Silver and Gold ‘nanocages’ might buy early detection

By Sara Braniecki

Researchers from Washington University and Purdue University collaborated to experiment with a new medical imaging technique that they hope will lead to early detection and treatment for cancer patients.  The procedure uses a pulsed laser and tiny metallic “nanocages, as the researchers call them, to create images much clearer than those created using previous techniques.

This composite image shows luminous nanocages, which appear like stars against a black background, and a living cell, at upper left. The gold-silver nanocages exhibit a bright "three-photon luminescence" when excited by the ultrafast pulsed laser, with 10-times greater intensity than pure gold or silver nanoparticles. The signal allows live cell imaging with negligible damage from heating.

The nanocages are injected into the bloodstream, and then laser pulses are shone through the patient’s skin to detect them. The nanocages are small, hollow spheres made of a combination of gold and silver. Both the nanocages are only 40 nanometers wide.  To put that into perspective, this is 100 times smaller than a red blood cell.  The laser shines light that is almost infrared and pulses 80 million times per second.

The procedure illuminates tissues and organs, allowing live cell imaging.  The precision of these images is important for accurate detection and thorough treatment of cancer.

The images produced using this technique provide a much better image than older techniques that used nanospheres made solely of gold.  The new images have greater contrast since there is less background glow of surrounding tissues.  One of the researchers from Purdue University, Ji-Xen Cheng, explains, “This lack of background fluorescence makes the images much more clear and is very important for disease detection.  It allows us to clearly identify the nanocages and the tissues.”

Another advantage of using the nanocages made of both silver and gold is that there is no resulting heat damage in the tissue.  Previously, the image needed to be enhanced to get a clear enough image that was usable.  To enhance the image, clouds of electrons moving in unison had to be induced in the tissue- this resulted in the heat damage.  Since this enhancement is no longer vital, the heat damage does not occur.

The researchers hope that the creation of the nanocages will lead to better detection and treatment.  Washington University researcher Younan Xia, whose team engineered the nanocages, explains that the productions of the nanocages will likely allow researchers “to combine imaging and therapy for better diagnosis and monitoring.”  He also foresees that the nanocages might be used to deliver time-released anticancer drugs to diseased tissue.

Further information.

Wait for Prostate Treatment May Be Over

April 18, 2010

By: Shelly Hwang

Prostate cancer is the second-leading cause of cancer death in men, with men having a one in six chance that they will get prostate cancer in their lifetime. While prostate cancer can be treated with surgery, a new treatment similar to radiation is being tested that may be able to more effectively target proteins on the surface of prostate tumors, providing hope even for patients with advanced prostate cancer.

Human prostate cancer cells can be recognized by overexpression of some proteins on their surface. The abundance of certain proteins provides a way to target these cancer cells by using antibodies. The antibodies will be binded to the isotope 212-lead, which is an altered form of the common element lead. When this antibody is injected into a patient’s veins, it will bind to a tumor’s surface and release particles and radiation that will destroy only the tumor cells.

Researchers in Zhongyun Dong’s laboratory at the University of Cincinnati are getting ready to test this new agent over the course of this year. They will measure how toxic and effective the treatment is in slowing down or blocking cancer cell growth. Then, the treatment will be used in clinical trials with patients with advanced prostate cancer.

Original Press Release

UC Academic Health Center

Our immune systems to blame for unsuccessful HIV vaccines?

By Johnathan Nieves ’11

Cells known as regulator T cells are being implicated in limiting the effectiveness of therapeutic vaccines for HIV by suppressing the immune system. This new knowledge may help researchers when developing future HIV vaccines.

Our immune system may be a little dumber than we thought. Cells involved in the body’s immune system are being implicated in limiting the effectiveness of therapeutic vaccines for HIV. A recent study published in the journal PLoS ONE on March 24th, demonstrated that regulatory T cells are involved in reducing the effectiveness of HIV vaccines by suppressing the immune system. The findings of the study may help researchers improve the effectiveness future therapeutic HIV vaccines.

