UK's "Super Mouse" Yielding Major Discoveries in Cancer Research

Newswise — LEXINGTON, Ky. (July 26, 2013) — It appears tiny and inconsequential enough, but the "super mouse" — created by researchers at the University of Kentucky Markey Cancer Center some six years ago — has spawned plenty of new research into preventing and/or treating many types of cancer.

Back in 2007, cancer researcher Vivek Rangnekar and his team announced that they discovered a gene — known as Par-4 —that specifically kills cancer cells without killing normal cells. Rangnekar's team used this gene to develop cancer-resistant mice that become known as "super mice" for their ability to stay healthy and tumor-free compared to normal mice.

Since that initial discovery, researchers across the country have built upon Rangnekar's discovery, including a team at the University of Pennsylvania, who recently published findings on how Par-4 downregulation affects breast cancer recurrence.

In a new article for Cancer Cell, UK researchers including Rangnekar as well as Tripti Shrestha-Bhattarai and Nikhil Hebbar discuss a recent study and how its findings may lead to the development of novel treatment strategies for breast cancer.

Breast cancer is the second leading cause of cancer death in women. Even with treatment, one in five patients will relapse from the disease within 10 years, and patients who have triple-negative breast cancer have an especially high risk of both local and distant recurrence. Treatment for these aggressive cancers is difficult because they tend to be resistant to "standard of care" therapies.

The study performed by the UPenn team showed that in women who experienced breast cancer relapse, the Par-4 protein was suppressed. These low levels of Par-4 allowed the cancerous cells to survive and multiply even after a full course of treatment. Conversely, tumor cells that have high levels of Par-4 are eliminated by apoptosis (cell death) following treatment. These new findings may provide insight into deciding which patients are at the highest risk for cancer recurrence.

"What this tells us is that low Par-4 may act as a predictor of breast cancer recurrence," said Rangnekar, associate director for the UK Markey Cancer Center. "This is important, because although this group studied only breast cancer, their observations may be relevant to recurrence in a broad range of cancer types because Par-4 is a general tumor suppressor gene."

Using Par-4 levels as a biomarker prior to treatment — and knowing whether that patient is at an elevated risk of recurrence — would give physicians another tool to use in determining the best course of treatment. Additionally, their findings may provide the basis for the development of novel treatment strategies for breast cancer.

Other 'tumor suppressor' genes exist, says Rangnekar, but what makes Par-4 so special is that it is not mutated as frequently as other known suppressors, and it's "selective" in its actions in that Par-4 will only kill cancer cells and not normal cells. Par-4 can become 'suppressed' or inactivated, leading to tumor re-growth, but Par-4 can be 'activated' again — and one of the next major steps is developing a safe and effective way to activate Par-4 in the cancerous cells.

"If Par-4 is still present in the cells, the strategy should be to try and utilize that Par-4, so as to restore it’s apoptotic function and bring about apoptosis of the cancer cells," Rangnekar said.

Researchers are still years away from being ready to test these theories in clinical trials, but Rangnekar says they have already begun looking at agents, both natural and synthetic, that may help restore the expression of Par-4 in human cells, allowing the cancerous cells to become susceptible to treatment. Each new study on Par-4 brings researchers one step closer to developing a powerful method for both treating and preventing many of the deadliest types of cancers.

The findings in the cancer-resistant mouse have stimulated several collaborative projects on Par-4 at UK. Several UK investigators are now examining the role of Par-4 in diverse types of tumors: recently, Rangnekar and UK cancer biologist and immunologist Subbarao Bondada were jointly funded by the National Institutes of Health to study the role of Par-4 in chronic lymphocytic leukemia; UK pathologist Craig Horbinski’s group is investigating Par-4 in aggressive brain tumors called glioblastomas; and UK chemist David Watt and cancer biologist Chunming Liu are developing small molecules that can activate Par-4 and kill cancer cells.

