bluuebunny/crossref_metadata_2025_split huggingface dataset:
p21/waf1 and Smooth-Muscle Actin α Expression in Stromal Fibroblasts of Oral Cancers
Authors: Chatzistamou Ioulia , Dioufa Nikolina , Trimis George , Sklavounou Alexandra , Kittas Christos , Kiaris Hippokratis , Papavassiliou Athanasios G. 
Published: January 2015

Background: Concerted alterations between stromal fibroblasts and neoplastic cells underline the carcinogenic process. Activation of alpha-smooth muscle actin (SMA) expression, a cytoskeleton protein normally expressed only in myoepithelial cells, is considered a landmark for the activation of stromal fibroblasts with little however being known regarding the mechanism governing the expression of SMA in the stroma.Methods: We have evaluated by immunohistochemistry the expression of SMA in the stroma of oral malignant and pre-malignant lesions, in association with the expression of p53 and p21 tumor suppressors that were shown previously to be deregulated and/or mutated in stromal fibroblasts of various cancers. The effects of p21 knockdown in SMA expression and cell migration and the mRNA levels of endogenous p21 in fibroblasts co-cultured with cancer cells were also assessed.Results: We found that both p21 and SMA expression was elevated in the stroma, but not the epithelium, of malignant as compared to pre-malignant lesions. We also noted that the expression of both was positively correlated, implying that SMA expression may be regulated by p21. Consistently with this notion we found that siRNA-mediated p21 suppression resulted in the reduction of SMA levels and also inhibited cell migration.Conclusion: Our results show that p21 deregulation is associated with the activation of stromal fibroblasts of oral cancers by a mechanism that involves the stimulation of SMA expression.
Rapid Quantification of Myocardial Fibrosis: A New Macro-Based Automated Analysis
Authors: Hadi Awal M. , Mouchaers Koen T. B. , Schalij Ingrid , Grunberg Katrien , Meijer Gerrit A. , Vonk-Noordegraaf Anton , van der Laarse Willem J. , Beliën Jeroen A. M. 
Published: January 2015

Background: Fibrosis is associated with various cardiac pathologies and dysfunction. Current quantification methods are time-consuming and laborious. We describe a semi-automated quantification technique for myocardial fibrosis and validated this using traditional methods.Methods: Pulmonary Hypertension (PH) was induced in adult Wistar rats by subcutaneous monocrotaline (MCT) injection (40 mg/kg). Cryosections of myocardial tissue (5 μm) of PH rats (n=9) and controls (n=9) were stained using Picrosirius red and scanned with a digital microscopic Mirax slide scanner. From these sections 21 images were taken randomly of each heart. Using ImageJ software a macro for automated image analysis of the amount of fibrosis was developed. For comparison, fibrosis was quantified using traditional polarisation microscopy. Both methods were correlated and validated against stereology as the gold standard. Furthermore, the method was tested in paraffin-embedded human tissues.Results: Automated analysis showed a significant increase of fibrosis in PH hearts vs. control. Automated analysis correlated with traditional polarisation and stereology analysis (r2=0.92 and r2=0.95, respectively). In human heart, lungs, kidney and liver, a similar correlation with stereology (r2=0.91) was observed. Time required for automated analysis was 22 and 33% of the time needed for stereology and polarisation analysis, respectively.Conclusion: Automated quantification of fibrosis is feasible, objective and time-efficient.
Tumor Necrosis Factor-αis Associated with Positive Lymph Node Status in Patients with Recurrence of Colorectal Cancer – Indications for Anti-TNF-αAgents in Cancer Treatment
Authors: Grimm M. , Lazariotou M. , Kircher S. , Höfelmayr A. , Germer C. T. , von Rahden B. H. A. , Waaga-Gasser A. M. , Gasser M. 
Published: January 2015

