Molecular Targeting of 15-Lipoxygenase-1 in Colon Cancer

15-脂氧合酶-1 在结肠癌中的分子靶向

基本信息

  • 批准号:
    6918660
  • 负责人:
  • 金额:
    $ 30.96万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2004
  • 资助国家:
    美国
  • 起止时间:
    2004-08-01 至 2008-05-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Apoptosis is being targeted to develop better therapies for colorectal cancer. We have found that (a) linoleic acid's product through 15-1ipoxygenase-1 (15-LOX-1), 13-S-hydroxyoctadecadienoic acid (13-S-HODE), restores apoptosis in colorectal cancer cells, (b) 13-S-HODE and 15-LOX-1 are downregulated in human colorectal cancer, and (c) NSAIDs restore 15-LOX-1 expression in human colorectal cancer cells to induce apoptosis and inhibit tumorigenesis. Human telomerase reverse transcriptase (hTERT) promoter can selectively express genes in cancer cells. The proposed research tests the following hypothesis: Selective restoration of 15-LOX-1 expression under the control of hTERT promoter in colorectal cancer cells via an adenoviral delivery system will reestablish apoptosis and inhibit tumorigenesis in colorectal cancer cells. Specific Aims: Aim 1: To determine whether hTERT-driven 15-LOX-1 expression via an adenoviral vector reestablishes apoptosis through the expression of 15-LOX-1 in colorectal cancer cells, we will transfect colorectal cancer cell lines with an adenoviral vector (Ad-15-LOX-1) that expresses 15-LOX-1 under the control of the hTERT promoter and will measure 15-LOX-1 expression, 13-S-HODE levels, and apoptosis rates in vitro. Aim 2: To assess whether 15-LOX-1 expression driven by hTERT promoter through an adenoviral transfection system suppresses colorectal tumorigenesis in vivo, we will transfect Ad-15-LOX-1 by intratumoral injections into subcutaneous xenografts of human colorectal cancer cells in nude mice and assess the effects of 15-LOX-1 expression on tumorigenesis and apoptosis rates. Aim 3: To determine whether the systemic administration of hTERT-15-LOX-1 adenovirus selectively expresses 15-LOX-1 in tumor cells suppressing tumor growth, we will administer Ad-15-LOX-1 intravenously to nude mice carrying human colon cancer cell liver metastases and evaluate the 15-LOX-1 expression effects on tumor growth. Aim 4: To determine whether 15-LOX-1 downregulates Bcl-2 to induce apoptosis in colorectal cancer cells, we will examine (a) the effects of transfecting Ad-15-LOX-1 into colorectal cancer cells on Bcl-2 expression and (b) if overexpressing Bcl-2 inhibits 15-LOX-1 induced apoptosis. Confirming the feasibility of tumor selective targeting of 15-LOX-1 to inhibit tumorigenesis will pave the way for future preclinical and clinical development of therapeutic strategies based on molecularly targeting 15-LOX-1

项目成果

期刊论文数量(0)
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科研奖励数量(0)
会议论文数量(0)
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Imad Shureiqi其他文献

Imad Shureiqi的其他文献

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{{ truncateString('Imad Shureiqi', 18)}}的其他基金

ALOX15 regulation of colon cancer invasiveness via PI3P-linoleic acid metabolism
ALOX15 通过 PI3P-亚油酸代谢调节结肠癌侵袭力
  • 批准号:
    10339182
  • 财政年份:
    2022
  • 资助金额:
    $ 30.96万
  • 项目类别:
ALOX15 regulation of colon cancer invasiveness via PI3P-linoleic acid metabolism
ALOX15 通过 PI3P-亚油酸代谢调节结肠癌侵袭性
  • 批准号:
    10545078
  • 财政年份:
    2022
  • 资助金额:
    $ 30.96万
  • 项目类别:
15-LOX-1 Modulation of Colon Cancer Promotion by Linoleic Acid
亚油酸对 15-LOX-1 促进结肠癌的调节
  • 批准号:
    10330050
  • 财政年份:
    2021
  • 资助金额:
    $ 30.96万
  • 项目类别:
15-LOX-1 regulation of resolving generation to modulate colon cancer
15-LOX-1 调节分解生成以调节结肠癌
  • 批准号:
    10301423
  • 财政年份:
    2016
  • 资助金额:
    $ 30.96万
  • 项目类别:
15-LOX-1 Regulation of Resolving Generation to Modulate Colon Cancer
15-LOX-1 调节分解生成以调节结肠癌
  • 批准号:
    9980183
  • 财政年份:
    2016
  • 资助金额:
    $ 30.96万
  • 项目类别:
15-LOX-1 Modulation of Colon Cancer Promotion by Linoleic Acid
亚油酸对 15-LOX-1 促进结肠癌的调节
  • 批准号:
    9886073
  • 财政年份:
    2016
  • 资助金额:
    $ 30.96万
  • 项目类别:
15-LOX-1 Regulation of Resolving Generation to Modulate Colon Cancer
15-LOX-1 调节分解生成以调节结肠癌
  • 批准号:
    9187612
  • 财政年份:
    2016
  • 资助金额:
    $ 30.96万
  • 项目类别:
Molecular targeting of PPAR-delta in colon cancer
结肠癌中 PPAR-δ 的分子靶向
  • 批准号:
    7987654
  • 财政年份:
    2010
  • 资助金额:
    $ 30.96万
  • 项目类别:
Molecular targeting of PPAR-delta in colon cancer
结肠癌中 PPAR-δ 的分子靶向
  • 批准号:
    8259197
  • 财政年份:
    2010
  • 资助金额:
    $ 30.96万
  • 项目类别:
Molecular targeting of PPAR-delta in colon cancer
结肠癌中 PPAR-δ 的分子靶向
  • 批准号:
    8091356
  • 财政年份:
    2010
  • 资助金额:
    $ 30.96万
  • 项目类别:

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  • 批准号:
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  • 资助金额:
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  • 项目类别:
Molecular Targeting of 15-Lipoxygenase-1 in Colon Cancer
15-脂氧合酶-1 在结肠癌中的分子靶向
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15-脂氧合酶-1 在结肠癌中的分子靶向
  • 批准号:
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  • 财政年份:
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  • 资助金额:
    $ 30.96万
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    $ 30.96万
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  • 财政年份:
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    $ 30.96万
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