Current Search: Cancer -- Genetic aspects (x)
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(1 - 12 of 12)
- 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.
Show less - Date Issued
- 1985
- PURL
- http://purl.flvc.org/fcla/dt/14260
- Subject Headings
- Carcinogenicity testing, Cancer--Genetic aspects, DNA
- Format
- Document (PDF)
- Title
- Cells and cocktails: antioxidants rescue carcinogen induced mitotic defects in both chromosomally stable and unstable cells.
- Creator
- Griffin, Isabel Sloan., Harriet L. Wilkes Honors College
- Abstract/Description
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Tumor cells are characterized by an increase in genomic instability, brought about by both chromosomal rearrangement and chromosomal instability. Both of these broad changes can be induced by exposure to carcinogens. During mitosis, cells can exhibit early and late lagging chromosomes, multipolar spindles or anaphase bridges, all of which contribute to genomic rearrantement. We have studied the link between exposure to carcinogen and prevalence of mitotic defect in both chromosomally stable...
Show moreTumor cells are characterized by an increase in genomic instability, brought about by both chromosomal rearrangement and chromosomal instability. Both of these broad changes can be induced by exposure to carcinogens. During mitosis, cells can exhibit early and late lagging chromosomes, multipolar spindles or anaphase bridges, all of which contribute to genomic rearrantement. We have studied the link between exposure to carcinogen and prevalence of mitotic defect in both chromosomally stable and unstable cell lines as well as ecamined the restorative effects of antioxidants in preventing mitotic defects. We have exposed MES-SA uterine cancer cells to vinyl chloride followed by exposure to an antioxidant : ascorbic acid, B-carotene, or lycopene. Treated cells were then scored for the prevalence of mitotic defects within the population and compared to controls. We have also investigated whether pre-treatment with the antioxidants will weaken the effects of carcinogen exposure in these cell lines.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3359304
- Subject Headings
- Cellular signal transduction, Cell differentiation, Medical genetics, Cancer, Genetic aspects, Antioxidants, Therapeutic use, Cancer, Chemoprevention, Apoptosis, Molecular aspects, Genetic regulation
- Format
- Document (PDF)
- Title
- Inflammatory response in stress and the role of autophagy in breast cancer.
- Creator
- Onwuha-Ekpete, Lillian C., Charles E. Schmidt College of Medicine, Department of Biomedical Science
- Abstract/Description
-
We attempted to understand the molecular regulators that impact inflammation using a rat model of human sensation-seeking/risk-taking trait for drug and stress vulnerability, based on their exploratory behavior displaying high rates (HRs) or low rates of locomotor reactivity (LRs) to environmental stress. We found that HRs have a pro-inflammatory phenotype as indicated by increased protein expression of the inflammatory cytokine TNF-(Sa(B. Furthermore, we found that HRs have a lower gene...
Show moreWe attempted to understand the molecular regulators that impact inflammation using a rat model of human sensation-seeking/risk-taking trait for drug and stress vulnerability, based on their exploratory behavior displaying high rates (HRs) or low rates of locomotor reactivity (LRs) to environmental stress. We found that HRs have a pro-inflammatory phenotype as indicated by increased protein expression of the inflammatory cytokine TNF-(Sa(B. Furthermore, we found that HRs have a lower gene expression of the glucocorticoid receptor and histone deacetylase 2 which are known to play an immunosuppressive role. Autophagy (macroautophagy) is a homeostatic process needed for cell maintenance, growth and proliferation and known to assist in tumor survival. FYVE and coiled-coil domain containing 1 (FYCO1) is a novel protein implicated to assist in the plus-end directed trafficking and fusion of autophagosomes. In these studies, we show that FYCO1 gene expression among human breast cell lines of varying degrees of malignancy.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/fcla/dt/3362042
- Subject Headings
- Breast, Cancer, Genetic aspects, Cancer, Molecular aspects, Carcinogenesis, Cellular signal transduction, Stress (Physiology)
- Format
- Document (PDF)
- Title
- Devising a noncancerous model system to study multipolar spindle formation.
