Proliferation Of Two Breast Cancer Lines Stymied By Low-Dose Aspirin

Proliferation Of Two Breast Cancer Lines Stymied By Low-Dose Aspirin

Regular use of low-dose aspirin may prevent the progression of breast cancer, according to results of a study by researchers at the Veterans Affairs Medical Center in Kansas City, Mo., and the University of Kansas Medical Center.

The study found that aspirin slowed the growth of breast cancer cell lines in the lab and significantly reduced the growth of tumors in mice. The age-old headache remedy also exhibits the ability to prevent tumor cells from spreading.

The lead author of the study, Gargi Maity, a postdoctoral fellow who works in the cancer research unit at the VA Medical Center, presented the team's findings at the annual meeting of the American Society for Biochemistry and Molecular Biology, which is being held in conjunction with the Experimental Biology 2013 conference in Boston. The senior author is Sushanta Banerjee, director of the cancer research unit and a professor at the University of Kansas Medical Center in Kansas City, Kan.

The role of aspirin, or acetylsalicylic acid, in preventing and treating cancer has intrigued researchers since the late 1980s, when an Australian study found that people who regularly used aspirin were less likely to develop colorectal cancer. Aspirin use also has been shown to reduce the risk of squamous cell esophageal cancer and prostate cancer.

Anecdotal evidence indicated that breast cancer was less likely to return in women who took aspirin to lower their risk of heart attack or stroke. But the science behind this relationship is not well understood.

The VA study found that aspirin may interfere with cancer cells' ability to find an aggressive, more primordial state. In the mouse model the researchers used, cancer cells treated with aspirin formed no or only partial stem cells, which are believed to fuel the growth and spread of tumors.

Banerjee, a professor of medicine in division of hematology and oncology, says first-line chemotherapy treatments do not destroy stem cells. Eventually, the tumor will grow again. "If you don't target the stemness, it is known you will not get any effect," he says. "It will relapse."

In lab tests, aspirin blocked the proliferation of two different breast cancer lines. One of the lines tested is often called triple-negative breast cancer, a less common but more difficult treat form of the disease. "We are mainly interested in triple negative breast cancer, because the prognosis is very poor," Banerjee says.

Triple-negative breast cancers, which will be addressed in a special thematic program at the ASBMB annual meeting, lack receptors for estrogen, progesterone and Her2. Aspirin also may improve the effectiveness of current treatments for women whose breast cancers are hormone-receptor positive. In the team's study, aspirin enhanced the effect of tamoxifen, the usual drug therapy for hormone-receptor positive breast cancer.

Aspirin is used in the treatment of a number of different conditions. Banerjee says its ability to attack multiple metabolic pathways is what makes it potentially useful in the fight against cancer. "Cancer is not a single-gene disease," he says. "Multiple genes are involved."

Aspirin is a medicine with side effects, including gastrointestinal bleeding. Researchers will continue to explore if the positive effects of regular use of the drug outweigh the risks. In 2012, the National Cancer Institute asked scientists to design studies that would illuminate the mechanisms by which aspirin and drugs with other uses appear to reduce the risk of cancer or improve the prognosis for those diagnosed with the disease. Banerjee says his lab will apply for one of the grants.

Two Studies Add New Data To Debate Over Safety Of N2O As Surgical Anesthetic

Two Studies Add New Data To Debate Over Safety Of N2O As Surgical Anesthetic

Giving nitrous oxide as part of general anesthesia for noncardiac surgery doesn't increase the rate of complications and death - and might even decrease the risk of such events, according to a pair of studies in the May issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

But an accompanying series of editorials points out some important limitations of the two studies - which can't completely overcome previous concerns about the safety of using nitrous oxide (N2O) as a surgical anesthetic.

Is Nitrous Oxide Safe for Surgical Anesthesia?

Nitrous oxide is the world's oldest general anesthetic, but there's a long history of debate regarding its appropriate role in modern surgical anesthesia. Although nitrous oxide provides effective sedation and pain control, it has known disadvantages and side effects. A previous study, called "ENIGMA-I," reported a small but significant increase in myocardial infarction (heart attack) among patients receiving nitrous oxide as part of anesthesia for noncardiac surgery (procedures other than heart surgery).

