TY  - JOUR
AB  - Gallbladder cancer (GBC) is an aggressive disease with limited treatment options but high prevention potential. GBC tumours take 10-20 years to develop, a timeframe that holds potential for early detection. MicroRNAs (miRNAs) play a central role in abnormal cell processes, and circulating miRNAs may constitute valuable biomarkers of early disease. We used microarray data to pre-select differentially expressed miRNAs in formalin-fixed paraffin-embedded (FFPE) gallbladder tissue samples (GBC n = 40, normal n = 8). We then applied small-RNA sequencing to screen for miRNA expression differences in serum samples from three European prospective cohorts (n = 37 GBC case-control pairs), and validated the most promising candidates in three independent cohorts (n = 36 GBC case- control pairs). Statistical analyses included robust linear regression, pathway and meta-analysis, and examination of expression correlation between miRNAs and target genes. MiR-4533 and miR-671-5p were overexpressed in GBC tissue and serum samples, and meta-analysis confirmed the overexpression of miR-4533 in GBC serum samples from the prospective cohorts (p-value = 4.1×10-4), especially in individuals of female sex, under 63.5 years, or with a BMI below 26.2 kg/m2. Pathway and correlation analyses revealed that miR-4533 targets SIPA1L2 in the Rap1 signalling pathway, and SIPA1L2 was downregulated in GBC serum samples. Our study highlights the advantage of integrating small-RNA sequencing results from different types of samples and independent datasets, and the need for international research collaborations to identify and validate biomarkers for secondary prevention of rare tumours such as GBC. The function of miR-4533 and its interaction with SIPA1L2 in GBC development need to be further investigated.
AU  - Blandino, A.*
AU  - Scherer, D.*
AU  - Boekstegers, F.*
AU  - Rounge, T.B.*
AU  - Langseth, H.*
AU  - Roessler, S.*
AU  - Hveem, K.*
AU  - Brenner, H.*
AU  - Pechlivanis, S.
AU  - Waldenberger, M.
AU  - Lorenzo Bermejo, J.*
C1  - 72499
C2  - 56634
CY  - 125 London Wall, London, England
TI  - Small-RNA sequencing reveals potential serum biomarkers for gallbladder cancer: Results from a three-stage collaborative study of large European prospective cohorts.
JO  - Eur. J. Cancer
VL  - 214
PB  - Elsevier Sci Ltd
PY  - 2025
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - BACKGROUND: Primary tumor sidedness (PTS) with discrimination of left-sided (LC) and right-sided tumors (RC) guides patient selection for targeted first-line therapy in RAS wild-type (RAS-WT) metastatic colorectal cancer (mCRC). This study assessed the hypothesis whether considering PTS with additional clinical parameters better predicts the treatment benefit of targeted first-line treatment. METHODS: In FIRE-3, first-line treatment with folinic acid, fluorouracil and irinotecan (FOLFIRI) plus cetuximab (FOLFIRI/Cet) was compared to FOLFIRI plus bevacizumab (FOLFIRI/Bev) in patients with RAS-WT mCRC and unresectable metastasis. We evaluated whether combining PTS with number of metastatic sites (NOM), liver-limited disease status (LLD), age, sex, or carcinoembryonic antigen level (CEA) better predicts treatment benefit regarding overall survival (OS). Here, Cox regression models with second-order interactions were applied. Further, the results were validated by policy learning and Lasso regression analysis. FINDINGS: Among 400 RAS-WT mCRC patients, combining PTS with LLD status in a Cox regression model outperformed PTS alone for predicted treatment benefit (P = 0·005; c‑index=0·603). Significant OS benefit from FOLFIRI/Cet over FOLFIRI/Bev was observed in LC/non-LLD patients (HR=0·62; 95 %-confidence interval [CI]=0·46-0·82; P = 0·002), but mitigated in LC/LLD patients (HR=0·83; 95 %-CI=0·53-1·29; P = 0·400). In RC/non-LLD patients, FOLFIRI/Bev demonstrated a significant OS advantage over FOLFIRI/Cet (HR=2·09; 95 %‑CI=1·20-3·63; P = 0·010). However, RC/LLD patients showed potential benefit from FOLFIRI/Cet, though not statistically significant (HR=0·59; 95 %-CI=0·25-1·39; P = 0·218). INTERPRETATION: Incorporating PTS and LLD status might improve selection of targeted first-line treatment in RAS-WT mCRC patients. FOLFIRI/Cet appears to be particularly beneficial for LC/non-LLD patients with mitigated benefit in patients with LC/LLD. In contrast, FOLFIRI/Bev is significantly favoured over FOLFIRI/Cet in patients with RC/non-LLD. Notably, RC/LLD patients may still benefit from anti-EGFR therapy despite right-sided primary tumor. These results are hypothesis-generating and warrant further validation.
AU  - Holch, J.W.*
AU  - Ohnmacht, A.
AU  - Stintzing, S.*
AU  - Heinrich, K.*
AU  - Weiss, L.*
AU  - Probst, V.*
AU  - Stahler, A.*
AU  - Fischer von Weikersthal, L.*
AU  - Decker, T.*
AU  - Kiani, A.*
AU  - Kaiser, F.*
AU  - Heintges, T.*
AU  - Kahl, C.*
AU  - Kullmann, F.*
AU  - Link, H.*
AU  - Höffkes, H.G.*
AU  - Moehler, M.*
AU  - Modest, D.P.*
AU  - Menden, M.P.
AU  - Heinemann, V.*
C1  - 73987
C2  - 57291
CY  - 125 London Wall, London, England
TI  - FOLFIRI with cetuximab or bevacizumab in RAS wild-type metastatic colorectal cancer: Refining first-line treatment selection by combining clinical parameters: A post hoc analysis of the randomized open-label phase III trial FIRE-3/AIO KRK0306.
JO  - Eur. J. Cancer
VL  - 220
PB  - Elsevier Sci Ltd
PY  - 2025
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - OBJECTIVE: HPV-associated head and neck cancer is correlated with favorable prognosis; however, its underlying biology is not fully understood. We propose an explainable convolutional neural network (CNN) classifier, DeepClassPathway, that predicts HPV-status and allows patient-specific identification of molecular pathways driving classifier decisions. METHODS: The CNN was trained to classify HPV-status on transcriptome data from 264 (13% HPV-positive) and tested on 85 (25% HPV-positive) head and neck squamous carcinoma patients after transformation into 2D-treemaps representing molecular pathways. Grad-CAM saliency was used to quantify pathways contribution to individual CNN decisions. Model stability was assessed by shuffling pathways within 2D-images. RESULTS: The classification performance of the CNN-ensembles achieved ROC-AUC/PR-AUC of 0.96/0.90 for all treemap variants. Quantification of the averaged pathway saliency heatmaps consistently identified KRAS, spermatogenesis, bile acid metabolism, and inflammation signaling pathways as the four most informative for classifying HPV-positive patients and MYC targets, epithelial-mesenchymal transition, and protein secretion pathways for HPV-negative patients. CONCLUSION: We have developed and applied an explainable CNN classification approach to transcriptome data from an oncology cohort with typical sample size that allows classification while accounting for the importance of molecular pathways in individual-level decisions.
