bluuebunny/crossref_metadata_2025_split huggingface dataset:
The Survivin −31 Snp in Human Colorectal Cancer Correlates with Survivin Splice Variant Expression and Improved Overall Survival
Authors: Antonacopoulou Anna G. , Floratou Konstantina , Bravou Vasiliki , Kottorou Anastasia , Dimitrakopoulos Fotinos-Ioannis , Marousi Stella , Stavropoulos Michalis , Koutras Agelos K. , Scopa Chrisoula D. , Kalofonos Haralabos P. 
Published: January 2015

Background: Survivin is involved in the regulation of cell division and survival, two key processes in cancer. The majority of studies on survivin in colorectal cancer (CRC) have focused on protein expression and less is known about the expression of survivin splicing variants or survivin gene polymorphisms in CRC. In the present study, the mRNA levels of the five known isoforms of survivin as well as survivin protein were assessed in matched normal and neoplastic colorectal tissue. Moreover, the 9386C/T and −31G/C polymorphisms were investigated.Methods: Quantitative RT-PCR was used to assess mRNA levels in fresh/frozen tissue samples. Protein levels were immunohistochemically evaluated on formalin-fixed paraffin-embedded tissue sections. Individuals were genotyped using real time PCR.Results: Expression of all 5 survivin splice variants as well as survivin protein was elevated in colorectal carcinomas compared to normal tissue. Specific splice variant expression differentially correlated with clinicopathological parameters. Furthermore, both snps correlated with splice variant levels or their ratios in colorectal carcinomas while the −31G/C snp may be related to CRC development and improved overall survival.Conclusion: Our results support a role of survivin in colorectal carcinogenesis while the −31G/C snp may constitute a marker of survival.
Genetic Profile of Adenoid Cystic Carcinomas (ACC) with High-Grade Transformation versus Solid Type
Authors: Costa Ana Flávia , Altemani Albina , Vékony Hedy , Bloemena Elisabeth , Fresno Florentino , Suárez Carlos , Llorente José Luis , Hermsen Mario 
Published: January 2015

Background: ACC can occasionally undergo dedifferentiation also referred to as high-grade transformation (ACC-HGT). However, ACC-HGT can also undergo transformation to adenocarcinomas which are not poorly differentiated. ACC-HGT is generally considered to be an aggressive variant of ACC, even more than solid ACC. This study was aimed to describe the genetic changes of ACC-HGT in relation to clinico-pathological features and to compare results to solid ACC.Methods: Genome-wide DNA copy number changes were analyzed by microarray CGH in ACC-HGT, 4 with transformation into moderately differentiated adenocarcinoma (MDA) and two into poorly differentiated carcinoma (PDC), 5 solid ACC. In addition, Ki-67 index and p53 immunopositivity was assessed.Results: ACC-HGT carried fewer copy number changes compared to solid ACC. Two ACC-HGT cases harboured a breakpoint at 6q23, near the cMYB oncogene. The complexity of the genomic profile concurred with the clinical course of the patient. Among the ACC-HGT, p53 positivity significantly increased from the conventional to the transformed (both MDA and PDC) component.Conclusion: ACC-HGT may not necessarily reflect a more advanced stage of tumor progression, but rather a transformation to another histological form in which the poorly differentiated forms (PDC) presents a genetic complexity similar to the solid ACC.
Molecular Differences between Ductal CarcinomaIn Situand Adjacent Invasive Breast Carcinoma: A Multiplex Ligation-Dependent Probe Amplification Study
Authors: Moelans Cathy B. , de Weger Roel A. , Monsuur Hanneke N. , Maes Anoek H. J. , van Diest Paul J. 
Published: January 2015

