Medicine and Health Sciences Commons^™

The Impact Of The Neuropeptide Y System On The Progression Of Breast Cancer, Philip J. Medeiros

Electronic Thesis and Dissertation Repository

Chronic stress is associated with elevated levels of sympathetic neurotransmitter release and immunosuppression. A growing body of evidence suggests that stress-related factors may contribute to the initiation, development and progression of breast cancer. Neuropeptide Y (NPY) has recently been determined as such a factor, however few investigations have addressed the functional effects of NPY on breast cells and tumors. Thus, the overall objective of this thesis was to elucidate the mechanisms by which NPY may contribute to the disease. Using the 4T1 murine breast cancer model, we began by first characterizing NPY receptor expression in cancer cells and tumors. Y1R, …

Development Of A Novel Technique For Predicting Tumor Response In Adaptive Radiation Therapy, Rebecca Marie Seibert

Doctoral Dissertations

This dissertation concentrates on the introduction of Predictive Adaptive Radiation Therapy (PART) as a potential method to improve cancer treatment. PART is a novel technique that utilizes volumetric image-guided radiation therapy treatment (IGRT) data to actively predict the tumor response to therapy and estimate clinical outcomes during the course of treatment. To implement PART, a patient database containing IGRT image data for 40 lesions obtained from patients who were imaged and treated with helical tomotherapy was constructed. The data was then modeled using locally weighted regression. This model predicts future tumor volumes and masses and the associated confidence intervals based …

Fibulin-2 Stabilizes Tumor Extracellular Matrix And Drives Malignant Progression Of Lung Adenocarcinoma, Brandi N. Baird

Dissertations & Theses (Open Access)

The ECM of epithelial carcinomas undergoes structural remodeling during periods of uncontrolled growth, creating regional heterogeneity and torsional stress. How tumors maintain ECM integrity in the face of dynamic biophysical forces is still largely unclear. This study addresses these deficiencies using mouse models of human lung adenocarcinoma. Spontaneous lung tumors were marked by disorganized basement membranes, dense collagen networks, and increased tissue stiffness. Metastasis-prone lung adenocarcinoma cells secreted fibulin-2 (Fbln2), a matrix glycoprotein involved in ECM supra-molecular assembly. Fibulin-2 depletion in tumor cells decreased the intra-tumoral abundance of matrix metalloproteinases and reduced collagen cross-linking and tumor compressive properties resulting in …

Characterization Of Beryllium As A Novel Agent To Study Cell Cycle Arrest And Cellular Senescence, Priyatham Gorjala

UNLV Theses, Dissertations, Professional Papers, and Capstones

Cancer cells evade senescence, apoptosis, and other constraints on proliferation, often via mutation of the p53 tumor suppressor gene (TP53). Normal human lung fibroblasts have been shown to enter premature senescence upon exposure to beryllium. In these cells, BeSO₄ stabilizes p53 protein, increases p21 gene expression, induces senescence-associated β-galactosidase activity and causes cell proliferation arrest. In the present study, we have investigated whether BeSO₄ is able to induce similar effects in cancer cells that have wildtype p53. We have demonstrated that beryllium salt at low concentration can induce molecular changes in the p53 signaling pathway leading to cell …

Real-Time Analysis Of Brain Tumor Cell Dynamics: Novel Thermoelectric Detection Of L-Glutamate And Cell Metabolism Using Microfluidics, Siva Mahesh Tangutooru

Doctoral Dissertations

This study describes the design, fabrication and applications of a novel thermoelectric microfluidic bio-sensor. The bio-sensor is used for real time detection of the L-glutamate (L-glu) dynamics and metabolism for brain tumor cells immobilized in a microfluidic device. The microfluidic device is fabricated using a polymer/glass laminating technique (Xurography). An antimony-bismuth thin-film thermopile (primary sensing element) is integrated to the microfluidic device. The brain tumor cells are immobilized over the thermopile covering measuring and reference junctions of the thermopile using a poly-l-lysine coating layer. L-glutamate oxidase (L-GLOD) is immobilized over the measuring junctions of the thermopile prior to the immobilization …

