Friday, October 29, 2010

Researchers Build Colony of Colon Cancer Stem Cells to Test New Approach to Therapy

University of Pittsburgh researchers have devised a three-dimensional system in laboratory culture that mimics the growth patterns of colon cancer stem cells in patients. Their findings were presented at the American Association for Cancer Research special conference on Colorectal Cancer: Biology to Therapy, held Oct. 27-30, 2010.
The assay, which uses green fluorescent "reporter" proteins to watch the process of stem cell differentiation, is designed to understand how these cancer stem cells behave, and to identify and test therapies that could halt production of the endless generations of new cancer stem cells that continually revive a tumor.

"Colon cancer stem cells are thought to be the root of therapy resistance, metastases and recurrence in colon cancer, so our approach is to find a way to remove the ability of these stem cells to self-renew," said the study's lead investigator, Julie Chandler, a graduate student in pathology.
"While many labs have investigated notch inhibitors and others have investigated cancer stem cells, our unique approach combines both in a three-dimensional culture that mimics what happens in patients," she said. Animal models, which are immunodeficient and use human xenografs, may not provide accurate information about colon cancer stem cell behavior, Chandler added.
Colon cancer stem cells have the ability to repopulate a tumor after treatment, using stem cells that are resistant to treatment. Such treatment forces a response in these cells, which are genetically unstable, forcing the cells to adapt and pass on resistance to daughter stem cells.
In the same way that adult intestinal stem cells self-renew, colon stem cells give rise to different kinds of cells, including daughter stem cells and fully differentiated cells, such as the goblet epithelial cells that line the colon. Researchers would like to force cancer stem cells to differentiate and behave like goblet cells because these cells do not self renew. Chandler said the notch pathway that controls differentiation in stem cells is inactivated in goblet cells. One way to possibly do that is to use agents that shut down the notch pathway, such as gamma secretase inhibitors, she said. Cancer treatment may then be able to destroy tumors that are now populated by fully differentiated goblet cells.
In their new assay, Chandler used a three-dimensional culture matrix in which she could watch a single cancer stem cell divide and produce progeny, which is called an "independent organoid."
To see the kind of cells a colon cancer stem cell produces, they labeled a protein that is specific only to goblet cells. To date, the researchers have found that some colon cancer stem cells produce many differentiated cells, such as goblets and others, while others produce more primitive, self-renewing cells.
In this way, the researchers can test the ability of notch pathway inhibitors to force progeny cancer stem cells to differentiate into harmless goblet cells.
"Green goblet cells are no longer capable of promoting cancer growth," Chandler said. "It may be that a certain notch inhibitor or similar drug is all that is needed to prevent cancer recurrence and metastasis that so often follows an initial response to treatment. This new tool will help us determine if that is so."

Is the Shape of a Genome as Important as Its Content?

 If there is one thing that recent advances in genomics have revealed, it is that our genes are interrelated, "chattering" to each other across separate chromosomes and vast stretches of DNA. According to researchers at The Wistar Institute, many of these complex associations may be explained in part by the three-dimensional structure of the entire genome.