AU  - Lombardo, E.*
AU  - Hess J.
AU  - Kurz, C.*
AU  - Riboldi, M.*
AU  - Marschner, S.*
AU  - Baumeister, P.
AU  - Lauber, K.
AU  - Pflugradt, U.
AU  - Walch, A.K.
AU  - Canis, M.
AU  - Klauschen, F.*
AU  - Zitzelsberger, H.
AU  - Belka, C.
AU  - Landry, G.*
AU  - Unger, K.
C1  - 66360
C2  - 52804
SP  - 41-49
TI  - DeepClassPathway: Molecular pathway aware classification using explainable deep learning.
JO  - Eur. J. Cancer
VL  - 176
PY  - 2022
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - Background: The EORTC 62961-ESHO 95 randomised trial showed improved long-term survival of patients with high-risk soft-tissue sarcoma by adding regional hyperthermia to neoadjuvant chemotherapy. We hypothesised that immune infiltrate of patients treated with neoadjuvant therapy associate with clinical outcome. Methods: Tumour infiltrating lymphocytes (TILs) and CD8, FOXP3, PD-1, and PD-L1 were evaluated in sequential biopsies of patients after four cycles of therapy. Results: From a subgroup of 109 patients who had been randomised between July 1997 and November 2006 to neoadjuvant chemotherapy (53 patients) or neoadjuvant chemotherapy with regional hyperthermia (56 patients), 137 biopsies were obtained. TILs increased in paired second biopsies independent of treatment allocation (p < 0.001). FOXP3 regulatory T cells decreased (p = 0.002), and PD-L1 expression of tumours became undetectable. In the multivariate analysis, post-treatment high TILs correlated to LPFS (HR: 0.34; 95% CI 0.15–0.75; p = 0.008) and DFS (HR: 0.38; 95% CI 0.17–0.82; p = 0.015). In comparing post-treatment immune infiltrate between treatment arms, tumour response was associated with neoadjuvant chemotherapy with regional hyperthermia (p = 0.013) and high TILs (p = 0.064). High CD8 cell infiltration was associated with improved LPFS (HR: 0.27; 95% CI 0.09–0.79; Log-rank p = 0.011) and DFS (HR: 0.25; 95% CI 0.09–0.73; Log-rank p = 0.006). Improved survival at 10 years was associated with immune infiltrate after neoadjuvant chemotherapy with regional hyperthermia. Conclusion: Preoperative therapy re-programs a non-inflamed tumour at baseline into an inflamed tumour. The post-treatment immune infiltrate became predictive for clinical outcomes. The combination with regional hyperthermia primes the tumour microenvironment, enabling enhanced anti-tumour immune activity in high-risk soft tissue sarcomas. Trial registration: ClinicalTrials.gov, NCT00003052.
AU  - Issels, R.D.*
AU  - Nößner, E.
AU  - Lindner, L.H.*
AU  - Schmidt, M.*
AU  - Albertsmeier, M.*
AU  - Blay, J.Y.*
AU  - Stutz, E.*
AU  - Xu, Y.*
AU  - Buecklein, V.*
AU  - Altendorf-Hofmann, A.*
AU  - Abdel-Rahman, S.*
AU  - Mansmann, U.*
AU  - von Bergwelt-Baildon, M.*
AU  - Knoesel, T.*
C1  - 63329
C2  - 51274
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
SP  - 123-132
TI  - Immune infiltrates in patients with localised high-risk soft tissue sarcoma treated with neoadjuvant chemotherapy without or with regional hyperthermia: A translational research program of the EORTC 62961-ESHO 95 randomised clinical trial.
JO  - Eur. J. Cancer
VL  - 158
PB  - Elsevier Sci Ltd
PY  - 2021
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Benmebarek, M.*
AU  - Karches, C.H.*
AU  - Schmidbauer, M.L.*
AU  - Kurzay, M.*
AU  - Klaus, R.*
AU  - Geiger, M.*
AU  - Rataj, F.*
AU  - Cadilha, B.*
AU  - Lesch, S.*
AU  - Heise, C.*
AU  - Murr, R.*
AU  - vom Berg, J.*
AU  - Jastroch, M.
AU  - Lamp, D.
AU  - Niederfellner, G.*
AU  - Sustmann, C.*
AU  - Endres, S.*
AU  - Klein, C.*
AU  - Kobold, S.*
C1  - 55883
C2  - 46631
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
SP  - S3-S3
TI  - Characterization of bispecific antibodies that drive synthetic agonistic receptor - transduced T cells to mediate specific and conditional therapy in human pancreatic cancer models.
JO  - Eur. J. Cancer
VL  - 110
PB  - Elsevier Sci Ltd
PY  - 2019
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Freudenreich, M.*
AU  - Tischer, J.*
AU  - Kroell, T.*
AU  - Kremser, A.*
AU  - Dreyssig, J.*
AU  - Grabrucker, C.*
AU  - Liepert, A.*
AU  - Kolb, H.*
AU  - Schmid, C.*
AU  - Schmetzer, H.
C1  - 55884
C2  - 46632
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
SP  - S29-S29
TI  - Clinical relevance of in vitro generated dendritic cells of leukemic origin to predict response to immunotherapy in patients with AML and MDS.
JO  - Eur. J. Cancer
VL  - 110
PB  - Elsevier Sci Ltd
PY  - 2019
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Merle, M.*
AU  - Fischbacher, D.*
AU  - Liepert, A.*
AU  - Grabrucker, C.*
AU  - Kroell, T.*
AU  - Kremser, A.*
AU  - Dreyssig, J.*
AU  - Freudenreich, M.*
AU  - Schuster, F.*
AU  - Borkhardt, A.*
AU  - Kraemer, D.*
AU  - Koehne, C.*
AU  - Kolb, H.J.
AU  - Schmid, C.*
AU  - Schmetzer, H.
C1  - 55882
C2  - 46633
CY  - The Boulevard, Langford Lane, Kidlington, Oxford Ox5 1gb, Oxon, England
SP  - S24-S24
TI  - Conversion of AML-blasts to leukemia-derived dendritic cells (DCleu) in 'DC-culture-media' shifts the (serum) chemokine-release profile to a more 'inflammatory' (in culture) going along with improved antileukemic T-cell-reactivity.
JO  - Eur. J. Cancer
VL  - 110
PB  - Elsevier Sci Ltd
PY  - 2019
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Fröhlich, F.
AU  - Shadrin, A.*
AU  - Kessler, T.*
AU  - Wierling, C.*
AU  - Heinig, M.
AU  - Theis, F.J.
