Masuda, Kenta

写真a

Affiliation

School of Medicine, Department of Obstetrics and Gynecology (Shinanomachi)

Position

Instructor

 

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Papers 【 Display / hide

  • MEK inhibition suppresses metastatic progression of KRAS-mutated gastric cancer.

    Yamasaki J, Hirata Y, Otsuki Y, Suina K, Saito Y, Masuda K, Okazaki S, Ishimoto T, Saya H, Nagano O

    Cancer science (Cancer Science)   2021.12

    ISSN  1347-9032

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    Metastatic progression of tumors is driven by genetic alterations and tumor-stroma interaction. To elucidate the mechanism underlying the oncogene-induced gastric tumor progression, we have developed an organoid-based model of gastric cancer from GAstric Neoplasia (GAN) mice, which express Wnt1 and the enzymes COX2 and microsomal prostaglandin E synthase 1 in the stomach. Both p53 knockout (GAN-p53KO) organoids and KRASG12V-expressing GAN-p53KO (GAN-KP) organoids were generated by genetic manipulation of GAN mouse-derived tumor (GAN wild-type [WT]) organoids. In contrast with GAN-WT and GAN-p53KO organoids, which manifested Wnt addiction, GAN-KP organoids showed a Wnt-independent phenotype and the ability to proliferate without formation of a Wnt-regulated three-dimensional epithelial architecture. After transplantation in syngeneic mouse stomach, GAN-p53KO cells formed only small tumors, whereas GAN-KP cells gave rise to invasive tumors associated with the development of hypoxia as well as to liver metastasis. Spatial transcriptomics analysis suggested that hypoxia signaling contributes to the metastatic progression of GAN-KP tumors. In particular, such analysis identified a cluster of stromal cells located at the tumor invasive front that expressed genes related to hypoxia signaling, angiogenesis, and cell migration. These cells were also positive for phosphorylated extracellular signal-regulated kinase (ERK), suggesting that mitogen-activated protein kinase (MAPK) signaling promotes development of both tumor and microenvironment. The MEK (MAPK kinase) inhibitor trametinib suppressed the development of GAN-KP gastric tumors, formation of a hypoxic microenvironment, tumor angiogenesis, and liver metastasis. Our findings therefore establish a rationale for application of trametinib to suppress metastatic progression of KRAS-mutated gastric cancer.

  • Meningitis caused by <i>Listeria monocytogenes</i> in a locally advanced cervical cancer patient with pyometra: A case report.

    Matoba Y, Nishio H, Sekiguchi K, Uno S, Masuda K, Hiramatsu M, Takahashi M, Oishi M, Uwamino Y, Uchida S, Daté Y, Morisada T, Banno K, Nakahara J, Aoki D

    Gynecologic oncology reports (Gynecologic Oncology Reports)  37   100799 2021.08

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    Locally advanced cervical cancer occasionally induces pyometra, but there have been no reports of meningitis where pyometra is the cause of infection. Here, we report a case of Listeria monocytogenes meningitis related to pyometra during concurrent chemoradiotherapy (CCRT) in a cervical cancer patient. The patient, a 77-year-old woman, was diagnosed with Stage IIB (FIGO 2018) cervical adenocarcinoma, and CCRT was initiated. Pyometra was exacerbated during CCRT, and after her first brachytherapy, she presented at our hospital with fever and decreased consciousness level. After admission to the Intensive Care Unit, the patient lost consciousness and experienced frequent seizures; tracheal intubation was required. Whole-body computed tomography revealed pyometra; therefore, transvaginal removal of the abscess was performed. Laboratory tests and vital signs indicated septic shock, and meropenem was administered. L. monocytogenes was detected in the abscess from the uterine cavity and the blood cultures on the third day of hospitalization. A lumbar puncture was performed on the same day to investigate whether the patient had meningitis. A FilmArray meningitis/encephalitis panel test of the spinal fluid revealed L. monocytogenes. After the diagnosis of meningitis with L. monocytogenes, ampicillin and gentamicin were started, and the blood test results gradually improved. Five months after the initial episode, her consciousness recovered, however she still received mechanical ventilatory support. L. monocytogenes infections can occur in patients undergoing chemotherapy, even without the use of steroids or immunosuppressive agents. In cases with pyometra, intrauterine manipulation can increase the risk of severe infection.

  • Adipocyte-like signature in ovarian cancer minimal residual disease identifies metabolic vulnerabilities of tumor-initiating cells.

