Biology Commons^™

Uncovering Molecular Targets To Overcome Immunosuppression In Non-Small Cell Lung Cancer With Acquired Tki Resistance, Sonia A. Patel

Dissertations & Theses (Open Access)

Non-small cell lung cancer (NSCLC) remains the leading cause of cancer-related deaths worldwide. Targeted therapeutic agents, such as epidermal-like growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) or monoclonal antibodies targeting vascular endothelial growth factor (VEGF/R), can effectively inhibit upregulated signaling pathways driving tumorigenesis in NSCLC and many other cancers. Unfortunately, however, resistance to such targeted therapies inevitably arise in most patients and can occur through a variety of resistance mechanisms including genomic alterations and upregulation of bypass pathways. Additionally, patients who have acquired resistance to these targeted agents typically have tumors characterized by an immunosuppressive tumor microenvironment and thus …

In Vivo Potentiation Of Muscle Torque Is Enhanced In Female Mice Through Estradiol-Estrogen Receptor Signaling, Gengyun Le, Cory W. Baumann, Dawn A. Lowe, Gordon L. Warren

Biology Faculty Publications

Estradiol affects several properties of skeletal muscle in females including strength. Here, we developed an approach to measure in vivo posttetanic twitch potentiation (PTP) of the anterior crural muscles of anesthetized mice and tested the hypothesis that 17b-estradiol (E2) enhances PTP through estrogen receptor (ER) signaling. Peak torques of potentiated twitches were 40%–60% greater than those of unpotentiated twitches and such PTP was greater in ovary-intact mice, or ovariectomized (Ovx) mice treated with E2, compared with Ovx mice (P < 0.047). PTP did not differ between mice with and without ERa ablated in skeletal muscle fibers (P = 0.347). Treatment of ovary-intact and Ovx mice with ERb antagonist and agonist (PHTPP and DPN, respectively) did not affect PTP (P = 0.258). Treatment with G1, an agonist of the G protein-coupled estrogen receptor (GPER), significantly increased PTP in Ovx mice from 41 ± 10% to 66 ± 21% (means ± SD; P = 0.034). Collectively, these data indicate that E2 signals through GPER, and not ERa or ERb, in skeletal muscles of female mice to augment an in vivo parameter of strength, namely, PTP.

Estrogen Regulation Of Daily Metabolic Rhythms In Female Mice, Oluwabukola Omotola

Theses and Dissertations--Biology

Circadian rhythms are approximately 24-hour cycles of behavior, physiology, and gene expression. In mammals, these circadian rhythms are generated by clocks located in nearly every tissue in the body. The function of circadian clocks is to synchronize physiology and behavior with environmental cycles such as the light-dark cycle. After menopause, when circulating levels of estrogens are very low, women are more susceptible to obesity comorbidities such as metabolic syndrome and cardiovascular disease, suggesting that estrogens regulate these processes. Estrogens could protect females from metabolic dysfunction by regulating circadian rhythms. Consumption of diets that are high in fat contribute to obesity. …

Sex Differences In The Co-Expression Of Estrogen Receptor Alpha With Corticotropin Releasing Factor, Deborah Ariyibi

Biological Sciences

Women are far more likely to develop anxiety and depression than men. It is believed that the dysregulation of the HPA axis by the binding of corticotropin -releasing factor (CRF) to the corticotropin-releasing factor receptor 1 (CRFR1) contributes to the likelihood of these stress- related disorders. Estrogens acting through Estrogen receptor alpha (ERa) have been shown to increase anxiety production upon activating the HPA axis. In this current study, we explored whether CRF-expressing neurons in various regions of the brain express ERa. The levels of ERa were counted in the bed nucleus of the stria terminalis (BST), the medial preoptic …

Estrogen Modulation Of Vta Dopamine Neuron Physiology And Behavioral Responsivity To Variable Social Stressors, Mary R. Shanley