AU  - Lange, B.M.*
AU  - Lehrach, H.*
AU  - Hasenauer, J.
C1  - 50277
C2  - 42144
CY  - Oxford
SP  - S44-S44
TI  - Large-scale modeling of cancer signaling: Mechanistic modeling meets Big Data.
JO  - Eur. J. Cancer
VL  - 68
PB  - Elsevier Sci Ltd
PY  - 2016
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Hensel, T.*
AU  - Giorgi, C.*
AU  - Becker-Dettling, F.*
AU  - Calzada-Wack, J.
AU  - Neff, F.
AU  - Schmidt, O.*
AU  - Schäfer, B.W.*
AU  - Burdach, S.*
AU  - Richter, G.H.*
C1  - 50276
C2  - 42143
CY  - Oxford
SP  - S48-S48
TI  - Inhibition of BET bromodomain proteins and the PI3K pathway in Ewing sarcoma down regulates the specific transcriptional program, inhibits tumorigenicity and increases apoptosis in Ewing sarcoma.
JO  - Eur. J. Cancer
VL  - 68
PB  - Elsevier Sci Ltd
PY  - 2016
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Luber, B.*
AU  - Keller, S.*
AU  - Zwingenberger, G.*
AU  - Ebert, K.*
AU  - Maier, D.*
AU  - Geier, B.*
AU  - Theis, F.J.
AU  - Hasenauer, J.
AU  - Huge, S.
AU  - Meyer-Hermann, M.
AU  - Dehghany, J.
AU  - Walch, A.K.
AU  - Aichler, M.
AU  - Lordick, F.*
AU  - Haffner, I.*
C1  - 50273
C2  - 42140
CY  - Oxford
SP  - S135-S135
TI  - Identification of predictive response and resistance factors to targeted therapy in gastric cancer using a systems medicine approach.
JO  - Eur. J. Cancer
VL  - 68
PB  - Elsevier Sci Ltd
PY  - 2016
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - BACKGROUND: Despite clear differences in clinical presentation and outcome, squamous cell carcinomas of the head and neck (SCCHN) arising from human papilloma virus (HPV) infection or heavy tobacco/alcohol consumption are treated equally. Next-generation sequencing is expected to reveal novel targets for more individualised treatment. PATIENTS AND METHODS: Tumour specimens from 208 patients with locally advanced squamous cell carcinoma of the hypopharynx, oropharynx or oral cavity, all uniformly treated with adjuvant cisplatin-based chemoradiation, were included. A customised panel covering 211 exons from 45 genes frequently altered in SCCHN was used for detection of non-synonymous point and frameshift mutations. Mutations were correlated with HPV status and treatment outcome. RESULTS: Mutational profiles and HPV status were successfully established for 179 cases. HPV- tumours showed an increased frequency of alterations in tumour suppressor genes compared to HPV+ cases (TP53 67% versus 4%, CDKN2A 18% versus 0%). Conversely, HPV+ carcinomas were enriched for activating mutations in driver genes compared to HPV- cases (PIK3CA 30% versus 12%, KRAS 6% versus 1%, and NRAS 4% versus 0%). Hotspot TP53 missense mutations in HPV- carcinomas correlated with an increased risk of locoregional recurrence (hazard ratio [HR] 4.3, 95% confidence interval [CI] 1.5-12.1, P=0.006) and death (HR 2.2, 95% CI 1.1-4.4, P=0.021). In HPV+ SCCHN, driver gene mutations were associated per trend with a higher risk of death (HR 3.9, 95% CI 0.7-21.1, P=0.11). CONCLUSIONS: Distinct mutation profiles in HPV- and HPV+ SCCHN identify subgroups with poor outcome after adjuvant chemoradiation. Mutant p53 and the phosphoinositide 3-kinase pathway were identified as potential druggable targets for subgroup-specific treatment optimisation.
AU  - Tinhofer, I.*
AU  - Budach, V.*
AU  - Saki, M.*
AU  - Konschak, R.*
AU  - Niehr, F.*
AU  - Jöhrens, K.*
AU  - Weichert, W.*
AU  - Linge, A.*
AU  - Lohaus, F.*
AU  - Krause, M.*
AU  - Neumann, K.*
AU  - Endris, V.*
AU  - Sak, A.*
AU  - Stuschke, M.*
AU  - Balermpas, P.*
AU  - Rödel, C.*
AU  - Avlar, M.*
AU  - Grosu, A.-L.*
AU  - Abdollahi, A.*
AU  - Debus, J.*
AU  - Belka, C.*
AU  - Pigorsch, S.*
AU  - Combs, S.E.
AU  - Mönnich, D.*
AU  - Zips, D.*
AU  - Baumann, M.*
C1  - 47939
C2  - 39748
CY  - Oxford
SP  - 78-86
TI  - Targeted next-generation sequencing of locally advanced squamous cell carcinomas of the head and neck reveals druggable targets for improving adjuvant chemoradiation.
JO  - Eur. J. Cancer
VL  - 57
PB  - Elsevier Sci Ltd
PY  - 2016
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Vergalli, J.
AU  - Carletl, M.
AU  - Hoffmann, T.*
AU  - Rothe, M.*
AU  - Zuber, J.*
AU  - Jeremias, I.
C1  - 50274
C2  - 42141
CY  - Oxford
SP  - S58-S59
TI  - X-Linked inhibitor of apoptosis protein (XIAP) exhibits an essential role of patients' acute lymphoblastic leukemia cells growing in vivo.
JO  - Eur. J. Cancer
VL  - 68
PB  - Elsevier Sci Ltd
PY  - 2016
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - von Heyking, K.*
AU  - Roth, L.C.*
AU  - Ertl, M.*
AU  - Schmidt, O.*
AU  - Calzada-Wack, J.
AU  - Neff, F.
AU  - Lawlor, E.R.*
AU  - Burdach, S.*
AU  - Richter, G.*
C1  - 50275
C2  - 42142
CY  - Oxford
SP  - S47-S47
TI  - The posterior HOXD locus: Its contribution to phenotype and malignancy of Ewing sarcoma.
JO  - Eur. J. Cancer
VL  - 68
PB  - Elsevier Sci Ltd
PY  - 2016
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Gimenez-Aznar, I.
AU  - Michna, A.
AU  - Ludwig, H.*
AU  - Braselmann, H.
AU  - Klein, D.*
AU  - Ohrt, M.*
AU  - Schoetz, U.*
AU  - Kuger, S.
AU  - Schneider, L.*
AU  - Schuettrumpf, L.
AU  - Jendrossek, V.*
AU  - Belka, C.
AU  - Zangen, V.
AU  - Unger, K.
AU  - Zitzelsberger, H.
AU  - Lauber, K.
AU  - Hess J.
C1  - 47139
C2  - 39230
SP  - S121
TI  - Fanconi anemia, complementation group A (FancA) overexpression confers radioresistance to oral keratinocytes.
