Faculty Profiles - NAKAMURA Keiichiro

Papers - NAKAMURA Keiichiro

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CD63 as a potential biomarker for patients with ovarian cancer. International journal

Keiichiro Nakamura, Naoyuki Ida, Akira Hirasawa, Kazuhiro Okamoto, Thuy Ha Vu, Dao Thi Hai Ly, Hisashi Masuyama

European journal of obstetrics, gynecology, and reproductive biology 306 87 - 93 2025.1

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Exosomes play an important role in regulating physiological processes and mediating the systemic dissemination of various types of cancer. We investigated the association of exosomal tetraspanins CD9, CD63, and CD81 in patients with ovarian cancer (OC). MATERIAL AND METHODS: We measured the plasma tetraspanins CD9, CD63, and CD81 by enzyme-linked immunosorbent assay in 91 patients who underwent treatment for OC between April 2018 and March 2024. Additionally, we analyzed clinical pathologic factors, chemotherapy response, and prognosis. RESULTS: In terms of stages, CD63 expression was significantly higher in patients with stage IV compared to those with stage I OC (p = 0.003). In terms of histological type, CD63 expression was significantly higher in high-grade serous carcinoma (HGSC) than in clear cell carcinoma (CCC) with OC (p = 0.009). Furthermore, CD63 levels were significantly higher in advanced-stage, HGSC than in patients with early-stage, non-HGSC and early-stage, HGSC OC (p = 0.045 and p = 0.002, respectively). In the Neoadjuvant chemotherapy (NAC) of 12 patients with OC assessed as having either a partial response (PR) or complete response (CR), CD63 was significantly decreased (p = 0.043), whereas perforin was significantly increased (p = 0.001). In the NAC of 16 patients with OC, CD63 of the response rate to chemotherapy tended to differ between the progressive disease (PD) and PR/CR groups (p = 0.056). A moderate inverse correlation was observed between CD63 and perforin levels (R = 0.638, R2 = 0.428, p = 0.008). CONCLUSIONS: CD63 could be a potential biomarker for all types of OC patients.

DOI： 10.1016/j.ejogrb.2025.01.011

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Declining Prevalence of Human Papillomavirus Co-Infections Among Young Japanese Women With Cervical Cancer and Its Precursors. Reviewed International journal

Eri Yoshiizumi, Mamiko Onuki, Iwao Kukimoto, Fumiaki Takahashi, Tomoya Matsui, Kyoko Hamasaki, Hiroyuki Kanao, Ai Nio, Hideaki Yahata, Mayuko Goda, Takanori Yokoyama, Tsuyoshi Hisa, Kazuto Tasaki, Yuri Tenjimbayashi, Haruya Saji, Wataru Kudaka, Yuji Takei, Shogo Shigeta, Takeshi Motohara, Hiroko Matsumiya, Keiichiro Nakamura, Hiroyuki Yoshida, Mitsuya Ishikawa, Junzo Hamanishi, Hidekatsu Nakai, Mayuyo Mori-Uchino, Yasuyuki Hirashima, Akihiko Sekizawa, Hiroyuki Yoshikawa, Nobuo Yaegashi, Koji Matsumoto

Journal of medical virology 96 ( 12 ) e70096 2024.12

Language：English Publishing type：Research paper (scientific journal)

Co-infections with human papillomavirus (HPV) of multiple genotypes mainly occur due to increased sexual activity. To address the prevalence and trend of HPV co-infections in Japan, HPV-type-specific data from Japanese women (n = 8128) aged < 40 years and newly diagnosed with cervical abnormalities at 24 hospitals between 2012 and 2023 were analyzed. These included cervical intraepithelial neoplasia grade 1/2 (CIN1/2, n = 2745), CIN3/adenocarcinoma in situ (AIS) (n = 3953), and invasive cervical cancer (ICC, n = 1430). For women enrolled in this study since 2019, information on sexual behaviors was collected via a self-administered questionnaire. Time-trend analyses by disease category showed significant declines in the prevalence of multiple HPV infections in CIN1/2 (49.1%-38.3%, ptrend = 0.0004), CIN3/AIS (44.7%-31.5%, ptrend = 0.0002), and ICC (26.7%-10.5%, ptrend < 0.0001) during the last decade. When these data were analyzed separately for women aged 20-29 and 30-39 years, similar declining trends were observed in each disease category. Using data from 2111 women for whom information on sexual history was available, the number of sexual partners was strongly associated with increased multiple HPV infections (p < 0.0001). In conclusion, the declining prevalence of HPV co-infections in cervical cancer and its precursors may reflect a decrease in sexual activity among Japanese women of reproductive age.

