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Full-Text Articles in Genetics and Genomics
Rna-Seq Reveals Transcriptomic Program Associated With Stemness In Taxane Resistant Prostate Cancer, Christina K. Cajigas-Du Ross
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 …
Fetal Programming By Nicotine Increases Cardiac Susceptibility To Ischemic Injury, Jennifer Charlotte Alexie Lawrence
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 …
Oxidative Stress-Mediated Anticancer Activity Of Novel Ahr Modulators Af & 5f203, Lancelot S. Mclean
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 …
Novel Binding Domains Mediate Binding Of Hpv 16 E6 To Fadd And Procaspase 8, Sandy S. Tungteakkhun
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, E6large and E6*, affect the stability of procaspase …
Influence Of Human Papillomavirus 16 E6 On Trail-Mediated Apoptosis, Theodore O. Garnett
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 …
The Potential Role Of Ledgf/P75 In Prostate Cancer, Tracy Ruth Daniels
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
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
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 …
Effects Of Liposome-Encapsulated Tnf-Alpha And Radiation Against Colon Cancer, Dong Won Kim
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 …
A Preclinical Model Of Ionizing Radiation And Tnf-Alpha Gene Therapy For Cancer, Jun Li
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 …
Antitumor Effect Of Il-2, P53, And Bax Naked Gene Transfer In C6 Glioma Cells, Peyman Haghighat
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]