Certain mutations in the DNA of the hepatitis B virus (HBV) are associated with the development of liver cancer and may help predict which patients with HBV infections are at increased risk of the disease, according to a large meta-analysis in the Journal of the National Cancer Institute, published online July 2.

HBV infection is a known cause of hepatocellular carcinoma (HCC), the most common form of liver cancer. Previous studies have looked at whether patients with specific mutations in the viral DNA may be at increased risk of developing the cancer, but most of the studies were small and they produced conflicting results.

This meta-analysis, conducted by Guangwen Cao, M.D., Ph.D., of the Second Military Medical University in Shanghai and colleagues, included 43 studies with a total of 11,582 HBV-infected participants, of whom 2,801 had HCC. The researchers found that certain mutations were associated with development of HCC and more prevalent as chronic HBV infection progressed from the asymptomatic state to liver cirrhosis or HCC.

“Frequent examination of patients with chronic HBV infections for the presence of these mutations may be useful for identifying which patients require preventive antiviral treatment and for the prediction of HCC,” the authors write.

Source:
Steve Graff

Journal of the National Cancer Institute

Several statistical and biological issues need to be addressed in order to improve biomarker identification for early detection of cancer, according to a commentary published online July 2 in the Journal of the National Cancer Institute.

The biomarker pipeline to develop and evaluate cancer screening tests includes the identification of promising biomarkers to detect cancers early and the initial and definitive evaluation of biomarkers for cancer screening.

In the commentary, Stuart G. Baker, ScD, of the National Cancer Institute in Bethesda, Md., discusses the various ways to improve this pipeline, including the need for more frequent specimen collection to help identify promising biomarkers and the use of the paired availability design, in which data are collected on the number of interval cases associated with screening in time periods before and after the introduction of the new biomarker test.

“…[S]ome important design and analysis considerations related to this biomarker pipeline have been underappreciated, insufficiently disseminated, or not previously discussed,” the author writes. “By taking these considerations into account, researchers can improve this biomarker pipeline.”

Source:
Steve Graff

Journal of the National Cancer Institute

A new three-dimensional computer protein map is helping researchers at the University of Alabama at Birmingham (UAB) unravel the biological pathways that control brain-cell death after a stroke.

The new map will help identify new drug targets and test compounds to slow brain-cell death, halt brain cancer and improve pain control, the study authors said. The findings are published online in the Journal of Biological Chemistry.

Starting with known cell coordinates, biological structures and other data, UAB researchers focused on a protein called acid-sensing ion channel-1, or ASIC-1. This protein acts as a gateway on the surface of brain cells called neurons. The researchers generated a 3-D computer map of ASIC-1, which greatly simplifies the testing of any drug or compound designed to protect neurons, regulate their molecular interactions or isolate brain tumors.

“This protein ASIC-1 has a lot of little nooks and crevices where other molecules can sit and interact with the channel,” said Yawar Qadri, a graduate student in the UAB Department of Physiology and Biophysics and the study’s lead author. “With the map we’ve generated and the area we’ve described, researchers can fine-tune their ideas and tailor experimental compounds.”

Dale Benos, Ph.D., chair of the Department of Physiology and Biophysics and a co-author on the study, said the ASIC-1 map is an invaluable tool in the ongoing search for new drugs that will specifically act on this biological pathway.

“The hope is that when a person has a stroke or they get diagnosed with a brain tumor, the patient can be given a drug that will keep his or her neurons alive and functioning longer, or we can keep cancer from migrating further,” Benos said.

The study began with a toxin found only in the venom of the Trinidad chevron tarantula. In earlier laboratory research, this venom toxin proved capable of slowing neuronal death, inhibiting cancer growth and improving other biological disorders. UAB researchers wanted to simplify the search for non-venom agents that interact with ASIC-1 for positive results.

Qadri and his UAB colleagues generated the map of ASIC-1 with a software program called Modeller, developed by engineers at the University of California, San Francisco. The UAB ASIC-l map study includes validation work confirming its accuracy.

Source: University of Alabama at Birmingham