Medicine and Health Sciences Commons^™

Uncovering A Myc-Driven Tumor-Suppressive Program In Proliferating Lymphocytes, Elena Tonc

Arts & Sciences Electronic Theses and Dissertations

Rapid cell proliferation is a hallmark feature of adaptive immune cells lymphocytes. It is essential for the establishment of diverse antigen receptor repertoires and amplification of antigen-specific immune responses. While such proliferation is beneficial for host protection from infections and cancers, it inevitably elevates the risk of oncogenic transformation. In developing and germinal center B lymphocytes, the risk is further increased by endogenous, genomic insults due to antigen receptor rearrangements and somatic mutations, with which expression of the proto-oncogene c-MYC is closely associated. Nonetheless, frequencies of cancers originated from B lymphocytes are relatively low, suggesting that they are protected from …

The Role Of Ifitm3 In The Immune Response Of Brca-Deficient High Grade Serous Ovarian Carcinoma, Han Cun

Dissertations & Theses (Open Access)

Background: Prior studies showed that BRCA-deficient high grade serous ovarian carcinoma (HGSOC) had increased tumor infiltrating lymphocytes (TILs) compared to BRCA-wildtype (WT). To better understand the underlying immune mechanism in these tumors, a preliminary transcriptome analysis was performed on a set of microdissected HGSOC tumor specimens with BRCA1-mutation, BRCA2-mutation, or WT. This demonstrated an upregulation of IFITM3, an essential gene in modulating immune function. Based on these findings, we hypothesized that BRCA-deficient HGSOC have increased DNA damage leading to upregulation of IFITM3 and subsequent increase in antigen presentation and T-cell activation.

Methods: Following IRB approval, preliminary transcriptome analysis was performed …

Incidence Of Cancer And Stage At Diagnosis Among People With Recent-Onset Psychotic Disorders, Jared C. Wootten

Electronic Thesis and Dissertation Repository

Evidence on cancer incidence in people with psychotic disorders, compared to the general population, is equivocal, although those with psychotic disorders so have more advanced stage of cancer at the time of diagnosis. The objective of this thesis was to compare cancer incidence and stage at diagnosis for people with psychotic disorders, relative to the general population. Our systematic review did not observe a significant difference in overall cancer incidence among people diagnosed with psychotic disorders (RR = 1.08, 95% CI: 1.00 to 1.16), however people with psychotic disorders were more likely to be present with advanced stage cancer at …

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 …

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 …

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 …

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 …

A Multilevel Mixed Methods Examination Of Treatment Nonadherence Among Rural Cancer Survivors, Bonny Morris

Theses and Dissertations

While mortality rates have been decreasing over the last 40 years, cancer remains a leading cause of death in the United States. Over 1.7 million people were diagnosed with cancer in 2019, and there were more than 600,000 cancer deaths. Of the 15 million cancer survivors in the US, nearly 3 million reside in rural areas and experience 3% higher cancer incidence and 10% higher cancer mortality compared to their nonrural counterparts. During 2006-2015, the annual age-adjusted mortality rates for all cancer sites combined decreased at a slower pace in rural areas versus nonrural areas (-1.0% vs -1.6% per year, …

Mechanisms Of Apoptosis Induced By Actinomycin D In Aerodigestive Tract Cancers, Adeoluwa Ayodeji Adeluola

Theses, Dissertations and Capstones

Upper aerodigestive tract cancers including cancers of the oral cavity, pharynx, larynx, esophagus, and lungs are the most prevalent cancers and leading causes of cancer-related deaths. Collectively, over 300,000 new cases and 146,500 deaths are projected within the US in the year 2021. Drug-associated toxicities, as well as resistance to therapy (intrinsic and acquired), are big challenges for successfully treating these cancers. Recent studies have shown that combining low-dose actinomycin D with existing therapies is a promising strategy to reduce toxicity (cyclotherapy) and to overcome resistance. The development of these treatment strategies however requires an understanding of the molecular mechanisms …

Association Of Incident Cancer To Low-Value Care And Healthcare Cost Burden Among Elderly Medicare Beneficiaries, Chibuzo Iloabuchi

Graduate Theses, Dissertations, and Problem Reports

In the United States (US), 25% of healthcare spending is considered wasteful because it is spent reimbursing low-value care. Low-value care is the utilization of healthcare services, medical tests, and procedures that have unclear or no clinical benefit to patients but still exposes them to risk. World-wide, low-value care imposes a significant economic burden on patients, payers, governments, and society. Cancer care among older adults > 65 years is one of the biggest drivers of healthcare expenditure in the US and accounts for nearly 40% of all spending, and low-value care among cancer patients is prevalent and contributes to the financial …

Qualitative Study Of Factors Contributing To Fertility Service Use Among Cancer Survivors Of Reproductive Age In The Us, Angela Rodgers Moore

Electronic Theses and Dissertations

Cancer remains the second leading cause of death in the United States; however, there has been a decline in incidence and mortality due to advances in screening and treatment. Currently 16.9 million survivors are thriving within the United States, and the population of cancer survivors has been projected to grow to 22.2 million by 2030. Although cancer survivors report an increased surge of vitality and vigor, they often face physical, mental, psychosocial, or financial challenges that threaten their quality of life. A late treatment effect of particular concern for cancer survivors of reproductive age that has both physical and psychosocial …

Using The Memorial Sloan Kettering Frailty Index To Identify Patients At High Risk For Postoperative Intensive Care Unit Admission, Specialized Advanced Care Unit Admission, And 30-Day Readmission, Timothy J. Donoghue

Theses and Dissertations

Frailty is roughly defined as an accumulation of physiological, emotional, cognitive, and social deficits that impair a person’s response to stressful events. A frailty diagnosis has been associated with poor outcomes following surgical procedures. Cancer surgical patients aged 65 or older represent a vulnerable population susceptible to being frail and the potential associated complications that can accompany frailty. Measuring frailty is an objective risk assessment that identifies increased risk better than age or American Society of Anesthesiologists Physical Status (ASA-PS) score such that frailty can independently predict poor surgical outcomes.

Frailty is not specifically a result of having cancer, disability, …

Applied Methodologies Demonstrated Through Three Independent Studies For Assessing The Effects Of Socioeconomic, Environmental Chemical Exposure, And Therapeutic Factors On Oncological Diseases And Covid-19, Bayarmagnai Maggie Munkhjargal

Legacy Theses & Dissertations (2009 - 2024)

When trying to understand risk factors for a disease, even before we know the causal agents, it is necessary to create a surveillance data set that answers the questions of who, when, and where, and includes any potential covariates which may either promote or prevent the disease. There are a wide variety of surveillance data. For example, hospital discharge data, such as the New York Statewide Planning and Research Cooperative System (SPARCS) data, encompass all hospitalized cases in the state, while clinical datasets cover a specially constructed population in pursuit of research of a certain disease type. Analysis of surveillance …