Researcher at Childrens Hospital LA discovers way to overcome radiation resistance in leukemia

Radiation-resistant leukemia cells can be killed by radiation after inhibition of a molecular target by a rationally designed new drug

2010-10-01

(Press-News.org) LOS ANGELES (September 29, 2010) – A team of researchers lead by Fatih M. Uckun, MD, PhD, of The Saban Research Institute of Childrens Hospital Los Angeles has determined that radiation resistance in leukemia can be overcome by selectively attacking a molecular target known as SYK tyrosine kinase.

B-lineage acute lymphoblastic leukemia (ALL) is the most common cancer occurring in children and adolescents. Despite having received intensive chemotherapy, some patients have recurring disease, known as relapse. For these individuals, the prospect of long-term survival is poor.

The standard approach to treating relapsed patients has been additional chemotherapy to achieve a second remission followed by very intensive treatment that could include "supralethal" chemotherapy, total-body irradiation (TBI), and hematopoietic stem cell transplantation. However, radiation resistance of leukemia cells hampers the success of these rigorous therapeutic approaches and results in poor survival.

"We knew that we could kill radiation-resistant leukemia cells if we only knew what made them so resistant. So we set out to determine the mechanism," said Dr. Uckun, who is also professor of Research Pediatrics at the Keck School of Medicine at the University of Southern California. "Once we determined the mechanism, the next step was obvious -- to rationally design a drug that would take out that specific target."

Uckun's research team has now provided the first proof-of-principle that radiation resistance of an aggressive leukemia can indeed be overcome using this rationally-designed specific drug directed against the resistance machinery of leukemia cells.

"Radiation therapy was much more effective against leukemia in mice when it was combined with this new drug candidate that we named C-61," said Dr. Uckun.

INFORMATION:

The results of the study will be published in the October 2010 issue of Radiation Research, the official journal of the Radiation Research Society.

The Saban Research Institute at Childrens Hospital Los Angeles is among the largest and most productive pediatric research facilities in the United States, with 100 investigators at work on 186 laboratory studies, clinical trials and community-based research and health services. The Saban Research Institute is ranked eighth in National Institutes of Health funding among children's hospitals in the United States.

Founded in 1901, Childrens Hospital Los Angeles is one of the nation's leading children's hospitals and is acknowledged worldwide for its leadership in pediatric and adolescent health. Childrens Hospital Los Angeles is one of only seven children's hospitals in the nation – and the only children's hospital on the West Coast – ranked for two consecutive years in all 10 pediatric specialties in the U.S. News & World Report rankings and named to the magazine's "Honor Roll" of children's hospitals.

Childrens Hospital Los Angeles is a premier teaching hospital and has been affiliated with the Keck School of Medicine of the University of Southern California since 1932.

Reference: F. M. Uckun, I. Dibirdik, S. Qazi (2010) Augmentation of the Antileukemia Potency of Total-Body Irradiation (TBI) by a Novel P-site Inhibitor of Spleen Tyrosine Kinase (SYK). Radiation Research: October 2010, Vol. 174, No. 4, pp. 526-531.

www.chla.org

[Attachments] See images for this press release:

ELSE PRESS RELEASES FROM THIS DATE:

How to improve health and reduce risk for dialysis patients

2010-10-01

Early Online Releases: 1. Depression Symptoms and Low Physical Activity May Keep Dialysis Patients from Working Efforts to Improve Mood and Activity Might Help Patients Remain Employed Many patients with kidney failure employed during the year before beginning dialysis are no longer employed early in their first year of treatment. A recent survey by Nancy Kutner, PhD (Emory University) and her colleagues indicates that depression and reduced physical activity may play a role. Among 585 dialysis patients who had worked in the previous year, only 191 (32.6%) continued ...

New method for generating human stem cells is remarkably efficient

2010-10-01

The ability to efficiently generate patient-specific stem cells from differentiated cells and then reliably direct them to form specialized cells (like neurons or muscle) has tremendous therapeutic potential for replacing diseased or damaged tissues. However, despite some successes, there have been significant limitations associated with existing methods used to generate human induced pluripotent stem cells (iPSCs). Now, a study published by Cell Press on September 30th in the journal Cell Stem Cell presents a novel strategy for creating iPSCs that exhibits some significant ...