JO  - Eur. J. Cancer
VL  - 51
PY  - 2015
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Neff, F.*
AU  - Kirsch, D.G.*
AU  - Saur, D.*
AU  - Schmid, R.M.*
AU  - Heikenwälder, M.
AU  - Siveke, J.T.*
C1  - 44897
C2  - 37157
CY  - Oxford
SP  - S2
TI  - Notch triggers myeloid reprogramming in murine pancreatic cancer.
JO  - Eur. J. Cancer
VL  - 51
PB  - Elsevier Sci Ltd
PY  - 2015
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Schnorfeil, F.M.
AU  - Lichtenegger, F.S.
AU  - Geiger, C.*
AU  - Henschler, R.*
AU  - Wagner, B.*
AU  - Bigalke, I.*
AU  - Kvalheim, G.*
AU  - Schendel, D.J.*
AU  - Hiddemann, W.*
AU  - Subklewe, M.
C1  - 44898
C2  - 37156
CY  - Oxford
SP  - S8
TI  - Vaccination with next-generation dendritic cells for aml postremission therapy induces antigen-specific T cell responses.
JO  - Eur. J. Cancer
VL  - 51
PB  - Elsevier Sci Ltd
PY  - 2015
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Bauer, J.
AU  - Sandhöfer, N.
AU  - Hiddemann, W.
AU  - Spiekermann, K.
C1  - 44411
C2  - 36898
CY  - Oxford
SP  - S121
TI  - Novel FLT3 mutation shows dominant negative effects on the wild-type FLT3 receptor.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Burton, N.*
AU  - Ulrich, A.*
AU  - Driessen, W.H.P.*
AU  - Morscher, S.*
AU  - Sardella, T.*
AU  - Nasanova, E.*
AU  - Razansky, D.
AU  - Ntziachristos, V.
C1  - 44401
C2  - 36909
CY  - Oxford
SP  - S157
TI  - Real time noninvasive 2D and 3D Multispectral Optoacoustic Tomography (MSOT) for clinical imaging of vessel oxygenation and melanin distribution.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Driessen, W.H.P.*
AU  - Morscher, S.*
AU  - Burton, N.C.*
AU  - Sardella, T.*
AU  - Razansky, D.
AU  - Ntziachristos, V.
C1  - 44409
C2  - 36901
CY  - Oxford
SP  - S55
TI  - Novel approaches for dynamic biomarker imaging by Multispectral Optoacoustic Tomography (MSOT).
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Gimenez-Aznar, I.
AU  - Michna, A.
AU  - Hieber, L.
AU  - Braselmann, H.
AU  - Jendrossek, V.*
AU  - Zangen, V.
AU  - Unger, K.
AU  - Zitzelsberger, H.
AU  - Lauber, K.*
AU  - Hess J.
C1  - 44404
C2  - 36906
CY  - Oxford
SP  - S229
TI  - FancA overexpression confers radioresistance to cells of head and neck squamous cell carcinoma.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Höfig, I.
AU  - Falkenberg, N.
AU  - Rosemann, M.
AU  - Szumielewski, J.
AU  - Richter, S.
AU  - Atkinson, M.J.
AU  - Aubele, M.
AU  - Anastasov, N.
C1  - 44406
C2  - 36904
CY  - Oxford
SP  - S226
TI  - Relevance of 3D-microtissues to investigate the therapeutic oncogenes HER2 and PTK6 in breast cancer.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Huber, M.
AU  - Falkenberg, N.
AU  - Schmitt, M.*
AU  - Braselmann, H.
AU  - Mall, R.
AU  - Jakovac, M.
AU  - Walch, A.K.
AU  - Höfler, H.
AU  - Aubele, M.
C1  - 44403
C2  - 36907
CY  - Oxford
SP  - S161-S162
TI  - uPAR and its interaction partners: potential new therapy targets in triple negative breast cancer.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Lee, M.S.
AU  - Gaertner, F.C.*
AU  - Pellegata, N.S.
C1  - 44414
C2  - 36895
CY  - Oxford
SP  - S154
TI  - Regulation of norepinephrine transporter expression in pheochromocytoma by dual PI3K/mTOR inhibition.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Leinhäuser, I.
AU  - Atkinson, M.J.
AU  - Pellegata, N.S.
C1  - 44415
C2  - 36894
CY  - Oxford
SP  - S160
TI  - The transcription factor Phox2a plays a pro-tumorigenic role in pheochromocytoma.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Martin, A.
AU  - Felipe-Abrio, I.*
AU  - Obrador-Hevia, A.*
AU  - Calabuig-Farinas, S.*
AU  - Alemany, R.*
AU  - Martin, J.*
C1  - 44412
C2  - 36897
CY  - Oxford
SP  - S159
TI  - Cullin-RING ligases inhibition is a potential new therapeutic strategy in soft tissue sarcomas.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Michna, A.
AU  - Braselmann, H.
AU  - Guertler, A.*
AU  - Gomolka, M.*
AU  - Hornhardt, S.*
AU  - Bluethgen, N.*
AU  - Sieber, A.*
AU  - Zitzelsberger, H.
AU  - Unger, K.
C1  - 44410
C2  - 36899
CY  - Oxford
SP  - S134
TI  - Identification of molecular targets and signalling networks that influence hypersensitivity to ionizing radiation.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Morscher, S.*
AU  - Driessen, W.H.P.*
AU  - Burton, N.C.B.*
AU  - Sardella, T.*
AU  - Razansky, D.
AU  - Ntziachristos, V.
C1  - 44402
C2  - 36908
CY  - Oxford
SP  - S160-S161
TI  - Pharmacokinetic modelling in Dynamic Contrast Enhanced Multispectral Optoacoustic Tomography (DCE-MSOT).
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Pastula, A.*
AU  - Hauck, S.M.
AU  - Janssen, K.P.*
AU  - Schmid, R.M.*
AU  - Quante, M.*
C1  - 44407
C2  - 36903
CY  - Oxford
SP  - S63
TI  - Mesenchymal cells regulate growth of intestinal crypts by a Wnt independent mechanism in 3D culture system.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Pellegata, N.S.
AU  - Molatore, S.
AU  - Neff, F.
AU  - Irmler, M.
AU  - Pulz, E.
AU  - Roncaroli, F.*
C1  - 44413
C2  - 36896
CY  - Oxford
SP  - S57
TI  - p27 is a haploinsufficient tumor suppressor in MENX rats and this associates with the development of invasive medullary thyroid carcinoma.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Selmansberger, M.
AU  - Feuchtinger, A.
AU  - Zurnadzhy, L.*
AU  - Höfig, I.
AU  - Bogdanova, T.*
AU  - Walch, A.K.
AU  - Unger, K.
AU  - Zitzelsberger, H.
AU  - Hess J.
C1  - 44408
C2  - 36902
CY  - Oxford
SP  - S113
TI  - CLIP2 as radiation biomarker in papillary thyroid carcinoma.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Simonavicius, N.
