Open Access. Powered by Scholars. Published by Universities.®
- Discipline
-
- Medical Specialties (5)
- Medical Cell Biology (4)
- Pharmacy and Pharmaceutical Sciences (4)
- Biological Phenomena, Cell Phenomena, and Immunity (3)
- Diseases (3)
-
- Neoplasms (3)
- Oncology (3)
- Pharmaceutics and Drug Design (3)
- Chemical and Pharmacologic Phenomena (2)
- Chemicals and Drugs (2)
- Life Sciences (2)
- Medical Microbiology (2)
- Medical Molecular Biology (2)
- Medical Toxicology (2)
- Behavior and Behavior Mechanisms (1)
- Biology (1)
- Carbohydrates (1)
- Cardiovascular Diseases (1)
- Digestive System Diseases (1)
- Hepatology (1)
- Macromolecular Substances (1)
- Medical Biochemistry (1)
- Medicinal and Pharmaceutical Chemistry (1)
- Natural Products Chemistry and Pharmacognosy (1)
- Nephrology (1)
- Other Chemicals and Drugs (1)
- Other Pharmacy and Pharmaceutical Sciences (1)
- Keyword
-
- Cannabinoid (12)
- Cancer (11)
- Autophagy (9)
- Nicotine (9)
- Ethanol (6)
-
- Pain (6)
- Opioid (5)
- Alcohol (4)
- Anxiety (4)
- Apoptosis (4)
- CB1 (4)
- Endocannabinoid (4)
- Epilepsy (4)
- Radiation (4)
- Self-administration (4)
- Senescence (4)
- Tolerance (4)
- Behavior (3)
- Breast cancer (3)
- C. elegans (3)
- Calcium (3)
- FAAH (3)
- Inflammation (3)
- MAGL (3)
- Reward (3)
- Status epilepticus (3)
- AUTOPHAGY (2)
- Abuse (2)
- Acute Functional Tolerance (2)
- Adolescent (2)
Articles 61 - 90 of 105
Full-Text Articles in Medical Pharmacology
Identifying Modulators Of The Development Of Acute Functional Tolerance To Ethanol In Caenorhabditis Elegans., Ka-Po Leung
Identifying Modulators Of The Development Of Acute Functional Tolerance To Ethanol In Caenorhabditis Elegans., Ka-Po Leung
Theses and Dissertations
Alcohol abuse is a problem in our society. There are few treatments available, in part due to the unclear molecular mechanisms of ethanol’s effects. Human studies indicate that there is a genetic component influencing disease susceptibility, and that an individual’s initial response to alcohol can predict their development of addiction. We have taken a forward genetics approach to study one component of initial response, acute functional tolerance (AFT), in Caenorhabditis elegans. We identified bet11, a mutation that causes animals to be defective in the development of AFT. Genetic analysis suggested that the gene that bet11 disrupts participates in a synthetic …
The Use Of Targeted Charge-Reversal Nanoparticles (Tcrns) To Investigate Nuclear Delivery Of Fluorescent Agents To Cancer Cells: Implications For Novel Prostate And Breast Cancer Therapy, Mario Dance
Theses and Dissertations
Nanotechnology has recently emerged as a strong contributor toward research efforts to develop targeted systems of drug delivery in cancer therapy. Our work investigates the therapeutic potential of Targeted Charge-Reversal Nanoparticles (TCRNs), a novel nanoparticle with in vitro evidence of nuclear drug delivery. Using M12 prostate cancer cells, MDA-MB-231 breast cancer cells, and modified derivatives of these cell lines, we investigated the ability of Folic Acid-tagged TCRNs to deliver Nile Red and Dimethyl Indole Redfluorescent (DiR) fluorescent dyes to the nucleus of cells using confocal microscopy and in vivo biphontonic imaging using Xenogen® Technology. Confocal imaging with the SCP28 derivative …
Role Of Autophagy In Radiosensitization Of Breast Tumor Cells, Molly L. Bristol
Role Of Autophagy In Radiosensitization Of Breast Tumor Cells, Molly L. Bristol
Theses and Dissertations
In MCF-7 breast tumor cells, ionizing radiation promoted autophagy that was cytoprotective; pharmacological or genetic interference with autophagy induced by radiation resulted in growth suppression and/or cell killing (primarily by apoptosis). The hormonally active form of vitamin D, 1,25D3, also promoted autophagy in irradiated MCF-7 cells, sensitized the cells to radiation and suppressed the proliferative recovery that occurs after radiation alone. 1,25D3 also enhanced radiosensitivity and promoted autophagy in MCF7 cells that overexpress Her-2/neu as well as in p53 mutant Hs578t breast tumor cells. In contrast, 1,25D3 failed to alter radiosensitivity or promote autophagy in the BT474 breast tumor cell …