Ductal carcinoma in situ (DCIS) accounts for approximately 20% of mammographically detected breast cancers. Although DCIS is generally highly curable, some women with DCIS will develop life-threatening invasive breast cancer, but the determinants of progression to infiltrating ductal cancer (IDC) are largely unknown. In the current study, we used multiplex ligation-dependent probe amplification (MLPA), a multiplex PCR-based test, to compare copy numbers of 21 breast cancer related genes between laser-microdissected DCIS and adjacent IDC lesions in 39 patients. Genes included in this study were ESR1, EGFR, FGFR1, ADAM9, IKBKB, PRDM14, MTDH, MYC, CCND1, EMSY, CDH1, TRAF4, CPD, MED1, HER2, CDC6, TOP2A, MAPT, BIRC5, CCNE1 and AURKA.There were no significant differences in copy number for the 21 genes between DCIS and adjacent IDC. Low/intermediate-grade DCIS showed on average 6 gains/amplifications versus 8 in high-grade DCIS (p=0.158). Furthermore, alterations of AURKA and CCNE1 were exclusively found in high-grade DCIS, and HER2, PRDM14 and EMSY amplification was more frequent in high-grade DCIS than in low/intermediate-grade DCIS. In contrast, the average number of alterations in low/intermediate and high-grade IDC was similar, and although EGFR alterations were exclusively found in high-grade IDC compared to low/intermediate-grade IDC, there were generally fewer differences between low/intermediate-grade and high-grade IDC than between low/intermediate-grade and high-grade DCIS.In conclusion, there were no significant differences in copy number for 21 breast cancer related genes between DCIS and adjacent IDC, indicating that DCIS is genetically as advanced as its invasive counterpart. However, high-grade DCIS showed more copy number changes than low/intermediate-grade DCIS with specifically involved genes, supporting a model in which different histological grades of DCIS are associated with distinct genomic changes that progress to IDC in different routes. These high-grade DCIS specific genes may be potential targets for treatment and/or predict progression.
Dual Effects ofβ3Integrin Subunit Expression on Human Pancreatic Cancer Models
Authors: Marchán S. , Pérez-Torras S. , Vidal A. , Adan J. , Mitjans F. , Carbó N. , Mazo A. 
Published: January 2015

Background: Pancreatic cancer, the fifth leading cause of adult cancer death in Western countries, lacks early detection, and displays significant dissemination ability. Accumulating evidence shows that integrin-mediated cell attachment to the extracellular matrix induces phenotypes and signaling pathways that regulate tumor cell growth and migration.Methods: In view of these findings, we examined the role ofβ3in pancreatic cancer by generating two stableβ3-expressing pancreatic human cell lines and characterizing their behavior in vitro and in vivo.Results: Transduction ofβ3selectively augmented the functional membraneαvβ3integrin levels, as evident from the enhanced adhesion and migration abilities related to active Rho GTPases. No effects on in vitro anchorage-dependent growth, but higher anoikis were detected inβ3-overexpressing cells. Moreover, tumors expressingβ3displayed reduced growth. Interestingly, treatment of mice with anαv-blocking antibody inhibited the growth ofβ3-expressing tumors to a higher extent.Conclusion: Our results collectively support the hypothesis thatαvβ3integrin has dual actions depending on the cell environment, and provide additional evidence on the role of integrins in pancreatic cancer, which should eventually aid in improving prediction of the effects of therapies addressed to modulate integrin activities in these tumors.
Digital Pathology – Implementation Challenges in Low-Resource Countries
Authors: Fontelo Paul , Faustorilla John , Gavino Alex , Marcelo Alvin 
Published: January 2015

Background: Medical education in pathology and histology in low-resource countries face many obstacles because of equipment cost and telecommunication deficiencies. Digital Pathology may provide solutions. We report student experience to virtual slides on a local network and a remote image server.Methods: Using an iPad tablet device, fifty 3rd and 4th year medical students viewed digital pathology slides from a Web server at the National Library of Medicine and a mirror server on the local network.Results: The quality of images from both servers was found to be satisfactory, but the local server was deemed faster and preferred by the participants in this study (p< 0.005).Conclusions: Virtual slides on a local network server may provide solutions to equipment and technical obstacles and could enhance student learning in developing countries.
Automated Sputum Cytometry for Detection of Intraepithelial Neoplasias in the Lung
Authors: Li Gerald , Guillaud Martial , LeRiche Jean , McWilliams Annette , Gazdar Adi , Lam Stephen , MacAulay Calum 
Published: January 2015

