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Tag: chronic inflammation

Published on Leave a comment on Can Exercise Slow Cancer Growth?

Some studies with humans suggest that cancer growth is slowed with exercise, better cancer prognosis with regular exercise, and lowered cancer recurrence (e.g., exercise after prostate cancer diagnosis), but a recent study looked at the issue more in depth.

Yes, it was done in mice, but this way mice could be randomly assigned to different treatments (including various cancers - both fast and slow growing ones) and conditions in ways you can't with humans.

Why does exercise have these beneficial effects? Various suggestions include exercise causing changes in body composition, or sex hormone levels, or systemic inflammation, and changes in immune cell function. The researchers point out that cells of the immune system play dual roles in cancer: the immune system has a powerful capacity to combat cancer, but chronic inflammation has also been linked to formation of tumors (cancer). Thus, "mobilization" of cancer killing "immune cells during exercise might represent an indirect defense mechanism against cancer growth."

Bottom line: research suggests that exercise or vigorous activity is beneficial in those with cancer diagnosis.

From Science Daily: Running helps mice slow cancer growth

Here's one more benefit of exercise: mice who spent their free time on a running wheel were better able to shrink tumors (a 50% reduction in tumor size) compared to their less active counterparts. Researchers found that the surge of adrenaline that comes with a high-intensity workout helped to move cancer-killing immune (NK) cells toward lung, liver, or skin tumors implanted into the mice. The study appears Feb. 16, 2016 in Cell Metabolism.

"It is known that infiltration of natural killer (NK) immune cells can control and regulate the size of tumors, but nobody had looked at how exercise regulates the system," says senior study author Pernille Hojman, at the University of Copenhagen. "In our experiments, we tried to inject our mice with adrenaline to mimic this increase you see during exercise, and when we do that we see that the NK cells are mobilized to the bloodstream, and if there's a tumor present then the NK cells will find the tumor and home to it."

Hojman and her colleagues next used mice depleted of NK cells to show that the increase in number of NK cells at the site of the tumor was directly contributing to the reduction in size. Even with exercise and a full suite of other immune cells, without the NK cells these mice experienced the normal rate of cancer growth. Blocking the function of adrenaline also blunted the cancer-killing benefits of the running wheel.

The research group also discovered that an immune signaling molecule called IL-6 was the link between adrenaline-dependent mobilization of NK cells and tumor infiltration. It's known that IL-6 is released from muscle tissue during exercise, but Hojman presents evidence that adrenaline specifically hails IL-6 sensitive NK cells and that the IL-6 molecules helped guide the immune cells to the tumors.

"As someone working in the field of exercise and oncology, one of the main questions that cancer patients always ask is: how should I exercise? Can we do anything?" she says. "While it has previously been difficult to advise people about the intensity at which they should exercise, our data suggest that it might be beneficial to exercise at a somewhat high intensity in order to provoke a good epinephrine surge and hence recruitment of NK cells." (http://www.cell.com/cell-metabolism/pdf/S1550-4131(16)30003-1.pdf)

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Some recent studies looked at aspirin use and cancer and found that consistent use for a number of years (5 to 10 years) lowers the rate of a number of cancers, including colon cancer. However, the longer one takes daily aspirin - then harms start adding up, with a major one being gastrointestinal bleeding. NSAIDs (non-steroidal anti-inflammatory drugs) are also linked to lower rates of various cancers, but harms with long-term use are cardiovascular risks (stroke and heart attack). The first article discusses that many doctors think this lower cancer rate occurs because aspirin and NSAIDs lower inflammation, and as we know, inflammation is linked to cancer.

From Science News: Aspirin reverses obesity cancer risk

Research has shown that a regular dose of aspirin reduces the long-term risk of cancer in those who are overweight in an international study of people with a family history of the disease....They found that being overweight more than doubles the risk of bowel cancer in people with Lynch Syndrome, an inherited genetic disorder which affects genes responsible for detecting and repairing damage in the DNA. Around half of these people develop cancer, mainly in the bowel and womb. However, over the course of a ten year study they found this risk could be counteracted by taking a regular dose of aspirin.

Lots of people struggle with their weight and this suggests the extra cancer risk can be cancelled by taking an aspirin.This research adds to the growing body of evidence which links an increased inflammatory process to an increased risk of cancer. Obesity increases the inflammatory response. One explanation for our findings is that the aspirin may be suppressing that inflammation which opens up new avenues of research into the cause of cancer."

