Medicine and Health Sciences Commons^™

A Time-Course Characterization Of Muscle Function And Mitochondrial Markers During Colorectal Cancer-Induced Cachexia In Tumor-Bearing Male Mice, Ana Cabrera Ayuso

Graduate Theses and Dissertations

Cachexia is a multisystemic and multifactorial syndrome prevalent in cancer patients. It is clinically defined by involuntary loss of >5% weight in a six-month window, despite nutritional interventions. A negative energy balance characterizes cancer cachexia (CC), it is associated with weakness and fatigue in skeletal muscle. Impaired muscle function is associated with lower quality of life in cancer patients. Defects in mitochondrial function are strongly associated with muscle wasting. This study explored muscular contractile function and mitochondrial quality control (MQC) markers in soleus, gastrocnemius, and tibialis anterior (TA) muscles of C26-induced male tumor-bearing mice during a 25-day time course. It …

A Comparative Study On Cannabidiol In Melanoma Migration And Invasion: Charlotte's Web Vs. Purified Cbd, 2020–2021, Ruby Thamert

Theses

Over the last decade, much attention has been focused on compounds from Cannabis sativa in treating a variety of diseases including cancer. This study examines the abilities of two different cannabidiol oils to decrease the migration and invasion of melanoma cells in vitro. Skin cancers are the most common cancers in the world. While malignant melanoma is the least common type of skin cancer, it is the deadliest. Patients diagnosed with stage IV disease have only a 15-20% five-year survival rate even with aggressive multimodal treatment, demonstrating the need for additional therapeutic options. Because melanoma is often fatal when …

Evolution Of Targeted Therapy Resistance In Eml4-Alk Positive Non-Small Cell Lung Cancer, Robert Vander Velde

USF Tampa Graduate Theses and Dissertations

Targeted therapies have emerged as potent treatments that lead to the remission of many tumors. However, they rarely cure cancers in advanced, metastatic settings. This is due to the evolution of resistance, which in turn can be ascribed to the survival of small subpopulations of tolerant and/or resistant cells. Here we investigated the evolution of resistance to EML4-ALK inhibitors in non-small cell lung cancer (NSCLC) and demonstrated that resistance evolves gradually, from unique pre-treatment sub-populations, as multiple resistance mechanisms accumulate in a Darwinian fashion. Despite accumulating multiple changes, cells evolved, in parallel, toward similar inhibitor specific phenotypes. Evolving cells have …

An Investigation On The Irish Population’S Attitudes And Knowledge Towards Genetic Screening For Cancer, Emer Mccarthy, Ada Fleming, Dawn Hannah Cronin

International Undergraduate Journal of Health Sciences

Genetic mutations are alterations in DNA that may result in the development of a disease later in life. A BRCA gene is a tumour suppressor gene that helps to prevent the development of some cancers, particularly breast cancer. If a mutation occurs, this gene no longer functions at preventing these cancers. Genetic screening is when a population is tested for a mutation in an attempt to identify a group of people that are positive for the mutation. This can help identify cancer in different populations as well as track their inheritance. This study was conducted online, questioning the Irish populations …

Full Issue: The International Undergraduate Journal Of Health Sciences, Volume 1, Issue 1, June 2021

International Undergraduate Journal of Health Sciences

The full June 2021 issue (Volume 1, Issue 1) of the International Undergraduate Journal of Health Sciences

Quantitative Analysis Of Cadaveric Pelvic Lymph Nodes, Brandon Y. Boeur, Matthew P. Kayal, Jade Johnson, Yuhyun Kang, Kelsey Rice, Alicia Schmidt, Shelley Dicecco

Research Day

Introduction: Lymphedema commonly develops as a result of cancer treatments, including surgical removal of lymph nodes (LN). Research suggests there are 500-800 (LN) throughout the body. Deciding how many LN to remove and predicting possible severity of damage can become problematic when the range of LN in one area can vary by 30 LN.

Objective: The purpose of this study was to investigate more precise ranges of pelvic LN within cadaver samples.

