Immunotherapy combination effective in patients with kidney cancer

Combining an anti-angiogenesis agent, which blocks blood vessel formation, with an immunotherapy agent, was found to have promising anti-tumor activity and no unexpected side effects in an early-phase clinical trial in patients with advanced kidney cancer who had not been previously treated, according to a researcher at the Georgetown Lombardi Comprehensive Cancer Center.

Axitinib inhibits angiogenesis, the process of blood vessels forming to feed a tumor. Inlyta was approved by the U.S. Food and Drug Administration in 2012 for the treatment of patients with advanced kidney cancer after one prior systemic therapy has failed, and has been shown to be selective in how it works, resulting in a strong effectiveness to toxicity ratio.

The immunotherapy agent, pembrolizumab, is an immune checkpoint inhibitor that blocks a self-defense mechanism used by cancer cells to evade attack and destruction by the body's immune cells. It is FDA-approved for the treatment of patients with several cancer types including melanoma, lung, bladder and head and neck cancers, but has only had limited study in patients with kidney cancer.

Earlier attempts to develop combinations of anti-angiogenesis agents and checkpoint-inhibitor-based immunotherapies to treat patients with advanced kidney cancer resulted in unacceptably high levels of toxicity and thus the combinations were not pursued further. In contrast, the axitinib-pembrolizumab combination was sufficiently tolerable to enable the agents to be given at their FDA-approved single-agent dose levels.

The combination doubled the efficacy of the drugs when used alone and the treatment was found to be tolerable," says Michael B. Atkins, MD, deputy director, Georgetown Lombardi Comprehensive Cancer Center and principal investigator for the study. "Specifically, over 90 percent of patients exhibited tumor shrinkage and the disease was kept under control for a median of over 20 months."

The investigators started their phase I clinical trial of this combination in 2014 and enrolled 52 advanced renal cell carcinoma (the most common form of kidney cancer ) patients who had not previously been treated for the disease. The enrollees received an intravenous infusion of pembrolizumab at the start of the trial and then every three weeks thereafter.

Patients also took axitinib twice daily until they could no longer tolerate the therapy or until no benefit was seen. The researchers looked at tumor size at trial enrollment, then 12 weeks later and every 6 weeks thereafter. In the 11-patient subgroup, three of the patients were not able to tolerate axitinib and received less than 75 percent of the planned dose due to toxicities, while eight patients experienced manageable side effects, thus establishing this dose level and the recommended dose level for further investigation in a group of 41 additional patients. Significantly, patients had fewer liver abnormalities and less fatigue than those treated with other similar combination therapies.

For the new combination therapy, tumor shrinkage or stabilization was better than what seen in patients taking just one of the two drugs alone. Seventy-three percent of patients experienced significant tumor shrinkage in response to the combination therapy and the median time in which there was no disease progression was 20.3 months. Overall survival results are still incomplete as 88 percent of the patients were still alive at a minimum 18 months after starting therapy.
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How to cure a burned mouth

Burns on the tongue heal faster than on the roof of the mouth, since the tongue has the most blood vessel supply in the entire body.

However, the pain can be searing since the skin here is more sensitive than other parts of the body, and it doesn't have any fat between the skin and the bones. As a result, it usually lingers two to three days.

Burned mouth can be healed quickly by sticking to a soft diet like yogurt and sushi, avoiding spice,noodles,soup, iced drink and hot foods eat lukewarm food - room temperature.

Coffee, wine and soda should all be off the menu for days. These foods are acidic, they will irritate skin as it's healing, potentially delaying the healing process.

Bacteria in an open wound can lead to infection and prevent healing. After a burn, brush your teeth thoroughly, use mouthwash, and drink plenty of water to wash out any built-up food or bacteria from your mouth.
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Nanoparticles can limit inflammation

An injection of nanoparticles may boost the immune system when it becomes weak. Inflammation is a double-edged sword. When it works, it helps the body heal and fights off infections. But sometimes, the immune system overreacts. An acute lung injury, sustained by inhaling smoke, for instance, can lead to runaway fluid production that essentially drowns a person.

Experiments in mice suggest that simple plastic nanoparticles, delivered by IV, may be able to keep a type of immune cell called a neutrophil too busy to cause inflammation. Other diseases in which neutrophils cause excessive inflammation include sepsis and the hardening of the arteries, or atherosclerosis.

