ScienceDaily (Apr. 30, 2012) — Vitamin D may be known as the sunshine vitamin, but a new research report appearing in the Journal of Leukocyte Biology shows that it is more than that. According to the report, insufficient levels of vitamin D are related to a deficiency in our innate immune defenses that protect us from infections, neoplasias or autoimmune diseases. Since vitamin D levels decrease during autumn and winter when days are shorter and sunlight is relatively weak, this may explain why people are more prone to viral infection during these times. It also suggests that increased vitamin D intake, especially in older populations, could strengthen people's innate immunity against viral infections.
"There are numerous studies showing the benefits of maintaining adequate Vitamin D levels. As more and more research into Vitamin D is conducted, we are learning that it is extremely important for human health. Our study is no different, and vitamin D supplements should be considered one of many tools that might help when conventional therapies are not enough," said Victor Manuel Martinez-Taboada, M.D., a researcher involved in the work from the Division of Rheumatology at the Hospital Universitario "Marque's de Valdecilla," Facultad de Medicina at the Unversidad de Cantabria, in Santander, Spain.
To make this discovery, the researchers compared the changes in the blood levels of vitamin D among three groups of healthy subjects: young (age range: 20-30), middle (age range: 31-59), and elderly (age range: 60-86). They found decreased levels of vitamin D with aging, prompting researchers to compare whether such changes kept any relationship with toll-like receptor (TLR) expression measured on lymphocytes and monocytes and function after in vitro stimulation with specific ligands for each of the nine human TLRs and measurement of effector molecules, such as proinflammatory cytokines. Specifically, they found that the TRL most affected by a vitamin D insufficiency is TLR7, which regulates the immune response against viruses. Finally, scientists studied whether there was any difference in the three age groups depending on the season of the year since it is well known that a limited sun exposure during darker winter months is related with vitamin D deficiency.
"Any school teacher will tell you that people tend to be sicker during the winter than any other time of the year," said John Wherry, Ph.D., Deputy Editor of the Journal of Leukocyte Biology. "There have been numerous studies showing several environmental factors during winter months may allow viruses to spread easier. This study shows that sunlight, or more precisely the lack of vitamin D, could have a role in the seasonally higher rates of infection. More extensive studies must be conducted for this link to be conclusive, but since vitamin D supplements are inexpensive and generally safe, this is a really exciting discovery."
Journal Reference:
L. Alvarez-Rodriguez, M. Lopez-Hoyos, M. Garcia-Unzueta, J. A. Amado, P. M. Cacho, V. M. Martinez-Taboada. Age and low levels of circulating vitamin D are associated with impaired innate immune function. Journal of Leukocyte Biology, 2012; 91 (5): 829 DOI: 10.1189/jlb.1011523
http://dx.doi.org/10.1189/jlb.1011523
http://www.sciencedaily.com/releases/2012/04/120430105402.htm
Monday, April 30, 2012
Sunday, April 22, 2012
Possible New Cancer Treatment Identified
Article Date: 22 Apr 2012 - 0:00 PDT
New research findings show how it may be possible to render cancer tumours harmless without affecting the other cells and tissues in the body. The findings apply to cancers including breast, lung and bowel cancer. The study was carried out at Lund University in Sweden.
Many of the most common chemotherapy drugs used to treat cancer have serious side effects because they not only affect the cells in the cancer tumour, but also the cells in the rest of the body.Researchers at Lund University have now found a connection between two proteins that in different ways control cell division and the possibilities for a cancer tumour to develop. The retinoblastoma protein obstructs cell division and is absent in most types of cancer tumour. The new findings show that its absence leads to an increase in another protein, gamma-tubulin, which, when present in high levels, encourages the development of cancer tumours. However, if gamma-tubulin is blocked, the tumour cells die while the healthy cells survive.
The researchers are now looking for substances that can stop the effect of gamma-tubulin on cell division. This could form the basis for a new drug that works on various types of cancer and has a low risk of side effects if the substance is directed to the right place. This is because it is only the tumour cells that die.
"I judge the chances of finding a basis for a drug to be good, partly because there are already substances that block 'cousins' of gamma-tubulin", says Maria Alvarado-Kristensson, a researcher at Lund University, who believes that, if all goes well, a drug could be ready for initial tests on patients, known as 'phase 1 testing', in 5-6 years' time.
In the study, tissue and genetic material from patients with various different types of cancer were studied: breast cancer, bladder cancer, small-cell lung cancer, colon cancer and eye cancer. The two proteins were seen to play an important role in all these diseases and the protein is also found in a number of other types of cancer tumour.
"It is exciting to have research findings that are significant for several common types of cancer. This means that many patients will be affected if our work proves successful", says Maria Alvarado Kristensson.
The search for effective substances will involve screening a large number of substances, both natural and synthetic.
http://www.medicalnewstoday.com/releases/244358.php
Tuesday, April 10, 2012
Compound Found In Red Wine, Fruit Could Help Block Fat Cell Formation
Date: 10 Apr 2012 - 1:00 PDT
A compound found in red wine, grapes and other fruits, and similar in structure to resveratrol, is able to block cellular processes that allow fat cells to develop, opening a door to a potential method to control obesity, according to a Purdue University study.
