TUESDAY, April 15 (HealthDay News) -- A germ that commonly causes food poisoning may be the next weapon in the fight against cervical cancer, a major cause of death among women worldwide.

A new trial shows that a live Listeria vaccine called Lovaxin C is safe and even showed some benefit in 15 women with advanced cervical cancer.

Listeria is a common bacteria found on leafy vegetables and dairy products. "Most of us eat it routinely but don't know it, because it generates a strong immune reaction," study lead author John Rothman, vice president of clinical development at Advaxis Inc. of North Brunswick, N.J., which makes the vaccine, said at a Tuesday news conference. "It can cause disease, but it's safe, because the lowest doses of any number of antibiotics will clear it and will do it without impeding the immune response."

This vigorous immune response is what researchers are hoping will give the vaccine a fighting chance against cervical cancer. According to Rothman, there are at least 10 ways that Listeria attacks tumors, and probably more.

Most of the women involved in this study had stage 4 disease and had failed prior surgery, chemotherapy or radiation. All women were given the vaccine as well as the antibiotic ampicillin.

By study's end, only five patients still had progressive disease, seven were stable and one demonstrated a partial response to the vaccine. Three of the seven stable patients showed tumor reductions of about 20 percent and one of more than 30 percent.

The vaccine did cause flu-like symptoms in all patients (fever, chills, nausea), but those who had received lower-dose vaccines were treated easily with over-the-counter drugs, the researchers said.

Rothman's study was just one of several showing promise that were presented Tuesday at the American Association for Cancer Research annual meeting, in San Diego.

A second study, out of the Netherlands, found that the GVAX vaccine stimulated a significant immune response in men with prostate cancer. Five out of six participants receiving the highest dose of vaccine showed declines in PSA (prostate-specific antigen) levels of 50 percent or more.

"This appears to be a promising approach," study lead author Saskia Santegoets of VU University Medical Center in Amsterdam, said at the news conference.

Another vaccine -- this one for prostate cancer that hasn't responded to other therapies -- also showed hope. Three of six patients who received the highest dose of the vaccine saw declines in PSA levels of more than 50 percent. The trial involved 24 patients overall.

According to lead author Dr. Lawrence Fong of the University of California, San Francisco, the vaccine works by "educating" the immune system."

And, finally, antibody directed enzyme pro-drug therapy (ADEPT) showed positive responses in 44 percent of patients with either colorectal, gastro-esophageal, breast, gallbladder, peritoneal, appendix, pancreas or cancer of unknown primary site. With ADEPT, an enzyme activates a drug that has been targeted to the tumor by an antibody, at the site of the tumor.

More information

The U.S. National Cancer Institute has more on cancer vaccines.

TUESDAY, April 15 (HealthDay News) -- The drug riluzole, approved in the United States to treat amyotrophic lateral sclerosis (ALS), slows the growth of highly aggressive melanoma skin cancer, according to a new study.

A common feature of both melanoma and ALS (also called Lou Gehrig's disease) is an excess amount of the protein glutamate, a cellular growth factor or food for cells. Too much glutamate can overstimulate neurons to the point where they burn out -- a possible explanation for what happens in ALS, according to background information in the study. Overproduction of glutamate causes the growth and expansion of melanoma.

Riluzole (brand name Rilutek) inhibits the release of glutamate.

In laboratory tests using cultures of human melanoma cell lines, researchers at Rutgers University and the Cancer Institute of New Jersey found that riluzole appeared to switch off overproduction of glutamate and slow the growth rate of the melanoma cells. In tests on animals, the drug showed the same suppression of melanoma cell growth.

The researchers then started testing the drug on 11 people with late-stage (stage 3 or 4) melanoma. The patients in this phase 0 (exploratory, first-in-humans) trial received riluzole for two weeks.

"Our preliminary results show three solid positive responses in nine of the patients who had been able to complete the trial to date," Dr. James Goydos, a surgical oncologist at the Cancer Institute of New Jersey, said in a prepared statement.

Other patients in the group showed some indications of responding to the drug, and they'll be reassessed at the end of the trial.

The research was to be presented April 15 at the annual meeting of the American Association for Cancer Research, in San Diego.

The findings provide "enough data to show that we should go on to a more extensive (phase 1/2) trial," Goydos said. He expects it will begin later this year and include 50 to 100 patients with stage 4 melanoma.

"I think this drug is going to be extremely important as an adjunct to surgical treatment of stage 3 or stage 4 melanoma," Goydos said. "The challenge is to keep it from recurring, which has happened in patients on the order of 50 percent. With low toxicity likely, riluzole could potentially be given for long periods of time to slow down the metabolic process responsible for the disease's recurrence."

More information

The U.S. National Cancer Institute has more about melanoma.

THURSDAY, April 3 (HealthDay News) -- Certain cancers tend to spread to specific tissues, and now researchers have gained a molecular handle on how that happens.

Working with breast tumors, Joan Massague, chairman of the Cancer Biology and Genetics Program at Memorial Sloan-Kettering Cancer Center in New York City, and his colleagues discovered a signaling "relay" that enables the cancer to molecularly "soften" its target tissue -- the lung in this case -- allowing circulating breast cancer cells to pass through capillary walls and penetrate the lung.

"It provides a very nice mechanism for how breast cancer cells specifically get out of the circulation and into the lungs. Nobody knew how they did that before," said Karl Saxe, a scientific program director at the American Cancer Society.

The results were published in the April 4 issue of Cell.

