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YOUR LIVER DISEASE COULD BE TOXIC TONKA BEAN, WARFARIN OR CINNAMON POISONING

Friday, June 23rd, 2017

DRIED TONKA BEANS ON KITCHEN CUTTING BOARD

Coumarin is mostly toxic to the liver, which plays a central role in mopping up poisons and clearing them from the body. As the front-line defence, the organ is extraordinarily resilient, able to regenerate from just a quarter of its original size. Just like alcohol, coumarin is thought to be toxic over the long term, with repeated bouts of damage.

“The problem is it’s not like you’re going to realise when you’ve got to the level where you’re eating too much – the effects build up over years,” says Dirk Lachenmeier from the Chemical and Veterinary Investigation Laboratory (CVUA) of Karlsruhe, Germany, who has developed a new way of detecting coumarin in foods.

The easy way to find out is obvious; alas, it turns out feeding people toxic chemicals isn’t allowed. Instead, the safe limits in humans are based on studies in animals, from baboons to dogs. To account for an any differences in our biology, the highest amount which hasn’t caused any harm in animals is multiplied by 100.

For most people, the current limit is probably ultra conservative

For an average-sized person, this works out at a measly one quarter of a tonka bean or a quarter of a cinnamon bun per day – though if you remove the safety factor, your allowance shoots up to more like 25 tonka beans or 20 cinnamon buns (5680 calories, a challenge for even the most hardened binge eaters).

For most people, the current limit is probably ultra conservative. Many animals, including rats and dogs, remove coumarin from the body in a completely different way, breaking it down into highly potent chemicals which are toxic in their own right. Instead, we have enzymes which subtly tweak coumarin’s structure to render it safe. But not all people can do this.

Back in the 90s, a woman arrived at Frankfurt University Hospital with severe liver disease. She was promptly diagnosed with “coumarin-induced hepatitis”, but in fact she hadn’t overdosed on tonka beans. She had been taking the drug warfarin.

What was going on?

MORE HERE

Henry Sapiecha

Latest Research Report highlights that Cancers are caused by sugar

Sunday, June 11th, 2017

It’s something that has been murmured about – especially in alternative health circles – for several years: The connection between sugar and cancer.

The roots of this idea come from the work of Dr. Otto Warburg, who won the Nobel Prize in 1931 for his work demonstrating that cancer cells in the human body derive nourishment through the fermentation of glucose. He wrote “Oxygen gas, the donor of energy in plants and animals, is dethroned in the cancer cells and replaced by an energy-yielding reaction of the lowest living forms; namely a fermentation of glucose.

The full science behind this branch of medicine is very complex but for those interested, wikipedia has a (difficult / technical) introduction here – http://en.wikipedia.org/wiki/Warburg_hypothesis

New scientific research however has identified sugar not only as the fuel source for an already existing cancer, but as a primary driver in oncogenesis – i.e. the initiation of cancerous characteristics within previously healthy cells. So could it be that too much sugar in the system actually causes our cells to “go over to the dark side”?

Read the full report at the link below: (brilliant tutorial on the health effects of sugar)

Research Reveals How Sugar CAUSES Cancer

Henry Sapiecha

 

Precision Medicine: What Is Cancer, Really? Scientists overview here.

Monday, May 22nd, 2017

The men and women who are trying to bring down cancer are starting to join forces rather than work alone. Together, they are winning a few of the battles against the world’s fiercest disease. For this unprecedented special report, we visited elite cancer research centers around the country to find out where we are in the war.

I. Precision Medicine: What Is Cancer, Really?

When you visit St. Jude Children’s Research Hospital in Memphis, Tennessee, you expect to feel devastated. It starts in the waiting room. Oh, here we go with the little red wagons, you think, observing the cattle herd of them rounded up by the entrance to the Patient Care Center. Oh, here we go with the crayon drawings of needles. The itch begins at the back of your throat, and you start blinking very fast and mentally researching how much money you could donate without starving. Near a row of arcade games, a preteen curls his face into his mother’s shoulder while she strokes his head. Oh, here we go.

But the more time you spend at St. Jude, the more that feeling is replaced with wonder. In a cruel world you’ve found a free hospital for children, started by a Hollywood entertainer as a shrine to the patron saint of lost causes. There is no other place like this. Corporations that have nothing to do with cancer—nothing to do with medicine, even—have donated vast sums of money just to be a part of it. There’s a Chili’s Care Center. The cafeteria is named for Kay Jewelers.

Scott Newman’s office is in the Brooks Brothers Computational Biology Center, where a team of researchers is applying computer science and mathematics to the question of why cancer happens to children. Like many computer people, Newman is very smart and a little quiet and doesn’t always exactly meet your eyes when he speaks to you. He works on St. Jude’s Genomes for Kids project, which invites newly diagnosed patients to have both their healthy and tumor cells genetically sequenced so researchers can poke around.

“Have you seen a circle plot before?” Newman asks, pulling out a diagram of the genes in a child’s cancer. “If I got a tattoo, it would be one of these.” Around the outside of the circle plot is something that looks like a colorful bar code. Inside, a series of city skylines. Through the center are colored arcs like those nail-and-string art projects students make in high school geometry class. The diagram represents everything that has gone wrong within a child’s cells to cause cancer. It’s beautiful.