When they were followed up ten years later, 55 had developed bowel cancers and those who were obese were more than twice as likely to develop this cancer -- in fact 2.75 times as likely. Following up on patients who were taking two aspirins a day revealed that their risk was the same whether they were obese or not....What is surprising is that even in people with a genetic predisposition for cancer, obesity is also a driver of the disease. 

The researchers believe the study shows that aspirin is affecting an underlying mechanism which pre-disposes someone to cancer and further study is needed in this area. Since the benefits are occurring before the very early stages of developing a tumour -- known as the adenoma carcinoma sequence -- the effect must be changing the cells which are predisposed to become cancerous in later years.

...continue reading "Aspirin and Cancer"

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The study results of 218 overweight, postmenopausal women who had insufficient levels of vitamin D (like most people) at the beginning of the study found that weight loss (including exercise), in combination with vitamin D supplementation, had a greater effect on reducing chronic inflammation than weight loss alone.

Current thinking is that chronic inflammation is linked to various chronic diseases as well as cancers. So reducing chronic inflammation is good. From Medical Xpress:

Weight loss plus vitamin D reduces inflammation linked to cancer, chronic disease

For the first time, researchers at Fred Hutchinson Cancer Research Center have found that weight loss, in combination with vitamin D supplementation, has a greater effect on reducing chronic inflammation than weight loss alone. Chronic inflammation is known to contribute to the development and progression of several diseases, including some cancers.

"We know from our previous studies that by losing weight, people can reduce their overall levels of inflammation, and there is some evidence suggesting that taking vitamin D supplements can have a similar effect if one has insufficient levels of the nutrient," said lead and corresponding author Catherine Duggan, Ph.D., a principal staff scientist in the Public Health Sciences Division at Fred Hutch. 

To explore this question, Duggan and colleagues recruited 218 healthy, overweight older women who had lower-than-recommended levels of vitamin D (less than 32 ng/mL). The women then took part in a 12-month diet and exercise program (including 45 minutes of moderate-to-vigorous exercise five days a week). Half of the study participants were randomly selected to receive 2,000 IU of vitamin D daily for the duration of the year-long trial, and the other half received an identical-appearing placebo, or dummy vitamin. 

At the end of the study, all of the participants had reduced levels of inflammation, regardless of whether they took vitamin D, "which highlights the importance of weight loss in reducing inflammation," Duggan said. However, those who saw the most significant decline in markers of inflammation were those who took vitamin D and lost 5 to 10 percent of their baseline weight. These study participants had a 37 percent reduction in a pro-inflammatory cytokine called interleukin-6, or IL-6, as compared to those in the placebo group, who saw a 17.2 percent reduction in IL-6. The researchers found similar results among women in the vitamin D group who lost more than 10 percent of their starting weight. While IL-6 has normal functions in the body, elevated levels are associated with an increased risk of developing certain cancers and diabetes and may be implicated as a cause of depression, Duggan said.

Inflammation occurs when the body is exposed to pathogens, such as bacteria or viruses, which puts the immune system in overdrive until the "attack" ceases and the inflammatory response abates. Overweight or obese people, however, exist in a state of chronic inflammation. This sustained upregulation of the inflammatory response occurs because fat tissue continually produces cytokines, molecules that are usually only present for a short time, while the body is fighting infection, for example.

"It is thought that this state of chronic inflammation is pro-tumorigenic, that is, it encourages the growth of cancer cells," she said. There is also some evidence that increased body mass "dilutes" vitamin D, possibly by sequestering it in fat tissue."Weight loss reduces inflammation, and thus represents another mechanism for reducing cancer risk," Duggan said. "If ensuring that vitamin D levels are replete, or at an optimum level, can decrease inflammation over and above that of weight loss alone, that can be an important addition to the tools people can use to reduce their cancer risk."

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Chronic inflammation can have a variety of negative health effects. From Time:

13 Ways Inflammation Can Affect Your Health

You can't live without inflammation, but it can also be hazardous to your health. You’ve heard of anti-inflammatory medications and anti-inflammatory diets, but do you really know what inflamation is? In short, it’s the body’s response to outside threats like stress, infection, or toxic chemicals. When the immune system senses one of these dangers, it responds by activating proteins meant to protect cells and tissues. “In a healthy situation, inflammation serves as a good friend to our body,” says Mansour Mohamadzadeh, PhD, director of the Center for Inflammation and Mucosal Immunology at the University of Florida.” “But if immune cells start to overreact, that inflammation can be totally directed against us.” This type of harmful, chronic inflammation can have a number of causes, including a virus or bacteria, an autoimmune disorder, sugary and fatty foods, or the way you handle stress. Here are a few ways it can affect your health, both short-term and long.

