Toshikazu Ishikita

1α-hydroxyvitamin D3, hypercalcemia, and growth suppression of 7,12-dimethylbenz[a]anthracene-induced rat mammary tumors

Summary1α-hydroxyvitamin D3 [1α(OH)D3] was administered to female Sprague-Dawley rats with 7,12-dimethylbenz[a]anthracene (DMBA)-induced mammary tumors. 1α(OH)D3 suppressed the growth of the rat mammary tumors dose-dependently, and in the high dose groups treated with 0.5–1.0µg/kg of 1α(OH)D3, significant inhibition of tumor growth was observed. But daily oral administration of 1α(OH)D3 for four consecutive weeks caused side effects such as hypercalcemia and weight loss. We compared 0.5 µg/kg of 1α(OH)D3 three times weekly with the same dose six times weekly to discover whether or not the side effects can be reduced by treatment schedule. Both groups showed a significant oncostatic effect, compared with the control group, while the side effects were relieved in the three times weekly group. Regarding estrogen receptors (ER) in the tumors, there was no significant difference among the groups. These results suggested that the antitumor effect of 1α(OH)D3 on DMBA-induced mammary tumors was not related to ER status. Combined use of 1α(OH)D3 with 5-fluorouracil (5-FU) or medroxyprogesterone acetate (MPA) was also examined. No significant augmentation of the antitumor effect was seen in the two combinations, although the combined therapy with MPA showed a significant inhibition of weight loss in the rats.

Screening for abdominal aortic aneurysm and occlusive peripheral vascular disease in Japanese residents

To evaluate the prevalence of abdominal aortic aneurysm (AAA) and occlusive peripheral vascular disease (PVD) in Japanese residents, and to examine the correlations between these diseases and the risk factors of atherosclerosis, 348 residents of a village in central Japan aged between 60 and 79 years were screened. The screening for AAA was performed using ultrasonography (US) and that for PVD was performed by palpation and Doppler US. No AAA was found, and a right common iliac arterial aneurysm was detected in a 79-year-old man (0.3%). The mean diameter of the infrarenal abdominal aorta was 18.7 mm and an abdominal aorta of 25 mm or greater in diameter was seen in 16 participants (4.6%), all of whom need to be followed up. PVD was suspected in two patients (0.6%) with a low ankle brachial pressure index. Of a total of five patients diagnosed or suspected of having a common iliac arterial aneurysm or PVD, four (80%) had at least one risk factor for atherosclerosis. Thus, we conclude that Japanese residents with risk factors predisposing them to atherosclerosis such as hypertension, obesity, abnormal serum lipid levels, and a history of smoking should be selectively screened for AAA and PVD due to the low prevalence of these diseases and from the viewpoint of cost-effectiveness.

Intersite Variation of Estrogen Receptors in Human Breast Cancers and Response to Endocrine Therapy

Estrogen receptor (ER) assays were performed by sucrose gradient centrifugation method at multiple sites in large breast cancers. Intersite variation of ER in a tumor was observed in 24 out of 35 cases. 16 tumors with relatively low ER levels showed different ER status with multiple assays. The results suggest that an assay performed on a small random part of a large tumor may not yield the true ER status. ER value at the largest cross-section was almost the same as the average ER values in each tumor. In addition, 21 cases were examined in relation to ER values at multiple sites in the large tumors and response to endocrine therapy. As the ER value at the largest cross-section was highly correlated with the therapeutic response to endocrine therapy of breast cancer, it would represent true ER status and level. The results suggest that the ER assay at the largest cross-section of a large tumor is an appropriate method to predict response to endocrine therapy.