New molecular therapy against gastroenterological malignancies targeting members of HER and VEGF family

• Project/Area Number: 21590457
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Aichi Cancer Center Research Institute
• Principal Investigator: NAKANISHI Hayao 愛知県がんセンター(研究所), 腫瘍病理学部, 室長 (20207830)
• Project Period (FY): 2009 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2011: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 腫瘍 / ERFR / HER2 / HER3 / VEGF / 胃癌・大腸癌 / Gefitinib

Research Abstract

In this study, we newly demonstrated following three findings. 1) HER3 is involved in the gefitinib-sensitivity of pooly-differentiated colonic cancer cell line (COLM-5).
2) VEGF-A is overexpressed in some HER2 gene-amplified gastric cancer cell lines and can be effectively targeted by bevacizumab alone and in combination with HER2 antagonists.
3) Subline showing EMT derived from parental HNSCC show gefitinib-resistance due to down regulation of EGFR and compensatory activation of alternative signaling pathway.

Research Products

• [Journal Article] Establishment and characterization of novel gastric signet-ring cell and non signet-ring cell, poorly-differentiated adenocarcinoma cell lines with low and high malignant potential (2012)
  • Author(s): Murakami H, Nakanishi H, Tanaka H, Ito S, Misawa K, Ito Y, Ikehara Y, Kondo E, Kodera Y.
  • Journal Title: Gastric Cancer Volume: (in press) Issue: 1 Pages: 74-83
  • DOI: 10.1007/s10120-012-0149-2
  • NAID: 40019557355
  • Peer Reviewed
• [Journal Article] TGF-β synergizes with defects in the Hippo pathway to stimulate human malignant mesothelioma growth (2012)
  • Author(s): Fujii M, Toyoda T, Nakanishi H, Yatabe Y, Sato A, Matsudaira Y, Ito H, Murakami H, Kondo Y, Kondo E, Hida T, Tsujimura T, Osada H, Sekido Y.
  • Journal Title: J Exp Med Volume: VOL.209(3) Issue: 3 Pages: 479-494
  • DOI: 10.1084/jem.20111653
  • Peer Reviewed
• [Journal Article] Acquisition of EMT phenotype in the gefitinib-resistant cells of a head and neck squamous cell carcinoma cell line through Akt/GS K3 β/snail signaling pathway (2012)
  • Author(s): Maseki S, Ijichi K, Tanaka H, Fujii M, Hasegawa Y, Ogawa T, Murakami S, Kondo E, Nakanishi H.
  • Journal Title: Br J Cancer Volume: VOL.106(6) Issue: 6 Pages: 1196-1204
  • DOI: 10.1038/bjc.2012.24
  • Peer Reviewed
• [Journal Article] Enhancement of metastatic ability by ectopic expression of ST6Ga lNAcI on a gastric cancer cell line in a mouse model (2012)
  • Author(s): Ozaki H, Matsuzaki H, Ando H, Kaji H, Nakanishi H, Ikehara Y, Narimatsu H.
  • Journal Title: Clin Exp Metastasis Volume: VOL.29(3) Issue: 3 Pages: 229-238
  • DOI: 10.1007/s10585-011-9445-1
  • Peer Reviewed
• [Journal Article] Different levels of Sialyl-Tn Antigen expressed on MUC16 in Patients With Endometriosis and Ovarian Cancer (2012)
  • Author(s): Akita K
  • Journal Title: Int J Gynecol Cancer Volume: VOL.22(4) Issue: 4 Pages: 531-8
  • DOI: 10.1097/igc.0b013e3182473292
  • Peer Reviewed
• [Journal Article] Different levels of Sialyl-Tn Antigen expressed on MUC16 in Endometriosis and Ovarian Cancer Patients (2011)
  • Author(s): Akita K, Yoshida S, Ikehara Y, Shirakawa S, Toda M, Inoue M, Kitawaki J, Nakanishi H, Narimatsu H, Nakada H.
  • Journal Title: Int J Gyneco Oncol Volume: VOL.22(4) Pages: 531-538
  • Peer Reviewed
• [Journal Article] Expression and the role of 3'-phosphoadenosine 5'-phosphosulfate transporters in human colorectal carcinoma (2011)
  • Author(s): Kamiyama S, Ichimiya T, Ikehara Y, Takase T, Fujimoto I, Suda T, Nakamori S, Nakamura M, Nakayama F, Irimura T, Nakanishi H, Watanabe M, Narimatsu H, Nishihara S.