Kee-Hong Kim, an assistant professor of food science, and Jung Yeon Kwon, a graduate student in Kim's laboratory, reported in the Journal of Biological Chemistry that the compound piceatannol blocks an immature fat cell's ability to develop and grow.
While similar in structure to resveratrol - the compound found in red wine, grapes and peanuts that is thought to combat cancer, heart disease and neurodegenerative diseases - piceatannol might be an important weapon against obesity. Resveratrol is converted to piceatannol in humans after consumption.
"Piceatannol actually alters the timing of gene expressions, gene functions and insulin action during adipogenesis, the process in which early stage fat cells become mature fat cells," Kim said. "In the presence of piceatannol, you can see delay or complete inhibition of adipogenesis."
Over a period of 10 days or more, immature fat cells, called preadipocytes, go through several stages to become mature fat cells, or adipocytes.
"These precursor cells, even though they have not accumulated lipids, have the potential to become fat cells," Kim said. "We consider that adipogenesis is an important molecular target to delay or prevent fat cell accumulation and, hopefully, body fat mass gain."
Kim found that piceatannol binds to insulin receptors of immature fat cells in the first stage of adipogenesis, blocking insulin's ability to control cell cycles and activate genes that carry out further stages of fat cell formation. Piceatannol essentially blocks the pathways necessary for immature fat cells to mature and grow.
Piceatannol is one of several compounds being studied in Kim's laboratory for its health benefits, and it is also present in different amounts in red grape seeds and skin, blueberries, passion fruit, and other fruits.
Kim would like to confirm his current finding, which is based on a cell culture system, using an animal model of obesity. His future work would also include determining methods for protecting piceatannol from degrading so that concentrations large enough would be available in the bloodstream to stop adipogenesis or body fat gain.
"We need to work on improving the stability and solubility of piceatannol to create a biological effect," Kim said.
ABSTRACT
Piceatannol, Natural Polyphenolic Stilbene, Inhibits Adipogenesis via Modulation of Mitotic Clonal Expansion and Insulin Receptor-dependent Insulin Signaling in Early Phase of Differentiation
Jung Yeon Kwon, Sang Gwon Seo, Yong-Seok Heo, Shuhua Yue, Ji-Xin Cheng, Ki Won Lee and Kee-Hong Kim
Piceatannol, a natural stilbene, is an analog and a metabolite of resveratrol. Despite a well-documented health benefit of resveratrol in intervention of the development of obesity, the role of piceatannol in the development of adipose tissue and related diseases is unknown. Here, we sought to determine the function of piceatannol in adipogenesis and elucidate the underlying mechanism. We show that piceatannol inhibits adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner at noncytotoxic concentrations. This anti-adipogenic property of piceatannol was largely limited to the early event of adipogenesis. In the early phase of adipogenesis, piceatannol-treated preadipocytes displayed a delayed cell cycle entry into G2/M phase at 24 h after initiation of adipogenesis. Furthermore, the piceatannol-suppressed mitotic clonal expansion was accompanied by reduced activation of the insulin-signaling pathway. Piceatannol dose-dependently inhibited differentiation mixture-induced phosphorylation of insulin receptor (IR)/insulin receptor substrate-1 (IRS-1)/Akt pathway in the early phase of adipogenesis. Moreover, we showed that piceatannol is an inhibitor of IR kinase activity and phosphatidylinositol 3-kinase (PI3K). Our kinetics study of IR further identified a Km value for ATP of 57.8 mM and a Ki value for piceatannol of 28.9 mM. We also showed that piceatannol directly binds to IR and inhibits IR kinase activity in a mixed noncompetitive manner to ATP, through which piceatannol appears to inhibit adipogenesis. Taken together, our study reveals an anti-adipogenic function of piceatannol and highlights IR and its downstream insulin signaling as novel targets for piceatannol in the early phase of adipogenesis.
http://www.jbc.org/content/287/14/11566.abstract
http://www.medicalnewstoday.com/releases/243843.php
A compound found in red wine, grapes and other fruits, and similar in structure to resveratrol, is able to block cellular processes that allow fat cells to develop, opening a door to a potential method to control obesity, according to a Purdue University study.
Kee-Hong Kim, an assistant professor of food science, and Jung Yeon Kwon, a graduate student in Kim's laboratory, reported in the Journal of Biological Chemistry that the compound piceatannol blocks an immature fat cell's ability to develop and grow.
While similar in structure to resveratrol - the compound found in red wine, grapes and peanuts that is thought to combat cancer, heart disease and neurodegenerative diseases - piceatannol might be an important weapon against obesity. Resveratrol is converted to piceatannol in humans after consumption.
"Piceatannol actually alters the timing of gene expressions, gene functions and insulin action during adipogenesis, the process in which early stage fat cells become mature fat cells," Kim said. "In the presence of piceatannol, you can see delay or complete inhibition of adipogenesis."