DOI： 10.1002/jmv.70096

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ADAR1 could be a potential diagnostic target for intrauterine infection patients. International journal

Keiichiro Nakamura, Kunitoshi Shigeyasu, Thuy Ha Vu, Jota Maki, Kazuhiro Okamoto, Hisashi Masuyama

Scientific reports 14 ( 1 ) 29419 - 29419 2024.11

Language：English Publishing type：Research paper (scientific journal)

Intrauterine infection (IUI) is mainly an ascending infection in which vaginal and cervical pathogens ascend to the uterus and can affect the fetus. Until now, there is still no effective diagnostic biomarker for IUI, such as chorioamnionitis (CAM) and funisitis (FUN). Deoxyribonucleic acid (DNA)/Ribonucleic acid (RNA) editing molecules such as apolipoprotein-B mRNA-editing complex (APOBEC) 3 families and Adenosine deaminase family acting on RNA (ADAR)1 were examined in chorioamniotic membranes and umbilical cord of 83 patient samples. Furthermore, Ureaplasma parvum induced ADAR1 was investigated in human HTR-8/SVneo EVT cell line. ADAR1 had a significantly higher area under the curve (AUC) (0.721 and 0.745) than other APOBEC3s or cytokines in CAM and FUN patients. In vitro, ureaplasma parvum was demonstrated to activate ADAR1 (p = 0.025) and reduce RIG-I, IRF3, IFN-[Formula: see text], and IFN-β expression in EVT cell line (p = 0.005, p = 0.010, p < 0.001, and p = 0.018, respectively). High expression of ADAR1 was strongly associated with CAM and FUN patients (multivariate analyses; p = 0.035 and p = 0.002). ADAR1 could be a potential diagnostic target for IUI, such as CAM and FUN patients.

DOI： 10.1038/s41598-024-81097-4

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Lymphadenectomy and chemotherapy are effective treatments for patients with 2023 international federation of gynecology and obstetrics stage IIC-high risk endometrial cancer in Japan.

Yoshinori Tani, Keiichiro Nakamura, Masae Yorimitsu, Noriko Seki, Mie Nakanishi, Hironori Itou, Miyuki Shimizu, Dan Yamamoto, Etsuko Takahara, Hisashi Masuyama

International journal of clinical oncology 2024.11

Language：English Publishing type：Research paper (scientific journal)

BACKGROUND: In early-stage endometrial cancer (EC), the treatment of aggressive histological subtypes (endometrioid carcinoma grade 3, serous carcinoma, clear-cell carcinoma, undifferentiated carcinoma, mixed carcinoma, and carcinosarcoma) is controversial. We aimed to investigate the treatment of patients with International Federation of Gynecology and Obstetrics (FIGO) stage IC and stage IIC EC according to the 2023 classification. METHODS: We retrospectively identified patients with FIGO 2023 stage IC, IIC-intermediate risk (IIC-I), and IIC-high risk (IIC-H) EC who underwent adjuvant therapy or observation after surgery at eight medical institutions from 2004 to 2023. Progression-free survival (PFS) and overall survival (OS) were evaluated using Kaplan-Meier estimates and univariate and multivariate analyses. RESULTS: The PFS and OS were significantly worse in patients with FIGO 2023 stage IIC-H EC than in those with FIGO 2023 stage IIC-I EC (PFS: p = 0.008 and OS: p = 0.006). According to the FIGO 2023 stage IIC-H classification, lymphadenectomy and chemotherapy resulted in better prognoses regarding both PFS and OS (p < 0.001 for both) than other treatments. Our findings suggest that lymphadenectomy and chemotherapy effectively reduced vaginal stump and lymph node metastases in FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.008, respectively). Furthermore, in the multivariate analysis, not undergoing lymphadenectomy or chemotherapy were independent predictors of recurrence and poor prognoses in patients with FIGO 2023 stage IIC-H EC (p < 0.001 and p = 0.031, respectively). CONCLUSION: Lymphadenectomy and chemotherapy resulted in better prognoses regarding both recurrence and survival in patients with FIGO 2023 stage IIC high-risk EC.

