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Basic study on chemotherapy combined with gene transfection for head and neck cancer

Research Project

Project/Area Number 10470354
Research Category

Grant-in-Aid for Scientific Research (B).

Allocation TypeSingle-year Grants
Section一般
Research Field Otorhinolaryngology
Research InstitutionFukui Medical University

Principal Investigator

SAITO Hitoshi  Fukui Medical University Medical Department Professor, 医学部, 教授 (90079898)

Co-Investigator(Kenkyū-buntansha) NODA Ichiro  Fukui Medical University Medical department Assistant, 医学部, 助手 (60283181)
FUJIEDA Shigeharu  Fukui Medical University University Hospital Assistant Professor, 医学部・付属病院, 講師 (30238539)
OHTSUBO Toshio  Fukui Medical University University Hospital Assistant Professor, 医学部・付属病院, 講師 (10223877)
SUGIMOTO Chizuru  Fukui Medical University University Hospital Assistant, 医学部・付属病院, 助手 (80283183)
YAMADA Takechiyo  Fukui Medical University Medical department Assistant, 医学部, 助手 (70283182)
森 繁人  福井医科大学, 医学部, 助手 (00221630)
Project Period (FY) 1998 – 2000
Project Status Completed (Fiscal Year 2000)
Budget Amount *help
¥6,900,000 (Direct Cost: ¥6,900,000)
Fiscal Year 2000: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1999: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 1998: ¥5,100,000 (Direct Cost: ¥5,100,000)
KeywordsHead and neck cancer / Apoptosis / bax / p53 / bcl-2 / CAD / Fas-Fas ligand / Chemotherapy / 頭頚部癌 / 遺伝子治療 / Fas / Fasリガンド / CDDP / 遺伝子銃 / CDDP耐性 / グルタチオン / MRP / Bax / Bcl-2 / 頭頸部癌 / 抗癌剤感受性試験 / 血小板由来増殖因子 / Tunicamycin / 顆粒球刺激因子 / Bax遺伝子
Research Abstract

The chemosensitive rate of 139 cases of head and neck cancer evaluated by ATP method was in the order of 5-FU (27%) >CDDP=CBDCA>MTX>PEP (23%). Therefore, the purpose of this study is to conquer the chemoresistance in combination with gene transfection relating to apoptosis.
1998 : Among the above 5 sensitive drugs, CDDP was employed for the further study, because CDDP is one of the apoptosis-promoting anticancer drugs. Apoptosis by CDDP is regulated with glutathione and with tunicamycin, an inhibitor of glycosylation. A correlation between Bax expression and 5-year survival rate in 57 cases of oropharyngeal squamous cell carcinomas was investigated by immunohistochemical analysis. The cases expressed high apoptosis-promoting gene bax showed significantly better 5-year survival rate.
1999 : Overexpression of p53 showed significantly poor prognosis, while that of Bcl-2 did not show any correlation to it. Correlation between the expressions of p53, Bax, Bcl-2 and apoptotic ratio evaluated b … More y TUNEL staining did not show significant relation, but Bax-positive group showed higher tendency to apoptosis. Since clinical cases highly expressed gene bax showed better prognosis, it was investigated whether the head and neck cancer cell line and CDDP-resistant cell line transfected gene bax by electroporation become more sensitive to CDDP in vitro. The cell lines transfected bax showed significantly higher sensitivity to CDDP.A cancer cell line expressing bcl-2 showed significantly increased CDDP sensitivity by its antisense.
2000 : In vivo study on chemotherapy with some genes promoting apoptosis was carried out.
(1) Anticancer effect of apoptosis-promoting bax gene and its combined effect with CDDP were investigated. Percutaneous transfer of bax gene by particle-mediated delivery (gene gun system) inhibited the growth of mouse CDDP-resistant SCC.Furthermore, a combination with bax gene and CDDP at 3-day intervals markedly inhibited the growth of mouse SCC (p<0.0001).
(2) Anticancer effect of CAD (caspase-activated DNase) and its combined effect with CDDP were investigated. The final DNA fragmentation during apoptosis is controlled by CAD.Although percutaneous transfer of CAD gene alone delivered by the gene gun did not show clear inhibition, a combination with CAD and CDDP significantly inhibited the growth of SCC (p<0.05).
(3) Anticanacer effect of Fas-Fas ligand system was investigated. Since the C3H mouse SCC did not express Fas ligand, this ligand was delivered into the SCC by the same gene gun, and examined the anticancer effect. The growth of SCC transfected Fas ligand was significantly inhibited (p<0.0003), and also significant elongation of the survival time was observed.
Among the above 3 apoptosis-promoting gene transfections, the anticancer effect of bax gene +CDDP seemed to be most effective. Less

Report

(4 results)
  • 2000 Annual Research Report   Final Research Report Summary
  • 1999 Annual Research Report
  • 1998 Annual Research Report
  • Research Products

    (54 results)

All Other

All Publications (54 results)