Over a period of 10 days or more, immature fat cells, called preadipocytes, go through several stages to become mature fat cells, or adipocytes.
"These precursor cells, even though they have not accumulated lipids, have the potential to become fat cells," Kim said. "We consider that adipogenesis is an important molecular target to delay or prevent fat cell accumulation and, hopefully, body fat mass gain."
Kim found that piceatannol binds to insulin receptors of immature fat cells in the first stage of adipogenesis, blocking insulin's ability to control cell cycles and activate genes that carry out further stages of fat cell formation. Piceatannol essentially blocks the pathways necessary for immature fat cells to mature and grow.
Piceatannol is one of several compounds being studied in Kim's laboratory for its health benefits, and it is also present in different amounts in red grape seeds and skin, blueberries, passion fruit, and other fruits.
Kim would like to confirm his current finding, which is based on a cell culture system, using an animal model of obesity. His future work would also include determining methods for protecting piceatannol from degrading so that concentrations large enough would be available in the bloodstream to stop adipogenesis or body fat gain.
"We need to work on improving the stability and solubility of piceatannol to create a biological effect," Kim said.
ABSTRACT
Piceatannol, Natural Polyphenolic Stilbene, Inhibits Adipogenesis via Modulation of Mitotic Clonal Expansion and Insulin Receptor-dependent Insulin Signaling in Early Phase of Differentiation
Jung Yeon Kwon, Sang Gwon Seo, Yong-Seok Heo, Shuhua Yue, Ji-Xin Cheng, Ki Won Lee and Kee-Hong Kim
Piceatannol, a natural stilbene, is an analog and a metabolite of resveratrol. Despite a well-documented health benefit of resveratrol in intervention of the development of obesity, the role of piceatannol in the development of adipose tissue and related diseases is unknown. Here, we sought to determine the function of piceatannol in adipogenesis and elucidate the underlying mechanism. We show that piceatannol inhibits adipogenesis of 3T3-L1 preadipocytes in a dose-dependent manner at noncytotoxic concentrations. This anti-adipogenic property of piceatannol was largely limited to the early event of adipogenesis. In the early phase of adipogenesis, piceatannol-treated preadipocytes displayed a delayed cell cycle entry into G2/M phase at 24 h after initiation of adipogenesis. Furthermore, the piceatannol-suppressed mitotic clonal expansion was accompanied by reduced activation of the insulin-signaling pathway. Piceatannol dose-dependently inhibited differentiation mixture-induced phosphorylation of insulin receptor (IR)/insulin receptor substrate-1 (IRS-1)/Akt pathway in the early phase of adipogenesis. Moreover, we showed that piceatannol is an inhibitor of IR kinase activity and phosphatidylinositol 3-kinase (PI3K). Our kinetics study of IR further identified a Km value for ATP of 57.8 mM and a Ki value for piceatannol of 28.9 mM. We also showed that piceatannol directly binds to IR and inhibits IR kinase activity in a mixed noncompetitive manner to ATP, through which piceatannol appears to inhibit adipogenesis. Taken together, our study reveals an anti-adipogenic function of piceatannol and highlights IR and its downstream insulin signaling as novel targets for piceatannol in the early phase of adipogenesis.
http://www.jbc.org/content/287/14/11566.abstract
http://www.medicalnewstoday.com/releases/243843.php
Thursday, April 5, 2012
Using Radio Waves to Bake Tumors
Nanotech News
April 2012
Nanothermal therapy – the use of nanoparticles to cook a tumor to death – is one of the many promising uses of nanotechnology to both improve the effectiveness of cancer therapy and reduce its side effects. Now, a team of investigators from theTexas Center for Cancer Nanomedicine has shown that liver cancer cells will take up targeted gold nanoparticles, absorb radio waves, and generate heat that damages the cells. In addition, the researchers have discovered how to increase the thermal toxicity of these nanoparticles.
This research was led by Steven A. Curley, of the University of Texas M.D. Anderson Cancer Center, and Lon Wilson, of Rice University. The investigators published their results in the journal Nanomedicine.
Biocompatible gold nanoparticles are ideal vehicles for delivering heat to tumors because they are non-toxic, stable, and can be coated with a variety of molecules to target them to tumors. Unlike conventional anticancer agents, gold nanoparticles are harmless unless first activated by an energy source, such as a near-infrared light delivered by a laser. In fact, laser-activated gold nanoparticles are being tested in human clinical trials for the treatment of head and neck cancer. Radio waves, however, have a potential advantage over laser energy because radio waves do not interact with biological tissues and thus can penetrate more deeply within the body than can laser light.
One of the major obstacles to using radiofrequency-activated gold nanoparticles to treat cancer is their tendency to clump together, which reduces their ability to absorb energy and convert it to heat. In the current study, the Texas researchers aimed to develop a precise understanding of why clumping occurs and develop the means to keep it from happening. Their experiments showed that the low pH within endosomes – the tiny vesicles that bring antibody-targeted nanoparticles into cells – is the primary cause of aggregation.
