Researchers discovered new potential treatment for gastrointestinal cancers

According to a study published online today in the Journal of Clinical Investigation, gastrointestinal cancers could benefit from a new treatment. Latest research conducted by researchers at the Walter and Eliza Hall Institute of Medical Research, Australia, reveals that by blocking a complex of proteins that promote the growth of gastrointestinal cancers associated with inflammation, �the disease could be eradicated.

Gastrointestinal Cancer

This newly identified protein complex, mTorc1 (mammalian target of rapamycin complex 1) is also involved in the development of other cancers, but this is the first time it has been shown to be involved in inflammatory pathology of gastric cancer and colon cancer. Gastrointestinal cancer is an important cause of mortality �in Australia and worldwide. Colon cancer is first in terms of digestive malignancies and is the second leading cause of cancer mortality. Regarding other gastrointestinal cancer, although the incidence declined in recent years, gastric cancer is the second most common gastrointestinal malignancy.

The mammalian target of rapamycin (mTOR) is a protein that regulates the growth, development, cell motility and protein synthesis in cells. It seems that mTOR is involved in many diseases such as cancer, neurodegenerative diseases, glycogen storage disease (GSD) etc.. Therefore, mTOR inhibition is a therapeutic target for treating various cancers or severe age-associated diseases (Alzheimer’s disease).

Associate Professor Ernst, from the Ludwig Institute for Cancer Research, said that there are several types of colon cancer and gastric cancer that are associated with inflammation. He added that the immune system response has already been shown to cause tumor growth. In the digestive system, inflammatory processes such as gastritis and colitis, which is an inflammatory bowel disease, increase the risk for developing gastrointestinal tumors. It seems that inflammation leads to activation of�mTorc1, which further trigger the mechanisms that lead to tumor growth. In recent years much attention has been given to�mTorc1 inhibitors as many cancers are dependent on the activity of this protein complex.

The researchers believe that inflammation-associated colon and gastric cancers may benefit from treatment with inhibitors mTorc1. Associate Professor Ernst said that this treatment is already in clinical trials for other cancers and that the experiments on laboratory animals had promising results. Although research on mTOR inhibitors are still under investigation, researchers hope to identify in future new treatments to eradicate gastrointestinal cancers associated with inflammation: “Since there are also other types of cancer that are associated with inflammation, we suspect that these could also be susceptible to treatment with mTorc1 inhibitors,” Ernst said.

New genetic mutation for ALS identified

According to a new study led by researchers at Western University in London, Canada, amyotrophic lateral sclerosis (ALS) could benefit from a new treatment as new genetic mutation has been identified. The study published online in Amyotrophic Lateral Sclerosis in and Frontotemporal Degeneratio, reveals that mutations within the ARHGEF28 gene �are present in both sporadic and familial forms of the disease.

Amyotrophic lateral sclerosis (ALS), which is also called Lou Gehrig’s disease, is one of the most devastating neurodegenerative diseases. It is a neurological disease that affects both central motor neuron and peripheral motor neuron, which means that the disease alters many fundamental actions such as swallowing, talking, walking etc. It is estimated that approximately 90% of patients die within 5 years of diagnosis. Symptoms reflect predominantly �the injury of peripheral motor neuron, such as muscle atrophy, fasciculations, but there are also signs of central motor neuron injury, such as exaggerated�reflexes (hyperreflexia) or spasticity. Usually cognitive function is not affected but there are cases associated with frontotemporal dementia, especially in familial ALS.

This disease has no clear etiology but there have been discussed many factors such as infections, poisoning, trauma, which could trigger motor neuron death. In addition to sporadic forms of ALS, there are familial forms of ALS, that is it �can run in family. Recent studies have questioned the role of glutamate in ALS, because it was found that patients with the disease have increased levels of glutamate in the cerebrospinal fluid.

Now the team of researchers from Western’s Robarts�Research Institute and from the Schulich�School of Medicine & Dentistry, have made new discoveries on ALS. They have discovered a new genetic mutation of this disease (ARHGEF28 gene) and showed that in almost all cases of ALS there are abnormal inclusions of the protein that arises from this gene. They started from the idea that ALS is a disease of RNA. RNA is involved in protein production, and is considered that abnormalities in RNA leads to abnormalities of this protein. In addition it was also found that unlike many proteins which have one function, this protein has two roles. Dr. Michael Strong explained that on the one hand, the protein must work with RNA and on the other hand it needs to repair the injury occurred. It seems that the two activities of the protein are competitive and if the protein is altered on RNA side, it will not be able to repair the injury.��“We need to understand what causes the switch between the two functions, and then can we modulate it,” Strong said.

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Obese mothers risk to have babies with low vitamin D levels

According to research conducted by scientists at Northwestern University Feinberg School of Medicine, women who are obese in early pregnancy have a higher risk of having �babies with lower levels of vitamin D, a fat soluble vitamin. The results show that children born to lean mothers have a vitamin D level about 3 times higher than children born to obese mothers. The study was published in the Journal of Clinical Endocrinology and Metabolism.

The fact that the level of vitamin D is lower in the obese is not new because there have been studies showing this so far. In the study conducted by researchers at Northwestern University Feinberg School of Medicine, it is revealed that both obese and lean women have normal levels of vitamin D in early pregnancy but children born to obese women have lower levels of this vitamin at birth.

Obesity

L. Jami Josefson, MD, first author of the study, said that almost all pregnant women who participated in the study said they took prenatal vitamins and this may be the explanation for the fact that they had normal levels of vitamin. Josefson said that a possible explanation of the low level of vitamin D in children born to obese women is that it could be stored in adipose tissue.

It should be noted that the study is part of a more extensive project, which aims to highlight the link between birth weight and obesity that may develop later in life. Researchers have sought to analyze vitamin D levels �too because deficiency of this vitamin is linked to many health problems, which include obesity.

Researchers measured vitamin D levels in pregnant women in the last trimester of pregnancy and in babies immediately after birth. There have been taken into account several parameters: body fat, weight, volume of the babies, etc. Josefson said the study revealed that children with high levels of vitamin D also had more body fat, which is a new thing. This finding contrasts with other studies published so far that have shown that the relationship between vitamin D levels and body fat is inverse. In other words, the amount of body fat is correlated with the level of vitamin D.

Josefson added that she is intending to do other studies in order to clarify the role of vitamin D in healthy children:�Obese women may need larger amounts of vitamin D supplementation to provide their babies with sufficient levels of vitamin D while they are in the womb,� she said.

�Neural stem cell transplant may be the new treatment for amyotrofic lateral sclerosis

According to a meta-analysis based on 11 clinical trials and published in Science Translational Medicine, amyotrophic lateral sclerosis, which is a currently incurable disease, could be treated with neural stem cells.

ALS is a progressive neurodegenerative�disease that�affects walking, talking, swallowing and other vital functions. No one knows exactly what triggers this debilitating and fatal disease, but there have been questioned environmental such as infections, poisonings or genetic factors (heredity).

ALS is a neurological disease characterized by degeneration and death of nerve cells in the spinal cord, leading to inability to walk and breathe. To date, there is no cure for this disease, but studies �conducted at��multiple institutions show that stem cell therapy may offer a chance for ALS patients. Experimental studies in rats have shown that transplantation of neural stem cells can slow the onset and the progression of ALS. Moreover, there was observed an improvement in motor and respiratory functions in mice treated as well as a longer survival.

stem cell transplant

It should be noted however that neural stem cells do not replace the degenerated nerve cells. What was found in the experiments with stem cells �was just an improvement of ALS, �and not a complete cure. What was also observed was that neural stem cells increased the survival rate. �The research showed that �the treatment increased the survival �by 3-4 times in transplanted mice than untreated mice. It was also noted an improvement in motor and respiratory functions in patients with neural stem cells transplant.

It seems that the new treatment reduces inflammation and stimulates the production of factors that maintain the remaining nerve cells of the host. Yang (Ted) Teng, HMS associate professor of surgery at Brigham and Women’s Hospital and one of the study’s co-lead authors, said this meta-analysis draws attention to the mechanisms underlying this disease and that these mechanisms should be targeted in the future therapies.

Neural stem cells are precursor cells that have the ability to renew, resulting in more stem cells, or can differentiate into nerve cells or other types of cells of the nervous system. Stem cells slow the progression of ALS by producing protective molecules that prevent the destruction of nerve cells in the spinal cord.

Stem cell therapy is one of the most promising medical treatment in the world today and is considered to be the future therapy in medicine for many diseases. However, �much research is needed in order to launch a well-established treatment.

Genetic basis for Atopic Dermatitis

Researchers at Oregon State University have made new discoveries about the genetic substrate of atopic dermatitis. It was found that inadequate Ctip2, a protein that has genetic functions, may trigger the disease through several mechanisms. These findings may provide new therapeutic targets for treating dermatitis.

It seems that Ctip2 is a protein that controls the synthesis of lipids in the skin and it can suppress TSLP, a cytokine produced by cells in the skin that can cause inflammation and thus dermatitis. It must be said that lipids form an important component of the skin structure and is essential in maintaining its integrity and hydration.

Atopic Dermatitis

The fact that inadequate functioning of Ctip2 can trigger dermatitis was demonstrated in experiments on animals. TSLP is not normally identified in the skin, but the rats that had no Ctip2 in their skins (the Ctip2 production was genetically suppressed) had high levels of inflammatory TSLP. Arup Indra, associate professor in the OSU year College of Pharmacy, �mentioned that inadequate Ctip2 leads to decreased lipid synthesis and this leads in turn to the production of inflammatory proteins. He added that atopic dermatitis is associated with an immune dysfunction but that researchers have failed so far to decipher what is the mechanism underlying this connection.

So far, atopic dermatitis has been treated with moisturizers that hydrate skin or corticosteroids that reduce inflammation. It is important to say that these treatments are symptomatic, in other words they do not cure dermatitis, they only alleviate symptoms. Indra said that by understanding the genetic mechanisms underlying this disease researchers can create new personalized and �more effective �therapies for treating atopic dermatitis.

Atopic dermatitis is a dermatological condition that is manifested by skin lesions, dry, itchy and inflamed skin. Disease generally begins in the first year of life and is associated with other diseases such as asthma, rhinitis, urticaria and food allergies. This �disease may remit in adolescence but there are situations where it persists in adulthood. Skin lesions can occur anywhere on the body. Lesions first appear in skin folds, then and in the cheeks, forehead and legs. Sweating or exposure to various allergens may increase erythema (redness) and itching and therefore excessive heat or synthetic fiber clothing should be avoided.

Topical corticosteroids are the main treatment for atopic dermatitis. Cortisone-based creams are applied 2 -3 times a day until the skin lesions resolve, but side effects can occur. Other treatments such as immunomodulators, phototherapy etc., may also be used.

Antidepressant Drug may prevent vascular complications of Diabetes

Researchers at the University of Texas Medical Branch at Galveston found that paroxetine, a drug used to treat depression, may be useful in management of vascular complications of diabetes.

UTMB professor Csaba Szabo, senior author of a paper on the research published online by Diabetes, said they came to these conclusions after analyzing 6766 clinically used drugs and pharmacologically active substances. He added that even they were surprised that paroxetine is an active substance that has an effect that is not related to antidepressant�effect, and that this effect is not found in other drugs used to treat depression.

Diabetes Treatment

The first selection process was to find those active substances which have protective effect against the harmful reactions of hyperglycemia on blood vessels. In diabetes, elevated glucose levels lead to the formation of oxygen free radicals that cause endothelial dysfunction, that is damage of the cells that make up the inner linings of blood vessels. This is one of the main mechanisms by which diabetes produces most of its vascular complications: retinopathy, stroke, myocardial infarction, nephropathy.

During the study, researchers found that paroxetine may prevent ROS damage to endothelial cells due to hyperglycemia in two ways. The first mechanism is by reducing superoxide levels, one of the most powerful antioxidants. The second mechanism is by influencing mitochondria to produce less superoxide. Hyperglycemia increases mitochondrial superoxide production. What is interesting is that paroxetine reduced ROS by influencing mitochondrial superoxide production without altering other mitochondrial processes.

The effects of paroxetine in terms of diabetes complications have been demonstrated by other researchers’ experiments. It was shown that the injection of paroxetine in mice in which diabetes was induced by a substance called streptozotocin, resulted in hypoglycemia. Szabo said the study could be the starting point for the development of therapies for cardiac complications of diabetes.