AU  - Seubert, B.*
AU  - Borsig, L.*
AU  - Wohlleber, D.*
AU  - Browning, J.*
AU  - Krueger, A.*
AU  - Heikenwälder, M.
C1  - 44416
C2  - 36893
CY  - Oxford
SP  - S88
TI  - Lymphotoxin signalling alters the vasculature to increase tumour cell metastasis.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - Expression of the forkhead transcription factor (FoxP3) - an established marker of regulatory T cells - has been found in other cell types as well, including tumour cells. Recent studies indicated that high tumour FoxP3 expression might be associated with a poor outcome of patients with several types of solid cancers. Here, we investigated the role of FoxP3 expressed by the tumour cells in the prognosis of larynx and oro-hypopharynx squamous cell carcinoma (LSCC and OHSCC) - two major subtypes of head and neck cancer. To this end, we analysed by immunohistochemistry the expression of tumour FoxP3 in tissues from 83 LSCC and 89 OHSCC patients in relation to overall survival. In multivariate analysis we found that high tumour FoxP3 expression significantly associated with poor survival in OHSCC but not in LSCC patients. In further studies, we combined the prognostic value of FoxP3 with selected markers of inflammation (cyclooxygenase-2; COX2) or with markers of enhanced tumour migration/invasion (AHNAK and CORTACTIN). Interestingly, we found that the combination of FoxP3 and AHNAK (in LSCC) or FoxP3 and CORTACTIN (in OHSCC) had significantly stronger prognostic values than either marker analysed individually. Combination of FoxP3 and COX2 enhanced the prognostic accuracy only in OHSCC. Thus, our study identifies novel individual and combination markers that might have enhanced and distinct prognostic relevance in different subtypes of head and neck cancer.
AU  - Weller, P.*
AU  - Bankfalvi, A.*
AU  - Gu, X.*
AU  - Dominas, N.*
AU  - Lehnerdt, G.F.*
AU  - Zeidler, R.
AU  - Lang, S.*
AU  - Brandau, S.*
AU  - Dumitru, C.A.*
C1  - 30908
C2  - 34005
CY  - Oxford
SP  - 1291-1300
TI  - The role of tumour FoxP3 as prognostic marker in different subtypes of head and neck cancer.
JO  - Eur. J. Cancer
VL  - 50
IS  - 7
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Wilke, C.
AU  - Hess J.
AU  - Pitea, A.
AU  - Schmidl, D.
AU  - Klymenko, S.*
AU  - Zitzelsberger, H.
AU  - Unger, K.
C1  - 44405
C2  - 36905
CY  - Oxford
SP  - S229
TI  - Comparative global characterisation of microRNA-expression in radiation-associated and sporadic breast carcinomas.
JO  - Eur. J. Cancer
VL  - 50
PB  - Elsevier Sci Ltd
PY  - 2014
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - Background and methods: Familial aggregation of lung cancer exists after accounting for cigarette smoking. However, the extent to which family history affects risk by smoking status, histology, relative type and ethnicity is not well described. This pooled analysis included 24 case-control studies in the International Lung Cancer Consortium. Each study collected age of onset/interview, gender, race/ethnicity, cigarette smoking, histology and first-degree family history of lung cancer. Data from 24,380 lung cancer cases and 23,305 healthy controls were analysed. Unconditional logistic regression models and generalised estimating equations were used to estimate odds ratios and 95% confidence intervals. Results: Individuals with a first-degree relative with lung cancer had a 1.51-fold increase in the risk of lung cancer, after adjustment for smoking and other potential confounders (95% CI: 1.39, 1.63). The association was strongest for those with a family history in a sibling, after adjustment (odds ratios (OR) = 1.82, 95% CI: 1.62, 2.05). No modifying effect by histologic type was found. Never smokers showed a lower association with positive familial history of lung cancer (OR = 1.25, 95% CI: 1.03, 1.52), slightly stronger for those with an affected sibling (OR = 1.44, 95% CI: 1.07, 1.93), after adjustment. Conclusions: The occurrence of lung cancer among never smokers and similar magnitudes of the effect of family history on lung cancer risk across histological types suggests familial aggregation of lung cancer is independent of those risks associated with cigarette smoking. While the role of genetic variation in the aetiology of lung cancer remains to be fully characterised, family history assessment is immediately available and those with a positive history represent a higher risk group.
AU  - Cote, M.L.*
AU  - Liu, M.*
AU  - Bonassi, S.*
AU  - Neri, M.*
AU  - Schwartz, A.G.*
AU  - Christiani, D.C.*
AU  - Spitz, M.R.*
AU  - Muscat, J.E.*
AU  - Rennert, G.*
AU  - Aben, K.K.*
AU  - Andrew, A.S.*
AU  - Bencko, V.*
AU  - Bickeböller, H.*
AU  - Boffetta, P.*
AU  - Brennan, P.*
AU  - Brenner, H.*
AU  - Duell, E.J.*
AU  - Fabianova, E.*
AU  - Field, J.K.*
AU  - Foretova, L.*
AU  - Friis, S.*
AU  - Harris, C.C.*
AU  - Holcatova, I.*
AU  - Hong, Y.C.*
AU  - Isla, D.*
AU  - Janout, V.*
AU  - Kiemeney, L.A.*
AU  - Kiyohara, C.*
AU  - Lan, Q.*
AU  - Lazarus, P.*
AU  - Lissowska, J.*
AU  - Le Marchand, L.*
AU  - Mates, D.*
AU  - Matsuo, K.*
AU  - Mayordomo, J.I.*
AU  - McLaughlin, J.R.*
AU  - Morgenstern, H.*
AU  - Mueller, H.*
AU  - Orlow, I.*
AU  - Park, B.J.*
AU  - Pinchev, M.*
AU  - Raji, O.Y.*
AU  - Rennert, H.S.*
AU  - Rudnai, P.*
AU  - Seow, A.*
AU  - Stücker, I.*
AU  - Szeszenia-Dabrowska, N.*
AU  - Teare, M.D.*
AU  - Tjonnelan, A.*
AU  - Ugolini, D.*
AU  - van der Heijden, H.F.M.*
AU  - Wichmann, H.-E.
AU  - Wiencke, J.K.*
AU  - Woll, P.J.*
AU  - Yang, P.*
AU  - Zaridze, D.*
AU  - Zhang, Z.F.*
AU  - Etzel, C.J.*
AU  - Hung, R.J.*
C1  - 10404
C2  - 30409
SP  - 1957-1968
TI  - Increased risk of lung cancer in individuals with a family history of the disease: A pooled analysis from the International Lung Cancer Consortium.
