https://www.youtube.com/watch?v=uQ91AxUqHck&sns=tw
watch carefully and think about the ways that we follow to save world to be lived long long years.
give a contribution by your activities make the world to be lived long days healthy.
Sunday, May 3, 2015
Saturday, May 2, 2015
Drugs that activate brain stem cells may reverse multiple sclerosis
NIH-funded study identifies over-the-counter compounds that may replace damaged cells
Two drugs already on the market — an antifungal and a steroid — may potentially take on new roles as treatments for multiple sclerosis. According to a study published in Nature today, researchers discovered that these drugs may activate stem cells in the brain to stimulate myelin producing cells and repair white matter, which is damaged in multiple sclerosis. The study was partially funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
An artist’s representation of the study. Scientists found that certain drugs were able to promote remyelination in mouse models of multiple sclerosis. Image courtesy of Case Western Reserve University; Illustrator: Megan Kern
Specialized cells called oligodendrocytes lay down multiple layers of a fatty white substance known as myelin around axons, the long “wires” that connect brain cells. Myelin acts as an insulator and enables fast communication between brain cells. In multiple sclerosis there is breakdown of myelin and this deterioration leads to muscle weakness, numbness and problems with vision, coordination and balance.
“To replace damaged cells, the scientific field has focused on direct transplantation of stem cell-derived tissues for regenerative medicine, and that approach is likely to provide enormous benefit down the road. We asked if we could find a faster and less invasive approach by using drugs to activate native nervous system stem cells and direct them to form new myelin. Our ultimate goal was to enhance the body’s ability to repair itself,” said Paul J. Tesar, Ph.D., associate professor at Case Western Reserve School of Medicine in Cleveland, and senior author of the study.
It is unknown how myelin-producing cells are damaged, but research suggests they may be targeted by malfunctioning immune cells and that multiple sclerosis may start as an autoimmune disorder. Current therapies for multiple sclerosis include anti-inflammatory drugs, which help prevent the episodic relapses common in multiple sclerosis, but are less effective at preventing long-term disability. Scientists believe that therapies that promote myelin repair might improve neurologic disability in people with multiple sclerosis.
Adult brains contain oligodendrocyte progenitor cells (OPCs), which are stem cells that generate myelin-producing cells. OPCs are found to multiply in the brains of multiple sclerosis patients as if to respond to myelin damage, but for unknown reasons they are not effective in restoring white matter. In the current study, Dr. Tesar wanted to see if drugs already approved for other uses were able to stimulate OPCs to increase myelination.
OPCs have been difficult to isolate and study, but Dr. Tesar and his colleagues, in collaboration with Robert Miller, Ph.D., professor at George Washington University School of Medicine and Health Sciences in Washington, D.C., developed a novel method to investigate these cells in a petri dish. Using this technique, they were able to quickly test the effects of hundreds of drugs on the stem cells.
The compounds screened in this study were obtained from a drug library maintained by NIH’s National Center for Advancing Translational Sciences (NCATS). All are approved for use in humans. NCATS and Dr. Tesar have an ongoing collaboration and plan to expand the library of drugs screened against OPCs in the near future to identify other promising compounds.
Dr. Tesar’s team found that two compounds in particular, miconazole (an antifungal) and clobetasol (a steroid), stimulated mouse and human OPCs into generating myelin-producing cells.
Next, they examined whether the drugs, when injected into a mouse model of multiple sclerosis, could improve re-myelination. They found that both drugs were effective in activating OPCs to enhance myelination and reverse paralysis. As a result, almost all of the animals regained the use of their hind limbs. They also found that the drugs acted through two very different molecular mechanisms.
“The ability to activate white matter cells in the brain, as shown in this study, opens up an exciting new avenue of therapy development for myelin disorders such as multiple sclerosis,” said Ursula Utz, Ph.D., program director at the NINDS.
Dr. Tesar and his colleagues caution that more research is needed before miconazole and clobetasol can be tested in multiple sclerosis clinical trials. They are currently approved for use as creams or powders on the surfaces of the body but their safety administered in other forms, such as injections, in humans is unknown.
“Off-label use of the current forms of these drugs is more likely to increase other health concerns than alleviate multiple sclerosis symptoms. We are working tirelessly to ready a safe and effective drug for clinical use,” Dr. Tesar said.
This work was supported by the NINDS (NS085246, NS030800, NS026543), the New York Stem Cell Foundation and the Myelin Repair Foundation, New York City.
The NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.
The National Center for Advancing Translational Sciences is a distinctly different entity in the research ecosystem. Rather than targeting a particular disease or fundamental science, NCATS focuses on what is common across diseases and the translational process. The Center emphasizes innovation and deliverables, relying on the power of data and new technologies to develop, demonstrate and disseminate advancements in translational science that bring about tangible improvements in human health. For more information, visit http://www.ncats.nih.gov.
Drugs that activate brain stem cells may reverse multiple sclerosis
NIH-funded study identifies over-the-counter compounds that may replace damaged cells
Two drugs already on the market — an antifungal and a steroid — may potentially take on new roles as treatments for multiple sclerosis. According to a study published in Nature today, researchers discovered that these drugs may activate stem cells in the brain to stimulate myelin producing cells and repair white matter, which is damaged in multiple sclerosis. The study was partially funded by the National Institute of Neurological Disorders and Stroke (NINDS), part of the National Institutes of Health.
An artist’s representation of the study. Scientists found that certain drugs were able to promote remyelination in mouse models of multiple sclerosis. Image courtesy of Case Western Reserve University; Illustrator: Megan Kern
Specialized cells called oligodendrocytes lay down multiple layers of a fatty white substance known as myelin around axons, the long “wires” that connect brain cells. Myelin acts as an insulator and enables fast communication between brain cells. In multiple sclerosis there is breakdown of myelin and this deterioration leads to muscle weakness, numbness and problems with vision, coordination and balance.
“To replace damaged cells, the scientific field has focused on direct transplantation of stem cell-derived tissues for regenerative medicine, and that approach is likely to provide enormous benefit down the road. We asked if we could find a faster and less invasive approach by using drugs to activate native nervous system stem cells and direct them to form new myelin. Our ultimate goal was to enhance the body’s ability to repair itself,” said Paul J. Tesar, Ph.D., associate professor at Case Western Reserve School of Medicine in Cleveland, and senior author of the study.
It is unknown how myelin-producing cells are damaged, but research suggests they may be targeted by malfunctioning immune cells and that multiple sclerosis may start as an autoimmune disorder. Current therapies for multiple sclerosis include anti-inflammatory drugs, which help prevent the episodic relapses common in multiple sclerosis, but are less effective at preventing long-term disability. Scientists believe that therapies that promote myelin repair might improve neurologic disability in people with multiple sclerosis.
Adult brains contain oligodendrocyte progenitor cells (OPCs), which are stem cells that generate myelin-producing cells. OPCs are found to multiply in the brains of multiple sclerosis patients as if to respond to myelin damage, but for unknown reasons they are not effective in restoring white matter. In the current study, Dr. Tesar wanted to see if drugs already approved for other uses were able to stimulate OPCs to increase myelination.
OPCs have been difficult to isolate and study, but Dr. Tesar and his colleagues, in collaboration with Robert Miller, Ph.D., professor at George Washington University School of Medicine and Health Sciences in Washington, D.C., developed a novel method to investigate these cells in a petri dish. Using this technique, they were able to quickly test the effects of hundreds of drugs on the stem cells.
The compounds screened in this study were obtained from a drug library maintained by NIH’s National Center for Advancing Translational Sciences (NCATS). All are approved for use in humans. NCATS and Dr. Tesar have an ongoing collaboration and plan to expand the library of drugs screened against OPCs in the near future to identify other promising compounds.
Dr. Tesar’s team found that two compounds in particular, miconazole (an antifungal) and clobetasol (a steroid), stimulated mouse and human OPCs into generating myelin-producing cells.
Next, they examined whether the drugs, when injected into a mouse model of multiple sclerosis, could improve re-myelination. They found that both drugs were effective in activating OPCs to enhance myelination and reverse paralysis. As a result, almost all of the animals regained the use of their hind limbs. They also found that the drugs acted through two very different molecular mechanisms.
“The ability to activate white matter cells in the brain, as shown in this study, opens up an exciting new avenue of therapy development for myelin disorders such as multiple sclerosis,” said Ursula Utz, Ph.D., program director at the NINDS.
Dr. Tesar and his colleagues caution that more research is needed before miconazole and clobetasol can be tested in multiple sclerosis clinical trials. They are currently approved for use as creams or powders on the surfaces of the body but their safety administered in other forms, such as injections, in humans is unknown.
“Off-label use of the current forms of these drugs is more likely to increase other health concerns than alleviate multiple sclerosis symptoms. We are working tirelessly to ready a safe and effective drug for clinical use,” Dr. Tesar said.
This work was supported by the NINDS (NS085246, NS030800, NS026543), the New York Stem Cell Foundation and the Myelin Repair Foundation, New York City.
The NINDS is the nation’s leading funder of research on the brain and nervous system. The mission of NINDS is to seek fundamental knowledge about the brain and nervous system and to use that knowledge to reduce the burden of neurological disease.
