Wolfgang Schulz | Heinrich Heine University Düsseldorf (original) (raw)

Papers by Wolfgang Schulz

International journal of cancer. Journal international du cancer, Jan 10, 2003

NQO1 is an antioxidant enzyme, important in the detoxification of environmental carcinogens. A si... more NQO1 is an antioxidant enzyme, important in the detoxification of environmental carcinogens. A single nucleotide polymorphism (C-->T) at position 609 of the NQO1 cDNA has been associated with susceptibility to tumours induced by chemical carcinogens. In our case-control study, we determined the prevalence of the C609T NQO1 polymorphism by PCR-RFLP analysis in Caucasian patients with oesophageal adenocarcinoma (OAC; n=61), cardiac adenocarcinoma (CAC; n=120) or gastric adenocarcinoma (GAC; n=203) vs. a control group that consisted of 252 healthy blood donors. Additionally, NQO1 mRNA expression and NQO1 protein expression were determined by RT-PCR and immunohistochemistry in a subset of cases. The NQO1 C609T genotype distribution was significantly different among controls (C/C, 73.4%; C/T, 25.0%; T/T, 1.6%) as compared to OAC patients (C/C, 49.2%; C/T, 47.5%; T/T, 3.3%; p=0.0004), CAC patients (C/C, 55.8%; C/T, 40.0%; T/T, 4.2%; p=0.0005) and with GAC patients (C/C, 65.5%; C/T; 30....

Alcoholism: Clinical and Experimental Research, 2006

Human Genetics

Two females showing partial expression of X-linked chondrodysplasia punctata were identified in a... more Two females showing partial expression of X-linked chondrodysplasia punctata were identified in a family. Bone dysplasia was caused by an aberrant X chromosome that had an inverse duplication of the segment Xp21.2-Xp22.2 and a deletion of Xp22.3-Xpter. To characterise the aberrant X chromosome, dosage blots were performed on genomic DNA from a carrier using a number of X-linked probes. Anonymous sequences from Xp21.2-Xp22.2 to which probes D2, 99.61, C7, pERT87-15, and 754 bind were duplicated on the aberrant X chromosome. The proposita was heterozygous for all these markers. Dosage blots also showed that the loci for steroid sulfatase and the cell surface antigen 12E7 (MIC2) were deleted as expected from the cytogenetic results. Mouse human cell hybrids were constructed that retained the normal X in the active state. Analysis of these hybrid clones for the markers from Xp21.2-Xp22.2 revealed that all the alleles of the informative markers, present in a single dosage in the genomic DNA, were carried on the normal X chromosome of the proposita. The duplicated X chromosome therefore had two identical alleles, indicating that the aberration resulted from an intrachromosomal rearrangement.

Biological chemistry Hoppe-Seyler

ABSTRACT

Journal of Biological Chemistry

The 5'-upstream region of the rat alpha-fetoprotein (AFP) gene strongly increased de novo... more The 5'-upstream region of the rat alpha-fetoprotein (AFP) gene strongly increased de novo methylation of an adjacent chloramphenicol acetyltransferase (CAT) gene upon transfection into F9 mouse embryonal carcinoma cells. The same effect was exerted by a distal 775-base pair (bp) fragment and by 300- and 1-kb fragments preceding the transcriptional start site, but not by other parts of the control region. Further division of the larger, strongly active fragments resulted in a gradual decrease of methylation and clonal variation in the methylation patterns. The effect of the 775-bp fragment did not depend on its orientation. It was ablated by insertion of the mouse metallothionein I promoter between the AFP gene fragment and the CAT gene, but not by its insertion upstream of the AFP gene fragment. Two fragments from the AFP control region increasing methylation contained B1 and B2 small interspersed repetitive elements, respectively. B1 and B2 sequences of different origin also acted strongly to increase methylation. These findings support the idea that mammalian genes contain specific sequences involved in regulating their methylation. The effects of these sequences appear to be exerted in cis, to be dependent on proximity, but not on orientation, and to require an optimal size of 500-700 bp. Small retrotransposon sequences within such elements may be particularly effective in attracting de novo methylation.