A Genetic Disaster: This circular visualization shows real gene mutations found in 3,000 pediatric cancers at St. Jude Children’s Research Hospital. Genes with sequence mutations are labeled in blue; those with structural variations are in red; and those

“These are the genes in this particular tumor that have been hit,” Newman says in a Yorkshire accent that emphasizes the t at the end of the word hit in a quietly violent way. “And that’s just one type of thing that’s going on. Chromosomes get gained or lost in cancer. This one has gained that one, that one, that one, that one,” he taps the page over and over. “And then there are structural rearrangements where little bits of genome get switched around.” He points to the arcs sweeping across the page. “There are no clearly defined rules.”

It’s not like you don’t have cancer and then one day you just do. Cancer—or, really, cancers, because cancer is not a single disease—happens when glitches in genes cause cells to grow out of control until they overtake the body, like a kudzu plant. Genes develop glitches all the time: There are roughly twenty thousand genes in the human body, any of which can get misspelled or chopped up. Bits can be inserted or deleted. Whole copies of genes can appear and disappear, or combine to form mutants. The circle plot Newman has shown me is not even the worst the body can do. He whips out another one, a snarl of lines and blocks and colors. This one would not make a good tattoo.

“As a tumor becomes cancerous and grows, it can accumulate many thousands of genetic mutations. When we do whole genome sequencing, we see all of them,” Newman says. To whittle down the complexity, he applies algorithms that pop out gene mutations most likely to be cancer-related, based on a database of all the mutations researchers have already found. Then, a genome analyst manually determines whether each specific change the algorithm found seems likely to cause problems. Finally, the department brings its list of potentially important changes to a committee of St. Jude’s top scientists to discuss and assign a triage score. The mutations that seem most likely to be important get investigated first.

It took thirteen years and cost $2.7 billion to sequence the first genome, which was completed in 2003. Today, it costs $1,000 and takes less than a week. Over the last two decades, as researchers like Newman have uncovered more and more of the individual genetic malfunctions that cause cancer, teams of researchers have begun to tinker with those mutations, trying to reverse the chaos they cause. (The first big success in precision medicine was Gleevec, a drug that treats leukemias that are positive for a common structural rearrangement called the Philadelphia chromosome. Its launch in 2001 was revolutionary.) Today, there are eleven genes that can be targeted with hyperspecific cancer therapies, and at least thirty more being studied. At Memorial Sloan Kettering Cancer Center in New York City, 30 to 40 percent of incoming patients now qualify for precision medicine studies.

Charles Mullighan,a tall, serious Australian who also works at St. Jude, is perhaps the ideal person to illustrate how difficult it will be to cure cancer using precision medicine. After patients’ cancer cells are sequenced, and the wonky mutations identified, Mullighan’s lab replicates those mutations in mice, then calls St. Jude’s chemical library to track down molecules—some of them approved medicines from all over the world, others compounds that can illuminate the biology of tumors—to see if any might help.

New York: Britta Weigelt and Jorge Reis-Filho use police forensics techniques to repair old tumor samples at Memorial Sloan Kettering so the samples can be genetically profiled.

If Mullighan is lucky, one of the compounds he finds will benefit the mice, and he’ll have the opportunity to test it in humans. Then he’ll hope there are no unexpected side effects, and that the cancer won’t develop resistance, which it often does when you futz with genetics. There are about twenty subtypes of the leukemia Mullighan studies, and that leukemia is one of a hundred different subtypes of cancer. This is the kind of precision required in precision cancer treatment—even if Mullighan succeeds in identifying a treatment that works as well as Gleevec, with the help of an entire, well-funded hospital, it still will work for only a tiny proportion of patients.

Cancer is not an ordinary disease. Cancer is the disease—a phenomenon that contains the whole of genetics and biology and human life in a single cell. It will take an army of researchers to defeat it.

Luckily, we’ve got one.

Interlude

“I used to do this job out in L.A.,” says the attendant at the Hertz counter at Houston’s George Bush Intercontinental Airport. “There, everyone is going on vacation. They’re going to the beaach or Disneyland or Hollywood or wherever.

“Because of MD Anderson, I see more cancer patients here. They’re so skinny. When they come through this counter, they’re leaning on someone’s arm. They can’t drive themselves. You think, there is no way this person will survive. And then they’re back in three weeks, and in six months, and a year. I’m sure I miss some, who don’t come through anymore because they’ve died. But the rest? They come back.”

II. Checkpoint Inhibitor Therapy: You Have the Power Within You!

On a bookshelf in Jim Allison’s office at MD Anderson Cancer Center in Houston (and on the floor surrounding it) are so many awards that some still sit in the boxes they came in. The Lasker-DeBakey Clinical Medical Research Award looks like the Winged Victory statue in the Louvre. The Breakthrough Prize in Life Sciences, whose benefactors include Sergey Brin, Anne Wojcicki, and Mark Zuckerberg, came with $3 million.

“I gotta tidy that up sometime,” Allison says.

Allison has just returned to the office from back surgery that fused his L3, L4, and L5 vertebrae, which has slightly diminished his Texas rambunctiousness. Even on painkillers, though, he can explain the work that many of his contemporaries believe will earn him the Nobel Prize: He figured out how to turn the immune system against tumors.

“One day, the miracles won’t be miracles at all. They’ll just be what happens.”

