Galectin-1 serum levels reflect tumor burden and adverse clinical features in classical Hodgkin lymphoma

Galectin-1 (Gal1) is a member of a highly conserved family of carbohydrate-binding proteins that modulates innate and adaptive immune responses and fosters tumor-immune escape. Hodgkin lymphoma (HL) Reed-Sternberg (RS) cells overexpress and secrete Gal1, which selectively kills Th1,Th17 and cytotoxic T cells and promotes the immunosuppressive Th2/Treg-predominant HL microenvironment. We developed a sandwich ELISA and assessed serum Gal1 levels in 315 newly diagnosed, previously untreated HL patients enrolled on 3 risk-adapted clinical trials. Serum Gal1 levels were significantly higher in HL patients than in normal controls (p < .0001). Gal1 serum levels also increased with Ann Arbor stage (p < .0001), areas of nodal involvement (p = .0001) and the International Prognostic Score (IPS) (2-7, p = .006). We conclude that Gal1 serum levels are significantly associated with tumor burden and additional adverse clinical characteristics in newly diagnosed HL Patients.Fil: Ouyang, Jing. Dana-Farber Cancer Institute. Department of Medical Oncology; Estados Unidos de América;Fil: Plütschow, Annette. German Hodgkin Study Group; Alemania;Fil: Von Strandmann, Elke Pogge. University Hospital of Cologne. Laboratory for Immunotherapy; Alemania;Fil: Reiners, Katrin S.. University Hospital of Cologne. Laboratory for Immunotherapy; Alemania;Fil: Ponader, Sabine. German Hodgkin Study Group; Alemania;Fil: Rabinovich, Gabriel Adrian. Consejo Nacional de Investigaciones Científicas y Técnicas. Instituto de Biología y Medicina Experimental (i); Argentina;Fil: Neuberg, Donna. Dana-Farber Cancer Institute. Department of Biostatistics; Estados Unidos de América;Fil: Engert, Andreas. German Hodgkin Study Group; Alemania;Fil: Shipp, Margaret A.. Dana-Farber Cancer Institute. Department of Medical Oncology; Estados Unidos de América

