A5084924207- Cancer Cells and Metastasis
- Ovarian cancer diagnosis and treatment
- Cancer Genomics and Diagnostics
- Mesenchymal stem cell research
- PARP inhibition in cancer therapy
- Cancer-related molecular mechanisms research
- Angiogenesis and VEGF in Cancer
- Bone health and treatments
- T-cell and B-cell Immunology
- DNA Repair Mechanisms
- Monoclonal and Polyclonal Antibodies Research
- Prostate Cancer Treatment and Research
- MicroRNA in disease regulation
- HER2/EGFR in Cancer Research
- Bone Metabolism and Diseases
- Cancer, Hypoxia, and Metabolism
- Immune Cell Function and Interaction
- Pancreatic and Hepatic Oncology Research
- Advanced Breast Cancer Therapies
- Cytokine Signaling Pathways and Interactions
- Biochemical Acid Research Studies
- Cancer-related Molecular Pathways
- RNA modifications and cancer
- CAR-T cell therapy research
- Cell Adhesion Molecules Research
University Hospital Carl Gustav Carus
2016-2025
Technische Universität Dresden
2016-2025
National Center for Tumor Diseases
2016-2025
German Cancer Research Center
2016-2025
Heidelberg University
2016-2025
Helmholtz-Zentrum Dresden-Rossendorf
2019-2025
University Hospital Heidelberg
2019-2025
Deutschen Konsortium für Translationale Krebsforschung
2016-2025
Heinrich Heine University Düsseldorf
2024
Düsseldorf University Hospital
2024
Extracellular vesicles (EVs) provide a complex means of intercellular signalling between cells at local and distant sites, both within different organs. According to their cell-type specific signatures, EVs can function as novel class biomarkers for variety diseases, be used drug-delivery vehicles. Furthermore, from certain cell types exert beneficial effects in regenerative medicine immune modulation. Several techniques are available harvest various body fluids or culture supernatants....
Abstract BACKGROUND Platinum resistance constitutes one of the most recognized clinical challenges for ovarian cancer. Notably, detection primary tumor-based excision repair cross-complementation group 1 (ERCC1) protein by immunohistochemistry was recently shown to be inaccurate prediction platinum resistance. On basis previous finding that circulating tumor cells (CTC) in blood cancer patients are prognostically significant, and given our hypothesis negative prognostic impact CTC may arise...
Abstract Background Multipotent mesenchymal stromal cells (MSCs) are precursors of various cell types. Through soluble factors, direct cell–cell interactions and other intercellular communication mechanisms such as extracellular vesicles tunneling nanotubes, MSCs support tissue homeostasis. In the bone marrow microenvironment, they promote hematopoiesis. The interaction between cancer enhances metastatic potential. Here, we have demonstrated that plastic-adherent isolated from human generate...
The presence of circulating tumor cells (CTCs) in the blood ovarian cancer patients was shown to correlate with decreased overall survival, whereby CTCs epithelial–mesenchymal‐transition (EMT) or stem‐like traits are supposed be involved metastatic progression and recurrence. Thus, investigating transcriptional profiles might help identify therapy resistant overcome treatment failure. For this purpose, we established a multi‐marker panel for molecular characterization single CTCs, detecting...
// Issam Chebouti 1, 4 , Sabine Kasimir-Bauer Paul Buderath Pauline Wimberger 2, 3, Siegfried Hauch 5 Rainer Kimmig and Jan Dominik Kuhlmann 1 Department of Gynecology Obstetrics, University Hospital Essen, 45147 Germany 2 Medical Faculty Carl Gustav Carus, Technische Universität Dresden, 01307 3 National Center for Tumor Diseases (NCT), Partner Site 69120 Heidelberg, German Cancer Consortium (DKTK), Dresden Research (DKFZ), QIAGEN, 40724 Hilden, Correspondence to: Kuhlmann, email:...
PARP-inhibitors (PARPi) are an integral part of ovarian cancer treatment. However, overcoming acquired PARPi resistance or increasing the benefit in patients without homologous recombination deficiency (HRD) remains unmet clinical need. We sought to identify genetic modulators response, guiding pharmacological sensitization. CRISPR-Cas9 mediated loss-of-function screen with a focused sgRNA library revealed that DNA-demethylases JMJD1B/JMJD1C, targetable by small inhibitor methylstat, promote...
Ovarian cancer is the leading cause of death among malignancies in women. Despite advances treatment, >50% patients relapse. For disease monitoring, identification a blood-based biomarker would be prime interest. In this regard, noncoding RNAs, such as microRNA (miRNA) or small nuclear RNA (snRNA), have been suggested biomarkers for noninvasive diagnosis. present study, we sought to identify differentially expressed miRNA/snRNA sera ovarian and investigate their potential aid therapy...