  • Journal Title: Glycobiology Volume: VOL.21(2) Issue: 2 Pages: 235-246
  • DOI: 10.1093/glycob/cwq154
  • Peer Reviewed
• [Journal Article] Expression and the role of 3'-phosphoadenosine 5'-phosphosulfate transporters in human colorectal carcinoma. (2011)
  • Author(s): Kamiyama S
  • Journal Title: Glycobiology Volume: VOL.21(2) Pages: 235-246
  • Peer Reviewed
• [Journal Article] The prognostic significance of isolated tumor cells in the lymph nodes of gastric cancer patients (2010)
  • Author(s): Fukagawa T, Sasako M, Ito S, Nakanishi H, Iinuma H, Natsugoe S, Katai H, Shimoda T.
  • Journal Title: Gastric Cancer Volume: 13 Issue: 3 Pages: 191
  • DOI: 10.1007/s10120-010-0556-1
  • Peer Reviewed
• [Journal Article] Phase II Clinical Trial of Postoperative S-1 Monotherapy for Gastric Cancer Patients with Free Intraperitoneal Cancer Cells Detected by Real-Time RT-PCR (2010)
  • Author(s): Ito S, Kodera Y, Mochizuki Y, Kojima T, Nakanishi H, Yamamura Y.
  • Journal Title: World Journal of Surgery Volume: VOL.34(9) Issue: 9 Pages: 2083-2089
  • DOI: 10.1007/s00268-010-0573-6
  • Peer Reviewed
• [Journal Article] Targeted delivery of oligomannose-coated liposome to the omental micrometastasis by peritoneal macrophages from patients with gastric cancer (2010)
  • Author(s): Matsui M, Shimizu Y, Ikehara Y, Kondo E, Kodera Y, Nakanishi H.
  • Journal Title: Cancer Science Volume: VOL.101(7) Issue: 7 Pages: 1670-1677
  • DOI: 10.1111/j.1349-7006.2010.01587.x
  • NAID: 10026594802
  • Peer Reviewed
• [Journal Article] Characterization of a novel lymph node metastasis model from human colonic cancer and its preclinical use for comparison of anti-metastatic efficacy between oral S-1 and UFT/LV (2010)
  • Author(s): Ito Y, Nakanishi H, Kodera Y, Hirai T, Nakao A and Kato T.
  • Journal Title: Cancer Science Volume: VOL.101(8) Issue: 8 Pages: 1853-1860
  • DOI: 10.1111/j.1349-7006.2010.01607.x
  • NAID: 10027830674
  • Peer Reviewed
• [Journal Article] Characterization of a novel lymph node metastasis model from human colonic cancer and its preclinical use for comparison of anti-metastatic efficacy between oral S-1 and UFT/LV. (2010)
  • Author(s): Ito Y
  • Journal Title: Cancer Science Volume: VOL.101(8) Pages: 1853-1860
  • Peer Reviewed
• [Journal Article] Targeted delivery of oligomannose-coated liposome to the omental micrometastasis by peritoneal macrophages from patients with gastric cancer. (2010)
  • Author(s): Matsui M
  • Journal Title: Cancer Science Volume: VOL.101(7) Pages: 1670-1677
  • Peer Reviewed
• [Journal Article] Phase II Clinical Trial of Postoperative S-1 Monotheherapy for Gastric Cancer Patients wish Free Intraperitoneal Cancer Cells Detected by Real-Time RT-PCR. (2010)
  • Author(s): Ito S
  • Journal Title: World Journal of Surgery Volume: VOL.34(9) Pages: 2083-2089
  • Peer Reviewed
• [Journal Article] The prognostic significance of isolated tumor cells in the lymph nodes of gastric cancer patients. (2010)
  • Author(s): Fukagawa T
  • Journal Title: Gastric Cancer Volume: VOL.13(3) Pages: 191-196
  • Peer Reviewed
• [Journal Article] Characterization of a novel lymph node metastasis model from human colonic cancer and its preclinical use for comparison of anti-metastatic efficacy between oral S-1 and UFT/LV. (2010)
  • Author(s): Ito Y
  • Journal Title: Cancer Science (in press)
  • Peer Reviewed
• [Journal Article] Targeted delivery of oligomannose-coated liposome to the omental micrometastasis by peritoneal macrophages from patients with gastric cancer. (2010)
  • Author(s): Matsui M
  • Journal Title: Cancer Science (in press)
  • Peer Reviewed
• [Journal Article] Phase II Clinical Trial of Postoperative S-1 Monotheherapy for Gastric Cancer Patients wish Free Intraperitoneal Cancer Cells Detected by Real-Time RT-PCR. (2010)
  • Author(s): Ito S
  • Journal Title: World Journal of Surgery (in press)
  • Peer Reviewed
• [Journal Article] Expression of L1 cell adhesion molecule is a significant prognostic fact or in pT3-stage gastric cancer (2009)
  • Author(s): Kodera Y, Nakanishi H, Ito S, Misawa K, Ito Y, Nakayama G, Koike M, Fujiwara M, Yamamura Y, Nakao A.