DOI： 10.1007/s10147-024-02647-4

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Apolipoprotein-B mRNA-editing complex 3B could be a new potential therapeutic target in endometriosis. International journal

Thuy Ha Vu, Keiichiro Nakamura, Kunitoshi Shigeyasu, Chiaki Kashino, Kazuhiro Okamoto, Kotaro Kubo, Yasuhiko Kamada, Hisashi Masuyama

Scientific reports 14 ( 1 ) 24968 - 24968 2024.10

Language：English Publishing type：Research paper (scientific journal)

This study investigated the correlation of Apolipoprotein-B mRNA-editing complex 3B (APOBEC3B) expression with hypoxia inducible factor 1α (HIF-1α), Kirsten rat sarcoma virus (KRAS) and phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA) in endometriosis patients, and the inhibitory effects of APOBEC3B knockdown in a human endometriotic cell line. Here, APOBEC3B, HIF-1α, KRAS, and PIK3CA were examined in patients with and without endometriosis using reverse transcription polymerase chain reaction (RT-PCR). The apoptosis, cell proliferation, invasion, migration, and biological function of APOBEC3B knockdown were explored in 12Z immortalized human endometriotic cell line. We observed APOBEC3B, HIF-1α, KRAS and PIK3CA expressions were significantly higher in endometriosis patients (p < 0.001, p < 0.001, p = 0.029, p = 0.001). Knockdown of APOBEC3B increased apoptosis, which was 28.03% and 22.27% higher than in mock and control siRNA samples, respectively. APOBEC3B knockdown also decreased PIK3CA expression and increased Caspase 8 expression, suggesting a potential role in the regulation of apoptosis. Furthermore, knockdown of APOBEC3B significantly inhibited cell proliferation, invasion, and migration compared to mock and control siRNA. (Cell proliferation: mock: p < 0.001 and control siRNA: p = 0.049. Cell invasion: mock: p < 0.001 and control siRNA: p = 0.029. Cell migration: mock: p = 0.004, and control siRNA: p = 0.014). In conclusion, this study suggests that APOBEC3B may be a new potential therapeutic target for endometriosis.

DOI： 10.1038/s41598-024-76589-2

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当院で施行した婦人科癌のがん遺伝子パネル検査の実施状況と課題

依田尚之, 長尾昌二, 谷岡桃子, 杉原花子, 谷佳紀, 白河伸介, 松岡敬典, 原賀順子, 小川千加子, 中村圭一郎, 増山寿, 平沢晃

日本癌治療学会学術集会抄録集 62回 P54 - 1 2024.10

婦人科がん患者の医療機関への就労相談は,有効な職場復帰のカギとなる

中村圭一郎, 谷佳紀, 大石恵一, 三苫智裕, 依田尚之, 樫野千明, 牧尉太, 光井崇, 鎌田泰彦, 増山寿

日本女性医学学会雑誌 32 ( 1 ) 125 - 125 2024.10

帝王切開後の子宮創部菲薄化予防に対するBarbed suturesの効果多施設共同ランダム化比較試験

牧尉太, 三苫智裕, 大石恵一, 中村圭一郎, 鎌田泰彦, 山本暖, 山本梨沙, 玉田隆, 河西邦浩, 増山寿

日本女性医学学会雑誌 32 ( 1 ) 131 - 131 2024.10

婦人科がん患者の長期治療は職場復帰に影響を与える

谷佳紀, 中村圭一郎, 坂田周治郎, 大石恵一, 三苫智裕, 依田尚之, 樫野千明, 牧尉太, 光井崇, 鎌田泰彦, 増山寿

日本女性医学学会雑誌 32 ( 1 ) 109 - 109 2024.10

妊娠関連腰痛・骨盤痛を有する妊婦へ運動指導を行うと疼痛改善効果がみられる

大石恵一, 牧尉太, 三苫智裕, 坂田周治郎, 中村圭一郎, 増山寿

日本女性医学学会雑誌 32 ( 1 ) 152 - 152 2024.10

The adenosine deaminase family acting on RNA 1 can be a useful diagnostic biomarker in chorioamnionitis. International journal

