Cell and Developmental Biology Commons^™

The P63 Isoform ∆Np63Α Inhibits Epithelial – Mesenchymal Transition By Promoting The Expression Of Mir-205 In Human Bladder Cancer Cells, Mai Tran

Dissertations and Theses (Open Access)

p63, a p53 family member, is a transcription factor that has complex roles in cancer. This study focuses on the role of the ∆Np63α isoform in bladder cancer (BC). Epithelial – mesenchymal transition (EMT) is a physiological process that plays an important part in metastasis and drug resistance. At the molecular level, EMT is characterized by the loss of the epithelial marker E-cadherin, and the acquisition of the transcriptional repressors of E-cadherin (ZEB1, ZEB2, TWIST, SNAI1 and SNAI2). Recent publications highlight the role of microRNAs belonging to the miR-200 family and miR-205 in preventing EMT through suppression of ZEB1 and …

The Role Of Nucleolin In B-Cell Lymphomas And Fas-Mediated Apoptotic Signaling, Jillian F. Wise

Dissertations and Theses (Open Access)

The death receptor Fas has a key role in mediating homeostasis, elimination of defective cells and more recently implicated in cancer promotion. Many effective anti-cancer therapies depend on Fas-mediated apoptosis to eradicate tumor cells and ineffective Fas-apoptotic signaling is a basis for primary as well as acquired resistance to chemotherapy. We hypothesized that Fas is subjected to direct regulation by inhibitory proteins attained by cancer cells. To screen for potential binding modulators of Fas, we analyzed lymphoma cells for Fas binding proteins. This purification scheme identified high scoring peptides derived from nucleolin, a nuclear protein known to be overexpressed in …

Galectin-3 Enhances The Malignant Melanoma Phenotype By Regulating Autotaxin, Russell R. Braeuer

Dissertations and Theses (Open Access)

In melanoma patient specimens and cell lines, the over expression of galectin-3 is associated with disease progression and metastatic potential. Herein, we have sought out to determine whether galectin-3 affects the malignant melanoma phenotype by regulating downstream target genes. To that end, galectin-3 was stably silenced by utilizing the lentivirus-incorporated small hairpin RNA in two metastatic melanoma cell lines, WM2664 and A375SM, and subjected to gene expression microarray analysis. We identified and validated the lysophospholipase D enzyme, autotaxin, a promoter of migration, invasion, and tumorigenesis, to be down regulated after silencing galectin-3. Silencing galectin-3 significantly reduced the promoter activity of …

Acceleration Of The Panin Development In Mice Expressing Oncogenic K-Ras Due To A High Fat Diet, Bincy Philip

Dissertations and Theses (Open Access)

Obesity is postulated to be one of the major risk factors for pancreatic cancer, and recently it was indicated that an elevated body mass index (BMI correlates strongly with a decrease in patient survival. Despite the evident relationship, the molecular mechanisms involved are unclear. Oncogenic mutation of K-Ras is found early and is universal in pancreatic cancer. Extensive evidence indicates oncogenic K-Ras is not entirely active and it requires a triggering event to surpass the activity of Ras beyond the threshold necessary for a Ras-inflammation feed-forward loop. We hypothesize that high fat intake induces a persistent low level inflammatory response …

Characterization Of Differentiation And Prognostic Biomarkers On Cd8+ Tumor-Infiltrating Lymphocytes In Metastatic Melanoma, Richard C. Wu

Dissertations and Theses (Open Access)

CD8⁺ cytotoxic T lymphocytes (CTL) frequently infiltrate tumors, yet most melanoma patients fail to undergo tumor regression. We studied the differentiation of the CD8⁺ tumor-infiltrating lymphocytes (TIL) from 44 metastatic melanoma patients using known T-cell differentiation markers. We also compared CD8⁺ TIL against the T cells from matched melanoma patients’ peripheral blood. We discovered a novel subset of CD8⁺ TIL co-expressing early-differentiation markers, CD27, CD28, and a late/senescent CTL differentiation marker, CD57. This CD8⁺CD57⁺ TIL expressed a cytolytic enzyme, granzyme B (GB), yet did not express another cytolytic pore-forming molecule, perforin (Perf). In …

