Cell and Developmental Biology Commons^™

Evaluating The Effects Of Antibody-Conjugated Multi-Walled Carbon Nanotubes In Combination With Microwave Irradiation, Amy Chall

College of Graduate Studies: Theses & Dissertations

Cancer remains one of the largest public health concerns of our day, particularly in developed countries where technological advances have allowed populations to live well into their eighth decade. In America, those in their 80’s have a 1 in 2 chance of developing cancer in their lifetime. Prostate cancer, specifically is the second leading cause of cancer deaths in males. Traditional cancer therapies cause high levels of toxicity to the patient due to mechanisms of action that often attack cancer cells and healthy cells alike. The holy grail of cancer research is to find a treatment that targets the cancer …

Misexpression Of Cancer/Testis (Ct) Genes In Tumor Cells And The Potential Role Of Dream Complex And The Retinoblastoma Protein Rb In Soma-To-Germline Transformation, Sabha M. Alhewati

Dissertations, Master's Theses and Master's Reports

Misexpression of germline genes like Cancer Testis (CT) genes, called a soma-to-germline transformation, is a phenomenon linked to tumorigenesis. However, the mechanisms underlying this phenomenon are poorly understood. A soma-to-germline transformation in Caenorhabditis elegans occurs due to the loss function of the highly conserved DREAM (Dp, Retinoblastoma (Rb)-like, E2F, and MuvB) transcriptional repressor complex. In mammalian cells, the DREAM complex (Muvb core complex, E2F4/5, DP1/2, and p130/p107 proteins), as well as the Retinoblastoma protein (pRb), are implicated in transcriptional repression of cell cycle genes in quiescence or G0. We hypothesize that the expression of CT genes in malignant cells occurs …

Microarray Data Analysis And Classification Of Cancers, Grant Gates

Williams Honors College, Honors Research Projects

When it comes to cancer, there is no standardized approach for identifying new cancer classes nor is there a standardized approach for assigning cancer tumors to existing classes. These two ideas are known as class discovery and class prediction. For a cancer patient to receive proper treatment, it is important that the type of cancer be accurately identified. For my Senior Honors Project, I would like to use this opportunity to research a topic in bioinformatics. Bioinformatics incorporates a few different subjects into one including biology, computer science and statistics. An intricate method for class discovery and class prediction is …

The Functional Role Of Rna Binding Protein Rbms3 As A Tumor Promoter In Triple-Negative Breast Cancer Cells, Yuting Zhou

Theses and Dissertations--Molecular and Cellular Biochemistry

RBMS3 belongs to the family of c-myc gene single-strand binding proteins (MSSPs) that play important roles in transcriptional regulation. Here, we show that RBMS3 functions as a tumor promoter in triple-negative breast cancer (TNBC), a highly aggressive BC subtype. Analysis of RBMS3 expression shows that RBMS3 is upregulated at both mRNA and protein levels in TNBC cells. Functionally, overexpression of RBMS3 increases cell migration, invasion and cancer stem cell (CSC) behaviors. Moreover, RBMS3 induces expression of epithelial-mesenchymal transition (EMT) and CSC markers. Conversely, loss of RBMS3 in TNBC BT549 cells inhibits cell proliferation, migration and mesenchymal phenotype. Correlation analysis shows …

Characterizing Chromosomal Aberrations In Cells Deficient For Both Atm And Msh2, Yeliz Inalman

Dissertations and Theses

Ataxia telangiectasia mutated (ATM) and mutS homologue 2 (MSH2) are important DNA repair proteins that participate in DNA repair pathways to maintain genomic integrity. Mice deficient for ATM and MSH2 mice are viable. However, ATM^-/- mice show growth retardation, neurological defects, and spontaneous lymphomagenesis. MSH2^-/- mice suffer from aggressive lymphoid tumors between two to five months of age and have increased microsatellite instability, which predisposes MSH2^-/- mice to carcinomas. However, mice deficient in both ATM and MSH2 are unable to survive beyond postnatal day 21 (P21). The observed lethality in ATM^-/-MSH2^-/- mice may result …

Regulation Of The Long Non-Coding Rna Fam83h-As1 By Human Papillomavirus In Cervical Cancer, Jamie Ann Barr Ph.D.

