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Association of SIM2 with cancer
Title
Association of SIM2 with cancer.
Creator
Narayanan, Ramaswamy, Florida Atlantic University
Date Issued
2004-08
PURL
http://purl.flvc.org/fcla/dt/15822
Format
Document (PDF)
Methods of detecting a colon cancer cell
Title
Methods of detecting a colon cancer cell.
Creator
Narayanan, Ramaswamy, Florida Atlantic University
Date Issued
2004-01
PURL
http://purl.flvc.org/fcla/dt/15819
Format
Document (PDF)
Colon carcinoma related oligonucleotides and methods of use
Title
Colon carcinoma related oligonucleotides and methods of use.
Creator
Narayanan, Ramaswamy, Florida Atlantic University
Date Issued
2004-06
PURL
http://purl.flvc.org/fcla/dt/15823
Format
Document (PDF)
Nucleic acids for detecting colon cancer related gene (CCRG) and methods of use
Title
Nucleic acids for detecting colon cancer related gene (CCRG) and methods of use.
Creator
Narayanan, Ramaswamy, Florida Atlantic University
Date Issued
2004-06
PURL
http://purl.flvc.org/fcla/dt/15816
Format
Document (PDF)
Discovery of novel molecular targets in cancer using bioinformatics
Title
Discovery of novel molecular targets in cancer using bioinformatics.
Creator
De Young, Maurice Phillip, V., Florida Atlantic University, Narayanan, Ramaswamy
Abstract/Description
The Cancer Genome Anatomy Project (CGAP) database of the National Cancer Institute contains thousands of expressed sequences, both known and novel, derived from diverse sets of normal, precancerous, and tumor cDNA libraries. This offers the possibility of using this database as a rational starting point for bioinformatics-based cancer gene discovery. Using the Digital Differential Display tool of the CGAP database, a hypothesis-driven gene discovery approach was undertaken to analyze...
Show moreThe Cancer Genome Anatomy Project (CGAP) database of the National Cancer Institute contains thousands of expressed sequences, both known and novel, derived from diverse sets of normal, precancerous, and tumor cDNA libraries. This offers the possibility of using this database as a rational starting point for bioinformatics-based cancer gene discovery. Using the Digital Differential Display tool of the CGAP database, a hypothesis-driven gene discovery approach was undertaken to analyze differential expression of various solid tumor types. Two hundred known genes and five hundred novel sequences were discovered to be differentially expressed, and a comprehensive database was established to facilitate identification of cancer diagnostic and therapeutic targets. To validate the use of bioinformatics in discovering genes with organ- and tumor-selectivity, novel ESTs predicted to be colon tumor-specific were analyzed further for expression specificity. Reverse Transcriptase-Polymerase Chain Reaction (RT-PCR) analysis using matched sets of colon normal- and tumor-derived cDNAs identified one EST to be specifically expressed in the majority of colon tumors and normal small intestine. Due to this apparent specificity, the gene was termed Colon Carcinoma Related Gene (CCRG). Based on protein sequence analysis, CCRG belongs to a novel class of secreted factors. Another gene identified in this study showed homology to Single Minded 2 gene (SIM2). Involvement between SIM2 and cancer has not yet been reported. Isoform-specific expression of SIM2 short-form (SIM2-s) was seen in colon, pancreas, and prostate carcinomas but not in most normal tissues. Using a large collection of paraffin sections from colon, pancreas, and prostate tumor and normal tissues, elevated protein expression was seen in tumors compared to normal tissue specimens, demonstrating the diagnostic potential of SIM2-s. Antisense inhibition of SIM2-s expression in colon and pancreatic cancer cell lines caused inhibition of gene expression, growth inhibition, and apoptosis. Administration of SIM2-s antisense in nude mice caused inhibition of colon tumor growth without pronounced gross toxicity. Using GeneChipRTM technology, a gene expression profile indicative of apoptosis was observed in the colon cancer model. CCRG and SIM2-s offer both a diagnostic and therapeutic potential in select cancers and validate the use of bioinformatics approaches in the gene discovery paradigm.
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Date Issued
2003
PURL
http://purl.flvc.org/fau/fd/FADT12053
Subject Headings
Bioinformatics, Gene expression, Oncogenes
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)
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)
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)
Evaluating The Kinetics Of Proinflammatory Immune Responses To Simian Immunodeficiency Virus Infection In Rhesus Macaques By Transcriptional Analysis
Title
Evaluating The Kinetics Of Proinflammatory Immune Responses To Simian Immunodeficiency Virus Infection In Rhesus Macaques By Transcriptional Analysis.
Creator
Cartwright, Michael, Cameron, Mark, Narayanan, Ramaswamy, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
Understanding the host response immediately following mucosal HIV-1 infection will be pivotal in determining whether the immune response induced by a vaccine will successfully sense and control viral replication. In order for effective vaccine strategies and modalities to be developed, these earliest immunological events must be fully assessed in a non-biased manner. Nonhuman primates (NHP), specifically Rhesus macaques (RM), serve as a model to investigate the immunological landscape...
