| Budget Amount *help |
¥3,400,000 (Direct Cost: ¥3,400,000)
Fiscal Year 2001: ¥1,300,000 (Direct Cost: ¥1,300,000)
Fiscal Year 2000: ¥2,100,000 (Direct Cost: ¥2,100,000)
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| Research Abstract |
Twenty-two families and 37 cases with iodide transport defect have been repor ted to date.We identified, for the first time, a NIS (sodium/iodide symporter) mutation (T354P) in a Japanese case with iodide transport defect and proved the identified mutation was the direct cause of the disease by expression experiments. One -third of the cases with iodide transport defect were Japanese. We identified T354P homozygous mutation in 7 cases among them, and found other kinds of NIS mutations in other three Japanese cases with iodide transport defect. Disease causing nature by these mutation s was shown also by expression studies. We analyzed more than half of the Japanese cases with iodide transport defect. T354P was frequently identified in Japanese patients but not found in patients outside Japan. It is interesting that clinical feature such as extent of hypothyroidism and goiter status was quite heterogeneous among patients with iodide transport defect and even among patients with identical T354P homozygous mutation. These facts suggest that there is/are other factor(s) modifying NIS function to a great extent. Further, we identified a novel homozygous NIS mutation in the largest family in the world with iodide transport defect which had 18 patients. In these cases, no goiter was found in the patients , showing clinical differences from Japanese patients. We identified other novel NIS mutations in Spanish siblings, African French, and a Japanese living in Kyushu. Thus, we analyzed about half of the cases with iodide transport defect in the world.
Gene therapy by introduction of NIS gene is one combined with radiation therapy with 131I. This can be applied not only to thyroid cancer but also to all kinds of malignancies. We established a cell line permanently and strongly expressing a number of NIS from breast cancer cells, opening a way to a new research for cancer treatment.
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