TY  - JOUR
A1  - Hacker, Ulrich T.
A1  - Escalona-Espinosa, Laura
A1  - Consalvo, Nicola
A1  - Goede, Valentin
A1  - Schiffmann, Lars
A1  - Scherer, Stefan J.
A1  - Hedge, Priti
A1  - Van Cutsem, Eric
A1  - Coutelle, Oliver
A1  - Büning, Hildegard
T1  - Evaluation of Angiopoietin-2 as a biomarker in gastric cancer: results from the randomised phase III AVAGAST trial
JF  - British Journal of Cancer
N2  - Background: In the phase III AVAGAST trial, the addition of bevacizumab to chemotherapy improved progression-free survival (PFS) but not overall survival (OS) in patients with advanced gastric cancer. We studied the role of Angiopoietin-2 (Ang-2), a key driver of tumour angiogenesis, metastasis and resistance to antiangiogenic treatment, as a biomarker. 
Methods: Previously untreated, advanced gastric cancer patients were randomly assigned to receive bevacizumab (n = 387) or placebo (n = 387) in combination with chemotherapy. Plasma collected at baseline and at progression was analysed by ELISA. The role of Ang-2 as a prognostic and a predictive biomarker of bevacizumab efficacy was studied using a Cox proportional hazards model. Logistic regression analysis was applied for correlations with metastasis. Results: Median baseline plasma Ang-2 levels were lower in Asian (2143 pg ml\(^-\)\(^1\)) vs non-Asian patients (3193 pg ml\(^-\)\(^1\)), P<0.0001. Baseline plasma Ang-2 was identified as an independent prognostic marker for OS but did not predict bevacizumab efficacy alone or in combination with baseline VEGF. Baseline plasma Ang-2 correlated with the frequency of liver metastasis (LM) at any time: Odds ratio per 1000 pg ml\(^-\)\(^1\) increase: 1.19; 95% CI 1.10-1.29; P<0.0001 (non-Asians) and 1.37; 95% CI 1.13-1.64; P = 0.0010 (Asians). 
Conclusions: Baseline plasma Ang-2 is a novel prognostic biomarker for OS in advanced gastric cancer strongly associated with LM. Differences in Ang-2 mediated vascular response may, in part, account for outcome differences between Asian and non-Asian patients; however, data have to be further validated. Ang-2 is a promising drug target in gastric cancer.
KW  - gastric cancer
KW  - angiogenesis
KW  - Angiopoietin-2
KW  - bevacizumab
KW  - liver metastasis
KW  - biomarker
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-189578
VL  - 114
IS  - 8
ER  - 
TY  - JOUR
A1  - Krebs, Markus
A1  - Solimando, Antonio Giovanni
A1  - Kalogirou, Charis
A1  - Marquardt, André
A1  - Frank, Torsten
A1  - Sokolakis, Ioannis
A1  - Hatzichristodoulou, Georgios
A1  - Kneitz, Susanne
A1  - Bargou, Ralf
A1  - Kübler, Hubert
A1  - Schilling, Bastian
A1  - Spahn, Martin
A1  - Kneitz, Burkhard
T1  - miR-221-3p Regulates VEGFR2 Expression in High-Risk Prostate Cancer and Represents an Escape Mechanism from Sunitinib In Vitro
JF  - Journal of Clinical Medicine
N2  - Downregulation of miR-221-3p expression in prostate cancer (PCa) predicted overall and cancer-specific survival of high-risk PCa patients. Apart from PCa, miR-221-3p expression levels predicted a response to tyrosine kinase inhibitors (TKI) in clear cell renal cell carcinoma (ccRCC) patients. Since this role of miR-221-3p was explained with a specific targeting of VEGFR2, we examined whether miR-221-3p regulated VEGFR2 in PCa. First, we confirmed VEGFR2/KDR as a target gene of miR-221-3p in PCa cells by applying Luciferase reporter assays and Western blotting experiments. Although VEGFR2 was mainly downregulated in the PCa cohort of the TCGA (The Cancer Genome Atlas) database, VEGFR2 was upregulated in our high-risk PCa cohort (n = 142) and predicted clinical progression. In vitro miR-221-3p acted as an escape mechanism from TKI in PC3 cells, as displayed by proliferation and apoptosis assays. Moreover, we confirmed that Sunitinib induced an interferon-related gene signature in PC3 cells by analyzing external microarray data and by demonstrating a significant upregulation of miR-221-3p/miR-222-3p after Sunitinib exposure. Our findings bear a clinical perspective for high-risk PCa patients with low miR-221-3p levels since this could predict a favorable TKI response. Apart from this therapeutic niche, we identified a partially oncogenic function of miR-221-3p as an escape mechanism from VEGFR2 inhibition.
KW  - microRNA-221
KW  - high-risk Prostate Cancer
KW  - angiogenesis
KW  - Sunitinib
KW  - Tyrosine kinase inhibition
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-203168
SN  - 2077-0383
VL  - 9
IS  - 3
ER  - 
TY  - JOUR
A1  - Meierjohann, Svenja
T1  - Hypoxia independent drivers of melanoma angiogenesis
JF  - Frontiers in Oncology
N2  - Tumor angiogenesis is a process which is traditionally regarded as the tumor’s response to low nutrient supply occurring under hypoxic conditions. However, hypoxia is not a pre-requisite for angiogenesis. The fact that even single tumor cells or small tumor cell aggregates are capable of attracting blood vessels reveals the early metastatic capability of tumor cells. This review sheds light on the hypoxia-independent mechanisms of tumor angiogenesis in melanoma.
KW  - melanoma
KW  - angiogenesis
KW  - hypoxia-independent
KW  - reactive oxygen species
KW  - NF-κB
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-125586
VL  - 5
IS  - 120
ER  -