Gene promoter hypermethylation is recognised as an important mechanism by which genes may be silenced both physiologically and in disease states. This mechanism of gene silencing has been shown to play a role in many common human tumours. A number of methods are available for the detection of pro ...
Whole genome amplification systems were developed to meet the increasing research demands on DNA resources and to avoid DNA shortage. The technology enables amplification of nanogram amounts of DNA into microgram quantities and is increasingly used in the amplification of DNA from mu ...
High-density oligonucleotide microarrays are commonly used for GWAS studies as well as for tumor genome alteration identifications. The recent Affymetrix Genome-Wide SNP 6.0 microarray generation has two major advantages: (1) showing high genome coverage and (2) starting with ve ...
Glucose metabolism plays an important role in cardiac bioenergetics that changes under various stress conditions including hypertrophy, diabetic cardiomyopathy, and ischemia-reperfusion injury. To understand the role of glycolysis under these conditions, we have alter ...
Increased interest in cardiac safety and renewed interest in drugs for treating myocardial ischemia and congestive heart failure have led to increased use of cardiovascular models. Unfortunately, many molecular or cell-based screens are not perfect predictors of activity in vivo. O ...
Cardiovascular disease is the leading cause of death in the industrialized world. Diabetes is a major risk factor for cardiovascular disease. Unchecked diabetes can also lead to renal failure, blindness, heart attack, stroke, and amputation. The focus of this chapter will be to review the dif ...
Hypertension affects approximately 25% of adults and is a major risk factor for cardiovascular disease. Although there are currently adequate therapeutic options for humans with hypertension, the molecular mechanisms underlying hypertension are still relatively unknown. T ...
In response to an increased afterload, the myocardium undergoes a complex adaptation by which wall stress is normalized and cardiac output is maintained. Although the consensus suggests that the increase of the myocardial mass is a necessary adaptive process to accommodate the increas ...
The liver consists of many cell types with specialized functions. Hepatocytes are one of the main players in the organ and therefore are the most vulnerable cells to damage. Since they are not everlasting cells, they need to be replenished throughout life. Although the capacity of hepatocytes to c ...
Liver progenitor cells may play an important role in carcinogenesis in vivo and represent therefore useful cellular materials for in vitro studies. The HepaRG cell line, which is a human bipotent progenitor cell line capable to differentiate toward two different cell phenotypes (i.e., bi ...
Highly differentiated normal human hepatocytes represent the gold standard cellular model for basic and applied research in liver physiopathology, pharmacology, toxicology, virology, and liver biotherapy. Nowadays, although livers from organ donors or medically required ...
Hepatocytes maintained in culture provide an attractive model system for the study of liver function. Furthermore, hepatocyte transplantation offers an alternative cellular therapy to orthotopic liver transplantation for the treatment of hepatic failure and hereditary li ...
Human-based in vitro hepatic experimental systems are now used routinely in drug development. The initial concept of the use of human-based in vitro systems is based on the known species–species differences in drug properties. Human-specific drug properties, by definition, cannot be de ...
Over the past two decades, attrition of new drug candidates which entered into development increased strongly mainly due to sub-optimal ADME profiles. Major problems were linked to poor metabolic stability and drug–drug interactions linked to inhibition or induction of metabolism. ...
Since phase II reactions quantitatively represent the most important pathways involved in drug biotransformation, the development and the use of in vitro approaches to predict glucuronidation and sulfation are currently attracting intense interest to assist in the selection of ...
Mechanisms involved in induction processes have been investigated using fresh human hepatocytes in culture as a cellular model and using mass spectrometry-based metabonomics as a global investigation tool. Sample preparation to data analysis have been detailed in an approach ena ...
The liver plays an important role in the clearance of endogenous and exogenous compounds, including drugs. As hepatic uptake is the first step in hepatic clearance, any change in the former process directly affects the overall intrinsic hepatic clearance. Several uptake transporters are ...
Early studies in hepatocyte turnover and liver regeneration showed that the parenchymal cell, the hepatocyte, was the primary and only cell involved in tissue renewal. However, new studies of liver regeneration, hepatocarcinogenesis, liver transplantation, and various cell lin ...
Liver transplantation is the preferred option to treat a number of hepatic diseases in adults and children, but the number of patients on the waiting list is exceeding the number of available livers for transplantation. Hepatocytes differentiated in vitro from stem cells are a promising and r ...
Hepatocytes in culture are a valuable tool to investigate mechanisms involved in the response of the liver to cytokines. However, it is well established that hepatocytes cultured as monolayers on dried stiff collagen dedifferentiate, loosing specialized liver functions. In contra ...