TY  - THES
A1  - Curtaz, Carolin Julia
T1  - \(In\) \(vitro\) Analysen der Wechselwirkung erhöhter Temperatur mit Zytostatika am Beispiel von Cisplatin
T1  - \(In\) \(vitro\) analysis of the interaction of hyperthermia with cytostatica in case of cisplatin
N2  - Neben der Chemotherapie ist heutzutage auch die Hyperthermie-Behandlung eine wichtige Säule der antitumorösen Therapie. Während der sogenannten HIPEC Therapie (Hypertherme intraperitoneale Chemoperfusion) werden die beiden Arten der Therapieformen kombiniert und in der klinischen Praxis erfolgreich angewendet. Genauere Kenntnisse über die zu Grunde liegenden toxikologischen in-vitro Mechanismen könnten zu neuen Möglichkeiten in der klinischen Anwendung führen. In unserer Arbeit untersuchten wir verschiedenen Tumorzelllinien (HT29,CaCo-2,HCT116,HaCaT) in Kombination mit Cisplatin und Hyperthermie mit verschiedenen Methoden, wie zum Beispiel Mikrokerntest, Comet-Assay, Durchflusszytometrie, Vitalitätstest und mikroskopischen Analysen. Unsere Ergebnisse führten uns zu der Hypothese, dass Hyperthermie alleine zu einer sogenannte mitotic catastrophe führt und zum Absterben der Tumorzellen. Im Gegensatz dazu zeigten Tumorzellen, welche mit Cisplatin alleine oder auch in Kombination mit Hyperthermie nicht in die Mitose eintreten und daher nicht durch Apoptose in den Zelltod gehen.
N2  - Nowadays the use of chemotherapy, but also hyperthermia are main columns of the anti- cancer treatment. In the so-called HIPEC therapy (hypertherme intraperitoneale chemoperfusion) these both kinds of treatments are combined and successfully applieded with clinical relevance. More detailed knowledge about the underlying in-vitro toxicological mechanism may lead to new opportunities in the clinical practice. In our work we examined different cancer cells (HT29, CaCo2,HCT116,HaCaT) in the combination of with cisplatin and hyperthermia by using different methods e.g. micronucleus test, comet-assay, flow cytometry, vitality test and microscopical analysis. Our aquired results lead to the postulation that hyperthermia alone induces a so- called mitotic catastrophe provoking the death of tumor cells. However tumor cells treated with cisplatin with or without combination with hyperthermia do not enter into mitosis and therefore cannot undergo apoptosis through a mitotic catastrophe.
KW  - Hyperthermie
KW  - cisplatin
KW  - HIPEC therapy
KW  - mitotic catastrophe
KW  - comet assay
KW  - micronucleus test
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-174543
ER  - 
TY  - JOUR
A1  - Curtaz, Carolin J.
A1  - Reifschläger, Leonie
A1  - Strähle, Linus
A1  - Feldheim, Jonas
A1  - Feldheim, Julia J.
A1  - Schmitt, Constanze
A1  - Kiesel, Matthias
A1  - Herbert, Saskia-Laureen
A1  - Wöckel, Achim
A1  - Meybohm, Patrick
A1  - Burek, Malgorzata
T1  - Analysis of microRNAs in exosomes of breast cancer patients in search of molecular prognostic factors in brain metastases
JF  - International Journal of Molecular Sciences
N2  - Brain metastases are the most severe tumorous spread during breast cancer disease. They are associated with a limited quality of life and a very poor overall survival. A subtype of extracellular vesicles, exosomes, are sequestered by all kinds of cells, including tumor cells, and play a role in cell-cell communication. Exosomes contain, among others, microRNAs (miRs). Exosomes can be taken up by other cells in the body, and their active molecules can affect the cellular process in target cells. Tumor-secreted exosomes can affect the integrity of the blood-brain barrier (BBB) and have an impact on brain metastases forming. Serum samples from healthy donors, breast cancer patients with primary tumors, or with brain, bone, or visceral metastases were used to isolate exosomes and exosomal miRs. Exosomes expressed exosomal markers CD63 and CD9, and their amount did not vary significantly between groups, as shown by Western blot and ELISA. The selected 48 miRs were detected using real-time PCR. Area under the receiver-operating characteristic curve (AUC) was used to evaluate the diagnostic accuracy. We identified two miRs with the potential to serve as prognostic markers for brain metastases. Hsa-miR-576-3p was significantly upregulated, and hsa-miR-130a-3p was significantly downregulated in exosomes from breast cancer patients with cerebral metastases with AUC: 0.705 and 0.699, respectively. Furthermore, correlation of miR levels with tumor markers revealed that hsa-miR-340-5p levels were significantly correlated with the percentage of Ki67-positive tumor cells, while hsa-miR-342-3p levels were inversely correlated with tumor staging. Analysis of the expression levels of miRs in serum exosomes from breast cancer patients has the potential to identify new, non-invasive, blood-borne prognostic molecular markers to predict the potential for brain metastasis in breast cancer. Additional functional analyzes and careful validation of the identified markers are required before their potential future diagnostic use.
KW  - breast cancer
KW  - breast cancer metastases
KW  - blood-brain barrier
KW  - patient serum
KW  - exosomes
KW  - microRNA
KW  - gene expression
KW  - prognostic marker
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-284476
SN  - 1422-0067
VL  - 23
IS  - 7
ER  -