  • [Publications] Fujieda S: "Expression of platelet-derived endothelial cell growth factor in oral and oropharyngeal carcinoma."Clin Cancer Res. 4. 1583-1590 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujieda S: "CD40 stimulation inhibits cell growth and Fas-mediated apoptosis in a thyroid cancer cell line."Oncology Res. 10. 433-439 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 斎藤 等: "抗癌剤の感受性テスについて-遺伝子診断を含めて:頭頸部癌"癌治療と宿主. 10. 416-427 (1998)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noda I: "Granulocyte-colony stimulating factor enhances invasive potential of human head-and -neck-carcinoma cell lines"Int J Cancer. 80. 78-84 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noda I: "Inhibition of N-linked glycosylation by tunicamycin enhances sensitivity to cisplatin in human head-and-neck carcinoma cells"Int J Cancer. 80. 279-284 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujieda S: "Staining of interleukin-10 predits clinical outcome in patents with nasopharyngeal carcinoma"Cancer. 85. 1439-1445 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saito H: "Free peroneal skin flap for oropharyngeal reconstruction."Scan J Plast Reconstr Hand Surg. 33. 41-45 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujieda S: "IL-10 expression with the expression of platelet-derived endothelial cell growth factor and prognosis in oral and oropharyngeal carcinoma"Cancer Lett. 136. 1-9 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sugimoto C: "Apoptosis-promoting gene (bax) transfer promotes sensitivity of squamous cell carcinoma to cisplatin invitro and invivo"Int J Cancer. 82. 860-867 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujieda S: "Expression of p27 is associated with bax expression and spontaneous apoptosis in oral and oropharyngeal carcinoma"Int J Cancer. 84. 315-320 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fan G-K: "Expression of protein p27 is associated with progression and prognosis in laryngeal cancer"Laryngoscope. 109. 815-820 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito T: "Decreased expression of Bax is correlated with poor prognosis in oral and pharyngeal carcinoma"Cancer Lett. 140. 81-91 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 田中信之: "頭頚部癌のCDDP耐性機序とその克服-GS-Xポンプによる薬剤排出とDNA修復能と亢進を中心に-"頭頸部腫瘍. 25. 153-158 (1999)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kimura Y: "Conventional tumor markers are prognostic indicators in patients with head and neck squamous cell carcinoma"Cancer Lett. 155. 163-168 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohtsubo T: "In vitro effects of hyperthermia combined with chemotherapeutic agents"Jpn J Hyperthermic Oncol. 16. 143-151 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohtsubo T: "Enhancement of heat-induced shock protein (hsp) 72 accumulation by doxorubicin (Dox) in vitro"Cancer Lett. 159. 49-55 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujieda S: "Expression of Fas (CD95) ligand is correlated with IL-10 and granulocyte colony-stimulating factor expression in oral and oropharyngeal……"Cancer Lett. 161. 73-81 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] 斎藤 等: "頭頸部腫瘍(犬山征夫編集)CLIENT 21,No17"中山書店,東京. 572 (2000)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohtsubo T: "Thermotherapy for Neoplasia, In flammation, and Pain (Kosaka M eds)"Springer-Verlag,Tokyo. 550 (2001)

    • Description
      「研究成果報告書概要(和文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujieda S: "Expression of platelet-derived endothelial cell growth factor in oral and oropharyngeal carcinoma."Clin Cancer Res. 4. 1583-1590 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujieda S: "CD 40 stimulation inhibits cell growth and Fas-mediated apoptosis in a thyroid cancer cell line."Oncology Res. 10. 433-439 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saito H: "Anticancer chemosesitivity including gene diagnosis (in Japanese)."Cancer Treatment and Host. 10. 416-427 (1998)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noda I: "Granulocyte-colony-stimulating factor enhances invasive potential of human head-and-neck-carcinoma cell lines."Int J Cancer. 80. 78-84 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Noda I: "Inhibition of N-linked glycosylation by tunicamycin enhances sensitivity to cisplatin in human head-and-neck-carcinoma cells."Int J Cancer. 80. 279-284 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujieda S: "Staining of interleukin-10 predicts clinical outcome in patients with nasopharyngeal carcinoma."Cancer. 85. 1439-1445 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Saito H: "Free peroneal skin flap for oropharyngeal reconstruction."Scan J Plast Reconstr Hand Surg. 33. 41-45 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujieda S: "IL-10 expression is associated with the expression of platelet-derived endothelial cell growth factor and prognosis in oral and oropharyngeal carcinoma."Cancer Lett. 136. 1-9 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Sugimoto C: "Apoptosis-promoting gene (bax) transfer promotes sensitivity of squamous cell carcinoma to cisplatin in vitro and in vivo."Int J Cancer. 82. 860-867 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujieda S: "Expression of p27 is associated with bax expression and spontaneous apoptosis in oral and oropharyngeal carcinoma."Int J Cancer. 84. 315-320 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fan G-K: "Expression of protein p27 is associated with progression and prognosis in laryngeal cancer."Laryngoscope. 109. 815-820 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ito T: "Decreased expression of Bax is correlated with poor prognosis in oral and pharyngeal carcinoma."Cancer Lett. 140. 81-91 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Tanaka N: "Enhanced drug efflux and DNA repair ability in a cisplatin-resistant cell line (in Japanese)."Head and Neck Cancer. 25. 153-158 (1999)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kimura Y: "Conventional tumor markers are prognostic indicators in patients with head and neck squamous cell carcinoma."Cancer Lett. 155. 163-168 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohtsubo T: "In vitro effects of hyperthermia combined with chemotherapeutic agents."Jpn J Hyperthermic Oncol. 16. 143-151 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Ohtsubo T: "Enhancement of heat-induced shock protein (hsp) 72 accumulation by doxorubicin (Dox) in vitro."Cancer Lett. 159. 49-55 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Fujieda S: "Expression of Fas (CD95) ligand is correlated with IL-10 and granulocyte colony-stimulating factor expression in oral and oropharyngeal squamous cell carcinoma."Cancer Lett. 161. 73-81 (2000)

