研究者詳細 - 山本　英子

論文 - 山本　英子

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*N-acetylglucosaminyltransferase V Regulates Extravillous Trophoblast Invasion through Glycosylation of alfa5beta1 integrin 査読有り

Yamamoto E, Ino K, Miyoshi E, Inamori KI, Abe A, Sumigama S, Iwase A, Kajiyama H, Shibata K, Nawa A, Kikkawa F.

Endocrinology 150 巻 ( 2 ) 頁： 990-999 2009年

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

For successful human placentation, invasion of trophoblast cells into the uterus and its associated vasculature is essential, and the regulation of this process is controlled by many factors at the fetal-maternal interface. N-acetylglucosaminyltransferase V (GnT-V) is a key enzyme that catalyzes beta1, 6-N-acetylglucosamine (beta1-6GlcNAc) branching on asparagine-linked oligosaccharides of cell proteins. GnT-V and its product, beta1-6GlcNAc, are known to regulate cellular transformation and correlate with the metastatic potential of various cancer cells. The aim of the present study was to determine whether extravillous trophoblast (EVT) expressed this molecule and examine the role of GnT-V in the regulation of human trophoblast invasion. Immunohistochemistry showed that GnT-V was strongly expressed within the cytoplasm of EVT in the anchoring villi; this expression was down-regulated in EVTs invading the decidua. Suppression of beta1-6GlcNAc glycosylation by swainsonine enhanced the migratory potential and invasive capability of both primary EVTs and the EVT cell line, HTR-8/SVneo. Down-regulation of GnT-V expression by small interfering RNA in the choriocarcinoma cell line Jar consistently enhanced the migration and invasive capacity of these cells and elevated cellular adhesion to extracellular matrix proteins, such as fibronectin and collagen type I/IV. The extent of beta1-6 branching of alpha5beta1 integrin was significantly reduced in small interfering GnT-V-transfected Jar cells compared with mock transfectants, although the expression of alpha1, alpha5, alpha6, and beta1 integrin on the cell surface was not changed. These results suggest that GnT-V is expressed in human EVT and is involved in regulating trophoblast invasion through modifications of the oligosaccharide chains of alpha5beta1 integrin.

*Ikaros is expressed in human extravillous trophoblasts and involved in their migration and invasion.

Yamamoto E, Ito T, Abe A, Sido F, Ino K, Itakura A, Mizutani S, Dovat S, Nomura S, Kikkawa F.

Molecular Human Reproduction 11 巻 ( 11 ) 頁： 825 2005年11月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

The transcriptional factor Ikaros was originally found to function as a key regulator of lymphocyte differentiation. In addition, we have reported that Ikaros regulates the human placental leucine aminopeptidase (P-LAP)/insulin-regulated aminopeptidase (IRAP) gene in choriocarcinoma trophoblastic cells, suggesting that Ikaros might be involved in placental development, while even its presence in human placenta remains undetermined. We therefore sought to clarify the location and roles of Ikaros in human placenta. Immunohistochemical analysis showed modest Ikaris expression in syncytium, and intense expression in extravillous trophoblasts (EVTs) in first trimester placenta. Western blot analysis showed that villous trophoblasts principally expressed Ikaros-2/3, while Ikaros-x (Ikx) was predominantly expressed in cultured EVTs. Furthermore, to investigate the functional role of Ikx in EVTs, the EVT cell line HTR-8/SVneo was infected with a retrovirus vector expressing the hemagglutinin (HA)-tagged dominant negative isoform Ikaros-6 (Ik6), which prevents the DNA-binding activity of Ikx. Antibody against HA showed successful transduction of Ik6 in HTR-8/SVneo cells on immunocytochemistry and Western blotting. Transduction of Ik6 significantly reduced the migratory and invasive abilities of HTR-8/SVneo cells. These results suggest that Ikx is involved in migration and invasion of EVTs in early placentation.