Regulatory T cells (Treg) are important because they prevent the body’s immune system from attacking itself. When the immune system attacks itself, it is the result of it mistaking a non-harmful entity, like a liver cell, for a harmful one. The non-harmful entity is then tagged for destruction and the body’s immune system would destroy it and anything similar to it. This is known as an auto-immune response. Without Treg, autoimmune diseases could flourish.

So what if Treg cells are suppressing the immune system so that novel therapeutic HIV vaccines cannot be recognized and targeted for destruction?  University of Pittsburgh health science researchers sought to answer this question as a follow-up to an HIV vaccine they developed and tested in 17 HIV positive patients in 2008 that produced unsatisfying results. In the study the researchers removed Treg cells from the patients’ blood samples to see what effect the HIV vaccine would have on the sample in the absence of Treg. To their surprise they found that Treg reduced the patients’ immune system’s ability to recognize the HIV vaccine and begin to target the actual HIV virus in the patients blood.

“When we removed Treg from blood cells, we found a much stronger immune response to the vaccine, giving us insight into how we can develop more effective HIV vaccines,” said Charles R. Rinaldo, Jr., Ph.D., the study’s lead author. “Treg normally shuts down [the immune response] once the infection has been controlled, but in this case it appears to be [suppressing the immune response] early and possibly limiting the vaccine’s ability to do its job effectively.”

One theory is that the HIV infection itself is responsible for increasing Treg levels in the blood which in turn results in the immune systems inability to recognize the HIV virus.

“We know how to treat HIV, but are still learning how to use immunotherapy strategies to completely flush it out of the body,” added Bernard J.C. Macatangay, M.D., co-author of the study. “Our findings show Treg plays an important role, but we need to figure out how to maintain the right balance by getting around these cells without blocking them completely.”

To view the press release pertaining to this article, click here

The journal article pertaining to this article may be obtained here.

Plant cancer leads a double life as a tailor

by Allison Younkins

“Corn Smut” is both a plant cancer and a tailor.  This maize fungus does not tailor clothes but it does tailor its genes to attack the host tissue it is infecting.  This April, researchers and Stanford unlocked some astonishing secrets about how corn smut manipulates genes in its genome to affect its host more severely.

The researchers used laboratory techniques such as DNA microarrays, which allowed them to seem which genes in the pathogen’s genome were activated.  What they found will inevitably change the way pathologist’s study plant pathogens and human cancers.  Their experiment showed that the pathogen had different active genes when it was infecting various parts of the plant including the seedlings or the adult leaves.  About 30% of the pathogen’s genome was activated no matter where the infection was located.  The activation of the remaining 70% varied depending on the location of the infection.  This phenomenon has been overlooked in the past because normally only tissues from one cell type are studied in an experiment.

These findings may allow scientists to return to pathogens retroactively and discover new information about the mechanism of plant diseases including corn smut.

This is a significant finding for the plan pathology community but it also has implications for human disorders.  Corn smut is a tumor-causing plant cancer, and researchers believe that information from this study could fuel new experiments in cancer research.  Their discoveries about this plant cancer suggest that diseases such as cancer can alter their genetic material to better infect a host.  If the activated genes can be targeted, this could create more specific treatments and medications for cancer.

Corn smut has traditionally been overlooked as a research interest because it does not devastate maize crops and is not harmful to humans who eat infected maize.  It is common in Mexico for the plant tumors to be used in food and can even be grown intentionally.  However, this seemingly unimportant pathogen may hold a wealth of information about how diseases attack their hosts and what we can do to stop them.

A maize tassel infected with corn smut. The tumors are the large white, bulbous growths, some of which have turned yellow or brown. Linda A. Cicero, Stanford University News Service

Want to hear a Stanford University researcher speak about her research on corn smut? Check out the link below

Plant Pathogen Tailors Attacks Genetically

Sleepy Soldiers’ Split-Second Situation Assessment Skewed

Study demonstrates decrease in ability to make rapid judgement calls due to sleep deprivation.

   By: Nicole Myers        

          In a study conducted at the University of Texas and published in the journal Sleep, researchers found that sleep deprivation negatively impacts information-integration, the type of cognitive processing that allows fast, accurate, gut-feeling decisions.

