Research in Medicine

Brain cancer cure closer to reality

Scientists have identified a mechanism that can help treat brain cancer and a drug that decreases brain tumour growth.

The researchers at the University of Calgary’s Hotchkiss Brain Institute (HBI) have made a discovery that could lead to better treatment for patients suffering from brain cancer.

HBI member V. Wee Yong, PhD and research associate Susobhan Sarkar, PhD, and their team including researchers from the Department of Clinical Neurosciences and the university’s Southern Alberta Cancer Research Institute, looked at human brain tumour samples and discovered that specialized immune cells in brain tumour patients are compromised.

The researchers took this discovery and, in an animal model, identified a drug that is able to re-activate those immune cells and reduce brain tumour growth, thereby increasing the lifespan of mice two to three times.

Our brains normally contain specialized cells, called microglia, that defend against injury or infection. “Microglia are the brain’s own dedicated immune system,” explains Yong. “And in this study, we have formally demonstrated for the first time that these cells are compromised in living brain tumour patients.”

As with other forms of cancer, brain tumours start as individual stem-like cells – called brain tumour initiating cells (BTICs). These cells quickly divide and grow, eventually forming a mass, or tumour. Yong and his team have discovered that the tumour disables microglia, permitting the rapid proliferation of BTICs, which ultimately leads to brain tumour growth.

In addition to discovering this mechanism, Yong and Sarkar also identified a drug – amphotericin B (AmpB) – to reactivate microglia that in an animal model, showed a significant reduction in brain tumour growth.

The study was published in the journal Nature Neuroscience.

Source: Ani news

New laser procedure treats gum disease with less pain

Years ago, 78-year-old Florence Lee underwent surgery for periodontitis, a severe form of gum disease. And her experience was horrible.

“I had pain during the procedure, I had pain after the procedure and I was frightened,” Lee said.

When Lee learned she might need to be treated again, she was fearful of the procedure, which involves cutting into the gums in order to remove the bacteria that leads to bone loss.

Luckily, Lee learned about a new treatment for gum disease, called laser-assisted new attachment procedure (LANAP). During the procedure, doctors place a tiny fiber in the pocket between the gum and the tooth, delivering the same results with less pain.

“What it does is it targets specifically the inflamed tissue, the infected tissue and the bacteria associated with causing the periodontal destruction,” said Dr. Sam Morhaim, a periodontist at the Great Neck & Mid-Island Dental Associates in New York.

Morhaim said patients typically come in for two visits, each of which last about two hours. Comparatively, traditional surgery can take four or more sessions.

If LANAP catches on, Morhaim said it could do for dentistry what LASIK surgery did for ophthalmology. Other benefits of LANAP include reduced pain, swelling and sensitivity, in addition to the fact that no cutting or sutures are involved in the procedure. Furthermore, it offers great results.

“”We’re starting to see regeneration of the lost tissues, which is very exciting for us, because now we can offer

Lee decided to undergo the LANAP procedure and said that after the surgery, she didn’t experience any pain. She was even able to drive herself home afterwards, because the procedure requires only local anesthesia. technology that is super conservative compared to our conventional means with less downtime,” Morhaim said.

“I would recommend anyone who was having (periodontitis) and (was) fearful of it would have laser (treatment) and not any other procedure,” Lee said.

While insurance plans typically cover LANAP, only a few doctors in the country are performing the procedure.

Source: inagist

Now, ‘biopen’ to draw new bones inside body

Australian scientists have developed a hi-tech handheld ‘biopen’ that can enable surgeons to draw new bone material onto seriously injured people.

The ‘bio pen’ contains stem cells and growth factors, and could eliminate the need to harvest cartilage and grow it for weeks in a lab.

The pen-like device developed at the University of Wollongong (UOW) will allow surgeons to design customised implants on-site and at the time of surgery.

The BioPen will give surgeons greater control over where the materials are deposited while also reducing the time the patient is in surgery by delivering live cells and growth factors directly to the site of injury, accelerating the regeneration of functional bone and cartilage, scientists say.

The BioPen works similar to 3D printing methods by delivering cell material inside a bio-polymer such as alginate, a seaweed extract, protected by a second, outer layer of gel material.

The two layers of gel are combined in the pen head as it is extruded onto the bone surface and the surgeon ‘draws’ with the ink to fill in the damaged bone section.

