Disease Markers - Volume 17, issue 2

Article Type: Other

Citation: Disease Markers, vol. 17, no. 2, pp. 39-39, 2001

Authors: Riggins, Gregory J.

Article Type: Research Article

Abstract: Tumor markers and antigens are normally highly expressed in malignant tissue, but not in the surrounding normal tissue. Serial Analysis of Gene Expression (SAGE) is a technology that counts mRNA transcripts and can be used to find those genes most highly induced in malignant tissues. SAGE produces a comprehensive profile of gene expression and can be used to search for tumor biomarkers in a limited number of samples. Public sources of SAGE data, in particular through …the Cancer Genome Anatomy Project, increase the value of this technology by making a large source of information on many tumors and normal tissues available for comparison. Although the perfect tumor-specific gene does not exist, the differences in gene expression between tumor and normal can be exploited for therapeutic or diagnostic purposes. Show more

Citation: Disease Markers, vol. 17, no. 2, pp. 41-48, 2001

Authors: Herrmann, Paul C. | Liotta, Lance A. | Petricoin III, Emanuel F.

Article Type: Research Article

Abstract: Now that the human genome has been determined, the field of proteomics is ramping up to tackle the vast protein networks that both control and are controlled by the information encoded by the genome. The study of proteomics should yield an unparalleled understanding of cancer as well as an invaluable new target for therapeutic intervention and markers for early detection. This rapidly expanding field attempts to track the protein interactions responsible for all cellular processes. By …careful analysis of these systems, a detailed understanding of the molecular causes and consequences of cancer should emerge. A brief overview of some of the cutting edge technologies employed by this rapidly expanding field is given, along with specific examples of how these technologies are employed. Soon cellular protein networks will be understood at a level that will permit a totally new paradigm of diagnosis and will allow therapy tailored to individual patients and situations. Show more

Keywords: proteomics, laser capture microdissection, cancer, signal transduction

Citation: Disease Markers, vol. 17, no. 2, pp. 49-57, 2001

Authors: Chen, Yidong | Yakhini, Zohar | Ben-Dor, Amir | Dougherty, Edward | Trent, Jeffrey M. | Bittner, Michael

Article Type: Research Article

Abstract: Studies of the expression patterns of many genes simultaneously lead to the observation that even in closely related pathologies, there are numerous genes that are differentially expressed in consistent patterns correlated to each sample type. The early uses of the enabling technology, microarrays, was focused on gathering mechanistic biological insights. The early findings now pose another clear challenge, finding ways to effectively use this kind of information to develop diagnostics.

Citation: Disease Markers, vol. 17, no. 2, pp. 59-65, 2001

Authors: Caballero, Otavia L. | Souza, Sandro J. de | Brentani, Ricardo R. | Simpson, Andrew J.G.

Article Type: Research Article

Abstract: Eukaryotic mRNAs are transcribed as precursors containing their intronic sequences. These are subsequently excised and the exons are spliced together to form mature mRNAs. This process can lead to transcript diversification through the phenomenon of alternative splicing. Alternative splicing can take the form of one or more skipped exons, variable position of intron splicing or intron retention. The effect of alternative splicing in expanding protein repertoire might partially underlie the apparent discrepancy …between gene number and the complexity of higher eukaryotes. It is likely that more than 50% form. Many cancer-associated genes, such as CD44 and WT1 are alternatively spliced. Variation of the splicing process occurs during tumor progression and may play a major role in tumorigenesis. Furthermore, alternatively spliced transcripts may be extremely useful as cancer markers, since it appears likely that there may be striking contrasts in usage of alternatively spliced transcript variants between normal and tumor tissue than in alterations in the general levels of gene expression. Show more

Citation: Disease Markers, vol. 17, no. 2, pp. 67-75, 2001

Authors: Weinstein, John N.

Article Type: Research Article

Abstract: With 35,000 genes and hundreds of thousands of protein states to identify, correlate, and understand, it no longer suffices to rely on studies of one gene, gene product, or process at a time. We have entered the ``omic'' era in biology. But large-scale omic studies of cellular molecules in aggregate rarely can answer interesting questions without the assistance of information from traditional hypothesis-driven research. The two types of science are synergistic. A case in point is …the set of pharmacogenomic studies that we and our collaborators have done with the 60 human cancer cell lines of the National Cancer Institute's drug discovery program. Those cells (the NCI-60) have been characterized pharmacologically with respect to their sensitivity to >70,000 chemical compounds. We are further characterizing them at the DNA, RNA, protein, and functional levels. Our major aim is to identify pharmacogenomic markers that can aid in drug discovery and design, as well as in individualization of cancer therapy. The bioinformatic and chemoinformatic challenges of this study have demanded novel methods for analysis and visualization of high-dimensional data. Included are the color-coded ``clustered image map'' and also the MedMiner program package, which captures and organizes the biomedical literature on gene-gene and gene-drug relationships. Microarray transcript expression studies of the 60 cell lines reveal, for example, a gene-drug correlation with potential clinical implications -- that between the asparagine synthetase gene and the enzyme-drug L-asparaginase in ovarian cancer cells. Show more

