Why Immunotherapy fails 60% of Metastatic Melanoma Patients

AHA Publisher — Sun, 29 Sep 2019 07:00:04 +0000

Brian Blum via Israel21c – The ultimate goal is to improve personalized medicine. “Can we predict who will respond?” asks Markel. “Can we alter treatment in order to increase responses?” Immunotherapy has transformed the treatment of many cancers, turning them from incurable to manageable as a kind of chronic illness. But not metastatic melanoma. More than half of patients (some 60 percent) with the disease do not respond to immunotherapy treatments. Researchers at Tel Aviv University’s Sackler School of Medicine and Sheba Medical Center’s Ella Lemelbaum Institute for Immuno-Oncology wanted to know why. The researchers reviewed the results of 116 melanoma patients treated with immunotherapy. Using a protein mapping technique called proteomics, the researchers discovered a difference in the metabolism, or energy production process, between melanoma patients for whom immunotherapy worked, and those whose cancer proved resistant. Prof. Tami Geiger, head of the Proteomics Lab at Tel Aviv University, explained that her team was able to map thousands of proteins using a mass spectrometer. “We then followed up with extensive computational analysis to identify the proteins that differentiated between the response groups,” Geiger said. The main distinction, according to Geiger: “In the responders, we found higher levels of proteins associated with lipid metabolism, which led to better recognition by the immune system.” Lipids are the building-block molecules of living cells; they are oxidized to create energy in the body in a process known as fatty acid metabolism. Patients whose cancer cells had a faster fatty acid metabolism responded to immunotherapy, while cancer cells that had a slower fatty acid metabolism were able to “hide” from the immune system’s T-cells that are supposed to destroy them. The research was done on mice in collaboration with the Salk Institute in San Diego and Yale School of Medicine. Using genetic engineering, the researchers “silenced” the mechanism responsible for fatty acid metabolism. “Cancer in these mice developed at a faster rate compared to the control group,” Geiger said. Predicting Who Will Respond Best The results could be significant – and not just for melanoma. “These findings can also be relevant to many other malignancies,” said Sheba Medical Center’s Prof. Gal Markel, who led the study with Geiger and Dr. Michal Harel. The ultimate goal is to improve personalized medicine. “Can we predict who will respond?” asks Markel. “Can we alter treatment in order to increase responses?” For the moment, the research will only indicate which patients should take the immunotherapy track and which patients should not because they will know in advance that treatment won’t help. In the future, if scientists can develop targeted medication to raise the levels of fatty acid metabolism, that may help make the 40% of unresponsive patients more receptive to immunotherapies. “In subsequent studies, we [will be] looking for ways to improve the response to immunotherapy and expand the circle of patients who benefit from it,” said Markel. Melanoma is the most dangerous type of skin cancer. Although it accounts for only about one percent of skin cancers, it causes a large percentage of skin cancer deaths, according to the American Cancer Society. Some 7,230 people are expected to die of melanoma in the United States this year. Melanoma is called metastatic when the cancer has spread to other parts of the body. The results of the Tel Aviv team’s research were published in the September issue of the medical journal Cell. To read the original article click here.

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Top 11 Omega-3 Benefits and How to Get More Omega-3 in Your Diet

