Cancer Biology Commons^™

Human Cancer And Platelet Interaction, A Potential Therapeutic Target, Shike Wang, Zhenyu Li, Ren Xu

Markey Cancer Center Faculty Publications

Cancer patients experience a four-fold increase in thrombosis risk, indicating that cancer development and progression are associated with platelet activation. Xenograft experiments and transgenic mouse models further demonstrate that platelet activation and platelet-cancer cell interaction are crucial for cancer metastasis. Direct or indirect interaction of platelets induces cancer cell plasticity and enhances survival and extravasation of circulating cancer cells during dissemination. In vivo and in vitro experiments also demonstrate that cancer cells induce platelet aggregation, suggesting that platelet-cancer interaction is bidirectional. Therefore, understanding how platelets crosstalk with cancer cells may identify potential strategies to inhibit cancer metastasis and to reduce …

Sirna Knock-Down Of Vav1 In Breast Cancer Cells: Effects On Pi3kinase And Akt, Tajai Sion-Milligan

Student Scholar Showcase

One in eight women in the United States will be diagnosed with breast cancer. Approximately 25-30% of these breast tumors will overexpress Human Epidermal Growth Factor Receptor 2 (HER2), associated with a worse prognosis and decreased survival rate. Stimulation of HER2 results in activation and production of many signaling molecules, ultimately resulting in increased cell division. Two of the downstream molecules activated are PI₃Kinase and, further downstream, the molecule Akt. Typically, overproduction and/or overactivation of PI₃Kinase can lead to oncogenesis. A molecule that may have a significant role in PI₃Kinase formation is VAV1. VAV1 …

Vesicles Mimicking Normal And Cancer Cell Membranes Exhibit Differential Responses To The Cell-Penetrating Peptide Pep-1, Bashiyar Almarwani, Esther Nzuzi Phambu, Christopher Alexander, Ha Aimee T. Nguyen, Nsoki Phambu, Anderson Sunda-Meya

Chemistry Faculty Research

The cell-penetrating peptide (CPP) Pep-1 presents a great potential in drug delivery due to its intrinsic property to cross plasma membrane. However, its mechanism of entry into the cell remains unresolved. In this study, we compare the selectivity of Pep-1 towards vesicles mimicking normal and cancer cell membranes. The interaction was performed in a wide range of peptide-to-lipid molar ratios using infrared (IR), fluorescence, scanning electron microscopy (SEM), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques. At low peptide concentration, fluorescence experiments show that lipid-phosphatidylserine (PS) seems to enable Pep-1 translocation into cancer cell membrane as evidenced by the …

Investigating The Apoptotic Effects Of Platinum(Ii) Amine Complexes With Only One Leaving Ligand On Zebrafish Auditory End Organs, Joshua Smith

Masters Theses & Specialist Projects

The FDA-approved platinum compound, cisplatin, is commonly used as a chemotherapy drug to treat many forms of cancer. However, this compound also has several associated side-effects, including ototoxicity. This has made the development of novel platinum compounds that reduce cancer cell viability, while causing fewer and milder side-effects, an area of significant research interest. In the present study, we examined the apoptotic effects that four monofunctional platinum compounds, pyriplatin, phenanthriplatin, Pt(diethylenetriamine)Cl, and Pt(N,Ndiethyldiethylenetriamine) Cl, had on zebrafish inner ear auditory epithelial cells. We then compared the apoptotic effects of these compounds to those of cisplatin, which is a bifunctional platinum …

Do Paraben Derivatives Alter T Cell Immunity?, Hailey Kintz

Spring Presentation of Undergraduate Research

T cells immunity is linked to a complex system of cytokines that determine differentiation of naïve T cells into Th1, Th2, Th17, and Treg cells. Estrogen production or periods of elevated production have been correlated with an anti-inflammatory state in which Th2 and Treg cells are up-regulated. Such responses in the immune system are capable of supporting pre-cancerous activity. We are investigating the tie between the xenoestrogen compounds found in cosmetics, parabens, and their ability to regulate T cell immunity. Testing parabens and paraben derivatives with weaker estrogen receptor association will allow for a better understanding of the interplay between …