“Our multi-disciplinary team, working together, uses a multi-faceted strategy in our research,” Rangnekar said. “This allows us to gain a better understanding of the complexities of cancer in order to effectively kill recurrent tumor cells, especially those that have spread from their origin to distant tissue sites.”

Scholarship Recipient Drawn to Neurosciences by Father’s Losing Fight Against Brain Cancer

Newswise — LOS ANGELES (July 25, 2013) – As the 2013 recipient of Cedars-Sinai Medical Center’s Pauletta and Denzel Washington Family Gifted Scholars Program in Neuroscience award, Christine R. Carico will spend the next year researching brain disorders like the one that took the life of her father, who survived four years after being diagnosed with a malignant brain tumor called an anaplastic astrocytoma.

“My interest in neuroscience started when my father was diagnosed, but it wasn’t until his death in 2007 that I realized academic medicine was my calling,” said Carico, who was 12 when her father’s cancer struck. “After witnessing the horrific course of the disease, I have made it my ultimate goal to find a cure for brain cancer so that no other families endure the suffering mine did. This scholarship will help propel me toward this goal by allowing me to learn from some of the most talented and renowned scientists in the field.”

Washington Scholars receive financial support and participate in cutting-edge scientific projects in Cedars-Sinai’s research labs. The Department of Neurosurgery began funding the scholarships in 2004 to support students who demonstrated the desire, initiative and aptitude to make significant contributions in the sciences. Pauletta and Denzel Washington gladly lent their names and continue to take an active role in the program.
The scholarship has provided summertime positions for two students each year but recently was reconfigured to give one recipient more in-depth exposure to research techniques, enabling the scholar to make more significant contributions, said Keith L. Black, MD, professor and chair of the department and the Ruth and Lawrence Harvey Chair in Neuroscience. The yearlong internship provides a stipend of $30,000 to $34,000, and the awardee is expected to submit a research paper or abstract to a national neuroscience, cancer or neurosurgery meeting.

Carico, born in Mountain View, Calif., and living in West Hollywood, soon will earn her bachelor’s degree in neuroscience at the University of California, Los Angeles. She took a course at UCLA’s Center for Prehospital Care and became a certified emergency medical technician, acquiring skills she hopes to put to work after graduating and before entering medical school. She served in 2009 and 2010 as a tutor in UCLA’s Watts Tutorial Program, which addresses the educational needs of students living in housing developments in Watts and East Los Angeles.

During her junior year of high school, Carico undertook an optional research project, working in Stanford University laboratories. She co-authored a journal article on cells and mechanisms involved in the development of leukemia and shadowed members of Stanford’s neurosurgical team to learn more about the field.

In a letter supporting Carico’s Washington Gifted Scholars application, Richard A. Jaffe, MD, PhD, professor of anesthesia and neurosurgery at Stanford, said, “Considering her level of education, she has an excellent scientific and medical knowledge base, in some areas exceeding that of our own medical students and residents.”

Carico was involved in basic research during a summer 2010 fellowship at UCLA through the Undergraduate Cancer Research Training Program sponsored by Charles R. Drew University of Medicine and Science. Starting in January 2011, she worked more than a year in a UCLA lab studying a signaling pathway involved in the transformation of normal tissue into abnormal masses. At the same time, and while carrying a full academic load, she started working at the Center for Neurosurgical Outcomes Research in the Department of Neurosurgery at Cedars-Sinai, where she continues today and has collaborated on six published studies.

Chirag Patil, MD, director of the Center for Neurosurgical Outcomes Research, has known Carico for more than six years — beginning when she was a high school student and shadowed him at Stanford, where he completed an internship in general surgery, a residency in neurosurgery, and a fellowship in stereotactic radiosurgery.

“Christine is the best and most dedicated undergraduate student I have ever mentored or come in contact with,” he said. “She is extremely bright and is very talented. Neuroscience and neuro-oncology have been a passion of hers since her father’s diagnosis with anaplastic astrocytoma in 2003. … Her story of fortitude, discipline and turning a big loss into a focused drive inspires me (and everyone around her).”

