Biomedical Engineering and Bioengineering Commons^™

Nanopulse Stimulation (Nps) Induces Tumor Ablation And Immunity In Orthotopic 4t1 Mouse Breast Cancer: A Review, Stephen J. Beebe, Brittany P. Lassiter, Siqi Guo

Bioelectrics Publications

Nanopulse Stimulation (NPS) eliminates mouse and rat tumor types in several different animal models. NPS induces protective, vaccine-like effects after ablation of orthotopic rat N1-S1 hepatocellular carcinoma. Here we review some general concepts of NPS in the context of studies with mouse metastatic 4T1 mammary cancer showing that the postablation, vaccine-like effect is initiated by dynamic, multilayered immune mechanisms. NPS eliminates primary 4T1 tumors by inducing immunogenic, caspase-independent programmed cell death (PCD). With lower electric fields, like those peripheral to the primary treatment zone, NPS can activate dendritic cells (DCs). The activation of DCs by dead/dying cells leads to increases …

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 …

Development And Evaluation Of A Connective Tissue Phantom Model For Subsurface Visualization Of Cancers Requiring Wide Local Excision, Kimberly S. Samkoe, Brent D. Bates, Niki N. Tselepidakis, Alisha V. Dsouza, Jason R. Gunn, Dipak B. Ramkumar, Keith D. Paulsen, Brian W. Pogue, Eric R. Henderson

Dartmouth Scholarship

Wide local excision (WLE) of tumors with negative margins remains a challenge because surgeons cannot directly visualize the mass. Fluorescence-guided surgery (FGS) may improve surgical accuracy; however, conventional methods with direct surface tumor visualization are not immediately applicable, and properties of tissues surrounding the cancer must be considered. We developed a phantom model for sarcoma resection with the near-infrared fluorophore IRDye 800CW and used it to iteratively define the properties of connective tissues that typically surround sarcoma tumors. We then tested the ability of a blinded surgeon to resect fluorescent tumor-simulating inclusions with ∼1-cm margins using predetermined target fluorescence intensities …

Photodynamic Therapy: Agents And Mechanisms, Rebecca Claire Gilson

McKelvey School of Engineering Graduate Student 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 …

Fundamental Characterization Of Oxygen Nanobubbles, John Hamlin, Yi Wen, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

A hypoxic environment is created by tumors’ incredible growth rate. Hypoxia provides radioresistance to the tumors, thus making radiation treatment less effective. The issue is that increasing the radiation leads to increased side effects in patients. Our goal for the oxygen-filled nanobubble is to deliver oxygen to the tumor to lessen radioresistance and make radiation treatment more efficient. However, we need preliminary research to understand and improve the nanobubbles before further research and implementation. To do this, we synthesized different batches of nanobubbles to optimize the production method and find the best container and temperature to store nanobubbles. We measured …

Temporal Resolution Of Cell Death Signaling Events Induced By Cold Atmospheric Plasma And Electroporation In Human Cancer Cells, Danielle M. Krug, Prasoon K. Diwakar, Ahmed Hassanein

The Summer Undergraduate Research Fellowship (SURF) Symposium

Cancer treatment resistance and their invasive and expensive nature is propelling research towards developing alternate approaches to eradicate cancer in patients. Non-thermal, i.e., cold atmospheric plasma (CAP) and electroporation (EP) applied to the surface of cancerous tissue are new methods that are minimally invasive, safe, and selective. These approaches, both independently and synergistically, have been shown to deplete cancer cell populations, but the signaling mechanisms of death and their timelines of action are still widely unknown. To better understand the timeframe of signaling events occurring upon treatment, human cancer cell lines were treated with CAP, EP, and combined CAP with …

Three-Dimensional Microfluidic Tumor Vascular Model For Investigating Breast Cancer Metastasis, Anastasiia Vasiukhina, Brian H. Jun, Luis Solorio, Pavlos P. Vlachos

The Summer Undergraduate Research Fellowship (SURF) Symposium

Metastasis is one of the primary reasons for the high mortality rates in female patients diagnosed with breast cancer. It involves the migration of cancer cells into the circulatory system allowing for the dissemination of cancer cells in distal tissues. Understanding the major processes that occur in cells and tissues during metastasis can help improve currently existing therapeutic methods. In order to understand such mechanisms, developing physiologically relevant tissue models is crucial. Advancements in microfluidics have led to the fabrication of 3D culture models with shear stress gradients and flow control that can recapitulate aspects of the tumor microenvironment in …

Establishing A Lung Model For Evaluation Of Engineered Lung Microbiome Therapies, Kathryn F. Atherton, Stephen Miloro, Jenna Rickus