In vitro and in vivo performance of biofunctionalized bone grafts

Der Ersatz großer Knochendefekte ist ein bisher noch ungelöstes Problem. Komplikationen bei der Gewinnung und die begrenzte Verfügbarkeit autologen Knochens sowie die Gefahr der Übertragung von Krankheitserregern beim Ein-satz allogener und xenogener Produkte fördern die Entwicklung immer neuer synthetischer Knochenersatzmaterialien. Kostengünstige biokompatible Materi-alien sind dabei von steigendem Interesse. Immer neue Variationen hinsichtlich Materialzusammensetzung und neueste Herstellungsverfahren bieten eine Fülle von möglichen Alternativen zu den bisher bekannten Werkstoffen. Ziel der vor-liegenden Arbeit war es, ausgewählte Knochenersatzmaterialien mit völlig neu-artigen Beschichtungssystemen auf ihre Toxizität auf Knochenzellen sowie auf ihre Eignung als Gerüste für die Adhäsion, Proliferation und Differenzierung von Osteoblasten (hFOB 1.19 Zellen) zu untersuchen sowie die biologische Körper-verträglichkeit in vivo zu studieren. Auf dreidimensionalen Cellulosegewirken sollten neuartige Beschichtungsmethoden auf Basis von bioaktivem Glas mit modernen Wirkstoffen wie Pamidronat und Strontium angewendet werden, um die Biokompatibilität des Materials zu verbessern und als Slow-Release-Systeme eine zeitlich gesteuerte Abgabe moderner Wachstumsfaktoren in den Defekt zu ermöglichen und auf diese Weise den Heilungsprozess noch zu opti-mieren. Bei dem zweiten untersuchten Werkstoff handelte es sich um kommer-ziell erhältliches TiAl6V4-Pulver, welches in einem neuartigen Fertigungsverfah-ren, dem Selektiven Elektronenstrahlschmelzen (SEBM), zu dreidimensionalen Strukturen gefertigt wurde. Dieses Verfahren erlaubt in weiten Bereichen frei einstellbare Oberflächentopographien und Porositäten. Zusätzlich sollte das In-vitro-Verhalten eines kürzlich zum ersten Mal erfolgreich durchgeführten Be-schichtungsverfahrens, der Abscheidung monomolekularer Oligoelektrolyt-schichten, auf den Titanoberflächen untersucht werden. Das Zellverhalten auf den unterschiedlichen Oberflächen wurde mittels Mes-sung der Zelladhäsion, -proliferation, -vitalität und -differenzierung sowie in mik-roskopischen Aufnahmen beurteilt. Die Osseointegration wurde mithilfe histolo-gischer und immunhistochemischer Methoden bzw. REM-Aufnahmen beurteilt. Sämtliche Oberflächen stellten sich als geeignete Gerüste für die Anheftung und darauf folgende zelluläre Vorgänge der Osteoblasten heraus. Durch die Bioglasbeschichtungen auf den Cellulosegewirken konnte positiv Einfluss auf das Zellverhalten genommen werden. Die eingebrachten Wirkstoffe Pamidronat und Strontium hatten in Abhängigkeit von der applizierten Konzentration hem-mende oder förderliche Effekte auf das Zellverhalten. Eine Direktfunktionalisie-rung der Cellulose mit Strontiumcarbonat stellte sich als förderlich für die Zellvi-talität heraus. Glatte Titanoberflächen hatten den günstigsten Effekt auf das Zellverhalten. Die Oligoelektrolytbeschichtungen stellten sich als nicht zytoto-xisch heraus. In vivo konnte der Cellulose selbst sowie den verwendeten Be-schichtungssystemen eine Bioaktivität nachgewiesen werden. Die Bioglasbe-schichtung stellte sich als Slow-Release-System heraus, welches über einen Zeitraum von über 90 Tagen kontinuierlich in den Defektbereich abgegeben wird. Das Porensystem der Cellulosegewirke konnte von Knochengewebe nur in sehr geringem Maße durchwachsen werden. Die porigen Titankonstrukte hingegen wurden weitgehend von Knochengewebe gefüllt und stellen damit geeignete Gerüste für die Knochenrekonstruktion dar.Substitutes for large-scale bone defects remain a problem since autologous donor tissues are limited and allografts and xenografts involve the risk of trans-mission of pathogens. Mainly economic biocompatible solutions for the substitu-tion of the defective tissue are of increasing interest. A rising number of new material compositions and fabrication methods provide possible alternatives to conventional materials. It was the aim of this study to evaluate cellulose-based and titanium scaf-folds for bone replacement with novel surface coatings. Cellulose-based scaf-folds coated with pure sodium silicate gel, sodium silicate gels accumulated with different concentrations of the bisphosphonate pamidronate and strontium and directly coated with strontianite, pure Ti-6Al-4V surfaces with different surface structures and porosities produced by the Selective Electron Beam Melting (SEBM) process and titanium surfaces coated with oligoelectrolytes were evaluated for their suitability as matrices for the attachment, proliferation and differentiation of human fetal osteoblasts (hFOB 1.19 cells). Furthermore, the osseointegration of these materials was evaluated in vivo. By means of cell pro-liferation, vitality, osteoblastic gene expression and micrographs cellular proc-esses were observed. To evaluate the in vivo performance of the materials his-tological, histomorphometric and microradiographic analyses were evaluated. All surfaces turned out to be suitable matrices for the adhesion and elemen-tary osteoblastic processes. The bioactive silica-based surface coating influ-enced positively the cellular behaviour. An inhibitory or promoting effect could be shown for the applied drugs, which depends on the applied concentration. The coating with strontianite turned out to increase cell vitality. Smooth titanium surfaces turned out to be best suited for cell adhesion and following cellular processes. The oligoelectrolyte coating survived the steam sterilisation and had no effect on cell proliferation. All cellulose matrices showed bioactivity in the in vivo experiments. It could be shown that the silica-based coating represents a slow-release system which dissolves continuously over a period of 90 days. In vivo only few osteoblasts could penetrate the pore system of the cellulose knits. In contrast, the porous titanium scaffolds were filled up with newly formed bone tissue during the study time. Altogether, the materials tested in this study are very suitable scaffolds for bone regenerative applications