Dissertations, Theses, and Capstone Projects

The behavioral output of different animals, or even the same animal in different contexts, is remarkably variable in response to the same external stimulus. This behavioral diversity is due to the complex integration of external and internal stimuli, through both neuronal and hormonal signals that selects the best behavioral response. By their nature as long-distance signaling molecules, hormones play a critical role in communicating information about internal states across the organism. Many hormones produced in the periphery target the central nervous system to modulate animal behavior, selecting for behaviors that are appropriate over behaviors that are maladaptive in that specific …

Effects Of Synthetic Estrogen (17Α-Ethinyl Estradiol) On Male Fiddler Crab Aggression, Micayla Shirley

Honors College Theses

Pharmaceuticals, including hormones and antibiotics, are considered contaminants due to their widespread use and release into the environment. Hormones, like the synthetic estrogen used in oral contraceptives (17α-ethinylestradiol), are present in freshwater and marine systems, but with relatively unknown effects on the organisms that live there. Ethinylestradiol (EE2) accumulates in waterlogged soil (sediment) with potential to harm sediment-dwelling animals. For example, fiddler crabs (Uca pugilator) are vital members of salt marsh communities. Their burrowing adds oxygen to sediments and cycles nutrients, and they are an important food resource to birds and raccoons. Male fiddler crabs are territorial, aggressively …

Estrogen Disruption Of Hypothalamic Neural Activity, Princess Dickson

Cal Poly Humboldt theses and projects

The brain is highly dependent on the endocrine system for proper neurodevelopment, as it plays a key role in many biological processes. Bisphenol A is a chemical found in plastics that has the potential to mimic the effects of Estrogen in the body, at least weakly. People interact with plastic that contains BPA regularly, and people are at risk for exposure even before being born. The abundance of BPA, along with other exogenous estrogens, makes examining the relationship between early exposure and changes in brain activity imperative. The current study aims to establish a relationship between disrupted estrogen function and …

Direct And Indirect Effects Of Sex Steroids On Gonadotrope Cell Plasticity In The Teleost Fish Pituitary, Romain Fontaine, Muhammad Rahmad Royan, Kristine Von Krogh, Finn-Arne Weltzien, Dianne M. Baker

Biological Sciences Research

The pituitary gland controls many important physiological processes in vertebrates, including growth, homeostasis, and reproduction. As in mammals, the teleost pituitary exhibits a high degree of plasticity. This plasticity permits changes in hormone production and secretion necessary to meet the fluctuating demands over the life of an animal. Pituitary plasticity is achieved at both cellular and population levels. At the cellular level, hormone synthesis and release can be regulated via changes in cell composition to modulate both sensitivity and response to different signals. At the cell population level, the number of cells producing a given hormone can change due to …

Effects Of Bisphenol-S And Estrogen On P53 Expression In Ovarian Tissue Of Zebrafish (Danio Rerio), Jess Fairbanks

Summer Research

Bisphenol A (BPA) is one the most widely used plasticizing compounds. As an endocrine disruptor, BPA could affect ovarian function and embryonic development. Bisphenol S (BPS) has been used in many plastics and resins in lieu of BPA. However, the effects of BPS are not widely known. Apoptosis is a type of genetically programmed cell death that is important in ovarian homeostasis. One of the genes that regulates apoptosis, p53, has been shown to respond to estrogen in maintaining ovarian homeostasis. We have investigated how exposure to estrogen and to BPS affects p53 expression in ovarian tissue in vitro …

Examining The Effects Of Fadrozole, An Aromatase Inhibitor, On Testosterone And Estrogen Production Of Domestic Chicken Embryos (Gallus Gallus), Abby E. Joseph