The Effects Of Hypothermia On Status Epilepticus-Induced Acquired Epilepsy, Kristin Phillips
The Effects Of Hypothermia On Status Epilepticus-Induced Acquired Epilepsy, Kristin Phillips
Theses and Dissertations
Status epilepticus (SE) is a type of neurological injury characterized by continuous seizure activity and can lead to molecular and pathophysiological alterations leading to plasticity changes. SE can lead to the development of AE by the process of epileptogenesis, which is a phenomenon that describes the transformation of normal brain tissue into a hyperexcitable neuronal population. It has been demonstrated both in vivo and in vitro that calcium (Ca2+) dynamics are severely altered during and after SE, and these changes play a major role in the progression of epileptogenesis. It has also been reported that preventing the rise in intracellular …
Intracellular Signaling Contributions To Behaviors Relevant To Nicotine Addiction, Lauren Thompson
Intracellular Signaling Contributions To Behaviors Relevant To Nicotine Addiction, Lauren Thompson
Theses and Dissertations
Nicotine is the primary addictive substance in tobacco, and most smokers who quit will relapse within a year. Evidence shows that cigarette craving increases over time, termed “incubation.” The purpose of these studies was to see if protracted abstinence from chronic nicotine increases rat self-administration, an animal model with good face validity for human tobacco use, and if nicotine self-administration during daily exposure/after 8+ days of abstinence is regulated by extracellular signal-regulated kinase (ERK) signaling in the nucleus accumbens (NAc) shell or anterior cingulate cortex (PFC). ERK kinase inhibitor U0126 was infused in the NAc shell or PFC of Long …
Cis 3,4', 5-Trimethoxy-3'-Aminostilbene (Stilbene 5c) Induces Apoptosis And Protective Autophagy In B16f10 Melanoma Cells, Betelehem Asnake
Cis 3,4', 5-Trimethoxy-3'-Aminostilbene (Stilbene 5c) Induces Apoptosis And Protective Autophagy In B16f10 Melanoma Cells, Betelehem Asnake
Theses and Dissertations
The weak selectivity of chemotherapeutic drugs against tumors has sustained efforts to develop better chemotherapeutic agents that are more potent and selective at destroying tumor cell populations versus normal tissues. This project focuses on evaluating the cell killing effects of the microtubule inhibitor, stilbene 5c, against melanoma cancer. We utilized an in vitro murine melanoma model to study the effects of stilbene 5c on tumor proliferation and survival, as well as growth arrest and cell death. Our findings indicate that stilbene 5c promotes dose dependent cell death in melanomas with the induction of apoptosis and autophagy. The role of autophagy …
Targeting The Endocannabinoid System To Reduce Nociception, Lamont Booker
Targeting The Endocannabinoid System To Reduce Nociception, Lamont Booker
Theses and Dissertations
Pain of various etiologies (e.g., visceral, inflammatory) can be a debilitating disorder that presents a problem of clinical relevance. While it is known that ∆9-tetrahydrocannabinol (THC) the primary psychoactive constituent found in marijuana produces analgesia in various rodent models of pain, its pharmacological properties are overshadowed by its psychomimetic effects. THC is the primary phytocannabinoid found in marijuana though other prevalent constituents such as the phytocannabinoids (e.g., cannabidiol (CBD), cannabinol (CBN), cannabichromene (CBC), tetrahydrocannabivarin (THCV)) may possess antinociceptive actions without the psychomimetic effects associated with THC. Indeed, these phytocannabinoids act upon the endocannabinoid system (ECS) that is comprised of the …
Electrophysiological Characterization Of Enteric Neurons Isolated From The Immortomouse, Edward G. Hawkins
Electrophysiological Characterization Of Enteric Neurons Isolated From The Immortomouse, Edward G. Hawkins
Theses and Dissertations