Introduction: The progressive growth of malignancies is accompanied by a decline in the immune response through mechanisms which are poorly understood. Apoptosis and induction of inflammation by tumor released cytokines as tumor escape mechanisms have been proposed to play an important role in colorectal carcinogenesis.Methods: Expression of Tumor necrosis factor-alpha (TNF-α) was analyzed in colorectal cancer specimen and the cancer cell line HT-29 by immunohistochemistry and RT-PCR. TNF-αexpression on protein and mRNA level were correlated with clinical characteristics and impact on survival. TNFR-1 was co-labelled with TNF-αand CD8+ cytotoxic T cells in immunofluorescence double staining experiments.Results: 94% (n=98/104) of the patients with CRC expressed TNF-α. High TNF-αexpression was significantly associated with positive lymph node stage and recurrence of the tumor. Multivariate analysis revealed high TNF-αexpression as an independent prognostic factor. Immunohistochemistry was correlated with RT-PCR results (τ=0.794). Immunofluorescence double staining experiments revealed increased TNFR-1 expression by CD8+ cells.Conclusion: TNF-αexpression by tumor cells may be an efficient immunological escape mechanism by inflammation-enhanced metastases and probably by induction of apoptosis in tumor-infiltrating CD8+ immune cells resulting in a down regulation of the tumoral immune response. Our data support the role of tumor-derived TNF-αexpression as an important promoter of tumoral immune escape mechanisms and malignant progression, and suggest that analysis on either protein (immunohistochemistry) or RNA level (RT-PCR) can be used effectively in this respect. Targeting TNF-αmay be a promising option, especially in cases with high TNF-αexpression and positive lymph node metastases.
Inhibition of IGF-1R-Dependent PI3K Activation Sensitizes Colon Cancer Cells Specifically to DR5-Mediated Apoptosis But Not to rhTRAIL
Authors: Pennarun Bodvael , Kleibeuker Jan H. , Oenema Tjitske , Stegehuis Janet H. , de Vries Elisabeth G.E. , de Jong Steven 
Published: January 2015

Background: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) initiates apoptosis in tumor cells upon binding to its cognate agonistic receptors, death receptors 4 and 5 (DR4 and DR5). The activity of the insulin-like growth factor 1 (IGF-1) survival pathway is often increased in cancer, influencing both cell proliferation and apoptosis. We hypothesized that inhibiting the IGF-1 receptor (IGF-1R) using NVP-AEW541, a small molecular weight tyrosine kinase inhibitor of the IGF-1R, could increase death receptor (DR)-mediated apoptosis in colon cancer cells.Methods: The analyses were performed by caspase assay, flow cytometry, Western blotting, immunoprecipitation and fluorescent microscopy.Results: Preincubation with NVP-AEW541 surprisingly decreased apoptosis induced by recombinant human TRAIL (rhTRAIL) or an agonistic DR4 antibody while sensitivity to an agonistic DR5 antibody was increased. NVP-AEW541 could inhibit IGF-1-induced activation of the phosphatidylinositol 3-kinase (PI3K) pathway. The effects of the PI3K inhibitor LY294002 on TRAIL-induced apoptosis were similar to those of NVP-AEW541, further supporting a role for IGF-1R-mediated activation of PI3K. We show that PI3K inhibition enhances DR5-mediated caspase 8 processing but also lowers DR4 membrane expression and DR4-mediated caspase 8 processing. Inhibition of PI3K reduced rhTRAIL sensitivity independently of the cell line preference for either DR4- or DR5-mediated apoptosis signaling.Conclusion: Our study indicates that individual effects on DR4 and DR5 apoptosis signaling should be taken into consideration when combining DR-ligands with PI3K inhibition.
Virtual Microscopy Beyond the Pyramids, Applications of WSI in Cairo University for E-Education & Telepathology
Authors: Ayad Essam , Yagi Yukako 
Published: January 2015