Researchers designed an experiment injuring part of the blood vessel wall in the microfluidic chips and confirmed that the neutrophils were redirecting their attention from creating inflammation at the injury site to carting the foreign particles away. In mice with acute lung injury, they found that injecting nanoparticles by IV could reduce the number of neutrophils congregating at the injury site by half or more.

The neutrophil concentration was similar to the concentration found in the blood of uninjured mice. Instead, the neutrophils were taking the particles to the liver, where they could be removed from circulation. The chemicals that the team uses to attach the nanoparticles to the blood vessel walls are the same as those used by the neutrophils themselves, a coating that combines nonfouling materials with the targeting chemicals will throw most white blood cells off.
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Links between poor diet and untimely death

Inadequate nutrition and unhealthy eating habits are associated with untimely death. Many people are eating a diet which consists of too much salt and saturated fat, and less fruit, vegetables, nuts, seeds and whole grains.

Western diet comprises of processed foods that have little or no nutrients, it is linked to hypertension, heart disease, diabetes, obesity, colorectal cancer and hepatitis. Low intake of healthy foods is the major cause of mortality, poor nutrition habits can be a behavioral health issue, because nutrition and diet affect feeling, thinking and behavior. Poor diet results in lower strength.

According to National Institutes of Health, hypertension is one of the results of poor nutrition. Eating too much junk food, fried food, salt, sugar, dairy products, caffeine and refined food can cause hypertension.

Poor nutrition can lead to high cholesterol, which is the major cause of heart disease. High cholesterol foods contain large amount of saturated fat. Ice cream, Eggs, Cheese, Butter and Beef can cause high cholesterol. Diabetes also can be linked to poor diet.

A stroke is caused by plaque that builds up in a blood vessel, then breaks free as a clot that moves to the brain and creates a blockage can be linked to poor nutrition. Strokes damage the brain and impair functioning, sometimes leading to death. Foods high in salt, fat and cholesterol increase the risk for stroke.

Different types of cancer like bladder, colon and breast cancers, may be caused by poor dietary habits. Avoid foods that contains refined sugars, nitrates and hydrogenated oils. Eat fruits and vegetables everyday to remain healthy and avoid untimely death.
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E-cigarette speed up cardiovascular aging

Aortic stiffness is an age-related complication in the heart's main artery-aorta that can be an indicator of cardiovascular disease.

The researchers studied artery diameter, the blood vessels' ability to widen and aortic stiffness in female mice after short- and long-term exposure to flavored e-cigarette vapor.

They discovered that within an hour of the five-minute e-cigarette exposure, the short-term group's arteries narrowed by thirty percent. Long-term exposure to e-cigarette vapor  leads to aortic stiffness.

These showed that e-cigarettes are not safe and they induce significant deleterious effects on blood vessel function. Exposure to e-cigarette vapor can impair vascular function.
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Aspiring not effective for stroke prevention in atrial fibrillation patients

Atrial fibrillation (A-fib) is a condition of irregular heartbeat, it can leads to cardiovascular events like: stroke, blood clots and heart failure.

The most common treatment for A-fib patients is prescribing anticoagulants, or blood thinners. Some people with A-fib may also have a catheter ablation - a medical procedure that uses energy to damage a small part of heart tissue, thus stopping abnormal electrical signals from traveling through the heart.

Some of the risks associated with cardiac catheter ablation include bleeding or blood vessel damage.

However, as Dr. Jared Bunch - the lead author of the new research - explains, when patients with A-fib have had an ablation and also have a low risk of stroke, physicians prefer to treat them with aspirin instead of blood thinners in order to further reduce the risk of stroke.

In the new study, Dr. Bunch and his colleagues examined the effect of long-term aspirin use on patients with A-fib who underwent an ablation.

Putting their new research into perspective, Dr. Bunch explains, "What was unknown was if aspirin was a safe and effective stroke prevention treatment after an ablation in lower-risk AF [atrial fibrillation] patients.

Aspirin has no benefit for stroke prevention in patients with A- fib. The study examined 4,124 patients with A-fib over a period of 3 years. The participants had a low risk of stroke, and they had undergone catheter ablation.

Dr Bunch and colleagues discovered that patients that used aspiring were significantly more likely to have gastrointestinal and genitourinary bleeding than those who took anticoagulants such as warfarin, or compared with those who did not receive any treatment.