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Cancer

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Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott Jan 2019

Towards The Rational Design And Application Of Polymers For Gene Therapy: Internalization And Intracellular Fate, Landon Alexander Mott

Theses and Dissertations--Chemical and Materials Engineering

Gene therapy is an approach for the treatment of acquired cancers, infectious disease, degenerative disease, and inherited genetic indications. Developments in the fields of immunotherapies and CRISPR/Cas9 genome editing are revitalizing the efforts to move gene therapy to the forefront of modern medicine. However, slow progress and poor clinical outcomes have plagued the field due to regulatory and safety concerns associated with the flagship delivery vector, the recombinant virus. Immunogenicity and poor transduction in certain cell types severely limits the utility of viruses as a delivery agent of nucleic acids. As a result, significant efforts are being made to ...


Characterizing Targeted Therapeutic Delivery And Cellular Dynamics Using In Vitro Cancer Disease Models, Christopher George Uhl Aug 2018

Characterizing Targeted Therapeutic Delivery And Cellular Dynamics Using In Vitro Cancer Disease Models, Christopher George Uhl

Theses and Dissertations

Cancer is a significant health risk to people living in developed and developing countries, which continues to prove difficult to treat. Common treatment options of cancers include surgical removal, radiation, and chemotherapies, which are often used in combination to improve the likelihood of successful treatment. Such combinatory approaches towards treatment are often taken because each approach is not targeted enough to function perfectly on its own. Being able to delivery therapeutic loads in a more targeted manner to sites of cancer has the capability of improving therapeutic efficiency and improving patient responses. The development of improved therapeutic delivery vehicles and ...


Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller Aug 2018

Evaluation Of Drug-Loaded Gold Nanoparticle Cytotoxicity As A Function Of Tumor Tissue Heterogeneity., Hunter Allan Miller

Electronic Theses and Dissertations

The inherent heterogeneity of tumor tissue presents a major challenge to nanoparticle-medicated drug delivery. This heterogeneity spans from the molecular to the cellular (cell types) and to the tissue (vasculature, extra-cellular matrix) scales. Here we employ computational modeling to evaluate therapeutic response as a function of vascular-induced tumor tissue heterogeneity. Using data with three-layered gold nanoparticles loaded with cisplatin, nanotherapy is simulated with different levels of tissue heterogeneity, and the treatment response is measured in terms of tumor regression. The results show that tumor vascular density non-trivially influences the nanoparticle uptake and washout, and the associated tissue response. The drug ...


Fluorescence Guided Tumor Imaging: Foundations For Translational Applications, Jessica P. Miller May 2018

Fluorescence Guided Tumor Imaging: Foundations For Translational Applications, Jessica P. Miller

Engineering and Applied Science Theses & Dissertations

Optical imaging for medical applications is a growing field, and it has the potential to improve medical outcomes through its increased sensitivity and specificity, lower cost, and small instrumentation footprint as compared to other imaging modalities. The method holds great promise, ranging from direct clinical use as a diagnostic or therapeutic tool, to pre-clinical applications for increased understanding of pathology. Additionally, optical imaging uses non-ionizing radiation which is safe for patients, so it can be used for repeated imaging procedures to monitor therapy, guide treatment, and provide real-time feedback. The versatile features of fluorescence-based optical imaging make it suited for ...


A Novel Approach For Cancer Characterization Using Latent Dirichlet Allocation And Disease-Specific Genomic Analysis, Hima Bindu Yalamanchili Jan 2018

A Novel Approach For Cancer Characterization Using Latent Dirichlet Allocation And Disease-Specific Genomic Analysis, Hima Bindu Yalamanchili

Browse all Theses and Dissertations

Two challenging problems in the clinical study of cancer are the characterization of cancer subtypes and the classification of individual patients according to those subtypes. Further, understanding the role of differential gene expression in the development of and molecular response to cancer is a complex problem that remains challenging, in part due to the sheer number of genes and gene products involved. Traditional statistical approaches addressing these problems are hindered by within-class heterogeneity and challenges inherent in data integration across high-dimensional data. In addition, many current machine learning methods do not lend themselves to biological interpretation. We have developed a ...