The availability of murine genetic models is extremely advantageous to studying gastrointestinal function, but the benefits afforded by studying enteric neurons in mice has been hindered by their accessibility. Fetal (E13) and 2 day post-natal (P2) enteric neuron cell lines (IM-FEN and IM-PEN, respectively) were recently developed from the H-2Kb-tsA58 immortomouse. Our goal was to identify the electrophysiological properties of these cell lines and clarify their utility as a model of enteric neurons. IM-PEN cells stained positively for the neuron specific markers βIII-tubulin and PGP9.5 and were negative for the glial cell marker S100. Detection of mRNA for TRPA1, TRPV1, …
Involvement Of P53 In The S-Phase Checkpoint During Nucleotide Deficiencies, Cortney Heyer
Involvement Of P53 In The S-Phase Checkpoint During Nucleotide Deficiencies, Cortney Heyer
Theses and Dissertations
Several classes of antimetabolites have been developed for the treatment of cancer, including numerous inhibitors of nucleotide biosynthesis. N-(phosphonacetyl)-L-aspartate (PALA) and hydroxyurea (HU) are two antimetabolites that inhibit nucleotide biosynthesis; PALA inhibits de novo pyrimidine synthesis and HU inhibits the conversion of ribonucleotide diphosphates to deoxyribonucleotide diphosphates. Due to the similar mechanisms, it was thought that cancer cells would respond similarly to HU and PALA treatment. However, studies in this dissertation revealed strikingly different responses to either HU or PALA treatment in HCT116 cells. A cytoprotective S-phase arrest was activated upon HU treatment while PALA treatment failed to activate the …
Antifolate Modulators Of Amp-Activated Protein Kinase Signaling As Cancer Therapeutics, Scott Rothbart
Antifolate Modulators Of Amp-Activated Protein Kinase Signaling As Cancer Therapeutics, Scott Rothbart
Theses and Dissertations
Since its discovery, it was appreciated that the antifolate pemetrexed had multiple targets within folate metabolism. This laboratory was instrumental in showing that pemetrexed elicited its primary action as a thymidylate synthase inhibitor. Unusual for an antifolate, pemetrexed showed significant clinical activity against malignant pleural mesothelioma and non-small cell lung cancer. Accordingly, the FDA recently issued first-line approvals for pemetrexed in these diseases, leading us to question whether the effects of pemetrexed on other folate-dependent targets could explain this atypical clinical activity of the drug. Studies in this dissertation showed that in addition to thymidylate synthase inhibition, pemetrexed was also …
Cannabinoid Receptors In The 3d Reconstructed Mouse Brain: Function And Regulation, Peter Nguyen
Cannabinoid Receptors In The 3d Reconstructed Mouse Brain: Function And Regulation, Peter Nguyen
Theses and Dissertations
CB1 receptors (CB1R) mediate the psychoactive and therapeutic effects of cannabinoids including ∆9-tetrahydrocannabinol (THC), the main psychoactive constituent in marijuana. However, therapeutic use is limited by side effects and tolerance and dependence with chronic administration. Tolerance to cannabinoid-mediated effects is associated with CB1R adaptations, including desensitization (receptor-G-protein uncoupling) and downregulation (receptor degradation). The objectives of this thesis are to investigate the regional-specificity in CB1R function and regulation. Previous studies have investigated CB1Rs in a subset of regions involved in cannabinoid effects, but an inclusive regional comparison of the relative efficacies of different classes of cannabinoids to activate G-proteins has not …
The Impact Of Adolescent Nicotine Exposure On Drug Dependence In Adulthood, Mai Alajaji
The Impact Of Adolescent Nicotine Exposure On Drug Dependence In Adulthood, Mai Alajaji
Theses and Dissertations
Nicotine is one of the first and most commonly abused drugs in adolescence. According to The Center for Disease Control, every day more than 6000 adolescents try their first cigarette and over 3000 of them become daily smokers. Smoking among adolescents is a strong predictor of future drug abuse and dependence in adulthood. A number of studies has suggests that adolescents pre-exposed to nicotine may suffer permanent disruption of the brain’s reward systems through changes in dopamine receptor function. We hypothesize that nicotine exposure during adolescence causes long lasting neurobiological alterations that increase the likelihood of cocaine use in adulthood. …
