Open Access

The proliferative stimulus of the epidermal growth factor (EGF) in human epithelial cells is mediated by its binding to the external domain of the EGF receptor (EGF-R). The purpose of this study was to investigate whether growth arrest of tumors treated with anti-EGFR MAb (EMD 55900) was dependent on EGF-R expression and distinct histopathologic criteria of those neoplasms. Nine different adenocarcinomas, squamous cell carcinomas and two neoplastic epithelial cell lines (A431 and Detroit 562), which were characterized by high EGF-R expression, were xenotransplanted onto NMRI-nu/nu mice and treated with an anti-EGF-R antibody (EMD 55900). Results revealed that EGF-R expression and distinct histopathologic growth patterns play an important role for the therapeutic effect of the EGF-R antibody treatment. Tumors with high epithelial cellularity and little connective tissue responded to EMD 55900 treatment to a greater degree of growth reduction than tumors with lower cellularity. These results will be helpful for evaluation of patients who would benefit from tumor therapy with anti-EGF-R antibody.

The three-dimensional quantification of small scale processes in the upper troposphere and lower stratosphere is one of the challenges of current atmospheric research and requires the development of new measurement strategies. This work presents first results from the newly developed Gimballed Limb Observer for Radiance Imaging of the Atmosphere (GLORIA) obtained during the ESSenCe and TACTS/ESMVal aircraft campaigns. The focus of this work is on the so-called dynamics mode data characterized by a medium spectral and a very high spatial resolution. The retrieval strategy for the derivation of two- and three-dimensional constituent fields in the upper troposphere and lower stratosphere is presented. Uncertainties of the main retrieval targets (temperature, O3, HNO3 and CFC-12) and their spatial resolution are discussed. During ESSenCe, high resolution two-dimensional cross-sections have been obtained. Comparisons to collocated remote-sensing and in-situ data indicate a good agreement between the data sets. During TACTS/ESMVal a tomographic flight pattern to sense an intrusion of stratospheric air deep into the troposphere has been performed. This filament could be reconstructed with an unprecedented spatial resolution of better than 500 m vertically and 20 km × 20 km horizontally.

Brustkrebs ist die häufigste Krebserkrankung und Todesursache bei Frauen. Die Forschung der letzten Jahrzehnte hat gezeigt, dass es sich dabei nicht um eine einzelne, immer gleich verlaufende Erkrankung handelt. Vielmehr geht man heute davon aus, dass Brustkrebs eine heterogene Erkrankung mit verschiedenen Subtypen darstellt. Sie lassen sich klinisch und molekular deutlich von einander unterscheiden. Wichtiges Ziel der modernen Forschung und ihrer Methoden ist daher die Entwicklung einer individuellen Therapie für jede einzelne Patientin.

Introduction To investigate the predictive value of clinical and biological markers for a pathological complete remission after a preoperative dose-dense regimen of doxorubicin and docetaxel, with or without tamoxifen, in primary operable breast cancer. Methods Patients with a histologically confirmed diagnosis of previously untreated, operable, and measurable primary breast cancer (tumour (T), nodes (N) and metastases (M) score: T2-3(>= 3 cm) N0-2 M0) were treated in a prospectively randomised trial with four cycles of dose-dense (bi-weekly) doxorubicin and docetaxel (ddAT) chemotherapy, with or without tamoxifen, prior to surgery. Clinical and pathological parameters (menopausal status, clinical tumour size and nodal status, grade, and clinical response after two cycles) and a panel of biomarkers (oestrogen and progesterone receptors, Ki-67, human epidermal growth factor receptor 2 (HER2), p53, bcl-2, all detected by immunohistochemistry) were correlated with the detection of a pathological complete response (pCR). Results A pCR was observed in 9.7% in 248 patients randomised in the study and in 8.6% in the subset of 196 patients with available tumour tissue. Clinically negative axillary lymph nodes, poor tumour differentiation, negative oestrogen receptor status, negative progesterone receptor status, and loss of bcl-2 were significantly predictive for a pCR in a univariate logistic regression model, whereas in a multivariate analysis only the clinical nodal status and hormonal receptor status provided significantly independent information. Backward stepwise logistic regression revealed a response after two cycles, with hormone receptor status and lymph-node status as significant predictors. Patients with a low percentage of cells stained positive for Ki-67 showed a better response when treated with tamoxifen, whereas patients with a high percentage of Ki-67 positive cells did not have an additional benefit when treated with tamoxifen. Tumours overexpressing HER2 showed a similar response to that in HER2-negative patients when treated without tamoxifen, but when HER2-positive tumours were treated with tamoxifen, no pCR was observed. Conclusion Reliable prediction of a pathological complete response after preoperative chemotherapy is not possible with clinical and biological factors routinely determined before start of treatment. The response after two cycles of chemotherapy is a strong but dependent predictor. The only independent factor in this subset of patients was bcl-2. Trial registration number NCT00543829

Following publication of the data presented by von Minckwitz and colleagues it has been brought to our attention that some patients should be scored differently. Stable disease was seen in three of the eighteen patients instead of two of the eighteen patients: one patient with transitional cell carcinoma treated at 4 µg/kg scFv(FRP5)-ETA per day, and two breast cancer patients treated at 4 and 12.5 µg/kg scFv(FRP5)-ETA per day. Disease progression occured in 9 of the eighteen patients evaluated (see corrected Table 2 overleaf). This does not affect the conclusions of our study. In addition we would like to correct the following errors: patient IDs for patients U01 and U02 in the original Table 2 were interchanged. In addition, patient N03 had a grade 3 elevation of gamma-glutamyl transferase, and not grade 2 (see corrected Table 2 overleaf).