Reinhard Büttner

Bio: Reinhard Büttner is an academic researcher from University Hospital Bonn. The author has contributed to research in topics: Sarcoma & Prostate cancer. The author has an hindex of 18, co-authored 55 publications receiving 2532 citations. Previous affiliations of Reinhard Büttner include RWTH Aachen University & University Medical Center Freiburg.

Integrated THz technology for label-free genetic diagnostics

Abstract: We report on a promising approach for the label-free analysis of DNA molecules using direct probing of the binding state of DNA with electromagnetic waves at THz frequencies. Passive THz resonator devices based on planar waveguides are used as sample carriers and transducers for THz transmission analysis. In comparison to a formerly used free-space detection scheme, this method provides a drastically enhanced sensitivity enabling analysis down to femtomol levels. We examine the potential of our approach on biologically relevant DNA samples and demonstrate the detection of single base mutations on DNA molecules.

Label-free probing of the binding state of DNA by time-domain terahertz sensing

Abstract: We present a promising approach for the label-free characterization of genetic material. Time-resolved terahertz (THz) transmission analysis of polynucleotides demonstrate a strong dependence of the complex refractive index on the binding state (hybridized/denatured) of deoxyribonucleic acid (DNA) molecules. By monitoring THz transients, one can thus infer the binding state of oligo- and polynucleotides, and hence identify polynucleotides by detecting the binding of unknown polynucleotide DNA sequences to known probe molecules. A broadband experimental demonstration in a free-space configuration, as well as a discussion of the potential application for next generation gene chips is presented.

Global levels of histone modifications predict prostate cancer recurrence

Abstract: PURPOSE Epigenetic alterations such as DNA methylation and histone modifications play important roles in carcinogenesis. It was reported that global histone modification patterns are predictors of cancer recurrence in various tumor entities. Our study was performed to evaluate histone lysine (HxKy) and histone acetyl (HxAc) modifications in prostate tissue. MATERIALS AND METHODS A tissue microarray with 113 prostate cancer (PCA), 23 non-malignant prostate tissues was stained with antibodies against H3K4 mono-(H3K4me1), di-(H3K4me2), tri-(H3K4me3) methylation, H3K9me1, H3K9me2, H3K9me3, H3 and H4 pan-acetylation (H3Ac, H4Ac). We also analyzed H3K4 methylation in patients with advanced PCA (hormone-refractory PCA—HRPC, n = 34; hormone-dependent PCA, n = 30). Sections were scored according the staining intensity and the proportion of epithelial cells showing nuclear staining. RESULTS H3K4me1, H3K9me2, H3K9me3, H3Ac, and H4Ac were significantly reduced in PCA compared to non-malignant prostate tissue. H3Ac and H3K9me2 levels allowed discrimination of PCA and non-malignant prostate tissue highly specifically (>91%) and sensitively (>78%) as determined via ROC analyses (AUC >0.91). Histone lysine methylation and histone acetylation marks were correlated with clinical–pathological parameters (i.e., digital rectal examination, preoperative PSA, pT-stage, lymph node metastasis, Gleason score). In addition, H3K4me1 was a significant predictor of PSA recurrence following radical prostatectomy. H3K4me1, H3K4me2, and H3K4me3 levels were significantly increased in HRPC. CONCLUSIONS Global histone modification levels may help to identify patients with adverse prognosis, and represent a target for the future therapy of PCA. Prostate 70: 61–69, 2010. © 2009 Wiley-Liss, Inc.

CpG Island Hypermethylation in Cell-Free Serum DNA Identifies Patients With Localized Prostate Cancer

