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New Route To Potential Breast Cancer Cure Discovered

January 4th, 2010

UK scientists have discovered a new route to a potential cure for breast cancer, one that focuses on how the cancer manipulates genetic pathways to spread through the body, rather than on how tumors develop in the first place. They are already working on a new drug to switch off the cancer’s effect on the pathways and say it could be ready in a couple of years, but experts suggest this could be rather optimistic.

The landmark study was the work Dr Justin Stebbing of Imperial College London (ICL) and other colleagues from ICL and also from the Howard Hughes Medical Institute, Cold Spring Harbor Laboratory in New York, USA. They have written a paper on it in the 24 August online before print issue of the Proceedings of the National Academy of Sciences, PNAS.

Stebbing, who is senior lecturer and consultant medical oncologist at ICL was reported by the Daily Express as telling the media that the new discovery was a “step on the way” to a potential cure for breast cancer.

“It helps us understand the way breast cancer cells grow and divide and if we understand this then we understand how to stop it,” said Stebbing.

Breast cancer is the most common cancer of women in the western world, in Britain alone it kills 12,000 women a year.

In most cases the cancer depends on estrogen to fuel tumor growth, and current treatments focus on inhibiting the activity of the estrogen receptor. These treatments, for example tamoxifen, have been very successful at reducing deaths from breast cancer.

“The estrogen receptor is incredibly important in breast cancer,” said Stebbing.

“Most of the treatments around treating breast cancer are blocking it or inhibiting the oestrogen but despite that about half of all women relapse,” he added.

Many patients relapse because they eventually become resistant to hormone therapies.

Cancer is essentially a process where cell growth gets out of control. One of the ways that healthy cells stop growth getting out of control is via microRNA molecules that use genetic pathways to control various cellular processes in the body, such as making proteins.

As Stebbing explained:

“The way to cure breast cancer or any cancer is by fundamental biological understanding of what turns cells on and off, stopping the way tumours grow.”

Stebbing and colleagues’ breakthrough has been to discover how cancer cells switch off the microRNA molecules that control cell division to unleash the growth and proliferation of malignant cells.

“We can use these microRNAs as a new treatment and make them do what current drugs don’t do,” said Stebbing.

He said they had found a new microRNA pathway that the estrogen receptor activates. In normal cells estrogen encourages the production of microRNAs, but then as more of them are produced, they switch off estrogen activity, and this keeps cell division under control. Stebbing described this as a “perfect circle”.

“But in breast cancer cells, production of the molecules is turned off,” said Stebbing, and this is how the control over cell division is then lost and the malignant cells proliferate.

So their aim is to produce a drug that restores the “perfect circle” by stopping the deactivation of the microRNAs.

“If we know how to stop it then we can cure it. This only applies in oestrogen positive breast cancer but this could save millions of lives,” said Stebbing.

Experts welcomed the discovery but had reservations about a drug being available soon.

According to the Daily Express, Dr Laura Bell, of Cancer Research UK, said it was far too early to say whether the discovery will “translate into clinical benefits for people with cancer”. She said there was still a lot of work to be done.

Agreeing, Dr Alexis Willett, of Breakthrough Breast Cancer reportedly said, “this research is still at a very early stage”.

Better cooperation through testosterone?

December 10th, 2009

Everyone knows that testosterone makes people more aggressive, right?

Scientists have found that administering the hormone to rodents prompts a surge in aggressive behavior. In humans, prisoners with higher levels of testosterone are more likely to break the rules and get into fights. One study of 692 adult male inmates found that those serving time for crimes like rape, murder and armed robbery had more testosterone than their counterparts convicted of nonviolent offenses like theft and drug abuse.

But a group of European researchers decided to challenge this conventional wisdom. They wondered whether testosterone induced people to seek a higher social status. In prisons, this would play out by breaking rules and starting fights. But in other situations, testosterone might make actually encourage people to cooperate.

To test this theory, they recruited 60 women to play the “ultimatum bargaining game.” In this game, players A and B try to agree on a way to split a certain amount of money. Player A proposes a split to Player B, who can either accept or reject it. If she accepts, they both keep the money. If not, they both wind up empty-handed.