Methods: Quantification of LN for number occurred on cadavers simultaneous with DO, PT, and PA students’ dissections. Demographics of the cadavers were 27 female, 16 male, 39 Caucasian, …

Unraveling Host-Gut Microbiota Dialogue And Its Impact On Response To Immune Checkpoint Blockade, Alexandria Cogdill

Dissertations & Theses (Open Access)

Cancer is a disease with only one degree of separation, affecting one in two men and one in three women in their lifetimes; accounting for 1 of every 6 deaths. While cancer mortality rates continue to improve, incidence rates are expected to rise and shift through 2050 due to epidemiological and demographic transitions worldwide. As such, it is imperative to continue to investigate and improve our understanding of both disease etiology and hallmarks of response to treatment. Currently, conventional therapies include, but are not limited to, surgery, chemotherapy, and radiotherapy. However, within the past decade, major advances have been made …

Mixture Model Approaches To Integrative Analysis Of Multi-Omics Data And Spatially Correlated Genomic Data, Ziqiao Wang

Dissertations & Theses (Open Access)

Integrative genomic data analysis is a powerful tool to study the complex biological processes behind a disease. Statistical methods can model the interrelationships of the involved gene activities through jointly analyzing multiple types of genomic data from different platforms (vertical integration), or improve the power of a study through aggregating the same type of genomic data across studies (horizontal integration). In this dissertation, we propose statistical methods and strategies for integrative multi-omics data in association analysis of disease phenotypes, with an emphasis on cancer applications.

We develop a new strategy based on horizontal integration by leveraging publicly available datasets into …

Investigating Bmp7 Expression In Glioblastoma Multiforme, Yajaira Janett Macias

Theses and Dissertations

The PI3K/AKT/mTOR pathway regulates important cell processes such as growth, survival, motility, inflammation, proliferation, and apoptosis. In Glioblastoma multiforme (GBM) the PI3K/AKT/mTOR pathway is aberrant as it is almost always active. This results in the deregulation of downstream molecules and ultimately leads to cancer progression and maintenance in GBM tumors. In this study, we used RNA-sequencing to identify differentially expressed genes (DEGs) in U87MG GBM cells treated with NVP-BEZ235, a dual inhibitory drug targeting PI3K and mTOR. A total of 7,803 differentially expressed genes were identified via RNA-seq. GEPIA2 online tool was used to assess differential gene expression …

Understanding The Role Of Ano1 In Oral Cancer, Mallary Forrest

UNLV Theses, Dissertations, Professional Papers, and Capstones

In 2008, the gene ANO1 was discovered to encode a calcium activated chloride channel. This gene is located on the 11q13 locus, a locus that is commonly amplified in many cancers including cancer of the head and neck. ANO1 is situated in close proximity to genes associated with growth and apoptosis. As rapid proliferation and lack of apoptosis are hallmark characteristics of cancer, growth factors and apoptosis mediators are expected to be altered in cancer. But what does a calcium activated chloride channel have to contribute to cancer’s pathogenesis? Is it an active gene in cancer progression or is it …

Assessing Genetic Counselors' Clinical Approach And Practices Regarding Pathogenic/Likely Pathogenic Variant Downgrades, Grant Bonesteele

Dissertations & Theses (Open Access)

Although rare, variant downgrades from a pathogenic/likely pathogenic (P/LP) variant to a variant of uncertain significance can have a significant impact on patients and their families in the clinical cancer setting. However, there is a lack of literature about how to approach these potentially challenging cases as a genetic counselor. Therefore, we aimed to characterize genetic counselors’ experiences, approach, and practices to variant downgrade cases using an online survey. The survey asked participants how they would approach variant downgrade scenarios involving the CDH1 or ATM genes with variable family histories. Genetic counselors appear to be united in whether they would …

Differential Effects Of Kim-1 In Subcutaneous And Orthotopic Renca Models Of Kidney Cancer, Demitra M. Yotis Dy

Electronic Thesis and Dissertation Repository

Renal Cell Carcinoma (RCC) is the most common and fatal type of kidney cancer. Over 30% of patients that are diagnosed with RCC exhibit metastases. Almost 88% of patients with distant metastases succumb to the disease within 5 years of diagnosis. Kidney Injury Molecule-1 (KIM-1) is a cell surface glycoprotein that is not expressed in a healthy kidney but becomes highly expressed on proximal tubular epithelial cells (PTECs) following injury. Data from the Cancer Genome Atlas (TCGA) reveals that >90% of RCC tumours express KIM-1 mRNA and that higher expression levels correlate with increased overall survival rates of patients. The …