It fights infection.Inflammation is most visible (and most beneficial) when it’s helping to repair a wound or fight off an illness...It prepares you for battles Another type of inflammation occurs in response to emotional stress. Instead of blood cells rushing to one part of the body, however, inflammatory markers called C-reactive proteins are released into the blood stream and travel throughout the body.

It can harm your gut Many of the body’s immune cells cluster around the intestines, says Denning. Most of the time, those immune cells ignore the trillions of healthy bacteria that live in the gut. “But for some people, that tolerance seems to be broken,” says Denning, “and their immune cells begin to react to the bacteria, creating chronic inflammation.” The immune cells can attack the digestive tract itself, an autoimmune condition known as inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn’s disease. 

It can harm your joints When inflammation occurs in the joints, it’s can cause serious damage. One joint-damaging condition is rheumatoid arthritis(RA)—another example of an autoimmune disorder that appears to have a genetic component, but is also linked to smoking, a lack of vitamin D, and other risk factors.

It’s linked to heart disease Any part of your body that’s been injured or damaged can trigger inflammation, even the insides of blood vessels. The formation of fatty plaque in the arteries can trigger chronic inflammation. The fatty plaques attract white blood cells, grow larger, and can form blood clots, which can cause a heart attack.Obesity and unhealthy eating increases inflammation in the body.

It’s linked to a higher risk of cancer Chronic inflammation has been linked to cancers of the lung, esophagus, cervix, and digestive tract, among others..The inflammation may be due to obesity, a chronic infection, a chemical irritant, or chronic condition; all have been linked to a higher cancer risk....It may sabotage your sleep In a 2009 study from Case Western Reserve University, people who reported sleeping more or less than average had higher levels of inflammation-related proteins in their blood than those who said they slept about 7.6 hours a night.

It’s bad for your lungs When inflammation occurs in the lungs, it can cause fluid accumulation and narrowing of the airways, making it difficult to breathe...Smoking, exposure to air pollution or household chemicals, being overweight, and even consumption of cured meats have been linked to lung inflammation... It damages gums Inflammation can also wreak havoc on your mouth in the form of periodontitis, a chronic inflammation of the gums caused by bacteria accumulation. 

It makes weight loss more difficult Obesity is a major cause of inflammation in the body, and losing weight is one of the most effective ways to fight it. But that’s sometimes easier said than done, because elevated levels of inflammation-related proteins can also make weight loss more difficult than it should be.... Inflammation can also increase insulin resistance (which raises your risk for diabetes) and has been linked with future weight gain.

It damages bones Inflammation throughout the body can interfere with bone growth and even promote increased bone loss, according to a 2009 review study published in the Journal of Endocrinology.  It affects your skin The effects of inflammation aren’t just internal: They can also be reflected on your skin. Psoriasis, for example, is an inflammatory condition that occurs when the immune system causes skin cells to grow too quickly. .... It’s linked with depression 

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This recent scientific (and yes, technical) article discusses the tantalizing promise of treating cancer, especially melanoma, with infections and certain vaccines. Much discussion of how two vaccines that are already out there may prevent some cancers such as melanoma and leukemia (vaccination with Bacille Calmette-Guerin (BCG) of newborns and vaccination with the yellow fever 17D vaccine of adults).This recent article is a further development on what was discussed in the last post (Injecting a person with a bacterial extract - called Coley's toxins or Coley toxins - to cause an infection, and so treat cancer). From BioMed Central:

The biography of the immune system and the control of cancer: from St Peregrine to contemporary vaccination strategies

In 1875 Campbell de Morgan, a surgeon at the Middlesex Hospital in London, reported that regressions and remissions of cancers sometimes occurred after post-operative infections, particularly the streptococcal infection erysipelas...