In an attempt to neutralize the acidic pH within endosomes, the investigators treated the cells with one of two different drugs – concanamycin A, an antibiotic not designed for use in humans, and chloroquine, an approved antimalarial agent – that are known to prevent endosome acidification. When the treated cells were exposed to antibody-targeted gold nanoparticles and then radiofrequency activation, heat-triggered cell death increased markedly compared to that seen with cells that were not pre-treated with the acid blockers, by preserving the protein coating on the gold nanoparticle surface. Based on these results, the investigators are now developing antibody-targeted nanoparticles with coatings that will prevent aggregation in the acidic environment of the endosome.
This work, which is detailed in a paper titled, "Stability of antibody-conjugated gold nanoparticles in the endo-lysosomal nanoenvironment: Implications for non-invasive radiofrequency-based cancer therapy," was supported in part by the NCI's Physical Sciences-Oncology Center program, a comprehensive initiative designed to accelerate the application of nanotechnology to the prevention, diagnosis, and treatment of cancer. An abstract of this paper is available at the journal's website.
Sunday, April 1, 2012
Trials Show Promise of Human Virus to Treat Head and Neck Cancer Patients
Released: 3/29/2012 9:00 AM EDT
Embargo expired:
Source: Institute of Cancer Research
Source: Institute of Cancer Research
Newswise — A naturally-occurring harmless human virus may be able to boost the effects of two standard chemotherapy drugs in some cancer patients, according to early stage trial data published today in Clinical Cancer Research.
RT3D, trade name Reolysin, is a new drug developed byOncolytics Biotech Inc with preclinical and clinical studies conducted at The Institute of Cancer Research (ICR) and The Royal Marsden Hospital. It is based on a virus (reovirus type 3 Dearing) that is found in almost all adults’ respiratory and gastrointestinal tracts without causing any symptoms.
RT3D has the ability to grow in and kill certain types of cancer cells, but does not grow in normal cells.
Previous trials injecting patients with the virus on its own showed limited effectiveness, but the team found that RT3D appeared to magnify the effects of platin and taxane-based chemotherapy on tumour cells.
Dr Kevin Harrington and colleagues in Leeds therefore started a clinical trial testing intravenous RT3D in combination with chemotherapeutics carboplatin and paclitaxel in 31 patients with advanced cancers who had stopped responding to standard treatments.
An initial Phase I study was carried out in patients with a range of advanced cancers, which showed the drug combination was safe. Side-effects were found to be generally mild, and consistent with chemotherapy alone.
Patients with head and neck cancers were found to have the best responses, so a Phase II expansion study at The Royal Marsden Hospital, London, and St James’s Hospital, Leeds, was therefore targeted to patients with these types of cancers.
Cancers shrank for about one third of the patients who could be evaluated, and disease stabilised for a further third. For one patient, all signs of their cancer disappeared.
“We saw really very impressive response rates in these patients. These are patients whose cancers had grown despite a great deal of previous treatment, including platinum-based chemotherapy for many,” Dr Harrington, Leader of the ICR’s Targeted Therapy Team and Consultant Oncologist at The Royal Marsden, said. “Under those circumstances, we’d expect that the average response rate to chemotherapy alone might be as low as single digits figures and the average survival would be somewhere between three to four months. In our Phase I/II study we show this had been prolonged to an average of seven months, albeit not in a randomised trial.”
“Based on the results of this study we’ve now started recruiting patients with advanced head and neck cancer to a randomised Phase III trial, in which all patients will receive chemotherapy and half will receive Reolysin as well. We are extremely excited about this progress.”
“Based on the results of this study we’ve now started recruiting patients with advanced head and neck cancer to a randomised Phase III trial, in which all patients will receive chemotherapy and half will receive Reolysin as well. We are extremely excited about this progress.”
The study also found the virus was not shed after treatment. This means people could be given the drug as outpatients as no risk was found that they could transmit the virus to others.
Head and neck cancers include tumours of the eye, nasal cavity, tongue, gums, lip, cheeks, voice box and oesophagus. Around 650,000 people are diagnosed with squamous cell cancer of the head and neck each year worldwide, and around 350,000 die from the disease annually.
Notes to editors:
Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies with first author Eleni M. Karapanagiotou from the ICR and The Royal Marsden publishes in the print edition of Clinical Cancer Research on April 1.
Phase I/II trial of carboplatin and paclitaxel chemotherapy in combination with intravenous oncolytic reovirus in patients with advanced malignancies with first author Eleni M. Karapanagiotou from the ICR and The Royal Marsden publishes in the print edition of Clinical Cancer Research on April 1.
The Phase III trial is recruiting patients with head and neck cancer who have already been treated with platinum but not taxane. More details at:http://clinicaltrials.gov/ct2/show/NCT01166542
The Institute of Cancer Research (ICR) is one of the world’s most influential cancer research institutes.
Scientists and clinicians at the ICR are working every day to make a real impact on cancer patients’ lives. Through its unique partnership with The Royal Marsden Hospital and ‘bench-to-bedside’ approach, the ICR is able to create and deliver results in a way that other institutions cannot. Together the two organisations are rated in the top four cancer centres globally.