The National Center for Advancing Translational Sciences is a distinctly different entity in the research ecosystem. Rather than targeting a particular disease or fundamental science, NCATS focuses on what is common across diseases and the translational process. The Center emphasizes innovation and deliverables, relying on the power of data and new technologies to develop, demonstrate and disseminate advancements in translational science that bring about tangible improvements in human health. For more information, visit http://www.ncats.nih.gov.
How to identify drugs that work best for each patient
Implantable device could allow doctors to test cancer drugs in patients before prescribing chemotherapy.
More than 100 drugs have been approved to treat cancer, but predicting which ones will help a particular patient is an inexact science at best.
A new device developed at MIT may change that. The implantable device, about the size of the grain of rice, can carry small doses of up to 30 different drugs. After implanting it in a tumor and letting the drugs diffuse into the tissue, researchers can measure how effectively each one kills the patient’s cancer cells.
Such a device could eliminate much of the guesswork now involved in choosing cancer treatments, says Oliver Jonas, a postdoc at MIT’s Koch Institute for Integrative Cancer Research and lead author of a paper describing the device in the April 22 online edition ofScience Translational Medicine.
“You can use it to test a patient for a range of available drugs, and pick the one that works best,” Jonas says.
The paper’s senior authors are Robert Langer, the David H. Koch Professor at MIT and a member of the Koch Institute, the Institute for Medical Engineering and Science, and the Department of Chemical Engineering; and Michael Cima, the David H. Koch Professor of Engineering at MIT and a member of the Koch Institute and the Department of Materials Science and Engineering.
Putting the lab in the patient
Most of the commonly used cancer drugs work by damaging DNA or otherwise interfering with cell function. Recently, scientists have also developed more targeted drugs designed to kill tumor cells that carry a specific genetic mutation. However, it is usually difficult to predict whether a particular drug will be effective in an individual patient.
In some cases, doctors extract tumor cells, grow them in a lab dish, and treat them with different drugs to see which ones are most effective. However, this process removes the cells from their natural environment, which can play an important role in how a tumor responds to drug treatment, Jonas says.
“The approach that we thought would be good to try is to essentially put the lab into the patient,” he says. “It’s safe and you can do all of your sensitivity testing in the native microenvironment.”
The device, made from a stiff, crystalline polymer, can be implanted in a patient’s tumor using a biopsy needle. After implantation, drugs seep 200 to 300 microns into the tumor, but do not overlap with each other. Any type of drug can go into the reservoir, and the researchers can formulate the drugs so that the doses that reach the cancer cells are similar to what they would receive if the drug were given by typical delivery methods such as intravenous injection.
After one day of drug exposure, the implant is removed, along with a small sample of the tumor tissue surrounding it, and the researchers analyze the drug effects by slicing up the tissue sample and staining it with antibodies that can detect markers of cell death or proliferation.
Ranking cancer drugs
To test the device, the researchers implanted it in mice that had been grafted with human prostate, breast, and melanoma tumors. These tumors are known to have varying sensitivity to different cancer drugs, and the MIT team’s results corresponded to those previously seen differences.
The researchers then tested the device with a type of breast cancer known as triple negative, which lacks the three most common breast cancer markers: estrogen receptor, progesterone receptor, and Her2. This form of cancer is particularly aggressive, and none of the drugs used against it are targeted to a specific genetic marker.
Using the device, the researchers found that triple negative tumors responded differently to five of the drugs commonly used to treat them. The most effective was paclitaxel, followed by doxorubicin, cisplatin, gemcitabine, and lapatinib. They found the same results when delivering these drugs by intravenous injection, suggesting that the device is an accurate predictor of drug sensitivity.
In this study, the researchers compared single drugs to each other, but the device could also be used to test different drug combinations by putting two or three drugs into the same reservoir, Jonas says.
“This device could help us identify the best chemotherapy agents and combinations for every tumor prior to starting systemic administration of chemotherapy, as opposed to making choices based on population-based statistics. This has been a longstanding pursuit of the oncology community and an important step toward our goal of developing precision-based cancer therapy,” says Jose Baselga, chief medical officer at Memorial Sloan Kettering Cancer Center and an author of the paper.
The researchers are now working on ways to make the device easier to read while it is still inside the patient, allowing them to get results faster. They are also planning to launch a clinical trial in breast cancer patients next year.
“This is a stunning advance in the approach to treating complex cancers,” says Henry Brem, a professor of neurosurgery and oncology at Johns Hopkins School of Medicine who was not involved in the research. “This work is transformative in that it now opens the doors to truly personalized medicine with the right drug or drug combination being utilized for each tumor.”
Another possible application for this device is to guide the development and testing of new cancer drugs. Researchers could create several different variants of a promising compound and test them all at once in a small trial of human patients, allowing them to choose the best one to carry on to a larger clinical trial.
How to identify drugs that work best for each patient
Implantable device could allow doctors to test cancer drugs in patients before prescribing chemotherapy.
More than 100 drugs have been approved to treat cancer, but predicting which ones will help a particular patient is an inexact science at best.
A new device developed at MIT may change that. The implantable device, about the size of the grain of rice, can carry small doses of up to 30 different drugs. After implanting it in a tumor and letting the drugs diffuse into the tissue, researchers can measure how effectively each one kills the patient’s cancer cells.
Such a device could eliminate much of the guesswork now involved in choosing cancer treatments, says Oliver Jonas, a postdoc at MIT’s Koch Institute for Integrative Cancer Research and lead author of a paper describing the device in the April 22 online edition ofScience Translational Medicine.
“You can use it to test a patient for a range of available drugs, and pick the one that works best,” Jonas says.
The paper’s senior authors are Robert Langer, the David H. Koch Professor at MIT and a member of the Koch Institute, the Institute for Medical Engineering and Science, and the Department of Chemical Engineering; and Michael Cima, the David H. Koch Professor of Engineering at MIT and a member of the Koch Institute and the Department of Materials Science and Engineering.
Putting the lab in the patient
Most of the commonly used cancer drugs work by damaging DNA or otherwise interfering with cell function. Recently, scientists have also developed more targeted drugs designed to kill tumor cells that carry a specific genetic mutation. However, it is usually difficult to predict whether a particular drug will be effective in an individual patient.
In some cases, doctors extract tumor cells, grow them in a lab dish, and treat them with different drugs to see which ones are most effective. However, this process removes the cells from their natural environment, which can play an important role in how a tumor responds to drug treatment, Jonas says.
“The approach that we thought would be good to try is to essentially put the lab into the patient,” he says. “It’s safe and you can do all of your sensitivity testing in the native microenvironment.”
The device, made from a stiff, crystalline polymer, can be implanted in a patient’s tumor using a biopsy needle. After implantation, drugs seep 200 to 300 microns into the tumor, but do not overlap with each other. Any type of drug can go into the reservoir, and the researchers can formulate the drugs so that the doses that reach the cancer cells are similar to what they would receive if the drug were given by typical delivery methods such as intravenous injection.
After one day of drug exposure, the implant is removed, along with a small sample of the tumor tissue surrounding it, and the researchers analyze the drug effects by slicing up the tissue sample and staining it with antibodies that can detect markers of cell death or proliferation.
Ranking cancer drugs
To test the device, the researchers implanted it in mice that had been grafted with human prostate, breast, and melanoma tumors. These tumors are known to have varying sensitivity to different cancer drugs, and the MIT team’s results corresponded to those previously seen differences.
The researchers then tested the device with a type of breast cancer known as triple negative, which lacks the three most common breast cancer markers: estrogen receptor, progesterone receptor, and Her2. This form of cancer is particularly aggressive, and none of the drugs used against it are targeted to a specific genetic marker.
Using the device, the researchers found that triple negative tumors responded differently to five of the drugs commonly used to treat them. The most effective was paclitaxel, followed by doxorubicin, cisplatin, gemcitabine, and lapatinib. They found the same results when delivering these drugs by intravenous injection, suggesting that the device is an accurate predictor of drug sensitivity.
In this study, the researchers compared single drugs to each other, but the device could also be used to test different drug combinations by putting two or three drugs into the same reservoir, Jonas says.
“This device could help us identify the best chemotherapy agents and combinations for every tumor prior to starting systemic administration of chemotherapy, as opposed to making choices based on population-based statistics. This has been a longstanding pursuit of the oncology community and an important step toward our goal of developing precision-based cancer therapy,” says Jose Baselga, chief medical officer at Memorial Sloan Kettering Cancer Center and an author of the paper.
The researchers are now working on ways to make the device easier to read while it is still inside the patient, allowing them to get results faster. They are also planning to launch a clinical trial in breast cancer patients next year.
“This is a stunning advance in the approach to treating complex cancers,” says Henry Brem, a professor of neurosurgery and oncology at Johns Hopkins School of Medicine who was not involved in the research. “This work is transformative in that it now opens the doors to truly personalized medicine with the right drug or drug combination being utilized for each tumor.”
Another possible application for this device is to guide the development and testing of new cancer drugs. Researchers could create several different variants of a promising compound and test them all at once in a small trial of human patients, allowing them to choose the best one to carry on to a larger clinical trial.