The Relationship Between Cancer-Related Fatigue And Upper Extremity Function In Breast Cancer Survivors, Meryl Marger Picard

Seton Hall University Dissertations and Theses (ETDs)

Background: Cancer-related fatigue (CRF) and arm morbidity constitute the two most common symptom complexes impacting breast cancer survivors (BCS) following surgery and adjuvant treatment, but these multifaceted entities have traditionally been researched as if they were separately occurring events in the survivor’s recovery. Objective: This study examined the relationship between breast cancer survivors’ perceptions of CRF and upper extremity function one to six years post-diagnosis. The study further investigated the impact of multiple adjuvant therapies, node dissection procedures, caring for dependent children, and physical aspects of employment on CRF and upper extremity function. Methods: One hundred fifty-eight BCS responded to …

The Relationship Between Self-Reported Cancer Pain And Personality In Black And White Older Adults Receiving Outpatient Cancer Care, Jessica Krok

USF Tampa Graduate Theses and Dissertations

It is well-established that personality not only affects physical health and longevity, but also mental health and coping mechanisms. One area of limited research is the relationship between cancer pain and personality. This study examined how personality traits affect reported cancer pain severity in older patients (N = 150) receiving outpatient treatment at a comprehensive cancer center. Participants were interviewed regarding their pain severity, personality, affect, and self-efficacy for pain management. Symptom data were collected from the Brief Pain Inventory, while personality data were gathered from the Ten Item Personality Inventory and the Positive and Negative Affect Schedule. Self-efficacy for …

A Study Of Potential Risk Factors Of Depression Among Latina Breast Cancer Survivors, Claudia Ximena Aguado Loi

USF Tampa Graduate Theses and Dissertations

Women with breast cancer commonly experience depression. However, this condition often goes unrecognized, undertreated, and understudied, especially in ethnic minorities. If left untreated, co-existing depression in women with cancer can complicate cancer treatment, lead to poor treatment adherence for both conditions, and decrease survival. These negative consequences are considerably higher among Latinas. With the growing number of Latinos and diversity within the Latino community, the literature has identified the need to disaggregate Latinos by region of origin. Unfortunately, few studies account for these differences and no study to date has examined risk factors of depression among Latinas diagnosed with breast …

Diffusion Of The Egfr Assay: The Underutilization And The Urban/Rural Divide, Julie Ann Lynch

Graduate Doctoral Dissertations

Purpose - The EGFR assay is a molecular diagnostic test which identifies a targetable mutation in lung tumors. Guidelines call for EGFR testing for non-small cell lung cancer patients to direct first line treatment. We explored institutional and regional factors predicting the likelihood acute care hospitals ordered the assay. Methods: This was a retrospective study which analyzed US acute care hospitals (n=4780). We linked proprietary industry data for orders of the EGFR assay to public datasets that provided hospital and regional characteristics. We conducted logistic regression to identify significant characteristics that predict likelihood a hospital ordered the assay. Results - …

Taz As A Regulator Of Mesenchymal Transformation And Clinical Aggressiveness In Gliomas, Katrina Salazar

Dissertations & Theses (Open Access)

Glioblastoma multiforme (GBM) is an aggressive, high grade brain tumor. Microarray studies have shown a subset of GBMs with a mesenchymal gene signature. This subset is associated with poor clinical outcome and resistance to treatment. To establish the molecular drivers of this mesenchymal transition, we correlated transcription factor expression to the mesenchymal signature and identified transcriptional co-activator with PDZ-binding motif (TAZ) to be highly associated with the mesenchymal shift. High TAZ expression correlated with worse clinical outcome and higher grade. These data led to the hypothesis that TAZ is critical to the mesenchymal transition and aggressive clinical behavior seen in …

