Posts Tagged ‘people’

Being overweight causes hazardous inflammations

“We believe that there is a connection between metabolism, inflammation, heart attack and stroke,” says Bente Halvorsen, professor at the Research Institute for Internal Medicine, University of Oslo, Norway. Together with the research group’s leader, Pål Aukrust, who last year received the university’s research award for his work on inflammatory diseases, and researcher Arne Yndestad, she has looked deeply into the molecular explanation of why overweight is harmful. “With this new knowledge, we can better understand why too much food can cause such serious diseases as heart attack, stroke, cancer and chronic intestinal inflammation.”

We eat too much

Malnutrition and insufficient nutrition lower the immune response, and this increases the risk of infections. If the immune defense system functioned normally, the body would respond with an inflammation to rid itself of the infection. When the immune defense system is impaired, the body is unable to defend itself through inflammation.

Overeating increases the immune response. This increased immune response causes the body to generate excessive inflammation, which may lead to a number of chronic diseases.

“It is therefore important to keep a balance. Too little and too much nutrition may both upset the immune defense system and increase the risk of disease.”

A number of diseases are caused by inflammation. Arthritis is a chronic inflammatory disease. Heart attack is an example of a disease that causes an acute and powerful inflammatory reaction.

“We can reduce the inflammatory reaction by losing weight. Some people risk never getting rid of the inflammation. We have attempted to understand what is needed to reduce the inflammatory reaction without having to lose weight,” Halvorsen explains.

Unfortunately, storage of energy causes an inflammatory reaction. The explanation lies in the close connection between the body’s immune system, energy conversion and the way in which we store energy. It can all be explained in terms of evolution. In our ancestors many hundred million years ago, this was all concentrated in one single organ, like in the modern-day fruit fly. Even though in humans this task is divided among three organs — the fatty tissue that stores energy, the liver that converts energy and the immune system — these organs still communicate closely with each other.

Evolutionarily speaking, humans are not made to eat so much on the contrary; they are intended to toil for their food.

“Mankind’s great challenge has consisted in obtaining sufficient food and surviving infections. Today, we rarely die of infections, but on the other hand we eat too much,” says Arne Yndestad.

Damage to the powerhouse in the cells

The researchers believe that overeating may cause stress to the mitochondria. The mitochondria are the cells’ powerhouses, converting fatty acids to energy.

Evolutionary biologists believe that mitochondria were bacteria that as life has developed have become an integrated part of our cells. The immune system may nevertheless perceive the mitochondria as foreign bodies. Much immunological research therefore focuses on the mitochondria.

When fatty acids accumulate in the cells, the mitochondria become stressed and gradually also damaged.

“When the cells receive excessive energy, the system starts to falter, and the engine may stall. Too much fatty acid causes an oxidative stress in the cells. We believe that long-term stress on the mitochondria may cause metaflammation. A metaflammation is a low-grade chronic inflammation over many years, and unfortunately it’s a condition that’s difficult to detect,” says Yndestad.

The body has its own defense system, called autophagy, which should eliminate damaged mitochondria. When we overeat, free fatty acids accumulate in the cells. This stresses the mitochondria. The stress in the cells causes damage to the mechanism that should eliminate the mitochondria.

When damaged mitochondria accumulate, the immune response is activated. This immune response is exactly what causes the inflammation.

Key signal molecules have been found

The UiO researchers, who also work at the new K.G. Jebsen Inflammation Research Centre, have studied some of the signal molecules inside the cells that trigger the inflammatory reaction. In other words, they have found one element of the energy conversion that may explain what happens when the mitochondria are dealing with the fatty acids. The special element, which is also an enzyme, has previously been studied in stroke patients.

“We believe that this enzyme can be regulated by overnutrition and that it is a key constituent in the inflammatory reaction. We have found that the plaque in the arteries of patients with arteriosclerosis contained a lot of this enzyme. When the plaque bursts, the patient may suffer a stroke,” Halvorsen points out.

In trials with mice, the researchers have tested what happens when the amount of this special enzyme is increased. It reduced the degree of arteriosclerosis.

Strengthening the theory

Their theory was strengthened when they studied how the absence of inflammasomes had an effect on heart function. Inflammasomes are part of the intra-cellular immune defense system.

“When the cells received excessive amounts of fatty acids, the inflammasomes were activated, causing an inflammation.”

Mice with heart attacks functioned better when the inflammasomes were removed.

“So this is about restoring the balance in the immune defense system,” says Yndestad .

A correlation with cancer

The researchers believe that their new discovery may also be a key mechanism in the development of cancer.

“Cancer cells need access to a lot of energy to divide. The cellular stress may transform cells to cancer. Studies of overweight may therefore give us a better understanding of cancer,” Halvorsen explains.

One who is particularly interested in this research is Professor Kristin Austlid Taskén at the Institute for Cancer Research.