Allison is a basic scientist. He has a Ph.D., rather than an M.D., and works primarily with cells and molecules rather than patients. When T-cells, the most powerful “killer cells” in the immune system, became better understood in the late 1960s, Allison became fascinated with them. He wanted to know how it was possible that a cell roaming around your body knew to kill infected cells but not healthy ones. In the mid-1990s, both Allison’s lab and the lab of Jeffrey Bluestone at the University of Chicago noticed that a molecule called CTLA-4 acted as a brake on T-cells, preventing them from wildly attacking the body’s own cells, as they do in autoimmune diseases.

Allison’s mother died of lymphoma when he was a child and he has since lost two uncles and a brother to the disease. “Every time I found something new about how the immune system works, I would think, I wonder how this works on cancer?” he says. When the scientific world discovered that CTLA-4 was a brake, Allison alone wondered if it might be important in cancer treatment. He launched an experiment to see if blocking CTLA-4 would allow the immune system to attack cancer tumors in mice. Not only did the mice’s tumors disappear, the mice were thereafter immune to cancer of the same type.

Ipilimumab (“ipi” for short) was the name a small drug company called Medarex gave the compound it created to shut off CTLA-4 in humans. Early trials of the drug, designed just to show whether ipi was safe, succeeded so wildly that Bristol Myers Squibb bought Medarex for $2.4 billion. Ipilimumab (now marketed as Yervoy) became the first “checkpoint inhibitor”: It blocks one of the brakes, or checkpoints, the immune system has in place to prevent it from attacking healthy cells. Without the brakes the immune system can suddenly, incredibly, recognize cancer as the enemy.

“You see the picture of that woman over there?” Allison points over at his desk. Past his lumbar-support chair, the desk is covered in papers and awards and knickknacks and frames, including one containing a black card with the words “Never never never give up” printed on it. Finally, the photo reveals itself, on a little piece of blue card stock.

That’s the first patient I met,” Allison says. “She was about twenty-four years old. She had metastatic melanoma. It was in her brain, her lungs, her liver. She had failed everything. She had just graduated from college, just gotten married. They gave her a month.”

The woman, Sharon Belvin, enrolled in a phase-two trial of ipilimumab at Memorial Sloan Kettering, where Allison worked at the time. Today, Belvin is thirty-five, cancer- free, and the mother of two children. When Allison won the Lasker prize, in 2015, the committee flew Belvin to New York City with her husband and her parents to see him receive it. “She picked me up and started squeezing me,” Allison says. “I walked back to my lab and thought, Wow, I cure mice of tumors and all they do is bite me.” He adds, dryly, “Of course, we gave them the tumors in the first place.”

After ipi, Allison could have taken a break and waited for his Nobel, driving his Porsche Boxster with the license plate CTLA-4 around Houston and playing the occasional harmonica gig. (Allison, who grew up in rural Texas, has played since he was a teenager and once performed “Blue Eyes Crying in the Rain” onstage with Willie Nelson.) Instead, his focus has become one of two serious problems with immunotherapy: It only works for some people.

So far, the beneficiaries of immune checkpoint therapy appear to be those with cancer that develops after repeated genetic mutations—metastatic melanoma, non-small-cell lung cancer, and bladder cancer, for example. These are cancers that often result from bad habits like smoking and sun exposure. But even within these types of cancer, immune checkpoint therapies improve long-term survival in only about 20 to 25 percent of patients. In the rest the treatment fails, and researchers have no idea why.

Lately, Allison considers immune checkpoint therapy a “platform”—a menu of treatments that can be amended and combined to increase the percentage of people for whom it works. A newer drug called Keytruda that acts on a different immune checkpoint, PD-1, knocked former president Jimmy Carter’s metastatic melanoma into remission in 2015. Recent trials that blocked both PD-1 and CTLA-4 in combination improved long-term survival in 60 percent of melanoma patients. Now, doctors are combining checkpoint therapies with precision cancer drugs, or with radiation, or with chemotherapy. Allison refers to this as “one from column A, and one from column B.”

The thing about checkpoint inhibitor therapy that is so exciting—despite the circumscribed group of patients for whom it works, and despite sometimes mortal side effects from the immune system going buck-wild once the brakes come off—is the length of time it can potentially give people. Before therapies that exploited the immune system, response rates were measured in a few extra months of life. Checkpoint inhibitor therapy helps extremely sick people live for years. So what if it doesn’t work for everyone? Every cancer patient you can add to the success pile is essentially cured.

Jennifer Wargo and team remove lymph nodes from a melanoma patient.

Most cancers are caused by DNA replication errors, landmark study reveals

Friday, March 24th, 2017

Halfway through her HSC, Rachel Woolley suffered exhaustion and a stiff neck.

“All my friends were tired, but it got to the point where I couldn’t get up the stairs,” Ms Woolley said.

Rachel Woolley at home in Sydney. She is a candidate for a bachelor of music at UNSW and is recovering from Hodgkin lymphoma image www.newcures.info

Rachel was diagnosed with Hodgkin lymphoma, a cancer of the lymphatic system.

“It was just completely random,” Ms Woolley said.

“You certainly go through a ‘why me?’ phase. What had I done?” she said.

Now 19, Ms Woolley is studying for her bachelor of music at the University of NSW. Despite the cancer then coming back last year, she was given the all-clear again in January.

What triggered Ms Woolley’s cancer is not known, but a landmark study published on Friday shows that about two-thirds of all cancers are caused by random errors made during normal cell division.