Investigating The Roles Of The P63 Isoforms In The Microrna Biogenesis Pathway, Deepavali Chakravarti

Dissertations and Theses (Open Access)

MicroRNAs play roles in various biological processes like development, tumorigenesis, metastasis and pluripotency. My thesis work has demonstrated roles for p63, a p53 family member, in the upstream regulation of microRNA biogenesis. The p63 gene has a complex gene structure and has multiple isoforms. The TAp63 isoforms contain an acidic transcription activation domain. The ΔNp63 isoforms, lack the TA domain, but have a proline rich region critical for gene transactivation. To understand the functions of these isoforms, the Flores lab generated TAp63 and ΔNp63 conditional knock out mice. Using these mice and tissues and cells from these mice we have …

The Role Of Type I Insulin-Like Growth Factor Receptor Signaling In Breast Cancer Brain Metastasis, Sandra M. Saldana

Dissertations and Theses (Open Access)

Brain metastasis is a common cause of mortality in cancer patients. Approximately 20-30% of breast cancer patients acquire brain metastasis, yet potential therapeutic targets remain largely unknown. The type I insulin-like growth factor receptor (IGF- IR) is known to play a role in the progression of breast cancer and is currently being investigated in the clinical setting for various types of cancer. The present study demonstrates that the IGF-IR signaling axis is constitutively active in brain-seeking sublines of breast cancer cells, driving an increase in in vitro metastatic properties. We demonstrate that IGF-IR signaling is activated in an autocrine manner …

Early Skeletal Morphogenesis: The Role Of Pharyngeal Endoderm Derived Signaling During Specification Of Craniofacial Skeleton And Interplay Of Mechanical Forces And Molecular Signaling During Skeletal Condensation, Poulomi Ray

All Dissertations

This study examines the fundamental principles governing the early
stages of skeletal morphogenesis. I specifically investigate the specification of mesenchymal progenitor cells to a skeletal fate. Using explant culture system, I determine that the pharyngeal endoderm was sufficient, but not necessary for specifying pre-chondrogenic identity. FGF signaling is both sufficient and required for specification of Sox9 expression and specification of prechondrogenic identity, as demonstrated by the addition of recombinant FGF protein or the FGF receptor inhibitor (SU5402) to explanted tissue, respectively. However, FGF signaling cannot maintain Sox9 expression or initiate the chondrogenic program as indicated by the absence of Col2a1 …

Oxidative Stress For An Acute Bout Of Bikram Yoga In Healthy, Trained Adults, Kimberly Anne Trocio

UNLV Theses, Dissertations, Professional Papers, and Capstones

BACKGROUND:Generation of free radicals resulting in oxidative damage has been linked to cellular damage, aging, and human disease. Many studies have reported that physical exercise can contribute to oxidative stress. Further, exercise in a hyperthermic environment can promote additional oxidative stress. It is important to consider that practices in yoga may be beneficial in reducing oxidative stress according to some studies. The compound effects of exercise and hyperthermic exposure are experienced in the practice of Bikram yoga, the original "hot" yoga. Because Bikram yoga and other hot exercise classes are an increasingly growing fitness trend, it is necessary to investigate …

Nuclear Localization Of Cpi-17, A Protein Phosphatase-1 Inhibitor Protein, Affects Histone H3 Phosphorylation And Corresponds To Proliferation Of Cancer And Smooth Muscle Cells., Masumi Eto, Jason A Kirkbride, Rishika Chugh, Nana Kofi Karikari, Jee In Kim

