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Third-party-funded project

Title:
Redifferentiation of thyroid carcinoma with retinoic acid

Project management at the University of Würzburg:

Participating scientists:

Abstract:
For the treatment of differentiated thyroid carcinoma, surgical intervention and radioiodide therapy are the only available therapeutic measures with prognostic relevance for the patient, whereas chemotherapy is only of minor importance. Usually, these tumors have a favorable prognosis. However, during the course of the disease in about one third of the patients de-differentiation is observed, which is accompanied by resistance to TSH and a loss of iodide uptake and accumulation. Therefore, in these patients, radioiodide therapy and TSH suppression by levothyroxin are no longer effective. Our studies in vitro and in vivo have
demonstrated a re-differentiating effect of retinoic acid on thyroid carcinoma cell lines similar to that observed in the case of acute promyelocytic leukemia. In poorly differentiated thyroid tumor cells, type I 5´-deiodinase activity was induced and the expression of the sodium-iodide symporter mRNA was stimulated. Subject of this clinical pilot study is the administration of retinoic acid to patients with poorly
differentiated and inoperable thyroid carcinomas with the aim to achieve re-differentiation and stimulation of radioiodide uptake. The effect will be measured by dosimetry using whole body scans and by follow-up of the tumor growth applying imaging techniques CT or MRT. In parallel, fine needle aspiration biopsies of accessible tumors or metastases will be taken; the material will be examined by a cytopathologist to detect cytological alterations and, in parallel, used for RT-PCR to document changes in the expression of tumor markers like Tg, TPO, and TSH receptor triggered by retinoic acid.

Key words:
    thyroid cancer
    thyroid tumor
    retinoic acid
    retinoid
    redifferentiation therapy
    NIS
    sodium iodide symporter
    deiodinase

Projekt period: from 1.1997 to 12.2001

Funding institution:
Sonstige Stiftung ( Wilhelm Sander Stiftung )

Publications:

Links:
website Inst Exp Endocrinology Charité
website Clinical Research Group