Honokoil Treatment On Glioblastoma Cells, Julianne Weaver

Honors Theses

Glioblastoma is a malignant brain tumor without effective treatment options available because of its resistance to chemotherapy and radiation. This specific type of cancer is difficult to treat because the cancer stem cells that are not actively growing. These cells are dormant, which means they will not react to treatment because they are not dividing, and it is these cells that result in the high prevalence of relapse. Honokiol is a Chinese magnolia species that is known for its anti-inflammatory, anti-proliferative, and proapoptotic effects which make it an optimal candidate for glioma cell treatment. Honokiol was used in this experiment …

Biophysical Characterization Of The Par-4 Tumor Suppressor: Evidence Of Structure Outside The Coiled Coil Domain And Interactions With Platinum Chemotherapeutics, Andrea Megan Clark

Chemistry & Biochemistry Theses & Dissertations

Prostate apoptosis response-4 (Par-4) is an apoptosis-inducing tumor suppressor protein. Full-length Par-4 has previously been shown to be a predominantly intrinsically disordered protein (IDP) under neutral conditions, with significant regular secondary structure evident only within the C-terminal coiled coil domain. However, IDPs can gain ordered structure through the process of induced folding, which often occurs under non-neutral conditions. Previous work has shown that the Par-4 leucine zipper, which is a subset of the C-terminal coiled coil domain, is disordered under neutral conditions, but forms a dimeric coiled coil at acidic pH. Increase in ionic strength was also shown to increase …

Examining The Mechanistic Roles Of Integrin Alpha-6 In Cancer Metastasis., Chase T. Clark

Honors College Theses

Metastasis- the spread of cancer cells from the primary tumor to the surrounding tissues- is responsible for 90% of cancer deaths. Integrin alpha-6 (ITGA6) is a specific transmembrane cell surface protein that functions in cell surface adhesion and signaling. ITGA6 is upregulated in many types of cancers and promotes the migration and invasion of cancer cells to surrounding tissues. It is my objective to determine the mechanism through which ITGA6 facilitates the migration of cancer cells through the extracellular matrix (ECM). These experiments helped to establish the role of ITGA6 in tumor development and provide focus for possible chemotherapeutic treatment. …

Transcriptomic Profiling Of Fibropapillomatosis In Green Sea Turtles (Chelonia Mydas) From South Texas, Nicholas B. Blackburn, Ana C. Leandro, Nina Nahvi, Mariana A. Devlin, Marcelo Leandro, Ignacio Martinez Escobedo, Juan M. Peralta, Jeff George, Thomas W. Demaar, John Blangero, Megan Keniry, Joanne E. Curran

School of Medicine Publications and Presentations

Sea turtle fibropapillomatosis (FP) is a tumor promoting disease that is one of several threats globally to endangered sea turtle populations. The prevalence of FP is highest in green sea turtle (Chelonia mydas) populations, and historically has shown considerable temporal growth. FP tumors can significantly affect the ability of turtles to forage for food and avoid predation and can grow to debilitating sizes. In the current study, based in South Texas, we have applied transcriptome sequencing to FP tumors and healthy control tissue to study the gene expression profiles of FP. By identifying differentially expressed turtle genes in …

The Ant Home Care Model In Palliative And End-Of-Life Care. An Investigation On Family Caregivers’ Satisfaction With The Services Provided., Veronica Zavagli

Translational Medicine @ UniSa

The World Health Organization plan for a Decade of Healthy Ageing 2020-2030 has established some priorities in the field of palliative and end-of-life care. It states that “people require non-discriminatory access to good-quality palliative and end-of-life care” and recommends the “implementation of strategies for the provision of information, training, respite and support for informal caregivers”. The priorities described are in line with the home care services that National Tumor Assistance (ANT) Foundation has been providing in Italy. This 5-years investigation was designed to measure caregivers’ satisfaction and determine what types of support services are associated with greater satisfaction. 5.441 family …

Molecular Characterization Of A Marine Turtle Tumor Epizootic, Profiling External, Internal And Postsurgical Regrowth Tumors, Kelsey Yetsko, Jessica A. Farrell, Nicholas B. Blackburn, Liam Whitmore, Maximilian R. Stammnitz, Jenny Whilde, Catherine B. Eastman, Devon Rollinson Ramia, Ana C. Leandro

School of Medicine Publications and Presentations

Sea turtle populations are under threat from an epizootic tumor disease (animal epidemic) known as fibropapillomatosis. Fibropapillomatosis continues to spread geographically, with prevalence of the disease also growing at many longer-affected sites globally. However, we do not yet understand the precise environmental, mutational and viral events driving fibropapillomatosis tumor formation and progression.

