Breast Cancer Gene Permanently Silenced

RNA interference shuts it down to reduce disease's invasiveness
Betterhumans Staff



A breast cancer gene has been permanently silenced in a treatment approach that could reduce the disease's invasiveness.

The gene, STAT3, was turned off with RNA interference (RNAi), which prevents genes from being translated into proteins.

"We are a long way from using this technique in patients, but this study shows that that it may be possible to use RNAi in more than just experiments that silence genes temporarily," says study principal investigator Ralph Arlinghaus of The University of Texas M. D. Anderson Cancer Center.

Reduced expression

For their study, Arlinghaus and colleagues used a type of retrovirus called a lentivirus to deliver interfering RNA called short hairpin RNA (shRNA) into a mouse breast cancer cell line.

They targeted STAT3 because it is involved in the formation of many types of tumors, including breast tumors. It is thought that cancer cells activate the gene to interfere with the ability of immune cells to attack growing tumors.

After a single exposure, 75% of breast cancer cells stopped expressing the STAT3 protein. Another protein called TWIST known to be involved in cancer metastasis was also drastically reduced.

Furthermore, when the approach was tested in mice, treated breast cancer cells were unable to form breast tumors at the site of injection or at distant sites typically involved in metastatic breast cancer.

Treatment potential

The approach has potential application for treating breast cancer, says Arlinghaus, but likely won't be used in humans in the near future.

For one thing, lentivirus delivery systems haven't been approved for human use yet.

The study is published in the journal Cancer Research (read abstract) and was reported in Anaheim, California at the annual meeting of the American Association for Cancer Research.

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Engineered Virus Destroys Advanced Brain Tumors

Extends survival of mice with late-stage cancer
Betterhumans Staff


Credit: CDC/Dr. Erskine Palmer
Helpful infection: An engineered strain of herpes simplex virus has extended the lifespan of mice with advanced brain tumors, holding promise for a disease that usually kills soon after diagnosis

A virus engineered to kill cancer can significantly increase survival of mice with advanced human brain tumors.

Infecting and reproducing only in malignant glioma cells, killing them while leaving normal tissue unharmed, the virus's ability to prolong the life of mice with advanced tumors is considered important because such tumors are often diagnosed late in humans.

"Unfortunately, the average survival time for these patients has not improved in more than 30 years," says E. Antonio Chiocca of The Ohio State University Medical Center.

Malignant gliomas progress quickly after diagnosis and are nearly always fatal, says Chiocca. Average survival following diagnosis is about a year.

People with malignant gliomas are usually treated using surgery, chemotherapy and radiation.

"There is a real need for new therapies," says Chiocca.

Restoring reproduction

Initially, Chiocca and colleagues engineered a herpes simplex virus that could infect only malignant glioma cells. But the original virus reproduced poorly and therefore had a weak ability to kill cancer.

"Instead of making 1,000 copies of itself, it might only make 10," says Chiocca.

So the researchers went back to the drawing board and restored a deleted gene called ICP34.5 to increase the reproduction rate.

However, they modified the gene so that it was only active in cells producing a protein called nestin, a protein that sets malignant glioma and some other cancers apart from normal cells.

In lab-grown malignant glioma cells, the virus replicated at high levels.

Then the researchers tested it in mice with implanted human gliomas.

Simulated diagnoses

In one set of experiments, the virus was given seven days after tumor implantation. Untreated mice lived for 21 days while eight of 10 mice treated with the virus survived 90 days.

To simulate the reality of human glioma diagnoses, which usually come late in the disease's development, the researchers also conducted an experiment in which they injected the virus into tumors 19 days after implantation.

In this experiment, two of 10 animals treated with the virus survived 24 days after implantation while all 10 mice treated with a control virus had died by day 21.

"The treatment extended the animals' lives by several days," Chiocca says. "If we could achieve a proportional increase in humans with malignant glioma, that would be a very significant advance."

Chiocca cautions, however, that the study is preliminary and the virus cannot yet be used in humans.

The study is reported in the journal Cancer Research (read abstract).

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Onions May Fight Osteoporosis

Compound within decreases bone loss in rat cells
Betterhumans Staff


While it might not further your social life, eating onions could help you fight osteoporosis.

Researchers at the University of Bern in Switzerland have found that a compound in onions fights bone loss in laboratory studies using rat bone cells.

The researchers analyzed the active chemical components of white onions and found a peptide called GPCS most likely responsible for the protective effect.

To test the peptide's effects, the researchers exposed bone cells from newborn rats to parathyroid hormone to stimulate bone loss.

They then exposed some of the cells to GPCS.

The treatment significantly inhibited loss of bone minerals, including calcium, compared to cells not exposed to GPCS.

Additional studies are needed to help determine whether GPCS has a similar effect in people, how much onion or peptide would be needed for a protective effect and how, exactly, GPCS works on bone cells, the researchers say.

The research is published in the Journal of Agricultural and Food Chemistry.

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Zinc Boosts Adolescent Brainpower

Daily supplementation improves mental performance on attention and memory tasks
Betterhumans Staff



Daily zinc supplements can boost adolescents' mental performance, according to a new study in seventh graders.

Given 20 mg of zinc five days a week for 10 to 12 weeks, participants showed improved mental performance, responding faster, more accurately and with greater sustained attention on memory tasks than classmates not taking the supplements.