Campbell de Morgan’s observation that remissions sometimes occurred after post-operative streptococcal infections inspired some workers to undertake the risky procedure of deliberately inducing erysipelas in cancer patients. Subsequently, an American surgeon, William Coley, developed bacteria-free extracts of streptococci and other bacteria (“Coley toxins”) and reported their successful use in the therapy of cancers, especially sarcomas, between 1881 and 1936 . Unfortunately Coley, a mild mannered and unassuming gentleman, did not adhere to rigorous scientific protocols in his studies and he was marginalized by forceful personalities advocating radiotherapy. Notwithstanding, an analysis of his results with cancer deemed inoperable undertaken in 1994 revealed a remission rate of 64% and a five-year survival rate of 44%, results equal to or better than those with modern therapies [14]. 

It is also now appreciated that chronic inflammation is an essential element of cancers and it has indeed been termed ‘the other half of the tumour’ [37]. The normal healing process relies on inflammation, collagen production, angiogenesis and cell proliferation and, in a description of the similarities between tumour stroma formation and wound healing, tumours have been referred to as “wounds that do not heal” [38], 

The relationship between infection, and associated inflammation, and cancer is a complex and paradoxical one and there are several well described examples of cancer being the direct consequence of infection [41]. Around 2 million of the 12.7 million new cancer cases worldwide in 2008 (16.1%) were assumed to be related to infection, principally Helicobacter pylori, hepatitis viruses, and the human papilloma virus, with a higher proportion in developing countries (22.9%) than in developed ones (7.4%) [42]. The large majority of cases of cancer, especially those in the developed nations, are therefore not caused by infection – on the contrary, there is growing evidence that a history of certain infections and environmental exposure to certain populations of micro-organisms, as well as some types of vaccination, may induce patterns of immune reactivity that reduce the risk of at least some cancers. 

A study of an adult population in Italy demonstrated an association between a history of common childhood infectious diseases (measles, chickenpox, rubella, mumps and pertussis) and the risk of developing chronic lymphatic leukaemia (CLL), with a strong inverse relationship between the risk of CLL and the number of infections (p = 0.002) [47]. 

In the 1990s Kölmel and colleagues established a working group – Febrile Infections and Melanoma (FEBIM) – within the European Organization for Research and Treatment of Cancer (EORTC). Based on a pilot study [79] this group undertook a series of studies to establish the relationship between the risk for developing melanoma and a history of, initially, infectious diseases [80], and, subsequently, also of vaccinations [81,82].

In the first report of the FEBIM group a significant level of protection against melanoma in those with a history of certain severe infections (sepsis, Staph. aureus infection, pneumonia, pulmonary tuberculosis) with fever of over 38.5°C was demonstrated [80]. It should, however, be noted that these apparently melanoma-protective infectious diseases have become rare in the industrialized nations. 

It is claimed that, as a result of recent observational studies, measures for prevention of some malignancies such as melanoma and certain forms of leukaemia are already at hand: vaccination with Bacille Calmette-Guérin (BCG) of new-borns and vaccination with the yellow fever 17D (YFV) vaccine of adults. While the evidence of their benefit for prevention of malignancies requires substantiation, the observations that vaccinations with BCG and/or vaccinia early in life improved the outcome of patients after surgical therapy of melanoma are of practical relevance as the survival advantage conferred by prior vaccination is greater than any contemporary adjuvant therapy.

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The following is from a presentation from The American Association of Diabetes Educators Annual Meeting August 6-9, 2014 by M.Jardin and C.Kafity. But the coffee and tea statement is different from what I've read elsewhere, specifically that coffee is beneficial, is a source of soluble fiber, and may keep pathogenic bacteria in check. From Endocrinology Today:

Plant-based diet helps grow healthy microbiota, halt diabetes disease process

With research mounting on the onslaught the body’s microbiota take from human eating patterns and the environment, making choices to maintain inner ecosystem health is essential, according to presenters at the American Association of Diabetes Educators Annual Meeting. Choosing a plant-based diet is one way people can increase the diversity of bacteria in their biome, reduce inflammation and begin to reverse the diseases processes involved in obesity and diabetes — often in just a few days.

“We know obesity and diabetes have increased tremendously in the last 20 years and we know that our genes haven’t changed, so that can’t account for the change,” Meghan Jardine, MS, MBA, RD, LD, CDE, RDN, of Parkland Health and Hospital System, said during a presentation. “Many scientists believe the changes in our diet and physical activity can’t really account for the change either, that there’s something else at work here.”