            Soldiers in combat rely heavily on the ability to instantly make the right decisions in high pressure situations. Researcher Tom Maddox explains, “information-integration… is critical in situations when solders need to make split-second decisions about whether a potential target is an enemy soldier, a civilian, or one of their own.” Unfortunately, combat missions don’t exactly lend themselves to full nights of sleep, and soldiers in these operations are often extremely sleep- deprived.

            The study tested 49 West Point Cadets on information-integration tasks, once as a baseline and then again after 24 hours of either sleep deprivation or a normal sleep-wake cycle. While the rested cadets significantly improved their scores in the second round of testing, the sleep-deprived cadets’ scores dropped slightly. This indicates that even the mild sleep-deprivation of one night’s sleep loss impacted the cadets’ ability to use this crucial form of decision making.

          Researchers observed that one way sleep-deprivation impaired decision making was by causing subjects to shift from the fast and accurate cognitive strategy of information integration to a slower, more controlled, but less-effective rule-based approach, in which they tended to over-think the problems.

          The effect that sleep-deprivation had on decision making varied among individuals. Those who had a tendency to use a rule-based approach to problem solving in the first place were more vulnerable to the effects of sleep-deprivation. Some subjects continued to use an information-integration approach despite sleep-deprivation, and their performance showed no decline in the second set of testing. This suggests that the cognitive function necessary for information-integration strategies is not necessarily strongly affected by sleep deprivation. But, the use of an information-integration strategy in a task may require active inhibition of rule-based strategies, and this inhibitory process is what is vulnerable to the effects of sleep deprivation.

          An understanding of the effects of sleep-deprivation on various cognitive functions and decision making abilities is critical for a military in a time of war, when enormous physical demands are placed on soldiers who are often deprived of sleep and sustenance and who must make split-second life or death decisions. 

For the original research click: http://www.journalsleep.org/ViewAbstract.aspx?pid=27617

Change Your Mind: How Stress Reshapes Your Brain

The hippocampus in a human brain.

By Kelly Lohr

It has been known for a while that too much stress can be bad for your health.  A new study now shows that it can affect your brain too.  Research through a collaboration between Rockefeller University and Cornell University suggests that stress can been linked to harmful changes in some brain structures.  Sometimes these brain changes can be advantageous, such as making new synaptic connections to remember and learn from a stressful, life-threatening event.  However, some changes can  be detrimental.

A mouse hippocampus labeled with NeuroTrace® green fluorescent Nissl stain

The project has identified a protein possibly involved in remodeling the brain under stress.  It was found that the brains of mice lacking the protein called brain-derived neurotrophic factor (BDNF) look like the brains of stressed mice.  The study examined changes in the neurons of the hippocampus, a brain area important in memory, mood, and cognition.  When normal mice were stressed through confinement to a small space, the tiny projections on their neurons called dendrites retracted in the hippocampus.  The hippocampus itself was also reduced in overall volume.  The study compared these mice to other mice that were missing a copy of the gene that produces BDNF.  It was found that these genetically-altered mice had brains resembling those of stressed mice.

Not only does this finding show that stress can produce brain changes.  Bruce McEwan of Rockefeller University suggested that BDNF also may be “one of the proteins that play a role in mediating the brain’s plasticity.” This holds promise for a better understanding of the role of neuronal remodeling in the hippocampus and its importance in memory and emotion.

Written April 13, 2010

For more information, visit http://www3.interscience.wiley.com/journal/123249229/abstract?CRETRY=1&SRETRY=0.

CO2 Into Fuel?

Dan Conant

Scientists from the University of Bath will be working on capturing CO2 and recycling it into usable materials such as fuel thanks to funding provided by the Engineering & Physical Sciences Research Council (EPSRC).  This is a massive undertaking of a project, but if all goes well then these scientists may end up helping to reduce the world’s leading greenhouse gas.  This project has only begun, but the scientists already have a good idea of how they might go about capturing this CO2.

