A5042748396- Estrogen and related hormone effects
- Organic Chemistry Cycloaddition Reactions
- Phenothiazines and Benzothiazines Synthesis and Activities
- Pharmacogenetics and Drug Metabolism
- Synthesis and Reactivity of Sulfur-Containing Compounds
- Inorganic and Organometallic Chemistry
- Synthesis and Reactions of Organic Compounds
- Fluorine in Organic Chemistry
- Synthesis of heterocyclic compounds
- Synthesis and Catalytic Reactions
- Asymmetric Synthesis and Catalysis
- Synthesis and Characterization of Heterocyclic Compounds
- Synthesis and Reactivity of Heterocycles
- Chemical Reactions and Mechanisms
- Structural and Chemical Analysis of Organic and Inorganic Compounds
- Synthesis and Biological Evaluation
- Chemical Reaction Mechanisms
- Chemical Synthesis and Reactions
- Chemical Synthesis and Analysis
- Oxidative Organic Chemistry Reactions
- Cancer Treatment and Pharmacology
- Porphyrin and Phthalocyanine Chemistry
- Inflammatory mediators and NSAID effects
- Synthesis and Characterization of Pyrroles
- Coordination Chemistry and Organometallics
Dr. Margarete Fischer-Bosch-Institute of Clinical Pharmacology
2015-2025
University of Tübingen
2013-2025
Heidelberg University
2010-2019
German Cancer Research Center
2019
Deutschen Konsortium für Translationale Krebsforschung
2019
Federal Institute for Risk Assessment
2015
University Hospital Regensburg
2015
Robert Bosch (Germany)
2005-2013
Temple University
2013
Robert Bosch Hospital
2006-2011
According to current guidelines, molecular tests predicting the outcome of breast cancer patients can be used assist in making treatment decisions after consideration conventional markers. We developed and validated a gene expression signature likelihood distant recurrence with estrogen receptor (ER)-positive, HER2-negative treated adjuvant endocrine therapy.RNA levels assessed by quantitative reverse transcriptase PCR formalin-fixed, paraffin-embedded tumor tissue were calculate risk score...
<h3>Context</h3>The growth inhibitory effect of tamoxifen, which is used for the treatment hormone receptor–positive breast cancer, mediated by its metabolites, 4-hydroxytamoxifen and endoxifen. The formation active metabolites catalyzed polymorphic cytochrome P450 2D6 (CYP2D6) enzyme.<h3>Objective</h3>To determine whether CYP2D6 variation associated with clinical outcomes in women receiving adjuvant tamoxifen.<h3>Design, Setting, Patients</h3>Retrospective analysis German US cohorts...
The clinical outcome of tamoxifen-treated breast cancer patients may be influenced by the activity cytochrome P450 enzymes that catalyze formation antiestrogenic metabolites endoxifen and 4-hydroxytamoxifen. We investigated predictive value genetic variants CYP2D6, CYP2C19, three other for tamoxifen treatment outcome.DNA from 206 receiving adjuvant monotherapy 280 not therapy (71 months median follow-up) was isolated archival material genotyped 16 polymorphisms CYP2B6, CYP2C9, CYP3A5...
The therapeutic effect of tamoxifen depends on active metabolites, e.g., cytochrome P450 2D6 (CYP2D6) mediated formation endoxifen. To test for additional relationships, 236 breast cancer patients were genotyped CYP2D6, CYP2C9, CYP2B6, CYP2C19, CYP3A5, UGT1A4, UGT2B7, and UGT2B15; also, plasma concentrations 22 its including the (E)-, (Z)-, 3-, 4′-hydroxymetabolites as well their glucuronides, quantified using liquid chromatography–tandem mass spectrometry (MS). activity levels metabolites...
The cosmopolitan moon jelly Aurelia is characterized by high degrees of morphological and ecological plasticity, subsequently an unclear taxonomic status. latter has been revised repeatedly over the last century, dividing genus in as many 12 or little two species. We used molecular data phenotypic traits to unravel speciation processes phylogeographic patterns Aurelia. Mitochondrial nuclear DNA (16S ITS-1/5.8S rDNA) from 66 world-wide sampled specimens reveal star-like tree topologies,...
Based on an extensive sampling regime from both nesting populations and bycatch, frequency analyses of mitochondrial (mt) DNA control region haplotypes in the Mediterranean were used to assess genetic structure stock composition loggerhead sea turtle, Caretta caretta, different marine fisheries. The show following. (i) In drifting longline fisheries working pelagic habitats 53–55% turtles caught originated stock; (ii) bottom‐trawl all turtle bycatch is derived this regional (iii) This...