Unique UIC Center Will Study Alcohol's Effect on Genes
Newswise — Funded by a five-year, $7 million federal grant, the University of Illinois at Chicago College of Medicine will create a new center, the first of its kind, to study the effect of long-term alcohol exposure on genes.
The National Institute on Alcohol Abuse and Alcoholism, one of the National Institutes of Health, awarded the funding to establish a Center for Alcohol Research in Epigenetics (CARE). Subhash Pandey, UIC professor of psychiatry, will direct the center.
"Epigenetics" refers to chemical changes to DNA, RNA, or specific proteins, that change the activity of genes without changing the genes themselves. Epigenetic changes can occur in response to environmental or even social factors, such as alcohol and stress -- and these changes have been linked to changes in behavior and disease.
Epigenetics plays a role in the development and persistence of neurological changes associated with alcoholism, says Pandey, who is director of neuroscience alcoholism research at UIC and research career scientist at the Jesse Brown VA Medical Center.
The CARE researchers will investigate how alcohol-related epigenetic changes influence gene expression and "synaptic remodeling" -- the networking of nerve cells to each other. They will also look closely at how these changes correlate with behavior, such as anxiety and depression, and whether epigenetics may play a role in the withdrawal symptoms that make abstinence difficult.
“This award will allow the College of Medicine to build on Professor Pandey’s exemplary research on chronic alcohol use and alcoholism in addition to bolstering our leadership in understanding the causes of alcoholism as well as finding new ways to treat this devastating disease,” said Dr. Dimitri Azar, dean of the University of Illinois College of Medicine.
In a recent study using an animal model, Pandey and colleagues at UIC found that epigenetic changes resulting from exposure to alcohol during adolescence were associated with abnormal brain development and anxiety and alcohol preference in adulthood. In earlier work, the researchers were able to show that reshaping of the DNA scaffolding that supports and controls the expression of genes in the brain may play a major role in alcohol withdrawal symptoms, particularly anxiety.
Several brain regions play a crucial role in regulating both the positive and negative emotional states associated with alcohol addiction. Pandey said the center will look at the circuitry involved in reward and pleasure, depression, cognition, and anxiety.
CARE researchers will study disease using preclinical animal models and post-mortem examination of human brain. Investigators will also do neuroimaging of patients diagnosed with alcohol abuse and dependence and search for "biomarkers" of alcoholism -- measurable indicators in blood that correlate with alcohol addiction.
There are two causes of dependence on alcohol, said Pandey -- people may drink to get pleasure, or to self-medicate to relieve depression or anxiety. But alcohol addiction may itself cause depression and anxiety, feeding into a cycle.
“Ultimately, we hope these studies may lead to the identification of molecular cellular targets and gene networks which can be used to develop new pharmacotherapies to treat or prevent alcoholism,” Pandey said.
UIC's CARE is the only NIH-funded alcohol research center in Illinois, said Dr. Anand Kumar, Lizzie Gilman Professor and head of psychiatry, and is "well positioned to perform state-of-the-art basic translational and clinical research in alcoholism.”
In addition to its research projects, CARE will provide resources for training and community outreach. Based in the UIC psychiatry department, it includes collaborators from biophysics and physiology, anesthesiology, the Jesse Brown VA Medical Center, and the University of Illinois Urbana-Champaign campus.
Other members of the CARE research team are Alessandro Guidotti, Mark Brodie, Amy Lasek, Rajiv Sharma, Dennis Grayson, Harish Krishnan, David Gavin, Douglas Feinstein, Chunyu Liu, Dulal Bhaumik, Mark Rasenick and Marc Atkins of UIC; and Alvaro Hernandez and Victor Jongeneel from the Roy J. Carver Biotechnology Center at UIUC.
Unique UIC Center Will Study Alcohol's Effect on Genes
Newswise — Funded by a five-year, $7 million federal grant, the University of Illinois at Chicago College of Medicine will create a new center, the first of its kind, to study the effect of long-term alcohol exposure on genes.
The National Institute on Alcohol Abuse and Alcoholism, one of the National Institutes of Health, awarded the funding to establish a Center for Alcohol Research in Epigenetics (CARE). Subhash Pandey, UIC professor of psychiatry, will direct the center.
"Epigenetics" refers to chemical changes to DNA, RNA, or specific proteins, that change the activity of genes without changing the genes themselves. Epigenetic changes can occur in response to environmental or even social factors, such as alcohol and stress -- and these changes have been linked to changes in behavior and disease.
Epigenetics plays a role in the development and persistence of neurological changes associated with alcoholism, says Pandey, who is director of neuroscience alcoholism research at UIC and research career scientist at the Jesse Brown VA Medical Center.
The CARE researchers will investigate how alcohol-related epigenetic changes influence gene expression and "synaptic remodeling" -- the networking of nerve cells to each other. They will also look closely at how these changes correlate with behavior, such as anxiety and depression, and whether epigenetics may play a role in the withdrawal symptoms that make abstinence difficult.
“This award will allow the College of Medicine to build on Professor Pandey’s exemplary research on chronic alcohol use and alcoholism in addition to bolstering our leadership in understanding the causes of alcoholism as well as finding new ways to treat this devastating disease,” said Dr. Dimitri Azar, dean of the University of Illinois College of Medicine.
In a recent study using an animal model, Pandey and colleagues at UIC found that epigenetic changes resulting from exposure to alcohol during adolescence were associated with abnormal brain development and anxiety and alcohol preference in adulthood. In earlier work, the researchers were able to show that reshaping of the DNA scaffolding that supports and controls the expression of genes in the brain may play a major role in alcohol withdrawal symptoms, particularly anxiety.
Several brain regions play a crucial role in regulating both the positive and negative emotional states associated with alcohol addiction. Pandey said the center will look at the circuitry involved in reward and pleasure, depression, cognition, and anxiety.
CARE researchers will study disease using preclinical animal models and post-mortem examination of human brain. Investigators will also do neuroimaging of patients diagnosed with alcohol abuse and dependence and search for "biomarkers" of alcoholism -- measurable indicators in blood that correlate with alcohol addiction.
There are two causes of dependence on alcohol, said Pandey -- people may drink to get pleasure, or to self-medicate to relieve depression or anxiety. But alcohol addiction may itself cause depression and anxiety, feeding into a cycle.
“Ultimately, we hope these studies may lead to the identification of molecular cellular targets and gene networks which can be used to develop new pharmacotherapies to treat or prevent alcoholism,” Pandey said.
UIC's CARE is the only NIH-funded alcohol research center in Illinois, said Dr. Anand Kumar, Lizzie Gilman Professor and head of psychiatry, and is "well positioned to perform state-of-the-art basic translational and clinical research in alcoholism.”
In addition to its research projects, CARE will provide resources for training and community outreach. Based in the UIC psychiatry department, it includes collaborators from biophysics and physiology, anesthesiology, the Jesse Brown VA Medical Center, and the University of Illinois Urbana-Champaign campus.
Other members of the CARE research team are Alessandro Guidotti, Mark Brodie, Amy Lasek, Rajiv Sharma, Dennis Grayson, Harish Krishnan, David Gavin, Douglas Feinstein, Chunyu Liu, Dulal Bhaumik, Mark Rasenick and Marc Atkins of UIC; and Alvaro Hernandez and Victor Jongeneel from the Roy J. Carver Biotechnology Center at UIUC.
Key Tissue Engineering Step Taken in Forming New Blood Vessels
Researchers moved a step closer toward coaxing the body into producing its own replacement blood vessels after discovering that suppressing parts of the innate immune system may raise the chances of a tissue engineered vascular graft's success.
In a study (“The innate immune system contributes to tissue-engineered vascular graft performance”) appearing in The FASEB Journal, scientists showed that by controlling the reaction that natural killer cells, platelets, and the acute inflammatory response have to the graft, they could also reduce the abnormal narrowing of the grafts (stenosis), which is the cause of most failures. This discovery sets the stage for a second, more successful, generation of tissue engineered grafts designed to help regenerate components of the cardiovascular system, according to Cameron Best, a researcher involved in the work from the tissue engineering and surgical research department at the research institute at Nationwide Children's Hospital in Columbus, OH.
“Implicating the initial innate immune response as a critical factor in graft stenosis may provide a strategy for prognosis and therapy of second-generation TEVGs [tissue engineered vascular grafts],” wrote the investigators.
"Our aim is to extend these findings toward the development of a safe and effective tissue engineered vascular grafts for the management of congenital heart disease," said Mr. Best. "We hope that our translational approach is applicable to other areas of regenerative medicine and a model for investigators in the field."
Mr. Best and colleagues made this discovery by observing that immunodeficient mice mount a blunted acute inflammatory response to implanted TEVGs grafts and that stenosis, or narrowing of the blood vessel, did not occur. Researchers then treated wild type mice with either a natural killer cell depleting antibody or anti-platelet drugs and found that the rate of stenosis in each of these models was about half of that observed in the normal, untreated, mouse. This suggests that the combined effects of acute inflammation, natural killer cells and platelets are critical to TEVG performance.
