Beating bone marrow cancer

Saturday 26 October 2013

Islamabad, Oct 27 (Newswire): To lessen the impact of chemotherapy on bone marrow cancer patients, hematologists are recruiting the patients' own immune systems to help.

White blood cells are extracted before a bone marrow transplant, treated to up their activity, and injected back after chemotherapy. Doctors hope to test technique on other patients with immune deficiencies, including HIV.

A heavy dose of chemo takes a huge toll on cancer patients' bodies, making them weak and prone to infection. Now, a new, life-saving therapy is helping some cancer patients win the war against a deadly disease.

Having bone marrow cancer hasn't slowed down Todd Ewell, but the chemotherapy to fight the disease stopped him in his tracks. "It's kind of like if you had the worst flu in your life for about six weeks straight," he says.

The body's immune system takes a beating from chemotherapy. Patients can't fight off infection or disease, but Todd's body fought back, thanks to a new immune-boosting therapy.

Aaron Rapoport, a hematologist and oncologist at the University of Maryland Greenebaum Cancer Center in Baltimore, says, "What we're seeking to do is to harness the power of the patient's own immune system."

Before a bone marrow transplant, hematologists collect a patient's own immune cells, then activate, or turn on, the cells in a lab. The enhanced cells are injected back into the patient, along with a pneumonia vaccine, jump-starting the immune system. "It will be better able to respond to infections and also be better able to attack and eliminate cancer cells that may remain," Dr. Rapoport tells DBIS.

The new therapy worked wonders for Todd. "It's going fantastic. It's almost like it never happened." His cancer is in complete remission, and now he's focused on rebuilding his life cancer free.

Doctors are hopeful the new therapy could be tested and used to treat other people with compromised immune systems liked HIV patients and the elderly.

A new form of immunotherapy combines a vaccine with an infusion of a person's own T-cells that have been given a "jump start" and then are grown in the laboratory. The new approach helps to restore cancer patients' ability to fight off infection after high-dose chemotherapy. It could also one day be used to treat others with compromised immune systems, such as those with HIV and the elderly.

Patients with advanced myeloma, a cancer of the plasma cells in the bone marrow, received high-dose chemotherapy and a bone marrow transplant.

They received a series of vaccinations against a common bacterial form of pneumonia as well as an injection of their own lab-enhanced immune cells.

Researchers found the therapy was most effective when patients received vaccinations before the bone marrow transplant to jump-start their immune system, and then collected the "vaccine-primed" T cells, activated them in the lab, and gave them back to the patients 12 days after the transplant.

Within one month, those patients showed significant improvement in their immune response. The researchers will next combine this T-cell therapy with a cancer vaccine that would target tumor cells, hopefully to one day enhance the body's immune response to cancer.

A slow or non-functioning immune system is a serious problem for cancer patients, especially those who receive intensive chemotherapy prior to bone marrow transplants.

Patients are at high risk of developing infections and recurrence of their cancer. Immunotherapy stimulates a patient's own immune system to work harder. It's often used in conjunction with other forms of therapy -- in the case of cancer, it is combined with surgery, radiation therapy, or chemotherapy.

In general, immunotherapy is most likely to be effective when treating small cancers and is less effective for advanced stages of the disease.

T-cells are a type of white blood cell called lymphocytes, and help the immune system fight off diseases. There are two kinds of T-cells. T4 cells are "helper" cells that lead the attack against infections.

T8 cells are "suppressor cells" that end the immune response, although they can also kill cancer cells and cells infected with a virus. Scientists tell T4 and T8 cells apart by the different proteins attached to the outside of each cell. The number of T4 cells in your blood tells you how healthy your immune system is. A person with a healthy immune system has an average T-cell percentage of more than 30 percent.

Chemotherapy is a treatment for cancer, in which certain drugs (poisonous to cancer cells) are injected into the blood to kill cancer cells or to stop them from spreading. They can travel around the body and attack cancer cells wherever they find them, so chemotherapy is used when cancers have spread beyond one region of the body.

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Synthetic molecule makes cancer cells commit suicide

Islamabad, Oct 27 (Newswire): Howard Hughes Medical Institute researchers have developed a small molecule that can turn the survival signal for a variety of cancer cells into a death signal. The molecule mimics the activity of Smac, a protein that triggers the suicide of some types of cancer cells.

The researchers say their findings suggest that Smac-mimetic compounds could be useful as targeted cancer treatments for lung and other cancers. Such therapy may be less toxic to healthy cells than current compounds used in cancer chemotherapy.

The researchers, led by Howard Hughes Medical Institute investigator Xiaodong Wang, published their findings in the journal Cancer Cell. Wang is at the University of Texas Southwestern Medical Center.

Cells that are defective or that become unnecessary during growth and development are induced to commit suicide through a finely balanced process known as apoptosis, or programmed cell death. A protein called Smac, which is a shortened version of "second mitochondria-derived activator of apoptosis," is a part of the cell's programmed cell death machinery. When that machinery is switched on, Smac is released from the mitochondria and triggers the pathway that kills damaged or abnormal cells. Cancer cells, however, can survive Smac's death signal by switching off the apoptotic machinery.

To see if they could get around this problem, Wang and other researchers have developed small-molecule mimetics of Smac that can enter the cell and trigger apoptosis. These mimetic molecules do their damage without the need for the Smac signal from the mitochondria. In earlier studies, Wang and his colleagues found that a Smac mimetic that they developed in the lab could kill cancer cells in culture. But they found that the cancer cells are only killed when the mimetic molecule is introduced in conjunction with another component of the apoptotic machinery known as TNFá.

In the new studies published in Cancer Cell, Wang and his colleagues found that a significant percentage of human non-small-cell lung cancer cell lines were sensitive to treatment by the Smac mimetic alone. When the researchers introduced those sensitive cells into mice and allowed them to produce tumors, they found that the Smac mimetic caused the tumors to regress and, in some cases, even disappear.

"These findings made us wonder what it was about these cell lines that made them sensitive to the Smac mimetic alone," said Wang. "Cancer cells are hard to kill, but these cell lines seemed to have already become sensitized to apoptosis."

The researchers' studies revealed that the sensitive cell lines produced their own TNFá, so they were already "primed" for apoptosis. The paradox, said Wang, is that TNFá signaling is also part of a complex pathway that gives cancer cells a "survival" signal, offering them a growth advantage. The researchers also found that some breast cancer and melanoma cell lines were sensitive to the Smac mimetic alone.

"Thus, in these cancer cell lines, the TNFá survival advantage turns out to be a fatal flaw, because the same pathway can be switched to apoptosis by Smac mimetics," said Wang. "So, for some cancers, we might be able to use Smac mimetics as a single treatment agent. And we can use the presence of TNFá as a marker to tell us which tumors will respond to the Smac mimetic alone."

"People have been suspecting for a long time that some cancer cells may somehow turn on their apoptotic pathway already," said Wang. "And now we know what pathway they turn on and why. We can take advantage of this phenomenon for potential cancer therapy by switching a signal into a deadly one with Smac mimetics."

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'Reaper' protein strikes at mitochondria to kill cells

Islamabad, Oct 27 (Newswire): Our cells live ever on the verge of suicide, requiring the close attention of a team of molecules to prevent the cells from pulling the trigger.

This self-destructive tendency can be a very good thing, as when dangerous precancerous cells are permitted to kill themselves, but it can also go horribly wrong, destroying brain cells that store memories, for instance.

Rockefeller University scientists are parsing this perilous arrangement in ever finer detail in hopes that understanding the basic mechanisms of programmed cell death, or apoptosis, will enable them eventually to manipulate the process to kill the cells we want to kill and protect the ones we don't.

In experiments published in the Journal of Cell Biology, researchers led by postdoctoral associate Cristinel Sandu in Hermann Steller's Strang Laboratory of Apoptosis and Cancer Biology drilled down on a protein aptly named Reaper, which was first described in a 1994 paper by Steller in Science.

Under the right conditions, Reaper interferes with molecules called inhibitor of apoptosis proteins (IAPs), which prevent the cell from irrevocably initiating its autodestruct sequence. By inhibiting these inhibitors, Reaper essentially takes the brakes off the process of apoptosis, pronouncing a cell's death sentence. Other molecules called caspases then carry that sentence out.

"Like the grim reaper, Reaper is an announcer of death, but not the executioner," says Steller, who is also a Howard Hughes Medical Institute investigator. "It's like the key that starts the engine."

Reaper and the other Drosophila IAP antagonists Hid and Grim are known to trigger apoptosis in flies, and related proteins serve a similar function in humans and other mammals.

But exactly how and where Reaper initiates apoptosis has not been well understood. Sandu and colleagues bred genetically modified strains of flies that expressed variations on the Reaper protein specifically in flies' eyes.

This allowed them to assess the contribution of individual protein motifs to Reaper's apoptosis inducing powers, and what they found was that a particular helical domain was crucial for the formation of Reaper complexes, and could be modified to be even more powerful than the regular protein. The more deadly Reaper variants were obvious by the damage caused to the flies' eyes.

In a series of biochemical experiments, the researchers also found that Reaper must travel to the mitochondria, the cell's energy factories, to effectively deliver its death sentence, and that to get there, it must hitch a ride on the Hid protein, with which it interacts.

By tagging Hid and Reaper fluorescently, Sandu could visualize Hid and Reaper acting in a complex and gathering at the membrane of the mitochondria. When Reaper was engineered to go directly to the mitochondrial membrane, it resulted in a molecule that is far superior at triggering cell death than regular Reaper.

Further experiments suggested that in a complex with Hid, Reaper is protected from degradation as the cells began to die.

"So now we have Hid and Reaper working very closely together," Sandu says. "And the localization to the mitochondria is crucial to the initiation of apoptosis."

Drugs that mimic a small part of the function of Reaper are already in clinical trials. The discovery of a way to make Reaper a much better killer, namely by targeting it directly to the mitochondria, provides new avenues to explore for improving cancer therapies.

"Adding this element that takes Reaper directly to the mitochondria is not something people would have thought of before this," Steller says.

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Proteins regulating water retention in salt-sensitive hypertension identified

Friday 25 October 2013

Islamabad, Oct 26 (Newswire): Research conducted by scientists at LSU Health Sciences Center New Orleans has found that two proteins in the brain act as valves to turn the hormone that regulates water retention in the body on and off.