Recent results in cancer research. Fortschritte der Krebsforschung. Progrès dans les recherches sur le cancer

BioMed Research International

Experimental Cell Research

... Hepatic cell lines McARH7777 (7777) [20], NHTu6 (Tu6) [21, 22], and MHiCi (MHC) [23], were pr... more ... Hepatic cell lines McARH7777 (7777) [20], NHTu6 (Tu6) [21, 22], and MHiCi (MHC) [23], were provided by Patricia A. Hoffee, University of Pittsburgh; HTCSR (HTC) [24] by Peter Ove, University of Pittsburgh; EOCST1269 (EOC) [25, 26] by Benito Lombardi, University of ...

European Journal of Cancer

Carcinogenesis

NAD(P)H:quinone oxidoreductase (NQOR) and glutathione S-transferases (GST) are enzymes of interes... more NAD(P)H:quinone oxidoreductase (NQOR) and glutathione S-transferases (GST) are enzymes of interest in cell defence and drug resistance. Relative levels of NQOR mRNA in renal cell carcinomas were 28 +/- 24% (n = 21) of those in non-neoplastic tissue and the enzyme activity decreased from 41 +/- 39 to 18 +/- 27 mU/mg protein (n = 23). In three of the cases, there was no measurable NQOR enzyme activity at all, indicating a polymorphism in the population for this gene. Relative GST-alpha mRNA levels in the tumours were on average 6 +/- 6% (n = 22) of the control value, whereas for GST-pi mRNA smaller decreases as well as increases were found in the tumours as compared to control tissue, but, on average, the level remained unchanged. Overall GST activity measured with CDNB as a substrate was 152 +/- 157 mU/mg protein in tumour tissue and 342 +/- 177 mU/mg protein in non-neoplastic tissue (n = 23). In all kidney tumour-derived cell lines NQOR mRNA was strongly expressed and on a per protein basis NQOR activity was about 10-fold higher than in the kidney tumour samples. GST-pi but not GST-alpha mRNA was also present. Total GST enzyme activities in these cell lines were similar to those in kidney tumour samples. HepG2 cells exhibited expression of NQOR and GST-alpha; GST-pi was not detectable. NQOR activity in HepG2 was about four-fold higher than in kidney-derived cell lines. Thus, NQOR and GST-alpha are both down-regulated in renal carcinoma, but their expression diverges in carcinoma cell lines.

European Urology Supplements, 2006

Anticancer research

p27Kip1 (p27) protein is an inhibitor of cyclin-dependent kinase complexes and prevents progressi... more p27Kip1 (p27) protein is an inhibitor of cyclin-dependent kinase complexes and prevents progression of cells from the G1- to the S-phase of the cell cycle. Decreased p27 expression has been shown to be associated with aggressive tumor behavior and decreased patient survival in numerous human malignancies. The aim of this study was to evaluate p27 expression in renal cell cancer and to assess its association with stage and grade as well as its relationship to patient outcome. One hundred and fifty-four renal cell carcinoma specimens were evaluated for p27 expression by immunohistochemical staining. Immunohistochemical findings were correlated with tumor grade, tumor stage and patient outcome. A progressive loss of nuclear p27 expression was observed with increasing tumor grade. In poorly-differentiated tumors, p27 expression was significantly lower compared to well- and moderately-differentiated tumors (p = 0.025). p27 expression tended to decrease with increasing tumor stage, but the correlation was not statistically significant (p = 0.068). The present study suggests that renal cell carcinomas showed increased aggressiveness with loss of p27 expression. A longer follow-up period will demonstrate whether this cell cycle regulator will provide additional prognostic information in patients with renal cell carcinoma.

American Journal Of Pathology

Cancer Research

Eight cell lines from transitional cell carcinoma of the urinary bladder were analyzed by compara... more Eight cell lines from transitional cell carcinoma of the urinary bladder were analyzed by comparative genomic hybridization. All tumor lines exhibited frequent chromosome gains (11.5/cell line) and losses (8.4/cell line). In six cell lines, gain of chromosome 5p was associated with gains of 6p and 20q. In five of these cell lines, amplification of parts of 6p was observed. Cytogenetic investigation combined with fluorescence in situ hybridization analysis revealed typical marker chromosomes with homogeneously staining regions (HSRs) containing material from 6p. By hybridizing individual yeast artificial chromosome probes from a chromosome 6p contig to these HSRs, a contig of three yeast artificial chromosomes common to all 6p HSRs was identified that spans less than 2 Mb. The genes SOX4 and PRL were shown to map to this region and to be coamplified in the cell lines. However, SOX4 was not overexpressed in any cell line and PRL was not expressed at all. Thus, the presumptive 6p oncog...