"When most people think of regenerative medicine, they think of growing new hearts or kidneys," said Gerald Weissmann, M.D., editor-in-chief of The FASEB Journal. "What most people don't realize is that just being able to engineer new blood vessels would go a long way toward saving lives and alleviating suffering. This research is significant because it identifies what goes wrong with today's engineered blood vessels, and reveals a solution on what to do to fix this problem."
Key Tissue Engineering Step Taken in Forming New Blood Vessels
Researchers moved a step closer toward coaxing the body into producing its own replacement blood vessels after discovering that suppressing parts of the innate immune system may raise the chances of a tissue engineered vascular graft's success.
In a study (“The innate immune system contributes to tissue-engineered vascular graft performance”) appearing in The FASEB Journal, scientists showed that by controlling the reaction that natural killer cells, platelets, and the acute inflammatory response have to the graft, they could also reduce the abnormal narrowing of the grafts (stenosis), which is the cause of most failures. This discovery sets the stage for a second, more successful, generation of tissue engineered grafts designed to help regenerate components of the cardiovascular system, according to Cameron Best, a researcher involved in the work from the tissue engineering and surgical research department at the research institute at Nationwide Children's Hospital in Columbus, OH.
“Implicating the initial innate immune response as a critical factor in graft stenosis may provide a strategy for prognosis and therapy of second-generation TEVGs [tissue engineered vascular grafts],” wrote the investigators.
"Our aim is to extend these findings toward the development of a safe and effective tissue engineered vascular grafts for the management of congenital heart disease," said Mr. Best. "We hope that our translational approach is applicable to other areas of regenerative medicine and a model for investigators in the field."
Mr. Best and colleagues made this discovery by observing that immunodeficient mice mount a blunted acute inflammatory response to implanted TEVGs grafts and that stenosis, or narrowing of the blood vessel, did not occur. Researchers then treated wild type mice with either a natural killer cell depleting antibody or anti-platelet drugs and found that the rate of stenosis in each of these models was about half of that observed in the normal, untreated, mouse. This suggests that the combined effects of acute inflammation, natural killer cells and platelets are critical to TEVG performance.
"When most people think of regenerative medicine, they think of growing new hearts or kidneys," said Gerald Weissmann, M.D., editor-in-chief of The FASEB Journal. "What most people don't realize is that just being able to engineer new blood vessels would go a long way toward saving lives and alleviating suffering. This research is significant because it identifies what goes wrong with today's engineered blood vessels, and reveals a solution on what to do to fix this problem."
New Study Data Could Lead to Reversal of Aging Process
Scientists believe they have discovered the key driver in the human aging process, which could lead to preventing age-related disease or even reversing the aging process itself. [evgenyatamanenko/iStock]
There are many among us who believe that time is a predator, patiently waiting for our bodies to age and yield toward its inevitable fate. However, there are few within the sciences that look at the ageing process through a different lens—viewing it as a disease, one that can be treated, slowed, and possibly even reversed.
Scientists from the Salk Institute and the Chinese Academy of Science have published new data that they believe identifies a key driver in the aging process. The researchers found that the genetic mutations associated with Werner syndrome, a disorder that leads to premature aging and death is triggered by the deterioration of DNA bundles known as heterochromatin. A greater understanding of this process could lead to the treatment and prevention of age-related disorders such as Alzheimer’s,diabetes, and even cancer.
"Our findings show that the gene mutation that causes Werner syndrome results in the disorganization of heterochromatin, and that this disruption of normal DNA packaging is a key driver of aging," explained Juan Carlos Izpisua Belmonte, Ph.D., professor in the gene expression laboratory at the Salk Institute and senior author on the paper. "This has implications beyond Werner syndrome, as it identifies a central mechanism of aging—heterochromatin disorganization—which has been shown to be reversible."
The findings from this study were published recently in Science through an article entitled "A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging."
Werner syndrome (WS), also known as adult progeria, is a genetic disorder that causes rapid aging and recapitulates certain aspects of the human physiological aging process. The disease is caused by a mutation within the Werner syndrome, RecQ helicase like gene (WRN). This enzyme typically helps maintain genomic stability and integrity, however in WS, the mutant protein disrupts DNA replication, repair, and gene expression.
Dr. Izpisua Belmonte and his colleagues sought to determine how mutated WRN could wreak so much havoc on cellular process. To that end, the researchers generated an in vitro model of WS employing human embryonic stem cells that contained a genetic deletion of the WRN gene.
The investigators observed that the altered stem cells recapitulated the WS phenotype and began to age more rapidly. At the molecular level they found that the deletion of WRN led to disruptions within the structure of heterochromatin, a scenario that could lead to global gene expression changes through epigenetic regulation.
"Our study connects the dots between Werner syndrome and heterochromatin disorganization, outlining a molecular mechanism by which a genetic mutation leads to a general disruption of cellular processes by disrupting epigenetic regulation," stated Dr. Izpisua Belmonte. "More broadly, it suggests that accumulated alterations in the structure of heterochromatin may be a major underlying cause of cellular aging. This begs the question of whether we can reverse these alterations—like remodeling an old house or car—to prevent, or even reverse, age-related declines and diseases."
While their results are exciting and could have a major impact for age-related disease research, Dr. Izpisua Belmonte expressed caution in over interpreting the results, as more extensive studies will be required to fully understand the relationship between heterochromatin disorganization and aging
New Study Data Could Lead to Reversal of Aging Process
Scientists believe they have discovered the key driver in the human aging process, which could lead to preventing age-related disease or even reversing the aging process itself. [evgenyatamanenko/iStock]
There are many among us who believe that time is a predator, patiently waiting for our bodies to age and yield toward its inevitable fate. However, there are few within the sciences that look at the ageing process through a different lens—viewing it as a disease, one that can be treated, slowed, and possibly even reversed.
Scientists from the Salk Institute and the Chinese Academy of Science have published new data that they believe identifies a key driver in the aging process. The researchers found that the genetic mutations associated with Werner syndrome, a disorder that leads to premature aging and death is triggered by the deterioration of DNA bundles known as heterochromatin. A greater understanding of this process could lead to the treatment and prevention of age-related disorders such as Alzheimer’s,diabetes, and even cancer.
"Our findings show that the gene mutation that causes Werner syndrome results in the disorganization of heterochromatin, and that this disruption of normal DNA packaging is a key driver of aging," explained Juan Carlos Izpisua Belmonte, Ph.D., professor in the gene expression laboratory at the Salk Institute and senior author on the paper. "This has implications beyond Werner syndrome, as it identifies a central mechanism of aging—heterochromatin disorganization—which has been shown to be reversible."
The findings from this study were published recently in Science through an article entitled "A Werner syndrome stem cell model unveils heterochromatin alterations as a driver of human aging."
Werner syndrome (WS), also known as adult progeria, is a genetic disorder that causes rapid aging and recapitulates certain aspects of the human physiological aging process. The disease is caused by a mutation within the Werner syndrome, RecQ helicase like gene (WRN). This enzyme typically helps maintain genomic stability and integrity, however in WS, the mutant protein disrupts DNA replication, repair, and gene expression.
Dr. Izpisua Belmonte and his colleagues sought to determine how mutated WRN could wreak so much havoc on cellular process. To that end, the researchers generated an in vitro model of WS employing human embryonic stem cells that contained a genetic deletion of the WRN gene.
The investigators observed that the altered stem cells recapitulated the WS phenotype and began to age more rapidly. At the molecular level they found that the deletion of WRN led to disruptions within the structure of heterochromatin, a scenario that could lead to global gene expression changes through epigenetic regulation.
"Our study connects the dots between Werner syndrome and heterochromatin disorganization, outlining a molecular mechanism by which a genetic mutation leads to a general disruption of cellular processes by disrupting epigenetic regulation," stated Dr. Izpisua Belmonte. "More broadly, it suggests that accumulated alterations in the structure of heterochromatin may be a major underlying cause of cellular aging. This begs the question of whether we can reverse these alterations—like remodeling an old house or car—to prevent, or even reverse, age-related declines and diseases."
While their results are exciting and could have a major impact for age-related disease research, Dr. Izpisua Belmonte expressed caution in over interpreting the results, as more extensive studies will be required to fully understand the relationship between heterochromatin disorganization and aging
Friday, May 1, 2015
Thursday, April 30, 2015
Grace Myu: Malaysia Beauty, Fashion, Lifestyle Blogger: VS Sassoon iPink Instant Studio Professional Hair ...
Grace Myu: Malaysia Beauty, Fashion, Lifestyle Blogger: VS Sassoon iPink Instant Studio Professional Hair ...: When I was younger, my mom was always spotted with hair rollers on (imagine that vintage looking image of stay-at-home-moms) and she ma...
Grace Myu: Malaysia Beauty, Fashion, Lifestyle Blogger: VS Sassoon iPink Instant Studio Professional Hair ...
Grace Myu: Malaysia Beauty, Fashion, Lifestyle Blogger: VS Sassoon iPink Instant Studio Professional Hair ...: When I was younger, my mom was always spotted with hair rollers on (imagine that vintage looking image of stay-at-home-moms) and she ma...
Review provides further insight into link between hormone therapy and breast cancer
A review of data from two Women's Health Initiative clinical trials reveals the varying effects of menopausal hormone therapy on the incidence of breast cancer over time. The results are published in the journal JAMA Oncology.