Their findings may lead to advances in treatment for diseases like high blood pressure, congestive heart failure, and cirrhosis of the liver.

Daniel Kapusta, PhD, Professor of Pharmacology at LSU Health Sciences Center New Orleans, and Richard Wainford, PhD, LSUHSC Instructor of Pharmacology, report the role of these brain proteins, called Gaq and Gaz, in producing elevated secretion of the hormone, vasopressin, and water retention in salt-sensitive hypertension, a condition in which blood pressure becomes elevated when salt is consumed. It is estimated that salt-sensitive hypertension occurs in about 26% of Americans with normal blood pressure and in 58% of those whose blood pressure is already high.

"Throughout the day, vasopressin, a peptide hormone produced by the hypothalamus, is released into the circulation from the pituitary gland and plays a vital role as the flood-gate keeper to prevent excessive loss of water from the kidneys," notes Dr. Kapusta.

"Under most conditions, the water-retaining action of vasopressin is vital for survival. However, it has remained essentially a black box as to why, in susceptible individuals, the regulatory mechanisms that control vasopressin secretion cannot turn off when the body already has elevated water content."

For 21-days, the research team fed groups of male salt-resistant and salt-sensitive rats a diet containing either normal or high salt. Then they measured how the treatments influenced the animal's ability to excrete water and how the salt stress altered levels of vasopressin, Gaq and Gaz.

The consumption of high salt triggered a decrease in Gaq proteins in the brain of salt-resistant, but not salt-sensitive, rats. In salt-sensitive rats, the team demonstrated that reducing brain Gaq proteins returned plasma vasopressin to normal levels, decreased salt-induced water retention, and restored the animal's ability to excrete water.

"Our findings are novel and provide evidence that the Gaq sub-unit proteins in the hypothalamus act as a molecular/cellular switch to control the level of vasopressin secretion," says Dr. Wainford.

The researchers concluded that reducing brain Gaq proteins plays a critical counter-regulatory role in preventing the secretion of too much vasopressin in those with salt-resistance and may represent a new therapeutic target in diseases associated with fluid retention.

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'Fruity vegetables' and fish reduce asthma and allergies

Islamabad, Oct 26 (Newswire): Giving children a diet rich in fish and "fruity vegetables" can reduce asthma and allergies, according to a seven-year study of 460 Spanish children.

The findings also reinforce the researchers' earlier findings that a fish-rich diet in pregnancy can help to protect children from asthma and allergies.

"We believe that this is the first study that has assessed the impact of a child's diet on asthma and allergies and also taken into account the food their mother ate during pregnancy" says lead author Dr Leda Chatzi from the Department of Social Medicine at the University of Crete, Greece.

"Because we studied the children from pregnancy to childhood, we were able to include a wide range of elements in our analysis, including maternal diet during pregnancy, breastfeeding, smoking, the mother's health history, parental education and social class."

Researchers followed the progress of the children, on the Spanish island of Menorca, at regular intervals from before they were born until they were six-and-a-half.

They discovered that children who consumed more than 40 grams of "fruity vegetables" a day -- namely tomatoes, eggplants (aubergines), cucumber, green beans and zucchini (courgettes) - were much less likely to suffer from childhood asthma.

And children who consumed more than 60 grams of fish a day also suffered less childhood allergies, echoing the protective effects they experienced when their mothers ate fish during pregnancy.

However the researchers noted that the dietary effects were quite specific and that other fruits and vegetables examined did not provide the same protective effect. Nor did other food groups included in the study, such as dairy products, meat, poultry and bread.

The mothers of 232 boys and 228 girls, who had been recruited during antenatal classes, completed detailed questionnaires on their children's health, weight, diet and any breathing problems every year until their child was six-and-a-half.

90 per cent of the children also underwent allergy testing -- skin prick tests were used to check their response to the six most common allergens, including grass pollen and cats.

The researchers found that just under nine per cent of the children suffered from some degree of wheezing, including six per cent with an allergy-related wheeze. And 17 per cent reacted to at least one of the allergens in the skin prick test.

"After adjusting the results for a wide range of variables, we concluded that the link between symptom-free children and a diet rich in fruity vegetables and fish was statistically significant" says Dr Chatzi.

"The biological mechanisms that underlie the protective affect of these foods is not fully understood, but we btelieve that the fruity vegetables and fish reduce the inflammation associated with asthma and allergies.

"The interesting thing about this study is that it followed a large number of children from the womb to the age of six-and-a-half and incorporated a wide range of dietary, social and health factors" says the Journal's Editor, Professor John Warner, Head of the Department of Paediatrics at Imperial College London.

"It provides parents with specific advice about the health promotion benefits of including fish and fruity vegetables as part of a balanced diet for both their children and the rest of the family."

Reference: "Diet, wheeze and atophy in school children in Menorca, Spain." Chatzi et al. Pediatric Allergy and Immunology. 18, pages 480 to 485. (September 2007).

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Allergies and wheezing illnesses in childhood may be determined in the womb

Islamabad, Oct 26 (Newswire): A child's chances of developing allergies or wheezing is related to how he or she grew at vital stages in the womb, according to scientists from the University of Southampton.

The new research, funded by the Medical Research Council (MRC) and the British Lung Foundation, and undertaken at Southampton General Hospital, reveals that fetuses which develop quickly in early pregnancy but falter later in pregnancy are likely to go on to develop allergies and asthma as children. Scientists believe this is due to changes in the development of their immune system and lungs.

A fetus that grows too slowly in the womb is also more likely to become an infant who wheezes with common colds, possibly as a result of narrower airways in its lungs.

"Childhood allergies and asthma have become an epidemic in developed countries over the last 50 years. This research shows that in order to combat this, we need to understand more about how babies develop in the womb," comments Keith Godfrey, Professor of Epidemiology and Human Development at the University of Southampton and Deputy Director of the NIHR Nutrition Biomedical Research Unit at Southampton General Hospital.

"We already know that a baby's growth in the womb has an important influence on susceptibility to obesity and heart disease in later life, but this research provides some of the most direct evidence yet that changes in how the baby's immune system and lungs develops before birth can predispose them to some of the commonest childhood illnesses."

For the research, published in the journal Thorax, University of Southampton scientists at the MRC Lifecourse Epidemiology Unit based at Southampton General Hospital studied more than 1,500 three year-old children who were taking part in the Southampton Women's Survey, the UK's largest study of women and their offspring. The Survey has studied how a woman's diet and lifestyle before and during pregnancy affects their baby's growth in the womb, and is monitoring how these early life influences determine health and development during childhood.

The team discovered evidence of sensitivity to common allergens (atopy) in 27 per cent of children who had developed quickly in early pregnancy but faltered later in pregnancy, as compared with 4 per cent in those with a slow early growth trajectory and quicker growth in late pregnancy.

Professor Stephen Holgate, from the Medical Research Council, says: "Unravelling the complex interplay between immunity and disease, over the course of a person's life, including before they are even born, is a core part of the MRC's research strategy. Furthering our understanding of the body's natural resilience is critical to developing new advances in the treatment of infectious diseases, autoimmune diseases and allergies."

Ian Jarrold, Research Manager at the British Lung Foundation, adds: "Children's lung health can be complex so this research, funded by the British Lung Foundation, is a considerable step forward in understanding why some children are more likely to develop allergies and asthma.

"The most commonly reported long-term illnesses in children and babies are conditions of the respiratory system. Increasing our understanding of childhood lung conditions is vital for developing new ways of diagnosing and treating lung diseases earlier in life."

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Change in how paramedics use oxygen could reduce deaths

Thursday 24 October 2013

Islamabad, Oct 25 (Newswire): A change to the way paramedics use oxygen when treating patients with chronic lung disease could cut the death rate in these cases by up to 78%, according to a new study published on the British Medical Journal website.

Researchers based in Australia found the risk of death in patients with chronic obstructive pulmonary disease (COPD) was significantly reduced by using titrated (controlled) oxygen therapy instead of the current common approach of high concentration oxygen.

High concentration oxygen is used routinely by many paramedics in emergency situations for patients with acute breathlessness caused by episodes of COPD, a condition that affects over 200 million people across the world.

However, giving high concentration oxygen to patients with severe lung disease can lead to a build up of carbon dioxide in the blood, which can induce respiratory failure.

Hospital audits have also shown an association between using high concentration oxygen and adverse outcomes such as an increase in mortality, length of hospital stay, need for ventilation and admission to high dependency units.

For these reasons, the British Thoracic Society together with 21 other UK Colleges and Societies produced a guideline in 2008 which recommended that oxygen therapy for patients with COPD should be titrated to achieve a blood oxygen saturation of 88-92% compared with a target saturation range of 94-98% for most other medical emergencies. This guidance was implemented by the UK ambulance service in 2009.

Researchers from Tasmania carried out a study involving 405 patients aged 35 and over who were treated by 62 paramedics from the Tasmanian Ambulance Service and transported to a local hospital.

The participants were split into two groups -- one group (226) was treated with the standard high concentration oxygen approach and the other (179) with titrated oxygen therapy -- and data collected over a 13-month period between 2006 and 2007.

A confirmed COPD subgroup was identified retrospectively as those patients with a definite diagnosis of COPD during the study and this included 214 patients, 117 of whom were treated using high concentration oxygen and 97 with titrated oxygen with a target range of 88-92%.

Results showed significant differences in outcomes, depending on which approach was used.

Overall mortality was 9% (21 deaths) in the high concentration oxygen group and 4% (7 deaths) in the titrated oxygen group. This difference was more pronounced in the confirmed COPD subgroup for which there was a 9% (11 deaths) mortality rate in the high concentration group compared with a 2% mortality rate (2 deaths) in the titrated group.

Overall, titrated oxygen therapy reduced the risk of death from respiratory failure by 58% for all patients and 78% for confirmed COPD patients compared to high concentration oxygen therapy.

Patients who received high concentration oxygen were also significantly more likely to develop respiratory acidosis (a condition in which decreased respiration causes increased blood carbon dioxide and decreased pH) or hypercapnia, when there is too much carbon dioxide in the blood.

The researchers conclude: "Our findings provide the first high quality evidence from a randomised controlled trial for the development of universal guidelines and support the British Thoracic Society's recent guidelines on acute oxygen treatment, which recommend that oxygen should be administered only at concentrations sufficient to maintain adequate oxygen saturations."

