TY  - JOUR
A1  - Schmitz, Werner
A1  - Ries, Elena
A1  - Koderer, Corinna
A1  - Völter, Maximilian Friedrich
A1  - Wünsch, Anna Chiara
A1  - El-Mesery, Mohamed
A1  - Frackmann, Kyra
A1  - Kübler, Alexander Christian
A1  - Linz, Christian
A1  - Seher, Axel
T1  - Cysteine restriction in murine L929 fibroblasts as an alternative strategy to methionine restriction in cancer therapy
JF  - International Journal of Molecular Sciences
N2  - Methionine restriction (MetR) is an efficient method of amino acid restriction (AR) in cells and organisms that induces low energy metabolism (LEM) similar to caloric restriction (CR). The implementation of MetR as a therapy for cancer or other diseases is not simple since the elimination of a single amino acid in the diet is difficult. However, the in vivo turnover rate of cysteine is usually higher than the rate of intake through food. For this reason, every cell can enzymatically synthesize cysteine from methionine, which enables the use of specific enzymatic inhibitors. In this work, we analysed the potential of cysteine restriction (CysR) in the murine cell line L929. This study determined metabolic fingerprints using mass spectrometry (LC/MS). The profiles were compared with profiles created in an earlier work under MetR. The study was supplemented by proliferation studies using D-amino acid analogues and inhibitors of intracellular cysteine synthesis. CysR showed a proliferation inhibition potential comparable to that of MetR. However, the metabolic footprints differed significantly and showed that CysR does not induce classic LEM at the metabolic level. Nevertheless, CysR offers great potential as an alternative for decisive interventions in general and tumour metabolism at the metabolic level.
KW  - methionine restriction
KW  - cysteine restriction
KW  - mass spectrometry
KW  - LC/MS
KW  - cancer therapy
KW  - caloric restriction
KW  - homocysteine
KW  - amino acid analogues
KW  - cysteine synthase inhibitor
Y1  - 2021
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-265486
SN  - 1422-0067
VL  - 22
IS  - 21
ER  - 
TY  - JOUR
A1  - Cecil, Alexander
A1  - Gentschev, Ivaylo
A1  - Adelfinger, Marion
A1  - Dandekar, Thomas
A1  - Szalay, Aladar A.
T1  - Vaccinia virus injected human tumors: oncolytic virus efficiency predicted by antigen profiling analysis fitted boolean models
JF  - Bioengineered
N2  - Virotherapy on the basis of oncolytic vaccinia virus (VACV) strains is a promising approach for cancer therapy. Recently, we showed that the oncolytic vaccinia virus GLV-1h68 has a therapeutic potential in treating human prostate and hepatocellular carcinomas in xenografted mice. In this study, we describe the use of dynamic boolean modeling for tumor growth prediction of vaccinia virus-injected human tumors. Antigen profiling data of vaccinia virus GLV-1h68-injected human xenografted mice were obtained, analyzed and used to calculate differences in the tumor growth signaling network by tumor type and gender. Our model combines networks for apoptosis, MAPK, p53, WNT, Hedgehog, the T-killer cell mediated cell death, Interferon and Interleukin signaling networks. The in silico findings conform very well with in vivo findings of tumor growth. Similar to a previously published analysis of vaccinia virus-injected canine tumors, we were able to confirm the suitability of our boolean modeling for prediction of human tumor growth after virus infection in the current study as well. In summary, these findings indicate that our boolean models could be a useful tool for testing of the efficacy of VACV-mediated cancer therapy already before its use in human patients.
KW  - boolean modeling
KW  - oncolytic virus
KW  - human xenografted mouse models
KW  - cancer therapy
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-200507
VL  - 10
IS  - 1
ER  -