Showing papers by "Christine Lautenschläger published in 2002"

Anemia and elevated systemic levels of vascular endothelial growth factor (VEGF).

Abstract: Tissue hypoxia is a major stimulus for the up-regulation of vascular endothelial growth factor (VEGF). Anemia might theoretically impact on angiogenesis via impairment of tissue oxygenation. We have investigated this hypothesis in patients with solid cancers and benign diseases. Patients and Methods: 49 patients with untreated locoregionally confined solid cancers of the head and neck, cervix, rectum and lung and 59 additional patients with non-malignant diseases (36 normemic patients without serious diseases and 23 patients with renal anemia) were enrolled and the impact of anemia on plasma VEGF levels were determined. VEGF was measured with a commercially available sandwich enzyme immunoassay technique. Results: Plasma levels of VEGF were 16.2±12.7 pg/ml in 36 normemic patients without malignant disease, 49.2±34.5 pg/ml in 49 patients with cancers (p<0.001), and 89.9±67.8 pg/ml in 23 patients with renal anemia (p=0.001). VEGF levels in cancer patients were significantly correlated with hemoglobin (hb) levels and platelet counts (each p=0.001), but not with type of tumor, stage, histology or age. Patients with cancers had higher plasma levels of VEGF than patients with non-malignant diseases in case of hb≥12 g/dl (33.1±17.5 vs 16.6±13.0 pg/ml, p<0.001) and in case of hb between 11.0 and 11.9 g/dl (56.1±26.4 vs 18.5±14.5 pg/ml, p=0.038). In case of a hb<11 g/dl, plasma VEGF levels were significantly elevated in patients with and without cancers (67.0±47.5 vs 88.9±68.8 pg/ml, n.s.). In a multivariate model, a signifiant association between low hb levels and increased plasma levels of VEGF was confirmed. In 16 patients with renal anemia, changes in hb under erythropoietin treatment were inversely correlated with changes in plasma VEGF levels with decreasing VEGF after increase in hb (p=0.01). Conclusions: Anemic patients have elevated levels of VEGF. The data suggest than anemia might impact on the progression of angeiogenesis in malignant and benign diseases.

Microscopic (R1) and macroscopic (R2) residual disease in patients with resected non-small cell lung cancer

Abstract: Objectives: This retrospective study evaluates the probability of survival in patients who had undergone resection for non-small cell lung cancer (NSCLC) and in whom residual disease at the resection margins was found. Methods: During a period of 6 years, 596 patients with NSCLC were operated upon with curative intention. Residual disease at the resection margin was divided into microscopic (R1) and macroscopic (R2). Results: Twenty-six patients (4.4%) showed R1 and 12 (2%) R2 residual disease. An extrabronchial (thoracic wall, vessels) R1 situation was found in five patients and a bronchial R1 infiltration in 21 cases. The bronchial resection margin was subject to peribronchial infiltration in most cases (16/21). A total of 17/21 (65%) patients with bronchial infiltration had N2 disease. Thirty day lethality was 3.8% in the R1 group. Fifteen patients had postoperative irradiation. The 5-year survival rate for patients with R1 resection was 14%. The differences in survival between patients with extrabronchial vs. bronchial infiltration and N0/N1 vs. N2 were significant using univariate analysis. Adjuvant radiation did not result (especially in N2 disease) in a survival benefit. Among 12 patients with macroscopic residual disease (R2), 3/12 (25%) died within the first 30 days after the operation, and none of the R2 patients survived the first year after the operation. Conclusions: Patients with an R1 situation have a survival rate of 14% comparable to curative resected patients (RO) in stage III. Adjuvant radiation had no clear effect on survival. Patients with macroscopic tumor (R2) should receive palliative treatment after the operation depending on their condition. q 2002 Elsevier Science B.V. All rights reserved.

The effect of external fractionated irradiation on the distribution pattern of extracellular matrix proteins in submandibular salivary glands of the rat.

Abstract: Introduction: The aim of this study was to analyse the distribution pattern of extracellular matrix proteins in the irradiated and non-irradiated rat submandibular salivary gland in order to provide a more detailed profile of the radiation injury following radiotherapy of the head and neck. Material and Methods: External X-ray exposure, restricted to the left skull base and neck region, was performed in 60 female Wistar rats, fractionated to daily applications of 2 Gy, up to total dosages of 20, 40 or 60 Gy. Both submandibular glands were excised after supravital anaesthesia 6 months or 1 year after completion of the irradiation. Spatial and temporal patterns of extracelluar matrix proteins were investigated histologically and immunohistochemically. Results: The polyclonal anti-human antisera used, identified the same antigens in rat tissue as in human tissues. The alterations in staining patterns and staining intensities between irradiated and non-irradiated salivary glands showed statistically significant differences. Different structures in irradiated glands reacted with different intensities, e.g. nerve tissue and the basement membranes of excretory ducts were intensely laminin-positive, fibronectin was predominantly found around the excretory ducts with transition to the interstitial tissues. Conclusion: Irradiation leads to statistically significant differences in the amount and composition of the extracellular matrix in salivary glands. The amount of extracellular matrix proteins in irradiated glands is dose-dependent. The higher the dosage the more extracellular matrix can be expected. Consecutively, total dosage is associated with greater loss of acini. Scatter effects of irradiation have also to be recognized. Immunohistochemical studies on salivary glands have to consider the pretreatment status, in particular those studies that investigate degenerative changes. Copyright 2002 European Association for Cranio-Maxillofacial Surgery. Published by Elsevier Science Ltd. All rights reserved.

High bad and bcl-xL gene expression and combined bad, bcl-xL, bax and bcl-2 mRNA levels: molecular predictors for survival of stage 2 soft tissue sarcoma patients.

Abstract: The role of the bcl-2 gene family members in promoting or antagonizing apoptosis in malignant tumors, including soft tissue sarcomas (STS), is well known. However, the impact of mRNA expression of bcl-2 family genes on prognosis has not been thoroughly investigated in STS. Samples from 82 STS patients were analyzed for mRNA expression of bad, bax, bcl-xL and bcl-2 by a high-throughput quantitative RT-PCR approach, using validated assays based on TaqMan technology. The mRNA data, related to glyceraldehyde-3-phosphate dehydrogenase expression measured in the same sample, were analysed for their correlation to tumor stage and overall survival of patients. In a Kaplan-Meier analysis none of the mRNA levels investigated differed significantly with regard to their impact on survival (log-rank test). However, after including the tumor stage in the statistical analysis, a borderline significance was observed for bad mRNA expression (p=0.068) indicating a stage-specific impact of mRNA expression on prognosis. Considering STS patients of tumor stage 2, multivariate Cox analysis revealed that bad mRNA values > or = 10 (p=0.0039; RR=9.08), bcl-xL > or = 1.5 (p=0.067; RR=4.59), bax > or = 0.005 (p=0.1; RR=2.84) and bcl-2 < 3 (p=0.42; RR=1.7) were associated with a poor prognosis. Combined high bad/bcl-xL mRNA expression levels revealed a 20-fold increase in the relative risk of tumor-related death (p=0.016) when comparing the poor and good prognosis groups. There was a 14.5-fold and 6.5-fold increase in the risk for the combinations of high bax/bcl-xL mRNA (p=0.018) and bax/bcl-2 mRNA expression (p=0.017), respectively. In conclusion, high bad mRNA levels and combined values of bad/bcl-xL bax/bcl-xL and bax/bcl-2 appear to be independent prognostic factors at least for stage 2 STS patients. In the combinations of mRNA levels there was more than an additive effect pointing to different pathways of prognostic relevance.