In an accompanying editorial, senior doctors Ronan O'Driscoll and Richard Beasley warn that routine use of high concentration oxygen may also be harmful in several other medical emergencies, including heart attack and stroke."

They conclude: "After more than 200 years of haphazard use, it should be recognised that oxygen should be prescribed for defined indications in which its benefits outweigh its risks and that the patient's response must be monitored."

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Dad's weight and diet linked to offspring's risk of diabetes

Islamabad, Oct 25 (Newswire): Medical researchers have for the first time shown a link between a father's weight and diet at the time of conception and an increased risk of diabetes in his offspring.

The finding, reported in the journal Nature, is the first in any species to show that paternal exposure to a high-fat diet initiates progression to metabolic disease in the next generation.

"We've known for a while that overweight mums are more likely to have chubby babies, and that a woman's weight before and during pregnancy can play a role in future disease in her children, partly due to the critical role the intrauterine environment plays in development," said study leader Professor Margaret Morris, from UNSW's School of Medical Sciences.

"But until now, the impact of the father's environment -- in terms of his diet -- on his offspring had not been investigated." The work formed the basis of the PhD study of Dr Sheau-Fang Ng, who showed that paternal environmental factors such as diet and weight are important contributors to disease in the next generation.

In the Nature study, male rats were fed a high fat diet to induce obesity and glucose intolerance and then mated with normal weight females. The resulting female offspring exhibited impaired glucose tolerance and insulin secretion as young adults.

"This is the first report of non-genetic, intergenerational transmission of metabolic consequences of a high fat diet from father to offspring," Professor Morris said.

"A family history of diabetes is one of the strongest risk factors for the disease; however until now, the extent of any influence of non-genetic paternal factors has been unclear."

Professor Morris said the research showed that overweight fathers can play a role in "programming" epigenetic changes in their offspring, possibly through effects on their sperm caused by their consumption of high-fat food. Epigenetics is a process whereby changes in gene expression -- and hence function -- can occur even when there are no alterations in the DNA sequence.

Professor Morris said the study expands our understanding of the role environmental factors might play on a child's physiology and metabolism.

"It adds another level to our understanding of the causes of the growing epidemics in obesity and diabetes," she said. "While here we studied female offspring, we need to examine whether the effect is also found in males."

The work was carried out in collaboration with scientists in the UNSW Schools of Medical Sciences and Biotechnology and Biomolecular Sciences, the Garvan Institute, and the University of Adelaide.

Professor Morris will present the findings at the Australia and New Zealand Obesity Society meeting in Sydney.

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Major component in turmeric enhance effect of chemotherapy drug in head and neck cancer

Islamabad, Oct 25 (Newswire): Curcumin, the major component in the spice turmeric, when combined with the drug cisplatin enhances the chemotherapy's suppression of head and neck cancer cell growth, researchers with UCLA's Jonsson Cancer Center have found.

A naturally occurring spice widely used in South Asian and Middle Eastern cooking, Turmeric has long been known to have medicinal properties, attributed to its anti-inflammatory effects.

Previous studies have shown it can suppress the growth of certain cancers, said Dr. Marilene Wang, a professor of head and neck surgery, lead author of the study and a Jonsson Cancer Center researcher.

"Head and neck cancers, particularly cases diagnosed in a later stage, are terrible cancers that often require very radical surgeries and chemotherapy and radiation," Wang said.

"They often don't present until late, and the structures in the head and neck are so vital that our treatments often cause disfigurement and severe loss of function. So using non-toxic curcumin as a treatment was a very appealing idea."

The study, done in cells in Petri dishes and then in mouse models, appears in the October issue of the journal Molecular Cancer Therapeutics.

In India, women for years have been using turmeric for medicinal purposes, as an anti-aging agent rubbed into their ski, to treat cramps during menstruation, as a poultice on the skin to promote wound healing and as an additive in cosmetics, said scientist Eri Srivatsan, an adjunct professor of surgery and a Jonsson Cancer Center researcher who, along with Wang, has been studying curcumin and its anti-cancer properties for six years.

A 2005 study by Wang and Srivatsan first showed that curcumin suppressed the growth of head and neck cancer cells, first in cells and then in mouse models. In the animal studies, the curcumin was applied directly onto the tumors in paste form because it did not dissolve in saline, which would have allowed it to be injected.

In need of a better way to deliver the curcumin, the team collaborated with Dr. Kapil Mehta of M.D. Anderson Cancer Center and found that encapsulating the tumor in a liposome, an artificially prepared vehicle that enclosed the spice component within its membrane, made the treatment injectable.

The curcumin was injected into the tail vein of a mouse, where it circulated into the blood stream, slowing down and eventually stopping the cancer growth, a study in 2008 found.

"This was a very positive finding, developing an efficient way to deliver the treatment," Wang said. "Our study also showed that the curcumin was very well tolerated."

In this study, the team wanted to combine the curcumin with the chemotherapeutic drug cisplatin, which is very toxic at the doses needed to fight head and neck cancers, damaging kidneys, the ears and the bone marrow.

They hoped that if they added curcumin to the mix, they might be able to lower the cisplatin dose and cause less organ damage. Their finding, that the curcumin made the cisplatin work better, was very promising, Wang said.

"We knew that both the curcumin and the cisplatin, when given alone, had an effect against head and neck cancers," Wang said. "This finding that curcumin enhances cisplatin means that, in the future, we may be able to give this chemotherapy in lower doses."

The study noted that "the mechanisms of the two agents through different growth signaling pathways suggest potential for the clinical use of sub-therapeutic doses of cisplatin in combination with curcumin, which will allow effective suppression of tumor growth while minimizing the toxic side effects."

The study found that curcumin suppressed head and neck cancer growth by regulating cell cycling, Srivatsan said. It binds to an enzyme and prevents the enzyme IKK, an inhibitor of kappa B kinase, from activating a transcription factor called nuclear factor kappa B (NF?B), which promotes cancer growth. Cisplatin's suppressive action involves a different pathway through the tumor suppressor proteins p16 and p53, both proteins that again inhibit the activity of cancer growth promoter NF?B.

"We needed to know the mechanism to help us translate this from the lab into the clinic," Wang said. "That information will help us make better decisions on how to design therapies."

The next step in the clinical setting is to give patients oral curcumin prior to surgery and, after surgery, study the excised tumors to determine curcumin's effect on tumor markers, specifically whether there is reduced expression of markers such as growth promoting NF?B.

They also will be monitoring to determine if the curcumin results in any side effects. After that, the team would give curcumin to patients also getting chemotherapy and radiation to see if the tumor suppression found in the cells lines and mouse models can be replicated in humans.

Although turmeric is used in cooking, the amount of curcumin needed to produce a clinical response is much larger, about 500 milligrams. Expecting a positive effect through eating foods spiced with turmeric is not realistic, the researchers said.

Curcumin also has a suppressive effect on other cancers, Wang said, including breast, colon and pancreatic cancers. However, the mechanism of suppression in those cancers has not yet been uncovered. It also may be effective against Alzheimer's and aging, Wang said.

The study was funded by the VA Greater Los Angeles Surgical Education Research Center, UCLA Academic Senate, the National Institutes of Health and the Veterans Administration.

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Spinal cord stimulators tested as treatment for patients with migraine headaches

Wednesday 23 October 2013

Islamabad, Oct 24 (Newswire): Researchers at Rush University Medical Center are testing a new treatment for migraine headaches: occipital nerve stimulation, a surgical procedure in which an implanted neurostimulator delivers electrical impulses to nerves under the skin at the base of the head at the back of the neck.

This therapy may help migraine sufferers who do not respond to other available therapies, or who cannot tolerate the side effects of existing medications.

"The purpose of the randomized, double-blinded study is to evaluate the safety and efficacy of occipital nerve stimulation as a treatment for refractory migraine headache," says Dr. Sandeep Amin, Rush study investigator and anesthesiologist who surgically implants the device in the two-visit operation.

Rush is recruiting patients through the Diamond Headache Clinic and is the only site in Illinois in the trial.

The study, known as PRISM (Precision Implantable Stimulator for Migraine), uses Boston Scientific's Precision neurostimulator with approximately 150 patients at up to 15 sites in the U.S. The implantable pulse generator will deliver electrical impulses to the occipital nerves located just under the skin at the base of the skull at the back of the neck.

The Precision device is the smallest rechargeable neurostimulator on the market today and is already approved by the FDA for spinal cord stimulation to treat chronic pain.

There are more than 28 million migraine sufferers in the U.S., and up to 10 percent of these patients may not respond to existing treatments.

"Occipital nerve stimulation has the potential to provide relief to the large population of migraine sufferers who currently have no other medical treatments available to them that bring them relief," said Amin. "If effective, the implantable neurostimulator would provide a new treatment option to free these patients from their long-standing headache pain."

The smallest rechargeable neurostimulator available, the Precision device has been used in the treatment of more than 6,000 patients suffering from chronic pain, according to Boston Scientific.

The Precision neurostimulator is currently FDA approved for spinal cord to treat chronic pain by precisely delivering tiny electrical signals to the spinal cord that mask the perception of pain. Spinal cord stimulation is prescribed for patients with chronic pain in the limbs, trunk and back.

Migraine sufferers are monitored and complete a month-long pain diary as the first part of the study. Patients then undergo a two-part operation in which thin electrode leads are placed under the skin at the back of the neck.

A week later, the patient returns for the 45 minute procedure in which the neurostimulator is placed on one side in the lowest part of the back, and the leads are connected and the device activated. Patients then return to the neurologist for monitoring of their headaches.

During the first 3 months after the Precision neurostimulator is implanted, two different stimulation settings will be tried in different groups of patients. One group of patients is programmed to settings more likely to show a response, while the control group of patients is programmed to settings rather unlikely to be effective.

After the first three months, the control group of patients will have their devices programmed to the stimulation settings more likely to show a response.

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First implanted device to treat balance disorder developed

Islamabad, Oct 24 (Newswire): A University of Washington Medical Center patient on Thursday, Oct. 21, became the world's first recipient of a device that aims to quell the disabling vertigo associated with Meniere's disease.

The UW Medicine clinicians who developed the implantable device hope that success in a 10-person surgical trial of Meniere's patients will lead to exploration of its usefulness against other common balance disorders that torment millions of people worldwide.