Cell Death And Sustained Senescence Arrest In Colon Carcinoma And Melanoma Tumor Cells In Response To The Novel Microtubule Poison, Jg-03-14, Jonathan Biggers
Cell Death And Sustained Senescence Arrest In Colon Carcinoma And Melanoma Tumor Cells In Response To The Novel Microtubule Poison, Jg-03-14, Jonathan Biggers
Theses and Dissertations
Previous studies from this and other laboratories have shown that the novel microtubule poison, JG-03-14, which binds to the colchicine binding site of tubulin, has the capacity to promote both autophagy and apoptosis in breast tumor cells, as well as interfering with endothelial cell function and potentially disrupting tumor vasculature. The current work was designed to investigate the interaction between JG-03-14 and cell culture models of colon carcinoma and melanoma, specifically HCT116 human colon carcinoma cells and B16F10 murine melanoma cells. In both cases, JG-03-14 promoted death in the bulk of the treated population. FACS analysis, DAPI and TUNEL staining …
The Mechanism Of Mitochondrial Folate Transport By The Mitochondrial Folate Transporter, Scott Alan Lawrence
The Mechanism Of Mitochondrial Folate Transport By The Mitochondrial Folate Transporter, Scott Alan Lawrence
Theses and Dissertations
The mitochondrial folate transport protein (MFT) functions to transport folates into the mitochondrial matrix. The MFT is a member of a mitochondrial carrier family (MCF) of proteins that have a high degree of sequence and structural similarities, yet they transport vastly different substrates at high specificities. In this dissertation research, the folate-specific transport mechanism of the MFT was explored using experimental and computational techniques. MFT residues that differed from MCF consensus residues in conserved PxD/ExxK/R motifs and at a predicted substrate-binding site common to all MCF proteins were investigated. Site-directed mutagenesis of these anomalous residues in the MFT revealed that …
Differential Roles Of The Two Major Endocannabinoid Hydrolyzing Enzymes In Cannabinoid Receptor Tolerance And Somatic Withdrawal, Joel Schlosburg
Differential Roles Of The Two Major Endocannabinoid Hydrolyzing Enzymes In Cannabinoid Receptor Tolerance And Somatic Withdrawal, Joel Schlosburg
Theses and Dissertations
While there is currently active debate over possible therapeutic applications of marijuana and cannabis-based compounds, consistently their primary drawbacks have been the psychoactive properties, dependence, and abuse potential. Prolonged administration of ∆9-tetrahydrocannabinol (THC), the primary psychoactive constituent in marijuana, demonstrates both tolerance and physical withdrawal in both preclinical and clinical studies. Repeated THC administration also produces CB1 receptor adaptations in the form of reduced activation of receptors, along with a downregulation of membrane surface receptors, in many brain regions involved in THC-associated behaviors. The increased need for drug to maintain therapeutic effects, and a withdrawal syndrome following discontinuation of use, …
Modulation Of Cocaine-Like Behavioural Activity By Serotonin Uptake Inhibition Relative To The Effects Of The Novel And Selective Dopamine Transporter Inhibitor, D-84, Angela Batman
Theses and Dissertations
Cocaine dependence is a major health concern worldwide, but despite this high rate of abuse there are currently no approved therapies for cocaine dependence. Replacement pharmacotherapies are one possible approach for treating cocaine dependence, and identification of such therapeutics for cocaine abuse is the long-term goal of this research. Cocaine binds to, and inhibits uptake at the dopamine (DAT), serotonergic (SERT) and noradrenaline (NET) uptake transporters, but studies have shown that cocaine produces its strong behavioural and positive reinforcing effects through inhibition of the DAT. To this end a great number of diverse, non-selective DAT-inhibiting compounds have been investigated as …
Effects Of Cannabinoid Receptor Interacting Protein (Crip1a) On Cannabinoid Receptor (Cb1) Function, Tricia Smith
