小林 佑介 (コバヤシ ユウスケ)

Kobayashi, Yusuke

写真a

所属(所属キャンパス)

医学部 産婦人科学教室 (信濃町)

職名

助教(有期)

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  • 博士(医学), 慶應義塾, 課程, 2011年09月

 
 

論文 【 表示 / 非表示

  • Clinical management of epithelial ovarian cancer

    Kobayashi Y., Nomura H., Kataoka F., Tominaga E., Banno K., Aoki D.

    Cell Biology of the Ovary: Stem Cells, Development, Cancer, and Clinical Aspects (Cell Biology of the Ovary: Stem Cells, Development, Cancer, and Clinical Aspects)     135 - 151 2018年06月

    ISSN  9789811079405

     概要を見る

    © Springer Nature Singapore Pte Ltd 2018. Ovarian cancer has high morbidity and mortality worldwide, and its mortality is the highest among female genital cancers. Improvement in clinical outcome is an urgent issue for ovarian cancer, and clinical management including treatment has been repeatedly studied. Tumor markers such as CA125, CA19-9, and HE4 and image diagnosis using MRI, CT, PET, etc. are indispensable diagnostic aid tools. In the initial treatment, primary debulking surgery (PDS) is basically effective, but fertility preservation can be considered depending on the case. For advanced cancers, interval debulking surgery (IDS) is considered after several cycles of neoadjuvant chemotherapy (NAC). Although the combination of paclitaxel and carboplatin (TC) regimen was originally established as the standard chemotherapy for ovarian cancer regardless of tissue type, new treatments in clinical trials, including molecular-targeted therapeutic agents, are being investigated. The main treatment for recurrent cancer is chemotherapy, and sensitivity to chemotherapy based on the disease-free interval has been considered in the choice of treatment. Furthermore, in recent years, risk-reducing bilateral salpingo-oophorectomy has been undertaken to prevent the onset of hereditary breast and ovarian cancer. It is also being studied how to manage the follow-up after treatment and hormone replacement.

  • Screening for Lynch syndrome using risk assessment criteria in patients with ovarian cancer

    Takeda T., Tsuji K., Banno K., Yanokura M., Kobayashi Y., Tominaga E., Aoki D.

    Journal of Gynecologic Oncology (Journal of Gynecologic Oncology)  29 ( 3 )  2018年05月

    ISSN  20050380

     概要を見る

    © 2018, Korean Society of Gynecologic Oncology and Colposcopy. All rights reserved. Objective: Lynch syndrome is a cancer predisposition syndrome caused by germline mutation of DNA mismatch repair (MMR) genes. Lynch syndrome only causes about 0.4% of cases of ovarian cancer, which suggests that universal screening may not be cost-efficient. However, the frequency of Lynch syndrome in ovarian cancer is unclear in the Asian population. The goal of the study was to investigate a screening strategy using family history. Methods: The subjects were 129 patients with ovarian cancer. Clinical and family history were collected using a self-administered questionnaire, and Society of Gynecologic Oncology (SGO) criteria 2007 and PREMM 5 were used for risk assessment. Microsatellite instability, immunohistochemistry, and methylation of MMR genes were analyzed. Results: Of the 129 cases, 25 (19.4%) met the SGO criteria, and 4 of these 25 had MSI-high and MMR deficiency. Two cases had loss of MSH2 and MSH6, indicating MSH2 mutation, and the other two had loss of MLH1 and PMS2, including one without MLH1 methylation indicating MLH1 mutation. These results show that screening using family history can detect Lynch syndrome in 12.0% (3/25) of ovarian cancer cases. The 3 cases were positive for PREMM 5 , but negative for Amsterdam II criteria and revised Bethesda guidelines. Genetic testing in one case with MSH2 and MSH6 deficiency confirmed the diagnosis of Lynch syndrome with MSH2 mutation. Conclusion: This is the first study of screening for Lynch syndrome in ovarian cancer using clinical and family history in an Asian population. This approach may be effective for diagnosis in these patients.

  • Cost-effectiveness of surveillance and prevention strategies in BRCA1/2 mutation carriers

    Yamauchi H., Nakagawa C., Kobayashi M., Kobayashi Y., Mano T., Nakamura S., Arai M.

    Breast Cancer (Breast Cancer)  25 ( 2 ) 141 - 150 2018年03月

    ISSN  13406868

     概要を見る

    © 2017, The Japanese Breast Cancer Society. Background: Cost-effectiveness analysis is an important aspect of healthcare, including in Japan, where preventive measures for BRCA1/2 mutation carriers are not covered by health insurance. Methods: We developed Markov models in a simulated cohort of women aged 35–70 years, and compared outcomes of surveillance with risk-reducing mastectomy (RRM) at age 35, risk-reducing salpingo-oophorectomy (RRSO) at age 45, and both (RRM&RRSO). We used breast and ovarian cancer incidences and adverse event rates from the previous studies, adjuvant chemotherapy, and hormonal therapy rates from the Hereditary Breast and Ovarian Cancer Registration 2015 in Japan, mortality rates from the National Cancer Center Hospital, Japan Society of Clinical Oncology, and Ministry of Health, Labour and Welfare, and direct costs from St. Luke’s International Hospital and Keio University Hospital. We used previously published preference ratings of women without known high risk to adjust survival for quality of life. The discount rate was 2%. Results: Compared with surveillance, RRSO and RRM&RRSO were dominant (both cost-saving and more effective), and RRM was cost-effective in BRCA1 mutation carriers, while RRM and RRM&RRSO were dominant and RRSO was cost-effective in BRCA2. Among the four strategies including surveillance, RRM&RRSO and RRM were the most cost-effective in BRCA1 and BRCA2 mutation carriers, respectively. Conclusions: With quality adjustment, RRM, RRSO, and RRM&RRSO were all cost-effective preventive strategies in BRCA1/2 mutation carriers, with RRM&RRSO being the most cost-effective in BRCA1 and RRM in BRCA2. This result supports the inclusion of insurance coverage for BRCA mutation carriers in Japan.