The Summer Undergraduate Research Fellowship (SURF) Symposium

Benzene, a toxin and carcinogen found in air polluted by cigarette smoke, car exhaust, and industrial processes, is associated with the development of leukemia and lymphoma. Other than avoiding exposure, there is no current method to deter the effects of benzene. One potential strategy to prevent these effects is to engineer the bacteria of the human lung microbiome to degrade benzene. To evaluate this novel approach, we must verify that the bacteria remain viable within the lung microenvironment. To do so, lungs were harvested from rats and swabbed to determine the contents of the original lung microbiome. Then green fluorescent …

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

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

Graduate 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, …

Electrotransfer Of Plasmid Dna Radiosensitizes B16f10 Tumors Through Activation Of Immune Response, Monika Savarin, Urska Kamensek, Maja Cemazar, Richard Heller, Gregor Sersa

Bioelectrics Publications

Background. Tumor irradiation combined with adjuvant treatments, either vascular targeted or immunomodulatory, is under intense investigation. Gene electrotransfer of therapeutic genes is one of these approaches. The aim of this study was to determine, whether gene electrotransfer of plasmid encoding shRNA for silencing endoglin, with vascular targeted effectiveness, can radiosensitize melanoma B16F10 tumors.

Materials and methods. The murine melanoma Bl6F10 tumors, growing on the back of C57BI/6 mice, were treated by triple gene electrotransfer and irradiation. The antitumor effect was evaluated by determination of tumor growth delay and proportion of tumor free mice. Furthermore, histological analysis of tumors (necrosis, apoptosis, …

Regulation Of The Expression And Activity Of Extracellular Signal-Regulated Kinase 3 (Erk3), Lobna Elkhadragy

Browse all Theses and Dissertations

Mitogen-activated protein kinases (MAPKs) are Ser/Thr kinases that regulate diverse cellular processes. Extracellular signal-regulated kinase 3 (ERK3) is an atypical MAPK that has recently gained interest for its roles in cancer. ERK3 promotes cancer cell migration, invasion and drug resistance, and its expression is upregulated in multiple cancers. However, little is known about the molecular mechanisms that regulate ERK3’s expression and kinase activity. Here, we have identified the oncogenic polycomb group protein BMI1 as a positive regulator of ERK3 level in cancer cells. Mechanistically, BMI1 upregulates ERK3 expression by inhibiting the expression of the tumor suppressor microRNA (miRNA) let-7i, which …

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 …

Nanobubbles Provide Theranostic Relief To Cancer Hypoxia, Christopher M. Long, Pushpak N. Bhandari, Joseph Irudayaraj

The Summer Undergraduate Research Fellowship (SURF) Symposium

Hypoxia is a common motif among tumors, contributing to metastasis, angiogenesis, cellular epigenetic abnormality, and resistance to cancer therapy. Hypoxia also plays a pivotal role in oncological studies, where it can be used as a principal target for new anti-cancer therapeutic methods. Oxygen nanobubbles were designed in an effort to target the hypoxic tumor regions, thus interrupting the hypoxia-inducible factor-1α (HIF-1α) regulatory pathway and inhibiting tumor progression. At less than 100nm, oxygen nanobubbles act as a vehicle for site-specific oxygen delivery, while also serving as an ultrasound contrast agent for advanced imaging purposes. Through in vitro and in vivo studies, …

Functional Studies Of The Human Telomerase Holoenzyme, Mohammed E. Sayed

Bioengineering Dissertations - Archive

Telomeres are the DNA structures that cap the ends of linear chromosomes. In humans, telomeres are composed of the hexameric repeats TTAGGG. The reverse transcriptase, telomerase maintains the telomeres by adding the TTAGGG repeats to the chromosomes during cell division. In the absence of telomerase, telomere length limits the self-renewal capabilities of cells. Telomerase is expressed in approximately 90% of all human cancers, making it an almost universal therapeutic target as well as an important player in the progression from healthy to cancerous cell. The biophysical studies discussed in this thesis focus on expanding the understanding of the function and …

An Actomyosin Driven, Pressure Based Adhesion Model Of Confined Glioblastoma Multiforme Cell Migration, Jamie Wright

Bioengineering Dissertations - Archive

Glioblastoma multiforme (GBM) is the most aggressive and common form of glial tumors arising in the support cells of the brain. Cell migration plays a critical role in undermining the surgical resection of tumors. Peripheral cells freely detach and invade the surrounding tissue, preferentially collecting and migrating within confined, mechanically distinct environments such as along the borders of white matter tracts and vasculature. These tracks have been mimicked experimentally using small, rectangular PDMS micro-channels. GBM cells will readily enter and migrate through these micro-channels in the absence of any chemoattractant, even without specific cell-substrate adhesion (integrins) if channel dimensions decrease …

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

USF Tampa 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 …

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 …

Restriction And Characterization Of Human Breast Cancer Using A Three-Dimensional Embryonic Stem Cell Model, Bridget Mooney

Legacy Theses & Dissertations (2009 - 2024)