  • Journal Title: Anti Cancer Res Volume: VOL.29(10) Pages: 4033-4039
  • URL: http://ar.iiarjournals.org/content/29/10/4033.abstract
  • Peer Reviewed
• [Journal Article] Bone Marrow and Peripheral Blood Expression of ID1 in Human Gastric Carcinoma Patients Is a Bona Fide Indicator of Lymph Node and Peritoneal Metastasis (2009)
  • Author(s): Iwatsuki M, Fukagawa T, Mimori K, Nakanishi H, Ito S, Ishii H, Yokobori T, Sasako M, Baba H, Mori M.
  • Journal Title: Br J Cancer Volume: VOL.100 Pages: 1937-1942
  • Peer Reviewed
• [Journal Article] Bone Marrow and Peripheral Blood Expression of ID1 in Human Gastric Carcinoma Patients Is a Bona Fide Indicator of Lymph Node and Peritoneal Metastasis. (2009)
  • Author(s): Iwatsuki M
  • Journal Title: Br J cancer 100 Pages: 1937-1942
  • Peer Reviewed
• [Journal Article] Expression of L1 Cell Adhesion Molecule is a Significant Prognostic Factor in pT3-stage Gastric Cancer. (2009)
  • Author(s): Kodera Y
  • Journal Title: AntiCancer Res 29(10) Pages: 4033-4039
  • Peer Reviewed
• [Presentation] HER2陽性胃がん細胞のTrastuzumab耐性株におけるp95HER2およびMUC4の発現 (2012)
  • Author(s): 中西速夫
  • Organizer: 第84回日本胃癌学会総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2012-02-09
• [Presentation] HER2陽性胃がん細胞のTrastuzumab耐性株におけるP95HER2およびMUC4の発現 (2012)
  • Author(s): 中西速夫
  • Organizer: 第84回日本胃癌学会総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2012-02-09
• [Presentation] Molecular optical imaging of peritoneal metastasis of gastric cancer using near-infrared (NIR)-labeled antibody (2011)
  • Author(s): 中西速夫
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-04
• [Presentation] 蛍光標識抗体を用いた胃がん腹膜転移の光イメージング (2011)
  • Author(s): 中西速夫
  • Organizer: 第100回日本病理学会総会
  • Place of Presentation: パシフィコ横浜(横浜)
  • Year and Date: 2011-04-30
• [Presentation] Molecular aspect of peritoneal metastasis; A new diagnostic and therapeutic strategy in gastric cancer (2011)
  • Author(s): Nakanishi H
  • Organizer: 第9回国際胃がん学会(IGCC2011)
  • Place of Presentation: Coex Convention Center(ソウル)
  • Year and Date: 2011-04-22
• [Presentation] Molecular aspect of peritoneal metastasis ; A new diagnostic and therapeutic strategy in gastric cancer (2011)
  • Author(s): Nakanishi H
  • Organizer: 第9回国際胃がん学会(IGCC2011)
  • Place of Presentation: Coex Convention Center(韓国ソウル)
  • Year and Date: 2011-04-22
• [Presentation] Molecular targeting and imaging of gastric cancer metastasis (2011)
  • Author(s): 中西速夫
  • Organizer: BIT's 3rd International Congress of Antibodies-2011(ICA-2011)
  • Place of Presentation: 中国国立会議場(北京)
  • Year and Date: 2011-03-24
• [Presentation] HER2過剰発現胃癌細胞に対するの分子標的治療の検討 (2011)
  • Author(s): 中西速夫
  • Organizer: 第83回日本胃癌学会総会
  • Place of Presentation: 青森屋(青森)
  • Year and Date: 2011-03-05
• [Presentation] HER2過剰発現胃癌細胞に対するの分子標的治療の検討 (2011)
  • Author(s): 中西速夫
  • Organizer: 第83回日本胃癌学会総会
  • Place of Presentation: 青森屋(青森県)
  • Year and Date: 2011-03-05
• [Presentation] HER2遺伝子増幅胃がんに対するTrastuzumabとLapatinibの抗腫瘍効果の差異とその分子機構の解析 (2010)
  • Author(s): 中西速夫
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪)
  • Year and Date: 2010-09-23
• [Presentation] HER2遺伝子増幅胃がんに対するTrastuzumabとLapatinibの抗腫瘍効果の差異とその分子機構の解析 (2010)
  • Author(s): 中西速夫
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-23
• [Presentation] がん幹細胞様形質を示す口腔扁平上皮癌細胞株のGefitinib感受性とその機構 (2010)
  • Author(s): 中西速夫
