Clinical usefulness and application of Taxol-resisitance molecules

• Project/Area Number: 20592014
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: University of Yamanashi
• Principal Investigator: MASUYAMA Keisuke University of Yamanashi, 大学院・医学工学総合研究部, 教授 (30181663)
• Co-Investigator(Kenkyū-buntansha): CHIKAMATSU Ichiro 山梨大学, 医学部附属病院, 講師 (30301378)
• Co-Investigator(Renkei-kenkyūsha): MATSUOKA Tomokazu 山梨大学, 大学院・医学工学総合研究部, 助教 (30313810)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2008: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
• Keywords: 抗癌剤耐性分子 / 癌幹細胞 / 制御性T細胞 / 頭頸部癌 / タキサン系抗癌剤 / 免疫療法 / TRAG-3 / 免疫化学療法

Research Abstract

We found that head and neck cancer stem cells appeared to be resistant to the treatment of anti-cancer drugs. We did not find any differences of TRAG-3 mRNA expressions between CD44+ and CD44- cells of head and neck cancer cell lines. In addition, CD44+ cells significantly suppressed T cell proliferation. As for cytokine production, IFN・was reduced, however, IL-10 was increased when co-cultured with CD44+ cells. Thus, immunosuppressive mechanisims other than TRAG-3 expression may have a role for anti-cancer drug resistance.

Research Products

• [Journal Article] Resistance to apoptosis-inducing stimuli in CD44+ head and neck squamous cell carcinoma cells. (2011)
  • Author(s): Chikamatsu K, Ishii H, Takahashi, G, Okamoto A, Moriyama M, Sakakura K, Masuyama K.
  • Journal Title: Head Neck (in press)
  • Peer Reviewed
• [Journal Article] Immune regulation by CD4+CD25+ regulatory T cells in patients with Japanese cedar pollinosis. (2011)
  • Author(s): Yamanishi T, Chikamatsu K, Takahashi G, Endo S, Masuyama K.
  • Journal Title: Int Arch Allergy Immunol. (in press)
  • Peer Reviewed
• [Journal Article] Immunoregulatory properties of CD44+ cancer stem-like cells in squamous cell carcinoma of the head and neck. (2011)
  • Author(s): Chikamatsu K, Takahashi G, Sakakura K, Ferrone S, Masuyama K.
  • Journal Title: Head Neck 33 Pages: 208-215
  • Peer Reviewed
• [Journal Article] Resistance to apoptosis-inducing stimuli in CD44+ head and neck squamous cell carcinoma cells. (2011)
  • Author(s): Chikamatsu K, et al.
  • Journal Title: Head Neck Volume: (In press)
  • Peer Reviewed
• [Journal Article] Immunoregulatory properties of CD44+ cancer stem-like cells in squamous cell carcinoma of the head and neck. (2011)
  • Author(s): Chikamatsu K, et al.
  • Journal Title: Head Neck Volume: 33 Pages: 208-215
  • Peer Reviewed
• [Journal Article] Primary tumor induces sentinel lymph node lymphangiogenesis in oral squamous cell carcinoma. (2010)
  • Author(s): Ishii H, Chikamatsu K, Sakakura K, Miyata M, Furuya N, Masuyama K.
  • Journal Title: Oral Oncol. 46 Pages: 373-378
  • Peer Reviewed
• [Journal Article] Primary tumor induces sentinel lymph node lymphangiogenesis in oral squamous cell carcinoma. (2010)
  • Author(s): Ishii H, et al.
  • Journal Title: Oral Oncol Volume: 46 Pages: 373-378
  • Peer Reviewed
• [Journal Article] Endoscopic mucosal resecyion with cap (EMRC)を行った下咽頭表在癌の1例 (2010)
  • Author(s): 大高雅彦, 他
  • Journal Title: 山梨医学 Volume: 38 Pages: 107-111
  • Peer Reviewed
• [Journal Article] TGF-βsignaling may play a role in the development of goblet cell hyperplasia in a mouse model of allergic rhinitis. (2010)
  • Author(s): Ouyang Y, et a1.