Background: Despite the benefits of early lung cancer detection, no effective strategy for early screening and treatment exists, partly due to a lack of effective surrogate biomarkers. Our novel sputum biomarker, the Combined Score (CS), uses automated image cytometric analysis of ploidy and nuclear morphology to detect subtle intraepithelial changes that often precede lung tumours.Methods: 2249 sputum samples from 1795 high-risk patients enrolled in ongoing chemoprevention trials were subjected to automated quantitative image cytometry after Feulgen-thionin staining. Samples from normal histopathology patients were compared against samples from carcinomain situ(CIS) and cancer patients to train the CS.Results: CS correlates with several lung cancer risk factors, including histopathological grade, age, smoking status, and p53 and Ki67 immunostaining. At 50% specificity, CS detected 78% of all highest-risk subjects—those with CIS or worse plus those with moderate or severe dysplasia and abnormal nuclear morphology.Conclusion: CS is a powerful yet minimally invasive tool for rapid and inexpensive risk assessment for the presence of precancerous lung lesions, enabling enrichment of chemoprevention trials with highest-risk dysplasias. CS correlates with other biomarkers, so CS may find use as a surrogate biomarker for patient assessment and as an endpoint in chemoprevention clinical trials.
A Comparison of Digitized Frozen Section and Smear Preparations for Intraoperative Neurotelepathology
Authors: Gould Peter V. , Saikali Stephan 
Published: January 2015

Background: Intraoperative consultations in neuropathology are often assessed by smear preparations rather than by frozen sections. Both techniques are standard practice for light microscopic examination on site, but there is little data comparing these techniques in a telepathology setting.Methods: Thirty cases of brain tumours submitted for intraoperative consultation at our institution between July and December 2010 were identified in which both frozen section and tissue smear preparations were available for digitization at 20× magnification. Slides were digitized using a Hamamatsu Nanozoomer 2.0 HT whole slide scanner, and resulting digital images were visualized at 1680 × 1050 pixel resolution with NDP. view software.Results: The original intraoperative diagnosis was concordant with the sign out diagnosis in 29/30 cases; one tumeur was initially interpreted as a high grade glioma but proved to be a lymphoma at sign out.Digitized frozen section slides were sufficient for diagnosis at 10× magnification in 27/30 cases. Digitized tissue smears were sufficient for diagnosis at 10× magnification in 28/30 cases. In two cases tumour was present on the tissue smear but not the frozen section (one case of recurrent astrocytoma, one case of meningeal carcinomatosis). In one case of lymphoma, tumour was present on frozen section only. These discrepancies were attributed to tissue sampling rather than image quality.Examination of digitized slides at higher magnfication (20×) permitted confirmation of mitoses and Rosenthal fibers on tissue smear preparations, but did not change the primary diagnosis. Intra-slide variations in tissue thickness on smear preparations led to variable loss of focus in digitized images, but did not affect image quality in thinner areas of the smear or impede diagnosis.Conclusion: Digitized tissue smears are suitable for intraoperative neurotelepathology and provide comparable information to digitized frozen sections at medium power magnification.
Histopathologic Patterns of Nervous System Tumors Based on Computer Vision Methods and Whole Slide Imaging (WSI)
Authors: Walkowski Slawomir , Szymas Janusz 
Published: January 2015

Background: Making an automatic diagnosis based on virtual slides and whole slide imaging or even determining whether a case belongs to a single class, representing a specific disease, is a big challenge. In this work we focus on WHO Classification of Tumours of the Central Nervous System. We try to design a method which allows to automatically distinguish virtual slides which contain histopathologic patterns characteristic of glioblastoma – pseudopalisading necrosis and discriminate cases with neurinoma (schwannoma), which contain similar structures – palisading (Verocay bodies).Methods: Our method is based on computer vision approaches like structural analysis and shape descriptors. We start with image segmentation in a virtual slide, find specific patterns and use a set of features which can describe pseudopalisading necrosis and distinguish it from palisades. Type of structures found in a slide decides about its classification.Results: Described method is tested on a set of 49 virtual slides, captured using robotic microscope. Results show that 82% of glioblastoma cases and 90% of neurinoma cases were correctly identified by the proposed algorithm.Conclusion: Our method is a promising approach to automatic detection of nervous system tumors using virtual slides.
Static Digital Telepathology: A Model for Diagnostic and Educational Support to Pathologists in the Developing World
Authors: Sohani Aliyah R. , Sohani Moez A. 
Published: January 2015