*Expression of N-acetylglucosaminyltransferase V in Endometrial Cancer Correlates with Poor Prognosis 査読有り

Yamamoto E, Ino K, Miyoshi E, Shibata K, Takahashi N, Kajiyama H, Nawa A, Nomura S, Nagasaka T, Kikkawa F

British Journal of Cancer 97 巻 ( 11 ) 頁： 1538-1544 2007年12月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyses beta1-6 branching of N-acetylglucosamine on asparagine-linked oligosaccharides of cell proteins. The present study aimed to investigate GnT-V expression and its prognostic significance in endometrial cancer. N-acetylglucosaminyltransferase V expression was studied by immunohistochemistry in 74 surgically resected endometrial cancers, and the staining intensity was evaluated. High GnT-V expression in tumour cells was found in 43 (58.1%) of the 74 cases, and was positively correlated with advanced patient age, histological grade, and lymph vascular space involvement. Patients with high GnT-V expression had significantly impaired overall survival and progression-free survival (PFS) (P=0.0041 and P=0.0023, respectively) compared to patients with low expression of GnT-V. On multivariate analysis, GnT-V expression was an independent prognostic factor for PFS (P=0.0364). beta1-6 branching of asparagine-linked oligosaccharides was also detected in GnT-V-positive endometrial cancer cells by leukoagglutinating phytohaemagglutinin (L(4)-PHA) staining, and the molecular size of the major glycoproteins recognised by L(4)-PHA was approximately 60-200 kDa by lectin blot analysis. These results suggested that high GnT-V expression was correlated with an unfavourable clinical outcome, and that GnT-V is involved in the malignant potential of endometrial cancer by increasing the synthesis of beta1-6 branching of asparagine-linked oligosaccharides.

*A pure nongestational choriocarcinoma of the ovary diagnosed with short tandem repeat analysis: case report and review of the literature. 査読有り

Yamamoto E, Ino K, Yamamoto T, Sumigama S, Nawa A, Nomura S, Kikkawa F.

International Journal of Gynecologic Cancer 17 巻 ( 1 ) 頁： 254-8 2007年1月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

Nongestational pure choriocarcinoma of the ovary is a very rare germ cell tumor. Except in women before menarche, determination of the origin is very difficult without genetic analysis. We present a pure nongestational choriocarcinoma arising in the left ovary of a 19-year-old woman. Following surgery, pathologic findings of the tumor demonstrated pure choriocarcinoma without combination of other germ cell tumor elements. We confirmed its nongestational origin by DNA polymorphism analysis at 15 short tandem repeat loci. Multiple courses of chemotherapy with methotrexate, etoposide, and actinomycin-D were effective for this case. DNA polymorphism analysis is useful to determine genetic origin in pure choriocarcinoma of the ovary.

Activator protein-2 impairs the invasion of a human extravillous trophoblast cell line. 査読有り

Kotani Tomomi, Iwase Akira, Ino Kazuhiko, Sumigama Seiji, Yamamoto Eiko, Hayakawa Hiromi, Nagasaka Toshiro, Itakura Atsuo, Nomura Seiji, Kikkawa Fumitaka.

Endocrinology 150 巻 ( 9 ) 頁： 4376-4385 2009年11月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

The reduced migration/invasion of extravillous trophoblasts (EVTs) is a key feature of the genesis of preeclampsia. We and others previously reported that transcriptional factors activator protein-2 (AP-2) alpha and AP-2gamma act as suppressors of tumor invasion. The present study examined the expressions of AP-2alpha and AP-2gamma in preeclamptic placenta vs. control placenta and investigated their effect on the function of EVTs. The expressions of AP-2alpha and AP-2gamma were elevated in the preeclamptic placentas in comparison with the gestational age-matched control placentas. Their expressions also increased in EVTs of the preeclamptic placentas. Thereafter, we transfected AP-2alpha or AP-2gamma into human EVT cell line, HTR-8/SVneo. The overexpression of AP-2alpha or AP-2gamma decreased the migratory and invasive abilities in HTR-8/SVneo cells. This was followed by the reduction of protease activated receptor-1 and matrix metalloproteinases and a significant induction of plasminogen activator inhibitor-1 and the tissue inhibitor of metalloproteinase-1. AP-2alpha and AP-2gamma were weakly expressed in the cultured EVTs and HTR-8/SVneo cells, whereas they were induced by TNF-alpha, which increases in preeclamptic placenta and impairs trophoblast invasion. In the presence of TNF-alpha, the invasion of the HTR-8/SVneo cells was partially restored by a blocking of AP-2 induction using small interfering RNA of AP-2. The present data suggest that AP-2 may suppress trophoblast migration and invasion, thus leading to a shallow placentation in preeclampsia.

