Combined microPET/CT for imaging of hepatocellular carcinoma in mice (2009)
Falck, C. Von, Rodt, T., Halter, R., Spanel, R., Galanski, M., Borlak, J.
The EGF-transgenic mouse is a genetic model of hepatocellular carcinoma that allows for a comprehensive study of signal pathways, molecular interactions and the evaluation of novel therapeutic...
In vivo microCT quantification of lung tumor growth in SPC-raf transgenic mice (2009)
Rodt, T., Falck, C. Von, Halter, R., Ringe, K., Shin, H.O., Galanski, M., ...
Lung cancer is the most common cancer worldwide. Early detection might reduce morbidity. In this study we evaluate a microCT imaging algorithm to assess in-vivo tumour load and quantification of...
Posttransplantation diabetes mellitus (PTDM) is a frequent complication in immunosuppressive therapy. To better understand the molecular events associated with PTDM we investigated the effect of...
Posttransplantation diabetes mellitus (PTDM) is a frequent complication in immunosuppressive therapy. To better understand the molecular events associated with PTDM we investigated the effect of...
We previously reported targeted overexpression of c-myc to alveolar epithelium to cause lung cancer. We now extended our studies to the serum proteome of tumor bearing mice. Proteins were extracted...
Molecular characterization of lung dysplasia induced by c-Raf-1 (2009)
Rohrbeck, A., Müller, V.S., Borlak, J.
BACKGROUND: Lung cancer is a multistage process with poor prognosis and high morbidity. Importantly, the genetics of dysplasia, a facultative cancer, at the edge of malignant transformation is...
Molecular characterization of lung dysplasia induced by c-Raf-1 (2009)
Rohrbeck, A., Müller, V.S., Borlak, J.
BACKGROUND: Lung cancer is a multistage process with poor prognosis and high morbidity. Importantly, the genetics of dysplasia, a facultative cancer, at the edge of malignant transformation is...
A functional genetic study identifies HAND1 mutations in septation defects of the human heart (2009)
Reamon-Buettner, S.M., Ciribilli, Y., Traverso, I., Kuhls, B., Inga, A., Borlak, J.
HAND1 is a basic helix-loop-helix (bHLH) transcription factor essential for mammalian heart development. Absence of Hand1 in mice results in embryonal lethality, as well as in a wide spectrum of...
BACKGROUND: The choroid plexus consists of highly differentiated epithelium and functions as a barrier at the interface of the blood-cerebrospinal-fluid (CSF). This tissue may therefore determine the...
BACKGROUND: The choroid plexus consists of highly differentiated epithelium and functions as a barrier at the interface of the blood-cerebrospinal-fluid (CSF). This tissue may therefore determine the...
Kosacka, J., Gericke, M., Nowicki, M., Kacza, J., Borlak, J., Spanel-Borowski, K.
Co-cultures of 3T3-L1 adipocytes with neurons from the rat dorsal root ganglia (DRG) showed enhanced neuritogenesis and synaptogenesis. Microarray analysis for upregulated genes in adipocyte/DRG...
Nowicki, M., Kosacka, J., Spanel-Borowski, K., Borlak, J.
Deferoxamine (DFO) was granted orphan drug status for the treatment of traumatic spinal cord injury but its neuroprotective mechanism is not well understood. We therefore investigated the mode of...
An update on the mouse liver proteome (2009)
Background: Decoding of the liver proteome is subject of intense research, but hampered by methodological constraints. We recently developed an improved protocol for studying rat liver proteins based...
Identifying proteins of signaling networks has received much attention, because an array of biological processes are entirely dependent on protein cross-talk and protein-protein interactions. Protein...
Xenobiotic induced liver injury is a leading cause for drug withdrawal and toxicogenomics may help to identify molecular causes. Here we report studies with cultures of human hepatocytes to detect...
Kel, A.E., Niehof, M., Matys, V., Zemlin, R., Borlak, J.
We report an application of machine learning algorithms that enables prediction of the functional context of transcription factor binding sites in the human genome. We demonstrate that our method...
Epidermal growth factor (EGF) is an important mitogen for hepatocytes. Its targeted overexpression induced hepatocellular carcinomas (HCC), as recently reported by us (Borlak et al. 2005). Early...
HNF4 alpha and the Ca-Channel TRPC1 are novel disease candidate genes in diabetic nephropathy (2008)
OBJECTIVE-The nuclear receptor hepatic nuclear factor 40. (HNF4 alpha) is a master regulatory protein and an essential player in the control of a wide range of metabolic processes. Dysfunction of...
Nuclear factor-eythroid 2-related factor 2 prevents alcohol-induced fulminant liver injury (2008)
Lamle, J., Marhenke, S., Borlak, J., Wasielewski, R. Von, Eriksson, C.J.P., Geffers, R., ...
Background & Aims: The transcription factor nuclear factor-eythroid 2-related factor 2 (Nrf2(-/-)) is essential for protecting cells against xenobiotic and oxidative stress. Increased oxidative...
Background Aims: The orphan nuclear receptor HNF4 alpha is a member of the hepatic transcription factor network. This protein plays a pivotal role in liver development and hepatocellular...
Activation of the lectin-like oxLDL receptor (LOX-1) promotes atherosclerosis. Oxidized LDL (OxLDL) increases production of reactive oxygen species (ROS) and leads to the development of endothelial...
