Cold atmospheric plasma provides new hope for brain cancer treatment

Researchers at the Max Planck Institute for Extraterrestrial Physics (MPE) showed that cold atmospheric plasma and chemo therapy together can eradicate brain cancer due to a synergistic effect. Experiments conducted so far have shown that this new combined treatment could destroy glioblastoma cells (even the most resistant cell populations that are sensitive to chemotherapy). This is clearly a breakthrough in oncology and could represent a new hope in the fight against this cancer.

Glioblastoma is one of the most common and aggressive primary brain tumors with a poor prognosis. The average length of survival is about one year, although there have been studies that have shown that combination therapy including radiation and chemotherapy can increase survival time to 15 months. Nobody knows exactly what causes this type of cancer (it seems that there are involved some genetic factors, radiation, smoking, viruses, certain chemicals), and it was found to occur more frequently in men. Treatment includes chemotherapy, radiation and surgery, but most times it is a palliative treatment meaning it is aimed only to relieve symptoms, not to cure cancer. There are situations in which, although initially the treatment was successful, though there is a high relapse rate.

Brain Tumor

But now a recent therapy could offer new hope in the fight against glioblastoma. CAP, which means cold atmospheric plasma,  has been shown to have multiple applications in medicine, such as sterilization, disinfection, and anticancer properties. CAP, a partly ionized gas, inactivates viruses, bacteria and parasites without harming healthy tissue in any way. Julia Zimmermann, who Manages the Plasma Healthcare Group at MPE, said that for many patients the standard treatment is not effective, because tumors contain subpopulations of cells that are resistant to chemotherapy. She added that their goal was to see if the CAP is effective against these resistant tumor cells.

The researchers tested various combinations of treatments on glioblastoma cells that were grown in cell culture dishes. It was found that in both normal cells and the resistant cells, growth inhibition was stronger after plasma treatment compared to chemotherapy alone. The researchers found that the strongest effect was obtained after application of 120 seconds and that CAP blocks the cell cycle and inhibits cell property to clone. What is interesting is that so far no resistance has emerged against CAP. “It is a first step, now we have to further investigate the effects gained in the cell culture and integrate them for the application,” she said.

Chemicals exposure found in plastics may cause arterial hypertension in teens

A new study reveals that phthalates, some chemicals found in some plastics and processed foods, are associated with high blood pressure in children and adolescents. These chemicals are found almost everywhere today: in plastic cups, intravenous tubes, beach balloons, and other plastic products. Lately there have been many studies which suggested  that dietary exposure to phthalates (that can contaminate food from plastic packaging) can cause metabolic and hormonal changes, especially in children.

Now, according to an article published in the Journal of Pediatrics, another negative effect of phthalates may be the cardiovascular risk that it poses. To verify this hypothesis, researchers at NYU Langone Medical Center, in collaboration with researchers at the University of Washington and Penn State University School of Medicine, conducted a study involving approximately 3,000 children and adolescents. They wanted to see for the first time whether a class quite commonly of phthalates used in food production industries (DEHP di-2-ethyhexylphthalate) is associated with increased systolic blood pressure.

plastics

Lead author Leonardo Trasande, MD, MPP, associate professor of Pediatrics, Environmental Medicine and Population Health at NYU Langone Medical Center, said that phthalates can inhibit oxidative function of cardiac cells and cause oxidative stress which may affect the functioning of the arteries, But no one so far has revealed a link between exposure to phthalates and heart health in adolescents. He added that their aim was to highlight the connection between phthalates and high blood pressure that occurs in children.

Hypertension is one of the most common disorders that occur with age and is defined as an increase in arterial pressure over 140mmHg/90mmHg. Although it is considered a specific medical condition in elderly, hypertension has become increasingly common among young people due to the global obesity epidemic. According to a nationwide survey, 14% of American teens already have hypertension or pre-hypertension. One of the factors contributing to the increasing incidence of obesity among young people is obesity but it seems that environmental factors play an important role also, which is important because exposure to phthalates can be controlled.

Researchers measured the concentration of phthalates in urine samples and found that every three-fold increase of degradation products of DEHP in urine resulted in one-millimeter mercury increase in the child’s blood pressure. Dr. Trasande said that although this increase may seem modest at the individual level, however at a population level these shifts  in blood pressure can significantly increase the number of children with hypertension.