Emissions

The scientsits are going to try to develop a porus material that would be in the chimneys of factories to help capture CO2.  Porus materials are ideal because they absorb gas from the air easily.  Once captured, the scientists  will be experimenting with solar power to convert the CO2 into fuels and other products.  Dr. David Fermin from Bristol College (a collaborator in this endeavor) helped to provide the science behind this project’s vision;“Currently, there are no large-scale technologies available for capturing and processing CO2 from air. The facts are that CO2 is rather diluted in the atmosphere and its chemical reactivity is very low. By combining clever material design with heterogeneous catalysis, electrocatalysis and biocatalysis, we aim at developing an effective carbon neutral technology.”

This project has a lot of potential for helping to reduce greenhouse gas emissions, as it could be applied to factories and other large scale CO2 emission contributors.  There is even hope that eventually this technology might be able to be applied to automobiles, but that is in the distant future. 

Information was collected from here.

Could we re-grow lost limbs?

Researchers discover gene deletion that allows tissue regeneration in mammals.

By: Nicole M. Myers 

     Mar. 2010- Researchers at the Wistar Institute, a international leader in biomedical research, have discovered a gene that could regulate regeneration in mammals, bringing the possibility of re-growing amputated extremities one step closer to reality. The lab identified a gene called p21, that when turned off confers to mice the ability to regenerate lost tissue.

          The ability to regenerate lost appendages is common but sporadically observed in nature, as in animals such as flatworms, sponges, and salamanders, but the phenomenon was previously unknown in mammals. Mammals are capable of replacing some types of tissue, such as liver lobes, damaged skeletal muscle cells, epithelium, the gut lining, and even brain cells to some extent. Typically though, the mammalian healing process involves the formation of scar tissue, rather than new cells. Animals like salamanders begin healing with the formation of a blastema, a structure that allows cells to rapidly proliferate and differentiate as embryonic stem cells do, until the appendage is replaced without scarring.

          This research began with a chance observation in a particular strain of laboratory mice, known as MRL mice. Researchers used the standard technique of piercing holes in the mice’s ears for identification. However, within a couple weeks, the holes had unexpectedly closed without a trace. The researchers then began to investigate the genetics of the MRL mice to see what might be behind their unique healing ability, and they found that the p21 gene was inactivated. Further research indicated that mice lacking the p21 gene were able to completely regenerate lost or damaged tissue without forming a scar, re-grow cartilage, and partially regenerate amputated digits.

          The p21 gene is a cell cycle regulator that blocks the cell cycle progression when there is damage to the DNA, preventing the cells from dividing and potentially becoming cancerous. Similar to naturally regenerative creatures, mice that lack p21 show an increase in DNA damage, but also an increase in apoptosis, or the programmed death of impaired cells. Researchers suggest that “The combined effects of an increase in highly regenerative cells and apoptosis may allow the cells of these organisms to divide rapidly without getting out of control and becoming cancerous.”

         Amputation injuries are some of the most devastating and debilitating wounds soldiers sustain in combat. According to the Army Office of the Surgeon General, between September 2001 and January 2009, 1,286 soldiers suffered amputation injuries in Operation Iraqi Freedom and Operation Enduring Freedom. This is the first research to succeed in this degree of tissue regeneration in mammals, giving hope that someday, we may have the ability to restore these lost limbs.

To read the original research published in Proceedings of the National Academy of Science, click: http://www.pnas.org/content/107/13/5845.full

A Fungus with a Deadly Sweet Tooth

By: Kristen Kocher

severe brain swelling caused by a Cryptococcal infection

As it turns out, humans aren’t the only ones with a sweet tooth. According to an article published last week (April 5, 2010) in mBio online microbiology journal, a certain species of fungus, Cryptococcus, were found to thrive and reproduce through consumption of a sugar, inositol, which is commonly found in the human brain and spinal cord.