Passarella, D., Giardini, A., Peretto, B., Fontana, G., Sacchetti, A., Silvani, A., ...
A series of novel hybrid compounds obtained by the attachment of anhydrovinblastine, vinorelbine, and vindoline to thiocolchicine, podophyllotoxin, and baccatin III are described. Two types of diacyl...
Reamon-Büttner, S.M., Ciribilli, Y., Inga, A., Borlak, J.
Hypoplasia of the human heart is the most severe form of congenital heart disease (CHD) and usually lethal during early infancy. It is a leading cause of neonatal loss, especially in infants...
The next innovation cycle in toxicogenomics: Environmental epigenetics (2008)
Reamon-Büttner, S.M., Mutschler, V., Borlak, J.
Toxicogenomics is a field that emerged from the combination of conventional toxicology with functional genomics. In recent years, this field contributed immensely in defining adverse biological...
Graft rejection: Pharmacogenetic analysis or drug anamnesis (2008)
Pham, V.V., Stichtenoth, D.O., Borlak, J.
AIMS: A 23-year-old Caucasian woman, with cystic fibrosis, bilateral lung-transplantation and immunosuppressive therapy with prednisolone, tacrolimus and sirolimus, presented with clinical symptoms...
The analytical performance of MALDI-MS is highly influenced by sample preparation and the choice of matrix. Here we present an improved MALDI-MS sample preparation method for peptide mass mapping and...
C-raf is a serine-threonine kinase and a downstream effector of ras signaling. This kinase plays an essential role in cell proliferation, differentiation, and apoptosis. In the past, we reported...
Topoisomerase II inhibition involves characteristic chromosomal expression patterns (2008)
Background: The phenomenon of co-localization of transcriptionally upregulated genes showing similar expression levels is known across all eukaryotic genomes. We recently mapped the Aroclor...
Abstract Based on an increasing knowledge in cancer biology researcher have become increasingly interested in studying signal transduction pathways that regulate cellular growth, cell cycle and...
Molecular mechanisms and therapeutic targets in steatosis and steatohepatitis (2008)
Steatosis of the liver may arise from a variety of conditions, but the molecular basis for lipid droplet formation is poorly understood. Although a certain amount of lipid storage may even be...
Kleine, M., Schrem, H., Borlak, J., Klempnauer, J.
Background and aims: In fulminant hepatic failure, the clinical use of bioartifical liver support with porcine hepatocytes is the subject of a controversial debate. Cytochrome P450 (CYP) metabolic...
Reamon-Büttner, S.M., Borlak, J.
Understanding molecular mechanisms underlying lung cancer is a prerequisite toward treatment. To enable mechanistic investigations into the epigenetic regulation of the tumor suppressor gene cell...
Background: Unravelling the serum proteome is the subject of intensified research. In this regard, two-dimensional electrophoresis coupled with MALDI MS analysis is still one of the most commonly...
A genome-wide expression analysis identifies a network of EpCAM-induced cell cycle regulators (2008)
Expression of the epithelial cell adhesion molecule EpCAM is upregulated in a variety of carcinomas. This antigen is therefore explored in tumour diagnosis, and clinical trials have been initiated to...
Gender-incompatible liver transplantation is not a risk factor for patient survival (2008)
Lehner, F., Becker, T., Klempnauer, J., Borlak, J.
Background/Aims: Clinical data may be suggestive for differences in patient survival in gender-incompatible orthotopic liver transplantation (OLT), but findings are inconsistent and are putatively...
BACKGROUND: The transcriptional regulator c-Myc is the most frequently deregulated oncogene in human tumors. Targeted overexpression of this gene in mice results in distinct types of lung...
BACKGROUND: The transcriptional regulator c-Myc is the most frequently deregulated oncogene in human tumors. Targeted overexpression of this gene in mice results in distinct types of lung...
Background: Unravelling the serum proteome is the subject of intensified research. In this regard, two-dimensional electrophoresis coupled with MALDI MS analysis is still one of the most commonly...
Beineke, A, Markus, S., Borlak, J., Thum, T., Baumgärtner, W.
Canine distemper virus (CDV) infection of the central nervous system results in lesions of the gray and white matter. While a biphasic disease process has been discussed for leukoencephalitis with a...
Kel, A.E., Niehof, M., Matys, V., Zemlin, R., Borlak, J.
We report an application of machine learning algorithms that enables prediction of the functional context of transcription factor binding sites in the human genome. We demonstrate that our method...
Background Aims: The orphan nuclear receptor HNF4 alpha is a member of the hepatic transcription factor network. This protein plays a pivotal role in liver development and hepatocellular...
Thum, T., Hoeber, S., Froese, S., Klink, I., Stichtenoth, D.O., Galuppo, P., ...
Aging is associated with an increased risk for atherosclerosis. A possible cause is low numbers and dysfunction of endothelial progenitor cells (EPC) which insufficiently repair damaged vascular...
Hansen, T., Seidel, A., Borlak, J.
The environmental contaminant 3-nitrobenzanthrone (3-NBA) is highly mutagenic and a suspected human carcinogen. We aimed to evaluate whether 3-NBA is able to deregulate critical steps in cell cycle...