Background: The practice of pathology in the developing world presents challenges in terms of limited resources, shortages of trained personnel, and lack of continuing education programs. Telepathology holds promise as a means of diagnostic and educational support.Methods: We donated multiheaded teaching microscopes equipped with digital cameras to four hospitals in Eastern Africa and trained local pathologists on their use. Static images of challenging cases were posted on a web-based telepathology platform. A U.S.-based pathologist reviewed images in consultation with subspecialist colleagues.Results: Over a period of 40 months, 109 cases were submitted for second opinion consultation, including 29 dermatopathology cases (26.6%), 14 hematopathology cases (12.8%), and 13 cases each (11.9%) in cytopathology and bone and soft tissue pathology. Static images enabled a complete or partial diagnosis in 100/109 cases (91.7%). Factors precluding a definitive diagnosis included absence of confirmatory immunophenotyping, technical issues, or lack of clinical history. Case responses included a diagnosis and discussion, including differential diagnosis, references, and treatment recommendations.Conclusion: Static digital telepathology is a simple, cost-effective, reliable and efficient means to provide diagnostic and educational support to pathologists in the developing world. Additional training may help overcome technical factors precluding a definitive diagnosis in certain cases.
The Challenges of Implementing a “Patient-Oriented” Telepathology Network; the Eastern Québec Telepathology Project Experience
Authors: Têtu Bernard , Fortin Jean-Paul , Gagnon Marie-Pierre , Louahlia Said 
Published: January 2015

Background: The aim of the Eastern Québec telepathology project is to provide uniform diagnostic telepathology services across a huge geographic region with a low population density. This project is intended to provide surgeons and pathologists with frozen section and second opinion services anywhere and at any time across the entire region in order to avoid unnecessary patient transfer.Methods: The project has been implemented in 21 sites, each equipped with a whole slide scanner, a macroscopy station, two videoconferencing devices and a viewer/case management and collaboration solution. Of the 21 sites, 6 are devoid of a pathology laboratory. Of the remaining 15 sites, two have no pathologists, 6 have one and 7 have two or more.Results: The project has been successful and most appreciated by pathologists and surgeons. We report a number of challenges related to change management that we had to take into account in the course of implementation of this network. The challenges underscore the need for regular visits and active support to participating centers by the project team.Conclusion: The Eastern Québec telepathology network is successful and improves medical care in this region. In the course of implementation, we encountered a number of challenges which required innovative solutions.
Age Dependent Switching Role of Cyclin D1 in Breast Cancer
Authors: Rinaldi Carmela , Malara Natalia Maria , D’Angelo Rosalia , Sidoti Antonina , Leotta Attilio , Lio Santo , Caparello Basilio , Ruggeri Alessia , Mollace Vincenzo , Amato Aldo 
Published: January 2015

Background: Cyclin D1 gene (CCND1) plays pivotal roles in the development of several human cancers, including breast cancer, functioning as an oncogene. The aim of this study was to better understand the molecular dynamics of ductal carcinomas with regard to proliferation and the ageing process.Methods: 130 cases of ductal breast cancer in postmenopausal women, aged 52–96 in 3 age classes were selected. Tumoral tissues preserved in formaldehyde solution and subsequently embedded in paraffin were subjected to analysis Fluorescencein situHybridization (FISH), Reverse Transcription-Polymerase Chain Reaction (RT- PCR) and immuno-histochemical tests. The molecular variables studied were estimated in relation to the patients’ age.Results: The results obtained suggest that the increment of the levels of cyclin D1 in intra-ductal breast tumors in older woman that we have examined is significantly associated with a lower proliferation rate.Conclusion: Cyclin D1, which characterizes tumor in young women as molecular director involved in strengthening tumoral proliferation mechanisms, may be seen as a potential blocking molecular switch in corresponding tumours in old women.
How to Introduce Virtual Microscopy (VM) in Routine Diagnostic Pathology: Constraints, Ideas, and Solutions
Authors: Kayser Klaus , Borkenfeld Stephan , Kayser Gian 
Published: January 2015