Hiv Suppresses Cervical Neutrophil Infiltration In Women With Normal Or Abnormal Pap Smears, Mika Caplan, Peter C. Angeletti, Duan Loy, Kandali Samwel, Daniela Gonzalez, Crispin Chisanga, Julius Mwaiselage, Asafu Munema, Brenda Bashekera, Kessy Goodwin, John Dustin Loy, John T. West, Charles Wood

UCARE: Research Products

Human immunodeficiency virus (HIV) infection of CD4+ T cells results in a weakened immune system due to decreased white blood cells, particularly multi-lobed neutrophils (neutropenia) and other granulocytes.¹ The purpose of this study was to determine whether a correlation exists between HPV/HIV status and presence of neutrophils. To test this, we used a computer software program (QuPath) to analyze neutrophil infiltration seen in pap smears of both HIV+ and HIV- patients from samples collected in Tanzania from three different sites: Bagamoyo, Chalinze, and Dar es Salaam. The software was used to quantify neutrophils per image based on the size …

Extracellular Vesicles Released By Cardiomyocytes In A Doxorubicin-Induced Cardiac Injury Mouse Model Contain Protein Biomarkers Of Early Cardiac Injury, Chontida Yarana, Dustin W. Carroll, Jing Chen, Luksana Chaiswing, Yanming Zhao, Teresa Noel, Michael Alstott, Younsoo Bae, Emily V. Dressler, Jeffrey A. Moscow, D. Allan Butterfield, Haining Zhu, Daret K. St. Clair

Toxicology and Cancer Biology Faculty Publications

Purpose—Cardiac injury is a major cause of death in cancer survivors, and biomarkers for it are detectable only after tissue injury has occurred. Extracellular vesicles (EV) remove toxic biomolecules from tissues and can be detected in the blood. Here, we evaluate the potential of using circulating EVs as early diagnostic markers for long-term cardiac injury.

Experimental Design—Using a mouse model of doxorubicin (DOX)-induced cardiac injury, we quantified serum EVs, analyzed proteomes, measured oxidized protein levels in serum EVs released after DOX treatment, and investigated the alteration of EV content.

Results—Treatment with DOX caused a significant increase in …

Cold Atmospheric Plasma Induces Atp-Dependent Endocytosis Of Nanoparticles And Synergistic U373mg Cancer Cell Death, Zhonglei He, Kangze Liu, Eline Manaloto, Alan Casey, George P. Cribaro, Hugh Byrne, Furong Tian, Carlos Barcia, Gillian Conway, Patrick J. Cullen, James Curtin

Articles

Gold nanoparticles (AuNP) have potential as both diagnostic and therapeutic vehicles. However, selective targeting and uptake in cancer cells remains challenging. Cold atmospheric plasma (CAP) can be combined with AuNP to achieve synergistic anti-cancer cytotoxicity. To explore synergistic mechanisms, we demonstrate both rate of AuNP uptake and total amount accumulated in U373MG Glioblastoma multiforme (GBM) cells are signifcantly increased when exposed to 75kV CAP generated by dielectric barrier discharge. No signifcant changes in the physical parameters of AuNP were caused by CAP but active transport mechanisms were stimulated in cells. Unlike many other biological efects of CAP, long-lived reactive species …

Changes In The Proliferation And Gene Expression Of Huvecs In Response To Treatment With Plant Secondary Metabolites, Caleigh Howard

Seaver College Research And Scholarly Achievement Symposium

Medicinal plants have historically been a valuable source of new drugs, and Southern California possesses a rich collection of native plants which have been used as medicines by native people groups for thousands of years. Angiogenesis is the biological process of new blood-vessel growth from endothelial cells. It is an essential part of the wound-healing process, and increased angiogenesis has also been implicated in the growth of some types of cancerous tumors. In this study, extracts of the Southern Californian native plants Red shanks (Adenostoma sparsifolium) and the alkaloid extract of Jimson weed (Datura wrightii) were …