Keywords: microarray, genomics, proteomics, omics, cancer, cell line, pharmacology, pharmacogenomics, molecular marker, cancer therapy, clustered image map, MedMiner

Citation: Disease Markers, vol. 17, no. 2, pp. 77-88, 2001

Authors: Chanock, Stephen

Article Type: Research Article

Abstract: The genomic revolution has generated an extraordinary resource, the catalog of variation within the human genome, for investigating biological, evolutionary and medical questions. Together with new, more efficient platforms for high-throughput genotyping, it is possible to begin to dissect genetic contributions to complex trait diseases, specifically examining common variants, such as the single nucleotide polymorphism (SNP). At the same time, these tools will make it possible to identify determinants of disease with the …expectation of eventually, tailoring therapies based upon specific profiles. However, a number of methodological, practical and ethical issues must be addressed before the analysis of genetic variation becomes a standard of clinical medicine. The currents of variation in human biology are reviewed here, with a specific emphasis on future challenges and directions. Show more

Keywords: variation, genome, genetic, mutation, disease susceptibility

Citation: Disease Markers, vol. 17, no. 2, pp. 89-98, 2001

Authors: Ross, Douglas T. | Perou, Charles M.

Article Type: Research Article

Abstract: Cell lines derived from human tumors have historically served as the primary experimental model system for exploration of tumor cell biology and pharmacology. Cell line studies, however, must be interpreted in the context of artifacts introduced by selection and establishment of cell lines {\it in vitro}. This complication has led to difficulty in the extrapolation of biology observed in cell lines to tumor biology {\it in vivo}. Modern genomic analysis tool like DNA microarrays and gene …expression profiling now provide a platform for the systematic characterization and classification of both cell lines and tumor samples. Studies using clinical samples have begun to identify classes of tumors that appear both biologically and clinically unique as inferred from their distinctive patterns of expressed genes. In this review, we explore the relationships between patterns of gene expression in breast tumor derived cell lines to those from clinical tumor specimens. This analysis demonstrates that cell lines and tumor samples have distinctive gene expression patterns in common and underscores the need for careful assessment of the appropriateness of any given cell line as a model for a given tumor subtype. Show more

Citation: Disease Markers, vol. 17, no. 2, pp. 99-109, 2001

Authors: Alvarez, S. | Mesa, M.S. | Bandrés, F. | Arroyo, E.

Article Type: Research Article

Abstract: {\it Objectives:} To determine the frequency of hereditary hemochromatosis gene mutations, C282Y and H63D, from 125 autochthonous blood donors originating from a Central region of Spain, to provide epidemiological data about HFE gene in the Iberian Peninsula. {\it Methods:} DNA extracted from blood samples was analyzed by PCR-RFLP. Restriction enzimes were Snab I and Bcl I for C282Y and H63D, respectively. Results were visualized with Ethidium Bromide staining after gel electrophoresis. {\it Results …and discussion:} C282Y frequency was 0.02 and that of H63D was 0.16. Result for C282Y mutation falls within the range of variation of the Mediterranean populations. H63D frequency agrees with those reported for other European populations. In both cases frequencies obtained are the lowest of compared Spanish data. {\it Conclusions:} This study is useful to compare expected versus presented C282Y and H63D frequencies in Spanish populations and to contribute to the knowledge of Spanish variability, rarely analyzed until now for HFE gene mutations. Show more

Citation: Disease Markers, vol. 17, no. 2, pp. 111-114, 2001

Authors: Srivastava, Meera | Bubendorf, Lukas | Nolan, Lisa | Glasman, Mirta | Leighton, Ximena | Miller, Georgina | Fehrle, Wilfred | Raffeld, Mark | Eidelman, Ofer | Kallioniemi, Olli P. | Srivastava, Shiv | Pollard, Harvey B.

Article Type: Research Article

Abstract: The ANX7 gene codes for a Ca^{2+} -activated GTPase, which has been implicated in both exocytotic secretion in cells and control of growth. In this review, we summarize information regarding increased tumor frequency in the Anx7 knockout mice, ANX7 growth suppression of human cancer cell lines, and ANX7 expression in human tumor tissue micro-arrays. The loss of ANX7 is significant in metastatic and hormone refractory prostate cancer compared to benign prostatic hyperplasia. In addition, ANX7 …expression has prognostic value for predicting survival of breast cancer patients. Show more

Citation: Disease Markers, vol. 17, no. 2, pp. 115-120, 2001