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Alternate applications of anticancer drugs on COS-7 normal cells
Title
Alternate applications of anticancer drugs on COS-7 normal cells.
Creator
Morris, Deborah., Harriet L. Wilkes Honors College
Abstract/Description
Anticancer drugs, including nocodazole and vinblastine, work by disrupting the dynamics of microtubules. Unfortunately, these drugs often produce numerous side effects, including nausea, vomiting, loss of appetite, loss of hair, increased chance of infection, and fatigue. My thesis research evaluated the efficacy of using repeated low doses of microtubule drugs instead of a single high dose, in an attempt to minimize side effects. Using nocodazole and vinblastine, I first established the...
Show moreAnticancer drugs, including nocodazole and vinblastine, work by disrupting the dynamics of microtubules. Unfortunately, these drugs often produce numerous side effects, including nausea, vomiting, loss of appetite, loss of hair, increased chance of infection, and fatigue. My thesis research evaluated the efficacy of using repeated low doses of microtubule drugs instead of a single high dose, in an attempt to minimize side effects. Using nocodazole and vinblastine, I first established the minimum effective concentration that disrupts the microtubules in normal human cells grown in vitro and treated cells with those concentrations over a period of several days. I found that microtubules were increasingly depolymerized as the days progressed. Next, I tested a combination of nocodazole and vinblastine at low concentrations.
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Date Issued
2009
PURL
http://purl.flvc.org/FAU/209996
Subject Headings
Cancer cells, Growth, Regulation, Antineoplastic agents, Physiological effect, Cell cycle, Effect of drugs on, Cancer, Chemotherapy
Format
Document (PDF)
Cells and cocktails
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
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.
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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)
Correlation between specific carcinogenic chemicals and specific mitotic defects and the restorative role of antioxidants
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.
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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)
Deamplification of supernumerary centrosomes by centrosomal clustering
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.
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Date Issued
2012
PURL
http://purl.flvc.org/FAU/3359328
Subject Headings
Centrosomes, Cell division, Cellular signal transduction, Cancer, Genetic aspects
Format
Document (PDF)
Devising a noncancerous model system to study multipolar spindle formation
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.
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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)
Manipulation of normal cells to produce a cancer-like mitotic phenotype
Title
Manipulation of normal cells to produce a cancer-like mitotic phenotype.
Creator
Luffman, Christina., Harriet L. Wilkes Honors College
Abstract/Description
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.
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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)