Hansen, T., Seidel, A., Borlak, J.
The environmental contaminant 3-nitrobenzanthrone (3-NBA) is highly mutagenic and a suspected human carcinogen. We aimed to evaluate whether 3-NBA is able to deregulate critical steps in cell cycle...
Lehner, F., Kulik, U., Klempnauer, J., Borlak, J.
The molecular causes leading to secondary liver malignancies are unknown. Here we report regulation of major hepatic nuclear factors in human colorectal liver metastases and primary colonic cancer....
MicroRNAs in the human heart: A clue to fetal gene reprogramming in heart failure (2007)
Thum, T., Galuppo, P., Wolf, C., Fiedler, J., Kneitz, S., Laake, L.W. Van, ...
Background - Chronic heart failure is characterized by left ventricular remodeling and reactivation of a fetal gene program; the underlying mechanisms are only partly understood. Here we provide...
Improved method for proteome mapping of the liver by 2-DE MALDI-TOF MS (2007)
Identifying the liver proteome has been the subject of intensified research. Notably, due to their strong heterogeneity in size, charge, solubility, and relative abundance, different strategies of...
Reamon-Buettner, S.M., Borlak, J.
'Epigenetics' is a heritable phenomenon without change in primary DNA sequence. In recent years, this field has attracted much attention as more epigenetic controls of gene activities are being...
Reamon-Buettner, S.M., Cho, S.H., Borlak, J.
Background: The 3'-untranslated region (3'-UTR) of mRNA contains regulatory elements that are essential for the appropriate expression of many genes. These regulatory elements are involved in the...
Borlak, J., Salinas-Riester, G.
DE 102005052384 A1 UPAB: 20070719 NOVELTY - Method for diagnosis, labeling and treatment of lung tumors in which a biological or biotechnical system is contacted with at least one substance (X), at...
Nowicki, M., Zabirnyk, O., Duerrschmidt, N., Borlak, J., Spanel-Borowski, K.
The oxidized low-density lipoprotein (oxLDL)-dependent activation of the lectin-like oxLDL receptor-1 (LOX-1) triggers apoptosis in vascular cells and appears to be involved in atherosclerosis....
Kuntz, E., Borlak, J., Riss, G., Aebischer, C.P., Bachmann, H., Seifert, N., ...
Beta-Carotene (BetaC) supplementation in smokers was unexpectedly associated with increased incidence of lung cancer versus smoking alone. We performed a study in A/J mice to explore possible...
We previously reported a proteome map of lung adenocarcinomas in serine-threonine kinase of the Raf family (c-raf) transgenic mice. We now extend our initial studies to serum proteins at early stage...
Nowicki, M., Kosacka, J., Brossmer, R., Spanel-Borowski, K., Borlak, J.
The novel myelin-associated glycoprotein (MAG) inhibitor BENZ binds to the N-acetylneuraminic acid (Neu5Ac) portion of the N-terminal Ig-like domain of MAG. Treatment of rat dorsal root ganglion...
Leberspezifische Transkriptionsfaktoren und deren Bedeutung in kolorektalen Lebermetastasen (2007)
Lehner, F., Klempnauer, J., Borlak, J.
Background and Aims: The molecular causes leading to secondary liver malignancies are unknown. We therefore investigated regulation of major hepatic nuclear factors in primary human colonic cancer...
Halter, R., Hansen, T., Seidel, A., Ziemann, C., Borlak, J.
The equivocal experimental and epidemiological evidence of bitumen fumes and the possible mechanisms of toxicity remain uncertain. This study therefore aimed at investigating the genotoxicity of...
Neue Biomarker für Leberkrebs (2007)
Ritorto, M.S., Chatterji, B., Borlak, J.
Bekannte diagnostische Marker für Leberkrebs eignen sich nur unzureichend für eine sichere Diagnose. Die Serumproteomik unterstützt die Entdeckung neuer Biomarker. Eine besondere Rolle in der...
Doppelt transgenes nicht menschliches Saeugetier (2007)
(A1) Die Erfindung betrifft transgene nicht menschliche Saeugetiere, die zwei Transgene in ihrem Genom tragen, ein Verfahren zu deren Herstellung, deren Verwendung und Zellgewebe daraus....
Somatic mutations in cardiac malformations (2006)
Reamon-Büttner, S.M., Borlak, J.
It has come to our attention that there may be some confusion about the relationship of the data in two of our NKX2-5 papers. Therefore, this correspondence aims to address the following issues:...
Onkoproteomics von Lungentumoren (2006)
Chatterji, B., Ritorto, M.S., Garaguso, I., Belau, E., Gazzana, G., Borlak, J.
Background Aroclor 1254 is a well-known hepatotoxin and consists of a complex mixture of polychlorinated biphenyls (PCBs), some of which have the ability to activate the aryl hydrocarbon receptor...
Primary rat alveolar epithelial cells for use in biotransformation and toxicity studies (2006)
Hansen, T., Blickwede, M., Borlak, J.
The alveolar epithelium may function as a barrier for airborne xenobiotics, and in vitro models mimicking this barrier are useful for metabolism and toxicity studies. To gain insight into the...
N-acetyltransferase 2 (NAT2) gene polymorphisms in colon and lung cancer patients (2006)
Borlak, J., Reamon-Büttner, S.
