Obiekt
Tytuł: Evaluation of endothelial function during cancer progression and in response to chemotherapy in the in vivo and ex vivo models
Abstrakt:
Oncological patients are at higher risk of the cardiovascular complications associated with endothelial dysfunction, which may be a consequence of both cancer and its treatment. Understanding the mechanisms underlying endothelial dysfunction is crucial to develop better therapies. The aim of the study was to investigate how the cancer itself and chosen anticancer therapy affect the endothelium. In the first part of the study changes in endothelial function and local and systemie inflammatory response in a mouse model of breast cancer were examined. In the second part of the study the effect of BRAF and MEK inhibitors on the endothelium was assessed. In the early stage of cancer in mice, inflammation in the lungs and the decreased availability of NO in the lungs and peripheral circulation were found, while at the late stage of cancer systemie inflammation and impaired endothelial function in aorta appeared. In the second part of the work, it was shown that dabrafenib, but not trametinib, impairs endothelial function ex vivo and in vivo, and the mechanism of this dysfunction may include decreased eNOS activity, inereased ROS production and activity of some kinases, including ROCK and CAMK. Dabrafenib also affects cellular energy metabolism, which may be a compensatory mechanism in response to its toxicity. Ex vivo pharmacological interventions have shown that potential strategy t ; o counteract dabrafenib-induced endothelial dysfunction may be the use of CAMK and ROCK kinase inhibitors and inhibition of ROS production. These results have translational potential due to the need to protect the endothelium in oncological patients.
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Instytucja nadająca tytuł:
Rada Dyscypliny Nauki medyczne
Promotor:
Chłopicki, Stefan ; Smęda, Marta
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Data ostatniej modyfikacji:
23 lut 2026
Data dodania obiektu:
23 lut 2026
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2
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http://149.156.57.56:8080/publication/6108
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| Nazwa wydania | Data |
|---|---|
| ZB-143572 | 23 lut 2026 |
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