A given cell's DNA spends most of its active lifetime in a tangled clump of chromosomes, which positions groups of related genes near to each other and exposes them to the cell's gene-controlling machinery. This structure, the researchers say, is not merely the shape of the genome, but also a key to how it works.
Their study, published online as a featured article in the journal Nucleic Acids Research, is the first to combine microscopy with advanced genomic sequencing techniques, enabling researchers to literally see gene interactions. It is also the first to determine the three-dimensional structure of the fission yeast genome, S. pombe. Applying this technique to the human genome may provide both scientists and physicians a whole new framework from which to better understand genes and disease, the researchers say.
"People are familiar with the X-shapes our chromosomes form during cell division, but what they may not realize is that DNA only spends a relatively small amount of time in that conformation," said Ken-ichi Noma, Ph.D., an assistant professor in Wistar's Gene Expression and Regulation program and senior author of the study. "Chromosomes spend the majority of their time clumped together in these large, non-random structures, and I believe these shapes reflect various nuclear processes such as transcription."
To map both individual genes and the overall structure of the genome, Noma and his colleagues combined next generation DNA sequencing with a technique called chromosome conformation capture (3C). They then used fluorescent probes to pinpoint the exact location of specific genes through a microscope. With these data, the researchers were able to create detailed three-dimensional computer models of the yeast genome.
Using this novel approach, the researchers can view genes as they interact with each other. Noma and his colleagues can view where highly active genes are located, or see if genes that are turned on and off together also reside near each other in the three-dimensional structure of the genome. In total, the Wistar researchers also studied 465 so-called gene ontology groups -- groups of genes that share a related purpose in the cell, such as structure or metabolism.
"When the chromosomes come together, they fold into positions that bring genes from different chromosomes near each other," Noma said. "This positioning allows the processes that dictate how and when genes are read to operate efficiently on multiple genes at once."
This structure is not merely an accident of chemical attractions within and among the chromosomes -- although that is certainly a part of the larger whole -- but an arrangement guided by other molecules in the cell to create a mega-structure that dictates genetic function, Noma says. He envisions a scenario where accessory molecules, such as gene-promoting transcription factors, bind to DNA and contribute to the ultimate structure of the genome as the chromosomes fold together.
"I believe we are looking at a new way to visualize both the genome itself and the movements of all the various molecules that act on the genome," Noma said.
According to the Wistar scientists, their techniques are scalable to the human genome, even though fission yeast only has three chromosomes. In fact, the researchers found signs of "transcription factories" -- clusters of related genes that are read, or "transcribed," at discrete sites -- which have been proposed to exist in mammals.

Monday, October 18, 2010

Removing healthy cells surrounding tumours drastically cuts chances of breast cancer returning

Women suffering from breast cancer can reduce their chance of the disease returning if they let surgeons remove small amounts of the healthy tissue surrounding the tumour.
Research has shown that the chance of the disease returning can be reduced by more than 90 per cent if at least 2mm of normal cells surrounding the cancer are taken out.
Surgery to remove part of a woman's breast is often an extremely distressing experience and many specialists will try and preserve as much healthy tissue as possible for cosmetic reasons.
Treatment: Early screening is vital but now doctors say that reducing the chances of breast cancer returning can depend on how much healthy tissue around the tumour is removed
But this latest research has prompted doctors to call for new guidelines to try and reduce the chances of the cancer returning.
The amount of breast tissue cut away varies between individual surgeons. 
While some will cut away just 1mm surrounding the tumours, others will remove more than 1cm in the hope the tumours will be less likely to return.
Doctors at the Good Hope Hospital in Sutton Coldfield, Birmingham found there was a dramatic reduction in tumour recurrence rates if more healthy tissue was cut out, particularly amongst women suffering from invasive breast cancer, the deadlier of the two types which often spreads to other organs.
In a study of 303 women they found that if at least 2mm of healthy surrounding tissue was removed there was a 2.4 per cent risk that tumours would return, compared to a 35 per cent risk if 1mm of surrounding cells were removed.
Lead author Dr Stephen Ward, from the hospital's department of breast surgery said: 'Patients undergoing breast conserving surgery are more likely to have recurrent cancer and the amount of tissue removed around the tumour, known as the free margin, remains controversial.
'A survey of 200 UK breast surgeons published in 2007 revealed wide variations in what they considered to be an adequate margin, with 24 per cent wanting a clear margin of 1mm and 65 per cent wanting a margin of 2mm or more.
'This study highlighted differences in practice across different units and the need for evidence-based guidelines.'
But the study, published in the International Journal of Clinical Practice, did not find a strong link between the amount of breast tissue removed and recurrence rates for non-invasive cancer, the less serious form.
Dr Ward added: 'Our research found that the overall probability of finding residual disease was 2.4 per cent if a woman had surgery where the free margin was 2mm or more from the invasive cancer.
'Based on these results, we feel confident that a free margin of 2mm from the area of invasive cancer is adequate to minimise residual disease, but the equivalent free margin for non-invasive cancer remains unclear.
'Eliminating the possibility of residual disease during breast conserving surgery is very important as nearly 50 per cent of patients with local recurrence go on to develop secondary breast cancer, which is a progressive incurable disease.'
Up to 45,700 women are diagnosed with breast cancer every year and 12,000 die.
Survival rates have dramatically improved over the last thirty years and now more than 8 in 10 sufferers will still be alive five years on from the first diagnosis.

