Alcohol and hepatitis C are a dangerous cocktail, Keck researchers find
The study appeared earlier this month in the Proceedings of the National Academy of Sciences.
The research clarifies the complex molecular events that link alcoholism and HCV to increased risk of hepatocellular carcinoma (HCC), the fifth most common cancer worldwide, said Keigo Machida, Ph.D., assistant professor of molecular microbiology and immunology at the Keck School.
There is ample evidence that chronic liver damage caused by viral infection, alcohol, metabolic syndrome or these factors in combination can increase the risk for HCC, Machida said. However, the molecular mechanism for the synergy among alcohol, HCV and liver cancer has remained unclear.
“Understanding the molecular link holds great potential for future treatment of this particular form of liver cancer,” Machida said. “The signaling mechanism gives researchers a new drug therapy target for treating HCC.”
Machida and his colleagues focused their research on a viral protein, NS5A, which they had found in earlier experiments stimulated high expression of a receptor for bacterial endotoxins, known as Toll-like receptor 4 (TLR4). Alcohol intake increases the risk of leaking bacterial toxin from the gut, which the researchers believe causes over-activation of endotoxin receptor signaling if patients are also infected by HCV.
This excess antibacterial reaction then results in an increased risk of tumor growth should the body’s natural anti-tumor response weaken as a result of the infection, Machida explained.
Researchers conducted a series of experiments with mice and also examined liver biopsy samples from human patients infected with HCV, and found high levels of the protein NS5A and TLR4. In the subset of patients who were also alcoholics, the researchers saw signs of increased antibacterial response. The research also identified a specific molecule called Nanog, which acts as a stem cell marker in tumor development when activated by TLR4.
“There were several major findings that resulted from this study,” Machida said. “We established a mouse model which will enable us to better understand alcohol and hepatitis C virus infection and we found the signaling that causes tumor development in mice through the receptor TLR4.”
“More research is needed, but if we are able to target and suppress these molecules identified in the study, we may be able to stop the cancer’s lifeline.”
The study was supported by National Institute on Alcohol Abuse and Alcoholism/National Institutes of Health-funded Southern California Research Center for Alcoholic Liver and Pancreatic Diseases and Cirrhosis (P50AA11199) headquartered at the Keck School of Medicine.
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USC in the News
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The Chronicle of Higher Education mentioned USC’s $6 billion fundraising campaign. The story noted that USC had already raised $1 billion in a “quiet phase,” including the $200 million naming gift from USC Trustee and alumnus David Dornsife and wife Dana Dornsife to the USC Dornsife College.
The Guardian (U.K.) highlighted two major gifts to USC in a list of the 10 biggest philanthropic benefactors in America. The list included the $200 million naming gift from USC Trustee and alumnus David Dornsife and wife Dana Dornsife to the USC Dornsife College, and the $110 million gift from USC Trustee and USC Viterbi School alumnus John Mork and wife Julie to create the USC Mork Family Scholars Program.
The New York Times featured the USC U.S.-China Institute documentary “Assignment: China — The Week that Changed the World.” The documentary, part of a series, examines media coverage of the 1972 Nixon trip that reshaped U.S.-China relations after a quarter century of isolation and hostility. “People look back now and take it for granted that the outcome was preordained,” said the institute’s Mike Chinoy, who produced the documentary. Voice of America also featured the story.
Los Angeles Times featured the Oscar Senti-meter, a tool developed by the USC Annenberg School, Los Angeles Times and IBM that analyzes thousands of tweets about the Academy Awards nominees. The story noted that Mexican actor Demian Bechir received an enormous boost on Twitter the day of the nominations, with a total of 6,893 tweets mentioning him, a 47-fold increase from the day before. The story noted the tool uses language-recognition technology developed in collaboration with USC Viterbi School’s Signal Analysis and Interpretation Lab.
The Times of India (India) featured a three-day medical emergency training workshop organized in association with USC. At the workshop, held at GCS Medical College in India, 50 doctors and more than 100 paramedics learned how to improve emergency support systems. William Mallon of the Keck School of USC said that discussion topics included the use of portable ultrasonic devices to scan patients. “The ultrasound applications help physicians make accurate and timely decisions,” he noted. Daily News & Analysis (India) also featured the workshop.
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