Context: Virtual microscopy which is the diagnostic work with digitized microscopic images in tissue – based diagnosis is in its childhood in being implemented in routine diagnosis. Until today, only a few pathology institutions take use of this new technology, although it is available since several years. Why?Design: Virtual microscopy requires a new workflow organisation in the pathologist's diagnostic procedure. At a first view, the laboratory workflow seems to remain untouched to a high degree. However, the used laboratory information system (LIS), which is commonly built in a hierarchic order, has to be adjusted at its highest levels, i.e., diagnosis statement, quality evaluation, submission to the clinician (hospital information system), and feedback to the laboratory. Therefore, the laboratory's workflow is involved at all levels too, and the LIS has to be changed or adjusted to the requirements of VM. VM systems are usually equipped with a viewer that mimics the viewing of a conventional microscope, and do not offer access to sensitive nodes of the LIS. Similar, LIS are usually closed and fixed systems because of data security and certification demands. Thus, VM systems have to possess communication access at different LIS levels together with steering commands for the LIS in close association with the diagnostic quality and efficiency (for example demands for additional stains, immunohistochemical or quantitative image methods, etc.), as well as expert consultation, or panel discussion.Outcome: An implementation of an open and active LIS – VM management system could significantly promote the introduction of VM into routine diagnostic surgical pathology. The management system has to coordinate and translate the demands of VM to LIS (and vice versa), and to assure the communication with HIS. Mandatory features include streaming of the laboratory workflow, feedback commands to LIS, as well as regulation of temporary priority levels.Conclusion: A successful implementation of VM systems in routine tissue-based diagnosis requires communicative management systems as long as VM is considered to be a “stand alone system” that just mimics a conventional microscope.
Balancing Image Quality and Compression Factor for Special Stains Whole Slide Images
Authors: Sharma Anurag , Bautista Pinky , Yagi Yukako 
Published: January 2015

The objective is to find a practical balance between quality and performance for daily high volume whole slide imaging. We evaluated whole slide images created by various scanners at different compression factors to determine the best suitable quality factor (QF) needed for pathological images of special stains.Method: We scanned two sets of eight special stains slides each at 0.50 μm/pixel resolution in Hamamatsu scanner at six and fiveQFlevels respectively to generate 72 images which were observed at a calibrated monitor by imaging specialists, a histo-technician, and a pathologist to find the most suitableQFlevel for special stains in digital slides.Results: Most special stains images were acceptable at QF 30 except for the stain Reticulin where the lowest acceptableQFwas 50. The compression of images fromQF90 toQF50 reduced the size of the images by 62.73%.Conclusion: 0.50 μm/pixel images atQF50 or above were found suitable 12 special stain.
Chromosomal Aneuploidy Affects the Global Proteome Equilibrium of Colorectal Cancer Cells
Authors: Gemoll Timo , Habermann Jens K. , Becker Susanne , Szymczak Silke , Upender Madhvi B. , Bruch Hans-Peter , Hellman Ulf , Ried Thomas , Auer Gert , Jörnvall Hans , Roblick Uwe J. 
Published: January 2015

Background: Chromosomal aneuploidy has been identified as a prognostic factor in the majority of sporadic carcinomas. However, it is not known how chromosomal aneuploidy affects chromosome-specific protein expression in particular, and the cellular proteome equilibrium in general.Objective: The aim was to detect chromosomal aneuploidy-associated expression changes in cell clones carrying trisomies found in colorectal cancer.Methods: We used microcell-mediated chromosomal transfer to generate three artificial trisomic cell clones of the karyotypically stable, diploid, yet mismatch-deficient, colorectal cancer cell line DLD1 - each of them harboring one extra copy of either chromosome 3, 7 or 13. Protein expression differences were assessed by two-dimensional gel electrophoresis and mass spectrometry, compared to whole-genome gene expression data, and evaluated by PANTHER classification system and Ingenuity Pathway Analysis (IPA).Results: In total, 79 differentially expressed proteins were identified between the trisomic clones and the parental cell line. Up-regulation of PCNA and HMGB1 as well as down-regulation of IDH3A and PSMB3 were revealed as trisomy-associated alterations involved in regulating genome stability.Conclusions: These results show that trisomies affect the expression of genes and proteins that are not necessarily located on the trisomic chromosome, but reflect a pathway-related alteration of the cellular equilibrium.