The device being tested -- a cochlear implant and processor with re-engineered software and electrode arrays -- represents four-plus years of work by Drs. Jay Rubinstein and James Phillips of UW's Department of Otolaryngology-Head and Neck Surgery. They worked with Drs. Steven Bierer, Albert Fuchs, Chris Kaneko, Leo Ling and Kaibao Nie, UW specialists in signal processing, brainstem physiology and vestibular neural coding.

"What we're proposing here is a potentially safer and more effective therapy than exists now," said Rubinstein, an ear surgeon and auditory scientist who has earned a doctoral degree in bioengineering and who holds multiple U.S. patents.

In the United States, Meniere's affects less than one percent of the population. The disease occurs mostly in people between ages 30 and 50, but can strike anyone. Patients more often experience the condition in one ear; about 30 percent of cases are bilateral.

The disease affects hearing and balance with varying intensity and frequency but can be extremely debilitating. Its episodic attacks are thought to stem from the rupture of an inner-ear membrane. Endolymphatic fluid leaks out of the vestibular system, causing havoc to the brain's perception of balance.

To stave off nausea, afflicted people must lie still, typically for several hours and sometimes up to half a day while the membrane self-repairs and equilibrium is restored, said Phillips, a UW research associate professor and director of the UW Dizziness and Balance Center. Because the attacks come with scant warning, a Meniere's diagnosis can cause people to change careers and curb their lifestyles.

Many patients respond to first-line treatments of medication and changes to diet and activity. When those therapies fail to reduce the rate of attacks, surgery is often an effective option but it typically is ablative (destructive) in nature. In essence, the patient sacrifices function in the affected ear to halt the vertigo -- akin to a pilot who shuts down an erratic engine during flight. Forever after, the person's balance and, often, hearing are based on one ear's function.

With their device, Phillips and Rubinstein aim to restore the patient's balance during attacks while leaving natural hearing and residual balance function intact.

A patient wears a processor behind the affected ear and activates it as an attack starts. The processor wirelessly signals the device, which is implanted almost directly underneath in a small well created in the temporal bone. The device in turn transmits electrical impulses through three electrodes inserted into the canals of the inner ear's bony labyrinth.

"It's an override," Phillips said. "It doesn't change what's happening in the ear, but it eliminates the symptoms while replacing the function of that ear until it recovers."

The specific placement of the electrodes in the bony labyrinth is determined by neuronal signal testing at the time of implant. The superior semicircular canal, lateral semicircular canal and posterior semicircular canal each receive one electrode array.

A National Institutes of Health grant funded the development of the device and its initial testing at the Washington National Primate Research Center. The promising results from those tests led the U.S. Food and Drug Administration, in June, to approve the device and the proposed surgical implantation procedure. Shortly thereafter, the limited surgical trial in humans won approval from the Western Institutional Review Board, an independent body charged with protecting the safety of research subjects.

By basing their invention on cochlear implants whose design and surgical implantation were already FDA-approved, Phillips and Rubinstein leapfrogged scientists at other institutions who had begun years earlier but chosen to develop novel prototypes.

"If you started from scratch, in a circumstance like this where no one has ever treated a vestibular disorder with a device, it probably would take 10 years to develop such a device," Rubinstein said.

The device epitomizes the translational advancements pursued at UW's academic medical centers, he said. He credited the team's skills and its access to the primate center, whose labs facilitated the quick turnaround of results that helped win the FDA's support.

A successful human trial could lead the implant to become the first-choice surgical intervention for Meniere's patients, Phillips said, and spark collaboration with other researchers who are studying more widespread balance disorders.

The first patient will be a 56-year-old man from Yakima, Wash. He has unilateral Meniere's disease and has been a patient of Rubinstein's for about two years.

See a related video at UW Medicine's YouTube site. Drs. Rubinstein and Phillips discuss the device: http://www.youtube.com/watch?v=iu047vTckvA

Cochlear Ltd. of Lane Cove, Australia, will manufacture the device. Cochlear is a medical equipment company and longtime maker of devices for hearing-impaired people.

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Younger brains are easier to rewire

Islamabad, Oct 24 (Newswire): A new paper from MIT neuroscientists, in collaboration with Alvaro Pascual-Leone at Beth Israel Deaconess Medical Center, offers evidence that it is easier to rewire the brain early in life.

The researchers found that a small part of the brain's visual cortex that processes motion became reorganized only in the brains of subjects who had been born blind, not those who became blind later in life.

The new findings, described in the journal Current Biology, shed light on how the brain wires itself during the first few years of life, and could help scientists understand how to optimize the brain's ability to be rewired later in life.

That could become increasingly important as medical advances make it possible for congenitally blind people to have their sight restored, said MIT postdoctoral associate Marina Bedny, lead author of the paper.

In the 1950s and '60s, scientists began to think that certain brain functions develop normally only if an individual is exposed to relevant information, such as language or visual information, within a specific time period early in life. After that, they theorized, the brain loses the ability to change in response to new input.

Animal studies supported this theory. For example, cats blindfolded during the first months of life are unable to see normally after the blindfolds are removed. Similar periods of blindfolding in adulthood have no effect on vision.

However, there have been indications in recent years that there is more wiggle room than previously thought, said Bedny, who works in the laboratory of MIT assistant professor Rebecca Saxe, also an author of the Current Biology paper. Many neuroscientists now support the idea of a period early in life after which it is difficult, but not impossible, to rewire the brain.

Bedny, Saxe and their colleagues wanted to determine if a part of the brain known as the middle temporal complex (MT/MST) can be rewired at any time or only early in life. They chose to study MT/MST in part because it is one of the most studied visual areas. In sighted people, the MT region is specialized for motion vision.

In the few rare cases where patients have lost MT function in both hemispheres of the brain, they were unable to sense motion in a visual scene. For example, if someone poured water into a glass, they would see only a standing, frozen stream of water.

Previous studies have shown that in blind people, MT is taken over by sound processing, but those studies didn't distinguish between people who became blind early and late in life.

In the new MIT study, the researchers studied three groups of subjects -- sighted, congenitally blind, and those who became blind later in life (age nine or older). Using functional magnetic resonance imaging (fMRI), they tested whether MT in these subjects responded to moving sounds -- for example, approaching footsteps.

The results were clear, said Bedny. MT reacted to moving sounds in congenitally blind people, but not in sighted people or people who became blind at a later age.

This suggests that in late-blind individuals, the visual input they received in early years allowed the MT complex to develop its typical visual function, and it couldn't be remade to process sound after the person lost sight. Congenitally blind people never received any visual input, so the region was taken over by auditory input after birth.

"We need to think of early life as a window of opportunity to shape how the brain works," said Bedny. "That's not to say that later experience can't alter things, but it's easier to get organized early on."

Bedny believes that by better understanding how the brain is wired early in life, scientists may be able to learn how to rewire it later in life. There are now very few cases of sight restoration, but if it becomes more common, scientists will need to figure out how to retrain the patient's brain so it can process the new visual input.

"The unresolved question is whether the brain can relearn, and how that learning differs in an adult brain versus a child's brain," said Bedny.

Bedny hopes to study the behavioral consequences of the MT switch in future studies. Those would include whether blind people have an advantage over sighted people in auditory motion processing, and if they have a disadvantage if sight is restored.

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Urologists use optics, chemistry to catch small tumors

Tuesday 22 October 2013

Islamabad, Oct 23 (Newswire): Some bladder cancer tumors are so small, surgeons can't see them. Urologist Edward Messing is using a new liquid dye that reacts to light to help him see all the small bladder tumors that might have been missed in conventional biopsies. 
The earlier the better, when it comes to detecting cancer. Now, doctors are shedding new light on detecting the deadly disease. Currently, 400-000 people suffer from it while 60,000 more will find out they have it, and bladder cancer usually strikes more than once.

Larry Sylvan, a cancer survivor, says, "At nine months it was back." He knows what it's like to battle bladder cancer. Sylvan's doctor, Edward Messing, says, "The surgery was successful; I got everything I could see." The doctor's key word -- see; some bladder cancer tumors are so small, surgeons can't see them.

Dr. Messing, a urologist at the James P. Wilmot Cancer Center in Rochester, N.Y., says, "Before it was sort of blind guessing." A new photo-sensitizer, a liquid dye inserted into the bladder, improves detection of those small tumors. Under ordinary light, everything looks fine, but when the florescent light is turned on, the entire background looks blue, except where the tumor is -- that shows up bright red.

Jerry Gulette was one of the first patients to use the dye. He's battled bladder cancer time and time again. Dr. Messing says, "I had seen maybe four, five tumors when I cystoscoped him with the white light. And when we turned on this pink light there were 12 or 13."

More than 94 percent of the people diagnosed with bladder cancer will survive it if it's caught in the early stages. That's why this new procedure is so critical for those diagnosed.

Urologists use a liquid dye to more easily find tiny cancers in the bladder that could grow after surgery.

The liquid dye helps identify all the tiny tumors in the bladder that can remain after a major surgery is done. The dye, called a photosensitizer, reacts with light to make the cancerous tissue look bright red during an examination. The photosensitizer even detects a rare form of bladder cancer that is hard to detect because it lies almost flush against the walls of the bladder.

The bladder stores urine, which is produced when the kidneys filter urea, a waste product of proteins, from the blood. The bladder is a hollow organ made of muscle, connected to the kidneys by the ureters, and empties through the urethra. Adults eliminate about a quart and a half of urine each day. The amount depends on many factors, especially the amounts of fluid and food a person consumes and how much fluid is lost through sweat and breathing.

About 90 percent of bladder cancers begin in the cells lining the bladder. Cancer that is confined to the lining of the bladder is called superficial bladder cancer and is sometimes removed by scraping away the cancerous cells with a small wire loop.

In some cases, cancer that begins in the transitional cells spreads through the lining of the bladder and invades the muscular wall of the bladder. This is known as invasive bladder cancer. Invasive cancer may grow through the bladder wall and spread to nearby organs.

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Molecular biologists devise strategy to starve brain tumors

Islamabad, Oct 23 (Newswire): Brain tumor researchers have found that brain tumors arise from cancer stem cells living within tiny protective areas formed by blood vessels in the brain. Killing those cells is a promising strategy to eliminate tumors and prevents them from re-growing.

