Oncology Commons^™

Development And Characterization Of An Autologous Whole Cell Breast Cancer Vaccine, Samantha Leigh Kurtz

Graduate Theses and Dissertations

Approximately 40,000 women will die from breast cancer in the United States in 2014. About 90% of these deaths will be due to metastases, rather than the primary tumor and majority of metastases are due to the recurrence and progression of non-metastatic disease. Current adjuvant treatments, such as chemotherapy and radiation, have severe side effects and may result in overtreatment and drug resistance.

Since greater than 90% of patients are diagnosed between stages I-III and have minimal residual disease after treatment, there is an opportunity to treat patients with an autologous breast cancer vaccine. Autologous vaccines under development have a …

The Impact Of Inflammatory And Immune Response-Related Genetic Variants On Prostate Cancer Risk Among Men Of African Descent., Dominique Zilpha Jones

Electronic Theses and Dissertations

Background: In the U.S., prostate cancer (PCA) metastasis is associated with a 5-yr survival rate of 29% and disproportionately affects men of African descent. Single nucleotide polymorphisms (SNPs) may serve as genetic markers to identify individuals at high risk of developing PCA. Methods: We examined main and joint effects of 119 inflammatory and immune response-associated SNPs among men of African descent (535 controls, 279 cases) via logistic regression (LR) and entropy-based-multi-factor dimensionality reduction (MDR) modeling. Results: MDR yielded highly synergistic [(TLR10, TLR6 and IRF3), (TLR2, IRAK4), (IL1R2, IL10, IL10RA)] interaction …

Modulation Of The Ovarian Cancer Humoral Response By Tumor-Derived Exosomes., Carolyn Denise Roberson

Electronic Theses and Dissertations

The pathogenesis of epithelial ovarian cancer is complicated by its diagnosis during the latter stages of the disease resulting from lack of symptoms or from presence of symptoms that mimic other conditions. Because of the often fatal prognosis by the time of actual detection, efforts are being made to better understand the host immune response to ovarian cancer. In this study, the contributions of the humoral immune response were investigated by focusing on the role of tumor-derived exosomes and their ability to modulate humoral immune responses. First, ovarian cancer patient-derived free circulating antibodies were investigated for immunoreactivity to patient antigen. …

Lung Cancer Survival Disparities In Nevada, Chima Osuoha

UNLV Theses, Dissertations, Professional Papers, and Capstones

Lung cancer is the leading cause of cancer death in both men and women in the United States. Nevada shows moderate incidence rates of lung cancer for men but high rates for women. Little is known about the lung cancer experience and survival characteristics of the nearly 2000 new cases occurring every year in the State. The purpose of this study was to measure the extent to which geographic area of residency, gender, race, health insurance, social economic status (SES) and stage at diagnosis were associated with survival in patients diagnosed with lung cancer in Nevada. This was a retrospective …

The Pathophysiology Of Tumor Lysis Syndrome In Oncology Patients, Jessica Richardson

Nursing Student Class Projects (Formerly MSN)

Patients with oncological conditions are at an increased risk of developing a wide variety of complications from chemotherapy that they would not otherwise be exposed too. One such life threatening complication is tumor lysis syndrome, which is an oncology emergency that frequently lands patients in the intensive care unit. Tumor lysis syndrome (TLS) occurs most frequently after the initiation of chemotherapy or other chemotoxic drugs during the patients’ treatment course [8]. It causes faster than normal tumor cell breakdown and release of intracellular contents into the general circulation. [8]. This leads to a very predictable development of electrolyte imbalances to …

Identification And Characterization Of Protein Kinase C Substrates In Human Breast Cells, Xin Zhao

Dissertations, Theses, and Capstone Projects

Aberrations in PKC signaling can lead to the development of multiple human diseases and the most prominent association of PKC with disease has been in tumor growth and metastasis. PKC and its related pathways have been recognized as promising targets for blocking the malignancy of breast cancer cells. To better understand PKC-mediated pathway in breast cancer cells, it is important to identify the cellular substrates of PKC. The main focus of this work is to identify physiologically relevant cellular substrates of PKC in human breast cells and to characterize their roles in cancer-related phenotypes. The work to be described consists …

Thrombospondin-1 Signaling Mechanisms Regulating Pigment Epithelium-Derived Factor Expression And Lipolytic Activity In Prostate Cancer, Nizar Khamjan

Theses and Dissertations

Background: Prostate cancer (PCa) is the most common cancer that occurs in men in the United States. To grow, tumors need to induce new blood vessels growth, a process called angiogenesis. Thus, tumors down regulate molecules that inhibit this process. Two such molecules that are down-regulated in PCa are thrombospondin-1 (TSP-1) and pigment epithelium-derived factor (PEDF). Interestingly, both of these proteins also function in regulating lipid metabolism. Our lab has data to suggest that TSP-1 induces PEDF expression and lipid catabolism (lipolysis), the hydrolysis of triglycerides into fatty acids and a glycerol, in PCa cells; however, the molecular pathway of …

Gate Monte Carlo Simulations In A Cloud Computing Environment, Blake Austin Rowedder

UNLV Theses, Dissertations, Professional Papers, and Capstones

The GEANT4-based GATE is a unique and powerful Monte Carlo (MC) platform, which provides a single code library allowing the simulation of specific medical physics applications, e.g. PET, SPECT, CT, radiotherapy, and hadron therapy. However, this rigorous yet flexible platform is used only sparingly in the clinic due to its lengthy calculation time. By accessing the powerful computational resources of a cloud computing environment, GATE's runtime can be significantly reduced to clinically feasible levels without the sizable investment of a local high performance cluster. This study investigated a reliable and efficient execution of GATE MC simulations using a commercial cloud …

Novel Serum Biomarkers For Lung Cancer Early Diagnosis And Clinical Outcome, Fanmao Zhang

Dissertations & Theses (Open Access)

The five-year survival rate for all stages of lung cancer combined is only 17%, which has changed little over the past 40 years. Despite the tremendous efforts made, serum biomarkers with clinical utility for lung cancer early detection and clinical outcome prediction are still lacking. Metabolic alterations have been recognized as an emerging hallmark of cancer. We aimed to investigate the metabolic changes associated with lung cancer and to identify novel clinically applicable serum biomarkers for lung cancer early diagnosis and clinical outcome.

Serum metabolites are potential biomarkers for lung cancer early detection. We first performed global metabolomic profiling followed …

Strategies To Sensitize Bladder Cancer Cells To Small Molecule Inhibitors Targeting The Pi3k Pathway, Giovanni Nitti

Dissertations & Theses (Open Access)

After many years of cancer research, it is well accepted by the scientific community that the future cure for this disease lies in a personalized therapeutic approach. Anticipating therapeutic outcome based on the genetic signature of a tumor has become the new paradigm. The PI3K pathway represents an ideal target for bladder cancer, as many of the key proteins of this pathway are altered or mutated in this particular type of cancer. Several small molecule inhibitors have been developed to target this pathway, but their efficacy has been shown to be heterogeneous among different cell lines and mostly cytostatic but …

Synthesis And Characterization Of Novel Platinum(Ii) And Platinum(Iv) Complexes Containing 4,4′--Disubstituted--2,2′--Bipyridine Ligands For The Treatment Of Cancer, Van Vo

UNLV Theses, Dissertations, Professional Papers, and Capstones

Three series of platinum(II) and platinum(IV) complexes containing 4,4′-disubstituted-2,2′-bipyridine ligands have been synthesized and characterized by 1H NMR, 13C NMR spectroscopy, elemental analysis, mass spectroscopy, and differential scanning calorimetry measurements. The MTS cell proliferation assay was used to examine the in vitro anti-proliferative activities of these complexes in various human breast, lung, and prostate cancer cells. The cell's response to the complexes varies between different cell lines; however, the low EC₅₀ values determined from the MTS data indicate that several of the complexes are much more potent than cisplatin.

Flow cytometric analysis of selected compounds revealed induction of apoptosis …

Overall Survival And Biochemical Failure-Free Survival Comparison Of Brachytherapy Treatment Options Versus External Beam Radiation Therapy For Both Low And Intermediate-Risk Prostate Cancer: A Propensity-Score Matched Analysis, Graham D. Smith

Electronic Thesis and Dissertation Repository

Purpose: This study compares overall survival (OS) and biochemical failure-free survival (bFFS) in low- and intermediate-risk prostate cancer patients that received brachytherapy [low-dose-rate brachytherapy (LDR-BT) or high-dose-rate brachytherapy with external beam radiation therapy (HDR-BT+EBRT)] versus external beam radiation therapy (EBRT) alone.

Materials/Methods: Patient data was obtained from the ProCaRS database, which contains 7974 prostate cancer patients treated at four Canadian institutions. Propensity score (PS) matching was used to generate matched cohorts with balanced baseline prognostic factors.

Results/Conclusions: Final PS matches included two 1:1 intermediate-risk patient matches, LDR-BT vs. EBRT (total n = 254) and HDR-BT+EBRT vs. EBRT (total n=388), and …

1,25-Dihydroxyvitamin D Alters Lipid Metabolism And Epithelialto- Mesenchymal Transition In Metastatic Epithelial Breast Cancer Cells, Alle Nicole Barnard

Open Access Theses

Evidence suggests that high vitamin D status (marked by serum 25-hydroxyvitamin D, 25(OH)2 D) is associated with a decreased risk of breast cancer. It has been established that 1,25-dihydroxyvitamin D (1,25(OH) 2 D) can alter glycolysis and the Krebs cycle of breast cancer cells (Jiang et al., 2010; Zheng et al., 2013) but little information is available on 1,25(OH) 2 D's alterations of lipid metabolism in breast cancer cells. Thus, the current research investigates if there was an effect of 1,25(OH) 2 D on proteins that regulate lipid metabolism in MCF10A, MCF10A-ras, MCF10CA1h, and MCF10CA1a epithelial breast cancer cells. While …

Pharmacokinetics And Toxicity Of The Novel Oral Demethylating Agent Zebularine In Laboratory And Tumor Bearing Dogs, Christopher Michael Fulkerson

Open Access Theses

The aim of this thesis is to investigate the pharmacokinetics and toxicity of the novel oral demethylating agent zebularine (zeb) in laboratory dogs and tumor bearing dogs. This thesis focuses on the application of this therapeutic strategy in dogs with naturally occurring invasive transitional cell carcinoma (InvTCC), which serve as a relevant model of the human disease.

DNA hypermethylation in the promoter region is a common epigenetic change in cancer that silences tumor suppressor genes. Zeb is an oral cytidine analog that acts as a demethylating agent. Zeb has been investigated extensively in vitro as well as in mice, rodents …

Mri Relaxation Rates: A Quantitative Approach To Track Tumour Cells Expressing Maga, Anindita Sengupta

Electronic Thesis and Dissertation Repository

Using magnetic resonance imaging, relaxation rate measurements were

performed in cancer cells overexpressing a magnetotactic bacterial gene, MagA.

Measurements of magnetic resonance relaxation rates in this expression

system is important for optimizing cell detection and specificity, for developing

quantification methods, and for refinement of gene-based iron contrast using

magnetosome associated genes. We measured the total transverse

relaxation rate (R2^*), its irreversible and reversible components (R2 and R2^′,

respectively) and the longitudinal relaxation rate (R1) in MDA-MB-435 tumor cells.

Clonal lines overexpressing MagA were cultured in the presence and absence of

iron supplementation, and mounted in a …

Targeting Cancer Metabolism With Ketosis And Hyperbaric Oxygen, Angela M. Poff

USF Tampa Graduate Theses and Dissertations

Cancer cells exhibit an abnormal metabolic phenotype characterized by glycolysis and lactate fermentation in the presence of oxygen, a phenomenon known as the Warburg effect. This dysregulated metabolism plays an important role in every aspect of cancer progression, from tumorigenesis to invasion and metastasis. The Warburg effect is a common phenotype shared by most, if not all, cancer types. It is especially prominent in metastatic tumors, which are notoriously resistant to treatment and responsible for the majority of cancer-related deaths. Thus, metabolic therapies which target the Warburg effect could offer novel therapeutic options for most cancer patients, including those with …

The Optimization Of Porosity And Pore Patterning For Patient-Specific Ti-6 Al-4v Femur Implants, Stephen Paolicelli

Honors Theses

Metastatic bone cancer often arises in the long bones of the body. Taking a patient specific approach by utilizing a customized implant is a superior method of treatment compared to today’s solutions, which often includes amputation. A titanium-alloy femur implant has been optimized by varying pore size, pore pattern, and porosity in order to maximize osseointegration. By maximizing osseointegration, the implant will remain firmly in place for a longer period of time because bone will grow throughout the implant, securing it. In addition, it is important for the bone to behave mechanically like bone. This requires the global elastic modulus …

The Role Of Lipocalin 2 In Early Stage Colon Cancer Metastasis To The Liver, Fides Elamparo

Senior Theses

Metastasis, frequently from the colon to the liver, is the major cause of death with colorectal cancer, reducing the five-year survival to less than 6%. Metastasis occurs due to productive collaborations between tumor cells and host-derived cells in the tumor microenvironment, where a pre-metastatic niche is created to prime for cancer cell invasion into the target organ. In a highly metastatic colorectal cancer cell line implanted into the cecum of Balb/c mice, microarray analysis showed lipocalin 2 (Lcn2) is one of the most highly expressed proteins in the liver of tumor-bearing mice prior to metastasis.

