Life Sciences Commons^™

Rna-Seq Reveals Transcriptomic Program Associated With Stemness In Taxane Resistant Prostate Cancer, Christina K. Cajigas-Du Ross

Loma Linda University Electronic Theses, Dissertations & Projects

There is no cure for advanced prostate cancer (PCa), and taxane chemotherapy is the only treatment option once other therapies have failed. However, this is problematic since all patients eventually develop chemoresistance. Emerging treatments for advanced PCa have shown promise at the benchside, but clinical trials have not resulted in newly approved drugs due in part to redundant survival pathways utilized by prostate tumor cells to maintain therapy-resistance. Using RNAsequencing—an innovative approach for quantifying gene expression changes—this dissertation sought to elucidate chemoresistance-associated molecular pathways as a catalyst to develop new therapeutic targets. Results revealed a differential upregulation of stemness-associated genes …

Behavioral Ecology And Associated Virology Of Mosquito-Host Interactions In Southern California, Oliver Eshun

Loma Linda University Electronic Theses, Dissertations & Projects

Elucidating characteristics of mosquito-host interactions are critical for understanding the ecology and epidemiology of mosquito-borne diseases. In this dissertation, I conducted three studies to explore potential mosquito-host interactions and associated virus infection rates. I first demonstrated that mosquito captures at CO2-baited traps decreased most markedly with height above ground, and also decreased with distance from water at a riparian area but not at an open water source lacking a vegetated border. Birds might therefore prefer elevated nests or roosts to avoid mosquitoes. The second study examined the anti-mosquito behaviors of budgerigars (Melopsittacus undulatus) in a laboratory study. The birds defended …

Proteomic Profiling Of Serum Derived Exosomes From Prostate Cancer Patients, David Turay

Loma Linda University Electronic Theses, Dissertations & Projects

Touted among the major achievements in the diagnosis and management of Prostate cancer (PCa) in the past few decades has been, the dramatic decline of men with advanced/metastatic PCa at diagnosis coupled with a significant improvement ( >90%) in the five and ten year survival rates of the disease. Non-palpable PCa (potentially clinically treatable disease) now accounts for 70-80% of all newly diagnosed cases of PCa. Preceding these changes by about a decade was the introduction of Prostatic Specific Antigen (PSA) into clinical practice; first as biomarker for monitoring response to therapy and subsequently as a complementary screening tool. It …

Benefits And Barriers To Hiv Testing In A Population Of Federal Detention Inmates, Nicole A. Knight

Loma Linda University Electronic Theses, Dissertations & Projects

Voluntary HIV testing in combination with early medical intervention has been shown to be effective in reducing the rate of new infections and improving the health and life expectancy of those living with HIV. There are however several high-risk populations in the US that remain largely unreached by HIV testing efforts, some of which could be reached while they spend time in prison or jail. Per current Bureau of Prisons (BOP) policy, HIV testing is routinely offered only to “high risk” pretrial and sentenced inmates. We conducted a cross-sectional study with 721 pretrial and sentenced inmates who entered a large …

Self-Reported Exercise And Risk Of Osteoporosis In Prostate Cancer Patients Receiving Androgen Deprivation Therapy, Lori J. Mennen-Winchell

Loma Linda University Electronic Theses, Dissertations & Projects

Prostate cancer is stimulated to grow in response to testosterone. Androgen deprivation therapy (ADT) leads to chemical castration and suppression of prostate cancer cell production. Testosterone levels less then 300ng/ml decreases bone mineral density and could result in osteoporosis. Studies have shown that during the first year of ADT, fracture risk, mainly in hips and spine increases about 50%. In men, 40% of hip fractures result in death. Exercise may reduce the risk of osteoporosis and thus contribute to the prevention of hip and other fractures. There is limited data regarding whether exercise is associated with a reduced risk of …

The Role Of Unrealistic Optimism In Explaining Preventive Behaviors In High Versus Low Endemic Malaria Settings In Belize, Daniel G. Handysides

Loma Linda University Electronic Theses, Dissertations & Projects

Background: Of all the diseases an individual can encounter in the world, malaria is one of the most destructive. Simple measures like sleeping under a bednet would greatly reduce the burden (Abeku, 2007). When people estimate their risk relative to others, they are most often unrealistically optimistic, which may explain why those at risk often fail to perform behaviors, such as using a bednet that will reduce their risk. However, one study showed that people at high risk for malaria held pessimistic perceptions of their risk for the disease, but the reasons for this finding are unclear (Morrison, Ager, & …

Fetal Programming By Nicotine Increases Cardiac Susceptibility To Ischemic Injury, Jennifer Charlotte Alexie Lawrence