New treatment for moderate-to-severe asthma is effective

According to an article published in the New England Journal of Medicine and presented at the American Thoracic Society 2013 International Conference, dupilumab, a fully human monoclonal antibody, is effective and safe in the treatment of persistent, moderate-to-severe asthma with high eosinophilia. The mechanism of action of this monoclonal antibody is to counteract the Th2 immune response by blocking the activation of two interleukins: interleukin 4 and interleukin 13. Asthma is a chronic inflammatory disease of the airways characterized by airway obstruction, coughing, shortness of breath and wheezing.

Asthma is a chronic respiratory disease that usually requires medication during lifetime. There are several drug classes to treat asthma: anti-inflammatory drugs (corticosteroids, mast cell stabilizers,  leukotriene antagonists) and bronchodilators (short-acting beta2-adrenoceptor agonists (SABA), long-acting beta-adrenoceptor agonists (LABA), anticholinergics) etc. It should be noted that the treatment is determined by the severity of symptoms. Lead author Sally Wenzel, MD, director of the University of Pittsburgh Asthma Institute, said that 10-20% of patients with moderate to severe asthma are unresponsive to standard therapy consisting of inhaled glucocorticosteroids (ICS) and long-acting beta agonists (LABA). She said that asthma that is difficult to treat expresses several phenotypes this is why new therapies are needed to control these respiratory symptoms.

Asthma

To test the effectiveness of dupilumab, researchers conducted a randomized, double-blind, placebo-controlled trial that included 104 patients: half of them were part of the dupilumab group and half were part of the placebo group. It should be noted that all study participants had moderate-to-severe asthma that do not respond well to treatment combined ICS and LABA. Also, all patients had increased levels of eosinophils in the blood or sputum.

During the 12 weeks of treatment and the 8 weeks of follow-up, patients who received injections of dupilumab had a reduction of asthma exacerbations by 87% compared with placebo group. Other improvements that were recorded were those related to lung function (forced expiratory volume in one second (FEV1) and morning peak expiratory flow). Also, it seems that dupilumab decreased the need for medication reliever use. Researchers have found that many of these improvements were seen especially when dupilumab was added to standard treatment ICS / LABA. Side effects have included nasopharyngitis, injection site irritation, nausea, vomiting, but none was serious.

Although dupilumab therapy did not decrease the level of eosinophils in the blood or sputum, though other biomarkers have declined: fractional exhaled nitric oxide, immunoglobulin E, eotaxina 3 and others, which demonstrates that dupilumab is biologically active.

Key inflammatory marker is linked to cancer

Researchers at the University of Illinois at Urbana-Champaign have made interesting progress in the fight against cancer. The new study, that was published in the journal Oncogene, shows how an important component of the inflammatory response and immune cell growth can become an important factor in tumor growth. Jekyll-and-Hyde molecule NF-kappa B, as the researchers called it, is a first responder in immune and inflammatory response. Jekyll-and-Hyde molecule NF-kappa B is found in the cell cytoplasm and when bacteria and viruses enter the body this molecule activates gene transcription leading to inflammation and cell proliferation.

cell

It was known for a long time that an overactive form of NF-kappa B  is involved in signaling pathways in the nucleus but no one knew what keeps it active in the nucleus. University of Illinois Medical Biochemistry professor Lin-Feng Chen, noted that in healthy cells NF-kappa B is found in the cytoplasm, not the nucleus, and is inactive. But in cancer cells without any stimulation you can see this nuclear form of NF-kappa B. The cell just won’t die because of this. That is why NF-kappa B is so important in cancer, ” Chen said. He added that in order to activate NF-kappa B,  normal cells must be stimulated. However, in cancer cells activation of this form nuclear NF-kappa B occurs without any stimulation, and this leads to cell proliferation.

Now, Chen and his team of researchers found that another molecule, called BRD4, which helps regulate gene expression, recognizes an acetylated amino acid of the a subunit of NF-kappa B protein complex. Only after that amino acid is acetylated, BRD4 can bind to NF-kappa B. This connection allows the activation of NF-kappa B and prevents its degradation in cancer cells. Researchers knew about this recognition, but what no one knew that this recognition has implications in cancer.

To see if BRD4 leads to sustained presence of NF-kappa B protein in the nucleus, the team of researchers led by Chen exposed lung cancer cells in cell culture and in immune-deficient mice to JQ1 (a drug that regulates the activity of BRD4). It was found that exposure to JQ1 interrupted the interaction between NF-kappa B. Thus the genes regulated by NF-kappa B were not expressed and proliferation of lung cancer cells decreased. In other words, researchers were able to suppress the ability of lung cancer cells to induce tumors in immune-deficient mice. Chen said that this study demonstrates that one day epigenetic regulators and NF-kappa B can be targets for cancer therapy.

