BRCA1 Expression is an Important Biomarker for Chemosensitivity: Suppression of BRCA1 Increases the Apoptosis via Up-regulation of p53 and p21 During Cisplatin Treatment in Ovarian Cancer Cells

BRCA1 is a tumor suppressor which plays a crucial role in the repair of DNA double-strand breaks, and its abnormality is responsible for hereditary ovarian cancer syndrome. It has recently been reported that reduced expression of BRCA1 is also common in sporadic ovarian carcinoma via its promoter hypermethylation, and that ovarian carcinoma patients negative for BRCA1 expression showed favorable prognosis. To address if BRCA1 expression plays a role in the chemotherapeutic response, we analyzed the effect of BRCA1 suppression on the sensitivity to cisplatin and paclitaxel in ovarian cancer cells. Specific siRNA for BRCA1 gene was transfected into 3 ovarian cancer cell lines with various p53 status. Reduced expression of BRCA1 by transfection of BRCA1-siRNA resulted in a 5.3-fold increase in sensitivity to cisplatin in p53-wild A2780 cells, but not in p53-mutated A2780/CDDP and p53-deleted SKOV3 cells. Regarding the sensitivity to paclitaxel, BRCA1 suppression caused no significant changes in all the 3 cell lines. For ionizing radiation sensitivity, BRCA1 suppression also showed a significant higher sensitivity in A2780 cells. Growth curve and cell cycle analyses showed no significant differences between BRCA1-siRNA-transfected A2780 cells and control cells. However, cisplatin treatment under suppression of BRCA1 showed a significantly increased apoptosis along with up-regulation of p53 and p21 in A2780 cells. Accordingly, reduced expression of BRCA1 enhances the cisplatin sensitivity and apoptosis via up-regulation of p53 and p21, but does not affect the paclitaxel sensitivity. Expression of BRCA1 might be an important biomarker for cisplatin resistance in ovarian carcinoma

Laparoscopic Splenectomy Using a Low-pressure Pneumoperitoneum for the Treatment of Immune Thrombocytopenic Purpura During Pregnancy : A Case Report

Article信州医学雑誌 62(6):441-446(2014)journal articl

Predicting the Route of Delivery in Women with Low-Lying Placenta Using Transvaginal Ultrasonography: Significance of Placental Migration and Marginal Sinus

Background/Aims: To examine the significance of placental migration and the presence of a placental marginal sinus to predict the eventual route of delivery in low-lying placenta. Methods: 49 women with a low-lying placenta after 30 weeks' gestation were studied. The distance between the internal os and leading edge of the placenta was measured weekly using transvaginal ultrasonography until 37 weeks' gestation. The relationship between the rate of placental migration, the presence of a placental marginal sinus and the eventual mode of delivery was investigated. Results: Although the cesarean section rate was 56.3% (9/16) in the 'slow' migration (0-2.0 mm/week) group, no patient (0/33) in the 'fast' (>2.0 mm/week) migration group underwent a cesarean section (p<0.01). The cesarean section rate was 71.4% (5/7) in patients with a placental marginal sinus, significantly greater than the rate of 9.5% (4/42) in patients without a marginal sinus (p<0.01). Conclusion:A decreased rate of placental migration until 37 weeks' gestation and the presence of a placental marginal sinus were associated with subsequent cesarean delivery because of antepartum vaginal bleeding. These parameters may be useful for predicting the route of delivery in women with a low-lying placenta.ArticleGYNECOLOGIC AND OBSTETRIC INVESTIGATION. 73(3):217-222 (2012)journal articl

Laser-captured microdissection-microarray analysis of the genes involved in endometrial carcinogenesis: stepwise up-regulation of lipocalin2 expression in normal and neoplastic endometria and its functional relevance

Endometrial carcinoma often arises from normal endometrial glandular cells via a precursor, atypical endometrial hyperplasia. However, the genetic changes involved in this carcinogenetic process are not fully understood. Differentially expressed genes were selected from glandular cells of normal proliferative-phase endometria, atypical endometrial hyperplasia, and endometrial carcinoma using laser-captured microdissection and microarray. The microarray analysis revealed a total of 51 genes to be up-regulated and 23 genes to be down-regulated in neoplastic endometrial epithelia. We focused on lipocalin2 (LCN2), which showed the largest magnitude of up-regulation. Immunostaining for lipocalin2 confirmed a stepwise increase in its expression in endometrial hyperplasia and carcinoma. In addition, elevated expression of lipocalin2 was correlated with the poor outcome of endometrial carcinoma patients. The subcellular distribution of lipocalin2 was both cytoplasmic and nuclear, despite reports that lipocalin2 is a secretory protein. Treatment of endometrial carcinoma cells with 5-azacytidine increased the expression of lipocalin2, suggesting the expression to be controlled by methylation of the promoter. The forced expression of lipocalin2 resulted in the enhanced cell proliferation and invasion in vitro. The expression of lipocalin2 increased with the endometrial carcinogenesis, and accumulation of the protein conferred biological aggressiveness to endometrial carcinoma cells. These results suggest lipocalin2 to be a novel target in the treatment of endometrial carcinoma.ArticleHUMAN PATHOLOGY. 42(9):1265-1274 (2011)journal articl

A Case of Vaginal Varices that Caused Massive Bleeding after Vaginal Delivery

Article信州医学雑誌 64(1):35-39 (2016)journal articl

Placental Mesenchymal Dysplasia: Chronological Observation of Placental Images during Gestation and Review of the Literature

