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Prognostic Significance of Pigment Epithelium-Derived Factor Expression in Patients with Non-Small-Cell-Lung Cancer  [PDF]
Alexander Emmert, Angelika Oellerich, Laszlo Füzesi, Regina Waldmann-Beushausen, Friedrich A. Sch？ndube, Hanibal Bohnenberger, Bernhard C. Danner
Advances in Lung Cancer (ALC) , 2016, DOI: 10.4236/alc.2016.53004
Abstract: The aims of this study were to examine prognostic significance of pigment epithelium-derived factor (PEDF) in patients with stage IA-IIIB non-small cell lung cancer (NSCLC). Using immunohistochemistry and multivariate analysis, we set out to investigate whether PEDF expression could provide prognostic information in NSCLC in a cohort of 69 patients who had undergone radical resection for NSCLC. The correlation between PEDF and the clinical pathological features of stage I-III NSCLC after radical surgery were analyzed as well as influence on long term survival. No correlation between PEDF intensity, PEDF area or PEDF area index and clinic opathologic parameters was seen. PEDF values showed a slight correlation to the tumor stage. There was a significant negative correlation (T = -0.288, p = 0.002) between pathologic T-stage and median PEDF area and vice versa a positive correlation (T = 0.227, p = 0.016) with median PEDF intensity. We could not detect any correlation between PEDF and long term survival. For PEDF analysis, there was only a slight correlation between expression and T-stage of the tumor.
Prognostic Significance of CD31 Expression in Patients with Non-Small-Cell-Lung Cancer  [PDF]
Alexander Emmert, Angelika Oellerich, Laszlo Füzesi, Regina Waldmann-Beushausen, Hanibal Bohnenberger, Friedrich A. Sch？ndube, Bernhard C. Danner
Advances in Lung Cancer (ALC) , 2016, DOI: 10.4236/alc.2016.53003
Abstract: Non-small cell lung cancer (NSCLC) is the primary cause of cancer related death worldwide. After resection of early stage NSCLC, the benefit of adjuvant chemotherapy for patient survival still remains unclear and investigations for further risk stratification are needed for an improved treatment decision. Microvessel density (MVD) influences both the nutrition of the cancer and the access to the bloodstream for the development of distant metastasis. The aim of this study was to examine the prognostic significance of microvessel density by CD31 staining in patients with resected stage IA-IIIB NSCLC. We used immunohistochemistry (IHC) of CD31 to examine the microvessel density in a cohort of 69 patients who had undergone radical resection for NSCLC. Correlation of IHC values and standard clinicopathologic parameters was analyzed as well as influence on long term survival. Survival analysis revealed a significant better overall survival for patients with higher median microvessel density (log rank p = 0.031) independent of clinicopathologic parameters. Regarding primary cancer related death, the survival was again significantly longer in patients with high CD31 count (log rank p = 0.036). A higher microvessel density was a strong predictor for a longer tumor related survival and could be used for therapeutic decisions of adjuvant chemotherapy after resection of early stage NSCLC.
Interplay between Platelet Endothelial Cell Adhesion Molecule-1 and Pigment Epithelium-Derived Factor in Non-Small-Cell-Lung Cancer  [PDF]
Alexander Emmert, Angelika Oellerich, Laszlo Füzesi, Regina Waldmann- Beushausen, Friedrich A. Sch？ndube, Hanibal Bohnenberger, Bernhard C. Danner
Open Journal of Thoracic Surgery (OJTS) , 2016, DOI: 10.4236/ojts.2016.64007
Abstract: Pigment epithelium-derived factor (PEDF), a potent antiangiogenesis agent, is a multifunctional protein with important roles in regulation of inflammation and angiogenesis. It has recently attracted attention for targeting tumor cells in several types of tumors. PECAM-1 is an integral membrane protein, a cell adhesion molecule with proangiogenic activity and plays an important role in the process of angiogenesis. The correlation between proangiogenic activity PECAM-1 and antiangiogenic activity PEDF in Non-Small-Cell-Lung Cancer has not been reported. The present study was designed to evaluate using immunohistochemical techniques and multivariate analysis the interplay between PECAM-1 and PEDF in NSCLC, especially in adenocarcinoma and in squamous cell carcinoma stage IA-IIIB. Analyzing the mixed study collectively (n = 69), there was no significant correlation (p = 0.553) between PECAM-1 signal and PEDF area. Only including patients with adenocarcinoma (Figure 2), we found a positive correlation between PECAM-1 signal and PEDF area (p = 0.025). In patients with squamous cell carcinoma, we did not find a significant correlation between PECAM-1 signal and PEDF area (p = 0.530). In patients with squamous cell carcinoma, PECAM-1 and PEDF show a significant different expression pattern, measured via staining intensity (p = 0.013). These results might support the hypothesis that squamous cell carcinomas heavily rely on angiogenic processes.