Friday, October 15, 2010

Walking may keep brain from shrinking in old age

Walking at least six miles a week may be one thing people can do to keep their brains from shrinking and fight off dementia, U.S. researchers said on Wednesday.

A study of nearly 300 people in Pittsburgh who kept track of how much they walked each week showed that those who walked at least six miles had less age-related brain shrinkage than people who walked less.
"Brain size shrinks in late adulthood, which can cause memory problems. Our results should encourage well-designed trials of physical exercise in older adults as a promising approach for preventing dementia and Alzheimer's disease," said Kirk Erickson of the University of Pittsburgh, whose study appears in the journal Neurology.
Alzheimer's disease, the most common form of dementia, slowly kills off brain cells, and activities like walking have been shown to build brain volume.
Erickson and colleagues tested to see if people who walk a lot might be better positioned to fight off the disease.
They studied 299 volunteers who were free of dementia and who kept track of how much they walked.
Nine years later, scientists took brain scans to measure their brain volume. After four more years, they tested to see if anyone in the study had cognitive impairment or dementia.
They found that people who walked roughly six to nine miles a week halved their risk of developing memory problems.
"Our results are in line with data that aerobic activity induces a host of cellular cascades that could conceivably increase gray matter volume," the team wrote.
They said more studies need to be done on the effects of exercise on dementia, but in the absence of any effective treatments for Alzheimer's, walking may be one thing people can do that may help down the road.
"If regular exercise in midlife could improve brain health and improve thinking and memory in later life, it would be one more reason to make regular exercise in people of all ages a public health imperative," Erickson said.
No current drugs can alter the progression of Alzheimer's, which affects more than 26 million people globally.

Gold Nanoparticles Create Visible-Light Catalysis in Nanowires

A scientist at the U.S. Department of Energy's (DOE) Argonne National Laboratory has created visible-light catalysis, using silver chloride nanowires decorated with gold nanoparticles, that may decompose organic molecules in polluted water.

"Silver nanowires have been extensively studied and used for a variety of applications, including transparent conductive electrodes for solar cells and optoelectronic devices," said nanoscientist Yugang Sun of Argonne's Center for Nanoscale Materials. "By chemically converting them into semiconducting silver chloride nanowires, followed by adding gold nanoparticles, we have created nanowires with a completely new set of properties that are significantly different from the original nanowires."
Traditional silver chloride photocatalytic properties are restricted to ultraviolet and blue light wavelengths, but with the addition of the gold nanoparticles, they become photocatalytic in visible light. The visible light excites the electrons in the gold nanoparticles and initiates reactions that culminate in charge separation on the silver chloride nanowires. Tests have already shown that gold-decorated nanowires can decompose organic molecules such as methylene blue.
"If you were to create a film of gold-decorated nanowires and allow polluted water to flow through it, the organic molecules may be destroyed with visible irradiation from conventional fluorescent light bulbs or the sun," Sun said.
Sun started with traditional silver nanowires that were oxidized with iron chloride to create silver chloride nanowires. A sequential reaction with sodium tetrachloroaurate deposited the gold nanoparticles on the wires.
Sun said it is possible to use a similar mechanism to deposit other metals such as palladium and platinum onto the silver chloride nanowires and create new properties, such as the ability to catalyze the splitting of water into hydrogen with sunlight.
A paper on this research was published in the Journal of Physical Chemistry C.
Funding was provided by the U.S. Department of Energy Office of Science. The Center for Nanoscale Materialsat Argonne National Laboratory is one of the five DOE Nanoscale Science Research Centers (NSRCs), premier national user facilities for interdisciplinary research at the nanoscale, supported by the DOE Office of Science.