The ICR has an outstanding record of achievement dating back more than 100 years. It provided the first convincing evidence that DNA damage is the basic cause of cancer, laying the foundation for the now universally accepted idea that cancer is a genetic disease. Today it leads the world at isolating cancer-related genes and discovering new targeted drugs for personalized cancer treatment.
As a college of the University of London, the ICR provides postgraduate higher education of international distinction. It has charitable status and relies on support from partner organisations, charities and the general public.
The ICR’s mission is to make the discoveries that defeat cancer. For more information visit www.icr.ac.uk
Age-Defying Therapies May Result From Rapamycin Study
The drug rapamycin has been shown to extend lifespan in lab animals, yet rapamycin has also been linked to impaired glucose tolerance and insulin sensitivity, two hallmarks of diabetes. By teasing apart rapamycin's activity at the cellular level, researchers at Whitehead Institute and the University of Pennsylvania have determined that inhibiting only the protein cluster known as the mechanistic target of rapamycin complex 1 (mTORC1) prolongs life in mice without adversely affecting glucose tolerance or insulin sensitivity.
With this novel understanding of how rapamycin produces its anti-aging effects, researchers may be able to develop a drug that specifically targets mTORC1, thereby promoting longevity while preventing the adverse effects associated with rapamycin.
One of the secrets to a longer, healthier life is simply to eat less. When subjected to calorie restriction (CR), typically defined as a 20-40% reduction in caloric intake with corresponding maintenance of proper nutrition, animals in labs not only live longer, but also have improved insulin sensitivity and glucose tolerance, both of which decline during aging.
Yet, for all of its benefits, CR's restricted diet is a stumbling block for most Americans. If only we had a drug that could do the same thing.
Well, we do, sort of. The drug rapamycin, which is used for immunosuppression in organ transplantations, mimics the longevity effects of CR and may tap into the same cellular pathway as CR. Unlike CR, however, rapamycin actually impairs glucose tolerance and insulin sensitivity, two hallmarks of diabetes. Clearly, rapamycin is doing something CR is not.
To understand better rapamycin's benefits and risks, researchers from the lab of Whitehead Institute Member David Sabatini and Joseph Baur, assistant professor of Physiology, at the University of Pennsylvania's Perelman School of Medicine, have discovered precisely how rapamycin is behaving at the cellular level. Their intriguing results are published in the journalScience.
http://www.sciencemag.org/content/335/6076/1638.abstract
"We know that despite its adverse effects, rapamycin still prolongs lifespan, so there's a potential that we could make it better by just having lifespan affected and not induce the adverse effects," says Sabatini, who is a professor of biology at MIT and a Howard Hughes Medical Institute (HHMI) investigator. "The data in this paper suggest that it's possible."
Rapamycin, which is also called sirolimus and marketed in the United States as Rapamune, is a known inhibitor of the mechanistic target of rapamycin complex 1 (mTORC1), a protein complex that regulates many cellular processes linked to growth and differentiation. mTORC1 is part of a cellular signaling pathway, called mTOR, which responds to nutrients and growth factors. Mechanistic target of rapamycin complex 2 (mTORC2) is also part of the mTOR pathway and regulates insulin signaling.
Rapamycin has generally been thought to target primarily mTORC1. But work by Dudley Lamming and Lan Ye, co-authors of the Science paper and postdoctoral fellows in the Sabatini and Baur labs respectively, indicates that in mice, rapamycin also inhibits mTORC2, thereby reducing insulin sensitivity.
To see if rapamycin's positive effects on lifespan effects could be separated from its negative metabolic effects, Lamming and Ye bred mice whose mTORC1 activity was partially inhibited but whose mTORC2 activity remained largely intact. The females of this mouse population lived longer than control mice while maintaining normal insulin sensitivity.
"This shows that disrupting mTORC1 alone is capable of extending lifespan, if you can find a way do that," says Lamming.
For Baur, the experiments' results indicate that there is a possibility of identifying a better anti-aging drug than rapamycin.
"Our work highlights the potential utility of molecules that target mTORC1 specifically and suggests there is hope that by targeting this pathway, you could really get something that ameloriates age-related diseases without causing more problems than it solves," says Baur. "If you're taking an anti-aging drug as a preventive measure, you probably don't want to pay the price of diabetes."
View drug information on Rapamune.