Here we perform transcriptomic and immunohistochemical profiling of five fibropapillomatosis tumor types: external new, established and postsurgical regrowth tumors, and internal lung and kidney tumors. We reveal that internal tumors are molecularly distinct from the more common external tumors. However, they have a small number of conserved potentially …

[(Wr)8Wkβa]-Doxorubicin Conjugate: A Delivery System To Overcome Multi-Drug Resistance Against Doxorubicin, Khalid Zoghebi, Hamidreza Montazeri Aliabadi, Rakesh Kumar Tiwari, Keykavous Parang

Pharmacy Faculty Articles and Research

Doxorubicin (Dox) is an anthracycline chemotherapeutic agent used to treat breast, leukemia, and lymphoma malignancies. However, cardiotoxicity and inherent acquired resistance are major drawbacks, limiting its clinical application. We have previously shown that cyclic peptide [WR]₉ containing alternate tryptophan (W) and arginine (R) residues acts as an efficient molecular transporter. An amphiphilic cyclic peptide containing a lysine (K) residue and alternative W and R was conjugated through a free side chain amino group with Dox via a glutarate linker to afford [(WR)₈WKβA]-Dox conjugate. Antiproliferative assays were performed in different cancer cell lines using the conjugate and the …

Cancer Patient Knowledge About And Behavioral Intentions After Germline Genome Sequencing, Christine E. Napier, Grace Davies, Phyllis N. Butow, Timothy E. Schlub, Megan C. Best, Nicci Bartley, Ilona Juraskova, Bettina Meiser, Katherine M. Tucker, Barbara B. Biesecker, David M. Thomas, Mandy L. Ballinger, Members Of The Pigeon Project

IES Papers and Journal Articles

Objectives: Germline genome sequencing (GS) is becoming mainstream in cancer diagnosis and risk management. Identifying knowledge gaps and determinants of health behavior change intentions will enable effective targeting of educational and management strategies to translate genomic findings into improved cancer outcomes.

Methods: Probands diagnosed with cancer of likely genetic origin that consented to but not yet undergone GS, and their biological relatives, completed a cross-sectional questionnaire assessing GS knowledge and hypothetical intention to change behaviors.

Results: Probands (n = 348; 57% university educated) and relatives (n = 213; 38% university educated) had moderate GS knowledge levels, with greater knowledge associated …

Use Of Small Molecule Fanconi Anemia Pathway Inhibitors As Sensitizing Agents To Laromustine., Sam W. Marchant

Honors Theses

Laromustine is an experimental chemotherapeutic sulfonyl hydrazine prodrug shown in clinical trials to be effective against acute myeloid leukemia. The mechanism of action of laromustine involves interstrand crosslinking, via chloroethylation, and enzyme inhibition, caused by carbamoylation. The work described herein aims to investigate whether inhibition of the replication-dependent interstrand crosslink repair Fanconi Anemia pathway further sensitizes cells to laromustine. By measuring metabolic activity immediately after drug exposure, we find laromustine to be equally as cytotoxic towards Fanconi Anemia deficient and wild type cells. However, through clonogenic assays we show Fanconi Anemia mutations sensitize cells to laromustine’s anti-proliferative effect. Furthermore, we …

Association Between Plasma Genistein And Health-Related Quality Of Life In Breast Cancer Survivors, Tran Pham

Honors Undergraduate Theses

According to the American Cancer Society, breast cancer is the most commonly diagnosed cancer and is the second leading cause of cancer death in American women. Breast cancer screenings and improvement in treatments have resulted in the rising number of survivors in the recent decade. This urged the need for post-diagnosis lifestyle changes to improve breast cancer patients' quality of life. Many studies found soy food, the primary dietary source of phytoestrogens, has a protective effect against breast cancer recurrence and mortality. Dietary phytoestrogens can be classified into two groups: isoflavones and lignans. Daidzein and genistein were identified as the …

Investigation Of Proliferation Suppressors In Genetic Fitness Screens, Walter Frank Lenoir Iv

Dissertations & Theses (Open Access)

Innovation of CRISPR gene-editing technology has provided scientists genome manipulation tools that allowed rapid advancement of scientific capabilities and thus improved our ability to systematically study mammalian genetic functional profiles. Genome-wide CRISPR knockout screens conducted in collections of human cell lines can knock out genes at multiple loci, and have provided new insights into functional roles for independent genes. This method has launched massive efforts in looking across genetic backgrounds for context specific genetic vulnerabilities within cancer. Much of the research effort thus far has been spent on optimizing phenotype distinctions between essential, genes required for cell fitness, and non-essential, …

