Biomedical subjects

Jürgen Dippon

Publications and source records attributed to Jürgen Dippon.

5 recordsLinked to original sources

PubMed2006

Systematic interpretation of microarray data using experiment annotations.

BACKGROUND: Up to now, microarray data are mostly assessed in context with only one or few parameters characterizing the experimental conditions under study. More explicit experiment annotations, however, are highly useful for interpreting microarray data, when available in a statistically accessible format. RESULTS: We provide means to preprocess these additional data, and to extract relevant traits corresponding to the transcription patterns under study. We found correspondence analysis particularly well-suited for mapping such extracted traits. It visualizes associations both among and between the traits, the hereby annotated experiments, and the genes, revealing how they are all interrelated. Here, we apply our methods to the systematic interpretation of radioactive (single channel) and two-channel data, stemming from model organisms such as yeast and drosophila up to complex human cancer samples. Inclusion of technical parameters allows for identification of artifacts and flaws in experimental design. CONCLUSION: Biological and clinical traits can act as landmarks in transcription space, systematically mapping the variance of large datasets from the predominant changes down toward intricate details.

Cluster Analysis↗

PubMed2006

A novel functional polymorphism in the transforming growth factor-beta2 gene promoter and tumor progression in breast cancer.

Transforming growth factor-beta (TGF-beta), a multifunctional growth factor, plays an important role in breast cancer. There is increasing evidence that enhanced expression of TGF-beta promotes breast cancer progression contributing to metastasis and invasiveness of the tumor. We identified a functional polymorphism in the TGFB2 promoter, a 4-bp insertion at position -246 relative to the transcriptional start site (-246ins). Transient transfection experiments showed that the -246ins polymorphism significantly increased TGFB2 promoter activity in breast cancer cells. Electrophoretic mobility shift assays revealed binding of the transcription factor Sp1 to the -246ins allele. Overexpression of Sp1 enhanced promoter activity of the -246ins allele, demonstrating that Sp1 mediates transcriptional activation. Furthermore, the -246ins allele was associated with enhanced TGF-beta(2) expression in breast cancer tissue (P = 0.0005). To evaluate the role of the polymorphism in breast cancer, frequency of the -246ins allele was determined in breast cancer patients (n = 78) and healthy female controls (n = 143). No significant differences were found. However, the presence of the -246ins allele was associated with lymph node metastasis (P = 0.003). The -246ins allele was a significant predictor for lymph node metastasis independent of estrogen and progesterone receptor status in a multivariate logistic regression analysis (P = 0.0118, odds ratio, 5.18; 95% confidence interval, 1.44-18.62). We provide evidence that the TGFB2 -246ins polymorphism leads to enhanced TGF-beta(2) expression levels in vivo and might thereby contribute to tumor progression and development of metastases.

Alleles↗

PubMed2005

c-erbB2 and topoisomerase IIalpha protein expression independently predict poor survival in primary human breast cancer: a retrospective study.

INTRODUCTION: c-erbB2 (also known as HER-2/neu) and topoisomerase IIalpha are frequently overexpressed in breast cancer. The aim of the study was to analyze retrospectively whether the expression of c-erbB2 and topoisomerase IIalpha protein influences the long-term outcome of patients with primary breast cancer. METHODS: In this study c-erbB2 and topoisomerase IIalpha protein were evaluated by immunohistochemistry in formalin-fixed paraffin-embedded tissue from 225 samples of primary breast cancer, obtained between 1986 and 1998. The prognostic value of these markers was analyzed. RESULTS: Of 225 primary breast tumor samples, 78 (34.7%) showed overexpression of either c-erbB2 (9.8%) or topoisomerase IIalpha protein (24.9%), whereas in 21 tumors (9.3%) both proteins were found to be overexpressed. Patients lacking both c-erbB2 and topoisomerase IIalpha overexpression had the best long-term survival. Overexpression of either c-erbB2 or topoisomerase IIalpha was associated with shortened survival, whereas patients overexpressing both c-erbB2 and topoisomerase IIalpha showed the worst disease outcome (P < 0.0001). Treatment with anthracyclines was not capable of reversing the negative prognostic impact of topoisomerase IIalpha or c-erbB2 overexpression. CONCLUSION: The results of this exploratory study suggest that protein expression of c-erbB2 and topoisomerase IIalpha in primary breast cancer tissues are independent prognostic factors and are not exclusively predictive factors for anthracycline response in patients with primary breast cancer.

Adult↗

PubMed2005

Integration of GO annotations in Correspondence Analysis: facilitating the interpretation of microarray data.

MOTIVATION: The functional interpretation of microarray datasets still represents a time-consuming and challenging task. Up to now functional categories that are relevant for one or more experimental context(s) have been commonly extracted from a set of regulated genes and presented in long lists. RESULTS: To facilitate interpretation, we integrated Gene Ontology (GO) annotations into Correspondence Analysis to display genes, experimental conditions and gene-annotations in a single plot. The position of the annotations in these plots can be directly used for the functional interpretation of clusters of genes or experimental conditions without the need for comparing long lists of annotations. Correspondence Analysis is not limited in the number of experimental conditions that can be compared simultaneously, allowing an easy identification of characterizing annotations even in complex experimental settings. Due to the rapidly increasing amount of annotation data available, we apply an annotation filter. Hereby the number of displayed annotations can be significantly reduced to a set of descriptive ones, further enhancing the interpretability of the plot. We validated the method on transcription data from Saccharomyces cerevisiae and human pancreatic adenocarcinomas. AVAILABILITY: The M-CHiPS software is accessible for collaborators at http://www.mchips.org

Algorithms↗

PubMedDate not supplied

Impact of mistletoe lectin binding in breast cancer.

BACKGROUND: One of the most often used complementary or alternative anticancer therapeutics for breast cancer is mistletoe extract with Viscum album lectin (VAA-1) as the leading component. The aim of this study was to determine the correlation between VAA-1 binding in breast cancer and disease outcome. MATERIALS AND METHODS: VAA-1 binding to either tumour cells or tumour infiltrating inflammatory cells was examined by immunohistochemical staining of paraffin tissue sections from breast cancer patients (n=226). RESULTS: About 34% of breast cancer tumour cells displayed a strong VAA-1 binding. Kaplan-Meier statistics revealed an inverse correlation between disease outcome and presence of strong VAA-1 binding to tumour cells. CONCLUSION: As binding of VAA-1 indicates the presence of galactose molecules in saccharide structures of the cytoplasm or cell membrane, we conclude that the amount of galactose-containing glycoproteins, mucoproteins and glycolipids in breast cancer tumour cells is related to disease outcome.

Breast Neoplasms↗