The two new studies, based on large patient databases, question the harmful effects of nitrous oxide. Dr Kate Leslie of Royal Melbourne Hospital, Australia, and colleagues analyzed data from a previous study of more than 8,300 patients undergoing surgery. That study was designed to assess the effects of giving one type of blood pressure drug (beta-blockers) during surgery, not the effects of nitrous oxide.

Dr Leslie and colleagues compared the risk of death or serious complications after surgery for patients who versus did not receive nitrous oxide as part of anesthesia. Twenty-nine percent of patients in the study received nitrous oxide.

The results showed comparable rates of adverse outcomes between groups. With or without nitrous oxide, the overall rate of death or serious complications was approximately seven percent, including about a six percent rate of myocardial infarction. Risk of death after surgery was about three percent in both groups.

Outcomes remained similar on "propensity score" analysis - a technique accounting for characteristics making patients more or less likely to receive nitrous oxide. Use of nitrous oxide varied widely between the different countries and hospitals participating in the study.

No Increase in Risks with N2O - But 'More Definitive' Studies Needed

Dr Alparslan Turan of the Cleveland Clinic and colleagues outcomes reviewed more than 49,000 patients undergoing noncardiac surgery between 2005 and 2009. In this study, 45 percent of patients received nitrous oxide.

The results suggested a significant reduction in the risk of death after surgery for patients receiving nitrous oxide: about one-third lower than in patients who did not receive nitrous oxide. There was also a significant 17 percent reduction in the combined rate of major complications and death.

Surprisingly, nitrous oxide was specifically associated with a 40 percent reduction in the risk of major lung- and breathing-related complications. However, the authors acknowledge the risk of "selection bias" - anesthesiologists may have avoided using nitrous oxide in patients at risk of lung problems. Again, the findings remained significant on propensity score analysis.

In one of three accompanying editorials, Thomas R. Vetter, MD, MPH, and Gerald McGwin, Jr, MS, PhD, of University of Alabama at Birmingham highlight some important limitations of the study data. They note that, although both studies were large, they were not randomized trials - the strongest type of scientific evidence.

Drs Vetter and McGwin emphasize that even sophisticated techniques like propensity score analysis can't account for all of the differences between groups that may have affected responses to nitrous oxide. They note that a randomized "ENIGMA-II" study is underway, and may provide "additional, perhaps more definitive insight" on the risks and potential benefits of using nitrous oxide as part of general anesthesia.

Success Rates Of Turning Breech Babies Increased By Anesthesia, Delivery Costs Reduced

Success Rates Of Turning Breech Babies Increased By Anesthesia, Delivery Costs Reduced

When a baby is in the breech position at the end of pregnancy, obstetricians can sometimes turn the baby head-down to enable a safer vaginal birth. In the past, women were not given anesthesia during the turning procedure, which requires the physician to push on the woman's abdomen while monitoring the baby with ultrasound. But a new study from the Stanford University School of Medicine and Lucile Packard Children's Hospital shows anesthesia is cost-effective because it increases the likelihood the procedure will work.

The turning procedure, called an external cephalic version, or simply a "version," can allow some women with breech babies to avoid a cesarean section and have a head-first vaginal delivery instead. Prior studies have shown that spinal or epidural anesthesia - similar to the anesthetic techniques offered during childbirth - can help more babies to be turned successfully. Many obstetricians still do not use anesthesia when doing a version.

"We've been looking at reasons physicians don't offer anesthesia during this procedure, and one reason may be that they think it may add extra costs," said the study's lead author, Brendan Carvalho, MD, associate professor of anesthesia at Stanford and chief of obstetric anesthesia at Packard Children's. "But our work shows that it doesn't add significant costs, and most likely reduces overall costs because more women can avoid cesareans."

The study was published online in Anesthesia & Analgesia.

Because a breech vaginal delivery, in which a baby is born feet-first or bottom-first, is more dangerous for the mother and baby than a head-first vaginal delivery, many breech babies are delivered by cesarean section. But cesarean sections have their own disadvantages, such as increased risk of maternal hemorrhage, more pain and longer recovery times for the mother after birth, as well as higher hospital costs. As part of their effort to reduce cesarean rates, Packard Children's obstetric anesthesiologists have been offering anesthesia during version procedures for the last two years, making Packard Children's a Bay Area leader in studying and providing anesthesia for versions.

