Medicine and Health Sciences Commons^™

Cancer Stem Cells In The Screening Of Anticancer Drugs For Central Nervous System Tumors, Sarah Elizabeth Daron-Mathis

Theses, Dissertations and Capstones

There is a growing need (in the medical field) to design personalized therapy for cancer patients. Decades of cancer research have found no silver bullet that can cure all or even most patients. This study evaluated four patients affected by central nervous system (CNS) tumors (Ependymoma and Glioblastoma), and found that tumors with the same histology had unique responses to treatment. Each sample presented different levels of heterogeneity in expressed biomarkers and responded to drugs at varying levels.

Oncologists conventionally treat cancer patients with drugs tested in large clinical trials. However, often patients do not experience positive outcomes following treatments …

Investigation Of Ultrasound Targeted Microbubbles As A Therapeutic Gene Delivery System For Prostate Cancer, Rounak Paramjeet Nande

Theses, Dissertations and Capstones

A major challenge for effective gene therapy is systemic delivery of viruses carrying therapeutic genes into affected tissue. The immunogenic nature of human adenoviruses (Ads) limits their use for intratumoral (IT) injection in gene therapy. Ads transfection is further hampered by the fluctuating presence of Coxsackie and Adenovirus Receptor (CAR) and integrins on the cells’ surface. To circumvent these limitations we developed a novel approach wherein Ads are encapsulated inside the shell of lyophilized, lipid-encapsulated, perfluorocarbon microbubbles (MBs)/ultrasound (US) contrast agents, which act as delivery vehicles for a sitespecific gene transfer system.

We performed infection studies with Ad.GFP (Green Fluorescent …

Tell Me A Story: The Relationship Between Identity And Life Stories Following Brain Injury, Sara Henson

Theses, Dissertations and Capstones

Following brain injury, people can demonstrate cognitive-linguistic deficits as well as a shift in their identities. Clinicians use assessment and treatment methods that focus on cognitive-linguistic deficits with this population; however, they rarely (if ever) consider identity as a viable and necessary target for intervention efforts. For individuals with brain injury, life narratives can be used to assess and treat the cognitive-linguistic skills and discourse at a macro-systemic level, build relationships through the use of a client-centered approach, develop a strong sense of self-identity that aids in goal setting, establish life purpose that motivates greater participation and effort in rehabilitation, …

Effects Of Ondansetron 4 Milligrams Compared With Ondansetron 8 Milligrams On The Incidence Of Post-Operative Nausea And Vomiting In Patients With Body Mass Index Greater Than 30kg/M2 Undergoing Mastectomy, Diego Alejandro Arroyo

Theses, Dissertations and Capstones

Introduction: Post-Operative Nausea and Vomiting (PONV) is a recurrent and frequent issue for the patient, the anesthesia team, and Post Anesthesia Care Unit (PACU) team. Both pharmacologic and non-pharmacologic recommended modalities have been utilized for both the prevention and treatment of PONV in the surgical-anesthesia setting. The 5-HT3-receptor antagonist ondansetron is one of the many known pharmacological modalities commonly utilized by anesthesia providers in preventing PONV.

Methodology: The design used for this research was a quantitative, retrospective case control study that evaluated existing data enclosed in the Electronic Medical Records (EMR) from Charleston Area Medical Center (CAMC), which is …

Inhalation Anesthesia Vs. Total Intravenous Anesthesia For Ambulatory Dental Surgery In Children, Kristin D. Neal

Theses, Dissertations and Capstones

Abstract: The purpose of this study was to compare inhalation anesthesia with sevoflurane versus Total Intra Venous Anesthesia (TIVA) with propofol infusion as it relates to the quality of recovery including postoperative pain, Post Operative Nausea and Vomiting (PONV), and Post Anesthesia Care Unit (PACU) Length Of Stay (LOS) in pediatric patients undergoing ambulatory dental surgery. Introduction: Pediatric dental procedures are increasingly performed in an outpatient setting under general anesthesia due to inadequate cooperation, circumstantial anxiety, and other behavioral and health issues. Commonly used inhalation anesthetics, such as sevoflurane, can induce hyperalgesia in children. While sevoflurane increases the risk PONV, …

