Olive Skins Provide Natural Defense Against Colon Cancer, Study Suggests

Researchers from the University of Granada and the University of Barcelona have shown that treatment with maslinic acid, a triterpenoid compound isolated from olive-skin pomace, results in a significant inhibition of cell proliferation and causes apoptotic death in colon-cancer cells. Maslinic acid is a novel natural compound and it is able to induce apoptosis or programmed death in human HT29 colon-cancer cells via the intrinsic mitochondrial pathway.

New research suggest this could be a useful new therapeutic strategy for the treatment of colon carcinoma.

This study is the first to investigate the precise molecular mechanisms of the anti-tumoral and pro-apoptotic effects of maslinic acid against colon-cancer. Chemopreventive agents of a natural origin, often a part of our daily diet, may provide a cheap, effective way of controlling such diseases as cancer of the colon. A wide range of studies in recent years has shown that triterpenoids hinder carcinogenesis by intervening in pathways such as carcinogen activation, DNA repair, cell cycle arrest, cell differentiation and the induction of apoptosis in cancer cells.

Triterpenoids are compounds present in a wide range of plants used in traditional medicine and known to have antitumoral properties. Low concentrations of maslinic acid are to be found in plants with medicinal properties, but its concentration in the waxy skin of olives may be as high as 80%.

The results of the study could contribute to the development of maslinic acid for use as cancer chemotherapeutic or chemopreventive agents.

Scientists See Brain Aging Before Symptoms Appear

UCLA scientists have used innovative brain-scan technology developed at UCLA, along with patient-specific information on Alzheimer's disease risk, to help diagnose brain aging, often before symptoms appear. Published in the January issue of Archives of General Psychiatry, their study may offer a more accurate method for tracking brain aging.

Researchers used positron emission tomography (PET), which allows "a window into the brain" of living people and specifically reveals plaques and tangles, the hallmarks of neurodegeneration. The PET scans were complemented by information on patients' age and congnitive status and a genetic profile.

"Combining key patient information with a brain scan may give us better predictive power in targeting those who may benefit from early interventions, as well as help test how well treatments are working," said study author Dr. Gary Small, who holds UCLA's Parlow-Solomon Chair on Aging and is a professor at the Semel Institute for Neuroscience and Human Behavior at UCLA.

Scientists took PET brain scans of 76 non-demented volunteers after they had been intravenously injected with a new chemical marker called FDDNP, which binds to plaque and tangle deposits in the brain. Researchers were then able to pinpoint where these abnormal protein deposits were accumulating.

They reported that older age correlated with higher concentrations of FDDNP in the medial and lateral temporal regions of the brain, areas involved with memory, where plaques and tangles usually collect. The average age of study volunteers was 67.

Thirty-four of the 76 volunteers carried the APOE-4 gene allele, which heightens the risk for developing Alzheimer's disease. This group demonstrated higher FDDNP levels in the frontal region of the brain, also involved in memory, than study participants without allele.

"We found that for many volunteers, the imaging scans reflected subtle brain changes, which take place before symptoms manifest," said Small, who is also director of the UCLA Center on Aging.

Small noted that the brain will try to compensate for any problems, which is why cognitive symptoms may not become apparent until much later.

"This type of scan offers an opportunity to see what is really going on in the brain," he said.

Another subset of the volunteers had mild cognitive impairment (MCI), a condition that increases the risk of developing Alzheimer's disease. These 36 volunteers had higher measures of FDDNP in the medial temporal brain regions than normal volunteers. Those who had both MCI and the APOE-4 gene had higher concentrations of FDDNP in the medial temporal brain regions than volunteers who had MCI but not APOE-4.

"We could see more advancing disease in those with mild cognitive impairment, who are already demonstrating some minimal symptoms," Small said. "Eventually, this imaging method, together with patient information like age, cognitive status and genetics, may help us better manage brain aging."

According to Small, in the future, brain aging may be controlled similarly to high cholesterol or high blood pressure. Patients would receive a brain scan and perhaps a genetic test to predict their risk. Medications and other interventions could be prescribed, if necessary, to prevent or delay future neurodegeneration, allowing doctors to protect a healthy brain before extensive damage occurs. The brain scans may also prove helpful in tracking the effectiveness of treatments.

PET, combined with the FDDNP probe, is the only imaging technology that offers a full profile of neurodegeneration that includes measures of both plaques and tangles — the physical evidence of Alzheimer's disease in the brain.