Joseph Heitman, M.D. and Ph.D. and his team of researchers who have been studying Cryptococcus at the Duke Department of Molecular Research believe they have identified a set of almost a dozen genes that code for sugar transport molecules. Sugar transport molecules are important in borrowing sugars from parts of the body to use where they are needed. Normal fungi have only two genes that code for these sugar transport molecules. It is therefore hypothesized that because of the increased number of genes coding for sugar transport molecules in Cryptococcus, this fungus is able to more quickly gather sugars to consume. According to Heitman, “Inositol is abundant in the human brain and in the fluid that bathes it (cerebral spinal fluid), which may be why this fungus has a predilection to infect the brain and cause meningitis. It has the machinery to efficiently move sugar molecules inside of its cells and thrive.” Meningitis is a serious health problem that involves the swelling of the area around the brain, causing a build up of fluid, which can have negative effects on brain function. Meningitis is a medical emergency because it occurs quickly and often results in permanent brain damage or death.

Before it was able to infect the brain, it is believed that Cryptococcus originally localized itself on plants. Plants are rich in inositol and most likely caused Cryptococcus to adapt and change its genome to produce more sugar transport molecules in order to survive and replicate. Because the brain and spinal cord naturally have very high concentrations of inositol it makes sense that Cryptococcus would target the brain as a niche.

Furthermore, it has been found that inositol stimulates sexual reproduction in Cryptococcus, so in areas of plentiful inositol concentrations, such as the brain, reproduction occurs often and rapidly.

Cryptococcus

Chaoyang Xue, Ph.D., formerly a postdoctoral research associate in the Heitman lab and now an assistant professor at the Public Health Research Institute at the University of Medicine and Dentistry of New Jersey, comments, “A connection between the high concentration of free inositol and fungal infection in the human brain is suggested by our studies. Establishing such a connection could open up a new way to control this deadly fungus.”

While Cryptococcus’ love for sugar may seem only beneficial, it turns out that because the fungus relies so heavily on inositol for nutrition, scientists have found a way to essentially put the fungus on an “Atkin’s-esque low-carb diet”. This “diet” would greatly reduce the ability of Cryptococcus to multiply, thus lessening its effects on the human brain.

Original Press Release

Check out mBio online microbiology journal for more articles and other information on this research.

Click here information on the Heitman lab

Melanoma, Soon to be “Mela-no-more”?

By Nick Gubitosi

Just last week (April 6, 2010), scientists at the Rush University Medical Center in Chicago completed the second phase of trials for a very promising melanoma vaccine.  The trial, which had stunning results, was conducted on 50 patients with metastatic melanoma, which is melanoma that had spread to multiple parts of the body.  Currently treatments for advanced melanoma include chemotherapy and immunological drugs which are only effective 15 % of the time.  This new vaccine is not only easy to administer, but it also appears to have a much higher response rate in patients, potentially making it the best treatment option for anyone with advanced melanoma.

Melanoma is a rare but deadly cancer that typically begins in a mole or other pigmented tissue and can easily be removed if caught early.  If it advances it is much harder to treat and without treatment the patient usually has only a few years to live.

The vaccine being tested in this study is known as OncoVEX.  OncoVEX is effective because it is composed of an oncolytic virus, or a reprogrammed virus that is made to attack cancerous cells while leaving healthy cells undamaged.  The vaccine is injected directly into lesions that can be felt or seen, and its ease of administration allows it to be given right in a physician’s office.

According to Dr. Howard Kaufman, the director of the Rush Cancer Program, “The vaccine worked not just on the cells we injected, but on lesions in other parts of the body that we couldn’t reach.”  He explains how these injections prompt an immune response that circulates through the bloodstream to other affected parts of the body.

In the second phase of trials for OncoVEX, 50 patients were given up to 24 injections of the vaccine over the course of several months, leading to 4 partial and 8 full recoveries.  The scientists found these results very promising and Kaufman stated that, “These are the best results to date for any vaccine developed for melanoma, but they need to be confirmed in a larger population.”

To confirm these results, Kaufman is set to lead a third phase of trials which will enroll approximately 430 patients from cancer centers across the U.S.  These patients will be tracked for two years after their first dose and if the results are anything like the previous trial, this vaccine could turn an advanced melanoma diagnosis from a death notice into a treatable disease.

Click here for source