A5071582648- Acute Myeloid Leukemia Research
- Myeloproliferative Neoplasms: Diagnosis and Treatment
- Hemoglobinopathies and Related Disorders
- Cancer Genomics and Diagnostics
- Glioma Diagnosis and Treatment
- CAR-T cell therapy research
- Thyroid Cancer Diagnosis and Treatment
- Extracellular vesicles in disease
- Histone Deacetylase Inhibitors Research
- Acute Lymphoblastic Leukemia research
- Hematopoietic Stem Cell Transplantation
- Epigenetics and DNA Methylation
- Cancer, Hypoxia, and Metabolism
- Science, Research, and Medicine
- Cancer-related Molecular Pathways
- T-cell and Retrovirus Studies
- Effects of Radiation Exposure
- Mitochondrial Function and Pathology
- Gene expression and cancer classification
- CRISPR and Genetic Engineering
- Autophagy in Disease and Therapy
- Glutathione Transferases and Polymorphisms
- Spaceflight effects on biology
- Cancer Risks and Factors
- Transplantation: Methods and Outcomes
Goethe University Frankfurt
2017-2023
University Hospital Frankfurt
2018-2022
German Cancer Research Center
2016-2021
Heidelberg University
2016-2021
Frankfurt Cancer Institute
2020-2021
Deutschen Konsortium für Translationale Krebsforschung
2016-2020
TU Dresden
2013-2019
University Hospital Carl Gustav Carus
2014-2019
Klinik und Poliklinik für Psychotherapie und Psychosomatik
2016
National Center for Tumor Diseases
2016
<h3>Importance</h3> Somatic mutations causing clonal expansion of hematopoietic cells (clonal hematopoiesis indeterminate potential [CHIP]) are increased with age and associated atherosclerosis inflammation. Age inflammation the major risk factors for heart failure, yet association CHIP failure in humans is unknown. <h3>Objective</h3> To assess prognostic significance patients chronic (CHF) owing to ischemic origin. <h3>Design, Setting, Participants</h3> We analyzed bone marrow–derived...
Somatic mutations of the epigenetic regulators DNMT3A and TET2 causing clonal expansion haematopoietic cells (clonal haematopoiesis; CH) were shown to be associated with poor prognosis in chronic ischaemic heart failure (CHF). The aim our analysis was define a threshold variant allele frequency (VAF) for prognostic significance CH CHF.We analysed bone marrow peripheral blood-derived from 419 patients CHF by error-corrected amplicon sequencing. Cut-off VAFs optimized maximizing sensitivity...
The evolution of primary glioblastoma (GBM) is poorly understood. Multifocal GBM (ie, multiple synchronous lesions in one patient) could elucidate development.We present the first comprehensive study 12 foci from 6 patients using array-CGH, spectral karyotyping, gene expression arrays, and next-generation sequencing.Multifocal GBMs genetically resemble GBMs. Comparing same patient proved their monoclonal origin. All tumors harbored alterations 3 core pathways: RTK/PI3K, p53, RB regulatory...
This study focused on the effects induced by a random positioning machine (RPM) FTC-133 thyroid cancer cells and evaluated signaling elements involved in 3-dimensional multicellular tumor spheroid (MCTS) formation. The were cultured RPM, device developed to simulate microgravity, under static 1-g conditions. After 24 h MCTSs swimming culture supernatants found, addition growth of adherent (AD) cells. Cells grown RPM showed higher levels NF-κB p65 protein apoptosis than controls, result also...
Abstract Autophagy is a well-described degradation mechanism that promotes cell survival upon nutrient starvation and other forms of cellular stresses. In addition, there growing evidence showing autophagy can exert lethal function via autophagic death (ACD). As ACD has been implicated in apoptosis-resistant glioblastoma (GBM), high medical need for identifying novel ACD-inducing drugs. Therefore, we screened library containing 70 autophagy-inducing compounds to induce ATG5-dependent human...
Clonal hematopoiesis of indeterminate potential (CHIP) is caused by recurrent somatic mutations leading to clonal blood cell expansion. However, direct evidence the fitness CHIP-mutated human hematopoietic stem cells (HSCs) in reconstitution lacking. Because myeloablative treatment and transplantation enforce stress on HSCs, we followed 81 patients with solid tumors or lymphoid diseases undergoing autologous (ASCT) for development CHIP. We found a high incidence CHIP (22%) after ASCT mean...
Despite a high clinical need for the treatment of colorectal carcinoma (CRC) as second leading cause cancer-related deaths, targeted therapies are still limited. The multifunctional enzyme Transglutaminase 2 (TGM2), which harbors transamidation and GTPase activity, has been implicated in development progression different types human cancers. However, mechanism role TGM2 cancer poorly understood. Here, we present promising drug target.In primary patient material CRC patients, detected an...
Microgravity and cosmic rays as found in space are difficult to recreate on earth. However, ground-based models exist simulate flight experiments. In the present study, an experimental model was utilized monitor gene expression changes fetal skin fibroblasts of murine origin. Cells were continuously subjected for 65 h a low dose (55 mSv) ionizing radiation (IR), comprising mixture high‑linear energy transfer (LET) neutrons low-LET gamma-rays, and/or simulated microgravity using random...