Effects Of Cannabinoid Receptor Interacting Protein (Crip1a) On Cannabinoid Receptor (Cb1) Function, Tricia Smith
Theses and Dissertations
EFFECTS OF CANNABINOID RECEPTOR INTERACTING PROTEIN (CRIP1a) ON CANNABINOID (CB1) RECEPTOR FUNCTION. By Tricia Hardt Smith, B.S., M.S. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University Virginia Commonwealth University, 2009. Major Director: Dana E. Selley, Ph.D., Department of Pharmacology and Toxicology This dissertation examines modulation of cannabinoid CB1 receptor function by Cannabinoid Receptor Interacting Protein (CRIP1a), a novel protein that binds the C-terminus of CB1 receptors. In Human embryonic kidney cells expressing human CB1 receptors (hCB1-HEK) and hCB1-HEK cells stably co-expressing CRIP1a (hCB1-HEK-CRIP1a), quantitative immunoblotting revealed a CRIP1a/CB1 …
Denitration In Colonic Smooth Muscle, Seemab Malick
Denitration In Colonic Smooth Muscle, Seemab Malick
Theses and Dissertations
Tyrosine nitration results in altered function of smooth muscle voltage-gated L-type calcium channel. We explored the possibility that smooth muscle contains denitrase activity to allow functional recovery of the calcium channel without requiring synthesis of new channel proteins. Following peroxynitrite treatment of mouse colonic smooth muscle strips, CaCl2 (1 mM)-induced smooth muscle contraction was significantly reduced by 67% (P ≤ 0.05), which reversed by approximately 86% upon periodic washing within 2 hr period (P ≤ 0.001). The effect of the c-Src kinase inhibitor, PP2, on muscle contraction was also restored after 2 hr post-peroxynitrite treatment consistent with the thesis that …
Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti
Inhibition Of The Calcium Plateau Following In Vitro Status Epilepticus Prevents The Development Of Spontaneous Recurrent Epileptiform Discharges, Nisha Nagarkatti
Theses and Dissertations
Status epilepticus (SE) is a major clinical emergency resulting in continuous seizure activity that can cause brain injury and many molecular and pathophysiologic changes leading to neuronal plasticity. The neuronal plasticity following SE-induced brain injury can initiate epileptogenesis and lead to the ultimate expression of acquired epilepsy (AE), characterized clinically by spontaneous, recurrent seizures. Epileptogenesis is the process wherein healthy brain tissue is transformed into hyperexcitable neuronal networks that produce AE. Understanding these alterations induced by brain injury is an important clinical challenge and can lend insight into possible new therapeutic targets to halt the development of AE. Currently there …
Behavioral And Molecular Analysis Of Individual Variation In Ethanol Drinking, Jennifer Wolstenholme
Behavioral And Molecular Analysis Of Individual Variation In Ethanol Drinking, Jennifer Wolstenholme
Theses and Dissertations
A majority of Americans regularly consume alcohol, but the risk factors leading to excessive drinking and alcohol abuse are unevenly distributed throughout the population. Genetic differences can account for only 40-60% of this variability. While variations in ethanol preference drinking in rodent models have been reported, the neurobiological factors underlying these behaviors are still not completely understood. Thus, these studies were designed to determine behavioral and molecular factors associated with the initiation of ethanol drinking preference in an inbred mouse model. We harnessed the power of inter-individual variation of ethanol drinking within an inbred mouse strain to essentially eliminate genetic …
Enzymatic Regulation Of Opioid Antinociception And Tolerance, Lynn Hull
Enzymatic Regulation Of Opioid Antinociception And Tolerance, Lynn Hull
Theses and Dissertations
ENZYMATIC REGULATION OF OPIOID ANTINOCICEPTION AND TOLERANCE By Lynn C. Hull, Ph.D. A dissertation submitted in partial fulfillment of the requirements for the degree of Doctor of Philosophy at Virginia Commonwealth University. Virginia Commonwealth University, 2009 Director: William L. Dewey, Ph.D. Department of Pharmacology and Toxicology The involvement of kinases in opioid actions has long been established. The acute actions of opioids, through the Gi/Go G-proteins, cause the inhibition of adenylyl cyclase and therefore a decrease in protein kinase A (PKA) activation. Additionally, acute opioid administration may cause the G-protein to activate the phospholipase C (PLC)-mediated cascade leading to the …
