Are you Christian Kugler?

Claim your profile

Publications (7)35.13 Total impact

  • [Show abstract] [Hide abstract]
    ABSTRACT: Several clinical studies indicate that primary tumour cells with high metastatic potential often show aberrant glycosylation as detected by lectin histochemistry. However, it is unclear whether aberrant glycosylation is still present in metastatic deposits. The aim of the present investigation was thus to analyse a possible association between the presence of lectin binding sites of pulmonary adenocarcinoma cells and their lymph node and haematogenous metastatic cells. For this purpose, the expression of HPA, PHA-L and UEA-I was assessed in primary tumours, lymph node metastases and haematogenous metastases of 96 patients with metastatic adenocarcinomas of the lung that underwent surgery between 1999 and 2002. Besides, lectin-binding data and other known prognostic factors were correlated with survival. We found a significant positive correlation between the binding of the lectins HPA (p=0.002), PHA-L (p<0.00001) and UEA-I (p<0.00001) to the cells of the primary tumour and to their lymph node metastases. There was a positive correlation between the binding of HPA to the cells of the primary tumour and the haematogenous metastases as well. Patients with tumours which did not show HPA binding sites had a median overall survival of 27.9 months (95%-CI 7.7-infinity months). Patients with a HPA binding tumour had a median overall survival of 20.9 months (95%-CI 18.5-28.7 months). This is the first investigation to demonstrate a positive correlation between the binding of the lectins HPA, PHA-L and UEA-I to the cells of the primary tumour and to their lymph node metastases. Expression of HPA binding sites is also preserved in the haematogenous metastases. In summary, our results support the hypothesis that altered glycosylation of the membrane-bound glycoproteins of the tumour cells is associated with, but not sufficient for promotion of lymphogenic and haematogenous metastasis.
    Lung Cancer 06/2007; 56(3):391-7. · 3.39 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Lectins, carbohydrate proteins, bind to glycoconjugates of all mammalian cells, including cancer cells. Aberrant glycosylation, detected by lectin histochemistry, can predict outcome in some tumour entities. One such lectin is aviscumine (recombinant mistletoe lectin). Aviscumine has cytotoxic effects and can therefore be used as anti-tumour therapy. Lectin histochemistry with aviscumine was performed on primary tumour sections from resected adenocarcinoma of the lung. Staining results were then correlated with the clinical course of the patients. Most of the adenocarcinomas (92.5%) bound aviscumine. Kaplan-Meier analysis revealed no correlation between aviscumine binding and progression-free survival or overall survival. These results suggest that for the selected group of patients with adenocarcinoma of the lung aviscumine binding activity can not serve as a prognostic factor. More strikingly, however, aviscumine binds to malignant cells in 92.5% of the patients. This is an indicator for the use of aviscumine as a possible target for tumour therapy.
    Anticancer research 01/2005; 25(5):3303-7. · 1.71 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: To evaluate the prognostic relevance of CEACAM1 and sialyl Lewis X expression in adenocarcinomas of the lung. Paraffin wax sections of 93 patients with adenocarcinomas of the lung who underwent surgery between 1990 and 1995 were immunohistochemically investigated using monoclonal anti-CEACAM1 and sialyl Lewis X antibodies. The clinical course of all patients was followed up for a minimum of 5 years. Sixty-one tumors were classified as CEACAM1-positive, and 32 were classified as CEACAM1-negative. Patients with CEACAM1-positive tumors had a significantly poorer overall (P =.00025) and relapse-free (P =.00029) survival than those with CEACAM1-negative tumors. Only three patients did not express the sialyl Lewis X glycotope, whereas 90 tumors (97%) were sialyl Lewis X-positive. In multivariate Cox regression analysis, next to tumor stage and sex, only the expression of CEACAM1 was a significant independent prognostic factor for survival. Expression of CEACAM1 was an independent prognostic factor in our patient population and can be used to stratify patients with adenocarcinomas of the lung into low-risk and high-risk groups. In contrast, the expression of sialyl Lewis X was of no prognostic relevance because it was expressed in 97% of all investigated tumors, and most likely has no influence on the function of CEACAM1 in this tumor entity.
    Journal of Clinical Oncology 12/2002; 20(21):4279-84. · 18.04 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Matrix metalloproteinase (MMP)-9 and vascular endothelial growth factor (VEGF) are two proteins involved in angiogenesis. In the present study we investigated the association of pretreatment MMP-9 and VEGF serum levels with clinicopathological parameters and outcome in patients with non-small-cell lung cancer (NSCLC). From February 1998 to October 1999, pretreatment serum levels of MMP-9 and VEGF were analysed in 118 patients with enzyme-linked immunoassays. At diagnosis 50 patients (42%) were staged as early disease (I/II), 27 patients (23%) as locally advanced (IIIA/IIIB), and 41 patients (35%) had metastatic disease (IV). In 72 of the 118 patients tumours were resected and 46 patients received combination chemotherapy with gemcitabine and vinorelbine. The median survival of all 118 patients was 602 days. The 72 patients who had undergone surgery had a median survival of 972 days and the 46 patients who were treated with chemotherapy had a median survival of 298 days (P <0.001). Resected patients with stage I/II disease and an MMP-9 serum level <or=1293 ng/ml or a VEGF serum level <or=630 pg/ml had a significantly longer survival (median survival longer than 1218 days) than patients with higher serum levels (median survival 421 days) (P = 0.001 for MMP-9; P = 0.04 for VEGF). No significant difference in survival was observed in patients with resected stage III disease. Besides tumour stage, Karnofsky performance status and gender, the pretreatment serum level of MMP-9 was identified as an independent prognostic factor in a multivariate Cox regression analysis. Future studies may support our hypothesis that the pretreatment serum level of MMP-9 is a new powerful prognostic marker and can help to stratify NSCLC patients with stage I/II disease into low- and high-risk groups.
    Annals of Oncology 10/2002; 13(10):1550-7. · 7.38 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: The worldwide incidence of adenocarcinoma of the lung is rising. Unfortunately, no significant prognostic marker beyond the classical TNM staging exists to stratify these patients for appropriate therapy. Because lectins, carbohydrate-binding proteins, have been shown to be useful prognostic markers in several other adenocarcinomas, a panel of lectins [Helix pomatia agglutinin (HPA), Phaseolus vulgaris leukoagglutinin, Ulex europaeus agglutinin, Maackia amurenis agglutinin, Sambucus nigra agglutinin] with different carbohydrate-binding specificities were tested for their prognostic relevance. Paraffin wax sections of 93 patients with adenocarcinomas of the lung who had undergone surgery between 1990 and 1995 were investigated by lectin histochemistry. Lectin-binding data and other known prognostic factors were correlated with survival. In univariate analysis, binding of HPA, Phaseolus vulgaris leukoagglutinin, and Ulex europaeus agglutinin to adenocarcinoma cells were prognostic indicators for overall and relapse-free survival, whereas Maackia amurenis agglutinin and Sambucus nigra agglutinin binding had no prognostic value. However, in a multivariate analysis next to stage and gender only HPA was a significant independent prognostic factor on survival. In conclusion, HPA binding was the primary marker-based predictor of prognosis in our patient population and allows to stratify patients with adenocarcinomas of the lung into a low- and a high-risk group.
    American Journal Of Pathology 04/2002; 160(3):1001-8. · 4.60 Impact Factor
  • American Journal of Pathology - AMER J PATHOL. 01/2002; 160(3):1001-1008.
  • European Journal of Cancer - EUR J CANCER. 01/2001; 37.