“Our research has broken the paradigm that most cancers are environmental or inherited,” said Assistant Professor Cristian Tomasetti of the Johns Hopkins University school of medicine.

His study with Bert Vogelstein, published in Science, evaluated cancer occurrence in 69 countries, including Australia, covering 4.8 billion people.

Professor Vogelstein said: “Most of the time random mutations during cell division don’t do any harm. That’s good luck.

“Occasionally they occur in a cancer-driver gene. That’s bad luck.”

The study reviewed 32 types of cancer and found that about 66 per cent of cancer mutations result from random DNA copying errors, 29 per cent can be attributed to lifestyle or environmental factors and the remaining 5 per cent are inherited.

Comparative rates of cancer by heredity, random and environmental causes. Most cancers are caused by random errors in DNA replication during cell division. ScienceTomasetti image www.newcures.info

Comparative rates of cancer by heredity, random and environmental causes. Most cancers are caused by random errors in DNA replication during cell division. Photo: Science/Tomasetti

“Detecting cancers earlier can save lives regardless of what caused the mutation,” Assistant Professor Tomasetti and Professor Vogelstein said in a statement. “More research to find better ways to detect cancers earlier is urgently needed.”

The researchers are at pains to say that a cancer is very rarely caused by a single error in cell division, but is often a cumulative process, which is why cancers are more common in older people.

Professor David Thomas is head of the Garvan Institute’s cancer division and director of the Kinghorn Cancer Centre.

“The first Vogelstein study in 2015 was important and heretical. Here they have got a much larger data set that expands to the entire globe.

“I’m not surprised at the ratios of random errors to environmentally-induced mutations and hereditary causes. They seem about right.”

However, Professor Thomas said that in his view some of the assumptions made in the modelling “are very rubbery”, and there will be strong debate about the paper.

Despite his reservations, Professor Thomas said the paper is important: “I do think the broad balance is accurate.”

The overall balance also matches the expectations of Professor Sanchia Aranda, chief executive of the Cancer Council.

“We already know that about one-third of cancers are preventable,” she said. “Very few cancers are truly inherited.”

Professor Thomas said just because most cancers are caused by random mutation, it doesn’t mean environmental factors don’t play a role.

“Even if the bulk of mutations are random, a cell needs to get to the final step to become malignant. Environment and heredity play a role here,” he said.

Assistant Professor Tomasetti said: “Cancer rates vary widely by organ. If you look at lung cancer the concentration is in the environmental component.

“However, with brain cancers, bone cancers or childhood cancers the concentration is in the random component.

“That means virtually all the cancerous mutations are caused by simple mistakes caused by every cell when it divides.”

Is this any comfort to Ms Woolley?

“One perspective is ‘At least I didn’t do anything wrong’,” she said. “But you still feel ‘Why me?'”

Professor Thomas said that while the study was important it won’t change clinical practice.

“The fundamental advice we give as clinicians about how to manage and look out for cancer are not affected by this study.

“People should still try to minimise and manage their exposure to environmental or inherited risk factors.”

While the study won’t immediately impact clinical practice it could assist in the management of the psychological impacts of cancer.

Dr Pandora Patterson is general manager of research at CanTeen, the charity that supports young people living with cancer.

“People digest information in different ways, so it could be helpful to know ‘This is not my fault, it’s just random’,” she said.

Ms Woolley is a member of CanTeen. “By talking to people who have been through all this you can learn stuff that the doctors don’t tell you,” she said.

“It’s such a relief not feeling you’re on your own. You can just sit around with people talking about life – people just get you.”

Her message is that while going through treatment is “very shitty”, things can get better. “It’s really important to stay positive and look forward to the future.”

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Henry Sapiecha

WHY IS BRAIN CANCER THE BIGGEST KILLER OF YOUNG CHILDREN??

Monday, August 25th, 2014

family shadow symbol image www.newcures.info

It’s a good question. The simple answer is threefold:

  • We don’t know what causes brain cancer
  • Current treatments are not good enough
  • We don’t have enough money for research to change this

But in addition, there are specific issues to deal with in paediatric or childhood cases.

Let’s start with the cause: the fact is we don’t know what causes children to develop brain cancer, or adults for that matter. There are various theories, from genetic mutations to epigenetic or environmental factors to viral infections, and research is continually making new discoveries which improve our understanding of the disease. But the more we discover about brain cancer, the more we realise there is still so much more to find out. Take medulloblastoma, for example, which is a common paediatric brain tumour. Because of research and a greater understanding of how brain cancer operates on a molecular level, what was previously thought of as one type of brain cancer is now known to have at least four genetic sub-types, which all require different treatments. As we discover more about the disease, we discover there are even more questions to answer regarding how to treat it.

As well as genetic mutations there are epigenetic factors to consider. A recent Australian study found that fathers working in jobs where they are regularly exposed to benzene in the year before their child is conceived are more than twice as likely to have that child develop a brain tumour. Women working in occupations that expose them chlorinated solvents – found in degreasers, cleaning solutions, paint thinners, pesticides and resins – at any time in their lives also have a much higher risk of their child developing a brain tumour. The researchers stressed that it’s still too early to say whether solvent exposure causes brain tumours. But it is an example of research pointing to epigenetic factors in the development of brain tumours, and specifically the vulnerability of children to brain cancer even before they are born. What we suspect at this stage is that it is likely to be a combination of genetic and environmental factors that lead to increased risk.

