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This publication is protected and can be accessed only from certain IPs.

Title: Mechanisms of vascular endothelial dysfunction induced by neoadjuvant chemotherapy in patients with breast cancer

Abstract:

The main aim of the project was to determine the mechanism of action of chemotherapy (docetaxel, cyclophosphamide, doxorubicin) on endothelial function in patients with breast cancer undergoing neoadjuvant chemotherapy. Patients who received NACT had significantly impaired endothelium dependent vascular function, compared to patients who did not receive NACT, which was improved by in the presence of N-acetylcysteine . NACT induced O2- level, H2O2 level and NADPH activity. NOX2, NOX4, CAT, SOD1 and SOD2 significantly increased in blood vessels of patients with NACT. Elevated levels of NOX4 expression were determined by a reduced amount of methylated CpG counts within the promoter. NACT induced phosphorylation of T495 eNOS and PKCɑ activity. Docetaxel caused impairment of vascular endothelial function compared to vehicle, while no differences were observed after exposure to cyclophosphamide, 4-hydroperoxycyclophosphamide and doxorubicin. Docetaxel induced the following in vessels: CYBB, CAT, NOX4, SOD1 and SOD2 (compared to the control). T495 eNOS phosphorylation induced by docetaxel was inhibited by ROCK inhibitor and not by PKCɑ inhibitor in vitro. Control mice injected with docetaxel had impaired endothelial function. The control mice in the influence of docetaxel produced significantly more O2- and H2O2 compared to mice injected with placebo. NACT caused the impairment of b ; lood vessel function by increasing the level of reactive oxygen species in blood vessels in patients with breast cancer. Docetaxel, as a component of NACT, is responsible for impaired vascular endothelial function.

Place of publishing:

Kraków

Level of degree:

2 - studia doktoranckie

Degree discipline:

onkologia ; choroby układu krążenia

Degree grantor:

Rada Dyscypliny Nauki medyczne

Promoter:

Guzik, Tomasz

Date issued:

2019

Identifier:

oai:dl.cm-uj.krakow.pl:4587

Call number:

ZB-132290

Language:

pol

Access rights:

tylko w bibliotece

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Last modified:

Apr 8, 2024

In our library since:

Mar 30, 2022

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6

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All available object's versions:

http://dl.cm-uj.krakow.pl:8080/publication/4588

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ZB-132290 Apr 8, 2024
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