Background: N-acetyltransferase 2 (NAT2) metabolizes arylamines and hydrazines moeities found in many therapeutic drugs, chemicals and carcinogens. The gene encoding NAT2 is polymorphic, thus...
Gebel, S., Gerstmayer, B., Kuhl, P., Borlak, J., Meurrens, K., Müller, T.
Gene expression profiling in animal models exposed to cigarette mainstream smoke (CS) shapes up as a promising tool for investigating the molecular mechanisms involved in the onset and development of...
Drug-induced phospholipidosis (2006)
Drug-induced phospholipidosis is characterized by intracellular accumulation of phospholipids with lamellar bodies, most likely from an impaired phospholipid metabolism of the lysosome. Organs...
Zschemisch, N.H., Liedtke, C., Dierssen, U., Nevzorova, Y.A., Wustefeld, T., Borlak, J., ...
Cyclin E1 controls G1/S phase transition of the eukaryotic cell cycle. We report the impact of alternative spliced cyclin E1 isoforms on cell cycle regulation in hepatocytes. We show that expression...
Duerrschmidt, N., Zabirnyk, O., Nowicki, M., Ricken, A., Hmeidan, F.A., Blumenauer, V., ...
The LOX-1 receptor, identified on endothelial cells, mediates the uptake of oxidized low-density lipoprotein (oxLDL). The oxLDL-dependent LOX-1 activation causes endothelial cell apoptosis. We here...
Thum, T., Erpenbeck, V.J., Moeller, J., Hohlfeld, J.M., Krug, N., Borlak, J.
Background. Cytochrome P450 monooxygenases (CYP) play an important role in the defense against inhaled toxicants and expression of CYP enzymes may differ amongst various lung cells and tissue...
Reamon-Buettner, S.M., Spanel-Borowski, K., Borlak, J.
Birth defects are the leading cause of infant mortality and malformations in congenital heart disease (CHD) are among the most prevalent and fatal of all birth defects. Yet the molecular mechanisms...
Vitamin E in heart transplantation: Effects on cardiac gene expression (2006)
Schulte, I., Bektas, H., Klempnauer, J., Borlak, J.
BACKGROUND: Oxidative stress, as induced in organ storage or upon reperfusion, may impact the quality of the transplant. Vitamin E, a radical scavenger, may alleviate stress associated with cardiac...
Towards a lung adenocarcinoma proteome map: Studies with SP-C/c-raf transgenic mice (2006)
Rütters, H., Zürbig, P., Halter, R., Borlak, J.
We report mapping of proteins of adenocarcinomas of the lung as a result of overexpression of the oncogenically activated N-terminal deletion mutant c-raf-1 BxB through usage of the human SP-C...
Hermann, R., Borlak, J., Munzel, U., Niebch, G., Fuhr, U., Maus, J.E.K., ...
Retigabine (RGB) is an investigational antiepileptic drug, which undergoes extensive UGT1A1, 1A9 and 1A4-mediated N-glucuronidation and N-acetylation. The mono-acetylated metabolite of RGB has some...
Borlak, J., Gasparic, A., Locher, M., Schupke, H., Hermann, R.
Retigabine (D-23129), an N-2-amino-4-(4-fluorobenzylamino)phenylcarbamine acid ethyl ester, is a novel antiepileptic drug which is currently in phase II clinical development. This drug undergoes...
Kosacka, J., Nowicki, M., Kacza, J., Borlak, J., Engele, J., Spanel-Borowski, K.
Sensory and sympathetic innervation of the white fat tissue (WAT) contributes to lipolysis. In addition, both fiber types adapt in density to weight gain and loss. Because these findings are...
N-acetyltransferase 2 (NAT2) gene polymorphisms in Parkinson's disease (2006)
Borlak, J., Reamon-Büttner, S.M.
BACKGROUND: Parkinson's disease (PD) is a movement disorder caused by the degeneration of dopaminergic neurons in the substantia nigra of the midbrain. The molecular basis of this neural death is...
The Ca(2+) antagonists nifedipine has been used for more than three decades to treat hypertension, but its effects on the transcriptional regulation of cardiac genes are basically unknown. We...
HEY2 mutations in malformed hearts (2006)
Reamon-Buettner, S.M., Borlak, J.
The basic helix-loop-helix (bHLH) transcription factor Hey2 (gridlock) is an important determinant of mammalian heart development, but its role in human ventricular septal defects is unknown. Hey2...
Acetylsalicylic acid (aspirin) reduces endothelial cell senescence (2006)
Scalera, F., Borlak, J., Schubert, B., Martens-Lobenhoffer, J., Thum, T., Frolich, J.C., ...
Physiological incompatibilities of porcine hepatocytes for clinical liver support (2006)
Schrem, H., Kleine, M., Borlak, J., Klempnauer, J.
In fulminant hepatic failure, the use of bioartificial liver support (BAL) with porcine hepatocytes is the subject of a current and controversial debate.(1) Specifically, the issue of cross-species...
Statins delay endothelial cell senescence (2006)
Scalera, F., Borlak, J., Schubert, B., Martens-Lobenhoffer, J., Thum, T., Frölich, J.C., ...
