A5025282123- Chronic Lymphocytic Leukemia Research
- Acute Lymphoblastic Leukemia research
- Cancer Research and Treatments
- Chronic Myeloid Leukemia Treatments
- PI3K/AKT/mTOR signaling in cancer
- Pancreatic and Hepatic Oncology Research
- GDF15 and Related Biomarkers
- Nanoplatforms for cancer theranostics
- Protein Degradation and Inhibitors
- Cancer-related Molecular Pathways
- Genetics, Aging, and Longevity in Model Organisms
- Cancer-related gene regulation
- Lymphoma Diagnosis and Treatment
- Multiple Myeloma Research and Treatments
- Advanced Breast Cancer Therapies
- Laser-Ablation Synthesis of Nanoparticles
- Virus-based gene therapy research
- Biochemical Acid Research Studies
- Mitochondrial Function and Pathology
- Laser Material Processing Techniques
- Medical Imaging Techniques and Applications
- Biochemical and Molecular Research
- Gene Regulatory Network Analysis
- Bioinformatics and Genomic Networks
- Immunodeficiency and Autoimmune Disorders
University of Rostock
2017-2022
Universitätsmedizin Rostock
2020-2021
Laser Zentrum Hannover
2015
The tumor suppressor protein phosphatase and tensin homolog (PTEN) is a key regulator of the PI3K/AKT pathway which frequently altered in variety tumors including subset acute B-lymphoblastic leukemias (B-ALL). While PTEN mutations deletions are rare B-ALL, promoter hypermethylation posttranslational modifications main pathways inactivation. Casein Kinase II (CK2) often upregulated B-ALL phosphorylates both DNA methyltransferase 3A, resulting increased signaling offering potential mechanism...
Abstract Background Casein kinase II (CK2) is involved in multiple tumor-relevant signaling pathways affecting proliferation and apoptosis. CK2 frequently upregulated acute B-lymphoblastic leukemia (B-ALL) can be targeted by the ATP-competitive inhibitor CX-4945. While reduced of tumor entities including B-ALL after CX-4945 incubation has been shown vitro vivo, detailed way action unknown. Here, we investigated influence on PI3K/AKT apoptosis cascades vivo for further clarification. Methods...
Kirsten rat sarcoma virus (KRAS) mutations are widespread in pancreatic ductal adenocarcinoma (PDAC) and contribute significantly to tumor initiation, progression, relapse/resistance, prognosis of patients. Although inhibitors against KRAS have been developed, this therapeutic approach is not routinely used PDAC We investigated the anti-tumor efficacy two BI-3406 (KRAS::SOS1 inhibitor) sotorasib (KRAS G12C alone or combination with MEK1/2 inhibitor trametinib and/or PI3K buparlisib seven...
Abstract To identify genes contributing to disease phenotypes remains a challenge for bioinformatics. Static knowledge on biological networks is often combined with the dynamics observed in gene expression levels over development, find markers diagnostics and therapy, also putative disease-modulatory drug targets drugs. The basis of current methods ranges from focus expression-levels (Limma) concentrating network characteristics (PageRank, HITS/Authority Score), both (DeMAND, Local...
The aberrant activation of the phosphoinositide 3-kinase (PI3K)/ protein kinase B (AKT) pathway is common in pancreatic ductal adenocarcinomas (PDAC). application inhibitors against PI3K and AKT has been considered as a therapeutic option. We investigated PDAC cell lines exposed to increasing concentrations MK-2206 (an AKT1/2/3 inhibitor) Buparlisib (a pan-PI3K inhibitor). Cell proliferation, metabolic activity, biomass, apoptosis/necrosis were evaluated. Further, whole-exome sequencing...
In dogs as well humans, lymphoma is one of the most common hematopoietic malignancies. Furthermore, due to its characteristics, canine recognized a clinically relevant in vivo model study corresponding human disease. Immortalized cell lines are widely used vitro models evaluate novel therapeutic agents and characterize their molecular mechanisms. However, it known that long-term cultivation leads clonal selection, genetic instability, loss initial heterogenic character, limiting usefulness...
Laser-based transfection techniques have proven high applicability in several cell biologic applications. The delivery of different molecules using these has been extensively investigated. In particular, new high-throughput approaches such as gold nanoparticle–mediated laser allow efficient antisense or proteins into cells preserving viabilities. However, the cellular response to perforation procedure is not well understood. We herein analyzed kinetics single during resonant manipulation...
Bruton's tyrosine kinase (BTK) and phosphoinositide 3-kinase (PI3K) in the B-cell receptor (BCR) signaling pathway are considered potential therapeutic targets for treatment of lymphomas, among which, diffuse large lymphoma (DLBCL) is most common type. Herein, we comparatively evaluated single combined application BTK inhibitor ibrutinib selective PI3Kγ AS-605240 canine DLBCL cell line CLBL-1. For further comparison, key findings were additionally analyzed leukemia GL-1 human SU-DHL-4. While...
