Medicine and Health Sciences Commons^™

Transport Barriers Influence The Activation Of Anti-Tumor Immunity: A Systems Biology Analysis, Mohammad R. Nikmaneshi, James W. Baish, Hengbo Zhou, Lance L. Munn

Faculty Journal Articles

Effective anti-cancer immune responses require activation of one or more naïve T cells. If the correct naïve T cell encounters its cognate antigen presented by an antigen presenting cell, then the T cell can activate and proliferate. Here, mathematical modeling is used to explore the possibility that immune activation in lymph nodes is a rate-limiting step in anti-cancer immunity and can affect response rates to immune checkpoint therapy. The model provides a mechanistic framework for optimizing cancer immunotherapy and developing testable solutions to unleash anti-tumor immune responses for more patients with cancer. The results show that antigen production rate and …

An In Vivo Biocompatibility Analysis Of A Novel Tissue Regeneration Matrix Using A Pig Model, Shamar Thomas

All Theses

The goal of this project is to develop an injectable bead scaffold to promote tissue regeneration in the void created by lumpectomy and to alleviate post lumpectomy problems by preventing local recurrence and minimizing surgical-related infections. Microbeads were synthesized from collagen type I and crosslinked with tannic acid to form the basis for this injectable therapeutic. Tannic acid acts as a therapeutic anticancer agent. The action mechanisms of tannins in breast cancer cells have been studied with studies showing tannins to be cytotoxic to cancer cells in a dose-dependent manner. Tannic acid induces apoptosis in breast cancer cells via caspase …

Development Of A Computational Model To Investigate Pathways And The Effects Of Treatment In Fanconi Anemia, Sabrina Kellett

Biological Sciences Undergraduate Honors Theses

Fanconi Anemia (FA) is a rare type of anemia that is not easily studied and can have very detrimental effects. This disease compromises the bone marrow, resulting in decreased hemopoiesis. Symptoms of FA also include abnormalities in the brain and spinal cord, incorrect formation of the kidneys, abnormal formation of the heart and lungs, and a dramatically increased risk of developing cancer. FA can be caused by various mutations in any of the 22 genes that encode for proteins involved in what is called the FA DNA repair pathway. In healthy individuals, this pathway specifically repairs interstrand cross-links (ICLs) recognized …

Cost-Benefit Analysis Of Increased Water Treatment Plant Service Goals On Reducing Water Quality Risk, Briton Polen, Kendra Sanner

Williams Honors College, Honors Research Projects

To treat water to make it safe to drink, disinfection processes are used in water treatment plants. These disinfection processes produce disinfection byproducts (DBPs) through the reaction of organic matter and the disinfectant, such as chlorine. DBPs have been shown to pose a cancer risk to consumers. In this report, the focus is on two types of DBPs, trihalomethanes (THMs) and haloacetic acids (HAAs). The cancer risks associated with DBPs are analyzed through ingestion and inhalation pathways. Ingestion and inhalation consist of common water uses like drinking, cooking, or bathing. In addition to this, DBPs have been shown to increase …

Foundations Of Plasmas For Medical Applications, T. Von Woedtke, Mounir Laroussi, M. Gherardi

Electrical & Computer Engineering Faculty Publications

Plasma medicine refers to the application of nonequilibrium plasmas at approximately body temperature, for therapeutic purposes. Nonequilibrium plasmas are weakly ionized gases which contain charged and neutral species and electric fields, and emit radiation, particularly in the visible and ultraviolet range. Medically-relevant cold atmospheric pressure plasma (CAP) sources and devices are usually dielectric barrier discharges and nonequilibrium atmospheric pressure plasma jets. Plasma diagnostic methods and modelling approaches are used to characterize the densities and fluxes of active plasma species and their interaction with surrounding matter. In addition to the direct application of plasma onto living tissue, the treatment of liquids …

A Machine Learning Framework For Identifying Molecular Biomarkers From Transcriptomic Cancer Data, Md Abdullah Al Mamun

FIU Electronic Theses and Dissertations

Cancer is a complex molecular process due to abnormal changes in the genome, such as mutation and copy number variation, and epigenetic aberrations such as dysregulations of long non-coding RNA (lncRNA). These abnormal changes are reflected in transcriptome by turning oncogenes on and tumor suppressor genes off, which are considered cancer biomarkers.

However, transcriptomic data is high dimensional, and finding the best subset of genes (features) related to causing cancer is computationally challenging and expensive. Thus, developing a feature selection framework to discover molecular biomarkers for cancer is critical.

