News 15 juni 2009
Low-fat diet helps genetically
predisposed animals avoid liver cancer
In a study comparing two strains of mice, one susceptible to developing cancer and the
other not, researchers found that a high-fat diet predisposed the cancer-susceptible
strain to liver cancer, and that by switching to a low-fat diet early in the experiment,
the same high-risk mice avoided the malignancy. The switched mice were lean rather than
obese and had healthy livers at the end of the study. The findings, from a joint
University of Pennsylvania School of Medicine and Case Western Reserve University study,
appear online this month in Human Molecular Genetics. The investigators studied
hepatocellular carcinoma (HCC), a type of liver cancer that is one of the leading causes
of cancer death worldwide. Thirty percent of cases of this type of liver cancer are
associated with obesity, type 2 diabetes, and related metabolic diseases, although a
direct link between these and liver cell cancer has not been completely established.
"The connection between obesity and cancer is not well understood at this
point," says senior co-author John Lambris, PhD, the Dr. Ralph and Sallie Weaver
Professor of Research Medicine at Penn. The researchers hope the results will lead to the
development of blood tests that can detect precancerous conditions related to diet. The
remaining seventy percent of HCC cases result from hepatitis B and C viral infections,
exposure to the fungal toxin aflatoxin, chronic alcohol use, or genetic liver diseases.
The usual outcome of hepatocellular carcinoma is poor, because only 10 to 20 percent of
these tumors can be surgically removed. If the cancer cannot be completely removed, the
disease is usually deadly within 3 to 6 months. Hepatocellular carcinoma causes close to
700,000 deaths worldwide per year, mostly outside the US. The researchers tested the
long-term effects of high-fat and low-fat diets on males of two inbred strains of mice and
discovered that one strain, named C57BL/6J, was susceptible to non-alcoholic
steatohepatitis (NASH) and hepatocellular carcinoma on a high-fat, but not a low-fat diet.
The other strain, called A/J, was not susceptible to disease on a high-fat diet. The mice
were fed their respective diets for close to 500 days, weighed periodically, and then
analyzed for the presence of disease.
Jumping genes discovery 'challenges
current assumptions'
Jumping genes do most of their jumping, not during the development of sperm and egg cells,
but during the development of the embryo itself. The research, published this month in
Genes and Development, "challenges standard assumptions on the timing of when mobile
DNA, so-called jumping genes, insert into the human genome," says senior author Haig
H. Kazazian Jr., MD, Seymour Gray Professor of Molecular Medicine in Genetics at the
University of Pennsylvania School of Medicine. Jumping genes – also called
transposons – are sequences of DNA that can move or jump to different areas of the
genome within the same cell. Jumping gene insertions do cause disease; however, it's not
known how frequently diseases due to insertions can be inherited in the next generation.
They are a rare cause of several genetic diseases, such as hemophilia and Duchenne
muscular dystrophy. In addition, transposon insertion into the genome could play a role in
the development of cancer. The current work alters thinking in the field of jumping genes,
challenging standard assumptions that mobile DNA inserts only in eggs and sperm during
their respective early development. In this study, the researchers found that insertions
took place during embryogenesis after fertilization, at a time when nearly all of the
changes can't be inherited. The researchers now purport, based on the study's findings,
that many of those insertions occur in the early embryo, perhaps in the 4- or 8-cell
stage. The study looked at retrotransposons, one class of jumping genes, with the L1
family the most abundant type of retrotransposon in the human genome. Retrotransposons
move by having their DNA sequence transcribed or copied to RNA, and then instead of the
genetic code being translated directly into a protein sequence, the RNA is copied back to
DNA by the retrotransposon's own enzyme called reverse transcriptase. This new DNA is then
inserted back into the genome. The process of copying is similar to that of retroviruses,
such as HIV, leading scientists to speculate that retroviruses were derived from
retrotransposons. The L1 family of retrotransposons comprises about 17 percent of the
human genome. Eventually, continuous jumping by retrotransposons expands the size of the
human genome and may cause shuffling of genome content. For example, when retrotransposons
jump, they may take portions of nearby gene sequences with them, inserting these where
they land, and thereby allowing for the creation of new genes. Even otherwise unremarkable
insertions of L1 may cause significant effects on nearby genes, such as lowering their
expression.
Waste disposal protein is mechanism
behind cancer tumor suppression
"Taking out the trash" takes on a whole new meaning, as investigators at The
Cancer Institute of New Jersey (CINJ) and Rutgers, The State University of New Jersey,
have discovered that a waste disposal protein is the key to cancer tumor suppression in a
process known as autophagy. CINJ is a Center of Excellence of UMDNJ-Robert Wood Johnson
Medical School. Autophagy is a process in which cancer cells eat themselves. Previous
study from the lab of Eileen White, PhD, associate director for basic science at CINJ, and
a number of other groups has shown that autophagy is a pathway to cancer tumor
suppression, but scientists did not know the mechanism behind it, until now. The latest
research, which appears in this week's print and online editions of Cell, focuses on a
protein known as p62. This protein is responsible for disposing of damaged proteins that
accumulate in a cell when it is no longer receiving nourishment for growth and is under
other environmental stress. In order for cells to prevent themselves from becoming a
cancer tumor, they need to rid themselves of this waste. The p62 protein packages the
damaged materials and prepares these materials, along with itself, to be degraded through
the autophagy process. Disruption in the process or failure to dispose of p62 from the
cell can result in toxicity, genome damage and inflammation, which in turn can promote
tumor progression. Dr. White, who is an adjunct professor of surgery at UMDNJ-Robert Wood
Johnson Medical School, and a professor of molecular biology and biochemistry at Rutgers
University, is the senior author of the research publication. She notes this is the first
time the disposal of p62 has been linked with tumor suppression, which can be key in
cancer prevention. "This discovery is important, because we now have an opportunity
to look at people at risk for cancer before it develops," she notes. "These
latest findings show that p62 can act as a marker to identify certain cancers and that we
can manipulate p62 levels to stimulate the process of autophagy and ultimately tumor
suppression."
Researcher explores why smoking
increases the risk of heart disease and strokes
Researchers at Charles Drew University of Medicine and Science in Los Angeles and Western
University of Health Sciences in Pomona have discovered a reason why smoking increases the
risk of heart disease and strokes. The study, which will be presented Thursday, June 11 at
The Endocrine Society's 91st annual meeting in Washington, D.C., found that nicotine in
cigarettes promotes insulin resistance, a pre-diabetic condition that raises blood sugar
levels higher than normal. People with pre-diabetes are at greater risk of developing
cardiovascular disease. Theodore Friedman, MD, Ph.D., chief of the endocrinology division
at Charles Drew University, said the findings help explain a "paradox" that
links smoking to heart disease. Smokers experience a high degree of cardiovascular deaths,
Friedman said. "This is surprising considering both smoking and nicotine may cause
weight loss and weight loss should protect against cardiovascular disease." The
researchers studied the effects of twice-daily injections of nicotine on 24 adult mice
over two weeks. The nicotine-injected mice ate less food, lost weight and had less fat
than control mice that received injections without nicotine ."Our results in mice
show that nicotine administration leads to both weight loss and decreased food
intake," Friedman said. "Mice exposed to nicotine have less fat. In spite of
this, mice have abnormal glucose tolerance and are insulin resistant (pre-diabetes)."
