YAMANOI Kazuhiro

写真a

Affiliation

School of Medicine, Department of Pathology (Shinanomachi)

Position

Senior Assistant Professor (Non-tenured)/Assistant Professor (Non-tenured)

Other Affiliation 【 Display / hide

  • Shinshu Univ., School of Medicine, Molecular Pathology, Project recturer

Career 【 Display / hide

  • 2010.03
    -
    2012.03

    National Cancer Center Institute, Dep. of Pathology, Trainee

  • 2012.04
    -
    2014.12

    Aizawa Hospital, Dep. of Pathology, Medical Doctor

  • 2015.01
    -
    2016.05

    Asama General Hospital, Dep. of Clinical Laboratory, Chief Doctor

  • 2016.05
    -
    2019.03

    Shinshu Univ., ICCER, Inst. of Biomedical Sciences, Assistant Professor

Academic Background 【 Display / hide

  • 1999.04
    -
    2005.03

    Keio University, School of medicine

    University, Graduated

  • 2008
    -
    2012

    Keio University, Graduate School of medicine, Department of pathology

    Graduate School, Withdrawal after completion of doctoral course requirements, Doctoral course

Academic Degrees 【 Display / hide

  • Doctor of Medicine, Keio University, Coursework, 2013.09

Licenses and Qualifications 【 Display / hide

  • 医師免許, 2005.04

  • 臨床研修指導医, 2012.10

  • 病理専門医研修指導医, 2018.04

  • 細胞診教育研修指導医, 2019.04

  • 臨床検査管理医, 2014.12

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Research Areas 【 Display / hide

  • Human pathology

  • Tumor diagnostics

Research Keywords 【 Display / hide

  • Pathology

  • Oncology

  • multi-step carcinogenesis

  • glycobiology

Research Themes 【 Display / hide

  • Significance of glycosilation in carcinogenesis, 

    2014.01
    -
    Present

  • Clinico-pathological feature of familial tumor, 

    2012.04
    -
    Present

  • Molecular mechanisms of gastric carcinogenesis, 

    2008.04
    -
    Present

 

Papers 【 Display / hide

  • Decreased αGlcNAc glycosylation in biliary tract cancer progression from BilIN to invasive adenocarcinoma

    Motohiro Okumura, Kazuhiro Yamanoi, Takeshi Uehara, Jun Nakayama

    CANCER SCIENCE  2020.10

    Research paper (scientific journal), Joint Work, Accepted

  • Diffuse MIST1 expression and decreased αGlcNAc glycosylation on MUC6 are distinct hallmark for gastric neoplasms exhibiting oxyntic gland differentiation

    Shigenori Yamada, Kazuhiro Yamanoi, Yoshiko Sato, Jun Nakayama

    HISTOPATHOLOGY 77 ( 3 ) 413 2020.09

    Research paper (scientific journal), Joint Work, Accepted

  • αGlcNAc and its catalyst α4GnT are diagnostic and prognostic markers in uterine cervical tumor, gastric type.

    Ida K, Yamanoi K, Asaka S, Takeuchi H, Miyamoto T, Shiozawa T, Nakayama J.