A map of the rat liver proteome: Abstract 35.4 (2005)
The number of proteins expressed in eukaryotic cells may vary between several thousands to half a million. Single hepatic cells express on average about 10,000 different proteins. Due to their strong...
Jacobs, T., Andra, J., Gaworski, I., Graefe, S., Mellenthin, K., Kromer, M., ...
To elucidate the role of complement-mediated uptake in Leishmania major infection in vivo, transgenic BALB/c mice that express the cobra venom factor (CVF) under control of the 1-antitrypsin promoter...
Gerhard, R., Tatge, H., Genth, H., Thum, T., Borlak, J., Fritz, G., ...
Clostridium difficile toxin A mono-glucosylates the Rho family GTPases Rho, Rac, and Cdc42. Glucosylation leads to functional inactivation of Rho GTPases and causes disruption of the actin...
PCR-Reaktionsgemisch fuer Fluoreszenz-basierende Genexpressions- und Genmutationsanalysen (2005)
WO 200222865 A UPAB: 20020618 NOVELTY - Polymerase chain reaction (PCR) mixture (A) for fluorescent-based gene expression and gene mutation analysis comprising: a Taq polymerase (I); bovine serum...
Administration of drugs by inhalation opens new possibilities for entry into the systemic circulation and cultures of porcine pulmonary epithelial cells (PECs) may prove to be valuable in the...
Liedtke, C., Zschemisch, N.H., Cohrs, A., Roskams, T., Borlak, J., Manns, M.P., ...
Background & Aims: Caspase-8 is the apical caspase essential for triggering Fas-induced apoptosis. In this study, we investigated caspase-8 expression in hepatocellular carcinomas (HCCs) using...
Epoxyeicosatrienoic acids (EETs) and hydroxyeicosatetraenoic acids (HETEs) are oxidative products of arachidonic acid, some of which participate in the regulation of vascular tone. Little is known...
The molecular pathology of cardiac hypertrophy is multifactorial with transcript regulation of ion channels, ion exchangers and Ca(2+)-handling proteins being speculative. We therefore investigated...
Carcinogenicity of polycyclic aromatic hydrocarbons (2005)
Straif, K., Baan, R., Grosse, Y., Secretan, B., El Ghissassi, F., Cogliano, V., ...
Reamon-Buettner, S.M., Borlak, J.
Heart development is complex and requires the sequential and timely interplay of regulatory master proteins, notably several transcription factors. Germline mutations in the human transcription...
GATA4 zinc finger mutations as a molecular rationale for septation defects of the human heart (2005)
Reamon-Buettner, S.M., Borlak, J.
GATA4 is localised on human chromosome 8p23.1-p22 and codes for a zinc finger transcription factor. Mice lacking Gata4 suffer from defective ventral morphogenesis and heart tube formation.1,2 This...
Borlak, J., Meier, T., Halter, R., Spanel, R., Spanel-Borowski, K.
Epidermal growth factor is an important mitogen for hepatocytes. Its overexpression promotes hepatocellular carcinogenesis. To identify the network of genes regulated through EGF, we investigated the...
Chromatin immunoprecipitation-based identification of gene regulatory networks (2005)
Administered in critical doses, drugs and chemicals can damage organs and tissues by turning numerous genes on or off. Changes in the expression patterns of target genes indicate toxic action and are...
Toxicogenomics applied to teratogenicity studies (2005)
Teratology is the study of birth defects S structural or functional abnormalities that are present at birth. In humans, most of the observed birth defects are caused by random genetic errors;...
Toxicogenomics applied to cardiovascular toxicity (2005)
Toxicogenomics is an emerging discipline that uses genomics tools, including gene expression profiling technologies, to address problems of toxicological significance. Initial results are now...
Regulatory networks of liver enriched transcription factors in liver biology and disease (2005)
Borlak, J., Klempnauer, J., Schrem, H.
New genomic platform technologies enable the study of complex genomes and proteomes for improved target identification and validation. This leads to high-density datasets, on the order of millions of...
Databases and tools for in silico analysis of regulation of gene expression (2005)
Kel, A., Kel-Margoulis, O., Borlak, J., Tchehekmenev, D., Wingender, E.
Regulation of gene expression is the key problem of the era of functional genomics. Now we know that genes in genomes of higher eukaryotic organisms are regulated mainly by means of multiple...
Handbook of toxicogenomics: Strategies and applications (2005)
Toxicogenomics promises to speed toxicity analyses, streamline drug development, and improve consumer safety. It is a rapidly evolving field of life sciences research that is highly relevant both for...
RSK4 and PAK5 are novel candidate genes in diabetic rat kidney and brain (2005)
The orphan hepatic nuclear factor (HNF) HNF4alpha is of pivotal importance for liver development and hepatocellular differentiation and plays an essential role in a regulatory circuitry to control a...
Borlak, J., Blickwede, M., Hansen, T., Koch, W., Walles, M., Levsen, K.
Administration of therapeutic entities by inhalation opens new possibilities for drug entry into systemic circulation, but this requires passage through the alveolar epithelium. Little is known about...
Inga, A., Reamon-Büttner, S.M., Borlak, J., Resnick, M.A.
Human heart development requires an orderly coordination of transcriptional programs, with the homeodomain protein NKX2-5 being one of the key transcription factors required for the differentiation...