We recently showed that the presence of ERCC1+CTCs is an independent predictive biomarker for platinum-resistance and poor prognosis ovarian cancer. The goal our current research was to determine how auxiliary assessment ERCC1-transcripts influences overall CTC-detection rate. extended this investigation from initially setting paired pre- post-therapeutic blood analysis in order see, whether dynamics mirror response chemotherapy.65 Paired samples (10ml) primary cancer patients at diagnosis...
Metastasis-associated in colon cancer 1 (MACC1) and S100 calcium-binding protein A4 (S100A4) are prominent inducers of tumor progression metastasis. For the first time, we systematically tracked circulating serum levels MACC1 S100A4 transcripts course surgery chemotherapy analyzed their clinical relevance for ovarian cancer. were quantified a total 318 samples from 79 patients by RT-qPCR digital droplet PCR, respectively. significantly elevated patients, compared to healthy controls (P =...
Abstract Background Extracellular vesicle (EV)-associated microRNAs (miRNAs) have been suggested as promising biomarkers for blood-based cancer diagnosis. However, one of the major limitations use EVs with diagnostic purpose is lack standardized EV-profiling techniques. In this regard, objective our study was to design an integrated next-generation sequencing (NGS)-based workflow analyzing signature EV-associated miRNA in plasma platinum-resistant ovarian patients. Methods For EV-extraction,...
Abstract Background Ovarian cancer remains the most fatal gynecological malignancy. Current therapeutic options are limited due to late diagnosis in majority of cases, metastatic spread peritoneal cavity and onset chemo-resistance. Thus, novel approaches required. Statins amino-bisphosphonates inhibitors mevalonate pathway, which is a fundamental pathway cellular metabolism, essential for cholesterol production posttranslational protein farnesylation geranylgeranylation. While this has...
Rationale: Fibrosis promotes the maintenance of atrial fibrillation (AF), making it resistant to therapy. Improved understanding molecular mechanisms leading fibrosis will open new pathways toward effective antifibrotic therapies. Objective: This study aims decipher mechanistic interplay between PLK2 (polo-like kinase 2) and profibrotic cytokine OPN (osteopontin) in pathogenesis AF. Methods Results: Atrial mRNA expression was 10-fold higher human fibroblasts than cardiomyocytes. Compared...
We recently showed that LOH proximal to M6P/IGF2R locus (D6S1581) in primary ovarian tumors is predictive for the presence of disseminated tumor cells (DTC) bone marrow (BM). For therapy-monitoring, it would be highly desirable establish a blood-based biomarker. Therefore, we quantified circulating DNA (cirDNA) sera 63 cancer patients before surgery and after chemotherapy, measured incidence at four cancer-relevant chromosomal loci, correlated with cell spread BM evaluated prognostic...
Kynurenine formation by tryptophan-catabolic indoleamine-2,3-dioxygenase 1 (IDO1) plays a key role in tumor immune evasion and inhibition of IDO1 is efficacious preclinical models breast cancer. As the response cancer to checkpoint inhibitors may be limited, better understanding expression additional targetable immunomodulatory pathways importance. We therefore investigated regulation different subtypes. identified estrogen receptor α (ER) as negative regulator expression. Serum kynurenine...
Abstract Breast and prostate cancer cells home to the bone marrow, where they presumably hijack hematopoietic stem cell niche. We characterize here elusive premetastatic niche by examining role of mesenchymal stromal (MSC) in homing. Decreasing number MSC pharmacologically enhanced homing marrow mice. In contrast, increasing these MSCs various interventions including G-CSF administration diminished The subpopulation that correlated best with expressed stem, endothelial, pericytic markers,...
The increasing application of gene panels for familial cancer susceptibility disorders will probably lead to an increased proposal candidates. Using ERCC2 DNA repair as example, we show that proof a possible role in requires detailed dissection and characterization the underlying mutations genes with diverse cellular functions (in this case mainly basic transcription). In ERCC2, panel sequencing 1345 index cases from 587 German, 405 Lithuanian 353 Czech families breast ovarian (BC/OC)...
Abstract Objectives We analysed whether temporal heterogeneity of ctDNA encodes evolutionary patterns in ovarian cancer. Methods Targeted sequencing 275 cancer-associated genes was performed a primary tumor biopsy and six longitudinal plasma samples from 15 patients, using the Illumina platform. Results While there low overall concordance between mutational spectrum biopsies vs. ctDNA, TP53 variants were most commonly shared somatic alterations. Up to three variant clusters detected each...
The TCR/CD3 complex is a multimeric protein composed of minimum seven transmembrane chains (TCR alpha beta-CD3 gamma delta epsilon zeta 2). Whereas earlier studies have demonstrated that both the TCR-alpha and -beta are required for cell surface expression complex, role CD3 not been experimentally addressed in human T cells. In this study function CD3-zeta chain assembly, intracellular processing, leukemic line Jurkat was investigated. results indicate that: 1) complex; 2) pentameric form...