Keiichiro Nakamura, Kunitoshi Shigeyasu, Jota Maki, Eriko Eto, Hisashi Masuyama

Placenta 153 53 - 58 2024.8

Language：English Publishing type：Research paper (scientific journal)

INTRODUCTION: Chorioamnionitis (CAM) involves infection and inflammation of the chorion and amniotic membrane, but there are still no effective diagnostic biomarkers for CAM. METHODS: We investigated the correlation between RNA editing enzyme Adenosine deaminase family acting on RNA 1 (ADAR1) and CAM in chorion and amniotic membrane specimens derived from premature rupture of the membrane (PROM), CAM (pathologically diagnosed), and clinical CAM (clinically diagnosed) patients using reverse transcription polymerase chain reaction (RT-PCR). RESULTS: ADAR1 was upregulated in the chorion and amniotic membrane specimens of CAM and clinical CAM patients (p < 0.001 and p = 0.005). ADAR1 had a significantly higher area under the curve (AUC) (0.735 and 0.828) than markers of inflammation characteristics in diagnosing CAM and clinical CAM patients. ADAR1 also had significantly higher AUC (0.701 and 0.837) than clinical characteristics for CAM and clinical CAM patients. DISCUSSION: ADAR1 can be a useful diagnostic biomarker in CAM patients.

DOI： 10.1016/j.placenta.2024.05.133

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婦人科悪性手術後のアセトアミノフェン定期静脈投与に関する検討