The researchers have found that drugs that block new blood vessel formation can destroy the protected areas and stop cancer from developing.

Brain tumors are often deadly. Figuring out a way to wipe them out has been a mystery for scientists. But now, a new discovery may offer clues and hope for those with even the most hard-to-treat tumors.

In the last two months, Will Pappas has had three surgeries, chemo and radiation.

"You hold out hope that well, it's just something little, and they can get it all. And then it wasn't. Then you think, well, at least it's not cancerous, and then it is," Cayce Pappas, Will's mom, says.

"It" is a brain tumor -- the stubborn kind that's hard to treat. In fact, doctors gave this seven-year-old only a 20 percent chance of surviving. Stories like Will's have molecular biologists determined to find a way to destroy brain tumors.

"It's what makes us all come to work in the morning," Richard Gilbertson, a molecular biologist from St. Jude Children's Hospital, says.

For years, researchers thought all cells inside a tumor were the same. But recently, they've discovered something different -- a small group of cancer stem cells.

"They give rise to all the cells that make up the cancer," Dr. Gilbertson explains.

Dr. Gilbertson's research shows those cancer stem cells live close to blood vessels, which fuel them. In lab experiments, he's proven drugs that target the blood vessels also destroy the cancer stem cells and can ultimately wipe out the tumor.

"So, if you can target those cells, you can have a devastating effect on the disease," Dr. Gilbertson says. Drugs like Avastin and Tarceva are now being tested in humans to see if they can target the cancer stem cells. "It's this tangible way of actually getting at the heart of the disease," Dr. Gilbertson says.

Will is taking the drug Tarceva. His mom is hoping it will work a miracle.

"That would be amazing. We would jump at the opportunity to increase our odds. He's still got a lot left to do," Cayce says.

Dr. Gilbertson says other cancers, like those of the blood, breast and colon, also contain cancer stem cells and may be treated in a similar way in the future.

Researchers at St. Jude Children's Hospital have found that brain tumors appear to arise from cancer stem cells that live inside tiny protective 'niches' formed by blood vessels in the brain. Breaking down these niches is a promising strategy for eliminating the tumors and preventing them from regrowing.

Scientists previously believed that tumors are lumps of cancerous tissue that must be completely removed or destroyed to cure a patient. But over the last five years, cancer researchers have learned that not all cancer cells are created equal. In the same way that normal tissue in the body is generated from stem cells, so is cancer.

CSCs are the ultimate source of the tumor, consistently supplying it with new cells. Researchers have identified the CSCs for acute myeloma leukemia, four types of brain cancer, and breast cancer. So it is possible that we need not kill all cancer cells to rid a patient of the disease. Targeting the CSCs specifically might be much more efficient.

To find a weakness for CSCs, neurobiologists at St. Jude compared them to noncancerous neural stem cells. These neural tissue generators are concentrated in regions rich in blood vessels. The vessels are lined with endothelial cells, which secrete chemical signals that help stem cells survive. CSCs, they discovered, required similar conditions to flourish: in over 70 human brain tumors, the CSCs were frequently located close to tiny vessels called capillaries.

When the researchers injected mice with a mix of stem and endothelial cells from human brain tumors, those animals sprouted larger tumors than the mice that received stem cells alone.

The new findings from St. Jude indicates that it is possible to kill the cancer by disrupting the shielded compartments in the small capillaries of the brain where CSCs reside. Anti-angiogenic drugs, such as Avastin, block the formation of new blood vessels.

In tests with mice, those same drugs cause a significant drop in cancer stem cells and slow tumor growth. Human clinical trials are currently in progress at St. Jude to determine the effectiveness of Avastin and another anti-angiogenic drug in eliminating tumors and preventing their recurrence in children with brain cancers.

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Skin cancer linked to loss of protein that hooks skin cells together

Islamabad, Oct 23 (Newswire): In a study to be published in PLoS Genetics, researchers at the Stanford University School of Medicine have implicated the lack of a protein important in hooking our skin cells together in the most common variety of skin cancer.

Depletion of this protein, called Perp, could be an early indicator of skin cancer development, and could be useful for staging and establishing prognoses.

These findings' significance may extend beyond skin cancer, as Perp is found in the linings of many of our internal organs, where it plays the same role it does in the skin: maintaining cell-to-cell adherence.

This suggests that Perp could be a useful tool for classifying tumors in these internal organs, which are often diagnosed too late to be effectively treated.

Skin is the largest organ in the body by weight, consisting of several sheets of cells layered one atop the next. The bottom layer is composed of basal cells, which, after proliferating for a while, migrate upward toward the skin surface, differentiating from one cell type to another several times along the way.

Skin's outermost layer consists mainly of closely knit squamous cells. Perp is a critical player in maintaining this cell-cell adhesion in these cell types, which makes our skin such an effective barrier against pathogens and toxic and allergenic substances.

Skin belongs to a class of tissues known collectively as epithelium. Epithelial tissue also lines many internal organs such as the lungs, colon, breast, esophagus and pancreas. Several organs' epithelial linings, like skin, are multilayered.

"A good 90 percent of all human cancers originate in epithelial tissue," noted Laura Attardi, PhD, senior author of the study and associate professor of radiation oncology and of genetics at the medical school. "Epithelial tissues are constantly regenerating, creating ample opportunities for errors to occur during DNA replication that can promote tumor growth.

Also, these tissues are particularly exposed to the environment -- the skin to UV radiation, the colon to dietary carcinogens, the lungs to inhaled toxins, and so forth."

Perp, first identified by Attardi in the late 1990s, is a key protein in desmosomes, multi-protein structures found on the surfaces of epithelial cells. Desmosomes are one kind of so-called adhesion junction, cell-surface features that bind fiercely to one another from one cell to the next. Adhesion junctions cause cells to stick together and form a barrier.

Perp, a desmosomal component, weaves in and out of a cell's surface like a thread through fabric. The protein's intercellular tail wraps around structures in the cell, firmly anchoring the desmosome on the membrane. The desmosome's outward-facing features bind strongly to their counterparts on neighboring cells, creating a tight seal.

"People have long assumed that this was desmosomes' only function," said Attardi, who is also a member of the Stanford Cancer Center. The new study shows not only that desmosomes are crucial to maintaining epithelial tissues' integrity, but that the loss of Perp, which is crucial to desmosomes' function, promotes cancer. Disrupted function of another kind of adhesion junction has, indeed, been implicated in late-stage cancers. But desmosome disturbances may occur earlier on, during tumors' initial development.

In 2005, in a study published in Cell, Attardi first showed that Perp is integral to desmosomes. She and her associates produced mice lacking Perp, allowing them, unexpectedly, to identify a role that Perp plays in the skin.

Mice whose skin was deficient in Perp exhibited desmosome loss as well as blistering and increased skin-cell proliferation. In these mice, moreover, so-called p53 tumor suppression -- a mechanism widely acclaimed for its importance in shutting down cell division when genetic damage can't be properly repaired -- fails to function normally, implying that Perp played some as-yet-unspecified role in that pathway. (The p53 protein has been found to be mutated in at least half of all human tumors.)

"In this new study, we attempted to mimic the way skin cancers originate in people," said Attardi. She and her colleagues exposed both normal mice and the bioengineered Perp-deficient mice to UVB light -- a range of ultraviolet wavelengths known to induce the great majority of human skin cancers -- and compared the incidence of squamous-cell carcinoma in the two groups. In the mice lacking Perp, skin tumors arose faster, and were both more abundant and aggressive, than in normal mice.

"Perp loss promotes cancer in three different ways," Attardi said. The scientists observed the overproduction of inflammatory molecules (known to promote cancer), the increased survival of cells that should have committed suicide in response to excessive UVB and a loss of cell-cell adhesion commensurate with the loss of desmosomes.

At the same time, the mice with early stages of skin cancer continued to retain normal function of another variety of adhesion junction complex that has been observed to be dysfunctional in advanced cancer stages, such as metastasis. What the researchers have shown in this study is that the earlier loss of desmosome function is enough, by itself, to promote tumor growth.

The investigators also observed a substantial disappearance of Perp in biopsied human squamous-cell carcinoma samples. Once again, the alternative adhesion junction complexes that have been implicated in later stages of cancer appeared to be present and functioning normally in almost all of these samples, further supporting the idea that desmosome loss due to Perp inactivation can be an early, defining event in cancer progression.

Squamous-cell cancer is the second-most common of all human skin cancers after basal-cell carcinoma, striking hundreds of thousands per year in the United States. The Attardi lab findings could be applicable to basal-cell carcinoma, too. On the order of 1 million new cases of basal-cell carcinoma, by far the most common skin cancer, are reported in the United States each year. Fortunately these cancer types have very high cure rates -- largely because they're so easily spotted that tumors can be removed long before they advance to a dangerous state.

But epithelial tissues at many far less accessible sites (for example, internal organs such as esophagus and pancreas) develop cancers that are caught late -- often too late for effective treatment. Most healthy epithelial cells harbor desmosomes on their surfaces, suggesting that these ubiquitous structures' depletion or dysfunction may factor into a number of different tumor types.

"We think our study may also be relevant to other cancers, such as head-and-neck cancer, which is much deadly than skin cancer," she said. More than 35,000 new head-and-neck cancer cases are diagnosed each year in the United States.

A tumor-progression marker that could be detected early might prove useful not only in diagnosing and staging tumors but also in enhancing physicians' treatment decisions. "You might use more aggressive treatment on tumors lacking Perp, but spare patients with tumors that have Perp from the most-aggressive treatments," said Attardi. "Understanding this protein's role better may also point to new therapeutic approaches."

The study, whose first author was Veronica Beaudry, a graduate student in Attardi's laboratory, was supported by funding from the National Institutes of Health. Other Stanford co-authors were Dadi Jiang, PhD, and Rachel Dusek, PhD, postdoctoral researchers in Attardi's lab; research associate Eunice Park; Hannes Vogel, MD, professor of pathology; and Stevan Knezevich, MD, PhD, Vogel's former associate in pathology.

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Sleepy head?

Monday 21 October 2013

Islamabad, Oct 22 (Newswire):, Sleep is one of the most essential and relaxing ways for the body to recuperate.

Unfortunately, some people have trouble sleeping due to various causes and as a result of sleep deprivation; the individual becomes vulnerable to several illnesses. This inability to sleep is termed insomnia.