    Scientific Reports (Nature publishing)  9 ( 1 ) 13043 2019.09

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  2045-2322

     View Summary

    © 2019, The Author(s). Cervical adenocarcinoma, gastric type (GAS) is not associated with human papilloma virus (HPV) infection. GAS patients prognoses are significantly worse compared with cervical adenocarcinoma associated with HPV infection, as their tumors exhibit resistance to conventional chemotherapy and radiotherapy. GAS is often associated with lobular endocervical glandular hyperplasia (LEGH), which is regarded as a precursor to GAS in the latest WHO classification. Recently, we reported that a decrease in expression of terminal α1,4-linked N-acetylglucosamine (αGlcNAc) relative to that of MUC6 was already apparent in atypical LEGH in the LEGH-GAS sequence. Here, we analyzed expression of α1,4-N-acetylglucosaminyltransferase (α4GnT), the sole enzyme catalyzing αGlcNAc biosynthesis, and that of αGlcNAc and MUC6 in cases representing non-neoplastic endocervical gland (NNEG) (11 cases), LEGH (26 cases) and GAS (12 cases). α4GnT protein was detected in a “dot-like” pattern, indicating localization in the Golgi apparatus in all 26 LEGH cases and 5 of 12 GAS cases. α4GnT- and αGlcNAc-positive cells largely overlapped, suggesting that α4GnT gene expression regulates αGlcNAc biosynthesis. Interestingly, all NNEG cases were negative for α4GnT and αGlcNAc expression, but 7 of 11 NNEG and all LEGH cases were MUC6-positive. In GAS cases, patients whose tumors were α4GnT- and αGlcNAc-positive had more favorable prognosis than others. Multivariate analysis revealed that positive expressions of α4GnT and αGlcNAc were independent prognostic indicators. These results indicate that α4GnT and αGlcNAc could serve as useful markers not only to distinguish LEGH from NNEG but to evaluate prognoses of GAS patients.

  • Analysis of A4gnt Knockout Mice Reveals an Essential Role for Gastric Sulfomucins in Preventing Gastritis Cystica Profunda.

    Masatomo Kawakubo, Hitomi Komura, Yukinobu Goso, Motohiro Okumura, Yoshiko Sato, Chifumi Fujii, Masaki Miyashita, Nobuhiko Arisaka, Satoru Harumiya, Kazuhiro Yamanoi, Shigenori Yamada, Shigeru Kakuta, Hiroto Kawashima, Michiko N. Fukuda, Minoru Fukuda, and Jun Nakayama

    Journal of Histochemistry & Cytochemistry (Journal of Histochemistry and Cytochemistry)  67 ( 10 ) 759 - 770 2019.06

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  00221554

     View Summary

    © The Author(s) 2019. Gastric adenocarcinoma cells secrete sulfomucins, but their role in gastric tumorigenesis remains unclear. To address that question, we generated A4gnt/Chst4 double-knockout (DKO) mice by crossing A4gnt knockout (KO) mice, which spontaneously develop gastric adenocarcinoma, with Chst4 KO mice, which are deficient in the sulfotransferase GlcNAc6ST-2. A4gnt/Chst4 DKO mice lack gastric sulfomucins but developed gastric adenocarcinoma. Unexpectedly, severe gastric erosion occurred in A4gnt/Chst4 DKO mice at as early as 3 weeks of age, and with aging these lesions were accompanied by gastritis cystica profunda (GCP). Cxcl1, Cxcl5, Ccl2, and Cxcr2 transcripts in gastric mucosa of 5-week-old A4gnt/Chst4 DKO mice exhibiting both hyperplasia and severe erosion were significantly upregulated relative to age-matched A4gnt KO mice, which showed hyperplasia alone. However, upregulation of these genes disappeared in 50-week-old A4gnt/Chst4 DKO mice exhibiting high-grade dysplasia/adenocarcinoma and GCP. Moreover, Cxcl1 and Cxcr2 were downregulated in A4gnt/Chst4 DKO mice relative to age-matched A4gnt KO mice exhibiting adenocarcinoma alone. These combined results indicate that the presence of sulfomucins prevents severe gastric erosion followed by GCP in A4gnt KO mice by transiently regulating a set of inflammation-related genes, Cxcl1, Cxcl5, Ccl2, and Cxcr2 at 5 weeks of age, although sulfomucins were not directly associated with gastric cancer development:.

