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National Institutes of Health (NIH) scientists investigating how prion diseases destroy the brain have observed a new form of the disease in mice that does not cause the sponge-like brain deterioration typically seen in prion diseases. Instead, it resembles a form of human Alzheimer’s disease, cerebral amyloid angiopathy, that damages brain arteries.

The study results, reported by NIH scientists at the National Institute of Allergy and Infectious Diseases (NIAID), are similar to findings from two newly reported human cases of the prion disease Gerstmann-Straussler-Scheinker syndrome (GSS). This finding represents a new mechanism of prion disease brain damage, according to study author Bruce Chesebro, M.D., chief of the Laboratory of Persistent Viral Diseases at NIAID’s Rocky Mountain Laboratories.

Prion diseases, also known as transmissible spongiform encephalopathies, primarily damage the brain. Prion diseases include mad cow disease or bovine spongiform encephalopathy in cattle; scrapie in sheep; sporadic Creutzfeldt-Jakob disease (CJD), variant CJD and GSS in humans; and chronic wasting disease in deer, elk and moose.

The role of a specific cell anchor for prion protein is at the crux of the NIAID study. Normal prion protein uses a specific molecule, glycophosphoinositol (GPI), to fasten to host cells in the brain and other organs. In their study, the NIAID scientists genetically removed the GPI anchor from study mice, preventing the prion protein from fastening to cells and thereby enabling it to diffuse freely in the fluid outside the cells.

The scientists then exposed those mice to infectious scrapie and observed them for up to 500 days to see if they became sick. The researchers documented signs typical of prion disease including weight loss, lack of grooming, gait abnormalities and inactivity. But when they examined the brain tissue, they did not observe the sponge-like holes in and around nerve cells typical of prion disease. Instead, the brains contained large accumulations of prion protein plaques trapped outside blood vessels in a disease process known as cerebral amyloid angiopathy, which damages arteries, veins and capillaries in the brain. In addition, the normal pathway by which fluid drains from the brain appeared to be blocked.

Their study, Dr. Chesebro says, indicates that prion diseases can be divided into two groups: those with plaques that destroy brain blood vessels and those without plaques that lead to the sponge-like damage to nerve cells. Dr. Chesebro says the presence or absence of the prion protein anchor appears to determine which form of disease develops.

The new mouse model used in the study and the two new human GSS cases, which also lack the usual prion protein cell anchor, are the first to show that in prion diseases, the plaque-associated damage to blood vessels can occur without the sponge-like damage to the brain. If scientists can find an inhibitor for the new form of prion disease, they might be able to use the same inhibitor to treat similar types of damage in Alzheimer’s disease, Dr. Chesebro says.
Scientists from the Veterinary Laboratories Agency in Scotland also participated in the study.

Scientists are making headway in finding ways to treat and detect stubborn forms of prostate cancer.

The new hope comes from three studies being presented this week at the annual Genitourinary Cancers Symposium in San Francisco.

“Genitourinary cancers include cancers of the prostate, kidney, bladder and testicles,” Dr. Nicholas J. Vogelzang, chairman and medical director of the developmental therapeutics committee at U.S. Oncology, explained at a Wednesday teleconference announcing the various findings. “The most common of these is prostate cancer, which is diagnosed in 192,000 men and claims 27,000 lives each year.”

The first study, led by Dr. Oliver Sartor of Tulane Cancer Center, New Orleans, found that a new investigational drug called cabazitaxel improved overall survival in men whose prostate cancer had progressed despite being treated with hormone therapy and docetaxel-containing chemotherapy.

Men receiving cabazitaxel plus mitoxantrone (a chemotherapy drug) lived 15.1 months compared to 12.7 months for patients who received mitoxantrone plus prednisone. This represents a 30 percent increase in survival, which may not seem long but is seen as significant for men with a poor prognosis.

“Advances in cancer therapy have always been incremental. We have only a few examples of massive improvements with one drug,” Vogelzang noted. “Three months is a major clinical advance.”

Other studies are looking at whether giving the drug earlier in the course of the cancer would improve survival even more.

