11938
2014
eng
e104337
8
9
article
1
2015-09-29
--
--
Evaluation of a New Recombinant Oncolytic Vaccinia Virus Strain GLV-5b451 for Feline Mammary Carcinoma Therapy
Virotherapy on the basis of oncolytic vaccinia virus (VACV) infection is a promising approach for cancer therapy. In this study we describe the establishment of a new preclinical model of feline mammary carcinoma (FMC) using a recently established cancer cell line, DT09/06. In addition, we evaluated a recombinant vaccinia virus strain, GLV-5b451, expressing the anti-vascular endothelial growth factor (VEGF) single-chain antibody (scAb) GLAF-2 as an oncolytic agent against FMC. Cell culture data demonstrate that GLV-5b451 virus efficiently infected, replicated in and destroyed DT09/06 cancer cells. In the selected xenografts of FMC, a single systemic administration of GLV-5b451 led to significant inhibition of tumor growth in comparison to untreated tumor-bearing mice. Furthermore, tumor-specific virus infection led to overproduction of functional scAb GLAF-2, which caused drastic reduction of intratumoral VEGF levels and inhibition of angiogenesis.
In summary, here we have shown, for the first time, that the vaccinia virus strains and especially GLV-5b451 have great potential for effective treatment of FMC in animal model.
PLoS ONE
10.1371/journal.pone.0104337
urn:nbn:de:bvb:20-opus-119387
PLoS ONE 9(8): e104337. doi:10.1371/journal.pone.0104337
Marion Adelfinger
Ivaylo Gentschev
Julio Grimm de Guibert
Stephanie Weibel
Johanna Langbein-Laugwitz
Barbara Härtl
Hugo Murua Escobar
Ingo Nolte
Nanhai G. Chen
Richard J. Aguilar
Yong A. Yu
Qian Zhang
Alexa Frentzen
Aladar A. Szalay
eng
uncontrolled
antibodies
eng
uncontrolled
cancer treatment
eng
uncontrolled
carcinomas
eng
uncontrolled
vaccinia virus
eng
uncontrolled
oncolytic viruses
eng
uncontrolled
viral replication
eng
uncontrolled
cell cultures
eng
uncontrolled
enzyme-linked immunoassays
Krankheiten
open_access
Institut für Molekulare Infektionsbiologie
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/11938/033_Adelfinger_PLOS_ONE.pdf
17089
2017
eng
e0177442
5
12
article
1
2018-10-31
--
--
Analysis of global DNA methylation changes in primary human fibroblasts in the early phase following X-ray irradiation
Epigenetic alterations may contribute to the generation of cancer cells in a multi-step process of tumorigenesis following irradiation of normal body cells. Primary human fibroblasts with intact cell cycle checkpoints were used as a model to test whether X-ray irradiation with 2 and 4 Gray induces direct epigenetic effects (within the first cell cycle) in the exposed cells. ELISA-based fluorometric assays were consistent with slightly reduced global DNA methylation and hydroxymethylation, however the observed between-group differences were usually not significant. Similarly, bisulfite pyrosequencing of interspersed LINE-1 repeats and centromeric α-satellite DNA did not detect significant methylation differences between irradiated and non-irradiated cultures. Methylation of interspersed ALU repeats appeared to be slightly increased (one percentage point; p = 0.01) at 6 h after irradiation with 4 Gy. Single-cell analysis showed comparable variations in repeat methylation among individual cells in both irradiated and control cultures. Radiation-induced changes in global repeat methylation, if any, were much smaller than methylation variation between different fibroblast strains. Interestingly, α-satellite DNA methylation positively correlated with gestational age. Finally, 450K methylation arrays mainly targeting genes and CpG islands were used for global DNA methylation analysis. There were no detectable methylation differences in genic (promoter, 5' UTR, first exon, gene body, 3' UTR) and intergenic regions between irradiated and control fibroblast cultures. Although we cannot exclude minor effects, i.e. on individual CpG sites, collectively our data suggest that global DNA methylation remains rather stable in irradiated normal body cells in the early phase of DNA damage response.
PLoS ONE
10.1371/journal.pone.0177442
28489894
urn:nbn:de:bvb:20-opus-170895
PLoS ONE 12(5):e0177442 (2017). DOI: 10.1371/journal.pone.0177442
false
true
CC BY: Creative-Commons-Lizenz: Namensnennung 4.0 International
Anna Maierhofer
Julia Flunkert
Marcus Dittrich
Tobias Müller
Detlev Schindler
Indrajit Nanda
Thomas Haaf
eng
uncontrolled
DNA methylation
eng
uncontrolled
fibroblasts
eng
uncontrolled
methylation
eng
uncontrolled
alu elements
eng
uncontrolled
DNA damage
eng
uncontrolled
epigenetics
eng
uncontrolled
cancer treatment
Menschliche Anatomie, Zytologie, Histologie
open_access
Institut für Humangenetik
Theodor-Boveri-Institut für Biowissenschaften
Universität Würzburg
https://opus.bibliothek.uni-wuerzburg.de/files/17089/073_Maierhofer_PLOS-ONE.pdf