Beitrag zur Untersuchung der Elementverteilungsmuster und zur Elementspeziesanalyse bei Neoplasien des Gastrointestinaltraktes - Investigation of element distribution pattern and analysis of element species in neoplasia of the gastrointestinal tract
Mineral and trace elements are excellent markers for altered cell metabolism. The reason is that both have multiple relations to proteins especially to enzymes. This is reflected in the processes of cell differentiation, growth and regeneration.
Diverse physiological and toxic elements were quantitatively determined in 68 malignant tissue samples and in their corresponding healthy tissue samples (gut, colon, and rectum) by different analytical methods. The analytical data were evaluated under consideration of the histopathological and individual patient data by chemometric methods (cluster analysis, principal component analysis, linear discriminant analysis, multiple linear regression). A significant dependence of the element contents on the tumour stage and on malignancy could be shown. Additionally interactions of mineral and trace elements in neoplastic and normal tissues could be observed. The most important correlation was found between as well phosphorus, potassium and rubidium as chromium and nickel.
In the ongoing investigation the element contents - related to the cytosolic protein concentration - of the cytosols from malignant and healthy tissues of colon samples were determined. It was shown that the pattern of element distribution is altered in the malignant transformed cells compared with the normal ones. This alteration can be considered as a consequence of an increased or a decreased cell metabolism. Additionally the cytosolic calcium content showed a dependency on the tumour stage according to Duke which can be seen as a characteristic value for the breakdown of cell proliferation and apoptosis. In the case that the relationship between the cytosolic Ca content (Ca in the ionic and bounded form) could be use as a molecular marker for the prognosis of the overall survival of colorectal cancer patients.
A further correlation of interest could be obtained determining the activities of enzymes which are involved in the redox system of cells. For example both the activity of glutathione peroxidase and the activity of the Zn/Cu superoxide dismutase showed a strong correlation to the malignancy. It can be concluded that both enzymes effect the tumour progression.
The species of several elements were analysed by application of different coupling techniques in a final study. One of the important aspects were the results of the analysis of nickel species. In the near future the results could be use as a prognostic factor on molecular basis. I t has to be proved if the prognostic factor and his tumour biological information offer new therapy strategies in colon cancer treatment.
Advisor:Prof. Dr. Alfred Golloch; Prof. Dr. Klaus Günther; Prof. Dr. Reinhard Niessner
School:Universität Duisburg-Essen, Standort Essen
Source Type:Master's Thesis
Keywords:chemie universitaet duisburg essen
Date of Publication:08/13/2003