The next thing to consider is how effective treatments for children with brain cancer are. The answer: not effective enough. In fact, the internationally recognised expert in childhood brain cancer, Dr Nick Gottardo, describes current treatments as “woefully ineffective”.

Brain cancer is different in children than in adults. There are forms which more commonly affect kids, such as medulloblastoma. But even when typically adult tumours such as high grade gliomas do occur in children, they present very differently on a molecular level.

 

“They look the same under the microscope, but molecularly they are very distinct diseases….Having more information on these tumours can only benefit us in being able to choose more rational therapies in the near future.”

– Dr. Nick Gottardo

Again, we don’t know why children manifest their own versions of this disease. And some paediatric brain tumours, such as DIPG (Diffuse Intrinsic Pontine Glioma) are brain-stem based and therefore usually inoperable; with the limited treatments available, without surgery, the prognosis is very bleak.

Plus, children’s brains are still developing so the standard treatments for brain cancer, which include surgery, radiotherapy and chemotherapy, can result in more substantial and permanent side effects than they would for an adult. This is a massive problem with childhood cases; applying treatment is harder than in the case of adults. Hence a major consideration when developing new treatments for paediatric brain cancer is how to provide quality of life as well as increasing survival.

“We’re all aiming for 100%, that’s our goal – to cure all children. But we also want to cure them, leaving them with a good quality of life in the long term.”

– Dr. Nick Gottardo

Research funded by The Brain Tumour Charity in the UK has been investigating ways to improve quality of life for children diagnosed with a brain tumour. The team at the University of Southampton collected data on children surviving a brain tumour, including looking at the use of an alternative radiotherapy technique called hyperfractionated radiotherapy, which involves dividing the total dose of radiation into a larger number of smaller doses or fractions, to decrease the effect of the radiation on other tissues, such as the brain. The clinical trial was run by the European International Society for Paediatric Oncology and found that hyperfractionated radiotherapy had less of an impact on children’s memory, planning and organisational skills than conventional radiotherapy. The team says this is an example of how adjusting radiation dose can help reduce side effects while still treating the tumour. In a separate study the researchers looked into different tumour types and observed that different tumours have an impact on quality of life. Furthermore, tumour sub-type is important, with children with medulloblastoma tumours containing the ‘sonic hedgehog’ gene experiencing a better quality of life after treatment than those with other medulloblastoma sub-types. This is the first time that tumour biology has been related to quality of life in medulloblastoma sub-types.

“What we want to do is find new therapies that will be more specific against the tumour and with fewer side effects, so that the children are cured and also cured with excellent quality of life in the future”.

– Dr. Nick Gottardo

The next problem is not insignificant, but nor is it insurmountable: funding. Survival rates for brain cancer have hardly changed in 30 years and remain far too low, with only 2 in 10 people surviving for 5 years. The reason for this – and by association, the reason why brain cancer kills more children than any other disease in Australia – is largely that not enough money has been invested in research. Cure Brain Cancer is doing things differently to improve outcomes for patients and one of things that makes us different is our approach and outlook. Our question is not ‘why?’ but ‘why not?’ and – more importantly – ‘how can we?’ Perhaps this is the more pertinent question here; not why brain cancer kills these children, but how are we going to change this

Research into paediatric brain tumours has come a long way already. Yes, there is a long way to go; survival rates for brain cancer have hardly improved for 30 years. But that’s not because nothing has been done. However, the number of clinical trials for children and access to these trials is limited; with a disease of such low incidence, the clinical research has historically tended to follow what has been done in adult trials, but this is changing.

Professor Stewart Kellie, a paediatric neuro-oncologist & oncologist at The Children’s Hospital at Westmead, says there have already been huge advances, but says global collaboration is key to success when it comes to paediatric clinical trials and research. By pooling resources, answers can be arrived at more quickly.

“I think the biggest change that I’ve seen in my professional career has been the incorporation of research – and particularly clinical trials – into the frontline treatment of children”.

– Prof. Stewart Kellie

Back in April, four international studies made breakthroughs simultaneously in a fatal form of brain cancer, Diffuse Intrinsic Pontine Glioma (DIPG). All of them focused on mutations in the ACVR1 gene. (We published an article at the time looking in more detail at these studies.) Discovering these links between ACRV1 and DIPG opens up many more questions, but that’s not necessarily a bad thing, because it also opens up many more possibilities. One of those studies, led by scientists at the Institute of Cancer Research in London, identified recurrent activating mutations in the ACVR1 gene in DIPG, but also found that those mutations are identical to ones found in people with the congenital childhood developmental disorder fibrodysplasia ossificans progressiva (FOP). What this means is that they can start to investigate whether drugs that have already been developed for FOP could be repurposed to treat DIPG. By discovering common gene mutations between paediatric brain cancer and other diseases or cancers, new treatment options present themselves. This discovery was made possible in part because of international collaboration.