Photodynamic Therapy: Agents And Mechanisms, Rebecca Claire Gilson Aug 2017

Photodynamic Therapy: Agents And Mechanisms, Rebecca Claire Gilson

Engineering and Applied Science Theses & Dissertations

Despite enormous efforts, cancer remains a leading cause of morbidity and mortality world-wide. The main challenges currently facing cancer therapy include lack of adequate tumor targeting, failure to treat hypoxic tumor cells, and induction therapy resistant tumors. A solution to these limitations can be found in photodynamic therapy (PDT) which combines light and light activatable compounds, photosensitizers (PSs), to produce cytotoxic reactive oxygen species (ROS) to damage tumor tissue. This creates a spatiotemporal therapeutic effect, where cell damage only occurs at the intersection of the PS and light. PDT can treat tumors through unique mechanisms which reduce induction of tumor ...


High Throughput Analysis Of The Penetration Of Iron Oxide/Polyethylene Glycol Nanoparticles Into Multicellular Breast Cancer Tumor Spheroids, Jonathan Robert Gabriel Jul 2017

High Throughput Analysis Of The Penetration Of Iron Oxide/Polyethylene Glycol Nanoparticles Into Multicellular Breast Cancer Tumor Spheroids, Jonathan Robert Gabriel

Theses and Dissertations

The purpose of this study was to design and optimize a system for the high-throughput analysis of multicellular tumor spheroids (MCTS), and validate the system through the study of a complex biological model. The system was successfully created and optimized, allowing the histological recovery of MCTS at rates up to 90% for microarrays of 24-spheroids. Arrays of 96-spheroids were recovered at rates up to 86%. The system was used to study the penetration of 5k Da-polyethylene coated superparamagnetic iron-oxide nanoparticles (5k-PEG SPIONs) into HTB-126 breast cancer spheroids cultured to a mean diameter of 486 micrometer (± 25.2 micrometer). Results were ...


Examining The Effects Of Macrophage Populations On Cancerous Tumor Growth., Grace E. Mahlbacher May 2017

Examining The Effects Of Macrophage Populations On Cancerous Tumor Growth., Grace E. Mahlbacher

Electronic Theses and Dissertations

The most abundant immune cell types of the tumor microenvironment macrophages recruited there by tumor-eluted factors. The role of these immune cells in tumor progression, and the interplay between tumor and immune cells is an emerging field of research with potential for novel treatment strategies. Here, a TIE2 expressing macrophage (TEM) subtype is integrated into a virtual tumor model. Within the 2D microenvironment, the TEM will differentiate from an extravasated monocyte precursor, congregate around the abluminal side of the vasculature in response to a chemoattractant gradient, secrete cytokines which favor differentiation of a separate angiogenic macrophage subtype [1]. The effects ...


Sensitivity Of Diffuse Reflectance Spectroscopy To Dose- And Depth-Dependent Changes In Tumor Oxygenation After Radiation Therapy, Daria Semeniak May 2017

Sensitivity Of Diffuse Reflectance Spectroscopy To Dose- And Depth-Dependent Changes In Tumor Oxygenation After Radiation Therapy, Daria Semeniak

Theses and Dissertations

Along with chemotherapy, immunotherapy, and surgery, radiotherapy is one of the most common treatments used against cancer. Around 50% of all cancer patients undergo radiation therapy. While for some patients radiotherapy works efficiently and lead to a complete cancer disappearance, for others treatment outcome may be less favorable due to radioresistance processes happening within a tumor on the molecular level. Radioresistance remains a big challenge for modern oncology. The ability to identify radioresistance at the early stage of radiotherapy would help physicians to improve therapy efficiency. At the current moment, despite the rapid progress in cancer understanding and diagnostic modalities ...


Utilizing Tumor Exome Variation To Predict Cancer Treatment Outcomes, Michael Rendleman Jan 2017

Utilizing Tumor Exome Variation To Predict Cancer Treatment Outcomes, Michael Rendleman

Honors Theses at the University of Iowa

Cancer genomics, in the context of informing clinical decisions with tumor genotype, is a field characterized by high-dimensional data. Computational approaches for evaluating sets of features to be utilized in machine learning methods are essential for yielding accurate predictive and prognostic models. Additionally, the publicly-available results of the Broad Institute’s Firehose cancer genomics analysis pipeline presents a wealth of information that may be useful for cancer genotyping. Power analysis and classifier comparison are performed with the goal of evaluating a gene-based mutation significance feature set (MutSig) from Firehose. They reveal that while the MutSig features likely contain some prognostic ...