If You Do Good, You Look Good
In today's economy, it's increasingly difficult to elicit donations for charitable causes
— but new research from Dr. Anat Bracha of the Eitan Berglas School of Economics at
Tel Aviv University can provide fundraising organizations with a potent tool. A powerful
spur to giving, Dr. Bracha's research demonstrates, is "image motivation," the
positive recognition a giver gets from other members of the community. Her study,
published in American Economic Review, can help organizations understand how to elicit
maximum donor response in today's tough times.
Wii-hab may enhance Parkinson's
treatment
The Nintendo Wii may help treat symptoms of Parkinson's disease, including depression, a
Medical College of Georgia researcher says. Parkinson’s disease is a degenerative
disease that impairs motor skills. Dr. Herz theorized that the popular computer game
console, which simulates various sports and activities, could improve coordination,
reflexes and other movement-related skills, but he found additional benefits as well.
"The Wii allows patients to work in a virtual environment that's safe, fun and
motivational," says Dr. Ben Herz, program director and assistant professor in the
School of Allied Health Sciences Department of Occupational Therapy. "The games
require visual perception, eye-hand coordination, figure-ground relationships and
sequenced movement, so it's a huge treatment tool from an occupational therapy
perspective."
New images may improve vaccine
design for deadly rotavirus
Howard Hughes Medical Institute researchers are reporting the first detailed molecular
snapshots of a deadly gastrointestinal virus as it is caught in the grasp of an immune
system molecule with the capacity to destroy it. The images could help scientists design a
more effective vaccine against rotavirus, a lethal infection that kills more than 500,000
children worldwide each year. The discovery is timely. Last week the World Health
Organization recommended that rotavirus vaccination be included in all national
immunization programs worldwide. Virtually every child in the world becomes infected with
rotaviruses before developing natural immunity. But each year an estimated two million
children are hospitalized because rotavirus infection results in severe dehydration caused
by diarrhea and vomiting. Both natural and vaccine-induced immunity occur only after the
immune system has "seen" the virus and generates neutralizing antibodies. These
soldiers of the immune system seek out and attach to rotavirus particles, rendering them
unable to infect cells. In the new experiments, Howard Hughes Medical Institute (HHMI)
researchers have mapped the structure of an antiviral antibody clamped onto a protein
called VP7 that stipples the surface of rotavirus. The structural map reveals intimate new
details about how the antibody interferes with VP7, a protein that helps the virus infect
cells. The information may be useful in designing a new generation of rotavirus vaccines
that could be easier to store and administer than current vaccines, said the researchers.
HHMI investigator Stephen C. Harrison and colleagues at Children's Hospital Boston and
Harvard University published their findings in the June 12, 2009, issue of the journal
Science.
Researchers at Case Western Reserve
discover a new way the body fights fungal infection
A team of researchers led by Amy G. Hise, M.D., M.P.H., assistant professor at the Center
for Global Health and Diseases, Case Western Reserve University School of Medicine, is the
first to discover how the body fights off oral yeast infections caused by the most common
human fungal pathogen, Candida. As fungal infections become more resistant to current
drugs, this groundbreaking research may directly lead to the development of new drugs and
therapies that will help limit and/or prevent Candida infections in the future for
millions of sufferers. Candida albicans is the most common species of the Candida fungus
and is the leading cause of vaginal and oral yeast infections, including thrush and
denture stomatitis. It is the fourth most common hospital acquired bloodborne pathogen in
the United States and surprisingly, it is present in the mouths of 30 to 50 percent of
healthy adults. Because of the widespread nature of Candida, the potential for overgrowth
and infection is common in the young, elderly, immuno-compromised and people receiving
corticosteroid or chemotherapy treatments.
Diagnosis of arthritis 5 years
earlier in childless women compared to those with children
Nulliparous women (those who have not given birth to children) are diagnosed with chronic
arthritides (including ankylosing spondylitis, psoriatic arthritis and rheumatoid
arthritis (RA) an average of 5.2 years before parous women (those who have given birth to
children), according to a new study presented today at EULAR 2009, the Annual Congress of
the European League Against Rheumatism in Copenhagen, Denmark. Previous studies have
highlighted that pregnancy may be a protective factor against the development of RA,
whereas this is the first study to assess the effect of pregnancy and having children on
the development of chronic arthritic conditions in premenopausal women. Within the study,
the mean age at time of diagnosis for nulliparous women was 26 years, compared with 31.2
years for parous women (p< 0.001). Rheumatoid factor (an autoantibody sometimes found
in the immune systems of people with RA) was also present in 37.1% of the nulliparous
women compared with 41.1% of the parous women (p=0.21), which, although not statistically
significant, may indicate that the parous women studied may possess a higher disposition
to developing arthritis than the nulliparous women. Dr Marianne Wallenius, of the
Norwegian University of Science and Technology, Norway, who led the study, said:
"Arthritic conditions tend to occur more commonly in women, particularly those of
childbearing age. Some symptoms of RA, for example, can improve during pregnancy, but our
study indicates that the processes of pregnancy and childbearing could delay the onset of
arthritic conditions. Continued examination of the complex interactions between the female
reproductive processes and the epidemiology of RA could yield further interesting
insights." The retrospective study analysed 557 women aged 18-45 years from the
Norwegian Disease Modifying Antirheumatic Drug (NOR-DMARD) study, who were all diagnosed
with chronic arthritides before the age of 45 years. Information about parous status was
confirmed through linking the NOR-DMARD patient cohort with the Medical Birth Registry of
Norway (MBRN).
What are the risk factors of
sporadic colorectal cancer?
Colorectal cancer (CRC) is one of the most common cancers in China. Although the
association between the epidemiological factors and sporadic colorectal cancer has been
studied, the relation between smoking, alcohol drinking, family history of cancer, body
mass index (BMI) and sporadic colorectal cancer still remains uncertain. So it is
important to investigate the role of these factors in the development of sporadic
colorectal cancer. A research team led by Professor Jian-Ping Wang from the
Gastrointestinal Institute of Sun Yat-Sen University addressed this question. Their study
will be published on May 28, 2009 in the World Journal of Gastroenterology They conducted
a hospital-based case-control study from July 2002 to December 2008 in Guangzhou city.
There were 706 cases and 723 controls with their sex and age (within 5 years) matched. An
unconditional logistic regression model was used to analyze the association between
smoking, alcohol drinking, family history of cancer, BMI and sporadic colorectal cancer.
They found that current alcohol drinking and greater BMI (? 24.0 kg/m2) are the
independent risk factors for colon and rectal cancer, while former alcohol drinking and
positive family history of cancer are the independent risk factors for colon cancer in
southern Chinese. Their findings may contribute to the prevention and control of sporadic
colorectal cancer. However, because of the uncontrolled bias in selection participants and
retrospective design, their findings need to be further evaluated in well-designed larger
epidemiological studies with different ethnic populations.