JO  - Eur. J. Cancer
VL  - 48
IS  - 13
PB  - Elsevier
PY  - 2012
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - Mucins represent major components of the mucous layer in the stomach, protecting the underlying epithelium from acid, mechanical trauma, proteases and pathogenic bacteria. Previous studies have shown an association of neoplastic transformation in the stomach with aberrant mucin levels, suggesting a potential role of genetic variation in mucin genes in the development of gastric cancer (GC). We assessed the association of genetic variation in candidate single nucleotide polymorphisms (SNPs) in mucin genes with the risk of chronic atrophic gastritis (CAG), a well-established precursor of GC in the German population-based ESTHER study. We genotyped MUC1 T31T, MUC2 L58P, MUC2 V116M, MUC5B E34G, MUC5B R51W, MUC5B rs2014486 (intronic) and MUC6 V619M for 533 serologically defined CAG cases and 1054 age- and sex-matched controls. None of the analysed SNPs was associated with CAG. However, large studies are needed to disclose or exclude potential weak associations of these SNPs with CAG risk.
AU  - Frank, B.*
AU  - Weck, M.N.*
AU  - Müller, H.*
AU  - Klopp, N.
AU  - Illig, T.
AU  - Raum, E.*
AU  - Brenner, H.*
C1  - 8011
C2  - 29982
SP  - 114-120
TI  - Polymorphisms in MUC1, MUC2, MUC5B and MUC6 genes are not associated with the risk of chronic atrophic gastritis.
JO  - Eur. J. Cancer
VL  - 48
IS  - 1
PB  - Elsevier 
PY  - 2012
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - PURPOSE: DNA methylation contributes to carcinogenesis by mediating transcriptional regulation and chromatin remodelling, which may influence the effect of DNA-damaging drugs. We examined the prognostic and predictive impact of DNA methyltransferase (DNMT) 1 and 3b expression in gastric carcinomas (GC) treated by neoadjuvant chemotherapy. In vitro, DNMT1 expression and chemosensitivity were investigated for a functional relationship and the DNMT inhibitor decitabine (DAC) was tested as an alternative treatment option. PATIENTS AND METHODS: DNMT1/3b expression was analysed immunohistochemically in 127 pretherapeutic biopsies of neoadjuvant (platinum/5-fluorouracil)-treated GC patients and correlated with response and overall survival (OS). Short hairpin RNA technology was used to knockdown DNMT1 in the GC cell line, AGS. The chemosensitivity of GC cell lines to DAC alone and to DAC in combination with cisplatin was analysed by XTT or colony formation assays. RESULTS: High DNMT1 and DNMT3b expression was found in 105/127 (83%) and 79/127 (62%) carcinomas, respectively. Patients with low DNMT1 expression demonstrated a significantly better histopathological/clinical response (P=0.03/P=0.008) and OS (P(log-rank)=0.001). In vitro, knockdown of DNMT1 caused an increased chemosensitivity towards cisplatin. Combined treatment with cisplatin and DAC showed a synergistic effect leading to increased cytotoxicity in the cisplatin-resistant cell line AGS. CONCLUSION: Low DNMT1 expression defines a subgroup of GC patients with better outcomes following platinum/5FU-based neoadjuvant chemotherapy. In vitro data support a functional relationship between DNMT1 and cisplatin sensitivity. Besides its potential use as a predictive biomarker, DNMT1 may represent a promising target for alternative therapeutic strategies for a subset of GC patients.
AU  - Mutze, K.*
AU  - Langer, R.*
AU  - Schumacher, F.*
AU  - Becker, K.*
AU  - Ott, K.*
AU  - Novotny, A.*
AU  - Hapfelmeier, A.*
AU  - Höfler, H.
AU  - Keller, G.*
C1  - 6895
C2  - 29419
SP  - 1817-1825
TI  - DNA methyltransferase 1 as a predictive biomarker and potential therapeutic target for chemotherapy in gastric cancer.
JO  - Eur. J. Cancer
VL  - 47
IS  - 12
PB  - Elsevier
PY  - 2011
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - The immune response against prostate cancer seems to be inefficient although tumour cells show an over-expression of tumour-associated antigens suggesting that regulatory networks inhibit immune cell function locally. To address this proposition, lymphocytes within prostate cancer-inflicted tissue were analysed for the expression of markers associated with negative regulatory function and exhaustion. Prostate cancer, benign prostatic hyperplasia and healthy prostate tissues were investigated by immunohistology for CD25, FOXP3, PD-1 and B7-H1. We had previously documented that prostate cancer islets are surrounded by clustered accumulations of CD3(+) lymphocytes, which lack perforin and interferon-gamma (IFN gamma) expression, thus are apparently quiescent. Here, we report that these clusters contain numerous CD25(+) and FOXP3(+) cells. These markers are associated with regulatory T cells, and their presence in lymphocyte clusters near prostate cancer regions indicates an environment with negative impact on immune response against cancer cells. Consistent with this hypothesis, cells expressing PD-1 and its ligand B7-H1, which are markers associated with exhaustion of lymphocyte function, were also detected in the lymphocyte clusters. Expression of molecules associated with inhibition and exhaustion of lymphocytes may reflect events contributing to ineffective immune responses against cancer cells.
AU  - Ebelt, K.
AU  - Babaryka, G.*
AU  - Frankenberger, B.
AU  - Stief, C.G.*
AU  - Eisenmenger, W.*
AU  - Kirchner, T.*
AU  - Schendel, D.J.
AU  - Nößner, E.
C1  - 1234
C2  - 26892
SP  - 1664-1672
TI  - Prostate cancer lesions are surrounded by FOXP3⁺, PD-1⁺ and B7-H1⁺ lymphocyte clusters.
JO  - Eur. J. Cancer
VL  - 45
IS  - 9
PB  - Elsevier
PY  - 2009
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - The hallmarks of hyperthermia and its pleotropic effects are in favour of its combined use with chemotherapy. Preclinical research reveals that for heat killing and synergistic effects the thermal dose is most critical. Thermal enhancement of drug cytotoxicity is accompanied by cellular death and necrosis without increasing its oncogenic potential. The induction of genetically defined stress responses can deliver danger signals to activate the host's immune system. The positive results of randomised trials have definitely established hyperthermia in combination with chemotherapy as a novel clinical modality for the treatment of cancer. Hyperthermia targets the action of chemotherapy within the heated tumour region without affecting systemic toxicity. In specific clinical settings regional hyperthermia (RHT) or hyperthermic perfusion has proved its value and deserve a greater focus and investigation in other malignancies. In Europe, more specialised centres should be created and maintained as network of excellence for hyperthermia in the field of oncology.
AU  - Issels, R.D.
C1  - 2981
C2  - 25837
SP  - 2546-2554
TI  - Hyperthermia adds to chemotherapy.
