Cancer therapy by the adenovirus expressing p53 and miRNA

• Project/Area Number: 20790501
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Sapporo Medical University
• Principal Investigator: IDOGAWA Masashi Sapporo Medical University, 医学部, 助教 (00404749)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 遺伝子治療 / p53 / miRNA / p21 / アデノウイルスベクター / 癌 / アポトーシス / 治療抵抗性

Research Abstract

We examined the therapeutic effectiveness of adenovirus (Ad-p53/miR-p21) that encoded co-cistronic p53 and artificial microRNAs (miRNAs) that targeted p21. Tumor volume was significantly decreased following the direct injection of Ad-p53/miR-p21 into the tumor, as compared to the injection of Ad-p53/miR-control. Our results suggest that adenovirus-mediated transduction of p53 and p21-specific miRNAs may be useful for gene therapy of human cancers.

Research Products

• [Journal Article] A single recombinant adenovirus expressing p53 and p21-targeting artificial microRNAs efficiently induces apoptosis in human cancer cells. Idogawa M (2009)
  • Author(s): Sasaki Y, Suzuki H, Mita H, Imai K, Shinomura Y, Tokino T
  • Journal Title: Clinical Cancer Research 15(11) Pages: 3725-32
  • Peer Reviewed
• [Journal Article] CHFR, a potential tumor suppressor, downregulates interleukin-8 through the inhibition of NF-kappaB. (2009)
  • Author(s): Kashima L, Toyota M, Mita H, Suzuki H, Idogawa M, Ogi K, Sasaki Y, Tokino T
  • Journal Title: Oncogene 28(29) Pages: 2643-53
  • Peer Reviewed
• [Journal Article] p53 family members regulate the expression of the apolipoprotein D gene. (2009)
  • Author(s): Sasaki Y, Negishi H, Koyama R, Anbo N, Ohori K, Idogawa M, Mita H, Toyota M, Imai K, Shinomura Y, Tokino T
  • Journal Title: Journal of Biological Chemistry 284(2) Pages: 872-83
  • Peer Reviewed
• [Journal Article] A novel method, digital genome scanning detects KRAS gene amplification in gastric cancers: involvement of overexpressed wild-type KRAS in downstream signaling and cancer cell growth. (2009)
  • Author(s): Mita H, Toyota M, Aoki F, Akashi H, Maruyama R, Sasaki Y, Suzuki H, Idogawa M, Kahima R, Yanagihara K, Fujita M, Hosokawa M, Kusano M, Sabau SV, Tatsumi H, Imai K, Shinomura Y, Tokino T
  • Journal Title: BMC Cancer 9 Pages: 198-198
  • Peer Reviewed
• [Journal Article] Histone deacetylase inhibitor FK228 enhances adenovirus-mediated p53 family gene therapy in cancer models. (2009)
  • Author(s): Idogwa M, et al.
  • Journal Title: Clinical Cancer Research 15 Pages: 3725-3732
  • Peer Reviewed
• [Journal Article] CHFR, a potential tumor suppressor, downregulates interleukin-8 through the inhibition of NF-kappaB. (2009)
  • Author(s): Kashima L, et al.
  • Journal Title: Oncogene 28 Pages: 2643-2653
  • Peer Reviewed
• [Journal Article] p53 family members regulate the expression of the apolipoprotein D gene. (2009)
  • Author(s): Sasaki Y, et al.
  • Journal Title: Journal of Biological Chemistry 284 Pages: 872-883
  • Peer Reviewed
• [Journal Article] A novel method, digital genome scanning detects KRAS gene amplificati on in gastric cancers : involvement of overexpressed wild-type KRAS in downstream signaling and cance cell growth. (2009)
  • Author(s): Mita H, et al.
  • Journal Title: BMC Cancer 9
  • Peer Reviewed
• [Journal Article] Histone deacetylase inhibitor FK228 enhances adenovirus-mediated p53 family gene therapy in cancer models. (2008)
  • Author(s): Sasaki Y, Negishi H, Idogawa M, Suzuki H, Mita H, Toyota M, Shinomura Y, Imai K, Tokino T
  • Journal Title: Molecular Cancer Therapeutics 7(4) Pages: 779-87