Knowledge, Attitudes, And Utilization Of Brca Testing Among Obstetricians And Gynecologists, Salma Nassef

Dissertations & Theses (Open Access)

Hereditary breast and ovarian cancer (HBOC) is an inherited cancer syndrome that is associated with mutations in the BRCA1 and BRCA2 genes. Carriers of BRCA mutations, both men and women, are at an increased risk for developing certain cancers. Carriers are most notably at an increased risk to develop breast and ovarian cancers; however an increased risk for prostate cancer, melanoma, and pancreatic cancers has also been associated with these mutations. In 2009 the American Congress of Obstetricians and Gynecologists (ACOG) released a practice bulletin stating that evaluating a patient’s risk for HBOC should be a routine part of obstetric …

Predictors Of Contralateral Breast Cancer In Brca Negative Women, Ann E. Simmons

Dissertations & Theses (Open Access)

Breast cancer is the most common cancer diagnosis and second leading cause of death in women. Risk factors associated with breast cancer include: increased age, alcohol consumption, cigarette smoking, white race, physical inactivity, benign breast conditions, reproductive and hormonal factors, dietary factors, and family history. Hereditary breast and ovarian cancer syndrome (HBOC) is caused by mutations in the BRCA1 and BRCA2 genes. Women carrying a mutation in these genes are at an increased risk to develop a second breast cancer. Contralateral breast cancer is the most common second primary cancer in patients treated for a first breast cancer. Other risk …

Bim Mediates Imatinib-Induced Apoptosis Of Gastrointestinal Stromal Tumors: Translational Implications, David Reynoso

Dissertations & Theses (Open Access)

Gastrointestinal stromal tumors (GISTs) are oncogene-addicted cancers driven by activating mutations in the genes encoding receptor tyrosine kinases KIT and PDGFR-α. Imatinib mesylate, a specific inhibitor of KIT and PDGFR-α signaling, delays progression of GIST, but is incapable of achieving cure. Thus, most patients who initially respond to imatinib therapy eventually experience tumor progression, and have limited therapeutic options thereafter. To address imatinib-resistance and tumor progression, these studies sought to understand the molecular mechanisms that regulate apoptosis in GIST, and evaluate combination therapies that kill GISTs cells via complementary, but independent, mechanisms. BIM (Bcl-2 interacting mediator …

Effects Of Hyperthermia On Photochemical Internalization-Mediated Delivery Of Bleomycin, Christina Schlazer

UNLV Theses, Dissertations, Professional Papers, and Capstones

Standard treatment protocols for high-grade gliomas, such as glioblastoma multiforme (GBM), are highly ineffective due to their inability to eradicate infiltrating tumor cells. Improvements in overall survival are likely to be realized only with the development of more effective localized therapies capable of eradicating tumor cells in the surgical resection margin and beyond. Photochemical internalization (PCI) is a localized light-based therapeutic modality that enhances the efficacy of therapeutic macromolecules including chemotherapeutic agents such as bleomycin. A number of studies have shown that this photodynamic therapy (PDT) - based modality may prove effective in the treatment of high-grade gliomas.

Three-dimensional multicell …

Enhancing The Immune Response Through Ikkbeta-Induced Activation Of Nf-Kappab, Emily Hopewell

USF Tampa Graduate Theses and Dissertations

Nuclear factor-κB (NF-κB) is one of the main regulators of inflammatory and immune responses. It is a family of transcription factors composed of five members: RelA, RelB, cRel, NF-κB1 (p105/p50), and NF-κB2 (p100/p52). Homo- and hetero-dimers of family members are inhibited by inhibitor of &klappaB (IκB) family members and activated by IκB kinase (IKK) family members. The IKK family is comprised of IKKα, IKKΒ, and IKKγ. The focus of my dissertation delves into the role of NF-κB activation by IKKΒ in both an immunotherapy setting and its role in T cell mediated anti-tumor immune responses.

