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EFFECT OF N-METHYL-N'-NITRO-N-NITROSOGUANIDINE (MNNG) ON DNA OF CULTURED RAT HEPATOMA CELLS
Title
EFFECT OF N-METHYL-N'-NITRO-N-NITROSOGUANIDINE (MNNG) ON DNA OF CULTURED RAT HEPATOMA CELLS.
Creator
JHABVALA, PERSEUS, Florida Atlantic University, Stein, Abraham, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
The objective of this study was to elucidate the interaction of the carcinogen MNNG with nuclear DNA of Rat Hepatoma cells. The effect of a range of MNNG concentrations on RH cell DNA was studied by an analysis of the DNA fragments obtained in linear alkaline sucrose gradients. A macromolecular analysis of the sedimentation profile for 0.06 mM MNNG (Experiment I), and 0.1 mM MNNG (Experiment III), suggested that the system was paucidisperse and contained at least three components. The major...
Show moreThe objective of this study was to elucidate the interaction of the carcinogen MNNG with nuclear DNA of Rat Hepatoma cells. The effect of a range of MNNG concentrations on RH cell DNA was studied by an analysis of the DNA fragments obtained in linear alkaline sucrose gradients. A macromolecular analysis of the sedimentation profile for 0.06 mM MNNG (Experiment I), and 0.1 mM MNNG (Experiment III), suggested that the system was paucidisperse and contained at least three components. The major component Max 1 has a molecular weight comparable to that known for the mammalian replicon. Max 2 has a molecular weight twice that of Max 1 and Max 3 has a molecular weight half that of Max 1. The size of the replicon is comparable to that obtained by others. Inferences were drawn regarding the structure of chromatin and the role of the distribution of sites hypersensitive to methylation with respect to the oncogenes.
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Date Issued
1985
PURL
http://purl.flvc.org/fcla/dt/14260
Subject Headings
Carcinogenicity testing, Cancer--Genetic aspects, DNA
Format
Document (PDF)
Effects of gene selection and data sampling on prediction of breast cancer treatments
Title
Effects of gene selection and data sampling on prediction of breast cancer treatments.
Creator
Heredia, Brian, Khoshgoftaar, Taghi M., Florida Atlantic University, College of Engineering and Computer Science, Department of Computer and Electrical Engineering and Computer Science
Abstract/Description
In recent years more and more researchers have begun to use data mining and machine learning tools to analyze gene microarray data. In this thesis we have collected a selection of datasets revolving around prediction of patient response in the specific area of breast cancer treatment. The datasets collected in this paper are all obtained from gene chips, which have become the industry standard in measurement of gene expression. In this thesis we will discuss the methods and procedures used in...
Show moreIn recent years more and more researchers have begun to use data mining and machine learning tools to analyze gene microarray data. In this thesis we have collected a selection of datasets revolving around prediction of patient response in the specific area of breast cancer treatment. The datasets collected in this paper are all obtained from gene chips, which have become the industry standard in measurement of gene expression. In this thesis we will discuss the methods and procedures used in the studies to analyze the datasets and their effects on treatment prediction with a particular interest in the selection of genes for predicting patient response. We will also analyze the datasets on our own in a uniform manner to determine the validity of these datasets in terms of learning potential and provide strategies for future work which explore how to best identify gene signatures.
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Date Issued
2014
PURL
http://purl.flvc.org/fau/fd/FA00004292, http://purl.flvc.org/fau/fd/FA00004292
Subject Headings
Antineoplastic agents -- Development, Breast -- Cancer -- Treatment, Cancer -- Genetic aspects, DNA mircroarrays, Estimation theory, Gene expression
Format
Document (PDF)
Bioinformatics mining of the dark matter proteome for cancer targets discovery
Title
Bioinformatics mining of the dark matter proteome for cancer targets discovery.
Creator
Delgado, Ana Paula, Narayanan, Ramaswamy, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
Mining the human genome for therapeutic target(s) discovery promises novel outcome. Over half of the proteins in the human genome however, remain uncharacterized. These proteins offer a potential for new target(s) discovery for diverse diseases. Additional targets for cancer diagnosis and therapy are urgently needed to help move away from the cytotoxic era to a targeted therapy approach. Bioinformatics and proteomics approaches can be used to characterize novel sequences in the genome...
Show moreMining the human genome for therapeutic target(s) discovery promises novel outcome. Over half of the proteins in the human genome however, remain uncharacterized. These proteins offer a potential for new target(s) discovery for diverse diseases. Additional targets for cancer diagnosis and therapy are urgently needed to help move away from the cytotoxic era to a targeted therapy approach. Bioinformatics and proteomics approaches can be used to characterize novel sequences in the genome database to infer putative function. The hypothesis that the amino acid motifs and proteins domains of the uncharacterized proteins can be used as a starting point to predict putative function of these proteins provided the framework for the research discussed in this dissertation.