When RT-PCR was performed, greater …

Novel Roles Of The Protein Tyrosine Phosphatase Shp2 In Non-Small Cell Lung Cancer, Valentina Schneeberger

USF Tampa Graduate Theses and Dissertations

The gene PTPN11 was identified in the early 1990s, and encodes the non-transmembrane protein tyrosine phosphatase SHP2. SHP2 is expressed ubiquitously in cells, and plays an important role in cancer. Unlike most phosphatases, SHP2 positively regulates several signaling pathways including the Ras/MAPK and Src signaling pathways and acts as a proto-oncogene. SHP2 is also a cancer essential gene in certain types of carcinomas, and promotes growth, survival, and epithelial to mesenchymal transformation. Gain of function (GOF) SHP2 mutations are known leukemic oncogenes, and have been identified to a smaller extent in solid tumors as well. Currently, the roles of SHP2 …

Image-Guided Proton Therapy For Online Dose-Evaluation And Adaptive Planning, Joey P. Cheung

Dissertations & Theses (Open Access)

The main advantage for using protons in radiotherapy is their finite range in patients, allowing for potential improved sparing of normal tissues. However, this comes at a cost of increased sensitivity to range uncertainties. Density changes along the beam path will affect the proton range and the resultant dose distribution, making it difficult to estimate the impact of visible anatomic changes to the patient dose distribution. In order to better understand the effect of anatomy change on proton dose, some form of treatment-time verification is required and methods to correct for observed changes would be beneficial. Therefore, this project aims …

Cancers Associated With Brca1 And Brca2 Mutations Other Than Breast And Ovarian, Jacqueline Mersch

Dissertations & Theses (Open Access)

Mutations in BRCA1 and BRCA2 cause tumor development in Hereditary Breast and Ovarian Cancer syndrome (HBOC) through accumulation of unrepaired DNA damage. Extensive research of BRCA1 and BRCA2 mutations has led to well-defined breast and ovarian cancer risks in individuals with HBOC. Previous studies have reported additional cancers associated with BRCA mutations; however, the type of cancer, magnitude of risk, and differences between sexes remains to be clarified. Ultimately, a consensus of additional cancer risks can aid in better recommendations for genetic testing and more effective screening and prevention guidelines.

A retrospective chart review of MD Anderson Cancer Center patients …

Cancer Diagnosis During Pregnancy: Evaluating The Challenges Faced By Oncologists, Shannon Kaye Mulligan

Dissertations & Theses (Open Access)

Cancer during pregnancy is occurring more often than in the past, and it is estimated that cancer is diagnosed in approximately 1/1000 pregnancies. A consensus exists that management of these patients should prioritize survival of the mother and minimize teratogenic effects to the fetus, and utilize a multidisciplinary approach, involving medical oncology, surgical oncology, radiation oncology, radiology, and a maternal fetal medicine specialist. In spite of this consensus, there is not a standardized approach for treating cancer in women diagnosed during pregnancy. Due to the relative infrequency of this situation in the oncologic setting, the aims of this study were …

Investigation Of Rice Bran Derived Anti-Cancer Pentapeptide For Mechanistic Potency In Breast Cancer Cell Models, Ruiqi Li

Graduate Theses and Dissertations

Bioactive peptides derived from food sources with anti-proliferative properties against cancer have drawn more attention in recent years. A pentapeptide derived from rice bran has shown anti-proliferative propertiesagainst human breast cancer cells. The objective of this study was to investigate the mechanistic action of the pentapeptide-induced apoptosis in breast cancer cell models (MCF-7 and MDA-MB-231). The growth inhibition activity of the pentapeptide was

evaluated by MTS[3-(4,5-dimethylthiazol-2-yl)-5-(3- arboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium, inner salt] assayand trypan blue assay in a dose- and time-dependent manner.

The apoptotic properties of pentapeptide-induced apoptosis on cancerous breast cells were evaluated by morphological changes, DNA fragmentation, and caspases-3/7, -8,and -9 …

Evaluation Of Current Clinical Criteria For Li-Fraumeni Syndrome In A Diverse Sample Of Tp53 Mutation Carriers, Emily A. Parham

Dissertations & Theses (Open Access)

Li-Fraumeni syndrome (LFS) is a hereditary cancer predisposition syndrome caused by heterozyogous germline mutations in the TP53 gene and characterized by an excess of early-onset cancers, high lifetime risk of cancer, and a wide range of tumor types. Recent studies suggesting a benefit in comprehensive screening protocols for both children and adults make the timely identification of individuals with LFS increasingly important.