The researchers gave 30 women a 0.5-milligram dose of testosterone and gave the rest a placebo without telling them which was which. Then they played the game. The researchers predicted that the women who got testosterone would go to greater lengths to make sure their offers weren’t rejected; therefore, their offers would be more generous.

And they were. The total pot was 10 monetary units, and players were allowed to offer 0, 2, 3 or 5 units. Women who took testosterone offered an average of 3.9 units, compared with only 3.4 units for women who got the placebo, according to a study online today by the journal Nature. The difference was statistically significant.

If you’re surprised, you’re not alone. The researchers asked the women whether they thought they got testosterone or the placebo. In accordance with the conventional wisdom, women who believed they had ingested the hormone made lower offers than those who guessed they got a dummy pill.

Nine Lives: Cats’ Central Nervous System Can Repair Itself And Restore Function

December 3rd, 2009

From ScienceDaily.com:

Scientists studying a mysterious neurological affliction in cats have discovered a surprising ability of the central nervous system to repair itself and restore function.
In a study published March 30, 2009 in the Proceedings of the National Academy of Sciences, a team of researchers from the University of Wisconsin-Madison reports that the restoration in cats of myelin — a fatty insulator of nerve fibers that degrades in a host of human central nervous system disorders, the most common of which is multiple sclerosis — can lead to functional recovery.
“The fundamental point of the study is that it proves unequivocally that extensive remyelination can lead to recovery from a severe neurological disorder,” says Ian Duncan, the UW-Madison neuroscientist who led the research. “It indicates the profound ability of the central nervous system to repair itself.”
The finding is important because it underscores the validity of strategies to reestablish myelin as a therapy for treating a range of severe neurological diseases associated with the loss or damage of myelin, but where the nerves themselves remain intact.
Myelin is a fatty substance that forms a sheath for nerve fibers, known as axons, and facilitates the conduction of nerve signals. Its loss through disease causes impairment of sensation, movement, cognition and other functions, depending on which nerves are affected.
The new study arose from a mysterious affliction of pregnant cats. A company testing the effects on growth and development in cats using diets that had been irradiated reported that some cats developed severe neurological dysfunction, including movement disorders, vision loss and paralysis. Taken off the diet, the cats recovered slowly, but eventually all lost functions were restored.
“After being on the diet for three to four months, the pregnant cats started to develop progressive neurological disease,” says Duncan, a professor of medical sciences at the UW-Madison School of Veterinary Medicine and an authority on demyelinating diseases. “Cats put back on a normal diet recovered. It’s a very puzzling demyelinating disease.”
The afflicted cats were shown to have severe and widely distributed demyelination of the central nervous system, according to Duncan. And while the neurological symptoms exhibited by the cats are similar to those experienced by humans with demyelination disorders, the malady does not seem to be like any of the known myelin-related diseases of humans.
In cats removed from the diet, recovery was slow, but all of the previously demyelinated axons became remyelinated. The restored myelin sheaths, however, were not as thick as healthy myelin, Duncan notes.
“It’s not normal, but from a physiological standpoint, the thin myelin membrane restores function,” he says. “It’s doing what it is supposed to do.”
Knowing that the central nervous system retains the ability to forge new myelin sheaths anywhere the nerves themselves are preserved provides strong support for the idea that if myelin can be restored in diseases such as multiple sclerosis, it may be possible for patients to regain lost or impaired functions: “The key thing is that it absolutely confirms the notion that remyelinating strategies are clinically important,” Duncan says.
The exact cause of the neurological affliction in the cats on the experimental diet is unknown, says Duncan, who was not involved in the original study of diet.
“We think it is extremely unlikely that [irradiated food] could become a human health problem,” Duncan explains. “We think it is species specific. It’s important to note these cats were fed a diet of irradiated food for a period of time.”
In addition to Duncan, authors of the new PNAS study include Alexandra Brower of the Wisconsin Veterinary Diagnostic Laboratory; Yoichi Kondo and Ronald Schultz of the UW-Madison School of Veterinary Medicine; and Joseph Curlee, Jr. of Harlan Laboratories in Madison.

Fantastic Stem Cell News !!

November 6th, 2009

The California Institute for Regenerative Medicine, the state stem cell agency, and two international partners awarded more than $250 million to 14 multidisciplinary teams of researchers in California, the UK and Canada to develop stem cell-based therapies for 11 diseases. The Disease Team Research Awards include approximately $8 million from the Medical Research Council, UK, and approximately $35 million from the Cancer Stem Cell Consortium, Canada, to fund the international portions of the collaborations.