Department of Molecular Physiology and Biophysics Faculty Papers

CPI-17 (C-kinase-activated protein phosphatase-1 (PP1) inhibitor, 17kDa) is a cytoplasmic protein predominantly expressed in mature smooth muscle (SM) that regulates the myosin-associated PP1 holoenzyme (MLCP). Here, we show CPI-17 expression in proliferating cells, such as pancreatic cancer and hyperplastic SM cells. Immunofluorescence showed that CPI-17 was concentrated in nuclei of human pancreatic cancer (Panc1) cells. Nuclear accumulation of CPI-17 was also detected in the proliferating vascular SM cell culture and cells at neointima of rat vascular injury model. The N-terminal 21-residue tail domain of CPI-17 was necessary for the nuclear localization. Phospho-mimetic Asp-substitution of CPI-17 at Ser12 attenuated the nuclear …

Intrinsic Apoptotic Pathway: Effects Of Calcium On Murine Cytochrome C Release In Brain And Liver Mitochondria, Dane M. Edwards

Senior Honors Theses

A cell may use one of three main apoptotic pathways leading to programmed cell death: the extrinsic pathway, the perforin/granzyme pathway and the intrinsic pathway. The most pertinent to this discussion is the intrinsic pathway, which utilizes the mitochondria as an essential intermediary. Mitochondria’s primary function in relation to this pathway is the subsequent release of pro-apoptotic factors including cytochrome c, which activate a caspase cascade leading to the death of the cell. Cytochrome c is released partly due to an increase in cytosolic calcium levels. Two methods of the release of cytochrome c have been proposed. The first is …

In Vitro Anticancer Screening Of 24 Locally Used Nigerian Medicinal Plants, Saudat Adamson Fadeyi, Olugbeminiyi O. Fadeyi, Adedeji A. Adejumo, Cosmas Okoro, Elbert L. Myles

Chemistry Faculty Research

Background

Plants that are used as traditional medicine represent a relevant pool for selecting plant candidates that may have anticancer properties. In this study, the ethnomedicinal approach was used to select several medicinal plants native to Nigeria, on the basis of their local or traditional uses. The collected plants were then evaluated for cytoxicity.

Methods

The antitumor activity of methanolic extracts obtained from 24 of the selected plants, were evaluated in vitro on five human cancer cell lines.

Results

Results obtained from the plants screened indicate that 18 plant extracts of folk medicine exhibited promising cytotoxic activity against human carcinoma …

Hsv In Cervical Cancer, Bruce Bejcek

Faculty Research and Creative Activities Award (FRACAA)

No abstract provided.

Cellular Life Beyond An Individual’S Death, Emily Schmitt

CAHSS Intellectual Conversations

One of the most famous examples of cell lines surviving long after a person has died comes from a tumor found in the body of Henrietta Lacks, who died of cervical cancer in 1950. The study of approximately 50 million tons of her cells, which would conservatively equal the amount of cells in one billion people, has resulted in nearly 11,000 patents, including the polio vaccine. These cells have become a focus of public attention since Rebecca Skloot’s 2010 book, The Immortal Life of Henrietta Lacks. This talk will discuss what happens to cells once they leave our bodies, …

Defining The Efficacy Of Aortic Root Enlargement Procedures: A Comparative Analysis Of Surgical Techniques, Katie L. Losenno, Jill J. Gelinas, Marjorie Johnson, Michael W. A. Chu

Anatomy and Cell Biology Publications

Background: Aortic root enlargement (ARE) procedures are believed to allow implantation of larger valve prostheses; however, little evidence exists to support the specific efficacy of various techniques. Methods: Using a cadaveric model, 20 adult (72.4 +/- 15.3 years) hearts were stratified into 4 groups based on annular diameter: <20 mm, 20-22 mm, 22-24 mm, and >24 mm. Each heart underwent an aortic valve replacement following a Nicks, Manougian, aortoventriculoplasty and modified Bentall procedure, with appropriate reversals between procedures. Results: All 4 groups experienced similar increases in annular diameter (P = 0.43) and prosthesis size implanted (P = 0.51) with each enlargement technique. The Nicks, Manougian, modified Bentall …

Improved Tolerance To Freeze And Salt Stress In Mitochondria Of Drosophilia Melanogaster Cells Conferred By Lea Protein, Matthew R. Marunde