A number of criteria have been proposed to identify patients with LFS. The National Comprehensive Cancer Network (NCCN) combines several in its Clinical Practice Guidelines for TP53 genetic testing. Prior studies have shown that the cumulative sensitivity of …

Combination Therapy With Aerosol Il-2 And Nk Cells For The Treatment Of Osteosarcoma Lung Metastasis, Sergei R. Guma

Dissertations & Theses (Open Access)

The survival of patients with osteosarcoma lung metastases has not improved in the last 20 years. Novel alternative therapies are needed. The purpose of this investigation was to evaluate the efficacy of combining natural killer [NK] cell therapy with aerosol interleukin-2 [IL-2] for the treatment of osteosarcoma lung metastasis. The expression of NKG2D ligands was analyzed in five different human osteosarcoma cell lines and 103 patient samples (47 from primary tumors and 56 from lung metastases). We discovered that osteosarcoma expresses the ligands for the NKG2D. In vitro studies demonstrated that NK-mediated killing of osteosarcoma cells is dependent on the …

Feasibility Of Pulsed Proton Induced Acoustics For 3d Dosimetry, Fahed M. Alsanea

Open Access Theses

Proton therapy has the potential to deposit its energy in tissue with high conformity to the tumor and significantly reduced integral dose to normal tissue compared to conventional radiation, such as x-rays. As a result, local control can be enhanced while reducing side-effects and secondary cancers. This is due to the way charged Particles deposit their energy or dose, where protons form a Bragg peak and establish a well-defined distal edge as a function of depth (range). To date, the dose delivered to a patient from proton therapy remains uncertain, in particular the positioning of the distal edge of the …

Multiparametric Imaging And Mr Image Texture Analysis In Brain Tumors, Harish A. Sharma

Electronic Thesis and Dissertation Repository

Discrimination of tumor from radiation injured (RI) tissues and differentiation of tumor types using noninvasive imaging is essential for guiding surgical and radiotherapy treatments are some of the challenges that clinicians face in the course of treatment of brain tumors. The first objective in this thesis was to develop a method to discriminate between glioblastoma tumor recurrences and radiation injury using multiparametric characterization of the tissue incorporating conventional magnetic resonance imaging signal intensities and diffusion tensor imaging parameters. Our results show significant correlations in the RI that was missing in the tumor regions. These correlations may aid in differentiating between …

Characterization Of Iron Response In Gynecological Cell Lines, Kyle A. Bauckman

USF Tampa Graduate Theses and Dissertations

Ovarian carcinoma afflicts over 22,000 women each year with a 5 year survival rate of only 18% for stage IV patients [23]. Current treatment options are limited due to high rates of drug resistance and recurrence. Further, the identity of "precursor lesions" which give rise to various subclasses of epithelial ovarian cancer has been evasive. This is due to discovery of the cancer at already an advanced stage. Interestingly, endometriosis a benign but invasive gynecological disease has been described as a "precursor lesion" in the development of specific subtypes of ovarian cancer. Endometriotic cyst development involves the accumulation of "old …

Relationships Between Parenting Self-Efficacy And Distress In Parents With And Without Cancer, Julie Marie Cessna

USF Tampa Graduate Theses and Dissertations

Despite the relatively large number of parents with cancer, relatively little is known about the extent to which having cancer affects the parenting experience. Qualitative studies have identified issues and concerns that create distress among parents with cancer, but quantitative studies have yet to be conducted. Studies demonstrate that parents with cancer experience psychological distress, and that parenting self-efficacy is related to psychological distress among parents without cancer. However, no study to date has examined the relationships between parenting self-efficacy and psychological distress among parents with cancer. This study sought to address these gaps in the literature by comparing parents …

Pathway Profiling Of Replicative And Induced Senescence, Maggie Purcell

Wayne State University Dissertations

Senescence is a permanent withdrawal from cell cycle that occurs naturally in cells in response to the shortening of telomeres. This natural "clock" serves to limit the number of cell divisions and therefore protects the cell from potentially carcinogenic mutations. However, senescence also occurs in response to external stresses to the cell, which is known as induced senescence. This study compares the mechanisms of natural senescence, a response to the shortening of telomeres during replication, with induced senescence by using various drugs to induce senescence: 5-aza-2-deoxycytidine (a demethylating agent), Adriamycin (a chemotherapeutic drug), and H2O2 (an agent causing oxidative stress). …