Evaluating The Microbial Experience Influence On Anti-Tumor Immune Response, Jessica A. Ensing

Student Summer Scholars Manuscripts

Despite the steady increase of hygienic standards, the CDC continues to report an increase of immune-mediated diseases such as allergies and asthma. Human avoidance of microbial exposure and subsequently less experienced immune systems may be the cause for this increase. We investigated if increased microbial exposure results in increased immunity to cancer (B16 melanoma) by measuring activated lymphocytes between two groups of C57Bl/6 mice: specific pathogen free (SPF) mice (which had little microbial exposure) and cohoused (COH) mice (which were exposed to numerous microbes). Previous research shows that the CoH mouse model mimics a human adult’s immune system, while the …

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 …

Integrated Multiparametric Radiomics And Informatics System For Characterizing Breast Tumor Characteristics With The Oncotypedx Gene Assay, Michael A. Jacobs, Christopher B. Umbricht, Vishwa S. Parekh, Riham H. El Khouli, Leslie Cope, Katarzyna J. Macura, Susan Harvey, Antonio C. Wolff

Radiology Faculty Publications

Optimal use of multiparametric magnetic resonance imaging (mpMRI) can identify key MRI parameters and provide unique tissue signatures defining phenotypes of breast cancer. We have developed and implemented a new machine-learning informatic system, termed Informatics Radiomics Integration System (IRIS) that integrates clinical variables, derived from imaging and electronic medical health records (EHR) with multiparametric radiomics (mpRad) for identifying potential risk of local or systemic recurrence in breast cancer patients. We tested the model in patients (n = 80) who had Estrogen Receptor positive disease and underwent OncotypeDX gene testing, radiomic analysis, and breast mpMRI. The IRIS method was trained …

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, …

Mechanisms Of Cross-Presentation By Cdc1s, Derek James Theisen

Arts & Sciences Electronic Theses and Dissertations

Classical dendritic cells (cDCs) are specialized antigen presenting cells that can be divided into distinct subsets based on the types of pathogens they respond to and the type of immune response they generate. The cDC1 subset is specialized in priming CD8 T cell responses through the process of cross-presentation. During cross-presentation, exogenous protein antigens are taken up by cDC1 and presented on MHCI molecules, allowing for the priming of CD8 T cells during conditions when DCs themselves are not directly infected. The ability to cross-present in vivo is unique to cDC1, and is essential for anti-viral responses and rejection of …

Statistical Methods For Resolving Intratumor Heterogeneity With Single-Cell Dna Sequencing, Alexander Davis

Dissertations & Theses (Open Access)

Tumor cells have heterogeneous genotypes, which drives progression and treatment resistance. Such genetic intratumor heterogeneity plays a role in the process of clonal evolution that underlies tumor progression and treatment resistance. Single-cell DNA sequencing is a promising experimental method for studying intratumor heterogeneity, but brings unique statistical challenges in interpreting the resulting data. Researchers lack methods to determine whether sufficiently many cells have been sampled from a tumor. In addition, there are no proven computational methods for determining the ploidy of a cell, a necessary step in the determination of copy number. In this work, software for calculating probabilities from …

Topological And System‑Level Protein Interaction Network (Pin) Analyses To Deduce Molecular Mechanism Of Curcumin, Anupam Dhasmana, Swati Uniyal, Anukriti -, Vivek Kumar Kashyap, Pallavi Somvanshi, Meenu Gupta, Uma Bhardwaj, Meena Jaggi, Murali M. Yallapu, Shafiul Haque, Subhash C. Chauhan

School of Medicine Publications and Presentations

Curcumin is an important bioactive component of turmeric and also one of the important natural products, which has been investigated extensively. The precise mode of action of curcumin and its impact on system level protein networks are still not well studied. To identify the curcumin governed regulatory action on protein interaction network (PIN), an interectome was created based on 788 key proteins, extracted from PubMed literatures, and constructed by using STRING and Cytoscape programs. The PIN rewired by curcumin was a scale-free, extremely linked biological system. MCODE plug-in was used for sub-modulization analysis, wherein we identified 25 modules; ClueGo plug-in …