The review revealed that use of estrogen plus progestin was associated with a steady increase in breast cancer incidence, while estrogen alone was found to reduce breast cancer risk.
Hormone replacement therapy was once considered the standard treatment for women suffering menopausal symptoms. It involves the use of medications that contain female hormones - commonlyestrogen or a combination of estrogen and progestin (a form of progesterone) - to replace those lost followingmenopause.
But in 2002 came the results of a clinical trial as part of the Women's Health Initiative (WHI), which found a link between use of combined hormone therapy and increased risk of breast cancer - a finding that was supported by another WHI trial a year later.
According to Dr. Rowan T. Chlebowski, of the Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center in Torrance, CA, and colleagues, the results of these trials led to a significant reduction in the use of hormone therapy.
However, the authors point out that while combined hormone therapy was associated with increased breast cancer risk in these trials, the use of estrogen alone was not. In fact, estrogen use was associated with reduced breast cancer incidence and deaths.
"Such results raised questions regarding the short- and long-term postintervention effects of these two regimens on breast cancer," say the authors.
As such, Dr. Chlebowski and colleagues conducted a longer-term review of the two WHI trials with the aim of going a better understanding of how the use of hormone therapy influences the risk of breast cancer.
Hormone therapy with estrogen alone reduced breast cancer risk
One trial involved 16,608 women with an intact uterus who were randomized to receive combined hormone therapy - estrogen plus progestin - or a placebo for an average of 5.6 years.
The other trial involved 10,739 women who had undergone a hysterectomy who were randomly assigned to receive estrogen alone or a placebo for an average of 7.2 years.
The review revealed that use of estrogen plus progestin throughout the entire intervention period was associated with a steady increase in breast cancer incidence.
However, around 2.75 years after combined hormone therapy began - deemed the early postintervention period - the researchers identified a sharp reduction in breast cancer incidence among women whose therapy had been discontinued.
"This likely represents a therapeutic influence of change in hormone environment on preclinical breast cancers similar to that seen with adjuvant aromatase inhibitor or tamoxifen use in early-stage breast cancer," the authors note.
An increased risk of breast cancer remained for years after treatment ceased, however.
In the estrogen-only trial, the researchers identified an overall significant reduction in breast cancer incidence throughout the entire intervention period. This risk was lowest in the early postintervention period, the team found, though they note it increased over time.
"Nonetheless," say the authors, "use of estrogen alone reduced breast cancer risk throughout the cumulative follow-up."
The researchers say the early reduction in breast cancer risk with estrogen therapy alone may reflect a treatment effect on preclinical breast cancers. "Estrogen receptor-positive cancers respond to sudden lowering of estrogen exposure with tumor reduction," they note.
Commenting on their findings, the team says:
"With longer follow-up of the two WHI hormone therapy trials, a complex pattern of changing year-to-year influences on breast cancer was observed.
The ongoing influences on breast cancer after stopping hormone therapy in the WHI trials require recalibration of breast cancer risk and benefit calculation for both regimens, with greater adverse influence for estrogen and progestin use and somewhat greater benefit for use of estrogen alone."
Review offers 'compelling new evidence' of progesterone's role in breast cancer
In an editorial linked to the study, Rama Khoka, PhD, of the Princess Margaret Cancer Center in Toronto, Canada, and colleagues say this latest review of the WHI trials reveals "compelling new evidence" for the significant role progesterone plays in breast cancer, noting that it has "traditionally taken a backseat to estrogen."
"Although the WHI trials relate to the menopausal setting, lessons learned from them continue to provide additional value in appreciating a potential role of progesterone even in premenopausal breast cancer," they add.
"Furthermore, investigation into the cellular and mechanistic underpinnings of progesterone's impact on the normal breast and breast cancer may provide new opportunities for knowledge translation and therapeutic intervention in breast cancer."
Coffee 'could halve breast cancer recurrence' in tamoxifen-treated patients
A new study led by researchers from Lund University in Sweden claims women diagnosed with breast cancer who are taking the drug tamoxifen could halve their risk of recurrence by drinking coffee.
The findings - published in the journal Clinical Cancer Research - build on those from a previous study conducted by Lund University researchers in 2013, in which the team found a link between coffeeconsumption and reduced breast cancer recurrence in 300 women who used tamoxifen.
In that study, however, the researchers were unable to explain why coffee appeared to protect against the return of breast cancer in these women.
"Now, unlike in the previous study, we have combined information about the patients' lifestyle and clinical data from 1,090 breast cancer patients with studies on breast cancer cells," say researchers Ann Rosendahl and Helena Jernström, both of Lund University and Skåne University Hospital, also in Sweden.
After skin cancer, breast cancer is the most common cancer among women in the US, affecting around 1 in 8 women in their lifetime.
Hormone therapy is a standard treatment for patients with estrogen receptor-positive (ER+) breast cancer, most commonly administered after a patient undergoes surgery for the disease. Tamoxifen is one drug used for hormone therapy. It works by preventing estrogen from binding to breast cancer cells, which stops them growing and dividing.
Of the 1,090 women with breast cancer included in the study, around 500 were treated with tamoxifen. The women's coffee consumption was assessed and allocated to one of three categories: low consumption (less than one cup a day), moderate consumption (two to four cups and day) and high consumption (five or more cups a day).
The researchers found that among the women who were treated with tamoxifen, those who had moderate or high coffee consumption had half the likelihood of breast cancer recurrence than those who had low coffee consumption or did not drink the beverage at all.
What is more, the team found that tamoxifen-treated women who consumed at least two cups of coffee a day had smaller tumors and a lower proportion of hormone-dependent tumors than women who consumed less coffee.
Caffeine, caffeic acid 'reduces cell division and increases cell death'
Next, the researchers analyzed the effects of two substances present in coffee - caffeine and caffeic acid - on breast cancer cells.
The team found that both of these compounds - particularly caffeine - reduced cell division and increased cell death among both ER+ and estrogen receptor-negative (ER-) breast cancer cells. When tamoxifen was applied, the effect was even stronger.
"This shows that these substances have an effect on the breast cancer cells and turn off signaling pathways that the cancer cells require to grow," say Rosendahl and Jernström.
The researchers add:
"The clinical and experimental findings demonstrate various anticancer properties of caffeine and caffeic acid against both ER+ and ER- breast cancer that may sensitize tumor cells to tamoxifen and reduce breast cancer growth."
The team stresses, however, that breast cancer patients should not swap their medication for coffee. "But if you like coffee and are also taking tamoxifen," add Rosendahl and Jernström, "there is no reason to stop drinking it. Just two cups a day is sufficient to make a difference."
Last month, Medical News Today reported on a study claiming just one cup of coffee a day could significantly reduce the risk of liver cancer, while another study found consuming five cups a day could reduce the risk of heart attack.
The findings - published in the journal Clinical Cancer Research - build on those from a previous study conducted by Lund University researchers in 2013, in which the team found a link between coffeeconsumption and reduced breast cancer recurrence in 300 women who used tamoxifen.
In that study, however, the researchers were unable to explain why coffee appeared to protect against the return of breast cancer in these women.
"Now, unlike in the previous study, we have combined information about the patients' lifestyle and clinical data from 1,090 breast cancer patients with studies on breast cancer cells," say researchers Ann Rosendahl and Helena Jernström, both of Lund University and Skåne University Hospital, also in Sweden.
After skin cancer, breast cancer is the most common cancer among women in the US, affecting around 1 in 8 women in their lifetime.
Hormone therapy is a standard treatment for patients with estrogen receptor-positive (ER+) breast cancer, most commonly administered after a patient undergoes surgery for the disease. Tamoxifen is one drug used for hormone therapy. It works by preventing estrogen from binding to breast cancer cells, which stops them growing and dividing.
Of the 1,090 women with breast cancer included in the study, around 500 were treated with tamoxifen. The women's coffee consumption was assessed and allocated to one of three categories: low consumption (less than one cup a day), moderate consumption (two to four cups and day) and high consumption (five or more cups a day).
The researchers found that among the women who were treated with tamoxifen, those who had moderate or high coffee consumption had half the likelihood of breast cancer recurrence than those who had low coffee consumption or did not drink the beverage at all.
What is more, the team found that tamoxifen-treated women who consumed at least two cups of coffee a day had smaller tumors and a lower proportion of hormone-dependent tumors than women who consumed less coffee.
Caffeine, caffeic acid 'reduces cell division and increases cell death'
Next, the researchers analyzed the effects of two substances present in coffee - caffeine and caffeic acid - on breast cancer cells.
The team found that both of these compounds - particularly caffeine - reduced cell division and increased cell death among both ER+ and estrogen receptor-negative (ER-) breast cancer cells. When tamoxifen was applied, the effect was even stronger.
"This shows that these substances have an effect on the breast cancer cells and turn off signaling pathways that the cancer cells require to grow," say Rosendahl and Jernström.
The researchers add:
"The clinical and experimental findings demonstrate various anticancer properties of caffeine and caffeic acid against both ER+ and ER- breast cancer that may sensitize tumor cells to tamoxifen and reduce breast cancer growth."