Benzyl Isothiocyanate As An Adjuvant Chemotherapy Option For Head And Neck Squamous Cell Carcinoma, Mary Allison Wolf

Theses, Dissertations and Capstones

Isothiocyanates (ITCs) are natural phytochemicals produced by cruciferous vegetables. Recent evidence supports that, in addition to cancer prevention, ITCs can use various mechanisms to target malignant cells. Current therapies for cancer often provoke detrimental side effects, however clinical evidence supports that ITCs have little to no side effects in patients. Consequently, ITCs may be a promising treatment option for cancer patients, especially patients suffering from head and neck squamous cell carcinoma (HNSCC).

Despite recent improvements in cancer treatment, overall survival of advanced HNSCC has not improved in the past three decades. Metastasis and chemoresistance represent two detrimental events that greatly …

Secondhand Smoke Exposure As A Risk Factor For Perioperative Airway Complications In Pediatric Outpatient Procedures, Ashlee Denise Loudin

Theses, Dissertations and Capstones

Abstract: The purpose of this study is to assess the risk of perioperative airway complications, analyze extubation times, and PACU Length Of Stay (LOS), and their association with secondhand smoke exposure in pediatric populations receiving outpatient procedures that require general anesthesia.

Introduction: Tobacco Smoke Exposure (TSE), is well documented to cause physiologic changes in lung tissue that are associated with decreased lung function, increased risk of lower and upper respiratory tract illness, exacerbation of asthma or increased risk of asthma, increased prevalence of non-allergic bronchial hyperresponsiveness, sudden infant death syndrome, and a host of other respiratory complications in adult and …

Intraoperative Hyperglycemia In Adult Patients Undergoing An Emergency Craniotomy Following A Traumatic Brain Injury As A Predictor Of Postoperative Outcomes And Mortality, Sara Lynn Hoover

Theses, Dissertations and Capstones

Abstract: The purpose of this study was to determine if there was an association between intraoperative blood glucose ≥150 mg/dl in patients undergoing an emergency craniotomy and Intensive Care Unit (ICU) Length of Stay (LOS), hospital LOS and mortality.

Introduction: Traumatic Brain Injuries (TBI)’s are associated with increased morbidity and mortality. The stress response by the body may cause an increase in blood glucose levels which can cause secondary brain injury. When a patient undergoes an emergency craniotomy following a TBI the increased stress on the body can cause an even higher blood glucose. There is no consensus in …

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 …

Factors That Motivate Certified Registered Nurse Anesthetists To Practice Independently In The Appalachian Region, Michael Lee Frame Jr.

Theses, Dissertations and Capstones

Introduction: Independent Certified Registered Nurse Anesthetists (CRNAs) provide anesthesia services without the supervision or medical direction of anesthesiologists in healthcare facilities throughout the United States. The present literature is limited concerning the factors that motivate CRNAs to choose employment in rural independent practice.

Research Hypothesis: In a sample of CRNAs who practice independently in one of the 13 states of the Appalachian region there will be no differences between the CRNAs from Appalachian and Non-Appalachian counties in their responses to the motivation factors of achievement, recognition, responsibility, advancement, work itself, salary, working conditions, company and administrative policies, supervision, and …

Risk Factors For Ventilator-Associated Pneumonia In The Adult Trauma Patient: A Retrospective Case-Control Study From A Level I Trauma Center, Summer L. Chapman

Theses, Dissertations and Capstones

Introduction: Ventilator-Associated Pneumonia (VAP) continues to be a common complication among the adult trauma population. Little advancements have been made to decrease the incidence, suggesting further research is needed to establish modifiable risk factors. The purpose of this study was to test for an associated link between prehospital intubation and the development of VAP in the adult trauma patient.

