Rodent of the Week: Implanted vaccine attacks cancer

Several cancer vaccines that are delivered via injections or intravenous lines are in development. Another approach to a vaccine, however, is to implant a small disk containing cancer-fighting substances under the skin, according to researchers from Harvard University and the Dana-Farber Cancer Institute.

The scientists showed they could implant a plastic disk containing tumor-specific antigens under the skin of mice. The substances on the disk caused the immune system to mount an attack on cancer cells and eliminated melanoma tumors. The study was published this week in the journal Science Translational Medicine.

"Inserted anywhere under the skin - much like the implantable contraceptives that can be placed in a woman's arm - the implants activate an immune response that destroys tumor cells," the lead author of the study, David J. Mooney. a professor of bioengineering at Harvard, said in a news release.

The implant approach may be less cumbersome and and more effective than other types of cancer vaccines. Most cancer vaccines remove immune cells from the body, reprogram them to attack cancer and return them to the body. But the re-injected cells can die before completing their task. The implant harnesses several types of cells that direct potent immune responses while protecting healthy tissue.

-- Shari Roan

Photo credit: Advanced Cell Technology Inc.

Rodent of the Week: Drug shows effect on lung cancer tumors

Small-cell lung cancer is a disease sorely in need of better therapies. Now a study in mice has found a promising drug that may enter clinical trials in humans within a year.

One in five people with lung cancer has small-cell lung cancer. The disease has a poor long-term survival rate because the tumors spread quickly. Previous research has shown that these tumor cells grow faster because they are fueled by a growth hormone called FGF-2.

The study, published this week in the journal Cancer Research, examined a drug called PD173074 because it is known to block the receptor that FGF-2 uses to attach to tumor cells. Given to mice with the disease, the drug eliminated tumors in 50% of cases. Another test showed the compound increased the effect of chemotherapy.

"We urgently need to develop new treatments for this disease," the lead author of the study, Dr. Michael Seckl of Imperial College London, said in a news release. Although small-cell lung cancer "responds to chemotherapy initially, the tumors soon become resistant to treatment and sadly nearly all people with the disease do not survive. ... We hope to take this drug, or a similar drug that also stops FGF-2 from working, into clinical trials next year to see if it is a successful treatment for lung cancer in humans."

— Shari Roan

Photo credit: Advanced Cell Technology, Inc.

Rodent of the Week: New use for an old drug

Research can be serendipitous. Sometimes doctors will stumble on an effective medication or they will find a drug they expected to work on one condition actually helps another.

Such is the case with a gonorrhea medication developed in the 1930s. Preliminary evidence published this week shows that the substance, called acriflavine, may work as a cancer therapy. Researchers from Johns Hopkins University discovered that the drug has the ability to stop the growth of new blood vessels, which may then curb tumor growth. Mice who were engineered to develop cancer showed no tumor growth when they were injected with acriflavine daily. The study showed that acriflavine inhibits the function of a protein called HIF-1, which promotes new blood vessel formation.

"Mechanistically, this is the first drug of its kind," Jun Liu, an author of the paper and a professor of pharmacology and molecular sciences, said in a news release. "It is acting in a way that is never seen for this family of proteins."

Researchers at Johns Hopkins continue to explore new uses for old drugs in the school's expansive drug library.

"The more drugs you have, the more possibilities, the higher the chance you rediscover something that will help," Liu said. "Oftentimes, we are surprised that a drug known to do something else has another hidden property."

The study is published in the Proceedings of the National Academy of Sciences.

-- Shari Roan

Photo credit: Advanced Cell Technology Inc.

Rodent of the Week: Axons regenerate long after injury

Scientists have been working for more than a decade on methods to treat spinal cord injuries by attempting to regrow injured nerves. Some success has been achieved in animals that are treated immediately after the injury.

However, new research shows it's possible to coax the regeneration of nerve axons in rats as long as a year after injury. Axons are the part of the nerve that carries signals away from the nerve body. In the experiment, researchers were able to stimulate the growth of axons in the damaged part of the spinal cord and somewhat beyond the site.

It's difficult to get injured axons to grow because of scar tissue at the injury site, inflammation and chemical processes that inhibit the growth. Thus, the treatment was dependent on a complex and sophisticated process that included a cellular bridge to the injury site, a nervous-system growth factor to guide axons to the correct target and a stimulus to the injured neurons that turns on genes to promote growth.

Using this formula, researchers were able to demonstrate successful regeneration of axons. Rats that did not receive the full combination treatment did not exhibit growth.

"The good news is that when axons have been cut due to spinal cord injury, they can be coaxed to regenerate if a combination of treatments is applied," the lead author of the study, Dr. Mark Tuszynski of UC San Diego, said in a news release. "The chronically injured axon is not dead.