A central focus of immunotherapy …

Regulation Of Natural Killer Cells: Ship-1, 2b4, And Immunomodulation By Lenalidomide, Nicole Renee Fortenbery

USF Tampa Graduate Theses and Dissertations

Natural Killer cells (NK) are critical components of the innate immune system. Often referred to by their morphology, these large granular lymphocytes (LGLs) are bone marrow-derived lymphocytes and can be found throughout the body. NK cells reside in the liver, lymph nodes, spleen, thymus, and mucosal-associated lymphoid tissues (MALT). Importantly, NK cells also circulate throughout the blood where they function as surveyors of the body and are armed to eliminate malignant, infected, damaged, or foreign cells.

NK cells function by a dual receptor system. That is, NK receptors are broadly categorized as inhibitory or activating. It is a fine balance, …

Synergistic Effect Of Subnanosecond Pulsed Electric Fields And Temperature On The Viability Of Biological Cells, James Thomas Camp

Electrical & Computer Engineering Theses & Dissertations

Pulsed electric fields have been used to induce a biological response in cells, and at sufficient energy, can cause cell death. By reducing the pulse duration from presently used nanosecond to subnanosecond ranges, the electric field can be delivered to biological tissue non-invasively by the use of an antenna instead of electrodes, such as needles. Studies have previously been completed in which the aim was to determine the energy density (electric field strength, number of pulses) required to induce cell death with 800 ps pulses. Based on this data, it was concluded that for pulse durations of 200 ps, with …

Matrix Metalloproteinase Genes Are Transcriptionally Regulated By E2f Transcription Factors: A Link Between Cell Cycle Control And Metastatic Progression, Jacqueline Lea Johnson

USF Tampa Graduate Theses and Dissertations

The RbµE2F transcriptional regulatory pathway plays a critical role in the cell cycle. Rb is inactivated through multiple waves of phosphorylation, mediated mainly by cyclin D and cyclin E associated kinases. Once Rb is inactivated, cells can enter Sµphase. Collectively, three Rb family members and ten E2F proteins coordinate every additional stage of the cell cycle, from quiescence to mitosis. However the RbµE2F pathway is frequently altered in cancer. Aside from cell proliferation, the RbµE2F pathway regulates other essential cellular processes including apoptosis, cell differentiation, angiogenesis and DNA damage repair pathways, but its role in invasion and cancer progression is …

Targeted Intracellular Therapeutic Delivery Using Liposomes Formulated With Multifunctional Fast Proteins, Rae L. Nesbitt

Electronic Thesis and Dissertation Repository

Prostate cancer is the most common malignancy in North American men and there is no treatment currently available which offers a clear survival advantage to patients with prostate cancer. We studied liposomes formulated with the fusion-associated small transmembrane (FAST) protein, p14. In this study, we hypothesized that therapeutics delivered in molecular targeted fusogenic liposomes will increase intracellular delivery and specificity for prostate cancer. We demonstrated that liposomes formulated with p14-bombesin significantly increased the delivery of fluorescein isothiocyanate (FITC) into human prostate cancer (PC-3) cells compared to either standard liposomes or non-targeted fusogenic liposomes. Delivery of FITC to benign prostate hyperplasia …

The Proton-Coupled Folate Transporter: Biology And Therapeutic Applications To Cancer, Sita Desmoulin

Wayne State University Dissertations

Folates are essential cofactors of tumor cell proliferation and survival required for nucleotide biosynthesis and amino acid metabolism. In cancer therapy, inhibition of folate-dependent metabolic pathways has been achieved through the use of antifolates. Unfortunately, the efficacy of many clinically approved antifolates is limited by a lack of tumor selectivity. Facilitative transport of folates into mammalian cells is achieved by the reduced folate carrier (RFC) and proton-coupled folate transporter (PCFT). As PCFT is a folate-proton symporter with an acidic pH optimum, PCFT may provide a mechanism for targeting cytotoxic antifolates to tumors, based on their acidic microenvironments. To establish the …

