Biomedical Engineering and Bioengineering Commons^™

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 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 …

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 …

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 …

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 …

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, …

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 …

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, …

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 …