New treatment for B cell lymphoma

Researchers at Weill Cornell Medical College are investigating a new treatment for a particular type of B cell lymphoma , that is with protein EZH2 mutations. The results so far have been promising and it seems that this new treatment could benefit a broader set of patients with lymphoma.

The study, which was published in Cancer Cell, points out that this particular subtype of B-cell lymphoma responds to EZH2 inhibitors, which target a key molecules  in B lymphocytes.  Weill Cornell Medical College’s Dr. Ari Melnick, the study’s lead investigator, says that follicular lymphoma may respond better to combination therapy formed of  EZH2 inhibitors and another targeted therapy.  He also said that this treatment is a non-toxic alternative to chemotherapy for a third of diffuse large B-cell lymphomas. Dr. Melnick believes that this new treatment could help patients with a wide range of lymphoma subtypes since both represent about 75% of all lymphomas in adults. “Researchers had thought EZH2 inhibitors would only help patients with a mutation EZH2 in their genes, which represents a small subset of lymphoma patients. What we found is that the majority of lymphomas turn out to be dependent on normal EZH2, not just mutated EZH2”.

B cell

Because there was little knowledge about the role of EZH2 in B cells, the researchers decided to conduct the study in order to understand the function of both normal and mutated EZH2 in B cells.  B cells are part of the immune system (along with other cells such as T cells, macrophages, etc.), and their function is to produce antibodies. Antibodies are produced when the body comes in contact with microorganisms (bacteria, viruses, parasites) and their role is to destroy them. What the researchers found was that EZH2 is necessary for the immune system to produce one of the strongest antibody subtypes, which are the germinal center B-cells. These B cells are highly efficient because they  divide extremely fast and generate specific antibodies to quickly eradicate the infection from the body.

Dr. Melnick said that most B-cell lymphomas derived from these germinal center B-cells and that the reason for this is that they have rapid division cycle which increases the number of causes genetic mutations. It seems that EZH2 stimulates B cell division  and, in addition,  has another important function in the immune system namely that it regulates B cell antibody production. Now, researchers want to combine EZH2 inhibitors with BCL2 inhibitors so that the treatment has a much greater effect.

Multiple Sclerosis Treatment

Researchers at Stanford University Medical Center have made new advances in the treatment of multiple sclerosis. Experiments conducted on laboratory animals have shown that blocking the expression of the protein, SIRT1, delays the onset of paralysis on multiple sclerosis.  Multiple sclerosis is a neurodegenerative disease characterized by demyelination of the nervous system, leading to a wide range of neurological signs and symptoms. Anne Brunet, PhD, an associate professor of genetics, says they are  excited about the potential this finding has in the treatment of neurodegenerative diseases. “Our study highlights the possibility of pharmacological manipulation of multiple nodes of the pathway to expand the population of oligodendrocyte precursors,” said Brunet.

However it is not known the exact mechanism by which blocking SIRT1 protein delays paralysis in multiple sclerosis. One possible explanation would be that by blocking this protein it is stimulated the production of insulating myelin sheath that is required for nerve transmission. Dr Brunet said that their discovery is intriguing because activation of SIRT1 is considered beneficial for health and in this case inactivation of SIRT1 protects against demyelination. Although other studies are needed in this direction, researchers are optimistic that someday patients with multiple sclerosis symptoms will be alleviated by interfering SIRT1 protein in the brain.

MultipleSclerosis

It seems that blocking SIRT1 leads to the transformation of neural stem cells into oligodendrocyte precursors, which is a type of brain cell. These precursors are transformed into mature cells, that is oligodendrocytes, which help myelination of axons. It should be noted that myelin is composed of lipid material and has an essential role in nerve transmission. Multiple sclerosis means diffuse demyelination of neurons and this can lead to a range of symptoms such as optic neuritis (impaired vision), motor deficits, paresthesia, diplopia (double vision), ataxia, vertigo, etc..

Brunet and her colleagues conducted several experiments on laboratory animals and found that by turning off the expression of SIRT1 in mice, the production of oligodendrocytes increased. Furthermore, when the researchers injected a compound that caused demyelination in both healthy mice and in those with inhibited SIRT1 expression, it was found that the latter recovered faster. To understand more about how work SIRT1 works in the brain, researchers searched and identified a number of genes that were expressed more intensely when SIRT1 is inhibited. These genes are related to cell metabolism, growth factor signaling and protein production. It seems that one of them, PDGFRalpha, is associated with the production of oligodendrocytes and inactivation of SIRT1.