“Until today, experimental agents have never been shown to have a survival advantage in this group of patients,” said Sartor, who is Piltz Professor for Cancer Research at Tulane. “This potentially represents a new therapy option for these patients who are very difficult to treat. We don’t know when this is going to the FDA [U.S. Food and Drug Administration] for approval, but we’re working very hard to prepare the submission.”

A second group of researchers reported that the PCA3 urine test, which measures levels of prostate cancer gene 3, can predict when a biopsy of the prostate gland will come out positive.

The PCA3 gene is overexpressed in men who have prostate cancer, but not in men with benign disease, raising the possibility that the finding may cut down on the number of unnecessary prostate biopsies.

According to study author Jack Groskopf, director of research and development in cancer diagnostics at Gen-Probe Inc., which makes the test, most prostate biopsies that are currently performed after elevated prostate-specific antigen (PSA) test results actually turn out to be negative for cancer.

“The ability of this test to predict biopsies positively could potentially be very helpful and may also may help us identify those more aggressive cancers, which we still do not have a great way to identify other than [with] repeat biopsies,” said Vogelzang.

The final prostate cancer study found that short-term hormone therapy — either before or during radiation therapy — could help men with intermediate-risk, early-stage prostate cancer live longer and live longer without a recurrence.

But the therapy did not seem to help men with low-risk, early-stage tumors.

Since that study was conducted, however, standard radiation doses to treat prostate cancer have become higher and more efficient, raising the question as to whether these results are applicable to modern-day procedures.

In addition, said study co-author Dr. Christopher Jones, a partner of Radiological Associates of Sacramento, Calif., “there are consequences from short-course hormone therapy such as hot flashes and impotence, and we don’t know the long-term effect on sexual function. We need to know if there’s a real benefit to the individual patient of adding hormones to radiation before adopting this as standard practice.”

A final study demonstrated that adding high-tech urine biomarker tests to regular cystoscopy was not cost-effective in detecting recurrences of bladder cancer. Adding the biomarker screen also increased the risk for false-positive results, the researchers found.

Cystoscopy involves looking at the inside of the bladder with a camera.

“This data suggest that cystoscopy alone remains the most cost-effective strategy,” said study author Dr. Jose Karam, a urologic oncology fellow at The University of Texas M.D. Anderson Cancer Center in Houston. “The addition of urine tests adds to the cost without detection of invasive disease, suggesting that we should be using these markers carefully and judiciously when surveying patients with bladder cancer.”

Both Vogelzang and Sartor disclosed numerous ties with pharmaceutical companies.

The Genitourinary Cancers Symposium is sponsored jointly by the American Society for Clinical Oncology, the American Society for Radiation Oncology and the Society of Urologic Oncology.

SOURCES: teleconference with Nicholas J. Vogelzang, M.D., chair and medical director, developmental therapeutics committee, U.S. Oncology; Oliver Sartor, M.D., Piltz Professor for Cancer Research, Tulane Cancer Center, New Orleans; Jack Groskopf, Ph.D., director of research and development in cancer diagnostics, Gen-Probe Inc., San Diego; Christopher Jones, M.D., partner, Radiological Associates of Sacramento; and Jose Karam, M.D., urologic oncology fellow, The University of Texas M. D. Anderson Cancer Center, Houston; study abstracts

Cholesterol-lowering statins significantly reduce prostate tumor inflammation, which may help lower the risk of disease progression, new study findings suggest.

Duke University Medical Center researchers found that the use of statins before prostate cancer surgery was associated with a 69 percent reduced likelihood of inflammation inside prostate tumors.

For the study, the researchers examined tissue samples of prostate tumors from 236 men undergoing prostate cancer surgery. The patients included 37 who took statins during the year prior to their surgery.

Overall, 82 percent of the men had inflammatory cells in their prostate tumors and about one-third had marked tumor inflammation. After they accounted for factors such as age, race and body-mass index (a measurement that is based on weight and height), the Duke team concluded that statin use was associated with reduced inflammation within tumors. They also determined that inflammation was more likely among older men with more advanced prostate cancer who’d waited a longer time between prostate biopsy and surgery.

The findings are published in the Feb. 22 online edition of the journal Cancer Epidemiology, Biomarkers & Prevention.