A breakthrough in gastric
carcinogenesis
Checkpoint with forkhead and ring finger (CHFR) is a mitotic stress checkpoint gene whose
promoter is frequently methylated in various kinds of cancer. In gastric cancer, CHFR
promoter hypermethylation has been reported to lead to chromosome instability (CIN) and
genetic instability is one of the hallmarks of human cancer. A research team led by Dr
Eiji Oki from Kyushu University examined the methylation status of the promoter region of
CHFR and microsatellite instability (MIN) status in primary gastric cancers. Their study
will be published on May 28, 2009 in the World Journal of Gastroenterology They
investigated the promoter methylation of CHFR in 59 cases of gastric cancer using
methylation-specific PCR. Five microsatellite loci were analyzed using high-intensity
microsatellite analysis reported previously, and p53 gene mutations were investigated by
direct sequencing. They found that twenty cases (33.9%) showed promoter methylation and no
relation was observed with the clinicopathological factors. The promoter methylation of
CHFR was frequently accompanied with MIN. Seven of 20 (35.0%) cases showed MIN in
hypermethylation of the CHFR tumor, while three of 39 (7.7%) cases showed MIN in the
non-methylated CHFR tumor (P < 0.01). However, they failed to find any relationship
between CHFR methylation and p53 mutation status. In conclusion, they demonstrated a
correlation between the hypermethylation of CHFR and the MIN of gastric cancer patients.
Both MIN and CHFR hypermethylation induce mitotic check point disruption and confer a
survival advantage to the cells, however, this survival advantage does not lead to either
p53 mutation or CIN in gastric cancer. This is the first study to show the striking
relationship between CHFR silencing and microsatellite alteration in gastric cancer.
What is the relationship between
hepatocellular carcinoma and type 2 diabetes mellitus?
Hepatocellular carcinoma (HCC) is the fifth most common malignancy worldwide and the third
leading cause of cancer-related deaths. Type 2 diabetes mellitus has been associated with
HCC. However, the relationship between type 2 diabetes mellitus and the underlying liver
cirrhosis, and the effects of antidiabetic therapy on HCC risk have not yet been fully
evaluated. A research team led by Dr. Valter Donadon from Pordenone Hospital addressed
this question. Their study will be published on May 28, 2009 in the World Journal of
Gastroenterology. Four hundred and sixty five HCC patients, 618 cirrhosis patients and 490
control subjects were enrolled in this study. They evaluated the odds ratio (OR) for HCC
by univariate and multivariate analysis. Moreover, OR for HCC in diabetic subjects treated
with insulin or sulphanylureas and with metformin were calculated. The prevalence of
diabetes mellitus was 31.2% in HCC, 23.3% in cirrhotic patients and 12.7% in the Control
group. By univariate and multivariate analysis, the OR for HCC in diabetic patients were
respectively 3.12 (95%CI: 2.2-4.4, P < 0.001) and 2.2 (95%CI: 1.2-4.4, P = 0.01). In
84.9% of cases, type 2 diabetes mellitus was present before the diagnosis of HCC.
Moreover, we report an OR for HCC of 2.99 (95%CI: 1.34-6.65, P = 0.007) in diabetic
patients treated with insulin or sulphanylureas, and an OR of 0.33 (CI 0.1-0.7, P = 0.006)
in diabetic patients treated with metformin. This study demonstrates that type 2 diabetes
mellitus is an independent risk factor for HCC and pre-exists in the majority of HCC
patients. In male HCC, patients with type 2 diabetes mellitus, their data shows a direct
association of HCC risk with insulin and sulphanylureas treatment and an inverse
relationship with metformin therapy.
A new 'idol' grabs the spotlight
Low-density lipoprotein (LDL) is the so-called "bad cholesterol" often linked to
medical problems like heart disease and clogged arteries. Cells in the liver produce a
specific receptor that sticks to LDL and removes it from the blood, lowering cholesterol
levels. Statin drugs also reduce LDL cholesterol levels by boosting cells' production of
the receptor. FINDINGS - Using a mouse model, UCLA scientists discovered a new mechanism
that controls cells' production of LDL receptor. The team identified an enzyme called Idol
that destroys the receptor, permitting more LDL cholesterol to circulate in the blood. In
blocking Idol's activity, the researchers triggered cells to make more receptor and absorb
more cholesterol from the body. "We only know of three pathways that regulate the LDL
receptor. The first two are already targeted by existing drugs," explained Dr. Peter
Tontonoz, professor of pathology and laboratory medicine at the David Geffen School of
Medicine at UCLA and an investigator at the Howard Hughes Medical Institute. "Idol is
the first mechanism discovered in several years that may lead to a new medication designed
to control cholesterol levels."
Adults, especially women, have
calorie-burning 'brown fat'
Keeping your baby fat turns out to be a good thing, as long as it is "brown fat"—the
kind that burns calories, according to a study that found adults have much more of this
type of fat than previously thought. The results, which suggest a new way to treat
obesity, were presented at The Endocrine Society's 91st Annual Meeting in Washington, D.C.
Brown fat burns off calories and generates heat in babies and small mammals. Most of our
body fat is white fat, which also provides insulation but stores calories. It becomes
"bad" fat when you have too much. The "good" fat—brown fat—was
considered essentially nonexistent in human adults. "We now know that it is present
and functional in adults," said the study's lead author, Aaron Cypess, MD, PhD, MMSc,
of the Joslin Diabetes Center in Boston. "Three ounces of brown fat can burn several
hundred calories a day." For the first time, the researchers were able to measure
patches of brown adipose tissue—brown fat—in people, thanks to a high-tech
imaging method that combines positron emission tomography and computed tomography, called
PET/CT. By evaluating biopsy tissue of what appeared to be brown fat on PET/CT scans in
some patients who had neck surgery, the authors confirmed that they were, indeed, looking
at stores of brown fat. More than 1,970 study participants had PET/CT scans, from
mid-skull to mid-thigh.
Successful weight loss with dieting
is linked to vitamin D levels
Vitamin D levels in the body at the start of a low-calorie diet predict weight loss
success, a new study found. The results, which suggest a possible role for vitamin D in
weight loss, were presented at The Endocrine Society's 91st Annual Meeting in Washington,
D.C. "Vitamin D deficiency is associated with obesity, but it is not clear if
inadequate vitamin D causes obesity or the other way around," said the study's lead
author, Shalamar Sibley, MD, MPH, an assistant professor of medicine at the University of
Minnesota. In this study, the authors attempted to determine whether baseline vitamin D
levels before calorie restriction affect subsequent weight loss. They measured circulating
blood levels of vitamin D in 38 overweight men and women before and after the subjects
followed a diet plan for 11 weeks consisting of 750 calories a day fewer than their
estimated total needs. Subjects also had their fat distribution measured with DXA (bone
densitometry) scans. On average, subjects had vitamin D levels that many experts would
consider to be in the insufficient range, according to Sibley. However, the authors found
that baseline, or pre-diet, vitamin D levels predicted weight loss in a linear
relationship. For every increase of 1 ng/mL in level of 25-hydroxycholecalciferol—the
precursor form of vitamin D and a commonly used indicator of vitamin D status—subjects
ended up losing almost a half pound (0.196 kg) more on their calorie-restricted diet. For
each 1-ng/mL increase in the active or "hormonal" form of vitamin D
(1,25-dihydroxycholecalciferol), subjects lost nearly one-quarter pound (0.107 kg) more.
Additionally, higher baseline vitamin D levels (both the precursor and active forms)
predicted greater loss of abdominal fat. "Our results suggest the possibility that
the addition of vitamin D to a reduced-calorie diet will lead to better weight loss,"
Sibley said.