Methodology: A retrospective, case-control study design was utilized. The sample included 494 adult trauma patients who required endotracheal intubation and mechanical ventilation for a minimum of 24 hours. All patients presented as a priority one or two trauma to the Charleston …

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 …

Dietary Interventions Against Mammary Glands And Prostate Cancers, Juliana Adedayo Akinsete

Theses, Dissertations and Capstones

Dietary components modulate normal cellular functions and, in cancer cells, alter processes that lead to cancer and/or its progression. The change in the patterns of human food production and consumption over time has contributed to increasing risk for diseases including cancer. Omega-3 and omega-6 fatty acids are classes of essential polyunsaturated fatty acids in the human diet and are required for normal growth and development. Omega-3 and omega-6 fats are thought to be required in the ratio of 1:1 to 1:4 on which humans are thought to have evolved. However, the Western diet has greatly shifted from this ratio. The …

Identification Of Genes Involved In Hematopoietic Stem Cell Differentiation And Leukemia Differentiation And Leukemia, Jasjeet Bhullar

Theses, Dissertations and Capstones

Hematopoiesis is maintained by a proper balance between self renewal and multipotent differentiation of the hematopoietic stem cells (HSC). Acute myelogenous leukemia (AML) is characterized by the blockage in the differentiation of HSC, while self renewal and proliferation is preserved. It is important to understand the mechanisms involved in the inhibition of hematopoietic differentiation and maintenance of the HSC state in order to develop better therapies for AML. In these studies I have explored the role of Hsp90, omega-3 fatty acids and YB-1 in hematopoietic differentiation. EML, a hematopoietic precursor cell line, was used as a model for the hematopoietic …

Pitx2 Is Overexpressed In Follicular Cell-Derived Thyroid Cancer And Promotes Thyroid Cancer Proliferation By Regulating Cell Cycle, Yue Huang

Theses, Dissertations and Capstones

Thyroid cancer is the most prevailing malignancy of the endocrine system. Its incidence is rapidly rising at the second fastest rate of all malignancies in the United States, making it a significant health problem. Although the majority of thyroid cancer is slowly-growing and well-differentiated, available treatment options are very limited, and most of them require complete removal of the thyroid gland and surrounding tissues. Patients who have undergone thyroid removal have to take life-long hormone replacement therapy, which is very inconvenient and costly. Therefore, there is an urgent need to develop new treatments for this disease. As a prerequisite for …

Cancer Cachexia And Cardiac Atrophy In The Apcmin/+ Mice Model Of Colon Cancer, Nandini Durga Prasanna Kumar Manne

Theses, Dissertations and Capstones

Cancer cachexia is a muscle wasting condition that occurs in response to a malignant growth in the body. Cachexia is associated with heart failure and is estimated to be the immediate cause of death in about a third of all cancer patients. The purpose of this study was to investigate cardiac atrophy in the APCmin/+ mouse model of colorectal cancer. Compared to age matched C57BL/6 (BL6) mice, APCmin/+ body mass and heart mass were lower at 12 (11.1 Ѡ4.5% and 7.6 Ѡ2.8%, respectively) and 20-weeks (26.1 Ѡ2.5% and 6.0 Ѡ3.8%, respectively) of age (P < 0.05). Immunoblot analysis revealed that these changes in mass were accompanied by increased activation of protein kinase B (Akt Thr 473: 74.4 Ѡ10.9% and 216.0 Ѡ19.6% ; Akt Ser 308: 161.6 Ѡ31.7% and 367.4 Ѡ41.6% at 12- and 20-weeks, respectively, (P < 0.05)), mammalian target of rapamycin (mTOR Ser2448: 23.2 Ѡ13.2% and 44.0 Ѡ16.4% at 12- and 20-weeks, respectively, (P < 0.05)), 5' adenosine monophosphate-activated protein kinase (AMPK: 19.6 Ѡ5.2% and 22.5 Ѡ5.5% at 12- and 20-weeks, respectively, (P < 0.05)) and elevated levels of the autophagy regulator beclin1 (4.7 Ѡ3.3% and 9.5 Ѡ3.0% at 12- and 20-weeks, respectively, (P < 0.05)). No evidence of increased cardiac apoptosis, protein ubiquitination or activation of cardiac caspases or calpains was noted. Taken together, these data suggest that the cardiac atrophy that occurs in the 12- and 20-week old APCmin/+ mouse is relatively modest compared to that seen with other tumor models [1] and is associated with evidence of increased cardiac autophagy.

