2-Methoxyestradiol reduces monocyte adhesion to aortic endothelial cells in ovariectomized rats.

2-Methoxyestradiol (2-ME) is an endogenous metabolite of estradiol with no affinity for estrogen receptors. It inhibits cell proliferation, thus is a potentially useful drug to block the progression of atherosclerosis. As a first step to examining the anti-atherosclerotic effects of 2-ME, we investigated monocyte adhesion to aortic endothelial cells, which is considered a prerequisite to atherosclerosis in vivo. Eight-week-old Sprague-Dawley rats were ovariectomized then treated by slow-release pellets with placebo, 17-beta-estradiol (5 microg/day), low-dose 2-ME (10 microg/day), or high-dose 2-ME (100 microg/day). After 6 weeks, en face analysis showed an increased number of monocytes adhering to endothelial cells of the thoracic aorta in ovariectomized rats compared with sham-operated controls. This increase was predominantly inhibited by treatment with 17beta-estradiol, and low-dose or high-dose 2-ME. The observed effects were unrelated to changes in serum lipids, blood glucose, or blood pressure. Our data suggested that 2-ME mediates the anti-atherosclerotic actions of estradiol at least in part by preventing monocyte adhesion to the aortic endothelium.

Insulin and nateglinide reduce monocyte adhesion to endothelial cells in Goto-Kakizaki rats exhibiting repetitive blood glucose fluctuation.

Epidemiological studies demonstrated the importance of postprandial hyperglycemia on the progression of atherosclerosis. However, whether treatment of postprandial hyperglycemia by insulin or insulin secretagogues has a beneficial effect on atherosclerosis has not been elucidated. To elucidate the effects of reduction of postprandial rise of blood glucose by insulin and nateglinide on monocyte adhesion to endothelial cells, we used non-obese type 2 diabetic Goto-Kakizaki (GK) rats fed twice daily, as a model of repetitive postprandial hyperglycemia. We investigated the effects of insulin injection and nateglinide administration just before each meal for 12 weeks on monocyte adhesion to endothelial cells. By setting the doses of insulin and nateglinide, both treatment significantly reduced postprandial hyperglycemia without significant reduction of HbA1c. Nateglinide also reduced serum insulin level just after 1 h meal. Both nateglinide and insulin therapy reduced the number of monocytes adherent to the aortic endothelial layer. Nateglinide, but not insulin, reduced intimal thickness of the thoracic aorta. While increased serum insulin level might be regarded as a factor responsible for the progression of atherosclerosis, our data showed that treatment with pre-meal insulin or nateglinide, which reduces postprandial hyperglycemia, reduced monocyte adhesion to endothelial cells.

[Combination chemotherapy with docetaxel+carboplatin in the treatment of cancer of the ovary and fallopian tube].

Docetaxel and carboplatin were used as adjuvant chemotherapy or maintenance chemotherapy for cancer of the ovary and fallopian tube. Docetaxel 70 mg/m2 and carboplatin (area under the concentration-versus-time curve of 5) were administered intravenously every 3 weeks. Thirty-two patients (median age, 54 years) were assessable. We had objective responses from 5 of 7 (70%) assessable patients. Our toxicity findings included the following: grade 3 or 4 neutropenia (70% of courses); grade 3 or 4 leucocytopenia (35% of courses); hypersensitive reaction (25% of patients, none requiring discontinuation of therapy): edema (30% of patients): peripheral neuropathy (6% of patients). The combination of docetaxel and carboplatin is highly active in cancer of the ovary and follapian tube. The adverse effect was significant neutropenia, but peripheral neuropathy was rare. This regimen represents a reasonable first-line option for patients with ovarian cancer.