A description is presented of the first documented case of placental aromatase deficiency. The deficiency caused maternal virilization during pregnancy and pseudohermaphroditism of the female fetus. A 24-yr-old primigravida showed progressive virilization during the third trimester. Urinary excretion of estrogen was less than 14 mumol/day between 35-38 weeks of pregnancy, although nonstress tests showed reactive patterns and serum levels of human placental lactogen were above 460 nmol/L. Maternal serum levels of estrogens were low, and those of androgens were high in the third trimester. A dehydroepiandrosterone sulfate loading test induced a marked increase in maternal serum levels of androgens, whereas no such increase was observed in estrogens. The woman delivered vaginally a live full-term infant who exhibited female pseudohermaphroditism. Cord serum levels of estrogens were extremely low, while those of androgens were high. The aromatase activity of the placenta, determined by the conversion of [7-3H]androstenedione to 17 beta-[7-3H]estradiol and [7-3H]estrone, were less than 0.03 fmol/microgram protein.min (control, 9.6 +/- 2.2 fmol/microgram protein.min). The sulfatase activity of the placenta was 0.63 pmol/microgram protein.min compared to 0.46 +/- 0.16 pmol/microgram protein.min in controls. The rate of aromatization by normal control placentas was the same as that obtained during coincubation of samples of normal placentas and that of the patient. Thus, the presence of aromatase inhibitor in the patient's placenta was excluded.
The production of MCP-1 reached 70-80 ng/ml in vitro when transfectant cells were cultured at a cell density of 1 x 10(5) cells/ml for 3 days. Transfection of MCP-1 cDNA did not affect the growth rate in vitro. Also, MCP-1-transfectants formed tumors after intra-footpad inoculation similar in size to the parental cells. The number of infiltrating macrophages in the primary tumor of the transfectant rapidly increased from the 3rd to 5th day after inoculation as revealed by immunohistochemical staining using an antibody against mouse macrophages. An earlier, greater, but no longer-lasting increase in tumor-infiltrating macrophages was induced in tumors by MCP-1 transfection was compared to that induced by the parent cells. On the 10th day after the inoculation, the tumor-infiltrating macrophages in mice inoculated MCP-1 transfectants were decreased to a level similar to that of the parent cells. Groups of mice were treated intraperitoneally with LPS at different times after the inoculation. Tumor cells producing high levels of MCP-1 were significantly lysed by macrophages treated with LPS, whereas parental or control transfected cells were not. Conclusions. Combination immunotherapy can provide a rationale for the application of MCP-1 treatment to increase immunological responses to cancer.
These results suggest that MCAF may augment the metastastic potential by modulating tumor associated angiogenesis.
The rejection of the cells depends on cytolysis and generates potent and long lasting antitumor immunity. These data suggest that tumor cells transfected with the MIP-1 alpha gene might be useful as an effective therapy for the treatment of certain tumors.
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