AHA Publisher — Sat, 14 Sep 2019 20:27:02 +0000

Dr. Josh Axe, DC, DMN, CNS – Getting plenty omega-3 fats in your diet is associated with a ton of great omega-3 health benefits. Some of the most notable omega-3 benefits include promoting heart health, preventing or improving symptoms of mental illness or brain decline, reducing disease-causing inflammation, and reducing your risk for autoimmune diseases and cancer. Omega-3 (or omega three) fatty acids get a fair amount of time in the press and a great deal of respect at this point, but do you know what omega-3s are? What omega-3 benefits could convince you to add more oily fish (or maybe a supplement) to your diet? Are omega-3 foods really that big of a deal when it comes to eating a nutrient-dense diet? Could you be deficient in these fatty acids? We’ll unpack these questions one by one, but let’s start by saying that omega-3 fatty acids are crucial nutrients for overall health. Your body doesn’t produce omega-3s on its own, which means they are “essential fatty acids” — you have to consume them. When it comes to omega-3 benefits, there are rarely nutrients that pack this many positive health outcomes into one compound. The most commonly known benefit of omega-3s is a reduced risk of heart disease, but that’s not the only studied plus of getting lots of omega-3s in your diet. In fact, omega-3 benefits everything from from fetal development to retinal function, weight management and a lot more in between. These acids support and promote optimal health for anyone. In fact, the FDA has already approved two omega-3 formulations as approved treatments for high triglycerides. One contains just one compound, and the other contains two of the animal-based omega-3 fatty acids, EPA and DHA. That’s not all. There are omega-3 for dogs benefits as well. So, what are they, why do you need them and what omega-3 fatty acids benefits are there? What Are Omega-3 Fatty Acids? What Does Omega-3 Do? Omega-3s are a specific type of polyunsaturated fatty acid. That means they contain more than one double bond in their chemical structure. The “3” refers to where in the chemical structure the first double bond occurs. Your body is able to synthesize saturated fatty acids, but you don’t have an enzyme that allows you to stick a double bond in the right spot to create omega-3s yourself. The four most common omega-3s found in food are ALA, EPA, ETA and DHA. Alpha-linolenic Acid (ALA): This plant-based omega-3 is found in green, leafy vegetables; flaxseeds and chia seeds; and canola, walnut and soybean oils (although those rancid oils are not ones I generally recommend). ALA is known as a short-chain omega-3. This means your body has to convert it into longer-chained EPA and DHA to synthesize it. This process is rather inefficient, and only about one percent of the ALA you consume is converted to the long-chain version your body needs (although this percentage is slightly higher for women). Eicosapentaenoic Acid (EPA): EPA is a 20-carbon fatty acid found in oily fish, algae oil and krill oil. Your body is able to synthesize this molecule in its original form. EPA and DHA are the omega-3s your body needs in high quantities to achieve the benefits they offer. Eicosatetraenoic Acid (ETA): ETA is a lesser-known omega-3 fatty acid that also contains 20 carbons, like EPA, but only four bonds instead of five. It is found richly in roe oil and green-lipped mussel. It has only recently been recognized for its potent health benefits. Not only is it anti-inflammatory, like the other omega-3s, but ETA can also limit your body’s production of the inflammatory omega-6 fatty acid arachidonic acid (ARA). In fact, ETA redirects the enzyme that normally creates ARA to convert it to EPA instead. Docosahexaenoic Acid (DHA): This 22-carbon molecule is also found in oily fish, krill oil and algae oil. Your body converts some DHA molecules back to EPA in order to keep them at fairly equal levels if you consume more DHA. Your body also needs omega-6s, another type of fatty acid, to function properly and prevent disease. Unfortunately, these are found in much more abundance than omega-3s in the standard American diet, although your body craves a 1:1 ratio to keep inflammation low. Most modern diets contain a ratio closer to 20:1 or 30:1 omega-6 to omega-3 fatty acids. Omega-6s come in some form of linoleic acid. They are found in vegetable oils, safflower oils, meat, poultry and eggs. Can You Have an Omega-3 Deficiency? Most people don’t get enough omega-3 fatty acids, according to an analysis and systematic review of dietary data about U.S. adults spanning 2003–2008. There is no official daily value assigned to omega-3s, but the American Heart Association recommends two or more 3.5-ounce fish servings (oily, if possible) each week in this systematic review. In general, most health organizations agree 250–500 milligrams of EPA and DHA combined each day is a reasonable amount to support healthy individuals. However, people with heart problems (or those with a high risk of heart disease), depression, anxiety and cancer (and possibly more conditions) may benefit from higher doses — up to 4,000 milligrams per day for some heart-related conditions. In 2009, the Harvard School of Public Health published a review of individual risk factors that are attributable to specific deaths. By its estimates, low omega-3 intake is eighth on the list of the most serious risk factors that contribute to death, labeling it responsible for up to 96,000 deaths in the U.S. each year. To reap all the omega-3 benefits, it may be difficult for some people to eat the required amounts of oily fish, particularly with the well-known dangers of farmed fish, which are more readily available to most Americans. That’s why some people consider a high-quality omega-3 supplement in addition to a well-rounded diet. I’ll discuss supplements in a moment, though. First, let’s look at why it’s so very important to get enough omega-3s. Omega-3 foods are believed to help lower the risk for heart disease due to their inflammation-reducing abilities. They also are needed for proper neurological function, cell membrane maintenance, mood regulation and hormone production. This is the reason omega-3 foods are known as “good fat” sources, the kinds that provide polyunsaturated fatty acids (PUFAS) known as alpha-linolenic acids. While