- Creator
- Nagarsheth, Nisha., Harriet L. Wilkes Honors College
- Abstract/Description
-
Aneuploid tumor cells have characteristically unstable genomes which can be caused by mitotic defects such as multipolar spindles. Multipolarity relies upon the presence of extra centrosomes to form. However, some cells, both cancerous and noncancerous are able to avoid the formation of multipolar spindles through centrosomal clustering. Previous research has shown that there are a large number of genes whose activity contributes to the clustering activity, making analysis of individual...
Show moreAneuploid tumor cells have characteristically unstable genomes which can be caused by mitotic defects such as multipolar spindles. Multipolarity relies upon the presence of extra centrosomes to form. However, some cells, both cancerous and noncancerous are able to avoid the formation of multipolar spindles through centrosomal clustering. Previous research has shown that there are a large number of genes whose activity contributes to the clustering activity, making analysis of individual components of the process difficult. In order to better understand centrosomal clustering in cancer cells, we induced supernumerary centrosomes in a genomically normal cell line, RPE, to observe how the normal cells cope with extra centrosomes. Using colcemid to induce extra centrosomes in the RPE cell line, we observed an intact clustering mechanism in fixed cells. Further manipulation of the cells has allowed us to induce multipolarity in this cell line using various disrupters of cell-cycle checkpoint and dynein function.
Show less - Date Issued
- 2010
- PURL
- http://purl.flvc.org/FAU/3335107
- Subject Headings
- Centrosomes, Research, Cancer, Genetic aspects, Cellular signal transduction, Cell division
- Format
- Document (PDF)
- Title
- Deamplification of supernumerary centrosomes by centrosomal clustering.
- Creator
- Thomas, Ezekiel., Harriet L. Wilkes Honors College
- Abstract/Description
-
Supernumerary centrosomes can arise in a cell through a variety of methods. The presence of supernumerary centrosomes has been observed in nearly all types of cancer and promotes chromosomal instability, with rates of incident increasing as the cancer progresses. An oral squamous cell carcinoma line was treated with hydroxyurea to induce supernumerary centrosomes in the cells. NuMA was then knocked down using shRNA to promote centrosomal clustering and bipolar mitotic division in cells with...
Show moreSupernumerary centrosomes can arise in a cell through a variety of methods. The presence of supernumerary centrosomes has been observed in nearly all types of cancer and promotes chromosomal instability, with rates of incident increasing as the cancer progresses. An oral squamous cell carcinoma line was treated with hydroxyurea to induce supernumerary centrosomes in the cells. NuMA was then knocked down using shRNA to promote centrosomal clustering and bipolar mitotic division in cells with supernumerary centrosomes. Immunofluorescence with an antibody against SAS 6 accuately stained the centrioles for observation. The cells exhibiting supernumerary centrosomes undergoing bipolar mitotic division were studied to look for a possible pattern in centrosomal clustering where the majority of centrosomes are at one pole with a single centrosome at the other pole. Initial results suggest the presence of such a mechanism, which would describe a previously unknown mechanism for cells to deamplify supernumerary centrosomes by centrosomal clustering.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3359328
- Subject Headings
- Centrosomes, Cell division, Cellular signal transduction, Cancer, Genetic aspects
- Format
- Document (PDF)
- 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
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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.
Show less - 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)
- Title
- Cytogenic bioinformatics of chromosomal aberrations and genetic disorders: data-mining of relevant biostatistical features.
- Creator
- Karri, Jagadeshwari., College of Engineering and Computer Science, Department of Computer and Electrical Engineering and Computer Science
- Abstract/Description
-
Cytogenetics is a study on the genetic considerations associated with structural and functional aspects of the cells with reference to chromosomal inclusions. Chromosomes are structures within the cells containing body's information in the form of strings of DNA. When atypical version or structural abnormality in one or more chromosomes prevails, it is defined as chromosomal aberrations (CA) depicting certain genetic pathogeny (known as genetic disorders). The present study assumes the...