The team stresses, however, that breast cancer patients should not swap their medication for coffee. "But if you like coffee and are also taking tamoxifen," add Rosendahl and Jernström, "there is no reason to stop drinking it. Just two cups a day is sufficient to make a difference."
Last month, Medical News Today reported on a study claiming just one cup of coffee a day could significantly reduce the risk of liver cancer, while another study found consuming five cups a day could reduce the risk of heart attack.
Coffee 'could halve breast cancer recurrence' in tamoxifen-treated patients
A new study led by researchers from Lund University in Sweden claims women diagnosed with breast cancer who are taking the drug tamoxifen could halve their risk of recurrence by drinking coffee.
The findings - published in the journal Clinical Cancer Research - build on those from a previous study conducted by Lund University researchers in 2013, in which the team found a link between coffeeconsumption and reduced breast cancer recurrence in 300 women who used tamoxifen.
In that study, however, the researchers were unable to explain why coffee appeared to protect against the return of breast cancer in these women.
"Now, unlike in the previous study, we have combined information about the patients' lifestyle and clinical data from 1,090 breast cancer patients with studies on breast cancer cells," say researchers Ann Rosendahl and Helena Jernström, both of Lund University and Skåne University Hospital, also in Sweden.
After skin cancer, breast cancer is the most common cancer among women in the US, affecting around 1 in 8 women in their lifetime.
Hormone therapy is a standard treatment for patients with estrogen receptor-positive (ER+) breast cancer, most commonly administered after a patient undergoes surgery for the disease. Tamoxifen is one drug used for hormone therapy. It works by preventing estrogen from binding to breast cancer cells, which stops them growing and dividing.
Of the 1,090 women with breast cancer included in the study, around 500 were treated with tamoxifen. The women's coffee consumption was assessed and allocated to one of three categories: low consumption (less than one cup a day), moderate consumption (two to four cups and day) and high consumption (five or more cups a day).
The researchers found that among the women who were treated with tamoxifen, those who had moderate or high coffee consumption had half the likelihood of breast cancer recurrence than those who had low coffee consumption or did not drink the beverage at all.
What is more, the team found that tamoxifen-treated women who consumed at least two cups of coffee a day had smaller tumors and a lower proportion of hormone-dependent tumors than women who consumed less coffee.
Caffeine, caffeic acid 'reduces cell division and increases cell death'
Next, the researchers analyzed the effects of two substances present in coffee - caffeine and caffeic acid - on breast cancer cells.
The team found that both of these compounds - particularly caffeine - reduced cell division and increased cell death among both ER+ and estrogen receptor-negative (ER-) breast cancer cells. When tamoxifen was applied, the effect was even stronger.
"This shows that these substances have an effect on the breast cancer cells and turn off signaling pathways that the cancer cells require to grow," say Rosendahl and Jernström.
The researchers add:
"The clinical and experimental findings demonstrate various anticancer properties of caffeine and caffeic acid against both ER+ and ER- breast cancer that may sensitize tumor cells to tamoxifen and reduce breast cancer growth."
The team stresses, however, that breast cancer patients should not swap their medication for coffee. "But if you like coffee and are also taking tamoxifen," add Rosendahl and Jernström, "there is no reason to stop drinking it. Just two cups a day is sufficient to make a difference."
Last month, Medical News Today reported on a study claiming just one cup of coffee a day could significantly reduce the risk of liver cancer, while another study found consuming five cups a day could reduce the risk of heart attack.
The findings - published in the journal Clinical Cancer Research - build on those from a previous study conducted by Lund University researchers in 2013, in which the team found a link between coffeeconsumption and reduced breast cancer recurrence in 300 women who used tamoxifen.
In that study, however, the researchers were unable to explain why coffee appeared to protect against the return of breast cancer in these women.
"Now, unlike in the previous study, we have combined information about the patients' lifestyle and clinical data from 1,090 breast cancer patients with studies on breast cancer cells," say researchers Ann Rosendahl and Helena Jernström, both of Lund University and Skåne University Hospital, also in Sweden.
After skin cancer, breast cancer is the most common cancer among women in the US, affecting around 1 in 8 women in their lifetime.
Hormone therapy is a standard treatment for patients with estrogen receptor-positive (ER+) breast cancer, most commonly administered after a patient undergoes surgery for the disease. Tamoxifen is one drug used for hormone therapy. It works by preventing estrogen from binding to breast cancer cells, which stops them growing and dividing.
Of the 1,090 women with breast cancer included in the study, around 500 were treated with tamoxifen. The women's coffee consumption was assessed and allocated to one of three categories: low consumption (less than one cup a day), moderate consumption (two to four cups and day) and high consumption (five or more cups a day).
The researchers found that among the women who were treated with tamoxifen, those who had moderate or high coffee consumption had half the likelihood of breast cancer recurrence than those who had low coffee consumption or did not drink the beverage at all.
What is more, the team found that tamoxifen-treated women who consumed at least two cups of coffee a day had smaller tumors and a lower proportion of hormone-dependent tumors than women who consumed less coffee.
Caffeine, caffeic acid 'reduces cell division and increases cell death'
Next, the researchers analyzed the effects of two substances present in coffee - caffeine and caffeic acid - on breast cancer cells.
The team found that both of these compounds - particularly caffeine - reduced cell division and increased cell death among both ER+ and estrogen receptor-negative (ER-) breast cancer cells. When tamoxifen was applied, the effect was even stronger.
"This shows that these substances have an effect on the breast cancer cells and turn off signaling pathways that the cancer cells require to grow," say Rosendahl and Jernström.
The researchers add:
"The clinical and experimental findings demonstrate various anticancer properties of caffeine and caffeic acid against both ER+ and ER- breast cancer that may sensitize tumor cells to tamoxifen and reduce breast cancer growth."
The team stresses, however, that breast cancer patients should not swap their medication for coffee. "But if you like coffee and are also taking tamoxifen," add Rosendahl and Jernström, "there is no reason to stop drinking it. Just two cups a day is sufficient to make a difference."
Last month, Medical News Today reported on a study claiming just one cup of coffee a day could significantly reduce the risk of liver cancer, while another study found consuming five cups a day could reduce the risk of heart attack.
World First Remote Heart Surgery Using Robotic Arm
A pioneering world first robotics system operation is to be conducted at Glenfield Hospital Leicester thanks to expertise at the University of Leicester and University Hospitals of Leicester.
Dr André Ng, Senior Lecturer in Cardiovascular Sciences at the University of Leicester and Consultant Cardiologist and Electrophysiologist, Glenfield Hospital, University Hospitals of Leicester, is the first person in the world to carry out the operation remotely on patients using this system.
He will use the Catheter Robotics Remote Catheter Manipulation System for the first time in a heart rhythm treatment procedure.
The system is novel because it allows a doctor to carry out a common heart treatment procedure remotely using a robotic arm.
These procedures involve inserting thin wires, called catheters, into blood vessels at the top of the groin and advanced into the heart chambers. Electrodes on the catheters record and stimulate different regions of the heart to help the doctor identify the cause of the heart rhythm problem which usually involves an abnormality in the electrical wiring system of the heart. Once this area is identified, one of the catheters will be placed at the location to ablate or "burn" the tissue to cure the problem. Catheter ablation has been developed and used over the past 2 decades effectively in many patients suffering palpitations due to heart rhythm disturbances.
Dr Ng said: "The new Robotic procedure is an important step forward because, while some procedures are straightforward, others can take several hours. Because X-rays are used to allow the doctor to monitor what is going on inside the patient, it means that doctors standing close to the patient wear radiation shields such as lead aprons which are burdensome. Protracted procedures can lead to clinician fatigue and high cumulative radiation exposure.
"The benefit of the Robotics system to the patient is that movement of the catheter could be done with great precision. It is anticipated that further developments of the system may allow complex procedures to be made more streamlined. On the other hand, benefits to the doctor are that heavy lead aprons would not be necessary as he / she will be controlling the movements of the catheter using the Remote Controller at a distance from the patient outside the radiation area and that he / she can be sitting closer to the monitors displaying electrical signals and x-ray images as opposed to standing at some distance across the room from them which is current practice."
Dr Ng and his team's international standing and leading position in the management of heart rhythm disorders are reflected in the invitation to be the first to apply this new Robotics System in clinical procedures which also affirms the world-class research and pioneering work at the University of Leicester.
The Remote Catheter Manipulation System (RCMS, Catheter Robotics Inc., New Jersey) is a new system and Dr André Ng, who has extensive experience in EPS procedures, has been selected to apply the system in human studies for the first time in the world. Two other remote navigation systems are commercially available but one uses a huge magnetic field to control a magnetic tip catheter whilst the other uses a large deflectable sheath to move the catheter. The RCMS has the benefit of using standard EPS catheters which can be dismounted and remounted onto the system with ease. The technology has obtained CE mark through rigorous bench safety testing and pre-clinical studies and has now arrived at a stage where it can be applied to clinical procedures.