Influence Of Fibroblasts On Metastatic Cancer Cell Drug Resistance In A 3d Microfluidic Cell Array, Elizabeth C. Benoy Jan 2017

Influence Of Fibroblasts On Metastatic Cancer Cell Drug Resistance In A 3d Microfluidic Cell Array, Elizabeth C. Benoy

Dissertations and Theses

Modeling an accurate depiction of the tumor microenvironment, (TME), is essential to observe the effect external factors might have on the tumor in vivo. In cancer therapy specifically, the outcomes of clinical treatments are heavily dependent on drug testing methods despite the cytotoxic effects these methods might have on the patient. Our lab has previously developed a three layered microfluidic cell array (3D μFCA) to reconstruct the relevantly spatial configuration of tumor and microvasculature found in vivo in order to develop a more efficient tool of high throughput drug discovery and screening. In this study, we optimized this device to ...


Epithelial-Mesenchymal Crosstalk Influences Cancer-Related Cell Behavior: A 3d Lung Alveolus-Fibroblast Co-Culture System, Jessica Kole Hall Jan 2017

Epithelial-Mesenchymal Crosstalk Influences Cancer-Related Cell Behavior: A 3d Lung Alveolus-Fibroblast Co-Culture System, Jessica Kole Hall

Undergraduate Honors Theses

Lung cancer is a devastating disease that kills more individuals in the United States than any other cancer. The tumor microenvironment is increasingly recognized as playing a major role in the progression of cancer. Thus, studying the interactions among lung cancer cells, non-malignant cells and the surrounding matrix is critical for understanding and treating lung cancer. Three-dimensional in vitro co-culture systems allow for tissue-relevant platforms that better recapitulate the native cell environment. In this work, we employed a cyst templating technique to culture alveolar epithelial cells on photodegradable microspheres and subsequently encapsulated the cell-covered spheres within poly(ethylene glycol) (PEG ...


A Novel Minimally Invasive Tumour Localization Device, Doran Avivi Apr 2016

A Novel Minimally Invasive Tumour Localization Device, Doran Avivi

Electronic Thesis and Dissertation Repository

Lung cancer is one of the leading causes of death, by cancer. The usual treatment is surgical resection of tumours. However, patients who are weak or have poor pulmonary function are deemed unfit for surgery. For these patients, a minimally-invasive approach is desired. A major problem associated with minimally-invasive approaches is tumour localization in real time and accurate measurement of tool--tissue forces.

This thesis describes the design, analysis, manufacturing and validation of a minimally-invasive instrument for tumour localization, named Palpatron. The instrument has an end effector that is able to support two previously designed jaws, one containing an ultrasound sensor ...


A Trans-Dimensional View Of Drug Resistance Evolution In Multiple Myeloma Patients, Timothy Jacobson Mar 2016

A Trans-Dimensional View Of Drug Resistance Evolution In Multiple Myeloma Patients, Timothy Jacobson

Graduate Theses and Dissertations

Multiple Myeloma (MM) is a treatable, yet incurable, malignancy of bone marrowplasma cells. This cancer affects many patients and many succumb to relapse of tumor burden despite a large number of available chemotherapeutic agents developed for therapy. This is because MM tumors are heterogeneous and receive protection from therapeutic agents by the microenvironment and other mechanisms including homologous MM-MM aggregation. Therefore, therapy failure and frequent patient relapse is due to the evolution of drug resistance, not a lack of available drugs. To analyze and understand this problem, the evolution of drug resistance has been explored and presented herein. We seek ...


Enhancement Of Cancer Vaccine Efficacy Via Nanoparticle Or Molecular-Based Adjuvants, Myunggi An Jan 2016

Enhancement Of Cancer Vaccine Efficacy Via Nanoparticle Or Molecular-Based Adjuvants, Myunggi An

Wayne State University Theses

Adjuvants are immunomodulators which enhance immune responses to vaccines. However, parenteral administration of unformulated adjuvants fails to reach lymph nodes (LNs), the anatomic organ where the primary functions of immune cells are orchestrated. The LN-targeting delivery plays the key roles in promoting immune activation and has the great potential to transform disease treatment. The main goal of this thesis is to develop efficient vaccine delivery systems to target therapeutics into draining lymph nodes (dLNs) for ensuring their immunostimulatory activity. We introduced therapeutic applications of activating TLR9 with synthetic CpG oligodeoxynucleotide (ODN) agonists in nanoparticle or molecular form to activate immune ...


