Devanand Sarkar and colleagues, at Virginia Commonwealth University School of Medicine, Richmond, have now identified a gene that is expressed at high levels in human HCC tumor samples and generates a protein important for HCC progression. They therefore suggest that targeting this gene (AEG1), or the protein that it generates, might provide a new therapeutic strategy for the treatment of HCC.

In the study, human liver cells were found to express only low levels of the protein AEG1, whereas human HCC tumor samples expressed very high levels. This was associated with an increase in the number of copies of the AEG1 gene in human HCC tumor samples. Functionally, human liver cell lines engineered to overexpress AEG1 grew faster than nonengineered cells and developed into highly aggressive tumors when transplanted into mice. In addition, knocking down levels of AEG1 in human HCC cell lines after they had been allowed to form a tumor in mice limited further growth. Further analysis revealed that the effects of AEG1 were mediated, in part, via its ability to activate the Wnt signaling pathway.

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HAPI study participants drank a 782-calorie per m(2) body surface area milkshake and were then monitored for the next six hours with blood tests - including the VAP Test - plus ultrasound tests of the brachial artery to determine how they were reacting to the high-fat meal. Results showed that Amish who were carriers of the gene mutation - only one copy of the APOC3 gene instead of two - would rapidly break down triglycerides, the fat particles in the blood associated with an increased risk of coronary artery disease. Those with the gene abnormality also had lower triglycerides both before and after the fat load and better lipid profiles overall.

"This is a brilliant GWAS study that beautifully illustrates the value of advanced lipid profiling, direct LDL determination and the value of postprandial measurement of remnant lipoproteins," said James Ehrlich, M.D., Atherotech's Chief Medical Officer and an expert in coronary calcification imaging. And beyond research, the accurate identification of lipid profiles and subclasses can have a major impact on proper individualized therapy and improved cardiac risk assessment, which may also include imaging tests and endothelial function testing, as in this research."

The improved lipid profile of mutation carriers included: significantly lower levels of non-HDL, very low density lipoprotein (VLDL), VLDL3 (the most-dense VLDL subfraction), intermediate density lipoprotein (IDL), real LDL, and remnant lipoprotein cholesterol. Higher (cardioprotective) levels of both HDL2 and HDL3 cholesterol were also reported along with apparent cardioprotection as measured by decreased prevalence of coronary artery calcification.

The VAP Test, which is covered by most insurance carriers and Medicare, provides physicians with direct measurement of LDL, HDL and all relevant cholesterol subclasses. These important but often overlooked subclasses include non-HDL, particle number as determined by accurate apoB, and emerging risk factors such as Lp(a), low-density lipoprotein remnants and small dense LDL.

VAP technology has been used in more than 100 clinical trials and will continue to play an important role in clinical practice and as a valuable analytical research tool. The VAP Test is available nationwide.

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