Walter Jaeger

Walter Jaeger
University of Vienna | UniWien · Department für Klinische Pharmazie und Diagnostik

About

427
Publications
50,026
Reads
How we measure 'reads'
A 'read' is counted each time someone views a publication summary (such as the title, abstract, and list of authors), clicks on a figure, or views or downloads the full-text. Learn more
9,971
Citations
Citations since 2017
83 Research Items
3757 Citations
20172018201920202021202220230100200300400500600700
20172018201920202021202220230100200300400500600700
20172018201920202021202220230100200300400500600700
20172018201920202021202220230100200300400500600700
Additional affiliations
January 2013 - present
Ludwig Boltzmann-Cluster Oncology (LB-CO) | Medical University Vienna
Ludwig Boltzmann-Cluster Oncology (LB-CO) | Medical University Vienna
January 2005 - December 2012
University of Barcelona
January 2004 - December 2013
Medical University of Vienna

Publications

Publications (427)
Article
Full-text available
Background and objective: Exhaustive pharmacokinetic (PK) studies in paediatric patients are unavailable for most antibiotics and feasibility of PK studies is limited by challenges, such as low blood volume and venipuncture-related pain. Microdialysis (MD) represents a promising method to overcome these obstacles. The aim of this proof-of-concept...
Article
Full-text available
Patients with high-grade serous ovarian cancer (HGSOC) have a very poor overall survival. Current therapeutic approaches do not bring benefit to all patients. Although genetic alterations and molecular mechanisms are well characterized, the molecular pathological conditions are poorly investigated. Solute carrier organic anion transporter family me...
Article
Meropenem is a broad spectrum carbapenem used for the treatment of cerebral infections. There is a need for data describing meropenem pharmacokinetics (PK) in the brain tissue to optimize therapy in these infections. Here, we present a meropenem PK model in the central nervous system and simulate dosing regimens. This was a population PK analysis o...
Article
Full-text available
Purpose Although temozolomide is widely used in the treatment of childhood central nervous system (CNS) tumors, information on its pharmacokinetic profile in the brain or cerebrospinal fluid (CSF) is sparse. This study aimed at investigating whether measurable and clinically relevant concentrations of temozolomide are reached and maintained in CSF...
Article
Full-text available
Background and Objective In microdose studies, drug pharmacokinetics is measured in humans after administration of subtherapeutic doses. While previous microdose studies focused primarily on plasma pharmacokinetics, we set out to evaluate the feasibility of microdosing for a pharmacokinetic assessment in subcutaneous tissue and epithelial lining fl...
Article
Full-text available
Endometrial cancer (EC) is the most common gynecological malignancy in resource-abundant countries. The majority of EC cases are estrogen dependent but the mechanisms of estrogen biosynthesis and oxidative metabolism and estrogen action are not completely understood. Here, we evaluated formation of estrogens in models of moderately and poorly diffe...
Conference Paper
Full-text available
Introduction/Background* Endometrial cancer (EC) is the most common gynecological malignancy in the western world. EC has traditionally been divided into type I, which is estrogen dependent, and type II, where associations with estrogens were only recently uncovered. Both types of EC arise after menopause when tumor tissue depends on formation of e...
Article
Full-text available
Background Inadequate antibiotic exposure in cerebral infections might have detrimental effects on clinical outcome. Commonly, antibiotic concentrations within the CSF were used to estimate cerebral target levels. However, the actual pharmacological active unbound drug concentration beyond the blood–brain barrier is unknown. Objectives To compare...
Article
Background: Ceftaroline fosamil, a 5th generation cephalosporin antibiotic with activity against MRSA, is currently approved for the treatment of pneumonia and complicated skin and soft tissue infections. However, pharmacokinetic data on free lung tissue concentrations in critical patient populations are lacking. Objectives: The aim of this stud...
Article
Full-text available
Background: Elimination of a drug during renal replacement therapy is not only dependent on flow rates, molecular size and protein binding, but is often influenced by difficult to predict drug membrane interactions. In vitro models allow for extensive profiling of drug clearance using a wide array of hemofilters and flow rates. We present a bovine...