Loma Linda University Electronic Theses, Dissertations & Projects

Fetal programming is the area of study that focuses on the prenatal origins of adult onset disorders. Previous studies have associated an adverse prenatal environment with the onset of physiologic and metabolic diseases during adulthood. Fetal malnutrition, hypoxia, and exposure to drugs - such as cocaine and nicotine - have been associated with adult disease states. Cigarette smoking is the number one cause of preventable death in the developed world. Among the many dangerous chemicals found in tobacco products is nicotine, the compound responsible for the addictive nature of tobacco use. Nicotine use during pregnancy is a known cause of …

Novel Binding Domains Mediate Binding Of Hpv 16 E6 To Fadd And Procaspase 8, Sandy S. Tungteakkhun

Loma Linda University Electronic Theses, Dissertations & Projects

To evade the host response to infection, viruses have developed means to survive and propagate. HPV 16, a causative agent of cervical cancer and of some cases of oropharyngeal cancers, is one example. We have reported that the early viral protein E6 binds to proteins necessary for propagation of the apoptotic signal following receptor/ligand interactions, such as those mediated by FADD DED and procaspase 8 DED. E6 expression leads to the dose-dependent accelerated degradation of FADD and the protection of E6-expressing cells from Fas-induced apoptosis. Surprisingly, the splice isoforms of E6, E6_large and E6*, affect the stability of procaspase …

Oxidative Stress-Mediated Anticancer Activity Of Novel Ahr Modulators Af & 5f203, Lancelot S. Mclean

Loma Linda University Electronic Theses, Dissertations & Projects

Estrogen receptor positive (ER+) breast cancer tends to respond to anti-estrogen agents such as Tamoxifen. Approximately 40% of ER+ breast cancer is resistant to these agents and those that initially respond often acquire resistance. Estrogen receptor negative (ER-) breast cancer remains largely unresponsive to these agents. It is therefore vital to discover drugs that are potent in both forms of breast cancer. Aminoflavone, (5-amino-2, 3-fluorophenyl)-6,8-difluoro-7-methyl-4H-l-benzopyran-4-one; AF; NSC 686288) and 5F203, (2-[-Amino-3-methy phenyl]-5-flurobenzothiazole) are novel anticancer candidate agents that display potent in vitro and in vivo anti-proliferative activity against select human tumor cells with a unique anticancer activity profile in the …

The Effect Of Walnuts Compared To Fatty Fish On Plasma And Erythrocyte Fatty Acid Composition, Lymphocyte Subsets And Inflammatory Mediators, Yu-Lan Ching

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to compare the effects of walnuts vs. fatty fish on circulating inflammatory markers, on lymphocyte subsets, on plasma concentrations of eicosanoids precursor polyunsaturated fatty acid and on erythrocyte membrane fatty acid composition. Under controlled metabolic feeding conditions and randomized crossover (3x3 Latin-square) design, 27 subjects alternately consumed a control diet, a walnut diet (1.5 oz (42.5g) /day of walnuts, 6 times/week) or a fish diet (8 oz (226g) /week of salmon) for 4 weeks each. Consumption of the walnut diet (ALA 5.43 g/day) compared to the fish diet (EPA 170 mg/day and DHA 590 …

Influence Of Human Papillomavirus 16 E6 On Trail-Mediated Apoptosis, Theodore O. Garnett

Loma Linda University Electronic Theses, Dissertations & Projects

Viruses have developed sophisticated strategies to evade host defenses and facilitate the production and spread of progeny. HPV 16, whose immune evasion activities can contribute to cervical cancer, is a prime example of such a virus. In this study, we examined the influence of HPV 16 E6 on TRAIL-induced FADD-dependent and -independent pathways in two cellular models: HCT116 colon carcinoma cells and U2OS osteosarcoma cells. We show that transfection of the HPV 16 E6 oncogene into HCT116 cells provides protection from TRAIL-mediated apoptosis. Additionally, we demonstrate that the protection provided by E6 is dose-dependent because higher levels of E6 provide …

Validation Of A Serotonin Depletion Checklist In Parkinson’S Disease, Kelly Diane Darby Holder

Loma Linda University Electronic Theses, Dissertations & Projects

The distinctive pathological marker of Parkinson’s Disease (PD) is the progressive death of neurons that produce dopamine; however, there are also major alterations in the production of quantities of other neurotransmitters, such as norepinephrine and serotonin that contribute to the signs, symptoms, neuropsychological manifestations of the diseases. PD patients can be divided into classes based on the manifestation of motor symptoms, type A, classified as tremor dominant, and type B PD, classified as akinetic. Type B PD patients, often manifest symptoms in which serotonin deficiency plays an important role, such as frontal cognitive impairments, which often includes a history of …