Graduate Theses, Dissertations, and Problem Reports (ETD)

Non-coding RNAs (NcRNAs), such as long non-coding RNAs (lncRNAs) and microRNAs (miRNAs), have been found to be involved in a variety of critical biological processes, and dysregulation of ncRNAs have been involved with several human diseases including cancer.

High-risk human papillomavirus (HPV) infection is one of the first events in the process of carcinogenesis in cervical and a subset of head and neck cancers. The expression of the viral oncoproteins E6 and E7 is essential in this process by inactivating the tumor suppressor proteins p53 and Rb, respectively, in addition to their interactions with other host proteins and regulation of …

End-To-End Learning Via A Convolutional Neural Network For Cancer Cell Line Classification, Darlington A. Akogo, Xavier-Lewis Palmer

Electrical & Computer Engineering Faculty Publications

Purpose: Computer vision for automated analysis of cells and tissues usually include extracting features from images before analyzing such features via various machine learning and machine vision algorithms. The purpose of this work is to explore and demonstrate the ability of a Convolutional Neural Network (CNN) to classify cells pictured via brightfield microscopy without the need of any feature extraction, using a minimum of images, improving work-flows that involve cancer cell identification.

Design/methodology/approach: The methodology involved a quantitative measure of the performance of a Convolutional Neural Network in distinguishing between two cancer lines. In their approach, they trained, validated and …

Investigation Of The Interactions Between The Dream Complex And Hpv16, Kevin Ko

Theses and Dissertations

According to the American Cancer Society, it has been estimated that in 2019 alone, there will be approximately 53,000 new cases of oropharyngeal cancers. Oropharyngeal cancers are the largest subset of head and neck squamous cell carcinomas (HNSCCs), which are the sixth most common cancer across worldwide populations. They, along with other HNSCCs, fall under a category of cancers known as Human papillomavirus (HPV)-associated cancers, and it has been found that upwards of 70% of these cancers can be attributed to high-risk HPV infections.

Specifically, the high-risk HPV gene, E7, plays a key role in relieving cell cycle repression by …

Critical Physicochemical Properties For Nanoparticle Toxicity: Impact Of Surface Coating And Size On Particle-Induced Cell Transformation And Inflammatory Response, Tiffany Kornberg

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nanoparticles, which measure 100 nm in at least one dimension, have surged in development, production, and use for a wide range of applications. However, the rapid pace of development for these emerging materials with unclear/unknown toxicity profiles makes it difficult to adequately assess health risk associated with exposure. One critical obstacle which limits scientific research to fill these critical knowledge gaps is the lack of accurate and predictive models for nanotoxicology studies, particularly those which involve occupationally relevant exposure scenarios (pulmonary exposure to low dose of particles in the circulating air). Typically, animal models are used to assess potential systemic …

Regulatory T Cells Promote Breast Cancer Progression Through Inhibiting Classical Activation Of Macrophages, Nicholas M. Clark

Theses and Dissertations

Transient ablation of regulatory T cells has been shown to be effective at hindering tumor growth and metastasis in murine breast cancer model. Based on our lab’s previous work, we have demonstrated that NK cells and CD8+ cytotoxic T cells were not required for the protective effect of Treg cell ablation. However, we also reported that CD4+ helper T cells and IFN-γ were required for the protective effect of Treg cell ablation. Furthermore, we observed that CD11B+ cells responded to Treg ablation therapy by up-regulating target genes of IFN-γ. Therefore, this study aimed to investigate the connection between the myeloid …

The Role Of Kras In Mechanosensing In Non-Small Cell Lung Cancer, Krista M. Powell