Human breast cancer is currently the highest diagnosed form of cancer and the second leading cause of cancer-related deaths in American women. Triple negative breast cancer is of the basal subtype and displays the worst prognosis owing to its highly metastatic properties. Current treatments focused on eradicating breast tumors in lieu of or following local therapy include chemotherapy, hormonal therapy, and targeted therapy. Hormonal therapy is not an option for triple negative breast cancer as it does not contain hormone receptors and there are currently no approved biological targeted therapies. Chemotherapy has proven unsuccessful because triple negative breast cancer is …

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 …

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 …

Raman Spectroscopy As A Tool For Single Circulating Tumor Cell (Ctc) Detection And Imaging, Zeid A. Nima

Theses and Dissertations

Breast cancer is the most common type of cancers in the United States. It is imperative that a quick and reliable method for the early detection of circulating tumor cells (CTCs) be identified and tested. In this research several new detection and imaging techniques based on using Raman spectroscopy have been invented. Raman active nano-complex agents based on single-walled carbon nanotubes (SWCNTs) were prepared and used for the swift and specific detection of breast cancer cells. SWCNTs are functionalized with the anti-epithelial cell adhesion molecule (anti-EpCAM) antibody, were able to detect CTCs within 30 min and discriminate few CTCs among …

Creation Of A 3d Construct To Aid Cell Migration And Promote Cell Capture, Joseph Michael Sanders

Legacy Theses & Dissertations (2009 - 2024)

Most cancer-related deaths are attributed to metastasis. The tumor microenvironment is a complex environment which is not fully understood. The Nano Intravital Device (NANIVID) is a versatile, biocompatible device that allows for the manipulation of the tumor microenvironment in vitro and in vivo, providing a platform to study various aspects of tumor progression. The purpose of this study is to modify the NANIVID to resemble the tumor microenvironment in order to allow for a seamless transition from the in vivo environment into the engineered environment within the NANIVID. This engineered microenvironment will promote cell migration and cell capture. It has …

Evaluation Of The Effects Of A Plasma Activated Medium On Cancer Cells, S. Mohades, M. Laroussi, J. Sears, N. Barekzi, H. Razavi

Electrical & Computer Engineering Faculty Publications

The interaction of low temperature plasma with liquids is a relevant topic of study to the field of plasma medicine. This is because cells and tissues are normally surrounded or covered by biological fluids. Therefore, the chemistry induced by the plasma in the aqueous state becomes crucial and usually dictates the biological outcomes. This process became even more important after the discovery that plasma activated media can be useful in killing various cancer cell lines. Here, we report on the measurements of concentrations of hydrogen peroxide, a species known to have strong biological effects, produced by application of plasma to …

Killing Adherent And Nonadherent Cancer Cells With The Plasma Pencil, Mounir Laroussi, Soheila Mohades, Nazir Barekzi

Electrical & Computer Engineering Faculty Publications

The application of low temperature plasmas in biology and medicine may lead to a paradigm shift in the way various diseases can be treated without serious side effects. Low temperature plasmas generated in gas mixtures that contain oxygen or air produce several chemically reactive species that have important biological implications when they interact with eukaryotic or prokaryotic cells. Here, a review of the effects of low temperature plasma generated by the plasma pencil on different cancerous cells is presented. Results indicate that plasma consistently shows a delayed killing effect that is dose dependent. In addition, there is some evidence that …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

University Scholar Projects

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Modeling The Adaptive Immune Response To Mutation-Generated Antigens, Rory J. Geyer

Honors Scholar Theses

Somatic mutations may drive tumorigenesis or lead to new, immunogenic epitopes (neoantigens). The immune system is thought to represses neoplastic growths through the recognition of neoantigens presented only by tumor cells. To study mutations as well as the immune response to mutation-generated antigens, we have created a conditional knockin mouse line with a gene encoding, 5’ to 3’, yellow fluorescent protein (YFP), ovalbumin (which is processed to the immunologically recognizable peptide, SIINFEKL), and cyan fluorescent protein (CFP), or, YFP-ovalbumin-CFP. A frame shift mutation has been created at the 5’ end of the ovalbumin gene, hence YFP should always be expressed, …

Expanding Applications Of The Nano Intravital Device As A Platform For Exploring Tumor Microenvironments, Michael Padgen

Legacy Theses & Dissertations (2009 - 2024)

The tumor microenvironment has been demonstrated to be a key determinant in the progression of cancer. Unfortunately, the mechanisms behind the different microenvironments (cytokine gradients, hypoxia, hypoglycemia, etc) have not been fully elucidated. Identifying these mechanisms can lead to targeted, individualized therapy to prevent metastasis. The Nano Intravital Device (NANIVID) is a microfabricated, implantable device designed to initiate specific microenvironments in vivo so that the time course of the effects can be observed. With both spatial and temporal control over the induced environments, the affected regions of the tumor can be compared to the rest of the tumor. The NANIVID …

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 …