Carbon Dioxide Controls Earth's Temperature, New Modeling Study Shows

Water vapor and clouds are the major contributors to Earth's greenhouse effect, but a new atmosphere-ocean climate modeling study shows that the planet's temperature ultimately depends on the atmospheric level of carbon dioxide.

The study, conducted by Andrew Lacis and colleagues at NASA's Goddard Institute for Space Studies (GISS) in New York, examined the nature of Earth's greenhouse effect and clarified the role that greenhouse gases and clouds play in absorbing outgoing infrared radiation. Notably, the team identified non-condensing greenhouse gases -- such as carbon dioxide, methane, nitrous oxide, ozone, and chlorofluorocarbons -- as providing the core support for the terrestrial greenhouse effect.
Without non-condensing greenhouse gases, water vapor and clouds would be unable to provide the feedback mechanisms that amplify the greenhouse effect. The study's results are published Oct. 15 inScience.
A companion study led by GISS co-author Gavin Schmidt that has been accepted for publication in the Journal of Geophysical Research shows that carbon dioxide accounts for about 20 percent of the greenhouse effect, water vapor and clouds together account for 75 percent, and minor gases and aerosols make up the remaining five percent. However, it is the 25 percent non-condensing greenhouse gas component, which includes carbon dioxide, that is the key factor in sustaining Earth's greenhouse effect. By this accounting, carbon dioxide is responsible for 80 percent of the radiative forcing that sustains the Earth's greenhouse effect.
The climate forcing experiment described in Science was simple in design and concept -- all of the non-condensing greenhouse gases and aerosols were zeroed out, and the global climate model was run forward in time to see what would happen to the greenhouse effect.
Without the sustaining support by the non-condensing greenhouse gases, Earth's greenhouse effect collapsed as water vapor quickly precipitated from the atmosphere, plunging the model Earth into an icebound state -- a clear demonstration that water vapor, although contributing 50 percent of the total greenhouse warming, acts as a feedback process, and as such, cannot by itself uphold the Earth's greenhouse effect.
"Our climate modeling simulation should be viewed as an experiment in atmospheric physics, illustrating a cause and effect problem which allowed us to gain a better understanding of the working mechanics of Earth's greenhouse effect, and enabled us to demonstrate the direct relationship that exists between rising atmospheric carbon dioxide and rising global temperature," Lacis said.
The study ties in to the geologic record in which carbon dioxide levels have oscillated between approximately 180 parts per million during ice ages, and about 280 parts per million during warmer interglacial periods. To provide perspective to the nearly 1 C (1.8 F) increase in global temperature over the past century, it is estimated that the global mean temperature difference between the extremes of the ice age and interglacial periods is only about 5 C (9 F).
"When carbon dioxide increases, more water vapor returns to the atmosphere. This is what helped to melt the glaciers that once covered New York City," said co-author David Rind, of NASA's Goddard Institute for Space Studies. "Today we are in uncharted territory as carbon dioxide approaches 390 parts per million in what has been referred to as the 'superinterglacial.'"
"The bottom line is that atmospheric carbon dioxide acts as a thermostat in regulating the temperature of Earth," Lacis said. "The Intergovernmental Panel on Climate Change has fully documented the fact that industrial activity is responsible for the rapidly increasing levels of atmospheric carbon dioxide and other greenhouse gases. It is not surprising then that global warming can be linked directly to the observed increase in atmospheric carbon dioxide and to human industrial activity in general."