Access to children’s tissue samples to facilitate research is also vital, not just because it can provide insights into that particular patient’s tumour, but because developing tissue banks enables researchers to compare and cross reference data from across brain tumours and across other cancers and diseases. In a recent blog for Cure Brain Cancer, Barrie Littlefield, whose own daughter died from glioblastoma in 2011, said he thinks quick and accurate tumour pathology and up-to-date genetic testing should happen regardless of whether there are clear clinical implications, as the information may be useful at a later stage if not immediately. Tissue banks are invaluable resources when it comes to developing new therapies and understanding the molecular biology of brain tumours. Just last week, a study using data from The Cancer Genome Atlas (a large scale genomic sequencing project) suggested that 1 in 10 cancers could be diagnosed more accurately based on genetic makeup, rather than where they occur in the body. The researchers genetically profiled and compared 3,500 samples of tumor tissue and identified 12 sub-types of cancer, only five of which correlated with their tissue-of-origin classifications. The other seven were newly identified genetic subtypes of cancer which affect more than one type of tissue. They say it ultimately provides the biologic foundation for a new era of personalized cancer treatment, in which cancers are diagnosed based on genetics rather than tissue of origin.

As you can see, many questions remain regarding childhood brain tumours. We don’t know why brain cancer occurs. But crucially we need to answer the question ‘how?’ How do we treat this disease? How do we improve survival, as investment in research has done for other diseases such as leukaemia and breast cancer? How do we give children diagnosed with brain cancer a more hopeful prognosis? The urgency and focus is on finding new treatments but epidemiological advances (which have been hampered by low incidence in children thus far) could ultimately be critical, and this too could be unlocked through further research investment and collaboration. Research will answer these big questions. All that’s required is funding.

Don’t let kids fight brain cancer alone
Henry Sapiecha

BREAST CANCER POSSIBLY CAUSED BY STIFFNESS IN TISSUE SAY UNIVERSITY SCIENTISTS

Wednesday, July 2nd, 2014

Fluorescence microscopy helps explain how stiffness in breast tissue contributes to breast cancer

06/18/2014
breast-cancer-and-lymphedema-image www.newcures.info

A team of researchers at the Harvard School of Engineering and Applied Sciences (SEAS) have—with the help of fluorescence microscopy—identified a possible mechanism by which normal cells turn malignant in mammary epithelial tissues, the tissues frequently involved in breast cancer. Dense mammary tissue has long been recognized as a strong indicator of risk for breast cancer; until now, however, the significance of that tissue density has been poorly understood.

Related: Photoacoustic mammoscopy aims for safer, earlier breast cancer screening

By isolating mechanical and biological variables one by one in vitro, David J. Mooney, Robert P. Pinkas Family Professor of Bioengineering at SEAS, and his research team have discovered how the physical forces and chemical environment in those dense tissues can drive cells into a dangerously invasive, proliferating mode.

Mammary epithelial tissue structures undergo characteristic changes as tumors progress from benign to invasive. These human breast cancer tissue samples illustrate the difference image www.newcures.info

“While genetic mutations are at the root of cancer, a number of studies over the last 10 to 20 years have implicated the cellular microenvironment as playing a key role in promoting or suppressing tumor progression,” says lead author Ovijit Chaudhuri, a former postdoctoral fellow in the Mooney Lab at Harvard who recently joined the mechanical engineering faculty at Stanford University. The new research finds that the stiffness of the extracellular matrix and the availability of certain ligands (molecules that bind to cell membranes) can together determine which genes are actually called on—and whether normal epithelial cells begin to exhibit the behaviors characteristic of highly malignant cancer cells. “Our findings suggest that evaluating the composition of this microenvironment, in addition to mammographic density, could potentially provide a better assessment of breast cancer risk,” Chaudhuri says.

Research in the Mooney Laboratory explores how the physical properties of natural biomaterials and synthetic polymers can affect how cells sense their environment, react to it, and signal to one another. The extracellular matrix—the complex network of crosslinked proteins and polymers that connects living cells to one another and facilitates communication between them—offers a challenging subject for study. The usual two-dimensional culture of cells on petri dishes has proven to be a poor model of three-dimensional tissues.

“As bioengineers, we can now design 3D culture systems where environmental parameters such as composition, porosity, and stiffness can be precisely tuned to study the importance of these cues on tumorigenesis,” says coauthor Sandeep Koshy, a Harvard graduate student in the Harvard-MIT Program in Health Sciences and Technology, who works in Mooney’s lab at Harvard SEAS and at the Wyss Institute for Biologically Inspired Engineering. “We’re seeing that some of these factors have a major impact on cell behavior that is not possible to observe in conventional 2D cell cultures.”

Prior studies have used varying amounts of a fibrous protein called collagen to adjust the stiffness of the extracellular matrix, but Mooney’s team recognized early on that collagen has more than a simple mechanical effect on cells: it can also trigger certain signaling pathways. Fibrous collagen is not normally found in the basement membrane that surrounds the mammary epithelium, so any collagen signaling could confound the conclusions of those studies.

This diagram shows a cell encapsulated in an interpenetrating network of alginate (blue) and reconstituted basement membrane matrix (green). image www.newcures.info

To eliminate uncontrolled variables, the team designed a new material model that uses alginate gel, instead of collagen, to stiffen the extracellular matrix without binding to any cell receptors. When this model was in its softest mode, normal (benign) mammary epithelial cells behaved normally within it, forming cellular structures referred to as acini that capture many key features of the normal in vivo mammary epithelium. But when the gel was stiffer, the cells began to upregulate the expression of cancer-related genes, and activity of the PI3K pathway that is known to drive cell proliferation and invasion increased.

