The pathophysiology of cancer involves uncontrolled cellular proliferation–that we know–but the process doesn’t go on forever. After reaching a certain size, tumors do stop growing. This phenomenon is probably driven by growth-inhibiting chemicals that are released by tumor cells themselves.

Scientists are now trying to harness this phenomenon using a decidedly counterintuitive strategy: introducing cancer cells into the bodies of mammals–including humans–that are already afflicted with cancer. The strategy amounts to fighting cancer with cancer. Remarkably, early results from studies of the technique have been positive.

The technique was developed by Barry Smith and colleagues at the Rogosin Institute, an independent treatment and research center in New York. Smith’s group creates pea-sized beads of mouse kidney cancer cells that are encapsulated in a growth-restricting shell.

Initially, the beads contain about 150,000 cancer cells. During an incubation period however, all but 1% of those cells die, according to Smith. The remaining ones secrete proteins or peptides that inhibit tumor growth. Some of the chemicals promote cell death directly; others impair a cell’s ability to stimulate new blood vessel formation which is  needed for cellular survival.

“They reach a stable state in which there is cell division and cell death,” Smith said in an interview. “They are producing inhibitory factors that regulate their growth.”

Once the encapsulated concoction is “mature” in this way, Smith’s group  implants the beads into the abdominal cavities of cancer patients.

In a pair of studies released last week in Cancer Research, Smith’s group reported that their treatment reduced tumor size in laboratory mice, dogs and cats. Many cancer-stricken animals survived longer than expected. (more…)

Hot flashes are a common symptom of menopause. Lasting from two to 30 minutes per episode, they usually begin with a sensation of intense heat on the face or chest which then spreads to other parts of the body. This sensation is often associated with sweating and tachycardia.

Not all women experience hot flashes, and for many others the symptoms amount to little more than a minor annoyance. But for some, hot flashes are down right debilitating. They have been known to precipitate fainting, for example. Some women experience several dozen hot flashes per day, and each one is severe enough to interrupt sleep or force them to cease normal activities until it subsides.
 
Hormone replacement therapy works like a charm for nearly all affected women, but it has fallen out of favor in the last decade or so, after scientists showed the therapy increased the risk of cardiovascular disease and breast cancer, among other things.

Women who suffer debilitating hot flashes, and the physicians who treat them will thus be heartened to learn that the antidepressant Lexapro reduces the frequency and severity of hot flash symptoms.

That’s the conclusion reached by Ellen Freeman and colleagues at the University of Pennsylvania, who recently published their findings in JAMA.

To reach this conclusion, Freeman’s team randomized 205 healthy menopausal women to receive either Lexapro or a placebo. Each volunteer reported experiencing at least 28 hot flashes per week. As a group, they averaged 9.8 hot flashes per day before the study began. (more…)

In 2003 and 2004, bird flu outbreaks devastated the economies of several Southeast Asian countries. More than 140 million birds either succumbed to the virus or were culled by humans in an attempt to control the epidemic. Poultry producers lost more than $10 billion.

Thankfully, those strains of avian flu weren’t adept at infecting humans. If a future strain manages to do so in a big way, the resulting pandemic could cost the global economy $1.25 trillion.

Those predictions have ruffled feathers among politicians and scientists alike, and a serious effort has begun to prevent such an occurrence. Unfortunately, research on anti-viral drugs and vaccines is going nowhere fast.

Now however, scientists at the Universities of Cambridge and Edinburgh have chosen to attack the problem in a different way: they’ve created a better chicken.

In a paper published in Science, Laurence Tiley and colleagues report having genetically re-engineered the standard chicken into a version that doesn’t transmit avian flu to its coop-mates. The scientists assert their super-chicken may prevent outbreaks of avian flu among birds and yes, reduce the chances that the virus could jump to humans, who have no immunity to bird flu.

“Preventing virus transmission in chickens should reduce the economic impact of the disease and reduce the risk posed to people exposed to the infected birds,” Tiley said in an interview. “The genetic modification we describe is a significant first step along the path to developing chickens that are completely resistant to avian flu.”

