Through novel experiments involving small nematode worms, scientists from Wyoming have discovered several genes that may be potential targets for drug development in the ongoing war against cancer.
Specifically, researchers hypothesize that inhibiting these genes could reverse certain key traits associated with cancer cells.
This discovery is published in the August 2012 issue of the Genetics Society of America’s journal GENETICS (www.genetics.org).
“Cancer is a leading cause of death worldwide,” said David S. Fay, Ph.D., a researcher involved in the work from the Molecular Biology Department at the University of Wyoming in Laramie. “We hope that by carrying out basic genetic research on one of the most widely implicated human cancer genes, that we can contribute to the arsenal of diverse therapeutic approaches used to treat and cure many types of cancer.”
To make this discovery, Dr. Fay and his colleagues used a strain of nematode worms that carried a mutation in a gene similar to one that is inactivated in many human cancers.
This gene, called “LIN-35” in worms and “pRb” in humans, is thought to control at least several aspects of tumor progression including cancer cell growth and survival.
The researchers systematically inactivated other individual genes in the genome of the mutant LIN-35 worms.
As they deactivated various genes, scientists identified those that led to a reversal of defects caused by the loss of LIN-35, suggesting that they could be used as targets for anti-cancer therapies.
“This research is important because it offers possible new ways to shut down the genetic machinery that contributes to cancer growth and progression,” said Mark Johnston, Ph.D., editor-in-chief of the journal GENETICS. “The causes of cancer are complex and varied, so we must approach this disease from many angles. Using simple ‘model organisms,’ such as nematode worms to find new drug targets, is becoming an increasingly important and effective strategy.”
Vaccination against the hepatitis A virus (HAV) in children 2 years of age and younger remains effective for at least 10 years, according to new research available in the August issue of Hepatology, a journal of the American Association for the Study of Liver Diseases (AASLD).
The study found that any transfer of the mother’s HAV antibodies does not lower the child’s immune response to the vaccine.
The World Health Organization (WHO) estimates that 1.4 million cases of HAV occur worldwide each year.
HAV affects the liver and typically occurs in areas with poor sanitation where ingestion of contaminated food or water can transmit the virus.
In the U.S., HAV cases have decreased by 90 percent in the past 20 years, with roughly 20,000 new cases reported each year according to the Centers for Disease Control and Prevention (CDC).
Experts attribute the decline in HAV cases in the U.S. to routine vaccination of children 12 to 18 months.
According to lead author Dr. Umid Sharapov, an epidemiologist with the CDC and his coauthors, this is the first study to examine the effectiveness of a two-dose inactivated hepatitis A vaccine in children younger than two years of age over a 10-year period.
In addition, the researchers investigated whether maternal anti-HAV antibody transfer to their children impacts the vaccine protection against HAV.
With parental consent, researchers enrolled full-term infants who were healthy at six-months of age. Mothers were tested for total antibody to HAV.
The 197 infants and toddlers were broken into three groups to receive a two-dose hepatitis A vaccine: group one at 6 and 12 months; group two at 12 and 18 months; and group three at 15 and 21 months of age.
Within each group, children were randomized by maternal anti-HAV status. HAV antibody levels were measured at one and six months, and additional follow-up took place at three, five, seven and 10 years after the second dose of hepatitis A vaccine.
At one month following the second dose of the hepatitis A vaccine children in all groups showed signs of protection from the virus. At the 10-year followup most children retained anti-HAV protection.
In the first group, 7 percent and 11 percent of children born to mother’s without and with antibodies to the HAV virus, did not retain HAV protection from vaccination, respectively. Additionally, 4 percent of group three children born to anti-HAV negative mothers lost HAV protection.
“Our study demonstrates that seropositivity to hepatitis A persists for at least 10 years after primary vaccination with two-dose inactivated HAV vaccine when administered to children at ages 12 months and older, regardless of their mothers’ anti-HAV status,” concluded Dr. Sharapov. “These findings support current CDC/ACIP guidelines for routine administration of two doses of inactivated hepatitis A vaccine to all children in the U.S. beginning at the age of 12 months.”
The authors point out that a future booster dose may be necessary to maintain protection against HAV and they will continue followup participants into their teens to monitor benefit of the initial immunization.
Eighty-nine million Americans were without health insurance for at least one month during the period from 2004 to 2007, and 23 million lost coverage more than once during that time, according to researchers at Penn State and Harvard University.
“These findings call attention to the continuing instability and insecurity of health insurance in our country,” said Pamela Farley Short, professor of health policy and administration, Penn State. “With more than a third of all Americans under age 65 being uninsured at some point in a four-year period, it’s easy to see that the problem of being uninsured is a big one that affects lots of people.”
