(Press-News.org) COLUMBUS, Ohio – Two studies suggest that two peptide agents used either together or individually with a low-dose of a standard chemotherapy drug might offer more effective cancer therapy than current standard single-drug treatments.
The studies used animal models of breast cancer to show that the peptide combinations dramatically delay tumor onset and progression by both inhibiting tumor growth and blocking the formation of new tumor blood vessels, say the researchers at the Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC – James) who conducted the study. In addition, the treatments caused few side effects.
The findings are described in two papers published online in the journal OncoImmunology. The first paper describes how vaccination with a HER2 peptide followed by treatment with a VEGF peptide inhibitor prevents tumor formation in a transplantable mammary tumor model. The second paper documents how either HER2 peptide or VEGF peptide treatment combined with low-dose paclitaxel effectively kills tumor cells in both the transplantable tumor model and a transgenic mammary tumor model.
"For treating cancer, combination therapies are much more effective than individual therapies, and peptides in combination, whether by vaccination or as therapy, appear to be safer, nontoxic, and taking us closer to a cure," says principle investigator Dr. Pravin Kaumaya, director of the division of vaccine development at the OSUCCC – James.
Kaumaya, who is a professor of obstetrics and gynecology, of molecular and cellular biochemistry, and of microbiology at Ohio State, led the research that developed the peptide agents. Peptides are short chains of amino acids, and the HER2 peptide and VEGF peptide are short amino-acid chains that mimic full-length HER2 and VEGF molecules.
The HER2 receptor molecule is important for controlling tumor growth in many cancers; the VEGF receptor molecule controls the formation of new blood vessels needed to feed tumors. Both molecules are overexpressed in many cancers.
In the new studies, the researchers investigated whether the peptide vaccine and the peptide inhibitor worked more effectively in combination, and also whether they could synergize with a standard chemotherapy agent, paclitaxel.
The HER2 peptide vaccine is injected into the body where it causes the immune system to generate antibodies to the HER2 receptor. These antibodies then bind to the overexpressed HER2 receptors on cancer cells, preventing them from stimulating tumor-cell proliferation. The VEGF therapeutic peptide binds directly to the VEGF receptor molecule, preventing it from directing the formation of new blood vessels.
In the first paper, the team shows that vaccinating mice with the HER2 peptide before aggressive mammary cancer cells are transplanted into the mice can delay the onset of the tumors. When this vaccination treatment was combined with weekly treatments of the VEGF peptide, tumor growth was significantly delayed. In animals given the VEGF peptide, which is engineered not to break down in the body, 40 percent of the animals did not develop tumors at all by the end of the experiment.
In theory, Kaumaya explains, such a peptide vaccine could prevent HER2-driven breast cancer from developing in a daughter who inherited the genetic risk for this cancer from her mother. "We could vaccinate a person who doesn't have the cancer and create a memory for HER2 overexpression in her immune system," he says. "Then, when a tumor starts growing and over-expressing HER2, it would crank up her immune system to produce antibodies to shut the cancer down." This study's results suggest that adding VEGF peptide therapy might halt tumor progression altogether.
The second paper lays groundwork for testing peptide therapies in clinical trials. These experiments tested whether the HER2 peptide vaccine or the VEGF peptide therapy would boost the effectiveness of paclitaxel, a standard chemotherapy drug, when the drug is used at low dose to reduce its toxicity.
"We know from other people's work that treating patients with a low-dose chemotherapy agent like paclitaxel primes the system to be more responsive to other targeted treatments," Kaumaya says. Indeed, the team showed that both peptide treatments used individually with paclitaxel delayed tumor growth and development and produced better response rates than either agent without the drug in both transplanted and transgenic mouse breast cancer models.
Importantly, the combined therapies showed no toxic side effects. In contrast, paclitaxel and the current standard anti-HER2 therapy, trastuzumab, both had toxic effects on the heart.
"Our goal is to find a cure by interfering with various cancer-cell pathways using medicines that are not toxic," Kaumaya says.
###
Other Ohio State researchers involved in the two studies were Kevin Foy, Megan Miller, Nicanor Moldovan, Tatjana Bozanovic, and William E. Carson, III.
The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 41 National Cancer Institute (NCI)-designated Comprehensive Cancer Centers and one of only seven centers funded by the NCI to conduct both phase I and phase II clinical trials. The NCI recently rated Ohio State's cancer program as "exceptional," the highest rating given by NCI survey teams. As the cancer program's 210-bed adult patient-care component, The James is a "Top Hospital" as named by the Leapfrog Group and one of the top cancer hospitals in the nation as ranked by U.S. News & World Report.