Symptoms of depression in obese
children linked to elevated cortisol
A new study connects abnormalities of the "stress" hormone cortisol with
symptoms of depression in obese children, and confirms that obesity and depression often
occur together, even in children. The results were presented at The Endocrine Society's
91st Annual Meeting in Washington, D.C. "There is evidence in adults that abnormal
regulation of cortisol plays a role in both obesity and depression," said the study's
lead author, Panagiota Pervanidou, MD, of Athens University Medical School in Athens,
Greece. "Our study indicates that cortisol abnormalities may underlie obesity and
depression starting in childhood." Cortisol is a steroid hormone that helps the body
respond to stress but also has other functions, including converting fat, protein and
carbohydrates into energy. Normally, levels of this hormone peak in the early morning,
start to drop in late morning and reach their low point at night. However, depressed
adults have slightly elevated cortisol levels at night—"the endocrine equivalent
of chronic stress," Pervanidou said. This chronic elevation of cortisol contributes
to development of the metabolic syndrome, which includes abdominal obesity and other risk
factors for diabetes and cardiovascular disease. In this new study, Pervanidou and
colleagues measured cortisol five times a day in the saliva of 50 obese children and
teenagers as well as in their blood in the morning. The 20 boys and 30 girls, ages 8 to 15
years, were patients in the Athens University pediatric obesity clinic and did not have a
prior diagnosis of depression. All subjects completed the Children's Depression Inventory
(CDI), a questionnaire that assesses self-reported symptoms of depression.
Nicotine induces prediabetes,
likely contributes to high prevalence of heart disease in smokers
Researchers have discovered a reason why smoking greatly increases the risk of heart
disease and stroke. Nicotine promotes insulin resistance, also called prediabetes, which
is a risk factor for cardiovascular disease, according to the new study, which was
presented at The Endocrine Society's 91st Annual Meeting in Washington, D.C. Additionally,
the study authors were able to partially reverse this harmful effect of nicotine in mice
by treating them with the nicotine antagonist mecamylamine, a drug that blunts the action
of nicotine. The study, which the National Institutes of Health funded, was conducted by
researchers at Charles Drew University of Medicine and Science in Los Angeles and Western
University of Health Sciences in Pomona, Calif. Their results may explain why cigarette
smokers have a high cardiovascular death rate, even though "smoking causes weight
loss, which should protect against heart disease," said the study's lead author,
Theodore Friedman, MD, PhD, chief of the endocrinology division at Charles Drew
University. Prediabetes and diabetes are known risk factors for cardiovascular disease.
Past studies show that cigarette smokers tend to be insulin resistant, meaning that their
hormone insulin does not work properly. To compensate, their blood glucose (sugar) levels
become higher than normal but not yet high enough for diabetes. Smokers also have higher
rates of diabetes, but it is not clear whether smoking is the cause, because they could
have other risk factors, Friedman explained. Some studies demonstrate that nicotine and
cigarette smoking induce high levels of the stress hormone cortisol. "As cortisol
excess is known to induce insulin resistance, it has been suggested that glucocorticoids,
such as cortisol, are the missing [causative] link between cigarette smoking and insulin
resistance," Friedman said. The new study results suggest this theory is correct, he
said. The researchers studied the effects, on 24 adult mice, of twice-daily injections of
nicotine for 2 weeks. The mice ate less food than control mice that received injections
without nicotine, and they also lost weight and had less fat. Despite this, the mice
receiving nicotine developed prediabetes (insulin resistance), which subsequent
mecamylamine treatment improved somewhat. These mice also had high cortisol levels in
their blood and tissues, and mecamylamine blocked this effect.
Moderately reduced carbohydrate
diet keeps people feeling full longer
A modest reduction in the amount of carbohydrates eaten, without calorie restriction and
weight loss, appears to increase a sense of fullness, which may help people eat less, a
preliminary study found. The results were presented at The Endocrine Society's 91st Annual
Meeting in Washington, D.C. "There has been great public interest in low-carbohydrate
diets for weight loss, but they are difficult to maintain, in part because of the drastic
reduction in carbohydrates," said coauthor Barbara Gower, PhD, a professor in the
Department of Nutrition Sciences, University of Alabama at Birmingham. In this study
funded by the National Institutes of Health, Gower and her co-workers investigated whether
a modest reduction in dietary carbohydrates, or "carbs," would improve feelings
of fullness better than a carbohydrate level comparable to that of the typical U.S. diet.
In a standard American diet, according to Gower, 55 percent of daily calories consumed
come from carbohydrates: sugars, starches and fiber. The control diet used in their study
contained 55 percent of daily calories from carbohydrates, in contrast to their
"moderate-carb diet" which was 43 percent of calories from carbohydrates. The
moderate-carb diet had more fat than their control diet—39 percent versus 27 percent
of calories—so that protein intake could be the same percentage. The researchers
matched the protein intake of both diets studied (18 percent of calories) because protein
may influence both satiety ("fullness") and insulin secretion. The authors
assigned the moderate-carb diet to 16 adults and the standard diet to 14 adults for a
month. Subjects received enough calories to maintain their weight at what it was before
the study. During the study they were weighed each weekday, and if a participant gained or
lost weight, the amount of food was modified individually so weight could stay the same.
After the subjects adjusted to their diet for 4 weeks, they ate a test meal, a breakfast
that was specific to their diet.
Blocking a muscle growth-limiting
hormone protects against obesity and atherosclerosis
Knockout of myostatin, a growth factor that limits muscle growth, can decrease body fat
and promote resistance against developing atherosclerosis, or "hardening" of the
arteries, according to a new study conducted in mice. The results will be presented
Thursday at The Endocrine Society's 91st Annual Meeting in Washington, D.C. "Obesity
increases the risk of atherosclerosis, which accounts for 75% of all cardiovascular
events, such as heart attacks and strokes," said study co-author Shalender Bhasin,
MD, professor of medicine at Boston University School of Medicine and chief of the Section
of Endocrinology, Diabetes, and Nutrition at Boston Medical Center. "Current
strategies aimed at preventing heart disease consist primarily of lowering cholesterol
levels, but patients reaching the desired cholesterol levels are still at risk for
atherosclerosis if they have other risk factors, such as obesity." Humans and animals
with a mutation in the myostatin gene are extremely muscular and have little fat, past
research shows. Also, when the gene encoding myostatin is knocked out in mice, their
muscle mass increases. Bhasin and his co-workers wanted to find out if inhibiting
myostatin in mice could resist the development of diet-induced obesity and of
atherosclerosis, the buildup of lipid deposits called plaque that can narrow and clog
coronary arteries. The researchers took mice that were genetically altered to develop
atherosclerosis and then cross-bred them with myostatin knockout mice. Ten generations
later, they had mice who were genetically predisposed to both atherosclerosis and
inactivation of myostatin. For controls, they studied mice with a genetic predisposition
for atherosclerosis but with intact myostatin gene. All mice received a high-fat diet for
12 weeks, to spur the development of atherosclerosis.
A natural hormone may protect
muscle from atrophy
Researchers have found a potential new treatment for the common problem of muscle atrophy.