Monday, March 26, 2012
Nanoscale 'spaghetti' could become tools of regenerative medicine
| Posted: Mar 26th, 2012 | |
| (Nanowerk News) Medicine's recipe for keeping older people active and functioning in their homes and workplaces — and healing younger people injured in catastrophic accidents — may include "noodle gels" and other lab-made invisible filaments that resemble uncooked spaghetti with nanoscale dimensions, a scientist said here today at the 243rd National Meeting & Exposition of the American Chemical Society (ACS). The world's largest scientific society, ACS is meeting here this week with reports on more than 11,000 reports on new advances in science on its schedule. | |
| Samuel I. Stupp, Ph.D., who presented an ACS plenary lecture, explained that the synthetic pasta-like objects actually are major chemistry advances for regenerative medicine that his research team has accomplished. Regenerative medicine is an emerging field that combines chemistry, biology and engineering. It focuses on the regeneration of tissues and organs for the human body, to repair or replace those damaged through illness, injury, aging or birth defects. Those tissues range from cartilage in joints damaged by arthritis to heart muscle scarred by a heart attack and nerves severed in auto accidents. | |
| "A graying of the population is underway in industrialized countries," Stupp said. "In the U.S., we have the 'baby boom' generation — 75 million people born between 1946 and 1964, who now are reaching their mid-60s. At the same time, people are living longer — into their 80s, 90s and even 100s. With that comes an expectation of a better quality of life. It's also an economic issue because with lifespan rising, we're going to have to think about how to provide healthcare and keep people functional for longer periods of time, perhaps to keep them in the workforce longer." | |
| Stupp explained that advances in regenerative medicine also hold promise to improve people's lives at any age. For example, a young person could survive a car accident, but emerge with a spinal cord injury and be paralyzed. Also, cardiovascular disease and heart attacks are a leading cause of premature death around the world. Cartilage wears away and does not regenerate on its own in the body, leading to painful osteoarthritis. Some bones do not mend correctly. And the millions of people with diabetes face complications, including blocked blood vessels that result in an increased risk of heart attacks and limb amputations. Regenerative medical techniques could coax cells to grow and repair all of these types of damage, said Stupp, who is with Northwestern University. He is Board of Trustees Professor of Chemistry, Materials Science and Engineering, and Medicine and director of the Institute for BioNanotechnology in Medicine. | |
| One type of spaghetti-like filament developed by Stupp's team is a nanostructure of small bits of protein that glue themselves together spontaneously. These nanofilaments are so small that more than 50,000 would fit across the width of a human hair, and they can serve as smart scaffolds for many uses. For example, Stupp attached to these fibers signaling substances that mimic a powerful substance called VEGF that can promote the formation of new blood vessels. The VEGF-mimic caused new blood vessels to form in mice (stand-ins for humans) with blood vessel damage. | |
| "When VEGF itself was used in clinical trials on humans, it didn't work, despite a lot of laboratory research that suggested otherwise," said Stupp. "The problem was that VEGF was quickly broken down in the body. The nanofilament scaffold, however, lasts in the body for weeks, which allows the VEGF-mimic more time to grow vessels." Eventually, the nanofilaments break down and disappear, leaving only the new blood vessels behind. | |
| In other research, his group developed so-called "noodle gels," which are nanofibers that form long, noodle-like gels when they are heated, cooled and then squeezed out from a pipette (much like frosting from a piping bag) into salty water. These gels can be more than half an inch long and are visible with the naked eye. | |
| These noodle gels are a potential solution to a long-standing problem in regenerative medicine. It involves delivering proteins, biological signals and stem cells in a specific direction to target precisely the damaged parts of the heart, brain, spinal cord or other organs. Noodle gels can align stem cells in the linear fashion needed for proper repair of damaged tissue. Those strings could also serve as "spaghetti highways" to guide cells in our bodies to a specific location where repair is needed. Alternatively, the noodle gels containing aligned filaments could deliver signaling proteins and other beneficial substances to diseased locales. | |
| Many of Stupp's innovations are in the preclinical stage of testing by various companies, including his own company called Nanotope. These include materials for spinal cord, cartilage, blood vessel and bone regeneration. He predicts that some of these could be in clinical trials within the next five years. Eventually, the nanofibers and gels might someday allow doctors to simply "fix" damage that is currently impossible to treat, improving the quality of life for millions of people with devastating injuries and conditions. |
| Source: American Chemical Society http://www.nanowerk.com/news/newsid=24712.php |
Tuesday, January 31, 2012
Honey Helps Heal Wounds
Manuka honey stopped a skin strep in its tracks. Katherine Harmon reports.
January 31, 2012
Honey soothes a sore throat. Now research suggests that it could also help fight serious skin infections.
People have used honey's antibacterial properties for centuries. Now, scientists are discovering just how it works—and that it might be even better than antibiotics.
After surgery or a skin injury, many otherwise harmless bacteria that live on the skin can infect the wound site. One type of strep is particularly common and can lead to stubborn wounds that refuse to heal. But researchers found that honey—in particular that made from bees foraging on manuka flowers—stopped this strep in its tracks. The study is in the journal Microbiology. [Sarah Maddocks et al, Manuka Honey Inhibits the Development of Streptococcus pyogenes Biofilms and Causes Reduced Expression of Two Fibronectin Binding Proteins]
In lab tests, just a bit of the honey killed off the majority of bacterial cells—and cut down dramatically on the stubborn biofilms they formed.
It could also be used to prevent wounds from becoming infected in the first place. Hospital-borne infections are all too common, with more and more strains developing resistance to standard antibiotic treatments. So if the honey works in clinical trials, too, this sweet news will be all the buzz.
