Many patients with acute myeloid leukemia, a cancer of the blood, have poor treatment outcomes because they cannot tolerate chemotherapy. In others, chemotherapy treatment simply does not work. It is very important to find new therapies for this disease that work better and that are tolerated by all patients.

The researchers investigated whether common genetic changes in a gene called glutathione s-transferase, or GST, can influence how people with leukemia react to chemotherapy. The GST gene influences the levels of GST enzymes in the body. GST enzymes are involved in breaking down (i.e., metabolizing) chemotherapy agents given to leukemia patients.

Patients with higher GST enzyme levels may break down the chemotherapeutic agents more rapidly than those with lower GST enzyme levels. This may lead to better tolerance of therapy, but poorer clinical outcomes because the chemotherapy agents were broken down before they could damage the leukemia cells.

This study of GST genes included 273 acute leukemia patients from Roswell Park Cancer Institute who received chemotherapy. Results indicate that while the GSTs may not play a significant role in survival outcomes or relapse-free survival, they may play an important role in determining toxicities to therapy.

The researchers concluded that the GST genes might not influence major clinical milestones in acute leukemia, but might play a role in how well chemotherapy is tolerated by leukemia patients.

Founded in 1907, the American Association for Cancer Research is the world's oldest and largest professional organization dedicated to advancing cancer research. Members include more than 24,000 basic, translational and clinical researchers, health care professionals and cancer survivors and advocates in the United States and more than 60 other countries.

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"The beauty of this study is that we are showing that a substance of abuse, if used prudently, may offer a new road to therapy against lung cancer," said Anju Preet, Ph.D., a researcher in the Division of Experimental Medicine.

Acting through cannabinoid receptors CB1 and CB2, endocannabinoids (as well as THC) are thought to play a role in variety of biological functions, including pain and anxiety control, and inflammation. Although a medical derivative of THC, known as Marinol, has been approved for use as an appetite stimulant for cancer patients, and a small number of U.S. states allow use of medical marijuana to treat the same side effect, few studies have shown that THC might have anti-tumor activity, Preet says. The only clinical trial testing THC as a treatment against cancer growth was a recently completed British pilot study in human glioblastoma.

In the present study, the researchers first demonstrated that two different lung cancer cell lines as well as patient lung tumor samples express CB1 and CB2, and that non-toxic doses of THC inhibited growth and spread in the cell lines. "When the cells are pretreated with THC, they have less EGFR stimulated invasion as measured by various in-vitro assays," Preet said.

Then, for three weeks, researchers injected standard doses of THC into mice that had been implanted with human lung cancer cells, and found that tumors were reduced in size and weight by about 50 percent in treated animals compared to a control group. There was also about a 60 percent reduction in cancer lesions on the lungs in these mice as well as a significant reduction in protein markers associated with cancer progression, Preet says.

Although the researchers do not know why THC inhibits tumor growth, they say the substance could be activating molecules that arrest the cell cycle. They speculate that THC may also interfere with angiogenesis and vascularization, which promotes cancer growth.

Preet says much work is needed to clarify the pathway by which THC functions, and cautions that some animal studies have shown that THC can stimulate some cancers. "THC offers some promise, but we have a long way to go before we know what its potential is," she said.

Targeted release of oncolytic measles virus by blood outgrowth endothelial cells in situ inhibits orthotopic gliomas: Abstract 4185

Researchers in Germany have hidden vaccine-grade measles virus inside artificially generated blood cells in order to devise a search-and-destroy therapy for human brain cancer that can?t be "seen" by the immune system.

They say their mouse experiments show a proof of principle that this non-pathogenic virus can attack glioma by getting inside tumor cells and replicating, destroying the common brain tumors from the inside out. This and other so-called "oncolytic" viruses are already being tested in clinical trials, but their effectiveness has been limited by an immediate human immune response, the researchers say.

"In an immune-competent patient, the immune system will fight the virus, and most adults are immune against measles since they have been vaccinated against the disease in childhood or have had measles," said Christian Beltinger, M.D., an associate professor at the University Children?s Hospital in Ulm. "Although cancer patients are immune-compromised by their disease or because of therapy, they still may mount a sufficient attack against vaccine measles virus."

To trick this immune surveillance, the researchers generated blood outgrowth endothelial cells (BOECs), which are produced outside of the body using human blood bathed in a cocktail of growth factors. "They do not naturally occur in the blood, but they are derived from endothelial progenitor cells, rare cells that are produced in the bone marrow and shed into the blood," Dr. Beltinger said.

These cells are well suited for cancer therapy for two reasons, he said. If a vaccine measles virus is tucked within them, it can?t be reached by the immune system?s neutralizing antibodies. Also, they are endothelial progenitor cells, which are recruited in the body wherever new blood vessels are formed.

"Tumors need vessels to grow, hence they recruit these blood progenitor cells," Dr. Beltinger said. "That makes them home to the tumors."

BOECs have been used for other gene therapeutic approaches, such as for hemophilia, but this is the first time they have been adapted to carry vaccine measles virus, he said.

To test how well they functioned as a cancer therapy, the researchers injected U87 cells (the most commonly used human glioma cancer cell line) into the brains of immune-compromised mice. Once the tumors were established, BOECs recently infected with vaccine measles virus were injected around, but not into, the brain tumor. These loaded blood cells navigated through normal brain tissue to the tumor mass, and once inside, the BOECs released the virus into surrounding tumor cells. It then spread to other tumor cells.

Eventually the blood cells died. This delay of death, however, was sufficient to allow the infected cells to home to the tumor and release the virus, the researchers say.

They found that mice treated with BOECs survived significantly longer than mice receiving just empty blood cells or "naked" measles virus. But the researchers say that all mice eventually died, showing that the therapy could not completely eradicate the tumors.

"While these modified blood cells carrying vaccine measles virus look like a promising novel therapy for gliomas, it is still a preclinical experimental approach," Dr. Beltinger said. "Potentially it could be used on most malignant gliomas, including glioblastomas, because the targeting of the virus can be genetically modified."

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