Mesothelioma, a rare but aggressive form of cancer that occurs in the lining of the lungs, heart and abdomen, is associated with exposure to asbestos. There is no known cure.
In the study, patients receiving pemetrexed and cisplatin along with the vitamin supplements folic acid and B12 survived nearly three months longer than patients getting cisplatin alone.
Researchers led by John Green, M.D., at the Clatterbridge Center for Oncology in England, reviewed a study of 448 patients with advanced mesothelioma who were treated with either the single drug or the combination.
Pemetrexed used in combination with cisplatin significantly increases the length of survival, when compared with cisplatin alone, the researchers say. Further research is needed into the optimum treatment regimen for pleural mesothelioma.
The review appears in the current issue of The Cochrane Library, a publication of The Cochrane Collaboration, an international organization that evaluates medical research. Systematic reviews draw evidence-based conclusions about medical practice after considering both the content and quality of existing medical trials on a topic.

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ASTRO is pleased to announce the launch of its all-new patient Web site located at www.rtanswers.org. The site is dedicated to providing knowledge on radiation therapy treatment for people suffering with cancer. RT Answers includes up-to-date information on many diseases commonly treated with radiation therapy, including brain tumors, breast cancer, colorectal cancer, gynecologic cancers, head and neck cancer, Hodgkins lymphoma, lung cancer, non-Hodgkins lymphoma, prostate cancer and skin cancer. In addition, the site offers a section on understanding clinical trials and a list of questions patients can ask their doctors. RT Answers also adds valuable new information on what to expect before, during and after radiation therapy as well as a search function to allow patients to find a radiation oncologist in their area.

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nianews3@mail.nih.gov
SCIENTISTS ISOLATE A TOXIC KEY TO ALZHEIMER'S DISEASE IN HUMAN
AINS
Soluble Beta-Amyloid Protein Fragments May Damage Brain Cells, Study Finds
Scientists have long questioned whether the abundant amounts of amyloid plaques found in the brains of patients with Alzheimer's actually caused the neurological disease or were a by-product of its progress. Now, using new research techniques, scientists have shown that a two-molecule aggregate (or dimer) of beta-amyloid protein fragments may play a role in initiating the disease. The study, supported by the National Institutes of Health, suggests a possible new target for developing drug therapies to combat the irreversible and progressive disorder.
Ganesh M. Shankar, Ph.D., and Dennis J. Selkoe, M.D., of Brigham and Women's Hospital and Harvard Medical School, conducted the study in collaboration with other researchers at Harvard and in Ireland at University College Dublin, Beaumont Hospital and Royal College of Surgeons Ireland, and Trinity College Dublin. The National Institute on Aging (NIA), part of NIH, funded the study which appears online in the June 22, 2008, Nature Medicine.
Alzheimer's disease is marked by the build-up of plaques consisting of beta-amyloid protein fragments, as well as abnormal tangles of tau protein found inside brain cells. Early in the disease, Alzheimer's pathology is first observed in the hippocampus, the part of the brain important to memory, and gradually spreads to the cerebral cortex, the outer layer of the brain. In this study, researchers tested cerebral cortex extracts from brains donated for autopsy by people aged 65 and older with Alzheimer's and other dementias, as well as those without dementia. The extracts contained soluble one-molecule (monomer), two-molecule (dimer), three-molecule (trimer) or larger aggregates of beta-amyloid, as well as insoluble plaque cores. The researchers then injected the extracts into normal rats or added the extracts to slices of normal mouse hippocampus.
Shankar, Selkoe and colleagues discovered that both the soluble monomers and the insoluble plaque cores had no detectable effect on the hyppocampal slices. However, the soluble dimers induced certain key characteristics of Alzheimer's in the rats. The dimers impaired memory function, specifically the memories of newly learned behaviors. In the mouse hippocampal slices, the dimers also reduced by 47 percent the density of the dendrite spines that receive messages sent by other brain cells. The dimers seemed to be directly acting on synapses, the connections between neurons that are essential for communication between them.
To confirm this effect, the researchers then injected certain antibodies against beta-amyloid protein fragments. These latched onto and inactivated the dimers, preventing their toxic effects in the animal models. However, much work remains to be done before inactivation of dimers could move into the clinic.
Scientists have theorized for many years that soluble beta-amyloid may be critical to the development and progression of this devastating disease. Now these researchers have isolated a candidate causative agent from brains of people with typical Alzheimer's and directly tested it in an animal model, said NIA Director Richard J. Hodes, M.D. While more research is needed to replicate and extend these findings, this study has put yet one more piece into place in the puzzle that is Alzheimer's.
The animal findings were consistent with what the researchers found when they examined the brain tissues of people who had been clinically diagnosed with Alzheimer's and those without dementia. They detected soluble dimers and some trimers of amyloid in the brains of patients with Alzheimer's, but none or very low levels in those free of the disorder. Some people free of the disorder, however, did have insoluble amyloid plaques in their brains.
These findings may help explain why people with normal cognitive function are sometimes found to have large amounts of amyloid plaques in their brains, which has been a puzzle for some time, said Marcelle Morrison-Bogorad, Ph.D., director of the NIA Division of Neuroscience. Their findings noted that the brain of an individual who was never clinically diagnosed with dementia was found with abundant insoluble Alzheimer's plaques, but no soluble beta-amyloid.
Selkoe and Shankar noted that further insights into the early stages of this disease process may answer questions not only about Alzheimer's, but also about age-related memory impairments. The approaches we used to isolate dimers and the widespread availability of tissues from brain banks, open new avenues of investigation into how these aggregates induce Alzheimer's disease, said Selkoe. We still need to find out why dimers in particular are so destructive to neurons.
NIA leads the federal government effort conducting and supporting research on the biomedical and social and behavioral aspects of aging and the problems of older people.