Tide is Turning in Skin Cancer Battle

Originally published here: http://msutoday.msu.edu/news/2013/tide-is-turning-in-skin-cancer-battle/#sthash.ISRDakUN.ohK9VbCJ.dpuf

A decade ago there was little doctors could do to help a patient with advanced-stage melanoma.

Now it seems each week yields important new discoveries about the deadly skin cancer.

“I’ve been doing this for 30 years, and now is by any measure the most exciting time for melanoma research,” said Brian Nickoloff, director of the Nicholas V. Perricone, M.D., Division of Dermatology and Cutaneous Sciences at Michigan State University’s College of Human Medicine.

In the research journal Laboratory Investigation, Nickoloff and colleagues outline recent advances that have put melanoma at the forefront of cancer research, raising hopes that scientists and clinicians may have cornered the deadliest of all skin cancers.

“In the past melanoma outsmarted us, but now we’re starting to outsmart melanoma,” said Nickoloff, who also is director of cutaneous oncology at Van Andel Research Institute in Grand Rapids and a member of the Stand Up to Cancer Dream Team for melanoma research. “Go back 10 years and you’ll see we had almost nothing to offer patients with advanced disease, but now we’re definitely getting the upper hand on this cancer.”

Melanoma is really a catch-all term for the most virulent types of skin cancer. The disease’s complexity is staggering – melanoma tumors have more mutations per cell than any other type of cancer – but new diagnostic tools such as DNA sequencing are helping scientists sort through troves of data to decode each tumor’s “fingerprint.”

And while the list of known mutations that cause melanoma keeps growing, researchers can target most of them by blocking a handful of the “signaling pathways” that control normal cell function and can cause tumors to form and spread.

Meanwhile, about 100 new drugs with melanoma in their sights are in development, and new combinations of drugs show promise for blocking cancer-causing signaling pathways.

Still, optimism about such progress is tempered by the fact that someone dies from melanoma every hour.

Besides being deadly, melanoma is one of the fastest growing cancers worldwide. Melanoma also is unusual among cancers in how often it develops in young people; it is one of the leading causes of cancer-related deaths in 25- to 29-year-old women.

Science’s rapid progress in understanding and treating melanoma must be coupled with prevention efforts to educate people about the dangers of sun exposure and artificial tanning, Nickoloff said.

“It’s entirely preventable,” he said. “Nobody should die from advanced-stage melanoma.”

Education was part of the goal of the College of Human Medicine’s Gran Fondo, a June bicycling event in Grand Rapids that in its first year attracted 1,500 cyclists and raised about $100,000 for MSU melanoma research.

Nickoloff said that community support is matched by an increasingly collaborative research atmosphere in Grand Rapids – his co-authors on the new paper included Michigan State medical students and cancer experts from Van Andel and Mercy Health Saint Mary’s – that will keep MSU and its West Michigan partners at the leading edge of melanoma research.

“I wish I were 20 years younger, because we’re going to see more and more long-term remissions,” he said. “We’ll get better every year we’re at this.”

Canada and Asbestos Today - A Guest Post from Kathleen Ruff

The following post first appeared on the Canadian Meso blog, which is a part of the Canadian Cancer Survivor Network's recent project committed to providing survivors, patients, families, and the wider public with information and news about asbestos and asbestos-related diseases like mesothelioma. 

Now that Canada no longer mines or exports asbestos, what are the next steps we should be taking as a country?

The last two asbestos mines in Quebec have finally shut down after more than a century of operation. Other asbestos mines in BC, Ontario, Newfoundland and the Yukon closed down years ago.

Finally, Canada, which, for the past century, was a leading world producer, exporter and promoter of asbestos, is no longer in the asbestos business.

But much remains to be done. While the asbestos mines have shut down for economic reasons, the Canadian government continues to support asbestos use, continues to fail to protect Canadians from asbestos harm and continues to fail to provide assistance and support to asbestos victims and their families.

