Einfluss der Blockade des Kaliumkanals Eag1 durch trizyklische und nicht-trizyklische Antidepressiva auf die Überlebenszeit von Patienten mit Glioblastoma multiforme bzw. Hirnmetastasen und Depression: Eine klinische und immunhistochemische Analyse.

Impact of Eag1 inhibition with tricyclic and non-tricyclic antidepressants on survival in patients with glioblastoma multiforme or brain metastases and depression. Clinical and immunhistochemical analysis.

by Julian Michael Schell
Doctoral thesis
Date of Examination:2015-04-20
Date of issue:2015-03-16
Advisor:PD Dr. Ramon Martínez-Olivera
Referee:PD Dr. Ramon Martínez-Olivera
Referee:Prof. Dr. Walter Stühmer
Persistent Address: http://dx.doi.org/10.53846/goediss-4975

 

 

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Abstract

English

Glioblastoma multiforme (GBM) is a malignant neoplasia with astrocytic respectively oligoastrocytic origin. In adults, it is the most common primary brain tumor. Brain metastases are secondary brain tumors. Mostly, these malignancies are originated from lung and breast cancer or melanoma. Despite multimodal therapies, prognosis of patients with GBM and brain metastases is limited. Reducing of tumor progression by inhibition of molecular marker in tumor cells represents a possibility to increase the prognosis of patients. The voltage-gated potassium channel Eag1 is overexpressed in extracerebral carcinoma associated with overexpression of VEGF and inhibition of p53, resulting in increased tumor progression and worse prognosis. Eag1 was found to be a molecular marker because in vitro inhibition of Eag1 with tricyclic antidepressants or monoclonal antibodies led to reducing of tumor progression. In this study, Eag1 expression in tumor tissue of patients with GBM and brain metastases in combination with impact on survival was analyzed. Moreover, the influence of inhibition of Eag1 with tricyclic and non-tricyclic antidepressants on survival was examined. The results showed that Eag1 is overexpressed in GBM and brain metastases. In brain metastases, overexpression of Eag1 was significantly associated with limited survival time. Respectively, patients with low Eag1 expression had a better prognosis. In this patients, inhibition of Eag1 with tricyclic antidepressants showed a significant longer survival time in addition. However, the results didn't show significant effects on survival in patients with GBM. Our data strongly suggest that Eag1 is a tumor marker in brain metastases and GBM. In patients with brain metastases, Eag1 is a potential prognosis marker and oncotarget for a personalized therapy.
Keywords: Eag1; Ether-a-go-go 1; Brain metastases; Glioblastoma multiforme
 
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