Results of the animal study were presented at The Endocrine Society's 91st Annual Meeting
in Washington, D.C. Muscular atrophy is a debilitating process that results in an
extensive loss of muscle mass and function, which greatly worsens quality of life. It
occurs in diseases such as cancer, diabetes, AIDS and heart failure, negatively affecting
the patients' prognosis. Also, muscular atrophy can occur with aging, inadequate food
intake such as in anorexia nervosa, or disuse (in those who are bedridden or who must keep
a limb immobile) or as a side effect of glucocorticoid steroid therapy. Nerve injury also
triggers severe muscular atrophy. Currently, there are few options to treat the problem.
Some of the treatments, such as anabolic steroids (testosterone) and insulin-like growth
factor 1 (IFG-1), raise concerns about safety and effectiveness, said study co-author
Andrea Graziani, PhD. He is a molecular biologist with the Department of Clinical and
Experimental Medicine and the Biotechnology Center for Applied Medical Research,
University of Piemonte Orientale, Novara, Italy. "Because of the wide impact of
muscular atrophy on public health, it is of pivotal importance to find new and better drug
strategies to treat it," Graziani said.
Stress makes your hair go gray
Those pesky graying hairs that tend to crop up with age really are signs of stress,
reveals a new report in the June 12 issue of Cell, a Cell Press publication. Researchers
have discovered that the kind of "genotoxic stress" that does damage to DNA
depletes the melanocyte stem cells (MSCs) within hair follicles that are responsible for
making those pigment-producing cells. Rather than dying off, when the going gets tough,
those precious stem cells differentiate, forming fully mature melanocytes themselves.
Anything that can limit the stress might stop the graying from happening, the researchers
said. "The DNA in cells is under constant attack by exogenously- and
endogenously-arising DNA-damaging agents such as mutagenic chemicals, ultraviolet light
and ionizing radiation," said Emi Nishimura of Tokyo Medical and Dental University.
"It is estimated that a single cell in mammals can encounter approximately 100,000
DNA damaging events per day." Consequently, she explained, cells have elaborate ways
to repair damaged DNA and prevent the lesions from being passed on to their daughter
cells. "Once stem cells are damaged irreversibly, the damaged stem cells need to be
eliminated to maintain the quality of the stem cell pools," Nishimura continued.
"We found that excessive genotoxic stress triggers differentiation of melanocyte stem
cells." She says that differentiation might be a more sophisticated way to get rid of
those cells than stimulating their death. Nishimura's group earlier traced the loss of
hair color to the gradual dying off of the stem cells that maintain a continuous supply of
new melanocytes, giving hair its youthful color. Those specialized stem cells are not only
lost, they also turn into fully committed pigment cells and in the wrong place. Now, they
show in mice that irreparable DNA damage, as caused by ionizing radiation, is responsible.
They further found that the "caretaker gene" known as ATM (for ataxia
telangiectasia mutated) serves as a so-called stemness checkpoint, protecting against MSCs
differentiation. That's why people with Ataxia-telangiectasia, an aging syndrome caused by
a mutation in the ATM gene, go gray prematurely.
Lost molecule is lethal for liver
cancer cells in mice
Scientists at Johns Hopkins have discovered a potential strategy for cancer therapy by
focusing on what's missing in tumors. Noticing the conspicuous absence of single-stranded
genetic snippets called microRNAs in cancer cells, a team of researchers from Johns
Hopkins and Nationwide Children's Hospital delivered these tiny regulators of genes to
mice with liver cancer and found that tumor cells rapidly died while healthy cells
remained unaffected. Publishing results of the study June 12 in Cell, the researchers say
they have provided one of the first demonstrations that microRNA replacement provides an
effective therapy in an animal model of human disease. "This work suggests that
microRNA replacement may be a highly effective and nontoxic treatment strategy for some
cancers or even other diseases," says Josh Mendell, M.D., Ph.D., an associate
professor in the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University
School of Medicine. "We set out to learn whether tumors in a mouse model of liver
cancer had reduced levels of specific microRNAs and to determine the effects of restoring
normal levels of these microRNAs to these cancer cells. We were very excited to see that
the tumors were, in fact, very vulnerable to microRNA replacement." His team had
considered the possibility that the replacement of a single small RNA might have little if
any effect, especially in the setting of all the complex changes that drive the aberrant
behavior of a cancer cell. But the tumor cells in the mouse were indeed sensitive to the
restoration of the microRNA—so much so that they died, rapidly. "This concept of
replacing microRNAs that are expressed in high levels in normal tissues but lost in
diseases hasn't been explored before," Mendell says. "Our work raises the
possibility of a more general therapeutic approach that is based on restoring microRNAs to
diseased tissues."
Snoring pregnant women at higher
risk for gestational diabetes
If you are pregnant and your mate complains your frequent snoring is rattling the bedroom
windows, you may have bigger problems than an annoyed, sleep-deprived partner. A new study
from researchers at the Northwestern University Feinberg School of Medicine has found that
women who reported frequent snoring during their pregnancy were more likely to develop
gestational diabetes -- a condition than can cause health problems for the mother and
baby. The study also found pregnancy increases the likelihood that a woman will snore.
This is the first study to report a link between snoring and gestational diabetes. For the
study, 189 healthy women completed a sleep survey at the time of enrollment (six to 20
weeks gestation) and in the third trimester. Pregnant women who were frequent snorers had
a 14.3 percent chance of developing gestational diabetes, while women who did not snore
had a 3.3 percent chance. Even when researchers controlled for other factors that could
contribute to gestational diabetes such as body mass index, age, race and ethnicity,
frequent snoring was still associated with the disease. Principal investigator Francesca
Facco, M.D., a fellow at Northwestern's Feinberg School, will present her findings at the
SLEEP 2009 23rd Annual Meeting of the Associated Professional Sleep Societies June 11.
A red-wine polyphenol called
resveratrol demonstrates significant health benefits
The benefits of alcohol are all about moderation. Low to moderate drinking –
especially of red wine – appears to reduce all causes of mortality, while too much
drinking causes multiple organ damage. A mini-review of recent findings on red wine's
polyphenols, particularly one called resveratrol, will be published in the September issue
of Alcoholism: Clinical & Experimental Research; the review is also available at Early
View. "Reports on the benefits of red wine are almost two centuries old," said
Lindsay Brown, associate professor in the School of Biomedical Sciences at The University
of Queensland and corresponding author for the study. "The media developed the more
recent story of the French paradox in the early 1990s. However, studies on the actions of
resveratrol, one of the active non-alcoholic ingredients, were uncommon until research
around 1997 showed prevention of cancers. This led to a dramatic interest in this
compound." (See attached figure.) Red wine contains a complex mixture of bioactive
compounds, including flavonols, monomeric and polymeric flavan-3-ols, highly colored
anthocyanins, as well as phenolic acids and the stilbene polyphenol, resveratrol. Brown
said that some of these compounds, particularly resveratrol, appear to have health
benefits. "The breadth of benefits is remarkable – cancer prevention, protection
of the heart and brain from damage, reducing age-related diseases such as inflammation,
reversing diabetes and obesity, and many more," said Brown. "It has long been a
question as to how such a simple compound could have these effects but now the puzzle is
becoming clearer with the discovery of the pathways, especially the sirtuins, a family of
enzymes that regulate the production of cellular components by the nucleus. 'Is
resveratrol the only compound with these properties?' This would seem unlikely, with
similar effects reported for other components of wine and for other natural products such
as curcumin. However, we know much more about resveratrol relative to these other
compounds."
