母体血中における分娩形式による分娩前後の、羊水塞栓症のバイオマーカーとなりうるSCC 抗原の大きな変化

Amniotic fluid embolism (AFE) is a serious disease in which amniotic fluid components enter the maternal systemic circulation, causing cardiopulmonary collapse in pregnant women. It has been previously reported that amniotic fluid contains extremely high levels of squamous cell carcinoma antigen (SCCA), and that pregnant women who do not survive due to AFE have high blood SCCA levels. The aim of the present study was to determine the possible mechanisms through which SCCA in amniotic fluid enters the maternal blood, as well as the potential origin of SCCA. The prospective study included a cohort of 464 women (339 normal vaginal deliveries, 97 cesarean deliveries without labor, and 28 cesarean deliveries with labor). The dynamic changes in maternal serum SCCA levels were determined before and after delivery in relation to the mode of delivery, and SCCA levels were measured in the placenta, fetal skin, amniotic fluid cell components, amniotic fluid and neonatal urine. Serial serum samples collected at the time of admission, at 2 h postpartum, and on postpartum day 3 were quantitatively measured for SCCA by enzyme‑linked immunosorbent assay. Amniotic fluid and neonatal urine SCCA levels were also measured. The protein expression of SCCA in the placenta and fetal skin was assessed by immunohistochemistry. In vaginal deliveries, there was a significant increase in serum SCCA levels from admission to 2 h postpartum, and SCCA levels decreased on postpartum day 3. In cesarean deliveries, the SCCA levels at the time of admission and 2 h postpartum did not differ. The SCCA levels were significantly higher in women who underwent vaginal deliveries compared to those that underwent cesarean deliveries without labor (P=0.033). Immunohistochemical staining revealed no SCCA expression in the placenta and fetal skin. The SCCA levels in neonatal urine immediately after birth were as high as those in the amniotic fluid, suggesting that SCCA may originate from fetal urine. The present study thus suggests that amniotic fluid SCCA levels, which may be derived from fetal urine, can enter the maternal circulation during vaginal delivery. The onset of labor and full cervical dilatation are the main causes of entry of amniotic fluid components into the maternal circulation.博士（医学）・甲第796号・令和3年6月25日Copyright: © Nakano et al. This is an open access article distributed under the terms of Creative Commons Attribution License (https://creativecommons.org/licenses/by-nc-nd/4.0/)

子宮内膜症性嚢胞の悪性転化におけるHO-1発現マクロファージの特徴

Malignant transformation of endometriosis is a rare and still poorly understood event, but is associated with the distortion of the pro-oxidant and anti-oxidant balance. The aim of the present study was to quantify the numbers of macrophages polarized as M1 or M2 phenotypes and the expression of heme oxygenase (HO)-1 in tissue sections from patients with benign ovarian endometrioma (OE) and its malignant transformation (endometriosis-associated ovarian cancer, EAOC). We performed a retrospective study at the Department of Gynecology, Nara Medical University hospital from December 2012 to March 2015. This study included 53 patients with OE (n = 33) and EAOC (n = 20), and we evaluated polarized functional status of macrophages by immunohistochemical staining of CD68, CD11c, CD163 and HO-1. The number of the M1 phenotype (CD11c+, p = 0.001) and the M2 phenotype (CD163+, p = 0.009) was significantly lower in EAOC patients than in OE patients. Analyzing the correlations between the studied markers, the expression of CD68, CD11c, and CD163 proteins significantly correlated with each other (p < 0.001). The number of M2 phenotypes expressing HO-1 was significantly decreased in the EAOC group, compared with the OE group (P < 0.001), demonstrating sustained downregulation of an antioxidant marker, HO-1, in EAOC. In conclusion, reduced number of M2 macrophages expressing HO-1 may have an important role in promoting malignant transformation of OE.博士（医学）・乙第1434号・令和元年9月27日Copyright © 2018. Published by Elsevier GmbH