Monoclonal antibody reduces wheezing in preterm babies

According to a study published in The New England Journal of Medicine, pavilizumab, a monoclonal antibody given to prevent respiratory syncytial virus infection, has proven effective in reducing the number of days of wheezing in preterm babies. Researchers say that wheezing episodes in late preterm children are mostly caused by respiratory syncytial virus and that these episodes of wheezing can be prevented by administering pavilizumab.

To demonstrate the efficacy of this monoclonal antibody in preventing the infection with RSV, researchers conducted a study that included 400 children born between 33 and 35 weeks’ gestational, that is late preterm. They were randomized to receive either injections of pavilizumab or placebo injections. The drug was well tolerated and the only adverse reactions that occurred were redness and swelling at the injection site. The study showed that the number of days of wheezing decreased to 60% among children who received injections with pavilizumab. In addition, it seems that the effect lasted even after cessation of treatment. Dr. Robert Lemanske Jr., a professor of pediatrics and medicine at the University of Wisconsin School of Medicine and Public Health in Madison, said that in preterm babies, RSV infections are a risk factor for wheezing and that this treatment reduces this risk.

Pavilizumab

Lead author Dr. Louis Bont, a pediatric infectious disease specialist at the University Medical Center Utrecht in the Netherlands, explained that RSV is a major health problem among preterm infants in the first year of life and it is the second cause of death after malaria. He added that if in healthy late pre-term, RSV is associated with 5% hospitalization, for others preterm babies the rate is higher. Moreover, nearly half of the healthy preterm babies develop wheezing illness.

RSV infection in the first year of life leads to wheezing and this in turn leads to the development of asthma later in life. Therefore, RSV infection is associated with long-term consequences. Bont wanted to clarify that it is not known yet if pavilizumab will also decrease the risk of asthma. According to the U.S. Centers for Disease Control and Prevention, RSV infection lasts for several months per year, four or five months, in winter and spring, but in America the exact timing varies depending on the region. It should be noted that there is no vaccine to protect against this virus and that in older children and adults RSV gives mild symptoms. In preterm babies however it is an important cause of morbidity and mortality.

The only drawback is that this treatment is quite expensive: it can reach up to 10,000 dollars per season in America. Although Bont believes pavilizumab should become the standard treatment for preterm babies during RSV season, he nevertheless highlights that: “Society needs to define whether its cost-effectiveness is acceptable”.

Factor D inhibitors may cure rheumatoid arthritis

Researchers at the University of Colorado School of Medicine have made interesting discoveries about rheumatoid arthritis. It looks like the knee fat cells secrete a protein called pro-factor D Called, which could be involved in rheumatoid arthritis. Rheumatoid arthritis is a rare autoimmune disease that affects approximately 1% or 1.3 million Americans.

Rheumatoid arthritis is manifested by damage to the joints, especially the small joints of the hand, bone erosion, cartilage damage. It must be said that rheumatoid arthritis is a systemic inflammatory disease of unknown etiology that may have, besides joint symptoms, systemic manifestations ( pulmonary, digestive, etc). The disease can occur at any age but typically begins in 4th and 5th decades. Regarding the possible causes of the disease, there were described hormonal factors, genetic and environmental factors, such as estrogen, smoking, infection, occupational exposure to silica and asbestos.

Rheumatoid arthritis must be differentiated from other diseases affecting joints such as rheumatic fever or arthritis. Rheumatoid arthritis is characterized by impaired symmetric small joints of the hand, morning stiffness, rheumatoid nodules, myalgia, asthenia, weight loss etc.. Treatment consists of analgesic, NSAIDs, corticotherapy (but in this disease it requires great care as it can worsen  bone erosions) and DMARDs (disease modifying antirheumatic drugs).

Nirmal Banda, Ph.D., associate professor of medicine in the Division of Rheumatology at the University of Colorado School of Medicine, said that what they found in the knee joint was a protein called profactor D, which is converted to factor D, and the factor D is linked to arthritis. Experiments on rats showed that the disease does not manifest without factor D. This discovery could lead to new treatments in the future because now Banda is investigating gene therapies to eliminate this protein in localized areas. Obviously these findings will be investigated in humans. Banda added that they seek vaccines, drugs or inhibitors that stop local profactor D secretion in joints. The goal is to find a drug to stop the progression of the disease before cartilage destruction and bone erosion have occurred.