Extended or shortened sleep
duration linked to weight gain
Body Mass Index (BMI) varies as a function of habitual sleep duration, according to a
research abstract that will be presented on Thursday, June 11, at SLEEP 2009, the 23rd
Annual Meeting of the Associated Professional Sleep Societies. Results indicate that twins
who slept between 7 and 8.9 hours each night had a lower mean BMI (25.0 kg/m2) compared to
those who regularly slept either more (25.2 kg/m2) or less (26.4 kg/m2) per night. The
relationship between sleep duration and BMI remained after controlling for genetics and
shared environment. According to the lead author of the story, Nathaniel Watson, MD,
co-director at the University of Washington Sleep Institute, in Seattle, sleep habits have
a significant impact on weight and BMI. "Findings of the study point towards an
environmental cause of the relationship between sleep duration and BMI," said Watson.
"Results were robust enough to be present when the sample was limited to identical
twins." The study included data from 1,797 twins, including 634 twin pairs (437
monozygotic, 150 dizygotic and 47 indeterminate pairs) and 529 individual twins with a
mean age of 36.8. Habitual sleep duration was obtained by self-reported length of sleep
per night and BMI was calculated by self-reported height and weight. Of the sample, 68.3
percent female, 88.2 percent were Caucasian. Results persisted in a co-twin control
analysis of within twin pair differences in sleep duration and BMI.
Spanish researchers advance Natural
Computing and Synthetic Biology techniques for treating diseases
Researchers from the Artificial Intelligence Group (LIA) at the Universidad Politécnica
de Madrid's School of Computing have designed a biomolecular automaton and several genetic
circuits with potential future applications in the field of vanguard medicine. Depending
on how it is programmed, the molecular automaton detects DNA or RNA signals in vitro. In
the future, though, provided it passes all the experimental tests, it will be able to
operate inside the human organism. The ultimate aim of a molecular automaton is to detect
and treat diseases in situ inside a human organism. Fitted inside the organism, the
automaton detects anomalies and dispenses the right medicine at the right time.
Biomolecular automata are artificial devices built with biomolecules and designed to
operate inside a living organism.
Transparent solar cells
Offering a view of the garden and an adjacent field, it looks like any other window. But
this window offers an additional feature: it also produces electricity. The facades of the
house, too, harness solar energy to supply the occupants with electrical power. This is
what the domestic power supply of the future could look like. The surface area used to
produce energy would increase greatly with transparent solar cells. To translate the
vision of see-through solar cells and transparent electronics into reality, two different
transparent coatings would be required – one to conduct the electricity via
electrons, the n-conductors, and one in which electron holes enable the electricity to
flow, the p-conductors. To produce these coatings the engineers dope the base material
with a few other atoms. Depending on which atoms they use, they obtain the differently
conducting coatings. N-conducting transparent materials are state of the art, but the
p-conductors are problematic. Their conductivity is too low and often their transparency
is poor. Manufacturers need a transparent base material which is amenable to both n- and
p-doping.
Greenland ice sheet larger
contributor to sea-level rise
The Greenland ice sheet is melting faster than expected according to a new study led by a
University of Alaska Fairbanks researcher and published in the journal Hydrological
Processes. Study results indicate that the ice sheet may be responsible for nearly 25
percent of global sea rise in the past 13 years. The study also shows that seas now are
rising by more than 3 millimeters a year--more than 50 percent faster than the average for
the 20th century. UAF researcher Sebastian H. Mernild and colleagues from the United
States, United Kingdom and Denmark discovered that from 1995 to 2007, overall
precipitation on the ice sheet decreased while surface ablation--the combination of
evaporation, melting and calving of the ice sheet--increased. According to Mernild’s
new data, since 1995 the ice sheet lost an average of 265 cubic kilometers per year, which
has contributed to about 0.7 millimeters per year in global sea level rise. These figures
do not include thermal expansion--the expansion of the ice volume in response to heat--so
the contribution could be up to twice that. The Greenland ice sheet has been of
considerable interest to researchers over the last few years as one of the major
indicators of climate change. In late 2000/early 2001 and in 2007, major glacier calving
events sent up to 44 square miles of ice into the sea at a time. Researchers are studying
these major events as well as the less dramatic ongoing melting of the ice sheet through
runoff and surface processes.
New study reveals structure of the
HIV protein shell
New research by scientists at The Scripps Research Institute and other institutions
provides a close-up look at the cone-shaped shell that is the hallmark of human
immunodeficiency virus (HIV), revealing how it is held together—and possible ways to
break it apart. Previously, scientists had known that the genetic material within HIV is
enclosed within a shell called the capsid, which is formed by a honeycomb arrangement of
about 250 hexagonal protein building blocks. For HIV to infect human cells, the virus
binds to cell surface receptors, and then the capsid is delivered into the cytoplasm of
the cell. Now, in an advance, online issue of the journal Cell published on June 11, 2009,
Professor Mark Yeager and colleagues at The Scripps Research Institute, the University of
Virginia, and the University of Utah describethe first high-resolution molecular structure
of the hexagonal protein building block, called CA, that makes up the HIV capsid. This
detailed description may help scientists identify new ways to block HIV infection.
Scripps Research Team Creates
Simple Chemical System that Mimics DNA
A team of Scripps Research scientists has created a new analog to DNA that assembles and
disassembles itself without the need for enzymes. Because the new system comprises
components that might reasonably be expected in a primordial world, the new chemical
system could answer questions about how life could emerge. The work, reported in the June
11, 2009 issue of Science Express, an advance, online publication of the journal Science,
might also be a starting point on the way to exotic new materials that repair themselves
or transform in response to their environment. Scientists are both bemused and fascinated
by the question of how life could have arisen on Earth. One of the most prominent theories
is that, before the emergence of DNA, the earliest forms of life used RNA to transmit
their genetic codes. The late Leslie Orgel, a co-author of the new paper, first suggested
this idea, known as the "RNA World." One of the theory's challenges is that RNA
is still so complex that many researchers believer something still simpler must have
preceded it. "I have been working for years to learn what replicators and genetic
systems might have come before the advent of the RNA World," says team leader of the
new research Professor Reza Ghadiri, a Scripps Research chemist.
Texas wines fight cancer growth
Research now shows that wines produced in the Lone Star State share the anti-cancer traits
known to exist in wines from other producing regions. Extracts from two Texas red wines
decreased cancer cell growth in a comparable magnitude as other wines previously studied,
according to Dr. Susanne Talcott, Texas AgriLife Research food and nutrition scientist.
Her study, which concluded in May, showed decreased growth of colon and breast cancer
cells treated with port and syrah (or shiraz) wine. It was the first such study of the
health components of Texas wines, she said. "These results could definitely be
projected to all Texas wines containing similar amounts of bioactive compounds,"
Talcott said. "And this will be the basis for a continued intensive study of all the
health benefits of wines made in this state." Talcott presented her findings at the
recent Texas Viticulture and Enology Research Symposium. She said the findings suggest
that people who consume regular, moderate amounts of Texas wine daily -- up to a glass and
a half -- may profit from similar health benefits ascribed to wines from other regions.
