Indoloquinone tumor radiation sensitization

A technology for indoloquinone and tumors, which is applied in the field of radiosensitization of indoloquinone tumors, and can solve the problems of reduced efficacy

Inactive Publication Date: 2008-06-25
癌症治疗公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Although radiation therapy is one of the most widely used cancer treatments, it is less effective when used to treat tumors containing hypoxic cells

Method used

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  • Indoloquinone tumor radiation sensitization
  • Indoloquinone tumor radiation sensitization
  • Indoloquinone tumor radiation sensitization

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0043] Example 1: Effect of Tumor Volume on Tumor Oxygen Tension

[0044] U-87 human glioblastoma cells (American Type Culture Collection) were maintained in alpha MEM medium (Sigma) containing 10% fetal calf serum (Atlanta Biologicals). U-87 human glioblastoma cells (5 x 105 cells in 100 μl PBS) were injected subcutaneously into the right hind limb of athymic NCRNUM nude mice (Taconic Farms) and allowed to grow to ~550 mm 3 of hypoxic volume. Tumor oxygen tension was measured using an Oxford Oxylite fiber optic probe (Oxford, England). The detection system is based on blue light excitation of the ruthenium pigment at the end of the fiber optic probe, which is quenched by oxygen. Measurements were performed on anesthetized mice (75 mg / kg ketamine and 0.3 mg / kg acepromazine) while body temperature was maintained at 37°C using a heating plate. A 25-gauge needle was used to puncture the tumor capsule to facilitate insertion of the fiber optic probe. The probe was inserted i...

Embodiment 2

[0045] Example 2: NQO1 and Cytochrome P450 Reductase Levels in Hypoxic Tumors

[0046] U-87 human glioblastoma cells were injected subcutaneously into the right hindlimb of athymic NCR NUM mice as described and allowed to grow to ~550 mm 3 diameter to induce hypoxia. LDS sample buffer (Invitrogen, Carlsbad, Tumor samples were prepared in CA). Samples were dissolved in NuPage 10% bis-Tris gels (Invitrogen, Carlsbad, CA). Proteins were transferred to polyvinylidene difluoride membranes (Amersham Pharmacia Biotech, Piscataway, NJ) using a semi-dry transfer apparatus (Pharmacia-LKB multiphor II). Western blotting was performed using monoclonal and polyclonal antibodies: anti-human NQO1, anti-human cytochrome P450 reductase, and anti-GAPDH. Immunodetection was performed by enhanced chemiluminescence using the Tropix Western-Star protein detection kit (Applied Biosystems; Foster City, CA).

[0047] Figure 2 shows Western blot analysis of normoxic U87 cells and U87 cells treat...

Embodiment 3

[0048] Example 3: Effect of EO9 & Radiation Therapy on Mean Tumor Volume

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Abstract

This invention generally relates to Indoloquinone caused tumor radiation therapy sensitization. More specifically, this invention relates to the discovery of indoloquinones as a radiation sensitizer (radiation therapy adjuvant) due to its ability to selectively target hypoxic cells and to damage the DNA of these hypoxic cells. Indoloquinones do so with minimal normal cell and tissue toxicity.

Description

technical field [0001] The present invention relates to the sensitization of tumor cells to radiation therapy by administering one or more indoloquinones. More particularly, the invention relates to sensitization of hypoxic tumor cells to radiation therapy by administering one or more indoloquinones. Background technique [0002] Radiation therapy (radiation) is an effective method for treating many types of tumors. Half of all cancer patients receive radiation therapy as part of their cancer treatment. Although radiation therapy is one of the most widely used cancer treatments, it is less effective when used to treat tumors containing hypoxic cells. [0003] Hypoxic cells are cells that receive less oxygen than other cells. Typically, hypoxic cells are more resistant to radiation therapy or chemotherapy due to their low oxygen content. Cells that are more resistant to radiation therapy or chemotherapy can pose a greater risk to cancer patients because of their increased...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/404A61P35/00A61K41/00
CPCA61K41/0038A61K31/404A61P35/00A61K41/00
Inventor 兰迪·伯德路吉·莱纳兹尚塔·乔拉古鲁·雷迪阿达姆·P·迪克尔
Owner 癌症治疗公司
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