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Date Issued
2015
PURL
http://purl.flvc.org/fau/fd/FA00004361, http://purl.flvc.org/fau/fd/FA00004361
Subject Headings
Bioinformatics, Cancer -- Genetic aspects, Drug development -- Data processing, Genomics, Medical informatics, Proteomes -- Data processing, Tumors -- Immunological aspects
Format
Document (PDF)
The Single Minded 2 Gene (SIM2) and Cancer: Harnessing Micro-Array Data to Facilitate Pathway Discovery and Validation
Title
The Single Minded 2 Gene (SIM2) and Cancer: Harnessing Micro-Array Data to Facilitate Pathway Discovery and Validation.
Creator
Aleman, Mireille J., Narayanan, Ramaswamy, Florida Atlantic University
Abstract/Description
A Down's Syndrome related Single Minded 2 gene (SIM2), previously known to be associated with Trisomy 21 was predicted by bioinformatics to be colon cancer specific. In previous work from the laboratory using a patient tissue repository, an isoform of this gene, short form (SIM2-s) was shown to be colon cancer specific. Inhibition of SIM2-s expression by antisense technology resulted in cancer-cell specific apoptosis within 24 hours. Microarray-based gene expression profiling of the antisense...
Show moreA Down's Syndrome related Single Minded 2 gene (SIM2), previously known to be associated with Trisomy 21 was predicted by bioinformatics to be colon cancer specific. In previous work from the laboratory using a patient tissue repository, an isoform of this gene, short form (SIM2-s) was shown to be colon cancer specific. Inhibition of SIM2-s expression by antisense technology resulted in cancer-cell specific apoptosis within 24 hours. Microarray-based gene expression profiling of the antisense-treated colon cancer cells provided a fingerprint of genes involving key cell cycle, apoptosis, DNA damage and differentiation genes. Taking hints from the microarray database, experiments were initiated to decipher the molecular mechanism underlying the cancer specific function of the SIM2-s gene. Using an isogenic cell system, apoptosis was found to be dependent on DNA damage and repair gene, GADD45-a. Further, key pathways including p38 MAP kinase (MAPK) and specific caspases were essential for apoptosis. Programmed cell death was not dependant on cell cycle and was preceded by the induction of terminal differentiation. To clarify whether SIM2-s function is a critical determinant of differentiation, stable transfectants of SIM2-s were established in a murine adipocytic cell line (3T3-L 1 ). SIM2-s overexpression caused a pronounced block of differentiation of the pre-adipocytes into mature adipocytes. A study of the differentiation pathway in 3T3-L 1 cells suggested that this block occurs early on in the cascade. These results supported the starting premise that SIM2-s is a critical mediator of cell differentiation. To clarify whether the SIM2-s gene has transforming potential, the SIM2-s gene was overexpressed in the NIH3T3 murine fibroblast cell line. The cells expressing the human SIM2-s gene exhibited shorter doubling time, abrogation of growth serum requirement, greater cell number at saturation density and focus formation. In vivo tumorigenicity assays showed tumor formation with long latency. These results provide strong evidence for the role of SIM2-s gene in tumor cell growth and differentiation, and validate drug therapy use for the gene.
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Date Issued
2007
PURL
http://purl.flvc.org/fau/fd/FA00000845
Subject Headings
Cancer--Genetic aspects, DNA microarrays--Diagnostic use, Apoptosis--Molecular aspects, Medical informatics, Gene expression--Research--Methodology
Format
Document (PDF)
Molecular pathway identification using microarray technology
Title
Molecular pathway identification using microarray technology.
Creator
Tress, Matthew David., Florida Atlantic University, Narayanan, Ramaswamy
Abstract/Description
Harnessing the human genome using bioinformatics lead to the discovery of a highly cancer-selective gene, Single Minded 2 gene (SIM2). An isoform of the SIM2 gene, the short-form (SIM2-s), was shown to be specific to colon, pancreas, and prostate tumors. Antisense inhibition of SIM2-s in a colon carcinoma derived cell line (RKO) caused inhibition of gene expression, growth inhibition and apoptosis in vitro and in nude mice tumorigenicity models. To understand the mechanism of Sim2-s antisense...
Show moreHarnessing the human genome using bioinformatics lead to the discovery of a highly cancer-selective gene, Single Minded 2 gene (SIM2). An isoform of the SIM2 gene, the short-form (SIM2-s), was shown to be specific to colon, pancreas, and prostate tumors. Antisense inhibition of SIM2-s in a colon carcinoma derived cell line (RKO) caused inhibition of gene expression, growth inhibition and apoptosis in vitro and in nude mice tumorigenicity models. To understand the mechanism of Sim2-s antisense, the antisense treated RKO colon cancer cells were monitored for genome wide expression using Affymetrix GeneChipRTM technology. A list of apoptosis related genes was generated using GeneSpringRTM software. Select GeneChip RTM output was validated by Quantitative RT-PCR. Relevance of a key gene, Growth arrest and DNA damage inducible (GADD45a), in the SIM2-s pathway was established. These results will provide a basis for the future experiments to understand the mechanism underlying Sim2-s activation in specific tumors.
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Date Issued
2004
PURL
http://purl.flvc.org/fcla/dt/13146
Subject Headings
Medical informatics, DNA microarrays--Diagnostic use, Cancer--Genetic aspects, Apoptosis--Molecular aspects, Human genetics--Variation, Gene expression--Research--Methodology
Format
Document (PDF)