Dr Ng is an expert in the management of heart rhythm disturbances especially in catheter ablation and the use of mapping systems in such procedures. The Department of Cardiology at Glenfield Hospital is one of the largest Electrophysiology Centres in the UK performing over 600 EPS procedures every year. Dr Ng has a distinguished research profile in investigations into cardiac electrophysiology and arrhythmia mechanisms, leading both non-clinical and clinical teams of talented researchers. At the cutting edge of scientific research and development, the innovative work in his group has been acknowledged with many accolades including Young Investigator and Da Vinci Awards. He is also Director of pan-European training programmes on advanced three-dimensional mapping systems and arrhythmia ablation
Dr André Ng, Senior Lecturer in Cardiovascular Sciences at the University of Leicester and Consultant Cardiologist and Electrophysiologist, Glenfield Hospital, University Hospitals of Leicester, is the first person in the world to carry out the operation remotely on patients using this system.
He will use the Catheter Robotics Remote Catheter Manipulation System for the first time in a heart rhythm treatment procedure.
The system is novel because it allows a doctor to carry out a common heart treatment procedure remotely using a robotic arm.
These procedures involve inserting thin wires, called catheters, into blood vessels at the top of the groin and advanced into the heart chambers. Electrodes on the catheters record and stimulate different regions of the heart to help the doctor identify the cause of the heart rhythm problem which usually involves an abnormality in the electrical wiring system of the heart. Once this area is identified, one of the catheters will be placed at the location to ablate or "burn" the tissue to cure the problem. Catheter ablation has been developed and used over the past 2 decades effectively in many patients suffering palpitations due to heart rhythm disturbances.
Dr Ng said: "The new Robotic procedure is an important step forward because, while some procedures are straightforward, others can take several hours. Because X-rays are used to allow the doctor to monitor what is going on inside the patient, it means that doctors standing close to the patient wear radiation shields such as lead aprons which are burdensome. Protracted procedures can lead to clinician fatigue and high cumulative radiation exposure.
"The benefit of the Robotics system to the patient is that movement of the catheter could be done with great precision. It is anticipated that further developments of the system may allow complex procedures to be made more streamlined. On the other hand, benefits to the doctor are that heavy lead aprons would not be necessary as he / she will be controlling the movements of the catheter using the Remote Controller at a distance from the patient outside the radiation area and that he / she can be sitting closer to the monitors displaying electrical signals and x-ray images as opposed to standing at some distance across the room from them which is current practice."
Dr Ng and his team's international standing and leading position in the management of heart rhythm disorders are reflected in the invitation to be the first to apply this new Robotics System in clinical procedures which also affirms the world-class research and pioneering work at the University of Leicester.
The Remote Catheter Manipulation System (RCMS, Catheter Robotics Inc., New Jersey) is a new system and Dr André Ng, who has extensive experience in EPS procedures, has been selected to apply the system in human studies for the first time in the world. Two other remote navigation systems are commercially available but one uses a huge magnetic field to control a magnetic tip catheter whilst the other uses a large deflectable sheath to move the catheter. The RCMS has the benefit of using standard EPS catheters which can be dismounted and remounted onto the system with ease. The technology has obtained CE mark through rigorous bench safety testing and pre-clinical studies and has now arrived at a stage where it can be applied to clinical procedures.
Dr Ng is an expert in the management of heart rhythm disturbances especially in catheter ablation and the use of mapping systems in such procedures. The Department of Cardiology at Glenfield Hospital is one of the largest Electrophysiology Centres in the UK performing over 600 EPS procedures every year. Dr Ng has a distinguished research profile in investigations into cardiac electrophysiology and arrhythmia mechanisms, leading both non-clinical and clinical teams of talented researchers. At the cutting edge of scientific research and development, the innovative work in his group has been acknowledged with many accolades including Young Investigator and Da Vinci Awards. He is also Director of pan-European training programmes on advanced three-dimensional mapping systems and arrhythmia ablation
World First Remote Heart Surgery Using Robotic Arm
A pioneering world first robotics system operation is to be conducted at Glenfield Hospital Leicester thanks to expertise at the University of Leicester and University Hospitals of Leicester.
Dr André Ng, Senior Lecturer in Cardiovascular Sciences at the University of Leicester and Consultant Cardiologist and Electrophysiologist, Glenfield Hospital, University Hospitals of Leicester, is the first person in the world to carry out the operation remotely on patients using this system.
He will use the Catheter Robotics Remote Catheter Manipulation System for the first time in a heart rhythm treatment procedure.
The system is novel because it allows a doctor to carry out a common heart treatment procedure remotely using a robotic arm.
These procedures involve inserting thin wires, called catheters, into blood vessels at the top of the groin and advanced into the heart chambers. Electrodes on the catheters record and stimulate different regions of the heart to help the doctor identify the cause of the heart rhythm problem which usually involves an abnormality in the electrical wiring system of the heart. Once this area is identified, one of the catheters will be placed at the location to ablate or "burn" the tissue to cure the problem. Catheter ablation has been developed and used over the past 2 decades effectively in many patients suffering palpitations due to heart rhythm disturbances.
Dr Ng said: "The new Robotic procedure is an important step forward because, while some procedures are straightforward, others can take several hours. Because X-rays are used to allow the doctor to monitor what is going on inside the patient, it means that doctors standing close to the patient wear radiation shields such as lead aprons which are burdensome. Protracted procedures can lead to clinician fatigue and high cumulative radiation exposure.
"The benefit of the Robotics system to the patient is that movement of the catheter could be done with great precision. It is anticipated that further developments of the system may allow complex procedures to be made more streamlined. On the other hand, benefits to the doctor are that heavy lead aprons would not be necessary as he / she will be controlling the movements of the catheter using the Remote Controller at a distance from the patient outside the radiation area and that he / she can be sitting closer to the monitors displaying electrical signals and x-ray images as opposed to standing at some distance across the room from them which is current practice."
Dr Ng and his team's international standing and leading position in the management of heart rhythm disorders are reflected in the invitation to be the first to apply this new Robotics System in clinical procedures which also affirms the world-class research and pioneering work at the University of Leicester.
The Remote Catheter Manipulation System (RCMS, Catheter Robotics Inc., New Jersey) is a new system and Dr André Ng, who has extensive experience in EPS procedures, has been selected to apply the system in human studies for the first time in the world. Two other remote navigation systems are commercially available but one uses a huge magnetic field to control a magnetic tip catheter whilst the other uses a large deflectable sheath to move the catheter. The RCMS has the benefit of using standard EPS catheters which can be dismounted and remounted onto the system with ease. The technology has obtained CE mark through rigorous bench safety testing and pre-clinical studies and has now arrived at a stage where it can be applied to clinical procedures.
Dr Ng is an expert in the management of heart rhythm disturbances especially in catheter ablation and the use of mapping systems in such procedures. The Department of Cardiology at Glenfield Hospital is one of the largest Electrophysiology Centres in the UK performing over 600 EPS procedures every year. Dr Ng has a distinguished research profile in investigations into cardiac electrophysiology and arrhythmia mechanisms, leading both non-clinical and clinical teams of talented researchers. At the cutting edge of scientific research and development, the innovative work in his group has been acknowledged with many accolades including Young Investigator and Da Vinci Awards. He is also Director of pan-European training programmes on advanced three-dimensional mapping systems and arrhythmia ablation
Dr André Ng, Senior Lecturer in Cardiovascular Sciences at the University of Leicester and Consultant Cardiologist and Electrophysiologist, Glenfield Hospital, University Hospitals of Leicester, is the first person in the world to carry out the operation remotely on patients using this system.
He will use the Catheter Robotics Remote Catheter Manipulation System for the first time in a heart rhythm treatment procedure.
The system is novel because it allows a doctor to carry out a common heart treatment procedure remotely using a robotic arm.
These procedures involve inserting thin wires, called catheters, into blood vessels at the top of the groin and advanced into the heart chambers. Electrodes on the catheters record and stimulate different regions of the heart to help the doctor identify the cause of the heart rhythm problem which usually involves an abnormality in the electrical wiring system of the heart. Once this area is identified, one of the catheters will be placed at the location to ablate or "burn" the tissue to cure the problem. Catheter ablation has been developed and used over the past 2 decades effectively in many patients suffering palpitations due to heart rhythm disturbances.
Dr Ng said: "The new Robotic procedure is an important step forward because, while some procedures are straightforward, others can take several hours. Because X-rays are used to allow the doctor to monitor what is going on inside the patient, it means that doctors standing close to the patient wear radiation shields such as lead aprons which are burdensome. Protracted procedures can lead to clinician fatigue and high cumulative radiation exposure.
"The benefit of the Robotics system to the patient is that movement of the catheter could be done with great precision. It is anticipated that further developments of the system may allow complex procedures to be made more streamlined. On the other hand, benefits to the doctor are that heavy lead aprons would not be necessary as he / she will be controlling the movements of the catheter using the Remote Controller at a distance from the patient outside the radiation area and that he / she can be sitting closer to the monitors displaying electrical signals and x-ray images as opposed to standing at some distance across the room from them which is current practice."
Dr Ng and his team's international standing and leading position in the management of heart rhythm disorders are reflected in the invitation to be the first to apply this new Robotics System in clinical procedures which also affirms the world-class research and pioneering work at the University of Leicester.
