The thyrotropin receptor in thyroid carcinoma

Hovens, G.C.J. (2008)

Doctoral Thesis

A subgroup of patients with thyroid cancer (10-15% of patients with DTC) with distant metastases have high remission rates after conventional RaI-treatment. We have explored several routes which in time may help to improve the prognosis for this subset of patients, focussing on the TSHR. The combination of troglitazone and lovastatin may have potential use in DTC as we observed a strong reduction of growth and distinct changes in morphology in the follicular thyroid carcinoma cell-line FTC-133 at clinically achievable concentrations. Furthermore, the combination of troglitazone and lovastatin was able to increase the expression of NIS and the TSHR which may prove to be beneficial in sensitizing thyroid tumor cells to conventional RaI therapy. Secondly, we explored the possibility of thyroid specific membrane associated therapy by using the TSHR as a target. We succeeded in modifying TSH into a potential vehicle for toxins by converting it into a single chain protein with improved binding to the TSHR. The fusion of short proteins to our modified single chain TSH did not impair binding thus confirming the potential in using modified TSH as a vehicle for therapeutic proteins. We have demonstrated in our studies that a balanced attitude is feasible in commonly used TSH suppressing thyroxine replacement therapy, thus preventing those patients from the potential negative effects of long term TSH suppression on other organs.

• DTC
• Follicular
• Graves
• Radioiodine
• Redifferentiation
• Thyroid
• Thyrotropin
• TSH
• TSH-receptor

• All authors: Hovens, G.C.J.
• Supervisor: Smit, J.W.A.; Romijn, J.A.
• Co-supervisor: Karperien, H.B.J.
• Qualification: Doctor (dr.)
• Awarding Institution: Leiden University Medical Center (LUMC), Leiden University
• Date: 2008-09-18
• ISBN (print): 9789064642807