Insomnia includes a general dissatisfaction about one's quality of sleep, or about sleep being delayed at night or shortened in the morning.

The good news is that there are several psychological strategies that have been evaluated as potentially useful treatments for insomnia.

These behavioural techniques can be effective alternatives to many sleep inducing drugs that have addictive properties and other side effects. Read on to know some useful strategies to get that essential good night's rest.

It is essential to abide by these principles for several weeks to establish an efficient and regular sleep-wake pattern. Insomnia is secondary to many psychological disorders, and a diagnosis and management of this primary condition by a trained mental health professional is absolutely necessary to resolve insomnia.

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Soybeans no longer 'a musical fruit?'

slamabad, Oct 22 (Newswire): Soybeans may drop off the list of musical fruit. Scientists in Singapore are reporting victory over some consumers' No. 1 complaint about soy products — the "flatulence factor" caused by indigestible sugars found in soy.

Scientists have now developed a method for significantly reducing the amount of flatulence-causing carbohydrates in soy yogurt while raising the levels of healthy antioxidants known as isoflavones.

In the study, Dejian Huang and colleagues note that soy yogurt has a global market share of only 1.9 percent, even though it has a number of health advantages over dairy-based yogurt. That's partly because of the flatulence-causing compounds in soy.

"It would be desirable to remove the flatulence-causing raffinose and stachyose from the soy yogurt to improve consumers' preferences. The objective of this study was to develop a new soy yogurt enriched with isoflavones with reduced levels of flatulence-causing oligosaccharides," the scientists said.

The researchers grew soybeans in the presence of a fungus that produced enzymes capable of degrading the undesired sugars.

"We have demonstrated for the first time that germinated black soybeans under fungal stress can be fermented into a soy yogurt which features a low amount of flatulence-causing oligosaccharides but with a significant level of isoflavones," says Huang.

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Cataract surgery saves lives, dollars by reducing auto crashes, research finds

Islamabad, Oct 22 (Newswire): Cataract surgery not only improves vision and quality of life for older people, but is also apparently a way to reduce the number of car crashes.

The research is being presented at the Scientific Program of the 2010 American Academy of Ophthalmology (AAO) -- Middle East-Africa Council of Ophthalmology (MEACO) Joint Meeting.

There's no question that good vision is essential to avoiding auto crashes. But what's the actual impact of a common, vision-improving treatment like cataract removal on crash rates?

And is it significant enough that health systems should make sure people don't wait months between cataract diagnosis and surgery? To answer these questions researcher Jonathon Ng, MD, studied accident rates for Western Australian residents before and after cataract surgery on the first eye.

Cataract-when the eye's crystalline lens becomes clouded and hardens-is the leading cause of vision impairment in older people. By age 60 many people have some lens opacity, and by 70 nearly all have cataract in one or both eyes. Surgical removal of cataract followed by implantation of intraocular lenses dramatically improves vision for most patients.

In Dr. Ng's study, 27,827 patients who had a cataract removed from one eye between 1997 and 2006 were included. Patient records were linked to the Western Australian Road Injury Database to identify those involved in a motor vehicle crash 12 months prior to and 12 months following their surgery dates. All patients were aged 60+ years. The majority of patients involved in crashes were males aged 70-79 who lived in metropolitan areas. Dr. Ng's research colleagues were based at Curtin University and the Eye & Vision Epidemiology Research Group.

"We found cataract surgery reduced the frequency of all crashes by 12.6% after accounting for other potential confounders, " Dr. Ng said, "and the cost savings from this reduction amounted to AUD $4.3 million. Each operation saved about $150 in crash costs. By including all crashes rather than just fatal and hospitalization crashes, all possible benefits of cataract surgery were taken into account."

In Australia and other countries, people often have to wait weeks or months to receive surgery after cataract is diagnosed.

This study argues that this delay significantly impacts not only patients' quality of life, but public safety and healthcare, and property costs. The authors say research is needed to compare crash rates before and after cataract surgery on patients' second eyes.

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Pill can make women 'overly jealous, possessive'

Sunday 20 October 2013

Islamabad, Oct 21 (Newswire): The next time you see your woman acting overly jealous or possessive, you might want to take a peek into her medicine cabinet, for it might be the Pill to blame.

A study by Stirling University's Dr Craig Roberts claims sex hormones in the contraceptive Pill bring out the green-eyed monster, making a woman more possessive and more likely to fret about her husband or boyfriend's fidelity.

The drug is also credited with making women broody, changing their taste in men and even boosting intelligence.

Progesterone, however, was not implicated in jealousy, suggesting that progesterone-only versions of the Pill play less havoc with women's emotions.

"It seems that women, and perhaps pharmaceutical providers, are not fully aware of the range of potential psychological side-effects associated with pill use and more specifically brand choice", Roberts said.

Other studies have suggested that the Pill makes certain areas of women's brains bigger, makes women broody and may also alter a sense of smell.

The study is published in the journal Personality and Individual Differences.

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Food allergies likely to afflict autumn babies

Islamabad, Oct 21 (Newswire): Babies born in autumn are at a higher risk of developing food allergies, a new study says.

Those born in October and November are almost twice as likely to show a form of food intolerance by four years, than those born in June and July.

Some 9.5 percent of autumn babies had an allergic response compared to five percent of summer babies, says a Finnish study.

Autumn babies were three times as likely to have an allergy to milk and eggs as summer babies.

The researchers believe the variation is due to the foetus's exposure to pollen at a critical time during pregnancy, according to the Journal of Epidemiology and Community Health.

At around the end of the third month the foetus begins to produce antibodies.

Pollen appears to trigger the development of a type of antibody known as immunoglobin E, which is well known to be linked to food allergies, according to the study authors.

Kaisa Pyrhönen, of the Institute of Health Sciences at the University of Oulu in Finland, wrote: "Children having their early gestational period in the pollen season for broad-leafed trees are more prone to sensitisation to food allergies than other children."

Exactly why pollen exposure appears to trigger immunoglobin E remains unknown.

The study looked at 5,920 children born in one region of Finland between April 2001 and March 2006, of which 961 had been tested for food allergies.

Previous research has shown that babies born in autumn or winter are more prone to eczema and wheezing, identified by higher levels of circulating antibodies to allergies in their blood than those born in spring or summer.

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Testosterone protects against heart disease

Islamabad, Oct 21 (Newswire): Aggressive men with higher testosterone levels are less likely to die of heart disease, says a new study.

Medical scientists who followed 930 men diagnosed with coronary heart disease found that those with low testosterone were almost twice as likely to die over a seven-year period, than those with normal levels of the hormone.

The study, led by Professor Kevin Channer of Royal Hallamshire Hospital in Sheffield, adds weight to recent research overturning the widely-held belief that testosterone increases heart disease risk.

During the monitoring period one in five of those with low testosterone levels died, compared to one in eight (12 percent) of those with normal levels.

Even having what the researchers described as 'borderline' low levels of testosterone raised the risk of an early death, both from heart disease and other causes, according to the journal Online First Heart.

Previous studies have shown that healthy men with low testosterone are more likely to die before those with normal levels.

This study, published on Wednesday, shows a similar effect in those already diagnosed with heart disease.

Channer, a cardiologist, said testosterone was struggling to overcome an image problem caused by the mistaken belief that it caused health problems.

He said there were no studies that showed normal, physiological levels of the hormone were harmful.

The mistaken belief that it was harmful was based on studies of "testosterone abuse" among athletes, who had injected "industrial quantities" of it, giving themselves levels more than 100 times what the body produced.

Theirs was the fourth study showing testosterone's protective properties at normal levels, he added.

Prescription of replacement testosterone for men with low levels, who also have Type-2 diabetes or heart disease, has risen markedly in recent years.

"If it can be shown beyond reasonable doubt that mortality is reduced by replacement testosterone to physiological levels, then it should be given to all men with low levels," Channer argued.

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HRT raises risk of kidney stones

Sunday 13 October 2013

Islamabad, Oct 14 (Newswire): Women who undergo hormone replacement therapy (HRT) for menopause are much more likely to develop painful kidney stones.

Researchers from the University of Texas, US, studied 24,000 post-menopausal women over five years. They found that those who took hormones had a 21 per cent higher risk of getting kidney stones compared to those who took a dummy pill.

The risks were similar for women taking Prempro, pills containing estrogen plus progestin - or Premarin, estrogen-only pills.

Recent data suggests that about six per cent of postmenopausal women develop kidney stones, according to the journal Archives of Internal Medicine.

The kidneys remove waste products from the blood and transfer them into the ureter. Occasionally, this waste can form into crystals that collect together into stone-like lumps.

They can grow to the size of golf balls and cause severe pain. If the stones block the urinary system, they can cause infection and kidney damage.

Large stones are sometimes treated with non-invasive shock wave therapy or surgery.

Study leader, Naim Maalouf, said women considering HRT to ease hot flushes and other symptoms such as mood swings should look at the bigger picture, weighing those benefits against the risks for kidney stones.

He added that HRT has also been linked with far more serious health problems such as breast cancer and heart attacks.

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Toothpaste may be spread superbugs

Islamabad, Oct 14 (Newswire): An antibacterial chemical commonly used in toothpastes may pose a threat to your health, a European Union committee has warned.

The EU's Scientific Committee on Consumer Safety, which provide scientific advice to the European Commission related to non-food issues, has said that triclosan may promote widespread bacterial resistance to antibiotics.

The committee has also called for further safety studies to reconfirm its role in spreading superbugs.

The chemical is also used in handwashes and cosmetics.
Laboratory studies have shown triclosan can trigger gene mutations in bacteria, enabling them to protect themselves against it.

When this happens, the bacteria release proteins which transport this new-found protection to other bacteria.

This 'cross-resistance' has the potential to undermine the effectiveness of antibiotics and other life-saving medicines.
Studies have shown there are already bacterial mutations of E. coli, salmonella and listeria, which have some degree of resistance to triclosan.

Some strains of the hospital superbug MRSA have also developed low levels of triclosan resistance.
Triclosan was developed almost 50 years ago and was first used as a surgical scrub.

The US Food & Drug Administration has also found evidence that triclosan is a hormone disruptor. But the chemical is so commonly used that it is found in the urine of 75 per cent of the American population, a recent CDC report said.