Modeling Alveolar Epithelial Cell Behavior In Spatially Designed Hydrogel Microenvironments, Katherine Jean Reeder Lewis Jan 2016

Modeling Alveolar Epithelial Cell Behavior In Spatially Designed Hydrogel Microenvironments, Katherine Jean Reeder Lewis

Chemical & Biological Engineering Graduate Theses & Dissertations

The alveolar epithelium consists of two cell phenotypes, elongated alveolar type I cells (AT1) and rounded alveolar type II cells (ATII), and exists in a complex three-dimensional environment as a polarized cell layer attached to a thin basement membrane and enclosing a roughly spherical lumen. Closely surrounding the alveolar cysts are capillary endothelial cells as well as interstitial pulmonary fibroblasts. Many factors are thought to influence alveolar epithelial cell differentiation during lung development and wound repair, including physical and biochemical signals from the extracellular matrix (ECM), and paracrine signals from the surrounding mesenchyme. In particular, disrupted signaling between the alveolar ...


Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly Jan 2016

Surface-Initiated Polymerizations For The Rapid Sorting Of Rare Cancer Cells, Jacob L. Lilly

Theses and Dissertations--Chemical and Materials Engineering

Cancer metastasis directly accounts for an estimated 90% of all cancer related deaths and is correlated with the presence of malignant cells in systemic circulation. This observed relationship has prompted efforts to develop a fluid biopsy, with the goal of detecting these rare cells in patient peripheral blood as surrogate markers for metastatic disease as a partial replacement or supplement to tissue biopsies. Numerous platforms have been designed, yet these have generally failed to support a reliable fluid biopsy due to poor performance parameters such as low throughput, low purity of enriched antigen positive cells, and insufficiently low detection thresholds ...


Decitabine-Loaded Nanogel Treatment To Reverse Cancer Drug Resistance, Samantha A. Cramer Jan 2016

Decitabine-Loaded Nanogel Treatment To Reverse Cancer Drug Resistance, Samantha A. Cramer

ETD Archive

Cancers in which epigenetic changes, such as hypermethylation of DNA, lead to drug resistance cause the cancer to become unresponsive to existing chemotherapeutic treatments. The epigenetic drug – 5-aza-2’-deoxycytidine (decitabine, DAC) – is a potent hypomethylating agent, but its effect is transient due to its instability. Previous studies have shown that loading DAC into nanogel significantly enhances its antiproliferative effect (compared to DAC in solution) in drug-resistant breast cancer cells (MCF-7/ADR). Further, the previous studies demonstrated changes in the membrane lipid profile of resistant cells following treatment with DAC either as solution or in nanogels. The objective of the present ...


Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen Jan 2016

Bioengineered Platforms To Study Carcinoma Cell Response To Drug Treatment, Thuy V. Nguyen

Doctoral Dissertations

The tumor extracellular matrix (ECM) plays an important role in facilitating tumor growth and mediating tumor cells' resistance to drugs. However, during drug development, potential chemotherapeutics are screened in plastic plates, which lack relevant ECM physicochemical cues. In order to improve drug development process, this dissertation includes the development of relevant 2D and 3D biomaterial systems that can be used to study carcinoma cell response to drug treatment.

A novel poly(ethylene glycol)-phosphorylcholine (PEG-PC) high-throughput biomaterial platform was developed to study how the ECM mechanochemical properties affect cancer cells' response to drug. The PEG-PC biomaterial is optically transparent, has ...


The Effects Of Weak Static And Pulsed Magnetic Fields On Fibroblast And Fibrosarcoma Cells Under A Controlled Magnetic Environment, Julian Brandon Cyrus Apr 2015

The Effects Of Weak Static And Pulsed Magnetic Fields On Fibroblast And Fibrosarcoma Cells Under A Controlled Magnetic Environment, Julian Brandon Cyrus

Electrical, Computer & Energy Engineering Graduate Theses & Dissertations

This thesis provides evidence supporting the claim that weak static and pulsed magnetic fields have measureable effects upon fibrosarcoma cells. Fibroblast and fibrosarcoma cell lines were exposed to 0, 100, and 200μT fields, with a static 45μT field as the control. Each exposure intensity, other than 0μT, was conducted at a 20 sec pulse repetition rate, as well as the normal static conditions. The cells were tested for variations in oxidative stress, membrane potential, and cell viability. The fibrosarcoma cells were also tested for cell count. The trials were conducted using an electromagnetic system that provided a controlled magnetic environment ...