*High expression of N-acetylglucosaminyltransferase V in mucinous tumors of the ovary. 査読有り

Takahashi Noriko, Yamamoto Eiko, Ino Kazuhiko, Miyoshi Eiji, Nagasaka Toshiro, Kajiyama Hiroaki, Shibata Kiyosumi, Nawa Akihiro, Kikkawa Fumitaka

Oncology Report 22 巻 ( 5 ) 頁： 1027-1032 2009年11月

記述言語：英語掲載種別：研究論文（学術雑誌）

N-acetylglucosaminyltransferase V (GnT-V) is an enzyme that catalyzes beta1-6 branching of N-acetylglucosamine (GlcNAc) on asparagine-linked oligosaccharides of cell proteins. The present study aimed to investigate GnT-V expression and its prognostic significance in epithelial ovarian cancer. GnT-V expression was studied by immunohistochemistry in 83 surgically resected ovarian cancers, and the staining intensity was evaluated. High GnT-V expression in cancer cells was found in 17 (20.5%) of the 83 cases, and was positively correlated with early FIGO staging. In the histological type, mucinous adenocarcinoma showed significantly strong immunostaining compared to the non-mucinous type (P<0.001). In 36 mucinous tumors, the GnT-V immunostaining score was significantly higher in cancer than in benign and borderline tumors (P<0.001). NOM-1, a human ovarian mucinous adenocarcinoma cell line, expressed strong GnT-V protein and swainsonine treatment suppressed beta1-6GlcNAc branching and reduced migration ability significantly (P<0.001). These results suggested that GnT-V might be involved in the malignant potential of mucinous ovarian cancer.

Tocilizumab inhibits interleukin-6-mediated matrix metalloproteinase-2 and -9 secretions from human amnion cells in preterm premature rupture of membranes. 査読有り

Mano Y, Shibata K, Sumigama S, Hayakawa H, Ino K, Yamamoto E, Kajiyama H, Nawa A, Kikkawa F.

Gynecol Obstet Invest. 68 巻 ( 3 ) 頁： 145-153. 2009年7月

担当区分：筆頭著者記述言語：英語掲載種別：研究論文（学術雑誌）

BACKGROUND/AIMS: In the present study, we investigated the participation of inflammatory cytokine-induced mediated matrix metalloproteinase (MMP) expressions and inhibition of interleukin (IL)-6-induced MMP secretion in amniotic epithelial cells by tocilizumab. METHODS: To investigate the role of MMP expressions, immunohistochemical staining was performed using membranes obtained from 10 patients with preterm premature rupture of membranes (PPROM) and from 10 patients who underwent a nonlabor cesarean section. We also investigated the regulation of MMP expression by inflammatory cytokines in human amnion cells. RESULTS: Immunohistochemical staining showed a significantly higher expression of MMP-2 and -9 in PPROM. Treatment of cultured WISH and primary amniotic epithelial cells with 10(-8) or 10(-7)M IL-6 or tumor necrosis factor (TNF)-alpha clearly increased the secretion of MMP-2 and -9. Treatment with 10(-8)M TNF-alpha or IL-6 significantly increased the invasion of WISH or primary amniotic epithelial cells, respectively, compared with the control. At a low concentration of 1 microg/ml, tocilizumab (anti-human IL-6 receptor monoclonal antibody) inhibited the IL-6-induced MMP secretion. CONCLUSIONS: This paper is the 1st report of tocilizumab inhibiting IL-6-induced MMP-2 and MMP-9 secretions from human amnion cells in PPROM.

Fertility-sparing operation for recurrence of uterine cervical perivascular epithelioid cell tumor 査読有り

Yamamoto E, Ino K, Sakurai M, Takigawa S, Iwase A, Kikkawa F.