Theses and Dissertations

Lung cancer is the number one cause of cancer related death worldwide, with more than 1.6 million fatalities each year. Non-small cell lung cancer (NSCLC) accounts for 80-85% of all lung cancers, with KRAS being one of the most prevalent oncogenic driver mutations. Therapeutic approaches for KRAS-mutated NSCLC have been extensively explored due to the US National Cancer Institute RAS Initiative, but methods of directly targeting KRAS or downstream effectors, such as MEK, still have poor results. Previous reports have shown that KRAS-mutated NSCLC activate distinct receptor tyrosine kinases (RTKs) depending on the epithelial or mesenchymal state. Epithelial-to-mesenchymal transition (EMT) …

Eralpha Isoforms Modulate The Tumorigenicity Of 24r,25(Oh)2d3 In Estrogen-Responsive Cancer, Anjali Verma

Theses and Dissertations

Over 200,000 cases of breast cancer are diagnosed every year. Nearly 20% of these patients supplement their diets with some form of vitamin D. This high frequency of vitamin D supplement use may be due in part to research suggesting that cancer patients with higher serum vitamin D₃ levels have better prognoses than patients with low serum vitamin D_3. However, double-blind clinical trials on the efficacy of vitamin D₃ supplementation in breast cancer have been inconclusive. A recent meta-analysis showed evidence of reduced cancer recurrence in patients taking vitamin D₃ supplements who had ‘estrogen receptor positive’ …

Cyclophilin A As A Molecular Switch Regulating Prolactin Receptor Mediated Signaling, Mammary Tumorigenesis And Metastasis, Shawn Hakim

Theses and Dissertations

Prolactin (PRL) and its receptor (PRLr) have been implicated in the development and progression of human breast cancer. PRL activates its receptor and induces activation of proximal Janus kinase 2 (Jak2) for signal transduction. Here, we sought to determine the role of PRLr-associated peptidyl-prolyl isomerase, cyclophilin A (CypA), in modulating structure/function relationships of the PRLr. It was demonstrated that CypA mediated PRL-induced conformational change of the CFP- and -YFP tagged forms of the PRLr cytoplasmic-tail, whereas CypA inhibition by NIM811 (N-methyl-4-isoleucine cyclosporin) or knockdown blocked the conformational change of the PRLr assessed by Fluorescence Resonance Energy Transfer (FRET) signal or …

Is The Blood An Alternative For Programmed Cell Death Ligand 1 Assessment In Non-Small Cell Lung Cancer?, Emmanuel Acheampong, Isaac Spencer, Weitao Lin, Melanie Ziman, Michael Millward, Elin Gray

Research outputs 2014 to 2021

Anti-programmed cell death (PD)-1/PD-ligand 1 (L1) therapies have significantly improved the outcomes for non-small cell lung cancer (NSCLC) patients in recent years. These therapies work by reactivating the immune system and enabling it to target cancer cells once more. There is a general agreement that expression of PD-L1 on tumour cells predicts the therapeutic response to PD-1/PD-L1 inhibitors in NSCLC. Hence, immunohistochemical staining of tumour tissue biopsies from NSCLC patients with PD-L1 antibodies is the current standard used to aid selection of patients for treatment with anti-PD-1 as first line therapy. However, issues of small tissue samples, tissue heterogeneity, the …

Delineation Of New Mechanisms Of Dna Double Strand Break Repair, Songli Zhu

Theses & Dissertations

DNA damage is frequently induced in cells by both endogenous and exogenous agents. DNA damage, particular double strand breaks (DSBs) may lead to genomic instability, and the progression of cancer, aging, neurodegeneration, and other human diseases. The cell employs two major DSB repair pathways, including homologous recombination (HR) and Non-homologous end joining (NHEJ), but the detailed mechanisms of DSB repair remain to be further revealed.