Placental mesenchymal dysplasia (PMD) is characterized by multiple hypoechoic vesicles which are similar to molar changes in the placenta; however, the process of such morphological changes of PMD during pregnancy has not been fully understood. We performed a review of all PMD cases published in English and identified 49 articles including 110 cases. With regard to the gestational age at which the multicystic pattern was seen, approximately 70% of cases were diagnosed at 13-20 weeks of gestation. Another characteristic feature of PMD is varicose dilation of fetal chorionic vessels. As many as 90% of cases were diagnosed as placenta with dilated fetal chorionic vessels in the third trimester. We also report a case of PMD which was found at 10 weeks of gestation according to ultrasonic molar patterns. Serial observations of the placenta using ultrasound and magnetic resonance imaging revealed that multicystic lesions became smaller after 23 weeks. In contrast, dilated placental vessels on the fetal side became apparent at 38 weeks. The present review highlights that placental vesicular lesions of PMD may precede dilation of fetal chorionic vessels during pregnancy. It also indicates the potential of a gradual reduction in size of PMD's placental vesicular lesions by serial study of placental images.ArticleGYNECOLOGIC AND OBSTETRIC INVESTIGATION. 75(4):217-223 (2013)journal articl

Fetal Goitrous Hypothyroidism due to Maternal Thyroid Stimulation-Blocking Antibody: A Case Report

Most fetal goitrous hypothyroidisms are reportedly caused by the maternal use of an antithyroid drug or fetal dyshormonogenesis. However, fetal goitrous hypothyroidism due to the transplacental passage of maternal thyroid stimulation-blocking antibody (TSBAb) is extremely rare. A woman at 28 weeks of gestation was found to have a fetal goiter by ultrasonography. Because the maternal serum showed hypothyroidism with an elevated titer of TSBAb, levothyroxine sodium was administered. The patient delivered a male infant, 3,412 g, with a goiter at term. Umbilical blood revealed primary hypothyroidism with increased TSBAb, and the infant was given levothyroxine sodium. After a month, neonatal thyroid function and TSBAb levels became normal. Attention should be paid to possible fetal hypothyroidism when a fetal goiter is observed to avoid impaired mental development of the neonate.ArticleFETAL DIAGNOSIS AND THERAPY. 28(4):220-224 (2010)journal articl

Placental Mesenchymal Dysplasia: Chronological Observation of Placental Images during Gestation and Review of the Literature

Placental mesenchymal dysplasia (PMD) is characterized by multiple hypoechoic vesicles which are similar to molar changes in the placenta; however, the process of such morphological changes of PMD during pregnancy has not been fully understood. We performed a review of all PMD cases published in English and identified 49 articles including 110 cases. With regard to the gestational age at which the multicystic pattern was seen, approximately 70% of cases were diagnosed at 13-20 weeks of gestation. Another characteristic feature of PMD is varicose dilation of fetal chorionic vessels. As many as 90% of cases were diagnosed as placenta with dilated fetal chorionic vessels in the third trimester. We also report a case of PMD which was found at 10 weeks of gestation according to ultrasonic molar patterns. Serial observations of the placenta using ultrasound and magnetic resonance imaging revealed that multicystic lesions became smaller after 23 weeks. In contrast, dilated placental vessels on the fetal side became apparent at 38 weeks. The present review highlights that placental vesicular lesions of PMD may precede dilation of fetal chorionic vessels during pregnancy. It also indicates the potential of a gradual reduction in size of PMD's placental vesicular lesions by serial study of placental images.ArticleGYNECOLOGIC AND OBSTETRIC INVESTIGATION. 75(4):217-223 (2013)journal articl

Predicting the Route of Delivery in Women with Low-Lying Placenta Using Transvaginal Ultrasonography: Significance of Placental Migration and Marginal Sinus

Background/Aims: To examine the significance of placental migration and the presence of a placental marginal sinus to predict the eventual route of delivery in low-lying placenta. Methods: 49 women with a low-lying placenta after 30 weeks' gestation were studied. The distance between the internal os and leading edge of the placenta was measured weekly using transvaginal ultrasonography until 37 weeks' gestation. The relationship between the rate of placental migration, the presence of a placental marginal sinus and the eventual mode of delivery was investigated. Results: Although the cesarean section rate was 56.3% (9/16) in the 'slow' migration (0-2.0 mm/week) group, no patient (0/33) in the 'fast' (>2.0 mm/week) migration group underwent a cesarean section (p<0.01). The cesarean section rate was 71.4% (5/7) in patients with a placental marginal sinus, significantly greater than the rate of 9.5% (4/42) in patients without a marginal sinus (p<0.01). Conclusion:A decreased rate of placental migration until 37 weeks' gestation and the presence of a placental marginal sinus were associated with subsequent cesarean delivery because of antepartum vaginal bleeding. These parameters may be useful for predicting the route of delivery in women with a low-lying placenta.ArticleGYNECOLOGIC AND OBSTETRIC INVESTIGATION. 73(3):217-222 (2012)journal articl

Fetal Goitrous Hypothyroidism due to Maternal Thyroid Stimulation-Blocking Antibody: A Case Report

Most fetal goitrous hypothyroidisms are reportedly caused by the maternal use of an antithyroid drug or fetal dyshormonogenesis. However, fetal goitrous hypothyroidism due to the transplacental passage of maternal thyroid stimulation-blocking antibody (TSBAb) is extremely rare. A woman at 28 weeks of gestation was found to have a fetal goiter by ultrasonography. Because the maternal serum showed hypothyroidism with an elevated titer of TSBAb, levothyroxine sodium was administered. The patient delivered a male infant, 3,412 g, with a goiter at term. Umbilical blood revealed primary hypothyroidism with increased TSBAb, and the infant was given levothyroxine sodium. After a month, neonatal thyroid function and TSBAb levels became normal. Attention should be paid to possible fetal hypothyroidism when a fetal goiter is observed to avoid impaired mental development of the neonate.ArticleFETAL DIAGNOSIS AND THERAPY. 28(4):220-224 (2010)journal articl