Article
Full-text available
Endometrial cancer (EC) is associated with increased estrogen actions. Locally, estrogens can be formed from estrone-sulphate (E1-S) after cellular uptake by organic anion-transporting polypeptides (OATP) or organic anion transporters (OAT). Efflux of E1-S is enabled by ATP Binding Cassette transporters (ABC) and organic solute transporter (OST)αβ....
Article
Full-text available
Background Actaea racemosa L., also known as black cohosh, is a popular herb commonly used for the treatment of menopausal symptoms. Because of its purported estrogenic activity, black cohosh root extract (BCE) may trigger breast cancer growth. Study design/methods The potential effects of standardized BCE and its main constituent actein on cellul...
Article
Full-text available
The antiemetic and gastroprokinetic drug metoclopramide is a weak substrate of the blood-brain barrier (BBB) efflux transporter P-glycoprotein (P-gp) and displays central nervous system (CNS) side effects (i.e. extrapyramidal symptoms, tardive dyskinesia) caused by dopamine D2 receptor blockade in the basal ganglia. These side effects occur with a...
Article
Full-text available
Genetic variations in the organic-anion-transporting polypeptide (OATP)-encoding solute carrier of organic anions (SLCO) genes can promote cancer development and progression. The overexpression of solute carrier organic anion transporter family member 4A1 (OATP4A1), a transporter for steroid hormones, prostaglandins, and bile acids, has been previo...
Article
Aim of this study was to investigate the impact of advanced wastewater treatment techniques (combining ozonation with activated carbon filtration) on acute and genotoxic activities of tertiary treated wastewater. Concentrated samples were tested in Salmonella/microsome assays. Furthermore, induction of DNA damage was measured in liver-derived cells...
Article
Full-text available
In vitro pharmacodynamic models are used to optimize in vivo dosing regimens in antimicrobial drug development. One limiting factor of such models is the lack of host factors such as corpuscular blood components as erythrocytes which have already been shown to impact activity of antibiotics and/or growth of the pathogen. However, the impact of thro...
Article
Full-text available
Ponatinib is a small molecule multi‐tyrosine kinase inhibitor clinically approved for anticancer therapy. Molecular mechanisms by which cancer cells develop resistance against ponatinib are currently poorly understood. Likewise, intracellular drug dynamics, as well as potential microenvironmental factors affecting the activity of this compound are...
Article
Full-text available
Bioavailability of nutrients is highly diverse and depends on a variety of endogenous and exogenous factors in humans. This data article reports on the plasma response of 10 human subjects (5 females, 5 males) to a single dose of a multivitamin drink within 6h (blood taken after 1, 2, 4, and 6h). Nutrients, which were considered in the assessment,...
Article
P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) in the canalicular membrane of hepatocytes mediate the biliary excretion of drugs and drug metabolites. To measure hepatic ABCB1 and ABCG2 activity, we performed positron emission tomography (PET) scans with the ABCB1/ABCG2 substrate [11C]tariquidar in healthy volunteers and wild-t...
Article
Background We previously identified preparation of the internal mammary artery as a risk factor significantly impairing antibiotic tissue penetration into the presternal subcutaneous tissue. We, therefore, adapted our dosing schema regarding preoperative timing to overcome this risk factor. Methods Eight patients who underwent coronary artery bypas...
Article
Full-text available
Cannabinoids (CBs) from Cannabis sativa provide relief for tumor-associated symptoms (including nausea, anorexia, and neuropathic pain) in the palliative treatment of cancer patients. Additionally, they may decelerate tumor progression in breast cancer patients. Indeed, the psychoactive delta-9-tetrahydrocannabinol (THC), non-psychoactive cannabidi...
Article
Full-text available
It has been shown that protein binding, temperature, and pH influence in vitro pharmacodynamic (PD) models. The fact that corpuscular blood compounds might also have an important impact is something which has, until now, often been neglected. We investigated if the addition of human erythrocytes to standard growth media (Mueller Hinton Broth, MHBII...
Article
Polyphenols in foods and dietary supplements are commonly used for the prevention and treatment of a variety of malignancies, including breast cancer. However, daily intake by patients with breast cancer is controversial, as these compounds may stimulate cancer growth. Estrogens serve key roles in breast cancer cell proliferation; therefore, unders...
