University of Twente Student Theses


An optimal therapeutic window in a transdermal treatment against circulating tumor cells (CTCs), in terms of CTC behavior, perfusion limits and time frame.

Kloosterman, M. and Schulten, M.K. and Tanis, D.C. and Vulders, L.A.T. (2018) An optimal therapeutic window in a transdermal treatment against circulating tumor cells (CTCs), in terms of CTC behavior, perfusion limits and time frame.

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Abstract:Introduction: In the Netherlands, cancer is the number one cause of death, often induced by metastasis. Metastasis is induced by circulating tumor cells (CTCs), individual cells that are shed from the primary tumor and are distributed through the lymphatic and hematogenous system. Many methods for the elimination of CTCs have been developed, but most of them are invasive and damaging. Therefore, a non-invasive and more accurate therapy should be developed. This research is a continuation on the peppered skin project of the Biomedical Photonic Imaging (BMPI) research group. The aim is to enhance the perfusion of the skin, ultimately in order to collect and destroy CTCs transdermally. First, the BMPI group has focused on a model to link temperature change to perfusion, in order to determine the absolute amount of skin blood flow. To validate this model, more test subjects are required, for which accordance of the medical ethics review (METC) is needed. Before detection and elimination methods can be assessed, an optimal therapeutic window should be found. This involves finding the highest achievable perfusion to clear the blood from CTCs in an optimal time frame. Besides that, the behavior of CTCs in the microcirculation can influence the transdermal treatment possibilities of CTCs. These matters combined give rise to the following research question: ‘How can the therapeutic window in a transdermal treatment against CTCs be optimized, in terms of CTC behavior, perfusion limits and timeframe?’ Method: A proof of concept study has been performed, in which six different rubefacients are compared with each other: Midalgan (methyl-nicotinate, glycol-salicylate), Tigerbalm (Menthol), Tantum (capsaicin, benzyl-nicotinate) and Capsaicin cream with 0,025%, 0,075% and 0,1% capsaicin concentrations. In this experiment three parameters were determined for each rubefacient. The parameters are the relative increase in perfusion, the effect duration and the effect of reapplication. Furthermore, a literature study was performed on the behavior of CTCs in the microcirculation, the possibilities of detection and elimination and on the requirements for an METC request. Results: Midalgan, Capsaicin 0,075% and Tantum were found to be the most promising and were therefore further investigated. Reapplication had little effect for Midalgan but did cause a repeated increase of perfusion for Capsaicin 0,075% and Tantum. After correcting the arbitrary units of perfusion for their baseline, it was seen that Tantum causes the highest relative increase in perfusion (factor 10-25) for the longest period of time. Literature study showed that CTCs appear in clusters and as individual cells, but clusters are more likely to create metastasis and might need a different therapeutic approach. Furthermore, CTCs not only appear in the microcirculation but also in the lymphatic system, which is important to take into consideration when developing an elimination method. Conclusion: Tantum shows the highest perfusion increase and has the longest effect duration and would therefore be the most valuable with a view to a future treatment. From the literature research can be concluded that the presence of CTCs in the lymphatic system cannot be ignored in a novel treatment method. Secondly, the penetration depth of the therapy is paramount to the therapeutic window given the vessel plexuses. Furthermore, CTCs can enter the smallest capillaries and therefore reach the entire microcirculation. Finally, clusters of CTCs might need a different therapeutic approach than single cells, because of their size and higher risk of metastasis compared to single cells. An METC approach is needed for further research with test subjects in order to validate the model of the BMPI group.
Item Type:Essay (Bachelor)
Faculty:TNW: Science and Technology
Subject:44 medicine
Programme:Technical Medicine BSc (50033)
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