“Increasing evidence suggests that statins may reduce risk of prostate cancer progression, and some studies have even suggested that widespread statin use over the past 15 years has contributed to a decline in prostate cancer mortality,” lead author Dr. Lionel Banez, an assistant professor of surgery and urology, said in a Duke news release.

But that doesn’t mean that all prostate cancer patients should take statins, said study senior author Dr. Stephen Freedland, an associate professor of urology and pathology at the Duke Prostate Cancer Center.

“More studies have to be done before such a recommendation can be made. However, men taking statins for heart health may already be enjoying a beneficial side effect against prostate cancer,” Freedland said in the news release.

Testosterone deficiency in young male cancer survivors often causes low energy levels and reduced quality of life, and these patients may benefit from testosterone replacement therapy, a new study suggests.

About 15 percent of male cancer survivors experience testosterone deficiency, which is a late side effect of chemotherapy or radiation therapy.

In this study of 176 young male cancer survivors and 213 young men without cancer, English researchers looked at the association between testosterone levels, quality of life, self-esteem, fatigue and sexual function.

The young male cancer survivors reported reduced energy levels, impaired sexual function and a markedly reduced quality of life. These problems were most severe in those with testosterone deficiency.

However, the cancer survivors had no problems with self-esteem, sexual relationships or mental health.

“This is an important study demonstrating that low testosterone levels are common in male cancer survivors and associated with an impaired quality of life,” said lead investigator Dr. Richard Ross, of the University of Sheffield. “However, the relationship between testosterone levels and quality of life is complex and appears to depend on a threshold level rather than on a direct correlation. We now need interventional trials with testosterone to determine which young male cancer survivors will benefit from replacement therapy.”

Results are similar for men with prostate cancer whether they have open surgery or laparoscopic surgery, a new study has found.

Currently, open radical prostatectomy (ORP) is considered the standard treatment but the use of laparoscopic radical prostatectomy (LRP), with or without robotic assistance, is becoming more widespread.

In the new study, researchers at Memorial Sloan-Kettering Cancer Center in New York City compared ORP and LRP outcomes in nearly 6,000 men, age 66 or older, with localized prostate cancer.

After they adjusted for patient and tumor characteristics, the researchers found no differences in the rates of general medical/surgical complications, genital/urinary/bowel complications, or in use of postoperative radiation and/or androgen deprivation.

Patients in the LRP group had a 35 percent shorter hospital stay and a lower rate of bladder neck/urethral obstruction, the study authors noted.

“All men considering radical prostatectomy should be clearly informed about the differences between the two techniques and similarities in their expected outcomes, and make treatment decisions in collaboration with an experienced surgeon,” Dr. William T. Lowrance and colleagues wrote in their report, which is published in issue of the Journal of Urology.

A new treatment for overuse injury of the Achilles tendon doesn’t appear to be effective, a new study shows.

Researchers in the Netherlands concluded that platelet-rich plasma (PRP) injections are no better than placebo in reducing pain or improving a patient’s ability to be active.

The study included 54 patients, aged 18 to 70, with chronic Achilles tendinopathy. All the patients did eccentric exercises (stretching the Achilles tendon while contracting the calf muscle) and were randomly selected to receive either a PRP injection or saline injection. Both groups showed significant improvement in pain reduction and increased activity within 24 weeks after the start of the study.

“Among patients with chronic midportion Achilles tendinopathy treated with an eccentric exercise program, a PRP injection compared with a saline injection did not result in greater improvement in pain and activity. Therefore, we do not recommend this treatment for chronic midportion Achilles tendinopathy,” wrote Dr. Robert J. de Vos, of Erasmus University Medical Center in Rotterdam, and colleagues.

“These findings are important and clinically relevant as PRP is thought to be growing in popularity and recent reviews supported its use for chronic tendon disorders,” they added.

The study appears in the Jan. 13 issue of the Journal of the American Medical Association.

New research is giving scientists a greater understanding of how a brain becomes susceptible to depression and anxiety on a molecular level and why some people are resistant to antidepressants.

Scientists think two things — biological factors and stressful life events — cause the mental disorders. Antidepressants (such as Prozac) are available to treat them, often by increasing serotonin levels, but they don’t always work.

