Molecular and genetic targets in early detection.
ABSTRACT Recent research has revealed the existence of specific mutations in cancer. These mutations are being investigated as targets to find subjects at high risk for cancer, to detect early cancer, to detect the early recurrence of established cancer, and to find micrometastasis. These mutations are reviewed for the major anatomic sites. Some of the clinical issues related to the application of these mutations and the limitations of using molecular targets are also considered. Current methods for determining the risk of cancer are reviewed. Risk assessment is essential for defining cohorts for chemoprevention and other interventions. The concept of using surrogate anatomic and functional sites for estimating risk is introduced. Finally, the increasing complexity of molecular genetic analysis and the biologic heterogeneity of cancer are discussed in relation to early detection.
SourceAvailable from: ncbi.nlm.nih.gov[Show abstract] [Hide abstract]
ABSTRACT: It has become increasingly evident that the study of DNA is inadequate to explain many, if not most, aspects of the development and progression of neoplastic lesions from pre-invasive lesions to metastasis. Thus, the term "genetic" can no longer refer to just the study of the genome. Much of the action in genetic research now shifts to the methods by which the pre-mRNA from one gene is processed to yield multiple different proteins, different quantities of the same protein as well as other forms of regulating RNA. Thus, the age of post-transcriptional processing and epigenetic control of the transfer of information from the genome has arrived. The mechanisms of post-transcriptional processing and epigenetic control that must be characterized in greater detail including alternate splicing, regulation of mRNA degradation, RNA regulatory factors including those factors which extensively edit mRNAs, control of translation, and control of protein stability and degradation. This chapter reviews many of the processes that control information from the genome to proteins and how these factors lead from less than 40,000 genes to more than an order of magnitude increase more proteins which actually control the phenotypes of cells - normal or neoplastic. It is usually the products of genes (e.g., mRNA, microRNA and proteins) that are the molecular markers that will control translational research and ultimately, individualized (personal) medical approaches to disease. This chapter emphasizes how the process of neoplasia "hijacks" the normal processes of cellular operations, especially those processes that are important in the normal development of the organisms - including proliferation, cellular death, angiogenesis, cellular mobility and invasion, and immunoregulation to ensure neoplastic development, survival and progression. This chapter reviews the wide range of processes controlling the information that flows from the genome to proteins and emphasizes how molecular steps in pure processes can be used as biomarkers to study prevention, treatment and/or management of diseases.Cancer biomarkers: section A of Disease markers 01/2011; 9(1-6):41-64. DOI:10.3233/CBM-2011-0204 · 1.19 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: Osteopontin (OPN) is a glycoprotein expressed by various tissues and cells. It is also implicated in tumor progression. The protein can mediate cell adhesion and is strongly associated with transformation and tumorigenesis. Overexpression of OPN influences invasion and metastasis of different human tumors, and OPN expression may be use as a possible prognostic marker. It has been detected in a growing number of human tumor types, by immunohistochemistry on tumor tissue sections. The objective of this study was to assess the immunohistochemical expression of OPN in different canine and feline tumors and to examine any possible relation with malignancy. To achieve these aim 40 different kinds of canine and feline tumors were evaluated. OPN was either not expressed or at low levels in benign tumors, but strongly expressed in malign tumors. This study showed that OPN may be associated with malignancy of cat and dog tumors. Keywords: Osteopontin (OPN), immunohistochemistry, dog, cat, tumorRevue de médecine vétérinaire 01/2015; 1-2:2-10. · 0.25 Impact Factor
[Show abstract] [Hide abstract]
ABSTRACT: The efficacy of capillary electrophoresis for detecting DNA mutations via heteroduplex analysis (HDA) is dependent upon both the effective passivition of the capillary surface and the choice of the correct polymer network for sieving. Using HDA with laser-induced fluorescence detection of fluorescently labeled DNA fragments, an effective coating and optimal polymer matrix were sought. Optimized separation conditions were determined through the methodological evaluation of a number of different silanizing reagents, polymeric coatings, and polymer networks for resolving the PCR-amplified DNA fragments associated with five mutations (185delAG, 1294del40, 4446C>G, 5382insC, 5677insA) in the breast cancer susceptibility gene (BRCA1). For capillary coating, allyldimethylchlorosilane, 4-chlorobutyldimethylchlorosilane, (γ-methacryloxypropyl)trimethoxysilane, chlorodimethyloctylsilane (OCT), and 7-octenyltrimethoxysilane were evaluated as silanizing reagents in combination with poly(vinylpyrrolidone) (PVP) and polyacrylamide (PA) as the polymeric coat. The HDA results were compared with those obtained using a commercial (FC) coated capillary. Of these, the OCT−PVP combination was found to be most effective. Using this modified capillary, HDA with polymer networks that included hydroxyethylcellulose (HEC), linear polyacrylamide, and PVP showed that a PVP-, PA-, or FC-coated capillary, in combination with HEC as the sieving polymer, could be used effectively to discriminate the mutations in less than 10 min. However, optimal performance was observed with the OCT−PVP-coated capillary and HEC as the polymer network.Analytical Chemistry 10/2000; 72(21). DOI:10.1021/ac0004916 · 5.83 Impact Factor