Mitogen-dependent progression through the first gap phase (G1) of the mammalian cell-division cycle is precisely regulated so that normal cell division is coordinated with cell growth, while the initiation of DNA synthesis (S phase) is precisely ordered to prevent inappropriate amp ...
Linkage analysis has aided in the identification of genes involved in many diseases, including several cancers. It relies on using family-based data to detect genetic loci that may harbor disease predisposing genes. Although linkage studies were first designed to find the genes respons ...
The management of patients with pancreatic cancer is a multidisciplinary approach that presents enormous challenges to the clinician. Overall 5-yr survival for all patients remains
Elucidation of basic mechanisms that regulate pancreatic organogenesis may help define molecular pathways involved in the development of exocrine pancreas cancer. The zebrafish has emerged as a powerful model for genetic dissection of the mechanisms underlying vertebrate or ...
The developmental plasticity of adult pancreas is evidenced by the ability to undergo conversion between different epithelial cell types. Specific examples of such conversions include acinar to ductal metaplasia, ductal to islet metaplasia, and generation of ductal structures ...
Conventional gene targeting has been very useful in the study of gene function and regulation in mice. However, the methodologies involved have several limitations. First, mutations that cause embryonic lethality largely preclude studies of gene function at a later stage in developme ...
Multiple experimental approaches have been employed to study exocrine pancreatic cancer, including the use of animals as surrogates for the human disease. Animals have the advantage that they can be manipulated to address specific hypotheses regarding mechanisms underlying this ...
SEREX (serological analysis of recombinant tumor cDNA expression libraries) is a technique designed to isolate tumor antigens that have elicited high-titer IgG responses in human hosts. This is an immunoscreening method for gene cloning, with two key features that distinguish it from e ...
Telomerase, which ensures the unlimited proliferation by adding TTAGGG repeat at the end of the chromosome, is strongly activated at a very high incidence in a variety of malignant neoplasms including pancreatic cancer. In addition to the acquisition of the immortality, telomerase plays ...
Proteomics is the term used for the large-scale analysis of proteins in biological fluids or cells by biochemical methods. Two approaches are used for proteomics analysis: two-dimensional polyacrylamide gel electrophoresis (2D-PA GE) and a mass-spectrometry-based approach, su ...
Successful gene profiling studies involve careful experimental design, use of sensitive and accurate technologies, and statistically valid analysis of experimental results. In this chapter we describe our approach to the profiling of pancreatic adenocarcinoma to illustra ...
Serial analysis of gene expression (SAGE) is a molecular biology technique that was developed to measure the global gene expression levels. It has been applied successfully to characterize transcriptomes, compare the transcript levels between normal and diseased tissues, and unco ...
The recognition of a homozygous deletion of genetic material in a tumor genome has been instrumental in several tumor suppressor gene searches. The representational difference analysis (RDA) allows one to identify homozygous deletions even from among the high background of allelic l ...
Digital single-nucleotide polymorphism (SNP) analysis is developed to amplify a single template from a pool of DNA samples, thereby generating the amplicons that are homogeneous in sequence. Different fluorophores are then applied as probes to detect and discriminate different al ...
Many tumor suppressor genes (such as p16, Rb, VHL, E-cadherin, and hMLH1) that are silenced by mutation are also inactivated by gene silencing through DNA methylation. Characterization of genes hypermethylated in human cancers but not in normal tissues not only provides insights into canc ...
Some populations of the epithelial cells from the duct and ductular network of the mammalian pancreas have been isolated and maintained in vitro for up to 3 mo. These cells express many of the surface factors that are unique to them in vivo. They also retain significant drug-and carcinogen-metabol ...
Xenotransplantation (xenografting) of primary cancers or cancer cell lines into immunodeficient mice is a commonly used technique to assess tumor growth in response to a variety of experimental agents. When primary pancreatic cancers are xenografted, cancer cells proliferate in ...
The tissue microarray (TMA) of Kononen et al. is an extension of an idea originally developed by Battifora and consists of an array of cylindrical cores of paraffin-embedded tissue that are removed from preexisting “donor” paraffin blocks. The donor block is a standard tissue block that may be from ...
There are many types of pancreatic neoplasms. Pathologic examination, which includes both routine (e.g., hematoxylin-and-eosin staining) and ancillary (e.g., immunohistochemistry and in situ hybridization) techniques, is essential in correctly typing a pancreatic neopla ...
Isolation of well-preserved pure cell populations is a prerequisite for sound studies of the molecular basis of pancreatic malignancy and other biological phenomena. This chapter reviews current methods for obtaining anatomically specific signals from molecules isolated fr ...