Factor D is a component of the complement system, which is composed of 40 proteins with a role in defending the body against bacteria and other microorganisms. In experiments on rats it was shown that complement pathway including factor D was related to inflammatory arthritis in mice. Banda said that fat cells have the same function in all joints (ie secret profactor D) not only in the knee-joint.

Vagus nerve stimulation for severe depression

Researchers from Washington University School of Medicine in St. Louis are investigating a new method of treating severe depression, that is nerve stimulation. The results are promising and researchers found that  after several months of vagus nerve stimulation changes in brain metabolism occur. Furthermore, it seems that these changes in brain metabolism appear before patients begin to feel better. First author Charles R. Conway, MD, associate professor of psychiatry, said that previous studies involving large numbers of participants have shown that vagus nerve stimulation improves the condition of patients with treatment-resistant depression. He added that however little is known about the mechanism by which vagus nerve stimulation helps treat depression and this is why they focused on those brain regions involved in depression.

Conway and his team conducted a study that included 13 patients who had treatment-resistant depression (that is they have not responded to any of the 5 different medications that they received). Most patients were depressed for about 2 years but there were patients suffering from depression for more than 20 years. All patients underwent surgery to implant a device to stimulate the left vagus nerve, which goes from the brainstem to the abdomen. The stimulator was set to send up to 30-second electronic stimulus every 5 minutes.

Depression

To quantify the effects of treatment, the researchers performed positron emission tomography (PET) imaging  in patients both before brain stimulation and at 3 and 12 months after treatment. The results appeared a few months after the stimulation in 9 of the 13 patients included in the study. In those who responded to this treatment, imaging investigations have shown that electrical stimulation of the vagus nerve led to changes in brain metabolism, and this happened at 3 months after treatment. Conway said that they noticed major changes in brain metabolism long before clinical changes were visible. He explained that it is like as an adaptation process: first, the brain begins to function differently and then the patient begins to feel the changes.

Even though many patients continued therapy with antidepressants after stimulation, those who responded to treatment were able to quit drugs. “Sometimes the antidepressant drugs work in concert with the stimulator, but it appears to us that when people get better, it is the vagus nerve stimulator that is doing the heavy lifting,” Conway stressed. He added  that in treatment-resistant depression an important role is played by dopamine pathways and that these pathways are influenced by the vagus nerve stimulators.

Physical exercise improves Osteoporosis Prognosis

A new study reveals that postmenopausal osteoporotic women can improve their symptoms with a basic exercise program. The program was invented by Montserrat Otero, PhD holder in Physical Activity and Sports Sciences of the UPV / EHU-University of the Basque Country, and significantly improves strength in the upper and lower limbs and as well as static and dynamic balance.

Osteoporosis is characterized by decreased bone mass and bone architecture alterations that lead to increased risk of fractures. Women begin to lose bone mass after the age of 35 years, and this process is accelerated after menopause. Osteoporosis is a common disease in older women, as the risk  increases with age, but it can occur secondary to endocrine diseases (such as Cushing syndrome, acromegaly, hyperthyroidism, hypogonadism) or digestive diseases (malabsobtion, gastric resection, etc.). What characterizes osteoporosis is that bone loss causes no pain and symptoms (ie fractures) occur after the disease is at a relatively advanced stage.

Physical exercise

It is known as one of the means to improve osteoporosis prognosis is physical exercise, because physical exercise helps strengthen muscles and thus prevents fractures. But up to date there have been promoted programms that involved sophisticated machinery that are not available to all older women. This is why Montserrat Otero thought to invent an exercise program that uses basic materials such as chairs, bottles filled with sand, ropes etc.

Otero wanted to test the programme and followed 68 women aged between 50 and 72 years who had postmenopausal osteoporosis. The participants were randomly divided into two groups: Exercise Group and the Control Group. The 34 women who were part of Exercise Group followed a supervised exercise program for 6 months. In the six months there have been 72 sessions and each session consisted of 5 or 8 balance exercises and between 8 or 12 strength exercises. Women in the control group did not follow the exercise program (balance or strength). At the beginning of the program there were no significant differences between groups in any of the variables.

However, after the program, the women in the exercise group noted a significant improvement in strength in the upper and the lower limbs. “If there is no access to sophisticated equipment due to the economic cost involved, today we know that even without it, the risk factors of the main consequence of the disease can be reduced, which are the falls,” explained Otero. Otero believes that an exercise program that includes static and dynamic balance three days a week, significantly improves balance and muscle strength in women with postmenopausal osteoporosis.