CIRM’s 29-member Governing Board voted to approve funding for the four-year grants, which mark the first CIRM funding explicitly expected to result in a filing with the FDA to begin a clinical trial. The Disease Team Research Awards fund research teams that include basic scientists and clinicians from both academia and industry. These collaborations speed the process of establishing clinical trials by insuring that clinically relevant issues are considered early and avoiding potential safety issues being discovered late in the process.

CIRM President Alan Trounson said the pace of the Disease Team projects stands in contrast to the decade or more that’s usually required to reach clinical trials. “Scientists have talked for years about the need to find ways to speed the pace of discovery. By encouraging applicants to form teams composed of the best researchers from around the world we think CIRM will set a new standard for how translational research should be funded,” he said.

Each team will be actively managed by CIRM and the agency’s international partners for those teams with cross-border collaborations. Decisions to move forward with the project will be made at key points in the development cycle.

“This unique partnership is another opportunity for the people of California to lead the way in this important research and advance potentially life-saving science,” said Governor Schwarzenegger. “These grants will help unite some of the best scientists throughout the world, including right here in California, to find new therapies and cures for people suffering from chronic and life-debilitating diseases. I am proud California remains at the forefront of this innovative research and I look forward to the results of this international collaboration.”

“This initiative is bringing together the leading minds in cancer and stem cell research from Canada and California,” said Dr. Morag Park, Scientific Director of the Institute of Cancer Research, part of the Canadian Institutes of Health Research (CIHR), the Government of Canada’s health research agency. “CIHR, in conjunction with Genome Canada and through the Cancer Stem Cell Consortium, is proud to fund Canadian Scientists in this cross-border collaboration that will engage scientists from many disciplines, combine resources, technologies and knowledge to find more effective treatments for leukemia and solid cell tumours.”

Sir Leszek Borysiewicz, Chief Executive of the Medical Research Council: “The partnerships that have been established between the UK and CIRM have brought us closer to delivering the promise of stem cell treatments for debilitating conditions. We hope these projects will accelerate treatments to early clinical trials, eventually leading to a direct benefit for people suffering from age-related macular degeneration, which up until now has been regarded as incurable and also acute myeloid leukaemia. The MRC has led the way for UK translational researchers and together with our partners at CIRM we look forward to realising the full potential of stem cell research”

Other diseases being targeted by the teams include HIV/AIDS, type 1 diabetes, damage from heart attack, sickle cell anemia, amyotrophic lateral sclerosis also known as Lou Gehrig’s disease, and epidermolysis bullosa, a hereditary life-threatening condition of the skin’s connective layer. The 14 awards will go to seven not-for-profit institutions and one for-profit institution. The award to the one for-profit grantee will take the form of a loan.

“CIRM’s loan program will recycle money back into future awards and leverage the voter’s commitment to the field,” said Robert Klein, Chair of the CIRM Governing Board. “In providing stem cell funding in the form of loans, CIRM is able to fund more science and make a more significant impact on the speed of bringing new stem cell-based therapies to the people of California and the world.”

Neuroscientists Find Brain Region Responsible For Our Sense Of Personal Space

October 23rd, 2009

From ScienceDaily.com:

In a finding that sheds new light on the neural mechanisms involved in social behavior, neuroscientists at the California Institute of Technology (Caltech) have pinpointed the brain structure responsible for our sense of personal space.

The discovery, described in the August 30 issue of the journal Nature Neuroscience, could offer insight into autism and other disorders where social distance is an issue.

The structure, the amygdala—a pair of almond-shaped regions located in the medial temporal lobes—was previously known to process strong negative emotions, such as anger and fear, and is considered the seat of emotion in the brain. However, it had never been linked rigorously to real-life human social interaction.

The scientists, led by Ralph Adolphs, Bren Professor of Psychology and Neuroscience and professor of biology and postdoctoral scholar Daniel P. Kennedy, were able to make this link with the help of a unique patient, a 42-year-old woman known as SM, who has extensive damage to the amygdala on both sides of her brain.

