Wirkung und Wirkmechanismus von AEZS 126 auf verschiedene Subentitäten des Mammakarzinoms

Anti-tumour activity of phosphoinositide-3-kinase antagonist AEZS 126 in models of triple-negative breast cancer

Please always quote using this URN: urn:nbn:de:bvb:20-opus-81959
  • Untersuchung des Wirkmechanismus von AEZS 126 auf drei triple negative Mammakarzinomzelllinien HCC1937, HCC1806 und MDA-MB468 und eine Oestrogenrezeptor positive Zelllinie MCF-7 mittels Kristallviolett assay, FACS und Western Blot. Es konnte gute Antitumorwirkung des Inhibitors in vitro gezeigt werden.
  • Of more than one million global cases of breastcancer diagnosed each year, a high percentage are characterized as triple-negative, lacking the oestrogen, progesterone and Her2/neu receptors. The incidence exceeds the incidence of malignancies like CML by far. Lack of effective therapies, younger age at onset and early metastatic spread have contributed to the poor prognosis and outcomes associated with these malignancies. Here, we investigate the ability of the PI3 K/AKT inhibitor AEZS 126 to selectively target the triple negative breast cancerOf more than one million global cases of breastcancer diagnosed each year, a high percentage are characterized as triple-negative, lacking the oestrogen, progesterone and Her2/neu receptors. The incidence exceeds the incidence of malignancies like CML by far. Lack of effective therapies, younger age at onset and early metastatic spread have contributed to the poor prognosis and outcomes associated with these malignancies. Here, we investigate the ability of the PI3 K/AKT inhibitor AEZS 126 to selectively target the triple negative breast cancer (TNBC) cell proliferation and survival in vitro by MTT-assays and FACS-based analysis. Furthermore, the mechanism of cytotoxicity is analysed by FACS-based assays and Western blots. Results AEZS 126 showed good antitumour activity in in vitro models of TNBC as well as in MCF-7 cells. We demonstrated the highly efficient antitumour activity of AEZS 126 in in vitro models of TNBC. Due to the good anti-tumour activity and the expected favourable toxicity profile, AEZS 126 in combination with chemotherapy seems to be a promising candidate for clinical testing in TNBC especially in the basal-like subgroup of TNBC.show moreshow less

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Metadaten
Author: Heike Schmidt
URN:urn:nbn:de:bvb:20-opus-81959
Document Type:Doctoral Thesis
Granting Institution:Universität Würzburg, Medizinische Fakultät
Faculties:Medizinische Fakultät / Frauenklinik und Poliklinik
Date of final exam:2013/08/28
Language:German
Year of Completion:2013
Dewey Decimal Classification:6 Technik, Medizin, angewandte Wissenschaften / 61 Medizin und Gesundheit / 610 Medizin und Gesundheit
GND Keyword:Brustkrebs; TNBC; PI3K/AKT Inhibitor; PARP; Nekroptose
Tag:Breast cancer; Caspase; PARP; PI3K/AKT inhibitor; RIP-1; TNBC
Release Date:2013/10/15
Advisor:Prof. Dr. med. Arnd Hönig
Licence (German):License LogoCC BY: Creative-Commons-Lizenz: Namensnennung