"While the regenerating axons grow for relatively short distances, even this degree of growth could be useful. For example, restoration of nerve function even one level below an injury in the neck might improve movement of a wrist or hand, providing greater quality of life or independence."

The study is published in the journal Neuron.

- Shari Roan

Photo credit: Advanced Cell Technology Inc.

Rodent of the Week: Light at night linked to depression

Lots of research suggests that our bodies are adapted to sleep during darkness and become active during daylight. Disruptions in circadian rhythms may increase the risk of metabolic diseases and some types of cancer. Now, a study in mice has found, being exposed to light at night for prolonged periods of time may contribute to depression.

Researchers at Ohio State University found that mice housed in a lighted room 24 hours a day exhibited more symptoms of depression than did mice that had a normal light-dark cycle. When mice that lived in constant light had the option to escape into an opaque tube, they showed fewer symptoms of depression than mice who did not have an escape from 24-hour light. The depression tests in mice involved things like measuring how much sugar water they drank.

One interesting twist in the study, however, revealed that mice housed in constant light seemed to have lower levels of anxiety; they had lower levels of corticosterone, a stress hormone linked to anxiety. But these mice may simply have adapted to the constant light, which resulted in fewer signs of anxiety, the researchers said.

The study contributes to the growing body of research that circadian rhythms are highly influential in health.

"The increasing rate of depressive disorders in humans corresponds with the increasing use of light at night in modern society," Randy Nelson, a co-author of the paper and professor of neuroscience, said in a news release. "Many people are now exposed to unnatural light cycles, and that may have real consequences for our health."

The study was presented this week at the annual meeting of the Society for Neuroscience in Chicago. It will be published in December in the journal Behavioural Brain Research.

-- Shari Roan

Photo: Advanced Cell Technology Inc.

Rodent of the Week: How to mend a broken heart

The promise of stem-cell therapy is that researchers might be able to grow cells into specific tissue or organs that can replace or repair damaged parts. Researchers at Duke reported progress this week in developing a tissue patch that can be used for heart disease.

The scientists used mouse embryonic stem cells to grow a three-dimensional patch made up of heart muscle cells called cardiomyocytes. The tissue was able to contract and to conduct electrical impulses -- just like a real, beating heart. The patch, which looks like a piece of Chex cereal, was grown in biological substances, such as the blood-clotting protein fibrin and helper cells known as cardiac fibroblasts. These substances were crucial in coaxing the cells to grow in an organized manner that allowed them to function.

"When we tested the patch, we found that because the cells aligned themselves in the same direction, they were able to contract like native cells," a coauthor of the study, Brian Liau, said in a news release. "They were also able to carry the electrical signals that make cardiomyocytes function in a coordinated fashion."

More research is needed before heart patches could be used for humans with cardiovascular disease, Liau said. One of the major challenges is establishing a blood vessel supply to sustain the patch. The researchers will also test their model using non-embryonic stem cells. That could speed up the growth of the tissue since a human heart requires nine months for complete development. Moreover, if they could use a patient's own cells, it might prevent an immune system reaction.

The study was presented at the Biomedical Engineering Society annual meeting in Pittsburgh.

-- Shari Roan

Photo courtesy of Advanced Cell Technology Inc.

Rodent of the week: Gabapentin may be unsafe for developing brains

A study performed in mice and in cell culture suggests that the heavily prescribed drug gabapentin halts the formation of new synapses, or nerve connections, in the brain. That ability may be the reason the drug is effective in treating epileptic seizures and pain. But the findings also suggest that the medication may harm fetuses and young children, whose brains are still developing.

Stanford University researchers examined the interaction between neurons and brain cells called astrocytes. Previous studies showed that a protein that astrocytes secrete, thrombospondin, is critical to the formation of the brain's circuitry. In the study, researchers found that thrombospondin binds to a receptor, called alpha2delta-1, on the outer membrane of neurons. In a study in mice, they showed that the neurons that lacked alpha2delta-1 could not form synapses in response to the presence of thrombospondin.

Alpha2delta-1 is the receptor for gabapentin. That has been known, although scientists did not understand how gabapentin worked. But the new research revealed that when gabapentin was given to mice, it prevented thrombospondin from binding to the receptor, thus stopping the synapse formation.

While gabapentin, which is sold under the trade name Neurontin, does not dissolve pre-existing synapses, it prevents the formation of new ones. That's why the medication may be dangerous if given to pregnant women or young children, the authors said. The majority of the brain's synapses are formed in utero and early childhood.