The new research drew upon data from several earlier studies that compared version success rates with and without anesthesia. The scientists also used national data on the cost of the version procedure with and without anesthesia, and the costs of vaginal and cesarean deliveries. All of the data was entered into a mathematical model that allowed the scientists to predict whether anesthesia use during a version was cost-effective.

The study found that using anesthesia increased average success rates of version procedures from 38 percent to 60 percent. Because it led to fewer cesareans, use of anesthesia also decreased the total cost of delivery by an average of $276; the range of cost differences estimated by the model extended from a $720 savings to a $112 additional cost.

Looking at the question of cost-effectiveness in a different way, the success rates of versions had to be improved at least 11 percent with anesthesia for the cost of the anesthesia to be negated, the researchers calculated.

Prior research has also shown that women are happier with version procedures when they receive anesthesia, Carvalho noted. "The pain of this procedure is variable, but it certainly is uncomfortable," he said. "If you have anesthesia, you feel pressure more than pain. Several studies have shown lower pain scores and higher patient satisfaction with anesthesia."

Abdominal muscle relaxation likely contributes to the higher success rates of the procedures performed with anesthesia, Carvalho said, adding that muscle relaxation caused by anesthesia may allow practitioners to apply less pressure to turn the baby. A previous study by these investigators demonstrated that anesthesia does not increase the risk of performing a version.

Simple Brace Can Significantly Reduce Pain Of Kneecap Osteoarthritis

Simple Brace Can Significantly Reduce Pain Of Kneecap Osteoarthritis

Arthritis Research UK-funded researchers at The University of Manchester claim their findings, presented at the Osteoarthritis Research Society International meeting in Philadelphia have enormous potential for treating this common joint condition effectively - as well as providing a simple and cheap alternative to painkillers.

Osteoarthritis of the knee affects around six million people in the UK and is increasing as the population ages and becomes more obese. Current treatments are limited to pain relief and joint replacement.

Osteoarthritis of the knee affecting the kneecap (patellofemoral osteoarthritis) accounts for about 20% of patients with knee pain. They typically experience pain that is made worse by going up and down stairs, kneeling, squatting and prolonged sitting.

"There's a pressing need for non-surgical interventions for knee osteoarthritis, and little attention has been paid to treatments particularly aimed at the kneecap (the patellofemoral joint), a major source of knee pain," explained Dr Michael Callaghan, research associate in rehabilitation science at the University of Manchester.

"We've shown that something as simple as a lightweight knee brace can dramatically improve the symptoms and function for people with this particular type of knee osteoarthritis."

The research team conducted a randomised controlled trial of a lightweight lycra flexible knee brace fitted around the knee with a support strap for the kneecap. One hundred and 26 patients between the ages of 40 and 70 were treated over a 12-week period. All had suffered from arthritic knee pain for the previous three months.

They were randomly allocated to either immediate brace treatment or delayed treatment (i.e. after six weeks.) Both groups of patients eventually wore the brace for a period of 12 weeks and averaged roughly seven hours a day.

After six weeks of brace wearing there were significant improvements between the brace wearing group and the no treatment group in scores for pain, symptoms, knee stiffness, muscle strength and function. After 12 weeks there were significant improvements in these scores for all patients compared to when they started.

"Patients repeatedly told us that wearing the brace made their knee feel more secure, stable, and supported," Dr Callaghan added. "Our theory is that these sensations gave the patient confidence to move the knee more normally and this helped in improving muscle strength, knee function and symptoms."

Professor Alan Silman, medical director of Arthritis Research UK, which funded the trial, said: "Osteoarthritis of the knee is a painful disorder that affects millions of people in the UK, causing pain and reducing activities. We know that in patients with arthritis, the knee joint is frequently out of normal alignment, which might be an underlying cause of the problem, as well as making it worse.

"By using a simple brace, the researchers have been able not only to correct the alignment but achieve a very worthwhile benefit in terms of reducing pain and function. This approach is a real advance over relying on pain killers and has the potential to reduce the end for joint surgery and replacement, procedures often employed when the symptoms become uncontrollable."