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.
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.
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.
Scientists have developed an extremely small probing device that is capable of binding to a cells surface and eavesdropping on its internal electrical activity. This may help to provide insight into how cells communicate and how they respond to medication delivered through the probe.
Ever think we could spy on a cell? We have been able to for almost thirty years now, but a new technique is purported to no do it substantially better. Stanford Researchers recently (March 30) published a paper describing their success in developing a nanometer-scale probe capable of binding and becoming a part of a single cell’s membrane. The paper, published in Proceedings of the National Academy of Science, offers insight into the ability for researchers to eavesdrop on the inner electrical activity of individual cells. The use of the nano probe as a conduit for inserting medication into a cell’s interior is also being cited by the Stanford researchers.
The study, spearheaded by Nick Melosh and Benjamin Almquist, focused on designing a probe in a way that allowed it to mimic a component of the cell membrane. The cell membrane, or cell wall, is the outermost encapsulating structure of a cell that protects it from the outside environment. The key to the probe’s easy insertion and the great affinity it has for the cell membrane is due to its engineering. The probe was engineered in a way that allowed it to mimic a type of cell membrane gatekeeper protein – a molecule naturally found in the cell membrane that regulates what enters and exits the cell.
Image depicting the nano-probe binding to the cell membrane. (Credit: Benjamin Almquist, Stanford University)
“What we have done is make an inorganic version of one of those membrane proteins, which sits in the membrane without disrupting it,” said Melosh. “The probes fuse into the membranes spontaneously and form good, strong junctions there.” The attachment is so strong, “we cannot pull them out. The membrane will just keep deforming rather than let go of the probes.” The 600-nanometer-long probe has integrated so well into membranes that the researchers have dubbed it the “stealth” probe.
Current methods involved in cell probing are limited in that they only allow access to the cell for few hours. Additionally, the methods are extremely destructive and damaging to cells. Melosh and Almquist are the first to implant a cell probe with very little damage to the cell.
Up to now, poking a hole in a cell membrane has largely relied on brute force, Melosh said. “We can basically rip holes in the cells using suction, we can use high voltage to puncture holes in their membranes, both of which are fairly destructive […]; many of the cells don’t survive.” That limits the duration of any observations, particularly electrical measurements of cell function.
“Ideally, what you’d like to be able to do is have an access port through the cell membrane that you can put things in or take things out, measure electrical currents … basically full control,” commented Melosh. “That’s really what we’ve shown – this is a platform upon which you can start building those kinds of devices.”
Melosh and Almquist are currently working with human red blood cells, cervical and ovary cancer cells to demonstrate the functionality of the probes in living cells.
To view the press release pertaining to this article, click here.
Two weeks ago (March 19, 2010), scientists from the University of Michigan published a study about an ingredient known as BanLec which is derived from bananas and acts as a potent inhibitor of the HIV virus. What stands out about BanLec is that it is a cheaper form of therapy that may provide a wider range of protection when compared to current anti-retrovirals which are commonly synthetic and made ineffective after small mutations to the virus. The cost and effectiveness of BanLec make it a promising candidate for the future prevention of HIV and AIDS, giving it the potential to save millions of lives.
BanLec is a type of lectin found in bananas that can identify foreign invaders such as a virus and attach to it. A lectin is a naturally occurring chemical in plants that is of great interest to scientists because of its ability to halt the chain of reaction that leads to a variety of infections. The researchers in this study discovered that BanLec inhibits HIV infection by binding to the virus’s protein envelope, therefore blocking it from entering the body.
According to Michael D. Swanson, the lead author of the study, “The problem with some HIV drugs is that the virus can mutate and become resistant, but that is much harder to do in the presence of lectins.” He goes on to explain that the lectins work by binding to sugars found all over the envelope of the HIV virus, and because of this the virus would have to go through multiple mutations for the lectin to stop working. This makes drugs such as BanLec more effective than some current anti-retrovirals which could become ineffective after one mutation to the virus.
So far all tests have been conducted in the laboratory, but Swanson is currently working on making BanLec suitable for human patients. Its clinical use is still considered to be far away but researchers believe it could ultimately be used as a self applied microbicide for the prevention of HIV infection.
While BanLec is no cure to AIDS, the information gained from this study is very exciting because according to researchers, millions of lives could be saved over the course of a few years with just a moderately successful treatment.
This past Friday (February 26, 2010) a group of scientists led by a virologist from the University of Wisconsin published a study about a new antiviral, which was found to be highly effective against the pathogenic H5N1 avian influenza virus. What stands out about this new antiviral, known as CS-8958, is that it has been proven to be effective against Tamiflu resistant strains of H5N1. This makes it a promising candidate for the future treatment and prevention of the bird flu.
Antiviral drugs are used in the treatment of viral infections by inhibiting the development of disease causing pathogens, and are a vital component in the countermeasure against human influenza viruses. Recently many new strains have been emerging, which show resistance to Tamiflu, an antiviral that slows the spread of the influenza virus within the body. These resistant strains pose a threat and make the development of new antivirals a pressing issue.