Show moreCytogenetics is a study on the genetic considerations associated with structural and functional aspects of the cells with reference to chromosomal inclusions. Chromosomes are structures within the cells containing body's information in the form of strings of DNA. When atypical version or structural abnormality in one or more chromosomes prevails, it is defined as chromosomal aberrations (CA) depicting certain genetic pathogeny (known as genetic disorders). The present study assumes the presence of normal and abnormal chromosomal sets in varying proportions in the cytogenetic complex ; and, stochastical mixture theory is invoked to ascertain the information redundancy as a function of fractional abnormal chromosome population. This bioinformatic measure of redundancy is indicated as a track-parameter towards the progression of genetic disorder, for example, the growth of cancer. Lastly, using the results obtained, conclusions are enumerated, inferences are outlined and directions for future studies are considered.
Show less - Date Issued
- 2012
- PURL
- http://purl.flvc.org/FAU/3358597
- Subject Headings
- Medical genetics, Chromosome abnormalities, Cancer, Genetic aspects, Mutation (Biology), DNA damage
- Format
- Document (PDF)
- Title
- Manipulation of normal cells to produce a cancer-like mitotic phenotype.
- Creator
- Luffman, Christina., Harriet L. Wilkes Honors College
- Abstract/Description
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Most tumors contain multiple karyotypes due to genomic instability gained through chromosomal segregational defects. The variability of genomic changes within a population makes it difficult to study specific processes without the existence of confounding mutations. My project is to create a model system for observation of mitotic defects, specifically multipolar spindles, in a normal cell line, where the genome is intact. Induction of centrosome amplification is required for formation of...
Show moreMost tumors contain multiple karyotypes due to genomic instability gained through chromosomal segregational defects. The variability of genomic changes within a population makes it difficult to study specific processes without the existence of confounding mutations. My project is to create a model system for observation of mitotic defects, specifically multipolar spindles, in a normal cell line, where the genome is intact. Induction of centrosome amplification is required for formation of multipolar spindles. Treatments with colcemid showed a 10% increase in abnormal centrosome numbers over control. However, treatment with hydroxyurea and transfection of hMPSl showed little increase. Extra centrosomes are insufficient to drive multipolarity, therefore, I am using siRNA-mediated knockdown of Nek2 or HSET to decluster the extra centrosomes. Successful declustering will preferably show an increase in multipolar frequency, allowing us to study the formation and resolution of these structres to better understand how they contribute to aneuploidy and tumor progression.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/3325079
- Subject Headings
- Cell division, Karyokinesis, Cancer, Genetic aspects, Genomics, Cellular signal transduction, Centrosomes
- Format
- Document (PDF)
- Title
- Correlation between specific carcinogenic chemicals and specific mitotic defects and the restorative role of antioxidants.
- Creator
- Yates, Travis., Harriet L. Wilkes Honors College
- Abstract/Description
-
The progression of cancerous cells towards a more aggressive tumor can be linked to external elements called carcinogens. The goal of this project is to examine the correlation between exposure to specific carcinogens and an increase of mitotic defects. These defects can manifest as lagging chromosomes, multipolar spindles, and anaphase bridges. Some of these instabilities are associated with the formation of reactive oxygen species (ROS), which are known to damage DNA. The potential for...
Show moreThe progression of cancerous cells towards a more aggressive tumor can be linked to external elements called carcinogens. The goal of this project is to examine the correlation between exposure to specific carcinogens and an increase of mitotic defects. These defects can manifest as lagging chromosomes, multipolar spindles, and anaphase bridges. Some of these instabilities are associated with the formation of reactive oxygen species (ROS), which are known to damage DNA. The potential for damage to the genome can be averted via antioxidants. Using the oral cancer cell line UPCI:SCC103, we established a baseline for the mitotic defects in the absence and presence of various ROS-inducing carcinogens using DAPI-stained fixed cells examined by immunofluorescent microscopy, The cells were treated with varying concentrations of the antioxidants, Vitamin C, (Sb(B-Carotene, and Vitamin E. The reactive oxygen scavengers significantly reduced the number of mitotic defects. A possible link between the carcinogens and lagging chromosomes was established.
Show less - Date Issued
- 2009
- PURL
- http://purl.flvc.org/FAU/210007
- Subject Headings
- Cellular signal transduction, Genetic regulation, Antioxidants, Therapeutic use, Apoptosis, Molecular aspects, Cancer, Chemoprevention
- Format
- Document (PDF)
- 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.
Show less - 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)
- 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.
Show less - 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)
- 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.
Show less - 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)
