TY  - JOUR
AU  - Ferronika, P.*
AU  - van den Bos, H.*
AU  - Taudt, A.
AU  - Spierings, D.C.J.*
AU  - Saber, A.T.*
AU  - Hiltermann, T.J.N.*
AU  - Kok, K.*
AU  - Porubsky, D.*
AU  - van der Wekken, A.J.*
AU  - Timens, W.*
AU  - Foijer, F.*
AU  - Colomé-Tatché, M.
AU  - Groen, H.J.M.*
AU  - Lansdorp, P.M.*
AU  - van den Berg, A.*
C1  - 51512
C2  - 43486
CY  - Oxford
SP  - 1668-1670
TI  - Copy number alterations assessed at the single-cell level revealed mono- and polyclonal seeding patterns of distant metastasis in a small-cell lung cancer patient.
JO  - Ann. Oncol.
VL  - 28
IS  - 7
PB  - Oxford Univ Press
PY  - 2017
SN  - 0923-7534
ER  - 

TY  - JOUR
AU  - Issels, R.D.*
AU  - Bueclein, V.*
AU  - Kampmann, E.*
AU  - Knoesel, T.*
AU  - Nößner, E.
AU  - Subklewe, M.*
AU  - Lindner, L.*
C1  - 50668
C2  - 42440
CY  - Oxford
SP  - vi488
TI  - Dissecting the role of tumor-infiltrating lymphocytes (TIL) in patients with high-risk soft-tissue sarcoma (STS) receiving neo-adjuvant chemotherapy (NAC) with regional hyperthermia (RHT).
JO  - Ann. Oncol.
VL  - 27
PB  - Oxford Univ Press
PY  - 2016
SN  - 0923-7534
ER  - 

TY  - JOUR
AU  - Huber, M.
AU  - Falkenberg, N.
AU  - Gross, E.*
AU  - Mall, R.
AU  - Braselmann, H.
AU  - Schmitt, M.*
AU  - Aubele, M.
C1  - 45324
C2  - 37289
CY  - Oxford
TI  - The impact of the uPAR system and its interaction partners as potential therapeutic targets in TNBC.
JO  - Ann. Oncol.
VL  - 26
PB  - Oxford Univ Press
PY  - 2015
SN  - 0923-7534
ER  - 

TY  - JOUR
AU  - Issels, R.D.*
AU  - Kampmann, E.*
AU  - Buecklein, V.*
AU  - Nößner, E.
AU  - Lindner, L.H.*
AU  - Schmidt, M.*
AU  - Mansmann, U.*
AU  - Hiddemann, W.*
AU  - Subklewe, M.*
AU  - Knoesel, T.*
C1  - 47512
C2  - 40632
SP  - 3
TI  - Impact of tumor infiltrating lymphocytes (TILs) on 
      local progression-free (LPFS) and disease-free (DFS) survival in 
      localized high-risk soft tissue sarcoma (HR-STS) after neo-adjuvant 
      chemotherapy (NAC) with regional hyperthermia (RHT).
JO  - Ann. Oncol.
VL  - 26
PY  - 2015
SN  - 0923-7534
ER  - 