Shockingly, the Canadian government continues to deny the science on asbestos and, instead, supports the discredited propaganda of the asbestos industry, which claims, against all the evidence, that asbestos can be safely used.

The Harper government opposes the recommendation of the World Health Organization that all use of asbestos should stop. And the government has rejected requests from the Canadian Medical Association, the Canadian Cancer Society, the Canadian Public Health Association and many other health, labour and public interest organisations that the Canadian government take action to stop the use of asbestos in Canada and to protect Canadians from asbestos harm.

Over 50 countries have banned asbestos, including all the countries of the European Union. Because Canada has not banned asbestos, products are allowed to be imported into Canada that contain asbestos. Millions of dollars’ worth of asbestos-containing car brakes, for example, are imported into Canada each year. Over past decades, many auto mechanics have died from having been exposed to asbestos when grinding and repairing brakes. This will continue to happen, as long as Canada does not ban asbestos.

The Canadian government needs to show leadership on the threat to the health of Canadians posed by asbestos that was placed in thousands of homes and buildings decades ago. Construction workers, carpenters and electricians are especially at risk when they renovate or demolish old buildings.

Many people cannot afford to hire trained professionals to do renovation work on their homes and so they do the work themselves. They usually lack protective equipment and training regarding asbestos and are thus at risk of being exposed to asbestos fibres, as they are unlikely to even recognize it in the walls, ceilings and floors they are cutting into.

While the Canadian government is failing to protect Canadians from asbestos harm, it is spending millions of taxpayers’ dollars on removing asbestos from the Parliament Buildings and from the Prime Minister’s residence. Apparently, the government believes that members of Parliament and the Prime Minister should be protected from asbestos harm.

Many Canadians think, wrongly, that asbestos is a problem of the past. Other countries have national programs to inform and educate the public about the continuing dangers of asbestos. But not Canada. This, in spite of the fact that, every day, more Canadians fall victim to an asbestos-related disease.

When Canadian workers are repeatedly exposed to asbestos because of wanton negligence on the part of their employers, the Canadian government does not lay charges of criminal negligence against the employers, even though the Criminal Code has a provision allowing for such charges to be laid. Thus there are no serious repercussions. The employer may have to pay a fine under occupational health regulations, but, when an employer repeatedly pays the fine and continues to expose workers to asbestos harm, clearly the fine is not a sufficient deterrent.

Because the last asbestos mines have been closed down,Canadians can be glad that we are no longer exporting asbestos to harm people overseas.

The Canadian government should, however, set up reparation funds in those countries to which, to our financial profit, we exported huge amounts of asbestos for decades. These funds would help pay for health care and compensation to all those whose lives will be harmed and help pay for removing asbestos from schools, homes and buildings overseas once those buildings begin to deteriorate and threaten to release asbestos fibres into the air.

As an immediate priority, the Canadian government should take action to protect Canadians from further asbestos harm by banning asbestos, by setting up an asbestos registry and initiating a national program to inform Canadians of the ongoing threat posed by asbestos already placed in so many buildings.

Furthermore, the Canadian government should take responsibility for the asbestos the government itself placed in homes on First Nations reserves and in homes on military bases. The government has washed its hands of this problem and the deaths it has caused.

It is time for this callous and irresponsible conduct to stop.

Kathleen Ruff is founder of the human rights website RightOnCanada.ca and author of Exporting Harm: How Canada markets asbestos to thedeveloping world

Why, when the cancer tie is clear, do people still sunbathe?

(Originally posted here: http://medicalxpress.com/news/2013-07-cancer-people-sunbathe.html)

Jenna Hoffman thinks that people, herself included, generally look better with a tan - "better than bright white," she says.

So most weekends, she's lying outside with her eyes closed, listening to music while the sun darkens her skin. If she knows she'll be outside all day, she wears sunscreen. Otherwise, "I don't wear it every time because I'm trying to get a tan," says Hoffman, 29, who lives in Dallas.