"In general, studies show that wine may either prevent cells from mutating into
cancer cells, or stop existing cancer cells from growing and causing them to die,"
Talcott noted.
Children At Risk in Hot Cars
With summer approaching, the danger of children dying from being left unattended in
vehicles increases, a Texas AgriLife Extension Service specialist warns. "The problem
is that temperatures in parked vehicles rise very quickly," said Bev Kellner,
AgriLife Extension passenger safety specialist. In just 10 minutes the temperature can
increase by almost 20 degrees, according to figures from San Francisco State University's
department of geosciences. A child’s body temperature rises three to five times
faster than an adult making children more vulnerable to a deadly condition known as
hyperthermia or heat stroke, Kellner noted. Heat stroke can occur at body temperatures
above 104 degrees.
Appetite-stimulating hormone is
first potential medical treatment for frailty in older women
Older women suffering from clinical frailty stand to benefit from the first potential
medical treatment for the condition, according to a study presented today by Penn Medicine
researchers at ENDO, The Endocrine Society's 91st Annual Meeting. Ghrelin, a hormone that
stimulates appetite, was administered to older women diagnosed with frailty, a common
geriatric syndrome characterized by unintentional weight loss, weakness, exhaustion and
low levels of anabolic hormones which increases risk of falls, hospitalizations,
disability, and death. Those who received ghrelin infusions consumed 51 percent more
calories than the placebo group, with an increase in carbohydrate and protein intake, not
fat. Their growth hormone levels were also higher throughout the ghrelin infusion.
"As Americans are increasingly living into their 80s and 90s, we need to identify
ways to prevent or treat common geriatric conditions, such as unexplained weight loss and
frailty, which have serious health consequences," said senior author Anne Cappola,
MD, ScM, Assistant Professor of Medicine in Endocrinology, Diabetes, and Metabolism at the
University of Pennsylvania School of Medicine. "We're gaining a better understanding
of the hormonal changes that occur as we get older and, with treatments like ghrelin, we
can start intervening to prevent some of the common health problems that keep elderly
people from living their most productive lives." In the pilot study, funded by the
National Institutes of Health and Penn's Institute on Aging, five frail women and five
healthy women, all over the age of seventy, were randomized to receive an infusion of the
hormone ghrelin or placebo. After a ghrelin transfusion, frail women in the study had a
stronger, healthy appetite and increased anabolic hormone activity. The only side effect
reported during the treatment was a transient sense of warmth that occurred in four women
who received the ghrelin transfusion. Now that safety and initial efficacy has been proven
in this pilot study, larger follow-up studies will look at the potential therapeutic role
of ghrelin or ghrelin mimetic agents in the frail population. At this time, these agents
are only available for research use.
Over half of people with rheumatoid
arthritis have periodontitis
Over half (56%) of people with rheumatoid arthritis (RA) also have periodontitis (a
chronic inflammatory disease of the gum and surrounding ligaments and bones that hold the
teeth in place), displaying fewer teeth than healthy matched controls, high prevalence of
oral sites presenting dental plaque and advanced attachment loss (the extent of
periodontal support that has been destroyed around a tooth) (chi square p<0.05),
according to the results of a new study presented today at EULAR 2009, the Annual Congress
of the European League Against Rheumatism in Copenhagen, Denmark. In addition, these
patients were found to have significantly higher RA disease activity and anti-CCP (cyclic
citrullinated peptide) antibody levels than others with RA who did not exhibit
periodontitis (r=0.84, p<0.05; r=0.78, p<0.05). The study also showed that, after
six months of anti-TNF therapy (prescribed to control RA inflammation and destruction), a
statistically significant improvement in periodontal status was seen in 20 (80%) of the 25
participants (mean age 41.5+3.7 years; mean disease duration 7.2+4.8 years), suggesting
that the biological therapy may also be able to modulate the inflammatory process in the
periodontium (the tissues investing and supporting the teeth, including the cementum,
periodontal ligament, alveolar bone, and gingival / gums). Dr Codrina Ancuta of the
Grigore T Popa University of Medicine and Pharmacy, Rehabilitation Hospital, Iasi,
Romania, who led the study, said: "There is a growing body of evidence to demonstrate
an association between periodontal disease and systemic conditions involving inflammatory
rheumatic disease (especially RA), cardiovascular disease and diabetes. However, further
cross-disciplinary research among rheumatologists and periodontologists is required to
fully understand the underlying mechanisms that link RA and periodontitis, and to explore
how patients can be managed more holistically using treatments such as anti-TNFs and some
lifestyle approached that may simultaneously address both conditions."
Anxiety and depression lower
quality of life in majority of systemic lupus erythematosus patients
92.8% of patients with systemic lupus erythematosus (SLE) suffer anxiety and depression
which significantly affects both their physical and emotional quality of life (QoL),
according to the results of a new study presented today at EULAR 2009, the Annual Congress
of the European League Against Rheumatism in Copenhagen, Denmark. Logistic regression
analysis revealed that depression was the most significant factor shown to affect QoL
(p=0.015; OR=0.18; CI 95%:0.045-0.72). In the study, 92.8% (52 of 56) of the patients who
were diagnosed with SLE had an element of confirmed neuropsychiatric (NP) involvement
(including anxiety, depression, mild cognitive deficits and major NP involvement).
Dual role in breast tissue for a
protein involved in leukemia
A protein known to play a role in growth of some types of leukemia appears to have a mixed
function in breast cancer development, say researchers from the Lombardi Comprehensive
Cancer Center at Georgetown University Medical Center (GUMC). The findings, presented at
the annual meeting of the Endocrine Society in Washington, DC, indicate that the function
of this protein, known as Stat5a, may be different in developing breast cancer cells that
are estrogen receptor-positive as compared to estrogen receptor-negative. When estrogen
receptor levels were overexpressed, loss of Stat5a reduced development of a lobular type
of preneoplasia. However, when estrogen receptor levels were normal, loss of Stat5a not
only had no effect on reducing preneoplasia, but increased susceptibility to
carcinogen-induced breast cancer. The results illustrate the importance of breast cancer
heterogeneity when testing new therapeutic targets. The researchers say Stat5a could be a
target for treatment of leukemia, but add, "If Stat5a is to be used as a drug target
for leukemia or other cancers, it is important to fully understand how altering its
function impacts the breast, especially since it appears it may play different roles in
different types of breast cancer," says the study's lead author, Anne Miermont, MS, a
doctoral graduate student in tumor biology at Georgetown University Medical Center. Stat5a
is a member of the STAT family of proteins, which are key to regulating cell growth and
differentiation. Because they have been found to be over-expressed in leukemia, Miermont
and Priscilla Furth, MD, a professor of oncology, sought to see if they were important in
breast cancer development. Estrogen receptors are over-expressed in more than half of
human breast cancers, so the investigators set up studies to test if the function of
Stat5a was the same or different in cells with estrogen receptor overexpression.