Honors Theses

The hypothalamic-pituitary-gonadal (HPG) axis is responsible for the production of the hormones testosterone and estradiol, and testosterone is thought to contribute to regulation of the axis through a negative feedback mechanism. Regulation by negative feedback involves the product of a pathway turning off that pathway when enough product is made. However, because the enzyme P450 aromatase converts testosterone to estradiol, estradiol may also contribute to regulation of the HPG axis and other phenomena that have been attributed to testosterone, like the inhibition of immune function. Previous studies have injected birds with an aromatase inhibitor (presumably reducing estradiol production) and shown …

Method For The Detection Of 17-B-Estradiol In Wastewater Facility Effluents Using Hplc, Alexa Mariah Fisher, Benjamin J. Thornton

Research in Biology

Studies of the effects of estrogen in aquatic ecosystems largely focus on fish. In fish, estrogen reduces fecundity in females, reduces testicular development and fertility in males, and alters vitellogenin production in both sexes. One way estrogens enter aquatic environments is via wastewater effluents. Effluent samples from the Moccasin Bend Wastewater Treatment Facility in Chattanooga, Tennessee were tested for the presence of 17-beta-estradiol (E2), using an Agilent 1260 Infinity LC (HPLC). We were not able to detect the presence of E2 in these samples with the methods described. However, when effluent samples were spiked with stock E2 (final concentration of …

Hplc Detection Of The Possible Presence Of 17-A-Ethindyl Estradiol In Treated Effluents Released From The Chattanooga Water Treatment Plant, Jacqueline Dulanto, Benjamin Thornton, David Nelsen

Research in Biology

Research has confirmed that elevated synthetic estrogen in surface waters can lead to intersex characteristics in aquatic vertebrates. Unmetabolized antibiotics, hormones from animal wastes, including humans, and discarded pharmaceuticals are some ways synthetic estrogen enter aquatic ecosystems through the release of contaminated effluents. In this investigation, the Agilent 1260 Infinity HPLC was used to detect the possible presence of 17-α-ethindyl estradiol in effluents released from the Chattanooga Sewer Treatment Plant. Results were analyzed by comparing HPLC chromatograms from effluent and spiked samples. We detected a possible peak of synthetic estrogen in the effluent samples with a retention rate of 6 …

The Effect Of Target-Specific Biomolecules In Breast Cancer, Mohannad Garoub

FIU Electronic Theses and Dissertations

Cancer is the second leading cause of mortality in the United States and the World, therefore, early effective prevention, diagnosis, and therapy is needed. Estrogens play a major role in the initiation and progression of breast cancer. Elevated lifetime exposure to estrogens is associated with an increased risk of developing breast cancer. Estrogens through influencing mitochondria contribute to estrogen induced breast carcinogenesis; however, the exact mitochondrial mechanisms underlying the estrogen carcinogenic effect in breast tissue are not clearly understood. For this dissertation, the mitotoxic and cytotoxic effects of triphenylphosphonium cation (TPP) and Origanum majorana organic extract (OME) as well as …

The Effects Of The Environmental Estrogens Cadmium And Arsenite On Phosphorylation Of Erk1/2 Via Gpr30 In Human Lung Adenocarcinoma Cells, Katarzyna Krauss

Undergraduate Theses

Nanomolar concentrations of both cadmium and arsenite, two environmental estrogens present in cigarette smoke, have been documented in rapidly phosphorylating ERK1/2, a type of MAPK, in the human non-small cell lung cancer (NSCLC) line NHI-1793 in a manner similar to that of estrogen. Pretreatment of cells with a general, nonspecific estrogen receptor antagonist reduced the levels of phosphorylated MAPK, indicating that this phosphorylation event is achieved through use of an estrogen signaling pathway. The specific estrogen receptor involved in this process, however, is currently unknown. To determine whether GPR30, one of the three types of estrogen receptors, is necessary for …