European urology, Jan 16, 2015

The Notch pathway, which controls stem cell maintenance and cell differentiation, is activated in... more The Notch pathway, which controls stem cell maintenance and cell differentiation, is activated in certain cancers and therefore constitutes a therapeutic target. Especially in invasive urothelial carcinoma, the pathway is inactivated instead, and drugs inhibiting Notch signaling are likely contra-indicated.

Methods in molecular biology (Clifton, N.J.), 2015

Urothelial carcinoma is the most frequent type of bladder cancer. Improvements in diagnostics and... more Urothelial carcinoma is the most frequent type of bladder cancer. Improvements in diagnostics and therapy of this common tumor are urgently required and need to be based on a better understanding of its biology. Epigenetic aberrations are crucial to urothelial carcinoma development and progression. They affect DNA methylation, histone modifications, chromatin remodeling, long noncoding RNAs, and microRNAs. Compared to other cancers, DNA hypomethylation, especially at LINE-1 retrotransposons, and mutations in enzymes establishing or removing histone acetylation or methylation are particularly prominent. Accumulating evidence suggests that disturbances in DNA methylation, histone modifications and noncoding RNAs may contribute especially to altered differentiation and metastatic potential. With proper selection, histone-modifying enzymes may constitute good targets for therapy. For diagnostics, DNA methylation and miRNA biomarkers are well suited because of their relatively high stabi...

Oncology research and treatment, 2014

Several novel therapeutic agents have demonstrated ability to improve overall survival in metasta... more Several novel therapeutic agents have demonstrated ability to improve overall survival in metastatic castration-resistant prostate cancer (mCRPC) in recent years. With as many as 5 new agents approved within the last 5 years and an ongoing lack of comparative and prospective data, strategies for patient selection and sequencing of drug treatments are urgently needed. This review will summarize current clinical evidence and relevant molecular mechanisms in mCRPC. The understanding of these mechanisms may provide valuable assistance in making therapeutic decisions, especially while robust clinical data remain sparse.

Biological chemistry, 2014

Cancers, 2011

Overexpression of the classical homeobox transcription factor HOXC6 is frequent in prostate cance... more Overexpression of the classical homeobox transcription factor HOXC6 is frequent in prostate cancers and correlates with adverse clinical parameters. Since surprisingly many HOXC6 target genes are downregulated in prostate cancer, it has been posited that oncogenic effects of HOXC6 in prostate cancer may be unmasked by concurrent epigenetic downregulation of target genes exerting tumor suppressive effects. To test this hypothesis, we have studied the expression of three HOXC6 target genes, CNTN1 (encoding a cell adhesion protein), DKK3 and WIF1 (encoding WNT growth factor antagonists) as well as DNA methylation of DKK3 and WIF1. HOXC6 upregulation and association with poor prognosis were confirmed in our tissue series. The three target genes were each significantly downregulated in cancer tissues and expression of each one correlated inversely with that of HOXC6. Cases with lower WIF1 expression showed significantly earlier recurrence (p = 0.021), whereas no statistical significance ...

Methods in molecular biology (Clifton, N.J.), 2012

Epigenetic alterations contribute significantly to the development and progression of prostate ca... more Epigenetic alterations contribute significantly to the development and progression of prostate cancer, the most prevalent malignant tumor in males of Western industrialized countries. Here, we review recent research on DNA methylation alterations in this cancer type. Hypermethylation of several genes including GSTP1 is well known to occur in a consistent and apparently coordinate fashion during the transition from intraepithelial neoplasia to frank carcinoma. These hypermethylation events have shown promise as biomarkers for detection of prostate carcinoma. Many other individual genes have been shown to undergo hypermethylation, which is typically associated with diminished expression. These investigations indicate additional candidates for biomarkers; in particular, hypermethylation events associated with progression can be employed to identify more aggressive cases. In addition, some of genes silenced by aberrant methylation in prostate have been shown to exhibit properties of tum...