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This Week in the Journal of the National Cancer Institute: May 17, 2012

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In the Journal of the National Cancer Institute this week, researchers in China examine the role of glycogen synthase kinase-3β in human osteosarcoma. GSK-3β is a serine/threonine protein kinase that recent studies suggest may act as both tumor suppressor and oncogene, depending on the tumor type. For this study, the team used various assays to analyze the effect of altered GSK-3β expression on U2OS, MG63, SAOS2, U2OS/MTX300, and ZOS osteosarcoma cell lines and in nude mice injected with cancer cells and GSK-3β. "Osteosarcoma cells with low levels of inactive p-Ser9-GSK-3β formed colonies in vitro and tumors in vivo more readily than cells with higher levels and cells in which GSK-3β had been silenced formed fewer colonies and smaller tumors than parental cells," the authors found. Further, silencing or inhibition of GSK-3β led to apoptosis of the cancer cells. "Inhibition of GSK-3β resulted in inhibition of the NF-κB pathway and reduction of NF-κB-mediated transcription," they add. "Combination treatments with GSK-3β inhibitors, NF-κB inhibitors, and chemotherapy drugs increased the effectiveness of chemotherapy drugs in vitro and in vivo."

Also in the Journal of the National Cancer Institute this week, researchers in Italy examine the best way to devise a TNM — tumor, node, metastasis — staging system for pancreatic neuroendocrine neoplasms. Both the European Neuroendocrine Tumor Society and the International Union for Cancer Control/American Joint Cancer Committee/World Health Organization have described proposals for such systems. In this study, the team examined 1,072 patients who had undergone surgery for their disease and collected data on 28 variables. They found that only the ENETS TNM staging system "perfectly allocated patients into four statistically significantly different and equally populated risk groups." Both systems were independent predictors of survival, the researchers write, but "the UICC/AJCC/WHO 2010 TNM stages showed very large 95 percent confidence intervals for each stage, indicating an inaccurate predictive ability. …Our data suggest the ENETS TNM staging system is superior."

Finally in the Journal of the National Cancer Institute this week, NCI researchers examine the effect of body mass index on lung cancer risk for current, former, and never smokers. The team prospectively examined data from 448,732 men and women aged 50 to 71 who were recruited between 1995 and 1996 and identified 9,437 incident lung carcinomas during a mean follow-up of 9.7 years. They conclude that BMI was inversely associated with risk of lung cancer among both men and women, though this association was restricted to current and former smokers.

The Scan

Self-Reported Hearing Loss in Older Adults Begins Very Early in Life, Study Says

A JAMA Otolaryngology — Head & Neck Surgery study says polygenic risk scores associated with hearing loss in older adults is also associated with hearing decline in younger groups.

Genome-Wide Analysis Sheds Light on Genetics of ADHD

A genome-wide association study meta-analysis of attention-deficit hyperactivity disorder appearing in Nature Genetics links 76 genes to risk of having the disorder.

MicroRNA Cotargeting Linked to Lupus

A mouse-based study appearing in BMC Biology implicates two microRNAs with overlapping target sites in lupus.

Enzyme Involved in Lipid Metabolism Linked to Mutational Signatures

In Nature Genetics, a Wellcome Sanger Institute-led team found that APOBEC1 may contribute to the development of the SBS2 and SBS13 mutational signatures in the small intestine.