"It's a bit scary that a drug that can so powerfully block synapse formation is being used in pregnant women," Dr. Ben Barres, a professor of neurobiology and the senior author of the study, said in a news release. "This potential effect on fetal brains needs to be taken seriously. Right now, doctors have the view that gabapentin is the safest anticonvulsant. There is no question that pregnant women with epilepsy who have been advised by their neurologists to continue their anticonvulsant treatment with gabapentin during their pregnancy should definitely remain on this drug until instructed otherwise. But there is no long-term registry being kept to track gabapentin-exposed babies. Our findings are saying that we need to be following up on these newborns so that their cognitive performance can be studied as they grow older."

The study is published online in the journal Cell.

-- Shari Roan

Photo: Advanced Cell Technology Inc.

Rodent of the week: Social isolation worsens cancer

Social isolation may alter certain gene expressions which promote the growth of cancer, researchers from the University of Chicago reported this week.

People have long wondered if one's social environment affects disease survival rates. Studies of cancer patients who participate support groups have had mixed results. The new study used mice predisposed to develop breast cancer to study the phenomenon. The mice were raised in one of two environments: isolation or in a group. In the isolated mice, the breast cancer tumors were larger, and those mice also had a disrupted stress hormone response.

The researchers then studied gene expression in the breast tissue of the isolated mice and found alterations in metabolic pathway genes that  promote cancer growth.

The study "illustrates that the social environment, and a social animal's response to that environment, can indeed alter the level of gene expression in a wide variety of tissues, not only the brain," the senior author of the study, Dr. Suzanne D. Conzen, said in a news release.

The research could lead to treatments that might reverse the molecular processes caused by social isolation. The study is published online in the journal Cancer Prevention Research.

-- Shari Roan

Photo: Advanced Cell Technology Inc.

Rodent of the week: Sleep loss linked to Alzheimer's

Chronic sleep loss may play a role in the progression of Alzheimer's disease, according to researchers using a mouse model.

Researchers found that mice that were chronically deprived of sleep had more plaques and developed them earlier compared with mice that slept normally. Plaques, a hallmark of Alzheimer's disease, are made up of amyloid beta protein. The study also showed that the protein orexin, which helps regulate sleep cycles, appears to be involved in the process.

The research team, led by Dr. David M. Holtzman of Barnes Jewish Hospital and Washington University in St. Louis, monitored levels of beta amyloid in mice that were genetically engineered to model Alzheimer's disease. Investigators found that the amount of brain amyloid beta rose and fell in association with sleep and wakefulness (with lower levels during sleep). They then used electroencephalograph  scans to show that mice who stayed awake longer had higher amyloid beta levels. Depriving mice of sleep caused a 25% increase in levels.

Finally, when the scientists injected orexin into the brains of mice, they stayed awake longer and amyloid beta levels increased.

The results suggest that sleep loss may play a role in development of Alzheimer's disease, which affects 39 million Americans, and that treatments to promote sleep may be helpful.

"Orexin or compounds it interacts with may become new drug targets for treatment of Alzheimer's disease," Holtzman said in a news release. "The results also suggest that we may need to prioritize treating sleep disorders not only for their many acute effects but also for potential long-term impacts on brain health."

The study was published Thursday in the journal Science Express.

-- Shari Roan

Photo: Advanced Cell Technology Inc.

Rodent of the Week: Fat messes with your mind

The brain is increasingly the target for understanding why people overeat and become obese. A new study, in rodents, shows that some forms of dietary fat apparently sabotage a system in the body that is designed to prevent overeating.

The study, from researchers at UT Southwestern Medical Center, showed that certain fats cause the brain to send messages to the body to ignore the normal mechanisms involved in weight regulation. Those mechanisms are hormones, such as leptin and insulin, that normally work by telling us we're full and should stop eating, said Dr. Deborah Clegg, the lead author of the study. One type of saturated fat, palmitic acid, is particularly effective at blunting the normal hormone response. Palmitic acid is found in butter, cheese, ice cream, milk and beef.

"Normally, our body is primed to say when we've had enough," Clegg said in a news release. "But that doesn't always happen when we're eating something good. What we've shown in this study is that someone's entire brain chemistry can change in a very short period of time. Our findings suggest that when you eat something high in fat, your brain gets 'hit' with the fatty acids, and you become resistant to insulin and leptin. Since you're not being told by the brain to stop eating, you overeat."

The researchers also found that this effect lasts for about three days. So one splurge of foods high in fatty acids can cause a lengthy eating binge.

Though the study was in animals, Clegg said that saturated fat "causes you to eat more."

The study appears in the September issue of the Journal of Clinical Investigation.

-- Shari Roan

Photo credit: Advanced Cell Technology, Inc.