Key to this study is a signaling molecule called TGF-beta. Early in cancer progression, TGF-beta acts as a tumor suppressor, inhibiting cancer growth. Later, it actually stimulates cancer progression and metastasis. Massague was interested in how tumors trigger this molecular dichotomy.

His team began by identifying a molecular signature, a pattern of gene expression of 153 genes that identifies tumors that are both expressing and responding to TGF-beta. They then applied that signature to hundreds of primary breast tumors.

While there was no apparent correlation between TGF-beta signaling and metastasis in breast cancers that also express the estrogen receptor, the team found that tumors that were estrogen receptor-negative and signature-positive were much more likely to metastasize to lung. No similar correlation was found for metastasis to the bone, liver or brain.

When the team then asked which of the genes in the signature was responsible for this selectivity, they identified a second element in the relay, a signaling molecule called angiopoietin-like 4 (ANGPTL4), whose expression is induced by TGF-beta. ANGPTL4 disrupts capillary walls, loosening the connections between adjacent cells and allowing the metastasizing cells to "seed" the tissue.

Disrupt TGF-beta signaling, or ANGPTL4 expression, and lung metastasis is disrupted, the researchers found. Enhance that signaling, and lung metastasis is increased.

"This is a molecular and biological explanation of why and how responding to TGF-beta contributes to lung metastasis," concluded Massague.

This study also suggests anticancer therapies based on both TGF-beta (which are currently in development) and ANGPTL4 could be useful against metastatic breast cancer, he added.

According to Saxe, the observation that cancers have a way to select targets to spread to is not surprising. "Something like this had to be going on," he said. "But what is very nice and satisfying is to find a very clear mechanism like this to explain why some kinds of breast cell tumors metastasize to the bone and some to lung."

Massague said the reason ANGPTL4 helps cells colonize the lungs but not the bone has to do with the different architecture of the two tissues. Lung tissue is highly vascularized, yet capillaries present a relatively impenetrable barrier to metastasizing cells. Bone, on the other hand, is different, Massague explained, because it has windows and "...every day in the bone marrow, the capillaries have to let cells in and out."

Similar molecular discriminators may turn out to play a role in a variety of tumors, Saxe said. TGF-beta signaling in general, and ANGPTL4 in particular, may control metastasis in a variety of tumor types. Other signaling pathways could also be involved, and Saxe said he expects this study will spark new research to investigate those possibilities.

As Dr. Kornelia Polyak, a researcher with the Breast Cancer Genetics Lab at the Dana-Farber Cancer Institute at Harvard Medical School, pointed out, metastasis likely involves "an orchestra of genes that together can contribute to different steps" of the process. "It's likely to be a combination of genes, and this particular one [ANGPTL4] is one of them."

More information

For more on breast cancer, visit the National Cancer Institute.

THURSDAY, March 27 (HealthDay News) -- A sophisticated imaging technique can detect the changes in blood flow in the brain that often herald the emergence of highly malignant brain tumors, researchers report.

The British researchers said the discovery could one day help doctors time the treatment of brain tumors known as low-grade gliomas by using MRI technology to measure changes in "relative cerebral blood volume."

"The clinical treatment of low-grade gliomas is controversial because none of the therapeutic options is curative and patients are often young and clinically well," said Adam D. Waldman, one of the lead investigators and imaging research director at Imperial College National Health Service Trust in London.

"Almost all low-grade gliomas, however, transform into aggressive high-grade tumors, although the timing of that is unpredictable," Waldman added. High-grade tumors are considered very malignant and grow quickly, he explained.

Finding a "marker" for that transformation was the goal of a three-year study by Waldman and his colleagues. Using perfusion MRI imaging with 13 patients, they found that increases in relative cerebral blood volume are a signal that the low-grade glioma is turning into a high-grade glioma. For brain tumors to grow, new blood vessels are formed during a process known as angiogenesis. These abnormal vessels increase blood flow to the tumor, according to the study.

"Essentially what we think perfusion imaging is demonstrating are the earliest changes in the tumor that go along with malignant change," Waldman said.

The findings will be published in the April issue of Radiology.

Perfusion MRI can detect the progression of malignant brain tumors at least 12 months earlier than current monitoring, the study authors suggested. They recommend that it be used routinely to identify patients who could benefit from early treatment.

Dr. Annick Desjardins, a neuro-oncologist and associate in the department of medicine at Duke University Medical Center, said low-grade gliomas occur less frequently than high-grade gliomas and are difficult to treat. The lowest level of gliomas -- grade one -- hasn't infiltrated the brain yet and can be cut out, she explained. But grade two gliomas -- the type studied by Waldman and his team -- have infiltrated the brain and aren't easy to remove, she said.

A doctor who is following a patient has no way to tell if the tumor will be stable for 10 years or progress in the next three months, Desjardins said. "Early detection will probably allow us to control those tumors over a longer period of time," she said, before adding, "We don't have those data at this particular time to prove that."

Dr. Paul Graham Fisher, an associate professor of neurology and pediatrics at Stanford University School of Medicine, said perfusion MRI technology is widely available at bigger city and academic medical centers. The use of perfusion MRI detailed in the new study provides a noninvasive technique and "the less invasive you can be, the better it will be for patients in the long run," he said.

But, Fisher added, "The only sad part is that the imaging and diagnostics are advancing much faster than the therapeutics. Hand-in-hand, they are critical to each other." While the new ability to detect changes in low-grade gliomas suggested by Waldman's group doesn't promise better therapies or cure rates, "it is encouraging," he said.

More information

To learn more about brain tumors, visit the U.S. National Institute of Neurological Disorders and Stroke.