“Unfortunately, more than half of all depressed patients fail to respond to their first drug treatment,” senior study author Rene Hen, of Columbia University, said in a news release. “The reasons for this treatment resistance remain enigmatic. Elucidating the exact nature of both the factors predisposing to depression and the mechanisms underlying treatment resistance remains an important and unmet need.”

In the study, researchers used mice to investigate the way the brain deals with serotonin. The brain’s mechanism for handling serotonin appears to be related to levels of so-called “autoreceptors,” the study authors found. Mice with higher levels didn’t respond to treatment with antidepressants, but they did better when the levels went down, the study showed.

The research could lead to treatments to make people more responsive to antidepressants before they take them, Hen said.

The findings are published in the Jan. 14 issue of the journal Neuron.

A medicinal herb, milk thistle, appears to reduce liver damage resulting from chemotherapy, a new study finds.

Chemo drugs often cause liver inflammation, making it necessary to lower the dose or suspend treatment until the inflammation subsides. These interruptions in therapy can make treatment less effective, the researchers said.

“We found that milk thistle, compared to placebo, was more effective in reducing inflammation,” said lead researcher Dr. Kara Kelly, from New York-Presbyterian Hospital/Columbia University Medical Center’s Herbert Irving Comprehensive Cancer Center in New York City.

“If these results are confirmed, milk thistle may allow us to treat liver inflammation or prevent it from occurring, which will allow better delivery of chemotherapy drugs,” she added.

The report is published in the Dec. 14 online edition of Cancer.

Milk thistle, a longtime folk remedy, is often recommended to treat liver damage and mushroom poisoning. No other treatment for liver toxicity exists, Kelly said.

For the study, Kelly’s team randomly assigned 50 children undergoing chemotherapy for acute lymphoblastic leukemia to receive milk thistle or a placebo for 28 days. All the children had liver inflammation at the start of the study.

Twenty-eight days later, the children who had received milk thistle had improved liver enzymes, compared with the children who received a placebo, the researchers said.

The milk thistle group had significantly lower levels of one enzyme in particular, AST, and a trend towards lower levels of another enzyme called ALT, Kelly’s group found.

In addition, milk thistle appeared to help patients tolerate higher doses of chemotherapy. Sixty-one percent of the children receiving milk thistle needed dose reductions, compared with 72 percent of the children receiving placebo, but this difference is not significant, the researchers noted.

Related lab experiments showed the herb did not lessen the effectiveness of the chemotherapy drugs, and Kelly thinks milk thistle might reduce liver inflammation for patients with other cancers who are taking other types of chemotherapy as well. Further research is needed, she said, to determine the appropriate dose and duration of milk thistle therapy.

Her team also hopes to evaluate the herb’s ability to prevent chemo-induced liver inflammation.

Still, some experts remain unconvinced about the herb’s value in cancer treatment. Dr. Julio C. Barredo, director of pediatric hematology-oncology at the University of Miami Miller School of Medicine, said that the study’s small size, the low doses of milk thistle used and the short time frame of the study make the findings inconclusive.

Also, there was no difference in the delay of treatment in either group, he said.

“Improvement in one liver enzyme did not lead to patients who received the drug being delayed less than patients who received placebo in getting their chemotherapy,” Barredo said.

“I don’t think that you could recommend that people go and take this supplement when they are taking chemotherapy from the results of this study,” Barredo said. “Maybe a larger study, using a higher dose is warranted.”

Liver inflammation from chemotherapy usually abates when treatment stops or doses get reduced, Barredo added.

People who look younger than their age tend to live longer than those who look older than their years, a new study suggests.

The finding came from research that involved 1,826 Danish twins, aged 70 and older, who were given physical and cognitive tests and then had their faces photographed. Three groups of volunteers looked at the photos and indicated the age they perceived the participants to be. Twins were assessed individually, and on different days.

The researchers, from the University of Southern Denmark, then tracked the twins for seven years and found that perceived age was significantly associated with survival, even after adjustments were made for actual age, sex and the environment in which each pair of twins was raised. The bigger the difference in perceived age, the more likely it was that the older-looking twin died first, they noted.