EAST LANSING, Mich. — A parasite thought to be harmless and found in many people may actually be causing subtle changes in the brain, leading to suicide attempts.
New research appearing in the August issue of The Journal of Clinical Psychiatry adds to the growing work linking an infection caused by the Toxoplasma gondii parasite to suicide attempts. Michigan State University's Lena Brundin was one of the lead researchers on the team.
About 10-20 percent of people in the United States have Toxoplasma gondii, or T. gondii, in their bodies, but in most it was thought to ...
WASHINGTON – Blacks who survived a stroke caused by bleeding in the brain had higher blood pressure than whites a year later, according to a study published today in the journal Stroke. The finding might help explain why blacks have a greater risk of suffering a second stroke than whites.
The research, a part of the Georgetown University Medical Center (GUMC) Stroke Disparities Program led by Chelsea Kidwell, M.D., was designed to examine racial and ethnic differences in strokes known as intracranial hemorrhage or ICH. ICHs account for 10 percent of all strokes, but carry ...
LOS ANGELES — Research from the University of Southern California (USC) and Cancer Prevention Institute of California (CPIC) found that cooking red meats at high temperatures, especially pan-fried red meats, may increase the risk of advanced prostate cancer by as much as 40 percent.
Mariana Stern, Ph.D., associate professor of preventive medicine at the Keck School of Medicine of USC, led analyses for the study, "Red meat and poultry, cooking practices, genetic susceptibility and risk of prostate cancer: Results from the California Collaborative Prostate Cancer Study." ...
BEER-SHEVA, Israel, August 16, 2012 – Ben-Gurion University of the Negev (BGU) researchers revealed that a majority of children suffering from Obstructive Sleep Apnea (OSA) treated with montelukast, a drug approved for asthma or hay fever, showed significant improvement in respiratory disturbance and adenoid size, according to a new study published in Pediatrics Journal.
A considerable percentage of children who suffer from OSA and undergo tonsillectomies and polypectomies occasionally suffer from post-operative infection, bleeding and dehydration. Some children experience ...
Engineers at a company co-founded by a University of Texas at Dallas professor have identified a material that can reduce the pollution produced by vehicles that run on diesel fuel.
The material, from a family of minerals called oxides, could replace platinum, a rare and expensive metal that is currently used in diesel engines to try to control the amount of pollution released into the air.
In a study published in the August 17 issue of Science, researchers found that when a manmade version of the oxide mullite replaces platinum, pollution is up to 45 percent lower ...
To speed up the process of identifying threatened and endangered plant species, a team of New York Botanical Garden scientists has developed a streamlined method for evaluating the conservation status of large numbers of plant species, using information from plant research collections and Geographic Information Systems technology.
Faced with such threats as deforestation, climate change, and invasive species, a significant proportion of the world's plant species are commonly believed to be in serious decline and possibly headed toward extinction. For government officials, ...
DENVER — Almost half of college students judge men and women with similar sexual histories by the same standard and hold equally negative attitudes towards both their male and female peers who they believe hook up "too much," suggests new research to be presented at the 107th Annual Meeting of the American Sociological Association.
"Men and women are increasingly judging each other on the same level playing field," said Rachel Allison, co-author of the study and a doctoral candidate in the University of Illinois at Chicago's Department of Sociology. "But, gender equality ...
DENVER — Many have argued the Marxist theories of a classless society died with the collapse of the Soviet Union and a faltering Cuba, but a University of Dayton study has found a place where such approaches may have a shot of survival—Facebook, and other social networking sites.
University of Dayton sociologist and criminologist Art Jipson discovered in his most recent research that the homeless, along with everyone else, are turning to social media and that social media sites are turning into places where all people are truly equal.
Jipson, an associate sociology ...
DENVER — New research out of the University of Cincinnati is believed to be the first to examine the relative impact of militarization and corruption on civilian populations. The findings reveal that a specific form of military organization—praetorian militarization—as well as national-level corruption—both adversely affect the well-being of citizens. The findings by Steve Carlton-Ford, a professor and head of the UC sociology department, and T. David Evans, a UC emeritus associate professor of sociology, will be presented at the 107th Annual Meeting of the American Sociological ...
In a 2010 survey of laid-off workers across the United States, married moms spent more time between jobs and were overall less likely to find new jobs compared with married dads. Once re-employed, married moms experienced a decrease in earnings of $175 more per week compared with married dads.
The results suggest that the recent recession, dubbed the "man-cession" or "he-cession" because more men than women lost jobs, could also be viewed as a "mom-cession" as laid-off moms had the hardest time finding new jobs.
"These findings hold true across different backgrounds, ...