Cancer is a man-made disease, controversial study claims

Is the common nature of cancer worldwide purely a man-made phenomenon? That is what some researchers now suggest.
Still, other specialists in cancer and in human fossils have strong doubts about this notion.
Cancer is a leading cause of death worldwide, accounting for roughly one in eight of all deaths in 2004, according to the World Health Organization. However, scientists have only found one case of the disease in investigations of hundreds of Egyptian mummies, researcher Rosalie David at the University of Manchester in England said in a statement. (The researchers did not reply to repeated queries made via phone and e-mail.)
The rarity of cancer in mummies suggests it was scarce in antiquity, and "that cancer-causing factors are limited to societies affected by modern industrialization," researcher Michael Zimmerman at Villanova University in Pennsylvania said in a statement. "In an ancient society lacking surgical intervention, evidence of cancer should remain in all cases."
Zimmerman was the first to diagnose cancer in an Egyptian mummy by analyzing its tissues on a microscopic level, identifyingrectal cancer in an unnamed mummy who had lived in the Dakhleh Oasis during the Ptolemaic period 1,600 to 1,800 years ago.
Story: Is it time to return to caveman parenting?
David and Zimmerman also analyzed ancient literature from Egypt and Greece for hints of cancer, as well as medical studies of human and animal remains going back to the age of dinosaurs. They suggested evidence of cancer in animal fossils, non-human primates and early humans was scarce, with a few dozen uncertain examples. As they analyzed ancient literature, they did not find descriptions of operations for breast and other cancers until the 17th century, and the first reports in the scientific literature of distinctive tumors have only occurred in the past 200 years, such as scrotal cancer in chimney sweepers in 1775, nasal cancer in snuff users in 1761 and Hodgkin's disease in 1832.
One possible reason cancers might have been comparatively rare in antiquity is that the short life span of individuals back then precluded the development of the disease. Still, the researchers did note some people in ancient Egypt and Greece did live long enough to develop such diseases as atherosclerosis, Paget's disease of bone, and osteoporosis.
'Sin' of modern societies 
David and Zimmerman therefore argue that cancer nowadays is largely caused by man-made environmental factors such as pollution and diet. They detailed their findings in the October issue of the journal Nature Reviews Cancer.

"In industrialized societies, cancer is second only to cardiovascular disease as a cause of death, but in ancient times, it was extremely rare," David said in a statement. "There is nothing in the natural environment that can cause cancer."
Despite that statement, dinosaurs did develop cancer well before humans were on the scene. Also, others argue the short life spans of antiquity could be a profoundly effective reason as to why cancer might have been rare then.
"Cancer is very rare in modern societies in humans under age 30," oncologist Dr. John Glaspy at UCLA's Jonsson Comprehensive Cancer Center told LiveScience. "In ancient times, people rarely lived to be much older than that. So cancer was rare. The 'sin' of modern societies is having people live to be much older."
Story: 3 ways to lower your breast cancer risk
Another concern when examining the fossil record is that skeletal remains might not preserve cancers very well. "To see cancers with the skeletal record, you really have to have a tumor that's affecting bone," paleoanthropologist John Hawks at the University of Wisconsin at Madison said in a phone interview. "Although there might be few confirmed diagnoses of tumors in bones, it's because cancer is a difficult diagnosis to make from bone."
Hawks did note that modern lifestyles could certainly lead to much higher rates of cancer than in the past, but not necessarily due to pollution.

Monday, October 11, 2010

Not tonight, dear. My head's fine but my back's killing me

Back pain has replaced the headache as the country's biggest passion-killer, according to a survey.
One in ten of us has admitted our sex lives suffer due to back pain  -  with women more likely to give lovemaking a miss because of the problem.
More than half  -  55 per cent  -  of Britons suffer from back pain at least once a month. a quarter of those said they would avoid any strenuous activity when suffering  -  including sex.
One in ten said they had even left the bed to sleep on the floor in an effort to ease the discomfort.
Back pain costs an estimated £7billion every year through work-related absence.

Dr Ralph Rogers, a skeletal specialist at the London Orthopedic clinic, said many patients with back problems wrongly assumed sex would make the condition worse. 'But actually lying still in bed is one of the worst things you can do,' he added.
Physiotherapist Martin Haines said the consumer survey of 8,000 adults carried out by Dynaspine, showed that back pain was having a profound impact.
But he said the problem could be helped by keeping the spine moving and taking gentle exercise.
'The spine is designed to move, not stay still, so using a back support which allows the spine to move is really important,' he added.