Pre-Diagnostic Biomarkers Of Metabolic Dysregulation And Cancer Mortality, Tomi Akinyemiju, Justin Xavier Moore, Suzanne E. Judd, Maria Pisu, Michael Goodman, Virginia J. Howard, Leann Long, Monika Safford, Susan C. Gilchrist, Mary Cushman

Epidemiology and Environmental Health Faculty Publications

INTRODUCTION: The obesogenic milieu is a pro-tumorigenic environment that promotes tumor initiation, angiogenesis and metastasis. In this prospective cohort, we examined the association between pre-diagnostic metabolic biomarkers, plasma adiponectin, resistin, leptin and lipoprotein (a), and the risk of cancer mortality.

METHODS: Prospective data was obtained from the REasons for Geographic and Racial Differences in Stroke (REGARDS) cohort of Blacks and Whites followed from 2003 through 2012 for cancer mortality. We determined the association between metabolism biomarkers (log-transformed and tertiles) and risk of cancer mortality using Cox Proportional Hazards models with robust sandwich estimators to calculate the 95% confidence intervals (CIs), …

Profiling Prostate Cancer Therapeutic Resistance, Cameron A. Wade, Natasha Kyprianou

Urology Faculty Publications

The major challenge in the treatment of patients with advanced lethal prostate cancer is therapeutic resistance to androgen-deprivation therapy (ADT) and chemotherapy. Overriding this resistance requires understanding of the driving mechanisms of the tumor microenvironment, not just the androgen receptor (AR)-signaling cascade, that facilitate therapeutic resistance in order to identify new drug targets. The tumor microenvironment enables key signaling pathways promoting cancer cell survival and invasion via resistance to anoikis. In particular, the process of epithelial-mesenchymal-transition (EMT), directed by transforming growth factor-β (TGF-β), confers stem cell properties and acquisition of a migratory and invasive phenotype via resistance to anoikis. Our …

Acute Loss Of Iron-Sulfur Clusters Results In Metabolic Reprogramming And Generation Of Lipid Droplets In Mammalian Cells, Daniel R. Crooks, Nunziata Maio, Andrew N. Lane, Michal Jarnik, Richard M. Higashi, Ronald G. Haller, Ye Yang, Teresa Whei-Mei Fan, W. Marston Linehan, Tracey A. Rouault

Center for Environmental and Systems Biochemistry Faculty Publications

Iron–sulfur (Fe-S) clusters are ancient cofactors in cells and participate in diverse biochemical functions, including electron transfer and enzymatic catalysis. Although cell lines derived from individuals carrying mutations in the Fe-S cluster biogenesis pathway or siRNA-mediated knockdown of the Fe-S assembly components provide excellent models for investigating Fe-S cluster formation in mammalian cells, these experimental strategies focus on the consequences of prolonged impairment of Fe-S assembly. Here, we constructed and expressed dominant–negative variants of the primary Fe-S biogenesis scaffold protein iron–sulfur cluster assembly enzyme 2 (ISCU2) in human HEK293 cells. This approach enabled us to study the early metabolic reprogramming …

Ferrocenylchalcone-Uracil Conjugates: Synthesis And Cytotoxic Evaluation, Amandeep Singh, Vishu Mehra, Neda Sadeghiani, Saghar Mozaffari, Keykavous Parang, Vipan Kumar

Pharmacy Faculty Articles and Research

Huisgen’s azide-alkyne cycloaddition reaction was employed to synthesize a series of 1H-1,2,3-triazole-tethered uracil-ferrocenyl chalcone conjugates with the aim of evaluating their in vitro anti-proliferative efficacy on human leukemia (CCRF-CEM) and human breast adenocarcinoma (MDA-MB-468) cell lines. Cytotoxic evaluation studies identified a number of synthesized conjugates that inhibited the proliferation of leukemia cancer cells by ~70% after 72 h. The selected synthesized conjugates were found to be significantly less cytotoxic against normal kidney cell line (LLC-PK1) when compared with CCRF-CEM cancer cells.