Weighing at least two kilograms in all and accounting for more than 3 times the amount of the body’s human cells, gut bacteria is colonized after birth, stabilized by age 3 years but influenced by a number of external factors, Jardine explained. Areas of influence include nutrition and immune function, both priorities in treating obesity and diabetes.

“Microbiota releases enzymes that digest food so we can absorb nutrients, produces vitamins, combats opportunistic infections and works with the immune system,” Jardine said. “About 70% of our immune systems are in our gut.”

People who consume plant-based diets have “healthy” gut microbiota in terms of global parameters and functional and compositional features, Christina Kafity, RN, BSN,CHC... “Children and elderly individuals who consumed more plant carbohydrates versus the typical standard American diet had rapid, reproducible alterations of the gut microbiota for the better, and this happened within 24 hours to a week,” Kafity said.

Growing good bacteria depends on creating an environment in which they can thrive, Kafity explained, including choosing foods that contain certain fibers intact in plants and probiotics; among them are soluble, insoluble and functional fibers as well as psyllium and inulin.

Intake of cruciferous vegetables including Brussels sprouts, kale and cabbage can help boost healthy microbes and, further, provide glucosinolates to help to reduce inflammation, Kafity said. Yogurt, kefir and probiotics also promote the growth of good bacteria, Kafity noted, while some popular beverages may not be much help. “We’re considering that coffee and teas may actually sterilize the bacteria.”

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An argument for the need for human exposure to the microbes in rural environments. However, the role of diesel exhaust and other urban air pollutants is not discussed here (for example, diesel exhaust is linked to asthma). From Science Daily:

Rural microbes could boost city dwellers' health, study finds

The greater prevalence of asthma, allergies and other chronic inflammatory disorders among people of lower socioeconomic status might be due in part to their reduced exposure to the microbes that thrive in rural environments, according to a new scientific paper co-authored by a University of Colorado Boulder researcher.

The article, published in the journal Clinical & Experimental Immunology, argues that people living in urban centers who have less access to green spaces may be more apt to have chronic inflammation, a condition caused by immune system dysfunction.

When our immune systems are working properly, they trigger inflammation to fight off dangerous infections, but the inflammation disappears when the infection is gone. However, a breakdown in immune system function can cause a low level of inflammation to persist indefinitely. Such chronic inflammation can cause a host of health disorders.

Some scientists have hypothesized that the increase of chronic inflammation in wealthier Western countries is connected to lifestyles that have essentially become too clean. The so-called "hygiene hypothesis" is based on the notion that some microbes and infections interact with the immune system to suppress inflammation and that eliminating exposure to those things could compromise your health.

The authors agree that microbes and some types of infections are important because they can keep the immune system from triggering inflammation when it's not necessary, as happens with asthma attacks and allergic reactions.

But they say the infections that were historically important to immune system development have largely been eliminated in developed countries. The modern diseases we pick up from school, work and other crowded areas today do not actually lead to lower instances of inflammatory disorders.

During our evolutionary history, the human immune system was exposed to microbes and infections in three important ways: commensal microbes were passed to infants from their mothers and other family members; people came into contact with nonpathogenic microbes in the environment; and people lived with chronic infections, such as helminths, which are parasitic worms found in the gut and blood.

In order for those "old infections" to be tolerated in the body for long periods of time, they evolved a mechanism to keep the human immune system from triggering inflammation. Similarly, environmental bacteria, which were abundant and harmless, were tolerated by the immune system. According to Rook, a professor at UCL, "Helminthic parasites need to be tolerated by the immune system because, although not always harmless, once they are established in the host efforts by the immune system to eliminate them are futile, and merely cause tissue damage."

In contrast, relatively modern "crowd infections," such as measles or chicken pox, cause an inflammatory response. The result is that either the sick person dies or the infection is wiped out by the inflammation and the person becomes immune from having the same infection again in the future.

Collectively, the authors refer to the microbes and old infections that had a beneficial impact on the function of our immune systems as "old friends." Exposure to old friends plays an important role in guarding against inflammatory disorders, the authors said. Because the "old infections" are largely absent from the developed world, exposure to environmental microbes -- such as those found in rural environments, like farms and green spaces -- has likely become even more important.

The authors say this would explain why low-income urban residents -- who cannot easily afford to leave the city for rural vacations -- are more likely to suffer from inflammatory disorders. The problem is made worse because people who live in densely populated areas also are more likely to contract crowd infections, which cause more inflammation.