  • Journal Title: Allergology International Volume: 59 Pages: 313-319
  • Peer Reviewed
• [Journal Article] Primary tumor induces sentinel lymphangiogenesis in oral squamous cell carcinoma. (2010)
  • Author(s): Ishii H, et al.
  • Journal Title: Oral Oncol (In press)
  • Peer Reviewed
• [Journal Article] (2010)
  • Author(s): 増山敬祐
  • Journal Title: 19. 耳鼻咽喉科疾患 上顎癌 (今日の診断指針 第6版 総編集:金澤一郎、永井良三)(医学書院) Pages: 1665-1667
• [Journal Article] (2010)
  • Author(s): 柳原良次
  • Journal Title: 第2部 薬剤編 5. 鼻噴霧用薬 (薬剤ごとの違いが分かる ステロイドの使い分け 編集:山本一彦、鈴木洋司)(羊土社) Pages: 165-179
• [Journal Article] CD4+ T-cell responses to HLA-DP5-restricted wild-type sequence p53 peptides in patients with head and neck cancer. (2009)
  • Author(s): Chikamatsu K, Sakakura K, Takahashi G, Okamoto A, Furuya N, Whiteside TL, DeLeo AB, Masuyama K.
  • Journal Title: Cancer Immunol Immunother. 58 Pages: 1441-1448
  • Peer Reviewed
• [Journal Article] Expansion and characterization of cancer stem-like cells in squamous cell carcinoma of the head and neck. (2009)
  • Author(s): Okamoto A, Chikamatsu K, Sakakura K, Hatsushika K, Takahashi G, Masuyama K.
  • Journal Title: Oral Oncol. 45 Pages: 633-639
  • Peer Reviewed
• [Journal Article] Analysis of helper T cell responses to Cry j 1-derived peptides in patients with nasal allergy : candidate for peptide-based immunotherapy of Japanese cedar pollinosis. (2009)
  • Author(s): Masuyama K, Chikamatsu K, Ikagawa S, Matsuoka T, Takahashi G, Yamamoto T, Endo S.
  • Journal Title: Allergol Int. 58 Pages: 63-70
  • NAID: 10025109090
  • Peer Reviewed
• [Journal Article] CD4+T cell responses to HLA-DP5-restricted wild-type sequence p53 peptides in patients with head and neck cancer. (2009)
  • Author(s): Chikamatsu K, et al.
  • Journal Title: Cancer immunol Immunother 58 Pages: 1441-1448
  • Peer Reviewed
• [Journal Article] Expansion and characterization of cancer stem-like cells in squamous cell carcinoma of the head and neck. (2009)
  • Author(s): Okamoto A, et al.
  • Journal Title: Oral Oncol 45 Pages: 633-639
  • Peer Reviewed
• [Journal Article] Expansion and characterization of cancer ste-like cells in squamous cell careinoma of the head and neck. (2009)
  • Author(s): Okamoto A, et al.
  • Journal Title: Oral Oncol (in press)
  • Peer Reviewed
• [Journal Article] Analysis of T helper responses and FOXP3 gene expression in patients with Japanese cedar pollinosis. (2008)
  • Author(s): Chikamatsu K, Sakakura K, Matsuoka T, Endo S, Takahashi G, Matsuzaki Z, Masuyama K.
  • Journal Title: Am J Rhinol. 22 Pages: 582-588
  • Peer Reviewed
• [Journal Article] CD4+ T helper responses in squamous cell carcinoma of the head and neck. (2008)
  • Author(s): Chikamatsu K, Sakakura K, Yamamoto T, Furuya N, Whiteside TL, Masuyama K.
  • Journal Title: Oral Oncol. 44 Pages: 870-877
  • Peer Reviewed
• [Journal Article] CD4+Thelper responses in squamous cell careinoma of the head and neck (2008)
  • Author(s): Chikamatsu K, et al.
  • Journal Title: Oral Oncol 44 Pages: 870-877
  • Peer Reviewed
• [Presentation] 頭頸部扁平上皮癌患者の免疫制御に及ぼすmyeloid-dereived suppressor cellの役割 (2011)
  • Author(s): 近松一朗, 他
  • Organizer: 第29回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 大分県大分市
  • Year and Date: 2011-02-10
• [Presentation] 頭頸部扁平上皮癌患者の免疫抑制に及ぼすmyeloid-derived suppressor ce11の役割. (2011)
  • Author(s): 近松一朗, 坂倉浩一, 山本卓典, 森山元大, 増山敬祐.
