(Press-News.org) Irvine, Calif., Sept. 17, 2012 — Researchers with UC Irvine's Chao Family Comprehensive Cancer Center have identified a major reason why melanoma is largely resistant to chemotherapy.
UCI dermatologist Dr. Anand Ganesan and colleagues found a genetic pathway in melanoma cells that inhibits the cellular mechanism for detecting DNA damage wrought by chemotherapy, thereby building up tolerance to cancer-killing drugs.
Targeting this pathway, comprising the genes RhoJ and Pak1, heralds a new approach to treating the deadly skin cancer, which claims nearly 10,000 U.S. lives each year. Study results appear online in Cancer Research, a journal of the American Association for Cancer Research.
"If we can find a way to turn off the pathway responsible for this resistance, melanoma tumors would suddenly become sensitive to therapies we've been using for the last 20 years," said Ganesan, assistant professor of dermatology and biological chemistry at UCI.
In pursuit of a cause for the chemo tolerance, he and his colleagues performed a genome-wide scan for genes controlling drug resistance in melanoma cells. Their search identified RhoJ, a gene normally involved in blood vessel growth. They saw that in response to drug-induced DNA damage in a melanoma cell, RhoJ activated another gene, Pak1, which initiated a molecular cascade suppressing the cell's ability to sense this damage – and blocking the apoptosis process.
"Normally, such drug-induced DNA damage would result in cell death," Ganesan said. "But this blunting of DNA damage response allows melanoma cells to mutate and proliferate. Being capable of rapid adaptation and change is a hallmark feature of this challenging form of cancer and makes it very difficult to treat."
On the heels of this discovery, he and colleagues have begun exploring methods to inhibit the genes responsible for this DNA damage tolerance. What they come up with could one day supplement chemotherapy treatments for melanoma, Ganesan added.
INFORMATION:
Hsiang Ho, Jayavani Aruri, Rubina Kapadia and Hootan Mehr of UCI and Michael A. White of the University of Texas Southwestern Medical Center at Dallas participated in the study, which received support from the National Institutes of Health, the University of California Cancer Research Coordinating Committee, the American Cancer Society, Outrun the Sun Inc. and the Robert A. Welch Foundation.
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Boulder, Colo., USA – GSA Bulletin papers posted online from 20 July through 14 September 2012 elaborate on geoscience from Algeria, Mexico, Spain, Turkey, Nova Scotia, Switzerland, New Mexico, and the U.S. Rocky Mountains. Topics include tectonics, mineral formation, the Moho, age dating using zircon crystals, the Code of Stratigraphic Nomenclature, atmospheric CO2, and early animal evolution.
GSA Bulletin articles published ahead of print are online at http://gsabulletin.gsapubs.org/content/early/recent. Representatives of the media may obtain complimentary copies of ...
JACKSONVILLE, Fla. — An enzyme that could represent a powerful new tool for combating Alzheimer's disease has been discovered by researchers at Mayo Clinic in Florida. The enzyme — known as BACE2 — destroys beta-amyloid, a toxic protein fragment that litters the brains of patients who have the disease. The findings were published online Sept. 17 in the science journal Molecular Neurodegeneration.
Alzheimer's disease is the most common memory disorder. It affects more that 5.5 million people in the United States. Despite the disorder's enormous financial and personal ...
A new University of Iowa study suggests there are two root causes of a type of diabetes associated with cystic fibrosis (CF). The findings, which already have sparked a clinical trial, may guide development of new treatments or even help prevent diabetes in patients with CF.
Almost half of patients with CF will develop diabetes by age 30 and almost one quarter will develop it in their teens. In addition to the health problems caused by high blood sugar, diabetes also worsens lung disease and increases the risk of dying for people with CF. However, the underlying cause ...
Researchers from North Carolina State University have found identical strains of antibiotic-resistant Campylobacter coli (C. coli) in both antibiotic-free (ABF) and conventionally raised pigs. This finding may indicate that these antibiotic-resistant pathogens can persist and thrive in the environment, regardless of antimicrobial usage by pork producers.
Dr. Siddhartha Thakur, assistant professor of population health and pathobiology, had previously found that antibiotic-resistant C. coli, a leading cause of foodborne illness in the U.S., was present in both ABF-certified ...
New in our journals:
Your city matters: San Francisco v. Boston
Your home city matters for both who you are and how you feel, according to a new suite of studies. In seven studies, researchers examined the history and culture of San Francisco and Boston, as well as surveyed residents (including commuters, college students, and middle-aged residents) of each city. They found that San Francisco showed more emphasis on egalitarianism, innovation, and looser social norms, while Boston emphasizes tradition, community, and tighter social norms. As a result, for Bostonians, ...
Saturday, September 15, 2012, Cleveland: Cleveland Clinic researchers have discovered that vitamin E may prevent cancer in patients with an under-recognized genetic disorder.
Several genetic mutations are known to be present in Cowden Syndrome (CS) – a disease that predisposes individuals to several types of cancers, including breast and thyroid cancers. One type of mutation in the succinate dehydrogenase (SDH) genes may be responsible for cancer development, according to research by Charis Eng, M.D., Ph.D., Hardis Chair and Director of the Genomic Medicine Institute ...
TORONTO, Sept. 17, 2012—Whether your neighbourhood is conducive to walking could determine your risk for developing diabetes, according to a new study by researchers at St. Michael's Hospital and the Institute for Clinical Evaluative Sciences.
Researchers found this risk was particularly high for new immigrants living in low-income neighbourhoods. A new immigrant living in a less walkable neighbourhood – fewer destinations within a 10-minute walk, lower residential density, poorly connected streets – was about 50 per cent more likely to develop diabetes when compared ...
The NFL season is off and running and with it comes the proverbial hamstring injury, the torn tendon, the groin strain – injuries that players have come to expect as part of this high-energy contact sport. Far less top of mind is the rare but catastrophic cervical spine injury, but that's exactly the injury that Mercyhurst University researchers are working with Sports Medicine Concepts and the National Football League (NFL) to mitigate.
One tragic example came Sept. 8 when Tulane University safety Devon Walker fractured his spine in a head-on collision with a teammate ...
A new study that identifies ways to reduce the factors that lead to an asthma attack gives hope to asthma sufferers. A UCSF researcher and his colleagues believe they have found a way to help asthma sufferers by impeding the two most significant biological responses that lead to an asthma attack.
Asthma, a respiratory disorder that causes shortness of breath, coughing and chest discomfort, results from changes in the airways that lead to the lungs. It affects 18.7 million adults and 7.0 million children in the US, according to the Centers for Disease Control and Prevention.
In ...
EAST LANSING, Mich. — The discovery of a new gene could lead to better bug-resistant plants.
Research led by Michigan State University and appearing on the cover of this week's Proceedings of the National Academy of Sciences, demonstrates that domestic tomatoes could re-learn a thing or two from their wild cousins.
Long-term cultivation has led to tomato crops losing beneficial traits common to wild tomatoes. Anthony Schilmiller, MSU research assistant professor of biochemistry and molecular biology, was able to identify a gene that is involved in one of these beneficial ...