A low powered ultra-violet light source is fixed to the device that solidifies the inks during dispensing, providing protection for the embedded cells while they are built up layer-by-layer to construct a 3D scaffold in the wound site.

Once the cells are ‘drawn’ onto the surgery site they will multiply, become differentiated into nerve cells, muscle cells or bone cells and will eventually turn from individual cells into a thriving community of cells in the form of a functioning a tissue, such as nerves, or a muscle.

The device can also be seeded with growth factors or other drugs to assist regrowth and recovery, while the hand-held design allows for precision in theatre and ease of transportation.

The BioPen prototype was designed and built using the 3D printing equipment in the labs at Wollongong and was handed over to clinical partners at St Vincent’s Hospital Melbourne, led by Professor Peter Choong, who will work on optimising the cell material for use in clinical trials.

The BioPen will help build on recent work by researchers where they were able to grow new knee cartilage from stem cells on 3D-printed scaffolds to treat cancers, osteoarthritis and traumatic injury.

“This type of treatment may be suitable for repairing acutely damaged bone and cartilage, for example from sporting or motor vehicle injuries,” Choong, Director of Orthopaedics at St Vincent’s Hospital Melbourne said.

Source: Deccan Chroicle

 

Monthly injection to prevent Alzheimer’s in five years

Scientists are hopeful of a breakthrough in dementia within five years – with drugs that could be given to prevent disease

Scientists are hopeful of a breakthrough in dementia within five years – with drugs that could be given preventively to delay the onset of disease.

Researchers say a new drug has shown some promise in patients with mild dementia, and might be yet more effective if given to those at risk of disease long before they show any symptoms.

Dr Eric Karran, director of research at Alzheimer’s Research UK, said scientists were “full of hope” that a breakthrough in drug therapy to prevent dementia could come within five years.

If further trials on the drug succeed, it could mean that those with a family history of dementia are given monthly injections of the drug a decade before any signs of disease show – in the same way that millions of people now take statins to ward off heart disease, he said.
Speaking ahead of a G8 summit next week on dementia, Dr Karran said trials have suggested that a drug called solanezumab may delay the onset of disease, halting problems with brain function and behaviour in those with mild dementia.

The studies originally tested the drug on patients with mild to moderate dementia, where the treatement did not achieve effective results.
But when analysis examined the impact of the drug only on those with mild dementia, researchers found it had an effect both on their daily behaviour and the functioning of their brain and memory.
Now researchers in the US are recruiting to a new study which will examine the impact only on patients with mild dementia.

If the trials prove that the drugs work, it would be “logical” to prescribe them to patients preventively, Dr Karran said, given that changes in the brain associated with dementia occur as far as a decade before symptoms are shown.
Dr Karran said the promise from the drug, and from two other treatments now undergoing trials, left him optimistic that a breakthrough is on the horizon, despite years of disappointment in the field of dementia research.

He said: “I am full of hope that we are going to have a breakthrough in five years.”
If trials on sufferers with mild dementia succeed, “there is a logic” to use the drug therapies at least a decade earlier, to prevent the onset of dementia, he said, in the same way that statins have been widely prescribed for those at risk of heart attacks and strokes.

“That’s exactly the path that blood pressure-lowering agents have taken – people taking them before they have a stroke,” he said. “It’s the path that’s been taken with statins which first showed efficacy against the disease and then you go earlier. That has to be the pathway we take. There is very very good human genetic data which shows that if you can effect this amyloid early on – and only modestly – you have the potential to dealy the onset of that disease very significantly indeed.”

Currently, the only drugs used for dementia can mask symptoms, but do not delay the onset of disease.
Brain scans have found that changes in the brains of patients with diseases such as Alzheimer’s can occur a decade before you have symptoms.

Providing people with anti-body drugs five or 10 years before the condition would otherwise develop could have a “drastic impact” on prevalence of disease, he said.
Dr Doug Brown, director of research and development for the Alzheimer’s Society, said: “If we can delay the onset by five years we could probably cut the numbers with dementia in yhalf – and recent research evidence suggests this could be a possibility.”

Prof Nick Fox, from the Institute of Neurology, at University College London, said that preventing disease before symptoms were present offered the best “window of opportuntity” to halt the impact of disease.

He said: “Let’s just hope that we can slow the devastation at the stage when there is much to save … rather then when we are bed bound or mute – because that is the end result of these dreadful diseases.”
Next week science and health ministers from G8 countries will meet in London for the first ever G8 dementia summit.

