GOLD 1 COPD (p=0·014) and 43% in patients with GOLD 2 COPD (p=0·036), the number of transitional bronchioles decreased by 56% in patients with GOLD 1 COPD (p=0·0001) and 59% in patients with GOLD 2 COPD (p=0·0001), and alveolar surface area decreased by 33% in patients with GOLD 1 COPD (p=0·019) and 45% in patients with GOLD 2 COPD (p=0·0021). These pathological changes were found to correlate with lung function decline. We also showed significant loss of terminal and transitional bronchioles in lung samples from patients with GOLD 1 or GOLD 2 COPD that had a normal alveolar surface area. Remaining small airways were found to have thickened walls and narrowed lumens, which become more obstructed with increasing COPD GOLD stage. These data show that small airways disease is a pathological feature in mild and moderate COPD. Importantly, this study emphasises that early intervention for disease modification might be required by patients with mild or moderate COPD. Canadian Institutes of Health Research.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Wollatz2017,

title = {3D Histopathology—a Lung Tissue Segmentation Workflow for Microfocus X-ray-Computed Tomography Scans},

author = {Lasse Wollatz and Steven J Johnston and Peter M Lackie and Simon J Cox},

url = {https://link.springer.com/article/10.1007/s10278-017-9966-5},

doi = {10.1007/s10278-017-9966-5},

year  = {2017},

date = {2017-01-01},

journal = {Journal of Digital Imaging},

pages = {1–10},

publisher = {Springer},

abstract = {Lung histopathology is currently based on the analysis of 2D sections of tissue samples. The use of microfocus X-ray-computed tomography imaging of unstained soft tissue can provide high-resolution 3D image datasets in the range of 2–10 μm without affecting the current diagnostic workflow. Important details of structural features such as the tubular networks of airways and blood vessels are contained in these datasets but are difficult and time-consuming to identify by manual image segmentation. Providing 3D structures permits a better understanding of tissue functions and structural interrelationships. It also provides a more complete picture of heterogeneous samples. In addition, 3D analysis of tissue structure provides the potential for an entirely new level of quantitative measurements of this structure that have previously been based only on extrapolation from 2D sections. In this paper, a workflow for segmenting such 3D images semi-automatically has been created using and extending the ImageJ open-source software and key steps of the workflow have been integrated into a new ImageJ plug-in called LungJ. Results indicate an improved workflow with a modular organization of steps facilitating the optimization for different sample and scan properties with expert input as required. This allows for incremental and independent optimization of algorithms leading to faster segmentation. Representation of the tubular networks in samples of human lung, building on those segmentations, has been demonstrated using this approach.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}

@article{Apps2016,

title = {Imaging Invasion: Micro-CT imaging of adamantinomatous craniopharyngioma highlights cell type specific spatial relationships of tissue invasion.},

author = {John R. Apps and J. Ciaran Hutchinson and Owen J. Arthurs and Alex Virasami and Abhijit Joshi and Berit Zeller-Plumhoff and Dale Moulding and Thomas S. Jacques and Neil J. Sebire and Juan Pedro Martinez-Barbera},

url = {https://actaneurocomms.biomedcentral.com/articles/10.1186/s40478-016-0321-8},

doi = {10.1186/s40478-016-0321-8},

issn = {2051-5960},

year  = {2016},

date = {2016-06-01},

journal = {Acta neuropathologica communications},

volume = {4},

issue = {1},

pages = {57},

abstract = {Tissue invasion and infiltration by brain tumours poses a clinical challenge, with destruction of structures leading to morbidity. We assessed whether micro-CT could be used to map tumour invasion in adamantinomatous craniopharyngioma (ACP), and whether it could delineate ACPs and their intrinsic components from surrounding tissue.Three anonymised archival frozen ACP samples were fixed, iodinated and imaged using a micro-CT scanner prior to the use of standard histological processing and immunohistochemical techniques.We demonstrate that micro-CT imaging can non-destructively give detailed 3D structural information of tumours in volumes with isotropic voxel sizes of 4-6 microns, which can be correlated with traditional histology and immunohistochemistry.Such information complements classical histology by facilitating virtual slicing of the tissue in any plane and providing unique detail of the three dimensional relationships of tissue compartments.},

keywords = {},

pubstate = {epublish},

tppubtype = {article}

}

@article{Jones2016,

title = {Three-dimensional characterization of fibroblast foci in idiopathic pulmonary fibrosis},

author = {Mark G Jones and Aurélie Fabre and Philipp Schneider and Francesco Cinetto and Giacomo Sgalla and Mark Mavrogordato and Sanjay Jogai and Aiman Alzetani and Ben G Marshall and Katherine MA O’Reilly and others},

url = {https://insight.jci.org/articles/view/86375},

doi = {10.1172/jci.insight.86375},

year  = {2016},

date = {2016-01-01},

journal = {JCI insight},

volume = {1},

number = {5},

publisher = {NIH Public Access},

abstract = {In idiopathic pulmonary fibrosis (IPF), the fibroblast focus is a key histological feature representing active fibroproliferation. On standard 2D pathologic examination, fibroblast foci are considered small, distinct lesions, although they have been proposed to form a highly interconnected reticulum as the leading edge of a “wave” of fibrosis. Here, we characterized fibroblast focus morphology and interrelationships in 3D using an integrated micro-CT and histological methodology. In 3D, fibroblast foci were morphologically complex structures, with large variations in shape and volume (range, 1.3 × 104 to 9.9 × 107 μm3). Within each tissue sample numerous multiform foci were present, ranging from a minimum of 0.9 per mm3 of lung tissue to a maximum of 11.1 per mm3 of lung tissue. Each focus was an independent structure, and no interconnections were observed. Together, our data indicate that in 3D fibroblast foci form a constellation of heterogeneous structures with large variations in shape and volume, suggesting previously unrecognized plasticity. No evidence of interconnectivity was identified, consistent with the concept that foci represent discrete sites of lung injury and repair.},

keywords = {},

pubstate = {published},

tppubtype = {article}

}