Abstract Aims Somatic mutations in haematopoietic stem cells can lead to the clonal expansion of mutated blood cells, known as haematopoiesis (CH). Mutations most prevalent driver genes DNMT3A and TET2 with a variant allele frequency (VAF) ≥ 2% have been associated atherosclerosis chronic heart failure ischemic origin (CHF). However, effects other for CH low VAF (<2%) on CHF are still unknown. Methods results Therefore, we analysed mononuclear bone marrow from 399 patients by deep...
Changes in gene expression programs play a central role cancer. Chromosomal aberrations such as deletions, duplications and translocations of DNA segments can lead to highly significant positive correlations levels neighboring genes. This should be utilized improve the analysis tumor profiles. Here, we develop novel model class autoregressive higher-order Hidden Markov Models (HMMs) that carefully exploit local data-dependent chromosomal dependencies identification differentially expressed...
IDH1R132H (isocitrate dehydrogenase 1) mutations play a key role in the development of low-grade gliomas. IDH1wt converts isocitrate to α-ketoglutarate while reducing nicotinamide adenine dinucleotide phosphate (NADP+), whereas uses and NADPH generate oncometabolite 2-hydroxyglutarate (2-HG). While effects 2-HG have been subject intense research, independent are still ambiguous. The present study demonstrates that expression but not alone leads significantly decreased tricarboxylic acid...
Epigallocatechin-3-gallate (EGCG) is the most abundant polyphenol molecule from green tea and known to exhibit antioxidative as well tumor suppressing activity. In order examine EGCG invasion activity against adult T-cell leukemia (ATL), two HTLV-1 positive cells (HuT-102 C91-PL) were treated with non-cytotoxic concentrations of for 2 4 days. Proliferation was significantly inhibited by 100 <TEX>${\mu}M$</TEX> at days, low cell lysis or cytotoxicity. oncoprotein (Tax) expression in HuT-102...
Oligodendroglial tumors form a distinct subgroup of gliomas, characterized by better response to treatment and prolonged overall survival. Most oligodendrogliomas also some oligoastrocytomas are unique typical unbalanced translocation, der(1,19), resulting in 1p/19q co-deletion. Candidate tumor suppressor genes targeted these losses, CIC on 19q13.2 FUBP1 1p31.1, were only recently discovered. We analyzed 17 applying comprehensive approach consisting RNA expression analysis, DNA sequencing...
In the thyroid, iodine deficiency (ID) induces angiogenesis via a tightly controlled reactive oxygen species (ROS)-hypoxia inducible factor-1 (HIF-1)-vascular endothelial growth factor (VEGF) dependent pathway (ROS-HIF-VEGF). Deficient intake may be associated with increased thyroid cancer incidence. The hypothesis of this work is to test whether ID affects angiogenic processes in malignant cells by altering ROS-HIF-VEGF pathway.Goiters were obtained RET/PTC3 transgenic and wild-type (wt)...
Autophagy is an important survival mechanism that allows recycling of nutrients and removal damaged organelles has been shown to contribute the proliferation acute myeloid leukemia (AML) cells. However, little known about by which autophagy- dependent AML cells can overcome dysfunctional autophagy. In our study we identified autophagy related protein 3 (ATG3) as a crucial gene for cell conducting CRISPR/Cas9 dropout screen with library targeting around 200 autophagy-related genes....
The link between high doses of radiation and thyroid cancer has been well established in various studies, as opposed to the effects low doses. In this study, we investigated low-dose X-ray irradiation a papillary carcinoma model with wild-type mutated p53. A dose 62.5 mGy was enough cause an upregulation p16 decrease number TPC-1 cells S phase, but not BCPAP p53-mutant cells. At 0.5 Gy, visible signs senescence appeared only We conclude that X-rays are change cell cycle distribution,...
We previously reported the establishment of a rare xenograft derived from recurrent oligodendroglioma with 1p/19q codeletion. Here, we analyzed in detail exome sequencing datasets (WHO grade III, O2010) and first-generation (xenograft1). Somatic SNVs small InDels (n = 80) potential effects at protein level O2010 included variants IDH1 (NM_005896:c.395G>A; p. Arg132His), FUBP1 (NM_003902:c.1307_1310delTAGA; p.Ile436fs), CIC (NM_015125:c.4421T>G; p.Val1474Gly). All but 2 these 80 were also...
Abstract Background Recurrent somatic mutations in blood stem cells cause the emergence of mutated cell clones, known as clonal hematopoiesis (CH). Mutations most prevalent driver genes DNMT3A and TET2 with a variant allele frequency (VAF)≥2% have been associated atherosclerosis chronic heart failure (CHF). However, effects other for CH low VAF (&lt;2%) on CHF is still unknown. Purpose To assess potential prognostic significance distinct than causing at patients due to post-ischemic...