The Involvement Of Estrogen Receptors In Astrocyte Survival, Lauren M. Johnson

Theses and Dissertations

Estrogens are a class of hormones that are demonstrated to be neuroprotective. The levels of estrogen in the body decline during menopause which can cause a variety of symptoms. Hormone replacement therapy (HRT) is a treatment option for menopause, however, it has been demonstrated to have adverse side effects. Of the treatment options for adverse side effects of HRT, Selective estrogen Down-regulators do not appear to have an agonist effects on estrogen receptors while Selective estrogen receptor Modulators do. The aim of this study was to determine the role that estrogen receptors play in the survival of astrocytes when placed …

Estrogen-Dependent Expression And Subcellular Localization Of The Tight Junction Protein Claudin-4 In Hec-1a Endometrial Cancer Cells, M. E. Cuevas, J. M. Gaska, A. C. Gist, Jonathan M. King, R. A. Sheller, M. C. Todd

Biology Faculty Research

Endometrial cancer is the most common female reproductive cancer in the United States and is associated with deregulated tight junction protein expression. Given the highly estrogen-responsive nature of this tissue, we investigated the effects of estrogen and its agonist, 4-OH TAM, on the expression and subcellular localization of the tight junction protein claudin-4 (CLDN-4), in HEC-1A endometrial cancer cells. In untreated HEC-1A cells, we observed dramatic overexpression of claudin-4 protein. In addition, differential detergent extraction analysis indicated that claudin-4 was localized primarily in the membrane but also found in the cytosolic, nuclear and cytoskeletal fractions. Upon exposure of HEC-1A to …

The Rapid Effects Of Steroids On Reproductive Processes In Goldfish, Carassius Auratus, Kimberly Dao

Honors College

It is traditionally understood that sex steroid hormones work through slow genomic pathways. More recently, it has also been discovered that sex steroid hormones also mediate rapid effects through a non-genomic pathway. However, much is still unknown about this mechanism, such as the receptors that mediate these effects, the behavioral consequences, and the contexts in which they occur. Goldfish have been used to investigate these behavioral effects and the receptors used in a sexual social context. To explore these ideas, the Thompson Lab and I tested if sex pheromones that rapidly increase levels of testosterone could also rapidly increase milt …

Long-Term Effects Of Estradiol Replacement In The Olfactory System, Britto P. Nathan, Michael Tonsor, Robert G. Struble

Britto P. Nathan

Olfactory dysfunction often precedes other clinical symptoms in chronic neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Estrogen deficiency and apoE genotype are known risk factors in these diseases and these factors also affect olfaction. Therefore we examined the effects of estradiol replacement following ovariectomy on expression of apoE and markers of cell proliferation, neuronal maturation, synaptogenesis and reactive gliosis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Estradiol replacement increased apoE staining in the olfactory nerve and glomerular layers. Estradiol increased astrocyte density and olfactory epithelium (OE) thickness regardless of the genotype. In addition estradiol …

Long-Term Effects Of Estradiol Replacement In The Olfactory System, Britto P. Nathan, Michael Tonsor, Robert G. Struble

Faculty Research & Creative Activity

Olfactory dysfunction often precedes other clinical symptoms in chronic neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Estrogen deficiency and apoE genotype are known risk factors in these diseases and these factors also affect olfaction. Therefore we examined the effects of estradiol replacement following ovariectomy on expression of apoE and markers of cell proliferation, neuronal maturation, synaptogenesis and reactive gliosis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Estradiol replacement increased apoE staining in the olfactory nerve and glomerular layers. Estradiol increased astrocyte density and olfactory epithelium (OE) thickness regardless of the genotype. In addition estradiol …

Long-Term Effects Of Estradiol Replacement In The Olfactory System, Britto Nathan, Michael Tonsor, Robert Struble