Traditional approaches for biomarker discovery calculate the fold change for each …

The Investigations Of Nps Modulated Immunity And Immunometabolism, Brittney Leigh Ruedlinger

Biomedical Sciences Theses & Dissertations

Cancers remain in the top noncommunicable diseases responsible for premature mortality. The heterogeneity among cancers and within tumors makes treating them ever more challenging. Our misfortune for developing cures is mocked by cancer, with the lowest probability of success (PoS) through clinical trials and FDA approval. At the basic level, there are generally two broad gaps impeding cancer eradication: the unidentified shared mechanism(s) exploited by all cancers and the therapeutic approach to intervene. Nanosecond pulse stimulation (NPS) offers a unique approach since its broad impacts intersect those often hijacked by oncogenesis. Metabolic pathways, known for dysfunctions among cancers, share a …

Continuous Liquid-Liquid Extraction Of Lomustine Synthesis, Devna Grover

The Journal of Purdue Undergraduate Research

No abstract provided.

Synergistic Anticancer Response Of Curcumin And Piperine Loaded Lignin-G-P (Nipam-Co-Dmaema) Gold Nanogels Against Glioblastoma Multiforme, Xinyi Zhao, Bilal Javad, Daxing Cui, James Curtin, Furong Tian

Articles

Glioblastoma multiforme (GBM) is the most aggressive and commonly diag- 11 nosed brain cancer and presents a strong resistance to routine chemotherapeutic drugs. 12 The present study involves the synthesis of Lignin-g- p (NIPAM-co-DMAEMA) gold 13 nanogel, loaded with curcumin and piperine to treat GBM. The application has three 14 functions: (1) overcome the limitations of biodistribution, (2) enhance the toxicity of an- 15 ticancer drugs against GBM, (3) identify the uptake pathway. Atom transfer radical 16 polymerization was used to synthesize the Lignin-g-PNIPAM network, crosslinked with 17 the gold nanoparticles (GNPs) to self-assemble into nanogels. The size distribution and …

Development Of Biomaterials For Drug Delivery, Raquel De Castro

Graduate Theses and Dissertations

Drug delivery systems (DDS) have highly evolved in the last decades with the development of hydrogels and nanoparticles. However, high systemic uptake, side effects, low bioavailability, and encapsulation efficiency continue to be a major hurdle faced by such DDSs.

Nanoparticles and hydrogels can be specifically designed for targeted DDSs to mitigate some of the problems. This dissertation aimed to design two DDSs for ocular drug delivery and one for cancer treatment. The first project sought to develop chitosan nanoparticles (Cs-NP) using PEGDA as a copolymer to encapsulate gentamicin (GtS) for ocular drug delivery. Cs-NPs contain positive charges that can interact …

Bibliometric Analysis Of Named Entity Recognition For Chemoinformatics And Biomedical Information Extraction Of Ovarian Cancer, Vijayshri Khedkar, Charlotte Fernandes, Devshi Desai, Mansi R, Gurunath Chavan Dr, Sonali Tidke Dr., M. Karthikeyan Dr.

Library Philosophy and Practice (e-journal)

With the massive amount of data that has been generated in the form of unstructured text documents, Biomedical Named Entity Recognition (BioNER) is becoming increasingly important in the field of biomedical research. Since currently there does not exist any automatic archiving of the obtained results, a lot of this information remains hidden in the textual details and is not easily accessible for further analysis. Hence, text mining methods and natural language processing techniques are used for the extraction of information from such publications.Named entity recognition, is a subtask that comes under information extraction that focuses on finding and categorizing specific …

Modulation Of Ros In Nanosecond-Pulsed Plasma-Activated Media For Dosage-Dependent Cancer Cell Inactivation In Vitro, Chunqi Jiang, Esin Bengisu Sozer, Shutong Song, Nicola Lai, P. Thomas Vernier, Sigi Guo

Bioelectrics Publications

Dosage control of reactive oxygen and nitrogen species (RONS) is critical to low-temperature plasma applications in cancer therapy. Production of RONS by atmospheric pressure, nonequilibrium plasmas in contact with liquid may be modulated via plasma conditions including plasma treatment time and pulse voltage and repetition frequency. In this study, a terephthalic acid-based probe was used to measure hydroxyl radicals [OH_aq] in water exposed to plasma and to demonstrate that the OH_ag concentration increases linearly with treatment time. Fluorometric measurements of hydrogen peroxide concentration in plasma-activated water show a linear relationship between the H₂O₂ production …

Personalized Medicine: The Use Of Biomarkers And Molecularly Targeted Therapies For Patient Care And Cancer Intervention, Wafa Asad, Emily Schmitt Lavin