“People who are overweight more often develop an aggressive variant of prostate cancer. Although the connection between overweight and cancer is well known, however, little is known about the mechanisms involved” Taskén says.

Her specialty is prostate cancer, a disease that strikes 5000 Norwegians each year.

“Since this is the most common form of cancer among men, it is essential to obtain more knowledge about the way in which overweight affects the metabolism of the cancer cells and leads to aggressive prostate cancer. For the cancer cells to be able to divide rapidly, they make use of new metabolic pathways that are quite unknown to us today. It is therefore useful to have more knowledge that can help us find new drugs that can dispose of the cancer cells,” Taskén points out to the research magazine Apollon.

source : http://www.sciencedaily.com/releases/2014/08/140825084836.htm

Older patients with limited life expectancy still receiving cancer screenings

The authors are Trevor J. Royce, M.D., M.S., University of North Carolina at Chapel Hill, and colleagues.

An aim of Healthy People 2020 is to increase the proportion of individuals who receive cancer screening consistent with the U.S. Preventive Services Task Force’s (USPSTF) evidence-based guidelines. And there is general agreement that routine cancer screening is unlikely to benefit patients with limited life expectancy.

The authors examined rates of prostate, breast, cervical and colorectal cancer screening in patients 65 or older using data from the National Health Interview Survey from 2000 through 2010. The study included 27,404 participants who were grouped by risk (low to very high) of nine-year mortality. Low mortality risk was defined as less than 25 percent and very high mortality risk was 75 percent or more.

Results: In patients with very high mortality risk, 31 percent to 55 percent received recent cancer screening, with prostate cancer screening being the most common (55 percent). For women who had a hysterectomy for benign reasons, 34 percent to 56 percent had a Papanicolaou test within the past three years. The overall screening rates for the study group were prostate cancer, 64 percent (ranging from 70 percent in individuals with low mortality risk to 55 percent in those with very high mortality risk); breast cancer, 63 percent (ranging from 74 percent among people with low mortality risk to 38 percent in patients with very high mortality risk); cervical cancer, 57 percent (ranging from 70 percent among low mortality risk patients to 31 percent in patients with very high mortality risk); and colorectal cancer, 47 percent (ranging from 51 percent for low-mortality risk patients to 41 percent for patient with very high mortality risk). There was less screening for prostate and cervical cancers in more recent years compared with 2000. Older age was associated with less screening for all cancers. Patients who were married, had more education, had insurance, or had a usual place for care were more likely to be screened.

“These results raise concerns about overscreening in these individuals, which not only increases health care expenditure but can lead to patient net harm. Creating simple and reliable ways to assess life expectancy in the clinic may allow reduction of unnecessary cancer screening, which can benefit the patient and substantially reduce health care costs. There is considerable need for further dissemination efforts to educate physicians and patients regarding the existing screening guidelines and potential net harm from screening in individuals with limited life expectancy.”

In ‘Modeling Study Analyzes Colonoscopy Screening of Medicare Patients,’ author Frank van Hees, M.Sc., of Erasmus University Medical Center, the Netherlands, and colleagues concluded in a simulated modeling study that screening Medicare beneficiaries with colonoscopies more regularly than recommended resulted in only small increases in prevented colorectal cancer (CRC) deaths and life-years gained but large increases in colonoscopies performed and colonoscopy-related complications.

All guidelines for CRC screening recommend a screening interval of 10 years for colonoscopy screening in average-risk patients. The U.S. Preventive Services Task Force and the American College of Physicians recommend against routine screening in adults older than 75 years with an adequate screening history.

The authors used a microsimulation model to estimate whether more intensive screening than recommended was beneficial to Medicare beneficiaries, as well as whether any benefit justified the additional resources required.

Screening Medicare beneficiaries with a negative screening colonoscopy result at 55 years according to current guidelines (i.e. screening again at 65 and 75) resulted in 14.1 CRC cases prevented, 7.7 CRC deaths prevented and 63.1 life-years (LYs) gained per 1,000 beneficiaries compared with no screening. Compared with screening every 10 years, screening every five years resulted in 1.7 additional CRC cases prevented, 0.6 additional CRC deaths prevented, 5.8 additional LYs gained and prevented 10.9 additional LYs with CRC care per 1,000 beneficiaries. To achieve this small benefit, 783 more colonoscopies had to be performed.

“Screening Medicare beneficiaries more intensively than recommended is not only inefficient from a societal perspective; often it is also unfavorable for those being screened. This study provides strong evidence and a clear rationale for clinicians and policy makers to actively discourage this practice.”

In a related commentary, Cary P. Gross, M.D., of the Yale University School of Medicine, writes: “Cancer screening in the 21st century, however, is losing its luster. Increasing evidence suggests that many modalities of cancer screening may be far less beneficial than first thought.”

“It is particularly important to question screening strategies for older persons. Patients with a shorter life expectancy have less time to develop clinically significant cancers after a screening test and are more likely to die from noncancer health problems after a cancer diagnosis. In addition, older persons face a higher risk of complications from procedures such as screening colonoscopy. In this context, two articles in this issue of JAMA Internal Medicine are informative,” Gross continues.

