The aim of this thesis was to develop advanced body MR techniques that can contribute to the knowledge of the metabolic syndrome (MetS). Such techniques are important since the incidence of... Show moreThe aim of this thesis was to develop advanced body MR techniques that can contribute to the knowledge of the metabolic syndrome (MetS). Such techniques are important since the incidence of the metabolic syndrome is reaching pandemic proportions. We looked In the first part of this thesis, consisting of chapters 2, 3 and 4, new techniques for body MR were developed. Firstly high dielectric passive shimming was developed and applied on liver imaging to increase image quality. Furthermore, the required power was reduced by applying the passive shimming method. Secondly MR spectroscopy was optimized to reliably measure lipid levels in the heart and kidney. By looking at the various parameters and optimizing them individually very high measurement reproducibility was reached. Even though MR spectroscopy is a great tool for studying MetS the complexity of the technique hampers broad application therefore, extra emphasis was placed on the ease of use of the developed protocol. In the second part of the thesis the previously mentioned methods were applied in a more clinical setting. Show less
The current thesis discusses the use of molecular and biological tumor markers to predict clinical outcome. By studying several key processes in the develepment of cancer as regulation of cell... Show moreThe current thesis discusses the use of molecular and biological tumor markers to predict clinical outcome. By studying several key processes in the develepment of cancer as regulation of cell motility (non-receptor protein tyrosin adesion kinases, FAK, Src and paxillin, Apoptosis (caspase-3 activity and M30 expression) and regulation of cell growth (COX-2 expression). In addition the use of selective COX-2 inhibitors for the treatment of colorectal cancer liver metastases is investigated and discussed. The main outcomes of the thesis are that combined FAK/Src immunohistochemical expression is predictive of tumor recurrence in colorectal cancer, but is not overexpressed in liver metastases. Increased tumor cell apoptosis can have a positive or a negative impact on survival and local recurrence, depending on the location of the tumor in the large bowel . In rectal cancer caspase-3 activity can be used to preoperatively select patients who will not benefit from radiation therapy. COX-2 expression in rectal cancer is only of prognostic significance in irradiated rectal cancer patients, not in non-irradiated. Liver metastases in an animal model show deminished growth in the abcence of COX-2 expression and prostaglandin production. Show less