Charities called on them to draw up a shared global plan to tackle dementia, and invest heavily in research, which currently receives a fraction of the funds devoted to cancer in this country.
David Cameron has said he will use the UK’s presidency of the G8 to lead coordinated international action.

Source: Telegraph

Grape seed Extract Kills 76% of Leukemia Cancer Cells in 24 Hours

A new study by Indian origin researcher has revealed that the synthesis of the most active component of grape seed extract, B2G2, encourages the cell death known as apoptosis in prostate cancer cells while leaving healthy cells unharmed.

“We’ve shown similar anti-cancer activity in the past with grape seed extract (GSE), but now we know B2G2 is its most biologically active ingredient which can be synthesized in quantities that will allow us to study the detailed death mechanism in cancer cells,” Alpna Tyagi, PhD, of the University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, said.

Previous studies have shown the GSE effectiveness against cancer cells and have also shown its mechanism of action. However, Tyagi said that until recently, they didn’t know which constituent of GSE created this effect. This naturally occurring compound, GSE, is a complex mixture of polyphenols and also so far it has been unclear about the biologically active constituents of GSE against cancer cells.

Eventually the group pinpointed B2G2 as the most active compound, but, “it’s expensive and it takes a long time to isolate B2G2 from grape seed extract,” Tyagi says.

The current study reported the success of this effort, including the ability to synthesize gram-quantity of B2G2 reasonably quickly and inexpensively.

The study also showed anti-cancer activity of synthesized B2G2 similar in mechanism and degree to overall GSE effectiveness.

The study was published in the journal Nutrition and Cancer.

Source: Zee news

 

Pills of the future: nanoparticles

Researchers design drug-carrying nanoparticles that can be taken orally
Drugs delivered by nanoparticles hold promise for targeted treatment of many diseases, including cancer. However, the particles have to be injected into patients, which has limited their usefulness so far.

Now, researchers from MIT and Brigham and Women’s Hospital (BWH) have developed a new type of nanoparticle that can be delivered orally and absorbed through the digestive tract, allowing patients to simply take a pill instead of receiving injections.

In a paper appearing in the Nov. 27 online edition of Science Translational Medicine, the researchers used the particles to demonstrate oral delivery of insulin in mice, but they say the particles could be used to carry any kind of drug that can be encapsulated in a nanoparticle. The new nanoparticles are coated with antibodies that act as a key to unlock receptors found on the surfaces of cells that line the intestine, allowing the nanoparticles to break through the intestinal walls and enter the bloodstream.

This type of drug delivery could be especially useful in developing new treatments for conditions such as high cholesterol or arthritis. Patients with those diseases would be much more likely to take pills regularly than to make frequent visits to a doctor’s office to receive nanoparticle injections, say the researchers.

“If you were a patient and you had a choice, there’s just no question: Patients would always prefer drugs they can take orally,” says Robert Langer, the David H. Koch Institute Professor at MIT, a member of MIT’s Koch Institute for Integrative Cancer Research, and an author of the Science Translational Medicine paper.

Lead authors of the paper are former MIT grad student Eric Pridgen and former BWH postdoc Frank Alexis, and the senior author is Omid Farokhzad, director of the Laboratory of Nanomedicine and Biomaterials at BWH. Other authors are Timothy Kuo, a gastroenterologist at BWH; Etgar Levy-Nissenbaum, a former BWH postdoc; Rohit Karnik, an MIT associate professor of mechanical engineering; and Richard Blumberg, co-director of BWH’s Biomedical Research Institute.

No more injections

Several types of nanoparticles carrying chemotherapy drugs or short interfering RNA, which can turn off selected genes, are now in clinical trials to treat cancer and other diseases. These particles exploit the fact that tumors and other diseased tissues are surrounded by leaky blood vessels. After the particles are intravenously injected into patients, they seep through those leaky vessels and release their payload at the tumor site.

For nanoparticles to be taken orally, they need to be able to get through the intestinal lining, which is made of a layer of epithelial cells that join together to form impenetrable barriers called tight junctions.

“The key challenge is how to make a nanoparticle get through this barrier of cells. Whenever cells want to form a barrier, they make these attachments from cell to cell, analogous to a brick wall where the bricks are the cells and the mortar is the attachments, and nothing can penetrate that wall,” Farokhzad says.

Researchers have previously tried to break through this wall by temporarily disrupting the tight junctions, allowing drugs through. However, this approach can have unwanted side effects because when the barriers are broken, harmful bacteria can also get through.

