This indicates that GABAergic system may play an important role in the pathogenesis and development of malignant tumors, and their expression levels are important for prognosis.

A research to be published in the World Journal of Gastroenterology on December 21,2008 addresses a new finding about this hotpoint. The research team led by Prof. Li from Cancer Institute of Central South University used in silico databases to identify genes that were overexpressed in HCC. In this way, they identified the overexpression of GABA receptor 3 subunit (GABRA3) in HCC cells. Knockdown of endogenous GABRA3 expression in HepG2 attenuated HCC cell growth, suggesting its role in HCC cell viability. They also determined the in vitro and in vivo effect of GABA on the proliferation of GABRA3-positive cell lines, and found that GABA increased HCC growth in a dose-dependent manner. Notably, the addition of GABA into the cell culture medium promoted the proliferation of GABRA3-expressing HepG2 cells, but not GABRA3-knockdown HepG2 cells. That means GABA stimulates HepG2 cell growth through GABRA3.

These findings highlight the importance of elucidating the role GABAergic activity play in the pathogenesis of HCC. GABA and GABRA3 could play important roles in HCC development and progression and can be a promising molecular target for the development of new diagnostic and therapeutic strategies for HCC.

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Similar to mice, humans treated with ondansetron before or while receiving morphine showed a significant reduction in withdrawal signs compared with when they received morphine but not ondansetron. "A major accomplishment of this study was to take lab findings and translate them to humans," said principal investigator J. David Clark, MD, PhD, professor of anesthesia at Stanford University School of Medicine and the Palo Alto Veterans Affairs Health Care System.

Chu plans on conducting a clinical study to confirm the effectiveness of another ondansetron-like drug in treating opioid withdrawal symptoms in a larger group of healthy humans. And the research team will continue to test the effectiveness of ondansetron in treating opioid addiction.

The scientists warned that ondansetron will not by itself resolve the problems that arise with continued use of these painkillers. Addiction is a long-term, complex process, involving both physical and psychological factors that lead to compulsive drug use. "This is not a cure for addiction," said Clark. "It's na ve to think that any one receptor is a panacea for treatment. Treating the withdrawal component is only one way of alleviating the suffering. With luck and determination, we can identify additional targets and put together a comprehensive treatment program."

Collaborators on this study included De-Yong Liang, PhD, the study's co-lead author, previously a research associate in the Department of Anesthesia and currently a research associate at the Palo Alto Institute for Research and Education; Xiangqi Li, MD, a life science research assistant in the department; Nicole D'Arcy, a medical student: Peyman Sahbaie, MD, a research associate at the institute; and Guochun Liao, PhD, of the pharmaceutical company Hoffman-La Roche. This work was supported by grants to Clark from the National Institutes of Health and the National Institute on Drug Abuse, and grants to Chu from the NIH and the National Institute of General Medical Sciences.

The researchers are working with the Stanford University Office of Technology Licensing to seek a patent for the use of ondansetron and related medicines in the treatment of drug addiction.

med-www.stanford/