Tamoxifen is the standard-of-care treatment for estrogen receptor-positive premenopausal breast cancer. We examined tamoxifen metabolism via blood metabolite concentrations and germline variations of CYP3A5, CYP2C9, CYP2C19 CYP2D6 in 587 patients (Asians, Middle Eastern Arabs, Caucasian-UK; median age 39 years) clinical outcome 306 patients. N-desmethyltamoxifen (DM-Tam)/(Z)-endoxifen phenotype significantly correlated across ethnicities (R(2): 53%, P<10(-77)). CYP2C9 with norendoxifen...
The question of whether genetic polymorphisms CYP2D6 can affect treatment outcome in patients with early postmenopausal breast cancer has been a matter debate. With the recent negative results regard to genotyping from Breast International Group (BIG) 1-98 and Arimidex, Tamoxifen, Alone or Combination (ATAC) studies, study investigators suggest that testing for no value clinical practice.1,2 authors accompanying editorial conclude this be likely laid rest.3 However, pharmacogenetic experts...
Abstract Purpose: This study aimed to validate matrix-assisted laser desorption/ionization–time-of-flight mass spectrometry (MALDI-TOF MS)/Taqman copy number assay (CNA) CYP2D6 genotyping by AmpliChip CYP450 Test for the prediction of tamoxifen metabolizer phenotypes in breast cancer, and investigate influence variant coverage on genotype-phenotype relationships outcome. Experimental Design: Hormone receptor–positive postmenopausal cancer patients (n = 492) treated with adjuvant tamoxifen,...
The therapeutic efficacy of tamoxifen is predominantly mediated by its active metabolites 4-hydroxy-tamoxifen and endoxifen, whose formation catalyzed the polymorphic cytochrome P450 2D6 (CYP2D6). Yet, known CYP2D6 polymorphisms only partially determine metabolite concentrations in vivo. We performed first cross-ancestry genome-wide association study with well-characterized patients European, Middle-Eastern, Asian descent (n = 497) to identify genetic factors impacting parent formation....
There is an increasing need for the identification of both DNA and RNA biomarkers from pathodiagnostic formalin-fixed paraffin-embedded (FFPE) tissue samples exploration individualized therapy strategies in cancer. We investigated a fully automated, xylene-free nucleic acid extraction method simultaneous analysis related to breast cancer.We copurified single 10-μm section 210 paired FFPE tumor adjacent normal tissues (1-25 years archival time) using automated method. Half eluate was DNase I...
Purpose: Prediction of impaired tamoxifen (TAM) to endoxifen metabolism may be relevant improve breast cancer treatment, e.g. via TAM dose increase. The polymorphic cytochrome P450 2D6 (CYP2D6) strongly determines an individual's capacity for formation, however CYP2D6 phenotype assignments inferred from genotype widely differ between studies. Thus, we modeled plasma predictability depending on variable groupings. Methods: diplotype and metabolite concentrations were assessed in 908 pre-...
Abstract Background Carcinoma-associated fibroblasts (CAFs) can promote carcinogenesis and tumor progression. Only limited data on the response of CAFs to chemotherapy their potential impact therapy outcome are available. This study was undertaken analyze influence carcinoma-associated in vitro vivo . Methods The stromal cells investigated 22 neoadjuvant treated breast tumors tissue sections before after chemotherapy. Response analyzed primary cultures isolated from 28 human lung 9 cancer...
Oncogenic signalling via Ca
Clomiphene citrate is the most used drug for treatment of female infertility, a common condition in western societies and developing countries. Despite dose escalation, up to 30% women do not respond. Since clomiphene shares structural similarities with tamoxifen, which predominantly bioactivated by polymorphic cytochrome P450 (CYP) 2D6, we systematically explored metabolism action vitro vivo pharmacogenetic, -kinetic -dynamic investigations. Human liver microsomes were incubated nine...
Abstract Purpose: Patients with estrogen receptor– and/or progesterone receptor–positive, early breast cancer benefit from hormonal treatment, yet high global death burdens due to prevalence and long-term recurrence risk call for biomarkers guide additional treatment approaches. Experimental Design: From a prospective, observational study of postmenopausal patients treated tamoxifen or aromatase inhibitors, gene expression analyses 612 tumors was performed using the NanoString Breast Cancer...