A Novel Biomaterial Enables Chemotactic Study Of Motile Central Nervous System-Derived Tumor Cells, Tanya Singh Jan 2013

A Novel Biomaterial Enables Chemotactic Study Of Motile Central Nervous System-Derived Tumor Cells, Tanya Singh

Dissertations and Theses

"The local cell microenvironment plays an important role in maintaining the dynamics of the extracellular matrix (ECM) and the cell-ECM relationship. ECM is a complex network of macromolecules with distinct mechanical and biochemical characteristics [1]. The multifaceted interactions that occur between cells and the ECM are crucial to the regulation of processes that maintain homeostasis. These mechanisms are often deregulated during cancer onset and progression, which cause the ECM to become highly disorganized, alter the cell-matrix interactions, and promote increased hypervascularity and metastasis as these components are indicative of cancer progression. Medulloblastoma (MB) is one of the most common, malignant ...


Impedance Sensing Of N2a And Astrocytes As Grounds For A Central Nervous System Cancer Diagnostic Device, Fraser Traves Smith Grove Jun 2012

Impedance Sensing Of N2a And Astrocytes As Grounds For A Central Nervous System Cancer Diagnostic Device, Fraser Traves Smith Grove

Master's Theses and Project Reports

This thesis utilizes previously described manufacturing and design techniques for the creation of a PDMS-glass bonded microfluidic device, capable of electrochemical impedance spectroscopy (EIS). EIS has been used across various fields of research for different diagnostic needs. The major aim of this thesis was to capture cancerous and non-cancerous cells between micron sized electrodes within a microfluidic path, and to complete analysis on the measured impedances recorded from the two differing cell types. Two distinct ranges of impedance frequency were analyzed – the α dispersion range, which quantifies the impedance of the membranes of the cells of interest, and the β ...


Quantitative, Spatial Imaging Based Measurements To Assess Cellular Health And Oxygenation In A Tissue Engineered Test System, Erik Bland May 2012

Quantitative, Spatial Imaging Based Measurements To Assess Cellular Health And Oxygenation In A Tissue Engineered Test System, Erik Bland

All Dissertations

Three-dimensional in vitro tissue test systems are employed to examine cell behavior, test responses to drugs and vaccines, and answer basic biological questions. These systems are more physiologically relevant than two-dimensional cell cultures, and are more relevant, easier and less expensive to maintain than animal models. However, methods used to measure cell behavior and viability have been developed specifically for two-dimensional cell cultures or animal models, and are often not optimally translated to three-dimensional in vitro test systems. The purpose of this work was to aid in the development of three-dimensional, spatially controlled in vitro test systems, and to develop ...


Impedance-Based Detection Of Tissue Using A Multi-Electrode Device, Shane Killian Fleshman Dec 2011

Impedance-Based Detection Of Tissue Using A Multi-Electrode Device, Shane Killian Fleshman

Master's Theses and Project Reports

Melanoma skin cancer is the abnormal growth of the melanocytes – the pigmented cells located in the epidermis. The current gold standard diagnostic technique for determining whether a lesion is cancerous involves subjectively examining suspicious lesions and performing an invasive biopsy to confirm melanoma. This method may neglect some lesions or cause scarring from biopsies that turn out to be benign. Thus, impedance-based detection using a multi-electrode device was investigated as a noninvasive technique to diagnose melanoma skin cancer. The multi-electrode device was designed with 8 equally spaced Ag/AgCl electrodes surrounding one central electrode at a 5 mm radius. The ...


Multiscale Modeling Of The Erbb Receptor Tyrosine Kinase Signaling Network Through Theory And Experiment, Shannon E. Telesco Aug 2011

Multiscale Modeling Of The Erbb Receptor Tyrosine Kinase Signaling Network Through Theory And Experiment, Shannon E. Telesco

Publicly Accessible Penn Dissertations

The biochemical processes occurring within a living cell span a spectrum of scales in space and time, ranging from the nano- to the macro-scale. We note that a single cellular process often operates on multiple spatial and temporal scales, and thus it becomes necessary to combine modeling techniques in multiscale approaches, in which different levels of theory are synergized to describe a system at a number of scales or resolutions. In this work we apply a multiscale modeling framework to investigate the molecular regulatory mechanisms governing the activation of the ErbB receptor tyrosine kinases, a family of kinases which are ...