To build nanoparticles that can selectively break through the barrier, the researchers took advantage of previous work that revealed how babies absorb antibodies from their mothers’ milk, boosting their own immune defenses. Those antibodies grab onto a cell surface receptor called the FcRN, granting them access through the cells of the intestinal lining into adjacent blood vessels.

The researchers coated their nanoparticles with Fc proteins — the part of the antibody that binds to the FcRN receptor, which is also found in adult intestinal cells. The nanoparticles, made of a biocompatible polymer called PLA-PEG, can carry a large drug payload, such as insulin, in their core.

After the particles are ingested, the Fc proteins grab on to the FcRN in the intestinal lining and gain entry, bringing the entire nanoparticle along with them.

“It illustrates a very general concept where we can use these receptors to traffic nanoparticles that could contain pretty much anything. Any molecule that has difficulty crossing the barrier could be loaded in the nanoparticle and trafficked across,” Karnik says.

The researchers’ discovery of how this type of particle can penetrate cells is a key step to achieving oral nanoparticle delivery, says Edith Mathiowitz, a professor of molecular pharmacology, physiology, and biotechnology at Brown University.

“Before we understand how these particles are being transported, we can’t develop any delivery system,” says Mathiowitz, who was not part of the research team.

Breaking through barriers

In this study, the researchers demonstrated oral delivery of insulin in mice. Nanoparticles coated with Fc proteins reached the bloodstream 11-fold more efficiently than equivalent nanoparticles without the coating. Furthermore, the amount of insulin delivered was large enough to lower the mice’s blood sugar levels.

The researchers now hope to apply the same principles to designing nanoparticles that can cross other barriers, such as the blood-brain barrier, which prevents many drugs from reaching the brain.

“If you can penetrate the mucosa in the intestine, maybe next you can penetrate the mucosa in the lungs, maybe the blood-brain barrier, maybe the placental barrier,” Farokhzad says.

They are also working on optimizing drug release from the nanoparticles in preparation for further animal tests, either with insulin or other drugs.

The research was funded by a Koch-Prostate Cancer Foundation Award in Nanotherapeutics; the National Cancer Institute Center of Cancer Nanotechnology Excellence at MIT-Harvard; a National Heart, Lung, and Blood Institute Program of Excellence in Nanotechnology Award; and the National Institute of Biomedical Imaging and Bioengineering.

Source: MIT News

 

New treatment for osteoporosis discovered

After more than four years of investigation, researchers from the Ageing Bone Research Program (Sydney Medical School’s Nepean campus), have found the treatment has shown very promising results in animal experiments.

The compound is called picolinic acid, a product derived of the essential amino acid tryptophan.

Lead researcher Professor Gustavo Duque said the odorless compound can be easily dissolved in water.

“This is a major step in the development of a completely new type of medication for osteoporosis. Instead of stopping bone destruction, our compound instead stimulates bone formation,” he said.

“The product is easily dissolved in water, has a higher level of absorption and did not induce any side effects in the treated mice.

“When this medication was administered in the water of normal and menopausal mice, picolinic acid strongly and safely increased bone mass in normal mice and rescued bone from menopause-associated osteoporosis.”

Professor Duque said the team had patented the compound and will expand their trials to humans in the near future in a bid to address the increasing numbers of people developing the condition.

“Osteoporosis affects an estimated 300 million people worldwide. One in three women over 50 will experience osteoporotic fractures, as will one in five men.

“Despite the current treatments available, by 2050, the worldwide incidence of hip fracture in men is projected to increase by 310 percent and 240 percent in women.

“This increase is explained by the low rate of diagnosis and treatment for osteoporosis, as well as some concerns about the potential side effects of the current treatments.

“There are also close similarities between the majority of the osteoporosis medications in terms of their anti-fracture effect and mechanism of action.”

According to Professor Duque, there is a reduction in bone formation as part of the ageing process that predisposes people to osteoporosis.

“In this case we are targeting the real problem by stimulating the bone forming cells to work and produce more bone, thus increasing bone mass and hopefully preventing new fractures,” he said.

Source: The University of Sydney

 

New drug target to help fight malaria identified

A team of researchers has identified a key metabolic enzyme that is required by the common malaria parasites at all stages of its life cycle for survival in humans.