Altered regulation of Prox1-gene-expression in liver tumors
Jozsef Dudas, Tümen Mansuroglu, Federico Moriconi, Florian Haller, Joerg Wilting, Thomas Lorf, Laszlo Füzesi, Giuliano Ramadori
BMC Cancer , 2008, DOI: 10.1186/1471-2407-8-92
Abstract: We have studied the expression of Prox1 in normal liver, liver cirrhosis and peritumoral liver samples in comparison to hepatocellular (HCC) and cholangiocellular carcinoma (CCC) at mRNA, protein and functional levels.Prox1 was found in hepatocytes of normal liver, while normal bile duct epithelial cells were negative. However, Prox1+ cells, which co-expressed biliary epithelial makers and showed ductular morphology, could be detected within fibrotic septa of cirrhotic livers, and in both HCC and CCC. Two Prox1 mRNA isoforms (2.9 kb and 7.9 kb) were identified with a prevalence of the longer isoform in several HCC samples and the shorter in most CCC samples. Evidence was provided that Myc-associated zinc finger protein (MAZ) might significantly contribute to the gene expression of Prox1 in HCC, while neo-expression of Prox1 in CCC remains to be resolved. A point mutation in the prospero domain of Prox1 was found in one HCC sample.Our study shows dysregulation of Prox1 in liver cirrhosis, HCC and CCC, such as neo-expression in cells with biliary epithelial phenotype in liver cirrhosis, and in CCC. Altered Prox1 mRNA expression is partly regulated by MAZ, and mutation of the prospero domain in HCC indicates an involvement for Prox1 during tumor progression.Homeobox genes encode transcription factors that control cell differentiation and play essential roles during embryonic development [1,2]. The homeobox genes Hlx [3], Hex [4] and the prospero-related homeobox 1 (Prox1) [5] are involved in the development of the liver bud. Prox1 belongs to the earliest markers of mammalian foregut endoderm cells, where its expression is confined to a short segment that gives rise both to the liver and pancreas, remaining expressed during the adulthood [6,7]. In Prox1-deficient mice, the hepatoblasts fail to migrate into the neighboring mesenchyme [8]. Prox1-null mice die around embryonic day (ED) 14.5 and show a 70% reduction of liver size [8]. Besides albumin and α-fetoprotein (AFP)
Pitfalls in mutational testing and reporting of common KIT and PDGFRA mutations in gastrointestinal stromal tumors
Sabine Merkelbach-Bruse, Wolfgang Dietmaier, Laszlo Füzesi, Andreas Gaumann, Florian Haller, Julia Kitz, Antje Krohn, Gunhild Mechtersheimer, Roland Penzel, Hans-Ulrich Schildhaus, Regine Schneider-Stock, Ronald Simon, Eva Wardelmann
BMC Medical Genetics , 2010, DOI: 10.1186/1471-2350-11-106
Abstract: When comparing results from six different molecular laboratories we recognized the need of standardisation. Six German university laboratories with experience in mutation analysis in GISTs joined together to develop recommendations for the mutation analysis of the most common and clinically relevant hot spots, i. e. KIT exons 9 and 11 and PDGFRA exon 18. We performed a three-phased interlaboratory trial to identify pitfalls in performing molecular analysis in GISTs.We developed a design for a continuous external laboratory trial. In 2009 this external trial was conducted by 19 laboratories via the initiative for quality assurance in pathology (QuiP) of the German Society of Pathology and the Professional Association of German Pathologists.By performing a three-phased internal interlaboratory trial and conducting an external trial in Germany we were able to identify potential pitfalls when performing KIT and PDGFRA mutational analysis in gastrointestinal stromal tumors. We developed standard operation procedures which are provided with the manuscript to allow other laboratories to prevent these pitfalls.Gastrointestinal stromal tumors (GISTs) represent the most common mesenchymal tumors of the gastrointestinal tract. About 50% of GISTs behave clinically aggressive. Since 2001, treatment options have dramatically improved with the introduction of tyrosine kinase inhibitors. On the molecular level, the vast majority of tumors carries activating mutations in the KIT gene or the PDGFRA (platelet derived growth factor receptor alpha) gene, both genes encoding closely related type III tyrosine kinases. The relevance of the mutational status in these genes both for clinical prognosis and for prediction of response to treatment has been increasingly recognized[1,2]. Mutational analyses are now performed in many laboratories worldwide and several protocols have been published. Given the high impact on clinical decisions, mutational testing should meet the highest standard for