  • Peer Reviewed
• [Journal Article] Histone deacetylase inhibitor FK228 enhances adenovirusmediated p53 family gene therapy in cancer models (2008)
  • Author(s): Sasaki Y, et.al.
  • Journal Title: Molecular Cancer Therapeutics 284 Pages: 779-87
  • Peer Reviewed
• [Presentation] アデノウイルスを用いたp53蛋白とp21発現抑制人工miRNAの共発現による癌治療効果の改善 (2009)
  • Author(s): 井戸川雅史, 佐々木泰史, 篠村恭久, 今井浩三, 時野隆至
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [Presentation] miRNAによるp21発現誘導抑制能を付加したp53発現ベクターによる癌治療効果の増強 (2009)
  • Author(s): 井戸川雅史, 佐々木泰史, 篠村恭久, 今井浩三, 時野隆至
  • Organizer: 第25回日本DDS学会
  • Place of Presentation: 東京
  • Year and Date: 2009-07-03
• [Presentation] A single recombinant adenovirus expressing p53 and p21-targeting artificial microRNAs efficiently induces apoptosis in human cancer cells. (2009)
  • Author(s): Idogawa M, Sasaki Y, Imai K, Shinomura Y, Tokino T
  • Organizer: American Association of Cancer Research (AACR) annual meeting
  • Place of Presentation: Denver
  • Year and Date: 2009-04-21
• [Presentation] A single recombinant adenovirus expressing p53 and p21-targeting artificial microRNAs efficiently induces apoptosis in human cancer cells. (2009)
  • Author(s): Masashi Idogawa
  • Organizer: American Association of Cancer Research (AACR) annual meeting.
  • Place of Presentation: デンバー(米国)
  • Year and Date: 2009-04-21
• [Presentation] miRNAによるp21誘導抑制能をもつp53発現アデノウイルスベクターによる抗腫瘍効果の増強 (2008)
  • Author(s): 井戸川雅史, 佐々木泰史, 今井浩三, 篠村恭久, 時野隆至
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2008-10-28
• [Presentation] p53 expression with p21 suppression by single vector enhances antitumor effect. (2008)
  • Author(s): Idogawa M, Sasaki Y, Imai K, Shinomura Y, Tokino T
  • Organizer: The 36th Congress of the International Society of Oncology & BioMarkers
  • Place of Presentation: Tokyo
  • Year and Date: 2008-10-08
• [Presentation] p53 expression with p21 suppression by single vector enhances antitumor effect (2008)
  • Author(s): Masashi Idogawa
  • Organizer: The 36th Congress of the International Society of Oncology & BioMarkers(ISOBM)
  • Place of Presentation: 東京
  • Year and Date: 2008-10-08
• [Presentation] Enhancement of antitumor effect by adenovirus-mediated p53 expression with p21 suppression by miRNA. (2008)
  • Author(s): Idogawa M, Sasaki Y, Imai K, Shinomura Y, Tokino T
  • Organizer: American Association of Cancer Research (AACR) annual meeting
  • Place of Presentation: San Diego
  • Year and Date: 2008-04-13
• [Presentation] Enhancement of antitumor effect by adenovirusmediated p53 expression with p21 suppression by miRNA (2008)
  • Author(s): Masashi Idogawa
  • Organizer: American Association of Cancer Research (AACR) annual meeting
  • Place of Presentation: サンディエゴ(アメリカ)
  • Year and Date: 2008-04-13
• [Book] 最新医学(消化器系疾患の遺伝子学-消化器癌におけるmiRNA異常-, 9月増刊号) (2008)
  • Author(s): 井戸川雅史, 時野隆至, 篠村恭久, 今井浩三
• [Book] 消化器系疾患の遺伝子学-消化器癌におけるmiRNA異常- (2008)
  • Author(s): 井戸川雅史, ほか
  • Total Pages: 11
  • Publisher: 最新医学社
• [Patent(Industrial Property Rights)] APOPTOSIS INDUCER (2009)
  • Inventor(s): Idogawa M, Sasaki Y, Tokino T
  • Industrial Property Rights Holder: Idogawa M, Sasaki Y, Tokino T
  • Filing Date: 2009-04-13
• [Patent(Industrial Property Rights)] Apoptosis Inducer (2009)
  • Inventor(s): Idogawa M, et al.
  • Industrial Property Rights Holder: Idogawa M, et al.
  • Filing Date: 2009-04-13
  • Overseas
• [Patent(Industrial Property Rights)] アポトーシス誘導剤 (2008)
  • Inventor(s): 井戸川雅史ほか
  • Industrial Property Rights Holder: 井戸川雅史ほか
  • Filing Date: 2008-04-11
  • Overseas