TY  - JOUR
AB  - Aim: Trabectedin (Yondelis) is approved for the treatment of patients with advanced soft tissue sarcoma (STS) after failure of anthracyclines and ifosfamide. Its cytostatic activity is associated with the induction of DNA double-strand breaks (DSBs). Regional hyperthermia (RHT) improves chemotherapy of patients with high-risk STS (Issels, Lancet Oncol 2010). The rationale for combined treatment is that heat-mediated degradation of BRCA2 impairs DNA homologous recombination repair (HR) which is crucial for the repair of DSBs (Krawczyk, PNAS 2011). Previously, we have demonstrated that simultaneous treatment of trabectedin and RHT resulted in enhanced cytotoxicity accompanied by elevated DNA-damage (Kampmann, CTOS 2013). Methods: For treatment, trabectedin (5-20nM) was applied for 3 hours with or without RHT (41.8°C or 43°C) for 1.5 hours. Cell cycle arrest and apoptosis were analyzed in the following human cell lines: U2Os (osteosarcoma), SW872 (liposarcoma) DLD1 (colorectal cancer) and DLD1−/-BRCA2 by Nicoletti staining and measuring caspase-activity 24h, 48h and 72h after treatment. The extent of cellular senescence was analyzed by a senescence-associated beta-galactosidase assay 72h and 144h after treatment. Results: Trabectedin treatment induced G2 arrest which was increased and prolonged after adding RHT. Furthermore, trabectedin induced apoptosis dose dependently which was also significantly augmented by RHT. However, the relative amount of apoptosis in U2Os was only half as large as in SW872 or DLD1. Interestingly, trabectedin induced a remarkable amount of senescent cells in U2Os but not in SW872 which again was significantly augmented by RHT. In BRCA2-deficient cells, thermosensitization of trabectedin was significantly reduced. Conclusions: Simultaneous treatment of trabectedin and RHT results in enhanced cytotoxicity accompanied by elevated DNA-damage. BRCA2-degradation and impairment of HR dependent DSB-repair are involved in thermosensitization. Here we discovered cell specific differences in induction of apoptosis or senescence which warrants further investigation. Disclosure: A. Tanovic: Scientific writer of PharmaMar. All other authors have declared no conflicts of interest.
AU  - Harnicek, D.
AU  - Kampmann, E.*
AU  - Tanovic, A.*
AU  - Guo, Y.*
AU  - Gallmeier, E.*
AU  - Lauber, K.*
AU  - Lindner, L.*
AU  - Issels, R.D.
C1  - 51730
C2  - 43454
SP  - iv503
TI  - 1438P Trabectedin combined with hyperthermia: Characterization of enhanced drug-efficacy in human tumor cells.
JO  - Ann. Oncol.
VL  - 25
PY  - 2014
SN  - 0923-7534
ER  - 

TY  - JOUR
AB  - BACKGROUND: Ewing's sarcoma (ES) is the second most common bone or soft-tissue sarcoma in childhood and adolescence and features a high propensity to metastasize. The six-transmembrane epithelial antigen of the prostate 1 (STEAP1) is a membrane-bound mesenchymal stem cell marker highly expressed in ES. Here, we investigated the role of STEAP1 as an immunohistological marker for outcome prediction in patients with ES. PATIENTS AND METHODS: Membranous STEAP1 immunoreactivity was analyzed using immunohistochemistry in 114 primary pre-chemotherapy ES of patients diagnosed from 1983 to 2010 and compared with clinical parameters and patient outcome. Median follow-up was 3.85 years (range 0.43-17.51). RESULTS: A total of 62.3% of the ES samples displayed detectable STEAP1 expression with predominant localization of the protein at the plasma membrane. High membranous STEAP1 immunoreactivity was found in 53.5%, which correlated with better overall survival (P = 0.021). Accordingly, no or low membranous STEAP1 expression was identified as an independent risk factor in multivariate analysis (hazard ratio 2.65, P = 0.036). CONCLUSIONS: High membranous STEAP1 expression predicts improved outcome and may help to define a specific subgroup of ES patients, who might benefit from adapted therapy regimens.
AU  - Grunewald, T.G.*
AU  - Ranft, A.*
AU  - Esposito, I.
AU  - Da Silva-Buttkus, P.
AU  - Aichler, M.
AU  - Baumhoer, D.*
AU  - Schaefer, K.L.*
AU  - Ottaviano, L.*
AU  - Poremba, C.*
AU  - Jundt, G.*
AU  - Jürgens, H.*
AU  - Dirksen, U.*
AU  - Richter, G.H.*
AU  - Burdach, S.*
C1  - 7381
C2  - 29687
SP  - 2185-2190
TI  - High STEAP1 expression is associated with improved outcome of Ewing's sarcoma patients.
JO  - Ann. Oncol.
VL  - 23
IS  - 8
PB  - Oxford Univ. Press
PY  - 2012
SN  - 0923-7534
ER  -