Tadahiro Shimizu

Therapeutic efficacy of the angiogenesis inhibitor O- (Chloroacetyl- carbamoyl) fumagillol (TNP-470; AGM-1470) for human anaplastic thyroid carcinoma in nude mice

TNP-470 (AGM-1470), a synthetic analog of fumagillin (6-chloroacetyl-carbamoyloxy-4-(1,2-epoxy-1,5-dimethyl- 4-hexenyl)-5-methoxy-1-oxaspiro [2,5] octane 1, has been reported to reduce the supply of nutrients to experimental tumors by inhibiting angiogenesis. In this study, we investigated anti-tumor activity of TNP-470 against human thyroid anaplastic carcinoma with a view to developing a new treatment for this thyroid tumor. A transplantable tumor was established from thyroid anaplastic carcinoma of a 78-year-old woman, as a xenograft in nude mice (BALB/c, nu/nu, male). This transplantable tumor, with chromosomal abnormality was shown to be non-functional in excretory hormones and to preserve morphological characteristics of the original anaplastic tumor tissue. TNP-470 was given at a dose of 50 mg/kg b.w. to nude mice transplanted with human thyroid anaplastic carcinoma by different routes of administration: intratumoral, peritumoral, subcutaneous and intraperitoneal. Intratumoral and peritumoral administration were effective, and especially the TNP-470 administered by the former route completely inhibited tumor growth. Immunohistochemical analysis using anti-factor VIII antibody revealed the density of microvessels to be significantly decreased by local administration of TNP-470 (intratumoral administration, 7.8 +/- 2.9/mm2, control, 27.0 +/- 6.3/mm2; peritumoral administration, 9.7 +/- 2.6/mm2, control, 21.1 +/- 5.1/mm2). Our findings suggested the possibility of clinical application of TNP-470 to control the growth of human anaplastic thyroid carcinoma.

A case of papillary carcinoma of the thyroid with more than 30 years long-term asymptomatic pulmonary metastases

This is a case report of a patient with thyroid cancer with asymptomatic pulmonary metastases, and without obvious progression over 34 years.

The problems encountered in the surgical management of primary hyperparathyroidism

The problems encountered in the diagnosis and treatment of primary hyperparathyroidism were studied in 69 cases. The accuracy of imaging for hyperplasia was less than that for adenoma or carcinoma and the major causes for multiple operations were a failure to locate the four glands and mediastinal adenoma. The intravenous administration of high doses of calcitonin could reduce the serum calcium level of patients in hypercalcemic crisis. Carcinoma required ipsilateral modified radical neck dissection because of lymph node metastases, and non-medullary thyroid carcinoma was often associated with primary hyperparathyroidism. We found removal of the parathyroid adenoma and biopsy or extirpation of only one macroscopically normal gland to be a fully satisfactory procedure after bilateral neck exploration and attempting to identify at least four glands.