In the first part of this study, we characterized a plasmid-based assay to investigate NHEJ repair in Xenopus egg extracts. Our data argued for a preference for the precise repair by the NHEJ machinery and …

Regulation Of Canonical And Non-Canonical Hippo Pathway Components In Mitosis And Cancer, Seth Stauffer

Theses & Dissertations

The Hippo pathway is conserved regulator of organ size through control of proliferation, apoptosis, and stem-cell self-renewal. In addition to this important function, many of the canonical signaling members have also been shown to be regulated during mitosis. Importantly, Hippo pathway components are frequently dysregulated in cancers and have attracted attention as possible targets for improved cancer therapeutics. Further exploration of Hippo-YAP (yes-associated protein) signaling has revealed new regulators and effectors outside the canonical signaling network and has revealed a larger non-canonical network of signaling proteins in which canonical Hippo pathway components crosstalk with important cellular homeostasis and apoptosis signaling …

Obesity-Induced Peritoneal Dissemination Of Ovarian Cancer And Dominant Recruitment Of Macrophages In Ascites, Rosa Mistica C. Ignacio, Eun-Sook Lee, Andrew J. Wilson, Alicia Beeghly-Fadiel, Margaret M. Whalen, Deok-Soo Son

Chemistry Faculty Research

One-fifth of cancer deaths are associated with obesity. Because the molecular mechanisms by which obesity affects the progression of ovarian cancer (OC) are poorly understood, we investigated if obesity could promote the progression of OC cells using the postmenopausal ob/ob mouse model and peritoneal dissemination of mouse ID8 OC cells. Compared to lean mice, obese mice had earlier OC occurrence, greater metastasis throughout the peritoneal cavity, a trend toward shorter survival, and higher circulating glucose and proinflammatory chemokine CXCL1 levels. Ascites in obese mice had higher levels of macrophages (Mφ) and chemokines including CCL2, CXCL12, CXCL13, G-CSF and M-CSF. Omental …

Frost450, A Novel Microtubule Targeting Agent: Resistance And Cross-Resistance In An Ovarian Cancer Cell Line, Jonathan Chancellor Fox

Undergraduate Honors Theses

Drug resistance remains problematic for chemotherapy treatments. As primary treatment strategies tend to lose potency against cancer, there is a need for treatment options that overcome drug resistance mechanisms. FROST450, a novel microtubule destabilizing agent, has proven anticancer effects that overcome taxane and multidrug resistance. However, to better understand the clinical potential of FROST450, in this study we examine the mechanisms and implications of acquired FROST450 resistance in an A2780 ovarian cancer cell line. Results indicate FROST450 resistance is associated with increased mitochondrial respiration and with changes in gene sequence or expression level of proteins associated with microtubules, and that …

Structure-Activity Relationship Of Novel Rgd-Containing Cyclic Peptides Against Αvβ3 Integrin, Aaron Silva

Honors Theses

The αvβ3 integrin, a receptor for many extracellular matrix proteins with the RGD sequence motif, is involved in multiple physiological processes. The integrin is highly expressed on tumor cells, therefore making it a target for cancer therapy and imaging. Efforts have been made to develop an RGD-containing ligand against the αvβ3 integrin.

A series of RGD-containing cyclic octapeptides (LXW analogs) were previously synthesized, tested in vitro, and screened as integrin antagonists with a different binding affinity (Xiao et al., 2010; Wang et al., 2015), but the structure-activity relationship remains to be elucidated. In the current study, the structures of three …

Impedance Sensing Of Cancer Cells Directly On Sensory Bioscaffolds Of Bioceramics Nanofibers, Hanan Alismail

Graduate Theses and Dissertations

Cancer cell research has been growing for decades. In the field of cancer pathology, there is an increasing and long-unmet need to develop a new technology for low-cost, rapid, sensitive, selective, label-free (i.e. direct), simple and reliable screening, diagnosis, and monitoring of live cancer and normal cells in same shape and size from the same anatomic region. For the first time on using an impedance signal, the breast cancer and normal cells have been thus screened, diagnosed and monitored on a smart bioscaffold of entangled nanowires of bioceramics titanate grown directly on the surface of implantable Ti-metal and characterized by …

Role Of P300 Zz Domain In Chromatin Association And Histone Acetylation, Yongming Xue

Dissertations and Theses (Open Access)

Transcription is strictly regulated by numerous factors including transcription coactivators. The p300 protein and its close paralogue CREB-binding protein (CREBBP, aka CBP) are well-known transcriptional coactivators that have intrinsic lysine acetyltransferase activity. The functions of p300/CBP largely rely on their capabilities to bind to chromatin and to acetylate the histone substrates. However, the molecular mechanisms underlying the regulation of these processes are not fully understood.

