TY  - JOUR
A1  - Philipp-Abbrederis, Kathrin
A1  - Herrmann, Ken
A1  - Knop, Stefan
A1  - Schottelius, Margret
A1  - Eiber, Matthias
A1  - Lückerath, Katharina
A1  - Pietschmann, Elke
A1  - Habringer, Stefan
A1  - Gerngroß, Carlos
A1  - Franke, Katharina
A1  - Rudelius, Martina
A1  - Schirbel, Andreas
A1  - Lapa, Constantin
A1  - Schwamborn, Kristina
A1  - Steidle, Sabine
A1  - Hartmann, Elena
A1  - Rosenwald, Andreas
A1  - Kropf, Saskia
A1  - Beer, Ambros J
A1  - Peschel, Christian
A1  - Einsele, Hermann
A1  - Buck, Andreas K
A1  - Schwaiger, Markus
A1  - Götze, Katharina
A1  - Wester, Hans-Jürgen
A1  - Keller, Ulrich
T1  - In vivo molecular imaging of chemokine receptor CXCR4 expression in patients with advanced multiple myeloma
JF  - EMBO Molecular Medicine
N2  - CXCR4 is a G-protein-coupled receptor that mediates recruitment of blood cells toward its ligand SDF-1. In cancer, high CXCR4 expression is frequently associated with tumor dissemination andpoor prognosis. We evaluated the novel CXCR4 probe [\(^{68}\)Ga]Pentixafor for invivo mapping of CXCR4 expression density in mice xenografted with human CXCR4-positive MM cell lines and patients with advanced MM by means of positron emission tomography (PET). [\(^{68}\)Ga]Pentixafor PET provided images with excellent specificity and contrast. In 10 of 14 patients with advanced MM [\(^{68}\)Ga]Pentixafor PET/CT scans revealed MM manifestations, whereas only nine of 14 standard [\(^{18}\)F]fluorodeoxyglucose PET/CT scans were rated visually positive. Assessment of blood counts and standard CD34\(^{+}\) flow cytometry did not reveal significant blood count changes associated with tracer application. Based on these highly encouraging data on clinical PET imaging of CXCR4 expression in a cohort of MM patients, we conclude that [\(^{68}\)Ga]Pentixafor PET opens a broad field for clinical investigations on CXCR4 expression and for CXCR4-directed therapeutic approaches in MM and other diseases.
KW  - FDG PET/CT
KW  - cells
KW  - CXCR4/SDF-1
KW  - CXCR4
KW  - multiple myeloma
KW  - positron emission tomography
KW  - chemokine receptor
KW  - in vivo imaging
KW  - malignancies
KW  - involvement
KW  - microenvironment
KW  - survival
KW  - cancer
KW  - autologous transplantation
KW  - bone disease
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148738
VL  - 7
IS  - 4
ER  - 
TY  - JOUR
A1  - Altieri, Barbara
A1  - Sbiera, Silviu
A1  - Della Casa, Silvia
A1  - Weigand, Isabel
A1  - Wild, Vanessa
A1  - Steinhauer, Sonja
A1  - Fadda, Guido
A1  - Kocot, Arkadius
A1  - Bekteshi, Michaela
A1  - Mambretti, Egle M.
A1  - Rosenwald, Andreas
A1  - Pontecorvi, Alfredo
A1  - Fassnacht, Martin
A1  - Ronchi, Cristina L.
T1  - Livin/BIRC7 expression as malignancy marker in adrenocortical tumors
JF  - Oncotarget
N2  - Livin/BIRC7 is a member of the inhibitors of apoptosis proteins family, which are involved in tumor development through the inhibition of caspases. Aim was to investigate the expression of livin and other members of its pathway in adrenocortical tumors and in the adrenocortical carcinoma (ACC) cell line NCI-H295R.
The mRNA expression of livin, its isoforms α and β, XIAP, CASP3 and DIABLO was evaluated by qRT-PCR in 82 fresh-frozen adrenal tissues (34 ACC, 25 adenomas = ACA, 23 normal adrenal glands = NAG). Livin protein expression was assessed by immunohistochemistry in 270 paraffin-embedded tissues (192 ACC, 58 ACA, 20 NAG). Livin, CASP3 and cleaved caspase-3 were evaluated in NCI-H295R after induction of livin overexpression.
Relative livin mRNA expression was significantly higher in ACC than in ACA and NAG (0.060 ± 0.116 vs 0.004 ± 0.014 and 0.002 ± 0.009, respectively, p < 0.01), being consistently higher in tumors than in adjacent NAG and isoform β more expressed than α. No significant differences in CASP3, XIAP and DIABLO levels were found among these groups. In immunohistochemistry, livin was localized in both cytoplasm and nuclei. The ratio between cytoplasmic and nuclear staining was significantly higher in ACC (1.51 ± 0.66) than in ACA (0.80 ± 0.35) and NAG (0.88 ± 0.27; p < 0.0001). No significant correlations were observed between livin expression and histopathological parameters or clinical outcome. In NCI-H295R cells, the livin overexpression slightly reduced the activation of CASP3, but did not correlate with cell viability.
In conclusion, livin is specifically over-expressed in ACC, suggesting that it might be involved in adrenocortical tumorigenesis and represent a new molecular marker of malignancy.
KW  - cancer
KW  - livin
KW  - BIRC7
KW  - adrenocortical cancer
KW  - adrenal tumor
KW  - caspase-3
Y1  - 2017
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-171887
VL  - 8
IS  - 6
ER  -