High-intensity focused ultrasound (HIFU) has excellent potential as a non-invasive therapeutic tool in various CASE REPORTA 32-year-old woman, gravida 1 para 0, who was pregnant with twins, was referred to our hospital because of the absence of a heart beat in one fetus. Based on the ultrasonographic findings, we diagnosed twin reversed arterial perfusion (TRAP) sequence. Following ethics committee approval and counseling of the patient, Correspondence to: Dr K. Ichizuka, Showa University, School of Medicine, Department of Obstetrics and Gynecology, 142-8666 Hatanodai, Shinagawa-ku, Tokyo, Japan (e-mail: k.ichizuka@me.com) Accepted: 14 March 2013which included a thorough explanation of the procedure as well as the possible adverse effects on the mother and pump fetus and the results of our previous case 1 , we conducted high-intensity focused ultrasound (HIFU) treatment (Figure 1). The aim of HIFU was to noninvasively occlude blood flow in the acardiac fetus with the aim of diminishing the cardiac burden in the normal 'pump' fetus.The HIFU transducer used in this case was a prototype developed by us with a resonant frequency of 1.71 MHz, a spherical radius of curvature of 60 mm, and a focal length of 60 mm. The exposure method and conditions were derived from the findings of our previous animal experiments 2,3 and the first clinical case 1 . The blood vessel of the acardiac fetus at the point at which the umbilical cord entered the body was targeted for HIFU exposure through the maternal abdomen.HIFU irradiation was conducted at 13 + 5 weeks' gestation. The HIFU intensity at the focused area (3.6 mm 2 ) was set at approximately 2300 W/cm 2 with exposure times of 10 s repeated several times. Following this first round of irradiation, blood flow in the aorta of the acardiac fetus became very weak. However, the following day blood flow had recovered to its preoperative state (Figure 2a). The patient did not suffer any adverse events from the procedure, and she opted for a series of repeat procedures. We conducted three more courses of HIFU exposure in a similar manner at 3-day intervals. However, the results were similar to that of the first procedure. At 17 + 5 weeks' gestation, we decided to increase the emission power of the HIFU and performed the procedure at a higher power of 4600 W/cm 2 . This resulted in cessation of blood flow in the acardiac fetus and its umbilicus the following day, indicating complete occlusion (Figure 2b).

Estrogens play important roles in the development of breast cancer. Inflammatory cytokines such as interleukin-6 (IL-6) and interleukin-1 beta (IL-1 beta) exist at high concentrations in breast cancer tissue. Although these cytokines are thought to exert some effect on cancer growth, their precise mechanism is still unclear. In the present study, we investigated the effects of inflammatory cytokines on aromatase (Arom) and steroid sulfatase (STS), which are estrogen-producing enzymes, and cell proliferation using human breast cancer cell lines (SK-BR-3, MCF-7). IL-6 and IL-1 beta stimulated the activity of Arom and STS. Estrone sulfate (E1-S) had a stimulus effect on cell proliferation of MCF-7. Although IL-6 did not show significant effect on cell proliferation, cell proliferation was significantly increased when IL-6 and E1-S were simultaneously added to the incubation medium. This cell proliferative effect was apparently stronger than the addition of E1-S alone. Addition of IL-1 beta in the presence of E1-S also significantly enhanced cell proliferation though IL-1 beta alone did not show any effect. These results led us to the hypothesis that inflammatory cytokines such as IL-6 and IL-1 beta regulate proliferation of breast cancer cells through estrogen production by steroid-catalyzing enzymes in the tissue.

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SUMblARY: Both aromatase and 5a-reductase activities were found by whole-cell assay in osteoblastlike cells, MG-63 and HOS. Aromatase activity was measured by the [~H] water release method, and the formation of 5a-androstanedione from androstenedione was expressed as 5a-reductase activity. When CGS16949A, an inhibitor of aromatase, was added to the incubation medium at a concentration of 2 x 10 -9 M, sufficient to completely inhibit placental aromatase activity, only 63% to 68% inhibitions were observed.When progesterone, a competitive inhibitor of 5a-reductase, was added at a concentration of 10-s M, 28% to 40% inhibitions were recorded. Because the release of [~H] from [l~'3H] ' androstenedione into water by 5a-reductase is reported, results from the present study suggest that the measurement of aromatase activity in osteoblasts by the [3H] water release method may overestimate aromatase activity owing to the inclusion of 5a-reductase activity. The results also suggest that osteoblast cells may play an important role in bone metabolism by transforming androgens into estrogens and more biologically active androgen derivatives.

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