  • SIM2l attenuates resistance to hypoxia and tumor growth by transcriptional suppression of HIF1A in uterine cervical squamous cell carcinoma

    Nakamura, K., Komatsu, M., Chiwaki, F., Takeda, T., Kobayashi, Y., Banno, K., Aoki, D., Yoshida, T. and Sasaki, H.

    Sci Rep 7 ( 1 ) 14574 2017年11月

    ISSN  2045-2322

     概要を見る

    Despite chemoradiotherapy being one of the most important modalities in advanced cervical cancer, there is a lack of both usable biomarkers to predict treatment outcome and of knowledge about the mechanism of refractoriness to the therapy. Here we identified a transcriptional factor Single-minded homolog 2 (SIM2) as an independent predictive biomarker for uterine cervical squamous cell carcinoma (CvSCC). The retrospective study showed that high expression level of SIM2 was correlated to good survival in CvSCC patients. SIM2 knockdown in CvSCC cell lines showed resistance to hypoxia with increased expression of HIF1A and its target genes. Loss of SIM2 also caused growth promotion, resistance to ROS, and radiation in 3D culture. Furthermore, SIM2 knockdown suppressed tumor growth with increased HIF-1alpha expression and angiogenesis in vivo. On the other hand, SIM2 long isoform (SIM2l)-overexpressed cells had contrary results, indicating the long isoform plays a key role for maintenance of these phenotypes. These data indicated that SIM2l has a potential to be precision medicine for CvSCC patients and that anti-angiogenesis therapy might be usable for SIM2l(Low) poor survivors.

  • Recent findings on epigenetic gene abnormalities involved in uterine cancer

    Yanokura, M., Banno, K., Kobayashi, Y., Nomura, H., Hayashi, S., Tominaga, E. and Aoki, D.

    Mol Clin Oncol 7 ( 5 ) 733 - 737 2017年11月

    ISSN  2049-9450

     概要を見る

    Selective aberrant genetic effects that do not depend on abnormal DNA sequences are referred to as epigenetic abnormalities and are involved in carcinogenesis. In uterine cancer, various genes involved in apoptosis, cell cycle, DNA repair, cell proliferation and cell adhesion are abnormally methylated, resulting in gene silencing. Reversal of such epigenetic abnormalities in cancer cells is a potential strategy for cancer therapy, and studies on epigenetic abnormalities and treatment methods in uterine cancer are in progress. These include the evaluation of 5-hydroxymethylcytosine, which is present in cancer tissues at lower levels compared with those in normal tissues, as a prognostic marker in cervical cancer; combination therapy with 5-azacytidine and cisplatin; combination treatment focusing on tumor necrosis factor-related apoptosis-inducing ligand in cervical cancer; studies focusing on DNA mismatch repair in endometrial cancer; and use of a demethylating agent to reactivate tumor suppressor genes and inhibit tumor proliferation. Detection of epigenetic changes using biomarkers may be used for histological classification, evaluation of disease progression and identification of compounds that are able to modulate epigenetic changes and may be useful for uterine cancer treatment.

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総説・解説等 【 表示 / 非表示

競争的資金等の研究課題 【 表示 / 非表示

  • スタチン製剤の多面的効果とワールブルク効果への影響に着目した卵巣癌新規創薬研究

    2018年04月
    -
    2020年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 小林 佑介, 若手研究, 補助金,  代表

  • スタチン製剤を卵巣癌抑制薬として用いる臨床応用のための基礎的研究

    2016年04月
    -
    2018年03月

    文部科学省・日本学術振興会, 科学研究費助成事業, 小林 佑介, 若手研究(B), 補助金,  代表

受賞 【 表示 / 非表示

  • 第32回日本女性医学学会学術集会 優秀演題賞

    2017年11月, 第32回日本女性医学学会学術集会

  • Shan S. Ratnam Young Gynecologist Award

    2017年06月, 25th Asian & Oceanic Congress of Obstetrics and Gynaecology

  • 東京都医師会医学研究賞奨励賞

    2017年01月, 東京都医師会

  • 第68回日本産科婦人科学会学術講演会 International Session Encouragement Award

    2016年04月, 第68回日本産科婦人科学会学術講演会

  • 日本産科婦人科学会 優秀論文賞

    2016年04月, 日本産科婦人科学会

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担当授業科目 【 表示 / 非表示

  • 婦人科学講義

    2019年度