The Role Of Ptip In Breast Cancer, Lina Niu

Theses, Dissertations and Capstones

In the U.S., breast cancer comprises about 30% of all cancer cases (excluding skin cancer) in women. Such a high incidence makes breast cancer a significant health concern, but our understanding of the molecular and cellular mechanisms of this disease is still limited. Growing evidence suggests that the development of human breast cancer may involve epigenetics, which attributes changes in phenotype to mechanisms other than changes in the DNA sequence itself. Histones as the chief proteins of chromatin work on gene expression, and methylation of histone 3 lysine 4 (H3K4) results in transcriptional activation. Lately, Paired box (Pax) trans-activation domain-interacting …

Redox Regulation Of Differentiation In Neuroblastoma, Anne Marie Silvis

Theses, Dissertations and Capstones

Neuroblastoma is the most common extracranial solid tumor in childhood, ranking third in prevalence among infant cancers. Despite intensive therapy with surgery, radiation and chemotherapy, there is a high chance of tumor recurrence. These children are therefore given retinoids in the maintenance phase to differentiate the tumor cells and to avoid/lessen this incidence. Although 13-cis retinoic acid (13-cis RA) is currently used to treat neuroblastoma, there is much evidence supporting the prevalence of its metabolite, all-trans retinoic acid (ATRA), to be the main signaling retinoid in vivo.

The SK-N-SH neuroblastoma cell line, which is composed of three sub-types: sympatheoadrenal neuroblasts …

The Effect Of Education On Healthcare Personnel's Knowledge Of Lymphedema Detection And Prevention, Dolly Wilson

Nursing Theses and Capstone Projects

Secondary lymphedema (SLE) is a serious problem for many of the 2.6 million breast cancer survivors in the United States. It is estimated that 28 - 38% of breast cancer survivors develop lymphedema. The five-year incidence ranges from 43% to 94% (Armer, 2010). The purpose of this study was to evaluate the effectiveness of an education program on healthcare personnel's knowledge of the risk of and preventive measures for upper limb lymphedema in breast cancer patients. A sample of healthcare personnel (N = 32) included both trained healthcare personnel and ancillary staff who are employed in a single oncology center …

Is Allogeneic Stem Cell Transplantation Of High-Risk Pediatric Acute Lymphoblastic Leukemia (All) Patients More Effective In Preventing Future Relapses Of Disease And/ Or Mortality In Comparison With Chemotherapeutic Regimens Alone?, Patricia A. Ajizadeh

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not allogeneic SCT of HR pediatric ALL patients is more effective in preventing future relapses of disease and/or mortality in comparison with chemotherapeutic regimens alone.

STUDY DESIGN: Review of three English language primary randomized controlled trial studies published between 1996 and the present.

DATA SOURCES: Randomized controlled trial studies were found using PubMed.

OUTCOMES MEASURED: Each of the three studies evaluated the incidence of recurrent disease and/or mortality in high-risk pediatric ALL patients. These outcomes were analyzed according to the following categories: duration of event-free survival …

Does The Use Of Intravenous Zoledronic Acid, In Combination With Chemotherapy Regimens, Arrest The Development And Spread Of Cancer Cells To Increase Disease-Free Survival In Breast Cancer Patients?, Dara Colasurdo

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not “Does the use of intravenous zoledronic acid, in combination with chemotherapy regimens, arrest the development and spread of cancer cells to increase disease-free survival in breast cancer patients.“

STUDY DESIGN: Review of three English language primary randomized controlled trials published between 2009 and 2010.