Because skin cancer runs in her family, and because she's had a few pre-cancerous spots removed, she goes to the dermatologist every six months.

Sunbathing "is always taking a risk," says Hoffman, who is blond and fair-skinned. "If anything pops up, I'll get it removed," she says.

Despite well-publicized research about risks of sunbathing, despite skin cancer being the most common malignancy in the United States and despite a rise in melanoma rates - the American Cancer Society predicts 77,000 new cases and 9,000 deaths in 2013 - Hoffman's attitude isn't all that uncommon.

One reason is that tanning is like other unhealthful habits, says Richardson, Texas, dermatologist Dr. Cameron Coury.

"We know smoking is bad for us, but people still smoke," says Coury, a physician with Dermatology Specialists and on staff at Methodist Richardson Medical Center. "There's some sort of satisfaction."

Additionally, "there's a social component to being tan," she says.

"They're out at the lake and the pool and think it's fun. It's definitely a challenge trying to educate someone, especially living in Texas. We have 300-plus days of sun every year."

Dr. Jerald L. Sklar sighs when asked why, when sun exposure is responsible for so many types and cases of skin cancer, people continue to suntan.

"That's a good question," says Sklar, a physician on staff at Baylor University Medical Center. He offers three possibilities:

A tanning addiction: "They get a brain high that makes them happy," he says.

A vitamin D issue: Yes, some sun is needed to help strengthen bones, he says, "but not enough to risk skin cancer."

An invincible feeling: "The younger crowd - teenagers, young adults - think they're invincible," says Sklar, who is with Dallas Associated Dermatologists. "They think you have to have that 'healthy' tan. They're not realizing later in life the damage this causes."

Says Coury: "My younger patients don't see brown spots or wrinkles or changing moles. That doesn't mean when you're 50 and something pops up, you won't wish you'd lived your younger lives differently."

She's heartened by parents who won't let their children go outside without sunscreen and stores like J. Crew that sell sun-protective clothing.

"But you have to encourage that to continue when they hit the teen years and want to rebel," Coury says.

Many people - including Hoffman, who says she looks slimmer when she's tan - associate being bronze with being healthy. That wasn't always the case, Coury says. At some points in history, having pale skin showed you didn't have to earn a living working outdoors.

Now though, "We live in a time when everyone is aware of physical appearance and wants to look good and young and healthy and all those things," she says.

Often, in what she calls a "weird contradiction," people are obsessed about exercise, weight loss and quitting smoking but not about caring for their skin.

"People take their skin for granted a lot of times unless there's a problem," she says.

Or, in many cases, someone else has a problem.

"I can't tell you how many people come in and say someone they know has been diagnosed or died from melanoma," Sklar says.

When a close friend ended up with the disease, Rebecca Thompson changed her tanning habits. Thompson, 39, remembers coating her skin with baby oil in her teen years and climbing onto the roof of her house to sunbathe. During summer camp, she never wore sunscreen. In high school and college, she'd sometimes go to a tanning booth, especially if she had an important event coming up.

Although she likes feeling the sun on her skin as she reads a book by the pool, Thompson has cut way back on her sunbathing. She might go out about 10 times during the summer, and "I slather on the sunscreen."

"When my friend was diagnosed, it was a wake-up call," says Thompson, who teaches fourth grade. "I still like to tan; I still like to lay out. But my skin doesn't get as much sun because I use so much sunblock."

Another reason she "lathers up," she says, is to avoid getting wrinkles.

Sklar uses that potential outcome when he can't seem to reach young women about the skin cancer aspect, he says.

"I try to hit on both to get their attention," he says. "They're immortal at that age, so maybe the skin damage-wrinkle aspect is better."

Hoffman, who says she gets a sunburn about once a month, does make sure she wears sunglasses.

"It looks goofy having raccoon eyes," she says, "but I don't want wrinkles."