Predictors Of Postoperative Respiratory Failure In Patients Receiving Anesthesia, Marty Henley

Theses, Dissertations and Capstones

Introduction: Postoperative Respiratory failure has been identified as a prevention quality indicator by The Agency for Health Research and Quality (AHRQ). Postoperative Respiratory Failure is associated with increased length of stay, increased costs and increased morbidity and mortality. Unfortunately, current research is limited regarding scoring methods which are predictive for postoperative respiratory failure. This retrospective case control study was conducted to determine if the various tools of evaluation of risk currently available and to determine if any are predictive of the risk of developing postoperative respiratory failure.

Methodology: The design of this research was a retrospective case control study conducted …

Treatment Strategies In Acute Myelogenous Leukemia : Investigating Hsp90 And P53 As Targets, Jennifer M. Napper

Theses, Dissertations and Capstones

Acute myelogenous leukemia (AML) is the deadliest of the lymphatic and bone marrow cancers. Patients diagnosed with AML have a five year survival rate of 23.4%. AML is characterized by an accumulation of undifferentiated and functionless myeloid precursors in the bone marrow and blood. Heat shock protein 90 (Hsp90) inhibitors, such as 17-AAG, an analog of geldanamycin (GM), are currently undergoing phase I, and II and III clinical trials for various cancers with mixed results. I found distinct responses to 17-AAG treatment among the AML cell lines tested. I also discovered two mutant TP53 alleles in Kasumi-3 cells, an AML …

Genetic And Environmental Factors Suggest That Dietary Fatty Acid Content, Lipid Metabolism, And Bone Properties Are Key Regulators Of Myeloid Progenitor Cell Frequency, Melinda E. Varney

Theses, Dissertations and Capstones

Acute myelogenous leukemia (AML) and its precursors are the result of the dysregulation of hematopoiesis. Hematopoiesis proceeds in a stepwise manner, beginning with hematopoietic stem cells, continuing to develop into various stages of progenitor cells, and finally becoming fully functional blood cells. As this process goes awry, immature, functionless cells of the myeloid lineage proliferate out of control. Discerning how myeloid progenitor frequency is regulated allows for a better understanding of how the process may lose control. Hematopoiesis has been shown to depend on genetic and environmental factors. In this work, I have added to this knowledge base by providing …

The Expression And Function Of Hypoxia Inducible Factor-1Α In Human Melanoma, Sandeep S. Joshi

Theses, Dissertations and Capstones

Hypoxia inducible factor-1α (HIF-1α) protein, a key regulator of oxygen homeostasis, is stabilized under hypoxia and degraded under normal oxygen tension. Here, the human melanoma cells were found to express an elevated amount of HIF-1α mRNA and protein relative to normal human melanocytes under normoxic conditions. The amount of HIF-1α expressed is roughly correlated with the stage of melanoma from which the cell line was established. In addition, a splice variant mRNA of HIF-1α785 is expressed at higher levels than full-length HIF-1α mRNA in the more aggressive melanoma cells. This splice variant lacks part of the oxygen regulation domain. Ectopic …

Loss Of Ski Expression In Testicular Cancer Leads To An Enhanced Invasive Phenotype Through Both Bmp-Dependent And Bmp-Independent Pathways, Amy N. Nash

