New compound halts tumor spread in animal studies
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Treating invasive brain tumors with a combination of chemotherapy and radiation has improved clinical outcomes, but few patients survive longer than two years after diagnosis.
The treatment's effectiveness is limited by the tumor's aggressive invasion of healthy brain tissue, which restricts chemotherapy access to the cancer cells and complicates surgical removal of the tumor.
Emory and Georgia Tech researchers have designed a new treatment approach that appears to halt the spread of cancer cells into normal brain tissue in animal models. The researchers treated animals with an invasive tumor with a molecule called imipramine blue, followed by conventional doxorubicin chemotherapy. The tumors ceased their invasion of healthy tissue, and the animals survived longer than animals treated with chemotherapy alone.
Emory dermatologist Jack Arbiser designed the imipramine blue compound, which is an organic triphenylmethane dye. After in vitro experiments showed that the dye effectively inhibited movement of several cancer cell lines, the researchers tested the compound in an animal model with an aggressive cancer similar to a glioblastoma.
Because imipramine blue is hydrophobic and doxorubicin is cytotoxic, the researchers encapsulated each compound in a liposome that ensured that the drugs would not be released into tissue until they passed through leaky blood vessel walls, which are only present where a tumor is growing.
All of the animals that received the sequential treatment of imipramine blue followed by doxorubicin chemotherapy survived for 200 days with no observable tumor mass. Of the animals treated with doxorubicin chemotherapy alone, 33% were alive after 200 days, with a median survival time of 44 days. Animals that received capsules filled with saline or imipramine blue and no chemotherapy did not survive more than 19 days.
According to the researchers, imipramine blue appears to improve the outcome of brain cancer treatment by altering the regulation of actin, a protein found in all eukaryotic cells. Actin mediates a variety of essential biological functions, including the production of reactive oxygen species. Most cancer cells exhibit overproduction of reactive oxygen species, which are thought to stimulate cancer cells to invade healthy tissue. The dye's reorganization of the actin cytoskeleton is thought to inhibit production of enzymes that produce reactive oxygen species.
In future studies, the researchers plan to test imipramine blue's effect on animal models with invasive brain tumors, metastatic tumors, and other types of cancer such as prostate and breast.