Sunday, October 10, 2010

Important Misconceptions about sex

Mardon ki tarah aurtein bhi bohut sey jinsi maghaliton (sexual misconceptions) ka shikar hain jo inki azdwajii khushyion mein bohut bari rukawat sabit hote hain. Azdwajii khushyion kay liye khawateen ko na sirf apney bul kay mardon kay jinsi mughaliton ka zikar lya jaey  taa'hum khawateen kay chund ahem jinsi mughlitey kuch yun hain

Wednesday, October 6, 2010

Air pollution could increase breast cancer risk: study

Traffic-related air pollution may put women at risk for breast cancer, according to a new study from Quebec.
The study, published in the journal Environmental Health Perspectives, looks at links between the risk of breast cancer, a leading cause of death from cancer in women, and traffic pollution.
Researchers from McGill University and the Université de Montréal charted incidences of breast cancer and compared them with pollution maps.
“We’ve been watching breast cancer rates go up for some time,” study co-author Mark Goldberg, a researcher at McGill University Health Centre, said in a release on Wednesday.
“Nobody really knows why, and only about one-third of cases are attributable to known risk factors. Since no one had studied the connection between air pollution and breast cancer using detailed air pollution maps, we decided to investigate it.”
Dr. Goldberg and his colleagues combined data from several studies. They created two air pollution maps which showed levels of nitrogen dioxide, a byproduct of vehicle traffic, in different parts of Montreal in 1996 and 10 years earlier in 1986.
Then, the research team looked at the home addresses of women diagnosed with breast cancer in a 1996-97 study and charted that onto the air pollution maps.
The team says its results were “startling,” and showed the incidence of breast cancer was increased in areas with higher levels of air pollution.
“We found a link between post-menopausal breast cancer and exposure to nitrogen dioxide (NOsub2/sub), which is a marker for traffic-related air pollution,” Dr. Goldberg said in the release.
“Across Montreal, levels of NOsub2/sub varied between five parts per billion to over 30 parts per billion. We found that risk increased by about 25% with every increase of NOsub2/sub of five parts per billion.
“Another way of saying this is that women living in the areas with the highest levels of pollution were almost twice as likely to develop breast cancer as those living in the least polluted areas.”
Dr. Goldberg warns, however, that the study must be interpreted with caution.
“First of all, this doesn’t mean NOsub2/sub causes breast cancer,” he said. “This gas is not the only pollutant created by cars and trucks, but where it is present, so are the other gases, particles and compounds we associate with traffic — some of which are known carcinogens.”
Dr. Goldberg said the study can be subject to unknown variables and that some areas of uncertainty remain.
“For example, we don’t know how much the women in the study were exposed to pollution while at home or at work, because that would depend on their daily patterns of activity, how much time they spend outdoors and so on,” Dr. Goldberg said.
“At the moment, we are not in a position to say with assurance that air pollution causes breast cancer. However, we can say that the possible link merits serious investigation,” the team said in its release.
Studies published in the U.S, have also shown possible links between cancer and air pollution.
The study was funded by a research grant from the Canadian Cancer Society and another one from the Canadian Institutes of Health Research.

Sunday, October 3, 2010

Doctors give teenager artificial heart

Doctors in Italy have implanted an artificial heart into a 15-year-old boy, the first time the procedure has been performed on a child.
Heart surgeons at Rome's Bambino Gesu Children's Hospital carried out the 10-hour breakthrough operation on Thursday, and the hospital said it was "cautious" over the boy's condition.
"A permanent artificial heart in the inside of the chest was implanted for the first time on an (adolescent) patient. So far this type of implant has only taken place on adults," the hospital in a statement on Saturday.
Artificial hearts are usually used on a temporary basis for patients awaiting a suitable human transplant, but the boy suffered from an illness that made a long wait impossible.
The artificial heart is four centimetres wide and weighs 400 grams, and special measures were taken to reduce the risk of infection.
"The risk of infection represents the primary cause of failure of alternative solutions attempted to date worldwide," said the hospital.
The procedure "opened new therapeutic perspectives and hope for life for all patients with cardiac illnesses for whom a transplant is needed, especially for those like Thursday's patient who cannot receive a donated heart for clinical reasons," the statement said.