Theses, Dissertations and Capstones

The proto-oncogene SKI is a transcription factor and a co-repressor of the TGFβ superfamily, including TGF

β and BMP. However, additional data suggests that SKI may function as a tumor suppressor in some cell types. The TGFβ superfamily has been implicated in cancer progression and germ cell migration. Testicular cancer afflicts men during their peak reproductive years and is the most common cancer among men of this age group. Cisplatin-based chemotherapy is the standard treatment for testicular cancer. This treatment can lead to undesirable side effects, including infertility. We have shown that SKI expression is decreased in testicular germ cell …

The Function And Mechanism Of Chmp1a In Tumor Development, Jing Li

Theses, Dissertations and Capstones

Chmp1A (Chromatin modifying protein 1A/Charged multivesicular protein 1A) is a member of the ESCRT-III (Endosomal Sorting Complex Required for Transport) family, which mediates trafficking via MVB (multivesicular body) formation and sorting. Our studies suggest that Chmp1A is a novel tumor suppressor, especially in the pancreas. Knockdown of Chmp1A resulted in an increase of anchorage-independent growth of HEK 293T cells. Moreover, we showed that Chmp1A depleted HEK 293T cells forms tumor in xenograft mice. Knockdown of Chmp1A in PanC-1 cells promoted cell growth. In contrast, Doxycycline induced over-expression of Chmp1A in pancreatic cancer cells (PanC-1) resulted in cell growth inhibition, tumor …

Effects Of Retinoic Acid On Beta-Catenin Transcriptional Activity In Melanoma Cells, Fung Chan

Theses, Dissertations and Capstones

Melanoma is the most dangerous form of skin cancer and its incidence has been increasing in the United States. Most melanomas are resistant to current chemotherapies; therefore, understanding the mechanism of melanomagenesis is beneficial to treatment of the diseases. Accumulation of β-catenin has been shown in colon and other cancers, including melanomas, but the transcriptional role of β-catenin in melanomas is still unclear. All-trans retinoic acid (ATRA) is an anti-tumor agent that has an inhibitory effect on β-catenin, but this effect has not been studied in melanomas. It has been shown that Microphthalmia-associated transcription factor (MITF), a melanocyte specific protein, …

Effects Of Aging On Pressure-Induced Mapk Activation In The Rat Aorta, Kevin M. Rice

Theses, Dissertations and Capstones

With age, the cardiovascular system experiences substantial alterations in cellular morphology and function. The factors regulating these changes are unknown; however, the mitogen activated protein kinase (MAPK) pathways have emerged as critical components for mediating numerous cellular responses including control of cell growth, differentiation and adaptation. Here we compare the expression, basal activation and the ability of increased pressure to activate the MAPK pathways in adult (6 month old), aged (30 month old) and very aged (36 month old) Fischer 344 x Brown Norway F1 Hybrid rats. Histochemical analysis demonstrated an age-related increase in tunica media thickness of approximately 11% …

Effects Of Tamoxifen On Mitochondrial Nos Activity: Alteration In The Intramitochondrial Ca2+ Homeostasis, Sandeep S. Joshi

Theses, Dissertations and Capstones

Tamoxifen (Tam) is an anticancer drug that induces oxidative stress and apoptosis via mitochondria- and nitric oxide (NO)-dependent pathways. Here, we report that therapeutic concentrations of Tam stimulate the mitochondrial NO synthase (mtNOS) activity of isolated rat liver mitochondria by increasing the intramitochondrial ionized Ca²⁺ concentration ([Ca²⁺]_m). Tam decreases transmembrane potential (∆ψ) due to increased [Ca²⁺]_m that neutralizes the negative charges of the inner mitochondrial membrane. Thus, the present study reports a novel mechanism for the widely used anti- caner drug, Tam.