    Artibani M, Masuda K, Hu Z, Rauher PC, Mallett G, Wietek N, Morotti M, Chong K, KaramiNejadRanjbar M, Zois CE, Dhar S, El-Sahhar S, Campo L, Blagden SP, Damato S, Pathiraja PN, Nicum S, Gleeson F, Laios A, Alsaadi A, Santana Gonzalez L, Motohara T, Albukhari A, Lu Z, Bast RC Jr, Harris AL, Ejsing CS, Klemm RW, Yau C, Sauka-Spengler T, Ahmed AA

    JCI insight (American Society for Clinical Investigation)  6 ( 11 )  2021.06

    Research paper (scientific journal), Joint Work, Accepted

  • Prevalence of disease-causing genes in Japanese patients with BRCA1/2-wildtype hereditary breast and ovarian cancer syndrome

    Kaneyasu T., Mori S., Yamauchi H., Ohsumi S., Ohno S., Aoki D., Baba S., Kawano J., Miki Y., Matsumoto N., Nagasaki M., Yoshida R., Akashi-Tanaka S., Iwase T., Kitagawa D., Masuda K., Hirasawa A., Arai M., Takei J., Ide Y., Gotoh O., Yaguchi N., Nishi M., Kaneko K., Matsuyama Y., Okawa M., Suzuki M., Nezu A., Yokoyama S., Amino S., Inuzuka M., Noda T., Nakamura S.

    npj Breast Cancer (npj Breast Cancer)  6 ( 1 ) 25 - 25 2020.12

    Research paper (scientific journal), Joint Work

     View Summary

    © 2020, The Author(s). Panel sequencing of susceptibility genes for hereditary breast and ovarian cancer (HBOC) syndrome has uncovered numerous germline variants; however, their pathogenic relevance and ethnic diversity remain unclear. Here, we examined the prevalence of germline variants among 568 Japanese patients with BRCA1/2-wildtype HBOC syndrome and a strong family history. Pathogenic or likely pathogenic variants were identified on 12 causal genes for 37 cases (6.5%), with recurrence for 4 SNVs/indels and 1 CNV. Comparisons with non-cancer east-Asian populations and European familial breast cancer cohorts revealed significant enrichment of PALB2, BARD1, and BLM mutations. Younger onset was associated with but not predictive of these mutations. Significant somatic loss-of-function alterations were confirmed on the wildtype alleles of genes with germline mutations, including PALB2 additional somatic truncations. This study highlights Japanese-associated germline mutations among patients with BRCA1/2 wildtype HBOC syndrome and a strong family history, and provides evidence for the medical care of this high-risk population.

  • Retrospective evaluation of risk-reducing salpingo-oophorectomy for BRCA1/2 pathogenic variant carriers among a cohort study in a single institution.

    Kobayashi Y, Hirasawa A, Chiyoda T, Ueki A, Masuda K, Misu K, Kawaida M, Hayashi S, Kataoka F, Banno K, Kosaki K, Aoki D

    Japanese journal of clinical oncology (Japanese journal of clinical oncology)  51 ( 2 ) 213 - 217 2020.10

    Research paper (scientific journal), Joint Work,  ISSN  0368-2811

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    © The Author(s) 2020. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: journals.permission@oup.com. BACKGROUND: Risk-reducing salpingo-oophorectomy is performed for the primary prevention of ovarian cancer in patients with hereditary breast-ovarian cancer syndrome. We performed risk-reducing salpingo-oophorectomy for the first time in Japan in 2008, and we experienced 20 cases of risk-reducing salpingo-oophorectomy through 2019. In the past, the use of risk-reducing salpingo-oophorectomy in Japan was restricted because it was not covered by a Japanese National Health Insurance. Since April 2020, risk-reducing salpingo-oophorectomy has been covered by insurance for patients with breast-ovarian cancer syndrome and pre-existing breast cancer, and this surgery is expected to become more widely implemented in Japan. METHODS: To contribute to the widespread use of risk-reducing salpingo-oophorectomy in the future, we retrospectively reviewed 20 cases of risk-reducing salpingo-oophorectomy at our hospital cohort study to clarify the issues in its implementation. RESULTS: The variant genes for which risk-reducing salpingo-oophorectomy was indicated were BRCA1 and BRCA2 in 13 (65%) and 7 patients (35%), respectively. The median age at which risk-reducing salpingo-oophorectomy was performed was 49 years (range, 38-58), 13 patients (65%) had gone through menopause, and 16 patients (80%) had a history of breast cancer. Of the five patients (25%) with vasomotor symptoms, four received Chinese medicine, and only one received hormone replacement therapy. Occult cancer was detected in the removed ovaries in two patients (10%), although no postoperative peritoneal carcinogenesis has been observed to date. CONCLUSIONS: Women who paid for risk-reducing salpingo-oophorectomy out of pocket were older than the recommended age at which the procedure should be performed, and this may explain the higher rate of occult cancers than previously reported. We need to perform risk-reducing salpingo-oophorectomy at the recommended age to ensure that the procedure is effective for primary prevention.