JO  - Eur. J. Cancer
VL  - 44
IS  - 17
PB  - Pergamon Press
PY  - 2008
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - In Ewing's sarcoma family of tumours (ESFT), the clinically most adverse prognostic parameters are the presence of tumour metastasis at time of diagnosis and poor response to neoadjuvant chemotherapy. To identify genes differentially regulated between metastatic and localised tumours, we analysed 27 ESFT specimens using Affymetrix microarrays. Functional annotation of differentially regulated genes revealed 29 over-represented pathways including PDGF, TP53, NOTCH, and WNT1-signalling. Regression of primary tumours (n=20) induced by polychemotherapy was found to be correlated with the expression of genes involved in angiogenesis, apoptosis, ubiquitin proteasome pathway, and PI3 kinase and p53 pathways. These findings could be confirmed by in vitro cytotoxicity assays. A set of 46 marker genes correctly classifies these 20 tumours as responding versus non-responding. We conclude that expression signatures of initial tumour biopsies can help to identify ESFT patients at high risk to develop tumour metastasis or to suffer from a therapy refractory cancer.
AU  - Schaefer, K.L.*
AU  - Eisenacher, M.*
AU  - Braun, Y.*
AU  - Brachwitz, K.*
AU  - Wai, D.H.*
AU  - Dirksen, U.*
AU  - Lanvers-Kaminsky, C.*
AU  - Juergens, H.*
AU  - Herrero, D.*
AU  - Stegmaier, S.*
AU  - Koscielniak, E.*
AU  - Eggert, A.*
AU  - Nathrath, M.
AU  - Gosheger, G.*
AU  - Schneider, D.T.*
AU  - Bury, C.*
AU  - Diallo-Danebrock, R.*
AU  - Ottaviano, L.*
AU  - Gabbert, H.E.*
AU  - Poremba, C.*
C1  - 4529
C2  - 25543
SP  - 699-709
TI  - Microarray analysis of Ewing's sarcoma family of tumours reveals characteristic gene expression signatures associated with metastasis and resistance to chemotherapy.
JO  - Eur. J. Cancer
VL  - 44
IS  - 5
PB  - Elsevier
PY  - 2008
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - Recent publications have suggested that imatinib (Glivec) may be cardiotoxic. We have therefore assessed the largest study on the agent performed in patients with gastrointestinal stromal tumours, randomising a daily dose of 400 mg versus 800 mg. 946 Patients were entered, 942 patients received at least one dose of imatinib. The median time on treatment was 24 months. A total of 24,574 exposure months could be analysed. We could not identify an excess of cardiac events in the study population. In 2 patients (0.2%) a possible cardiotoxic effect of imatinib could not fully be excluded.The current analysis of a large randomised prospective study could not confirm previous suggestions of imatinib induced cardiac toxicity.
AU  - Verweij, J.*
AU  - Casali, P.G.*
AU  - Kotasek, D.*
AU  - LeCesne, A.L.*
AU  - Reichard, P.*
AU  - Judson, I.R.*
AU  - Issels, R.D.
AU  - van Oosterom, A.T.*
AU  - van Glabbeke, M.*
AU  - Blay, J.-Y.*
C1  - 5814
C2  - 24424
SP  - 974-978
TI  - Imatinib does not induce cardiac left ventricular failure in gastrointestinal stromal tumours patients: Analyis of EORTC-ISG-AGITG study 62005.
JO  - Eur. J. Cancer
VL  - 43
IS  - 6
PB  - Pergamon Press
PY  - 2007
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - A recent randomized EORTC phase III trial, comparing two doses of imatinib in patients with advanced gastrointestinal stromal tumours (GISTs), reported dose dependency for progression-free survival. The current analysis of that study aimed to assess if tumour mutational status correlates with clinical response to imatinib. Pre-treatment samples of GISTs from 377 patients enrolled in phase III study were analyzed for mutations of KIT or PDGFRA by combination of D-HPLC and direct sequencing of tumour genomic DNA. Mutation types were correlated with patients' survival data. The presence of exon 9-activating mutations in KIT was the strongest adverse prognostic factor for response to imatinib, increasing the relative risk of progression by 171% (P<0.0001) and the relative risk of death by 190% (P<0.0001) when compared with KIT exon 11 mutants. Similarly, the relative risk of progression was increased by 108% (P<0.0001) and the relative risk of death by 76% (P=0.028) in patients without detectable KIT or PDGFRA mutations. In patients whose tumours expressed an exon 9 KIT oncoprotein, treatment with the high-dose regimen resulted in a significantly superior progression-free survival (P=0.0013), with a reduction of the relative risk of 61%. We conclude that tumour genotype is of major prognostic significance for progression-free survival and overall survival in patients treated with imatinib for advanced GISTs. Our findings suggest the need for differential treatment of patients with GISTs, with KIT exon 9 mutant patients benefiting the most from the 800 mg daily dose of the drug.
AU  - Debiec-Rychter, M.*
AU  - Sciot, R.*
AU  - Le Cesne, A.*
AU  - Schlemmer, M.
AU  - Hohenberger, P.*
AU  - van Oosterom, A.T.*
AU  - Blay, J.Y.*
AU  - Leyvraz, S.*
AU  - Stul, M.*
AU  - Casali, P.G.*
AU  - Zalcberg, J.*
AU  - Verweij, J.*
AU  - van Glabbeke, M.*
AU  - Hagemeijer, A.*
AU  - Judson, I.*
AU  - EORTC Soft Tissue and Bone Sarcoma Group (*)
AU  - Italian Sarcoma Group (*)
C1  - 5222
C2  - 23591
SP  - 1093-1103
TI  - KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours.
JO  - Eur. J. Cancer
VL  - 42
IS  - 8
PY  - 2006
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Rashid, M.U.*
AU  - Wichmann, H.-E.
C1  - 4819
C2  - 23267
SP  - 2896-2903
TI  - German populations with infrequent CHEK2*1100delC and minor associations with early-onset and familial breast cancer.
JO  - Eur. J. Cancer
VL  - 41
PY  - 2005
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Zalcberg, J.R.*
AU  - Verweij, J.*
AU  - Casali, P.G.*
AU  - Le Cesne, A.*
AU  - Reichardt, P.*
AU  - Blay, J.-Y.*
AU  - Schlemmer, M.
AU  - van Glabbeke, M.*
AU  - Brown, M.*
AU  - Judson, I.R.*
C1  - 3697
C2  - 22938
SP  - 1751-1757
TI  - Outcome of patients with advanced gastro-intestinal stromal tumours crossing over to a daily imatinib dose 800 mg after progression on 400 mg.
