New Virus Found in Some Men with Prostate Cancer

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Researchers from the Cleveland Clinic and the University of California, San Francisco have identified a new virus, named XMRV, which may be linked to the development of prostate cancer. The preliminary results from their work were presented at the 2006 Prostate Cancer Symposium, held February 24-26 in San Francisco.

The researchers used a DNA ViroChip, which holds the genetic sequences of approximately 1,000 viruses - all known viruses of humans, animals, and plants - to screen prostate tumor samples from 86 men who underwent surgical resection of their tumors. They compared infection with the XMRV virus between men with mutations in both copies of the gene HPC1, which encodes the virus-fighting protein RNaseL, with men with one or both normal copies of the gene. Previous research had shown that mutations in HPC1 correlated with a higher risk of prostate cancer. In those studies, the presence of the virus also correlated strongly with mutations in HPC1: 45 percent of men with two mutated copies of HPC1 harbored the XMRV virus, compared with 1.5 percent of men with one or no mutated copies of HPC1. The virus was found to be actively expressing proteins within the prostate cells, not lying dormant.

It is not yet known if the virus plays a role in the development of prostate cancer. In a press release accompanying their presentation, lead investigator Dr. Eric Klein explained that previous studies had suggested an infectious origin for some types of prostate cancer: "The hypothesis is that infection leads to chronic inflammation of the prostate, which ultimately leads to cancer." Dr. Klein and his collaborators are currently working on an experimental design to examine whether XMRV does play a causative role in prostate carcinogenesis.

Tobacco Use Among Young People Is Rising Worldwide

The Global Youth Tobacco Survey (GYTS) has found that tobacco use is on the rise among young people worldwide, in a report published online February 17 in the Lancet.

GYTS, developed by the Centers for Disease Control and Prevention (CDC) and the World Health Organization (WHO), surveyed approximately 750,000 students aged 13 to 15 years from 131 countries, the Gaza Strip, and the West Bank about tobacco use, the leading cause of several cancers and cardiovascular and respiratory diseases. Results showed that overall, nearly 9 percent of students were current smokers and 11 percent were current users of tobacco products other than cigarettes. The GYTS also found that more than 30 percent of students in every region of the world were exposed to secondhand smoke at home, while more than 45 percent were exposed to secondhand smoke in public places.

Dr. Charles Warren, of CDC's Office of Smoking and Health, commented that the GYTS findings suggest that the effect of tobacco use on worldwide deaths could be far greater than expected. He added that current warnings of a doubling of the death toll to 10 million deaths per year by 2020 could be a conservative estimate. A Lancet editorial stated that unless the WHO Framework Convention on Tobacco Control signatories fully commit to enhancing their tobacco control and prevention efforts, the myriad achievements of these initiatives will be lost.

According to another article in the same issue of Lancet, one of the largest developing countries facing this alarming trend is India, where increased tobacco use among young people in urban areas is expected to result in a substantial burden of disease and health care expenditures.

The recent NCI-funded study was conducted by the University of Minnesota School of Public Health and Project Mobilizing Youth for Tobacco-Related Initiatives in India. The researchers surveyed over 11,600 students in sixth and eighth grades in 32 schools in Delhi and Chennai. A key finding was that students in sixth grade were two to four times more likely to use tobacco than those in eighth grade, and that psychosocial risk factors for tobacco were also greater in the younger students. As the authors note, "These findings might indicate the initial wave of a large increase in tobacco use in India, which is alarming and warrants confirmation and early intervention in young students."

New NSAID Reverses Ovarian Cancer Cell Resistance to Cisplatin

A new study indicates that NCX-4016, a nonsteroidal anti-inflammatory drug (NSAID) derived from aspirin, has cytotoxic effects in ovarian cancer cells and can reverse acquired resistance to cisplatin. The results were published in the February 23 Proceedings of the National Academy of Sciences.

NCX-4016 is being studied for a number of indications, including colon cancer prevention.

One proposed mechanism behind cisplatin resistance is an increase in the level of thiols - sulfur analogs of alcohols - within the cancer cells, which can inactivate platinum compounds. The release of nitrous oxide (NO) by compounds such as NCX-4016 is stimulated by high levels of cellular thiols. NO can then react with thiols in cytotoxic pathways. The investigators hypothesized that NCX-4016 not only would be toxic to ovarian cancer cells when administered alone, but also would decrease the thiol content in the cells through reactions with NO and resensitize the cells to cisplatin.

After identifying ovarian cancer cell lines as cisplatin sensitive (CS) or cisplatin resistant (CR), and confirming that NCX-4016 releases NO in vitro, the investigators exposed CS and CR cells to NCX-4016 and performed cell-survival assays. NCX-4016 alone caused cell death in both CS and CR lines; the magnitude of the effect depended on dose and exposure time.

When the investigators treated both CS and CR cell lines with cisplatin, the drug caused a significant reduction in colony formation in CS cells but not CR cells, as expected. Treatment with NCX-4016 before exposure to cisplatin caused significantly greater cell death in both CS and CR cells than treatment with cisplatin or NCX-4016 alone. Examination of the thiol content of CS and CR cells revealed that CR cells had approximately 75 percent more glutathione than CS cells, and that the levels of this thiol were substantially reduced by treatment with NCX-4016.

These results suggest "a dual role for NCX-4016 in CR cells," state the investigators, as it provides both an antiproliferative effect and thiol depletion. "The thiol depletion creates an opportunity for cisplatin for further cell killing."