To do their analysis, the researchers used data from the U.S. Census Bureau’s Survey of Income and Program Participation, which collects information from the same individuals every four months over a four-year period.
The team examined changes in insurance coverage among people ages 4 to 64 from 2004 to 2007, which is the most recent period for which four-year data are available.
The researchers found that, of the 89 million people who were uninsured during the period from 2004 to 2007, 12 million were continually uninsured; 11 million gained coverage at some point; 11.5 lost coverage; 14 million experienced a single gap in coverage; and 6 million had a temporary spell of coverage, but were otherwise uninsured.
In addition, 23 million people lost health insurance more than once during the four-year period.
The results of the analysis appeared online in a recent issue of Medical Care Research and Review.
“There is clear evidence that people who are uninsured use fewer services than people who have insurance; they postpone prevention and ignore serious problems because they don’t feel they can afford the care,” Short said. “As a result, some even die for lack of insurance.”
But not only do people with gaps in their coverage suffer; those who remain insured and pay premiums suffer as well.
“When people get caught without health insurance, hospitals and emergency rooms are still required to care for them,” Short said. “Someone has to pay for those services.”
According to the survey, low-income people are particularly susceptible to periodic losses of health insurance coverage.
The survey revealed that a little over 64 percent of adults and nearly 60 percent of children who are below 200 percent of the federal poverty level – equivalent to $46,100/year for a family of four – were uninsured for at least one month during the four-year period.
“Even though low-income people are disproportionately affected by gaps in health insurance, none of us is really safe,” Short said. “Any one of us could be afflicted with a serious health problem that could cause us to lose our jobs and our access to employment-based insurance, which is how most of us get insurance.”
In addition to losing or changing jobs, gaps in insurance coverage can occur when people divorce and when children age out of their parents’ plans or public insurance programs.
“We all have a stake in this problem of providing everyone with continuing access to affordable insurance,” Short said. “Promoting stability and minimizing uninsured gaps should be high priorities as federal and state officials proceed with the implementation of national health care reforms.”
The possibility of an inexpensive, convenient test for Alzheimer’s disease has been on the horizon for several years, but previous research leads have been hard to duplicate.
In a study to be published in the Aug. 28 issue of the journal Neurology, scientists have taken a step toward developing a blood test for Alzheimer’s, finding a group of markers that hold up in statistical analyses in three independent groups of patients.
“Reliability and failure to replicate initial results have been the biggest challenge in this field,” said lead author William Hu, MD, PhD, assistant professor of neurology at Emory University School of Medicine. “We demonstrate here that it is possible to show consistent findings.”
Hu and his collaborators at the University of Pennsylvania and Washington University, St. Louis, measured the levels of 190 proteins in the blood of 600 study participants at those institutions.
Study participants included healthy volunteers and those who had been diagnosed with Alzheimer’s disease or mild cognitive impairment (MCI). MCI, often considered a harbinger for Alzheimer’s disease, causes a slight but measurable decline in cognitive abilities.
A subset of the 190 protein levels (17) were significantly different in people with MCI or Alzheimer’s.
When those markers were checked against data from 566 people participating in the multicenter Alzheimer’s Disease Neuroimaging Initiative, only four markers remained: apolipoprotein E, B-type natriuretic peptide, C-reactive protein and pancreatic polypeptide.
Changes in levels of these four proteins in blood also correlated with measurements from the same patients of the levels of proteins [beta-amyloid] in cerebrospinal fluid that previously have been connected with Alzheimer’s.
The analysis grouped together people with MCI, who are at high risk of developing Alzheimer’s, and full Alzheimer’s.
“We were looking for a sensitive signal,” said Hu. “MCI has been hypothesized to be an early phase of AD, and sensitive markers that capture the physiological changes in both MCI and AD would be most helpful clinically.”
“The specificity of this panel still needs to be determined, since only a small number of patients with non-AD dementias were included,” Hu said. “In addition, the differing proportions of patients with MCI in each group make it more difficult to identify MCI- or AD-specific changes.”
Neurologists currently diagnose Alzheimer’s disease based mainly on clinical symptoms. Additional information can come from PET brain imaging, which tends to be expensive, or analysis of a spinal tap, which can be painful.
“Though a blood test to identify underlying Alzheimer’s disease is not quite ready for prime time given today’s technology, we now have identified ways to make sure that a test will be reliable,” said Hu. “In the meantime, the combination of a clinical exam and cerebrospinal fluid analysis remains the best tool for diagnosis in someone with mild memory or cognitive troubles.”
Hu’s research began while he was a fellow at the University of Pennsylvania. Collaborators included David Holtzman, MD, from Washington University at St Louis, Leslie Shaw, PhD and John Trojanowski, MD, PhD from the University of Pennsylvania, and Holly Soares, PhD from Bristol Myers Squibb.