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Both Bill Stall, a retired Pulitzer Prize winner for the L.A. Times, and Times state political columnist George Skelton have, most appropriately, been writing about California's ever more critical fiscal problems. Inspiration has come from editorial writer Bob Greene and editorial pages editor Jim Newton.

Looking far back in modern history, to the French Revolution, we can't forget that it began with a French fiscal crisis. The Estates-General was summoned to meet in the spring of 1789, because, over many years, the French government had been running out of money, its taxing system was inadequate, and the Revolution soon began. The deliberative body began talking May 5, 1789, and the Bastille fell just two months and nine days later, thrusting France into eventual chaos. When it was all over, after the reign of terror, Napoleon Bonaparte came to power.

Well, as Skelton and Stall have pointed out, and which really cannot be contradicted, California too is saddled with an antiquated, unworkable budget and tax process, and it would seem that reform or even upset, if not revolution, has to be around the corner. The state's needs exceed its tax revenues, and, more and more, a succession of fiscal tricks has not been able to resolve the discrepancy.

Skelton has concentrated on the obstacles in the Schwarzenegger Administration, and the Legislature, to passing a reasonable budget. The governor, after five long years of pledging no new taxes, now has come around to the concept. But he may not be able to command necessary legislative support.

Stall, in an Op Ed Page column yesterday, takes finally a more dire view than Skelton, who usually writes more about process than basic change. Stall, who also was a former gubernatorial press secretary under Jerry Brown, says the time has come for "a fair revision" of Proposition 13 under which property tax increases are supposedly limited to 2% a year, and assessments of real property value are not changed until a property is sold. Even then, they are capped at 1% of assessed property value. (Bond issues approved by the voters mean that in practice increases beyond these limits do occur, but not enough in most cases to allow the state to meet its needs).

Stall recognizes that reform will not be easy, and to get by the loathing of homeowners, particularly those straining to meet higher mortgage rates and living on fixed, or in inflationary terms, declining real incomes, he proposes that any change in Proposition 13 continue to protect their interests. But he would lift prohibitions on increases in commercial property taxes. Also, he would scrap the measure's requirement that tax increases secure a two thirds majority.

That's where he lost me in his column. He probably felt the column was long enough already, or maybe his editors did. But I don't think you can realistically consider any major change in Proposition 13 without considering the fact that both major parties in the Legislature, not to mention the governor's office, are owned by business interests. These entities are so corrupt that the notion they might voluntarily vote against the interests of their own major campaign contributors is close to impossible. Big special interests have the Legislature and the governor in their grip, and little of substance can occur until that grip is broken. We shouldn't hold our breath.

It was Bismarck who once made the sardonic crack that legislating, like sausage making, cannot be too carefully watched, because the process is too grim. The sausage making by the California Legislature is apt to be poisonous.

No, if Proposition 13 is going to be revised, this will take an initiative campaign, and, as we know, those are often fraught with almost insuperable difficulties. Those popular with the voters are often unacceptable to the courts, because they tend to be written in extravagant and constitutionally questionable terms. And the arguments made pro and con such initiatives sink into the irrationality of one-page campaign mailings and 30-second commercials.

Frankly, I have no idea how this will all turn out. It is true that progress in California is being stymied, the investments we need to make in our future are not forthcoming, the state is falling behind others with more reasonable tax systems. But the real-time political situation has led steadily toward paralysis, and it's going to take more than Skelton or Stall and all their progressive thoughts to bring about real change.

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