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Papers, etc., Registered in KOARA 【 Display / hide

Reviews, Commentaries, etc. 【 Display / hide

  • 当科における悪性腫瘍治療後患者へのホルモン補充療法(HRT)の有用性に関する検討

    谷本 慧子, 横田 めぐみ, 椎名 美希, 大野 あゆみ, 黒田 由香, 吉浜 智子, 千代田 達幸, 増田 健太, 西尾 浩, 仲村 勝, 山上 亘, 弟子丸 亮太, 岩田 卓, 阪埜 浩司, 青木 大輔

    日本女性医学学会雑誌 ((一社)日本女性医学学会)  29 ( 1 ) 114 - 114 2021.10

    ISSN  2185-8861

  • がん遺伝子パネル検査を通した子宮体癌におけるBRCAバリアント頻度の検討

    今枝 慶蓉, 小林 佑介, 増田 健太, 中村 康平, 四十物 絵理子, 植木 有紗, 千代田 達幸, 山上 亘, 阪埜 浩司, 西原 広史, 田中 守, 青木 大輔

    関東連合産科婦人科学会誌 ((一社)関東連合産科婦人科学会)  58 ( 3 ) 407 - 407 2021.10

    ISSN  2186-0610

  • 子宮体部漿液性癌に対するα線放出核種標識抗体の有用性に関する検討

    安康 真由香, 阪埜 浩司, 小林 佑介, 高橋 孝幸, 的場 優介, 野上 侑哉, 辻 浩介, 増田 健太, 冨永 英一郎, 長谷川 純崇, 田中 守, 青木 大輔, 放射線医学総合研究所放射線がん生物研究グループ

    日本産科婦人科学会雑誌 ((公社)日本産科婦人科学会)  73 ( 臨増 ) S - 318 2021.03

    ISSN  0300-9165

  • 卵巣漿液性癌細胞株において脂肪酸酸化阻害はオラパリブに対する感受性を増加させる

    増田 健太, Ahmed Ahmed, 永井 晋平, 小林 佑介, 冨永 英一郎, 阪埜 浩司, 田中 守, 青木 大輔

    日本産科婦人科学会雑誌 ((公社)日本産科婦人科学会)  73 ( 臨増 ) S - 485 2021.03

    ISSN  0300-9165

  • 人工知能を用いたCIN2の予後予測システムの開発のための予備的検討

    高橋 孝幸, 小林 佑介, 安康 真由香, 野上 侑哉, 辻 浩介, 増田 健太, 岩田 卓, 冨永 英一郎, 田宮 元, 阪埜 浩司, 田中 守, 青木 大輔

    日本産科婦人科学会雑誌 ((公社)日本産科婦人科学会)  73 ( 臨増 ) S - 391 2021.03

    ISSN  0300-9165

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Research Projects of Competitive Funds, etc. 【 Display / hide

  • 卵巣癌の微小残存病変に対する解析研究

    2020.04
    -
    2023.03

    MEXT,JSPS, Grant-in-Aid for Scientific Research, Grant-in-Aid for Early-Career Scientists , Principal investigator

     View Summary

    卵巣癌、特に漿液性癌は、化学療法に対する寛解率が高いものの、その後高確率で再発に至る。その事実は、化学療法後に微小残存病変が存在し、卵巣癌再発の直接的な要因となっていることを示唆している。しかしながら卵巣癌微小残存病変に対する解析方法は確立されておらず、有効な治療法はない。
    本研究では、卵巣癌再発の直接的原因である微小残存病変を治療標的とした”真の精密医療”を実現するため、化学療法前後の臨床検体を用いた網羅的遺伝子発現解析を行い、さらに卵巣癌の微小残存病変を模倣したin vitroモデルを開発を試み、新たな治療戦略を立案するための基礎データを得る。

  • 卵巣癌微小残存病変に対する癌-微小環境の相互作用に着目した新規治療法の開発

    2020.04
    -
    2021.03

    慶應義塾大学, 学事振興資金(個人研究), Principal investigator

  • 卵巣癌微小残存病変に対するシングルセル解析技術を用いた新規治療戦略の開発

    2020.04
    -
    2021.03

    慶應義塾大学医学研究助成, 坂口光洋記念慶應義塾医学振興基金, Principal investigator

  • 治療抵抗性卵巣癌の新規代謝制御機構の解明

    2017
    -
    2018

    日本学術振興会 , 海外特別研究員 , Principal investigator

  • 卵巣癌の治療抵抗性に関わる代謝特性の解明と新規治療標的の同定

    2016
    -
    2017

    文部科学省・日本学術振興会, 若手研究(B), Research grant, Principal investigator

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Courses Taught 【 Display / hide

  • LECTURE SERIES, GYNECOLOGY

    2022

  • LECTURE SERIES, GYNECOLOGY

    2021

  • 婦人科学講義

    2020