“SM is unique, because she is one of only a handful of individuals in the world with such a clear bilateral lesion of the amygdala, which gives us an opportunity to study the role of the amygdala in humans,” says Kennedy, the lead author of the new report.

SM has difficulty recognizing fear in the faces of others, and in judging the trustworthiness of someone, two consequences of amygdala lesions that Adolphs and colleagues published in prior studies.

During his years of studying her, Adolphs also noticed that the very outgoing SM is almost too friendly, to the point of “violating” what others might perceive as their own personal space. “She is extremely friendly, and she wants to approach people more than normal. It’s something that immediately becomes apparent as you interact with her,” says Kennedy.

Previous studies of humans never had revealed an association between the amygdala and personal space. From their knowledge of the literature, however, the researchers knew that monkeys with amygdala lesions preferred to stay in closer proximity to other monkeys and humans than did healthy monkeys.

Intrigued by SM’s unusual social behavior, Adolphs, Kennedy, and their colleagues devised a simple experiment to quantify and compare her sense of personal space with that of healthy volunteers.

The experiment used what is known as the stop-distance technique. Briefly, the subject (SM or one of 20 other volunteers, representing a cross-section of ages, ethnicities, educations, and genders) stands a predetermined distance from an experimenter, then walks toward the experimenter and stops at the point where they feel most comfortable. The chin-to-chin distance between the subject and the experimenter is determined with a digital laser measurer.

Among the 20 other subjects, the average preferred distance was .64 meters—roughly two feet. SM’s preferred distance was just .34 meters, or about one foot. Unlike other subjects, who reported feelings of discomfort when the experimenter went closer than their preferred distance, there was no point at which SM became uncomfortable; even nose-to-nose, she was at ease. Furthermore, her preferred distance didn’t change based on who the experimenter was and how well she knew them.

“Respecting someone’s space is a critical aspect of human social interaction, and something we do automatically and effortlessly,” Kennedy says. “These findings suggest that the amygdala, because it is necessary for the strong feelings of discomfort that help to repel people from one another, plays a central role in this process. They also help to expand our understanding of the role of the amygdala in real-world social interactions.”

Adolphs and colleagues then used a functional magnetic resonance imaging (fMRI) scanner to examine the activation of the amygdala in a separate group of healthy subjects who were told when an experimenter was either in close proximity or far away from them. When in the fMRI scanner, subjects could not see, feel, or hear the experimenter; nevertheless, their amygdalae lit up when they believed the experimenter to be close by. No activity was detected when subjects thought the experimenter was on the other side of the room.

“It was just the idea of another person being there, or not, that triggered the amygdala,” Kennedy says. The study shows, he says, that “the amygdala is involved in regulating social distance, independent of the specific sensory cues that are typically present when someone is standing close, like sounds, sights, and smells.”

The researchers believe that interpersonal distance is not something we consciously think about, although, unlike SM, we become acutely aware when our space is violated. Kennedy recounts his own experience with having his personal space violated during a wedding: “I felt really uncomfortable, and almost fell over a chair while backing up to get some space.”

Across cultures, accepted interpersonal distances can vary dramatically, with individuals who live in cultures where space is at a premium (say, China or Japan) seemingly tolerant of much closer distances than individuals in, say, the United States. (Meanwhile, our preferred personal distance can vary depending on our situation, making us far more willing to accept less space in a crowded subway car than we would be at the office.)

One explanation for this variation, Kennedy says, is that cultural preferences and experiences affect the brain over time and how it responds in particular situations. “If you’re in a culture where standing close to someone is the norm, you’d learn that was acceptable and your personal space would vary accordingly,” he says. “Even then, if you violate the accepted cultural distance, it will make people uncomfortable, and the amygdala will drive that feeling.”

The findings may have relevance to studies of autism, a complex neurodevelopmental disorder that affects an individual’s ability to interact socially and communicate with others. “We are really interested in looking at personal space in people with autism, especially given findings of amygdala dysfunction in autism. We know that some people with autism do have problems with personal space and have to be taught what it is and why it’s important,” Kennedy says.

He also adds a word of caution: “It’s clear that amygdala dysfunction cannot account for all the social impairments in autism, but likely contributes to some of them and is definitely something that needs to be studied further.”

The work was funded by the National Institute of Mental Health, the Simons Foundation, the Della Martin Foundation, and a global Center of Excellence grant from Japan.