A5020225544- Drug Transport and Resistance Mechanisms
- Pharmacogenetics and Drug Metabolism
- Pharmacological Effects and Toxicity Studies
- HIV/AIDS drug development and treatment
- Multiple Myeloma Research and Treatments
- Ubiquitin and proteasome pathways
- Estrogen and related hormone effects
- HER2/EGFR in Cancer Research
- Protein Degradation and Inhibitors
- Advanced biosensing and bioanalysis techniques
- Cancer therapeutics and mechanisms
- bioluminescence and chemiluminescence research
- DNA and Nucleic Acid Chemistry
- Cancer Genomics and Diagnostics
- Cholangiocarcinoma and Gallbladder Cancer Studies
- Molecular Biology Techniques and Applications
- Cancer-related Molecular Pathways
- Epigenetics and DNA Methylation
- PI3K/AKT/mTOR signaling in cancer
- Protein Kinase Regulation and GTPase Signaling
- Trace Elements in Health
- Receptor Mechanisms and Signaling
- Glioma Diagnosis and Treatment
- DNA Repair Mechanisms
- Pulmonary Hypertension Research and Treatments
Heidelberg University
2015-2024
University Hospital Heidelberg
2014-2024
City of Hope
2017
City Of Hope National Medical Center
2016
Heidelberg University
2014
Neoadjuvant chemotherapy can improve the survival of individuals with borderline and unresectable pancreatic ductal adenocarcinoma; however, heterogeneous responses to remain a significant clinical challenge. Here, we performed RNA sequencing (n = 97) multiplexed immunofluorescence 122) on chemo-naive postchemotherapy (post-CTX) resected patient samples (chemoradiotherapy excluded) define impact neoadjuvant chemotherapy. Transcriptome analysis combined high-resolution mapping whole-tissue...
Many drug interactions with drugs used for the therapy of human immunodeficiency virus (HIV) occur at level different cytochrome P450 isozymes. Increasing evidence suggests that antiretrovirals may also modify activity and expression active transport systems. Such alter absorption, elimination, distribution reach clinical importance if thereby access to target site is affected. Beyond P-glycoprotein, family multidrug resistance-related proteins (MRP/ABCC) substantially contributes...
Highly active antiretroviral therapy is complicated by drug-drug interactions and the development of viral resistance. Drug involve transporters that may critically affect pharmacokinetics many drugs contribute to formation functional sanctuary sites. We therefore investigated effect saquinavir darunavir on drug transporter expression consequences for cellular resistance towards these compounds.Induction was in LS180 cells over a period 4 weeks means RT-PCR, some also at protein levels....
Experimental data with cells often require normalization. The frequently used bicinchoninic acid (BCA) assay, in fact, indicates protein content but is influenced by incubation time, pH etc. A simple, rapid and reliable alternative desirable. Crystal violet stains nucleic acids proteins was to reflect the cell number 96-well plates. Calibration curves comparison BCA confirmed excellent goodness of fit (R2: 0.98), conformity (nonsignificant difference crystal violet) reliability this staining...
Drug transporters such as P-glycoprotein (ABCB1) have been associated with chemotherapy resistance and are considered unfavorable prognostic factors for survival of cancer patients. Analyzing mRNA expression levels a subset drug by quantitative reverse transcription polymerase chain reaction (qRT-PCR) or protein tissue microarray (TMA) in tumor samples therapy naïve stage IV head neck squamous cell carcinoma (HNSCC) (qRT-PCR, n = 40; TMA, 61), this situ study re-examined the significance...
Background Benznidazole (BZL) is the only antichagasic drug available in most endemic countries. Its effect on expression and activity of drug-metabolizing transporter proteins has not been studied yet. Methodology/Principal Findings Expression P-glycoprotein (P-gp), Multidrug resistance-associated protein 2 (MRP2), Cytochrome P450 3A4 (CYP3A4), Glutathione S-transferase (GST) were evaluated HepG2 cells after treatment with BZL. was estimated by immunoblotting real time PCR. P-gp MRP2...
Multidrug resistance (MDR) hampers chemotherapy in head and neck squamous cell carcinoma (HNSCC). There is little information about MDR mediating drug transporters HNSCC.Nine HNSCC lines were characterized concerning transporter expression susceptibility to cisplatin, paclitaxel, 5-fluorouracil (5-FU) using a DNA microarray proliferation assays. Three cells precisely investigated for reverse transcriptase-polymerase chain reaction (RT-PCR) before after simulated chemotherapies.The differed...
Compared to rifampicin (600 mg/day), standard doses of rifabutin (300 mg/day) have a lower risk drug-drug interactions due induction cytochrome P450 3A4 (CYP3A4) or P-glycoprotein (Pgp/ABCB1) mediated by the pregnane X receptor (PXR). However, clinical comparisons with equal rifamycin in vitro experiments respecting actual intracellular concentrations are lacking. Thus, genuine pharmacological differences and potential molecular mechanisms discordant perpetrator effects unknown....
Abstract Objectives In alcoholics without alcoholic liver disease, boosted drug elimination has been reported. However, mechanistic explanations for this phenomenon remain uncertain. particular, data on the potential role of transporters are sparse. Methods Using a well-established in-vitro model induction human drug-metabolizing and drug-transporting proteins, we evaluated potency ethanol major fermentation side-product isopentanol to alter expression function these proteins by quantitative...
Abstract Enzalutamide is a new drug against castration‐resistant prostate cancer. Recent data indicate profound induction of metabolizing enzymes (e.g. cytochrome P450 isoenzyme (CYP) 3A4) but comprehensive in vitro on other CYP enzymes, conjugating or transporters scarce. Moreover, the mechanisms are poorly investigated and effects active metabolite N ‐desmethyl enzalutamide unknown. Using LS180 cells as an model quantitative real‐time reverse transcription polymerase chain reaction, our...
Dovitinib (TKI-258) is under development for the treatment of diverse cancer entities. No published information on its pharmacokinetic drug interaction potential available. Thus, we assessed with important metabolising enzymes and transporters efficacy in multidrug resistant cells vitro. P-glycoprotein (P-gp, MDR1, ABCB1) inhibition was evaluated by calcein assay, breast resistance protein (BCRP, ABCG2) pheophorbide A efflux, organic anion transporting polypeptides (OATPs) 8-fluorescein-cAMP...
Background Enhanced drug elimination in alcoholics remains largely indefinable. In contrast, the reduced of drugs patients with advanced alcoholic liver disease ( ALD ) is normally owing to hepatic end‐stage such as cirrhosis. We here study mRNA expression various metabolizing enzymes and transporters association stiffness LS being a novel noninvasive parameter for assessment cirrhosis unravel dynamic relationship between determinants pharmacokinetics transporters. Methods quantified levels...