Early findings of a novel established molecular diagnostic technique for the prediction of malignant transformation in leukoplakia

To date, there are no objective parameters regarding the early prediction of malignant transformation in leukoplakia. Expression analysis of melanoma-associated antigens (MAGE-A) can differentiate between healthy and already malignant transformed tissues. Thus, expression analysis may also be used as an additional diagnostic tool for oral pre-malignant lesions to monitor potential malignant changes. In this study, four specimens collected from the same patient within a year were examined. Specimens were taken from the part of the lesion that displayed a rapid progression from fibroma to oral squamous cell carcinoma (OSCC). Clinically and histopathologically, the oral lesion was first diagnosed as fibroma with inflammatory infiltration, then as leukoplakia with hyperplasia, then as leukoplakia with severe dysplasia, and lastly as OSCC. Expression of MAGE-A1, -A3, -A4, -A6, -A10 and -A12 was investigated in the frozen tissue specimens using RT-PCR and quantitative real-time RT-PCR. There was no expression of MAGE-A in the specimen of fibroma with inflammatory infiltration. However, four genes were expressed by the second specimen of leukoplakia with hyperplasia. With the exception of MAGE-A1, all antigens were expressed in the specimens, which were histopathologically diagnosed as leukoplakia with severe dysplasia and OSCC. Expression analysis of six different MAGE-A genes indicated a high potential for malignant change in the specimens diagnosed as leukoplakia that eventually developed into OSCC. Thus, analysis of MAGE-A expression can predict malignant transformation in leukoplakia

A novel Multiple-Marker Method for the Early Diagnosis of Oral Squamous Cell Carcinoma

Objective: Melanoma associated antigens-A (MAGE-A) expression is highly specific to cancer cells. Thus, they can be the most suitable targets for the diagnosis of malignancy. The aim of this study was to evaluate the sensitivity of multiple MAGE-A expression analysis for the diagnosis of oral squamous cell carcinoma (OSCC)

A novel multiple-marker method for the early diagnosis of oral squamous cell carcinoma

Objective: Melanoma associated antigens-A (MAGE-A) expression is highly specific to cancer cells. Thus, they can be the most suitable targets for the diagnosis of malignancy. The aim of this study was to evaluate the sensitivity of multiple MAGE-A expression analysis for the diagnosis of oral squamous cell carcinoma (OSCC). Methods: Total of 70 OSSC and 20 normal oral mucosal (NOM) samples of otherwise healthy volunteers were examined for the expression of 10 different single antigens out of 12 different MAGE-A subtypes by highly sensitive reverse transcriptase polymerase chain reaction (RT-PCR) methods. The results were correlated to clinicopathological parameters of tumor samples. Results: Expression of MAGE-A was restricted to OSCC. The expression frequency of single antigen was between 10% and 55%. However, expression rate was increased up to 93% by the elevated number of genes examined. A significant correlation was found between the expression of MAGE-A and malignancy (p = 0.0001). In addition, multiple MAGE-A detection has also correlated to the incidence of lymph node metastasis, grading and advanced clinical stages. Conclusions: Analysis of multiple MAGE-A expression is more sensitive than the analysis of a single MAGE-A for the diagnostic evaluation of OSCC. Multiple MAGE-A expression analysis may be a very sensitive method to be used for the diagnosis even in the early stage of OSCC

Replicating Epley and Gilovich: Need for Cognition, Cognitive Load, and Forewarning do not Moderate Anchoring Effects