Genetic alteration linked with human male infertility

2010-10-01

One in seven couples worldwide has difficulty conceiving a child, and male infertility is thought to account for nearly half of those cases. Although the cause of male infertility is often unknown, scientists have now discovered a genetic alteration that disrupts sperm production in otherwise healthy men. The research, published by Cell Press on September 30th in the American Journal of Human Genetics, provides new insight into one cause of male infertility. "Many genes are known to be essential for the production of sperm, but there are surprisingly few single gene changes ...

Fossilized giant penguin reveals unusual colors, sheds light on bird evolution

2010-10-01

Paleontologists have unearthed the first extinct penguin with preserved evidence of scales and feathers. The 36-million-year-old fossil from Peru shows the new giant penguin's feathers were reddish brown and grey, distinct from the black tuxedoed look of living penguins. The new species, Inkayacu paracasensis, or Water King, was nearly five feet tall or about twice the size of an Emperor penguin, the largest living penguin today. "Before this fossil, we had no evidence about the feathers, colors and flipper shapes of ancient penguins. We had questions and this was ...

Researchers sequence genome of mosquito that spreads West Nile virus

2010-10-01

RIVERSIDE, Calif. – Last year, 720 people in the United States became infected with West Nile virus, a potentially serious illness that is spread through the bite of a mosquito – the Culex mosquito – that has first fed on infected birds. Such mosquitoes have the virus eventually located in their salivary glands and transmit the disease to humans and animals when they bite to draw blood. To understand the genetic makeup of the Culex mosquito, and how the insect is able to transmit this and other viruses, an international team of scientists, led by geneticists at the ...

Researchers advance biosynthesis of potent anti-cancer drug Taxol

2010-10-01

MEDFORD/SOMERVILLE, Mass.--Researchers from Tufts University School of Engineering and MIT have reported a new way to biosynthesize important precursors to the potent anti-cancer compound Taxol in an engineered strain of E. coli bacteria. The findings are significant steps on the way to achieving cost-effective, large-scale production of Taxol and the effort to design new Taxol-like pharmaceuticals. The work is reported in the October 1, 2010, issue of the journal Science. Taxol (paclitaxel) and its structural analogs are among the most powerful and commercially ...

Researchers decode genome of mosquito that spreads West Nile virus, encephalitis and elephantiasis

2010-10-01

Chestnut Hill, Mass. (9/30/2010) – Scientists have sequenced the genome of the Southern house mosquito, providing new insights into the most diverse and widespread of three groups of disease-bearing mosquitoes and shedding new light on the transmission of mosquito-borne diseases such as malaria, encephalitis, West Nile virus and filariasis, international teams of researchers report in the upcoming edition of the journal Science. Breeding in drains, cesspools and other polluted water bodies, Culex quinquefasciatus feeds on blood from birds, livestock and humans and transmits ...

Ethnicity: A reason for heart problems post-transplant in South Asians

2010-10-01

Ethnicity is a contributing risk factor of cardiovascular problems in kidney recipients of South Asian origin post-transplant, according to a study appearing in an upcoming issue of the Clinical Journal of the American Society Nephrology (CJASN). South Asians comprise 25% of all Canadian visible minorities and have a higher risk for cardiovascular disease in the general population. However, the risk of cardiovascular events has never been studied in this minority population. To investigate, G.V. Ramesh Prasad, MBBS, MSc, FRCPC, FACP, FASN (University of Toronto) and ...

Fossilized giant penguin feathers reveal color, feather structure of ancient birds

2010-10-01

A North Carolina State University researcher is part of a team that has discovered fossilized feathers from a giant penguin that lived near the Equator more than 36 million years ago. These feathery fossils reveal color patterns in an ancient extinct penguin species, and offer clues to how modern penguin feathers evolved. The penguin in question – dubbed Inkayacu paracasensis, or Water King – dates from the late Eocene period and stood almost five feet tall. The fossil was discovered near the Paracas Reserve, located along the eastern coastline of Peru. A research team ...

Dinosaurs significantly taller than previously thought, MU researcher finds

2010-10-01

COLUMBIA, Mo.– It might seem obvious that a dinosaur's leg bone connects to the hip bone, but what came between the bones has been less obvious. Now, researchers at the University of Missouri and Ohio University have found that dinosaurs had thick layers of cartilage in their joints, which means they may have been considerably taller than previously thought. The study is being published this week in the journal PLoS ONE (Public Library of Science). "Our study of the limbs of modern-day relatives of dinosaurs shows that dinosaurs were significantly taller than original ...

Researcher at Childrens Hospital LA discovers way to overcome radiation resistance in leukemia

ELSE PRESS RELEASES FROM THIS DATE:

LAST 30 PRESS RELEASES: