Capturing circulating cancer cells could provide insights into how disease spreads

A glass plate with a nanoscale roughness could be a simple way for scientists to capture and study the circulating tumor cells that carry cancer around the body through the bloodstream.
Engineering and medical researchers at the University of Michigan have devised such a set-up, which they say takes advantage of cancer cells' stronger drive to settle and bind compared with normal blood cells.
Circulating tumor cells are believed to contribute to cancer metastasis, the grim process of the disease spreading from its original site to distant tissues. Blood tests that count these cells can help doctors predict how long a patient with widespread cancer will live.
As important as the castaway cells are, scientists don't know a lot about them. They're rare, at about one per billion blood cells. And they are not all identical, even if they come from the same tumor. Existing tools for isolating them only catch certain types of cells—those that express specific surface proteins or are larger than normal blood cells.
For example, the commonly used, FDA-approved CellSearch system uses antibody- coated magnetic beads to seek out tumor cells and bind to them. But not all circulating tumor cells express the proteins these antibodies recognize. It is possible that the most dangerous ones, known as cancer stem or progenitor cells, may have shed that tell-tale coat, thereby evading approaches that rely on antibodies.
The researchers say their system could likely trap these stealth cancer stem cells—a feat no research team has accomplished yet.
"Our system can capture the majority of circulating tumor cells regardless of their surface proteins or their physical sizes, and this could include cancer progenitor or initiating cells," said Jianping Fu, assistant professor of mechanical engineering and biomedical engineering and a senior author of a paper on the technique published online in ACS Nano.
Fu and his engineering colleagues teamed up with U-M senior cancer researcher and breast cancer clinician Dr. Sofia Merajver and her team. This multidisciplinary group believes that while the device could one day improve cancer diagnosis and prognosis, its first uses would be for researchers to isolate live circulating tumor cells from blood specimens and study their biological and physical properties.
"Understanding the physical behavior and nature of these circulating tumor cells will certainly help us understand better one of the most difficult questions in cancer biology—the metastatic cascade, that is, how the disease spreads," Fu said. "Our system could provide an efficient and powerful way to capture the live circulating tumor cells and use them as a surrogate to study the metastatic process."
But capturing them, as challenging as it has proven to be, is only the beginning, said Merajver, who has spent the last 18 years studying cell signaling and the physical properties of highly aggressive cancer cells.
"The application of integrative biology is necessary to put together the story of how these cells behave in time to achieve successful metastases and thereby discover the routes to suppressing this deadly development," Merajver said. "Our collaboration with the Fu lab exemplifies the innovation needed for the war against cancer—team science from the lab all the way to the clinic."
In their experiments, the researchers used a standard and inexpensive microfabrication technique called "reactive ion etching" to roughen glass slides with a nanoscale resolution. Then, they spiked different blood samples with cancer cells derived from human breast, cervical and prostate tissues. When they poured the samples over the glass plates, the nanorough glass surfaces captured an average of 88 percent to 95 percent of the cancer cells.
Fu suggests why.
"Blood cells are intrinsically floating," Fu said. "Cancer cells including circulating tumor cells derived from solid tumors are presumably adherent cells. They can escape from the primary tumor while maintaining certain adhesion properties that allow them to attach and establish another tumor."
In other studies, researchers have noticed that circulating tumor cells tend to stick to rough surfaces. But the rough surfaces in those studies were coated with capture antibodies. These new nanorough surfaces do not require capture antibodies.
"Our method presents a significant improvement as it can be applied in principle to any cancer cell that comes from solid tumors," Fu said.
The paper is titled "Nanoroughened Surfaces for Efficient Capture of Circulating Tumor Cells without Using Capture Antibodies." The university is pursuing patent protection for the intellectual property and is seeking commercialization partners to help bring the technology to market.
Source:University of Michigan 