Mako: NSU Undergraduate Student Journal

Personalized medicine and targeted therapy have been emerging fields of study for the remediation and inhibition of cancer. Personalized medicine in the treatment of cancer involves using genetic, immune, and proteomic profiling to provide therapeutic options as well as prognostic background for every patient and their tumor’s genetic mutations. Targeted therapies allow researchers and medical personnel alike to determine the appropriate treatment for a patient based on the molecular basis and mechanistic actions of a cancerous tumor. The overall significance of this study was to express how these treatments use biomarkers to pinpoint the location, and severity of the cancer, …

Using Case-Level Context To Classify Cancer Pathology Reports, Shang Gao, Mohammed Alawad, Noah Schaefferkoetter, Lynne Penberthy, Xiao-Cheng Wu, Eric B. Durbin, Linda Coyle, Arvind Ramanathan, Georgia Tourassi

Kentucky Cancer Registry Faculty Publications

Individual electronic health records (EHRs) and clinical reports are often part of a larger sequence-for example, a single patient may generate multiple reports over the trajectory of a disease. In applications such as cancer pathology reports, it is necessary not only to extract information from individual reports, but also to capture aggregate information regarding the entire cancer case based off case-level context from all reports in the sequence. In this paper, we introduce a simple modular add-on for capturing case-level context that is designed to be compatible with most existing deep learning architectures for text classification on individual reports. We …

Engineered Nanoparticles For Site-Specific Bioorthogonal Catalysis: Imaging And Therapy, Riddha Das

Doctoral Dissertations

Bioorthogonal catalysis offers a strategy for chemical transformations complementary to bioprocesses and has proven to be a powerful tool in biochemistry and medical sciences. Transition metal catalysts (TMCs) have emerged as a powerful tool to execute selective chemical transformations, however, lack of biocompatibility and stability limits their use in biological applications. Incorporation of TMCs into nanoparticle monolayers provides a versatile strategy for the generation of bioorthogonal nanocatalysts known as “nanozymes”. We have fabricated a family of nanozymes using gold nanoparticles (AuNPs) as scaffolds featuring diverse chemical functional groups for controlled localization of nanozymes in biological environments, providing unique strategies for …

A Compendium Of Single Cell Analysis In Aging And Disease, Uday Chintapula, Samir M. Iqbal, Young-Tae Kim

Electrical and Computer Engineering Faculty Publications and Presentations

Cell is the fundamental structural and functional unit of complex multicellular organisms. Conventional methods which involve average analysis of cells in bulk populations can undermine physiologically significant cell populations, whereas analysis of cells at a single cell level may reveal unique biomarkers and other mechanisms that govern the genotype and phenotype in various physiological processes in presumed homogenous cell populations. Cellular abnormalities such as irregularities in cellular mechanisms have been linked to human aging and other major diseases including neurodegenerative, vascular, autoimmune, and cancer. Aging is a functional decline associated with various diseases in an organism, majorly arising from cellular …

Barn-Raising On The Digital Frontier: The L.A.U.N.C.H. Collaborative, Bradford W. Hesse, David Ahern, Michele Ellison, Eliah Aronoff-Spencer, Robin C. Vanderpool, Karen Onyeije, Michael C. Gibbons, Timothy W. Mullett, Ming-Yuan Chih, Victoria Attencio, Grant Patterson, Jessica Boten, Christopher Hartshorn, Ben Bartolome, Katie Gorscak, Melanie Mccomsey, Alexandra Hubenko, Bin Huang, Corey Baker, Don Norman

Journal of Appalachian Health

A meta-analysis of oncology papers from around the world revealed that cancer patients who lived more than 50 miles away from hospital centers routinely presented with more advanced stages of disease at diagnosis, exhibited lower adherence to prescribed treatments, presented with poorer diagnoses, and reported a lower quality of life than patients who lived nearer to care facilities. Connected health approaches—or the use of broadband and telecommunications technologies to evaluate, diagnose, and monitor patients beyond the clinic—are becoming an indispensable tool in medicine to overcome the obstacle of distance.

Investigation On Nanoparticle Based Combination Therapy For Targeted Cancer Treatment, Muhammad Raisul Abedin

Doctoral Dissertations

“The current treatment methods in cancer are associated with toxicity in healthy tissues, partial therapeutic response, drug resistance and finally recurrence of the disease. The cancer drugs are challenged by non-specific binding, undesired toxicity in healthy cells, low therapeutic index and finally poor therapeutic outcome. In this work, a targeted nanoscale therapeutic system Antibody Drug Nanoparticle (ADN) was engineered to selectively inhibit the breast cancer cell growth with reduced toxicity in healthy cells. The ADNs were designed by synthesizing rod shaped anoparticles using pure chemotherapeutic drug and covalently conjugating a therapeutic monoclonal antibody (mAb) on the surface of the drug …

