Establishment of assay method for p95HER2 protein that is a Resistance factor in anti-HER2 molecular-targeted therapy

• Project/Area Number: 22890004
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Single-year Grants
• Research Field: Laboratory medicine
• Research Institution: Hokkaido University
• Principal Investigator: HATANAKA Yutaka 北海道大学, 北海道大学病院, 特任助教 (30589924)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,042,000 (Direct Cost: ¥2,340,000、Indirect Cost: ¥702,000); Fiscal Year 2011: ¥1,456,000 (Direct Cost: ¥1,120,000、Indirect Cost: ¥336,000); Fiscal Year 2010: ¥1,586,000 (Direct Cost: ¥1,220,000、Indirect Cost: ¥366,000)
• Keywords: 分子標的治療 / 治療抵抗性 / コンパニオン診断

Research Abstract

In this study, we developed a monoclonal antibody to p95HER2 that is a resistance factor in anti-HER2 therapy. N-terminal synthetic peptides of p95HER2(Met611-Cys623) was conjugated with KLH, and used as immunogens. From the obtained hybridomas, we selected clones specific to the synthetic peptide by ELISA screening and dot blotting. Antibodies generated from the clones were avaliable in formalin-fixed, paraffin-embedded cell block. These results suggest that the antibodies would be useful to establish biochemical and immunohistochemical assays for selecting patients who exhibit resistance to HER2 therapy.

Research Products

• [Journal Article] 診断病理の精度管理:分子病理診断の標準化と精度管理 (2011)
  • Author(s): 畑中豊, 久保田佳奈子, 松野吉宏
  • Journal Title: 病理と臨床 Volume: 29 Pages: 346-352
• [Journal Article] Bright-field dua l-color chromogenic in situ hybridi zation for diagnosing echinoderm mi crotubule-associated protein-like 4-anaplastic lymphoma kinase-positiv e lung adenocarcinomas (2011)
  • Author(s): Yoshida A, Tsuta K, Nitta H, Hatana ka Y, Asamura H, Sekine I, Grogan T M, Fukayama M, Shibata T, Furuta K, Kohno T, Tsuda H.
  • Journal Title: J Thorac On col Volume: 6 Pages: 1677-86
  • Peer Reviewed
• [Journal Article] Bright-field dual-color chromogenic in situ hybridization for diagnosing echinoderm microtubule-associated protein-like 4-anaplastic lymphoma kinase-positive lung adenocarcinomas (2011)
  • Author(s): Yoshida A, et al.
  • Journal Title: J Thorac Oncol Volume: 10 Issue: 10 Pages: 1677-1686
  • DOI: 10.1097/jto.0b013e3182286d25
  • Peer Reviewed
• [Journal Article] 病理診断に役立つ分子生物学:Ki-67・細胞増殖マーカー (2011)
  • Author(s): 畑中豊, ら
  • Journal Title: 病理と臨床 Volume: 29・臨時増刊号 Pages: 298-307
• [Journal Article] Contrasting Prognostic Implications of Platelet-Derived Growth Factor Receptor-β and Vascular Endothelial Growth Factor Receptor-2 in Patients with Angiosarcoma. (2011)
  • Author(s): Yonemori K, et al.
  • Journal Title: Ann Surg Oncol.
  • Peer Reviewed
• [Journal Article] Immunohistochemical expression of HER1, HER3, and HER4 in HER2-positive breast cancer patients treated with trastuzumab-containing neoadjuvant chemotherapy (2010)
  • Author(s): Yonemori K, Tsuta K, Shimizu C, Hatanaka Y, Hirakawa A, Ono M, Kouno T, Katsumata N, Ando M, Tamura K, Hasegawa T, Kinoshita T, Fujiwara Y.
  • Journal Title: J Surg Oncol Volume: 101 Pages: 222-7
  • Peer Reviewed
• [Journal Article] Disruption of the blood brain barrier by brain metastases of triple negative and basal-type breast cancer but not HER2/neu-positive breast cancer (2010)
  • Author(s): Yonemori K, Tsuta K, Ono M, Shimizu C, Hirakawa A, Hasegawa T, Hatanaka Y, Nakanishi Y, Miyakita Y, Narita Y, Shibui S, Fujiwara Y.
  • Journal Title: Cancer Volume: 116 Pages: 302-8
  • Peer Reviewed
• [Journal Article] Evaluation of HER2 gene amplification in invasive breast cancer using a dual-color chromogenic in situ hybridization(dual CISH) (2010)
  • Author(s): Kato N, Itoh H, Serizawa A, Hatanaka Y, Umemura S, Osamura RY. Pathol Int.
  • Journal Title: Pathol Int Volume: 60(7) Pages: 510-5
  • NAID: 10027383191
  • Peer Reviewed
• [Journal Article] Evaluation of HER2 gene amplification in invasive breast cancer using adual-color chromogenic in situ hybridization (dual CISH). (2010)
  • Author(s): Kato N, et al.
  • Journal Title: Pathol Int. Volume: 60 Pages: 510-515
  • Peer Reviewed
• [Presentation] 分子病理診断の標準化と精度管理における課題と取り組み (2012)
  • Author(s): 畑中豊,松野吉宏
  • Organizer: 日本病理学会総会
  • Place of Presentation: 京王プラザ(東京)
  • Year and Date: 2012-04-27
• [Presentation] ヒト乳癌におけるNKG2Dリガンドの発現に関する検討 (2012)
  • Author(s): 藤田裕美,畑中豊,鈴木雄太,久保田佳奈子,大庭幸治,三橋智子,笠原正典,松野吉宏
  • Organizer: 日本病理学会総会
  • Place of Presentation: 京王プラザ(東京)
  • Year and Date: 2012-04-27
• [Presentation] 分子病理診断の標準化と精度管理における課題と取り組み (2012)
  • Author(s): 畑中豊, 松野吉宏
  • Organizer: 日本病理学会
  • Place of Presentation: 京王プラザ(東京)
  • Year and Date: 2012-04-27
• [Presentation] 抗体治療薬セツキシマブを用いた標的分子EGFRの組織発現分布に関する検討 (2011)
  • Author(s): 畑中豊, ら
  • Organizer: 日本病理学会
  • Place of Presentation: 横浜
  • Year and Date: 2011-04-24
• [Presentation] 原発性肺癌と胸膜悪性中皮腫の合併症例における遺伝子発現に関する検討 (2010)
  • Author(s): 田畑佑希子, ら
  • Organizer: 日本癌学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Book] 治療薬開発およびコンパニオン診断薬との同時開発の現状と今後 (2010)
  • Author(s): 畑中豊,松野吉宏
  • Publisher: 技術情報協会出版
• [Book] 体外診断用医薬品の開発と承認申請:治療薬開発およびコンパニオン診断薬との同時開発の現状と今後(分筆) (2010)
  • Author(s): 畑中豊, ら
  • Publisher: 技術情報協会