The Potential Role Of Ledgf/P75 In Prostate Cancer, Tracy Ruth Daniels

Loma Linda University Electronic Theses, Dissertations & Projects

The serum autoantibody repertoire from cancer patients is currently being exploited for the identification of tumor associated antigens (TAA) and the design of TAA arrays. Such arrays would facilitate autoantibody profiling and potentially aid in the serological diagnosis and prognosis of tumors. The goal of this study was to identify and characterize prostate-specific TAA. We observed that while the general frequency and titers of autoantibodies in PCa patients were relatively similar to those in matched controls, significant differences could be detected between the two groups in the autoantibody response to the lens epithelial-derived growth factor p75 (LEDGF/p75). LEDGF/p75 is a …

Ionizing Radiation And Endostatin Gene Therapy Against Lung Tumor, Xian Luo

Loma Linda University Electronic Theses, Dissertations & Projects

Although many advances have been made in radiotherapy, tumor radioresistance and normal tissue damage continue to always be important issues for radiation oncologists. Numerous reports have also documented that radiation exposure increases the risk for malignancy and suppresses immune mechanisms. However, increasing evidence has suggested that anti-angiogenic therapy that targets tumor blood supply may alter abnormal tumor vasculature, thus synergizing radiotherapy. The governing hypothesis of the present study was that modification of tumor vasculature by antiangiogenic gene therapy can increase the efficacy of radiotherapy and that radiation can also improve DNA transfection efficiency by increasing expression of the administered gene. …

Potential Mechanisms Explaining The Antitumor Effect Of Total-Body Irradiation, Glen Michael Miller

Loma Linda University Electronic Theses, Dissertations & Projects

While numerous reports have documented that radiation exposure increases the risk for malignancy and suppresses immune mechanisms, increasing evidence has suggested that low-dose total-body irradiation (TBI) may alter leukocyte composition and function leading to heightened immune responsiveness and long-term remission of certain cancers. Having observed that moderate-dose TBI produces an antitumor effect in the Lewis lung carcinoma (EEC) model, the major goal of this study was to determine whether changes in tumor growth could be correlated with radiation-induced alterations of immune system parameters. The governing hypothesis was that selective immune augmentation, i.e. upregulation of specific leukocyte subsets, is primarily responsible …

Il-10 And Alveolar Bone Loss, Abdulaziz Saud Al-Rasheed

Loma Linda University Electronic Theses, Dissertations & Projects

Interleukin-10 (IL-10) is a cytokine with anti-inflammatory activities. IL-10 knockout (KO) mice exhibit severe intestinal inflammation in the presence of normal gut flora. We hypothesized that IL-10 KO mice would also be susceptible to inflammatory periodontal disease resulting in alveolar bone loss (ABL). The purpose of this study was to compare naturally occurring ABL in IL-10 KO and wild type (WT) mice. Twelve IL-10 KO and 12 WT mice, age-(7 months) and sex-(male) matched, were used. Half of the mice were on 129/SvEv and half on C57BL/6J background. Animal heads were defleshed and treated to remove all organic material. ABL …

Enhancement Of Anti-Hiv-1 Ribozyme Activities By Rev Binding And Multimerization, Yuksel Yildiz

Loma Linda University Electronic Theses, Dissertations & Projects

To effectively apply hammerhead ribozymes as therapeutic agents it is necessary to co-localize them with the desired target. Human immunodeficiency virus type1 (HIV- 1) infectivity is dependent on env gene expression. HIV-1 Rev protein binds to a higher ordered RNA structure within the env transcript termed the Rev Binding Element (RBE). In anti-HIV gene therapy employing ribozymes to increase the co-localization of anti- HIV ribozymes with target HIV mRNAs, it has been proposed that when the native HIV- 1 RBE is appended to a ribozyme as a decoy molecule, simultaneous binding of Rev monomers to the RBE sequences in both …

Peer Nutrition Education: A Model For Nutrition Education Among Spanish-Language Participants Of The Special Supplemental Nutrition Program For Women, Infants And Children (Wic), Maximino Alfredo Mejía

Loma Linda University Electronic Theses, Dissertations & Projects

Despite the steady improvement in the health status of Americans, Hispanics are a minority in the United States with greater prevalence of several infectious and chronic diseases and less health knowledge than the average citizen. Nearly half of the Hispanics living in this country die of preventable nutrition-related conditions, with heart disease and cancer being the leading causes. Since this minority has limited access to health care and preventive services, there is a need for an inexpensive, viable model of health education for this underserved segment of the population in order to lower the excess of preventable diseases. We trained …