Dept of Ayush issues Drugs & Cosmetics (5th Amendment) Rules, 2012

Union government’s Department of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy (AYUSH) has now issued a notification vide G.S.R.844(E) F.No.K.11020/05/2011-DCC(Ayush) on the amendment of the of certain rules in the Drugs and Cosmetics Rules, 1945 dated November 26, 2012.
These rules are now referred to as Drugs and Cosmetics (5th Amendment) Rules, 2012 and would be enforced from 2013.
The Drugs and Cosmetics Rules, 1945, under rule 161, in sub-rule (1), after the words ‘true list’ of all ingredients” the new insertion is effective. This would be read as ‘with the botanical names of plant based ingredients along with plant part(s) and form of ingredients’.
The second change in the Rules is after ‘First Schedule of the Act’. A new insertion made is ‘in respect of Patent or Proprietary Ayurveda, Siddha or Unani drugs, the true list of all the ingredients with the botanical names of plant based ingredients along with plant part(s) and form of ingredients, in which, these are used in the formulation, with their quantity’.
If needed standardized abbreviations prescribed for part(s) and form of Ingredient(s) in the official Ayurveda, Siddha and Unani Pharmacopoeias and Formularies, maybe used on the label, stated the Notification.
Under the sub-rule (3), after ‘Ayurvedic (including Siddha) or Unani drug’ the words ‘and Patent or Proprietary Ayurveda, Siddha or Unani drugs’ shall be inserted.
In the item of sub rule (ii) in item (i), for the words ‘For this’, the words ‘For Ayurveda, Siddha or Unani Drug’ are substituted.
The  draft of certain rules to amend was published, vide notification G.S.R. 249(E), dated  March, 22, 2012 in the Gazette of India, Extraordinary, inviting objections and suggestions from industry likely to be affected thereby before the expiry of a period of 45  days from the date on which copies of the Official Gazette containing the said notification were made available to the public, said A K Ganeriwala, Jt. Secretary, Department of Ayurveda, Yoga and Naturopathy, Unani, Siddha and Homoeopathy, in the note addressed to the industry.
The Gazette was made available to the public on March 22, 2012 and the  objections or suggestions received from the public on the draft rules have been considered by the Central Government. Now under section 33-N of the Drugs and Cosmetics Act, 1940 (23 of 1940) the Central Government, has made the related changes to the rules  to amend the Drugs and Cosmetics Rules, 1945, which would come in to force after one year from the date of their final publication in the Official Gazette. The last amended notification was vide GSR No. 575(E) dated July 17, 2012, stated the note issued by the  secretary, department  of Ayush.

Source:Pharmabiz

Coming Soon, Personal DNA Code for 100 Pounds

Personalized medicine could be a possibility in near future as everybody will soon be able to have their DNA sequenced for 100 pounds, says a leading professor. 
Sir John Bell, professor of medical sciences at Oxford University, adviser on genetics to the government and chair of its human genomics strategy group, made his comments as David Cameron launched a national DNA database of up to 100,000 patients with cancer or rare diseases."The price of genome sequencing has been falling off a clliff. It has fallen by 100,000-fold in 10 years. We are headed for 100-pound a genome. That will happen in the very near future," the Telegraph quoted Sir John as saying. 
He told Radio 4's Today programme that that means everybody's genetic make up would therefore be available if they wish it to be. 
"Genetics is a key component of all common diseases. There is a possibility that this will help in a whole variety of ways including the use of new drugs," he said. 
The UK will be the first country to introduce hi-tech DNA mapping within a mainstream health system in a move designed to help it lead the world in tackling cancer and rare diseases, Downing Street said. 
"By unlocking the power of DNA data, the NHS will lead the global race for better tests, better drugs and above all better care," Cameron said. 
"We are turning an important scientific breakthrough into a potentially life-saving reality for NHS patients across the country. 
"If we get this right, we could transform how we diagnose and treat our most complex diseases not only here but across the world, while enabling our best scientists to discover the next wonder drug or breakthrough technology," he added. 
But campaigners warned the project, in which patients will have to opt out of having their personal DNA code sequenced if they do not wish to be involved, comes with "very real privacy concerns". 
If extended to the whole population, individuals and their relatives could be identified and tracked by matching their DNA to their genome stored in health care records in a move which could "wipe out privacy", GeneWatch UK said. 
Campaigners Big Brother Watch added the opt-out system for research was "wholly wrong", warning that marketing firms could try to use the data to sell medication to people at risk of becoming ill.
Source-ANI
 