JO  - Eur. J. Cancer
VL  - 41
PY  - 2005
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - Kaposi's sarcoma (KS) is an angioproliferative disease occurring in several different clinical-epidemiological forms that, however, share the same histological traits and are all associated with infection by the human herpesvirus 8 (HHV8). KS initiates in a context of immune dysregulation characterised by CD8+ T cell activation and the production of Th1-type cytokines that induce a generalised activation of endothelial cells leading to adhesion and tissue extravasation of lympho-monocytes, spindle cell formation and angiogenesis. These phenomena are triggered or enhanced by infection with HHV8 that, in turn, is reactivated by the same cytokines. Productively-infected circulating cells are recruited into ‘activated’ tissue sites where HHV8 finds an optimal environment for establishing a persistent, latent infection of KS spindle cells (KSC). HHV8 dissemination is favoured by virus escape mechanisms and immune dysregulation, and leads to immune responses that are not effective against the virus but, paradoxically, exacerbates the reactive process. Although early KS is a reactive process of polyclonal nature that can regress, in time it can progress in to a true sarcoma. The progression of KS appears to be due to the deregulated expression of oncogenes and oncosuppressor genes, to the long-lasting expression of the HHV8 latency genes and, for AIDS-KS, is promoted by the proliferative and angiogenic effects of the HIV-1 Tat protein.
AU  - Ensoli, B.*
AU  - Sgadari, C.*
AU  - Barillari, G.*
AU  - Sirianni, M.C.*
AU  - Stürzl, M.
AU  - Monini, P.*
C1  - 21700
C2  - 19892
SP  - 1251-1269
TI  - Biology of Kaposi's sarcoma.
JO  - Eur. J. Cancer
VL  - 37
IS  - 10
PY  - 2001
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - In this phase II study, activity and safety of neoadjuvant regional hyperthermia (RHT) combined with chemotherapy was investigated in 59 patients with primary advanced or recurrent high-risk soft-tissue sarcoma (STS). Patients received four EIA cycles consisting of etoposide, ifosfamide and doxorubicin combined with RHT followed by surgical resection and adjuvant treatment. The overall objective response (OR) rate was 17%, with one complete (2%) and eight partial (15%) responses. In addition, 13 minor reponses (25%) were seen. At time of surgery, complete necrosis (pCR) occurred in 6 patients and >75% necrosis (favourable histological response (FHR)) in 12 patients. At the completion of protocol treatment, 36 patients were rendered disease-free which was significantly associated with the initial radiographic and/or pathological tumour response (P=0.004). Treatment-related toxicity was acceptable overall. At a medium follow-up of 82 months, local treatment failure occurred in 33 patients, median overall survival (OS) was 52 months, and the 5-year survival rate was 49% (95% confidence interval (CI): 36–61%). OS which did not differ for extremity versus non-extremity STS (P=0.21) was better for patients responding to EIA combined with RHT (P<0.01).
AU  - Issels, R.D.
AU  - Abdel-Rahman, S.*
AU  - Wendtner, C.-M.
AU  - Falk, M.H.*
AU  - Kurze, V.*
AU  - Sauer, H.*
AU  - Aydemir, U.*
AU  - Hiddemann, W.*
C1  - 22180
C2  - 20884
SP  - 1599-1608
TI  - Neoadjuvant chemotherapy combined with regional hyperthermia (RHT) for locally advanced primary or recurrent high-risk adult soft-tissue sarcomas (STS) of adults : Long-term results of a phase II study.
JO  - Eur. J. Cancer
VL  - 37
IS  - 13
PY  - 2001
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - The efficacy of thermochemotherapy in adult patients with primary, recurrent or inadequately resected non-metastatic high-risk soft-tissue sarcomas (STS) was assessed. 54 patients were prospectively treated with four cycles of etoposide, ifosfamide and doxorubicin (EIA) combined with regional hyperthermia (RHT) followed by surgery, another four cycles of EIA without RHT and external beam radiation. The objective response rate was 16% and at a median follow-up time of 57 months, the 4-year estimated rates of local failure-free survival (LFFS), distant metastasis-free survival (DMFS), event-free survival (EFS) and overall survival (OS) were 59% (95% confidence interval (CI) 45–73%), 59% (95% CI 44–73%), 26% (95% CI 14–38%) and 40% (95% CI 27–53%), respectively. OS was in favour of patients responding to neoadjuvant treatment (P=0.073). In comparison to a preceding phase II study including pre- and postsurgical thermochemotherapy (RHT-91), at a 4-year follow-up the RHT-95 study cohort showed an inferior LFFS rate (P=0.027), but this did not affect DMFS (P=0.558) or OS (P=0.126). Hence, postsurgical thermochemotherapy seems critical for local tumour control without affecting survival.
AU  - Wendtner, C.-M.
AU  - Abdel-Rahman, S.*
AU  - Baumert, J.J.*
AU  - Falk, M.H.*
AU  - Krych, M.*
AU  - Santl, M.*
AU  - Hiddemann, W.*
AU  - Issels, R.D.
C1  - 22179
C2  - 20883
SP  - 1609-1616
TI  - Treatment of primary, recurrent or inadequately resected high-risk soft-tissue sarcomas (STS) of adults : Results of a phase II pilot study (RHT-95) of neoadjuvant chemotherapy combined with regional hyperthermia.
JO  - Eur. J. Cancer
VL  - 37
IS  - 13
PY  - 2001
SN  - 0959-8049
ER  - 

TY  - JOUR
AU  - Wollenberg, B.
AU  - Andratschke, M.*
AU  - Pauli, C.*
AU  - Ledderose, H.*
AU  - Lindhofet, H.*
AU  - Zeidler, R.
C1  - 27640
C2  - 32780
SP  - S61
TI  - Pilotstudy with a trifunctional bispecific antibody in patients with Head and Neck Cancer.
JO  - Eur. J. Cancer
VL  - 1
PY  - 2001
SN  - 0959-8049
ER  - 

TY  - JOUR
AB  - From 1963-1974, 62 cases of malignant lymphoma were treated: 24 patients with Hodgkin's lymphoma (HL) and 38 with non-Hodgkin's lymphoma (NHL). Relapse rate in children with HD before 1971 (pre-laparotomy data) was significantly higher than in the group after 1971, when explorative laparotomy, splenectomy and more aggressive radio- and chemotherapy were applied ( 10 15 vs 2 9). Since 1970 all children with NHL were entered in a modified leukaemia protocol combining radiotherapy to the primary site, prophylactic C.N.S.-irradiation and aggressive multiple drug chemotherapy. In this group 23 26 patients achieved complete remission vs 7 12 before 1970, when therapy consisted of low dose irradiation to the primary site, and/or single agent chemotherapy. Median survival in the group before 1970 was 5 months compared with 34+ months after 1970. Only 1 patient receiving prophylactic C.N.S.-irradiation developed C.N.S.-leukaemia vs 5 12 in the group before 1970.
AU  - Lau, B.
AU  - Janka, G.E.*
AU  - Meister, P.*
AU  - Lampert, F.H.*
AU  - Haas, R.J.*
C1  - 42247
C2  - 35672
SP  - 1237-1240
TI  - Childhood malignant lymphoma. Favourable outlook with aggressive combination chemotherapy and radiotherapy.
JO  - Eur. J. Cancer
VL  - 13
IS  - 11
PY  - 1977
SN  - 0959-8049
ER  -