Diabetes is a chronic disease that is characterized by high levels of blood glucose (hyperglycemia). The incidence of diabetes is increasing and although it is a disease which initially may seem harmless to some, diabetes can become a serious medical condition due to complications that may appear overtime: microangiopathy, neuropathy and renal complications. Patients with diabetes have a higher risk of cardiovascular disease because hyperglycemia affects blood vessels (microangiopathy). Higher cardiovascular risk is also given by neuropathy and renal complications not only by microangiophaty. For example, a diabetic patient, due to neuropathy, may not feel pain when he is having a �heart attack and in this way his life expectancy may be significantly decreased. It is therefore very important that a patient with diabetes to control their disease.

HIV and Hepatitis

According to a study published today in the journal Nature Immunology, researchers from the Institute’s Infection and Immunity division, with collaborators from the University of Toronto, Canada, have discovered a new gene that could be new target to treat chronic infections such as HIV infection , tuberculosis and hepatitis.

Arih2, the new discovered gene, that is essential for the survival of the embryo, plays a crucial role in immune system function. It seems that this gene is one that takes the decision to activate or not the immune system in infections. This gene is found in dendritic cells, cells of the immune system that alert the organism when a microorganism enters the body. Dr Marc Pellegrini, from the institute’s Infection and Immunity division, with collaborators from the University of Toronto, Canada, said Arih2 is responsible for the most important decision that the immune system makes, namely whether to activate or to switch off immunity in order to �prevent the development of chronic inflammation or autoimmune processes.

Gene

Dr Marc Pellegrini added that most of the times the body knows how to fight off an infection but there are microorganisms that have learned how to escape the immune system so as to �persist in the body. Certain bacteria or virus overstimulates the production of T lymphocytes which triggers immune exhaustion and leads to �lymphocytic depletion. It happens in HIV, tuberculosis and hepatitis B. In addition, new therapeutic target may be used in the treatment of chronic inflammatory diseases such as rheumatoid arthritis, which is an autoimmune disease.

Now researchers are trying to investigate what effects would have blocking the Arih2 gene�for short periods of time during chronic infection. Dr Greg Ebert said Arih2�has a unique structure which makes it an excellent candidate for a therapeutic target. He added that this unique structure is unlikely to produce adverse effects or interact with other proteins. Because it is a gene essential for survival, researchers must investigate the effects of switching off�Arih2 for short periods of time. Their goal is to find a way to stimulate the immune system against infection without unwanted or collateral damage or autoimmunity.

But researchers wanted to mention that anyway will take many years since the discovery of therapeutic targets to a drug to be used by people. However, scientists are excited by this finding. Dr Pellegrini wanted to highlight that Arih2�is one of the most important genes involved in the immune system. In other words, researchers can control the immune response in one direction or another by manipulating this gene: �they can either stimulate or block the immune system.

New Vaccine Against Methamphetamine Drug Addiction Shows Promising Results

A research team from TSRI (The Scripps Research Institute) have successfully conducted rat tests with a new methamphetamine vaccine. The laboratory rats that were injected with the new vaccine showed a high level of protection against �methamphetamine intoxication. According to the research team, if further tests reveal that the vaccine has the same effect on human subjects, it could lead to novel treatment for� methamphetamine �addiction. Methamphetamine� addiction is estimated to affect approximately 25 million people on the globe.

According to associate professor and lead author of the study, Michael Taffe, the result of this study indicates the possibility of consequent clinical trials. Taffe is an associate professor in the Committee on the Neurobiology of Addictive Disorders.

Throughout the last 20 years, methamphetamine became one of the most abused drugs in the world, along with Marijuana, Cocaine and�Hallucinogens. According to various studies, more than 400 thousand users are suspected in the United States. Furthermore, in several states, methamphetamine is accounted for the most treatment admissions, compared to other drugs. One of the reasons that holds methamphetamine from being approved for treatment is its increased addictiveness.

Methamphetamine Drug

In the past few years, several research teams have studied different vaccines against these addictive drugs. These specific vaccines work the same way as traditional antiviral and antibacterial vaccines, however, instead of targeting bacteria and viruses, they target drug molecules. The antibody response caused by the vaccines would stop the drug molecule from reaching its target, the brain, thus inhibiting the impulse to further take the respective drug.

Both anti-nicotine and anti-cocaine vaccines are already undergoing clinical trials. Precedent anti-methamphetamine vaccines have shown discouraging results. Due to its simple molecular structure, the immune system doesn’t easily recognize the methamphetamine molecule. Methamphetamine and amphetamine, which is the main metabolite, tend to loiter in the central nervous system, thus allowing even a small amount of drug molecules to have a major impact. “The simple structure and long half-life of this drug make it a particularly difficult vaccine target”, said chemistry professor Kim Janda from the Skaggs Institute for Chemical Biology at TSRI.