Background: Telepathology, the practice of pathology at a long distance, has advanced continuously since 1986. The progress of telepathology passed through four stages: Static, Dynamic, Hybrid & Whole Slide Imaging.Materials and Methods: A pilot project between the Italian Hospital in Cairo & the Civico Hospital in Palermo was completed successfully, applying the static & dynamic techniques of telepathology. This project began in 2003 and continued till now. In 2004, centers in Venice, London and Pittsburgh participated actively in our project.Results: Over eight years we consulted on many problematic pathological cases with specialized pathological centers in Italy, UK & USA. In addition to the highly specialized scientific value, we saved a lot of time and money.Conclusion: We concluded from our experience that telepathology is a very useful and applicable tool for additional consulting on difficult pathological cases especially for emerging countries. In view of this success we have already established our Digital Telepathology Unit in Cairo University, using the WSI technique in teaching which was greatly successful and encouraged us to build a huge digital pathology library which will expand our telepathology & E-learning programs to cover staff and students in Egypt and Eastern Mediterranean.
Integration of Architectural and Cytologic Driven Image Algorithms for Prostate Adenocarcinoma Identification
Authors: Hipp Jason , Monaco James , Kunju L. Priya , Cheng Jerome , Yagi Yukako , Rodriguez-Canales Jaime , Emmert-Buck Michael R. , Hewitt Stephen , Feldman Michael D. , Tomaszewski John E. , Toner Mehmet , Tompkins Ronald G. , Flotte Thomas , Lucas David , Gilbertson John R. , Madabhushi Anant , Balis Ulysses 
Published: January 2015

Introduction: The advent of digital slides offers new opportunities within the practice of pathology such as the use of image analysis techniques to facilitate computer aided diagnosis (CAD) solutions. Use of CAD holds promise to enable new levels of decision support and allow for additional layers of quality assurance and consistency in rendered diagnoses. However, the development and testing of prostate cancer CAD solutions requires a ground truth map of the cancer to enable the generation of receiver operator characteristic (ROC) curves. This requires a pathologist to annotate, or paint, each of the malignant glands in prostate cancer with an image editor software - a time consuming and exhaustive process.Recently, two CAD algorithms have been described: probabilistic pairwise Markov models (PPMM) and spatially-invariant vector quantization (SIVQ). Briefly, SIVQ operates as a highly sensitive and specific pattern matching algorithm, making it optimal for the identification of any epithelial morphology, whereas PPMM operates as a highly sensitive detector of malignant perturbations in glandular lumenal architecture.Methods: By recapitulating algorithmically how a pathologist reviews prostate tissue sections, we created an algorithmic cascade of PPMM and SIVQ algorithms as previously described by Doyle el al. [1] where PPMM identifies the glands with abnormal lumenal architecture, and this area is then screened by SIVQ to identify the epithelium.Results: The performance of this algorithm cascade was assessed qualitatively (with the use of heatmaps) and quantitatively (with the use of ROC curves) and demonstrates greater performance in the identification of malignant prostatic epithelium.Conclusion: This ability to semi-autonomously paint nearly all the malignant epithelium of prostate cancer has immediate applications to future prostate cancer CAD development as a validated ground truth generator. In addition, such an approach has potential applications as a pre-screening/quality assurance tool.
Targeting Focal Adhesion Assembly by Ethoxyfagaronine Prevents Lymphoblastic Cell Adhesion to Fibronectin
Authors: Ouchani F. , Devy J. , Rusciani A. , Helesbeux J. J. , Salesse S. , Letinois I. , Gras-Billart D. , Duca L. , Duval O. , Martiny L. , Charpentier E. 
Published: January 2015

Background: Leukemic cell adhesion to proteins of the bone marrow microenvironment provides signals which control morphology, motility and cell survival. We described herein the ability of ethoxyfagaronine (etxfag), a soluble synthetic derivative of fagaronine, to prevent leukemic cell adhesion to fibronectin peptide (FN/V).Methods: Phosphorylation of fak and pyk2 were evaluated by immunoblotting. Labelled proteins were localized by confocal microscopy. PI 3-kinase activity was evaluated byin vitrokinase assay.Results: Subtoxic concentration of etxfag reduced L1210 cell adhesion to FN/V dependently of β1 integrin engagement. Etxfag impaired FN-dependent formation of β1 clustering without modifying β1 expression at the cell membrane. This was accompanied by a decrease of focal adhesion number, a diminution of fak and pyk2 phosphorylation at Tyr-576, Tyr-861 and Tyr-579, respectively leading to their dissociations from β1 integrin and inhibition of PI 3-kinase activity. Etxfag also induced a cell retraction accompanied by a redistribution of phosphorylated fak and pyk2 in the perinuclear region and lipid raft relocalization.Conclusion: Through its anti-adhesive potential, etxfag, combined with conventional cytotoxic drugs could be potentially designed as a new anti-leukemic drug.
The Prognostic Value of Adaptive Nuclear Texture Features from Patient Gray Level Entropy Matrices in Early Stage Ovarian Cancer
Authors: Nielsen Birgitte , Albregtsen Fritz , Kildal Wanja , Abeler Vera M. , Kristensen Gunnar B. , Danielsen Håvard E. 
Published: January 2015