原賀順子, 杉原花子, 谷佳紀, 白河伸介, 入江恭平, 依田尚之, 松岡敬典, 小川千加子, 鎌田泰彦, 中村圭一郎, 長尾昌二, 増山寿

日本婦人科腫瘍学会学術講演会プログラム・抄録集 66回 391 - 391 2024.7

化学療法施行中の貧血に対する静注鉄剤製剤投与に関する検討

松岡敬典, 杉原花子, 谷佳紀, 白河伸介, 入江恭平, 依田尚之, 原賀順子, 小川千加子, 鎌田泰彦, 中村圭一郎, 長尾昌二, 増山寿

日本婦人科腫瘍学会学術講演会プログラム・抄録集 66回 427 - 427 2024.7

不妊治療中に子宮内膜異型増殖症・子宮体がんと診断され妊孕性温存治療後に生児を得た2例

鎌田泰彦, 杉原花子, 谷佳紀, 白河伸介, 入江恭平, 依田尚之, 松岡敬典, 原賀順子, 光井崇, 小川千加子, 中村圭一郎, 長尾昌二, 増山寿

日本婦人科腫瘍学会学術講演会プログラム・抄録集 66回 371 - 371 2024.7

がん対策基本法前後での離職状況の検討

谷佳紀, 中村圭一郎, 杉原花子, 白河伸介, 入江恭平, 松岡敬典, 依田尚之, 原賀順子, 小川千加子, 鎌田泰彦, 長尾昌二, 増山寿

日本婦人科腫瘍学会学術講演会プログラム・抄録集 66回 324 - 324 2024.7

進行上皮性卵巣癌に対する超音波ガイド下針生検

杉原花子, 谷佳紀, 白河伸介, 入江恭平, 依田尚之, 松岡敬典, 原賀順子, 小川千加子, 鎌田泰彦, 中村圭一郎, 長尾昌二, 増山寿

日本婦人科腫瘍学会学術講演会プログラム・抄録集 66回 415 - 415 2024.7

婦人科悪性手術後のアセトアミノフェン定期静脈投与に関する検討

原賀順子, 杉原花子, 谷佳紀, 白河伸介, 入江恭平, 依田尚之, 松岡敬典, 小川千加子, 鎌田泰彦, 中村圭一郎, 長尾昌二, 増山寿

日本婦人科腫瘍学会学術講演会プログラム・抄録集 66回 391 - 391 2024.7

当科におけるリスク低減卵管卵巣摘出術後の女性ヘルスケアについての検討

川口優里香, 小川千加子, 杉原花子, 谷佳紀, 白河伸介, 入江恭平, 松岡敬典, 依田尚之, 原賀順子, 中村圭一郎, 長尾昌二, 増山寿

現代産婦人科 72 ( 2 ) 239 - 244 2024.6

Language：Japanese Publisher：中国四国産科婦人科学会

【目的】遺伝性乳癌卵巣癌(Hereditary Brest and Ovarian Cancer:HBOC)では,卵巣癌未発症者の場合,リスク低減卵管卵巣摘出術(risk reducing salpingo-oophorectomy:RRSO)が唯一の卵巣癌予防法であり,通常35～40歳で出産完了時に行うことが推奨されている。そのため,至適時期でのRRSOは,外科的閉経を招き女性ヘルスケアに影響を与える。今回我々は,当院でRRSOを行った患者の現状と今後のヘルスケアにおけるマネジメントについて検討し,課題を抽出した。【方法】2016年4月～2023年9月にRRSOを施行された66例について,年齢,BRCA1/2バリアント,乳癌既往と治療,閉経の有無,術後更年期症状の有無,女性ヘルスケアの検査と治療などの診療情報を診療録より抽出し,検討した。【成績】RRSO実施時の年齢中央値は49歳,既閉経例は48/66例(73%)であった。7例でRRSO以前に乳癌への抗癌剤治療により早発閉経をきたしていた。術後更年期症状は,閉経患者の6/48例(12%),未閉経患者の8/18例(44%)に認めたが性機能障害などに踏み込めた問診は行われていなかった。更年期症状に対して8例で漢方療法やサプリメントなどの非ホルモン療法が,2例でホルモン補充療法(Hormone Replacement Therapy:HRT)が使用された。術後骨粗鬆症検査は16例で行われ,4例で薬物療法を要した。この4例はいずれも乳癌治療により閉経をした症例で,閉経年齢中央値は39.5歳であった。【結論】本邦のRRSO症例の多くは乳癌治療やそれに伴う閉経を経験しており,潜在的に女性ヘルスケアを必要としているが,その提供は未だ不十分である。適切に女性ヘルスケアを提供するためのシステムづくりが今後の課題と考えられた。(著者抄録)

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腫瘍の自然脱落により診断に至った子宮腺肉腫の一例

田中佑衣, 依田尚之, 白河伸介, 岡本和浩, 松岡敬典, 原賀順子, 小川千加子, 中村圭一郎, 長尾昌二, 増山寿

現代産婦人科 72 ( 2 ) 333 - 336 2024.6

Language：Japanese Publisher：中国四国産科婦人科学会

子宮腺肉腫は良性上皮性成分と肉腫成分から構成される上皮性・間葉性混合腫瘍で,子宮悪性腫瘍の約0.5%未満,肉腫の約5%を占める稀な疾患である。今回,我々は自然脱落した腫瘍組織から診断に至った子宮腺肉腫の一例を経験したので報告する。症例は69歳,2妊2産。不正性器出血を主訴に前医を受診し,子宮内膜ポリープの腟内脱出が疑われた。子宮内膜組織診で悪性所見を認めなかったが,MRIにて子宮体癌の可能性を指摘され,当科紹介となった。初診2日後,自宅にて中等量の性器出血と腟外への腫瘤の脱出を認め,緊急入院となった。入院中に手拳大の暗赤色腫瘤が自然脱落し,病理組織検査にて凝固壊死を伴う子宮腺肉腫と診断した。子宮腺肉腫IA期相当に対して腹式単純子宮全摘出術,両側付属器摘出術を施行し,術後病理学的診断は子宮腺肉腫IA期(pT1aNX)であった。術後補助療法は行わず,外来にて定期検診を施行しているが明らかな再発を認めない。子宮腺肉腫は主症状として不正性器出血を認めるが,術前の画像診断や組織診の正診率は低く,良性疾患との鑑別が困難である。不正性器出血や子宮口からの腫瘤脱出を伴う再発性のポリープ様病変を認めた際は,本疾患を鑑別に挙げることが重要である。(著者抄録)

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当科におけるリスク低減卵管卵巣摘出術後の女性ヘルスケアについての検討

川口優里香, 小川千加子, 杉原花子, 谷佳紀, 白河伸介, 入江恭平, 松岡敬典, 依田尚之, 原賀順子, 中村圭一郎, 長尾昌二, 増山寿

現代産婦人科 72 ( 2 ) 239 - 244 2024.6

Language：Japanese Publisher：中国四国産科婦人科学会

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Papers - NAKAMURA Keiichiro