信大医学部研究紹介2021(英語版)_プレス品質
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37Discovering new molecular targets!Gynecologic Cancer GroupGynecologic Cancer Group((Chief: Associate Prof. Tsutomu MiyamotoChief: Associate Prof. Tsutomu Miyamoto))Obstetrics and GynecologySummary of ActivityWe are conducting research to elucidate the genetic and biological mechanisms responsible for endometrial cancer (EMC) and ovarian cancer associated with endometriosis (OC-EMsis). We found that SIRT1, a well-known longevity gene, and LCN2, which is involved in iron transportation, are factors that enhance chemoresistance and accelerate the generation and progression of EMC and OC-Emsis (Fig. 2). Hence, we are continuing our research with the aim of de-veloping novel therapeutic methods that target these factors. We also conduct innovative research at our laboratory. Estrogen has commonly been regarded as a facilitator of endometrial carcinogenesis; however, we previously reported that estradiol may inhibit the generation of EMC. Furthermore, we clarified the rela-tionship between minimal deviation adenocarcinoma (MDA) and lobular endocer-vical glandular hyperplasia (LEGH), a benign lesion similar to MDA, and are the first to suggest a preoperative differential diagnosis method for these diseases.・Development of novel SIRT1-targeted therapy・Development of novel LCN2-targeted therapy・Development of novel CCNA-targeted therapy・Discovery of factors associated with the carcinogenesis of LEGHWe hope that our research results lead to the development of new preventive or therapeutic methods. Our aim is to reduce the incidence and improve the treatment outcomes of these cancers, while ensuring the preservation of fertility. After graduating and obtaining a Ph.D. degree, foreign students have returned to their own country or worked in the USA as postdoctoral fellows. Research subjectOutlook for researchOutlook for students after graduationMembers of the Gynecologic Cancer GroupSIRT1 knock-down by siRNA signifi-cantly reduced the proliferation of ES2 cells. (From Fig. 2 in Transl Oncol. 2017; 10: 621-631.)Dr. David H. Mvunta was a foreign graduate student from Tanzania (from 2013 to 2017). He worked hard and obtained a Ph.D. We were happy to work with him. The placenta is a mysterious organPlacenta GroupPlacenta Group((Chief: Senior Assistant Prof. Norihiko KikuchiChief: Senior Assistant Prof. Norihiko Kikuchi))Obstetrics and GynecologySummary of ActivityThe placenta is involved in not only the exchange of oxygen, nutrients, and waste, but also in hormone production and immunity. These functions affect fetal growth and the maintenance of pregnancy, but have not yet been elucidat-ed in detail. The insufficient invasion of extravillous trophoblasts (EVT) to the myometrium during placental formation in early pregnancy is a major cause of hypertensive disorders of pregnancy (HDP) and intrauterine growth restriction (IUGR), which significantly impair maternal and fetal health. Therefore, we focus on factors that regulate the invasion of EVT. We previously reported that LCN2, an iron transporter, promoted the invasion of EVT. Furthermore, among various biologically active substances secreted from the placenta, such as hormones, we have investigated NRG1 as a factor promoting fetal lung maturation. We also examined the senescence of trophoblastic cells in the placenta, which may regu-late gestational age in approximately 280 days.・Investigation of the effects of LCN2 and LCN2-related factors on EVT・Research on the mechanisms responsible for placental aging・Investigation of the utility of NRG1 as a diagnostic marker for fetal lung maturationWe hope that our research results lead to the establishment of screening and prevention methods for high-risk cases of HDP and IUGR. Our research results may lead to improve-ments in neonatal prognoses by establishing preterm birth prediction and prevention meth-ods and promoting fetal lung maturation.After graduating and obtaining a Ph.D. degree, foreign students have returned to their own country or worked in the USA as postdoctoral fellows.Research subjectOutlook for researchOutlook for students after graduationMembers of the Placenta GroupCell cultures are a basic experi-mental technique that is indispens-able for functional analyses. Early placental tissue immunostained by CK7, a marker for EVT, showed the inltration of EVT.

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