Antimicrobial And Spermicidal Activity Of Hydrogen Peroxide And Nonoxynol-9 Based Gel Preparations, Paul E. Grimmett

Theses, Dissertations and Capstones

Eighty gel formulations were prepared using five buffer systems (0.01M citrate, 0.02M citrate, 0.01M tartrate, 0.02M tartrate, and 0.01M citrate/0.01M tartrate), four hydrogen peroxide (H2O2) concentrations (0%, 0.3%, 0.9%, and 1.2%), and four nonoxynol-9 (N-9) concentrations (0%, 1%, 1.5%, and 2%). The eighty gel formulations were then tested for physio-chemical properties (viscosity and pH), antimicrobial effectiveness (Minimum Inhibitory Concentration Assay) against Candida albicans, Escherichia coli, and Streptococcus agalactiae, and finally, spermicidal effectiveness (Sander Cramer Assay). The gel formulation that contained the best combination of physio-chemical, antimicrobial, and spermicidal properties was a 0.01M citrate buffered hydrogel, which contained 0.9% H2O2 and …

Renal Basolateral Transport Of Glucuronides And Other Organic Anions In Rat In Vitro Models, Sarah L. Miles

Theses, Dissertations and Capstones

Glucuronidation is a common Phase II biotransformation reaction that increases the hydrophilicity, and thus elimination, of toxins, xenobiotics, and endogenous compounds. Previous studies suggest that the kidney can secrete glucuronide conjugates, but the renal transport mechanisms for glucuronide secretion have not been determined. Based on the chemical nature of glucuronide metabolites, it is hypothesized that organic anion transporter (OAT) proteins along the basolateral membrane of the renal proximal tubule promote renal accumulation of glucuronide conjugates. The purpose of this study was to develop a rat renal proximal tubule model which demonstrates OAT activity and by which the contribution of OAT …

Hk-2 Cells As A Human Model Of Glucuronide Transport, Eliza E. Robertson

Theses, Dissertations and Capstones

Glucuronidation is primarily a pathway of detoxification in most species, but many glucuronide conjugates are associated with toxicity. Numerous drugs are excreted in the urine as glucuronide conjugates. Being organic anions, it is likely that glucuronides are secreted into the urine by organic anion transporters found in renal proximal tubule cells (PTCs). Some drugs that are metabolized by glucuronidation have been shown to cause renal toxicity, yet little is known about the renal handling of glucuronide conjugates. It is hypothesized that glucuronides are transported into renal PTCs by an organic anion transporter (OAT) on the basolateral membrane of the cell. …

The Genetic And Molecular Characterization Of The Polycystic Kidney Disease-Causing Mouse Gene Bicc1, Sarah J. Price

Theses, Dissertations and Capstones

Polycystic kidney disease (PKD) is one of the most common hereditary diseases and is characterized by progressive cyst formation, substantial renal enlargement, and frequently, progression to end-stage renal disease. One way to learn more about the etiology of this disease is to study mouse models that imitate the human situation. The juvenile congenital polycystic kidney disease (jcpk) gene on mouse Chromosome 10 has been found to cause a severe, early onset form of PKD when inherited in an autosomal recessive manner (Flaherty et al., 1995). Previous genetic studies mapped the jcpk locus to a 1 cM region on mouse Chromosome …

Synergistic Interactions Of Chlorambucil, Dha, And Trail In Jurkat And H460 Human Cancer Cells, Jennifer Ellen Bush-O'Donnell

Theses, Dissertations and Capstones

Traditional chemotherapeutic drugs are prone to toxicity and may result in secondary cancers. In recent years much attention has been garnered by alternate methods of cancer treatment with fewer side effects, including immunotherapy and administration of ω-3 fatty acids, both of which have been shown to cause apoptosis in cancer cells. Docosahexaenoic acid (DHA), a fatty acid, is a normal component of cell membranes and is safe for systemic administration. The cytokine TRAIL (tumor necrosis factorrelated apoptosis-inducing ligand) is able to induce apoptosis in cancer cells while sparing normal tissue. In this study, the alkylating agent chlorambucil (CLB) was combined …