Show moreUnderstanding the host response immediately following mucosal HIV-1 infection will be pivotal in determining whether the immune response induced by a vaccine will successfully sense and control viral replication. In order for effective vaccine strategies and modalities to be developed, these earliest immunological events must be fully assessed in a non-biased manner. Nonhuman primates (NHP), specifically Rhesus macaques (RM), serve as a model to investigate the immunological landscape immediately post-challenge and to define the spatiotemporal path of simian immunodeficiency virus (SIV). SIV infection of RM serves as a model of human HIV infection as it recapitulates many of the virological, immunological, and pathological features of HIV infection in the human host. In this thesis I will test the hypothesis whether transcriptional analysis will allow a sensitive measure of the early innate immune responses that accompany detection of the SIV virus in the periphery. I have determined that an early inflammatory profile arises early in tissues proximal to the challenge site that precedes widespread immune activation and the systemic antiviral interferon response. This study defines in detail the spatiotemporal relationship between virus and host immune response and may be a valuable resource in guiding future vaccine design strategies.
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Date Issued
2016
PURL
http://purl.flvc.org/fau/fd/FA00004574, http://purl.flvc.org/fau/fd/FA00004574
Subject Headings
Rhesus monkeys., Monkeys as laboratory animals., Retrovirus infections., Veterinary virology., Simian immunodeficiency virus--Immunology., HIV infections--Immunology., AIDS (Disease), HIV (Viruses), Metaphor--Data processing., Language and languages--Political aspects--United States.
Format
Document (PDF)
Noncoding RNAs as novel pancreatic cancer targets
Title
Noncoding RNAs as novel pancreatic cancer targets.
Creator
Makler, Amy, Narayanan, Ramaswamy, Florida Atlantic University, Charles E. Schmidt College of Science, Department of Biological Sciences
Abstract/Description
Pancreatic cancer is an abhorrent malignancy with limited diagnostics and response to drug therapy. It is believed that noncoding RNAs (ncRNAs) will further the understanding behind the mechanisms of pancreatic cancer development and progression, providing a novel approach for drug development and biomarker discovery. Therefore, a database of pancreatic cancer ncRNAs was established using bioinformatics and text mining approaches. These ncRNAs were characterized for RNA expression, copy...
Show morePancreatic cancer is an abhorrent malignancy with limited diagnostics and response to drug therapy. It is believed that noncoding RNAs (ncRNAs) will further the understanding behind the mechanisms of pancreatic cancer development and progression, providing a novel approach for drug development and biomarker discovery. Therefore, a database of pancreatic cancer ncRNAs was established using bioinformatics and text mining approaches. These ncRNAs were characterized for RNA expression, copy number variation, disease association, single nucleotide polymorphisms, secretome analysis, and identification of protein targets. Exosomal proteins and ncRNA identified through this study provide the basis for noninvasive diagnostic potential. Additionally, a secreted microRNA, MIR3620, emerged from this study as a potential prognostic and diagnostic biomarker for pancreatic cancer. By analyzing MIR3620 and its protein targets, a mechanism of regulation for these genes in contributing to the progression and development of pancreatic cancer was established.
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Date Issued
2018
PURL
http://purl.flvc.org/fau/fd/FA00013086
Subject Headings
Pancreas--Cancer., Non-coding RNA., Pancreas--Cancer--Pathogenesis., Biomarkers.
Format
Document (PDF)
Functional genomics of a novel colon carcinoma-related gene (CCRG)
Title
Functional genomics of a novel colon carcinoma-related gene (CCRG).
Creator
Damania, Hema D., Florida Atlantic University, Narayanan, Ramaswamy, Department of Biological Sciences, Charles E. Schmidt College of Science
Abstract/Description
Recently Dr. Narayanan's laboratory, utilizing bioinformatics approaches, identified a novel gene which may play a role in colon cancer. This gene in view of its expression specificity was termed Colon Carcinoma Related Gene (CCRG). The CCRG belongs to a novel class of secreted molecules with a unique cysteine rich motif. The function of CCRG however, remains unknown. The basis of this project revolved around establishing the putative function (functional genomics) of CCRG. The rationale for...
Show moreRecently Dr. Narayanan's laboratory, utilizing bioinformatics approaches, identified a novel gene which may play a role in colon cancer. This gene in view of its expression specificity was termed Colon Carcinoma Related Gene (CCRG). The CCRG belongs to a novel class of secreted molecules with a unique cysteine rich motif. The function of CCRG however, remains unknown. The basis of this project revolved around establishing the putative function (functional genomics) of CCRG. The rationale for the project was to test a hypothesis that CCRG may offer a growth advantage to cancer cells. The availability of diverse tumor-derived cell lines, which were CCRG negative offered a possibility to study the consequence of enforced expression of CCRG. A breast carcinoma cell line was transfected with an exogenous CCRG expression vector and the stable clones were characterized. The stable transfectants of CCRG showed enhanced growth and a partial abrogation of serum growth factor(s) requirement. These results provide a framework for future experiments to further elucidate the function of CCRG.
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Date Issued
2002
PURL
http://purl.flvc.org/fcla/dt/12965
Subject Headings
Colon (Anatomy)--Cancer, Genomics, Bioinformatics, Gene expression
Format
Document (PDF)