Meanwhile, reacting to the reports, Colgate Palmolive has said the benefits of adding triclosan to its Total range outweigh the risk.
A spokeswoman said: "Colgate Total toothpaste is clinically proven to reduce the bacteria and plaque that can lead to gingivitis."

"This is an important benefit because there is a significant and growing body of scientific research on the association between periodontal disease and systemic health conditions, including heart disease, stroke and diabetes."

GlaxoSmithKline, a leading healthcare company, has however adopted a more cautious approach and decided to withdraw triclosan from its range of products.

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US begins first trial with human embryonic stem cells

Islamabad, Oct 14 (Newswire): US doctors have begun the first tests of human embryonic stem cells in patients, treating a man with spinal cord injuries in a landmark trial of the controversial process, the Geron Corporation said.

The patient began the pioneering treatment on Friday with an injection of the biotech company's human embryonic stem cells, as part of a clinical trial that aims to test safety and efficacy toward regaining sensation and movement.

The treatment took place at the Shepherd Center in Atlanta, Georgia, a spokeswoman for the hospital said, declining to give further details due to patient privacy concerns.

The Phase-I trial is expected to involve around 10 patients. Participants in the human trials must be severely injured and start treatment with Geron's product, GRNOPC1, seven to 14 days after sustaining their injury.

Patients will be given a single injection of two million of Geron's GRNOPC1 cells in the trial.

Those taking part will be followed up for one year to monitor safety and also to see if they have regained any sensory function or movement in their lower extremities.

If the initial group of subjects shows no negative side-effects, Geron plans to seek FDA approval to extend the study to increase the dose of GRNOPC1 and to include patients with "as broad a range of severe spinal cord-injured patients as medically appropriate.

"The ultimate goal for GRNOPC1 is to inject it directly into the spinal cord lesions of injured humans where it would, Geron hopes, prompt damaged nerve cells to regrow, enabling patients to eventually recover feeling and movement.

Geron began working with human embryonic stem cells in 1999.
Back then, "many predicted that it would be a number of decades before a cell therapy would be approved for human clinical trials," Geron's president and chief executive Thomas Okarma said in a statement.

Okarma described Monday's start of the clinical trial as "a milestone for the field of human embryonic stem cell-based therapies."GRNOPC1 is made up of cells containing precursors to oligodendrocytes — multi-tasking cells that occur in the nervous system.
Oligodendrocytes are lost in spinal cord injury, resulting in myelin and neuronal loss which cause paralysis in many patients.
Preclinical studies of GRNOPC1 found that when it was injected into the injury site of animals with spinal cord injuries, it migrated throughout the lesion site and matured into oligodendrocytes.

Those oligodendrocytes then re-lined axons with myelin, the insulating layers of cell membrane that wrap around the axons of neurons to enable them to conduct electrical impulses.

The process produced biologicals that enhance the survival and function of neurons, resulting in significantly improved locomotion in the treated animals.

In the animal trials, GRNOPC1 was injected seven days after the injury was sustained.

Every year, some 12,000 people in the United States sustain spinal cord injuries, usually in automobile accidents or from falls, gunshot wounds and sports.

Geron got clearance in January 2009 from the Food and Drug Administration to conduct human trials of GRNOPC1.

Around six weeks later, President, Barack Obama, reversed a ban on federal funding for research on human embryonic stem cells, which had been imposed by his predecessor at the White House, George W. Bush.

But the clinical trials of GRNOPC1 remained on hold for more than a year while the US courts wrangled about whether lifting the ban on embryonic stem cell research was legal.

Backers of the research believe the field holds huge potential for treating serious diseases including cancer and Alzheimer's, and even for reversing paralysis.

Opponents argue that living embryos are destroyed in order to obtain the potentially life-saving embryonic stem cells.

Legislation passed by Congress in 1996 bans federal funding for research in which human embryos are either destroyed or discarded.

In lifting the ban on embryonic stem cell research, the Obama administration argued the research does not require disposal or destruction of the embryos, which were created for in-vitro fertilization treatments but never used.

Last month, a US appeals court ruled that the federal funding can continue, dissolving a lower court's ban.

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Sleeping with light on may lead to weight gain: Study

Saturday 12 October 2013

Islamabad, Oct 13 (Newswire): Too much light at night appears to lead to weight gain, according to a report, based on studies of mice that provide fresh clues on obesity.

The researchers found that mice exposed to a dim light at night over eight weeks had a weight gain that was about 50 per cent more than other mice that lived in a standard light-dark cycle.

"Although there were no differences in activity levels or daily consumption of food, the mice that lived with light at night were getting fatter than the others," said Laura Fonken, the lead author of the study and a researcher at the Ohio State University.

The study, which appears in the Proceedings of the National Academy of Sciences journal, said the weight gain could be a sign that light has an effect on the metabolism.

"Something about light at night was making the mice in our study want to eat at the wrong times to properly metabolise their food," said Randy Nelson, co-author of the study and professor of neuroscience and psychology at Ohio State.

If these results are confirmed in humans, it would suggest that late-night eating might be a particular risk factor for obesity, Nelson said.

In one study, mice were housed in one of three conditions: 24 hours of constant light, a standard light-dark cycle that included 16 hours of light and eight hours of dark, or 16 hours of daylight and eight hours of dim light.

Results showed that, compared to mice in the standard light-dark cycle, those in dim light at night had significantly higher increases in body mass, beginning in the first week of the study and continuing throughout.

By the end of the experiment, dim-light-at-night mice had gained about 12 grams of body mass, compared to eight grams for those in the standard light-dark cycle.

Mice in constant bright light also gained more than those in the standard light-dark cycle, but Nelson said the mice exposed to dim light was a more important comparison for humans.

Although the mice exposed to dim light did not eat more than others, they did change when they ate, consuming more food at night.

Since the timing of eating seemed significant, the researchers did a second study, with a change: instead of having food freely available at all times, food was restricted to either the times when mice would normally be active or when they would normally be at rest.

In this experiment, mice exposed to the dim light at night did not have a greater gain in body mass than did the others when their food was restricted to times when they normally would be active.
"When we restricted their food intake to times when they would normally eat, we didn't see the weight gain," Fonken said.

"This further adds to the evidence that the timing of eating is critical to weight gain."The researchers said the findings offer clues for causes of the obesity epidemic in Western countries.

"Light at night is an environmental factor that may be contributing to the obesity epidemic in ways that people don't expect," Nelson said. "Societal obesity is correlated with a number of factors including the extent of light exposure at night."

He said prolonged computer use and television have previously been linked to obesity but because they are associated with a lack of physical activity.

"It may be that people who use the computer and watch the TV a lot at night may be eating at the wrong times, disrupting their metabolism," Nelson said.

"Clearly, maintaining body weight requires keeping caloric intake low and physical activity high, but this environmental factor may explain why some people who maintain good energy balance still gain weight."

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Newborns with jaundice more likely to develop autism: Study

Islamabad, Oct 13 (Newswire): Infants born with jaundice are at much greater risk of developing autism, a study showed.

The study published in the US journal 'Pediatrics' found full-term infants born in Denmark between 1994 and 2004 who had jaundice were 67 per cent more likely to develop autism.

Neonatal jaundice is usually caused by elevated production of bilirubin, a substance found in bile that results from the normal breakdown of red blood cells.

Jaundice is seen in 60 per cent of term infants and usually resolves within the first week of life, but prolonged exposure to high bilirubin levels is neurotoxic and can cause lifelong developmental problems, the study says.

In this study researchers found the risk of autism was higher if the mother had had previous children, or if the child was born between October and March.

The risk for autism disappeared if the child was a firstborn child or was born between April and September. Authors suggest the seasonal difference may be due to different levels of exposure to daylight, which has an effect on jaundice, or due to infections.

The difference in risk in firstborn versus subsequent children could be due to different levels of antibodies in women who have had multiple pregnancies, or it could reflect different levels of access to health care in the first days after delivery.

In Denmark, women with healthy term newborns who have already had children are discharged soon after delivery.

Women having their first child remain in the hospital for three to four days, and so jaundice may be diagnosed while the infant is still in the hospital.

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Excess tummy fat? Watch out!

Islamabad, Oct 13 (Newswire): The Imperial College, London and the University of Leeds reviewed seven research publications, all of which showed excess tummy fat or a potbelly to be predictors of bowel cancer.

Researchers from these universities have claimed that for every inch of waist size that is above a healthy waist measurement, the likelihood of bowel cancer can rise by up to three per cent.

Therefore, obesity, especially around the tummy area can lead to cancer. It is a fact that several people in India have potbellies and as a result, they are at a higher risk of developing bowel cancer. To understand how obesity leads to cancer, we need to first understand obesity and how it affects our health.

People who are obese have an abnormally high and unhealthy proportion of body fat. In fact, obesity and physical inactivity accounts for 25 to 30 per cent of cancers including colon cancer, breast cancer, cancer of the uterus and cancer of the oesophagus.
If a woman has a waist size of more than 32 inches and a man has a waist of more than 35 inches, it could mean that they are at a higher risk of getting cancer. In fact, according to a report published in the journal of the American College of Cardiology, people with large waist-to-hip ratios (WHRs) are almost twice as likely to have calcium deposits, which indicate the onset of atherosclerosis in the arteries of their hearts that can lead to heart attacks.

It has also been found the risk of developing breast cancer and dying from it after menopause is higher among obese women.

How to reduce the risk?
The most common form of cancer caused due to obesity is colon cancer. In 2002, a major review of observational trials found that physical activity reduced the risk of developing colon cancer by 50 per cent. This risk reduction occurred even with moderate levels of physical activity. Moderate exercise such as brisk walking for three to four hours a week has been shown to lower the risk.

Therefore, people should try to stay fit without being over or under weight. It is especially important to maintain a healthy waist size as even people who are seemingly thin, could get cancer if they carry a big belly. Individuals who have high saturated fats in their diet are at a risk of developing a potbelly. Foods rich in saturated fats like meat, butter, processed foods and many junk foods should be avoided.

It is a common misconception that "pot exercise" (exercising a specific muscle or location of the body) most effectively burns fat in the desired body part but this is not true.

Spot exercise is beneficial for building specific muscles, but it has little effect on the fat in that area of the body or on the body's distribution of fat.

The same applies to sit-ups, crunches and other abdominal exercises. These exercises may be useful in building the abdominal muscle but they have little effect on the adipose tissue located there.