Professor Yoshihiro Kawaoka from the University of Wisconsin and his team of scientists tested a drug created from a novel neuraminidase inhibitor on mice in order to see its effectiveness against H5N1 strains of influenza. Neuraminidase inhibitors are a class of antiviral drugs that specifically target the influenza virus by blocking one of its proteins, therefore preventing its replication within the body.
They began their tests by giving a single dose of the CS-8958 antiviral drug nasally to mice, two hours after infection with the H5N1 influenza virus. The results showed that the survival rates were higher in the mice given this new drug when compared to mice given a standard five day treatment with Tamiflu. In another experiment, CS-8958 was found to be effective against highly pathogenic and Tamiflu resistant strains of H5N1, while it was also shown to protect mice against lethal H5N1 infection when it was administered seven days before infection with the virus.
With the information gained from this study, future treatment and prevention of H5N1 with this CS-8958 antiviral could be the most effective treatment to date due to its ability to eliminate newly emerging drug resistant strains in only one dose. While future studies still need to be conducted to make sure that these results are the same when tested on humans, the potential of this new antiviral is promising and could possibly put an end to the fear of the bird flu pandemic.
When parachuting out of a plane into combat, there are two competing considerations at play. The soldier needs to reach the ground as quickly as possible (spending as little time in the air as an easy target for enemy fire as possible) without being injured on landing.
This first goal means that military parachutes do not provide the softest possible landings, and poor landing technique often leads to injuries. What happens when you add over 100lbs. of body armor, weaponry, ammunitions, communications equipment, and other combat gear to this equation?
A study carried out in January of 2010 at the University of Pittsburgh has demonstrated that the extra weight from combat equipment can alter soldiers’ landing mechanics and lead to increased incidence of musculoskeletal injury.
In this study, researchers compared the kinetics (the relationship between the motion of a body and the forces acting on it) of the landings of 70 active duty Air Assault soldiers with and without equipment. High-speed cameras and computer software were used to capture and analyze the soldiers’ landing biomechanics under the two conditions, and force plates were used to measure vertical ground reaction forces (force exerted by the ground on a body in contact with it) of the landings.
Soldiers performed two-legged drop landings from a height of less than two ft. with body armor, helmet, and rifle, weighing a total of less than 40lbs. Real parachute landings are more similar to dropping from a height of ten feet without a chute, and real weight of combat gear exceeds 100lbs. Even though experimental forces were far less than those typically experienced by soldiers in training and combat, the additional weight was still observed to significantly alter soldiers’ landings.
It was determined that with the additional weight, soldiers experienced significantly greater maximum knee flexion, significantly greater maximum ground reaction forces, and greater time between initial ground contact and these peak values.
These changes in landing biomechanics and force of impact increase the risk of musculoskeletal injuries in soldiers. Such injuries are a primary concern in the military. The Armed Forces Epidemiological Board reports that musculoskeletal injuries “impose a greater ongoing negative impact on the health and readiness of U.S. Armed forces than any other category of medical complaint during peacetime and combat.” According to records, 58% of hospitalization cases in 2005 in the Navy were due to musculoskeletal injuries. These types of injuries result in significant amounts of lost duty time and can often be long-lasting and difficult to make a full recovery from, so prevention is crucial.
While jumping into combat without equipment is obviously not an option, proper strengthening and conditioning of the lower extremities, incremental increases in the weight with which soldiers train, and emphasis on proper landing technique can help mitigate the increased risk of injury associated with the weight of combat gear.
A recent study showed that exposure to low levels of antibiotics increased mutations in bacteria hundreds of times more than normal, making the creation of drug-resistant bacteria more likely. A drug under development by Radnor, PA-based PolyMedix, Inc. shows promise for addressing the serious threat of drug resistance by mimicking the human body’s defenses.
Click on the Image above to see Polymedix's Drug In Action (Sources: Image, World Health Organization; Video, Polymedix, Inc. )
If you don’t take your prescription antibiotics as your doctor advises, then listen up. Just last week (February 12) a paper published in the journal Molecular Cell described how exposure to low levels of antibiotics increased mutations in bacteria hundreds of times more than normal, making the creation of drug-resistant bacteria more likely. A drug currently under development by Radnor, PA-based PolyMedix, Inc., however, shows promise for addressing the serious threat of drug resistance by mimicking the human body’s defenses.
Drug resistance has been a growing health concern for decades now since the introduction of penicillin in the 1940s, the first available antibiotic of its kind. Drug resistance occurs because of bacteria’s natural ability to evolve through mutations it incurs as it reproduces. As it turns out, researchers have found that low antibiotic dosages are triggers for increasing the rate at which bacteria mutate, thus, increasing the likelihood of drug resistance.
“Like anything in nature, bacteria have ways to fight its opponents, and do so either by pumping antibiotics out of themselves through a process called efflux, or by rapidly mutating and changing the shape of the target of attack of the antibiotic drug. They can do this, even with large doses of antibiotics, it’s their innate way to try to survive,” explains Bozena Korczak, Vice President of Drug Development at PolyMedix Inc..”