Oxidized low-density lipoprotein (oxLDL) is an important risk factor for vascular injury. Its role on coronary vasoconstriction remains speculative. Endothelial monooxygenases (cytochrome P450s...
Verbesserte Arzneitherapie (2004)
Menschen reagieren verschieden auf Medikamente. Mitunter wirken sie auch gar nicht oder haben Nebenwirkungen. Doch was bleibt dem Arzt übrig als auszuprobieren, wenn niemand im Voraus weiß, welches...
1. Basolateral and canalicular proteins are expressed in the liver and besides their role in the transport of bilirubin, glutathione, hormones and various glucuronides, they also function as...
Reamon-Büttner, S.M., Borlak, J.
Heart development is complex and requires the sequential and timely interplay of regulatory master proteins, notably several transcription factors. Germline mutations in the human transcription...
Scalera, F., Borlak, J., Beckmann, B., Martens-Lobenhoffer, J., Thum, T., Tager, M., ...
OBJECTIVE: Asymmetrical dimethylarginine (ADMA) is an endogenous inhibitor of nitric oxide synthase (NOS), and its accumulation has been associated with cardiovascular disease. We aimed to...
Somatic NKX2-5 mutations as a novel mechanism of disease in complex congenital heart disease (2004)
Reamon-Büttner, S.M., Borlak, J.
NKX2-5 is a pivotal transcription factor in heart development. Previous studies on lymphocytic DNA provided evidence of familial NKX2-5 gene mutations in cardiac malformations. Common mutations are...
TBX5 mutations in non-Holt-Oram syndrome (HOS) malformed heart (2004)
Reamon-Büttner, S.M., Borlak, J.
The T-box transcription factor Tbx5 is important in mammalian cardiac development. Mutations in the human TBX5 gene cause Holt-Oram syndrome (HOS), a disorder characterized by heart and upper limb...
Kel, A., Reymann, S., Matys, V., Nettesheim, P., Wingender, E., Borlak, J.
A novel computational method based on a genetic algorithm was developed to study composite structure of promoters of coexpressed genes. Our method enabled an identification of combinations of...
2,3-Butanedione monoxime (BDM) is a reversible myosin AT-Pase inhibitor with phosphatase-like activity. It is being evaluated for its therapeutic benefit in organ preservation in addition to its use...
Schrem, H., Klempnauer, J., Borlak, J.
In the first part of our review (see Pharmacol Rev 2002;54:129-158), we discussed the basic principles of gene transcription and the complex interactions within the network of hepatocyte nuclear...
Phenotyping of N-acetyltransferase type 2 by caffeine from uncontrolled dietary exposure (2004)
Jetter, A., Kinzig-Schippers, M., Illauer, M., Hermann, R., Erb, K., Borlak, J., ...
BACKGROUND AND OBJECTIVE: The standard approach for phenotyping of the human arylamine N-acetyltransferase 2 (NAT2) uses urinary caffeine metabolite ratios after a caffeine test dose taken in after...
Mullet, W.M., Walles, M., Levsen, K., Borlak, J., Pawliszyn, J.
A new molecularly imprinted polymer (MIP) material was synthesized selective for verapamil and utilized for on-line metabolic screening of this common calcium antagonist in biological samples. Since...
Androgen metabolism in thymus of fetal and adult rats (2004)
Borlak, J., Schulte, I., Thum, T.
Cytochrome P450 (P450) monooxygenases play a role in target tissue metabolic activation of xenobiotics and/or endogenous compounds, such as vasoactive molecules or hormones. Indeed, tissue-specific...
An "omics" approach to study lung carcinogenesis (2004)
Borlak, J., Meier, T., Rütters, H., Zürbig, P., Halter, R.
Lung cancer is the most common cancer in the world and smoking is the major risk factor, accounting for about 90% of the cases. In 1996, an estimated 1.3 million new cases were diagnosed worldwide,...
Novel NKX2-5 mutations in diseased heart tissues of patients with cardiac malformations (2004)
Reamon-Büttner, S.M., Hecker, H., Spanel-Borowski, K., Craatz, S., Kuenzel, E., Borlak, J.
NKX2-5 is a homeodomain-containing transcription factor important in cardiac development. Familial mutations in the NKX2-5 gene are associated with cardiac abnormalities, but mutations are rare in...
Verapamil: Metabolism in cultures of primary human coronary arterial endothelial cells (2003)
Borlak, J., Walles, M., Levsen, K., Thum, T.
Endothelium is a metabolically active secretory tissue and an important barrier for metabolic products. Little is known about its contribution to drug oxidation. We investigated the gene and protein...
1. Caco-2 cells are frequently used in intestinal drug absorption and metabolism studies, but little is known about the effects of drugs on the simultaneous expression of genes coding for...
Isolation and identification of Cyclin E1 isoforms in murine hepatocellular carcinomas (HCC) (2003)
Liedtke, C., Halter, R., Borlak, J., Manns, M.P., Trautwein, C.
Cyclin E1 is involved in controlling G1/S-phase progression during the cell cycle. Earlier results indicated that Cyclin E1 misregulation correlates with tumor progression in some types of human...
Hallmarks of ion channel gene expression in end-stage heart failure (2003)
Electrical conductance is greatly altered in end-stage heart failure, but little is known about the underlying events. We therefore investigated the expression of genes coding for major inward and...