To produce their super-chickens, Tiley’s group introduced a so-called RNA-expression cassette into their DNA. The cassette prompted the chickens to produce a hairpin-shaped piece of RNA that essentially tricks a viral enzyme known as polymerase into biding with it, rather than the native viral genome. This renders the enzyme useless and prevents the virus from replicating itself. (more…)

In developed nations, human life expectancy has increased steadily for over a century. One of the few negative consequences of this trend has been a marked increase in the prevalence of Alzheimer’s disease, an age-related untreatable condition that has driven enormous health spending on a national scale and wrecked the finances of millions of families in the US alone. Now, with the oldest Baby Boomers just reaching age 65, Alzheimer’s disease seems destined to become a true national health crisis.

Two of the most vexing problems with this nasty disease are determining who has it and diagnosing it early enough (so scientists can understand how it progresses and someday, intervene to either cure it or halt its progression).

With current technology, the only way to accurately diagnose Alzheimer’s disease is at autopsy. Special tests of the deceased’s brain reveal the sine qua non of Alzheimer’s disease: amyloid plaques.

But last week, 2 studies appearing in JAMA provided rays of hope in this otherwise dismal state of affairs. We review them both below:

Brain Scan Detects Plaques
In the first study, scientists injected a radioactive dye known as Flobetapir F 18 into the blood of elderly volunteers, and then used PET scans to image their brains.  Florbetapir F 18 had been designed by Christopher Clark and colleagues at Avid Radiopharmaceuticals to bind to amyloid proteins—which are the main constituents of amyloid plaques—and thus make them visible in vivo using the PET scan.

The PET scans correctly identified amyloid plaques in 97% of the volunteers that actually had them, as proven at autopsy. In addition, PET scans performed after the dye had been injected into young, healthy volunteers revealed no plaques.

Scientists believe the Florbetapir F 18 PET scans could be helpful as a means to exclude the diagnosis of Alzheimer’s. If no plaques are found in a patient with symptoms of dementia, physicians would be compelled to consider other causes of the symptom complex. The PET scans could also potentially be used to test drugs designed to remove amyloid from the brain.

A Blood Test for Alzheimer’s
The second study showed that blood levels of amyloid protein, as detected by a new blood test, were correlated with memory problems.

The study was directed by Kristine Yaffe at UCSF. Her group recruited 997 elderly volunteers and followed them with memory tests and amyloid blood tests for 9 years. (more…)

Humans are the only living things that cry when they are overcome with emotion. Why do we do this?

A study by Noam Sobel and colleagues at the Weizmann Institute provide part of the answer, at least as it relates to women. The scientists showed that when men get a whiff of women’s tears, they experience a temporary, generalized loss of libido and a dip in testosterone. Really.

(And you thought that red, runny nose was the turn-off, didn’t you?)

Scientists have known for decades that the chemical composition of “emotional tears” differs from tears shed due to simple irritation. But now, it appears that some of the chemicals contained in the former are actually pheromones; biological substances that create behavioral changes in others who are exposed to them. Such chemicals were known to exist in urine in anogenital gland secretions (dont ask), but not in tears.

Sobel’s team began its study by posting ads on Israeli college campus bulletin boards in which they sought volunteers who cried easily. Seventy-one people responded. All but one were women. From that group, the scientists identified 6 who were, like, seriously profuse criers and who could return to their labs every other day.

The scientists then asked each one to select a movie that was guaranteed to make them break down, to watch it in private, and to collect their tears in a vial. For the controls, Sobel’s group trickled a saline solution down the same women’s cheeks and collected that.

Sobel’s group subsequently asked male volunteers to sniff the contents of the 2 vials and ran a battery of psychological and physiological tests to measure their responses.

The men could not distinguish the odorless, colorless liquids, but boy oh boy did their responses differ! In one study, men rated women in photos as less sexually attractive after sniffing “emotional tears” than after they sniffed the saline solution. In another study, men watched scenes from a sad movie after sniffing either the real stuff or saline. They were equally sad regardless of which mixture they sniffed, but the tear-sniffers had lower sexual arousal and lower testosterone levels. (more…)

It’s well-known that the offspring of obese parents tend to become obese themselves. Both environmental and genetic factors govern this association. Recently, a pair of studies has shed considerable light on those genetic factors, and in particular the role that a father’s diet has on his kids.