Through combination of various biochemical, biophysical and molecular approaches, we show that the ZZ-type zinc finger (ZZ) domain of p300 functions as a histone reader that specifically binds the N-terminal tail of histone H3. Crystal …

Molecular Dynamics Of P21 And Fluorescent Sphingomyelin In Keratinocytes Exposed To Uvb, Tyler Malcolm Fraser

Master's Theses

Non-melanoma skin cancer (NMSC) is the most common malignant tumor, representing more than a third of all malignant tumors combined and the incidence is increasing every year. Ultraviolet (UV) radiation from the sun is the most dominant factor contributing to tumor initiation and progression. The condition is most prevalent in populations with lighter skin and older age. Current pharmaceutical molecular research targets the inhibition of the Epidermal Growth Factor Receptor (EGFR), a receptor which is commonly over-expressed or dysregulated in skin malignancies. This study evaluates the content and location of the damage marker p21 within keratinocytes that were incubated in …

Hdl In Endocrine Carcinomas: Biomarker, Drug Carrier, And Potential Therapeutic, Emily E. Morin, Xiang-An Li, Anna Schwendeman

Physiology Faculty Publications

High-density lipoprotein (HDL) have long been studied for their protective role against cardiovascular diseases, however recently relationship between HDL and cancer came into focus. Several epidemiological studies have shown an inverse correlation between HDL-cholesterol (HDL-C) and cancer risk, and some have even implied that HDL-C can be used as a predictive measure for survival prognosis in for specific sub-population of certain types of cancer. HDL itself is an endogenous nanoparticle capable of removing excess cholesterol from the periphery and returning it to the liver for excretion. One of the main receptors for HDL, scavenger receptor type B-I (SR-BI), is highly …

A Crispr Platform For Rapid And Inducible Genome Editing In Human Non-Small Cell Lung Cancer Cells, Lloyd Bartley

Posters-at-the-Capitol

Non-small cell lung cancer (NSCLC) accounts for about 85% of lung cancer, which is the leading cause of cancer death in the world. High mortality rate associated with NSCLC is partially attributed to the limited understanding of NSCLC as well as ineffective therapeutic treatments. The initiation and progression of NSCLC involves genetic changes leading to alterations in the control of tissue development and homeostatic maintenance. Better knowledge about these genetic abnormalities is imperative for developing new chemotherapeutic drugs for NSCLC. Recent research demonstrates that the expression of paraoxonase 2 (PON2), a lactonase/arylesterase with anti-oxidant properties, are markedly enhanced in cancer …

Characterization Of A Basement Membrane Associated Protein Encoding Gene In Drosophila Melanogaster, Aref Ranjbar, Ajay Srivastava

Posters-at-the-Capitol

Title: Characterization of a Basement Membrane Associated Protein Encoding Gene in Drosophila melanogaster

Authors: Aref Ranjbar, Mayank Kapadia, Ajay Srivastava, PhD(faculty member, mentor)

Basement Membranes (BM) are important for normal development and tumor progression. In order to get a better understanding of BM dynamics we identified genes that encoded BM interacting proteins. One such gene is predicted to be involved in vesicle-mediated transport in Drosophila melanogaster. Here we characterize this gene by utilizing molecular biology techniques like immunohistochemistry, RNA in situ hybridization, and Western blot analysis utilizing antibodies generated in the laboratory. Western blot analysis identified this protein to be …

Hnrnpa2 Mediated Acetylation Reduces Telomere Length In Response To Mitochondrial Dysfunction, Manti Guha, Satish Srinivasan, F. Bradley Johnson, Gordon Ruthel, Kip Guja, Miguel Garcia-Diaz, Brett A. Kaufman, M. Rebecca Glineburg, Jikang Fang, Hiroshi Nakagawa, Jeelan Basha, Tapas Kundu, Narayan G. Avadhani