Faculty Research & Creative Activity

Olfactory dysfunction often precedes other clinical symptoms in chronic neurodegenerative diseases like Alzheimer’s and Parkinson’s disease. Estrogen deficiency and apoE genotype are known risk factors in these diseases and these factors also affect olfaction. Therefore we examined the effects of estradiol replacement following ovariectomy on expression of apoE and markers of cell proliferation, neuronal maturation, synaptogenesis and reactive gliosis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Estradiol replacement increased apoE staining in the olfactory nerve and glomerular layers. Estradiol increased astrocyte density and olfactory epithelium (OE) thickness regardless of the genotype. In addition estradiol …

An Unbiased Approach To Identify Genes Involved In Development In A Turtle With Temperature-Dependent Sex Determination, Jena L. Chojnowski, Edward L. Braun

Faculty Publications

Many reptiles exhibit temperature-dependent sex determination (TSD). The initial cue in TSD is incubation temperature, unlike genotypic sex determination (GSD) where it is determined by the presence of specific alleles (or genetic loci). We used patterns of gene expression to identify candidates for genes with a role in TSD and other developmental processes without making a priori assumptions about the identity of these genes (ortholog-based approach). We identified genes with sexually dimorphic mRNA accumulation during the temperature sensitive period of development in the Red-eared slider turtle (Trachemys scripta), a turtle with TSD. Genes with differential mRNA accumulation in response to …

Influence Of Estradiol And Exercise On Foot Laxity, Ankle Laxity, And Plantar Loading In College Athletes, Kristina Teri Silke

Masters Theses, 2010-2019

As female participation in athletics has increased, it has become apparent that sex differences exist in sports-related injury types and frequencies. The purpose of this study is to examine the effects of exercise and the sex hormone estradiol on sex differences in foot and ankle laxity and plantar pressure. We measured serum estradiol, pre- and post-fatigue ankle and toe laxity, and pre- and post-fatigue plantar pressure in 47 subjects (34 female, 13 male) once a week for 12 weeks. We compared laxity and plantar pressure in females not using oral contraceptive (NOC) to females using oral contraceptives (OC) and males. …

Estrogenic Regulation Of The Immune System In A Murine Model For Systemic Lupus Erythematosus, Matthew James Zuber

Biology Honors Papers

Systemic Lupus Erythematosus is a damaging autoimmune disease afflicting millions of people worldwide. Lupus is characterized by an overabundance of autoantibodies, proteins directing the immune system to destroy a person's own body, what it would normally be protecting. The molecular mechanisms, environmental influences, and genetic predispositions of Lupus are not yet fully understood. However, nine out of ten Lupus patients are women between the age of puberty and menopause, when estrogen levels are highest. The fact that women are significantly more prone to suffer from Lupus than men leads experts to believe that the sex hormone estrogen which is present …

Creating Rna Aptamers To Modulate Function Of Human Estrogen Receptor Alpha, Daiying Xu

Legacy Theses & Dissertations (2009 - 2024)

ABSTRACT

Acute Responses To Estradiol Replacement In The Olfactory System Of Apoe-Deficient And Wild-Type Mice, Britto P. Nathan, Michael Tonsor, Robert G. Struble

Britto P. Nathan

Epidemiological studies suggest that estrogen therapy protects against clinical expression of chronic neurological diseases. These beneficial effects of estrogen therapy are highly modified by apolipoprotein E (apoE) through an unknown mechanism. We examined the short-term effects of estradiol replacement in ovariectomized mice on apoE expression and markers for cell proliferation, reactive gliosis, neuronal maturation, and synaptogenesis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Three days of estradiol replacement increased apoE expression in the olfactory nerve and in the glomerular layer. Estradiol treatment also increased cell proliferation, total cell numbers, number of mature neurons in …

Acute Responses To Estradiol Replacement In The Olfactory System Of Apoe-Deficient And Wild-Type Mice, Britto P. Nathan, Michael Tonsor, Robert G. Struble