Synthesis, Characterization, And In Vitro Cytotoxicity Of Fatty Acyl-Cgkrk-Chitosan Oligosaccharides Conjugates For Sirna Delivery, Naglaa Salem El-Sayed, Meenakshi Sharma, Hamidreza Montazeri Aliabadi, Magda Goda El-Meligy, Ahmed Kamed El-Zaity, Zenat Adeeb Nageib, Rakesh Tiwari

Pharmacy Faculty Articles and Research

In this studies, three fatty acyl derivatives of CGKRK homing peptides were coupled successfully to chitosan oligosaccharides (COS) using sulfosuccinimidyl-4-(N-maleimidomethyl)cyclohexane-1-carboxylate sodium salt (sulfo-SMCC). The COS-SMCC was prepared by direct coupling between COS and sulfo-SMCC in PBS (pH 7.5) at RT for 48 h. The structure of COS-SMCC and the three fatty acyl-CGKRK-SMCC-COS conjugates were characterized by FT-IR, ¹³C NMR, and SEM. The ability of three conjugates to condense siRNA into nanosized polyplexes and their efficacy in protecting siRNA from serum nucleases degradation were investigated. Among the investigated derivatives, S-CGKRK-COS showed higher siRNA binding affinity as compared to …

The Effect Of Grapefruit Intake On Endogenous Serum Estrogen Levels In Postmenopausal Women, Kristine R. Monroe, Frank Z. Stanczyk, Kathleen Hill-Besinque, Malcolm C. Pike

Pharmacy Faculty Articles and Research

Although grapefruit intake leads to elevated serum estrogen levels when hormones are taken orally, there are no published data on the effect on endogenous levels. We conducted a pilot dietary intervention study among healthy postmenopausal volunteers to test whole grapefruit, 2 juices, and 1 grapefruit soda. Fifty-nine participants were recruited through the Love/Avon Army of Women. The study consisted of a 3-wk run-in, 2 wk of grapefruit intake, and a 1-wk wash-out. Eight fasting blood samples were collected. An additional 5 samples drawn at 1, 2, 4, 8, and 10 hr after grapefruit intake were collected during an acute-phase study …

Inactivation Of Myeloma Cancer Cells By Helium And Argon Plasma Jets: The Effect Comparison And The Key Reactive Species, Zeyu Chen, Qingjie Cui, Chen Chen, Dehui Xu, Dingxin Liu, H. L. Chen, Michael G. Kong

Bioelectrics Publications

In plasma cancer therapy, the inactivation of cancer cells under plasma treatment is closely related to the reactive oxygen and nitrogen species (RONS) induced by plasmas. Quantitative study on the plasma-induced RONS that related to cancer cells apoptosis is critical for advancing the research of plasma cancer therapy. In this paper, the effects of several reactive species on the inactivation of LP-1 myeloma cancer cells are comparatively studied with variable working gas composition, surrounding gas composition, and discharge power. The results show that helium plasma jet has a higher cell inactivation efficiency than argon plasma jet under the same discharge …

Mechanisms For Survival And Drug Resistance In Cancer Cells, Matthew B. Utter

Dissertations, Theses, and Capstone Projects

PART I

Prostate cells are hormonally driven to grow and divide. Typical treatments for prostate cancer involve blocking the hormone androgen from activating the androgen receptor (AR) and thus inhibit growth and proliferation of the cancer. Androgen deprivation therapy (ADT) can lead to the selection of cancer cells that grow and divide independently of androgen receptor activation. Prostate cancer cells that are insensitive to androgens commonly display metastatic phenotypes and reduced long-term survival of patients. In this study, we provide evidence that androgen-insensitive prostate cancer cells have elevated phospholipase D (PLD) activity relative to the androgen-sensitive prostate cancer cells. PLD …

Anti-Proliferative Effects Of Garcinia Fruits In Breast Cancer Cells, Harini Anandhi Senthilkumar