IT applications in the quality management of Hungarian meat product chains
István Füzesi,Miklós Herdon
Agrárinformatika Folyóirat , 2010,
Abstract: The manufacture, distribution and retailing of foodstuffs became an extraordinarily complex business activity. The complete food chain must provide for the implementation of the strictest quality standards and safety regulations. Problems of food safety can be solved by keeping (and enforcing) applicable regulations, by introducing modern quality assurance systems, by making possible the traceability of products and their identification. The safety of product lines and tracing of products cannot be solved without using information systems in a certain level. Our research focused on the IT support and development of quality management systems in the Hungarian meat industry, especially on food tracing systems, and on the utilized identification systems. In the framework of our research, we developed a research portal that presents the results about the meat industry. The portal refers also to planned modern quality control and tracing systems and to the publication of the knowledge base connected with the topic. In our study, it came to light that, agrarian traceability struggles with many more problems in general. Companies try to live up to expectation, but they often apply different solutions with totally different approaches, while serving several different market aspects, depending on their customers.
Food Tracing and Interoperability of Information Systems in the Hungarian Meat Industry
I. Füzesi,M. Herdon,A. Péntek
AGRIS on-line Papers in Economics and Informatics , 2010,
Abstract: The manufacture, distribution and retailing of foodstuffs became an extraordinarily complex business activity. The complete food chain must provide for the implementation of the strictest quality standards and safety regulations. Problems of food safety can be solved by keeping (and enforcing) applicable regulations, by introducing modern quality assurance systems, by making possible the traceability of products and their identification. The safety of product lines and tracing of products cannot be solved without using information systems of a certain level. During our research, it came to light that, generally, agrarian traceability struggles with many more problems. Companies try to live up to expectation, but they often apply different solutions with totally different approaches, while serving several different market aspects, depending on their customers. The conception of the Digital Business Ecosystem (DBE) has come, to build an Internet-based environment in which businesses will be able to interact with each other efficiently. The DBE solutions based on community philosophy are able to create applications, which can solve most of food traceability problems.
The Dirichlet Portfolio Model: Uncovering the Hidden Composition of Hedge Fund Investments
Laszlo F. Korsos
Quantitative Finance , 2013,
Abstract: Hedge funds have long been viewed as a veritable "black box" of investing since outsiders may never view the exact composition of portfolio holdings. Therefore, the ability to estimate an informative set of asset weights is highly desirable for analysis. We present a compositional state space model for estimation of an investment portfolio's unobserved asset allocation weightings on a set of candidate assets when the only observed information is the time series of portfolio returns and the candidate asset returns. In this paper, we exhibit both sequential Monte Carlo numerical and conditionally Normal analytical approaches to solve for estimates of the unobserved asset weight time series. This methodology is motivated by the estimation of monthly asset class weights on the aggregate hedge fund industry from 1996 to 2012. Furthermore, we show how to implement the results as predictive investment weightings in order to construct hedge fund replicating portfolios.