In the first study, Sheau-Fang Ng and colleagues at the University of New South Wales randomized a cohort of male rats to receive either a high-calorie diet or a healthy diet, and then had them mate with normal, healthy female rats.

The scientists found that as the daughters of the obese dads grew to become adults, they exhibited impaired glucose tolerance and elevated insulin levels that were not seen in the daughters of normal-weight dads. This turned out to be true even though both sets of offspring had similar amounts of fat and muscle mass, and similar blood triglyceride and leptin levels.

The scientists performed genetic studies on the 2 groups to better understand the cause of these differences. These studies revealed that 642 genes were expressed differently in the 2 groups, and all of them were involved with glucose metabolism and insulin production. The anatomic site where the changes had their impact was localized to pancreatic B-cells which are known to produce insulin.

In their write-up, Sheau-Fang’s group claimed that theirs was “the first direct demonstration in any species that a paternal environmental exposure can induce intergenerational transmission of impaired glucose-insulin homeostasis in their female offspring.” (more…)

Dead Heads have experienced it while listening to Jerry Garcia transition from Not Fade Away into Goin’ Down the Road Feeling Bad on the 1971 album, Skull and Roses. Jazz aficionados have as well, during any one of several McCoy Tyner solos on John Coltrane’s classic, A Love Supreme. And so have connoisseurs of classical music, who marvel at Jascha Heifetz’ stunning interpretations of Tchaikovsky’s Violin Concerto in D major (below).

In fact, just about everyone has enjoyed a sensation of pure euphoria as “that riff” plays out during a favorite piece of music. 

Recently, Robert Zatorre and Valorie Salimpoor of McGill University decided to study the neurobehavioral underpinnings of the phenomenon. Perhaps not surprisingly, they found that regardless of the type of music or the age or sophistication of the listener, that euphoric feeling can indeed be measured, and its neurochemical roots are quite similar from person to person.

In fact, the scientists showed that musical epiphanies feature increased heart and breathing rates, and the release of dopamine in certain areas of the brain. Dopamine is the same neurotransmitter that’s released when humans experience similarly intense sensations of pleasure associated with tangible rewards like a good meal, sexual gratification, or the ingestion of certain addictive drugs.

To reach these conclusions, the scientists recruited 8 volunteers and asked them to listen to, in order, a favorite musical passage of their choosing and then a decidedly uninspiring selection that was chosen for them. (more…)

Although cocaine use has declined steadily since its peak in the early 1980s, public health officials estimate that about 7 million Americans used the drug at least once last year. Many of these folks are addicted to the drug, and its intense, short-lived euphoric effects mean the addiction is terribly difficult to overcome.

Addiction specialists believe existing treatment paradigms for cocaine addiction can be enhanced by a vaccine that prevents the drug from crossing the blood-brain barrier, thus blunting its euphoric effects. Scientists have worked hard to develop such a vaccine, but have had limited success so far. 

About a year ago for example, Thomas Kosten and colleagues at Baylor reported partial success in a human trial of a cocaine vaccine. In that trial, 38% of subjects who received all 5 shots in the vaccine series achieved sufficient antibody levels to blunt the effects of the drug. In that subset, 53% of the subjects stopped using cocaine, meaning that overall, the vaccine worked about 20% of the time.

Unfortunately, some subjects began snorting massive amounts of the drug in an effort to overcome the vaccine’s effects. Some people managed to amass 10 times more of the drug in their systems than was present before the trial began. Cocaine levels like that can kill people. In addition, the cocaine antibodies, when they developed at all, remained in the bloodstream of subjects for only 8-10 weeks; it takes longer than that to assure the behavioral aspects of the addiction are overcome.

What’s New?
Last week, Martin Hicks, Ronald Crystal and colleagues at Cornell reported that they had developed an alternative vaccine and that it was quite effective…in mice.

The Cornell team attached a chemical congener of cocaine onto a specially prepared version of an adenovirus, the virus responsible for many common colds. The latter vector was chosen to assure that the body’s immune system would recognize the newly created molecule as foreign and create antibodies against it. The trick of course, was to assure that the antibodies so created would recognize “pure” cocaine after it was ingested, and prevent it from crossing the blood brain barrier. (more…)

Cancer of the ovary is a particularly nasty disease. It often remains asymptomatic until it has reached an advanced, incurable stage, and scientists have been unable to develop an effective screening test for the disease like the ones in widespread use for cancers of the breast and cervix.