Article
P-glycoprotein (ABCB1) and breast cancer resistance protein (ABCG2) are two efflux transporters at the blood-brain barrier (BBB), which effectively restrict brain distribution of diverse drugs, such as tyrosine kinase inhibitors. There is a crucial need for pharmacological ABCB1 and ABCG2 inhibition protocols for a more effective treatment of brain...
Article
PET with avid substrates of P-glycoprotein (ABCB1) provided evidence of the role of this efflux transporter in effectively restricting the brain penetration of its substrates across the human blood-brain barrier (BBB). This may not reflect the situation for weak ABCB1 substrates including several antidepressants, antiepileptic drugs, and neurolepti...
Article
ABCB1 and ABCG2 are two efflux transporters at the blood-brain barrier (BBB) which effectively restrict brain distribution of dual ABCB1/ABCG2 substrate drugs, such as tyrosine kinase inhibitors. Pharmacological inhibition of ABCB1/ABCG2 may improve the efficacy of dual substrate drugs for treatment of brain tumors, but no marketed ABCB1/ABCG2 inhi...
Article
Organic anion-transporting polypeptides (OATPs) mediate the uptake of various drugs from blood into the liver in the basolateral membrane of hepatocytes. Positron emission tomography (PET) is a potentially powerful tool to assess the activity of hepatic OATPs in vivo, but its utility critically depends on the availability of transporter-selective p...
Article
Full-text available
High-grade serous ovarian cancer (HGSOC) is considered the most deadly and frequently occurring type of ovarian cancer and is associated with various molecular compositions and growth patterns. Evaluating the mRNA expression pattern of the organic anion transporters (OATPs) encoded by SLCO genes may allow for improved stratification of HGSOC patien...
Data
Expression of SLCOs and genes coding for putative related ABC-transporters, enzymes, nuclear receptors, and HER-2 in 135 HGSOC samples.
Data
Co-expressed gene networks. Genes used for GGM modeling are shown, which indicates the two networks that were revealed by the algorithm at the tuning parameter K = 4. The proportion of explained variation (PEV) values of the LASSO Cox regression models are shown for every tuning value between 1 and 8. As indicated, up to K = 4 a steady increase of...
Data
Scatter plots showing the correlations of genes of both co-expressed networks with their first principal components (PC). Size coded values in the top-right square represent correlation coefficients and significance levels are indicated by °p < 0.1, ***p < 0.001 (Spearman's correlations). Network 1: SLCO2B1/ABCC3 (A); Network 2: ABCB2/ABCB3/ABCC4/H...
Data
List of TaqMan® Gene Expression Assays for RT-qPCR. Assays were purchased from Applied Biosystems (Thermo Fisher, Waltham, MA) for RT-qPCR.
Article
Full-text available
Background: Treatment of skin and superficial soft tissue infections with topically applied antibiotics is a controversial topic, because only few clinical studies exist and target site concentrations after topical treatment are widely unknown. Objectives: This study aimed to investigate the target site concentration of topically applied gentami...
Article
Full-text available
The role of resveratrol (RES) in preventing breast cancer is controversial, as low concentrations may stimulate the proliferation of estrogen-receptor alpha positive (ERα+) breast cancer cells. As metabolism is the key factor in altering cellular estrogens, thereby influencing breast tumor growth, we investigated the effects of RES on the formation...
Article
Full-text available
Turmeric is a yellowish orange spice, widely used in Asian cuisine and obtained from the rhizome of Curcuma longa. It is a mixture of three curcuminoids namely, curcumin, demethoxycurcumin and bisdemethoxycurcumin. Turmeric has been used as a medicinal substance since ancient times for respiratory and gastrointestinal problems. The aim of the prese...
Article
Full-text available
Destruxins, secondary metabolites of entomopathogenic fungi, exert a wide variety of interesting characteristics ranging from antiviral to anticancer effects. Although their mode of action was evaluated previously, the molecular mechanisms of resistance development are unknown. Hence, we have established destruxin-resistant sublines of HCT116 colon...