Therefore, physical exercises that involve the entire body like jogging or brisk walking are most effective to help you stay in shape.

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New technique identifies first events in tumor development

Friday 11 October 2013

Islamabad, Oct 12 (Newswire): A novel technique that enables scientists to measure and document tumor-inducing changes in DNA is providing new insight into the earliest events involved in the formation of leukemias, lymphomas and sarcomas, and could potentially lead to the discovery of ways to stop those events.

Developed by a team of researchers at the National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS), and the National Cancer Institute (NCI), both parts of the National Institutes of Health, and The Rockefeller University, the technology focuses on chromosomal rearrangements known as translocations.

Translocations occur when a broken strand of DNA from one chromosome is erroneously joined with that of another chromosome. Sometimes these irregularities can be beneficial in that they enable the immune system to respond to a vast number of microorganisms and viruses. However, translocations can also result in tumors.

Translocations can take place during the course of normal cell division, when each chromosome -- a single strand of DNA containing many genes -- is copied verbatim to provide genetic information for the daughter cells. Sometimes, during this process, byproducts of normal metabolism or other factors can cause breaks in the DNA.

"The cell expresses specific enzymes whose primary purpose is to repair such lesions effectively, but when the enzymes mistakenly join pieces of two different chromosomes, the cell's genetic information is changed," said Rafael C. Casellas, Ph.D., senior investigator in the Genomics and Immunity Section at the NIAMS, who led the research team along with Michel C. Nussenzweig, M.D., Ph.D., from Rockefeller.

Casellas likens the phenomenon to breaking two sentences and then rejoining them incorrectly. For example, "The boy completed his homework." and "The dog went to the vet." might become "The dog completed his homework." or "The boy went to the vet." When a cell gets nonsensical information such as this, it can become deregulated and even malignant.

Scientists have known since the 1960s that recurrent translocations play a critical role in cancer. What was unclear was how these genetic abnormalities are created, since very few of them were studied, and only within the context of tumors, said Casellas. To better understand the nature of these tumor-inducing rearrangements, the authors had to create a system to visualize their appearance in normal, non-transformed cells.

The system the teams created involved introducing enzymes that recognize and cause damage at a particular sequence in the DNA into cells from mice, thereby constructing a genome where a unique site is broken continuously. The group then used a technique called polymerase chain reaction -- which allows scientists to quickly amplify short sequences of DNA -- to check all the sites in the genome that would get translocated to this particular break. Using this technique, they were able to examine more than 180,000 chromosomal rearrangements from 400 million white blood cells, called B cells.

Based on this large data set, the scientists were able to make several important observations about the translocation process. They learned that most of the translocations involve gene domains, rather than the space on the DNA between the genes. They also found that most translocations target active genes, with a clear bias for the beginning of the gene, as opposed to its middle or end. The team also showed that a particular enzyme that normally creates DNA breaks in B cells dramatically increases the incidence of translocations during the immune response. This feature explains the long-standing observation that more than 95 percent of human lymphomas and leukemias are of B cell origin.

"This knowledge is allowing us to understand how tumors are initiated," said Casellas. "It is the kind of information that in the near future, might help us prevent the development of cancer."

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Big tobacco knew radioactive particles in cigarettes posed cancer risk but kept quiet

Islamabad, Oct 12 (Newswire): Tobacco companies knew that cigarette smoke contained radioactive alpha particles for more than four decades and developed "deep and intimate" knowledge of these particles' cancer-causing potential, but they deliberately kept their findings from the public, according to a new study by UCLA researchers.

The analysis of dozens of previously unexamined internal tobacco industry documents, made available in 1998 as the result of a legal settlement, reveals that the industry was aware of cigarette radioactivity some five years earlier than previously thought and that tobacco companies, concerned about the potential lung cancer risk, began in-depth investigations into the possible effects of radioactivity on smokers as early as the 1960s.
"The documents show that the industry was well aware of the presence of a radioactive substance in tobacco as early as 1959," the authors write. "Furthermore, the industry was not only cognizant of the potential 'cancerous growth' in the lungs of regular smokers, but also did quantitative radiobiological calculations to estimate the long-term lung radiation absorption dose of ionizing alpha particles emitted from cigarette smoke." The study, published in Nicotine & Tobacco Research, the peer-reviewed journal of the Society for Research on Nicotine and Tobacco, adds to a growing body of research detailing the industry's knowledge of cigarette smoke radioactivity and its efforts to suppress that information.

"They knew that the cigarette smoke was radioactive way back then and that it could potentially result in cancer, and they deliberately kept that information under wraps," said the study's first author, Hrayr S. Karagueuzian, a professor of cardiology who conducts research at UCLA's Cardiovascular Research Laboratory, part of the David Geffen School of Medicine at UCLA. "Specifically, we show here that the industry used misleading statements to obfuscate the hazard of ionizing alpha particles to the lungs of smokers and, more importantly, banned any and all publication on tobacco smoke radioactivity."

The radioactive substance -- which the UCLA study shows was first brought to the attention of the tobacco industry in 1959 -- was identified in 1964 as the isotope polonium-210, which emits carcinogenic alpha radiation. Polonium-210 can be found in all commercially available domestic and foreign cigarette brands, Karagueuzian said, and is absorbed by tobacco leaves through naturally occurring radon gas in the atmosphere and through high-phosphate chemical fertilizers used by tobacco growers. The substance is eventually inhaled by smokers into the lungs.

The study outlines the industry's growing concerns about the cancer risk posed by polonium-210 inhalation and the research that industry scientists conducted over the decades to assess the radioactive isotope's potential effect on smokers -- including one study that quantitatively measured the potential lung burden from radiation exposure in a two-pack-a-day smoker over a two-decade period.

Karagueuzian and his colleagues made independent calculations using industry and academic data and arrived at results that very closely mirrored those of that industry study, which was conducted nearly a quarter-century ago. They then compared those results to rates used by the Environmental Protection Agency to estimate lung cancer risk among individuals exposed to similar amounts of alpha particle-emitting radon gas in their homes.

"The gathered data from the documents on the relevant radiobiological parameters of the alpha particles -- such as dose, distribution and retention time -- permitted us to duplicate the industry's secretly estimated radiation absorbed dose by regular smokers over a 20- or 25-year period, which equaled 40 to 50 rads," he said. "These levels of rads, according to the EPA's estimate of lung cancer risk in residents exposed to radon gas, equal 120 to 138 deaths per 1,000 regular smokers over a 25-year period."
Despite the potential risk of lung cancer, tobacco companies declined to adopt a technique discovered in 1959 and then another developed in 1980 that could have helped eliminate polonium-210 from tobacco, the researchers said. The 1980 technique, known as an acid-wash, was found to be highly effective in removing the radioisotope from tobacco plants, where it forms a water-insoluble complex with the sticky, hair-like structures called trichomes that cover the leaves.

And while the industry frequently cited concerns over the cost and the possible environmental impact as rationales for not using the acid wash, UCLA researchers uncovered documents that they say indicate the real reason may have been far different.

"The industry was concerned that the acid media would ionize the nicotine, making it more difficult to be absorbed into the brains of smokers and depriving them of that instant nicotine rush that fuels their addiction," Karagueuzian said. "The industry also were well aware that the curing of the tobacco leaves for more than a one-year period also would not eliminate the polonium-210, which has a half-life of 135 days, from the tobacco leaves because it was derived from its parent, lead-210, which has a half-life of 22 years."

Karagueuzian said the insoluble alpha particles bind with resins in the cigarette smoke and get stuck and accumulate at the bronchial bifurcations of the lungs, forming "hot spots," instead of dispersing throughout the lungs. In fact, previous research on lung autopsies in smokers who died of lung cancer showed that malignant growths were primarily located at the same bronchial bifurcations where these hot spots reside.

"We used to think that only the chemicals in the cigarettes were causing lung cancer," Karagueuzian said. "But the case of the these hot spots, acknowledged by the industry and academia alike, makes a strong case for an increased probability of long-term development of malignancies caused by the alpha particles. If we're lucky, the alpha particle-irradiated cell dies. If it doesn't, it could mutate and become cancerous."

Karagueuzian said the findings are very timely in light of the June 2009 passage of the Family Smoking Prevention and Tobacco Control Act, which grants the U.S. Food and Drug Administration broad authority to regulate and remove harmful substances -- with the exception of nicotine -- from tobacco products. The UCLA research, he said, makes a strong case that the FDA ought to consider making the removal of alpha particles from tobacco products a top priority.

"Such a move could have a considerable public health impact, due to the public's graphic perception of radiation hazards," he said.

To uncover the information, Karagueuzian and his team combed through the internal tobacco industry documents made available online as part of the landmark 1998 Tobacco Master Settlement Agreement. Documents from Philip Morris, R.J. Reynolds, Lorillard, Brown I Williamson, the American Tobacco Company, the Tobacco Institutes and the Council for Tobacco Research, as well as the Bliley documents, were examined, Karagueuzian said.

The team searched for key terms such as "polonium-210," "atmospheric fallout," "bronchial epithelium," "hot particle" and "lung cancer," among others.

Karagueuzian said the earliest causal link between alpha particles and cancer was made in around 1920, when alpha particle-emitting radium paint was used to paint luminescent numbers on watch dials. The painting was done by hand, and the workers commonly used their lips to produce a point on the tip of the paint brush. Many workers accumulated significant burdens of alpha particles through ingestion and absorption of radium-226 into the bones and subsequently developed jaw and mouth cancers. The practice was eventually discontinued.

Another example involves liver cancer in patients exposed to chronic low-dose internal alpha particles emitted from the poorly soluble deposits of thorium dioxide after receiving the contrast agent Thorotrast. It has been suggested that the liver cancers resulted from point mutations of the tumor suppressor gene p53 by the accumulated alpha particles present in the contrast media. The use of Thorotrast as contrast agent was stopped in the 1950s.

In addition to Karagueuzian, authors of the study include the late Amos Norman, professor emeritus in the departments of radiation oncology and radiological sciences at UCLA; James Sayre, of the departments of biostatistics and radiological sciences at UCLA; and Celia White, who served from 1999 to 2002 as director of content and services at the Legacy Tobacco Documents Library, which contains more than 13 million documents created by major tobacco companies related to their advertising, manufacturing, marketing, sales and scientific research activities.

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