  • A case of tubular adenoma of the breast diagnosed with fine-needle aspiration cytology

    MASUDA Hiroyuki, HAYASHI Kazuki, IDE Keiko, INOUE Hiroyuki, YAMANOI Kazuhiro

    The Journal of the Japanese Society of Clinical Cytology (The Japanese Society of Clinical Cytology)  58 ( 2 ) 82 - 86 2019.03

    Research paper (scientific journal), Joint Work, Accepted,  ISSN  1882-7233

     View Summary

    <p><i><b>Background</b></i> : Tubular adenomas of the breast are often diagnosed as a fibroadenoma from diagnostic imaging and fine-needle aspiration cytology.</p><p><i><b>Case</b></i> : A 27-year-old female presented with a right breast mass. Ultrasonography revealed a 9 mm irregularly-shaped hypoechoic mass in the outer layer of the breast on the inside of the fat tissue, and the depth-width ratio was more than 0.7. Elastography revealed a hard mass. Taking these observations into account, we thought the mass may be a malignant tumor. The cytological findings from the specimen showed a small lumen-like clump with secretion and a sheet-like mammary duct epithelial clump. These 2 types of clumps and the biphasic epithelium revealed that the mass was a tubular adenoma. Fibroadenoma was ruled out as there were few background stromal cells. The histological findings from the specimen showed tight small gland duct hyperplasia with scant stroma. The immunohistochemical assay revealed that the epithelial cells were positive for cytokeratin and the myoepithelial cells were positive for smooth muscle actin, which showed the biphasic nature of the epithelium. Thus, we finally confirmed the diagnosis that the tumor was a tubular adenoma.</p><p><i><b>Conclusion</b></i> : Based on the clinical imaging there was the possible suspicion that the tumor might have been breast cancer, however, the fine-needle aspiration cytology suggested that it was a tubular adenoma, and fibroadenoma and breast cancer were ruled out.</p>

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Reviews, Commentaries, etc. 【 Display / hide

Presentations 【 Display / hide

  • Significance of aGlcNAc expression in biliary ductal cancer progression

    山ノ井 一裕, 奥村 征大, 上原 剛, 尾島 英知, 中山 淳

    第109回日本病理学会総会, 2020.07, Oral Presentation(general)

  • 子宮頸部細胞診で胃型粘液性癌が疑われた通常型内頸部腺癌の一例

    服部 守恭, 藤井 真一, 山ノ井 一裕, 中山 淳, 福島 万奈, 的場 久典

    第58回日本臨床細胞学会秋期大会, 2019.11, Poster (general)

  • Significance of aGlcNAc expression during progression of cholangiocarcinoma

    Okumura M. Yamanoi K, Nakayama J

    78th Japanese cancer association annual meeting, 2019.09, Poster (general)

  • 免疫組織学的にPSA染色陽性であった原発性膀胱癌の1例

    野口 渉, 井上 善博, 山ノ井 一裕, 中山 淳

    第83回日本泌尿器科学会東部総会, 2018.10, Poster (general)

  • ALPHA-GLCNAC AND Α4GNT CAN BE FAVORABLE PROGNOSTIC MARKERS FOR CERVICAL MUCINOUS CARCINOMA, GASTRIC TYPE

    K. Ida, K. Yamanoi, H. Takeuchi, Y. Yamada, H. Kobara, H. Kashima, T. Miyamoto, J. Nakayama, T. Shiozawa

    17th Biennial Meeting of the International Gynecologic Cancer Society (Kyoto) , 2018.09, Poster (general)

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

  • 幽門腺粘液の糖鎖αGlcNAcの発現低下とがんの悪性度の分子機構の解明

    2019.04
    -
    2022.03

    Keio University, 日本学術振興会科学研究費, 山ノ井 一裕, Grant-in-Aid for Early-Career Scientists, Research grant, Principal Investigator

     View Summary

    本研究では、胃、膵臓、子宮頸部のがん病変、前がん病変におけるαGlcNAcの発現低下について、予後を含めた悪性度の関係まで調べ、対象臓器も肺、胆道などに広げて検討することを1つの目的とする。がん由来の培養細胞株を用いて、αGlcNAcの発現に呼応する細胞機能の変化と、関連する遺伝子発現やリン酸化の変化を調べ、αGlcNAcががんの悪性化を抑制する分子生物学的な機序を明らかにし、αGlcNAcの発現変化を基盤とした、新たな治療標的の知見を得ることが2つ目の目的である。
    本研究で、がんの悪性化に関わる糖鎖修飾の変化が臓器横断的に理解されれば、糖鎖修飾を鍵にした新たながんの治療標的の研究の基盤になる。

