Investigation to determine the cause of interstitial pneumonia by the EGFR inhibitors, and the development of that suppression method

2009 Fiscal Year Final Research Report

• Project/Area Number: 20791210
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Otorhinolaryngology
• Research Institution: Yokohama City University
• Principal Investigator: ISHIGURO Yukari Yokohama City University, 医学研究科, 特任助教 (00423830)
• Project Period (FY): 2008 – 2009
• Keywords: EGFR阻害剤

Research Abstract

Acute interstitial pneumonia is one of serious side effects of epidermal growth factor receptor (EGFR) inhibitor, although that cause is still unknown. Here we report that cancer cells treated with EGFR inhibitors induce fibrosis of normal lung cell. Human tangue squamous cell carcinoma (HSC-3) was cultured with EGFR-tyrosine kinase inhibitor (AG1478) or EGFR antibody. IL-6 expression level was elevated by EGFR inhibitors in HSC-3. Those supernatants were used as the conditioned medium. Then, OUS-11, normal human lung fibroblast-like cell line, was cultured with the conditioned medium. We investigated the expression of collagen, which was the marker for fibrosis, to confirm whether fibrosis was induced or not in OUS-11. That result showed that the expression level of collagen in OUS-11 treated with conditioned medium was higher than control cells. These data suggested that acute interstitial pneumonia was induced IL-6 from cancer cells treated with EGFR inhibitors.

Research Products

• [Journal Article] aPKClambda/iota promotes growth of prostate cancer cells in an autocrine manner through transcriptional activation of interleukin-6. (2009)
  • Author(s): Ishiguro H, Akimoto K, Nagashima Y, Kojima Y, Sasaki T, Ishiguro-Imagawa Y, Nakaigawa N, Ohno S, Kubota Y, Uemura H
  • Journal Title: Proc Natl Acad Sci U S A 106(38) Pages: 16369-74
  • Peer Reviewed
• [Journal Article] Restoration of BRAK / CXCL14 gene expression by gefitinib is associated with antitumor efficacy of the drug in head and neck squamous cell carcinoma. (2009)
  • Author(s): Ozawa S, Kato Y, Ito S, Komori R, Shiiki N, Tsukinoki K, Ozono S, Maehata Y, Taguchi T, Imagawa-Ishiguro Y, Tsukuda M, Kubota E, Hata R
  • Journal Title: Cancer Sci. 100(11) Pages: 2202-9
  • Peer Reviewed
• [Journal Article] Antitumor effects of lapatinib (GW572016), a dual inhibitor of EGFR and HER-2, in combination with cisplatin or paclitaxel on head and neck squamous cell carcinoma. (2009)
  • Author(s): Kondo N, Tsukuda M, Ishiguro Y, Kimura M, Fujita K, Sakakibara A, Takahashi H, Toth G, Matsuda H
  • Journal Title: Oncol Rep. 23(4) Pages: 957-63
  • Peer Reviewed
• [Journal Article] Involvement of EGFR in the response of squamous cell carcinoma of the head and neck cell lines to gefitinib. (2008)
  • Author(s): Taguchi T, Tsukuda M, Imagawa-Ishiguro Y, Kato Y, Sano D
  • Journal Title: Oncol Rep. 19(1) Pages: 65-71
  • Peer Reviewed
• [Presentation] 頭頸扁平上皮癌において、GefitinibはBRAK/CXCL14の発現を介して抗腫瘍効果を示す (2009)
  • Author(s): 加藤靖正, 田口享秀, 石黒由香利, 佃守
  • Organizer: 第22回日本バイオセラピィ学会学術集会総会
  • Place of Presentation: 大阪
  • Year and Date: 20091200
• [Presentation] ケモカインBRAK/CXCL14をマーカー分子とした頭頸部扁平上皮癌への新たな併用療法の試み (2009)
  • Author(s): 小澤重幸, 加藤靖正, 伊藤慎, 小森令賀, 椎木直人, 槻木恵一, 前畑洋次郎, 田口享秀, 石黒(今川)由香利, 佃守, 畑隆一郎, 久保田英朗
  • Organizer: 第19回日本口腔粘膜学会総会・学術集会
  • Place of Presentation: 葉山町
  • Year and Date: 20090600
• [Presentation] Fibrosis of normal lung cells is caused by some particular factors from cancer cells treated with EGFR-TKI. (2008)
  • Author(s): 石黒由香利, 石黒斉, 佃守
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20081000
• [Presentation] The role of aPKC lambda in prostate cancer progression. (2008)
  • Author(s): 石黒斉, 秋本和憲, 長嶋洋治, 小島康幸, 石黒由香利, 佐々木毅, 上村博司, 大野茂男, 窪田吉信
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 20081000