UK: Without Innovation, We’ll Never Cure Cancer

(Originally published by Maurice Saatchi at: http://www.telegraph.co.uk/health/10166690/Without-innovation-well-never-cure-cancer.html)

The Prime Minister reminds me of Adlai Stevenson’s striking description of President Kennedy as “an idealist without illusions”. He is a realist to say we have quite a way to go to get close to the Government’s goal of “every clinician a researcher” and “every willing patient a research patient”.

Speaking of Britain’s 34 Nobel prizes for medicine, David Cameron says: “We must ensure the UK stays ahead”, and that “to keep pace with what’s happening, we’ve got to change radically… the way we innovate.” And that would mean, he adds, that “every time you use the NHS you are playing a part in the fight against disease.”

Unfortunately, his vision is about to hit a roadblock. The irresistible force of his dream will soon meet an immovable object – the law. Scientific discovery is blocked by law. And all cancer deaths are wasted lives.

The law obliges the doctor to follow the status quo, even though he/she knows it leads only to poor life-quality followed by death. Science learns nothing from these thousands of deaths. Scientific knowledge does not advance by one centimetre, because the current law requires that the deceased receive only the “standard procedure” – the endless repetition of a failed experiment.

The pre-eminence in law of the standard procedure is a barrier to progress in curing cancer. Any deviation by a doctor is likely to result in a verdict of guilt for medical negligence. The law defines medical negligence as deviation from that standard procedure. But as innovation is deviation, non-deviation is non-innovation. This is why there is no cure for cancer.

The present emphasis of the law on medical negligence means the parties line up sets of opposing expert opinion and require the courts to choose between them. The ambiguity and uncertainty of a trial inevitably makes it the safest course to adhere to established practices, irrespective of how long and how unsuccessfully they have been applied.

The result is that a doctor deciding how to treat a case starts with the knowledge that as soon as he or she moves away from established standards within the profession, there is an automatic and serious risk that he or she will be found guilty of negligence if the treatment is less successful than hoped. Where there is only one established practice, even if it is the same treatment that has been applied unchanged for 40 years without any particular success, it will be impossible for a doctor to depart from it with confidence that he or she will not be exposed to litigation.

You will hear it said that the law of medical negligence hasn’t changed for decades and medical innovations have still been made – penicillin, for example. So why is a law change suddenly so urgent? The law may not have changed much, but society has. We are more informed, less deferential and more litigious. The number of lawsuits filed against the NHS has doubled in four years – last year’s pay-out was £1.2 billion, while the Treasury provision for claims against the NHS has now reached £19 billion.

So doctors are increasingly frightened of being sued, and even less likely to feel able to innovate. “Risk-management” processes within the NHS and insurers’ policies designed to stem the rise of litigation can only increase this anti-innovative pressure.

Growing fear of litigation leads to growing bias against innovation. This is why the Prime Minister’s vision – every clinician a researcher – cannot be realised without a change in the law.

We don’t want patients to be treated like mice. But, on the other hand, we do want bold scientific innovation, which alone can bring a cure for cancer. The Medical Innovation Bill, which arrives in the House of Commons today, supported by MPs George Freeman and Michael Ellis, sets out in law for the first time the difference between reckless experimentation and responsible, scientific innovation.

The Bill strengthens the ability of the medical profession to prevent irresponsible innovation and to control the manner in which responsible decisions to innovate are taken. The good doctor will feel safer, and the bad doctor revealed as negligent.

The Bill’s requirement for the approval of any proposed innovation by the hospital’s Multi-Disciplinary Team is a severe test – more severe than the “two doctors” authorisation required in order to carry out an abortion under the Abortion Act, or sectioning in an institution under the Mental Health Act. However severe, it is better than the current position, in which the road ahead to any innovation in cancer is closed by law.

The Bill will strike a better balance between therapeutic conservatism and therapeutic innovation. It will help the Government to move the culture safely towards the innovation Mr Cameron so wisely seeks. I intend to do everything in my power, to devote my life in fact, to make the Prime Minister’s dream come true.