Faculty Research & Creative Activity

Epidemiological studies suggest that estrogen therapy protects against clinical expression of chronic neurological diseases. These beneficial effects of estrogen therapy are highly modified by apolipoprotein E (apoE) through an unknown mechanism. We examined the short-term effects of estradiol replacement in ovariectomized mice on apoE expression and markers for cell proliferation, reactive gliosis, neuronal maturation, and synaptogenesis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Three days of estradiol replacement increased apoE expression in the olfactory nerve and in the glomerular layer. Estradiol treatment also increased cell proliferation, total cell numbers, number of mature neurons in …

Acute Responses To Estradiol Replacement In The Olfactory System Of Apoe-Deficient And Wild-Type Mice, Britto Nathan, Michael Tonsor, Robert Struble

Faculty Research & Creative Activity

Epidemiological studies suggest that estrogen therapy protects against clinical expression of chronic neurological diseases. These beneficial effects of estrogen therapy are highly modified by apolipoprotein E (apoE) through an unknown mechanism. We examined the short-term effects of estradiol replacement in ovariectomized mice on apoE expression and markers for cell proliferation, reactive gliosis, neuronal maturation, and synaptogenesis in the primary olfactory pathway of wild-type (WT) and apoE knockout (KO) mice. Three days of estradiol replacement increased apoE expression in the olfactory nerve and in the glomerular layer. Estradiol treatment also increased cell proliferation, total cell numbers, number of mature neurons in …

Anatomy And Physiology Of The Nucleus Paragigantocellularis: Neural Regulation Of Genital Reflexes In Male And Female Rats, Joseph Jeremy Normandin

Biology Dissertations

The supraspinal control of descending inhibition of genital reflexes (such as ejaculation) is poorly understood but is important in our global comprehension of how neural signals are integrated to produce sexual behavior, and in our understanding of sexual dysfunction. Sexual dysfunctions, such as premature ejaculation/delayed ejaculation in men, and involuntary vaginal spasms, dyspareunia, and anorgasmia in women, are common. An underlying dysregulation of genital reflexes may produce these dysfunctions, especially in those individuals being treated for depression and anxiety with serotonergic drugs. The nucleus paragigantocellularis (nPGi) of the rat medulla has been described as a descending inhibitory system for genital …

Erk Activation And Cell Growth Require Cam Kinases In Mcf-7 Breast Cancer Cells, John M. Schmitt, Ellen Abell, Andrea Wagner, Monika A. Davare

Faculty Publications - Department of Biological & Molecular Science

Previous studies on MCF-7 breast cancer cells have shown that the G-protein coupled receptor (GPCR) agonist carbachol increases intracellular calcium levels and the activation of extracellular signal-regulated kinase (ERK). Calcium and calmodulin regulate the calcium/calmodulin- dependent kinase (CaM kinase) family of proteins that have been proposed to regulate ERK and gene transcription. Our results suggest that both estrogen (E2) and carbachol treatment of MCF-7 breast cancer cells trigger phosphorylation of ERK I /2 and the transcription factor Elk-1. Carbachol and estrogen triggered nearly a four- to sixfold increase in MCF-7 cell proliferation by 96 h, respectively. Carbachol-stimulated ERK activation and …

Effects Of Estrogen On Muscle Damage In Response To An Acute Resistance Exercise Protocol, Megan R. Wolf

Honors Scholar Theses

Creatine Kinase (CK) is used as a measure of exercise-induced muscle membrane damage. During acute eccentric (muscle lengthening) exercise, muscle sarcolemma, sarcoplasmic reticulum, and Z-lines are damaged, thus causing muscle proteins and enzymes to leak into the interstitial fluid.

Strenuous eccentric exercise produces an elevation of oxygen free radicals, which further increases muscle damage. Muscle soreness and fatigue can be attributed to this membrane damage. Estradiol, however, may preserve membrane stability post-exercise (Brancaccio, Maffulli, & Limongelli, 2007; Carter, Dobridge, & Hackney, 2001; Tiidus, 2001). Because estradiol has a similar structure to Vitamin E, which is known to have antioxidant properties, …