“The invasive structures we observed in our stiff matrices resemble the morphology of early-stage invasive ductal carcinoma. They also show increased expression of the estrogen receptor alpha [ER+] gene that drives cell division,” says Koshy. “It is striking that these changes, found in many human cancers, can be induced in normal mammary epithelial cells simply by varying the stiffness or composition of the matrix surrounding them.”

Further experiments also indicated that the cells would recover their normal behavior in high-stiffness gels if they were exposed to increasing concentrations of laminin, a protein naturally found in the basement membrane.

These confocal immunofluorescence images show how stiffness disrupts the formation of hemidesmosomes in the cell membranes image www.newcures.info

When the extracellular matrix is very flexible, or when a high concentration of laminin is readily available, proteins called α6β4 integrins within the cell membrane bind with laminin to form small structures called hemidesmosomes, which anchor the epithelial cells to the basement membrane. But fluorescence microscopy revealed that the cells in a stiff matrix were not forming hemidesmosomes at all, so Mooney’s team hypothesized that a stiffer matrix and a shortage of laminin was leaving the α6β4 integrins with dangling, unbound tails.

The team’s final experiments demonstrated that these unbound integrin tails, indeed, get up to no good: they participate in the activation of two key biochemical pathways (PI3K and Rac1) that are necessary and sufficient to induce malignant cell behaviors in the in vitro epithelial tissue.

The Harvard researchers proposed a mechanism to explain how the stiffness and composition of the extracellular matrix could activate signaling pathways image www.newcures.info

“If further studies validate that these processes are critical in human breast cancers,” Koshy notes, “the possibility exists that agents that favorably modify the biophysical properties of the extracellular matrix, or that target the receptors and signaling molecules associated with how cells sense this matrix, could be used as a new avenue for the prevention or treatment of breast cancers.”

In addition to the implications of this research for cancer biology, the development of the alginate-based extracellular matrix model is also significant.

“Studies of many other biological processes could benefit from the use of this system,” says Mooney, who in addition to his role at Harvard SEAS is also a Core Faculty Member at the Wyss Institute. “Studies on stem cell biology, wound healing, and development in a variety of tissues and organs could utilize this system.”

To view more details on the work, which appears in the journal Nature Materials, please visit http://dx.doi.org/10.1038/nmat4009.

Henry Sapiecha

VIDEO INTERVIEW WITH DOCTOR EXPLAINING HOW ALL CANCERS CAN BE CURED IN THIS VIDEO

Sunday, December 23rd, 2012

THIS DOCTOR EXPLAINS HOW ALL CANCERS CAN BE STOPPED COLD
Natures Brands Natural Health & Beauty Products


Natures Brands Natural Health & Beauty Products

Sourced & published by Henry Sapiecha

DOES YOUR MOBILE PHONE SIZZLE YOUR BRAIN??

Wednesday, June 1st, 2011

Mobile phone users may be at increased risk from brain cancer and should use texting and hands-free devices to reduce exposure, the World Health Organisation’s cancer experts say.

Radio-frequency electromagnetic fields generated by such devices are “possibly carcinogenic to humans”, the International Agency for Research on Cancer (IARC) announced at the end of an eight-day meeting in Lyon, France.

Mobile phones ... a cancer risk.Mobile phones … a cancer risk. Photo: Jim Rice

Experts “reached this classification based on review of the human evidence coming from epidemiological studies”, pointing to an increased incidence of glioma, a malignant type of brain cancer, Jonathan Samet, president of the work group said.

Two studies in particular, the largest conducted over the last decade, showed a higher risk “in those that had the most intensive use of such phones”, he said in a telephone news conference.

Some individuals tracked in the studies had used their phones for an average of 30 minutes per day over a period of 10 years.

“We simply don’t know what might happen as people use their phones over longer time periods, possibly over a lifetime,” Samet said.

About 5 billion mobile phones are registered in the world. The number of phones and the average time spent using them have both climbed steadily in recent years.

The IARC cautioned that current scientific evidence showed only a possible link, not a proven one, between wireless devices and cancers.

“There is some evidence of increased risk of glioma” and another form of non-malignant tumour called acoustic neuroma, said Kurt Straif, the scientist in charge of editing the IARC reports on potentially carcinogenic agents.

“But it is not at the moment clearly established that the use of mobile phones does in fact cause cancer in humans,” he said.

The IARC does not issue formal recommendations, but experts pointed to a number of ways consumers can reduce risk.

“What probably entails some of the highest exposure is using your mobile for voice calls,” Straif said.

“If you use it for texting, or as a hands-free set for voice calls, this is clearly lowering the exposure by at least an order of magnitude,” or by tenfold, he said.

A year ago the IARC concluded that there was no link between mobile phones and brain cancer, but that earlier report was criticised as based on data that was out of date.

The new review, conducted by a panel of 31 scientists from 14 countries, was reached on the basis of a “full consensus”, said Robert Baan, in charge of the written report, yet to be released.

“This is the first scientific evaluation of all the literature published on the topic with regard to increased risk of cancer,” he said.

But the panel stressed the need for more research, pointing to incomplete data, evolving technology and changing consumer habits.

“There’s an improvement in the technology in terms of lower emissions but at the same time we see increased use, so it is hard to know how the two balance out,” Baan noted.