  • Organizer: 第29回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 大分
• [Presentation] 鼻中隔より発生した平滑筋腫の1例 (2010)
  • Author(s): 田中翔太, 他
  • Organizer: 第49回日本鼻科学会
  • Place of Presentation: 北海道札幌市
  • Year and Date: 2010-08-26
• [Presentation] Immunosuppressive properties of CD44+ cancer stem-like cells in squamous cell carcinoma of the head and neck. (2010)
  • Author(s): Chikamatsu K, et al.
  • Organizer: 4th World Congress of International Federation of Head and Neck Oncologic Societies.
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-06-15
• [Presentation] Primary tumor induces sentinel lymph node lymphangiogenesis in oral squamous cell carcinoma. (2010)
  • Author(s): Ishii H, et al.
  • Organizer: 4th World Congress of International Federation of Head and Neck Oncologic Societies.
  • Place of Presentation: Seoul, Korea
  • Year and Date: 2010-06-15
• [Presentation] サルベージ手術後の縫合不全に対して皮弁再建を試行した下咽頭癌の1症例 (2010)
  • Author(s): 森山元大, 他
  • Organizer: 第34回日本頭頸部癌学会
  • Place of Presentation: 東京都新宿区
  • Year and Date: 2010-06-10
• [Presentation] 口腔癌におけるリンパ節転移メカニズムの検討:原発巣とセンチネルリンパ節におけるリンパ管増生の関係 (2010)
  • Author(s): 近松一朗, 他
  • Organizer: 第111回日本耳鼻咽喉科学会
  • Place of Presentation: 宮城県仙台市
  • Year and Date: 2010-05-20
• [Presentation] CD44+ cancer stem-like cells are responsible for treatment resistance in squamouscellcarcinoma of the head and neck. (2010)
  • Author(s): Chikamatsu K, et al.
  • Organizer: American Head and Neck Society 2010 Annual Meeting.
  • Place of Presentation: Las Vegas, USA
  • Year and Date: 2010-04-28
• [Presentation] Expression of VEGF-C in oral squamous cell carcinoma correlates with sentinel lymph node lymphangiogenesis. (2010)
  • Author(s): Ishii H, et al.
  • Organizer: American Head and Neck Society 2010 Annual Meeting.
  • Place of Presentation: Las Vegas, USA
  • Year and Date: 2010-04-28
• [Presentation] Immunoregulatory properties of CD44+ cancer stem-like cells in squamous cell carcinoma of the head and neck. (2010)
  • Author(s): Chikamatsu K, et al.
  • Organizer: 101st Annual Meeting American Association for Cancer Research.
  • Place of Presentation: Washington DC, USA
  • Year and Date: 2010-04-17
• [Presentation] CD44+ cancer stem cellは様々なアポトーシス誘導刺激に対して抵抗性を示す (2010)
  • Author(s): 石井裕貴, 他
  • Organizer: 第28回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 福井
  • Year and Date: 2010-02-18
• [Presentation] Tumor microenvironmentにおけるCD44+ cancer stem cellの免疫抑制機構に果たす役割 (2010)
  • Author(s): 近松一郎, 他
  • Organizer: 第28回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 福井
  • Year and Date: 2010-02-18
• [Presentation] Immunosuppressive properties of CD44+ cancer stem-like cells in squamous cell carcinoma of the head and neck. (2010)
  • Author(s): Chikamatsu K, Ishii H, Takahashi G, Sakakura K, Ferrone S, Masuyama K
  • Organizer: 4^<th> World Congress of International Federation of Head and Neck Oncologic Societies.
  • Place of Presentation: Seoul, Korea
• [Presentation] Primary tumor induces sentinel lymph node lymphangiogenesis in oral squamous cell carcinoma. (2010)
  • Author(s): 石井裕貴, 近松一朗, 坂倉浩一, 宮田政則, 古屋信彦, 増山敬祐.