Background: Nuclear texture analysis gives information about the spatial arrangement of the pixel gray levels in a digitized microscopic nuclear image, providing texture features that may be used as quantitative tools for prognosis of human cancer. The aim of the study was to evaluate the prognostic value of adaptive nuclear texture features in early stage ovarian cancer.Methods: 246 cases of early stage ovarian cancer were included in the analysis. Isolated nuclei (monolayers) were prepared from 50 μm tissue sections and stained with Feulgen-Schiff. Local gray level entropy was measured within small windows of each nuclear image and stored in gray level entropy matrices. A compact set of adaptive features was computed from these matrices.Results: Univariate Kaplan-Meier analysis showed significantly better relapse-free survival (p < 0.001) for patients with low adaptive feature values compared to patients with high adaptive feature values. The 10-year relapse-free survival was about 78% for patients with low feature values and about 52% for patients with high feature values. Adaptive features were found to be of independent prognostic significance for relapse-free survival in a multivariate analysis.Conclusion: Adaptive nuclear texture features from entropy matrices contain prognostic information and are of independent
prognostic significance for relapse-free survival in early stage ovarian cancer.
An Ultra-High Speed Whole Slide Image Viewing System
Authors: Yagi Yukako , Yoshioka Shigeatsu , Kyusojin Hiroshi , Onozato Maristela , Mizutani Yoichi , Osato Kiyoshi , Yada Hiroaki , Mark Eugene J. , Frosch Matthew P. , Louis David N. 
Published: January 2015

Background: One of the goals for a Whole Slide Imaging (WSI) system is implementation in the clinical practice of pathology. One of the unresolved problems in accomplishing this goal is the speed of the entire process, i.e., from viewing the slides through making the final diagnosis. Most users are not satisfied with the correct viewing speeds of available systems. We have evaluated a new WSI viewing station and tool that focuses on speed.Method: A prototype WSI viewer based on PlayStation®3 with wireless controllers was evaluated at the Department of Pathology at MGH for the following reasons: 1. For the simulation of signing-out cases; 2. Enabling discussion at a consensus conference; and 3. Use at slide seminars during a Continuing Medical Education course.Results: Pathologists were being able to use the system comfortably after 0–15 min training. There were no complaints regarding speed. Most pathologists were satisfied with the functionality, usability and speed of the system. The most difficult situation was simulating diagnostic sign-out.Conclusion: The preliminary results of adapting the Sony PlayStation®3 (PS3®) as an ultra-high speed WSI viewing system were promising. The achieved speed is consistent with what would be needed to use WSI in daily practice.
Using Computerized Workflow Simulations to Assess the Feasibility of Whole Slide Imaging Full Adoption in a High-Volume Histology Laboratory
Authors: McClintock David S. , Lee Roy E. , Gilbertson John R. 
Published: January 2015

Background: Whole slide Imaging (WSI) has been touted by many as the future of pathology, with estimates of full adoption occurring sometime in the next 5 to 15 years. While WSI devices have become increasingly capable since their inception, there has been little consideration of how WSI will be implemented and subsequently affect the workflow of high volume histology laboratories.Methods: Histology workflow process data was collected from a high-volume histology laboratory (Massachusetts General Hospital) and a process model developed using business process management software. Computerized workflow simulations were performed and total histology process time evaluated under a number of different WSI conditions.Results: Total histology process time increased approximately 10-fold to 20-fold over baseline with the presence of one WSI robot in the histology workflow. Depending on the specifications of the WSI robot, anywhere from 9 to 14 WSI robots were required within the histology workflow to minimize the effects of WSI.Conclusion: Placing a WSI robot into the current workflow of a high-volume histology laboratory with the intent of full adoption is not feasible. Implementing WSI without making significant changes to the current workflow of the histology laboratory would prove to be both disruptive and costly to surgical pathology.
Standardization Efforts of Digital Pathology in Europe
Authors: Rojo Marcial García , Daniel Christel , Schrader Thomas 
Published: January 2015