Background: Both bromodomain and extra-terminal domain (BET) proteins spleen tyrosine kinase (SYK) represent promising targets in diffuse large B-cell (DLBCL) Burkitt's lymphoma (BL). We evaluated the anti-lymphoma activity of isoform-specific bivalent BET inhibitor AZD5153 (AZD) pan-BET I-BET151 (I-BET) as single agents combination with SYK Entospletinib (Ento) vitro. Methods: The effect on cell proliferation metabolic was two DLBCL BL lines. Proliferation, activity, apoptosis, cycle...
Impaired B-cell receptor (BCR) function has been associated with the progress of several malignancies. The spleen tyrosine kinase (SYK) represents a potential therapeutic target in subset neoplasias. In precursor B-acute lymphoblastic leukemia (B-ALL), pathogenic role and SYK is still controversially discussed. We evaluate application inhibitor entospletinib (Ento) pre- pro-B-ALL cell lines, characterizing biologic molecular effects. expression was characterized pre-B-ALL (NALM-6) lines (SEM...
The introduction of combined conventional cytostatics and pathway-specific inhibitors has opened new treatment options for several cancer types including hematologic neoplasia such as leukaemias. As the detailed understanding combination-induced molecular effects is often lacking, identification mechanisms bears significant value further development interventional approaches.Combined application cytostatic agents (cytarabine dexamethasone) with PI3K-inhibitor Idelalisib was analysed on...
Background/Aim: Canine B-cell lymphoma represents a useful in vivo model for human diffuse large (DLBCL). Pan-Bromodomain and extra-terminal (BET) inhibition targeting BRD2/3/4 selective of BRD4, as well spleen tyrosine kinase (SYK) inhibition, are currently evaluated haematologic cancer therapy. Herein, we characterized the differences biologic response isoform-specific or pan-BET alone combination with SYK inhibition. Materials Methods: I-BET151 (pan-inhibitor) AZD5153 (BRD4 inhibitor)...
Summary The molecular basis of aging and aging-associated diseases is being unraveled at an increasing pace. An extended healthspan, not merely extension lifespan, has become the aim medical practice. However, a precise definition health healthspan straightforward, causal “per se” largely unknown. Here, we define based on absence dysfunctions. Based extensive review literature, in particular for humans C. elegans , compile list features genes associated with them. Clusters these interaction...
Casein kinase II (CK2) and cyclin-dependent kinases (CDKs) frequently interact within multiple pathways in pancreatic ductal adenocarcinoma (PDAC). Application of CK2- CDK-inhibitors have been considered as a therapeutic option, but are currently not part routine chemotherapy regimens. We investigated ten PDAC cell lines exposed to increasing concentrations silmitasertib dinaciclib. Cell proliferation, metabolic activity, biomass, apoptosis/necrosis were evaluated, bioinformatic clustering...
Canine prostate cancer represents a unique model for human cancer. In vitro systems offer various possibilities but Xenograft in vivo imaging allows studying complex tasks as tumor progression and drug intervention longitudinal. Herein, we established three canine carcinoma cell lines stably expressing fluorescent proteins allowing deep tissue imaging.Three (cPC) were transfected with red, far-red near infra-red spectrum, followed by G418 selection. Fluorescent protein expression was...
Abstract Myeloproliferative neoplasms are characterized by mutations in JAK2, MPL and CALR genes. Commonly diagnostics previous studies mainly sequencing common PCR techniques under conventional detection limits used. Splanchnic vein thromboses rare, but often appear associated with myeloproliferative represent serious complications. Herein, blood from patients abdominal Mecklenburg-West Pomerania (federal district of northern Germany), included an ongoing prospective prevalence study, was...
Cancer cell inoculation is routinely used to evaluate novel therapeutic approaches in vivo. However, without reporter genes enabling deep tissue imaging, study of early tumor progression and responses often limited. We describe the establishment characterization two canine cancer lines stably expressing red fluorescence proteins as tools for later vivo imaging.Two were generated by plasmid transfection. Fluorescence protein expression was confirmed flow cytometry microscopy. Deep imaging...
The treatment of cancer is one the most important pharmacotherapeutic challenges. To this end, chemotherapy has for some time been complemented by targeted therapies against specific structures. PDA-66, a structural analogue inhibitor serine-threonine kinase glycogen synthase 3β SB216763, shown preclinical antitumour effects in various cell lines, with key pathways its anticancer activity being cycle modulation, DNA replication and p53 signalling. For monitoring drug context therapeutic...