A couple of years ago, a research team led by professor Janda created six new anti-methamphetamine vaccines. Each of the vaccines contained an active ingredient which was a molecule derived from the methamphetamine molecule. This molecule was linked to a carrier molecule. The link between the two molecules was needed because the derived molecule could not provoke an immune response by itself. According to the results of early tests conducted on laboratory mice, 3 of the 6 vaccines managed to provoke an immune response towards methamphetamine. Later studies conducted by professor Taffe showed that one particular vaccine, MH6, was able to block two specific effects of methamphetamine – the loss of the ability to regulate body temperature and the increase in physical activity.

In this current study, researchers investigated the effects of the MH6 vaccine more thoroughly. Through the use of a different technique, researchers reconfirmed that the vaccine can prevent both the hyperactivity and the rise in temperature associated with methamphetamine exposure. Crucial for these beneficial effects is a strong antibody response. In comparison with a control group, researchers observed that a larger quantity of the drug was held in the bloodstream when the rats were vaccinated.�“These are encouraging results that we’d like to follow-up with further animal tests, and, we hope, with clinical tests in humans some day”, said research associate Michelle Miller.

A different research group reports that studies for antibody-based addiction treatment also show promising results. For this treatment approach, anti-methamphetamine antibodies are grown through standard biotechnology methods. These antibodies are further injected into the animal in a highly concentrated dose. Antibody treatment approaches are used to treat chronic conditions of the immune system and different types of cancer. However, these particular methods are very expensive, thus making in an improbable treatment scheme because methamphetamine addicts usually have no health insurance and their treatment schemes are funded by the government.

In theory, this new active vaccine would be cheap to make and more efficient than the antibody therapy because of its longer period of protection. However, in practice, the vaccines that are being investigated last shorter than expected.

“Extending the duration of protection is the next big scientific challenge in this field”, concluded professor Taffe.

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Red pigment contributes to melanoma risk in fair-skinned individuals

Researchers at Massachusetts General Hospital in collaboration with those from Cancer Research have made new discoveries regarding melanoma, a type of skin cancer. According to the study published in Nature, antioxidants could be new way to prevent this type of cancer. Melanoma is a skin cancer that develops in melanocytes, the cells in which melanin, the pigment that gives skin color, forms.

There are two types of melanin: eumelanin, which is characteristic in individuals with dark hair and, and pheomelanin, which is characteristic in individuals with red hair and pale skin.

It seems that eumelanin protects better than pheomelanin regarding the appearance of skin cancers (basal cell carcinoma, squamous cell carcinoma). The incidence of these skin cancers that occur most frequently on sun-exposed areas, is lower in these individuals. Melanoma can occur in areas that were not exposed to the sun. Therefore, creams with SPF are not as useful for preventing melanoma.

Red Pigment

The team of researchers at MGH conducted their research on laboratory animals (red mice and dark mice, depending on the pigment in the skin) and found that the incidence of melanoma is higher in red mice following exposure to UV radiation. These results have led researchers to think if maybe the red pigment itself is responsible for the appearance of melanoma. Therefore, they continued their research and genetically disabled the red pigment in mice (albino redheads). After they removed the red pigment pathway, researchers found that these mice were protected from the development of melanoma.

Thus, the pigment itself and not skin type would be responsible for the appearance of this skin cancer.Then, assuming that the pigment itself would be responsible for developing melanoma, the researchers analyzed the DNA of red mice and without red pigment (albino).It was observed that red mice had altered DNA due to damage caused by reactive oxygen species. Reactive oxygen species are unstable and would be the mechanism by which red pigment causes melanoma.

This discovery is important because it can provide a basis for melanoma prevention. However, David Fisher, MD, PhD, chief of the MGH Department of Dermatology, director of the CBRC and senior author of the Nature paper, wanted to point out that treatment with antioxidants is difficult to handle. He said there were times when antioxidants did not prevent and conversely increased oxidative stress. He also stressed the importance of prevention of melanoma. 6 of 7 cases can be cured if the cancer is discovered in time. People who have suspicious lesions should not postpone visit to the dermatologist.