The researchers also found an association between perceived age and physical and mental functioning.

Common genetic factors that influence both survival and perceived age may help explain the findings, the study authors explained.

Despite progress in some areas, smoking rates among U.S. adults remained stalled in 2008, halting the nation’s progress in ending the tobacco epidemic, according to a CDC study.

The study, released in advance of the annual Great American Smokeout, found that 46 million Americans (20.6 percent) were current cigarette smokers in 2008, which is virtually unchanged since 2004 when 20.9 percent of adults reported being smokers. The study’s findings indicate an alarming trend, because smoking is the leading preventable cause of death, killing more than 443,000 people every year and costing the nation $96 billion in health care costs annually.

This new data, based on the 2008 National Health Interview Survey, shows little to no change over the past five years and hints that smoking rates may be moving in the wrong direction.

“Today tobacco will kill more than 1,000 people, but we can reduce smoking rates,” said CDC Director Thomas R. Frieden, M.D., M.P.H. “We must protect people from second-hand smoke, increase the price of tobacco, and support aggressive anti-tobacco campaigns that will reduce smoking and save lives. If every State had smoking rates similar to places which have implemented effective programs, there would be at least 10 million fewer smokers in the US, and millions of heart attacks, cancers, strokes, and deaths would be prevented.”

According to the study, the people hardest hit by the tobacco epidemic are those among vulnerable populations, including people with lower levels of educational attainment. In 2008, 41.3 percent of persons with a General Education Development certificate smoked cigarettes, compared to 5.7 percent of persons with a graduate degree.

In another study in this week’s CDC Morbidity and Mortality Weekly Report, the 2008 Behavioral Risk Factor Surveillance System reports that current adult smoking prevalence varied substantially across 50 states, the District of Columbia, and the three U.S. territories. Among states, smoking prevalence was highest in West Virginia (26.6 percent), Indiana (26.1 percent), and Kentucky (25.3 percent) and lowest in Utah (9.2 percent), California (14 percent), and New Jersey (14.8 percent).

In the same study, CDC also reported significant variation among 11 states in the proportion of adults protected by smoke-free workplace policies and the proportion of adults who protect themselves and their families from secondhand smoke in their homes.

Among the 11 states which asked questions about exposure to second-hand smoke, there was a large variation in indoor workplace exposure – from a high of 16 percent in Mississippi to a low of 6 percent in Connecticut and Tennessee. Second-hand smoke is known to cause cancer, heart disease, and many other health problems, and smoke-free laws have many benefits, including protecting non-smokers, reducing heart attacks in non-smokers, and encouraging smokers to quit. Past experience shows that smoke-free laws covering public places encourage people to adopt smoke-free policies in their homes. In these states, home exposure varied widely from 3 percent of adults exposed in their homes in Arizona to 10.1 percent and 10.6 percent, respectively, in Mississippi and West Virginia. This finding correlates with household policies about not allowing smoking in households with a smoker present – for example, two thirds of smokers in Arizona live in households where smoking is not allowed in the home, compared to 41 percent and 36 percent in Mississippi and West Virginia. Nationwide, 21 states and D.C. have implemented comprehensive smoke-free laws covering workplaces, restaurants, and bars, but more than half of the country still lives in areas where they are not protected by comprehensive smoke-free laws.

“Despite states having received more than $200 billion in tobacco-generated funds over the past 10 years, many Americans—particularly those with low educational attainment levels, and those who work in the hospitality, service, and other industries are exposed to smoke in their workplaces, and they do not have equal access to the support needed to help them quit,” said Matthew McKenna, M.D., M.P.H., director, CDC’s Office on Smoking and Health. “We need to make the investments so all people receive the same protections and adequate information to help them quit successfully.”

In an MMWR report last week, CDC noted that smoking rates among low-income adults enrolled in Medicaid programs are much higher than the general population (33 percent vs. 19 percent), and that only 6 Medicaid programs provided full access to all proven means to help smokers quit. Because access to tobacco cessation treatments (FDA-approved medications and counseling) has been shown to help smokers quit, providing coverage to all smokers, including the Medicaid population, would help reduce smoking rates.