    • Description
      「研究成果報告書概要(欧文)」より
    • Related Report
      2000 Final Research Report Summary
  • [Publications] Kimura,Y: "Conventional tumor markers are prognostic indicators in patients with head and neck squamous cell carcinoma"Cancer Letters. 155・. 163-168 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohtsubo,T: "In vitro effects of hyperthermia Combined with chemotherapeutic agents"Jap J Hyperthermic Oncology. 16・3. 143-151 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohtsubo,T: "Enhancement of heat-induced heat shock protein (hsp) 72 accumulation by doxorubicin in vitro"Cancer Letters. 159・. 49-55 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujieda,S: "Expression of Fas (CD95) ligand is correlated with IL-10 and granulocyte colony-stimulating factor expression in oral and oropharyngeal squamous cell carcinoma"Cancer Letters. 161・. 73-81 (2000)

    • Related Report
      2000 Annual Research Report
  • [Publications] Ohtsubo,T: "Thermotherapy for neoplasia, inflammation, and pain"Springer Verlag. 550 (2001)

    • Related Report
      2000 Annual Research Report
  • [Publications] Fujieda, S.: "CD40 stimulation inhibits cell growth and Fas-mediated apoptosis in a thyroid cancer cell line"Oncology Research. 10・. 433-439 (1998)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujieda, S.: "Staining of interleukin-10 predicts clinical outcome in patients with nasopharyngeal carcinoma"Cancer. 85・7. 1439-1445 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Saito, H.: "Free peroneal skin flap for oropharyngeal reconstruction"Scand. J. Plast. Reconstr. Hand Surg.. 33・. 41-45 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujieda, S.: "IL-10 expression is associated with the expression of platelet-derived endothelial cell growth factor and prognosis in oral and ・・・・・"Cancer Letters. 136・. 1-9 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Sugimoto, C.: "Apoptosis-promoting gene (bax) transfer potentiates sensitivity of squamous cell carcinoma to cisplatin in vitro and in vivo"Int. J. Cancer. 82・. 860-867 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fan, G-K.: "Expression of Protein p27 is associated with progression and prognosis in laryngeal cancer"Laryngoscope. 109・. 815-820 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Ito, T.: "Decreased expression of Bax is correlated with poor pragnosis in oral and oropharyngeal carcinoma"Cancer Letters. 140・. 81-91 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Fujieda, S.: "Expression of p27 is associated with Bax expression and spontaneous apoptosis in oral and oropharyngeal carcinoma"Int. J. Cancer. 84・. 315-320 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] 田中 信之: "頭頚部癌のCDDP耐性機序とその克服-GS-Xポンプによる薬剤排出とDNA修復能の亢進を中心に-"頭頚部腫瘍. 25・1. 153-158 (1999)

    • Related Report
      1999 Annual Research Report
  • [Publications] Noda, I.: "Granulocyte-colony-stimulating factor enhances in vasive potential of human head-and-neck-carcinoma cell lines" Int.J.Cancer. 80×. 78-84 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Noda, I.: "Inhibition of N-linked glycosylation by tunicamycin enhances sensitivity to cisplatin in human head-and-neck carcinoma cells" Int.J.Cancer. 80×. 279-284 (1999)

    • Related Report
      1998 Annual Research Report
  • [Publications] Fujieda, S.: "Expression of platelet-derived endothelial cell growth factor in oraland oropharyngeal carcinoma" Clinical Cancer Research. 4×. 1583-1590 (1998)

    • Related Report
      1998 Annual Research Report
  • [Publications] 斎藤 等: "抗癌剤の感受性テストについて-遺伝子診断を含めて : 頭頸部癌" 癌治療と宿主. 10・4. 416-427 (1998)

    • Related Report
      1998 Annual Research Report

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Published: 1998-04-01   Modified: 2016-04-21  

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