most consume enough of the other kinds of essential fatty acids known as omega-6s (found in modified cooking oils like canola, sunflower and safflower oil, plus some nuts), most people are low in omega-3s and can afford to up their intake of omega-3 foods. Studies show that a lower ratio of omega-6s to omega-3s is more desirable to reduce the risk of many chronic diseases that have become epidemics in most Western societies. For example, researchers from the Center for Genetics, Nutrition and Health of Washington, D.C. found that the lower the omega-6/omega-3 ratio was in women, the lower their risk of breast cancer. A ratio of 2:1 suppresses inflammation in patients with rheumatoid arthritis, and a ratio of 5:1 has a beneficial effect on patients with asthma. The average person suffers from omega-3 deficiency because she doesn’t include the best omega-3 foods in her weekly diet, such as fish, sea vegetables/algae, flaxseeds or grass-fed meat. Depending on whom you ask, these numbers vary, but I advise people that the ideal ratio of omega-6 foods to omega-3 foods is about equal to, or at least at, a 2:1 ratio of omega-6s to omega-3s. What are the risks of consuming too little omega-3s (plus too many omega-6s)? • Inflammation (sometimes severe) • Higher risk for heart disease and high cholesterol • Digestive disorders • Allergies • Arthritis • Joint and muscle pain • Mental disorders like depression • Poor brain development • Cognitive decline What Is Omega-3 Good For? 11 Health Benefits 1. Good for Heart Health One of the most well-known benefits of omega-3s is the way they positively affect risk factors associated with heart disease. That’s one reason the American Heart Association is very clear about encouraging people to get enough in their diets — according to AHA omega-3 research in regard to cardiovascular health. Heart disease and stroke are the leading causes of death worldwide, but communities who eat diets rich in fish have remarkably low instances of these diseases. This is at least partially due to their high omega-3 consumption. While some studies have found no correlation indicating omega-3s significantly reduce risk of stroke or heart attacks, other reviews disagree. Here is what we do know about cardiovascular disease risks, including strokes and heart attacks, and omega-3s: • Lowering High Triglycerides: The American Heart Association recognizes that the highest amount of omega-3s are generally needed for people with high triglycerides, a major risk factor for heart disease. Doses of omega-3 supplements are associated with lowered triglyceride levels in patients with or without other diseases. • Regulating Cholesterol: Research finds omega-3 benefits cholesterol levels by raising HDL (“good”) cholesterol levels, although some results also find a slight increase in LDL cholesterol. The ratio of HDL:LDL should be very close to 2:1. • Lowering High Blood Pressure: A 2010 study found that three servings of salmon each week successfully lowered blood pressure in young, overweight people over an eight-week period. While this is not definitive proof that omega-3s lower blood pressure, it’s an encouraging preliminary result. • Preventing Plaque Buildup: Keeping arteries clear of damage, omega-3s may aid your body in preventing plaque buildup responsible for hardening and restriction of the arteries. • Reduce Metabolic Syndrome Symptoms: The cluster of risk factors known as metabolic syndrome includes abdominal obesity, high blood sugar, high triglycerides, high blood pressure and low HDL cholesterol. These risk factors are indicative of a high chance you might develop heart disease, stroke or diabetes. Multiple studies have found omega-3 supplementation improves the symptoms of metabolic syndrome and may help to protect you from the related diseases. • Preventing Blood Clots: It’s possible omega-3s help your platelets not clump together, aiding in the prevention of blood clots that may cause major harm. 2. May Fight Mental Disorders and Decline There are a number of conditions related to brain and mental health that seem to improve when individuals get good omega-3s. Depression and Anxiety: These common mental health concerns are some of the most prevalent in the world today, and conventional remedies for depression are, for the most part, disappointingly ineffective. However, people who regularly get large amounts of omega-3s are less likely to be depressed than those who are deficient. Several studies suggest that people suffering signs of depression and/or anxiety see improvement after adding an omega-3 supplement to their routines, even in double-blinded, randomized, controlled trials. At least one study comparing a common depression medication found omega-3 supplements to be just as effective in combating depression symptoms. ADHD: Studies comparing omega-3 levels in children have discovered those with ADHD diagnoses have lower blood omega-3 fatty acids compared to healthy comparison subjects. Limited but promising results seem to agree that there is some effectiveness of omega-3s for ADHD. Schizophrenia: A meta-analysis conducted by the Saint Louis University School of Medicine found that multiple studies comparing omega-3s and schizophrenia found modestly positive results, specifically in the early stages of the disease. Bipolar Disorder: Also known as manic depression, bipolar disorder is a complex and sometimes debilitating condition. There is some evidence that omega-3 benefits bipolar sufferers by stabilizing mood. Other Mental Illness and Behaviors: Some studies have found correlations between omega-3s and a decrease in violence, antisocial behavior and borderline personality disorder. Alzheimer’s and Age-Related Mental Decline: Small clinical trials have seen a potentially neuroprotective effect of omega-3 fats on people suffering from dementia, age-related mental decline and even Alzheimer’s disease. It seems that high levels of omega-3s in the blood can help to slow or even reverse some cognitive decline. 3. Reduce Inflammation One reason omega-3 fatty acids may be so beneficial to this many aspects of health could be that they help decrease system-wide inflammation....

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Why Immunotherapy fails 60% of Metastatic Melanoma Patients

Top 11 Omega-3 Benefits and How to Get More Omega-3 in Your Diet