The dismal status of ovarian cancer screening was underscored a year ago when an NIH-sponsored study showed that over 70% of cancers detected by transvaginal ultrasound and CA 125 biomarker testing—the two best ovarian screening tests we’ve got—had reached stage III or IV at the time the patients screened positive. That’s about what happens when women aren’t screened at all.

That wasn’t the worst of it, however. In just the first year of that screening program, positive test results obligated 566 surgical procedures which uncovered only 18 cancers. That’s an awful lot of unnecessary surgery and associated morbidity right there. Things were no better on the false-negative side of things. Overall, 89 cases of ovarian cancer were diagnosed during the NIH study, and a third of them had been missed by both screening modalities.

What’s New?     The NIH study didn’t evaluate the impact of screening on ovarian cancer mortality, but a recent study by Laura Havrilesky and colleagues at Duke did indeed address the point. Sadly, the results were abysmal.

Havrilesky’s team developed a modified a Markov model to characterize the natural history of ovarian cancer, and used it to show that mortality would fall by a paltry 11% if a widespread screening program (in this case, CA 125 biomarker testing followed by pelvic ultrasound imaging for women with abnormal results) was put into place. 

The scientists emphasized that the protean nature of ovarian cancer—not just its tendency to remain asymptomatic until an advanced stage—was a huge challenge in developing an effective screening tool. According to their analysis, some ovarian cancers tend to grow slowly, taking nearly 3 years before progressing to an advanced stage. Other ovarian cancers are more aggressive, reaching an advanced stage after only 13 months.

“If we assume ovarian cancers grow and spread at different rates, the best screening strategy available will only reduce the number of women dying from the cancer by 11%,” Havrilesky said in a press release. “This is partially because the slower growing cancers are more likely to be caught by a screening test.”

The authors didn’t exactly throw up their hands in disgust at the poor prospects for ovarian screening, but they did suggest that policy makers consider directing funds towards prevention and treatment of the disease, and away from screening.

That said, most experts do recommend routine screening for ovarian cancer in women that have a family history of the disease and in those who carry genes known to increase the risk of developing it. As always, women with questions about these issues should consult their doctors.

Havrilesky’s write-up appears in Cancer.

Resveratrol, a naturally-occurring antioxidant found in blueberries, red grapes and red wine, had become a press-magnet over the last few years after studies showed it activated so-called Sirt1 metabolic pathways which control the differentiation, aging and death of mammalian cells.

The studies prompted scientists to speculate that resveratrol can be leveraged to fight cancer or even create a modern-day Fountain of Youth.

Amid the excitment, GlaxoSmithKline shelled-out $720 million to purchase Sirtris Pharmaceuticals, a Boston-based company that owned key patents in the area and that was headed by a controversial Harvard researcher, David Sinclair. Sinclair reportedly pocketed $8 million in the deal.

Alas, things haven’t gone well for GSK since the purchase. Last month in fact, the drug giant announced it was pulling the plug on further development of SRT 501, one of the proprietary resveratrol formulations it acquired from Sirtris.

GSK officials said at the time that the drug’s potential to cause harm outweighed any possible benefits, at least in relation to the treatment of multiple myeloma, a bone marrow cancer.

The announcement came a few months after GSK shut down a Phase 2 trial of the compound when several patients developed kidney failure.

The Myeloma Beacon, a blog that follows scientific advancements relevant to multiple myeloma, first broke the story. A GSK spokesperson told the Beacon that its decision allows the company to reassign development resources towards other resveratrol compounds with a more favorable risk/benefit ratio. The newer compounds are not being considered as treatments for myeloma.

“Currently, we have two of these latest generation compounds (SRT2104 and SRT2379) in several exploratory clinical trials,” the spokesperson added.

The GSK spokesperson did not indicate why the company decided to bag research on SRT501 altogether. Certainly, it could have continued to assess the compound for efficacy against other diseases.

Earlier scientific claims about resveratrol were based on laboratory studies involving mice and other rodents. GSK’s trial of SRT501 in myeloma patients was the first trial of the drug in humans.