The IARC ranks potentially cancer-causing elements as carcinogenic, probably carcinogenic, possibly carcinogenic or “probably not carcinogenic”. It can also determine that a material is “not classifiable”.

Cigarettes, sun beds and asbestos, for example, fall in “Group 1”, the top threat category.

Mobile phones now join glass wool and petrol exhaust in Group 2B as “possibly carcinogenic”.

Industry groups reacted cautiously, pointing to other common consumer items – including coffee and vegetables pickled in chemicals – that are included in the same category.

“In France, the health ministry already applies a precautionary approach to mobile phones because it considers that no danger has been established, that doubts remain and, thus, that more research is needed,” the French Federation of Telecoms said in a statement.

Some consumer advocacy groups said the new classification was overdue.

“As of today, no one can say the risk does not exist, and now everyone – politicians, telecoms, employers, consumers and parents – have to take this into account,” said Janine Le Calvez, head of PRIARTEM, a consumer advocacy group concerned with mobile phone safety.

AFP

Sourced & published by Henry Sapiecha

WHY DO DWARFS GET FEW CASES OF CANCER? SEE HERE WHY…

Friday, February 25th, 2011

Little people secret

that might save

big problems of

diabetes, cancer

Nicky Phillips

February 18, 2011

Then and now ... members of the group of 99 Ecuadorians with dwarfism who took part in a 22-year study, pictured at the start of the study in 1988, above, and in 2009.
Then and now … members of the group of 99 Ecuadorians with dwarfism who took part in a 22-year study, pictured at the start of the study in 1988, above, and in 2009.

A GROUP with dwarfism from a province in Ecuador could hold clues to preventing cancer.

Of the 99 individuals, who are in perfect proportion except for a genetic mutation that stunts their growth, only one developed cancer during a 22-year study.

Scientists researching the group believe this growth mutation is the key to their disease immunity, and suggest drugs could give a similar degree of protection to full-grown adults.

An Ecuadorian endocrinologist and co-author of the study, Jaime Guevara-Aguirre, said researchers first noticed the lack of chronic disease in the community while they were investigating their growth defect.

”[We] were more in search of problems than solutions,” he said.

After more than two decades of following those with Laron dwarfism, which is caused by a mutation in their growth hormone receptor gene, Dr Guevara-Aguirre and his American colleague Valter Longo found no cases of diabetes and only one non-lethal case of cancer.

When they looked at the group’s normal-sized relatives, who lived in the same town over the same period, around17 per cent had been diagnosed with cancer and 5 per cent had diabetes – the same rate found among other Ecuadorian adults.

The researchers concluded that growth hormone must have a downside in normal size adults. ”The growth hormone receptor-deficient people don’t get two of the major diseases of ageing,” said Associate Professor Longo, a biologist at the University of Southern California.

To understand how this mutation could protect against cancer and diabetes, the researchers studied the effects of compounds in the participants’ blood.

They found low levels of IGF-1 could reduce DNA damage and promote cell death when DNA damage did occur – two processes that decrease cancer-promoting behaviour in cells.

The Laron group also had lower blood insulin levels, which accounted for the absence of diabetes.

People with Loran dwarfism were instead more likely to die from accidents, cardiovascular disease or alcohol-related causes, the researchers found.

Drugs that reduce growth hormone are readily available and are used to treat people with gigantism. The risks and benefits of giving adults these or similar drugs to reduce growth hormones would need to be weighed up against the side-effects of drugs used to treat diabetes and cancer, said Professor Longo, whose findings are published in the journal Science Translational Medicine.

Sourced & published by Henry Sapiecha


LAYOFF THE PAIN KILLERS AND SAY GOODBYE TO HEART ATTACKS & STROKES

Thursday, February 3rd, 2011

Popular painkillers linked to heart and stroke risk

Feelin’ lucky? Then go ahead – pop that painkiller.

But you’d better hope that today’s not the day your luck finally runs out, because some of the most commonly used pain meds carry a major death risk.

The drugs are those nonsteroidal anti-inflammatories used by millions for everything from arthritis to headaches to back pain. And now, researchers say they can double, triple, and even quadruple your odds of heart attack, stroke, and an early death.

Swiss researchers looked at data from 31 “gold-standard” trials that included 116,429 patients, and found that ibuprofen – a med probably in your own home right now – can triple the risk of stroke.

And diclofenac, a widely used generic prescription NSAID, can quadruple the risk of death from heart attack and stroke.

These problems aren’t rare by any stretch. In fact, the researchers say that for every 25 to 50 patients who take NSAIDs for a year, there will be one extra heart attack or stroke.

That’s overall.

But they also believe that patients who already have heart problems could face a much higher risk when they pop those pills – like the millions of seniors who battle both heart disease and arthritis.

The researchers found naproxen (aka Aleve) to be the “safest” of the NSAIDs, but don’t kid yourself – “safest” doesn’t mean “safe.” All painkillers carry risk – and regular use of any NSAID can lead to bleeding problems, ulcers, and more.

And that means you need to be careful with how – and how often – you use these things, no matter how old you are or what risks you face.

If you need one from time to time, you need one – and I won’t stand in your way.

But if you’re taking one of these things regularly, there’s clearly something else going on – and you and your doc need to get to the bottom of it.

If you go looking for that answer at the bottom of a painkiller jar, you could find yourself at the bottom of a grave.

Sourced & published by Henry Sapiecha