Rare Tumors 頁： 72-73 2010年2月

肝転移巣の破裂による腹腔内出血を契機に診断された絨毛癌の１例査読有り

林加奈子,　山本英子,　新美薫,　近藤紳司,　稲葉智子,　井箟一彦, 吉川史隆

東海産科婦人科学会雑誌 46 巻頁： 209-212 2010年3月

7歳女児に発症した子宮原発横紋筋肉腫の1例査読有り

新美薫、山本英子、東真規子、林加奈子、近藤紳司、河合智子、井箟一彦、吉川史隆

日本婦人科腫瘍学会雑誌 28 巻 ( 4 ) 2010年10月

Factors associated with diabetes mellitus and hypertension among adults in the northern rural area, Afghanistan

Fayaz, SH; Hamajima, N; Frozanfar, MK; Hamrah, MH; Inthaphatha, S; Nishino, K; Yamamoto, E

NAGOYA JOURNAL OF MEDICAL SCIENCE 86 巻 ( 4 ) 頁： 564 - 577 2024年11月

Prognostic impact of peritoneal cytology on treating endometrial cancer using data from the Japan Society of Obstetrics and Gynecology cancer registry.

Sakai K, Yamagami W, Takahashi F, Tokunaga H, Yamamoto E, Yokoyama Y, Yoshino K, Kawana K, Nagase S

Journal of gynecologic oncology 2024年10月

Sex differences in the prevalence of metabolic syndrome and associated factors in the general population of Mongolia: A nationwide study

Byambadoo, LE; Davaakhuu, N; Surenjav, U; Norov, B; Tserennadmid, E; Inthaphatha, S; Nishino, K; Yamamoto, E

PLOS ONE 19 巻 ( 10 ) 頁： e0311320 2024年10月

Determinants of the Utilization of Recognized Traditional and Complementary Medicine Service in Malaysia: A Secondary Analysis of a Cross-Sectional Population-Based Survey 査読有り国際共著国際誌

Ng, SK; Nishino, K; Seman, Z; Inthaphatha, S; Yamamoto, E

COMPLEMENTARY MEDICINE RESEARCH 31 巻 ( 5 ) 頁： 427 - 437 2024年10月

ESTABLISHMENT OF MTX-RESISTANT CELL LINES OF CHORIOCARCINOMA AND SEARCH FOR THERAPEUTIC AGENTS BY DRUG REPOSITIONING

Nishiko, Y; Niimi, K; Yasui, Y; Yoshida, K; Nishino, K; Yamamoto, E; Kajiyama, H

PLACENTA 154 巻頁： 234 - 235 2024年9月

Factors associated with postpartum depression among Myanmar women in Yangon: A cross-sectional study 査読有り国際共著国際誌

Wyunn, KM; Wai, ZZT; Swe, KEE; Inthaphatha, S; Nishino, K; Yamamoto, E

HELIYON 10 巻 ( 13 ) 頁： e33425 2024年7月

Detailed report on the clinicopathological factors of patients with endometrial cancer in Japan: a JSOG gynecologic tumor registry-based study 査読有り国際共著国際誌

Makabe, T; Yamagami, W; Takahashi, F; Tokunaga, H; Yamamoto, E; Yokoyama, Y; Yoshino, K; Kawana, K; Nagase, S

JOURNAL OF GYNECOLOGIC ONCOLOGY 35 巻 ( 4 ) 頁： e54 2024年7月

Determinants of postpartum depression among women in Kampong Chhnang Province, Cambodia 査読有り国際共著国際誌

Guechhorng, I; Inthaphatha, S; Nishino, K; Takahashi, Y; Hamajima, N; Yamamoto, E

ARCHIVES OF PSYCHIATRIC NURSING 50 巻頁： 60 - 66 2024年6月

What inhibits "speaking up" for patient safety among healthcare workers? A cross-sectional study in Malaysia 査読有り国際共著国際誌

Kim, ARJ; Nishino, K; Bujang, MA; Zulkifli, Z; Inthaphatha, S; Yamamoto, E

HUMAN RESOURCES FOR HEALTH 22 巻 ( 1 ) 頁： 35 2024年5月

Comparison of the influenza vaccination coverage among high-risk people between the online registration system and walk-in service system in Bangkok, Thailand. 査読有り国際共著国際誌

Sairuk R, Nishino K, Inthaphatha S, Hamajima N, Yamamoto E

Nagoya journal of medical science 86 巻 ( 2 ) 頁： 252 - 261 2024年5月

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