TY  - JOUR
A1  - Hagemann, Carsten
A1  - Neuhaus, Nikolas
A1  - Dahlmann, Mathias
A1  - Kessler, Almuth F.
A1  - Kobelt, Dennis
A1  - Herrmann, Pia
A1  - Eyrich, Matthias
A1  - Freitag, Benjamin
A1  - Linsenmann, Thomas
A1  - Monoranu, Camelia M.
A1  - Ernestus, Ralf-Ingo
A1  - Löhr, Mario
A1  - Stein, Ulrike
T1  - Circulating MACC1 transcripts in glioblastoma patients predict prognosis and treatment response
JF  - Cancers
N2  - Glioblastoma multiforme is the most aggressive primary brain tumor of adults, but lacksreliable and liquid biomarkers. We evaluated circulating plasma transcripts of metastasis-associatedin colon cancer-1 (MACC1), a prognostic biomarker for solid cancer entities, for prediction of clinicaloutcome and therapy response in glioblastomas.  MACC1 transcripts were significantly higher inpatients compared to controls.  Low MACC1 levels clustered together with other prognosticallyfavorable markers.  It was associated with patients’ prognosis in conjunction with the isocitratedehydrogenase (IDH) mutation status: IDH1 R132H mutation and low MACC1 was most favorable(median overall survival (OS) not yet reached), IDH1 wildtype and high MACC1 was worst (medianOS 8.1 months), while IDH1 wildtype and low MACC1 was intermediate (median OS 9.1 months).No patients displayed IDH1 R132H mutation and high MACC1. Patients with low MACC1 levelsreceiving standard therapy survived longer (median OS 22.6 months) than patients with high MACC1levels (median OS 8.1 months).   Patients not receiving the standard regimen showed the worstprognosis, independent of MACC1 levels (low: 6.8 months, high: 4.4 months). Addition of circulatingMACC1 transcript levels to the existing prognostic workup may improve the accuracy of outcomeprediction and help define more precise risk categories of glioblastoma patients.
KW  - metastasis-associated in colon cancer 1 (MACC1)
KW  - glioblastoma multiforme
KW  - liquid biopsy
KW  - therapy response
KW  - prognostic marker
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-197327
SN  - 2072-6694
VL  - 11
IS  - 6
ER  - 
TY  - JOUR
A1  - Haarmann, Axel
A1  - Schuhmann, Michael K.
A1  - Silwedel, Christine
A1  - Monoranu, Camelia-Maria
A1  - Stoll, Guido
A1  - Buttmann, Mathias
T1  - Human brain endothelial CXCR2 is inflammation-inducible and mediates CXCL5- and CXCL8-triggered paraendothelial barrier breakdown
JF  - International Journal of Molecular Science
N2  - Chemokines (C-X-C) motif ligand (CXCL) 5 and 8 are overexpressed in patients with multiple sclerosis, where CXCL5 serum levels were shown to correlate with blood–brain barrier dysfunction as evidenced by gadolinium-enhanced magnetic resonance imaging. Here, we studied the potential role of CXCL5/CXCL8 receptor 2 (CXCR2) as a regulator of paraendothelial brain barrier function, using the well-characterized human cerebral microvascular endothelial cell line hCMEC/D3. Low basal CXCR2 mRNA and protein expression levels in hCMEC/D3 were found to strongly increase under inflammatory conditions. Correspondingly, immunohistochemistry of brain biopsies from two patients with active multiple sclerosis revealed upregulation of endothelial CXCR2 compared to healthy control tissue. Recombinant CXCL5 or CXCL8 rapidly and transiently activated Akt/protein kinase B in hCMEC/D3. This was followed by a redistribution of tight junction-associated protein zonula occludens-1 (ZO-1) and by the formation of actin stress fibers. Functionally, these morphological changes corresponded to a decrease of paracellular barrier function, as measured by a real-time electrical impedance-sensing system. Importantly, preincubation with the selective CXCR2 antagonist SB332235 partially prevented chemokine-induced disturbance of both tight junction morphology and function. We conclude that human brain endothelial CXCR2 may contribute to blood–brain barrier disturbance under inflammatory conditions with increased CXCL5 and CXCL8 expression, where CXCR2 may also represent a novel pharmacological target for blood–brain barrier stabilization.
KW  - blood–brain barrier
KW  - multiple sclerosis
KW  - human cerebral endothelial cells
KW  - CXCR2
KW  - CXCL5
KW  - CXCL8
KW  - interleukin-8
KW  - SB332235
Y1  - 2019
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-201297
SN  - 1422-0067
VL  - 20
IS  - 3
ER  -