  • Significance of alphaGlcNAc expression status in human tumors

    2017.04
    -
    2019.03

    Shinshu University, 科学研究費, Yamanoi Kazuhiro, Nakayama Jun, Fujii Chifumi, Ohya Ayumu, Ida Koichi, Ishii Keiko, Asaka Shiho, Shimojo Hisashi, Miyamoto Tsutomu, Shiozawa Tanri, Grant-in-Aid for Young Scientists (B), Research grant, Principal Investigator

     View Summary

    Gastric pyloric glands characteristically contain O-glycans having α1,4-linked N-acetylglucosamine residue (αGlcNAc) largely attached to MUC6 scaffold. In normal human gastric mucosa, αGlcNAc and MUC6 are co-expressed in pyloric gland cells. We examined αGlcNAc and MUC6 expression in human gastric, pancreas and uterine cervical tumors. We showed that reduced αGlcNAc expression relative to MUC6 was observed not only in invasive carcinoma lesions but also in their pre-malignant lesions, such as high-grade pyloric gland adenoma, high-grade intraepithelial neoplasia, high-grade intraductal papillary-mucinous neoplasm and atypical lobular endocervical gland hyperplasia. These results indicate that reduced αGlcNAc expression has already started in pre-malignant status in these organs. Thus, αGlcNAc could serve as a critical biomarker for malignant potential in early stage of gastric, pancreas and uterine cervical neoplasms.

  • 特殊型胃癌における幹細胞マーカーの発現とその意義

    2018.04
    -
    2019.03

    信州医学振興会, 平成30年度研究助成, Research grant, Principal Investigator

  • 粘液産生性肺腺癌において、幽門腺型粘液のコア蛋白であるMUC6が、がんの悪性化を抑制するメカニズムの解析

    2017.04
    -
    2018.03

    ノバルティスファーマ株式会社, Research grant, Principal Investigator

Awards 【 Display / hide

  • 日本病理学会学術奨励賞

    2020.07

    Type of Award: Awards of National Conference, Council and Symposium

Other 【 Display / hide

  •  View Details

    信州大学医学部附属病院 がんのクリニカルシークエンス コアメンバー

 

Courses Taught 【 Display / hide

  • 病理学総論

    2020, Spring Semester, Major subject, Laboratory work/practical work/exercise

  • 病理学総論

    2019, Spring Semester, Major subject, Laboratory work/practical work/exercise, Outside own faculty (within Keio), 120people

  • 病理学各論

    2019, Autumn Semester, Major subject, Laboratory work/practical work/exercise

Courses Previously Taught 【 Display / hide

  • 病理学各論

    信州大学医学部, 2020, Autumn Semester, Major subject, Lecture

  • 病理学総論

    信州大学医学部, 2019, Spring Semester

  • 病理学各論

    信州大学医学部, 2019, Autumn Semester

  • 病理学総論

    信州大学医学部, 2018

  • 病理学各論

    信州大学医学部, 2018

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Educational Activities and Special Notes 【 Display / hide

  • 学生指導者を対象とした医学教育FD 修了(信州大学医学部)

    2016
    -
    Present

    , Device of Educational Contents

  • CBT試験 学内ブラッシュアップ委員 (信州大学医学部)

    2018
    -
    Present

    , Special Affairs

  • CBT試験・追試験 試験監督(信州大学医学部)

    2018
    -
    Present

    , Special Affairs

 

Memberships in Academic Societies 【 Display / hide

  • 日本臨床細胞学会

     
  • 日本臨床検査医学会

     
  • 日本癌学会

     
  • 日本病理学会

     

Committee Experiences 【 Display / hide

  • 2017.05
    -
    Present

    学術評議員, 日本病理学会

  • 2021.06
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    Present

    評議員, 日本臨床細胞学会