  • Organizer: 4^,<th>World Congress of International Federation of Head and Neck Oncologic Societies.
  • Place of Presentation: Seoul, Korea
• [Presentation] 口腔癌におけるリンパ節転移メカニズムの検討:原発巣とセンチネルリンパ節におけるリンパ管増生の関係. (2010)
  • Author(s): 近松一朗, 石井裕貴, 宮田政則, 坂倉浩一, 古屋信彦, 増山敬祐.
  • Organizer: 第111回日本耳鼻咽喉科学会総会
  • Place of Presentation: 仙台
• [Presentation] Expression of VEGF-C in oral squamous cell carcinoma correlates with sentinel lymph node lymphangiogenesis. (2010)
  • Author(s): 石井裕貴, 近松一朗, 坂倉浩一, 宮田政則, 古屋信彦, 増山敬祐.
  • Organizer: American Head and Neck Society 2010 Annual Meeting.
  • Place of Presentation: Las Vegas, USA.
• [Presentation] CD44+ cancer stem-like cells are responsible for treatment resistance in squamous cell carcinoma of the head and neck. (2010)
  • Author(s): 近松一朗, 石井裕貴, 岡本篤司, 高橋吾郎, 坂倉浩一, 増山敬祐.
  • Organizer: American Head and Neck Society 2010 Annual Meeting.
  • Place of Presentation: Las Vegas, USA.
• [Presentation] Immunoregulatory properties of CD44+ cancer stem-like cells in squamous cell carcinoma of the head and neck. (2010)
  • Author(s): Chikamatsu K, Takahashi G, Sakakura K, Ferrone S, Masuyama K
  • Organizer: 101^<st> Annual Meeting American Association for Cancer Research.
  • Place of Presentation: Washington DC, USA
• [Presentation] Tumor microenvironmentにおけるCD44+cancer stem cellの免疫抑制機構に果たす役割. (2010)
  • Author(s): 近松一朗, 石井裕貴, 高橋吾郎, 坂倉浩一, 増山敬祐.
  • Organizer: 第28回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 福井
• [Presentation] CD44+ cencer stem cellは様々なアポトーシス誘導刺激に対して抵抗性を示す. (2010)
  • Author(s): 石井裕貴, 近松一朗, 高橋吾郎, 坂倉浩一, 増山敬祐.
  • Organizer: 第28回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 福井
• [Presentation] 当科における耳下腺腫瘍の臨床統計 (2009)
  • Author(s): 石井裕貴, 他
  • Organizer: 第22回日本口腔・咽頭科学会
  • Place of Presentation: 和歌山
  • Year and Date: 2009-09-10
• [Presentation] Immunological properties of CD44+ cancer stem cells in squamous cell carcinoma of the head and neck (2009)
  • Author(s): Chikamatsu K, et al
  • Organizer: 2^<nd> world congress of the international academy of oral oncology
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2009-07-11
• [Presentation] Cancer stem cells as mediators of treatment resistance in squamous cell carcinoma of the head and neck (2009)
  • Author(s): Okamoto A, et al
  • Organizer: 2^<nd> world congress of the international academy of oral oncology
  • Place of Presentation: Toronto, Canada
  • Year and Date: 2009-07-11
• [Presentation] 頭頸部扁平上皮癌における治療抵抗性細胞としての幹細胞の解析 (2009)
  • Author(s): 近松一郎, 他
  • Organizer: 第33回日本頭頸部癌学会
  • Place of Presentation: 札幌
  • Year and Date: 2009-06-10
• [Presentation] Immunological properties of CD44+ cancer stem cells in squamous cell carcinoma of the head and neck. (2009)
  • Author(s): 近松一朗, 岡本篤司, 坂倉浩一, 初鹿恭介, 高橋吾郎, 増山敬祐.
  • Organizer: 2^<nd> World Congress of the International Academy of Oral Oncology.
  • Place of Presentation: Toronto, Canada
• [Presentation] Cancer stem cells as mediators of treatment resistance in squamous cell carcinoma of the head and neck. (2009)
  • Author(s): 岡本篤司, 近松一朗, 坂倉浩一, 初鹿恭介, 高橋吾郎, 増山敬祐.