—Katherine Harmon
http://www.scientificamerican.com/podcast/episode.cfm?id=honey-helps-heal-wounds-12-01-31
Thursday, January 19, 2012
Novel strategy improves cancer cell uptake of nanoparticles
| Posted: Jan 19th, 2012 | |
| Novel strategy improves cancer cell uptake of nanoparticles | |
| (Nanowerk News) One of the promises of using nanoparticles to deliver potent anticancer agents to tumors is that it is easy to coat nanoparticles with tumor-targeting molecules that should increase the amount of drug that reaches a tumor while decreasing the amount of drug that hits healthy tissue. Taking this idea one step further, researchers at Harvard Medical School and the Massachusetts Institute of Technology have developed a strategy for identifying what could be called tumor uptake molecules for use on nanoparticles. This new class of tumor-targeting agents boosts the amount of drug-loaded nanoparticles that get into cancer cells. | |
| Omid Farokhzad and Robert Langer, both members of the MIT-Harvard Center for Cancer Nanotechnology Excellence (CCNE), led this study. The researchers published their findings in the journal ACS Nano ("Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection"). | |
| The MIT-Harvard CCNE team focused their discovery efforts on molecules known as aptamers, which are small pieces of RNA or DNA that form three-dimensional shapes capable of binding tightly and specifically to designated targets. In most instances, aptamers are constructed to target a known biomolecule—a disease-associated protein, for example. In this case, the investigators took a different approach and instead targeted two biological properties—the ability to distinguish a prostate cancer cell from a normal prostate cell and the ability to get into the diseased cells. They performed this feat by starting with a huge pool of random RNA sequences and through an iterative process gradually enriched this pool for RNAs that targeted and entered prostate cancer cells. After 12 cycles of this enrichment process, the investigators identified a small number of aptamers that each displayed superior tumor targeting and uptake properties. | |
| The researchers chose one of these aptamers and linked it to a polymer nanoparticle loaded with docetaxel, a potent anticancer agent. Experiments have so far shown that this construct has no effect on normal cells but is highly toxic to prostate cancer cells. The investigators are planning further studies in animal models of prostate cancer. They note that this approach is easily modified to finding targeting and uptake aptamers for any type of cancer cell. |
| Source: National Cancer Institute http://www.nanowerk.com/news/newsid=24007.php |
Friday, January 6, 2012
Old Mice Made "Young"—May Lead to Anti-Aging Treatments
Stem cell injections prolonged lives of rapidly aging mice.
Christine Dell'Amore
Published January 6, 2012
Aging mice can be made "young" again, according to findings one scientist initially found unbelievable.
The key is muscle-derived stem cells, which—like other stem cells—are unspecialized cells that can become any type of cell in the body.
When injected with muscle stem cells from young mice, older mice with a condition that causes them to age rapidly saw a threefold increase in their life spans, said study co-author Johnny Huard, a stem-cell expert at the McGowan Institute for Regenerative Medicine in Pittsburgh.
(See "Liposuction Fat Turned Into Stem Cells, Study Says.")
"I've been doing science for the last 20 years," Huard said. What "makes the story so amazing is that in the beginning, I didn't believe the result," he said.
"I bet that we mixed up the animals—you know, scientists are always skeptical."
"Tired" Stem Cells Reenergized
The study mice were genetically engineered to have a condition similar to a rare human syndrome called progeria, in which children age quickly and die young. (Learn more about the human body.)
The fast-aging mice typically die around 21 days after birth, far short of a normal mouse's two-year life span.
When scientists looked at the muscle stem cells of the fast-aging mice, they found what Huard called "tired" stem cells, which don't divide as quickly.
The team then examined mice that had aged normally and found their stem cells were similarly defective.
Curious if these deficient stem cells contribute to aging, Huard and colleagues injected stem cells from young, healthy mice into the fast-aging mice about four days before the older animals were expected to die.
To Huard's astonishment, the treated mice lived an average of 71 days—50 more than expected, and the equivalent of an 80-year-old human living to be 200, he said.
Not only did the animals live longer, they also seemed healthier, the scientists found.
(See "Drug Could Make Aging Brains More Youthful?")
Mysterious Secretions Make Cells Young
The "drastic" results bore out with repeated experiments, leaving the scientists to wonder how exactly the stem cells were working their magic, Huard said.
To find out, the team "tagged" stem cells injected into the fast-aging mice with a genetic marker that tracked where the cells went inside the body. Surprisingly, the team found only a few stem cells in the mouse organs, squashing a theory that the introduced cells were repairing organ tissues.
The scientists went back to the lab to test another idea: that stem cells secrete some kind of mysterious anti-aging substance.
The team put stem cells from the fast-aging mice on one side of a flask and stem cells from normal, young mice on the other side. The two sides were separated by a membrane that prevented the cells from touching.
Within days, the aging stem cells began acting "younger"—in other words, they began dividing more quickly.
"We can conclude that probably normal stem cells secrete something we don't know that seems to improve the defects in those aging stem cells," Huard said.
