H epatocellular carcinoma (HCC) is the most frequent type of liver cancer and is the third leading cause of cancer-related death worldwide. 1 Various etiologies have been linked to HCC development, the most relevant being chronic hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, chronic alcohol consumption, and, in certain geographical areas, aflatoxin B1 food contamination. 2 Approximately 10% of HCC patients show no signs of hepatitis virus infection, alcoholic history, or other defined causes, such as genetic hemochromatosis or ␣ 1 -antitrypsin deficiency. Most of these so-called cryptogenic HCCs evolve from nonalcoholic steatohepatitis (NASH). 3 Whereas generation of reactive oxygen species has been suggested to drive hepatocarcinogenesis in HCCs of alcoholic or cryptogenic etiology, viral-associated mechanisms are complex and involve both host and viral factors.Genomic instability is a common feature of human HCC. Using conventional and array-based comparative genomic hybridization (aCGH), frequent DNA copy number gains at 1q, 6p, 8q, 17q, and 20q and losses at 1p, 4q, 8p, 13q, 16q, and 17p have been identified as reviewed elsewhere. 4 Although target genes such as RB1 (13q14) and TP53 (17p13) have been identified and validated, the driving genes for most commonly altered loci remain unknown. Several CGH studies tried to identify chromosome aberrations that correlate specifically with HCC etiology; however, many failed to uncover significant differences in DNA copy number alteration or candidate genes, possibly due to underrepresentation of

Existing microarray-based approaches for screening of DNA methylation are hampered by a number of shortcomings, such as the introduction of bias by DNA copy-number imbalances in the test genome and negligence of tissue-specific methylation patterns. We developed a method designated array-based profiling of reference-independent methylation status (aPRIMES) that allows the detection of direct methylation status rather than relative methylation. Array-PRIMES is based on the differential restriction and competitive hybridization of methylated and unmethylated DNA by methylation-specific and methylation-sensitive restriction enzymes, respectively. We demonstrate the accuracy of aPRIMES in detecting the methylation status of CpG islands for different states of methylation. Application of aPRIMES to the DNA from desmoplastic medulloblastomas of monozygotic twins showed strikingly similar methylation profiles. Additional analysis of 18 sporadic medulloblastomas revealed an overall correlation between highly methylated tumors and poor clinical outcome and identified ZIC2 as a frequently methylated gene in pediatric medulloblastoma.

Hemoglobin A1c (HbA1c) is currently the most commonly used marker for the determination of the glycemic status in people with diabetes and it is frequently used to guide therapy and especially medical treatment of people with diabetes. The measurement of HbA1c has reached a high level of analytical quality and, therefore, this biomarker is currently also suggested to be used for the diagnosis of diabetes. Nevertheless, it is crucial for people with diabetes and their treating physicians to be aware of possible interferences during its measurement as well as physiological or pathological factors that contribute to the HbA1c concentration without being related to glycemia, which are discussed in this review. We performed a comprehensive review of the literature based on PubMed searches on HbA1c in the treatment and diagnosis of diabetes including its most relevant limitations, glycemic variability and self-monitoring of blood glucose (SMBG). Although the high analytical quality of the HbA1c test is widely acknowledged, the clinical relevance of this marker regarding risk reduction of cardiovascular morbidity and mortality is still under debate. In this respect, we argue that glycemic variability as a further risk factor should deserve more attention in the treatment of diabetes.

In Salmonella typhimurium, a single enzyme catalyzes both the acetyl CoA-dependent O-acetylation of hydroxylamines (a key step in the activation of mutagenic nitroaromatic compounds and related aromatic and heterocyclic amines) and the N-acetylation of aromatic amines. S. typhimurium Ames test mutants lacking this activity are highly resistant to the genotoxic effects of nitro compounds. However, such mutants have not yet been obtained in Escherichia coli. We used a PCR-based method to engineer a null mutation (deletion) of the nhoA gene encoding the enzyme in E. coli and we transduced this mutation into a lacZ strain background suitable for use in mutation assays. In E. coli, as in S. typhimurium, nhoA mutants show marked resistance to nitro compound mutagenicity. The new strains provide a clean background for expression of recombinant N-acetyltransferases.