Effect Of Monounsaturated Fat Rich Almonds On Hemostatic And Inflammatory Factors In Healthy Adults, Kristianne M. Connell

Loma Linda University Electronic Theses, Dissertations & Projects

Background: The frequent consumption of nuts is inversely associated with the incidence of cardiovascular disease. Nuts are known to decrease the risk of cardiovascular disease by reducing serum total and low-density lipoprotein (LDL) cholesterol. Markers of inflammation including C-reactive protein, E-selectin and interleukin-6 have been proposed to be newer risk factors for cardiovascular disease. However, the influence of nuts such as almonds on markers of inflammation and hemostasis that influence cardiovascular disease risk is not currently known.

Objective: The objective of this study was to determine the effect of almond consumption on markers of inflammation and hemostatic factors in healthy …

Effects Of Liposome-Encapsulated Tnf-Alpha And Radiation Against Colon Cancer, Dong Won Kim

Loma Linda University Electronic Theses, Dissertations & Projects

Previous studies have shown that tumor necrosis factor-α (TNF-α) can augment the antitumor effects of radiation, inhibiting tumor progression to a greater extent than either modality alone. However, nonspecific toxicities associated with TNF-α have limited its use as an adjuvant. This limitation is potentially resolved with the encapsulation of TNF-α in sterically stabilized, PEGylated liposomes (STEALTH®). Thus, the overall hypothesis of the research was that the combination of radiation with STEALTH® liposome encapsulated TNF-α (SL-TNF-α) will have greater efficacy and fewer dose-limiting side effects in the LS174T human colorectal tumor xenograft model compared to the combination of free TNF-α and …

Periradicular Response Of Immunodeficient Rats To Mechanical Pulpal Exposure, James E. Stich

Loma Linda University Electronic Theses, Dissertations & Projects

Periradicular lesions develop as a result of the interaction between root canal irritants and the immune system. The purpose of this study was to investigate the periradicular response of immunodeficient rats to their oral flora. Twenty Sprague-Dawley rats received a total body irradiation dose of 750 cGy one week prior to the investigation. The pulps of the mandibular first molars of these animals and six nonirradiated rats were exposed mechanically with a ½ round bur and left open to the oral cavity. Additional irradiation (350 cGy) was administered bi-weekly to maintain immunosuppression. Periradicular specimens were obtained after two and four …

A Preclinical Model Of Ionizing Radiation And Tnf-Alpha Gene Therapy For Cancer, Jun Li

Loma Linda University Electronic Theses, Dissertations & Projects

Long term control of high-grade brain tumors is rarely achieved with current therapeutic regimens. This study sought to determine if pretreatment with plasmid DNA expressing Tumor Necrosis Factor-α (TNF-α) could enhance the effect of ionizing radiation in an aggressive, rapidly growing glioma tumor (C6) model. Plasmid DNA is an attractive vector system for delivery of foreign genes into eukaryotic cells due to its advantages including low immunogenicity in vivo, lesser toxicity and relatively low cost. We have constructed a plasmid-based mammalian expression vector (pGL1-TNF) to secrete human TNF-α from cancer cells. Plasmid DNA was successfully transfected into C6 cells …

Neuronal And Metabolic Increases In Pedunculopontine Nucleus Of Parkinson's Rats, Jonathan Dennis Carlson

Loma Linda University Electronic Theses, Dissertations & Projects

The theoretical mechanisms underlying the symptoms of Parkinson’s disease are based on dysfunctional output from the basal ganglia projected to the cortex via the thalamus. However, the subthalamic nucleus (STN) and substantia nigra pars reticularis (SNr) as part of the basal ganglia, also project to the brainstem, in particular to the pedunculopontine nucleus (PPN). Both the STN and SNr have altered neuronal activity in the 6-hydroxydopamine (6-OHDA) Parkinson’s model rat. Thus, it is hypothesized that the PPN is altered in this model of Parkinson’s disease.

This hypothesis was examined by comparing the rates of glucose metabolism and spontaneous neuronal activity …

Antitumor Effect Of Il-2, P53, And Bax Naked Gene Transfer In C6 Glioma Cells, Peyman Haghighat

Loma Linda University Electronic Theses, Dissertations & Projects

[Abstract not included]

The Role Of Gap Junctions In Congenital Diseases Of The Heart, Scott Henry Britz-Cunningham

Loma Linda University Electronic Theses, Dissertations & Projects

Background. Gap junctions are thought to have a crucial role in the synchronized contraction of the heart and in embryonic development. Connexin43, the major protein of gap junctions in the heart, is targeted by several protein kinases that regulate myocardial cell-cell coupling. We hypothesized that mutations altering sites critical to this regulation would lead to functional or developmental abnormalities of the heart.