Abstract: BACKGROUND One of the earliest and most common epigenetic events in prostate carcinogenesis is DNA CpG island (CGI) hypermethylation. Our aim was to analyze the diagnostic and prognostic possibilities of multigene methylation analysis in cell-free serum DNA of prostate cancer (PCA) patients. METHODS We analyzed serum samples from 226 consecutive patients (168 PCA; 42 benign prostatic hyperplasia (BPH); 5 incidental PCA; 11 healthy individuals). Cell-free DNA was digested with methylation-sensitive restriction endonucleases (HpaII and HinP1I). Subsequently, CGI hypermethylation at GSTP1, PTGS2, Reprimo, and TIG1 was assessed using real-time PCR. RESULTS CGI hypermethylation at GSTP1, TIG1, PTGS2, and Reprimo was more frequent in PCA (42.3%, 9.5%, 2.4%, and 1.2%, respectively) compared to BPH (7.7%, 0%, 0%, and 0%, respectively) and healthy individuals (all 0%) with a statistical significant difference of GSTP1 (P < 0.0001) and TIG1 (P = 0.038). GSTP1 hypermethylation was also detected in four patients with incidental PCA. Hypermethylation in serum DNA at GSTP1 and hypermethylation at any gene site distinguished between PCA and BPH patients in a highly specific (92%) but less sensitive (42–47%) manner. Neither CGI hypermethylation at a single gene loci nor the combination of multiple gene sites was correlated to the pathological stage, grade or biochemical recurrence following radical prostatectomy. CONCLUSIONS The detection of aberrant hypermethylation in cell-free serum DNA allows the highly specific diagnosis of PCA. A test based on GSTP1 hypermethylation in serum samples of patients with suspected PCA may help to identify men with increased risk of harboring PCA despite negative prostate biopsy. Prostate 68: 42–49, 2008. © 2007 Wiley-Liss, Inc.

Cutting-edge terahertz technology

Abstract: Research into terahertz technology is now receiving increasing attention around the world, and devices exploiting this waveband are set to become increasingly important in a very diverse range of applications. Here, an overview of the status of the technology, its uses and its future prospects are presented.

Materials for terahertz science and technology

Abstract: Terahertz spectroscopy systems use far-infrared radiation to extract molecular spectral information in an otherwise inaccessible portion of the electromagnetic spectrum. Materials research is an essential component of modern terahertz systems: novel, higher-power terahertz sources rely heavily on new materials such as quantum cascade structures. At the same time, terahertz spectroscopy and imaging provide a powerful tool for the characterization of a broad range of materials, including semiconductors and biomolecules.

Cell-free nucleic acids as biomarkers in cancer patients

Abstract: 1described the presence of cell-free nucleic acid (cfNA) in human blood for the first time. This attracted little attention in the scientific community and it was not until 1994 that the importance of cfNA was recognized as a result of the detection of mutated RAS gene fragments in the blood of cancer patients 2,3 (TIMELINE). In 1996, microsatellite alterations on cell-free DNA (cfDNA) were shown in cancer patients 4

Integrating liquid biopsies into the management of cancer

Abstract: During cancer progression and treatment, multiple subclonal populations of tumour cells compete with one another, with selective pressures leading to the emergence of predominant subclones that replicate and spread most proficiently, and are least susceptible to treatment. At present, the molecular landscapes of solid tumours are established using surgical or biopsy tissue samples. Tissue-based tumour profiles are, however, subject to sampling bias, provide only a snapshot of tumour heterogeneity, and cannot be obtained repeatedly. Genomic profiles of circulating cell-free tumour DNA (ctDNA) have been shown to closely match those of the corresponding tumours, with important implications for both molecular pathology and clinical oncology. Analyses of circulating nucleic acids, commonly referred to as 'liquid biopsies', can be used to monitor response to treatment, assess the emergence of drug resistance, and quantify minimal residual disease. In addition to blood, several other body fluids, such as urine, saliva, pleural effusions, and cerebrospinal fluid, can contain tumour-derived genetic information. The molecular profiles gathered from ctDNA can be further complemented with those obtained through analysis of circulating tumour cells (CTCs), as well as RNA, proteins, and lipids contained within vesicles, such as exosomes. In this Review, we examine how different forms of liquid biopsies can be exploited to guide patient care and should ultimately be integrated into clinical practice, focusing on liquid biopsy of ctDNA - arguably the most clinically advanced approach.

Terahertz technology in biology and medicine

Abstract: Terahertz irradiation and sensing is being applied for the first time to a wide range of fields outside the traditional niches of space science, molecular line spectroscopy, and plasma diagnostics. This paper surveys some of the terahertz measurements and applications of interest in the biological and medical sciences.