This project contains the preregistration, materials, and results for the replications of three studies by Epley and Gilovich (2005, Study 2; 2006, Studies 2a and 2c). The replications were designed to shed light on contradictory findings regarding the difference between self-generated anchors and experimenter-provided anchors on people's numeric estimates

In vitro behavior of layer-by-layer deposited molecular oligoelectrolyte films on Ti-6Al-4V surfaces

Layer-by-layer self-assembled films of molecular oligoelectrolytes were used to modify Ti-6Al-4V surfaces in order to test their ability as potential drug delivery system. With regard to medical application the in vitro behavior of the modified material was investigated. The Ti-6Al-4V (6% aluminium, 4% vanadium) material was treated in a layer-by-layer (LbL) process with 2, 4, 6 and 8 layers of molecular oligoelectrolytes 1 and 2 and thereby doped with a fluorescent reporter molecule 2. Human osteoblasts were cultured for a period up to 5 days on the modified material. Ti-6Al-4V surfaces without modification were used as control. In order to investigate the in vitro behavior of the coating as well as the influence of components of the coating on osteoblastic cells, respectively, cell proliferation, differentiation and attachment of hFOB cells were observed by means of cell number, osteoblastic gene expression and fluorescence microscopy. Degradation behavior of the OEM (oligoelectrolyte multilayer film) was examined using optical spectroscopy. Measurement data imply that the layer-by-layer coating was successfully assembled on the Ti surface and endures steam sterilization. The fluorescence signal in cell culture medium increased strictly linear with increasing pre-assembled number of layers on the surface. Proliferation rates of the cells in experimental groups did not differ significantly from each other (P a parts per thousand yen 0.783). Differentiation pattern was not significantly changed by the coating. The fluorescent reporter component of the film was absorbed by osteoblastic cells and was detected by fluorescence microscopy

Replicating Epley and Gilovich: Need for Cognition, Cognitive Load, and Forewarning do not Moderate Anchoring Effects

Anchoring, the assimilation of numerical estimates toward previously considered numbers, has generally been separated into anchoring from self-generated anchors (e.g., people first thinking of 9 months when asked for the gestation period of an animal) and experimenter-provided anchors (e.g., experimenters letting participants spin fortune wheels). For some time, the two types of anchoring were believed to be explained by two different theoretical accounts. However, later research showed crossover between the accounts. What now remains are contradictions between past and recent findings, specifically, which moderators affect which type of anchoring. We conducted three replications (Ntotal = 653) of seminal studies on the distinction between self-generated and experimenter-provided anchoring effects where we investigated the moderators need for cognition, cognitive load, and forewarning. We found no evidence that either type of anchoring is moderated by any of the moderators. In line with recent replication efforts, we found that anchoring effects were robust, but the findings on moderators of anchoring effects should be treated with caution

Evidence of Inbreeding in Hodgkin Lymphoma

Genome-wide association studies (GWASs) have identified several, mainly co-dominantly acting, single-nucleotide polymorphisms (SNPs) associated with Hodgkin lymphoma (HL). We searched for recessively acting disease loci by performing an analysis of runs of homozygosity (ROH) based on windows of homozygous SNP-blocks and by calculating genomic inbreeding coefficients on a SNP-wise basis. We used data from a previous GWAS with 906 cases and 1217 controls from a population with a long history of no matings between relatives. Ten recurrent ROHs were identified among 25 055 ROHs across all individuals but their association with HL was not genome-wide significant. All recurrent ROHs showed significant evidence for natural selection. As a novel finding genomic inbreeding among cases was significantly higher than among controls (P = 2.11*10(-14)) even after correcting for covariates. Higher inbreeding among the cases was mainly based on a group of individuals with a higher average length of ROHs per person. This result suggests a correlation of higher levels of inbreeding with higher cancer incidence and might reflect the existence of recessive alleles causing HL. Genomic inbreeding may result in a higher expression of deleterious recessive genes within a population