TY  - THES
A1  - Calderón Giraldo, Jeniffer
T1  - Analysis of estrogen profiles including methoxyestrogen glucuronides: method validation and applicability to human plasma and breast tissue
T1  - Analyse von Estrogenprofilen einschließlich Methoxyestrogenglucuroniden: Methodenvalidierung und Anwendbarkeit auf menschliches Plasma und Brustgewebe
N2  - Estrogens, namely 17β-estradiol (E2) and estrone (E1) are considered to play an important role in the initiation and promotion of breast cancer (summarized in Raftogianis et al., 2000), a malignancy responsible for around 500,000 deaths per year (summarized in Ghislain et al., 2016). Two major mechanisms have been postulated to explain the carcinogenic effects of estrogens: (1) the estrogen receptor-mediated stimulation of breast cell proliferation with a concomitant enhanced rate of mutations and (2) the metabolism of hydroxylated estrogens to quinone derivatives which can react with the DNA (Russo and Russo, 2006, summarized in Yager and Davidson, 2006). Nevertheless, as a detoxifying mechanism, E1, E2, and their hydroxylated and methoxylated metabolites are reversibly conjugated into sulfates and glucuronides devoid of biological activity (summarized in Guillemette et al., 2004). Yet, despite the key detoxifying function of these conjugates, the study of their circulating levels face some significant problems: (1) analysis by techniques such as radioimmunoassay lack specificity and accuracy and requires enzymatic/chemical hydrolysis before analysis, being unable to differentiate between sulfates and glucuronides (summarized in Stanczyk et al., 2007, summarized in Wang et al., 2016), (2) very little knowledge in healthy women, which has been identified as a barrier to advance in breast cancer research (summarized in Liu, 2000), and (3) far fewer studies in pre- than in postmenopausal women (summarized in Samavat and Kurzer, 2015). Therefore, to get more insights into the research of breast cancer etiology and prevention, the analysis of circulating levels of estrogens (including metabolites and conjugates) in women without breast cancer through reliable analytical techniques, is required.
N2  - Estrogene spielen eine zentralle Rolle bei der Entstehung von Brustkrebs. Jedoch haben nicht alle Estrogenmetabolite die gleiche Wirkung. Deshalb ist das Wissen über das Profil der zikulierenden Estrogene bei gesunden Frauen von entscheidender Bedeutung. Die meisten Methoden zur Analyse von Estrogenen zielen jedoch entweder nicht auf konjugierte Estrogene ab oder erfassen nur die Summe der jeweiligen freien und konjugierten Form. Gegenstand der vorliegenden Arbeit war demzufolge, die Möglichkeit der Einbeziehung von Methoxyestrogenglucuroniden in eine bestehende Methode zur Analyse von Estrogenen zu evaluieren und somit die Analyse von Estrogenprofilen im menschlichen Plasma und im Brustgewebe von Frauen ohne Brustkrebs zu ergänzen. ...
KW  - Estrogens
KW  - profiles
KW  - human plasma
Y1  - 2022
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-209396
ER  - 
TY  - JOUR
A1  - Scherzad, Agmal
A1  - Meyer, Till
A1  - Ickrath, Pascal
A1  - Gehrke, Thomas Eckhart
A1  - Bregenzer, Maximillian
A1  - Hagen, Rudolf
A1  - Dembski, Sofia
A1  - Hackenberg, Stephan
T1  - Cultivation of hMSCs in human plasma prevents the cytotoxic and genotoxic potential of ZnO-NP in vitro
JF  - Applied Sciences
N2  - Zinc oxide nanoparticles (ZnO-NPs) are commonly used for industrial applications. Consequently, there is increasing exposure of humans to them. The in vitro analysis of cytotoxicity and genotoxicity is commonly performed under standard cell culture conditions. Thus, the question arises of how the results of genotoxicity and cytotoxicity experiments would alter if human plasma was used instead of cell culture medium containing of fetal calf serum (FCS). Human mesenchymal stem cells (hMSCs) were cultured in human plasma and exposed to ZnO-NPs. A cultivation in expansion medium made of DMEM consisting 10% FCS (DMEM-EM) served as control. Genotoxic and cytotoxic effects were evaluated with the comet and MTT assay, respectively. hMSC differentiation capacity and ZnO-NP disposition were evaluated by histology and transmission electron microscopy (TEM). The protein concentration and the amount of soluble Zn2+ were measured. The cultivation of hMSCs in plasma leads to an attenuation of genotoxic and cytotoxic effects of ZnO-NPs compared to control. The differentiation capacity of hMSCs was not altered. The TEM showed ZnO-NP persistence in cytoplasm in both groups. The concentrations of protein and Zn2+ were higher in plasma than in DMEM-EM. In conclusion, the cultivation of hMSCs in plasma compared to DMEM-EM leads to an attenuation of cytotoxicity and genotoxicity in vitro.
KW  - ZnO-NP
KW  - mesenchymal stem cells
KW  - genotoxicity
KW  - cytotoxicity
KW  - human plasma
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-193063
SN  - 2076-3417
VL  - 9
IS  - 23
ER  -