Co-first author Marcus C. S. Lee, PhD, associate research scientist in microbiology and immunology at Columbia University Medical Center (CUMC) said the study is important because most anti malarials are effective at killing the parasites only as they circulate in the bloodstream. However, the parasites can hide in the liver for years before reemerging and triggering a relapse of the disease.

The other co-first author is Case W. McNamara, PhD, research investigator at the Genomics Institute for the Novartis Research Foundation. The study leaders are Elizabeth A. Winzeler, PhD, professor of pharmacology and drug discovery at University of California San Diego, and Thierry Diagana, head of Novartis Institute for Tropical Diseases in Singapore.

The enzyme, phosphatidylinositol 4-kinase (PI4K), was found by screening more than a million drug compounds against Plasmodium falciparum, the parasite responsible for the most lethal form of malaria. Using this screen, the researchers found a class of compounds known as imidazopyrazines, which are capable of killing several species of Plasmodium at each stage of the parasites’ life cycle in its vertebrate host.

The researchers identified the target of the imidazopyrazines by evolving parasite cell lines that were resistant against the drugs and then analyzing the parasites’ genomes for the changes responsible for conferring resistance. Those genetic changes pointed to the gene that encodes PI4K.

The CUMC team, led by David Fidock, PhD, professor of microbiology and immunology and medical sciences (in medicine), used novel genetic tools to confirm that PI4K was being directly targeted by the imidazopyrazines.

Then, using cellular imaging, it was found that imidazopyrazines interfere with the function of PI4K on the parasite Golgi (the organelle that packages proteins for delivery to other cellular destinations). ”

The study is published in the journal Nature.

Source: top news

Fruit flies may harbor dementia cure

Researchers have taken a significant step forward in unraveling the mechanisms of Pavlovian conditioning and understanding this will help understand how memories form and, ultimately, provide better treatments to improve memory in all ages.

“Memory is essential to our daily function and is also central to our sense of self. To a large degree, we are the sum of our experiences. When memories can no longer be retrieved or we have difficulty in forming new memories, the effects are frequently tragic. In the future, our work will enable us to have a better understanding of how human memories form,” Gregg Roman, an associate professor of biology and biochemistry at University of Houston’s said.

Roman along with his team studied the brains of fruit flies (Drosophila). Within the fly brain, Roman said, there are nerve cells that play a role in olfactory learning and memory.

Roman said they found that these particular nerve cells- the gamma lobe neurons of the mushroom bodies in the insect brain- are activated by odours. Training the flies to associate an odour with an electric shock changed how these cells responded to odours by developing a modification in gamma lobe neuron activity, known as a memory trace.

They found that training caused the gamma lobe neurons to be more weakly activated by odours that were not paired with an electric shock, while the odours paired with electric shock maintained a strong activation of these neurons. Thus, the gamma lobe neurons responded more strongly to the trained odour than to the untrained odour.

The team also showed that a specific protein – the heterotrimeric G(o) protein – is naturally involved in inhibiting gamma lobe neurons.

Roman said removing the activity of this protein only within the gamma lobe neurons resulted in a loss of the memory trace and, thus, poor learning. Therefore, inhibiting the release of neurotransmitters from these neurons through the actions of the G(o) protein is key to forming the memory trace and associative memories.

The significance of using fruit flies is that while their brain structure is much simpler with far fewer neurons, the mushroom body is analogous to the perirhinal cortex in humans, which serves the same function of sensory integration and learning.

The study was published in journal Current Biology.

Times of India

Plant Nutrient ‘Cocktail’ Kills Breast Cancer Cells

A new study finds a cocktail of compounds found naturally in plants killed all of the breast cancer cells collected in a laboratory, without any toxic side effects on normal cells.

Researchers at Louisiana State University tested six known protective chemical nutrients from turmeric, soybeans, broccoli, grapes and tea. Individually, they were ineffective against cancer.

But combined, they suppressed breast cancer cell growth in the lab by more than 80 percent, and eventually triggered the process leading to cell death.

The next step for the scientists is to see whether the compounds can prevent tumor formation and growth in mice.

Dr. Madhwa Raj, who led the study published in the Journal of Cancer, points out that all the ingredients in the cocktail come from foods people eat every day, but at much higher levels than they could possibly get from their diet.

Because he “really believes it can help women now,” he has established a bio-tech start-up company to bring the super-cocktail to market as a nutritional supplement for breast health, which does not require approval from the Food and Drug Administration.

Source: Voice of America