 

Caffeinated coffee linked to lower risk of some oral cancers

A new American Cancer Society study finds a strong inverse association between caffeinated coffee intake and oral/pharyngeal cancer mortality. The authors say people who drank more than four cups of caffeinated coffee per day were at about half the risk of death of these often fatal cancers compared to those who only occasionally or who never drank coffee. The study is published online in the American Journal of Epidemiology. The authors say more research is needed to elucidate the biologic mechanisms that could be at work.
Previous epidemiologic studies have suggested that coffee intake is associated with reduced risk of oral/pharyngeal cancer. To explore the finding further, researchers examined associations of caffeinated coffee, decaffeinated coffee, and tea intake with fatal oral/pharyngeal cancer in the Cancer Prevention Study II, a prospective U.S. cohort study begun in 1982 by the American Cancer Society.
Among 968,432 men and women who were cancer-free at enrollment, 868 deaths due to oral/pharyngeal cancer occurred during 26 years of follow-up. The researchers found consuming more than four cups of caffeinated coffee per day was associated with a 49 percent lower risk of oral/pharyngeal cancer death relative to no/occasional coffee intake (RR 0.51, 95% confidence interval [CI] 0.40-0.64). A dose-related decline in relative risk was observed with each single cup per day consumed. The association was independent of sex, smoking status, or alcohol use. There was a suggestion of a similar link among those who drank more than two cups per day of decaffeinated coffee, although that finding was only marginally significant. No association was found for tea drinking.
The findings are novel in that they are based specifically upon fatal cases of oral/pharyngeal cancer occurring over a 26-year period in a population of prospectively-followed individuals who were cancer-free at enrollment in Cancer Prevention Study II.
"Coffee is one of the most widely consumed beverages in the world, and contains a variety of antioxidants, polyphenols, and other biologically active compounds that may help to protect against development or progression of cancers," said lead author Janet Hildebrand, MPH. "Although it is less common in the United States, oral/pharyngeal cancer is among the ten most common cancers in the world. Our finding strengthens the evidence of a possible protective effect of caffeinated coffee in the etiology and/or progression of cancers of the mouth and pharynx. It may be of considerable interest to investigate whether coffee consumption can lead to a better prognosis after oral/pharyngeal cancer diagnosis."
Source:American Cancer Society 