Gene expression profiles in the closing ductus and the great vessels (2003)
Bökenkamp, R., Thum, T., Borlak, J.
The pharmacological approach to ductal patency is currently focused on prostaglandin metabolism. The role of other vascular factors for ductal remodelling is under discussion. Aim of the present...
Borlak, J., Walles, M., Elend, M., Thum, T., Preiss, A., Levsen, K.
1. Verapamil is a well-known and world-wide prescribed calcium antagonist, but it suffers from extensive first-pass metabolism. Although it has been marketed for many years, a complete understanding...
DNA adducts in cultures of polychlorinated biphenyl-treated human hepatocytes (2003)
Borlak, J., Hock, A., Hansen, T., Richter, E.
Polychlorinated biphenyls (PCBs) are persistent environmental chemicals that accumulate at the apex of food chains. Several scientific committees support its designation as a human carcinogen, even...
An optimized method for the isolation and identification of membrane proteins (2003)
Lehner, I., Niehof, M., Borlak, J.
The purpose of this study was to develop a protocol suitable for membrane protein extraction from limited starting material and to identify appropriate conditions for two-dimensional (2-D) gel...
Thum, T., Tsikas, D., Frölich, J.F., Borlak, J.
Growth hormone deficiency is linked to cardiovascular disease and particularly increased peripheral vascular resistance. Surprisingly, its role in endothelial nitric oxide (NO) synthetase (eNOS)...
A rapid and simple CYP2D6 genotyping assay - Case study with the analgetic tramadol (2003)
Borlak, J., Hermann, R., Erb, K., Thum, T.
There is substantial evidence for a causal relationship between genetic variability of the CYP2D6 gene and changes in the pharmacokinetics of drugs. Therefore, knowledge of single-nucleotide...
Walles, M., Thum, T., Levsen, K., Borlak, J.
Verapamil is a widely prescribed calcium antagonist, but suffers from extensive first pass metabolism. Despite its frequent use in drug metabolism a complete understanding of its metabolic pathway is...
Aspirin reduces endothelial-cell senescence: Meeting Abstract (2003)
Scalera, F., Thum, T., Borlak, J., Schubert, B., Frolich, J.C., Bode-Boger, S.M.
Pharmacokinetic interaction between retigabine and lamotrigine in healthy-subjects (2003)
Hermann, R., Knebel, N.G., Niebch, G., Richards, L., Borlak, J., Locher, M.
Purpose. The antiepileptic drugs (AEDs) retigabine (RGB) and lamotrigine (LTG) undergo predominantly N-glucuronidation and renal excretion. This study was performed to evaluate potential...
Automated Gene Regulation Data Analysis Within the Helmholtz Network (2003)
Prof Dr, Ralf Hofestädt, Tanja Möller, Er Rüegg, L. Milanesi, A. Caprera, ...
Integration of data in bioinformatics: Example from own work
Borlak, J., Dangers, M., Thum, T.
Human exposure to polychlorinated biphenyls (PCBs) may lead to increased albumin serum levels, but little is known about the underlying events. Certain PCBs are also ligands for the aryl hydrocarbon...
1. Polychlorinated biphenyls (PCBs) are well-known environmental pollutants that bioaccumulate mainly in the fatty tissue of animals and humans. Although contamination occurs primarily via the food...
Hermann, R., Schneider, E., Menth, M., Knebel, N., Ferron, G., Borlak, J., ...
The Sixth Eilat Conference on New Antieliptic Drugs (AEDs) took place in Taormina, Sicily, Italy from 7th to 11th April, 2002. Basic scientists, clinical pharmacologists and neurologists from 27...
Testosterone, cytochrome P450, and cardiac hypertrophy (2002)
Cytochrome P450 mono-oxygenases (CYP) play an essential role in steroid metabolism, and there is speculation that sex hormones might influence cardiac mass and physiology. As CYP mono-oxygenases...
Toxicogenomics: Interspecies comparison and compound profiling using cDNA microarrays (2002)
Buss, K., Hansen, T., Tomiuk, S., Hofmann, K., Gerstmayer, B., Bosio, A., ...
Inhalation and intravenous plasma kinetics of Verapamil in cynomolgus monkeys (2002)
Appelqvist, T., Walles, M., Windt, H., Koch, W., Borlak, J., Forster, R.
Walles, M., Borlak, J., Levsen, K.
The potential of three genetic changes introduced into mice by the transgenic or knockout technology aimed at immortalizing hepatocytes in vitro and concomitantly preserving their differentiated...
Verapamil drug metabolism studies by automated in-tube solid phase microextraction (2002)
Walles, M., Mullett, W.M., Levsen, K., Borlak, J., Wünsch, G., Pawliszyn, J.
Verapamil is a common calcium antagonist described with antianginal, antihypertensive and antiarrythmic properties. The metabolites of verapamil have also shown pharmacological properties and...
Verapamil. New insight into the molecular mechanism of drug oxidation in the human heart (2002)
Walles, M., Thum, T., Levsen, K., Borlak, J.
Verapamil is a commonly prescribed cardiovascular drug, but surprisingly its metabolism in the target tissue of pharmacotherapy is basically unknown. We therefore investigated its biotransformation...