"The fact that we can see tau tangles as well as amyloid plaques is critically important in early detection of brain aging, since the tangles are the first abnormal proteins that appear in the brain, long before dementia is clinically obvious to the physician," said Dr. Jorge R. Barrio, a study author and professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA.

Such subtleties allow more insight into how the plaques and tangles spread and ultimately how Alzheimer's disease may develop.

Currently, the new FDDNP-PET scans are used in a research setting, but clinical trials are in development to bring the technology to wider patient use.

The study was funded by both government and nonprofit agencies, including the National Institutes of Health, the U.S. Department of Energy, the Ahmanson Foundation, the Larry L. Hillblom Foundation and the Tamkin Foundation.

Additional UCLA authors include Prabha Siddarth, Ph.D.; Alison C. Burggren, Ph.D.; Linda M. Ercoli, Ph.D.; Karen J. Miller, Ph.D.; Dr. Helen Lavretsky; and Susan Y. Bookheimer, Ph.D, all from the UCLA Department of Psychiatry and Biobehavioral Sciences and the Semel Institute for Neuroscience and Human Behavior at UCLA; Vladimir Kepe, Ph.D.; S.C. Huang, Ph.D.; and Michael E. Phelps, Ph.D. from the UCLA Department of Molecular and Medical Pharmacology; and Paul M. Thompson, Ph.D., and Greg M. Cole, Ph.D., from the UCLA Department of Neurology.

Brain Birth Defects Successfully Reversed Through Stem Cell Therapy

Scientists at the Hebrew University of Jerusalem have succeeded in reversing brain birth defects in animal models, using stem cells to replace defective brain cells.

The work of Prof. Joseph Yanai and his associates at the Hebrew University-Hadassah Medical School was presented at the Tel Aviv Stem Cells Conference last spring and is expected to be presented and published nest year at the seventh annual meeting of the International Society for Stem Cell Research in Barcelona, Spain.

Involved in the project with Prof. Yanai are Prof. Tamir Ben-Hur, head of the Department of Neurology at the Hebrew University-Hadassah Medical School, and his group, as well as Prof. Ted Slotkin at Duke University in North Carolina, where Prof. Yanai is an adjunct professor.

Neural and behavioral birth defects, such as learning disabilities, are particularly difficult to treat, compared to defects with known cause factors such as Parkinson’s or Alzheimer’s disease, because the prenatal teratogen – the substances that cause the abnormalities -- act diffusely in the fetal brain, resulting in multiple defects.

Prof. Yanai and his associates were able to overcome this obstacle in laboratory tests with mice by using mouse embryonic neural stem cells. These cells migrate in the brain, search for the deficiency that caused the defect, and then differentiate into becoming the cells needed to repair the damage.

Generally speaking, stem cells may develop into any type of cell in the body, however at a certain point they begin to commit to a general function, such as neural stem cells, destined to play a role in the brain/ nervous system. At more advanced developmental stages, the neural stem cells take on an even more specific role as neural or glial (supporting) cells within the brain/ nervous system.

In the researchers’ animal model, they were able to reverse learning deficits in the offspring of pregnant mice who were exposed to organophosphate (a pesticide) and heroin. This was done by direct neural stem cell transplantation into the brains of the offspring. The recovery was almost one hundred percent, as proved in behavioral tests in which the treated animals improved to normal behavior and learning scores after the transplantation. On the molecular level, brain chemistry of the treated animals was also restored to normal.

The researchers went one step further. Puzzled by the stem cells’ ability to work even in those cases where most of them died out in the host brain, the scientists went on to discover that the neural stem cells succeed before they die in inducing the host brain itself to produce large number of stem cells which repair the damage. This discovery, finally settling a major question in stem cell research, evoked great interest and was published earlier this year in one of the leading journals in the field, Molecular Psychiatry.

The scientists are now in the midst of developing procedures for the least invasive method for administering the neural stem cells, which is probably via blood vessels, thus making the therapy practical and clinically feasible.

Normally, stem cells are derived from individuals genetically different from the patient to be transplanted, and therefore the efficacy of the treatment suffers from immunological rejection. For this reason, another important avenue of the ongoing study, toward the same goals, will be to eliminate the immunological rejection of the transplant, which will become possible by taking cells from the patient’s own body -- from a place where they are easily obtained -- by manipulating them to return to their stem cell phase of development, and then transplanting them into the patient’s brain via the blood stream. One important advantage of this approach will be to eliminate the controversial ethical issues involved in the use of embryo stem cells.

The research on the project has been supported by the US National Institutes of Health, the US-Israel Binational Science Foundation and the Israel anti-drug authorities.