New Therapy Blocks the Effect of Protein and Boosts the Effects of Cancer Drugs

In mice, blocking a specific protein renders tumors more vulnerable to treatment, suggesting new therapies could eventually achieve the same in humans. 
This is according to new research from Fox Chase Cancer Center to be presented at the 2012 CTRC-AACR San Antonio Breast Cancer Symposium on Friday, December 7, 2012.
"Hopefully, with further testing, this research could one day result in a new therapy that blocks the effect of this protein and, in turn, boosts the effects of cancer drugs," says study author Elizabeth Hopper-Borge, PhD, Assistant Professor at Fox Chase. 
The protein in question is a type of ATP-binding cassette drug efflux pumps, known more simply as ABC proteins. These proteins sit on the membranes of cells, where they act just like pumps—removing cancer drugs from the cell, thereby making them less effective. The body contains close to 50 such proteins, explains Hopper-Borge, but only 3 appear capable of evading the effects of cancer drugs, including common types used to treat lung, ovarian, and breast cancers. 
The current research, supported by the National Institutes of Health, focuses on the protein ABCC10, which has not been studied in as much detail as some other ABC proteins, says Hopper-Borge. Last year, she and her colleagues found that mice lacking ABCC10 experienced physiological changes after taking a cancer drug, suggesting the drug was having an effect. 
As part of the latest project, the authors performed a similar experiment in mice engineered to develop breast cancer. They found that, 21 days after exposure to a cancer drug, the tumors that lacked ABCC10 were much smaller than the tumors that still carried the protein. "This is probably the first time it's been shown that removing this protein helps sensitize tumors to cancer drugs," says Hopper-Borge. 
Looking closely at the tumors, the researchers also found that cells that lacked ABCC10 grew faster. Strangely, this finding is encouraging, says Hopper-Borge, since chemotherapy targets proliferating cells—and so may explain why the drugs now act on the faster-growing cells that lack ABCC10. 
The next step, she says, is to try removing ABCC10 in more mouse models of breast cancer, and determine how active the protein is in different types of the disease. Eventually, if blocking the protein appears to consistently boost the effects of cancer drugs, researchers can identify and begin testing inhibitors of ABCC10 as additional treatments for cancer. 
"Although this research is promising, it's in its early stages," cautions Hopper-Borge. "Consequently, it's premature for patients to ask their doctors to test them for the presence of ABCC10, since knowing that can't yet affect their treatment. But these results suggest that may one day change." 

Source:Fox Chase Cancer Center 
 

Maintaining weight loss as important as losing it for older women

Wake Forest Baptist study looks at cardiometabolic risk factors

 When you're postmenopausal and overweight, losing weight is a good thing, but gaining back just a few pounds may actually be detrimental to your cardiovascular health.
New research from Wake Forest Baptist Medical Center found that gaining weight back after intentional weight loss is associated with negative long-term effects on some cardiometabolic (CM) risk factors in postmenopausal women.
In this paper, published online by the Journal of Gerontology: Medical Sciences, lead authors Daniel Beavers, Ph.D., and Kristen Beavers, Ph.D., wanted to look at how weight regain affects health risk in these women. The researchers looked specifically at CM risk factors – a cluster of risk factors that are indicators of a person's overall risk for type 2 diabetes and cardiovascular disease. They include blood pressure, HDL and LDL cholesterol, triglycerides, fasting glucose and insulin.
"In this group of women, weight loss and maintaining that loss offers the most health benefit, but therein lies the problem," Daniel Beavers said. "For most people, weight regain after intentional weight loss is an expected occurrence, and the long-term health ramifications of weight regain in older adults are not well understood."
Specifically, the researchers looked at how CM risk factors change in the year following significant, intentional weight loss and whether these changes are affected by weight regain.
"What we found was that all CM risk factors are improved with weight loss, which is not surprising, but most regressed back to their baseline values 12 months later, especially for women who were classified as 'regainers,'" Kristen Beavers said. "For women who had regained weight in the year after their weight loss, several risk factors were actually worse than before they lost the weight."
For the study, sponsored by the National Institute on Aging, the researchers evaluated 112 obese, postmenopausal women averaging 58 years of age, through a five-month weight loss intervention and a subsequent 12 month non-intervention period. Body weight/composition and CM risk factors were analyzed before and after the weight loss intervention and at six and 12 months after the intervention. During the intervention, women lost a significant amount of weight, an average of 25 pounds, and 80 women returned for at least one followup measurement. Weight regain status was based on whether a participant regained at least four pounds during the follow-up period. Two-thirds of the women fell into this category and, on average, regained approximately 70 percent of lost weight.
Beavers said these study results highlight the need for future research to better identify barriers to long-term weight loss success and develop effective strategies to promote the maintenance of weight loss in this population. These new findings build on previously published data from Wake Forest Baptist's gerontology research group that found when postmenopausal women lose weight and gain it back, they regain it mostly in the form of fat, rather than muscle.
"Our data suggest that for postmenopausal women, even partial weight regain following intentional weight loss is associated with increased cardiometabolic risk. Conversely, maintenance of or continued weight loss is associated with sustained improvement in the cardiometabolic profile," Beavers said. "The take away message for overweight, older women is to approach weight loss as a permanent lifestyle change, with weight maintenance just as important as weight loss."
Source:Wake Forest Baptist Medical Center 