Undergraduate Honors Theses

Mechanisms that govern anhydrobiosis involve the accumulation of highly hydrophilic macromolecules, such as late embryogenesis abundant (LEA) proteins. Group 1 LEA proteins comprised of 181 (AfLEA1.1) and 197 (AfLEA1.3) amino acids were cloned from embryos of Artemia franciscana and expressed in Drosophila melanogaster cells (Kc167). Confocal microscopy revealed accumulations of green fluorescence protein (GFP) and AfLEA1.3 constructs in the mitochondria (AfLEA1.3-GFP) and AfLEA1.1-GFP constructs in the cytoplasm. In the presence of mixed substrates, oxygen consumption was similar for permeabilized Kc167 control and Kc167-AfLEA1.3 cells. Acute titrations of NaCl (up to 500 mM) led to successive drops in oxygen flux of …

Evidence For The Requirement Of 14-3-3eta (Ywhah) In Meiotic Spindle Assembly During Mouse Oocyte Maturation, Santanu De, Douglas Kline

Biology Faculty Articles

Background

The 14-3-3 (YWHA) proteins are central mediators in various cellular signaling pathways regulating development and growth, including cell cycle regulation. We previously reported that all seven mammalian 14-3-3 isoforms are expressed in mouse oocytes and eggs and that, 14-3-3η (YWHAH) accumulates and co-localizes in the region of meiotic spindle in mouse eggs matured in vivo. Therefore, we investigated the role of 14-3-3η in spindle formation during mouse oocyte maturation.

Results

Examination of oocytes matured in vitro demonstrated that 14-3-3η accumulates in both meiosis I and II spindles. To explore if 14-3-3η interacts directly with α-tubulin in meiotic spindles, …

Effects Of Synthetic Histone Deacetylase Inhibitors On 3t3l1 Preadipocyte Adipogenic Differentiation Potential, Vikramjeet Singh

Honors Capstones

No abstract provided.

A Myosin-Va Tail Fragment Sequesters Dynein Light Chains Leading To Apoptosis In Melanoma Cells, Tc Izidoro-Toledo, Ac Borges, Dd Araujo, Dps Leitao Mazzi, Fo Nascimento Junior, Jf Sousa, Cp Alves, Apb Paiva, Dm Trindade, Ev Patussi, Pablo M. Peixoto, Kw Kinnally, Em Espreafico

Publications and Research

Previous studies proposed that myosin-Va regulates apoptosis by sequestering pro-apoptotic Bmf to the actin cytoskeleton through dynein light chain-2 (DLC2). Adhesion loss or other cytoskeletal perturbations would unleash Bmf, allowing it to bind and inhibit pro-survival Bcl2 proteins. Here, we demonstrated that over expression of a myosin-Va medial tail fragment (MVaf) harboring the binding site for DLC2 dramatically decreased melanoma cell viability. Morphological and molecular changes, including surface blebbing, mitochondrial outer membrane permeabilization, cytochrome-c and Smac release, as well as caspase-9/-3 activation and DNA fragmentation indicated that melanoma cells died of apoptosis. Immobilized MVaf interacted directly with DLCs, but complexed …

Expression Of Growth Arrest And Dna Damage Protein 45-Alpha (Gadd45-Alpha) And The Ccaat/Enhancer Binding Protein-Delta (C/Ebp-Delta) In Fishes Exposed To Heat And Hypoxia, Daniel Omar Hassumani

Dissertations and Theses

The cellular stress response (CSR) is one of the most highly conserved mechanisms among all organisms. Cellular stress can be defined as damage or the threat of damage to proteins, macromolecules and/or DNA. The response to damage can involve cell cycle regulation, protein chaperoning, DNA repair or, if macromolecular damage is too severe, apoptotic mechanisms can be initiated. This thesis details experiments that were designed to examine the cellular response to non-lethal environmental stressors at the protein level, using two fish species as study models. Two proteins that can cause cell cycle arrest and apoptosis mechanisms were examined. Expression of …