DATA SOURCES: Randomized controlled trials and open label, randomized, phase 2 trial comparing the use of zoledronic acid in combination with chemotherapy to the use of chemotherapy alone were found using Medline/PubMed and Cochrane Databases

OUTCOMES MEASURED: The outcomes measured were incidence …

Is Aspirin Effective In Helping To Prevent Breast Cancer In Women Ages 45 Years And Older?, Kristen M. Quartuccio

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not aspirin is effective in helping to prevent breast cancer in women ages 45 years and older.

STUDY DESIGN: Review of three English language primary studies published in 2005, 2007, and 2008

DATA SOURCES: Two randomized, double blind, placebo controlled clinical trials and one prospective, population based cohort study comparing aspirin to placebo were found using PubMed and Cochrane databases.

OUTCOMES MEASURED: Breast cancer development was measured in several ways. Tumor characteristics were measured at diagnosis, including size, metastasis to lymph nodes, histology of the mass, histology …

Is Weight Lifting Effective In Reducing Lymphedema In Breast Cancer Survivors?, Diana Petrucello

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not weight lifting is effective in reducing lymphedema in breast cancer survivors.

STUDY DESIGN: Systematic review of three English language primary studies published in 2009 and 2010.

DATA SOURCES: Three single blind, randomized controlled trials comparing progressive weight lifting and other treatments in breast cancer survivors were found using the Cochrane Database of Systematic Reviews and PubMed.

OUTCOMES MEASURED: Incidence of breast cancer-related lymphedema onset measured by blinded certified lymphedema therapists using a standardized clinical evaluation derived from the Common Toxicity Criteria version 3.0, comprising of interlimb …

Role Of Thromboxane Receptor-Alpha In Prostate Cancer Progression, Prasanna Ekambaram

Wayne State University Dissertations

Thromboxane A2 (TXA2) is a major arachidonic acid metabolite that signals through TXA2 receptors (TP) to induce platelet aggregation and smooth muscle contraction. TXA2 receptors are expressed as two different isoforms in humans, namely TP-alpha (TPα) and TP-beta (TPβ), which have common and distinct signaling pathways. Of the two TP receptor isoforms, studies have shown that TPα impacts tumor growth and progression of lung cancer. Previously our studies demonstrated that activation of Thromboxane receptor by TXA2 agonists could regulate prostate cancer (PCa) cell motility and cytoskeletal reorganization through activation of Rho-A. The primary objective of this study is to investigate …

Hdm2 Small-Molecule Inhibitors For Therapeutic Intervention In B-Cell Lymphoma, Angela Sosin

Wayne State University Dissertations

Lymphomas frequently retain wild-type (wt) p53 function but overexpress HDM2, compromising p53 activity. Therefore, lymphoma is a suitable model for studying therapeutic value of disrupting HDM2-p53 association by small-molecule inhibitors (SMIs). HDM2 SMIs have been developed and are currently under various stages of preclinical and clinical investigation. This study examined various molecular mechanisms associated and biological effects of two different classes of HDM2 SMIs: the spiro-oxindoles (MI-219) and cis-imidazoline (Nutlin-3) in lymphoma cell lines and patient-derived B-lymphoma cells. Surprisingly, results revealed significant quantitative and qualitative differences between these two agents. At the molecular level, effect of Nutlin-3 was generally more …

Modulation Of Anti-Tumor Immune Response By Tgf-Β-Inducible Early Gene 1 (Tieg1), Andi Cani

Wayne State University Theses

Cancer immunotherapy has had limited clinical efficacy partly because regulatory T cells (Treg) suppress the immune response to tumor-associated antigens. Inducible regulatory T cells (iTreg), which are converted from naïve CD4 T cells by TGF-β, an abundant cytokine in the tumor microenvironment, may contribute to this immune suppression. Induction of Foxp3 by TGF-β is mediated by the transcription factor TIEG1 and abrogation of this protein prevents Foxp3 expression. We are testing the hypothesis that blockade of TIEG1 to prevent iTreg conversion will enhance immune response in DNA vaccination to the tumor associated antigen Her-2. Wild type and TIEG1 knockout mice …