J-point elevation is found more frequently among patients with idiopathic VF than among healthy control subjects. The frequency of J-point elevation among young athletes is intermediate (higher than among healthy adults but lower than among patients with idiopathic VF).

CD24 is a potential oncogene reported to be overexpressed in a large variety of human malignancies. We have shown that CD24 is overexpressed in 90% of colorectal tumors at a fairly early stage in the multistep process of carcinogenesis. Anti-CD24 monoclonal antibodies (mAb) induce a significant growth inhibition in colorectal and pancreatic cancer cell lines that express the protein. This study is designed to investigate further the effects of CD24 down-regulation using mAb or small interfering RNA in vitro and in vivo. Western blot analysis showed that anti-CD24 mAb induced CD24 protein down-regulation through lysosomal degradation. mAb augmented growth inhibition in combination with five classic chemotherapies. Xenograft models in vivo showed that tumor growth was significantly reduced in mAb-treated mice. Similarly, stable growth inhibition of cancer cell lines was achieved by down-regulation of CD24 expression using short hairpin RNA (shRNA). The produced clones proliferated more slowly, reached lower saturation densities, and showed impaired motility. Most importantly, down-regulation of CD24 retarded tumorigenicity of human cancer cell lines in nude mice. Microarray analysis revealed a similar pattern of gene expression alterations when cells were subjected to anti-CD24 mAb or shRNA. Genes in the Ras pathway, mitogenactivated protein kinase, or BCL-2 family and others of oncogenic association were frequently down-regulated. As a putative new oncogene that is overexpressed in gastrointestinal malignancies early in the carcinogenesis process, CD24 is a potential target for early intervention in the prevention and treatment of cancer. [Cancer Res 2008;68(8):2803-12]

BACKGROUND Fever is known to unmask the Brugada pattern on the electrocardiogram (ECG) and trigger ventricular arrhythmias in patients with Brugada syndrome. Genetic studies in selected cases with fever-induced Brugada pattern have identified disease-causing mutations. Thus, “fever-induced Brugada” is a recognized clinical entity. However, its prevalence has not been systematically evaluated. OBJECTIVE The purpose of this study was to assess the prevalence of Brugada pattern in consecutive patients with fever. METHODS ECGs of patients with fever admitted to the emergency department were evaluated for the presence of Brugada pattern and compared with ECGs of consecutive nonfebrile patients. RESULTS ECGs of 402 patients with fever and 909 without were evaluated. Type I Brugada pattern was 20 times more common in the febrile group than in the afebrile group (2% vs 0.1%, respectively, P = .0001). All patients with fever-induced type I Brugada pattern were asymptomatic and remained so during 30 months of follow-up. CONCLUSION Type I Brugada pattern is definitively more common among patients with fever, suggesting that asymptomatic Brugada syndrome is more prevalent than previously estimated.

While reviewing chronic lymphocytic leukemia (CLL) bone marrow slides we identified cytoplasmic lipid vacuoles in CLL cells but not in normal B cells. Because lipoprotein lipase (LPL), which catalyzes hydrolysis of triglycerides into free fatty acids (FFAs), is aberrantly expressed in CLL, we investigated whether LPL regulates the oxidative metabolic capacity of CLL cells. We found that unlike normal B cells, CLL cells metabolize FFAs. Because STAT3 is constitutively activated in CLL cells and because we identified putative STAT3 binding sites in the LPL promoter, we sought to determine whether STAT3 drives the aberrant expression of LPL. Transfection of luciferase reporter gene constructs driven by LPL promoter fragments into MM1 cells revealed that STAT3 activates the LPL promoter. In addition, chromatin immunoprecipitation (ChIP) confirmed that STAT3 binds to the LPL promoter. Furthermore, transfection of CLL cells with STAT3-shRNA downregulated LPL transcripts and protein levels, confirming that STAT3 activates the LPL gene. Finally, transfection of CLL cells with LPL-siRNAs decreased the capacity of CLL cells to oxidize FFAs and reduced cell viability.

Key Points Stimulation of the BCR activates JAK2 and STAT3 in CLL cells. The JAK1/2 inhibitor ruxolitinib induces apoptosis of CLL cells.