Design Of A Bioinformatics System For Insertional Mutagenesis Analysis And Its Application To The Sleeping Beauty Transposon System, Kishore Nannapaneni May 2011

Design Of A Bioinformatics System For Insertional Mutagenesis Analysis And Its Application To The Sleeping Beauty Transposon System, Kishore Nannapaneni

Theses and Dissertations

Cancer is one of the leading causes of death in the world. Approximately one fifth of deaths in the western industrial nations are caused by cancer. Every year several hundreds of thousands of new patients are diagnosed with cancer and several thousands die of cancer. Scientists have been conducting research from different angles for effective prevention, diagnosis and cure of Cancer.

Ever since the genetic basis of cancer has been demonstrated, a race has been ignited globally in the scientific community to identify potential oncogenes and tumor suppressor genes. The genetics of the tumors are complex in nature where combinations ...


Understanding The Molecular Dynamics Of Ypel3 And Fhit Gene Expression, Kevin Daniel Kelley Jan 2010

Understanding The Molecular Dynamics Of Ypel3 And Fhit Gene Expression, Kevin Daniel Kelley

Browse all Theses and Dissertations

A comprehensive understanding of the molecular signaling pathways that regulate cell growth and proliferation is essential in the realization of new therapeutic options to facilitate early detection and eradication of malignancy. Understanding the transcriptional regulation of the YPEL3 and FHIT genes forms the basis of this dissertation. YPEL3, or Yippee-like 3, is a newly identified p53 target gene that inhibits tumor cell growth and is thus itself, a novel tumor suppressor gene. FHIT, or Fragile histidine triad, is a well known tumor suppressor gene and is regulated at the transcriptional level by another growth inhibitory protein, FOXO3a, a Forkhead box ...


Quantification Of Vascular Parametric Indices Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging, Areen Khaled Al.Bashir Jan 2010

Quantification Of Vascular Parametric Indices Using Dynamic Contrast-Enhanced Magnetic Resonance Imaging, Areen Khaled Al.Bashir

Wayne State University Dissertations

Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) is a non-invasive method used to evaluate the biological activity in early clinical trials of novel drugs targeting the tumor vasculature using gadolinium-DTPA (Gd) as a contrast agent. However, it has some limitations, such as reproducibility, data acquisition times, the presence of noise, extracting contrast concentration, estimating T1 relaxation and estimating pharmacokinetic parameters.

In this work, a new approach to used fixed T1(0) which provides more reproducible DCE results has been introduced. Using this new algorithm to quantify the vascular changes in DCE-MRI, a pre-clinical renal cell carcinoma (RCC) tumor model was used ...


Inducing A Normal Phenotype In Breast Epithelial Cells Using A Three-Dimensional Basement Membrane Extract Culture System: A Study On The Reversion Of Cancer, Ross H. Booth May 2009

Inducing A Normal Phenotype In Breast Epithelial Cells Using A Three-Dimensional Basement Membrane Extract Culture System: A Study On The Reversion Of Cancer, Ross H. Booth

All Graduate Theses and Dissertations

Experimentally, traditional developmental models and transgenic animals consistently underscore the importance of studying cell behavior in the correct tissue context. However, live animal experimentation is inherently complex, and systematic assessment of the effects of individual variables, such as cell shape and matrix compliance on cell behavior, is extremely difficult at best. Two-dimensional monolayer culture of key individual cell types has provided abundant, fundamental information on cell response, but cannot be used to show the normal phenotype of breast epithelial cells. Furthermore, their results often fail to translate into in vivo and clinical studies. It has been previously established that normal ...


Biochemical Characterization Of Htrf1 And Htep1, Two Proteins Involved In Telomere Maintenance, Kambiz Tahmaseb Jan 2007

Biochemical Characterization Of Htrf1 And Htep1, Two Proteins Involved In Telomere Maintenance, Kambiz Tahmaseb

Browse all Theses and Dissertations

Telomeres are the structures that protect the ends of linear chromosomes from fusion and degradation. The telomere consists of tandem repeated DNA sequences that can range from hundreds of bases to kilo-bases depending on the organism. As the cells of an organism replicate their DNA, these repeats are lost due to the end replication problem, where the ends of linear DNA cannot be fully replicated. As the telomeres are shortened through each round of replication, they eventually reach a critical point. Once the telomeres are too short and the cell risks losing coding sequences, a signaling pathway is initiated that ...