Preclinical models of pancreatic ductal adenocarcinoma.

Unlike many other cancers, pancreatic ductal adenocarcinoma (PDAC) has seen only incremental improvement in mortality despite significant advances in our understanding of the underlying biology. A primary obstacle to progress has been our inability to properly model PDAC in a preclinical setting. PDAC is difficult to study because of its genetic heterogeneity, intricate stromal microenvironment, and complex interplay with our immune system. Finding a model that properly accounts for all these criteria remains difficult. This review summarizes the five primary models currently in use: human PDAC cell line, cell line xenograft, patient derived xenograft, genetically engineered mouse model (GEMM), and organoids. We delve into the advantages of disadvantages of each model, while discussing how each model has been or could be used in the preclinical setting.

Influence of paternal preconception exposures on their offspring: through epigenetics to phenotype.

Historically, research into congenital defects has focused on maternal impacts on the fetal genome during gestation and prenatal periods. However, recent findings have sparked interest in epigenetic alterations of paternal genomes and its effects on offspring. This emergent field focuses on how environmental influences can epigenetically alter gene expression and ultimately change the phenotype and behavior of progeny. There are three primary mechanisms implicated in these changes: DNA methylation, histone modification, and miRNA expression. This paper provides a summary and subsequent review of past research, which highlights the significant impact of environmental factors on paternal germ cells during the lifetime of an individual as well as those of future generations. These findings support the existence of transgenerational epigenetic inheritance of paternal experiences. Specifically, we explore epidemiological and laboratory studies that demonstrate possible links between birth defects and paternal age, environmental factors, and alcohol consumption. Ultimately, our review highlights the clinical importance of these factors as well as the necessity for future research in the field.