Dissertations, Theses, and Capstone Projects

Breast cancer continues to be the second leading cause of death in women, even with the recent advances in research that has led to an improved understanding of molecular pathways and targets. Increasing mortality due to recurrence and lack of targeted drugs, especially in aggressive breast cancer subtypes such as triple negative breast cancer, has gained attention from the research community. With nearly 50% of the commonly used cancer drugs being sourced from plants, bioactive small molecules derived from a natural origin have immense potential as therapeutics. This study focuses on the anti-proliferative activities of benzophenones isolated from the edible …

Characterization Of Cytokeratin 8 In Cancer, Daniel S. Leventhal

The Pegasus Review: UCF Undergraduate Research Journal

A Cytokeratin 8 (K8)/Green Fluorescent Protein (GFP) fusion construct was created to better understand the behavior of K8 within cancer cells. This intermediate filament (IF) protein is a member of the cytoskeletal gene family, along with actin and tubulin. IFs are normally expressed in a tissue-specific and differentiation-dependent manner, in which their role is more supportive than essential to the cell. Such roles include rigidity of cellular shape, protein trafficking, cellular locomotion, and cell-signaling platforms. K8 mutation, over-expression, and aberrant post translational modifications have been observed in various carcinoma cell lines to be the cause of several phenotypes, including apoptosis …

Flame Retardants, Hexabromocyclododecane (Hcbd) And Tetrabromobisphenol A (Tbbpa), Alter Secretion Of Tumor Necrosis Factor Alpha (Tnfα) From Human Immune Cells, Sharia Yasmin, Margaret Whalen

Chemistry Faculty Research

Hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) are flame retardants, used in a variety of applications, which contaminate the environment and are found in human blood. HBCD and TBBPA have been shown to alter the tumor killing function of natural killer (NK) lymphocytes and the secretion of the inflammatory cytokines interferon gamma (IFNγ) and interleukin 1 beta (IL-1β). The current study examined the effects of HBCD and TBBPA on secretion of the critical pro-inflammatory cytokine tumor necrosis factor alpha (TNFα) from human immune cells. Preparations of human immune cells that ranged in complexity were studied to determine if the effects of …

Cxcr2 Is A Negative Regulator Of P21 In P53-Dependent And Independent Manner Via Akt-Mediated Mdm2 In Ovarian Cancer, Rosa Mistica C. Ignacio, Yuan-Lin Dong, Syeda M. Kabir, Hyeongjwa Choi, Eun-Sook Lee, Alicia Beeghly-Fadiel, Margaret M. Whalen, Deok-Soo Son

Chemistry Faculty Research

Ovarian cancer (OC) has the highest rate of mortality among gynecological malignancy. Chemokine receptor CXCR2 in OC is associated with poor outcomes. However, the mechanisms by which CXCR2 regulates OC proliferation remain poorly understood. We generated CXCR2-positive cells from parental p53 wild-type (WT), mutant and null OC cells, and assessed the roles of CXCR2 on proliferation of OC cells in p53-dependent and independent manner. CXCR2 promoted cell growth rate: p53WT > mutant = null cells. Nutlin-3, a p53 stabilizer, inhibited cell proliferation in p53WT cells, but had little effect in p53-mutant or null cells, indicating p53-dependence of CXCR2-mediated proliferation. CXCR2 decreased …

Target Engagement Imaging Of Parp Inhibitors In Small-Cell Lung Cancer, Brandon Carney, Susanne Kossatz, Benjamin H. Lok, Valentina Schneeberger, Kishore K. Gangangari, Naga Vara Kishore Pillarsetty, Wolfgang A. Weber, Charles M. Rudin, John T. Poirier, Thomas Reiner