Triptolide Is A Potential Therapeutic Agent For Alzheimer’S Disease, Matthew Allsbrook
Triptolide Is A Potential Therapeutic Agent For Alzheimer’S Disease, Matthew Allsbrook
Theses and Dissertations
Mounting evidence indicates an involvement of inflammation in the pathogenesis of Alzheimer’s disease. While there are other mechanisms involved, it is this role of inflammatory processes that we wish to investigate. Triptolide is the major constituent in the Chinese herb, Tripterygium wilfordii Hook F, and has been used for centuries as part of Chinese herbal medicine. The four ringed structure has close homology to drugs of the steroid class and it has been shown to be beneficial as an anti-inflammatory for rheumatoid arthritis and for treatment of certain cancers. The aim of this study was to evaluate the potential therapeutic …
Transcriptional, Epigenetic, And Signal Events In Antifolate Therapeutics, Alexandra Racanelli
Transcriptional, Epigenetic, And Signal Events In Antifolate Therapeutics, Alexandra Racanelli
Theses and Dissertations
A targeted approach to the development of antifolate therapies has been sought for many years. Central to the success of such development is an understanding of the molecular mechanisms dictating the sensitivity of cells to antifolates and the fundamental differences of these processes between normal and neoplastic phenotypes. This dissertation addressed transcriptional mechanisms and cell-signaling events responsible for the efficacy of antifolate therapies. Transcriptional processes and cell signaling pathways are often aberrant in neoplastic tissues, providing a potential point of distinction between a normal and neoplastic cellular state. Folylpolyglutamate synthetase (FPGS) catalyzes the formation of poly-γ-glutamate derivatives of folates and …
The Effect Of Chronic Constriction Injury On Cellular Systems Within Nociceptive Pathways In The Mouse, Michelle Hoot
The Effect Of Chronic Constriction Injury On Cellular Systems Within Nociceptive Pathways In The Mouse, Michelle Hoot
Theses and Dissertations
Chronic neuropathic pain is often difficult to treat due to its resistance to therapeutic intervention. This is due in part to the poor understanding of the physiological mechanisms involved in the establishment and maintenance of neuropathic pain states. The neuropathic pain model, chronic constriction injury of the sciatic nerve, produced robust pain hypersensitivity in our mice. It also induced significant changes in the mitogen activated protein kinase family, and the cannabinoid and µ-opioid systems in three different brain areas involved in the modulation or regulation of pain states. CCI induced a 2.5 fold increase in mRNA of the kinase Raf-1 …
Therapeutic Drugs In Cancer, Teneille Walker
Therapeutic Drugs In Cancer, Teneille Walker
Theses and Dissertations
The first study examined the interaction between low doses of the multi-kinase inhibitor sorafenib and the histone deacetylase inhibitor vorinostat in colon cancer cells. Sorafenib and vorinostat synergized to kill HCT116 and SW480 cells. In SW480 cells, sorafenib+vorinostat toxicity correlated with CD95 activation and CD95-stimulated autophagy. Drug lethality in SW480 cells was blocked by knock down of CD95. In SW620 cells that are patient matched to SW480 cells, sorafenib+vorinostat toxicity was significantly reduced that correlated with a lack of CD95 activation and lower expression of ceramide synthase 6 (LASS6). Overexpression of LASS6 in SW620 cells enhanced drug-induced CD95 activation and …
Therapeutic Drugs In Cancer And Resistance., Aditi Pandya Martin
Therapeutic Drugs In Cancer And Resistance., Aditi Pandya Martin
Theses and Dissertations