“Upping the antibiotic dosage may be a viable solution but not the ultimate one,” adds Korczak. Driven by science conducted at the University of Pennsylvania, PolyMedix is investigating a new type of antibiotic drug that works by imitating the human immune system.
PolyMedix’s investigational antibiotic agent, called PMX-30063, is the first of its kind with a new approach to address the serious health implications of drug resistance by mimicking host defense protiens. Unlike most antibiotics, host defense proteins work fundamentally different. Rather than crossing the bacterial membrane to find a target like most antibiotics, they selectively target the cell membranes integrity by poking holes into it. This diminishes the bacteria’s ability to remain intact and the bacteria and its internal components become degraded (See video demonstration by clicking on the image above).
Polymedix purports that this unique mechanism of action makes drug resistance unlikely to develop. Korczak insists that “the best approach to preventing this phenomenon is by directly attacking the bacteria’s cell membrane, rendering them destroyed and dead in a way that there is little chance of resistance.”
To study the ability of bacteria to resist an antibiotic drug, a laboratory experimental method known as “serial passage” is used by intentionally trying to create bacterial drug resistance. Using this experiment, PolyMedix has shown that resistance did not appear to its compounds in contrast to traditional antibiotics.
So far, data from two Phase I clinical studies demonstrate that the compound is safe and well-tolerated. PolyMedix is on schedule to complete the third and final segment of the ongoing Phase 1 study with PMX-30063 early this year and commence Phase 2 studies later this year.
PolyMedix has received 9 grants and research contracts from the National Institutes of Health and branches of the military to help support the development of its antibiotic compounds.
To view the press release associated with this piece, please click here.
To learn more about PolyMedix, Inc., please visit www.polymedix.com.
This past Thursday, a group of scientists from Boston University released a new study which revealed that treating bacteria with low levels of antibiotics produces mutations in the bacteria instead of killing them, allowing them to gain resistance to a wide range of antibiotics. This newly gained understanding for the biomolecular processes that produce these “superbugs” can lead to the development of new antibiotics or even enhanced treatments that could prevent the creation of these extremely dangerous cross-resistant bacteria.
The team of scientists led by Professor James Collins, performed their tests on strains of E. coli and Staphylococcus. They started by administering low levels of five different antibiotics to the bacteria, which caused the introduction of mutations into the bacterial DNA. They followed this by then giving lethal doses of antibiotics to these mutated bacteria. The results revealed that many of the bacteria initially exposed to low levels of antibiotics now exhibited cross-resistance to a variety of antibiotics.
In lethal levels, antibiotics cause bacterial DNA to be shredded. However, when the antibiotic is not at a lethal level, mutations are entered into the bacterial DNA instead. The bacteria not only survive with these mutations, but gain protection from antibiotics including ones that the bacteria weren’t even exposed to.
This study helps to show the serious dangers involved with taking low or incomplete doses of antibiotics, which is common practice in many areas today. Farmers who include antibiotics in their livestock feed, doctors who prescribe antibiotics at random, and patients who don’t follow their full course of drugs are all promoting the creation of these bacterial “superbugs.”
With the information gained from these findings, enhanced antibiotic treatments can be developed that could prevent the emergence of multi-drug resistant bacteria and even increase their DNA killing ability so that low doses of antibiotics would be enough to kill mutated bacterial cells.
This past winter, I had the opportunity to work as what you would call, a nurse’s assistant. Basically, I cleaned hospital beds. But during this glamorous experience I was able to see nurses and doctors interact with patients before and after surgery. One of the key issues that repeatedly came up was anesthesia. Patients would be asked questions such as “are you allergic to any medications?” and “have you had any reactions to anesthesia before?” before entering surgery. Afterwards, their vitals would be closely monitored to ensure they return to their normal state after the anesthesia wore off.
Anesthesia is essential for its frequent use in otherwise painful surgical and medical procedures. However, anesthesia is not without its flaws. While anesthesia helps to achieve nerve blocks that can eliminate the feeling of pain, it often affects and impairs motor function. This is why patients are often unconscious, immobile, and sometimes unable to breathe on their own. A recent press release reports on a study conducted by a group of researches at the Children’s Hospital Boston. The researchers, led by Daniel Kohane, MD, PhD, of the Division of Critical Care Medicine at Children’s were originally studying surfactants, naturally-occurring agents that allow drugs to travel more easily through tissue, that would prolong the effects of anesthesia. However, to the surprise of the researchers, they discovered a potential new approach to anesthesia that would prolong the effects of anesthesia without causing a motor block.
While testing three types of surfactants along with anesthetics, the researchers found that sensory block in rats’ nerves were lengthened for up to 7 hours or more, but in many cases the rats did not experience motor impairment or experienced it for a very short duration. What’s next is figuring out the mechanism by which this approach works, and looking at the effects of other drugs and chemicals that may be used in anesthesia. If this approach proves to work on humans, it would have a monumental impact on the fields of anesthesia and medicine. From allowing women in labor to receive anesthesia while giving birth, to relieving individuals with musculoskeletal disorders from pain while allowing for the maintenance of mobility, this anesthetic approach would bridge the gap between relief of pain and motor ability.
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.
