From OncoLog, June 2006, Vol. 51, No. 6

In Brief

Immune Response May Prevent Brain Tumor Development

Does immune system surveillance play a role in preventing the development of brain tumors? Researchers at M. D. Anderson Cancer Center think so, on the basis of their recent epidemiological study showing that allergies and asthma may have a protective effect against brain tumors. The researchers theorize that hay fever may produce enough inflammation in the brain to keep immune cells active and that this surveillance works to eliminate early signs of malignancy.

In the study, researchers compared the medical histories of 830 brain tumor patients with those of a control group of 831 individuals. They found that a history of allergies and asthma was significantly protective for the three different kinds of brain tumors examined in the study. Individuals with a history of allergies and asthma had a 35% reduced risk of developing glioblastoma, a 51% reduced risk of anaplastic astrocytoma, and a 36% reduced risk of low-grade gliomas.

Researchers also found, however, that use of antihistamines to counter inflammation in allergies eliminates the protective effect of allergies and asthma and increases the risk of developing brain tumors. Participants who used antihistamines had three times the risk of developing an anaplastic astrocytoma tumor and two times the risk of developing low-grade gliomas, compared with those who did not use antihistamines. The risk of developing a glioblastoma was also increased by 26%, but that was not statistically significant, the researchers said.

But researchers stress that no one should give up antihistamines because of this study. “Brain tumors are exceedingly rare, and many, many people use antihistamines, so we certainly are not suggesting a direct connection between the two,” said the study’s lead author, Melissa Bondy, Ph.D., a professor in the Department of Epidemiology.

“Our study suggests that those who have allergies and don’t do anything about it may be protected to some degree against brain tumors,” Dr. Bondy said. “But those who use antihistamines could decrease that protection and increase their risk. The real question is if there are particular gene variants that would make a person susceptible.”

“Our long-term goal is to look at genes that may be increasing or reducing the risk of developing these tumors, and then to assess whether some individuals might be genetically susceptible,” said Michael E. Scheurer, Ph.D., a postdoctoral fellow in the Department of Epidemiology and the study’s first author.

Targeted Molecular Imaging of Cancer

Researchers at M. D. Anderson Cancer Center have created a new class of a hybrid virus and demonstrated its ability to find, highlight, and deliver genes to tumors in mice.

Researchers say the advance, reported in the journal Cell, is potentially an important step in making human cancer both more visible and accessible to treatment; it may also allow prediction and monitoring of how specific anticancer agents are actually working.

“In tumor-bearing mice, we show that this hybrid virus can target tumors systemically to deliver an imaging or therapeutic gene,” said one co-leader of the study, Renata Pasqualini, Ph.D., professor of Medicine and Cancer Biology at M. D. Anderson. “The signal is specific only to tumors, so one can monitor drug effectiveness at the molecular level.”

The research team created and characterized the hybrid viruses by combining genetic elements and biological attributes of an animal virus (adeno-associated virus, or AAV) with those of a bacterial virus (phage). Unlike animal viruses that infect mammalian cells, bacterial viruses have evolved to infect only bacterial hosts. The research shows how particles of the hybrid virus, called AAV phage or AAVP, can serve as a vehicle for targeted delivery of genes to experimental tumors in mice and to the tumors’ blood vessel supply, providing a strategy for finding tumors and genetically marking them for imaging on a clinic-ready body scanner.

“We could see by using positron emission tomography that the reporter and therapeutic genes were being expressed throughout the tumors in the animals,” said Juri Gelovani, M.D., Ph.D., chair of the Department of Experimental Diagnostic Imaging. “This is an example of the so-called ‘theragnostic’ approach, a combination of the words therapeutic and diagnostic.”

The AAVP hybrid combines the ability of the bacterial virus to target specific tissues with the capability of the mammalian virus to actually deliver genes to cells. The vectors in the AAVP hybrid retained the properties of their parental viruses, which the researchers called a surprising outcome.

“This is only a proof of concept, and although we have yet to translate these hybrid viruses for use in humans, we hope that this new system will have important clinical applications in the future,” said Wadih Arap, M.D., the other co-leader of the study and professor of Medicine and Cancer Biology. “In addition to the obvious biological interest, when the vector is refined for patient use, it could perhaps help us diagnose, monitor, and treat human tumors more accurately.”

Avoiding Complications from Preoperative Chemotherapy

Physicians should exercise caution when selecting a preoperative chemotherapy drug to treat colorectal cancer that has spread to the liver, say researchers at M. D. Anderson Cancer Center, carefully matching the right drug with the patient.

Use of chemotherapy before surgery offers several important benefits, including reducing the size of tumors so that they are more easily removed, potentially doubling the survival rate. However, preoperative chemotherapy also has the potential to damage the liver.

New insight into the problem of chemotherapy-related hepatotoxicity emerged from a recent study conducted at M. D. Anderson and a hospital in Torino, Italy, and presented in the May 1 issue of the Journal of Clinical Oncology. The investigators found, in a cohort of 406 patients, that different drugs cause different types of liver injury. One drug, irinotecan, produced steatohepatitis, an inflamed “fatty” liver, in 20% of patients, while another drug called oxiliplatin caused sinusoidal dilatation, leading to the pooling of red blood cells in the liver, in 19% of patients.

Steatohepatitis was the sole injury associated with an increased risk of postoperative mortality after liver surgery. “Its presence in patients undergoing extensive liver surgery may result in failure to regenerate new liver tissue, leading to liver failure,” said lead author Jean-Nicolas Vauthey, M.D., professor in the Department of Surgical Oncology at M. D. Anderson.

Although steatohepatitis may affect people who have not undergone preoperative chemotherapy but who are overweight or who already have steatosis, researchers noted that irinotecan was associated with an increased risk of steatohepatitis with a more pronounced effect in patients with a higher body mass index (BMI).

“Most patients who are given preoperative chemotherapy when their colorectal cancer metastasizes to the liver do fine,” Dr. Vauthey said. “But this study shows us that we need to select the patients and use the drug that is right for them.”

Given these findings, researchers recommend that patients be screened in advance for high BMI and for preexisting steatosis, which can predispose patients to chemotherapy-induced steatohepatitis. Overall, these individuals are not the best candidates for irinotecan as a first-line treatment.

Vaccine Curbs Brain Tumor Growth

A novel vaccine has significantly increased life expectancy in patients with glioblastoma multiforme (GBM), the most dangerous type of brain tumor, a researcher from M. D. Anderson Cancer Center is reporting at the annual meeting of the American Association of Neurological Surgeons.

Median survival for the 23 patients who received the vaccine at M. D. Anderson and at Duke University Medical Center has been at least 19 months, and only four patients have died from the cancer, said Amy Heimberger, M.D., an assistant professor of Neurosurgery at M. D. Anderson. This figure surpasses the median survival of 14 months for patients with GBM who are treated with the most current chemotherapy and radiation and the 4-month median survival for untreated patients, she said.

“We can’t say this vaccine is better than chemotherapy because we haven’t tested the two treatments head-to-head yet,” she said. “However, so far, results have exceeded the expectations we had for this vaccine.”

Given the statistically significant findings, a pharmaceutical company has acquired the rights to the drug and a larger, multi-institutional, randomized study is being planned, Dr. Heimberger said.

She describes the vaccine as an easy-to-use treatment that can potentially help up to 50% of all GBM patients keep their cancer at bay for a period of time. Interim results of a phase II clinical trial show that the vaccine significantly delays progression of tumors until the cancer finds a new growth pathway.

For more information on this topic or for questions about M. D. Anderson’s treatments, programs, or services, call askMDAnderson at (877) MDA-6789.

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