Methods. Connexin43 DNA from 25 normal subjects and 30 children with a variety of congenital heart diseases was amplified by the polymerase chain reaction and sequenced. Mutant DNA was expressed in cell culture and examined for its effect …

Analysis Of Serotonin And Postural Instability In Parkinson’S Disease, Sandra Kuniyoshi

Loma Linda University Electronic Theses, Dissertations & Projects

Postural instability is one of the most debilitating symptoms of Parkinson’s disease and the best clinical prognostic indicator of progressive disease. Significant differences in neuropathology, neurochemistry, response to L-dopa therapy and stereotactic surgery as well as prognosis have been identified in subtypes when patients with predominant postural instability and gait difficulty (PIGD)/Type B were differentiated from those with predominant symptoms of tremor and rigidity/Type A. Postural instability is resistant to the therapeutic effects of L-dopa, despite its continued efficacy on other Parkinson’s symptomatology, implicating the nondopaminergic mechanism of postural instability in Parkinson’s disease. Patients with significant postural instability and gait …

The Effect Of Guidor™ And Hop-1 On Hard Tissue Healing : Following Periradicular Surgery In Cats, Hugh Maguire

Loma Linda University Electronic Theses, Dissertations & Projects

The purpose of this study was to evaluate the effects of the resorbable membrane Guidor™ and the osteogenic protein hOP-1 on hard tissue healing following periradicular surgery in cats.

Surgical endodontic therapy was performed on the maxillary canine teeth of twelve cats. After orthograde root canal therapy, flap reflection, osteotomy, resection of the root end, root end cavity preparation and the placement of a root end filling, eight of the surgical sites were treated with Guidor™ and eight with hOP-1. The remaining eight sites received no further treatment and served as controls.

The animals were sacrificed at twelve weeks following …

Periodontal Repair In Dogs : Effect Of Recombinant Human Transforming Growth Factor Beta-1 On Guided Tissue Regeneration, Saghi Shayan Razi

Loma Linda University Electronic Theses, Dissertations & Projects

The objective of this study was to evaluate bone and cementum regeneration in the critical size, supraalveolar, periodontal defect model following surgical implantation of recombinant human transforming growth factor beta-1 (rhTGFß-1) in conjunction with guided tissue regeneration (GTR). Five male beagle dogs were used in a split-mouth design. Alternate jaw quadrants in consecutive animals received GTR with rhTGFß-1 in a resorbable calcium carbonate carrier. Contralateral jaw quadrants received GTR with carrier only (control). The healing interval was 4 weeks. Clinical healing was generally uneventful, however, minor membrane exposures were observed for both treatments with limited gingival inflammation. All defects with …

Association Between Nutrient Intake And Risk Of Coronary Heart Disease In California Seventh-Day Adventists, Peter Pribiš

Loma Linda University Electronic Theses, Dissertations & Projects

Dietary habits are believed to be major determinants of risk of coronary heart disease (CHD). Studies of high and low risk populations have suggested several nutrients to be protective or hazardous against CHD. Most published work since 1984 on diet and CHD in the Adventist Health Study (AHS) population examined either foods or food groups. This study investigated ten nutrients as exposure variables and their relationship to CHD risk. A cohort of 23,616 nonsmoking, non-Hispanic white California Seventh-day Adventists was followed for six years beginning in 1976. Extensive dietary information was collected at baseline, as well as values of traditional …

Periodontal Repair In Dogs : Part I : Evaluation Of The Natural Disease Model ; Part Ii : Eptfe Barrier Membranes Support Wound Stabilization And Enhance Bone Regeneration, James Marc Haney

Loma Linda University Electronic Theses, Dissertations & Projects

Animal models are frequently consulted for histometric analysis of reconstructive periodontal therapy. Statistical analysis of induced lesion defects and surgically created defects from our laboratory suggest defect size homogeneity is critical for the model to discriminate treatment effects. This study characterizes natural disease defects in beagle dogs. Buccal-lingual histologic sections from the 2nd, 3rd, and 4th mandibular premolar teeth (P2, P3, P4) from 6 aged beagle dogs with natural disease defects were evaluated for variation in defect height between pair matched tooth types, and jaw quadrants, as well as estimated confidence intervals for treatment differences between left and right pair …