The use of toxicogenomics (2002)
Modulation of gene expression is of paramount importance in the mechanisms of drug-induced toxicity, and major efforts are being made to determine the relevance of gene expression in response to drug...
Schrem, H., Klempnauer, J., Borlak, J.
Numerous studies have established the pivotal role of liver-enriched transcription factors in organ development and cellular function, and there is conclusive evidence for transcription factors to...
Mullett, W.M., Levsen, K., Borlak, J., Wu, J.C., Pawliszyn, J.
An automated in-tube solid-phase microextraction (SPME) HPLC analysis method for 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK) and several metabolites has been developed. NNK is one of the...
Various protocols for the isolation and cultivation of adult rat cardiomyocytes were compared, and the cytoprotective potential of the reversible myosin ATPase inhibitor butanedione monoxime (BDM)...
BACKGROUND: Butanedione monoxime (BDM) is a reversible myosin ATPase inhibitor. Its use in transplantation medicine may be of benefit in the preservation of hearts. As little is known about its...
Walles, M., Thum, T., Levsen, K., Borlak, J.
A substantial number of drugs act either directly or indirectly on the heart, but surprisingly, little is known about drug oxidation in the heart. We therefore investigated the metabolism of the...
Aroclor 1254 is a complex mixture of polychlorinated biphenyls and is well known for its potency to induce drug-metabolising enzymes, but little is known about its ability to modulate gene expression...
Inhalation studies with the Göttingen minipig (2001)
Koch, W., Windt, H., Walles, M., Borlak, J., Clausing, P.
A method for inhalative exposure of minipigs to aerosols and gases has been developed. Minipigs are exposed via mask inhalation to the test substance using a computer-controlled exposure system that...
Pethig, K., Heublein, B., Hoffmann, A., Borlak, J., Wahlers, T., Haverich, H.
Cardiac allograft vascular disease is (CAVD) the most important cause of death following heart transplantation (HTX). Although in the past, researchers focused predominantly on mechanisms of...
1. Primary cultures of cardiomyocytes provide a valuable tool for the study of the pharmacological and toxicological properties of drugs and chemicals, but for several technical reasons...
There are a substantial number of drugs acting either directly or indirectly on the heart, but surprisingly, little is known about the metabolic capacity of heart muscle cells. We therefore...
Thum, T., Haverich, A., Borlak, J.
We investigated the gene expression of the nuclear transcription factors c/EBPalpha, GATA-2, and the silencer Oct-1 in conjunction with the gene expression of all major cytochrome P450 genes and of...
Borlak, J., Thum, T., Landt, O., Erb, K., Hermann, R.
Recent research has shown that congenital nonhemolytic low grade hyperbilirubinemias in patients with Gilbert's syndrome (GS) are linked to mutations in the TATA box upstream of the uridine...
Hansen, T., Borlak, J., Bader, A.
1. A method for the isolation and cultivation of porcine hepatocytes and porcine duodenal enterocytes for the investigation of drug oxidation reactions has been established. 2. Hepatocytes as well as...
Böger, R.H., Sydow, K., Borlak, J., Thum, T., Lenzen, H., Schubert, B., ...
Asymmetrical dimethylarginine (ADMA) is an endogenous nitric oxide synthase inhibitor. It is formed by protein arginine N-methyltransferases (PRMTs), which utilize S-adenosylmethionine as methyl...
Gene expression in distinct regions of the heart (2000)
BACKGROUND: Cytochrome P450 mono-oxygenases bring about metabolism of many drugs, including verapamil, but no information is available on the metabolism of such drugs in the human heart. METHODS: We...
Borlak, J., Hansen, T., Kumar, S., Sikka, H.C., Frank, H., ...
3-Nitrobezanthrone (NBA) is a suspected human carcinogen and has been identified is diesel exhaust and in airborne particulates. Human exposure to NBA is thought to occur primarily via the...
Primary porcine enterocyte and hepatocyte cultures to study drug oxidation reactions (2000)
Bader, A., Hansen, T., Kirchner, G., Allmeling, C., Haverich, A., Borlak, J.
1. Primary porcine hepatocytes and enterocytes were isolated and cultured in Williams' E medium for up to 10 days to investigate potential organ differences in the metabolism of the immunosuppressive...
Bader, A., Frühauf, N., Tiedge, M., Drinkgern, M., DeBartolo, L., Borlak, J., ...
It must be assumed that current petri dish primary hepatocyte culture models do not supply sufficient amounts of oxygen and thus cause anaerobic metabolism of the cells. This is contrary to the...
Hepatocytes sandwich cultures to study biotransformation of cytochrome P450 substrates (1997)
Bader, A., Borlak, J., Steinkamp, A., Zech, K., Fuhrmann, U., Frühauf, N., ...
Somatic NKX2-5 mutations as a novel mechanism of disease in complex congenital heart disease
NKX2–5 is a pivotal transcription factor in heart development. Previous studies on lymphocytic DNA provided evidence of familial NKX2–5 gene mutations in cardiac malformations. Common mutations...
A genome-wide expression analysis identifies a network of EpCAM-induced cell cycle regulators
Expression of the epithelial cell adhesion molecule EpCAM is upregulated in a variety of carcinomas. This antigen is therefore explored in tumour diagnosis, and clinical trials have been initiated to...