Publications and Research

Insufficient chemotherapy response and rapid disease progression remain concerns for smallcell lung cancer (SCLC). Oncologists rely on serial CT scanning to guide treatment decisions, but this cannot assess in vivo target engagement of therapeutic agents. Biomarker assessments in biopsy material do not assess contemporaneous target expression, intratumoral drug exposure, or drug-target engagement. Here, we report the use of PARP1/2-targeted imaging to measure target engagement of PARP inhibitors in vivo. Using a panel of clinical PARP inhibitors, we show that PARP imaging can quantify target engagement of chemically diverse small molecule inhibitors in vitro and in vivo. We measure PARP1/2 inhibition …

Inhibition Of Dihydrotestosterone Synthesis In Prostate Cancer By Combined Frontdoor And Backdoor Pathway Blockade, Michael V. Fiandalo, John J. Stocking, Elena A. Pop, John H. Wilton, Krystin M. Mantione, Yun Li, Kristopher M. Attwood, Gissou Azabdaftari, Yue Wu, David S. Watt, Elizabeth M. Wilson, James L. Mohler

Center for Pharmaceutical Research and Innovation Faculty Publications

Androgen deprivation therapy (ADT) is palliative and prostate cancer (CaP) recurs as lethal castration-recurrent/resistant CaP (CRPC). One mechanism that provides CaP resistance to ADT is primary backdoor androgen metabolism, which uses up to four 3α-oxidoreductases to convert 5α-androstane-3α,17β-diol (DIOL) to dihydrotestosterone (DHT). The goal was to determine whether inhibition of 3α-oxidoreductase activity decreased conversion of DIOL to DHT. Protein sequence analysis showed that the four 3α-oxidoreductases have identical catalytic amino acid residues. Mass spectrometry data showed combined treatment using catalytically inactive 3α-oxidoreductase mutants and the 5α-reductase inhibitor, dutasteride, decreased DHT levels in CaP cells better than dutasteride alone. Combined blockade …

The Role Of Mdm2 In Dna Damage Signaling, Stanley Tam

Theses and Dissertations

The overexpression of the oncogene MDM2 is common in a variety of human cancers. MDM2 overexpression is known to increase genome instability in cells by delaying DNA double strand break repair and γH2AX levels. This study explores the knockdown of MDM2 and how it may affect DNA damage signaling.

A Predictive 7-Gene Assay And Prognostic Protein Biomarkers For Non-Small Cell Lung Cancer, Nancy Lan Guo, Afshin Dowlati, Rebecca A. Raese, Chunlin Dong, Guoan Chen, David G. Beer, Justine Shaffer, Salvi Singh, Ujala Bokhary, Lin Liu, John Howingtown, Thomas Hensing, Yong Qian

Faculty & Staff Scholarship

This study aims to develop a multi-gene assay predictive of the clinical benefits of chemotherapy in non- small cell lung cancer (NSCLC) patients, and substantiate their protein expression as potential therapeutic tar- gets. Patients and methods: The mRNA expression of 160 genes identified from microarray was analyzed in qRT-PCR assays of independent 337 snap-frozen NSCLC tumors to develop a predictive signature. A clinical trial JBR.10 was included in the validation. Hazard ratio was used to select genes, and decision-trees were used to construct the predictive model. Protein expression was quantified with AQUA in 500 FFPE NSCLC samples.

Results: A 7-gene …

Spontaneous Dna Damage To The Nuclear Genome Promotes Senescence, T Redox Imbalance And Aging, Andria R. Robinson, Matthew J. Yousefzadeh, Tania A. Rozgaja, Jin Wang, Xuesen Li, Jeremy S. Tilstra, Chelsea H. Feldman, Siobhan Q. Gregg, Caroline H. Johnson, Erin M. Skoda, Marie-Celine Frantz, Harris Bell-Temin, Hannah Pope-Varsalona, Aditi U. Gurkar, Luigi A. Nasto, Rena A.S. Robinson, Heike Fuhrmann-Stroissnigg, Jolanta Czerwinska, Sara J. Mcgowan, Nadiezhda Cantu-Madellin, Jamie B. Harris, Salony Maniar, Mark A. Ross, Christy E. Trussoni, Nicholas F. Larusso, Eugenia Cifuentes-Pagano, Patrick J. Pagano, Barbara Tudek, Nam V. Vo, Lora H. Rigatti, Patricia L. Opresko, Donna B. Stolz, Simon C. Watkins, Christin E. Burd, Claudette M. St, Croix, Gary Siuzdak, Nathan A. Yates, Paul D. Robbins, Yinsheng Wang, Peter Wipf, Eric E. Kelley, Laura J. Neidernhofer