Thermal Analysis Of Infrared Irradiation-Assisted Nanosecond-Pulsed Tumor Ablation, James Hornef, Chelsea M. Edelblute, Karl H. Schoenbach, Richard Heller, Siqi Guo, Chunqi Jiang

Bioelectrics Publications

Nanosecond Pulsed Electric Fields (nsPEF) have the potential to treat a variety of cancer types including melanoma, pancreatic and lung squamous cancers. Recent studies show that nsPEF-based cancer therapy may be improved further with the assistance of moderate heating of the target. A feedbacklooped heating system, utilizing a 980-nm fiber optic laser, was integrated into nsPEF electrodes for tumor ablation. The laser beam profile was determined to be Gaussian using a knife-edge technique. Thermal properties of the biological target were evaluated based on the treatment area, penetration depth and thermal distribution due to laser irradiation with or without nsPEF. Synergistic …

Synthesis, Characterization, And Evaluation Of Metal Complexes With Cancer Selective Anti-Proliferative Effects And Hydrogen Evolution Catalytic Properties., Nicholas Vishnosky

Electronic Theses and Dissertations

Bis-thiosemicarbazones (BTSC) and their metal chelates have properties that are useful in several different scientific fields. These systems have already received attention in major fields of biology and engineering. Hydrogen evolution reaction (HER) catalysts need to be cheap and operate under minimal overpotentials with a long lifetime. The treatment of cancer requires, novel agents that have potent cytotoxic activity against cancer cells while displaying minimal side effects. In this dissertation the modular synthesis of these bis-thiosemicarbazone systems is utilized to regulate the redox chemistry for employment in the desired sector of chemistry. The ligand and metal chelates synthesized were characterized …

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 develop …

Ion-Sensitive Field-Effect Transistors With Micropillared Gates For Measuring Cell Ion Exchange At Molecular Levels, Mohammad G. Abdallah, Rayan Khan, Christian Garcia, Young-Tae Kim, Samir M. Iqbal

Electrical and Computer Engineering Faculty Publications and Presentations

The detection of small concentrations of cancer cells before cancer takes over the primary organ completely, or metastasizes to other areas of the body is important for early screening of cancer. One approach to address cancer early screening is through cell ion exchange bioelectricity, which characterizes voltage potential in non-neuronal cells to regulate shape changing, proliferation, differentiation, migration, and cancer formation. Herein, novel ion-sensitive field-effective transistor (ISFET) modality is shown to measure cell behavior during the change of cell properties at molecular levels. ISFETs produce low resistance signals and consume low power. The small size of ISFETs enables miniature diagnosis …

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 …

Increasing Ph In Cancer: Enabling A New Therapeutic Paradigm Using Novel Carbonate Nanoparticles, Avik Som

McKelvey School of Engineering Theses & Dissertations

Enormous progress has been made to treat cancer, and yet the mortality rate of cancer remains unacceptably high. High clinical resistance to molecularly targeted therapeutics has pushed interest again towards inhibiting universal biochemical hallmarks of cancer. Recent evidence suggests that malignant tumors acidify the local extracellular environment to activate proteases for degrading the tumor matrix, which facilitates metastasis, and explains why more aggressive tumors are more acidic. Current therapies have only focused on using the low pH for enhancing drug release in tumors, thereby still relying on the traditional paradigm of intracellular inhibition of pathways, a method that continues to …

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 …

Plasma Medicine: A Brief Introduction, Mounir Laroussi

Electrical & Computer Engineering Faculty Publications

This mini review is to introduce the readers of Plasma to the field of plasma medicine. This is a multidisciplinary field of research at the intersection of physics, engineering, biology and medicine. Plasma medicine is only about two decades old, but the research community active in this emerging field has grown tremendously in the last few years. Today, research is being conducted on a number of applications including wound healing and cancer treatment. Although a lot of knowledge has been created and our understanding of the fundamental mechanisms that play important roles in the interaction between low temperature plasma and …

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 …

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, …

Elucidating The Effects Of Metabolic State On Nanoparticle Distribution In Mice And In Vitro Uptake, Kevin James Quigley

Doctoral Dissertations

Since almost 70% of the U.S. population over 20 years old is overweight and 30% is obese, with much of the western world following suit, many patients that will potentially be administered circulating nanoparticles designed to localize to tumors and avoid non-target areas will have significant amounts of white adipose tissue (WAT), enlarged livers, and additional metabolic complications such as type 2 diabetes. However, studies on nanoparticle biodistribution and efficacy take place almost without exception in lean rodents with healthy metabolic states. In this work, I determined the biodistribution of model nanoparticles – neutral filomicelles and polystyrene spheres both carrying …