Biology, Chemistry, and Environmental Sciences Faculty Articles and Research

Telomeres protect against chromosomal damage. Accelerated telomere loss has been associated with premature aging syndromes such as Werner’s syndrome and Dyskeratosis Congenita, while, progressive telomere loss activates a DNA damage response leading to chromosomal instability, typically observed in cancer cells and senescent cells. Therefore, identifying mechanisms of telomere length maintenance is critical for understanding human pathologies. In this paper we demonstrate that mitochondrial dysfunction plays a causal role in telomere shortening. Furthermore, hnRNPA2, a mitochondrial stress responsive lysine acetyltransferase (KAT) acetylates telomere histone H4at lysine 8 of (H4K8) and this acetylation is associated with telomere attrition. Cells containing dysfunctional mitochondria …

Development Of A Pd-L1 Pet Imaging Biomarker, Caleb Jack Bridgwater

Posters-at-the-Capitol

Immunotherapy strategies are very promising treatments for cancer patients. Specifically, Immune checkpoint inhibitor therapy focusing on the PD-1/PD-L1 pathway shows long-lasting positive results in many cancer patients. Unfortunately, not all the patients can benefit from this highly effective treatment. Hence, there is a great need for predictive biomarkers. Immunohistochemical (IHC) staining has been used as a way of predicting patient response, yet shows many problems. For example, IHC utilizes an invasive biopsy and sample fixing, which creates an incomplete and delayed picture of the patient’s biochemistry and the tumor microenvironment, consequently ignoring metastases.

The purpose of this study is to …

Combined High-Speed Single Particle Tracking Of Membrane Proteins And Super-Resolution Of Membrane-Associated Structures, Hanieh Mazloom Farsibaf, Keith A. Lidke

Shared Knowledge Conference

Many experiments have shown that the diffusive motion of lipids and membrane proteins are slower on the cell surface than those in artificial lipid bilayers or blebs. One hypothesis that may partially explain this mystery is the effect of the cytoskeleton structures on the protein dynamics. A model proposed by Kusumi [1] is the Fence-Picket Model which describes the cell membrane as a set of compartment regions, each ~ 10 to 200 nm in size, created by direct or indirect interaction of lipids and proteins with actin filaments just below the membrane. To test this hypothesis, we have assembled a …

Histone Deacetylation Is The Primary Epigenetic Mechanism For Silencing Of Tumor Suppressor Gene - Tissue Factor Pathway Inhibitor-2 In Hepatocellular Carcinoma Cells, Alisha Deshmukh, Shirish Barve

Posters-at-the-Capitol

Hepatocellular carcinoma (HCC) is the third leading cause of cancer related mortality worldwide. With a survival rate of less than 5 percent, a therapeutic treatment is desperately needed to manage this disease. Many epigenetic mechanisms that underlay HCC are being identified. A frequently silenced pathway tissue factor pathway inhibitor-2 (TFPI-2) is a critical tumor suppressor gene. In HCC, inactivation of TFPI-2 leads to tumor growth. Recent research indicated Fas L plays a major role in apoptosis as part of HCC. For the purposes of this study, the phytochemical Curcumin was explored to observe its possible effects on the epigenetic mechanisms …

Pyronaridine Exerts Potent Cytotoxicity On Human Breast And Hematological Cancer Cells Through Induction Of Apoptosis, Paulina J. Villanueva, Alberto Martinez, Sarah T. Baca, Rebecca E. Dejesus, Manuel Larragoity, Lisett Contreras, Denisse A. Gutierrez, Armando Varela-Ramirez, Renato J. Aguilera

Publications and Research

The potent antimalarial drug pyronaridine (PND) was tested for its potential as an anticancer drug. After exposing cancerous (17) and non-cancerous (2) cells to PND for 72 hr, PND was found to exhibit consistent and potent cytotoxic activity at low micromolar (μM) concentrations that ranged from 1.6 μM to 9.4 μM. Moreover, PND exerted a significant selective cytotoxicity index (SCI) on five out of seven breast cancer cell lines tested, with favorable values of 2.5 to 4.4, as compared with the non-cancerous breast MCF-10A cell line. By using the same comparison, PND exhibited a significant SCI on three out of …