  • Organizer: 2^<nd> World Congress of the International Academy of Oral Oncology.
  • Place of Presentation: Toronto, Canada
• [Presentation] 頭頸部扁平上皮癌における癌幹細胞の免疫抑制機構に果たす役割. (2009)
  • Author(s): 近松一朗, 坂倉浩一, 増山敬祐.
  • Organizer: 第13回日本がん免疫学会
  • Place of Presentation: 北九州
• [Presentation] 頭頸部扁平上皮癌における治療抵抗性細胞としての癌幹細胞の解析. (2009)
  • Author(s): 近松一朗, 高橋吾郎, 増山敬祐.
  • Organizer: 第33回日本頭頸部癌学会
  • Place of Presentation: 札幌
• [Presentation] Expansion and characterization of CD44+ cancer stem-like cells in squamous cell carcinoma of the head and neck. (2009)
  • Author(s): 近松一朗, 岡本篤司, 坂倉浩一, 初鹿恭介, 高橋吾郎, 増山敬祐.
  • Organizer: 100^<th> Annual Meeting American Association for Cancer Research.
  • Place of Presentation: Denver, USA
• [Presentation] 頭頸部扁平上皮癌における癌幹細胞の同定とその免疫学的解析. (2009)
  • Author(s): 近松一朗, 岡本篤司, 初鹿恭介, 高橋吾郎, 増山敬祐.
  • Organizer: 第27回日本耳鼻咽喉科免疫アレルギー学会
  • Place of Presentation: 千葉
• [Presentation] Isolation and characterization of cancer stem cells in squamous cell carcinoma of the head and neck. (2008)
  • Author(s): 岡本篤司, 近松一朗, 坂倉浩一, 増山敬祐.
  • Organizer: 7^<th> International Conference on Head and Neck Cancer.
  • Place of Presentation: San Francisco
• [Presentation] Thl/Th2 CD4+ T helper responses against wild-type sequence p53 peptides in HLA-DP5 patients with head and neck cancer. (2008)
  • Author(s): Chikamatsu K, Sakakura K, Okamato A, Whiteside TL, DeLeo AB, Masuyam K
  • Organizer: 7^<th> International Conference on Head and Neck Cancer.
  • Place of Presentation: San Francisco
• [Presentation] CD4+ Th responses to HLA-DP5-restricted wild-type sequence p53 peptides in patients with head and neck cancer. (2008)
  • Author(s): Chikamatsu K, Sakakura K, Yamamoto T, Whiteside TL, DeLeo AB, Masuyama K
  • Organizer: 99^<th> Annual Meeting American Association for Cancer Research.
  • Place of Presentation: San Diego, USA
• [Presentation] 進行上顎癌における動注化学療法併用放射線治療の検討. (2008)
  • Author(s): 森山元大, 他
  • Organizer: 第47回日本鼻科学会
  • Place of Presentation: 名古屋
• [Presentation] Isolation and characterization of cancer stem cells in squamous cell carcinoma of the head and neck (2008)
  • Author(s): Okamoto A, et al.
  • Organizer: 7th International Conference on Headand Neck Cancer
  • Place of Presentation: San Francisco
• [Presentation] Th1/Th2 CD4+ T helper responses against wild-type sequence p53 peptides in HLA-DP5 patients with head and neck cancer (2008)
  • Author(s): Chikamatsu K, et al.
  • Organizer: 7th International Conference on Headand Neck Cancer
  • Place of Presentation: San Francisco
• [Presentation] 進行頭頚部扁平上皮癌に対するドセタキセル+シスプラチン+5-FU併用療法 第1/2相臨床試験 (2008)
  • Author(s): 高橋吾郎, 他
  • Organizer: 第32回頭頸部癌学会
  • Place of Presentation: 東京
• [Presentation] CD4+Th responses to HLA-DP5-restricted wild-type sequence p53 peptides in patients with head and neck cancer. (2008)
  • Author(s): Chikamatsu K, et al.
  • Organizer: 99th Annual Meeting American Associationfor Cancer Research
  • Place of Presentation: San Diego