The Remote Catheter Manipulation System (RCMS, Catheter Robotics Inc., New Jersey) is a new system and Dr André Ng, who has extensive experience in EPS procedures, has been selected to apply the system in human studies for the first time in the world. Two other remote navigation systems are commercially available but one uses a huge magnetic field to control a magnetic tip catheter whilst the other uses a large deflectable sheath to move the catheter. The RCMS has the benefit of using standard EPS catheters which can be dismounted and remounted onto the system with ease. The technology has obtained CE mark through rigorous bench safety testing and pre-clinical studies and has now arrived at a stage where it can be applied to clinical procedures.
Dr Ng is an expert in the management of heart rhythm disturbances especially in catheter ablation and the use of mapping systems in such procedures. The Department of Cardiology at Glenfield Hospital is one of the largest Electrophysiology Centres in the UK performing over 600 EPS procedures every year. Dr Ng has a distinguished research profile in investigations into cardiac electrophysiology and arrhythmia mechanisms, leading both non-clinical and clinical teams of talented researchers. At the cutting edge of scientific research and development, the innovative work in his group has been acknowledged with many accolades including Young Investigator and Da Vinci Awards. He is also Director of pan-European training programmes on advanced three-dimensional mapping systems and arrhythmia ablation
Robots taking over to help medical research
It has been a long and stealthy takeover, but robots now dominate many leading bioscience laboratories, doing in just hours what once took days or weeks. Now the convergence of automation with nanotechnologies, biomedics and advanced algorithms promises to take robotization of medical research much further.
In May of this year, Ross King, professor of machine intelligence at the UK's University of Manchester, traveled east to talk to students at the University of Nottingham campus in Ningbo, China. His paper "Robot scientists: Automating biology and chemistry" was a vindication of theories he and colleagues first proposed almost a decade ago.
In a 2004 letter to the journal Nature, they asked whether it might be possible to automate the actual "discovery" process of observation, deduction and conclusion. This would use a physically implemented robotic system that applied techniques from artificial intelligence (AI) to carry out cycles of scientific experimentation.
Meet Adam and Eve, robot scientists
In China, as he had earlier at Brunel University in London, Prof. King named the two "robot scientists" Adam and Eve, constructed at the University of Aberystwyth in Wales. These robots form hypotheses, select efficient experiments to discriminate between them, execute the experiments using laboratory automation equipment, and then analyze the results.
Both Adam and Eve have made actual discoveries.
Adam was developed to investigate the functional genomics of yeast (Saccharomyces cerevisiae) and the robot succeeded in autonomously identifying the genes that encode locally "orphan" enzymes in yeast.
Prof. Ross King at the controls for Adam the robot, Aberystwyth University
In biblical fashion, Adam was followed by Eve using similar techniques to create a machine tasked toward automation and integration of drug discovery: screening, hit conformation, and quantitative structure-activity relationship (QSAR) development. Eve uses novel synthetic biology screens that combine the advantages of computational, target-based, and cell-based assays.
Prof. Ross King says:
"Our focus has been on neglected tropical disease, and using Eve, we have discovered lead compounds for malaria, Chagas, African sleeping sickness and other conditions."
Humble origins
Analytical robots like Adam, Eve or the more advanced products now being developed at centers of excellence - such as at the Fraunhofer Institute for Factory Operation and Automation (IFF) in Magdeburg, Germany - are a far cry from the robotic systems that first entered the lab some three decades ago.
The history of a leading company in the field - Hamilton Robotics - demonstrates the progression:
From precision syringes in the 1940s
Through the first semi-automated diluter in 1970
To the first fully automated workstation for sample preparation in 1980.
Such workstations, which mechanically handle samples under full computer control, meet the core dictionary definition of a robot as "a machine capable of carrying out a complex series of actions automatically." Their actual mechanical or physical "work" component also satisfies Karel Čapek's original "forced labor" definition in his 1920 playR.U.R.. This is the play that introduced the word "robot" to the world.
Robots at work
Liquid handling is one of the four core applications for robotics in the laboratory. The others are:
Microplate handling: using robots to move plates around a workcell, between stacks and other devices (liquid handlers, readers, incubators, and so on). Advanced microplate robots integrate with third-party instruments to create work cells that automate applications and protocols to almost any level of complexity.
Automated biological research systems: robots provide automated handling and reading for various aspects of biological and biochemical research, ranging from flow cytometers to specific molecular biology applications such as PCR preparation and purification, colony picking or cell culture development.
Drug discovery screening: the most recent mainstream robotics application allows researchers to run a wide range of cell-based, receptor-based and enzyme-based assays typically used in high throughput screening (HTS).
Do robots offer an advantage?
The laboratory advantages of using robotics seem obvious, starting with the ergonomic benefits of automating tasks that would be tedious, repetitive, injurious or even hazardous for a human.
A robot makes no distinction between the backbreaking low rack a few centimeters off the floor and the one up high, for which a human would need to stand on a chair. Robots can also safely handle toxins, biohazards or operate in sealed or climate-controlled areas that we would find unbearable.
Laboratories originally embraced robotics because it seemed to offer an escape from the "quantity or quality" dilemma - the constant need to trade off speed for accuracy.
By contrast, it seemed robots could perform infinitely repeated operations to a supreme degree of precision that never varied and was infinitely controllable.
However, in practice, and particularly with high throughput screening, some limitations began to emerge. These included:
Long design and implementation time
Protracted transfer from manual to automated methods
Unstable robotic operation, and
Limited error recovery abilities.
Furthermore, the need to reduce steps in robotic processes tended to encourage the use of less accurate homogenous assays over the heterogenous ones that most companies would prefer.
Scaling up
Early 21st century adoption of Allegro and other technologies based on assembly-line techniques overcame many of these problems by passing microplates down a line to consecutive processing modules, each performing just one step of the assay. Speed could be multiplied into the process by making each step bigger, with the 96-well microplate giving way to 384 and now 1,536-well plates.
The new capability of robots to screen such enormous plates unsupervised paved the way for the quantitative high-throughput screening (qHTS) paradigm that can test each library compound at multiple concentrations.
Maximum efficiency and miniaturization gave qHTS the theoretical capacity to carry out cell-based and biochemical assays across libraries of more than 100,000 compounds, testing between 700,000 and 2 million sample wells within a few hours.
However, few companies actually need to screen that many compounds in-house each day, with the associated costs of consumables such as assay reagents, cell cultures, microplates, and pipet tips, as well as the cost of data handling and analysis time.
When you add in the investment overheads for associated infrastructure, robotics can seem like a rich kid's toy.
Robots for hire
During the first decade of the 21st century, growing numbers of contract companies doing high-throughput screening (HTS) offered assay development and screening, data analysis, and other library support.
The use of such contract robotics labs became a lot more popular after they stopped demanding royalty payments on any discovery. Such labs trade on the ability to offer ultra-fast turnaround times, running 24/7 on high-capacity HTS robotic workstations.
Some pharma and biotech companies began to outsource primary screening, keeping the higher-value, more proprietary secondary screening in-house, to enable higher hit rates for their teams. However, even these approaches are becoming redundant with new technology.
Rifle versus shotgun approach
Essentially, high-throughput screening is the shotgun approach to research - using robotics to throw many thousands of chemical compounds against a target pathogen to see if its cell growth accelerates, stops, or is eliminated. The capacity is awesome, but the costs are high and the unit-to-success ratio is low.
A more sophisticated robotics-enabled paradigm is high-content screening (HCS) - a "rifle" approach that applies molecular specificity based on fluorescence and takes advantage of more sophisticated reagent classes.
High-content screening has the ability to multiplex, along with image analysis coupled to data management, data mining, and data visualization. All these help researchers focus on biological and genomic information and make far more targeted decisions on which assays to run.
Latest technology takes this targeting still further. Hudson Robotics recently announced what it terms high-efficiency screening (HES) for small molecules and antibodies.
High-efficiency screening uses a proprietary algorithm to compile a shortlist of library samples that will be screened. This is then passed on to a robotic workstation where the molecules are cherry-picked and screened in the appropriate assay.
Any molecules found to be active are used to enhance the model and the process is repeated until the user has both a list of active molecules, as well as the final model that can be used to search additional compound collections and guide synthesis of optimized analogs.
In preliminary testing against known compound databases, Hudson says its high-efficiency screening consistently identified the majority of known inhibitors of ten different biological targets after screening under 10% of a library containing some 80,000 diverse molecules.
Future robot trends
Three decades in from the first laboratory use of robotics, it seems clear that the technology is still in its infancy. Robots may seem pervasive in today's biomedical research, but they have a long way to evolve.
For one thing, robots cannot easily coexist with humans, needing to work in safely enclosed areas. The Fraunhofer Institute has been studying this aspect and developed LISA, a prototype mobile lab assistant with touch sensitive "skin" and heat sensors to stop her bumping into humans and vice versa.
Meet LISA. She's the one on the left...
But even LISA is likely to look as clunky as the Wright Flyer once biomedics, 3D printing and nanotechnologies really come into play. A glimpse of the possibilities is offered by the robotic inchworm pioneered by Columbia University.
Biobots like these, or the DNA spiders developed at New York University and the University of Michigan are little more than fascinating, if rather scary, toys at the moment. But they point to a future where robotics moves beyond the research lab into the operating room - or even down into the molecular realm.
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