Background: EURO-TELEPATH is a European COST Action IC0604. It started in 2007 and will end in November 2011. Its main objectives are evaluating and validating the common technological framework and communication standards required to access, transmit, and manage digital medical records by pathologists and other medical specialties in a networked environment.Business Modelling: Working Group 1, “Business Modelling in Pathology,” has designed main pathology processes – Frozen Study, Formalin Fixed Specimen Study, Telepathology, Cytology, and Autopsy – using Business Process Modelling Notation (BPMN).Informatics Standards in Pathology: Working Group 2 has been dedicated to promoting the application of informatics standards in pathology, collaborating with Integrating Healthcare Enterprise (IHE), Digital Imaging and Communications in Medicine (DICOM), Health Level Seven (HL7), and other standardization bodies.Conclusion: Health terminology standardization research has become a topic of great interest. Future research work should focus on standardizing automatic image analysis and tissue microarrays imaging.
Multifractal Feature Descriptor for Histopathology
Authors: Atupelage Chamidu , Nagahashi Hiroshi , Yamaguchi Masahiro , Sakamoto Michiie , Hashiguchi Akinori 
Published: January 2015

Background: Histologic image analysis plays an important role in cancer diagnosis. It describes the structure of the body tissues and abnormal structure gives the suspicion of the cancer or some other diseases. Observing the structural changes of these chaotic textures from the human eye is challenging process. However, the challenge can be defeat by forming mathematical descriptor to represent the histologic texture and classify the structural changes via a sophisticated computational method.Objective: In this paper, we propose a texture descriptor to observe the histologic texture into highly discriminative feature space.Methods: Fractal dimension describes the self-similar structures in different and more accurate manner than topological dimension. Further, the fractal phenomenon has been extended to natural structures (images) as multifractal dimension. We exploited the multifractal analysis to represent the histologic texture, which derive more discriminative feature space for classification.Results: We utilized a set of histologic images (belongs to liver and prostate specimens) to assess the discriminative power of the multifractal features. The experiment was organized to classify the given histologic texture as cancer and non-cancer. The results show the discrimination capability of multifractal features by achieving approximately 95% of correct classification rate.Conclusion: Multifractal features are more effective to describe the histologic texture. The proposed feature descriptor showed high classification rate for both liver and prostate data sample datasets.
Karyometric Comparison of Splenic and Gastric Marginal Zone Lymphomas
Authors: Styczeń Magdalena , Szpor Joanna , Demczuk Sergiusz , Okoń Krzysztof 
Published: January 2015

Background: Marginal zone lymphomas are indolent B-cell lymphomas associated with autoimmunity and chronic inflammation. The two most frequent variants are mucosa associated lymphoid tissues marginal zone lymphomas and splenic marginal zone lymphomas. The aim of the study was to determine if it is possible to classify splenic and gastric lymphomas according to karyometric features.Methods: The material consisted of 16 splenic and 14 gastric lymphomas. The measurements were done with the AnalySIS image analysis system. In each case at least 100 nuclei were selected, and 19 different geometric parameters were measured.Results: On statistical analysis, the nuclei of splenic and gastric lymphomas showed differences in most parameters, but significant overlap of the values was present. Neural networks were trained and used for classification of the data. By this method, the nuclei were properly classified with a sensitivity of 0.75 and specificity of 0.71. In addition, in all the cases the majority of the nuclei were properly classified, thus allowing correct classification of all the cases into “splenic” or “gastric”.Conclusion: These results support the view that mucosa-associated lymphoid tissue lymphomas and splenic marginal-zone lymphomas are separate entities.