TY  - JOUR
A1  - Guo, Ke-Tai
A1  - Jürchott, Kathrin
A1  - Fu, Peng
A1  - Selbig, Joachim
A1  - Eigenbrod, Sabina
A1  - Tonn, Jörg-Christian
A1  - Schichor, Christian
T1  - Isolation and characterization of bone marrow-derived progenitor cells from malignant gliomas
JF  - Anticancer research : international journal of cancer research and treatment
N2  - Background: Malignant gliomas are highly-vascularised tumours. Neoangiogenesis is a crucial factor in the malignant behaviour of tumour and prognosis of patients. Several mechanisms are suspected to lead to neoangiogenesis, one of them is the recruitment of multipotent progenitor cells towards the tumour. Factors such as Vascular endothelial growth factor-A (VEGF-A) were described to recruit bone marrow-derived endothelial progenitor cells (EPCs) to the glioma stroma and vasculature. Little is known about isolating EPCs from normal or malignant tissues. Materials and Methods: In this study, we addressed the topic of characterization of tumour-isolated EPCs and re-defined the clonal relationship between EPCs and hematopoietic stem cells (HSCs) in gliomas. We first checked public gene expression data of glioma for putative marker expression, pointing towards a prevalence of EPCs and HSCs in glioma. Immunohistochemical staining of glioma tissue confirmed the higher expression of these progenitor markers in glioma tissue. EPCs and HSCs were consequently isolated and characterized at the phenotypic and functional levels. We applied a new isolation method, for the first time, to specimen from patients with high grade glioma including seven grade IV glioblastoma, five-grade III astrocytoma, and three grade III oligoastrocytoma. Results: In all samples, we were able to isolate the tumour-derived EPCs, which were positive for characteristic markers: CD31, CD34 and VEGFR2. The EPCs formed capillary networks in vitro and had the ability to take up acetylated low-density lipoprotein. Glioma-derived HSCs were positive for CD34 and CD45, but they were unable to form a capillary network in vitro. These findings on tumour-derived EPCs/HSCs were in concordance with the results, derived from peripheral blood of healthy volunteers. Conclusion: In our study, we established a new method for EPC/HSC isolation from human gliomas, defined the contribution of EPCs and HSCs to the tumour tissue, and highlighted the intense in vivo tumour host interaction.
KW  - Glioma
KW  - endothelial progenitor cell
KW  - hematopoietic stem cell
Y1  - 2012
SN  - 0250-7005
VL  - 32
IS  - 11
SP  - 4971
EP  - 4982
PB  - International Institute of Anticancer Research
CY  - Athens
ER  - 
TY  - JOUR
A1  - Bordag, Natalie
A1  - Klie, Sebastian
A1  - Jürchott, Kathrin
A1  - Vierheller, Janine
A1  - Schiewe, Hajo
A1  - Albrecht, Valerie
A1  - Tonn, Jörg-Christian
A1  - Schwartz, Christoph
A1  - Schichor, Christian
A1  - Selbig, Joachim
T1  - Glucocorticoid (dexamethasone)-induced metabolome changes in healthy males suggest prediction of response and side effects
JF  - Scientific reports
N2  - Glucocorticoids are indispensable anti-inflammatory and decongestant drugs with high prevalence of use at (similar to)0.9% of the adult population. Better holistic insights into glucocorticoid-induced changes are crucial for effective use as concurrent medication and management of adverse effects. The profiles of 214 metabolites from plasma of 20 male healthy volunteers were recorded prior to and after ingestion of a single dose of 4 mg dexamethasone (+20 mg pantoprazole). Samples were drawn at three predefined time points per day: seven untreated (day 1 midday - day 3 midday) and four treated (day 3 evening - day 4 evening) per volunteer. Statistical analysis revealed tremendous impact of dexamethasone on the metabolome with 150 of 214 metabolites being significantly deregulated on at least one time point after treatment (ANOVA, Benjamini-Hochberg corrected, q < 0.05). Inter-person variability was high and remained uninfluenced by treatment. The clearly visible circadian rhythm prior to treatment was almost completely suppressed and deregulated by dexamethasone. The results draw a holistic picture of the severe metabolic deregulation induced by single-dose, short-term glucocorticoid application. The observed metabolic changes suggest a potential for early detection of severe side effects, raising hope for personalized early countermeasures increasing quality of life and reducing health care costs.
Y1  - 2015
U6  - https://doi.org/10.1038/srep15954
SN  - 2045-2322
VL  - 5
PB  - Nature Publ. Group
CY  - London
ER  -