  • Organizer: 第19回日本がん転移学会
  • Place of Presentation: 金沢市文化ホール(金沢)
  • Year and Date: 2010-06-16
• [Presentation] がん幹細胞様形質を示す口腔扁平上皮癌細胞株のGefitinib感受性とその機構 (2010)
  • Author(s): 中西速夫
  • Organizer: 第19回日本がん転移学会
  • Place of Presentation: 金沢市文化ホール(石川県)
  • Year and Date: 2010-06-16
• [Presentation] がん幹細胞様形質を示す大腸がん低分化型腺癌細胞株のgefitinib高感受性第99回日本病理学会総会 (2010)
  • Author(s): 中西速夫
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 京王プラザホテル(東京)
  • Year and Date: 2010-04-28
• [Presentation] がん幹細胞様形質を示す大腸がん低分化型腺癌細胞株のgefitinib高感受性 (2010)
  • Author(s): 中西速夫
  • Organizer: 第99回日本病理学会総会
  • Place of Presentation: 京王プラザホテル(東京都)
  • Year and Date: 2010-04-28
• [Presentation] EMT様変化を伴う苦口腔扁平上皮がんのEGFR標的薬感受性の検討 (2009)
  • Author(s): 北島正一朗
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川)
  • Year and Date: 2009-10-03
• [Presentation] HER3の著明な発現低下を認める低分化型大腸癌細胞株のGefitinid感受性機構の解析 (2009)
  • Author(s): 中西速夫
  • Organizer: 第18回日本がん転移学会学術集会・総会
  • Place of Presentation: 旭川グランドホテル(旭川)
  • Year and Date: 2009-07-23
• [Presentation] HER3の著明な発現低下を認める低分化型大腸癌細胞株のGefitinid感受性機構の解析 (2009)
  • Author(s): 中西速夫
  • Organizer: 第18回日本がん転移学会学術集会・総会
  • Place of Presentation: 旭川グランドホテル(北海道)
  • Year and Date: 2009-07-23
• [Presentation] HER3低発現低分化型大腸癌細胞のGefitinib, Cetuximab感受性機構の解析 (2009)
  • Author(s): 中西速夫
  • Organizer: 第98回日本病理学会総会
  • Place of Presentation: 京都国際会館(京都)
  • Year and Date: 2009-05-02
• [Presentation] High gefitinib sensitvity of EGFR verpressing, HER3-deficient and metastatic poorly-differentiaed new human colonic cancer cell line (2009)
  • Author(s): Nakanishi H
  • Organizer: AACR 100th Annual Meeting
  • Place of Presentation: コロラドコンベンションセンター(米国、デンバー)
  • Year and Date: 2009-04-19
• [Presentation] High gefitinib sensitvity of EGFR venpressing,HER3-deficient and metastaticpoorly-differentiaednew human colonic cancer cell line (2009)
  • Author(s): Nakanishi H
  • Organizer: AACR 100th Annual Meeting 2009
  • Place of Presentation: コロラドコンベンションセンター(アメリカ合衆国・コロラド州・デンバー)
  • Year and Date: 2009-04-19
• [Book] "In Vivo Imaging" Methods and Protocols, Non invasive and real-time fluorescence imaging of peritoneal metastas is in nude mice(Hoffman, R.M.(ed.)) (2012)
  • Author(s): Nakanishi, H
  • Publisher: Humana Press, Totowa, NJ.(in press)
• [Book] "In Vivo Imaging" Methods and Protocols, Hoffman, R. M. (ed.), No invasive and real-time fluorescence imaging of peritoneal metastasis in nude mice (2011)
  • Author(s): Nakanishi H, Ito S, Matsui M, Murakami H, Kodera Y.
  • Publisher: Humana Press(in press)
• [Book] 病理診断医になじみのある疾患関連分子 "VEGF (vascular endothelial growth factor) family解説編・診断編" 病理診断に役立つ分子生物学、病理と臨床 臨時増刊号 Vol.29 (2011)
  • Author(s): 中西速夫
• [Book] 病理診断医になじみのある疾患関連分子"VEGF (vascular endothelial growth factor) family解説編・診断編"病理診断に役立つ分子生物学、病理と臨床臨時増刊号Vol.29 (2011)
  • Author(s): 中西速夫
  • Publisher: 文光堂
• [Book] "In Vivo Imaging" Methods and Protocols, Hoffman, R.M.(ed.), Non invasive and real-time fluorescence imaging of peritoneal metastasis in nude mice. (2010)
  • Author(s): Nakanishi, H
  • Publisher: Humana Press, Totowa, NJ.(in press)
• [Book] "In Vivo Imaging" Methods and Protocols, Hoffman, R.M.(ed.), Non invasive and real-time fluorescence imaging of peritoneal metastasis in nude mice. (2009)
  • Author(s): Nakanishi, H
  • Publisher: Humana Press, Totowa, NJ.(in press)