We investigated the mechanism of toxicity and resistance development of small molecule tyrosine kinase inhibitor lapatinib in HCT 116 colon cancer cells. Lapatinib mediated cell death in HCT 116 cells was caspase independent and involved cytosolic release of apoptosis inducing factor. Treatment of HCT 116 cells with 10µM Lapatinib lead to the outgrowth of lapatinib resistant HCT 116 cells. Our studies show that alterations in the expression and activation of Bcl-2 family proteins allow lapatinib resistant HCT 116 cells to resist cytotoxic effects of lapatinib as well as of other commonly used chemotherapeutic agents. In hepatoma and pancreatic cancer cells, …
Creation Of A Mouse With A Humanized Fpgs Gene Compatible With Normal Development, Linying Xie
Creation Of A Mouse With A Humanized Fpgs Gene Compatible With Normal Development, Linying Xie
Theses and Dissertations
Abstract: Folylpoly-γ-glutamate synthetase (FPGS) catalyzes the formation of polyglutamate forms of the reduced folates and antifolates such as methotrexate (MTX) and pemetrexed; this allows the retention of folates and antifolate cancer drugs inside the cell. The enzyme activity of FPGS is essential for cell proliferation and survival. The mouse fpgs gene contains two promoters spaced 10 kb apart which are activated in a tissue-specific manner. The upstream promoter (P1) and exons A1a and A1b are used in some differentiated tissues, mainly liver and kidney, whereas the downstream promoter (P2) and exon 1 are used in rapidly dividing cells. In contrast, …
Identification Of Pharmacological And Molecular Mechanisms Involved In Nicotine Withdrawal, Kia Jackson
Identification Of Pharmacological And Molecular Mechanisms Involved In Nicotine Withdrawal, Kia Jackson
Theses and Dissertations
Tobacco dependence is the leading cause of preventable death in the United States. Despite currently available smoking cessation therapies, there is a high rate of relapse in smoking among those attempting to quit. While the somatic signs of nicotine withdrawal (insomnia, increased appetite, weight gain) contribute to the continuation of smoking behavior, it has been hypothesized that the affective signs (depression, anxiety, craving, irritability) are greater motivators of relapse and continued tobacco use. There are few studies that assess the molecular and receptor-mediated mechanisms of nicotine withdrawal; therefore, our studies focus on identifying the nicotinic acetylcholine receptor (nAChR) subtypes and …
Promotion Of Tumor Cell Death Through The Induction Of, Tuyen Nguyen
Promotion Of Tumor Cell Death Through The Induction Of, Tuyen Nguyen
Theses and Dissertations
Microtubule poisons have proven to be effective in the treatment of a variety of malignancies. Although taxol-based derivatives promote microtubule stabilization, there is continuing interest in compounds that, like colchicines, act as microtubule destabilizing agents. Previous work from this laboratory showed that the novel microtubule poison, JG- 03-14, was active against breast tumor cells, promoting autophagic cell death. In the current work, we studied the influence of JG-03-14 on p53 wild type HCT116 colon carcinoma cells. A crystal violet sensitivity assay indicated that JG-03-14 induced growth inhibition, with 75% suppression of growth evident at a concentration of 500 nM. Time …
Endocannabinoid Modulation Of Spatial Memory In Aversively And Appetitively Motivated Barnes Maze Tasks, John Pinckney Harloe
Endocannabinoid Modulation Of Spatial Memory In Aversively And Appetitively Motivated Barnes Maze Tasks, John Pinckney Harloe
Theses and Dissertations
Genetic deletion or pharmacological blockade of the CB1 receptor has been reported to impair extinction learning in aversive conditioning (i.e., conditioned fear and Morris water maze) paradigms, but not in operant procedures in which food reinforcement is earned. It is difficult to discern whether the differential effects caused by CB1 receptor disruption on extinction result from the hedonics (i.e., aversive vs. appetitive) or is related to the required responses associated with these disparate tasks. In order to evaluate whether the hedonics is the determining factor, we used either aversive (i.e., escape from bright lights and air turbulence) or appetitive (i.e., …