Faculty & Staff Scholarship

Accumulation of senescent cells over time contributes to aging and age-related diseases. However, what drives senescence in vivo is not clear. Here we used a genetic approach to determine if spontaneous nuclear DNA damage is sufficient to initiate senescence in mammals. Ercc1-/Δ mice with reduced expression of ERCC1-XPF endonuclease have impaired capacity to repair the nuclear genome. Ercc1-/Δ mice accumulated spontaneous, oxidative DNA damage more rapidly than wild-type (WT) mice. As a consequence, senescent cells accumulated more rapidly in Ercc1-/Δ mice compared to repair-competent animals. However, the levels of DNA damage and senescent cells in Ercc1-/Δ mice never exceeded that …

Mlk Book Read 2018 (Research Materials), Holy Cross Libraries

Library Resources for Campus Events

A bibliography of resources available through the Holy Cross Libraries which provide additional information related to the MLK Winter Book Read, based on the best-seller “The Immortal LIfe of Henrietta Lacks” by Rebecca Skoot.

Studies Of Norspermidine Uptake In Drosophila Suggest The Existence Of Multiple Polyamine Transport Pathways, Michael Dieffenbach

Honors Undergraduate Theses

Polyamines are a class of essential nutrients involved in many basic cellular processes such as gene expression, cell proliferation, and apoptosis. Without polyamines, cell growth is delayed or halted. Cancerous cells require an abundance of polyamines through a combination of synthesis and transport from the extracellular environment. An FDA-approved drug, D,L-α-difluoromethylornithine (DFMO), blocks polyamine synthesis but is ineffective at inhibiting cell growth due to polyamine transport. Thus, there is a need to develop drugs that inhibit polyamine transport to use in combination with DFMO. Surprisingly, little is known about the polyamine transport system in humans and other eukaryotes. Understanding the …

The Identification And Segmentation Of Astrocytoma Prior To Critical Mass, By Means Of A Volumetric/Subregion Regression Analysis Of Normal And Neoplastic Brain Tissue, Lyn Higgins

Electronic Theses and Dissertations

As the underlying cause of Glioblastoma Multiforme (GBM) is presently unclear, this research implements a new approach to identifying and segmenting plausible instances of GBM prior to critical mass. Grade-IV Astrocytoma, or GBM, is an aggressive and malignant cancer arising from star-shaped glial cells, or astrocytes, where the astrocytes, functionally, assist in the support and protection of neurons within the central nervous system and spinal cord. Subsequently, our motivation for researching the ability to recognize GBM is that the underlying cause of the mutation is presently unclear, leading to the operative that GBM is only detectable through a combination of …

Design And Evaluation Of Gemini Surfactant-Based Lipoplexes Modified With Cell-Binding Peptide For Targeted Gene Therapy, Waleed Mohammed-Saeid, Rania Soudy, Richa Tikoo, Kamaljit Kaur, Ronald E. Verrall, Ildiko Badea

Pharmacy Faculty Articles and Research

Purpose Achieving successful gene therapy requires delivery of a gene vector specifically to the targeted tissue with efficient expression and a good safety profile. The objective of this work was to develop, characterize and determine if a novel gemini surfactant-based lipoplex systems, modified with a cancer-targeting peptide p18-4, could serve this role. Methods The targeting peptide p18-4 was either chemically coupled to a gemini surfactant backbone or physically co-formulated with the lipoplexes. The influence of targeting ligand and formulation strategies on essential physicochemical properties of the lipoplexes was evaluated by dynamic light scattering and small angle X-ray scattering techniques. In …