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

The PhoneBrasil Group is set to unveil its new Smartphone concept, The Glass

The PhoneBrasil Group is set to unveil its new Smartphone concept, The Glass

The PhoneBrasil Group is set to unveil its new Smartphone concept, The Glass

The PhoneBrasil Group is set to unveil its new Smartphone concept, The Glass

Humanitarian Organization Utilizes Jacada Visual IVR to Enhance Nepal Disaster Relief Donations

Humanitarian Organization Utilizes Jacada Visual IVR to Enhance Nepal Disaster Relief Donations

Humanitarian Organization Utilizes Jacada Visual IVR to Enhance Nepal Disaster Relief Donations

Humanitarian Organization Utilizes Jacada Visual IVR to Enhance Nepal Disaster Relief Donations

The Cigna Foundation to be Honored by Arogya World

The Cigna Foundation to be Honored by Arogya World

The Cigna Foundation to be Honored by Arogya World

The Cigna Foundation to be Honored by Arogya World

FedEx Pledges $1 Million in Aid to Support Relief of Nepal Earthquake Disaster

FedEx Pledges $1 Million in Aid to Support Relief of Nepal Earthquake Disaster

FedEx Pledges $1 Million in Aid to Support Relief of Nepal Earthquake Disaster

FedEx Pledges $1 Million in Aid to Support Relief of Nepal Earthquake Disaster

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.