Article
The abundance of OATP4A1 in colorectal cancer (CRC) might be related to tumor progression. This was studied by immunohistochemistry on paraffin-embedded samples obtained from 178 patients (43 patients with a relapse within 5 y) with early-stage CRC. Positivity for OATP4A1 in tumor cells and noncancerous mucosal cells was proved by double-immunofluo...
Article
Full-text available
Background and objective: P-glycoprotein (P-gp), a transmembrane transporter expressed at the blood-brain barrier, restricts the distribution of diverse central nervous system-targeted drugs from blood into brain, reducing their therapeutic efficacy. The third-generation P-gp inhibitor tariquidar (XR9576) was shown to enhance brain distribution of...
Article
Full-text available
Flavonoids, present in fruits, vegetables and traditional medicinal plants, show anticancer effects in experimental systems and are reportedly non-toxic. This is a favorable property for long term strategies for the attenuation of lymph node metastasis, which may effectively improve the prognostic states in breast cancer. Hence, we studied two flav...
Article
Objectives: Doripenem is a broad-spectrum parenteral carbapenem with enhanced activity against Pseudomonas aeruginosa and Enterobacteriaceae. Current dosing regimens recommend the administration of 0.25-0.5 g once daily in patients undergoing intermittent renal replacement therapy. As patients are usually dialyzed thrice weekly, we aimed to investi...
Article
Full-text available
Resveratrol (RES) is well known natural polyphenol with proven antioxidant, antiinflammatory and anticarcinogenic properties. Since mode of application may be important for cancer-preventive effects of RES, the aim of this study was to evaluate a possible delay in the initiation and progression of chemically induced mammary carcinogenesis in female...
Article
Full-text available
Gestational diabetes mellitus during pregnancy has severe implications for the health of the mother and the fetus. Therefore, early prediction and an understanding of the physiology are an important part of prenatal care. Metabolite profiling is a long established method for the analysis and prediction of metabolic diseases. Here, we applied untarg...
Article
Full-text available
Resveratrol is a naturally occurring polyphenolic compound with various pharmacological activities. It is unknown whether the expression of metabolizing enzymes correlates with resveratrol levels in organs and tissues. Therefore, we investigated the metabolism and tissue distribution of resveratrol in mice and assessed its association with the expr...
Article
Full-text available
Introduction Effective concentrations of antibiotics in brain tissue are essential for antimicrobial therapy of brain infections. However, data concerning cerebral penetration properties of antibiotics for treatment or prophylaxis of central nervous system infections are rare. Methods Six patients suffering subarachnoid hemorrhage and requiring cer...
Article
Full-text available
Purpose: In 2014, FDA released a warning for prescription of doripenem for ventilator-associated bacterial pneumonia due to unsatisfactory clinical cure rates. The present study explores if the observed lack of efficacy might be explained by insufficient target site pharmacokinetics in intensive care patients after two different infusion schemes....
Article
Full-text available
The beneficial effect of dietary soy food intake, especially for women diagnosed with breast cancer, is controversial, as in vitro data has shown that the soy isoflavones genistein and daidzein may even stimulate the proliferation of estrogen-receptor alpha positive (ERα+) breast cancer cells at low concentrations. As genistein and daidzein are kno...
Article
Full-text available
Background Studying the intracellular distribution of pharmacological agents, including anticancer compounds, is of central importance in biomedical research. It constitutes a prerequisite for a better understanding of the molecular mechanisms underlying drug action and resistance development. Hyperactivated fibroblast growth factor receptors (FGFR...
Article
Full-text available
To assess hepatic disposition of erlotinib, we performed positron emission tomography (PET) scans with [11C]erlotinib in healthy volunteers without and with oral pretreatment with a therapeutic erlotinib dose (300 mg). Erlotinib pretreatment significantly decreased the liver exposure to [11C]erlotinib with a concomitant increase in blood exposure,...
Article
Objective: The antimicrobial agent flucloxacillin is a potential cause of drug-induced liver disease, but the underlying mechanisms for toxicity have not been fully elucidated. As in-vitro and in-vivo findings suggest that biotransformation products contribute to hepatotoxicity, the purpose of this study was to characterize formation and accumulat...