TGF-beta and BMPs are members of the TGF-beta superfamily of cytokines which play an important role in a multitude of processes. In cancer, TGF-beta is known for its dual role: in early stages it... Show moreTGF-beta and BMPs are members of the TGF-beta superfamily of cytokines which play an important role in a multitude of processes. In cancer, TGF-beta is known for its dual role: in early stages it inhibits cancer cell proliferation, whereas in later stages it promotes invasion and metastasis. In this thesis, a 3 dimenstional model to monitor TGF-beta-induced invasion of breast cancer cells is presented and an important role for MMP2 and MMP9. Furthermore, BMP-7 could inhibit TGF-beta-induced invasion through inhibition of TGF-beta-induced integrin beta3 expression. The property of TGF-beta to induce epithelial to mesenchymal transition (EMT) is thought to contribute to its pro-invasive effect. We found that transcription factors involved in this process induce invasion. Lastly, we identified kinases involved in BMP signaling. These findings help the understanding of breast cancer cell invasion and a way to prevent this process. Show less
The aim of this work was to develop methods to measure structural changes in the skeleton using MicroCT. In addition, these new methods should be able to quantify biologically relevant changes. In... Show moreThe aim of this work was to develop methods to measure structural changes in the skeleton using MicroCT. In addition, these new methods should be able to quantify biologically relevant changes. In order to do this, normalized methods to analyse MicroCT scans and perform quantitative measurements within these datasets are described in this thesis. These techniques were combined with a biological angiogenesis assay and used as research tools in a study comparing various different combination treatments of bone metastases. Show less
Purpose: To determine the use of surgical clips as a surrogate for localization of the excision cavity and to quantify the stability of the clips' positions during the course of external beam... Show morePurpose: To determine the use of surgical clips as a surrogate for localization of the excision cavity and to quantify the stability of the clips' positions during the course of external beam radiotherapy for breast cancer patients, using cone beam computed tomography (CBCT) scans.Methods and Materials: Twenty-one breast cancer patients with surgical clips placed in the breast excision cavity were treated in a supine position with 28 daily fractions. CBCT scans were regularly acquired for a setup correction protocol. Retrospectively, the CBCT scans were registered to the planning CT scans, using gray-value registration of the excision cavity region and chamfer matching of the clips. Subsequently, residual setup errors (systematic [Sigma] and random [sigma]) of the excision cavity were estimated relative to the clips' registration. Finally, the stability of the clips' positions were quantified as the movement of each separate clip according to the center of gravity of the excision cavity.Results: When clips were used for online setup corrections, the residual errors of the excision cavity were Sigma(left-right) = 1.2, sigma(left-right) = 1.0; Sigma(cranial-caudal) = 1.3, sigma(cranial-caudal) = 1.2; and Sigma(anterior-posterior) = 0.7, sigma(anterior-posterior) = 0.9 mm. Furthermore, the average distance (over all patients) between the clips and centers of gravity of the excision cavities was 18.8 mm (on the planning CT) and was reduced to 17.4 mm (measured on the last CBCT scan).Conclusion: Clips move in the direction of the center of gravity of the excision cavity, on average, 1.4 mm. The clips are good surrogates for locating the excision cavity and providing small residual errors. (c) 2011 Elsevier Inc. Show less
This thesis consists of two parts. In part I, we have demonstrated that preoperatively administrated systemic (neoadjuvant) therapy is a feasible treatment strategy in early stage breast cancer to... Show moreThis thesis consists of two parts. In part I, we have demonstrated that preoperatively administrated systemic (neoadjuvant) therapy is a feasible treatment strategy in early stage breast cancer to achieve improved surgical options and to assess tumor response. We also demonstrated that overexpression of the breast cancer stem cell marker aldehyde dehydrogenase-1 in early stage breast cancer patients is inversely associated with age and is of prognostic importance. In part II, we have demonstrated proof-of-principle of intraoperative tumor detection and image-guided tumor resection by using the novel technique of near-infrared fluorescence imaging. We have performed two clinical trials to optimize the use of indocyanine green as a near-infrared fluorescence lymphatic tracer for the sentinel lymph node procedure in breast cancer patients. Show less