Characterization of Corticotropin-Releasing Hormone neurons in the Paraventricular Nucleus of the Hypothalamus of Crh-IRES-Cre Mutant Mice
Jaclyn I. Wamsteeker Cusulin, Tamás Füzesi, Alan G. Watts, Jaideep S. Bains
PLOS ONE , 2013, DOI: 10.1371/journal.pone.0064943
Abstract: Corticotropin-releasing hormone (CRH)-containing neurons in the paraventricular nucleus of the hypothalamus (PVN) initiate and control neuroendocrine responses to psychogenic and physical stress. Investigations into the physiology of CRH neurons, however, have been hampered by the lack of tools for adequately targeting or visualizing this cell population. Here we characterize CRH neurons in the PVN of mice that express tdTomato fluorophore, generated by crosses of recently developed Crh-IRES-Cre driver and Ai14 Cre-reporter mouse strains. tdTomato containing PVN neurons in Crh-IRES-Cre;Ai14 mice are readily visualized without secondary-detection methods. These neurons are predominantly neuroendocrine and abundantly express CRH protein, but not other PVN phenotypic neuropeptides. After an acute stress, a large majority of tdTomato cells express neuronal activation marker c-Fos. Finally, tdTomato PVN neurons exhibit homogenous intrinsic biophysical and synaptic properties, and can be optogenetically manipulated by viral Cre-driven expression of channelrhodopsin. These observations highlight basic cell-type characteristics of CRH neurons in a mutant mouse, providing validation for its future use in probing neurophysiology of endocrine stress responses.
Histone H1x is highly expressed in human neuroendocrine cells and tumours
Julia Warneboldt, Florian Haller, Olaf Horstmann, Bernhard C Danner, László Füzesi, Detlef Doenecke, Nicole Happel
BMC Cancer , 2008, DOI: 10.1186/1471-2407-8-388
Abstract: Based on results of a Blast data base search which revealed an accumulation of expressed sequence tags (ESTs) of H1x in libraries from neuroendocrine tumours (NETs), we evaluated the expression of H1x in NETs from lung and the gastrointestinal tract using immunohistochemisty. Relative protein and mRNA levels of H1x were analysed by Western blot analysis and quantitative real-time RT-PCR, respectively. Since several reports describe a change of the expression level of the replacement subtype H1.0 during tumourigenesis, the analysis of this subtype was included in this study.We found an increased expression of H1x but not of H1.0 in NET tissues in comparison to corresponding normal tissues. Even though the analysed NETs were heterogenous regarding their grade of malignancy, all except one showed a considerably higher protein amount of H1x compared with corresponding non-neoplastic tissue. Furthermore, double-labelling of H1x and chromogranin A in sections of pancreas and small intestine revealed that H1x is highly expressed in neuroendocrine cells of these tissues.We conclude that the high expression of histone H1x in NETs is probably due to the abundance of this protein in the cells from which these tumours originate.The nuclear DNA of eukaryotic cells is organised as chromatin in association with proteins. The basal structural organisation unit of chromatin is the nucleosome consisting of the nucleosome core particle, linker DNA and histone H1. The nucleosome core particle is composed of two molecules of each of the four core histones which form an octamer around which DNA with a length of 146 base pairs is wrapped. These nucleosome cores are connected by linker DNA of variable length. H1 histones are positioned at the linker DNA between the nucleosome cores and therefore they are also called linker histones [1,2]. To date, eleven H1 homologous proteins have been described in humans, including the ubiquitously expressed subtype H1x [3]. Comparison of the biochemical
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