"If we can identify that, we have found an anti-aging protein that is going to be important" for people, said Huard, whose study appeared January 3 in the journal Nature Communications. http://www.nature.com/ncomms/journal/v3/n1/full/ncomms1611.html
Stem-Cell Research "Intriguing" but Preliminary
But other scientists are cautious about how soon the discovery may help people delay the aging process or treat age-related disease.
"They did a beautiful job of showing that, when they put the muscle stem cells in [the mice], they improved function," said Justin Lathia, an assistant professor of cell biology at the Cleveland Clinic's Lerner Research Institute.
But as far as people go, it's still not clear what exactly stem cells do in the body, as well as what the mysterious stem cell secretion really is, Lathia emphasized.
Jeremy Rich, chair of the department of Stem Cell Biology and Regenerative Medicine at the Cleveland Clinic, also pointed out that the study is limited to muscle stem cells. That means the research can't be generalized to include all stem cell types, which are often very different from each other.
Paul Frenette, a stem cell and aging expert at the Albert Einstein College of Medicine in New York, called the research "intriguing," but said one of the messages for "patients is not to get too excited."
"You see all these clinics that are popping up all over the world—even in New York—where they're injecting stem cells" into people to treat disease, even though such therapies have not been proven.
"I don't think people should run to the clinic right now to have injections of stem cells to live longer."
(See "'Stem Cell Tourists' Go Abroad for Unproven Treatments.")
Stem Cell Therapy to Help People "Age Well"?
Indeed, study co-author Huard noted that before any human anti-aging trials can begin, scientists need to repeat the experiment in normally aging mice to show whether these mice also live longer.
If that turns out to be true, Huard could imagine a scenario in which some of a person's stem cells are harvested at about age 20 and then injected back into his or her body at around age 50 or 55.
Stem cell therapies do already exist for conditions such as incontinence and heart problems, so he thinks "we're not that far [from applying] this approach clinically down the road."
But Huard warned that such a treatment would not mean a 55-year-old will suddenly look and feel 25 again.
"The goal of doing this research is not to [be like a] movie star with a ton of money [who wants to] look great for the rest of their lives," he said.
"The goal is, if you delay aging, maybe you can delay Alzheimer's or cardiovascular problems."
In other words, he said, such stem cell treatments would help people "age well."
Wednesday, January 4, 2012
Dried licorice root fights the bacteria that cause tooth decay and gum disease
January 4, 2012
Scientists are reporting identification of two substances in licorice — used extensively in Chinese traditional medicine — that kill the major bacteria responsible for tooth decay and gum disease, the leading causes of tooth loss in children and adults. In a study in ACS' Journal of Natural Products, they say that these substances could have a role in treating and preventing tooth decay and gum disease.
Stefan Gafner and colleagues explain that the dried root of the licorice plant is a common treatment in Chinese traditional medicine, especially as a way to enhance the activity of other herbal ingredients or as a flavoring. Despite the popularity of licorice candy in the U.S., licorice root has been replaced in domestic candy with anise oil, which has a similar flavor. Traditional medical practitioners use dried licorice root to treat various ailments, such as respiratory and digestive problems, but few modern scientific studies address whether licorice really works. (Consumers should check with their health care provider before taking licorice root because it can have undesirable effects and interactions with prescription drugs.) To test whether the sweet root could combat the bacteria that cause gum disease and cavities, the researchers took a closer look at various substances in licorice.
They found that two of the licorice compounds, licoricidin and licorisoflavan A, were the most effective antibacterial substances. These substances killed two of the major bacteria responsible for dental cavities and two of the bacteria that promote gum disease. One of the compounds — licoricidin — also killed a third gum disease bacterium. The researchers say that these substances could treat or even prevent oral infections.
More information: Isoflavonoids and Coumarins from Glycyrrhiza uralensis: Antibacterial Activity against Oral Pathogens and Conversion of Isoflavans into Isoflavan-Quinones during Purification, J. Nat. Prod., 2011, 74 (12), pp 2514–2519. DOI: 10.1021/np2004775
Abstract
Phytochemical investigation of a supercritical fluid extract of Glycyrrhiza uralensis has led to the isolation of 20 known isoflavonoids and coumarins, and glycycarpan (7), a new pterocarpan. The presence of two isoflavan-quinones, licoriquinone A (8) and licoriquinone B (9), in a fraction subjected to gel filtration on Sephadex LH-20 is due to suspected metal-catalyzed oxidative degradation of licoricidin (1) and licorisoflavan A (2). The major compounds in the extract, as well as 8, were evaluated for their ability to inhibit the growth of several major oral pathogens. Compounds 1 and 2 showed the most potent antibacterial activities, causing a marked growth inhibition of the cariogenic species Streptococcus mutans and Streptococcus sobrinus at 10 μg/mL and the periodontopathogenic species Porphyromonas gingivalis (at 5 μg/mL) and Prevotella intermedia (at 5 μg/mL for 1 and 2.5 μg/mL for 2). Only 1 moderately inhibited growth of Fusobacterium nucleatum at the highest concentration tested (10 μg/mL).
Provided by American Chemical Society
http://medicalxpress.com/news/2012-01-dried-licorice-root-bacteria-tooth.html
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