“It truly will be a new era when providers will be evaluated, in part, by their ability to refrain from ordering cancer screening tests for some of their patients. We are moving toward a time when prevention efforts will be more evidence based, more effective and patient centered. What could be more wonderful than that?” Gross concludes.

source : http://www.sciencedaily.com/releases/2014/08/140818192639.htm

Microchip reveals how tumor cells transition to invasion

Using a microengineered device that acts as an obstacle course for cells, researchers have shed new light on a cellular metamorphosis thought to play a role in tumor cell invasion throughout the body.

The epithelial-mesenchymal transition (EMT) is a process in which epithelial cells, which tend to stick together within a tissue, change into mesenchymal cells, which can disperse and migrate individually. EMT is a beneficial process in developing embryos, allowing cells to travel throughout the embryo and establish specialized tissues. But recently it has been suggested that EMT might also play a role in cancer metastasis, allowing cancer cells to escape from tumor masses and colonize distant organs.

For this study, published in the journal Nature Materials, the researchers were able to image cancer cells that had undergone EMT as they migrated across a device that mimics the tissue surrounding a tumor.

“People are really interested in how EMT works and how it might be associated with tumor spread, but nobody has been able to see how it happens,” said lead author Ian Y. Wong, assistant professor in the Brown School of Engineering and the Center for Biomedical Engineering, who performed the research as a postdoctoral fellow at Massachusetts General Hospital. “We’ve been able to image these cells in a biomimetic system and carefully measure how they move.”

The experiments showed that the cells displayed two modes of motion. A majority plod along together in a collectively advancing group, while a few cells break off from the front, covering larger distances more quickly.

“In the context of cell migration, EMT upgrades cancer cells from an economy model to a fast sports car,” Wong said. “Our technology enabled us to track the motion of thousands of ‘cars’ simultaneously, revealing that many sports cars get stuck in traffic jams with the economy cars, but that some sports cars break out of traffic and make their way aggressively to distant locations.”

Armed with an understanding of how EMT cancer cells migrate, the researchers hope they can use this same device for preliminary testing of drugs aimed at inhibiting that migration. The work is part of a larger effort to understand the underpinnings of cancer metastasis, which is responsible for nine out of 10 cancer-related deaths.

Tumor cells on the move

Time-lapse microphotography shows a portion of the cancer cells making more rapid progress through the cellular obstacle course. Researchers were surprised to observe that cells remaining with the group began reverting to a less invasive cell type.

‘Obstacle course for cells’

To get this new view of how cancer cells move, the researchers borrowed microelectronics processing techniques to pattern miniaturized features on silicon wafers, which were then replicated in a rubber-like plastic called PDMS. The device consists of a small plate, about a half-millimeter square, covered in an array of microscopic pillars. The pillars, each about 10 micrometers in diameter and spaced about 10 micrometers apart, leave just enough space for the cells to weave their way through. Using microscopes and time-lapse photography, the researchers can watch cells as they travel across the plate.

“It’s basically an obstacle course for cells,” Wong said. “We can track individual cells, and because the size and spacing of these pillars is highly controlled, we can start to do statistical analysis and categorize these cells based on how they move.”

For their experiments, the researchers started with a line of benign cancer cells that were epithelial, as identified by specific proteins they express. They then applied a chemical that induced the cells to become malignant and mesenchymal. The transition was confirmed by looking for proteins associated with the mesenchymal cell type. Once all the cells had converted, they were set free on the obstacle course.

The study showed that about 84 percent of the cells stayed together and slowly advanced across the plate. The other 16 percent sped off the front and quickly made it all the way across the device. To the researchers’ surprise, they found that the cells that stayed with the group started to once again express the epithelial proteins, indicating that they had reverted back to the epithelial cell type.

“That was a remarkable result,” Wong said. “Based on these results, an interesting therapeutic strategy might be to develop drugs that downgrade mesenchymal sports cars back to epithelial economy models in order to keep them stuck in traffic, rather than aggressively invading surrounding tissues.”

As for the technology that made these findings possible, the researchers are hopeful that it can be used for further research and drug testing.

“We envision that this technology will be widely applicable for preclinical testing of anti-migration drugs against many different cancer cell lines or patient samples,” Wong said.

Other authors on the paper are Elisabeth A. Wong (no relation), now a medical student at the Alpert Medical School of Brown University, as well as Sarah Javaid, Sinem Perk, Daniel A. Haber, Mehmet Toner, and Daniel Irimia of Massachusetts General Hospital. The work was supported by the Damon Runyon Cancer Research Foundation (DRG-2065-10), the Howard Hughes Medical Institute and the National Institute of Health under (CA129933, EB002503, CA135601, GM092804).

source : http://www.sciencedaily.com/releases/2014/08/140817220021.htm