Protein Linked to Change in Tissue
That Surround and Support Breast Tumors
A protein known to be overly active in breast cancer can exist in a form that seems to
change the structural composition of mammary tissue, potentially making it more conducive
to tumor progression, say researchers from the Lombardi Comprehensive Cancer Center at
Georgetown University Medical Center (GUMC). At the annual meeting of the Endocrine
Society in Washington, DC, the scientists report that the protein, AIB1 (Amplified in
Breast Cancer 1), has a shorter form known as AIB1delta3 which turns breast tissue more
fibrous. The researchers say this shorter form may contribute to the dense breast tissue
that is a known risk factor for breast cancer. “We found that AIB1delta3 alters the
stroma, or environment that surrounds and supports cancer cells, producing excessive
fibrosis,” says the study’s lead author, Priscilla Furth, MD, Professor of
Oncology and Medicine. “This is significant, because disordered interactions between
the epithelial and stromal compartments are being increasingly recognized as an important
component of breast cancer risk.”
USC researchers identify DNA
mutation that occurs at beginning point of T-cell lymphoma
Researchers at the Keck School of Medicine of the University of Southern California (USC)
have identified a key mechanism that causes chromosomes within blood cells to break—an
occurrence that marks the first step in the development of human lymphoma. The study
provides researchers with the clearest insight yet into why these breakages—called
chromosomal translocations—occur at a specific points in the chromosome, says
principal investigator Michael R. Lieber, M.D., Ph.D., Rita and Edward Polusky Professor
in Basic Cancer Research at the Keck School of Medicine. The study appears as the featured
cover article in the June 12 issue of the journal Molecular Cell. The study is the second
led by Lieber to appear on the cover of a Cell journal in the past six months. "The
new findings go to the heart of why cancers begin. This is an opportunity to see the very
beginning step of human lymphoma," Lieber says. "With this information, we can
now begin to look at ways to interfere with this process in order to stop the lymphoma and
to develop more targeted therapies for treatment." There are two types of lymphoma: B
cell lymphomas and T cell lymphomas. Both B cells and T cells perform vital functions in
the immune system by creating antibodies and destroying virus-infected cells. However, the
beginning point, or inception, of most human lymphomas occurs when two chromosomes break
and the resulting fragments are reassembled in an exchange. Researchers specifically
looked at T cell acute lymphoblastic lymphomas (ALL). ALL accounts for half of all
childhood cancers under the age of five, and T cell ALL represents about 10 percent of
ALL. The USC scientists identified a specific enzyme known as the RAG complex that
occasionally cuts the chromosome at an off-target site, causing lymphocyte (blood) cells
to proliferate uncontrollably. They showed that the RAG complex selects the wrong target
largely because the proteins in which the wrong chromosome is wrapped (called chromatin)
lures the RAG complex to the wrong site.
Gene therapy technique thwarts
cancer by cutting off tumor blood supply
University of Florida researchers have come up with a new gene therapy method to disrupt
cancer growth by using a synthetic protein to induce blood clotting that cuts off a
tumor's blood and nutrient supply. In mice implanted with human colorectal cancer cells,
tumor volume decreased 53 percent and cancer cell growth slowed by 49 percent in those
treated with a gene that encodes for the artificial protein, compared with those that were
untreated. The research team, led by Dr. Bradley S. Fletcher, an assistant professor of
pharmacology and therapeutics in the College of Medicine, created the so-called fusion
protein to target another protein called tumor endothelial marker 8, or TEM8, which was
recently found to be preferentially expressed in the inner lining of tumor vessels. Such
differences in protein expression enable delivery of drug molecules to the cells that
harbor these proteins. "The protein we created did a very good job of homing to the
tumor and binding," said Stephen Fernando, who recently completed his doctoral
studies. "By targeting TEM8, we can potentially create a therapy against
cancer." The Fletcher group is the first to target cancer cells through protein
binding to TEM8. The findings, now available online, are featured on the cover of the June
15 edition of Cancer Research. "If you can cut off the blood supply, then you can
inhibit the tumor from growing -- there have been many attempts," said Brad St.
Croix, director of the National Cancer Institute's Tumor Angiogenesis Section, whose group
first identified the TEM genes that over-express in tumor endothelial cells. "The
concept of targeting tumor blood vessels has been around for many years, but it's good
that we're finally getting around to the stage where we can see the vessels being targeted
therapeutically -- it's pretty exciting, I think."
Majority won't have access to
antivirals in pandemic but generic drugs could help prevent deaths
Almost 90 per cent of the world's population will not have timely access to affordable
supplies of vaccines and antiviral agents in the current influenza pandemic, but it is
possible that inexpensive generic drugs that are readily available, even in developing
countries, could save millions of lives. That's the conclusion reached by an extensive
review and analysis by immunisation expert Dr David Fedson, published online by Influenza
and Other Respiratory Viruses within hours of the World Health Organization declaring a
pandemic. Dr Fedson points out that seasonal flu resistance to antiviral drugs like
Tamiflu may make them ineffective in the pandemic and maintains that without effective
drugs some countries will have to rely on 19th century public health measures to see them
through the outbreak. He is calling for urgent and sharply focused research to determine
whether drugs that reduce inflammation or modify the host response - the way that the body
responds to infection or injury - could be used to manage the pandemic. And he believes
that a lot could be learnt from the work done on these commonly available generic drugs -
which include drugs to lower cholesterol and treat diabetes - by scientists not involved
in influenza research. "Despite the best efforts of influenza scientists,
pharmaceutical companies and health officials, the stark reality is that although studies
of the molecular characteristics of influenza viruses have been enormously informative,
they have failed to explain the system-wide effects that flu has on people who contract
it. "For example we still don't understand why so many young adults died in the 1918
pandemic, while the death rate for children was much lower. I believe this is because
researchers have focused on studying the actual virus rather than how these particular
hosts – the children and young people – responded to the virus.
UK tops the list of 213 countries
at extreme risk to the spread of swine flu
A Warwick Business School professor and one of the founders of global risks specialist,
Maplecroft, has released three new maps and indices revealing the countries most at risk
from an influenza pandemic.Each index generates a list of countries most at risk and which
require a tailored policy response on the part of government and business. Maplecroft's
research focuses on global risks to business. The map of Risk of Spread shows the UK most
at risk to the spread of an influenza pandemic, ranking number 1 out of 213 countries. The
Netherlands, Germany, Italy, Russia, Canada and Japan are also categorised as extreme risk
because of their high population density, urbanisation and busy airports.
A research group focus on
neurobiology of Parkinson's disease an the early detection of the disease
A research group based at the University of Granada, in cooperation with the Neurology
Unit of the San Cecilio Hospital of Granada and the Department of Experimental Sciences of
the University of Jaen, is studying the Neurobiology of Parkinson's disease (PD). They
have developed a non-invasive method for serological diagnosis of Parkinson's disease,
which is being patented by the University of Granada. To this end, the scientists analyzed
and purified proteins associated with this disease, such as aminopeptidase. However, it is
not an easy task: "there are thousands of proteins in the blood, and only a few are
related to neurodegenerative diseases." Francisco Vives, Head of the Institute the
Neurosciences of Granada and coordinator of the University of Granada's research group for
the "Study of neurodegenerative diseases in Andalusia" says that "so far,
there is not effective treatment" for Parkinson's disease so, at the moment the only
solution is palliative treatment. Therefore, "finding plasma specific proteins in
patients before the first symptoms of Parkinson's disease appear, will allow us to use
drugs that either stop or at least slow down the disease. An early diagnose is important
to PD medication"
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