Study finds association between oxygen deprivation before birth and ADHD

Children who had in-utero exposure to ischemic-hypoxic conditions, situations during which the brain is deprived of oxygen, were significantly more likely to develop attention deficit hyperactivity disorder later in life as compared to unexposed children, according to a Kaiser Permanente study published in the journal Pediatrics. The findings suggest that events in pregnancy may contribute to the occurrence of ADHD over and above well-known familial and genetic influences of the disorder.
The population-based study examines the association between IHC and ADHD. Researchers examined the electronic health records of nearly 82,000 children ages 5 years old and found that prenatal exposure to IHC – especially birth asphyxia, neonatal respiratory distress syndrome, and preeclampsia – was associated with a 16 percent greater risk of developing ADHD. Specifically, exposure to birth asphyxia was associated with a 26 percent greater risk of developing ADHD, exposure to neonatal respiratory distress syndrome was associated with a 47 percent greater risk, and exposure to preeclampsia (high blood pressure during pregnancy) was associated with a 34 percent greater risk. The study also found that the increased risk of ADHD remained the same across all race and ethnicity groups.
"Previous studies have found that hypoxic injury during fetal development leads to significant structural and functional brain injuries in the offspring," said study lead author Darios Getahun, MD, PhD, of the Kaiser Permanente Southern California Department of Research & Evaluation. "However, this study suggests that the adverse effect of hypoxia and ischemia on prenatal brain development may lead to functional problems, including ADHD."
Researchers also found that the association between IHC and ADHD was strongest in preterm births and that deliveries that were breech, transverse (shoulder-first) or had cord complications were found to be associated with a 13 percent increased risk of ADHD. These associations were found to be the case even after controlling for gestational age and other potential risk factors.
"Our findings could have important clinical implications. They could help physicians identify newborns at-risk that could benefit from surveillance and early diagnosis, when treatment is more effective," said Getahun. "We suggest future research to focus on pre- and post-natal conditions and the associations with adverse outcomes, such as ADHD."
During critical periods of fetal organ development, IHC may result in a lack of oxygen and nutrient transport from the mother's blood to fetal circulation. The result may be compromised oxygen delivery to tissues and cerebrovascular complications. However, this study suggests that the adverse effect of hypoxia on prenatal brain development may lead to functional problems, including ADHD.
In 2005, the Centers for Disease Control and Prevention estimated the annual cost of ADHD-related illness in children under 18 years of age to be between $36 billion and $52.4 billion, making the condition a public health priority. In 2010, approximately 8.4 percent of children ages 3 to 17 had been diagnosed with ADHD. For about half the affected children, the disease persists into adulthood, according to CDC statistics. Symptoms of ADHD in children may include attention problems, acting without thinking, or an overly active temperament.
This study is part of Kaiser Permanente's ongoing research to understand the relationship between prenatal conditions and adverse medical outcomes. Earlier this year, Kaiser Permanente researchers found that in-utero exposure to relatively high magnetic field levels was associated with a 69 percent increased risk of being obese or overweight during childhood compared to lower in-utero magnetic field level exposure. And a Kaiser Permanente study conducted last year found exposure to selective serotonin reuptake inhibitors anti-depressants in early pregnancy may modestly increase the risk of autism spectrum disorders.
Kaiser Permanente can conduct transformational health research in part because it has the largest private patient-centered electronic health system in the world. The organization's electronic health record system, Kaiser Permanente HealthConnect®, securely connects 9 million people, 611 medical offices, and 37 hospitals, linking patients with their health care teams, their personal health information, and the latest medical knowledge. It also connects Kaiser Permanente's researcher scientists to one of the most extensive collections of longitudinal and medical data available, facilitating studies and important medical discoveries that shape the future of health and care delivery for patients and the medical community.
Source:Kaiser Permanente