Zinc nutrition has been linked to motor, cognitive and psychosocial function in adults and very young children, but this is reportedly the first study of its effect in adolescents, considered at risk of zinc deficiency due to rapid growth and often poor eating habits.

The findings also support previous research showing that zinc supplementation could improve the treatment of attention-deficit hyperactivity disorder.

Brain juice

For the new study, James Penland of the Grand Forks Human Nutrition Research Center in North Dakota and colleagues gave 209 seventh graders—111 girls and 98 boys—four ounces of fruit juice containing either 0 mg, 10 mg or 20 mg of zinc gluconate each school day for 10 to 12 weeks.

Before the study began, students were tested on mental and motor skills. Students, their parents and their teachers also filled out questionnaires on various mental, physical and social abilities and skills. Blood samples were also taken to measure zinc levels.

Against the baseline established by the tests, Penland and colleagues found that students who consumed an additional 20 mg of zinc each day decreased reaction time on a visual memory task by 12% versus 6%, increased correct answers on a word recognition task by 9% versus 3% and increased scores on a sustained attention and vigilance task by 6% versus 1%.

Beneficial effects were seen regardless of participants' previous zinc status.

Those who received 10 mg a day—the current US Recommended Dietary Allowance (RDA) for the age group—did not have significant improvements.

The research was reported in San Diego, California at Experimental Biology 2005.

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ADHD Drugs Raise Cancer Concern

Small study shows increased risk of chromosome abnormalities
Betterhumans Staff



Credit: Bonnie Jacobs
Attention needed: A small study connecting the main ingredient in many ADHD drugs with cancer-linked abnormalities is cause for further investigation, researchers say

A small study has found that after just three months, children treated with the common ADHD drug methylphenidate had a three-fold increase in cellular abnormalities linked with cancer.

The researchers who conducted the study, at The University of Texas M.D. Anderson Cancer Center in Houston and the University of Texas Medical Branch at Galveston (UTMB), aren't suggesting that parents take children off the drug—sold under such well-known brand names as Ritalin and Concerta.

However, says principal investigator Marvin Legator of UTMB, the study does suggest that the drug is an additional risk factor for cancer—if the findings hold up.

Widely prescribed

Methylphenidate is the most widely prescribed of a class of amphetamine-like drugs for ADHD.

While the drug has been approved for human use for more than 50 years, Legator and colleagues say there are few studies in animals or humans on the potential for serious side-effects such as cancer.

A 1996 report on animal studies showed that the highest levels of methylphenidate caused liver tumors in male and female mice, but similar studies in rats found no such effect.

Drawing blood

For their study, Legator and colleagues drew blood from 12 children diagnosed with ADHD before and three months after they started taking methylphenidate.

Examining chromosomal abnormalities, they found that after three months of treatment there were increases in chromosome breaks that have been associated with later development of cancer.

"It was pretty surprising that all of the children taking methylphenidate showed an increase in chromosome abnormalities in a relatively short period of time," says study lead author Randa El-Zein.

Much larger studies at several medical centers are needed to confirm the results, says El-Zein, and to answer other questions such as whether levels of chromosome abnormalities go back to normal after people stop taking methylphenidate.

The research is reported in the journal Cancer Letters (read abstract).

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Marijuana Mimic Fights Alzheimer's Damage

Synthetic compound reduces inflammation and prevents mental decline in animal model
Betterhumans Staff



A synthetic mimic of the active component in marijuana reduces inflammation and prevents mental decline in an animal model of Alzheimer's disease, suggesting that similar compounds—and perhaps marijuana itself—might do the same in humans.

The finding focuses on cannabinoids, compounds in marijuana that bind to cannabinoid receptors in the brain.

To test their preventive effect against Alzheimer's disease, Maria de Ceballos and colleagues at the Cajal Institute and Complutense University in Madrid conducted experiments on human brain tissue and rats.

They found that in the brain tissue of people who died from Alzheimer's, there was dramatically reduced functioning of cannabinoid receptors compared to people of the same age who died without the condition, meaning sufferers had lost the ability to benefit from cannabinoids' protective effects.

Supporting this finding, the researchers showed in rats that cannabinoids prevent cognitive decline.

Cannabinoid protection

Ceballos and colleagues injected either the Alzheimer's-linked protein amyloid or a control protein into the brain of rats. Some of the rats were also injected with a cannabinoid.

After two months, the rats were trained to find a platform hidden underwater, a test of learning and memory.

All rats who received the control protein could find the platform. Rats who received amyloid without cannabinoids did not learn how to do this. But rats given amyloid and cannabinoids did.

Examining the rats' brains, the researchers found that amyloid caused inflammation and activated microglia, which activate the brain's immune response. In cell cultures, cannabinoids counteracted this activation and reduced inflammation.

"These findings that cannabinoids work both to prevent inflammation and to protect the brain may set the stage for their use as a therapeutic approach for [Alzheimer's disease]," says de Ceballos says.

The researchers are now focusing on one of two main cannabinoid receptors that isn't involved in producing marijuana's high.

The research is reported in The Journal of Neuroscience.

http://www.betterhumans.com/News/news.aspx?articleID=2005-02-22-2