Experimentelle Onkologie, Palliativmedizin und Ethik in der Onkologie

Welcome to the division of experimental oncology and ethics in oncology

Laboratory of Extracellular Vesicles

The goal of our research is to understand the role extracellular vesicles (EVs) in the development of thrombophilia in the context of tumor diseases, as well as in cell-cell communication in the microenvironment of malignancies.

We have established methods to isolate and characterize EV from biological material such as blood, urine and ascites. This is intended to develop surrogate markers for thrombosis, tumor progression (metastasis) and tumor diagnostics in the sense of a "liquid biopsy". Corresponding studies are being carried out with several clinics on the campus.

Our research is funded by various industrial partners as well as by the Annelise Asmussen Foundation (DFG-compliant allocation of funds).

Ethics in oncology

Our research is focused on is the establishment of patient-oriented therapy documentation in oncology (PROM, PREM). The goal is the integration of PROM into clinical care and the clinical cancer registry. There are collaborations with the Institute for Cancer Epidemiology, the Schleswig-Holstein and German Cancer Societies, and on an international level with the Danish Ministry of Health ("Canging Cancer Care", InnoCan).

Research scope

The goal of our research is to understand the role of extracellular vesicles in the development of thrombophilia in the context of tumor diseases, as well as in cell-cell communication in the microenvironment of malignancies.

Extracellular vesicles in cancer pathogenesis

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We have shown that malignant effusions are a rich source of tumor cell-derived extracellular vesicles, which are correlated with inflammation as well as progressive and metastatic cancer. Using our established techniques for extracellular vesicles isolation and detailed characterization, we have discovered that tumor cell-derived extracellular vesicles are highly variable. We have investigated these variations in terms of molecular characteristics and functional potency (induction of coagulation) across different cancer cell models.

project 1: Modulation of the cancer progression by tumor cell-derived extracellular vesicles

project 2: Cell signaling mechanism (e.g. PAR/ERK pathway) involved in extracellular vesicles biological activity

Extracellular vesicles in cancer pathogenesis

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Particular molecular signature and functional potency of the tumor cell-derived extracellular vesicles (e.g. enrichment of tissue factor and phosphatidylserine) can be used to discern both at diagnosis and monitoring of cancer. We have established methods to isolate and characterize extracellular vesicles from biological material such as blood, urine and ascites. This is intended to develop surrogate markers for thrombosis, tumor progression (metastasis) and tumor diagnosis.

project 3: Liquid biopsy analysis of biomarkers associated to cellular microparticles

Structural and functional characterization of extracellular vesicles

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The tumor cell-derived extracellular vesicles provides a remodeled platform of bioactive constituent toward the external environment. Particular membrane domains created by physical partitioning gives further functional capacity to extracellular vesicles. Using combined compositional, functional and microspcopic analysis we charaterize cell-specific domains on the cellular microparticles.

project 4: Lipidomic characterization of the tumor cell-derived extracellular vesicles

project 5: Modulation of microparticles functional potency in response to metabolic reprogramming

Funded projects

LEO-Pharma GmbH, Copenhagen Denmark
"Possible use of extracellular vesicles (EV) in cancer diagnostics and as surrogate parameter for cancer associated venous thrombembolism"

Annelise Asmussen Foundation, Lübeck
"Extracellular vesicles as liquid biopsy ("liquid biopsy") in oncology: Molecular link between tumor biology and coagulation?"

Schleswig-Holsteinische-Krebsgesellschaft, Kiel
PROMs and PREMs in the palliative care of cancer patients ("PROpatient")

Selected publications

Steidel, C., Ender, F., Rody, A., von Bubnoff, N., & Gieseler, F. (2021). Biologically active tissue factor-bearing larger ectosome-like extracellular vesicles in malignant effusions from ovarian cancer patients: Correlation with incidence of thrombosis. International Journal of Molecular Sciences, 22(2), 790.

Rose, G., Rades, D., Dunst, J., von Bubnoff, N., Luebbe, A., & Gieseler, F. (2021). EORTC quality of lfe questionnaire with added subjective weighting for improving tailored treatment and therapy monitoring in oncology.

Hosseini, V., Kalantary-Charvadeh, A., Hajikarami, M., Fayyazpour, P., Rahbarghazi, R., Totonchi, M., & Darabi, M. (2021). A small molecule modulating monounsaturated fatty acids and Wnt signaling confers maintenance to induced pluripotent stem cells against endodermal differentiation. Stem cell research & therapy, 12(1), 1-14.

Ender, F., Freund, A., Quecke, T., Steidel, C., Zamzow, P., von Bubnoff, N., & Gieseler, F. (2020). Tissue factor activity on microvesicles from cancer patients. Journal of cancer research and clinical oncology, 146(2), 467-475.

Ender, F., Von Bubnoff, N., & Gieseler, F. (2019). Extracellular vesicles: subcellular organelles with the potential to spread cancer resistance. Anticancer Research, 39(7), 3395-3404.

Gieseler, F., Gamperl, H., Plattfaut, C., Theophil, R., & Quecke, T. (2015). Inhibition of microparticle induced tumor cell migration by LMWH tinzaparin. Journal of Thrombosis and Haemostasis, 13, 263-263.

Ungefroren, H., Sebens, S., Giehl, K., Helm, O., Groth, S., Fändrich, F., ... & Gieseler, F. (2014). Rac1b negatively regulates TGF-β1-induced cell motility in pancreatic ductal epithelial cells by suppressing Smad signalling. Oncotarget, 5(1), 277.

Ungefroren, H., Sebens, S., Giehl, K., Helm, O., Groth, S., Fändrich, F., ... & Gieseler, F. (2014). Rac1b negatively regulates TGF-β1-induced cell motility in pancreatic ductal epithelial cells by suppressing Smad signalling. Oncotarget, 5(1), 277.

Gieseler, F., Ungefroren, H., Settmacher, U., Hollenberg, M. D., & Kaufmann, R. (2013). Proteinase-activated receptors (PARs)–focus on receptor-receptor-interactions and their physiological and pathophysiological impact. Cell Communication and Signaling, 11(1), 1-26.

Gieseler, F., Lühr, I., Kunze, T., Mundhenke, C., Maass, N., Erhart, T., ... & Gespach, C. (2007). Activated coagulation factors in human malignant effusions and their contribution to cancer cell metastasis and therapy. Thrombosis and haemostasis, 97(06), 1023-1030.

Full list of publications:
https://scholar.google.com/citations?user=X6HiJK8AAAAJ&hl=de

People

Prof. Dr. med. Frank Gieseler

Bereichsleitung, Experimentelle Onkologie, Palliativmedizin und Ethik in der Onkologie
Tel.: 0451-3101 8812