Suppression of cancer recurrence by intercepting tumor blood flow after X-ir radiation

X-IR 辐射后通过拦截肿瘤血流来抑制癌症复发

基本信息

  • 批准号:
    17591242
  • 负责人:
  • 金额:
    $ 2.11万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
  • 财政年份:
    2005
  • 资助国家:
    日本
  • 起止时间:
    2005 至 2006
  • 项目状态:
    已结题

项目摘要

The purpose of this study was to investigate dynamic changes in the tumor microenvironment (tumor blood flow, vascular permeability, clearance, and interstitial fluid pressure) induced after a single dose of X-ray irradiation in a variant of Yoshida sarcoma, LY80, and to clarify the therapeutic significance of intercepting tumor blood flow (TBF) after irradiation. Radiation (10 Gy) was administered locally to tumors of anesthetized rats. A combretastatin derivative which intercepts TBF and disrupts tumor vessels, AC7700, was administered i.v. (10 mg/kg/ml). At 24 h after irradiation, TBF began to increase and showed an increase of 2-2.5 times at 72-96 h. All parameters used to assess the tumor microenvironment consistently showed improvement of tumor microcirculation. Apparently, improvement of this tumor microcirculation contributes to cancer recurrence. At all investigated times after irradiation, AC7700 stopped TBF completely and irreversibly. AC7700 administration after irradiation markedly enhanced of antitumor efficacy. Such a combination might have important therapeutic benefit, even in tumors which are insensitive to either treatment alone. We conclude that destruction of tumor microcirculatory function after irradiation is important for suppressing tumor growth. It is particularly for preventing cancer recurrence.
本研究的目的是调查吉田肉瘤LY80的单剂量X射线照射后引起的肿瘤微环境(肿瘤血流、血管通透性、间隙和间质液压力)的动态变化,并阐明照射后拦截肿瘤血流(TBF)的治疗意义。对麻醉大鼠的肿瘤进行局部放射(10 Gy)。静脉注射考布他汀衍生物 AC7700,它可以拦截 TBF 并破坏肿瘤血管。 (10 毫克/千克/毫升)。照射后24 h,TBF开始增加,72-96 h时增加2-2.5倍。用于评估肿瘤微环境的所有参数一致显示肿瘤微循环得到改善。显然,这种肿瘤微循环的改善有助于癌症复发。在照射后的所有研究时间中,AC7700 完全且不可逆地停止了 TBF。照射后给予AC7700显着增强抗肿瘤功效。这样的组合可能具有重要的治疗益处,即使对于单独治疗不敏感的肿瘤也是如此。我们的结论是,辐射后肿瘤微循环功能的破坏对于抑制肿瘤生长很重要。它特别适合预防癌症复发。

项目成果

期刊论文数量(4)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Cancer therapy by means of irreversible tumor blood flow stasis : starvation tactics against solid tumors
通过不可逆的肿瘤血流停滞进行癌症治疗:针对实体瘤的饥饿策略
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Yamada;M.;Iwabuchi;T.;Takahashi;K.;Kurahashi;C.;Higuchi;T.;Yamada;M.;Katsuyoshi Hori
  • 通讯作者:
    Katsuyoshi Hori
Antineoplastic strategy : irreversible tumor blood flow stasis induced by the combretastatin A-4 derivative AVE8062 (AC7700)
抗肿瘤策略:考布他汀A-4衍生物AVE8062(AC7700)诱导不可逆的肿瘤血流停滞
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Isobe K;Uno T;Kawakami H;et al.;Katsuyoshi Hori
  • 通讯作者:
    Katsuyoshi Hori
Antineoplastic strategy : irreversible tumor blood flow stasis induced by the combretastatin A-4 derivative AVE8062(AC7700)
抗肿瘤策略:考布他汀A-4衍生物AVE8062(AC7700)诱导不可逆的肿瘤血流停滞
  • DOI:
  • 发表时间:
    2005
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Wu J;et al.;Katsuyoshi Hori
  • 通讯作者:
    Katsuyoshi Hori
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HORI Katsuyoshi其他文献

HORI Katsuyoshi的其他文献

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{{ truncateString('HORI Katsuyoshi', 18)}}的其他基金

Induction of EPR effects on microtumors by combretastatin and its microcirculation mechanism
考布他汀诱导微肿瘤EPR作用及其微循环机制
  • 批准号:
    24650643
  • 财政年份:
    2012
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Challenging Exploratory Research
A novel chemoradiotherapy prolonging intratumoral retention of anticancer drugs by interrupting tumor blood flow
一种通过中断肿瘤血流延长抗癌药物在瘤内保留的新型放化疗
  • 批准号:
    19591449
  • 财政年份:
    2007
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Efficacy of microwave hyperthermia under condition of decrease in tumor blood flow
肿瘤血流减少条件下微波热疗的疗效
  • 批准号:
    09670912
  • 财政年份:
    1997
  • 资助金额:
    $ 2.11万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
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